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  1. 胃癌细胞p16和CDK4的表达及调控的分子机制%Molecular mechanism of p16 and CDK4 expression and regulation in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    马炬明; 王伟国; 胡慧珍; 施正杰

    2011-01-01

    目的 通过腺病毒携带p16基因感染胃癌细胞,研究p16功能恢复对CDK4表达的调节作用.方法 构建携带p16基因的重组腺病毒AdCMV-p16感染胃癌细胞系.Western blotting检测p16和CDK4的表达,MTT法检测癌细胞的增殖活性,DAPI染色计数癌细胞的凋亡比例.结果 胃癌细胞感染腺病毒载体AdCMV-p16后获得p16表达,对细胞整体CDK4表达无影响,但可明显降低细胞核CDK4的表达量;AdCMV-p16感染后引起癌细胞增殖活性下降,当感染复数(MOI)为1、10、20时,细胞存活率已经分别低于50%、20%和5%;p16表达可诱导癌细胞凋亡,细胞凋亡率达(13.86±4.65)%.结论 p16功能恢复后核CDK4含量减少,可能是诱导细胞周期阻滞和细胞凋亡、抑制癌细胞生长的主要分子机制.%Objective To investigate the regulation of CDK4 expression by reactivating p16 function through adenovirus vector in gastric cancer. Methods The adenovirus vector carrying p16 gene of AdCMV-p16 was constructed and used to infect gastric cancer cell lines. Western blotting was used to detect the expression of p16 and CDK4, MTT assay was used to detect the proliferation activity of cancer cells, and DAPI was used to stain and count the percentages of cancer cell apoptosis. Results After reactivation of p16 in gastric cancer cells, the expression level of CDK4 in whole cell extracts was not affected, but the nuclear CDK4 was decreased obviously. This phenomenon resulted in the depression of cancer cell proliferation activity, with the cell viability of lower than 50% ,20%, or 5% when MOl was 1, 10 or 20, respectively. p16 expression induced gastric cancer cells apoptosis with the apoptotic rate of ( 13. 86 ±4. 65)%. Conclusion The reactivation of p16 function in gastric cancer cells resulted in the decrease of nuclear CDK4,which may be the main molecular mechanism of pl6-induced cell cycle arrest and p16-mediated inhibition of cancer cell proliferation.

  2. The Cdk4-E2f1 pathway regulates early pancreas development by targeting Pdx1+ progenitors and Ngn3+ endocrine precursors.

    Science.gov (United States)

    Kim, So Yoon; Rane, Sushil G

    2011-05-01

    Cell division and cell differentiation are intricately regulated processes vital to organ development. Cyclin-dependent kinases (Cdks) are master regulators of the cell cycle that orchestrate the cell division and differentiation programs. Cdk1 is essential to drive cell division and is required for the first embryonic divisions, whereas Cdks 2, 4 and 6 are dispensable for organogenesis but vital for tissue-specific cell development. Here, we illustrate an important role for Cdk4 in regulating early pancreas development. Pancreatic development involves extensive morphogenesis, proliferation and differentiation of the epithelium to give rise to the distinct cell lineages of the adult pancreas. The cell cycle molecules that specify lineage commitment within the early pancreas are unknown. We show that Cdk4 and its downstream transcription factor E2f1 regulate mouse pancreas development prior to and during the secondary transition. Cdk4 deficiency reduces embryonic pancreas size owing to impaired mesenchyme development and fewer Pdx1(+) pancreatic progenitor cells. Expression of activated Cdk4(R24C) kinase leads to increased Nkx2.2(+) and Nkx6.1(+) cells and a rise in the number and proliferation of Ngn3(+) endocrine precursors, resulting in expansion of the β cell lineage. We show that E2f1 binds and activates the Ngn3 promoter to modulate Ngn3 expression levels in the embryonic pancreas in a Cdk4-dependent manner. These results suggest that Cdk4 promotes β cell development by directing E2f1-mediated activation of Ngn3 and increasing the pool of endocrine precursors, and identify Cdk4 as an important regulator of early pancreas development that modulates the proliferation potential of pancreatic progenitors and endocrine precursors.

  3. Regulation of Survivin and CDK4 by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Mi Dan AI; Li Li LI; Xiao Rong ZHAO; Yong WU; Jian Ping GONG; Ya CAO

    2005-01-01

    Latent membrane protein 1 (LMP1), an important protein encoded by Epstein Barr virus (EBV), has been implied to link with the pathogenesis of nasopharyngeal carcinoma (NPC). Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMP1. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.

  4. Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging

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    Franziska Graf

    2009-01-01

    Full Text Available The cyclin-dependent kinase (Cdk-cyclin D/retinoblastoma (pRb/E2F cascade, which controls the G1/S transition of cell cycle, has been found to be altered in many neoplasias. Inhibition of this pathway by using, for example, selective Cdk4 inhibitors has been suggested to be a promising approach for cancer therapy. We hypothesized that appropriately radiolabeled Cdk4 inhibitors are suitable probes for tumor imaging and may be helpful studying cell proliferation processes in vivo by positron emission tomography. Herein, we report the synthesis and biological, biochemical, and radiopharmacological characterizations of two I124-labeled small molecule Cdk4 inhibitors (8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-yl-phenylamino-8H-pyrido[2,3-d]-pyrimidin-7-one (CKIA and 8-cyclopentyl-6-iodo-5-methyl-2-(5-(piperazin-1-yl-pyridin-2-yl-amino-8H-pyrido[2,3-d]pyrimidin-7-one (CKIB. Our data demonstrate a defined and specific inhibition of tumor cell proliferation through CKIA and CKIB by inhibition of the Cdk4/pRb/E2F pathway emphasizing potential therapeutic benefit of CKIA and CKIB. Furthermore, radiopharmacological properties of [I124]CKIA and [I124]CKIB observed in human tumor cells are promising prerequisites for in vivo biodistribution and imaging studies.

  5. Expression and signification of cell cycle regulation protein Cyclin D1-CDK4-p21 in scar cancer%细胞周期调控系统相关因子 Cyclin D1-CDK4-p21在瘢痕癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    林宇静; 郭瑞珍; 王海青

    2014-01-01

    Objective Dysfunction of cell cycle regulation is one of the key factors for cellular carcinogenesis .This paper aimed to study the expression and significance of cell cycle regulation protein Cyclin D 1-CDK4-p21 in scar cancer . Methods The expressions of Cyclin D1, CDK4 and p21 protains were detected in scar cancer group , pathological scar group and normal skin group respectively by using immunohistochemical staining (SP).The mRNA expression levels of Cyclin D1, CDK4 and p21 were detected by the use of nucleic acid-mediated in-situ hybridization .Correlation analysis was made on the indexes , and the average optical density and positive area were analyzed using image analysis . Results The expressions of Cyclin D1, CDK4 and p21 protains and the mRNA ex-pression levels of cyclin D1, CDK4 and p21 were high in scar cancer group, low in pathological scar group , and negative in normal skin group.The mean optical density and positive area in scar cancer group were significantly different from pathological scar group and normal skin group (P0.05).In terms of correlation analysis , the expressions of Cyclin D 1 and CDK4 as well as p21 and CDK4 in scar cancer tissue were both in posi-tive correlations. Conclusion The occurrence of scar cancer is related to the abnormal expression of Cyclin D 1 and CDK4.The complex formed by Cyclin D1 and CDK4 may promote the G1/S transition, proliferation and tumorigenesis of scar cancer .In scar canc-er, the inhibition of Cyclin D1-CDK4 complex might be caused by other members of CKI family or even inbibitors of other families apart from CDK family.%目的:细胞周期调控机制失调是细胞增生肿瘤发生的重要因素。文中探讨细胞周期调控系统相关因子Cyclin D1-CDK4-p21在瘢痕癌中的表达及意义。方法选取遵义医学院病理教研室和中山大学附属第五医院病理科2005-2011年石蜡包埋标本,分为瘢痕癌组、病理性瘢痕组和正常皮肤组。应

  6. Targeting CDK4/6 in patients with cancer.

    Science.gov (United States)

    Hamilton, Erika; Infante, Jeffrey R

    2016-04-01

    The cyclin D-cyclin dependent kinase (CDK) 4/6-inhibitor of CDK4 (INK4)-retinoblastoma (Rb) pathway controls cell cycle progression by regulating the G1-S checkpoint. Dysregulation of the cyclin D-CDK4/6-INK4-Rb pathway results in increased proliferation, and is frequently observed in many types of cancer. Pathway activation can occur through a variety of mechanisms, including gene amplification or rearrangement, loss of negative regulators, epigenetic alterations, and point mutations in key pathway components. Due to the importance of CDK4/6 activity in cancer cells, CDK4/6 inhibitors have emerged as promising candidates for cancer treatment. Moreover, combination of a CDK4/6 inhibitor with other targeted therapies may help overcome acquired or de novo treatment resistance. Ongoing studies include combinations of CDK4/6 inhibitors with endocrine therapy and phosphatidylinositol 3-kinase (PI3K) pathway inhibitors for hormone receptor-positive (HR+) breast cancers, and with selective RAF and MEK inhibitors for tumors with alterations in the mitogen activated protein kinase (MAPK) pathway such as melanoma. In particular, the combination of CDK4/6 inhibitors with endocrine therapy, such as palbociclib's recent first-line approval in combination with letrozole, is expected to transform the treatment of HR+ breast cancer. Currently, three selective CDK4/6 inhibitors have been approved or are in late-stage development: palbociclib (PD-0332991), ribociclib (LEE011), and abemaciclib (LY2835219). Here we describe the current preclinical and clinical data for these novel agents and discuss combination strategies with other agents for the treatment of cancer.

  7. CDK4 is an essential insulin effector in adipocytes

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    Lagarrigue, Sylviane; Lopez-Mejia, Isabel C.; Denechaud, Pierre-Damien; Escoté, Xavier; Castillo-Armengol, Judit; Jimenez, Veronica; Chavey, Carine; Giralt, Albert; Lai, Qiuwen; Zhang, Lianjun; Martinez-Carreres, Laia; Delacuisine, Brigitte; Annicotte, Jean-Sébastien; Blanchet, Emilie; Huré, Sébastien; Abella, Anna; Tinahones, Francisco J.; Vendrell, Joan; Dubus, Pierre; Bosch, Fatima; Kahn, C. Ronald; Fajas, Lluis

    2015-01-01

    Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4R24C). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT. PMID:26657864

  8. The proline-histidine-rich CDK2/CDK4 interaction region of C/EBPalpha is dispensable for C/EBPalpha-mediated growth regulation in vivo

    DEFF Research Database (Denmark)

    Porse, Bo Torben; Pedersen, Thomas Askov; Hasemann, Marie Sigurd

    2006-01-01

    that a short, centrally located, 15-amino-acid proline-histidine-rich region (PHR) of C/EBPalpha is responsible for the growth-inhibitory function of the protein through its ability to interact with CDK2 and CDK4, thereby inhibiting their activities. Homozygous Cebpa(DeltaPHR/DeltaPHR) (DeltaPHR) mice...

  9. CDK4 T172 phosphorylation is central in a CDK7-dependent bidirectional CDK4/CDK2 interplay mediated by p21 phosphorylation at the restriction point.

    Directory of Open Access Journals (Sweden)

    Xavier Bisteau

    2013-05-01

    Full Text Available Cell cycle progression, including genome duplication, is orchestrated by cyclin-dependent kinases (CDKs. CDK activation depends on phosphorylation of their T-loop by a CDK-activating kinase (CAK. In animals, the only known CAK for CDK2 and CDK1 is cyclin H-CDK7, which is constitutively active. Therefore, the critical activation step is dephosphorylation of inhibitory sites by Cdc25 phosphatases rather than unrestricted T-loop phosphorylation. Homologous CDK4 and CDK6 bound to cyclins D are master integrators of mitogenic/oncogenic signaling cascades by initiating the inactivation of the central oncosuppressor pRb and cell cycle commitment at the restriction point. Unlike the situation in CDK1 and CDK2 cyclin complexes, and in contrast to the weak but constitutive T177 phosphorylation of CDK6, we have identified the T-loop phosphorylation at T172 as the highly regulated step determining CDK4 activity. Whether both CDK4 and CDK6 phosphorylations are catalyzed by CDK7 remains unclear. To answer this question, we took a chemical-genetics approach by using analogue-sensitive CDK7(as/as mutant HCT116 cells, in which CDK7 can be specifically inhibited by bulky adenine analogs. Intriguingly, CDK7 inhibition prevented activating phosphorylations of CDK4/6, but for CDK4 this was at least partly dependent on its binding to p21 (cip1 . In response to CDK7 inhibition, p21-binding to CDK4 increased concomitantly with disappearance of the most abundant phosphorylation of p21, which we localized at S130 and found to be catalyzed by both CDK4 and CDK2. The S130A mutation of p21 prevented the activating CDK4 phosphorylation, and inhibition of CDK4/6 and CDK2 impaired phosphorylations of both p21 and p21-bound CDK4. Therefore, specific CDK7 inhibition revealed the following: a crucial but partly indirect CDK7 involvement in phosphorylation/activation of CDK4 and CDK6; existence of CDK4-activating kinase(s other than CDK7; and novel CDK7-dependent positive

  10. DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21{sup Cip1}

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae-Woong; Kim, Hyeng-Soo; Kim, Seonggon; Hwang, Junmo; Kim, Young Hun; Lim, Ga Young [School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Sohn, Wern-Joo [Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu 700-412 (Korea, Republic of); Yoon, Suk-Ran [Cell Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon 305-806 (Korea, Republic of); Kim, Jae-Young [Department of Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu 700-412 (Korea, Republic of); Park, Tae Sung [Department of Laboratory Medicine, Kyung Hee University School of Medicine, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-702 (Korea, Republic of); Park, Kwon Moo [Department of Anatomy, Kyungpook National University School of Medicine, Daegu 700-422 (Korea, Republic of); Ryoo, Zae Young [School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lee, Sanggyu, E-mail: slee@knu.ac.kr [School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer DACH1 increases cyclin D, F and Cdk 1, 4, 6 in mouse myeloid progenitor cells. Black-Right-Pointing-Pointer The knockdown of DACH1 blocked the cell cycle progression of HL-60 cells. Black-Right-Pointing-Pointer The novel effect of DACH1 related with cell cycle regulation and leukemogenesis. -- Abstract: The cell-fate determination factor Dachshund, a component of the Retinal Determination Gene Network (RDGN), has a role in breast tumor proliferation through the repression of cyclin D1 and several key regulators of embryonic stem cell function, such as Nanog and Sox2. However, little is known about the role of DACH1 in a myeloid lineage as a cell cycle regulator. Here, we identified the differential expression levels of extensive cell cycle regulators controlled by DACH1 in myeloid progenitor cells. The forced expression of DACH1 induced p27{sup Kip1} and repressed p21{sup Cip1}, which is a pivotal characteristic of the myeloid progenitor. Furthermore, DACH1 significantly increased the expression of cyclin D1, D3, F, and Cdk 1, 4, and 6 in myeloid progenitor cells. The knockdown of DACH1 blocked the cell cycle progression of HL-60 promyeloblastic cells through the decrease of cyclin D1, D3, F, and Cdk 1, 4, and 6 and increase in p21{sup Cip1}, which in turn decreased the phosphorylation of the Rb protein. The expression of Sox2, Oct4, and Klf4 was significantly up-regulated by the forced expression of DACH1 in mouse myeloid progenitor cells.

  11. Cdk4 functions in multiple cell types to control Drosophila intestinal stem cell proliferation and differentiation

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    Mojca Adlesic

    2016-03-01

    Full Text Available The proliferation of intestinal stem cells (ISCs and differentiation of enteroblasts to form mature enteroendocrine cells and enterocytes in the Drosophila intestinal epithelium must be tightly regulated to maintain homeostasis. We show that genetic modulation of CyclinD/Cdk4 activity or mTOR-dependent signalling cell-autonomously regulates enterocyte growth, which influences ISC proliferation and enteroblast differentiation. Increased enterocyte growth results in higher numbers of ISCs and defective enterocyte growth reduces ISC abundance and proliferation in the midgut. Adult midguts deficient for Cdk4 show severe disruption of intestinal homeostasis characterised by decreased ISC self-renewal, enteroblast differentiation defects and low enteroendocrine cell and enterocyte numbers. The ISC/enteroblast phenotypes result from a combination of cell autonomous and non-autonomous requirements for Cdk4 function. One non-autonomous consequence of Cdk4-dependent deficient enterocyte growth is high expression of Delta in ISCs and Delta retention in enteroblasts. We postulate that aberrant activation of the Delta–Notch pathway is a possible partial cause of lost ISC stemness. These results support the idea that enterocytes contribute to a putative stem cell niche that maintains intestinal homeostasis in the Drosophila anterior midgut.

  12. MDM2 turnover and expression of ATRX determine the choice between quiescence and senescence in response to CDK4 inhibition.

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    Kovatcheva, Marta; Liu, David D; Dickson, Mark A; Klein, Mary E; O'Connor, Rachael; Wilder, Fatima O; Socci, Nicholas D; Tap, William D; Schwartz, Gary K; Singer, Samuel; Crago, Aimee M; Koff, Andrew

    2015-04-10

    CDK4 inhibitors (CDK4i) earned Breakthrough Therapy Designation from the FDA last year and are entering phase III clinical trials in several cancers. However, not all tumors respond favorably to these drugs. CDK4 activity is critical for progression through G1 phase and into the mitotic cell cycle. Inhibiting this kinase induces Rb-positive cells to exit the cell cycle into either a quiescent or senescent state. In this report, using well-differentiated and dedifferentiated liposarcoma (WD/DDLS) cell lines, we show that the proteolytic turnover of MDM2 is required for CDK4i-induced senescence. Failure to reduce MDM2 does not prevent CDK4i-induced withdrawal from the cell cycle but the cells remain in a reversible quiescent state. Reducing MDM2 in these cells drives them into the more stable senescent state. CDK4i-induced senescence associated with loss of MDM2 is also observed in some breast cancer, lung cancer and glioma cell lines indicating that this is not limited to WD/DDLS cells in which MDM2 is overexpressed or in cells that contain wild type p53. MDM2 turnover depends on its E3 ligase activity and expression of ATRX. Interestingly, in seven patients the changes in MDM2 expression were correlated with outcome. These insights identify MDM2 and ATRX as new regulators controlling geroconversion, the process by which quiescent cells become senescent, and this insight may be exploited to improve the activity of CDK4i in cancer therapy.

  13. Cyclin D and cdk4 Are Required for Normal Development beyond the Blastula Stage in Sea Urchin Embryos

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    Moore, Jennifer C.; Sumerel, Jan L.; Schnackenberg, Bradley J.; Nichols, Jason A.; Wikramanayake, Athula; Wessel, Gary M.; Marzluff, William F.

    2002-01-01

    cdk4 mRNA and protein are constitutively expressed in sea urchin eggs and throughout embryonic development. In contrast, cyclin D mRNA is barely detectable in eggs and early embryos, when the cell cycles consist of alternating S and M phases. Cyclin D mRNA increases dramatically in embryos at the early blastula stage and remains at a constant level throughout embryogenesis. An increase in cdk4 kinase activity occurs concomitantly with the increase in cyclin D mRNA. Ectopic expression of cyclin D mRNA in eggs arrests development before the 16-cell stage and causes eventual embryonic death, suggesting that activation of cyclin D/cdk4 in cleavage cell cycles is lethal to the embryo. In contrast, blocking cyclin D or cdk4 expression with morpholino antisense oligonucleotides results in normal development of early gastrula-stage embryos but abnormal, asymmetric larvae. These results suggest that in sea urchins, cyclin D and cdk4 are required for normal development and perhaps the patterning of the developing embryo, but may not be directly involved in regulating entry into the cell cycle. PMID:12052892

  14. Several noncontiguous domains of CDK4 are involved in binding to the P16 tumor suppressor protein

    NARCIS (Netherlands)

    Ceha, H.M.; Nasser, I.; Medema, R.H.; Slebos, R.J.C.

    1998-01-01

    Cyclin-dependent kinase 4 (CDK4) is a key molecule in the regulation of cell cycle progression at the G1-S phase restriction point. Its activity is specifically regulated by p16 (also known as p16/CDKN2A, p16INK4a, andMTS1), a tumor suppressor frequently altered in human cancers. A specific mutation

  15. Integrin Regulation during Leukocyte Recruitment.

    Science.gov (United States)

    Herter, Jan; Zarbock, Alexander

    2013-05-01

    Integrins are recognized as vital players in leukocyte recruitment. Integrin malfunction causes severe disease patterns characterized by the inability to fight pathogens. Although inflammatory reactions are beneficial and necessary for host defense, these reactions have to be controlled to prevent tissue destruction and harmful sequelae. In this review, we discuss the different signaling pathways leading to the change of integrin adhesiveness in neutrophils, monocytes, and lymphocytes. We thereby focus on the importance of integrin activation for the different steps of the leukocyte recruitment cascade, including rolling, adhesion, postadhesion strengthening, intravascular crawling, and transmigration, as each step necessitates the proper functioning of a distinct set of integrin molecules that has to be activated specifically. Additionally, we discuss endogenous mechanisms that balance and counteract integrin activation and limit leukocyte recruitment at the site of inflammation. Further insight into these complex mechanisms may provide new approaches for developing new anti-inflammatory therapies.

  16. CDK4, pRB and E2F1: connected to insulin

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    Blanchet Emilie

    2010-02-01

    Full Text Available Abstract Pancreatic β-cells are metabolic sensors involved in the control of glucose homeostasis. This particular cell type controls insulin secretion through a fine-tuned process, which dregulation have important pathological consequences, such as observed during type 2 diabetes. We recently implicated E2F1 in the control of glucose homeostasis. First we showed that E2f1-/- mice have decreased pancreatic size, as the result of impaired postnatal pancreatic growth. We observed in this study that E2F1 was highly expressed in non-proliferating pancreatic β-cells, suggesting that E2F1, besides the control of β-cell number could have a role in pancreatic β-cell function. We demonstrate in our recent study, both in vitro and in vivo that E2F1 directly regulates the expression of Kir6.2, a key component of the KATP channel involved in the regulation of glucose-induced insulin secretion in pancreatic β-cells. Expression of Kir6.2 is lost in pancreas of E2f1-/- mice, resulting in insulin secretion defects in these mice. Furthermore, we demonstrated by in tissue chromatin immunoprecipitation analysis that regulation of Kir6.2 expression by E2F1 follows the same regulatory pathway that the classical E2F1 target genes, implicating the participation of CDK4 and retinoblastoma protein. Moreover, in this context, E2F1 transcriptional activity is regulated by glucose and insulin through the CDK4-dependent inactivation of the pRB protein. In summary we provide evidence that the CDK4-pRB-E2F1 regulatory pathway is involved in glucose homeostasis. In our recent study we decipher a new function for these factors in the control of insulin secretion and open up new avenues for the treatment of metabolic diseases, in particular type 2 diabetes.

  17. Expressing patterns of p16 and CDK4 correlated to prognosis in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Po Zhao; Ying-Chuan Hu; Ian C. Talbot

    2003-01-01

    AIM: To describe the correlation between innunostaining patterns of p16 and CDK4 and prognosis in colorectal carcinoma.METHODS: Paraffin sections of 74 cases of colorectal carcinoma were analysed immunohistochemically for expression of p16 and CDK4 proteins.RESULTS: Most carcinomas showed stronger p16 and CDK4immunostaining in the cytoplasm than the adenomas or the adjacent normal mucosa. Strong immunostaining of p16 was a predictor for better prognosis whereas strong cytoplasmic immunostaining of CDK4 was a predictor for poor prognosis.Both p16 and CDK4 immunostainings were correlated with histological grade or Dukes' stage.CONCLUSION: These results support the experimental evidence that interaction of expression of p16 and CDK4may play an important role in the Rb/p16 pathway, and the expression paterns of CDK4 and p16 may be imperative in the development of colorectal carcinoma, thus becoming a new prognostic marker in colorectal cancer.

  18. The different roles of cyclinD1-CDK4 in STP and mGluR-LTD during the postnatal development in mice hippocampus area CA1

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    Wang Huili

    2007-05-01

    Full Text Available Abstract Background Cell-cycle-related proteins, such as cyclins or cyclin-dependent kinases, may have functions beyond that of cell cycle regulation. The expression and translocation of cyclinD1-CDK4 in post-mitotic neurons indicate that they may have supplementary functions in differentiated neurons that might be associated with neuronal plasticity. Results In the present study, our findings showed that the expression of CDK4 was localized mostly in nuclei and cytoplasm of pyramidal cells of CA1 at postnatal day 10 (P10; whereas at P28 staining of CDK4 could be detected predominantly in the cytoplasm but not nuclei. Basal synaptic transmission was normal in the presence of CDK4 inhibitor. Short-term synaptic plasticity (STP was impaired in CDK4 inhibitor pre-treated slices both from neonatal (P8-15 and adolescent (P21-35 animals; however there was no significant change in paired-pulse facilitation (PPF in slices pre-incubated with the CDK4 inhibitor from adolescent animals. By the treatment of CDK4 inhibitor, the induction or the maintenance of Long-term potentiation (LTP in response to a strong tetanus and NMDA receptor-dependent long-term depression (LTD were normal in hippocampus. However, long-term depression (LTD induced either by group I metabotropic glutamate receptors (mGluRs agonist or by paired-pulse low-frequency stimulation (PP-LFS was impaired in CDK4 inhibitor pretreated slices both from neonatal and adolescent animals. But the effects of the CDK4 inhibitor at slices from adolescent animals were not as robust as at slices from neonatal animals. Conclusion Our results indicated that the activation of cyclinD1-CDK4 is required for short-term synaptic plasticity and mGluR-dependent LTD, and suggested that this cyclin-dependent kinase may have different roles during the postnatal development in mice hippocampus area CA1.

  19. Activation of CDK4 Triggers Development of Non-alcoholic Fatty Liver Disease

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    Jingling Jin

    2016-07-01

    Full Text Available The development of non-alcoholic fatty liver disease (NAFLD is a multiple step process. Here, we show that activation of cdk4 triggers the development of NAFLD. We found that cdk4 protein levels are elevated in mouse models of NAFLD and in patients with fatty livers. This increase leads to C/EBPα phosphorylation on Ser193 and formation of C/EBPα-p300 complexes, resulting in hepatic steatosis, fibrosis, and hepatocellular carcinoma (HCC. The disruption of this pathway in cdk4-resistant C/EBPα-S193A mice dramatically reduces development of high-fat diet (HFD-mediated NAFLD. In addition, inhibition of cdk4 by flavopiridol or PD-0332991 significantly reduces development of hepatic steatosis, the first step of NAFLD. Thus, this study reveals that activation of cdk4 triggers NAFLD and that inhibitors of cdk4 may be used for the prevention/treatment of NAFLD.

  20. EXPRESSION OF CYCLIN D1 AND CDK4 IN OSTEOSARCOMA OF THE JAWS

    Institute of Scientific and Technical Information of China (English)

    司晓辉; 刘正

    2001-01-01

    Objective: To analyze cyclin D1 and cyclin- dependent kinase 4 (CDK4) expression and their significance in osteosarcoma of the jaws. Methods: Immunohistochemical ABC method was used to detect the expression of cyclin D1 and CDK4 in 20 cases of osteosarcoma and 8 cases of osteochondroma of the jaws. Results: The positive rates of cyclin D1 and CDK4 were 65% (13/20) and 60% (12/20), respectively. There was significant positive correlation between cyclin D1 and CDK4 expression (gs=0.48, P<0.05). Both cyclin D1 and CDK4 were present in 1/8 (12.5%) osteochondroma. The positive rate was remarkably different between osteosarcoma and osteochondroma (P<0.05). Conclusion: Cyclin D1 and CDK4 are overexpressed in osteosarcoma of the jaws and closely related to its occurrence and development.

  1. CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the abdomen.

    Directory of Open Access Journals (Sweden)

    Sanghoon Lee

    Full Text Available The absence of CDK4 amplification in liposarcomas is associated with favorable prognosis. We aimed to identify the factors associated with tumor recurrence in patients with well-differentiated (WD and dedifferentiated (DD liposarcomas.From 2000 to 2010, surgical resections for 101 WD and DD liposarcomas were performed. Cases in which complete surgical resections with curative intent were carried out were selected. MDM2 and CDK4 gene amplification were analyzed by quantitative real-time polymerase chain reaction (Q-PCR.There were 31 WD and 17 DD liposarcomas. Locoregional recurrence was observed in 11 WD and 3 DD liposarcomas. WD liposarcomas showed better patient survival compared to DD liposarcomas (P<0.05. Q-PCR analysis of the liposarcomas revealed the presence of CDK4 amplification in 44 cases (91.7% and MDM2 amplification in 46 cases (95.8%. WD liposarcomas with recurrence after surgical resection had significantly higher levels of CDK4 amplification compared to those without recurrence (P = 0.041. High level of CDK4 amplification (cases with CDK4 amplification higher than the median 7.54 was associated with poor recurrence-free survival compared to low CDK4 amplification in both univariate (P = 0.012 and multivariate analyses (P = 0.020.Level of CDK4 amplification determined by Q-PCR was associated with the recurrence of WD liposarcomas after surgical resection.

  2. Azolium analogues as CDK4 inhibitors: Pharmacophore modeling, 3D QSAR study and new lead drug discovery

    Science.gov (United States)

    Rondla, Rohini; Padma Rao, Lavanya Souda; Ramatenki, Vishwanath; Vadija, Rajender; Mukkera, Thirupathi; Potlapally, Sarita Rajender; Vuruputuri, Uma

    2017-04-01

    The cyclin-dependent kinase 4 (CDK4) enzyme is a key regulator in cell cycle G1 phase progression. It is often overexpressed in variety of cancer cells, which makes it an attractive therapeutic target for cancer treatment. A number of chemical scaffolds have been reported as CDK4 inhibitors in the literature, and in particular azolium scaffolds as potential inhibitors. Here, a ligand based pharmacophore modeling and an atom based 3D-QSAR analyses for a series of azolium based CDK4 inhibitors are presented. A five point pharmacophore hypothesis, i.e. APRRR with one H-bond acceptor (A), one positive cationic feature (P) and three ring aromatic sites (R) is developed, which yielded an atom based 3D-QSAR model that shows an excellent correlation coefficient value- R2 = 0.93, fisher ratio- F = 207, along with good predictive ability- Q2 = 0.79, and Pearson R value = 0.89. The visual inspection of the 3D-QSAR model, with the most active and the least active ligands, demonstrates the favorable and unfavorable structural regions for the activity towards CDK4. The roles of positively charged nitrogen, the steric effect, ligand flexibility, and the substituents on the activity are in good agreement with the previously reported experimental results. The generated 3D QSAR model is further applied as query for a 3D database screening, which identifies 23 lead drug candidates with good predicted activities and diverse scaffolds. The ADME analysis reveals that, the pharmacokinetic parameters of all the identified new leads are within the acceptable range.

  3. MicroRNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D.

    Science.gov (United States)

    Georgantas, Robert W; Streicher, Katie; Luo, Xiaobing; Greenlees, Lydia; Zhu, Wei; Liu, Zheng; Brohawn, Philip; Morehouse, Christopher; Higgs, Brandon W; Richman, Laura; Jallal, Bahija; Yao, Yihong; Ranade, Koustubh

    2014-03-01

    Expression profiling of microRNAs in melanoma lesional skin biopsies compared with normal donor skin biopsies, as well as melanoma cell lines compared with normal melanocytes, revealed that hsa-miR-206 was down-regulated in melanoma (-75.4-fold, P = 1.7 × 10(-4)). MiR-206 has been implicated in a large number of cancers, including breast, lung, colorectal, ovarian, and prostate cancers; however, its role in tumor development remains largely unknown, its biologic function is poorly characterized, and its targets affecting cancer cells are largely unknown. MiR-206 reduced growth and migration/invasion of multiple melanoma cell lines. Bioinformatics identified cell cycle genes CDK2, CDK4, Cyclin C, and Cyclin D1 as strong candidate targets. Western blots and 3'UTR reporter gene assays revealed that miR-206 inhibited translation of CDK4, Cyclin D1, and Cyclin C. Additionally, hsa-miR-206 transfection induced G1 arrest in multiple melanoma cell lines. These observations support hsa-miR-206 as a tumor suppressor in melanoma and identify Cyclin C, Cyclin D1, and CDK4 as miR-206 targets.

  4. Expression of Survivin, CDK4, Ki-67 and Clinical Significance in Pediatric Acute Leukemia

    Institute of Scientific and Technical Information of China (English)

    ZHANG Liuqing; LIU Jing; LIN Hanhua; HU Qun; LIU Aiguo; HU Ying

    2006-01-01

    The expression of Survivin, CDK4 and Ki-67 and the clinical significance in pediatric acute leukemia (AL) were investigated. The expression of Survivin, CDK4 and Ki-67 proteins was detected by using immunohistochemical assay in 37 children with AL and 10 children with normal bone marrow as controls. The positive expression rate of Survivin, CDK4 and Ki-67 was 45.9 %,56.8 %, and 40.5 % respectively in 37 AL children, which was significantly higher than in control group accordingly (P<0.05). The expression of Survivin was positively correlated with CDK4(P=0.007) and Ki-67 (P=0.008). In conclusion, all Survivin, CDK4 and Ki-67 proteins are over-expressed in pediatric AL and involved in the modulation of apoptosis and proliferation in pediatric AL.

  5. Germ Line Transmission of the Cdk4R24C Mutation Facilitates Tumorigenesis and Escape from Cellular Senescence

    OpenAIRE

    Sushil G Rane; Cosenza, Stephen C.; Mettus, Richard V.; Reddy, E. Premkumar

    2002-01-01

    Mutations in CDK4 and its key kinase inhibitor p16INK4a have been implicated in the genesis and progression of familial human melanoma. The importance of the CDK4 locus in human cancer first became evident following the identification of a germ line CDK4-Arg24Cys (R24C) mutation, which abolishes the ability of CDK4 to bind to p16INK4a. To determine the role of the Cdk4R24C germ line mutation in the genesis of other cancer types, we introduced the R24C mutation in the Cdk4 locus of mice by usi...

  6. Role of CyclinD1 and CDK4 in the Carcinogenesis Induced by Silica

    Institute of Scientific and Technical Information of China (English)

    KE-XIA YAN; BING-CI LIU; XIANG-LIN SHI; BAO-RONG YOU; MING XU

    2005-01-01

    Objective To study the role of cyclinD1 and CDK4 in malignant transformation of human fetal lung diploid fibroblast cell line(2BS) induced by silica. Methods Recombination vectors with sense and antisense pXJ41-cyclinD1 and pXJ41-CDK4 were constructed, and then transfected into the malignant transformed cells induced by silica, respectively. At the same time, pXJ41-neo was used as the control. Results During the progress of the malignant transformation of 2BS cells induced by silica, cyclinD1 and CDK4 were overexpressed. Antisense RNA suppressed cyclinD1 and CDK4 gene expression in the antisense pXJ41-cyclinD1 and pXJ41-CDK4 transfected cells. Antisense RNA led to cell cycle arrest, resulting in lengthened G1 phase (the percentages of cells in the G1 phase changed from 45.1% to 52.7% and 58.0% for cyclinD1 and CDK4 transfected cells, respectively), and eventually attenuated the increase of the proliferation of malignant transformed cells induced by silica. Compared with malignant transformed cells induced by silica, cells transfected with antisense pXJ41-cyclinD1 and pXJ41-CDK4 showed obviously reduced growth rates. On the 8th day, the suppression rates were 58.69 and 77.43% (the growth rate of malignant transformed cells induced by silica was 100%), doubling time changed from 21.0 h to 31.4 h and 21.0 h to 42.7 h, respectively, the growth capacities on soft agar of cells transfected by antisense pXJ41-cyclinD1 and pXJ41-CDK4 decreased obviously. Conclusion CyclinD1 and CDK4 play an important role in maintaining transformed phenotype of the cancer cells.

  7. p27Kip1 and p21Cip1 collaborate in the regulation of transcription by recruiting cyclin-Cdk complexes on the promoters of target genes.

    Science.gov (United States)

    Orlando, Serena; Gallastegui, Edurne; Besson, Arnaud; Abril, Gabriel; Aligué, Rosa; Pujol, Maria Jesus; Bachs, Oriol

    2015-08-18

    Transcriptional repressor complexes containing p130 and E2F4 regulate the expression of genes involved in DNA replication. During the G1 phase of the cell cycle, sequential phosphorylation of p130 by cyclin-dependent kinases (Cdks) disrupts these complexes allowing gene expression. The Cdk inhibitor and tumor suppressor p27(Kip1) associates with p130 and E2F4 by its carboxyl domain on the promoters of target genes but its role in the regulation of transcription remains unclear. We report here that p27(Kip1) recruits cyclin D2/D3-Cdk4 complexes on the promoters by its amino terminal domain in early and mid G1. In cells lacking p27(Kip1), cyclin D2/D3-Cdk4 did not associate to the promoters and phosphorylation of p130 and transcription of target genes was increased. In late G1, these complexes were substituted by p21(Cip1)-cyclin D1-Cdk2. In p21(Cip1) null cells cyclin D1-Cdk2 were not found on the promoters and transcription was elevated. In p21/p27 double null cells transcription was higher than in control cells and single knock out cells. Thus, our results clarify the role of p27(Kip1) and p21(Cip1) in transcriptional regulation of genes repressed by p130/E2F4 complexes in which p27(Kip1) and p21(Cip1) play a sequential role by recruiting and regulating the activity of specific cyclin-Cdk complexes on the promoters.

  8. Simulation of Different Truncated p16INK4a Forms and In Silico Study of Interaction with Cdk4

    Science.gov (United States)

    Fahham, Najmeh; Ghahremani, Mohammad Hossein; Sardari, Soroush; Vaziri, Behrouz; Ostad, Seyed Nasser

    2008-01-01

    Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex. In this study, we have focused on cyclin-dependent kinase 4 (Cdk4), a key molecule in the regulation of cell cycle progression at the G1-S phase restriction point and p16INK4a, a tumor suppressor which inhibits Cdk4 activity. Truncated structures were created to find the more critical regions of p16 for interaction. The tertiary structures were determined by ProSAL, GENO3D Web Server. We evaluated their interactions with Cdk4 using two docking systems, HEX 4.5 and DOT 1. Calculations were performed on a high-speed computer. Minimizations and visualizations were carried out by PdbViewer 3.7. Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms. The free energies were compatible with that of p16 full length original form, the full length. It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy. PMID:19352455

  9. Simulation of Different Truncated p16INK4a Forms and In Silico Study of Interaction with Cdk4

    Directory of Open Access Journals (Sweden)

    Najmeh Fahham

    2009-01-01

    Full Text Available Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex. In this study, we have focused on cyclin-dependent kinase 4 (Cdk4, a key molecule in the regulation of cell cycle progression at the G1-S phase restriction point and p16INK4a, a tumor suppressor which inhibits Cdk4 activity. Truncated structures were created to find the more critical regions of p16 for interaction. The tertiary structures were determined by ProSAL, GENO3D Web Server. We evaluated their interactions with Cdk4 using two docking systems, HEX 4.5 and DOT 1. Calculations were performed on a high-speed computer. Minimizations and visualizations were carried out by PdbViewer 3.7. Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fi t complexes among the p16 truncated forms. The free energies were compatible with that of p16 full length original form, the full length. It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy.

  10. A large Norwegian family with inherited malignant melanoma, multiple atypical nevi, and CDK4 mutation.

    Science.gov (United States)

    Molven, Anders; Grimstvedt, Magne B; Steine, Solrun J; Harland, Mark; Avril, Marie-Françoise; Hayward, Nicholas K; Akslen, Lars A

    2005-09-01

    Mutations in two loci encoding cell-cycle-regulatory proteins have been shown to cause familial malignant melanoma. About 20% of melanoma-prone families bear a mutation in the CDKN2A locus, which encodes two unrelated proteins, p16INK4A and p14ARF. Mutations in the other locus, CDK4, are much rarer and have been linked to the disease in only three families worldwide. In the 1960s, a large Norwegian pedigree with multiple atypical nevi and malignant melanomas was identified. Subsequently, six generations and more than 100 family members were traced and 20 cases of melanoma verified. In this article, we report that CDK4 codon 24 is mutated from CGT to CAT (Arg24His) in this unusually large melanoma kindred. Intriguingly, one of the family members had ocular melanoma, but the CDK4 mutation could not be detected in archival tissue samples from this subject. Thus, the case of ocular melanoma in this family was sporadic, suggesting an etiology different from that of the skin tumors. The CDK4 mutation in the Norwegian family was identical to that in melanoma families in France, Australia, and England. Haplotype analysis using microsatellite markers flanking the CDK4 gene and single-nucleotide polymorphisms within the gene did not support the possibility that there was a common founder, but rather indicated at least two independent mutational events. All CDK4 melanoma families known to date have a substitution of amino acid 24. In addition to resulting from selection pressure, this observation may be explained by the CG dinucleotide of codon 24 representing a mutational hot spot in the CDK4 gene.

  11. Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human cancer cells

    NARCIS (Netherlands)

    The, Inge; Ruijtenberg, Suzan; Bouchet, Benjamin P; Cristobal Gonzalez de Durana, Alba; Prinsen, Martine B W; van Mourik, Tim; Koreth, John; Xu, Huihong; Heck, Albert J R; Akhmanova, Anna; Cuppen, Edwin; Boxem, Mike; Munoz Murillo, Ara; van den Heuvel, Sander

    2015-01-01

    Cyclin-dependent kinases 4 and 6 (CDK4/6) in complex with D-type cyclins promote cell cycle entry. Most human cancers contain overactive CDK4/6-cyclin D, and CDK4/6-specific inhibitors are promising anti-cancer therapeutics. Here, we investigate the critical functions of CDK4/6-cyclin D kinases, sta

  12. 1α,25 dihydroxi-vitamin D{sub 3} modulates CDK4 and CDK6 expression and localization

    Energy Technology Data Exchange (ETDEWEB)

    Irazoqui, Ana P.; Heim, Nadia B.; Boland, Ricardo L.; Buitrago, Claudia G., E-mail: cbuitrag@criba.edu.ar

    2015-03-27

    We recently reported that the vitamin D receptor (VDR) and p38 MAPK participate in pro-differentiation events triggered by 1α,25(OH){sub 2}-vitamin D{sub 3} [1,25D] in skeletal muscle cells. Specifically, our studies demonstrated that 1,25D promotes G0/G1 arrest of cells inducing cyclin D3 and cyclin dependent kinases inhibitors (CKIs) p21{sup Waf1/Cip1} and p27{sup Kip1} expression in a VDR and p38 MAPK dependent manner. In this work we present data indicating that cyclin-dependent kinases (CDKs) 4 and 6 also play a role in the mechanism by which 1,25D stimulates myogenesis. To investigate VDR involvement in hormone regulation of CDKs 4 and 6, we significantly reduced its expression by the use of a shRNA against mouse VDR, generating the skeletal muscle cell line C2C12-VDR. Investigation of changes in cellular cycle regulating proteins by immunoblotting showed that the VDR is involved in the 1,25D –induced CDKs 4 and 6 protein levels at 6 h of hormone treatment. CDK4 levels remains high during S phase peak and G0/G1 arrest while CDK6 expression decreases at 12 h and increases again al 24 h. The up-regulation of CDKs 4 and 6 by 1,25D (6 h) was abolished in C2C12 cells pre-treated with the ERK1/2 inhibitor, UO126. Moreover, CDKs 4 and 6 expression induced by the hormone nor was detected when α and β isoforms of p38 MAPK were inhibited by compound SB203580. Confocal images show that there is not co-localization between VDR and CDKs at 6 h of hormone treatment, however CDK4 and VDR co-localizates in nucleus after 12 h of 1,25D exposure. Of relevance, at this time 1,25D promotes CDK6 localization in a peri-nuclear ring. Our data demonstrate that the VDR, ERK1/2 and p38 MAPK are involved in the control of CDKs 4 and 6 by 1,25D in skeletal muscle cells sustaining the operation of a VDR and MAPKs –dependent mechanism in hormone modulation of myogenesis. - Highlights: • 1,25D modulates CDKs 4 and 6 expression in skeletal muscle cells. • CDK4 co

  13. Germ line transmission of the Cdk4(R24C) mutation facilitates tumorigenesis and escape from cellular senescence.

    Science.gov (United States)

    Rane, Sushil G; Cosenza, Stephen C; Mettus, Richard V; Reddy, E Premkumar

    2002-01-01

    Mutations in CDK4 and its key kinase inhibitor p16(INK4a) have been implicated in the genesis and progression of familial human melanoma. The importance of the CDK4 locus in human cancer first became evident following the identification of a germ line CDK4-Arg24Cys (R24C) mutation, which abolishes the ability of CDK4 to bind to p16(INK4a). To determine the role of the Cdk4(R24C) germ line mutation in the genesis of other cancer types, we introduced the R24C mutation in the Cdk4 locus of mice by using Cre-loxP-mediated "knock-in" technology. Cdk4(R24C/R24C) mouse embryo fibroblasts (MEFs) displayed increased Cdk4 kinase activity resulting in hyperphosphorylation of all three members of the Rb family, pRb, p107, and p130. MEFs derived from Cdk4(R24C/R24C) mice displayed decreased doubling times, escape from replicative senescence, and escape sensitivity to contact-induced growth arrest. These MEFs also exhibited a high degree of susceptibility to oncogene-induced transformation, suggesting that the Cdk4(R24C) mutation can serve as a primary event in the progression towards a fully transformed phenotype. In agreement with the in vitro data, homozygous Cdk4(R24C/R24C) mice developed tumors of various etiology within 8 to 10 months of their life span. The majority of these tumors were found in the pancreas, pituitary, brain, mammary tissue, and skin. In addition, Cdk4(R24C/R24C) mice showed extraordinary susceptibility to carcinogens and developed papillomas within the first 8 to 10 weeks following cutaneous application of the carcinogens 9,10-di-methyl-1,2-benz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). This report formally establishes that the activation of Cdk4 is sufficient to promote cancer in many tissues. The observation that a wide variety of tumors develop in mice harboring the Cdk4(R24C) mutation offers a genetic proof that Cdk4 activation may constitute a central event in the genesis of many types of cancers in addition to melanoma.

  14. Structure-Based Design of Cdk4/6-Specific Inhibitors

    Science.gov (United States)

    2006-10-01

    AUTHOR(S) 5d. PROJECT NUMBER Ronen Marmorstein, Ph.D. 5e. TASK NUMBER E-Mail: marmor @wistar.org 5f. WORK UNIT NUMBER 7. PERFORMING...mail: marmor @wista.wistar.upenn.edu. 1 The abbreviations used are: CDK, cyclin-dependent kinase; INK4, inhibitors of CDK4. THE JOURNAL OF BIOLOGICAL

  15. CDK4/6 inhibitor PD0332991 in glioblastoma treatment: Does it have a future?

    NARCIS (Netherlands)

    L.B.W. Schröder (Lisette B.W.); K.L. McDonald (Kerrie L.)

    2015-01-01

    textabstractGlioblastoma is aggressive, highly infiltrating, and the most frequent malignant form of brain cancer. With a median survival time of only 14.6 months, when treated with the standard of care, it is essential to find new therapeutic options. A specific CDK4/6 inhibitor, PD0332991, obtaine

  16. Aberrant cytological localization of p16 and CDK4 in colorectal epithelia in the normal adenoma carcinoma sequence

    Institute of Scientific and Technical Information of China (English)

    Po Zhao; Xin Mao; Ian C Talbot

    2006-01-01

    AIM: To study the correlation between the patterns of subcellular expression of p16 and CDK4 in colorectal epithelia in the normal-adenoma-carcinoma sequence.METHODS: Paraffin sections of 43 cases of normal colorectal epithelia and corresponding adenomas as well as carcinomas were analysed immunocytochemically for subcellular expression of p16 and CDK4 proteins.RESULTS: Most carcinomas showed more cytoplasmic overexpression for p16 and CDK4 than the adenomas from which they arised or the adjacent normal mucosa.Most normal or non-neoplastic epithelia showed more p16 and CDK4 expression in the nucleus than their adjacent adenomas and carcinomas. There was a significant difference between the subcellular expression pattern of p16 and CDK4 in normal-adenoma-carcinoma sequence epithelia (P < 0.001). Neither p16 nor CDK4 subcellular patterns correlated with histological grade or Dukes' stage.CONCLUSION: Interaction of expression of p16 and CDK4 plays an important role in the Rb/p16 pathway.Overexpression of p16 and CDK4 in the cytoplasm, as well as loss expression of p16 in the nucleus might be important in the evolution of colorectal carcinoma from adenoma and, of adenoma from normal epithelia.

  17. Analysing the Effect of Mutation on Protein Function and Discovering Potential Inhibitors of CDK4: Molecular Modelling and Dynamics Studies.

    Directory of Open Access Journals (Sweden)

    Nagasundaram N

    Full Text Available The cyclin-dependent kinase 4 (CDK4-cyclin D1 complex plays a crucial role in the transition from the G1 phase to S phase of the cell cycle. Among the CDKs, CDK4 is one of the genes most frequently affected by somatic genetic variations that are associated with various forms of cancer. Thus, because the abnormal function of the CDK4-cyclin D1 protein complex might play a vital role in causing cancer, CDK4 can be considered a genetically validated therapeutic target. In this study, we used a systematic, integrated computational approach to identify deleterious nsSNPs and predict their effects on protein-protein (CDK4-cyclin D1 and protein-ligand (CDK4-flavopiridol interactions. This analysis resulted in the identification of possible inhibitors of mutant CDK4 proteins that bind the conformations induced by deleterious nsSNPs. Using computational prediction methods, we identified five nsSNPs as highly deleterious: R24C, Y180H, A205T, R210P, and R246C. From molecular docking and molecular dynamic studies, we observed that these deleterious nsSNPs affected CDK4-cyclin D1 and CDK4-flavopiridol interactions. Furthermore, in a virtual screening approach, the drug 5_7_DIHYDROXY_ 2_ (3_4_5_TRI HYDROXYPHENYL _4H_CHROMEN_ 4_ONE displayed good binding affinity for proteins with the mutations R24C or R246C, the drug diosmin displayed good binding affinity for the protein with the mutation Y180H, and the drug rutin displayed good binding affinity for proteins with the mutations A205T and R210P. Overall, this computational investigation of the CDK4 gene highlights the link between genetic variation and biological phenomena in human cancer and aids in the discovery of molecularly targeted therapies for personalized treatment.

  18. Cdk2 deficiency decreases ras/CDK4-dependent malignant progression, but not myc-induced tumorigenesis.

    Science.gov (United States)

    Macias, Everardo; Kim, Yongbaek; Miliani de Marval, Paula L; Klein-Szanto, Andres; Rodriguez-Puebla, Marcelo L

    2007-10-15

    We have previously shown that forced expression of CDK4 in mouse skin (K5CDK4 mice) results in increased susceptibility to squamous cell carcinoma (SCC) development in a chemical carcinogenesis protocol. This protocol induces skin papilloma development, causing a selection of cells bearing activating Ha-ras mutations. We have also shown that myc-induced epidermal proliferation and oral tumorigenesis (K5Myc mice) depends on CDK4 expression. Biochemical analysis of K5CDK4 and K5Myc epidermis as well as skin tumors showed that keratinocyte proliferation is mediated by CDK4 sequestration of p27Kip1 and p21Cip1, and activation of CDK2. Here, we studied the role of CDK2 in epithelial tumorigenesis. In normal skin, loss of CDK2 rescues CDK4-induced, but not myc-induced epidermal hyperproliferation. Ablation of CDK2 in K5CDK4 mice results in decreased incidences and multiplicity of skin tumors as well as malignant progression to SCC. Histopathologic analysis showed that K5CDK4 tumors are drastically more aggressive than K5CDK4/CDK2-/- tumors. On the other hand, we show that CDK2 is dispensable for myc-induced tumorigenesis. In contrast to our previous report of K5Myc/CDK4-/-, K5Myc/CDK2-/- mice developed oral tumors with the same frequency as K5Myc mice. Overall, we have established that ras-induced tumors are more susceptible to CDK2 ablation than myc-induced tumors, suggesting that the efficacy of targeting CDK2 in tumor development and malignant progression is dependent on the oncogenic pathway involved.

  19. 细胞周期调控因子p16和CDK4在肺癌中的表达%Expression of p16 and CDK4 in human lung carcinoma

    Institute of Scientific and Technical Information of China (English)

    路名芝; 刘勇

    2001-01-01

    Purpose:To study the expressions of p16 and CDK4 in human lung carcinoma. Methods:By using S-P immunohistochemical methods, the expressions of p16 and CDK4 in 62 cases of human lung carcnoma were studied. Results:The postive expressions for p16 and CDK4 protein were 58.1% and 48.4% respectively. A significant correlation was found between CDK4 overexpression and lymph node metastasis (P<0.01). A significant correlation between the under expression of p16 and overexpression of CDK4 was found.Conclusions:The results suggested that CDK4 overexpression plays an important role in metastasis of lung carcinoma.%目的:探讨肺癌中细胞周期调控因子p16和CDK4的表达意义。方法:应用S-P免疫组织化学方法检测62例肺癌组织中p16和CDK4的表达情况。结果:62例肺癌组织中p16和CDK4阳性率分别为58.1%和48.4%。腺癌中p16的阳性率明显高于小细胞癌(P<0.05);淋巴结转移阳性组p16的表达显著低于阴性组(P<0.05,r=0.27)。不同组织类型肺癌中CDK4的表达未见明显差异,淋巴结转移阳性组CDK4的表达高于阴性组(P<0.01,r=0.58)。p16和CDK4的表达呈明显负相关(P<0.01,r=-0.81)。结论:提示p16的表达与肺癌的组织学类型有关,CDK4高表达对肺癌细胞的淋巴结转移起重要作用。

  20. Effects of an Indolocarbazole-Derived CDK4 Inhibitor on Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yuan Sun, Ying-xia Li, Hai-jun Wu, Si-hung Wu, Y. Alan Wang, Dian-zhong Luo, D. Joshua Liao

    2011-01-01

    Full Text Available Introduction: Cyclin D1 (D1 binds to cyclin-dependent kinases (CDK 4 or 6 to form a holoenzyme that phosphorylates the Rb protein to promote cell cycle progression from G1 to S phase. Therefore, targeting CDK4/6 may be a good strategy for chemotherapy of cancer. We performed a proof-of-principle study to determine the effect of Naphtho [2, 1-α] pyrrolo [3, 4-c] carbazole-5, 7 (6H, 12H-dione (NPCD, a novel CDK4 inhibitor, on breast cancer cell lines.Methods: NPCD was synthesized and purified to over 99% purity verified by HPLC. MCF7, MB231, MCF15, T47D and GI101Ap human breast cancer cells were analyzed for the efficacy of NPCD with MTT and clonogenic assays, with FACS and staining for ethidium bromide and acridine orange for cell death and cell cycle profile. Western blot, reverse transcription and PCR were used for studies of gene expression, and co-immunoprecipitation for protein-complex formation.Results: MTT assay showed that NPCD caused growth arrest and apoptosis of MCF7, MDA-MB231, T47D, MCF15 and GI101Ap cells with an IC50 ranging between 3 to 8 µM given as a single dose. The growth arrest persisted for many days after cessation of the treatment, as shown in a clonogenic assay. NPCD could induce or reduce the D1 and CDK4 protein levels, depending on the cell line, but this effect was not correlated with its efficacy. Phosphorylation of D1 at Thr286 was decreased but it unexpectedly did not correlate with the change in D1 level in the cell lines studied. Phosphorylation of the Rb protein was decreased as expected whereas the p27kip1 protein level was decreased unexpectedly. Protein levels of p21cip1, CDK2 and cyclin E were also decreased in some, but not all, of the cell lines, whereas the mRNA levels of D1, CDK4, cyclin E, CDK2, p27kip1 and p21cip1 were increased in different cell lines.Conclusions: NPCD can cause long-lasting growth arrest and cell death of breast cancer cell lines at an IC50 of 3-8 µM. Decreased phosphorylation of

  1. Metabolic re-programming of pancreatic cancer mediated by CDK4/6 inhibition elicits unique vulnerabilities

    Science.gov (United States)

    Franco, Jorge; Balaji, Uthra; Freinkman, Elizaveta; Witkiewicz, Agnieszka K.; Knudsen, Erik S.

    2016-01-01

    Due to loss of p16ink4a in pancreatic ductal adenocarcinoma (PDA), pharmacological suppression of CDK4/6 could represent a potent target for treatment. In PDA models CDK4/6 inhibition had variable effect on cell cycle, but yielded accumulation of ATP and mitochondria. Pharmacological CDK4/6 inhibitors induce cyclin D1 protein levels; however, RB activation was required and sufficient for mitochondrial accumulation. CDK4/6 inhibition stimulated glycolytic and oxidative metabolism and was associated with an increase in mTORC1 activity. MTOR and MEK inhibitors potently cooperate with CDK4/6 inhibition in eliciting cell cycle exit. However, MTOR inhibition fully suppressed metabolism and yielded apoptosis and suppression of tumor growth. The metabolic state mediated by CDK4/6 inhibition increases mitochondrial number and ROS. Concordantly, the suppression of ROS scavenging or BCL2-antagonists cooperated with CDK4/6 inhibition. Together, these data define the impact of therapeutics on PDA metabolism and provide strategies for converting cytostatic response to tumor cell killing. PMID:26804906

  2. Different Patterns of Cyclin D1/CDK4-E2F-1/4 Pathways in Human Embryo Lung Fibroblasts Treated by Benzo[a]pyrene at Different Doses1

    Institute of Scientific and Technical Information of China (English)

    MENG YE; BING-CI LIU; XIANG-LIN SHI; BAO-RONG YOU; HONG-JU DU; XIAO-WEI JIA; FU-HAI SHEN

    2008-01-01

    Objective To investigate the roles of the cyclin D1/CDK4 and E2F-1/4 pathways and compare their work patterns in cell cycle changes induced by different doses of B[a]P. Methods Human embryo lung fibroblasts(HELFs)were treated with 2 μmol/L or 100 μmol/L B[a]P which were provided with some characteristics of transformed cells (T-HELFs).Cyclin D1,CDK4 and E2F-1/4 expressions were determined by Westem blotting.Flow cytometry was used to detect the distribution of cell cycle.Results After B[a]P treatment,the proportion of the first gap(G1)phase cells decreased.CDK4 and E2F-4 expression did not change significantly.In 2 μmol/L treated cells,a marked overexpression of cyclin D1 and E2F-1 was observed.However,in T-HELFs overexpression was limited to cyclin D1 only,and no overexpression of E2F-1 was observed.The decreases of G1 phase in response to B[a]P treatment were blocked in antisense cyclin D1 and antisense CDK4 transfected HELFs (A-D1 and A-K4)and T-HELFs(T-A-D1 and T-A-K4).Atier 2 μmol/L B[a]P treatment,overexpression of E2F-1 was attenuated in A-D1,and E2F-4 expression was decreased significantly in A-K4.In T-A-D1 and T-A-K4,E2F-4 expression was increased significantly,compared with T-HELFs.The E2F-1 expression remained unchanged in T-A-D1 and T-A-K4.Conclusions Cyclin D1/CDK4-E2F-1/4 pathways work in different patterns in response to low dose and high dose B[a]P treatment.In HELFs treated with 2 μmol/L B[a]P, cyclin D1 positively regulates the E2F-1 expression while CDK4 negatively regulates the E2F-4 expression;however,in HELFs treated with 100 μmol/L B[a]P,both cyclin D1 and CDK4 negatively regulate the E2F-4 expression.

  3. Fluorescent peptide biosensor for monitoring CDK4/cyclin D kinase activity in melanoma cell extracts, mouse xenografts and skin biopsies.

    Science.gov (United States)

    Prével, Camille; Pellerano, Morgan; González-Vera, Juan A; Henri, Pauline; Meunier, Laurent; Vollaire, Julien; Josserand, Véronique; Morris, May C

    2016-11-15

    Melanoma constitutes the most aggressive form of skin cancer, which further metastasizes into a deadly form of cancer. The p16(INK4a)-Cyclin D-CDK4/6-pRb pathway is dysregulated in 90% of melanomas. CDK4/Cyclin D kinase hyperactivation, associated with mutation of CDK4, amplification of Cyclin D or loss of p16(INK4a) leads to increased risk of developing melanoma. This kinase therefore constitutes a key biomarker in melanoma and an emerging pharmacological target, however there are no tools enabling direct detection or quantification of its activity. Here we report on the design and application of a fluorescent peptide biosensor to quantify CDK4 activity in melanoma cell extracts, skin biopsies and melanoma xenografts. This biosensor provides sensitive means of comparing CDK4 activity between different melanoma cell lines and further responds to CDK4 downregulation by siRNA or small-molecule inhibitors. By affording means of monitoring CDK4 hyperactivity consequent to cancer-associated molecular alterations in upstream signaling pathways that converge upon this kinase, this biosensor offers an alternative to immunological identification of melanoma-specific biomarkers, thereby constituting an attractive tool for diagnostic purposes, providing complementary functional information to histological analysis, of particular utility for detection of melanoma onset in precancerous lesions. This is indeed the first fluorescent peptide biosensor which has been successfully implemented to monitor kinase activity in skin samples and melanoma tumour xenografts. Moreover by enabling to monitor response to CDK4 inhibitors, this biosensor constitutes an attractive companion assay to identify compounds of therapeutic relevance for melanoma.

  4. Efficient Wnt mediated intestinal hyperproliferation requires the cyclin D2-CDK4/6 complex

    Directory of Open Access Journals (Sweden)

    Sansom Owen

    2011-02-01

    Full Text Available Abstract Inactivation of the gene encoding the adenomatous polyposis coli (APC tumour suppressor protein is recognized as the key early event in the development of colorectal cancers (CRC. Apc loss leads to nuclear localization of beta-catenin and constitutive activity of the beta-catenin-Tcf4 transcription complex. This complex drives the expression of genes involved in cell cycle progression such as c-Myc and cyclin D2. Acute loss of Apc in the small intestine leads to hyperproliferation within the intestinal crypt, increased levels of apoptosis, and perturbed differentiation and migration. It has been demonstrated that c-Myc is a critical mediator of the phenotypic abnormalities that follow Apc loss in the intestine. As it may be difficult to pharmacologically inhibit transcription factors such as c-Myc, investigating more druggable targets of the Wnt-c-Myc pathway within the intestine may reveal potential therapeutic targets for CRC. Recent work in our laboratory has shown that the cyclin D2-cyclin-dependent kinase 4/6 (CDK4/6 complex promotes hyperproliferation in Apc deficient intestinal tissue and ApcMin/+ adenomas. We showed that the hyperproliferative phenotype associated with Apc loss in vivo was partially dependent on the expression of cyclin D2. Most importantly, tumour growth and development in ApcMin/+ mice was strongly perturbed in mice lacking cyclin D2. Furthermore, pharmacological inhibition of CDK4/6 suppressed the proliferation of adenomatous cells. This commentary discusses the significance of this work in providing evidence for the importance of the cyclin D2-CDK4/6 complex in colorectal adenoma formation. It also argues that inhibition of this complex may be an effective chemopreventative strategy in CRC.

  5. ALTERATIONS OF pRb/CDK4/p16INK4a PATHWAY IN GASTRIC CARCINOMAS%胃癌中p16INK4a-CDK4-pRb通路蛋白表达异常

    Institute of Scientific and Technical Information of China (English)

    赵英芳; 田新霞; 卢阳

    2005-01-01

    目的:检测胃癌组织中p16INK4a-CDK4-pRb通路p16INK4a、CDK4、pRb蛋白表达状况,探讨蛋白表达与胃癌发生发展以及临床病理指标的关系.方法:采用免疫组织化学方法检测了胃癌组织中p16INK4a、CDK4、pRb蛋白表达.结果:10例正常胃黏膜中相应蛋白表达全部阳性,而肿瘤组织中p16INK4a、pRb蛋白表达阳性率分别为54%(44/81)和90%(73/81),p16INK4a蛋白表达显著低于正常组织(P=0.005),26%(21/81)的肿瘤组织中CDK4过表达.p16INK4a、pRb、CDK4蛋白表达与肿瘤组织学类型、淋巴结转移及性别、年龄均无相关性.结论:p16INK4a、CDK4、pRb蛋白表达异常是胃癌细胞常见的分子事件,p16INK4a-CDK4-pRb细胞周期调控通路异常可能参与了胃癌的发生发展.

  6. Evaluation of genetic melanoma vaccines in cdk4-mutant mice provides evidence for immunological tolerance against authochthonous melanomas in the skin.

    Science.gov (United States)

    Steitz, Julia; Büchs, Stefanie; Tormo, Damia; Ferrer, Aleix; Wenzel, Jörg; Huber, Christoph; Wölfel, Thomas; Barbacid, Mariano; Malumbres, Marcos; Tüting, Thomas

    2006-01-15

    We evaluated the efficacy of a candidate melanoma vaccine approach in mice genetically prone to develop melanoma due to the introduction of an oncogenic mutation (R24C) in the germline sequence of the cyclin-dependent kinase 4 (cdk4), a protein critically involved in cell cycle regulation. Melanomas were induced in cdk4-mutant mice by chemical carcinogenesis and UVB irradiation. A genetic prime-boost strategy targeting the clinically relevant differentiation antigen tyrosinase-related protein 2 (TRP2) was performed which was able to stimulate a melanocyte-specific cellular immune response associated with localized autoimmune vitiligo-like depigmentation. However, significant destruction of carcinogen-induced autochthonous melanocytic neoplasms in the skin was not observed following immunization. We provide evidence that autochthonous melanomas expressed TRP2 but not the MHC molecule H2-Kb and are immunologically tolerated in the skin. Our results highlight the importance of assessing melanoma vaccines in genetic mouse models that more adequately represent the expected clinical situation in order to identify strategies, which eventually may be of benefit for melanoma patients.

  7. Diverse models for the prediction of CDK4 inhibitory activity of substituted 4-aminomethylene isoquinoline-1, 3-diones

    Indian Academy of Sciences (India)

    Monika Gupta; A K Madan

    2013-05-01

    In the present study, both classification and correlation approaches have been successfully employed for development of models for the prediction of CDK4 inhibitory activity using a dataset comprising of 52 analogues of 4-aminomethylene isoquinoline-1,3-(2,4)-dione. Decision tree, random forest, moving average analysis (MAA), multiple linear regression (MLR), partial least square regression (PLSR) and principal component regression (PCR) were used to develop models for prediction of CDK4 inhibitory activity. The statistical significance of models was assessed through specificity, sensitivity, overall accuracy, Mathew’s correlation coefficient (MCC), cross validated correlation coefficient, test, 2 for external test set (pred_r2), coefficient of correlation of predicted dataset (pred_r2Se) and intercorrelation analysis. High accuracy of prediction offers proposed models a vast potential for providing lead structures for the development of potent therapeutic agents for CDK4 inhibition.

  8. 皮肤瘢痕癌中CDK4、CDK6蛋白的表达及意义%The expression and its significance of CDK4 and CDK6 in skin scar cancer

    Institute of Scientific and Technical Information of China (English)

    林宇静; 郭瑞珍

    2013-01-01

    目的 探讨细胞周期素依赖激酶CDK4、CDK6蛋白在皮肤瘢痕癌组织中的表达及意义.方法 采用免疫组织化学S-P法检测正常皮肤表皮、皮肤病理性瘢痕被覆上皮和瘢痕癌组织中CDK4、CDK6蛋白的表达.结果 CDK4、CDK6蛋白在皮肤瘢痕癌组中呈阳性或强阳性表达,在皮肤病理性瘢痕组中呈弱阳性表达,在正常皮肤组中呈阴性或弱阳性表达.瘢痕癌组分别与正常皮肤组和皮肤病理性瘢痕组比较,差别有统计学意义(P<0.01).结论 CDK4、CDK6蛋白的过表达可能与瘢痕癌的发生具有相关性.

  9. Involvement of PSMD10, CDK4, and Tumor Suppressors in Development of Intrahepatic Cholangiocarcinoma of Syrian Golden Hamsters Induced by Clonorchis sinensis and N-Nitrosodimethylamine.

    Directory of Open Access Journals (Sweden)

    Md Hafiz Uddin

    Full Text Available Clonorchis sinensis is a group-I bio-carcinogen for cholangiocarcinoma (CCA. Although the epidemiological evidence links clonorchiasis and CCA, the underlying molecular mechanism involved in this process is poorly understood. In the present study, we investigated expression of oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C. sinensis induced hamster CCA model.Different histochemical/immunohistochemical techniques were performed to detect CCA in 4 groups of hamsters: uninfected control (Ctrl., infected with C. sinensis (Cs, ingested N-nitrosodimethylamine (NDMA, and both Cs infected and NDMA introduced (Cs+NDMA. The liver tissues from all groups were analyzed for gene/protein expressions by quantitative PCR (qPCR and western blotting.CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly differentiated types measured in 21.8% ± 1.5%, 13.3% ± 1.3%, and 10.8% ± 1.3% of total tissue section areas respectively. All CCA differentiations progressed in a time dependent manner, starting from the 8th week of infection. CCA stroma was characterized with increased collagen type I, mucin, and proliferative cell nuclear antigen (PCNA. The qPCR analysis showed PSMD10, CDK4 and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA group. We observed no change in RB1 at mRNA level but found significant down-regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were found downregulated in the CCA tissue. Gene/protein expressions were matched well with the pathological changes of different groups except the NDMA group. Though the hamsters in the NDMA group showed no marked pathological lesions, we observed over-expression of Akt/PKB and p53 genes proposing molecular interplay in this group which might be related to the CCA initiation in this animal model.The present findings suggest that oncogenes, PSMD10 and CDK4, and tumor suppressors, p53 and RB, are involved in the

  10. 苏尼替尼对HeLa细胞中的CDK4的影响%Effects of Sutent on the CDK4 in HeLa Cell

    Institute of Scientific and Technical Information of China (English)

    郑昆; 张元新; 展瑞岩; 李世军

    2013-01-01

    以不同浓度的Sutent作用于HeLa细胞,采用MTT法检测Sutent对HeLa细胞增殖的影响.流式细胞术检测Sutent对HeLa细胞周期的影响;Western免疫印迹检测不同浓度的Sutent对HeLa细胞中CDK4蛋白表达的变化;探讨苏尼替尼(Sutent)对HeLa细胞中CDK4的影响.结果表明Sutent能够抑制HeLa细胞的增殖,引起HeLa细胞发生G2期周期阻滞,并且呈浓度依赖性降低HeLa细胞中CDK4蛋白表达量.显示了Sutent作为多靶点药物在药物研发中具有潜在的重要的研究价值.

  11. CLONING AND DETERMINING OF BAC GENE AND Bcl-2 AND CDK4 EXPRESSION ON ASCITES HEPATOMA CELL LINE Hca-F25/25CL-16A3

    Institute of Scientific and Technical Information of China (English)

    ZUO Yun-fei; ZHANG Yao-zheng; ZHANG Hong; REN Zhuang-yi

    1999-01-01

    Objective: To study the mechanism of cancer, the DNA for BAC was cloned from an ascites hepatoma cell line Hca-F25/CL-16A3 using PCR. Methods: The nucleotide sequences were determined using ABI PRISMTM 377 DNA sequencer. The expression of bcl-2 and CDK4gene were determined using immunohistochemistry.Results: The sequences of BAC segment on HcaF25/CL-16A3 have nearly identical sequences with human BAC. The bcl-2 and CDK4 are highly expression on this cell line. Conclusion: The highly expression of bcl-2 and CDK4 may the one of mechanisms for tumor growth.

  12. Développement de biosenseurs fluorescents et d’inhibiteurs pour suivre et cibler CDK4/cycline D dans le mélanome

    OpenAIRE

    Prevel, Camille

    2015-01-01

    CDK/cyclins play a central role in coordinating cell cycle progression, and in sustaining proliferation of cancer cells, thereby constituting established cancer biomarkers and attractive pharmacological targets. In particular, CDK4/cyclin D, which is responsible for coordinating cell cycle progression through G1 into S phase, is a relevant target in several cancers including melanoma, associated with mutation of CDK4, cyclin D, p16INK4a and pRb.As there are no sensitive and direct approaches ...

  13. DMPD: Regulation of phagocyte migration and recruitment by Src-family kinases. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18385944 Regulation of phagocyte migration and recruitment by Src-family kinases. B...how Regulation of phagocyte migration and recruitment by Src-family kinases. PubmedID 18385944 Title Regulat...ion of phagocyte migration and recruitment by Src-family kinases. Authors Baruzzi

  14. Differential diagnosis of atypical lipomatous tumor/well-differentiated liposarcoma and dedifferentiated liposarcoma: utility of p16 in combination with MDM2 and CDK4 immunohistochemistry.

    Science.gov (United States)

    Kammerer-Jacquet, Solène-Florence; Thierry, Sixte; Cabillic, Florian; Lannes, Morgane; Burtin, Florence; Henno, Sébastien; Dugay, Frédéric; Bouzillé, Guillaume; Rioux-Leclercq, Nathalie; Belaud-Rotureau, Marc-Antoine; Stock, Nathalie

    2017-01-01

    The differential diagnosis between atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) and dedifferentiated liposarcoma (DDLPS) from their morphologic counterparts is challenging. Currently, the diagnosis is guided by MDM2 and CDK4 immunohistochemistry (IHC) and is confirmed by the amplification of the corresponding genes. Recently, p16 IHC has been proposed as a useful diagnostic biomarker. The objective was to assess the utility of p16 IHC in the differential diagnosis of ALT/WDLPS and DDLPS. Our series included 101 tumors that were previously analyzed using fluorescence in situ hybridization for MDM2 and CDK4 amplification. We compared sensitivity and specificity of p16 IHC to MDM2 and CDK4 IHC in the differential diagnosis of ALT-WDLPS (n=19) versus benign adipocytic tumors (n=44) and DDLPS (n=18) versus mimicking sarcomas (n=20). In the differential diagnosis of ALT-WDLPS, p16 had a sensitivity of 89.5% but a specificity of 68.2%, which was impaired by false-positive lipomas with secondary changes, especially in biopsies. Likewise, in the differential diagnosis of DDLPS, p16 had a sensitivity of 94.4% and a specificity of 70%, which hampered its use as a single marker. However, adding p16 to MDM2 and/or CDK4 increased diagnostic specificity. Indeed, MDM2+/p16+ tumors were all ALT-WDLPS, and MDM2-/p16- tumors were all benign adipocytic tumors. Moreover, all MDM2+/CDK4+/p16+ tumors were DDLPS, and the MDM2-/CDK4-/p16- tumor was an undifferentiated sarcoma. Although the use of p16 as a single immunohistochemical marker is limited by its specificity, its combination with MDM2 and CDK4 IHC may help discriminate ALT-WDLPS/DDLPS.

  15. Digital expression profiling identifies RUNX2, CDC5L, MDM2, RECQL4, and CDK4 as potential predictive biomarkers for neo-adjuvant chemotherapy response in paediatric osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Jeffrey W Martin

    Full Text Available Osteosarcoma is the most common malignancy of bone, and occurs most frequently in children and adolescents. Currently, the most reliable technique for determining a patients' prognosis is measurement of histopathologic tumor necrosis following pre-operative neo-adjuvant chemotherapy. Unfavourable prognosis is indicated by less than 90% estimated necrosis of the tumor. Neither genetic testing nor molecular biomarkers for diagnosis and prognosis have been described for osteosarcomas. We used the novel nanoString mRNA digital expression analysis system to analyse gene expression in 32 patients with sporadic paediatric osteosarcoma. This system used specific molecular barcodes to quantify expression of a set of 17 genes associated with osteosarcoma tumorigenesis. Five genes, from this panel, which encoded the bone differentiation regulator RUNX2, the cell cycle regulator CDC5L, the TP53 transcriptional inactivator MDM2, the DNA helicase RECQL4, and the cyclin-dependent kinase gene CDK4, were differentially expressed in tumors that responded poorly to neo-adjuvant chemotherapy. Analysis of the signalling relationships of these genes, as well as other expression markers of osteosarcoma, indicated that gene networks linked to RB1, TP53, PI3K, PTEN/Akt, myc and RECQL4 are associated with osteosarcoma. The discovery of these networks provides a basis for further experimental studies of role of the five genes (RUNX2, CDC5L, MDM2, RECQL4, and CDK4 in differential response to chemotherapy.

  16. 首个CDK4/6抑制剂新药--Palbociclib%Palbociclib:a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer

    Institute of Scientific and Technical Information of China (English)

    康建磊; 王彦明

    2016-01-01

    palbociclib是辉瑞制药有限公司(Pfizer)研发的选择性CDK4/6抑制剂,2015年2月3日,基于临床试验证明的无进展生存期(PFS),FDA采用加快审评途径批准其上市,与来曲唑(Letrozole)联合使用作为以内分泌治疗为基础的初始方案,用于治疗雌激素受体阳性(ER+)、人表皮生长因子受体2阴性(HER2-)的绝经女性乳腺癌。笔者对其基本性质、作用机制、药代动力学、药物相互作用、临床研究、不良反应及国内研发现状等方面做一综述。%Palbociclib developed by Pifzer is an oral selective inhibitor of cyclin-dependent kinase (CDK) 4 and 6. On February 3rd, 2015, the US FDA granted to accelerate the approval of palbociclib (IBRANCE®), in combination with letrozole,as initial endocrine-based therapy for postmenopausal women with estrogen receptor-positive (ER), human epidermal growth factor receptor 2 (HER2)-negative advanced metastatic breast cancer. In this article, the properties, mechanism, pharmacokinetics, drug interactions, clinical studies, adverse reactions and domestic R&D status were reviewed.

  17. 抑癌基因蛋白p16在宫颈癌中过度表达对其结合Cdk4功能的影响%Effects of over-expressed p16 on its binding capacity with Cdk4 in cervical squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    庞天云; 邓飞; 郑晓娟; 邹琳; 李飞虹; 胡新荣

    2011-01-01

    目的 观察在宫颈癌中过度表达的p16是否仍然具有正常结合Cdk4的功能,进一步阐明过表达的p16不能抑制宫颈癌发生发展的原因.方法 对142例宫颈标本,包括慢性宫颈炎19例,CIN Ⅰ级(LCIN)15例,CIN Ⅱ/Ⅲ级(HCIN)42例,宫颈鳞状细胞癌(SCC)66例进行p16和Cdk4免疫组化染色分析.选取1例p16高表达SCC(22C)和1例p16低表达SCC(43C)的新鲜标本进行免疫沉淀和Western blot分析.结果 按照慢性宫颈炎、LCIN、HCIN和SCC的顺序,p16阳性率分别是0、60.0%、78.6%和92.4%;Cdk4 阳性率分别是21.1%、46.7%、73.2%和92.4%,表明p16和CDK4的表达随宫颈肿瘤的进展而协调性升高.在同一例标本中,83.9%的p16高表达SCC的Cdk4同时呈高表达;86.7%的p16低表达SCC的Cdk4呈高表达或平行低表达,表明大多数SCC含有足够的与p16结合的Cdk4.结合Cdk4的p16与总p16的比例在p16高表达SCC(22C)中是66.9%,在p16低表达SCC(43C)中是42.2%,表明在SCC中过表达p16的近半左右与Cdk4结合,且p16表达越高,其与Cdk4结合的总量也越多.结论 在宫颈癌中过度表达的p16 仍然具有结合Cdk4 的能力.本研究首次从宫颈癌组织水平证实过表达的p16可以结合Cdk4,为研究p16对宫颈癌的作用向前推进了一步.%Objective To observe the hinding capacity of over - expressed p16 with Cdk4 in cervical carcinoma.Methods Immunohistochemiscal staining of p16 and Cdk4 was performed on 142 samples of cervical tissues, including 19, 15 , 42 and 66 cases of cervicitis, low cervical intraepithelial neoplasm ( LCIN ) , high CIN ( HCIN ) and invasive cervical squamous cell carcinoma ( SCC ), respectively. Co - immunoprecipitation ( Co - IP ) and Western blot were used to test the activity of p16 binding Cdk4 in high p16 expression and low p16 expression SCC. Results In the lesions of cervicitis, LCIN, HCIN and SCC, the p16 positive rates were 0, 60. 0% , 78. 6% and 92. 4% , respectively, with Cdk4 positive rates of 21. 1

  18. Loss of Keratinocytic RXRα Combined with Activated CDK4 or oncogenic NRAS Generates UVB-induced Melanomas via Loss of p53 and PTEN in the Tumor Microenvironment

    OpenAIRE

    Coleman, Daniel J.; Chagani, Sharmeen; Hyter, Stephen; Sherman, Anna M.; Löhr, Christiane V.; Liang, Xiaobo; Ganguli-Indra, Gitali; Indra, Arup K.

    2014-01-01

    Understanding the molecular mechanisms behind formation of melanoma, the deadliest form of skin cancer, is crucial for improved diagnosis and treatment. One key is to better understand the cross-talk between epidermal keratinocytes and pigment-producing melanocytes. Here, using a bigenic mouse model system combining mutant oncogenic NRASQ61K (constitutively active RAS) or mutant activated CDK4R24C/R24C (prevents binding of CDK4 by kinase inhibitor p16INK4A) with an epidermis-specific knockout...

  19. 脑胶质瘤中pRb表达与CDK4、MTS基因异常的相关性研究%Molecular pathological study on expression of pRb and CDK4,MTS gene changes in human gliomas

    Institute of Scientific and Technical Information of China (English)

    田新华; 江澄川; 高翔; 陈商群; 许凯黎; 周瑾

    2001-01-01

    Objective To investigate expression of pRb and CDK4, MTS gene changes in human gliomas and relationship with the clinical pathology. Methods Brain gliomas with different pathologic types were detected by using PCR-SSCP, Southern blot, Slot blot and immunohistochemistry. Results The negative expression of p16 or pRb and CDK4 amplification often occurred independently. The total rate of negative expression of p16 and/or pRb and/or deletion of p15 and/or CDK4 amplification were in 89% (42/47).Conclusions The propensity was occurrence of singular (89%) rather than combined aberrant expression of p16 or pRb or CDK4 amplification. The suppression of p16, p15 or pRb or the increased activity of CDK4 were sufficient to disrupt this regulatory mechanism in a manner that favors cell proliferation and tissues canceration.%目的 探讨脑胶质瘤中CDK4、MTS基因异常及pRb表达改变与脑胶质瘤发生发展的相关性。方法 应用PCR-SSCP、分子杂交及免疫组化技术检测68例不同病理分级脑胶质瘤。结果 p16基因表达阴性或pRb无表达或CDK4扩增多为单独发生,其中III-IV级肿瘤中pRb、p16蛋白失表达或p15基因缺失或CDK4基因扩增的综合发生率为89%(42/47)。结论 脑胶质瘤中细胞生长周期“关卡”蛋白p16、pRb、或CDK4单因素的异常比交错并发的改变更为常见,p16、pRb失活或CDK4扩增的任一改变,即可能破坏细胞增殖的正常调控,促发脑胶质瘤细胞的癌性增殖或恶性演变。

  20. Quantitative analysis of expression of cyclin D1 and CDK4 in normal, inflammatory and malignant epithelia of cheek mucosa%cyclin D1和CDK4在口腔正常上皮、炎症及鳞癌中表达的定量分析

    Institute of Scientific and Technical Information of China (English)

    马妍; Tipoe,GL; 等

    2001-01-01

    AIM To evaluate the expression and significance of cyclinD1/CDK4in normal epithelia (N), inflammatory (IF) and squamous cell cacinoma (SCC) of cheek mucosa. METHODS Oringinal pathology specimens were collected cut and immunostained by cyclin D1 monoclonal antibody and CDK4 polyclonal antibody, using the avidin-biotin peroxidase complex technique (ABC). RESULTS There was statistical significance between the N group and SCC group, but not between the N group and IF group. Cyclin D1 and CDK4 were overexpressed in SCC. CONCLUSION Overexpression of cyclinD1 and CDK4 in SCC may be due to the gene amplification and/or other related factors. The variations of cyclin D1and CDK4 in different subgroups of SCC may be a helpful indicator for tumor grading.%目的 通过检测口腔粘膜的正常上皮、非特异性炎症上皮及鳞癌中cyclinD1与CDK4的表达,探讨其在上皮组织不同状态中的变化及意义.方法 用临床病理标本,设立对照,选择cyclinD1和CDK4抗体免疫组化染色.结果 cyclinD1和CDK4在正常口腔上皮与口腔鳞癌上皮、非特异性炎症与口腔鳞癌上皮中的表达间有统计学差别(P<0.05),正常组与炎症组间无差别,cyclinD1及CDK4在口腔鳞癌上皮中过表达(P<0.05).结论 cyclinD1与CDK4过表达的机制可能由于基因扩增或其他因素使其蓄积,口腔鳞癌组分级间的差异性提示其可作为肿瘤分级的评价指标之一.

  1. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures

    NARCIS (Netherlands)

    D. Splinter (Daniël); D.S. Razafsky (David); M.A. Schlager (Max); A. Serra-Marques (Andrea); I. Grigoriev (Ilya); J.A.A. Demmers (Jeroen); N. Keijzer (Nanda); K. Jiang (Kai); S. Poser; A. Hyman (Anthony); C.C. Hoogenraad (Casper); S.J. King (Stephen); A.S. Akhmanova (Anna)

    2012-01-01

    textabstractCytoplasmic dynein is the major microtubule minus-end-directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein-dynactin interaction are poorly understood. In this study, we focus on dynein-dynactin recruitment to cargo by the

  2. Molecular Mechanism of Enhanced Anticancer Effect of Nanoparticle Formulated LY2835219 via p16-CDK4/6-pRb Pathway in Colorectal Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Xu Tang

    2016-01-01

    Full Text Available LY2835219 is a dual inhibitor to CDK4 and CDK6. This study was to prepare LY2835219-loaded chitosan nanoparticles (CNP/LY and LY2835219-loaded hyaluronic acid-conjugated chitosan nanoparticles (HACNP/LY and revealed their anticancer effect and influence on p16-CDK4/6-pRb pathway against colon cell line. The nanoparticle sizes of CNP/LY and HACNP/LY were approximately 195±39.6 nm and 217±31.1 nm, respectively. The zeta potentials of CNP/LY and HACNP/LY were 37.3±1.5 mV and 30.3±2.2 mV, respectively. And the preparation process showed considerable drug encapsulation efficiency and loading efficiency. LY2835219, CNP/LY, and HACNP/LY inhibited HT29 cell proliferation with 0.68, 0.54, and 0.30 μM of IC50, respectively. G1 phase was arrested by LY2835219 and its formulations. Furthermore, inhibition of CDK4/6 by LY2835219 formulations induced CDK4, CDK6, cyclin D1, and pRb decrease and p16 increase at both protein and mRNA levels. Overall, nanoparticle formulated LY2835219 could enhance the cytotoxicity and cell cycle arrest, and HACNP/LY strengthened the trend furtherly compared to CNP/LY. It is the first time to demonstrate the anticancer effect and mechanism against HT29 by LY2835219 and its nanoparticles. The drug and its nanoparticle formulations delay the cell growth and arrest cell cycle through p16-CDK4/6-pRb pathway, while the nanoparticle formulated LY2835219 could strengthen the process.

  3. Progranulin Deficiency Reduces CDK4/6/pRb Activation and Survival of Human Neuroblastoma SH-SY5Y Cells.

    Science.gov (United States)

    de la Encarnación, Ana; Alquézar, Carolina; Esteras, Noemí; Martín-Requero, Ángeles

    2015-12-01

    Null mutations in GRN are associated with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). However, the influence of progranulin (PGRN) deficiency in neurodegeneration is largely unknown. In neuroblastoma cells, silencing of GRN gene causes significantly reduced cell survival after serum withdrawal. The following observations suggest that alterations of the CDK4/6/retinoblastoma protein (pRb) pathway, secondary to changes in PI3K/Akt and ERK1/2 activation induced by PGRN deficiency, are involved in the control of serum deprivation-induced apoptosis: (i) inhibiting CDK4/6 levels or their associated kinase activity by sodium butyrate or PD332991 sensitized control SH-SY5Y cells to serum deprivation-induced apoptosis without affecting survival of PGRN-deficient cells; (ii) CDK4/6/pRb seems to be downstream of the PI3K/Akt and ERK1/2 signaling pathways since their specific inhibitors, LY294002 and PD98059, were able to decrease CDK6-associated kinase activity and induce death of control SH-SY5Y cells; (iii) PGRN-deficient cells show reduced stimulation of PI3K/Akt, ERK1/2, and CDK4/6 activities compared with control cells in the absence of serum; and (iv) supplementation of recombinant human PGRN was able to rescue survival of PGRN-deficient cells. These observations highlight the important role of PGRN-mediated stimulation of the PI3K/Akt-ERK1/2/CDK4/6/pRb pathway in determining the cell fate survival/death under serum deprivation.

  4. 细胞周期调控相关蛋白Cyclin D1、CDK 4和pRb在新疆维吾尔族妇女宫颈癌中的表达及意义%Expression and Significance of CyclinD1, CDK4 and pRb in Cervical Carcinomas in Xinjiang Uigur Women

    Institute of Scientific and Technical Information of China (English)

    付锦艳; 潘晓琳; 杨安强

    2009-01-01

    Objective To study the expression and tsignificance of Cyclin D1, CDK4 and the levels of phosphorylated pRb in cervical carcinoma in Xinjiang Uigur Women. Methods The expression of Cyclin D1,CDK4 protein and phosphorylation status of pRb were detected by immunohistochemistry in 64 cervical carcinoma tissues and 43 normal cervical tissues. Results In cervical carcinomas, the positive rate of Cyclin D1 and CDK4 were 70% and 87%, respectively. There were significant differences of CyclinD1 and CDK4 protein compared with normal cervical tissues(P<0.01). Phosphorylation status of pRb had significant difference in the two groups (P<0.01). Conclusion The overexpression of Cyclin D1 and CDK4 and the hyperphosphorylation of pRb may have relationship with carcinogenesis and the development of cervical cancer in Xinjiang Uigur Women.%目的 探讨细胞周期调控相关蛋白Cyclin D1、CDK 4和pRb磷酸化状态在新疆维吾尔族妇女宫颈癌(简称维族)中表达及其意义.方法 应用免疫组织化学方法 检测64例维族宫颈癌及43例维族正常宫颈组织中Cyclin D1、CDK 4表达和pRb磷酸化状态.结果 Cyclin D1和CDK4在宫颈癌组中阳性率分别为70%、87%,与正常宫颈组相比,差异有统计学意义(P<0.05),pRb磷酸化在两组中差异有统计学意义(P<0.01).结论 Cyclin D1与CDK4蛋白的高表达及pRb高磷酸化可能与维族宫颈癌发生发展有关.

  5. Discovery of pyrrolospirooxindole derivatives as novel cyclin dependent kinase 4 (CDK4) inhibitors by catalyst-free, green approach.

    Science.gov (United States)

    Kamal, Ahmed; Mahesh, Rasala; Nayak, V Lakshma; Babu, Korrapati Suresh; Kumar, G Bharath; Shaik, Anver Basha; Kapure, Jeevak Sopanrao; Alarifi, Abdullah

    2016-01-27

    Aiming to develop a new target for the anticancer treatment, a series of 5'H-spiro[indoline-3,4'-pyrrolo [1,2-a]quinoxalin]-2-ones has been synthesized by simple, highly efficient and environmentally friendly method in excellent yields under catalyst-free conditions using ethanol as a green solvent. A simple filtration of the reaction mixture and subsequent drying affords analytically pure products. The synthesized derivatives were evaluated for their antiproliferative activity against five different human cancer cell lines, among the congeners compound 3n showed significant cytotoxicity against the human prostate cancer (DU-145). Flow cytometric analysis revealed that this compound induces cell cycle arrest in the G0/G1 phase and Western blot analysis suggested that reduction in Cdk4 expression level leads to apoptotic cell death. This was further confirmed by mitochondrial membrane potential ((ΔΨm), Annexin V-FITC assay and docking experiments. Furthermore, it was observed that there is an increase in expression levels of cyclin dependent kinase inhibitors like Cip1/p21 and Kip1/p27.

  6. COX assembly factor ccdc56 regulates mitochondrial morphology by affecting mitochondrial recruitment of Drp1.

    Science.gov (United States)

    Ban-Ishihara, Reiko; Tomohiro-Takamiya, Shiho; Tani, Motohiro; Baudier, Jacques; Ishihara, Naotada; Kuge, Osamu

    2015-10-07

    Mitochondria are dynamic organelles that alter their morphology in response to cellular signaling and differentiation through balanced fusion and fission. In this study, we found that the mitochondrial inner membrane ATPase ATAD3A interacted with ccdc56/MITRAC12/COA3, a subunit of the cytochrome oxidase (COX)-assembly complex. Overproduction of ccdc56 in HeLa cells resulted in fragmented mitochondrial morphology, while mitochondria were highly elongated in ccdc56-repressed cells by the defective recruitment of the fission factor Drp1. We also found that mild and chronic inhibition of COX led to mitochondrial elongation, as seen in ccdc56-repressed cells. These results indicate that ccdc56 positively regulates mitochondrial fission via regulation of COX activity and the mitochondrial recruitment of Drp1, and thus, suggest a novel relationship between COX assembly and mitochondrial morphology.

  7. CTCF regulates NELF, DSIF and P-TEFb recruitment during transcription.

    Science.gov (United States)

    Laitem, Clélia; Zaborowska, Justyna; Tellier, Michael; Yamaguchi, Yuki; Cao, Qingfu; Egloff, Sylvain; Handa, Hiroshi; Murphy, Shona

    2015-01-01

    CTCF is a versatile transcription factor with well-established roles in chromatin organization and insulator function. Recent findings also implicate CTCF in the control of elongation by RNA polymerase (RNAP) II. Here we show that CTCF knockdown abrogates RNAP II pausing at the early elongation checkpoint of c-myc by affecting recruitment of DRB-sensitivity-inducing factor (DSIF). CTCF knockdown also causes a termination defect on the U2 snRNA genes (U2), by affecting recruitment of negative elongation factor (NELF). In addition, CTCF is required for recruitment of positive elongation factor b (P-TEFb), which phosphorylates NELF, DSIF, and Ser2 of the RNAP II CTD to activate elongation of transcription of c-myc and recognition of the snRNA gene-specific 3' box RNA processing signal. These findings implicate CTCF in a complex network of protein:protein/protein:DNA interactions and assign a key role to CTCF in controlling RNAP II transcription through the elongation checkpoint of the protein-coding c-myc and the termination site of the non-coding U2, by regulating the recruitment and/or activity of key players in these processes.

  8. Metastasis Suppressors Regulate the Tumor Microenvironment by Blocking Recruitment of Prometastatic Tumor-Associated Macrophages.

    Science.gov (United States)

    Frankenberger, Casey; Rabe, Daniel; Bainer, Russell; Sankarasharma, Devipriya; Chada, Kiran; Krausz, Thomas; Gilad, Yoav; Becker, Lev; Rosner, Marsha Rich

    2015-10-01

    Triple-negative breast cancer (TNBC) patients have the highest risk of recurrence and metastasis. Because they cannot be treated with targeted therapies, and many do not respond to chemotherapy, they represent a clinically underserved group. TNBC is characterized by reduced expression of metastasis suppressors such as Raf kinase inhibitory protein (RKIP), which inhibits tumor invasiveness. Mechanisms by which metastasis suppressors alter tumor cells are well characterized; however, their ability to regulate the tumor microenvironment and the importance of such regulation to metastasis suppression are incompletely understood. Here, we use species-specific RNA sequencing to show that RKIP expression in tumors markedly reduces the number and metastatic potential of infiltrating tumor-associated macrophages (TAM). TAMs isolated from nonmetastatic RKIP(+) tumors, relative to metastatic RKIP(-) tumors, exhibit a reduced ability to drive tumor cell invasion and decreased secretion of prometastatic factors, including PRGN, and shed TNFR2. RKIP regulates TAM recruitment by blocking HMGA2, resulting in reduced expression of numerous macrophage chemotactic factors, including CCL5. CCL5 overexpression in RKIP(+) tumors restores recruitment of prometastatic TAMs and intravasation, whereas treatment with the CCL5 receptor antagonist Maraviroc reduces TAM infiltration. These results highlight the importance of RKIP as a regulator of TAM recruitment through chemokines such as CCL5. The clinical significance of these interactions is underscored by our demonstration that a signature comprised of RKIP signaling and prometastatic TAM factors strikingly separates TNBC patients based on survival outcome. Collectively, our findings identify TAMs as a previously unsuspected mechanism by which the metastasis-suppressor RKIP regulates tumor invasiveness, and further suggest that TNBC patients with decreased RKIP activity and increased TAM infiltration may respond to macrophage

  9. MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer.

    Science.gov (United States)

    Liu, Guoyan; Sun, Yan; Ji, Ping; Li, Xia; Cogdell, David; Yang, Da; Parker Kerrigan, Brittany C; Shmulevich, Ilya; Chen, Kexin; Sood, Anil K; Xue, Fengxia; Zhang, Wei

    2014-07-01

    Ovarian carcinoma is the most lethal gynaecological malignancy. Better understanding of the molecular pathogenesis of this disease and effective targeted therapies are needed to improve patient outcomes. MicroRNAs play important roles in cancer progression and have the potential for use as either therapeutic agents or targets. Studies in other cancers have suggested that miR-506 has anti-tumour activity, but its function has yet to be elucidated. We found that deregulation of miR-506 in ovarian carcinoma promotes an aggressive phenotype. Ectopic over-expression of miR-506 in ovarian cancer cells was sufficient to inhibit proliferation and to promote senescence. We also demonstrated that CDK4 and CDK6 are direct targets of miR-506, and that miR-506 can inhibit CDK4/6-FOXM1 signalling, which is activated in the majority of serous ovarian carcinomas. This newly recognized miR-506-CDK4/6-FOXM1 axis provides further insight into the pathogenesis of ovarian carcinoma and identifies a potential novel therapeutic agent.

  10. Normal repair of ultraviolet radiation-induced DNA damage in familial melanoma without CDKN2A or CDK4 gene mutation.

    Science.gov (United States)

    Shannon, J A; Matias, C; Luxford, C; Kefford, R F; Mann, G J

    1999-04-01

    Excessive sun exposure and family history are strong risk factors for the development of cutaneous melanoma. Inherited susceptibility to this type of skin cancer could therefore result from constitutively impaired capacity to repair ultraviolet (UV)-induced DNA lesions. While a proportion of familial melanoma kindreds exhibit germline mutations in the cell cycle regulatory gene CDKN2A (p16INK4a) or its protein target, cyclin-dependent kinase 4 (CDK4), the biochemical basis of most familial melanoma is unknown. We have examined lymphoblastoid cell lines from melanoma-affected and unaffected individuals from large hereditary melanoma kindreds which are not attributable to CDKN2A or CDK4 gene mutation. These lines were tested for sensitivity of clonogenic growth to UV radiation and for their ability to repair transfected UV-damaged plasmid templates (host cell reactivation). Two of seven affected-unaffected pairs differed in colony survival after exposure to UVB radiation; however, no significant differences were observed in the host-cell reactivation assays. These results indicate that melanoma susceptibility genes other than CDKN2A and CDK4 do not impair net capacity to repair UV-induced DNA damage.

  11. Adr1 and Cat8 mediate coactivator recruitment and chromatin remodeling at glucose-regulated genes.

    Directory of Open Access Journals (Sweden)

    Rhiannon K Biddick

    Full Text Available BACKGROUND: Adr1 and Cat8 co-regulate numerous glucose-repressed genes in S. cerevisiae, presenting a unique opportunity to explore their individual roles in coactivator recruitment, chromatin remodeling, and transcription. METHODOLOGY/PRINCIPAL FINDINGS: We determined the individual contributions of Cat8 and Adr1 on the expression of a cohort of glucose-repressed genes and found three broad categories: genes that need both activators for full derepression, genes that rely mostly on Cat8 and genes that require only Adr1. Through combined expression and recruitment data, along with analysis of chromatin remodeling at two of these genes, ADH2 and FBP1, we clarified how these activators achieve this wide range of co-regulation. We find that Adr1 and Cat8 are not intrinsically different in their abilities to recruit coactivators but rather, promoter context appears to dictate which activator is responsible for recruitment to specific genes. These promoter-specific contributions are also apparent in the chromatin remodeling that accompanies derepression: ADH2 requires both Adr1 and Cat8, whereas, at FBP1, significant remodeling occurs with Cat8 alone. Although over-expression of Adr1 can compensate for loss of Cat8 at many genes in terms of both activation and chromatin remodeling, this over-expression cannot complement all of the cat8Delta phenotypes. CONCLUSIONS/SIGNIFICANCE: Thus, at many of the glucose-repressed genes, Cat8 and Adr1 appear to have interchangeable roles and promoter architecture may dictate the roles of these activators.

  12. GPS2/KDM4A Pioneering Activity Regulates Promoter-Specific Recruitment of PPARγ

    Directory of Open Access Journals (Sweden)

    M. Dafne Cardamone

    2014-07-01

    Full Text Available Timely and selective recruitment of transcription factors to their appropriate DNA-binding sites represents a critical step in regulating gene activation; however, the regulatory strategies underlying each factor’s effective recruitment to specific promoter and/or enhancer regions are not fully understood. Here, we identify an unexpected regulatory mechanism by which promoter-specific binding, and therefore function, of peroxisome proliferator-activator receptor γ (PPARγ in adipocytes requires G protein suppressor 2 (GPS2 to prime the local chromatin environment via inhibition of the ubiquitin ligase RNF8 and stabilization of the H3K9 histone demethylase KDM4A/JMJD2. Integration of genome-wide profiling data indicates that the pioneering activity of GPS2/KDM4A is required for PPARγ-mediated regulation of a specific transcriptional program, including the lipolytic enzymes adipose triglyceride lipase (ATGL and hormone-sensitive lipase (HSL. Hence, our findings reveal that GPS2 exerts a biologically important function in adipose tissue lipid mobilization by directly regulating ubiquitin signaling and indirectly modulating chromatin remodeling to prime selected genes for activation.

  13. Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7

    Science.gov (United States)

    Rojas, Raul; van Vlijmen, Thijs; Mardones, Gonzalo A.; Prabhu, Yogikala; Rojas, Adriana L.; Mohammed, Shabaz; Heck, Albert J.R.; Raposo, Graça; van der Sluijs, Peter; Bonifacino, Juan S.

    2008-01-01

    The retromer complex mediates retrograde transport of transmembrane cargo from endosomes to the trans-Golgi network (TGN). Mammalian retromer is composed of a sorting nexin (SNX) dimer that binds to phosphatidylinositol 3-phosphate–enriched endosomal membranes and a vacuolar protein sorting (Vps) 26/29/35 trimer that participates in cargo recognition. The mammalian SNX dimer is necessary but not sufficient for recruitment of the Vps26/29/35 trimer to membranes. In this study, we demonstrate that the guanosine triphosphatase Rab7 contributes to this recruitment. The Vps26/29/35 trimer specifically binds to Rab7–guanosine triphosphate (GTP) and localizes to Rab7-containing endosomal domains. Interference with Rab7 function causes dissociation of the Vps26/29/35 trimer but not the SNX dimer from membranes. This blocks retrieval of mannose 6-phosphate receptors to the TGN and impairs cathepsin D sorting. Rab5-GTP does not bind to the Vps26/29/35 trimer, but perturbation of Rab5 function causes dissociation of both the SNX and Vps26/29/35 components from membranes through inhibition of a pathway involving phosphatidylinositol 3-kinase. These findings demonstrate that Rab5 and Rab7 act in concert to regulate retromer recruitment to endosomes. PMID:18981234

  14. NAC1 regulates the recruitment of the proteasome complex into dendritic spines.

    Science.gov (United States)

    Shen, Haowei; Korutla, Laxminarayana; Champtiaux, Nicholas; Toda, Shigenobu; LaLumiere, Ryan; Vallone, Joseph; Klugmann, Matthias; Blendy, Julie A; Mackler, Scott A; Kalivas, Peter W

    2007-08-15

    Coordinated proteolysis of synaptic proteins is required for synaptic plasticity, but a mechanism for recruiting the ubiquitin-proteasome system (UPS) into dendritic spines is not known. NAC1 is a cocaine-regulated transcriptional protein that was found to complex with proteins in the UPS, including cullins and Mov34. NAC1 and the proteasome were cotranslocated from the nucleus into dendritic spines in cortical neurons in response to proteasome inhibition or disinhibiting synaptic activity with bicuculline. Bicuculline also produced a progressive accumulation of the proteasome and NAC1 in the postsynaptic density. Recruitment of the proteasome into dendrites and postsynaptic density by bicuculline was prevented in neurons from mice harboring an NAC1 gene deletion or in neurons transfected with mutated NAC1 lacking the proteasome binding domain. These experiments show that NAC1 modulates the translocation of the UPS from the nucleus into dendritic spines, thereby suggesting a potential missing link in the recruitment of necessary proteolysis machinery for synaptic remodeling.

  15. The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin β1 endocytosis.

    Science.gov (United States)

    Teckchandani, Anjali; Mulkearns, Erin E; Randolph, Timothy W; Toida, Natalie; Cooper, Jonathan A

    2012-08-01

    Endocytic adaptor proteins facilitate cargo recruitment and clathrin-coated pit nucleation. The prototypical clathrin adaptor AP2 mediates cargo recruitment, maturation, and scission of the pit by binding cargo, clathrin, and accessory proteins, including the Eps-homology (EH) domain proteins Eps15 and intersectin. However, clathrin-mediated endocytosis of some cargoes proceeds efficiently in AP2-depleted cells. We found that Dab2, another endocytic adaptor, also binds to Eps15 and intersectin. Depletion of EH domain proteins altered the number and size of clathrin structures and impaired the endocytosis of the Dab2- and AP2-dependent cargoes, integrin β1 and transferrin receptor, respectively. To test the importance of Dab2 binding to EH domain proteins for endocytosis, we mutated the EH domain-binding sites. This mutant localized to clathrin structures with integrin β1, AP2, and reduced amounts of Eps15. Of interest, although integrin β1 endocytosis was impaired, transferrin receptor internalization was unaffected. Surprisingly, whereas clathrin structures contain both Dab2 and AP2, integrin β1 and transferrin localize in separate pits. These data suggest that Dab2-mediated recruitment of EH domain proteins selectively drives the internalization of the Dab2 cargo, integrin β1. We propose that adaptors may need to be bound to their cargo to regulate EH domain proteins and internalize efficiently.

  16. Platelet-Derived CCL5 Regulates CXC Chemokine Formation and Neutrophil Recruitment in Acute Experimental Colitis.

    Science.gov (United States)

    Yu, Changhui; Zhang, Songen; Wang, Yongzhi; Zhang, Su; Luo, Lingtao; Thorlacius, Henrik

    2016-02-01

    Accumulating data suggest that platelets not only regulate thrombosis and haemostasis but also inflammatory processes. Platelets contain numerous potent pro-inflammatory compounds, including the chemokines CCL5 and CXCL4, although their role in acute colitis remains elusive. The aim of this study is to examine the role of platelets and platelet-derived chemokines in acute colitis. Acute colitis is induced in female Balb/c mice by administration of 5% dextran sodium sulfate (DSS) for 5 days. Animals receive a platelet-depleting, anti-CCL5, anti-CXCL4, or a control antibody prior to DSS challenge. Colonic tissue is collected for quantification of myeloperoxidase (MPO) activity, CXCL5, CXCL2, interleukin-6 (IL-6), and CCL5 levels as well as morphological analyses. Platelet depletion reduce tissue damage and clinical disease activity index in DSS-exposed animals. Platelet depletion not only reduces levels of CXCL2 and CXCL5 but also levels of CCL5 in the inflamed colon. Immunoneutralization of CCL5 but not CXCL4 reduces tissue damage, CXC chemokine expression, and neutrophil recruitment in DSS-treated animals. These findings show that platelets play a key role in acute colitis by regulating CXC chemokine generation, neutrophil infiltration, and tissue damage in the colon. Moreover, our results suggest that platelet-derived CCL5 is an important link between platelet activation and neutrophil recruitment in acute colitis.

  17. Kinome-wide RNA interference screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer.

    Science.gov (United States)

    Jansen, Valerie M; Bhola, Neil E; Bauer, Joshua A; Formisano, Luigi; Lee, Kyung-Min; Hutchinson, Katherine E; Witkiewicz, Agnieszka K; Moore, Preston D; Estrada, Monica Valeria; Sanchez, Violeta; Ericsson, Paula G; Sanders, Melinda; Pohlmann, Paula R; Pishvaian, Michael J; Riddle, David A; Wei, Wenyi; Dugger, Teresa C; Knudsen, Erik; Arteaga, Carlos L

    2017-03-01

    To discover mechanisms of resistance to CDK4/6 inhibitors, we used a kinome-wide siRNA screen to identify kinases that, when downregulated, promote sensitivity to ribociclib. We identified 3-phosphoinositide dependent protein kinase 1 (PDK1) as the top siRNA that sensitized ER+ MCF-7 cells to ribociclib. Pharmacological inhibition of PDK1 with GSK2334470 in combination with ribociclib or palbociclib, synergistically inhibited proliferation and increased apoptosis in a panel of ER+ breast cancer cell lines. Ribociclib-resistant MCF-7, T47D and HCC1428 cells, selected after chronic drug exposure, displayed increased levels of PDK1, P-RSK2, P-AKT and P-S6 compared to parental drug-sensitive cells. Cell cycle analysis revealed that CDK4/6 inhibition failed to induce G1 arrest, a reduction in S phase, and senescence in ribociclib-resistant cells, suggesting an upregulation of S-phase cyclins/CDKs. The resistant cells exhibited significantly higher levels of P-CDK2, cyclin A, cyclin D1, cyclin E and S477/T479 P-AKT, a CDK2-dependent phosphorylation site within AKT required for full kinase activity and limited to the S-phase of the cell cycle. Treatment with GSK2334470 or the CDK2 inhibitor dinaciclib re-sensitized ribociclib-resistant cells to CDK4/6 inhibitors; however, ribociclib/GSK2334470 inhibited the ribociclib-resistant cells more potently than ribociclib/dinaciclib. Ribociclib/GSK2334470 but not ribociclib/dinaciclib completely abrogated P-Rb, P-S6, P-RSK2, P-CDK2, cyclin A, cyclin D1 and cyclin E expression. Further, ribociclib in combination with GSK2334470 or the PI3Kα inhibitor alpelisib induced regression of MCF-7 xenografts. Finally, primary ER+ tumors displayed increased PDK1, P-S6 and cyclin D1 levels after short treatment with palbociclib. These data support a role for PI3K/PDK1 in mediating acquired resistance to CDK4/6 inhibitors.

  18. BICD2, dynactin, and LIS1 cooperate in regulating dynein recruitment to cellular structures

    Science.gov (United States)

    Splinter, Daniël; Razafsky, David S.; Schlager, Max A.; Serra-Marques, Andrea; Grigoriev, Ilya; Demmers, Jeroen; Keijzer, Nanda; Jiang, Kai; Poser, Ina; Hyman, Anthony A.; Hoogenraad, Casper C.; King, Stephen J.; Akhmanova, Anna

    2012-01-01

    Cytoplasmic dynein is the major microtubule minus-end–directed cellular motor. Most dynein activities require dynactin, but the mechanisms regulating cargo-dependent dynein–dynactin interaction are poorly understood. In this study, we focus on dynein–dynactin recruitment to cargo by the conserved motor adaptor Bicaudal D2 (BICD2). We show that dynein and dynactin depend on each other for BICD2-mediated targeting to cargo and that BICD2 N-terminus (BICD2-N) strongly promotes stable interaction between dynein and dynactin both in vitro and in vivo. Direct visualization of dynein in live cells indicates that by itself the triple BICD2-N–dynein–dynactin complex is unable to interact with either cargo or microtubules. However, tethering of BICD2-N to different membranes promotes their microtubule minus-end–directed motility. We further show that LIS1 is required for dynein-mediated transport induced by membrane tethering of BICD2-N and that LIS1 contributes to dynein accumulation at microtubule plus ends and BICD2-positive cellular structures. Our results demonstrate that dynein recruitment to cargo requires concerted action of multiple dynein cofactors. PMID:22956769

  19. 氧化苦参碱对结肠癌LoVo细胞c-myc,PSMD9,CDK4mRNA表达的影响%Effect of Oxymatrine on Expression of c-myc, PSMD9 and CDK4 mRNA in Human Colon Carcinoma LoVo Cells

    Institute of Scientific and Technical Information of China (English)

    彭燕; 韩凌; 孙静; 危建安

    2012-01-01

    目的:探讨氧化苦参碱( oxymatrine,OM)抑制人结肠癌LoVo细胞增殖和诱导凋亡的分子作用机制.方法:采用流式细胞仪检测LoVo细胞凋亡率以及细胞周期分布;采用荧光定量PCR法检测0.25,0.5 g·L-1 OM对LoVo细胞增殖相关基因c -myc,蛋白酶调解因子9(PSMD9),CDK4的基因表达的影响.结果:0.5 g·L-1以下浓度的OM作用结肠癌LoVo细胞48 h,对细胞凋亡无明显影响.0.25 g·L-1 OM作用48 h时可明显抑制人结肠癌LoVo细胞c-myc基因表达(P<0.05).0.5g·L-1 OM作用48 h时可明显抑制LoVo细胞c-myc,CDK4的基因表达(P <0.01,P<0.01,).药物作用时间为96 h时,0.5g·L-1 OM可明显抑制c-myc,PSM D9,CDK4基因表达(P<0.05,或P<0.01).结论:较低剂量OM显著抑制人结肠癌LoVo细胞增殖的作用机制,可能与下调LoVo细胞c-myc,PSM D9,CDK4表达有关.%Objective: To explore the molecular mechanism of inhibiting colon cancer cell strein LoVo proliferation and inducing apoptosis by oxymatrine ( OM ) Method: Flow cytometry was used to detect the LoVo cells apoptosis and cell cycle distribution. Fluorescence quantitative PCR was used to detect cell proliferation-related genes like the c-myc, proteasome modulator 9 (PSMD9) , CDK4 gene expression when LoVo was treated with 0. 25, 0. 5 g · L-1OM. Result: OM had no significant effect on apoptosis in colon cancer LoVo cells when the treatment of OM lasted 48 h and the concentration was lower than 0.5, 0.25 g · L-1 OM can inhibit c-myc gene expression in LoVo when duration of action last 24 h ( P < 0. 05 ). When the dose increated to 0. 5 g · L-1 and duration of action was 48 h, OM could inhibit c-myc, CDK4 gene expression in LoVo cells (P <0. 01 , P < 0. 01). When duration of action was extended to 96 h, 0. 5 g · L-1 OM could inhibit the c-myc, PSMD9, CDK4 gene expression in LoVo cells ( P < 0. 05, P < 0. 01, P < 0. 01 ). Conclusion; OM at Lower dose could significantly inhibit the proliferation of human colon cancer Lo

  20. Global regulator SATB1 recruits beta-catenin and regulates T(H2 differentiation in Wnt-dependent manner.

    Directory of Open Access Journals (Sweden)

    Dimple Notani

    2010-01-01

    Full Text Available In vertebrates, the conserved Wnt signalling cascade promotes the stabilization and nuclear accumulation of beta-catenin, which then associates with the lymphoid enhancer factor/T cell factor proteins (LEF/TCFs to activate target genes. Wnt/beta -catenin signalling is essential for T cell development and differentiation. Here we show that special AT-rich binding protein 1 (SATB1, the T lineage-enriched chromatin organizer and global regulator, interacts with beta-catenin and recruits it to SATB1's genomic binding sites. Gene expression profiling revealed that the genes repressed by SATB1 are upregulated upon Wnt signalling. Competition between SATB1 and TCF affects the transcription of TCF-regulated genes upon beta-catenin signalling. GATA-3 is a T helper type 2 (T(H2 specific transcription factor that regulates production of T(H2 cytokines and functions as T(H2 lineage determinant. SATB1 positively regulated GATA-3 and siRNA-mediated knockdown of SATB1 downregulated GATA-3 expression in differentiating human CD4(+ T cells, suggesting that SATB1 influences T(H2 lineage commitment by reprogramming gene expression. In the presence of Dickkopf 1 (Dkk1, an inhibitor of Wnt signalling, GATA-3 is downregulated and the expression of signature T(H2 cytokines such as IL-4, IL-10, and IL-13 is reduced, indicating that Wnt signalling is essential for T(H2 differentiation. Knockdown of beta-catenin also produced similar results, confirming the role of Wnt/beta-catenin signalling in T(H2 differentiation. Furthermore, chromatin immunoprecipitation analysis revealed that SATB1 recruits beta-catenin and p300 acetyltransferase on GATA-3 promoter in differentiating T(H2 cells in a Wnt-dependent manner. SATB1 coordinates T(H2 lineage commitment by reprogramming gene expression. The SATB1:beta-catenin complex activates a number of SATB1 regulated genes, and hence this study has potential to find novel Wnt responsive genes. These results demonstrate that SATB1

  1. Marine steroids as potential anticancer drug candidates: In silico investigation in search of inhibitors of Bcl-2 and CDK-4/Cyclin D1.

    Science.gov (United States)

    Saikia, Surovi; Kolita, Bhaskor; Dutta, Partha P; Dutta, Deep J; Neipihoi; Nath, Shyamalendu; Bordoloi, Manobjyoti; Quan, Pham Minh; Thuy, Tran Thu; Phuong, Doan Lan; Long, Pham Quoc

    2015-10-01

    Star fishes (Asteroidea) are rich in polar steroids with diverse structural characteristics. The structural modifications of star fish steroids occur at 3β, 4β, 5α, 6α (or β), 7α (or β), 8, 15α (or β) and 16β positions of the steroidal nucleus and in the side chain. Widely found polar steroids in starfishes include polyhydroxysteroids, steroidal sulfates, glycosides, steroid oligoglycosides etc. Bioactivity of these steroids is less studied; only a few reports like antibacterial, cytotoxic activity etc. are available. In continuation of our search for bioactive molecules from natural sources, we undertook in silico screening of steroids from star fishes against Bcl-2 and CDK-4/Cyclin D1 - two important targets of progression and proliferation of cancer cells. We have screened 182 natural steroids from star fishes occurring in different parts of the world and their 282 soft-derivatives by in silico methods. Their physico-chemical properties, drug-likeliness, binding potential with the selected targets, ADMET (absorption, distribution, metabolism, toxicity) were predicted. Further, the results were compared with those of existing steroidal and non steroidal drugs and inhibitors of Bcl-2 and CDK-4/Cyclin D1. The results are promising and unveil that some of these steroids can be potent leads for cancer treatments.

  2. Bili inhibits Wnt/beta-catenin signaling by regulating the recruitment of axin to LRP6.

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    Lorna S Kategaya

    Full Text Available BACKGROUND: Insights into how the Frizzled/LRP6 receptor complex receives, transduces and terminates Wnt signals will enhance our understanding of the control of the Wnt/ss-catenin pathway. METHODOLOGY/PRINCIPAL FINDINGS: In pursuit of such insights, we performed a genome-wide RNAi screen in Drosophila cells expressing an activated form of LRP6 and a beta-catenin-responsive reporter. This screen resulted in the identification of Bili, a Band4.1-domain containing protein, as a negative regulator of Wnt/beta-catenin signaling. We found that the expression of Bili in Drosophila embryos and larval imaginal discs significantly overlaps with the expression of Wingless (Wg, the Drosophila Wnt ortholog, which is consistent with a potential function for Bili in the Wg pathway. We then tested the functions of Bili in both invertebrate and vertebrate animal model systems. Loss-of-function studies in Drosophila and zebrafish embryos, as well as human cultured cells, demonstrate that Bili is an evolutionarily conserved antagonist of Wnt/beta-catenin signaling. Mechanistically, we found that Bili exerts its antagonistic effects by inhibiting the recruitment of AXIN to LRP6 required during pathway activation. CONCLUSIONS: These studies identify Bili as an evolutionarily conserved negative regulator of the Wnt/beta-catenin pathway.

  3. Regulation of angiogenesis, mural cell recruitment and adventitial macrophage behavior by Toll-like receptors.

    Science.gov (United States)

    Aplin, Alfred C; Ligresti, Giovanni; Fogel, Eric; Zorzi, Penelope; Smith, Kelly; Nicosia, Roberto F

    2014-01-01

    The angiogenic response to injury can be studied by culturing rat or mouse aortic explants in collagen gels. Gene expression studies show that aortic angiogenesis is preceded by an immune reaction with overexpression of Toll-like receptors (TLRs) and TLR-inducible genes. TLR1, 3, and 6 are transiently upregulated at 24 h whereas TLR2, 4, and 8 expression peaks at 24 h but remains elevated during angiogenesis and vascular regression. Expression of TLR5, 7 and 9 steadily increases over time and is highest during vascular regression. Studies with isolated cells show that TLRs are expressed at higher levels in aortic macrophages compared to endothelial or mural cells with the exception of TLR2 and TLR9 which are more abundant in the aortic endothelium. LPS and other TLR ligands dose dependently stimulate angiogenesis and vascular endothelial growth factor production. TLR9 ligands also influence the behavior of nonendothelial cell types by blocking mural cell recruitment and inducing formation of multinucleated giant cells by macrophages. TLR9-induced mural cell depletion is associated with reduced expression of the mural cell recruiting factor PDGFB. The spontaneous angiogenic response of the aortic rings to injury is reduced in cultures from mice deficient in myeloid differentiation primary response 88 (MyD88), a key adapter molecule of TLRs, and following treatment with an inhibitor of the NFκB pathway. These results suggest that the TLR system participates in the angiogenic response of the vessel wall to injury and may play an important role in the regulation of inflammatory angiogenesis in reactive and pathologic processes.

  4. Detection of MDM2/CDK4 amplification in lipomatous soft tissue tumors from formalin-fixed, paraffin-embedded tissue: comparison of multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH).

    Science.gov (United States)

    Creytens, David; van Gorp, Joost; Ferdinande, Liesbeth; Speel, Ernst-Jan; Libbrecht, Louis

    2015-02-01

    In this study, the detection of MDM2 and CDK4 amplification was evaluated in lipomatous soft tissue tumors using multiplex ligation-dependent probe amplification (MLPA), a PCR-based technique, in comparison with fluorescence in situ hybridization (FISH). These 2 techniques were evaluated in a series of 77 formalin-fixed, paraffin-embedded lipomatous tumors (27 benign adipose tumors, 28 atypical lipomatous tumors/well-differentiated liposarcomas, 18 dedifferentiated liposarcomas, and 4 pleomorphic liposarcomas). Using MLPA, with a cut-off ratio of >2, 36/71 samples (22 atypical lipomatous tumors/well-differentiated liposarcomas, and 14 dedifferentiated liposarcomas) showed MDM2 and CDK4 amplification. Using FISH as gold standard, MLPA showed a sensitivity of 90% (36/40) and a specificity of 100% (31/31) in detecting amplification of MDM2 and CDK4 in lipomatous soft tissue tumors. In case of high-level amplification (MDM2-CDK4/CEP12 ratio >5), concordance was 100%. Four cases of atypical lipomatous tumor/well-differentiated liposarcoma (4/26, 15%) with a low MDM2 and CDK4 amplification level (MDM2-CDK4/CEP12 ratio ranging between 2 and 2.5) detected by FISH showed no amplification by MLPA, although gain of MDM2 and CDK4 (ratios ranging between 1.6 and 1.9) was seen with MLPA. No amplification was detected in benign lipomatous tumors and pleomorphic liposarcomas. Furthermore, there was a very high concordance between the ratios obtained by FISH and MLPA. In conclusion, MLPA proves to be an appropriate and straightforward technique for screening MDM2/CDK4 amplification in lipomatous tumors, especially when a correct cut-off value and reference samples are chosen, and could be considered a good alternative to FISH to determine MDM2 and CDK4 amplification in liposarcomas. Moreover, because MLPA, as a multiplex technique, allows simultaneous detection of multiple chromosomal changes of interest, it could be in the future a very reliable and fast molecular analysis on

  5. Age-Related Differences in Neural Recruitment During the Use of Cognitive Reappraisal and Selective Attention as Emotion Regulation Strategies

    Directory of Open Access Journals (Sweden)

    Eric S Allard

    2014-04-01

    Full Text Available The present study examined age differences in the timing and neural recruitment within lateral and medial PFC while younger and older adults hedonically regulated their responses to unpleasant film clips. When analyses focused on activity during the emotional peak of the film clip (the most emotionally salient portion of the film, several age differences emerged. When comparing regulation to passive viewing (combined effects of selective attention and reappraisal younger adults showed greater regulation related activity in lateral PFC (DLPFC, VLPFC, OFC and medial PFC (ACC while older adults showed greater activation within a region DLPFC. When assessing distinct effects of the regulation conditions, an ANOVA revealed a significant Age X Regulation Condition interaction within bilateral DLPFC and ACC; older adults but not young adults showed greater recruitment within these regions for reappraisal than selective attention. When examining activity at the onset of the film clip and at its emotional peak, the timing of reappraisal-related activity within VLPFC differed between age groups: Younger adults showed greater activity at film onset while older adults showed heightened activity during the peak. Our results suggest that older adults rely more heavily on PFC recruitment when engaging cognitively demanding reappraisal strategies while PFC-mediated regulation might not be as task-specific for younger adults. Older adults’ greater reliance on cognitive control processing during emotion regulation may also be reflected in the time needed to implement these strategies.

  6. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment.

    Science.gov (United States)

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-06-15

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf-GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs.

  7. Targeting P38 Pathway Regulates Bony Formation via MSC Recruitment during Mandibular Distraction Osteogenesis in Rats

    Science.gov (United States)

    Yang, Zi-hui; Wu, Bao-lei; Ye, Chen; Jia, Sen; Yang, Xin-jie; Hou, Rui; Lei, De-lin; Wang, Lei

    2016-01-01

    Distraction osteogenesis (DO) is a widely used self-tissue engineering. However, complications and discomfort due to the long treatment period are still the bottleneck of DO. Novel strategies to accelerate bone formation in DO are still needed. P38 is capable of regulating the osteogenic differentiation of both mesenchymal stem cells (MSCs) and osteoblasts, which are crucial to bone regeneration. However, it is not clear whether targeting p38 could regulate bony formation in DO. The purpose of the current work was to investigate the effects of local application of either p38 agonist anisomycin or p38 inhibitor SB203580 in a rat model of DO. 30 adult rats were randomly divided into 3 groups: (A) rats injected with DMSO served as the control group; (B) rats injected with p38 agonist anisomycin; (C) rats injected with p38 inhibitor SB203580. All the rats were subjected to mandibular distraction and the injection was performed daily during this period. The distracted mandibles were harvested on days 15 and 30 after surgery and subjected to the following analysis. Micro-computed tomography and histological evaluation results showed that local application of p38 agonist anisomycin increased new bone formation in DO, whereas p38 inhibitor SB203580 decreased it. Immunohistochemical analysis suggested that anisomycin promoted MSC recruitment in the distraction gap. In conclusion, this study demonstrated that local application of p38 agonist anisomycin can increase new bone formation during DO. This study may lead to a novel cell-based strategy for the improvement of bone regeneration. PMID:27766028

  8. Rho-kinase regulates adhesive and mechanical mechanisms of pulmonary recruitment of neutrophils in abdominal sepsis.

    Science.gov (United States)

    Palani, Karzan; Rahman, Milladur; Hasan, Zirak; Zhang, Su; Qi, Zhongquan; Jeppsson, Bengt; Thorlacius, Henrik

    2012-05-05

    We hypothesized that Rho-kinase signaling plays a role in mechanical and adhesive mechanisms of neutrophil accumulation in lung. Male C57BL/6 mice were treated with the Rho-kinase inhibitor Y-27632 prior to cecal ligation and puncture (CLP). Lung levels of myeloperoxidase (MPO) and histological tissue damage were determined 6h and 24h after CLP. Expression of Mac-1 and F-actin formation in neutrophils were quantified by using flow cytometry 6h after CLP. Mac-1 expression and F-actin formation were also determined in isolated neutrophils up to 3h after stimulation with CXCL2. Labeled and activated neutrophils co-incubated with Y-27632, an anti-Mac-1 antibody and cytochalasin B were adoptively transferred to CLP mice. Y-27632 reduced the CLP-induced pulmonary injury and MPO activity as well as Mac-1 on neutrophils. Neutrophil F-actin formation peaked at 6h and returned to baseline levels 24h after CLP induction. Rho-kinase inhibition decreased CLP-provoked F-actin formation in neutrophils. CXCL2 rapidly increased Mac-1 expression and F-actin formation in neutrophils. Co-incubation with Y-27632 abolished CXCL2-induced Mac-1 up-regulation and formation of F-actin in neutrophils. Notably, co-incubation with cytochalasin B inhibited formation of F-actin but did not reduce Mac-1 expression on activated neutrophils. Adoptive transfer experiments revealed that co-incubation of neutrophils with the anti-Mac-1 antibody or cytochalasin B significantly decreased pulmonary accumulation of neutrophils in septic mice. Our data show that targeting Rho-kinase effectively reduces neutrophil recruitment and tissue damage in abdominal sepsis. Moreover, these findings demonstrate that Rho-kinase-dependent neutrophil accumulation in septic lung injury is regulated by both adhesive and mechanical mechanisms.

  9. Dual Targeting of CDK4 and ARK5 Using a Novel Kinase Inhibitor ON123300 Exerts Potent Anticancer Activity against Multiple Myeloma.

    Science.gov (United States)

    Perumal, Deepak; Kuo, Pei-Yu; Leshchenko, Violetta V; Jiang, Zewei; Divakar, Sai Krishna Athaluri; Cho, Hearn Jay; Chari, Ajai; Brody, Joshua; Reddy, M V Ramana; Zhang, Weijia; Reddy, E Premkumar; Jagannath, Sundar; Parekh, Samir

    2016-03-01

    Multiple myeloma is a fatal plasma cell neoplasm accounting for over 10,000 deaths in the United States each year. Despite new therapies, multiple myeloma remains incurable, and patients ultimately develop drug resistance and succumb to the disease. The response to selective CDK4/6 inhibitors has been modest in multiple myeloma, potentially because of incomplete targeting of other critical myeloma oncogenic kinases. As a substantial number of multiple myeloma cell lines and primary samples were found to express AMPK-related protein kinase 5(ARK5), a member of the AMPK family associated with tumor growth and invasion, we examined whether dual inhibition of CDK4 and ARK5 kinases using ON123300 results in a better therapeutic outcome. Treatment of multiple myeloma cell lines and primary samples with ON123300 in vitro resulted in rapid induction of cell-cycle arrest followed by apoptosis. ON123300-mediated ARK5 inhibition or ARK5-specific siRNAs resulted in the inhibition of the mTOR/S6K pathway and upregulation of the AMPK kinase cascade. AMPK upregulation resulted in increased SIRT1 levels and destabilization of steady-state MYC protein. Furthermore, ON123300 was very effective in inhibiting tumor growth in mouse xenograft assays. In addition, multiple myeloma cells sensitive to ON123300 were found to have a unique genomic signature that can guide the clinical development of ON123300. Our study provides preclinical evidence that ON123300 is unique in simultaneously inhibiting key oncogenic pathways in multiple myeloma and supports further development of ARK5 inhibition as a therapeutic approach in multiple myeloma.

  10. Regulation of Ca2+ channels by SNAP-25 via recruitment of syntaxin-1 from plasma membrane clusters

    DEFF Research Database (Denmark)

    Toft-Bertelsen, Trine Lisberg; Ziomkiewicz, Iwona; Houy, Sébastien;

    2016-01-01

    SNAP-25 regulates Ca(2+) channels, with potentially important consequences for diseases involving an aberrant SNAP-25 expression level. How this regulation is executed mechanistically remains unknown. We investigated this question in mouse adrenal chromaffin cells and found that SNAP-25 inhibits Ca......(2+) currents, with the B-isoform being more potent than the A-isoform, but not when syntaxin-1 is cleaved by botulinum neurotoxin C. In contrast, syntaxin-1 inhibits Ca(2+) currents independently of SNAP-25. Further experiments using immunostaining showed that endogenous or exogenous SNAP-25...... expression recruits syntaxin-1 from clusters on the plasma membrane, thereby increasing the immunoavailability of syntaxin-1 and leading indirectly to Ca(2+) current inhibition. Expression of Munc18-1, which recruits syntaxin-1 within the exocytotic pathway, does not modulate Ca(2+) channels, whereas...

  11. Evaluation of MDM2 and CDK4 amplification by real-time PCR on paraffin wax-embedded material: a potential tool for the diagnosis of atypical lipomatous tumours/well-differentiated liposarcomas.

    Science.gov (United States)

    Hostein, I; Pelmus, M; Aurias, A; Pedeutour, F; Mathoulin-Pélissier, S; Coindre, J M

    2004-01-01

    Atypical lipomatous tumours/well-differentiated liposarcomas and dedifferentiated liposarcomas are characterized by 12q13-15 region amplification. In contrast, this molecular event has not been reported in benign lipomas. Within the 12q13-15 chromosomal region, the MDM2, SAS, HMGA2, and CDK4 genes are the most frequent targets of amplification. A series of lipomas (36 cases) and liposarcomas (48 cases) was analysed for MDM2 and CDK4 gene amplification by real-time PCR. MDM2 and CDK4 gene amplification was detected in 2.8% and 5.6% of lipomas and 98.2% and 82.4% of liposarcomas, respectively. Moreover, co-amplification of the two genes as well as a higher-level amplification was observed more frequently in dedifferentiated liposarcomas than in atypical lipomatous tumours/well-differentiated liposarcomas. Real-time PCR proved to be a fast and reliable method to characterize lipomas and liposarcomas by quantification of MDM2 and CDK4 gene amplification. It is applicable to paraffin wax-embedded tissues and could be useful when histological diagnosis is difficult.

  12. FANCI Regulates Recruitment of the FA Core Complex at Sites of DNA Damage Independently of FANCD2.

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    Maria Castella

    2015-10-01

    Full Text Available The Fanconi anemia (FA-BRCA pathway mediates repair of DNA interstrand crosslinks. The FA core complex, a multi-subunit ubiquitin ligase, participates in the detection of DNA lesions and monoubiquitinates two downstream FA proteins, FANCD2 and FANCI (or the ID complex. However, the regulation of the FA core complex itself is poorly understood. Here we show that the FA core complex proteins are recruited to sites of DNA damage and form nuclear foci in S and G2 phases of the cell cycle. ATR kinase activity, an intact FA core complex and FANCM-FAAP24 were crucial for this recruitment. Surprisingly, FANCI, but not its partner FANCD2, was needed for efficient FA core complex foci formation. Monoubiquitination or ATR-dependent phosphorylation of FANCI were not required for the FA core complex recruitment, but FANCI deubiquitination by USP1 was. Additionally, BRCA1 was required for efficient FA core complex foci formation. These findings indicate that FANCI functions upstream of FA core complex recruitment independently of FANCD2, and alter the current view of the FA-BRCA pathway.

  13. PEDF mediates pathological neovascularization by regulating macrophage recruitment and polarization in the mouse model of oxygen-induced retinopathy

    Science.gov (United States)

    Gao, Sha; Li, Changwei; Zhu, Yanji; Wang, Yanuo; Sui, Ailing; Zhong, Yisheng; Xie, Bing; Shen, Xi

    2017-01-01

    Macrophages have been demonstrated to play a proangiogenic role in retinal pathological vascular growth. Pigment epithelium-derived factor (PEDF) works as a powerful endogenous angiogenesis inhibitor, but its role in macrophage recruitment and polarization is largely unknown. To explore the underlying mechanisms, we first evaluated macrophage polarization in the retinas of the oxygen-induced retinopathy (OIR) mouse model. Compared to that in normal controls, M1- and M2-like macrophages were all abundantly increased in the retinas of OIR mice. In addition, both M1 and M2 subtypes significantly promoted neovascularization in vitro and in vivo. In addition, we found that PEDF inhibited retinal neovascularization by dampening macrophage recruitment and polarization. Furthermore, PEDF inhibited macrophage polarization through adipose triglyceride lipase (ATGL) by regulating the activation of MAPKs and the Notch1 pathway, as we found that the phosphorylation of MAPKs, including p38MAPK, JNK and ERK, as well as the accumulation of Notch1 were essential for hypoxia-induced macrophage polarization, while PEDF significantly dampened M1 subtype-related iNOS and M2 subtype-related Arg-1 expression by inhibiting hypoxia-induced activation of Notch1 and MAPKs through ATGL. These findings reveal a protective role of PEDF against retinal neovascularization by regulating macrophage recruitment and polarization. PMID:28211523

  14. Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1

    Directory of Open Access Journals (Sweden)

    Cornelia Kilchert

    2015-12-01

    Full Text Available In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these “decay-promoting” introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation.

  15. IN SITU HYBRIDIZATION OF CLONED TUMOR CELLS WITH cDNA-BIOTIN PROBES AMPLIFIED BY p53,CDK4 PRIMERS%p53、CDK4基因引物扩增的cDNA-Biotin探针与4株克隆瘤细胞原位杂交

    Institute of Scientific and Technical Information of China (English)

    牛彦平; 王秀芳; 徐增年; 吕占军

    2004-01-01

    目的用p53、CDK4基因引物扩增的生物素标记的互补DNA(cDNA-Biotin) 探针,检测S2D9、H2D8、E2G8及L3E11克隆瘤细胞株中p53、CDK4相关基因表达的差异.方法提取S2D9、H2D8、E2G8及L3E11克隆细胞总RNA,分别用p53、CDK4基因引物经反转录聚合酶链反应(reverse transcription polymerase chain reaction, RT-PCR)扩增.扩增产物用6%聚丙烯酰胺凝胶电泳,经银染显色后,切下4个克隆细胞间有差异的条带,回收DNA再次扩增,扩增产物经纯化后用生物素标记,制成生物素标记的cDNA探针,再与4株克隆瘤细胞涂片,做探针原位杂交.结果 4个克隆瘤细胞株的RNA与2种引物RT-PCR后,获得22条可以进行克隆的cDNA,取其中11条经生物素标记成cDNA探针.这些探针多数与不同瘤细胞株杂交显示较明显差异. 结论这些自制的cDNA-Biotin探针可以作为质控克隆瘤细胞株的试剂.

  16. Regulating infidelity: RNA-mediated recruitment of AID to DNA during class switch recombination.

    Science.gov (United States)

    DiMenna, Lauren J; Chaudhuri, Jayanta

    2016-03-01

    The mechanism by which the DNA deaminase activation-induced cytidine deaminase (AID) is specifically recruited to repetitive switch region DNA during class switch recombination is still poorly understood. Work over the past decade has revealed a strong link between transcription and RNA polymerase-associated factors in AID recruitment, yet none of these processes satisfactorily explain how AID specificity is affected. Here, we review a recent finding wherein AID is guided to switch regions not by a protein factor but by an RNA moiety, and especially one associated with a noncoding RNA that has been long thought of as being inert. This work explains the long-standing requirement of splicing of noncoding transcripts during class switching, and has implications in both B cell-mediated immunity as well as the underlying pathological syndromes associated with the recombination reaction.

  17. Distinct phosphorylation events regulate p130- and p107-mediated repression of E2F-4

    DEFF Research Database (Denmark)

    Farkas, Thomas; Hansen, Klaus; Holm, Karin;

    2002-01-01

    sites selectively targeted by cyclin D-Cdk4(6) kinases. Here we assessed the effects of alanine substitution at the individual or combined Cdk4(6)-specific sites in p130, compared with homologous sites in p107 (Thr(369)/Ser(650)/Ser(964)). In U-2-OS cells, the triple p107(DeltaCdk4)* mutant strongly...... inhibited E2F-4 activity and imposed a G(1) arrest resistant to cyclin D1 coexpression. In contrast, the p130(DeltaCdk4) mutant still responded to cyclin D1, suggesting the existence of additional phosphorylation sites critical for E2F-4 regulation. Extensive mutagenesis, sensitive E2F reporter assays...

  18. Ewing sarcoma EWS protein regulates midzone formation by recruiting Aurora B kinase to the midzone.

    Science.gov (United States)

    Park, Hyewon; Turkalo, Timothy K; Nelson, Kayla; Folmsbee, Stephen Sai; Robb, Caroline; Roper, Brittany; Azuma, Mizuki

    2014-01-01

    Ewing sarcoma is a malignant bone cancer that primarily occurs in children and adolescents. Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene. Previously, we demonstrated that an interaction between EWS/FLI1 and wild-type EWS led to the inhibition of EWS activity and mitotic dysfunction. Although defective mitosis is considered to be a critical step in cancer initiation, it is unknown how interference with EWS contributes to Ewing sarcoma formation. Here, we demonstrate that EWS/FLI1- and EWS-knockdown cells display a high incidence of defects in the midzone, a midline structure located between segregating chromatids during anaphase. Defects in the midzone can lead to the failure of cytokinesis and can result in the induction of aneuploidy. The similarity among the phenotypes of EWS/FLI1- and EWS siRNA-transfected HeLa cells points to the inhibition of EWS as the key mechanism for the induction of midzone defects. Supporting this observation, the ectopic expression of EWS rescues the high incidence of midzone defects observed in Ewing sarcoma A673 cells. We discovered that EWS interacts with Aurora B kinase, and that EWS is also required for recruiting Aurora B to the midzone. A domain analysis revealed that the R565 in the RGG3 domain of EWS is essential for both Aurora B interaction and the recruitment of Aurora B to the midzone. Here, we propose that the impairment of EWS-dependent midzone formation via the recruitment of Aurora B is a potential mechanism of Ewing sarcoma development.

  19. Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin D, cyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells.

    Science.gov (United States)

    Huang, Wen-Wen; Yang, Jai-Sing; Pai, Shu-Jen; Wu, Ping-Ping; Chang, Shu-Jen; Chueh, Fu-Shin; Fan, Ming-Jen; Chiou, Shang-Ming; Kuo, Hsiu-Maan; Yeh, Chin-Chung; Chen, Po-Yuan; Tsuzuki, Minoru; Chung, Jing-Gung

    2012-04-01

    Most of the chemotherapy treatments for bladder cancer aim to kill the cancer cells, but a high recurrence rate after medical treatments is still occurred. Bufalin from the skin and parotid venom glands of toad has been shown to induce apoptotic cell death in many types of cancer cell lines. However, there is no report addressing that bufalin induced cell death in human bladder cancer cells. The purpose of this study was investigated the mechanisms of bufalin-induced apoptosis in a human bladder cancer cell line (T24). We demonstrated the effects of bufalin on the cell growth and apoptosis in T24 cells by using DAPI/TUNEL double staining, a PI exclusion and flow cytometric analysis. The effects of bufalin on the production of reactive oxygen species (ROS), the level of mitochondrial membrane potential (ΔΨ(m)), and DNA content including sub-G1 (apoptosis) in T24 cells were also determined by flow cytometry. Western blot analysis was used to examine the expression of G(0)/G(1) phase-regulated and apoptosis-associated protein levels in bufalin-treated T24 cells. The results indicated that bufalin significantly decreased the percentage of viability, induced the G(0)/G(1) phase arrest and triggered apoptosis in T24 cells. The down-regulation of the protein levels for cyclin D, CDK4, cyclin E, CDK2, phospho-Rb, phospho-AKT and Bcl-2 with the simultaneous up-regulation of the cytochrome c, Apaf-1, AIF, caspase-3, -7 and -9 and Bax protein expressions and caspase activities were observed in T24 cells after bufalin treatment. Based on our results, bufalin induces apoptotic cell death in T24 cells through suppressing AKT activity and anti-apoptotic Bcl-2 protein as well as inducing pro-apoptotic Bax protein. The levels of caspase-3, -7 and -9 are also mediated apoptosis in bufalin-treated T24 cells. Therefore, bufalin might be used as a therapeutic agent for the treatment of human bladder cancer in the future.

  20. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment

    DEFF Research Database (Denmark)

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei

    2015-01-01

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study...... cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs...

  1. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment

    OpenAIRE

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-01-01

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1–coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf–GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD...

  2. Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells.

    Science.gov (United States)

    Roy, Ananya; Coum, Antoine; Marinescu, Voichita D; Põlajeva, Jelena; Smits, Anja; Nelander, Sven; Uhrbom, Lene; Westermark, Bengt; Forsberg-Nilsson, Karin; Pontén, Fredrik; Tchougounova, Elena

    2015-09-15

    Glioblastoma (GBM) is a high-grade glioma with a complex microenvironment, including various inflammatory cells and mast cells (MCs) as one of them. Previously we had identified glioma grade-dependent MC recruitment. In the present study we investigated the role of plasminogen activator inhibitor 1 (PAI-1) in MC recruitment.PAI-1, a primary regulator in the fibrinolytic cascade is capable of forming a complex with fibrinolytic system proteins together with low-density lipoprotein receptor-related protein 1 (LRP1). We found that neutralizing PAI-1 attenuated infiltration of MCs. To address the potential implication of LRP1 in this process, we used a LRP1 antagonist, receptor-associated protein (RAP), and demonstrated the attenuation of MC migration. Moreover, a positive correlation between the number of MCs and the level of PAI-1 in a large cohort of human glioma samples was observed. Our study demonstrated the expression of LRP1 in human MC line LAD2 and in MCs in human high-grade glioma. The activation of potential PAI-1/LRP1 axis with purified PAI-1 promoted increased phosphorylation of STAT3 and subsequently exocytosis in MCs.These findings indicate the influence of the PAI-1/LRP1 axis on the recruitment of MCs in glioma. The connection between high-grade glioma and MC infiltration could contribute to patient tailored therapy and improve patient stratification in future therapeutic trials.

  3. Recruitment of EB1, a Master Regulator of Microtubule Dynamics, to the Surface of the Theileria annulata Schizont

    KAUST Repository

    Woods, Kerry L.

    2013-05-09

    The apicomplexan parasite Theileria annulata transforms infected host cells, inducing uncontrolled proliferation and clonal expansion of the parasitized cell population. Shortly after sporozoite entry into the target cell, the surrounding host cell membrane is dissolved and an array of host cell microtubules (MTs) surrounds the parasite, which develops into the transforming schizont. The latter does not egress to invade and transform other cells. Instead, it remains tethered to host cell MTs and, during mitosis and cytokinesis, engages the cell\\'s astral and central spindle MTs to secure its distribution between the two daughter cells. The molecular mechanism by which the schizont recruits and stabilizes host cell MTs is not known. MT minus ends are mostly anchored in the MT organizing center, while the plus ends explore the cellular space, switching constantly between phases of growth and shrinkage (called dynamic instability). Assuming the plus ends of growing MTs provide the first point of contact with the parasite, we focused on the complex protein machinery associated with these structures. We now report how the schizont recruits end-binding protein 1 (EB1), a central component of the MT plus end protein interaction network and key regulator of host cell MT dynamics. Using a range of in vitro experiments, we demonstrate that T. annulata p104, a polymorphic antigen expressed on the schizont surface, functions as a genuine EB1-binding protein and can recruit EB1 in the absence of any other parasite proteins. Binding strictly depends on a consensus SxIP motif located in a highly disordered C-terminal region of p104. We further show that parasite interaction with host cell EB1 is cell cycle regulated. This is the first description of a pathogen-encoded protein to interact with EB1 via a bona-fide SxIP motif. Our findings provide important new insight into the mode of interaction between Theileria and the host cell cytoskeleton. 2013 Woods et al.

  4. Recruitment of EB1, a master regulator of microtubule dynamics, to the surface of the Theileria annulata schizont.

    Directory of Open Access Journals (Sweden)

    Kerry L Woods

    2013-05-01

    Full Text Available The apicomplexan parasite Theileria annulata transforms infected host cells, inducing uncontrolled proliferation and clonal expansion of the parasitized cell population. Shortly after sporozoite entry into the target cell, the surrounding host cell membrane is dissolved and an array of host cell microtubules (MTs surrounds the parasite, which develops into the transforming schizont. The latter does not egress to invade and transform other cells. Instead, it remains tethered to host cell MTs and, during mitosis and cytokinesis, engages the cell's astral and central spindle MTs to secure its distribution between the two daughter cells. The molecular mechanism by which the schizont recruits and stabilizes host cell MTs is not known. MT minus ends are mostly anchored in the MT organizing center, while the plus ends explore the cellular space, switching constantly between phases of growth and shrinkage (called dynamic instability. Assuming the plus ends of growing MTs provide the first point of contact with the parasite, we focused on the complex protein machinery associated with these structures. We now report how the schizont recruits end-binding protein 1 (EB1, a central component of the MT plus end protein interaction network and key regulator of host cell MT dynamics. Using a range of in vitro experiments, we demonstrate that T. annulata p104, a polymorphic antigen expressed on the schizont surface, functions as a genuine EB1-binding protein and can recruit EB1 in the absence of any other parasite proteins. Binding strictly depends on a consensus SxIP motif located in a highly disordered C-terminal region of p104. We further show that parasite interaction with host cell EB1 is cell cycle regulated. This is the first description of a pathogen-encoded protein to interact with EB1 via a bona-fide SxIP motif. Our findings provide important new insight into the mode of interaction between Theileria and the host cell cytoskeleton.

  5. miR-1 suppresses the growth of esophageal squamous cell carcinoma in vivo and in vitro through the downregulation of MET, cyclin D1 and CDK4 expression

    Science.gov (United States)

    JIANG, SEN; ZHAO, CHAO; YANG, XIAODI; LI, XIANGYANG; PAN, QING; HUANG, HAIJIN; WEN, XUYANG; SHAN, HUSHENG; LI, QIANWEN; DU, YUNXIANG; ZHAO, YAPING

    2016-01-01

    Several aberrant microRNAs (miRNAs or miRs) have been implicated in esophageal cancer (EC), which is widely prevalent in China. However, their role in EC tumorigenesis has not yet been fully elucidated. In the present study, we determined that miR-1 was downregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent non-neoplastic tissues using RT-qPCR, and confirmed this using an ESCC cell line. Using a nude mouse xenograft model, we confirmed that the re-expression of miR-1 significantly inhibited ESCC tumor growth. A tetrazolium assay and a trypan blue exclusion assay revealed that miR-1 suppressed ESCC cell proliferation and increased apoptosis, whereas the silencing of miR-1 promoted cell proliferation and decreased apoptosis, suggesting that miR-1 is a novel tumor suppressor. To elucidate the molecular mechanisms of action of miR-1 in ESCC, we investigated putative targets using bioinformatics tools. MET, cyclin D1 and cyclin-dependent kinase 4 (CDK4), which are involved in the hepatocyte growth factor (HGF)/MET signaling pathway, were found to be targets of miR-1. miR-1 expression inversely correlated with MET, cyclin D1 and CDK4 expression in ESCC cells. miR-1 directly targeted MET, cyclin D1 and CDK4, suppressing ESCC cell growth. The newly identified miR-1/MET/cyclin D1/CDK4 axis provides new insight into the molecular mechanisms of ESCC pathogenesis and indicates a novel strategy for the diagnosis and treatment of ESCC. PMID:27247259

  6. Adrenergic regulation of monocyte chemotactic protein 1 leads to enhanced macrophage recruitment and ovarian carcinoma growth

    Science.gov (United States)

    Armaiz-Pena, Guillermo N.; Gonzalez-Villasana, Vianey; Nagaraja, Archana S.; Rodriguez-Aguayo, Cristian; Sadaoui, Nouara C.; Stone, Rebecca L.; Matsuo, Koji; Dalton, Heather J.; Previs, Rebecca A.; Jennings, Nicholas B.; Dorniak, Piotr; Hansen, Jean M.; Arevalo, Jesusa M.G.; Cole, Steve W.; Lutgendorf, Susan K.; Sood, Anil K.; Lopez-Berestein, Gabriel

    2015-01-01

    Increased adrenergic signaling facilitates tumor progression, but the underlying mechanisms remain poorly understood. We examined factors responsible for stress-mediated effects on monocyte/macrophage recruitment into the tumor microenvironment, and the resultant effects on tumor growth. In vitro, MCP1 was significantly increased after catecholamine exposure, which was mediated by cAMP and PKA. Tumor samples from mice subjected to daily restraint stress had elevated MCP1 gene and protein levels, increased CD14+ cells, and increased infiltration of CD68+ cells. hMCP1 siRNA-DOPC nanoparticles significantly abrogated daily restraint stress-induced tumor growth and inhibited infiltration of CD68+ and F4/80+ cells. In ovarian cancer patients, elevated peripheral blood monocytes and tumoral macrophages were associated with worse overall survival. Collectively, we demonstrate that increased adrenergic signaling is associated with macrophage infiltration and mediated by tumor cell-derived MCP1 production. PMID:25738355

  7. Recruitment of calcineurin to the TCR positively regulates T cell activation.

    Science.gov (United States)

    Dutta, Debjani; Barr, Valarie A; Akpan, Itoro; Mittelstadt, Paul R; Singha, Laishram I; Samelson, Lawrence E; Ashwell, Jonathan D

    2017-02-01

    Calcineurin is a phosphatase whose primary targets in T cells are NFAT transcription factors, and inhibition of calcineurin activity by treatment with cyclosporin A (CsA) or FK506 is a cornerstone of immunosuppressive therapies. Here we found that calcineurin was recruited to the T cell antigen receptor (TCR) signaling complex, where it reversed inhibitory phosphorylation of the tyrosine kinase Lck on Ser59 (Lck(S59)). Loss of calcineurin activity impaired phosphorylation of Tyr493 of the tyrosine kinase ZAP-70 (ZAP-70(Y493)), as well as some downstream pathways in a manner consistent with signaling in cells expressing Lck(S59A) (Lck that cannot be phosphorylated) or Lck(S59E) (a phosphomimetic mutant). Notably, CsA inhibited integrin-LFA-1-dependent and NFAT-independent adhesion of T cells to the intercellular adhesion molecule ICAM-1, with little effect on cells expressing mutant Lck. These results provide new understanding of how widely used immunosuppressive drugs interfere with essential processes in the immune response.

  8. Biophysical regulation of Chlamydia pneumoniae-infected monocyte recruitment to atherosclerotic foci

    Science.gov (United States)

    Evani, Shankar J.; Ramasubramanian, Anand K.

    2016-01-01

    Chlamydia pneumoniae infection is implicated in atherosclerosis although the contributory mechanisms are poorly understood. We hypothesize that C. pneumoniae infection favors the recruitment of monocytes to atherosclerotic foci by altering monocyte biophysics. Primary, fresh human monocytes were infected with C. pneumoniae for 8 h, and the interactions between monocytes and E-selectin or aortic endothelium under flow were characterized by video microscopy and image analysis. The distribution of membrane lipid rafts and adhesion receptors were analyzed by imaging flow cytometry. Infected cells rolled on E-selectin and endothelial surfaces, and this rolling was slower, steady and uniform compared to uninfected cells. Infection decreases cholesterol levels, increases membrane fluidity, disrupts lipid rafts, and redistributes CD44, which is the primary mediator of rolling interactions. Together, these changes translate to higher firm adhesion of infected monocytes on endothelium, which is enhanced in the presence of LDL. Uninfected monocytes treated with LDL or left untreated were used as baseline control. Our results demonstrate that the membrane biophysical changes due to infection and hyperlipidemia are one of the key mechanisms by which C. pneumoniae can exacerbate atherosclerotic pathology. These findings provide a framework to characterize the role of ‘infectious burden’ in the development and progression of atherosclerosis.

  9. Macrophage dynamics are regulated by local macrophage proliferation and monocyte recruitment in injured pancreas.

    Science.gov (United States)

    Van Gassen, Naomi; Van Overmeire, Eva; Leuckx, Gunter; Heremans, Yves; De Groef, Sofie; Cai, Ying; Elkrim, Yvon; Gysemans, Conny; Stijlemans, Benoît; Van de Casteele, Mark; De Baetselier, Patrick; De Leu, Nico; Heimberg, Harry; Van Ginderachter, Jo A

    2015-05-01

    Pancreas injury by partial duct ligation (PDL) activates a healing response, encompassing β-cell neogenesis and proliferation. Macrophages (MΦs) were recently shown to promote β-cell proliferation after PDL, but they remain poorly characterized. We assessed myeloid cell diversity and the factors driving myeloid cell dynamics following acute pancreas injury by PDL. In naive and sham-operated pancreas, the myeloid cell compartment consisted mainly of two distinct tissue-resident MΦ types, designated MHC-II(lo) and MHC-II(hi) MΦs, the latter being predominant. MHC-II(lo) and MHC-II(hi) pancreas MΦs differed at the molecular level, with MHC-II(lo) MΦs being more M2-activated. After PDL, there was an early surge of Ly6C(hi) monocyte infiltration in the pancreas, followed by a transient MHC-II(lo) MΦ peak and ultimately a restoration of the MHC-II(hi) MΦ-dominated steady-state equilibrium. These intricate MΦ dynamics in PDL pancreas depended on monocyte recruitment by C-C chemokine receptor 2 and macrophage-colony stimulating factor receptor as well as on macrophage-colony stimulating factor receptor-dependent local MΦ proliferation. Functionally, MHC-II(lo) MΦs were more angiogenic. We further demonstrated that, at least in C-C chemokine receptor 2-KO mice, tissue MΦs, rather than Ly6C(hi) monocyte-derived MΦs, contributed to β-cell proliferation. Together, our study fully characterizes the MΦ subsets in the pancreas and clarifies the complex dynamics of MΦs after PDL injury.

  10. RACK1 regulates mesenchymal cell recruitment during sexual and asexual reproduction of budding tunicates.

    Science.gov (United States)

    Tatzuke, Yuki; Sunanaga, Takeshi; Fujiwara, Shigeki; Kawamura, Kaz

    2012-08-15

    A homolog of receptor for activated protein kinase C1 (RACK1) was cloned from the budding tunicate Polyandrocarpa misakiensis. By RT-PCR and in situ hybridization analyses, PmRACK1 showed biphasic gene expression during asexual and sexual reproduction. In developing buds, the signal was exclusively observed in the multipotent atrial epithelium and undifferentiated mesenchymal cells that contributed to morphogenesis by the mesenchymal-epithelial transition (MET). In juvenile zooids, the signal was first observable in germline precursor cells that arose as mesenchymal cell aggregated in the ventral hemocoel. In mature zooids, the germinal epithelium in the ovary and the pharynx were the most heavily stained parts. GFP reporter assay indicated that the ovarian expression of PmRACK1 was constitutive from germline precursor cells to oocytes. To elucidate the in vivo function of PmRACK1, RNA interference was challenged. When growing buds were incubated with 5 nmol/mL siRNA, most mesenchymal cells remained round and appeared to have no interactions with the extracellular matrix (ECM), causing lower activity of MET without any apparent effects on cell proliferation. The resultant zooids became growth-deficient. The dwarf zooids did not form buds or mature gonads. Prior to RNAi, buds were treated with human BMP4 that could induce PmRACK1 expression, which resulted in MET activity. We conclude that in P. misakiensis, PmRACK1 plays roles in mesenchymal cell recruitment during formation of somatic and gonad tissues, which contributes to zooidal growth and sexual and asexual reproduction.

  11. Endogenous thrombospondin-1 regulates leukocyte recruitment and activation and accelerates death from systemic candidiasis.

    Science.gov (United States)

    Martin-Manso, Gema; Navarathna, Dhammika H M L P; Galli, Susana; Soto-Pantoja, David R; Kuznetsova, Svetlana A; Tsokos, Maria; Roberts, David D

    2012-01-01

    Disseminated Candida albicans infection results in high morbidity and mortality despite treatment with existing antifungal drugs. Recent studies suggest that modulating the host immune response can improve survival, but specific host targets for accomplishing this goal remain to be identified. The extracellular matrix protein thrombospondin-1 is released at sites of tissue injury and modulates several immune functions, but its role in C. albicans pathogenesis has not been investigated. Here, we show that mice lacking thrombospondin-1 have an advantage in surviving disseminated candidiasis and more efficiently clear the initial colonization from kidneys despite exhibiting fewer infiltrating leukocytes. By examining local and systemic cytokine responses to C. albicans and other standard inflammatory stimuli, we identify a crucial function of phagocytes in this enhanced resistance. Subcutaneous air pouch and systemic candidiasis models demonstrated that endogenous thrombospondin-1 enhances the early innate immune response against C. albicans and promotes activation of inflammatory macrophages (inducible nitric oxide synthase⁺, IL-6(high), TNF-α(high), IL-10(low)), release of the chemokines MIP-2, JE, MIP-1α, and RANTES, and CXCR2-driven polymorphonuclear leukocytes recruitment. However, thrombospondin-1 inhibited the phagocytic capacity of inflammatory leukocytes in vivo and in vitro, resulting in increased fungal burden in the kidney and increased mortality in wild type mice. Thus, thrombospondin-1 enhances the pathogenesis of disseminated candidiasis by creating an imbalance in the host immune response that ultimately leads to reduced phagocytic function, impaired fungal clearance, and increased mortality. Conversely, inhibitors of thrombospondin-1 may be useful drugs to improve patient recovery from disseminated candidiasis.

  12. KSHV encoded LANA recruits Nucleosome Assembly Protein NAP1L1 for regulating viral DNA replication and transcription

    Science.gov (United States)

    Gupta, Namrata; Thakker, Suhani; Verma, Subhash C.

    2016-09-01

    The establishment of latency is an essential for lifelong persistence and pathogenesis of Kaposi’s sarcoma-associated herpesvirus (KSHV). Latency-associated nuclear antigen (LANA) is the most abundantly expressed protein during latency and is important for viral genome replication and transcription. Replication-coupled nucleosome assembly is a major step in packaging the newly synthesized DNA into chromatin, but the mechanism of KSHV genome chromatinization post-replication is not understood. Here, we show that nucleosome assembly protein 1-like protein 1 (NAP1L1) associates with LANA. Our binding assays revealed an association of LANA with NAP1L1 in KSHV-infected cells, which binds through its amino terminal domain. Association of these proteins confirmed their localization in specific nuclear compartments of the infected cells. Chromatin immunoprecipitation assays from NAP1L1-depleted cells showed LANA-mediated recruitment of NAP1L1 at the terminal repeat (TR) region of the viral genome. Presence of NAP1L1 stimulated LANA-mediated DNA replication and persistence of a TR-containing plasmid. Depletion of NAP1L1 led to a reduced nucleosome positioning on the viral genome. Furthermore, depletion of NAP1L1 increased the transcription of viral lytic genes and overexpression decreased the promoter activities of LANA-regulated genes. These results confirmed that LANA recruitment of NAP1L1 helps in assembling nucleosome for the chromatinization of newly synthesized viral DNA.

  13. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment

    OpenAIRE

    Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Chad S Boomershine; Ortiz, Camila; Sherrill, Taylor P.; McMahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.; Lawson, William E.

    2011-01-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice tha...

  14. ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

    Directory of Open Access Journals (Sweden)

    Wei Sheng Chia

    Full Text Available p97/Valosin-containing protein (VCP is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD. It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

  15. The STAR protein QKI-7 recruits PAPD4 to regulate post-transcriptional polyadenylation of target mRNAs

    Science.gov (United States)

    Yamagishi, Ryota; Tsusaka, Takeshi; Mitsunaga, Hiroko; Maehata, Takaharu; Hoshino, Shin-ichi

    2016-01-01

    Emerging evidence has demonstrated that regulating the length of the poly(A) tail on an mRNA is an efficient means of controlling gene expression at the post-transcriptional level. In early development, transcription is silenced and gene expression is primarily regulated by cytoplasmic polyadenylation. In somatic cells, considerable progress has been made toward understanding the mechanisms of negative regulation by deadenylation. However, positive regulation through elongation of the poly(A) tail has not been widely studied due to the difficulty in distinguishing whether any observed increase in length is due to the synthesis of new mRNA, reduced deadenylation or cytoplasmic polyadenylation. Here, we overcame this barrier by developing a method for transcriptional pulse-chase analysis under conditions where deadenylases are suppressed. This strategy was used to show that a member of the Star family of RNA binding proteins, QKI, promotes polyadenylation when tethered to a reporter mRNA. Although multiple RNA binding proteins have been implicated in cytoplasmic polyadenylation during early development, previously only CPEB was known to function in this capacity in somatic cells. Importantly, we show that only the cytoplasmic isoform QKI-7 promotes poly(A) tail extension, and that it does so by recruiting the non-canonical poly(A) polymerase PAPD4 through its unique carboxyl-terminal region. We further show that QKI-7 specifically promotes polyadenylation and translation of three natural target mRNAs (hnRNPA1, p27kip1 and β-catenin) in a manner that is dependent on the QKI response element. An anti-mitogenic signal that induces cell cycle arrest at G1 phase elicits polyadenylation and translation of p27kip1 mRNA via QKI and PAPD4. Taken together, our findings provide significant new insight into a general mechanism for positive regulation of gene expression by post-transcriptional polyadenylation in somatic cells. PMID:26926106

  16. Regulation of FeLV-945 by c-Myb binding and CBP recruitment to the LTR

    Directory of Open Access Journals (Sweden)

    Finstad Samantha L

    2004-09-01

    Full Text Available Abstract Background Feline leukemia virus (FeLV induces degenerative, proliferative and malignant hematologic disorders in its natural host, the domestic cat. FeLV-945 is a viral variant identified as predominant in a cohort of naturally infected animals. FeLV-945 contains a unique sequence motif in the long terminal repeat (LTR comprised of a single copy of transcriptional enhancer followed by a 21-bp sequence triplicated in tandem. The LTR is precisely conserved among independent cases of multicentric lymphoma, myeloproliferative disease and anemia in animals from the cohort. The 21-bp triplication was previously shown to act as a transcriptional enhancer preferentially in hematopoietic cells and to confer a replicative advantage. The objective of the present study was to examine the molecular mechanism by which the 21-bp triplication exerts its influence and the selective advantage responsible for its precise conservation. Results Potential binding sites for the transcription factor, c-Myb, were identified across the repeat junctions of the 21-bp triplication. Such sites would not occur in the absence of the repeat; thus, a requirement for c-Myb binding to the repeat junctions of the triplication would exert a selective pressure to conserve its sequence precisely. Electrophoretic mobility shift assays demonstrated specific binding of c-Myb to the 21-bp triplication. Reporter gene assays showed that the triplication-containing LTR is responsive to c-Myb, and that responsiveness requires the presence of both c-Myb binding sites. Results further indicated that c-Myb in complex with the 21-bp triplication recruits the transcriptional co-activator, CBP, a regulator of normal hematopoiesis. FeLV-945 replication was shown to be positively regulated by CBP in a manner dependent on the presence of the 21-bp triplication. Conclusion Binding sites for c-Myb across the repeat junctions of the 21-bp triplication may account for its precise conservation in

  17. NF-κB p65 recruited SHP regulates PDCD5-mediated apoptosis in cancer cells.

    Science.gov (United States)

    Murshed, Farhan; Farhana, Lulu; Dawson, Marcia I; Fontana, Joseph A

    2014-03-01

    Transcription factor NF-κB promotes cell proliferation in response to cell injury. Increasing evidence, however, suggests that NF-κB can also play an apoptotic role depending on the stimulus and cell type. We have previously demonstrated that novel retinoid 4-[3-Cl-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC)-mediated apoptosis in breast carcinoma cells requires activation of canonical and non-canonical NF-κB pathways. The mechanism NF-κB uses to induce apoptosis remains largely unknown. NF-κB subunit p65 (RelA) was identified as one potent transcriptional activator in 3-Cl-AHPC-mediated apoptosis in cells. Here we used ChIP-on-chip to identify NF-κB p65 genes activated in 3-Cl-AHPC mediated apoptosis. This paper focuses on one hit: pro-apoptotic protein programmed cell death 5 (PDCD5). 3-Cl-AHPC mediated apoptosis in MDA-MB-468 had three related effects on PDCD5: NF-κB p65 binding to the PDCD5 gene, enhanced PDCD5 promoter activity, and increased PDCD5 protein expression. Furthermore, 3-Cl-AHPC increased orphan nuclear receptor small heterodimer partner (SHP) mRNA expression, increased SHP protein bound to NF-κB p65, and found the SHP/NF-κB p65 complex attached to the PDCD5 gene. PDCD5 triggered apoptosis through increased Bax protein and release of cytochrome C from mitochondria to cytosol. Lastly, knockdown of PDCD5 protein expression blocked 3-Cl-AHPC mediated apoptosis, while over-expression of PDCD5 enhanced apoptosis, suggesting PDCD5 is necessary and sufficient for NF-κB p65 mediated apoptosis. Our results demonstrate a novel pathway for NF-κB p65 in regulating apoptosis through SHP and PDCD5.

  18. TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment.

    Science.gov (United States)

    Degryse, Amber L; Tanjore, Harikrishna; Xu, Xiaochuan C; Polosukhin, Vasiliy V; Jones, Brittany R; Boomershine, Chad S; Ortiz, Camila; Sherrill, Taylor P; McMahon, Frank B; Gleaves, Linda A; Blackwell, Timothy S; Lawson, William E

    2011-06-01

    The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice that express β-galactosidase (β-gal) in cells of lung epithelial lineage. Mice were given intratracheal bleomycin (0.08 U), and the following parameters were assessed: AEC death by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, inflammation by total and differential cell counts from bronchoalveolar lavage, fibrosis by scoring of trichrome-stained lung sections, and total lung collagen content. Mice with lung epithelial deficiency of TGFβR2 had improved AEC survival, despite greater lung inflammation, after bleomycin administration. At 3 wk after bleomycin administration, mice with epithelial TGFβR2 deficiency showed a significantly attenuated fibrotic response in the lungs, as determined by semiquantitatve scoring and total collagen content. The reduction in lung fibrosis in these mice was associated with a marked decrease in the lung fibroblast population, both total lung fibroblasts and epithelial-to-mesenchymal transition-derived (S100A4(+)/β-gal(+)) fibroblasts. Attenuation of TGFβ signaling in lung epithelium provides protection from bleomycin-induced fibrosis, indicating a critical role for the epithelium in transducing the profibrotic effects of this cytokine.

  19. Community regulation: the relative importance of recruitment and predation intensity of an intertidal community dominant in a seascape context.

    Directory of Open Access Journals (Sweden)

    Gil Rilov

    Full Text Available Predicting the strength and context-dependency of species interactions across multiple scales is a core area in ecology. This is especially challenging in the marine environment, where populations of most predators and prey are generally open, because of their pelagic larval phase, and recruitment of both is highly variable. In this study we use a comparative-experimental approach on small and large spatial scales to test the relationship between predation intensity and prey recruitment and their relative importance in shaping populations of a dominant rocky intertidal space occupier, mussels, in the context of seascape (availability of nearby subtidal reef habitat. Predation intensity on transplanted mussels was tested inside and outside cages and recruitment was measured with standard larval settlement collectors. We found that on intertidal rocky benches with contiguous subtidal reefs in New Zealand, mussel larval recruitment is usually low but predation on recruits by subtidal consumers (fish, crabs is intense during high tide. On nearby intertidal rocky benches with adjacent sandy subtidal habitats, larval recruitment is usually greater but subtidal predators are typically rare and predation is weaker. Multiple regression analysis showed that predation intensity accounts for most of the variability in the abundance of adult mussels compared to recruitment. This seascape-dependent, predation-recruitment relationship could scale up to explain regional community variability. We argue that community ecology models should include seascape context-dependency and its effects on recruitment and species interactions for better predictions of coastal community dynamics and structure.

  20. Nuclear factor of activated T cells regulates neutrophil recruitment, systemic inflammation, and T-cell dysfunction in abdominal sepsis.

    Science.gov (United States)

    Zhang, Su; Luo, Lingtao; Wang, Yongzhi; Gomez, Maria F; Thorlacius, Henrik

    2014-08-01

    The signaling mechanisms regulating neutrophil recruitment, systemic inflammation, and T-cell dysfunction in polymicrobial sepsis are not clear. This study explored the potential involvement of the calcium/calcineurin-dependent transcription factor, nuclear factor of activated T cells (NFAT), in abdominal sepsis. Cecal ligation and puncture (CLP) triggered NFAT-dependent transcriptional activity in the lung, spleen, liver, and aorta in NFAT-luciferase reporter mice. Treatment with the NFAT inhibitor A-285222 prior to CLP completely prevented sepsis-induced NFAT activation in all these organs. Inhibition of NFAT activity reduced sepsis-induced formation of CXCL1, CXCL2, and CXCL5 chemokines and edema as well as neutrophil infiltration in the lung. Notably, NFAT inhibition efficiently reduced the CLP-evoked increases in HMBG1, interleukin 6 (IL-6), and CXCL5 levels in plasma. Moreover, administration of A-285222 restored sepsis-induced T-cell dysfunction, as evidenced by markedly decreased apoptosis and restored proliferative capacity of CD4 T cells. Along these lines, treatment with A-285222 restored gamma interferon (IFN-γ) and IL-4 levels in the spleen, which were markedly reduced in septic mice. CLP-induced formation of regulatory T cells (CD4(+) CD25(+) Foxp3(+)) in the spleen was also abolished in A-285222-treated animals. All together, these novel findings suggest that NFAT is a powerful regulator of pathological inflammation and T-cell immune dysfunction in abdominal sepsis. Thus, our data suggest that NFAT signaling might be a useful target to protect against respiratory failure and immunosuppression in patients with sepsis.

  1. Seasonal regulation of herbivory and nutrient effects on macroalgal recruitment and succession in a Florida coral reef

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    Alain Duran

    2016-11-01

    Full Text Available Herbivory and nutrient enrichment are drivers of benthic dynamics of coral reef macroalgae; however, their impact may vary seasonally. In this study we evaluated the effects of herbivore pressure, nutrient availability and potential propagule supply on seasonal recruitment and succession of macroalgal communities on a Florida coral reef. Recruitment tiles, replaced every three months, and succession tiles, kept in the field for nine months, were established in an ongoing factorial nutrient enrichment-herbivore exclusion experiment. The ongoing experiment had already created very different algal communities across the different herbivory and nutrient treatments. We tracked algal recruitment, species richness, and species abundance through time. Our results show seasonal variation in the effect of herbivory and nutrient availability on recruitment of coral reef macroalgae. In the spring, when there was higher macroalgal species richness and abundance of recruits, herbivory appeared to have more control on macroalgal community structure than did nutrients. In contrast, there was no effect of either herbivory or nutrient enrichment on macroalgal communities on recruitment tiles in cooler seasons. The abundance of recruits on tiles was positively correlated with the abundance of algal in the ongoing, established experiment, suggesting that propagule abundance is likely a strong influence on algal recruitment and early succession. Results of the present study suggest that abundant herbivorous fishes control recruitment and succession of macroalgae, particularly in the warm season when macroalgal growth is higher. However, herbivory appears less impactful on algal recruitment and community dynamics in cooler seasons. Ultimately, our data suggest that the timing of coral mortality (e.g., summer vs. winter mortality and freeing of benthic space may strongly influence the dynamics of algae that colonize open space.

  2. Flow management and fish density regulate salmonid recruitment and adult size in tailwaters across western North America

    Science.gov (United States)

    Dibble, Kimberly L.; Yackulic, Charles B.; Kennedy, Theodore A.; Budy, Phaedra E.

    2015-01-01

    Rainbow and brown trout have been intentionally introduced into tailwaters downriver of dams globally and provide billions of dollars in economic benefits. At the same time, recruitment and maximum length of trout populations in tailwaters often fluctuate erratically, which negatively affects the value of fisheries. Large recruitment events may increase dispersal downriver where other fish species may be a priority (e.g., endangered species). There is an urgent need to understand the drivers of trout population dynamics in tailwaters, in particular the role of flow management. Here, we evaluate how flow, fish density, and other physical factors of the river influence recruitment and mean adult length in tailwaters across western North America using data from 29 dams spanning 1-19 years. Rainbow trout recruitment was negatively correlated with high annual, summer, and spring flow and dam latitude, and positively correlated with high winter flow, sub-adult brown trout catch, and reservoir storage capacity. Brown trout recruitment was negatively correlated with high water velocity and daily fluctuations in flow (i.e., hydropeaking) and positively correlated with adult rainbow trout catch. Among these many drivers, rainbow trout recruitment was primarily correlated with high winter flow combined with low spring flow, whereas brown trout recruitment was most related to high water velocity.

  3. Differential splicing of the apoptosis-associated speck like protein containing a caspase recruitment domain (ASC regulates inflammasomes

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    Rojanasakul Yon

    2010-05-01

    Full Text Available Abstract Background The apoptotic speck-like protein containing a caspase recruitment domain (ASC is the essential adaptor protein for caspase 1 mediated interleukin (IL-1β and IL-18 processing in inflammasomes. It bridges activated Nod like receptors (NLRs, which are a family of cytosolic pattern recognition receptors of the innate immune system, with caspase 1, resulting in caspase 1 activation and subsequent processing of caspase 1 substrates. Hence, macrophages from ASC deficient mice are impaired in their ability to produce bioactive IL-1β. Furthermore, we recently showed that ASC translocates from the nucleus to the cytosol in response to inflammatory stimulation in order to promote an inflammasome response, which triggers IL-1β processing and secretion. However, the precise regulation of inflammasomes at the level of ASC is still not completely understood. In this study we identified and characterized three novel ASC isoforms for their ability to function as an inflammasome adaptor. Methods To establish the ability of ASC and ASC isoforms as functional inflammasome adaptors, IL-1β processing and secretion was investigated by ELISA in inflammasome reconstitution assays, stable expression in THP-1 and J774A1 cells, and by restoring the lack of endogenous ASC in mouse RAW264.7 macrophages. In addition, the localization of ASC and ASC isoforms was determined by immunofluorescence staining. Results The three novel ASC isoforms, ASC-b, ASC-c and ASC-d display unique and distinct capabilities to each other and to full length ASC in respect to their function as an inflammasome adaptor, with one of the isoforms even showing an inhibitory effect. Consistently, only the activating isoforms of ASC, ASC and ASC-b, co-localized with NLRP3 and caspase 1, while the inhibitory isoform ASC-c, co-localized only with caspase 1, but not with NLRP3. ASC-d did not co-localize with NLRP3 or with caspase 1 and consistently lacked the ability to function as an

  4. Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis

    DEFF Research Database (Denmark)

    McGlashon, Jacob M; Gorecki, Michelle C; Kozlowski, Amanda E;

    2015-01-01

    diphtheria toxin receptor (DTR) was selectively expressed in central 5-HT neurons. Treatment with diphtheria toxin (DT) eliminated 5-HT neurons and caused loss of thermoregulation, brown adipose tissue (BAT) steatosis, and a >50% decrease in uncoupling protein 1 (Ucp1) expression in BAT and inguinal white...... glucose and lipid homeostasis, in part through recruitment and metabolic activation of brown and beige adipocytes....

  5. The Shc family protein adaptor, Rai, negatively regulates T cell antigen receptor signaling by inhibiting ZAP-70 recruitment and activation.

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    Micol Ferro

    Full Text Available Rai/ShcC is a member of the Shc family of protein adaptors expressed with the highest abundance in the central nervous system, where it exerts a protective function by coupling neurotrophic receptors to the PI3K/Akt survival pathway. Rai is also expressed, albeit at lower levels, in other cell types, including T and B lymphocytes. We have previously reported that in these cells Rai attenuates antigen receptor signaling, thereby impairing not only cell proliferation but also, opposite to neurons, cell survival. Here we have addressed the mechanism underlying the inhibitory activity of Rai on TCR signaling. We show that Rai interferes with the TCR signaling cascade one of the earliest steps--recruitment of the initiating kinase ZAP-70 to the phosphorylated subunit of the TCR/CD3 complex, which results in a generalized dampening of the downstream signaling events. The inhibitory activity of Rai is associated to its inducible recruitment to phosphorylated CD3, which occurs in the physiological signaling context of the immune synapse. Rai is moreover found as a pre-assembled complex with ZAP-70 and also constitutively interacts with the regulatory p85 subunit of PI3K, similar to neuronal cells, notwithstanding the opposite biological outcome, i.e. impairment of PI-3K/Akt activation. The data highlight the ability of Rai to establish interactions with the TCR and key signaling mediators which, either directly (e.g. by inhibiting ZAP-70 recruitment to the TCR or sequestering ZAP-70/PI3K in the cytosol or indirectly (e.g. by promoting the recruitment of effectors responsible for signal extinction prevent full triggering of the TCR signaling cascade.

  6. 细胞周期蛋白依赖性激酶cdk2和cdk4在前列腺增生和癌变组织中的表达%Expression of cyclin-dependent kinase 2 and 4 in benign prostatic hyperplasia and prostatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    谢庆祥; 林福地; 孟家榕; 汪鸿; 缪友仁; 李金雨

    1999-01-01

    目的:探讨细胞周期蛋白依赖性激酶cdk2和cdk4在前列腺增生(BPH)和前列腺癌(PC)的发生发展过程中作用及其与PCNA之间关系.方法:应用免疫组化S-P法检测18例正常前列腺(NP)、62例BPH和33例PC组织中cdk2、cdk4和PCNA的表达.结果:前列腺上皮和间质组织中均见cdk2和cdk4表达.NP中两者表达均分别显著低于BPH和PC;BPH的上皮细胞中两者表达均分别显著低于PC,但BPH的间质细胞中两者表达与PC相比均无显著性差异.BPH和PC中cdk2及cdk4表达与PCNA指数均呈正相关.结论:cdk2和cdk4异常表达参与BPH和PC的发生发展过程,其可能是通过改变细胞周期及促进细胞异常增殖而起作用的.

  7. Fatty acids modulate Toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner.

    Science.gov (United States)

    Wong, Scott W; Kwon, Myung-Ja; Choi, Augustine M K; Kim, Hong-Pyo; Nakahira, Kiichi; Hwang, Daniel H

    2009-10-02

    The saturated fatty acids acylated on Lipid A of lipopolysaccharide (LPS) or bacterial lipoproteins play critical roles in ligand recognition and receptor activation for Toll-like Receptor 4 (TLR4) and TLR2. The results from our previous studies demonstrated that saturated and polyunsaturated fatty acids reciprocally modulate the activation of TLR4. However, the underlying mechanism has not been understood. Here, we report for the first time that the saturated fatty acid lauric acid induced dimerization and recruitment of TLR4 into lipid rafts, however, dimerization was not observed in non-lipid raft fractions. Similarly, LPS and lauric acid enhanced the association of TLR4 with MD-2 and downstream adaptor molecules, TRIF and MyD88, into lipid rafts leading to the activation of downstream signaling pathways and target gene expression. However, docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, inhibited LPS- or lauric acid-induced dimerization and recruitment of TLR4 into lipid raft fractions. Together, these results demonstrate that lauric acid and DHA reciprocally modulate TLR4 activation by regulation of the dimerization and recruitment of TLR4 into lipid rafts. In addition, we showed that TLR4 recruitment to lipid rafts and dimerization were coupled events mediated at least in part by NADPH oxidase-dependent reactive oxygen species generation. These results provide a new insight in understanding the mechanism by which fatty acids differentially modulate TLR4-mediated signaling pathway and consequent inflammatory responses which are implicated in the development and progression of many chronic diseases.

  8. Reproduction, growth, and migration of fishes in a regulated lowland tributary: potential recruitment to the River Meuse

    NARCIS (Netherlands)

    Pollux, B.J.A.; Korosi, A.; Verberk, W.C.E.P.; Pollux, P.M.J.; Velde, G. van der

    2006-01-01

    Many European rivers are characterized by a canalized main channel, steep stony embankments, the absence of aquatic vegetation, regulated flow dynamics, reduced hydrological connectivity to the floodplains and a lack of spawning and nursery areas for many fish species. In such regulated rivers, trib

  9. Reproduction, growth and migration of fishes in a regulated lowland tributary: Potential recruitment to the River Meuse

    NARCIS (Netherlands)

    Pollux, B.J.A.; Korosi, A.; Verberk, W.C.E.P.; Pollux, P.M.J.; van der Velde, G.

    2006-01-01

    Many European rivers are characterized by a canalized main channel, steep stony embankments, the absence of aquatic vegetation, regulated flow dynamics, reduced hydrological connectivity to the floodplains and a lack of spawning and nursery areas for many fish species. In such regulated rivers, trib

  10. FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration.

    Directory of Open Access Journals (Sweden)

    Alessandra Castiglioni

    Full Text Available Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue.

  11. FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration.

    Science.gov (United States)

    Castiglioni, Alessandra; Corna, Gianfranca; Rigamonti, Elena; Basso, Veronica; Vezzoli, Michela; Monno, Antonella; Almada, Albert E; Mondino, Anna; Wagers, Amy J; Manfredi, Angelo A; Rovere-Querini, Patrizia

    2015-01-01

    Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the muscle after damage and appear to exert a pro-myogenic effect on muscle repair. We observed a decrease in the cross-sectional area of regenerating myofibers after injury in Rag2-/- γ-chain-/- mice, as compared to WT controls, suggesting that T cell recruitment promotes muscle regeneration. Skeletal muscle infiltrating T lymphocytes were enriched in CD4+CD25+FOXP3+ cells. Direct exposure of muscle satellite cells to in vitro induced Treg cells effectively enhanced their expansion, and concurrently inhibited their myogenic differentiation. In vivo, the recruitment of Tregs to acutely injured muscle was limited to the time period of satellite expansion, with possibly important implications for situations in which inflammatory conditions persist, such as muscular dystrophies and inflammatory myopathies. We conclude that the adaptive immune system, in particular T regulatory cells, is critically involved in effective skeletal muscle regeneration. Thus, in addition to their well-established role as regulators of the immune/inflammatory response, T regulatory cells also regulate the activity of skeletal muscle precursor cells, and are instrumental for the proper regeneration of this tissue.

  12. Enhancement of DNA repair using topical T4 endonuclease V does not inhibit melanoma formation in Cdk4(R24C/R24C)/Tyr-Nras(Q61K) mice following neonatal UVR.

    Science.gov (United States)

    Hacker, Elke; Muller, H Konrad; Hayward, Nicholas; Fahey, Paul; Walker, Graeme

    2010-02-01

    To further investigate the use of DNA repair-enhancing agents for skin cancer prevention, we treated Cdk4(R24C/R24C)/Nras(Q61K) mice topically with the T4 endonuclease V DNA repair enzyme (known as Dimericine) immediately prior to neonatal ultraviolet radiation (UVR) exposure, which has a powerful effect in exacerbating melanoma development in the mouse model. Dimericine has been shown to reduce the incidence of basal-cell and squamous cell carcinoma. Unexpectedly, we saw no difference in penetrance or age of onset of melanoma after neonatal UVR between Dimericine-treated and control animals, although the drug reduced DNA damage and cellular proliferation in the skin. Interestingly, epidermal melanocytes removed cyclobutane pyrimidine dimers (CPDs) more efficiently than surrounding keratinocytes. Our study indicates that neonatal UVR-initiated melanomas may be driven by mechanisms other than solely that of a large CPD load and/or their inefficient repair. This is further suggestive of different mechanisms by which UVR may enhance the transformation of keratinocytes and melanocytes.

  13. Specialized sorting of GLUT4 and its recruitment to the cell surface are independently regulated by distinct Rabs.

    Science.gov (United States)

    Sadacca, L Amanda; Bruno, Joanne; Wen, Jennifer; Xiong, Wenyong; McGraw, Timothy E

    2013-08-01

    Adipocyte glucose uptake in response to insulin is essential for physiological glucose homeostasis: stimulation of adipocytes with insulin results in insertion of the glucose transporter GLUT4 into the plasma membrane and subsequent glucose uptake. Here we establish that RAB10 and RAB14 are key regulators of GLUT4 trafficking that function at independent, sequential steps of GLUT4 translocation. RAB14 functions upstream of RAB10 in the sorting of GLUT4 to the specialized transport vesicles that ferry GLUT4 to the plasma membrane. RAB10 and its GTPase-activating protein (GAP) AS160 comprise the principal signaling module downstream of insulin receptor activation that regulates the accumulation of GLUT4 transport vesicles at the plasma membrane. Although both RAB10 and RAB14 are regulated by the GAP activity of AS160 in vitro, only RAB10 is under the control of AS160 in vivo. Insulin regulation of the pool of RAB10 required for GLUT4 translocation occurs through regulation of AS160, since activation of RAB10 by DENND4C, its GTP exchange factor, does not require insulin stimulation.

  14. Recruitment of the Mammalian Histone-modifying EMSY Complex to Target Genes Is Regulated by ZNF131.

    Science.gov (United States)

    Varier, Radhika A; Carrillo de Santa Pau, Enrique; van der Groep, Petra; Lindeboom, Rik G H; Matarese, Filomena; Mensinga, Anneloes; Smits, Arne H; Edupuganti, Raghu Ram; Baltissen, Marijke P; Jansen, Pascal W T C; Ter Hoeve, Natalie; van Weely, Danny R; Poser, Ina; van Diest, Paul J; Stunnenberg, Hendrik G; Vermeulen, Michiel

    2016-04-01

    Recent work from others and us revealed interactions between the Sin3/HDAC complex, the H3K4me3 demethylase KDM5A, GATAD1, and EMSY. Here, we characterize the EMSY/KDM5A/SIN3B complex in detail by quantitative interaction proteomics and ChIP-sequencing. We identify a novel substoichiometric interactor of the complex, transcription factor ZNF131, which recruits EMSY to a large number of active, H3K4me3 marked promoters. Interestingly, using an EMSY knock-out line and subsequent rescue experiments, we show that EMSY is in most cases positively correlated with transcriptional activity of its target genes and stimulates cell proliferation. Finally, by immunohistochemical staining of primary breast tissue microarrays we find that EMSY/KDM5A/SIN3B complex subunits are frequently overexpressed in primary breast cancer cases in a correlative manner. Taken together, these data open venues for exploring the possibility that sporadic breast cancer patients with EMSY amplification might benefit from epigenetic combination therapy targeting both the KDM5A demethylase and histone deacetylases.

  15. HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1.

    Directory of Open Access Journals (Sweden)

    Yanyan Peng

    2014-04-01

    Full Text Available RIG-I like receptors (RLRs recognize cytosolic viral RNA and initiate innate immunity; they increase the production of type I interferon (IFN and the transcription of a series of antiviral genes to protect the host organism. Accurate regulation of the RLR pathway is important for avoiding tissue injury induced by excessive immune response. HSCARG is a newly reported negative regulator of NF-κB. Here we demonstrated that HSCARG participates in innate immunity. HSCARG inhibited the cellular antiviral response in an NF-κB independent manner, whereas deficiency of HSCARG had an opposite effect. After viral infection, HSCARG interacted with tumor necrosis receptor-associated factor 3 (TRAF3 and inhibited its ubiquitination by promoting the recruitment of OTUB1 to TRAF3. Knockout of HSCARG attenuated the de-ubiquitination of TRAF3 by OTUB1, and knockdown of OTUB1 abolished the effect of HSCARG. HSCARG also interacted with Ikappa-B kinase epsilon (IKKε after viral infection and impaired the association between TRAF3 and IKKε, which further decreased the phosphorylation of IKKε and interferon response factor 3 (IRF3, thus suppressed the dimerization and nuclear translocation of IRF3. Moreover, knockdown of TRAF3 dampened the inhibitory effect of IFN-β transcription by HSCARG, suggesting that TRAF3 is necessary for HSCARG to down-regulate RLR pathway. This study demonstrated that HSCARG is a negative regulator that enables balanced antiviral innate immunity.

  16. C5a Regulates IL-1β Production and Leukocyte Recruitment in a Murine Model of Monosodium Urate Crystal-Induced Peritonitis

    Science.gov (United States)

    Khameneh, Hanif J.; Ho, Adrian W. S.; Laudisi, Federica; Derks, Heidi; Kandasamy, Matheswaran; Sivasankar, Baalasubramanian; Teng, Gim Gee; Mortellaro, Alessandra

    2017-01-01

    Gouty arthritis results from the generation of monosodium urate (MSU) crystals within joints. These MSU crystals elicit acute inflammation characterized by massive infiltration of neutrophils and monocytes that are mobilized by the pro-inflammatory cytokine IL-1β. MSU crystals also activate the complement system, which regulates the inflammatory response; however, it is unclear whether or how MSU-mediated complement activation is linked to IL-1β release in vivo, and the various roles that might be played by individual components of the complement cascade. Here we show that exposure to MSU crystals in vivo triggers the complement cascade, leading to the generation of the biologically active complement proteins C3a and C5a. C5a, but not C3a, potentiated IL-1β and IL-1α release from LPS–primed MSU-exposed peritoneal macrophages and human monocytic cells in vitro; while in vivo MSU–induced C5a mediated murine neutrophil recruitment as well as IL-1β production at the site of inflammation. These effects were significantly ameliorated by treatment of mice with a C5a receptor antagonist. Mechanistic studies revealed that C5a most likely increased NLRP3 inflammasome activation via production of reactive oxygen species (ROS), and not through increased transcription of inflammasome components. Therefore we conclude that C5a generated upon MSU-induced complement activation increases neutrophil recruitment in vivo by promoting IL-1 production via the generation of ROS, which activate the NLRP3 inflammasome. Identification of the C5a receptor as a key determinant of IL-1-mediated recruitment of inflammatory cells provides a novel potential target for therapeutic intervention to mitigate gouty arthritis. PMID:28167912

  17. Disruption of histone modification and CARM1 recruitment by arsenic represses transcription at glucocorticoid receptor-regulated promoters.

    Directory of Open Access Journals (Sweden)

    Fiona D Barr

    Full Text Available Chronic exposure to inorganic arsenic (iAs found in the environment is one of the most significant and widespread environmental health risks in the U.S. and throughout the world. It is associated with a broad range of health effects from cancer to diabetes as well as reproductive and developmental anomalies. This diversity of diseases can also result from disruption of metabolic and other cellular processes regulated by steroid hormone receptors via aberrant transcriptional regulation. Significantly, exposure to iAs inhibits steroid hormone-mediated gene activation. iAs exposure is associated with disease, but is also used therapeutically to treat specific cancers complicating an understanding of iAs action. Transcriptional activation by steroid hormone receptors is accompanied by changes in histone and non-histone protein post-translational modification (PTM that result from the enzymatic activity of coactivator and corepressor proteins such as GRIP1 and CARM1. This study addresses how iAs represses steroid receptor-regulated gene transcription. PTMs on histones H3 and H4 at the glucocorticoid receptor (GR-activated mouse mammary tumor virus (MMTV promoter were identified by chromatin immunoprecipitation analysis following exposure to steroid hormone+/-iAs. Histone H3K18 and H3R17 amino acid residues had significantly different patterns of PTMs after treatment with iAs. Promoter interaction of the coactivator CARM1 was disrupted, but the interaction of GRIP1, a p160 coactivator through which CARM1 interacts with a promoter, was intact. Over-expression of CARM1 was able to fully restore and GRIP1 partially restored iAs-repressed transcription indicating that these coactivators are functionally associated with iAs-mediated transcriptional repression. Both are essential for robust transcription at steroid hormone regulated genes and both are associated with disease when inappropriately expressed. We postulate that iAs effects on CARM1 and GRIP1

  18. Methoxychlor inhibits growth of antral follicles by altering cell cycle regulators.

    Science.gov (United States)

    Gupta, Rupesh K; Meachum, Sharon; Hernández-Ochoa, Isabel; Peretz, Jackye; Yao, Humphrey H; Flaws, Jodi A

    2009-10-01

    Methoxychlor (MXC) reduces fertility in female rodents, decreases antral follicle numbers, and increases atresia through oxidative stress pathways. MXC also inhibits antral follicle growth in vitro. The mechanism by which MXC inhibits growth of follicles is unknown. The growth of follicles is controlled, in part, by cell cycle regulators. Thus, we tested the hypothesis that MXC inhibits follicle growth by reducing the levels of selected cell cycle regulators. Further, we tested whether co-treatment with an antioxidant, N-acetyl cysteine (NAC), prevents the MXC-induced reduction in cell cycle regulators. For in vivo studies, adult cycling CD-1 mice were dosed with MXC or vehicle for 20 days. Treated ovaries were subjected to immunohistochemistry for proliferating cell nuclear antigen (PCNA) staining. For in vitro studies, antral follicles isolated from adult cycling CD-1 mouse ovaries were cultured with vehicle, MXC, and/or NAC for 48, 72 and 96 h. Levels of cyclin D2 (Ccnd2) and cyclin dependent kinase 4 (Cdk4) were measured using in vivo and in vitro samples. The results indicate that MXC decreased PCNA staining, and Ccnd2 and Cdk4 levels compared to controls. NAC co-treatment restored follicle growth and expression of Ccnd2 and Cdk4. Collectively, these data indicate that MXC exposure reduces the levels of Ccnd2 and Cdk4 in follicles, and that protection from oxidative stress restores Ccnd2 and Cdk4 levels. Therefore, MXC-induced oxidative stress may decrease the levels of cell cycle regulators, which in turn, results in inhibition of the growth of antral follicles.

  19. Phosphorylation of Def Regulates Nucleolar p53 Turnover and Cell Cycle Progression through Def Recruitment of Calpain3

    Science.gov (United States)

    Tao, Ting; Shi, Hui; Lo, Li Jan; Wang, Yingchun; Chen, Jun; Peng, Jinrong

    2016-01-01

    Digestive organ expansion factor (Def) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 (CAPN3). However, nothing is known about the exact relationship between Def and CAPN3 or the regulation of the Def function. In this report, we show that CAPN3 degrades p53 and its mutant proteins p53A138V, p53M237I, p53R248W, and p53R273P but not the p53R175H mutant protein. Importantly, we show that Def directly interacts with CAPN3 in the nucleoli and determines the nucleolar localisation of CAPN3, which is a prerequisite for the degradation of p53 in the nucleolus. Furthermore, we find that Def is modified by phosphorylation at five serine residues: S50, S58, S62, S87, and S92. We further show that simultaneous phosphorylations at S87 and S92 facilitate the nucleolar localisation of Capn3 that is not only essential for the degradation of p53 but is also important for regulating cell cycle progression. Hence, we propose that the Def-CAPN3 pathway serves as a nucleolar checkpoint for cell proliferation by selective inactivation of cell cycle-related substrates during organogenesis. PMID:27657329

  20. PI 3 kinase related kinases-independent proteolysis of BRCA1 regulates Rad51 recruitment during genotoxic stress in human cells.

    Directory of Open Access Journals (Sweden)

    Ian Hammond-Martel

    Full Text Available BACKGROUND: The function of BRCA1 in response to ionizing radiation, which directly generates DNA double strand breaks, has been extensively characterized. However previous investigations have produced conflicting data on mutagens that initially induce other classes of DNA adducts. Because of the fundamental and clinical importance of understanding BRCA1 function, we sought to rigorously evaluate the role of this tumor suppressor in response to diverse forms of genotoxic stress. METHODOLOGY/PRINCIPAL FINDINGS: We investigated BRCA1 stability and localization in various human cells treated with model mutagens that trigger different DNA damage signaling pathways. We established that, unlike ionizing radiation, either UVC or methylmethanesulfonate (MMS (generating bulky DNA adducts or alkylated bases respectively induces a transient downregulation of BRCA1 protein which is neither prevented nor enhanced by inhibition of PIKKs. Moreover, we found that the proteasome mediates early degradation of BRCA1, BARD1, BACH1, and Rad52 implying that critical components of the homologous recombination machinery need to be functionally abrogated as part of the early response to UV or MMS. Significantly, we found that inhibition of BRCA1/BARD1 downregulation is accompanied by the unscheduled recruitment of both proteins to chromatin along with Rad51. Consistently, treatment of cells with MMS engendered complete disassembly of Rad51 from pre-formed ionizing radiation-induced foci. Following the initial phase of BRCA1/BARD1 downregulation, we found that the recovery of these proteins in foci coincides with the formation of RPA and Rad51 foci. This indicates that homologous recombination is reactivated at later stage of the cellular response to MMS, most likely to repair DSBs generated by replication blocks. CONCLUSION/SIGNIFICANCE: Taken together our results demonstrate that (i the stabilities of BRCA1/BARD1 complexes are regulated in a mutagen-specific manner

  1. Ubiquitin regulates caspase recruitment domain-mediated signaling by nucleotide-binding oligomerization domain-containing proteins NOD1 and NOD2.

    Science.gov (United States)

    Ver Heul, Aaron M; Fowler, C Andrew; Ramaswamy, S; Piper, Robert C

    2013-03-08

    NOD1 and NOD2 (nucleotide-binding oligomerization domain-containing proteins) are intracellular pattern recognition receptors that activate inflammation and autophagy. These pathways rely on the caspase recruitment domains (CARDs) within the receptors, which serve as protein interaction platforms that coordinately regulate immune signaling. We show that NOD1 CARD binds ubiquitin (Ub), in addition to directly binding its downstream targets receptor-interacting protein kinase 2 (RIP2) and autophagy-related protein 16-1 (ATG16L1). NMR spectroscopy and structure-guided mutagenesis identified a small hydrophobic surface of NOD1 CARD that binds Ub. In vitro, Ub competes with RIP2 for association with NOD1 CARD. In vivo, we found that the ligand-stimulated activity of NOD1 with a mutant CARD lacking Ub binding but retaining ATG16L1 and RIP2 binding is increased relative to wild-type NOD1. Likewise, point mutations in the tandem NOD2 CARDs at positions analogous to the surface residues defining the Ub interface on NOD1 resulted in loss of Ub binding and increased ligand-stimulated NOD2 signaling. These data suggest that Ub binding provides a negative feedback loop upon NOD-dependent activation of RIP2.

  2. Dietary cholecalciferol regulates the recruitment and growth of skeletal muscle fibers and the expressions of myogenic regulatory factors and the myosin heavy chain in European sea bass larvae.

    Science.gov (United States)

    Alami-Durante, Hélène; Cluzeaud, Marianne; Bazin, Didier; Mazurais, David; Zambonino-Infante, José L

    2011-12-01

    The aim of this study was to determine whether dietary cholecalciferol affects the recruitment and growth of axial skeletal muscle fibers in first-feeding European sea bass. Larvae were fed diets containing 0.28 (VD-L, low dose), 0.69 (VD-C, control dose), or 3.00 (VD-H, high dose) mg cholecalciferol/kg from 9 to 44 d posthatching (dph). Larvae were sampled at 44 dph for quantification of somatic growth, muscle growth, and muscle growth dynamics and at 22 and 44 dph for the relative quantification of transcripts encoded by genes involved in myogenesis, cell proliferation, and muscle structure. The weight increase of the VD-L-fed larvae was less than that of the VD-H-fed group, whereas that of VD-C-fed larvae was intermediate. The level of expression of genes involved in cell proliferation (PCNA) and early myogenesis (Myf5) decreased between 22 and 44 dph, whereas that of the myogenic determination factor MyoD1 and that of genes involved in muscle structure and function (myosin heavy chain, myosin light chains 2 and 3) increased. Dietary cholecalciferol regulated Myf5, MyoD1, myogenin, and myosin heavy chain gene expression, with a gene-specific shape of response. The maximum hypertrophy of white muscle fibers was higher in larvae fed the VD-C and VD-H diets than in larvae fed the VD-L diet. White muscle hyperplasia was highly stimulated in VD-H-fed larvae compared to VD-L- and VD-C-fed ones. These findings demonstrate a dietary cholecalciferol effect on skeletal muscle growth mechanisms of a Teleost species.

  3. RECRUITMENT AND RECRUITMENT MODELS IN FISHERY SCIENCE

    Directory of Open Access Journals (Sweden)

    Merica Slišković

    2006-04-01

    Full Text Available Recruitment and growth of individuals bring the most to enlargement of fish stock biomass. Recruitment can be independent on stock size during the development of the fishery, but experience has showed that many fisheries have come to the point when recruitment decreases due to over fishing. Large parental stock does not give large number of juveniles because large number of individuals influences survival of juveniles (competition for food. In period between 1984 and 1987 this phenomenon was recorded in sardine population in the Adriatic Sea, when large biomass of parental stock resulted in twice less recruitment. In the period between 1993 and 2000 there was no significant recruitment of the sardine population in the Adriatic Sea and it reflected on biomass of the sardine. Large recruitment was recorded in 2001 and 2002. There are numerous mathematical models which give relation between stock and recruitment. Beverton–Holt’s and Ricker’s models are usually used. Beverton–Holt’s model assumes that recruitment depends on the density of population. Ricker’s model is based on assumption that all resources are evenly distributed among the individuals; therefore the rise in density causes the exhaustion of resources. This model is suitable for species as the sardine, which migrates in the breeding area.

  4. P-body components LSM1, GW182, DDX3, DDX6 and XRN1 are recruited to WNV replication sites and positively regulate viral replication.

    Science.gov (United States)

    Chahar, Harendra S; Chen, Shuiping; Manjunath, N

    2013-02-05

    In mammalian cells, proteins involved in mRNA silencing and degradation localize to discrete cytoplasmic foci called processing or P-bodies. Here we show that microscopically visible P-bodies are greatly diminished following West Nile viral infection, but the component proteins are not depleted. On the other hand, many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3. Kinetic studies suggest that the component proteins are first released from P-bodies in response to WNV infection within 12 h post-infection, followed by recruitment to the viral replication sites by 24-36 h post-infection. Silencing of the recruited proteins individually with siRNA interfered with viral replication to varying extents suggesting that the recruited proteins are required for efficient viral replication. Thus, the P-body proteins might provide novel drug targets for inhibiting viral infection.

  5. Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis.

    Science.gov (United States)

    Margheri, Francesca; Papucci, Laura; Schiavone, Nicola; D'Agostino, Riccardo; Trigari, Silvana; Serratì, Simona; Laurenzana, Anna; Biagioni, Alessio; Luciani, Cristina; Chillà, Anastasia; Andreucci, Elena; Del Rosso, Tommaso; Margheri, Giancarlo; Del Rosso, Mario; Fibbi, Gabriella

    2015-01-01

    Gangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid-rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar-lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro-angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid-supported mobile bilayer lipid membranes with raft-like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR-GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1-enriched biomimetic membranes, were validated by identifying a pro-angiogenic activity of GM1-enriched EPCs, based on GM1-dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti-angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar-raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar-raft partitioning of uPAR, as opposed to control and GM3-challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis.

  6. Differential uPAR recruitment in caveolar-lipid rafts by GM1 and GM3 gangliosides regulates endothelial progenitor cells angiogenesis

    Science.gov (United States)

    Margheri, Francesca; Papucci, Laura; Schiavone, Nicola; D'Agostino, Riccardo; Trigari, Silvana; Serratì, Simona; Laurenzana, Anna; Biagioni, Alessio; Luciani, Cristina; Chillà, Anastasia; Andreucci, Elena; Del Rosso, Tommaso; Margheri, Giancarlo; Del Rosso, Mario; Fibbi, Gabriella

    2015-01-01

    Gangliosides and the urokinase plasminogen activator receptor (uPAR) tipically partition in specialized membrane microdomains called lipid-rafts. uPAR becomes functionally important in fostering angiogenesis in endothelial progenitor cells (EPCs) upon recruitment in caveolar-lipid rafts. Moreover, cell membrane enrichment with exogenous GM1 ganglioside is pro-angiogenic and opposite to the activity of GM3 ganglioside. On these basis, we first checked the interaction of uPAR with membrane models enriched with GM1 or GM3, relying on the adoption of solid-supported mobile bilayer lipid membranes with raft-like composition formed onto solid hydrophilic surfaces, and evaluated by surface plasmon resonance (SPR) the extent of uPAR recruitment. We estimated the apparent dissociation constants of uPAR-GM1/GM3 complexes. These preliminary observations, indicating that uPAR binds preferentially to GM1-enriched biomimetic membranes, were validated by identifying a pro-angiogenic activity of GM1-enriched EPCs, based on GM1-dependent uPAR recruitment in caveolar rafts. We have observed that addition of GM1 to EPCs culture medium promotes matrigel invasion and capillary morphogenesis, as opposed to the anti-angiogenesis activity of GM3. Moreover, GM1 also stimulates MAPKinases signalling pathways, typically associated with an angiogenesis program. Caveolar-raft isolation and Western blotting of uPAR showed that GM1 promotes caveolar-raft partitioning of uPAR, as opposed to control and GM3-challenged EPCs. By confocal microscopy, we have shown that in EPCs uPAR is present on the surface in at least three compartments, respectively, associated to GM1, GM3 and caveolar rafts. Following GM1 exogenous addition, the GM3 compartment is depleted of uPAR which is recruited within caveolar rafts thereby triggering angiogenesis. PMID:25313007

  7. FOXP3+ T Cells Recruited to Sites of Sterile Skeletal Muscle Injury Regulate the Fate of Satellite Cells and Guide Effective Tissue Regeneration

    OpenAIRE

    Alessandra Castiglioni; Gianfranca Corna; Elena Rigamonti; Veronica Basso; Michela Vezzoli; Antonella Monno; Almada, Albert E; Anna Mondino; Wagers, Amy J.; Angelo A. Manfredi; Patrizia Rovere-Querini

    2015-01-01

    Muscle injury induces a classical inflammatory response in which cells of the innate immune system rapidly invade the tissue. Macrophages are prominently involved in this response and required for proper healing, as they are known to be important for clearing cellular debris and supporting satellite cell differentiation. Here, we sought to assess the role of the adaptive immune system in muscle regeneration after acute damage. We show that T lymphocytes are transiently recruited into the musc...

  8. E-recruitment

    DEFF Research Database (Denmark)

    Holm, Anna

    2012-01-01

    E-recruitment, also known as online or web-based recruitment, is little discussed in research from an organizational perspective. The purpose of this chapter is therefore to analyze and discuss the process of e-recruitment, its key constituents and organizing principles. In doing so I draw on the...

  9. Interactions between multiple recruitment drivers: post-settlement predation mortality and flow-mediated recruitment.

    Directory of Open Access Journals (Sweden)

    Antony M Knights

    Full Text Available BACKGROUND: Dispersal is a primary driver in shaping the future distribution of species in both terrestrial and marine systems. Physical transport by advection can regulate the distance travelled and rate of propagule supply to a habitat but post-settlement processes such as predation can decouple supply from recruitment. The effect of flow-mediated recruitment and predation on the recruitment success of an intertidal species, the eastern oyster Crassostrea virginica was evaluated in two-replicated field experiments. Two key crab species were manipulated to test predator identity effects on oyster mortality. FINDINGS: Recruitment was ∼58% higher in high flow compared to low flow, but predation masked those differences. Predation mortality was primarily attributed to the blue crab Callinectes sapidus, whilst the mud crab Panopeus herbstii had no effect on recruit mortality. Recruit mortality from predation was high when recruit densities were high, but when recruit density was low, predation effects were not seen. Under high recruitment (supply, predation determined maximum population size and in low flow environments, recruitment success is likely determined by a combination of recruitment and resource limitation but not predation. CONCLUSIONS: Four processes are demonstrated: (1 Increases in flow rate positively affect recruitment success; (2 In high flow (recruitment environments, resource availability is less important than predation; (3 predation is an important source of recruit mortality, but is dependent upon recruit density; and (4 recruitment and/or resource limitation is likely a major driver of population structure and functioning, modifying the interaction between predators and prey. Simultaneous testing of flow-mediated recruitment and predation was required to differentiate between the role of each process in determining population size. Our results reinforce the importance of propagule pressure, predation and post

  10. The Recruitment Process:

    DEFF Research Database (Denmark)

    Holm, Anna

    The aim of this research was to determine whether the introduction of e-recruitment has an impact on the process and underlying tasks, subtasks and activities of recruitment. Three large organizations with well-established e-recruitment practices were included in the study. The three case studies......, which were carried out in Denmark in 2008-2009 using qualitative research methods, revealed changes in the sequence, divisibility and repetitiveness of a number of recruitment tasks and subtasks. The new recruitment process design was identified and presented in the paper. The study concluded...... that the main task of the process shifted from processing applications to communicating with candidates....

  11. T-Cadherin Expression in Melanoma Cells Stimulates Stromal Cell Recruitment and Invasion by Regulating the Expression of Chemokines, Integrins and Adhesion Molecules

    Energy Technology Data Exchange (ETDEWEB)

    Rubina, Kseniya A., E-mail: rkseniya@mail.ru; Surkova, Ekaterina I.; Semina, Ekaterina V.; Sysoeva, Veronika Y.; Kalinina, Natalia I. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation); Poliakov, Alexei A. [Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA (United Kingdom); Treshalina, Helena M. [Federal State Budgetary Scietific Institution «N.N. Blokhin Russian Cancer Research Center» (FSBSI “N.N.Blokhin RCRC”), Kashirskoe Shosse 24, Moscow 115478 (Russian Federation); Tkachuk, Vsevolod A. [Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av., 31/5, Moscow 119192 (Russian Federation)

    2015-07-21

    T-cadherin is a glycosyl-phosphatidylinositol (GPI) anchored member of the cadherin superfamily involved in the guidance of migrating cells. We have previously shown that in vivo T-cadherin overexpression leads to increased melanoma primary tumor growth due to the recruitment of mesenchymal stromal cells as well as the enhanced metastasis. Since tumor progression is highly dependent upon cell migration and invasion, the aim of the present study was to elucidate the mechanisms of T-cadherin participation in these processes. Herein we show that T-cadherin expression results in the increased invasive potential due to the upregulated expression of pro-oncogenic integrins, chemokines, adhesion molecules and extracellular matrix components. The detected increase in chemokine expression could be responsible for the stromal cell recruitment. At the same time our previous data demonstrated that T-cadherin expression inhibited neoangiogenesis in the primary tumors. We demonstrate that T-cadherin overexpression leads to the increase in the expression of anti-angiogenic molecules and reduction in pro-angiogenic factors. Thus, T-cadherin plays a dual role in melanoma growth and progression: T-cadherin expression results in anti-angiogenic effects in melanoma, however, this also stimulates transcription of genes responsible for migration and invasion of melanoma cells.

  12. Effects of tachyplesin on the regulation of cell cycle in human hepatocarcinoma SMMC-7721 cells

    Institute of Scientific and Technical Information of China (English)

    Qi-Fu Li; Gao-Liang Ouyang; Xuan-Xian Peng; Shui-Gen Hong

    2003-01-01

    AIM: To investigate the effects of tachyplesin on the cell cycle regulation in human hepatcarcinoma cells.METHODS: Effects of tachyplesin on the cell cycle in human hepatocarcinoma SMMC-7721 cells were assayed with flow cytometry. The protein levels of p53, p16, cyclin D1 and CDK4 were assayed by immunocytochemistry. The mRNA levels of p21WAF1/CIP1 and c-myc genes were examined with in situ hybridization assay.RESULTS: After tachyplesin treatment, the cell cycle arrested at G0/G1 phase, the protein levels of mutant p53, cyclin D1 and CDK4 and the mRNA level of c-myc gene were decreased, whereas the levels of p16 protein and p21wWF1/CIP1 mRNA increased.CONCLUSION: Tachyplesin might arrest the cell at G0/G1 phase by upregulating the levels of p16 protein and p21WAF1/CIP1 mRNA and downregulating the levels of mutant p53, cyclin D1 and CDK4 proteins and c-myc mRNA, and induce the differentiation of human hepatocacinoma cells.

  13. Intramolecular Interactions and Regulation of Cofactor Binding by the Four Repressive Elements in the Caspase Recruitment Domain-containing Protein 11 (CARD11) Inhibitory Domain.

    Science.gov (United States)

    Jattani, Rakhi P; Tritapoe, Julia M; Pomerantz, Joel L

    2016-04-15

    The CARD11 signaling scaffold transmits signaling between antigen receptors on B and T lymphocytes and the transcription factor NF-κB during the adaptive immune response. CARD11 activity is controlled by an inhibitory domain (ID), which participates in intramolecular interactions and prevents cofactor binding prior to receptor triggering. Oncogenic CARD11 mutations associated with the activated B cell-like subtype of diffuse large B cell lymphoma somehow perturb ID-mediated autoinhibition to confer CARD11 with the dysregulated spontaneous signaling to NF-κB that is required for the proliferation and survival of the lymphoma. Here, we investigate how the four repressive elements (REs) we have discovered in the CARD11 ID function to inhibit CARD11 activity with cooperativity and redundancy. We find that each RE contributes to the maintenance of the closed inactive state of CARD11 that predominates in the absence of receptor engagement. Each RE also contributes to the prevention of Bcl10 binding in the basal unstimulated state. RE1, RE2, and RE3 participate in intramolecular interactions with other CARD11 domains and share domain targets for binding. Remarkably, diffuse large B cell lymphoma-associated gain-of-function mutations in the caspase recruitment domain, LATCH, or coiled coil can perturb intramolecular interactions mediated by multiple REs, suggesting how single amino acid oncogenic CARD11 mutations can perturb or bypass the action of redundant inhibitory REs to achieve the level of hyperactive CARD11 signaling required to support lymphoma growth.

  14. Transforming growth factor β3 attenuates the development of radiation-induced pulmonary fibrosis in mice by decreasing fibrocyte recruitment and regulating IFN-γ/IL-4 balance.

    Science.gov (United States)

    Xu, Long; Xiong, Shanshan; Guo, Renfeng; Yang, Zhihua; Wang, Qianjun; Xiao, Fengjun; Wang, Haibao; Pan, Xiujie; Zhu, Maoxiang

    2014-11-01

    Radiation-induced pulmonary fibrosis is a frequently occurred complication from radiotherapy of thoracic tumors. The transforming growth factor-β (TGF-β) superfamily plays a key regulatory role in pulmonary fibrosis. As TGF-β3 showed the potential anti-fibrotic properties especially in scar-less wound healing as opposed to the fibrotic function of TGF-β1, we sought to explore the role of TGF-β3 in radiation-induced pulmonary fibrosis. A single thoracic irradiation of 20 Gy was applied in mice to establish the model of radiation-induced pulmonary fibrosis and the mice were treated by intraperitoneal injections of recombinant TGF-β3 weekly after irradiation. We found that TGF-β3 decelerated the progress of radiation-induced pulmonary fibrosis and hindered the recruitment of fibrocytes to lung. In addition, Th1 response was suppressed as shown by diminished IFN-γ in bronchoalveolar lavage fluid (BALF) after irradiation, and enhancement of Th2 response was marked by increased IL-4 in BALF. TGF-β3 administration significantly attenuated these effects and increased the percentage of Tregs in lung during the progression of pulmonary fibrosis. Taken together, these data suggest that TGF-β3 might be involved in the regulatory mechanism for attenuation of radiation-induced pulmonary fibrosis.

  15. Seminal Fluid Regulates Accumulation of FOXP3(+) Regulatory T Cells in the Preimplantation Mouse Uterus Through Expanding the FOXP3(+) Cell Pool and CCL19-Mediated Recruitment

    NARCIS (Netherlands)

    Guerin, Leigh R.; Moldenhauer, Lachlan M.; Prins, Jelmer R.; Bromfield, John J.; Hayball, John D.; Robertson, Sarah A.

    2011-01-01

    Regulatory T (Treg) cells facilitate maternal immune tolerance of the semiallogeneic conceptus in early pregnancy, but the origin and regulation of these cells at embryo implantation is unclear. During the preimplantation period, factors in the seminal fluid delivered at coitus cause expansion of a

  16. Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation

    DEFF Research Database (Denmark)

    Wu, Xudong; Johansen, Jens Vilstrup; Helin, Kristian

    2013-01-01

    Polycomb repressive complex 1 (PRC1) catalyzes lysine 119 monoubiquitylation on H2A (H2AK119ub1) and regulates pluripotency in embryonic stem cells (ESCs). However, the mechanisms controlling the binding of PRC1 to genomic sites and its catalytic activity are poorly understood. Here, we show that...

  17. Activation of AMP-activated protein kinase regulates hippocampal neuronal pH by recruiting Na(+)/H(+) exchanger NHE5 to the cell surface.

    Science.gov (United States)

    Jinadasa, Tushare; Szabó, Elöd Z; Numat, Masayuki; Orlowski, John

    2014-07-25

    Strict regulation of intra- and extracellular pH is an important determinant of nervous system function as many voltage-, ligand-, and H(+)-gated cationic channels are exquisitely sensitive to transient fluctuations in pH elicited by neural activity and pathophysiologic events such as hypoxia-ischemia and seizures. Multiple Na(+)/H(+) exchangers (NHEs) are implicated in maintenance of neural pH homeostasis. However, aside from the ubiquitous NHE1 isoform, their relative contributions are poorly understood. NHE5 is of particular interest as it is preferentially expressed in brain relative to other tissues. In hippocampal neurons, NHE5 regulates steady-state cytoplasmic pH, but intriguingly the bulk of the transporter is stored in intracellular vesicles. Here, we show that NHE5 is a direct target for phosphorylation by the AMP-activated protein kinase (AMPK), a key sensor and regulator of cellular energy homeostasis in response to metabolic stresses. In NHE5-transfected non-neuronal cells, activation of AMPK by the AMP mimetic AICAR or by antimycin A, which blocks aerobic respiration and causes acidification, increased cell surface accumulation and activity of NHE5, and elevated intracellular pH. These effects were effectively blocked by the AMPK antagonist compound C, the NHE inhibitor HOE694, and mutation of a predicted AMPK recognition motif in the NHE5 C terminus. This regulatory pathway was also functional in primary hippocampal neurons, where AMPK activation of NHE5 protected the cells from sustained antimycin A-induced acidification. These data reveal a unique role for AMPK and NHE5 in regulating the pH homeostasis of hippocampal neurons during metabolic stress.

  18. Recruiter Selection Model

    Science.gov (United States)

    2006-05-01

    interests include feature selection, statistical learning, multivariate statistics, market research, and classification. He may be contacted at...current youth market , and reducing barriers to Army enlistment. Part of the Army Recruiting Initiatives was the creation of a recruiter selection...Selection Model DevelPed by the Openuier Reseach Crate of E...lneSstm Erapseeeng Depce-teo, WViitd Ntt. siliec Academy, NW..t Point, 271 Weau/’itt 21M

  19. Electronic Recruitment at CERN

    CERN Multimedia

    2004-01-01

    The Human Resources Department switches to electronic recruitment. From now on whenever you are involved in a recruitment action you will receive an e-mail giving you access to a Web folder. Inside you will find a shortlist of applications drawn up by the Human Resources Department. This will allow you to consult the folder, at the same time as everyone else involved in the recruitment process, for the vacancy you are interested in. This new electronic recruitment system, known as e-RT, will be introduced in a presentation given at 10 a.m. on 11 February in the Main Auditorium. Implemented by AIS (Administrative Information Services) and the Human Resources Department, e-RT will cover vacancies open in all of CERN's recruitment programmes. The electronic application system was initially made available to technical students in July 2003. By December it was extended to summer students, fellows, associates and Local Staff. Geraldine Ballet from the Recruitment Service prefers e-RT to mountains of paper! The Hu...

  20. Recruitment of general practices

    DEFF Research Database (Denmark)

    Riis, Allan; Jensen, Cathrine Elgaard; Maindal, Helle Terkildsen;

    2016-01-01

    Introduction: Health service research often involves the active participation of healthcare professionals. However, their ability and commitment to research varies. This can cause recruitment difficulties and thereby prolong the study period and inflate budgets. Solberg has identified seven R......, which was fewer than planned (100 practices). In this evaluation, five of Solberg’s seven R-factors were successfully addressed and two factors were not. The need to involve (reciprocity) end users in the development of new software and the amount of time needed to conduct recruitment (resolution) were...

  1. Re-thinking cell cycle regulators : the cross-talk with metabolism.

    Directory of Open Access Journals (Sweden)

    Lluis eFajas

    2013-01-01

    Full Text Available Analyses of genetically engineered mice deficient for cell cycle regulators, including E2F1, cdk4, or, pRB showed that the major phenotypes are metabolic perturbations. These key cell cycle regulators contribute to lipid synthesis, glucose production, insulin secretion, and glycolytic metabolism and it has been shown how deregulation of those pathways can lead to metabolic perturbations and related metabolic diseases, such as obesity and type II diabetes. The cyclin-cdk-Rb-E2F1 pathway regulates adipogenesis in addition to its well-described roles in cell cycle regulation and cancer. It was also proved that E2F1 directly participates in the regulation of pancreatic growth and function. Similarly, cyclin D3, cdk4, and cdk9 are also adipogenic factors with strong effects on whole organism metabolism. These examples illustrate the growing notion that cell cycle regulatory proteins can also modulate metabolic processes. Cell cycle regulators are activated by insulin and glucose, even in non-proliferating cells. Most importantly cell cycle regulators trigger the adaptive metabolic switch that normal and cancer cells require in order to proliferate. These changes include increased lipid synthesis, decreased oxidative, and increased glycolytic metabolism. In summary, cell cycle regulators are essential in the control of anabolic, biosynthetic processes, and block at the same time oxidative and catabolic pathways, which are the metabolic hallmarks of cancer.

  2. [Recruitment in presbycusis].

    Science.gov (United States)

    Sánchez Legaza, E; Ciges Juan, M; González Pérez, M; Miranda Caravallo, J I

    2006-01-01

    Presbycusis is characterised by a sensorineural hearing loss, mainly in high frequencies, symmetrical and progressive and poor understanding. Recuritment, typical in cochlear hearing loss, would be present in cases of sensorial presbycusis which runs mainly in cochlear pathologies. We analyse variables and their possible interrelations with recruitment in 241 presbycusic patients.

  3. Recruitment. Hello, goodbye.

    Science.gov (United States)

    Moore, Alison

    2008-07-10

    The UK is "moving to a policy of self-sufficiency" according to the Department of Health. The numbers of new overseas entrants into healthcare, including doctors, nurses and midwives has slumped. Several other countries, including Canada, the US and Australia, are aggressively recruiting from overseas, including from the UK. There is an increasing perception the UK does not want overseas staff.

  4. Modifications in cell cycle kinetics and in expression of G1 phase-regulating proteins in human amniotic cells after exposure to electromagnetic fields and ionizing radiation.

    Science.gov (United States)

    Lange, S; Viergutz, T; Simkó, M

    2004-10-01

    Low-frequency electromagnetic fields are suspected of being involved in carcinogenesis, particularly in processes that could be related to cancer promotion. Because development of cancer is associated with deregulated cell growth and we previously observed a magnetic field-induced decrease in DNA synthesis [Lange et al. (2002) Alterations in the cell cycle and in the protein level of cyclin D1p, 21CIP1, and p16INK4a after exposure to 50 HZ. MF in human cells. Radiat. Environ. Biophys.41, 131], this study aims to document the influence of 50 Hz, 1 mT magnetic fields (MF), with or without initial gamma-ionizing radiation (IR), on the following cell proliferation-relevant parameters in human amniotic fluid cells (AFC): cell cycle distribution, expression of the G1 phase-regulating proteins Cdk4, cyclin D1, p21CIP1 and p16INK4a, and Cdk4 activity. While IR induced a G1 delay and a dose-dependent G2 arrest, no discernible changes in cell cycle kinetics were observed due to MF exposure. However, a significant decrease in the protein expression of cyclin D1 and an increase in p21CIP1- and p16INK4a-expression could be detected after exposure to MF alone. IR-exposure caused an augmentation of p21CIP1- and p16INK4a- levels as well, but did not alter cyclin D1 expression. A slight diminution of Cdk4 activity was noticed after MF exposure only, indicating that Cdk4 appears not to act as a mediator of MF- or IR-induced changes in the cell cycle of AFC cells. Co-exposure to MF/IR affected neither cell cycle distribution nor protein expression or kinase activity additionally or synergistically, and therefore MF seems not to modify the mutagenic potency of IR.

  5. Single-molecule tracking in live Vibrio cholerae reveals that ToxR recruits the membrane-bound virulence regulator TcpP to the toxT promoter.

    Science.gov (United States)

    Haas, Beth L; Matson, Jyl S; DiRita, Victor J; Biteen, Julie S

    2015-04-01

    Vibrio cholerae causes the human disease cholera by producing a potent toxin. The V. cholerae virulence pathway involves an unusual transcription step: the bitopic inner-membrane proteins TcpP and ToxR activate toxT transcription. As ToxT is the primary direct transcription activator in V. cholerae pathogenicity, its regulation by membrane-localized activators is key in the disease process. However, the molecular mechanisms by which membrane-localized activators engage the transcription process have yet to be uncovered in live cells. Here we report the use of super-resolution microscopy, single-molecule tracking, and gene knockouts to examine the dynamics of individual TcpP proteins in live V. cholerae cells with cholerae to that in mutant strains lacking either toxR or the toxT promoter, we determine that TcpP mobility is greater in the presence of its interaction partners than in their absence. Our findings support a mechanism in which ToxR recruits TcpP to the toxT promoter for transcription activation.

  6. ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage.

    Science.gov (United States)

    Spruijt, Cornelia G; Luijsterburg, Martijn S; Menafra, Roberta; Lindeboom, Rik G H; Jansen, Pascal W T C; Edupuganti, Raghu Ram; Baltissen, Marijke P; Wiegant, Wouter W; Voelker-Albert, Moritz C; Matarese, Filomena; Mensinga, Anneloes; Poser, Ina; Vos, Harmjan R; Stunnenberg, Hendrik G; van Attikum, Haico; Vermeulen, Michiel

    2016-10-11

    NuRD (nucleosome remodeling and histone deacetylase) is a versatile multi-protein complex with roles in transcription regulation and the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The MYND domain of ZMYND8 directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A. Both GATAD2A and GATAD2B exclusively form homodimers and define mutually exclusive NuRD subcomplexes. ZMYND8 and NuRD share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and only slightly affects expression of NuRD/ZMYND8 target genes. In contrast, the MYND domain in ZMYND8 facilitates the rapid, poly(ADP-ribose)-dependent recruitment of GATAD2A/NuRD to sites of DNA damage to promote repair by homologous recombination. Thus, these results show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to distinct NuRD subcomplexes.

  7. ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage

    Directory of Open Access Journals (Sweden)

    Cornelia G. Spruijt

    2016-10-01

    Full Text Available NuRD (nucleosome remodeling and histone deacetylase is a versatile multi-protein complex with roles in transcription regulation and the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The MYND domain of ZMYND8 directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A. Both GATAD2A and GATAD2B exclusively form homodimers and define mutually exclusive NuRD subcomplexes. ZMYND8 and NuRD share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and only slightly affects expression of NuRD/ZMYND8 target genes. In contrast, the MYND domain in ZMYND8 facilitates the rapid, poly(ADP-ribose-dependent recruitment of GATAD2A/NuRD to sites of DNA damage to promote repair by homologous recombination. Thus, these results show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to distinct NuRD subcomplexes.

  8. Recruitment Requires an Informed Public

    Science.gov (United States)

    Boucher, Leon

    1975-01-01

    The personal approach of the Ohio Recruitment Commission for Agricultural Education has been very effective in recruiting potential vocational agriculture teachers from junior and senior high school classes. (EA)

  9. 10 Ways to Recruit Teachers.

    Science.gov (United States)

    Stewart, Daisy

    1999-01-01

    Suggestions for recruiting teachers are as follow: talk to teens, recruit from within, involve counselors, target uncertain students, network, build relationships with tech prep, enlist military personnel, recruit extension agents, contact outplacement and employment services, and use distance-learning methods. (JOW)

  10. Menin and RNF20 recruitment is associated with dynamic histone modifications that regulate signal transducer and activator of transcription 1 (STAT1-activated transcription of the interferon regulatory factor 1 gene (IRF1

    Directory of Open Access Journals (Sweden)

    Buro Lauren J

    2010-09-01

    Full Text Available Abstract Background Signal transducer and activator of transcription (STAT activation of gene expression is both rapid and transient, and when properly executed it affects growth, differentiation, homeostasis and the immune response, but when dysregulated it contributes to human disease. Transcriptional activation is regulated by alterations to the chromatin template. However, the role of histone modification at gene loci that are activated for transcription in response to STAT signaling is poorly defined. Results Using chromatin immunoprecipitation, we profiled several histone modifications during STAT1 activation of the interferon regulatory factor 1 gene (IRF1. Methylated lysine histone proteins H3K4me2, H3K4me3, H3K79me3, H3K36me3 and monoubiquitinated histone ubH2B are dynamic and correlate with interferon (IFNγ induction of STAT1 activity. Chemical inhibition of H3K4 methylation downregulates IRF1 transcription and decreases RNA polymerase II (Pol II occupancy at the IRF1 promoter. MEN1, a component of a complex proteins associated with Set1 (COMPASS-like complex and the hBRE1 component, RNF20, are localized to IRF1 in the uninduced state and are further recruited when IRF1 is activated. RNAi-mediated depletion of RNF20 lowers both ubH2B and H3K4me3, but surprisingly, upregulates IFNγ induced IRF1 transcription. The dynamics of phosphorylation in the C-terminal domain (CTD of Pol II are disrupted during gene activation as well. Conclusions H2B monoubiquitination promotes H3K4 methylation, but the E3 ubiquitin ligase, RNF20, is repressive of inducible transcription at the IRF1 gene locus, suggesting that ubH2B can, directly or indirectly, affect Pol II CTD phosphorylation cycling to exert control on ongoing transcription.

  11. An experimental study of extracellular signal-regulated kinase and its inter ventional treatments in hepatic ifbrosis

    Institute of Scientific and Technical Information of China (English)

    Ming-De Jiang; Shu-Mei Zheng; Hui Xu; Wei-Zheng Zeng; Yong Zhang; Hao-Ping Sun; Yun-Xia Wang; Jian-Ping Qin; Xiao-Ling Wu

    2008-01-01

    BACKGROUND:The pathogenesis of hepatic ifbrosis and cirrhosis is still not fully understood. The extracellular signal-regulated kinase (ERK) pathway is involved in the regulation of cell proliferation and differentiation. The aim of this study was to investigate the effects of PD98059, a speciifc inhibitor of ERK, on the cell cycle, cell proliferation, secretion of typeⅠcollagen and expression of cyclin D1 mRNA, CDK4 mRNA and transforming growth factor-β1 (TGF-β1) mRNA in rat hepatic stellate cells (HSCs) stimulated by acetaldehyde. METHODS:Rat HSCs stimulated by acetaldehyde were incubated with PD98059 at different concentrations. The cell cycle was analysed by lfow cytometry. Cell proliferation was assessed by the methyl thiazolyl tetrazolium colorimetric assay. The mRNA expression of cyclin D1, CDK4 and TGF-β1 was examined using the reverse transcriptase-polymerase chain reaction. Type Ⅰcollagen in the culture medium was detected by enzyme-linked immunosorbent assay. RESULTS: 20, 50 and 100 μmol/L PD98059 signiifcantly inhibited the proliferation and provoked a G0/G1-phase arrest of acetaldehyde-induced HSCs in a dose-dependent manner. The secretion of typeⅠ collagen and the expression of cyclin D1, CDK4 and TGF-β1 mRNA in acetaldehyde-induced HSCs were markedly inhibited by 50 and 100μmol/L PD98059, respectively. CONCLUSIONS:The ERK pathway regulates the cell proliferation, secretion of type Ⅰ collagen and the expression of TGF-β1 mRNA in rat HSCs stimulated by acetaldehyde, which is likely related to its regulative effect on the cell cycle.

  12. From Traditional Recruiting To E-Recruiting in Public Organizations

    Directory of Open Access Journals (Sweden)

    ARTENE Adela Suzana

    2013-05-01

    Full Text Available Recruiting is the activity that determines, in quantitative and qualitative terms, the structure of the sample of people from which the selection will be made for a specific position and / or public office, for a position that is already created in the organizational structure. The recruitment process is triggered when in the organizational structure of public institutions appear new functions or positions, or when the existing ones become vacant through retirement, death, transfer or dismissal. E-Recruiting represents the process through which the personnel is recruited using electronic resources.

  13. Differential responses of skin cancer-chemopreventive agents silibinin, quercetin, and epigallocatechin 3-gallate on mitogenic signaling and cell cycle regulators in human epidermoid carcinoma A431 cells.

    Science.gov (United States)

    Bhatia, N; Agarwal, C; Agarwal, R

    2001-01-01

    Silibinin, quercetin, and epigallocatechin 3-gallate (EGCG) have been shown to be skin cancer-preventive agents, albeit by several different mechanisms. Here, we assessed whether these agents show their cancer-preventive potential by a differential effect on mitogenic signaling molecules and cell cycle regulators. Treatment of human epidermoid carcinoma A431 cells with these agents inhibited the activation of the epidermal growth factor receptor and the downstream adapter protein Shc, but only silibinin showed a marked inhibition of mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation. In terms of cell cycle regulators, silibinin treatment showed an induction of Cip1/p21 and Kip1/p27 together with a significant decrease in cyclin-dependent kinase (CDK)-4, CDK2, and cyclin D1. Quercetin treatment, however, resulted in a moderate increase in Cip1/p21 with no change in Kip1/p27 and a decrease in CDK4 and cyclin D1. EGCG treatment also led to an induction of Cip1/p21 but no change in Kip1/27, CDK2, and cyclin D1 and a decrease in CDK4 only at low doses. Treatment of cells with these agents resulted in a strong dose- and time-dependent cell growth inhibition. A high dose of silibinin and low and high doses of quercetin and EGCG also led to cell death by apoptosis, suggesting that a lack of their inhibitory effect on mitogen-activated protein kinase-extracellular signal-regulated kinase-1 and -2 activation possibly "turns on" an apoptotic cell death response associated with their cancer-preventive and anticarcinogenic effects. Together, these results suggest that silibinin, quercetin, and EGCG exert their cancer-preventive effects by differential responses on mitogenic signaling and cell cycle regulators.

  14. Normal Proliferation and Tumorigenesis but Impaired Pancreatic Function in Mice Lacking the Cell Cycle Regulator Sei1

    OpenAIRE

    Fernandez-Marcos, Pablo J.; Cristina Pantoja; Agueda Gonzalez-Rodriguez; Nicholas Martin; Flores, Juana M.; Valverde, Angela M.; Eiji Hara; Manuel Serrano

    2010-01-01

    Sei1 is a positive regulator of proliferation that promotes the assembly of Cdk4-cyclin D complexes and enhances the transcriptional activity of E2f1. The potential oncogenic role of Sei1 is further suggested by its overexpression in various types of human cancers. To study the role of Sei1, we have generated a mouse line deficient for this gene. Sei1-null fibroblasts did not show abnormalities regarding proliferation or susceptibility to neoplastic transformation, nor did we observe defects ...

  15. General Recruiting Policy

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Basic Requirements 1) Volunteer to serve the Beijing Olympic and Paralympic Games; 2) Born prior to (but including) June 30, 1990, and in good health; 3) Abide by China’s laws and regulations; 4) Able to participate in pre-Games training and relat- ed ac

  16. Tubulin nucleotide status controls Sas-4-dependent pericentriolar material recruitment.

    Science.gov (United States)

    Gopalakrishnan, Jayachandran; Chim, Yiu-Cheung Frederick; Ha, Andrew; Basiri, Marcus L; Lerit, Dorothy A; Rusan, Nasser M; Avidor-Reiss, Tomer

    2012-08-01

    Regulated centrosome biogenesis is required for accurate cell division and for maintaining genome integrity. Centrosomes consist of a centriole pair surrounded by a protein network known as pericentriolar material (PCM). PCM assembly is a tightly regulated, critical step that determines the size and capability of centrosomes. Here, we report a role for tubulin in regulating PCM recruitment through the conserved centrosomal protein Sas-4. Tubulin directly binds to Sas-4; together they are components of cytoplasmic complexes of centrosomal proteins. A Sas-4 mutant, which cannot bind tubulin, enhances centrosomal protein complex formation and has abnormally large centrosomes with excessive activity. These results suggest that tubulin negatively regulates PCM recruitment. Whereas tubulin-GTP prevents Sas-4 from forming protein complexes, tubulin-GDP promotes it. Thus, the regulation of PCM recruitment by tubulin depends on its GTP/GDP-bound state. These results identify a role for tubulin in regulating PCM recruitment independent of its well-known role as a building block of microtubules. On the basis of its guanine-bound state, tubulin can act as a molecular switch in PCM recruitment.

  17. Recruit and ADVANCE

    Science.gov (United States)

    Rosser, Sue V.

    2007-04-01

    Beginning in 2001, the National Science Foundation launched the ADVANCE Initiative, which has now awarded more than 70 million to some thirty institutions for transformations to advance women. Results of studies on how to attract and retain women students and faculty underpinned our ADVANCE Institutional Transformation grant funded by the NSF for 3.7 million for five years, beginning in 2001. As co-principal investigator on this grant, I insured that this research informed the five major threads of the grant: 1) Four termed ADVANCE professors to mentor junior women faculty in each college; 2) Collection of MIT-Report-like data indicators to assess whether advancement of women really occurs during and after the institutional transformation undertaken through ADVANCE; 3) Family-friendly policies and practices to stop the tenure clock and provide active service, modified duties, lactation stations and day care; 4) Mini-retreats to facilitate access for tenure-track women faculty to male decision-makers and administrators for informal conversations and discussion on topics important to women faculty; 5) Removal of subtle gender, racial, and other biases in promotion and tenure. The dynamic changes resulting from the grant in quality of mentoring, new understanding of promotion and tenure, numbers of women retained and given endowed chairs, and emergence of new family friendly policies gave me hope for genuine diversification of leadership in science and technology. As the grant funding ends, the absence of NSF prestige and monitoring, coupled with a change in academic leadership at the top, provide new challenges for institutionalization, recruitment, and advancement of women into leadership positions in science and engineering.

  18. Recruitment Practices And Institutional Change

    DEFF Research Database (Denmark)

    Holm, Anna; Ulhøi, John Parm

    , and individuals’ social cognition. Among other things, this is reflected in the use of online recruitment and employer branding. The study concludes that the recruitment field has transformed and reviewed its practices due to institutional changes in how individuals search for employment and expect to be hired....

  19. Recruiting and Supporting Latino Volunteers.

    Science.gov (United States)

    Hobbs, Beverly B.

    This booklet is intended to help volunteer recruiters better understand characteristics of the Latino community that might impact volunteering. It also suggests strategies or steps to use in successfully recruiting and supporting Latino volunteers. Information is based on a study of Latinos and volunteerism conducted in Oregon in 1999. The…

  20. Diversity employment and recruitment sources

    Energy Technology Data Exchange (ETDEWEB)

    1994-08-01

    Effective human resources management has been identified as one of four critical success factors in the Department of Energy Strategic Plan. The Plan states relative to this factor: ``The Department seeks greater alignment of resources with agency priorities and increased diversification of the workforce, including gender, ethnicity, age, and skills. This diversification will bring new thinking and perspectives that heretofore have not had a voice in departmental decision-making.`` This Guide has been developed as a key tool to assist Department of Energy management and administrative staff in achieving Goal 2 of this critical success factor, which is to ``Ensure a diverse and talented workforce.`` There are numerous sources from which to recruit minorities, women and persons with disabilities. Applying creativity and proactive effort, using traditional and non-traditional approaches, and reaching out to various professional, academic and social communities will increase the reservoir of qualified candidates from which to make selections. In addition, outreach initiatives will undoubtedly yield further benefits such as a richer cultural understanding and diversity awareness. The resource listings presented in this Guide are offered to encourage active participation in the diversity recruitment process. This Guide contains resource listings by state for organizations in the following categories: (1) African American Recruitment Sources; (2) Asian American/Pacific Islander Recruitment Sources; (3) Hispanic Recruitment Sources; (4) Native American/Alaskan Native Recruitment Sources; (5) Persons with Disabilities Recruitment Sources; and (6) Women Recruitment Sources.

  1. Three Keys to Better Recruiting

    Science.gov (United States)

    Brazington, Alicia

    2012-01-01

    Recruitment is an expensive business: In 2010-2011, the median cost to recruit an undergraduate was $2,185 among private colleges and universities, according to Noel-Levitz, an enrollment management consultancy. In these tough fiscal times, admissions departments are under pressure to keep those costs down even as they pursue higher enrollment and…

  2. Human Resources Marketing and Recruiting: Essentials of Digital Recruiting

    CERN Document Server

    Purvis, James

    2016-01-01

    This chapter will cover digital recruitment from its definition thru to its history in recruitment and trends. The subject itself could cover an entire book or an entire module at university, so this chapter will broadly touch upon the key elements and considerations. Under cultural perspective, the recruitment life cycle will be broken down into its individual parts, and digital solutions will be examined for each individual part of the process together with the impact this has on the knowledge and challenges for the manager and team. The economic perspective will assist in prioritizing initiatives and building a business case for the introduction of digital recruiting solutions. The risk perspective will raise awareness of the potential pitfalls and the operational perspective on the key considerations for a successful implementation. Finally, the key messages of this chapter are summarized in the Do’s and Don’ts.

  3. Sales Training for Army Recruiter Success: Interviews with Excellent Recruiters

    Science.gov (United States)

    1987-11-01

    merit of an expert modeling system of the skills and strategies used by excel- lent Army recruiters. Neurolinguistic programming (NLP) was used as the...7. AUTHOR(&) 8. CONTRACT OR GRANT NUMBER(s) Steven R. Frieman 9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK U.S...Recruiting 2M AUSTIRACT (rcnttm ame r orw am nssry i Identify by block number) s-This report describes a program of research on communication strategies and

  4. Navy Enlisted Recruiting: Alternatives for Improving Recruiter Productivity

    Science.gov (United States)

    2013-03-01

    screening process and understanding the differences in cognitive ability, the different cultures of each rating, and their correlation to recruiting...process and understanding the differences in cognitive ability, the different cultures of each rating, and their correlation to recruiting performance...of the seven months that it took to complete this research. A special Bravo Zulu to my advisors, Professor Jeremy Arkes, Professor Steve Mehay, and

  5. Information networks and worker recruitment

    NARCIS (Netherlands)

    Schram, A.; Brandts, J.; Gërxhani, K.

    2007-01-01

    This paper studies experimentally how the existence of social information networks affects the ways in which firms recruit new personnel. Through such networks firms learn about prospective employees' performance in previous jobs. Assuming individualistic preferences social networks are predicted no

  6. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

    In this PhD work a new method for measuring microvascular recruitment was developed and evaluated, using continues real-time imaging of contrast enhanced ultrasound. Gas-filled microbubbles were infused intravenously and by taking advantage of the echogenic properties of the microbubbles the reso......In this PhD work a new method for measuring microvascular recruitment was developed and evaluated, using continues real-time imaging of contrast enhanced ultrasound. Gas-filled microbubbles were infused intravenously and by taking advantage of the echogenic properties of the microbubbles...... action in the microvasculature and restored normal microvascular function by increasing the microvascular recruitment similar to in control animals. This effect of GLP-1 on microvascular recruitment was associated with a restoration of both whole body insulin sensitivity and muscle glucose uptake when co...

  7. Recruiting for Prior Service Market

    Science.gov (United States)

    2008-06-01

    perceptions, expectations and issues for re-enlistment • Develop potential marketing and advertising tactics and strategies targeted to the defined...01 JUN 2008 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Recruiting for Prior Service Market 5a. CONTRACT NUMBER 5b. GRANT...Command First Handshake to First Unit of Assignment An Army of One Proud to Be e e to Serve Recruiting for Prior Service Market MAJ Eric Givens / MAJ Brian

  8. The Next Best Alternative to an Ideal Recruit: Attrition Characteristics of Recruits with Waivers and Low Educational Credentials in the U.S. Army

    Science.gov (United States)

    2009-03-01

    order to recruit more high quality recruits, services typically need to spend more money on enlistment bonuses, educational benefits , advertisements...policies can affect attrition rates: homeschooled students from states with minimal regulation have higher attrition rates than homeschooled students from...morale or motivation of other recruits. These factors should also be taken into account in making cost benefit analysis of increasing the number of

  9. Understanding Millennials to Improve Recruiting Efficiency

    Science.gov (United States)

    2011-03-24

    to the authors of Generations at Work, when recruiting Millennials one must “be tolerant of their “swiss cheese scheduling”-an hour or two here, a...Recruiting Command, Recruiting Operations, 4-3. 32 Ibid., 6-4. 33 U.S. Army Recruiting Command, The Recruiter Handbook , United States Army Recruiting...6-1. 35 U.S. Army Recruiting Command, The Recruiter Handbook , 1-3. 36 Lynn C. Lancaster and David Stillman, When Generations Collide: Who They Ar

  10. Spatial synchrony in cisco recruitment

    Science.gov (United States)

    Myers, Jared T.; Yule, Daniel L.; Jones, Michael L.; Ahrenstorff, Tyler D.; Hrabik, Thomas R.; Claramunt, Randall M.; Ebener, Mark P.; Berglund, Eric K.

    2015-01-01

    We examined the spatial scale of recruitment variability for disparate cisco (Coregonus artedi) populations in the Great Lakes (n = 8) and Minnesota inland lakes (n = 4). We found that the scale of synchrony was approximately 400 km when all available data were utilized; much greater than the 50-km scale suggested for freshwater fish populations in an earlier global analysis. The presence of recruitment synchrony between Great Lakes and inland lake cisco populations supports the hypothesis that synchronicity is driven by climate and not dispersal. We also found synchrony in larval densities among three Lake Superior populations separated by 25–275 km, which further supports the hypothesis that broad-scale climatic factors are the cause of spatial synchrony. Among several candidate climate variables measured during the period of larval cisco emergence, maximum wind speeds exhibited the most similar spatial scale of synchrony to that observed for cisco. Other factors, such as average water temperatures, exhibited synchrony on broader spatial scales, which suggests they could also be contributing to recruitment synchrony. Our results provide evidence that abiotic factors can induce synchronous patterns of recruitment for populations of cisco inhabiting waters across a broad geographic range, and show that broad-scale synchrony of recruitment can occur in freshwater fish populations as well as those from marine systems.

  11. Effect of androgen withdrawal on activation of ERKs and expression of cell cycle regulation molecules in human prostate carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    YE Ding-wei; LI Hui; TSENG Jane; CHAUVIN Priscilla; QIAN Song-xi; ZHENG Jia-fu; SUN Ying-hao; MA Yong-jiang

    2002-01-01

    Objective: To explore the possible mechanisms of growth regression of human androgen dependentprostate carcinoma cells caused by androgen withdrawal. Methods: After 24 h of treatment with 1×10-9mol/L dihydrotestosterone (DHT), the expression of phosphorylated ERK proteins and cell cycle regulationmolecules including CDK2, CDK4, CDK6 and P27kip1 in human androgen dependent prostate carcinoma cellline LNCaP was measured by Western blot analysis 0 h, 8 h and 24 h of after androgen withdrawal. Humanandrogen independent prostate carcinoma cell line PC-3 was also examined as control. Results: Down-regula-tion of phosphorylated ERK, CDK2, CDK4 and CDK6 and up-regulation of P27kip1 were found initially inLNCaP cell line 8 h after androgen withdrawal. The levels of phosphorylated ERK and CDKs decreased con-tinuously and reached the lowest after 24 h, while continuous elevation of P27kip1 was detected thereafter to 24h. No expression change of phosphorylated ERK, CDKs and P27kip1 were detected in PC-3 cell line. Conclu-sion: The androgen withdrawal can cause ERKs activation decrease and cell cycle regulation moleculeschanges, which may be one of the mechanisms for inhibited growth of androgen dependent prostate carcinomaafter androgen ablation by either operative or medicine methods.

  12. Uncover the recruiter in you!

    CERN Multimedia

    2013-01-01

    2013 saw the launch of the one-day training course "Selecting the best person for CERN". So far, 10 courses have taken place and over 100 participants have taken part in this interactive, hands on experience.   The course has been met with much enthusiasm and positive feedback, with participants not only feeling better prepared and organised for the recruitment boards, but also equipped with concrete tools on how to prepare and conduct an effective selection interview. Following on from this success, further sessions are planned in 2014: we look forward to welcoming recruiting supervisors and board members who are likely to take part in a recruitment process, whether for LD or LD2IC, and who are interested in finding out more about how to get the most out of this important process! To enrol to this course, please follow this link: "Selecting the best person for CERN".

  13. International Student Recruitment: Trends and Challenges

    Science.gov (United States)

    Falcone, Santa

    2017-01-01

    This paper provides a review of current trends in international student recruitment. Focusing specifically on recruitment of Chinese students, important aspects of China's educational system relevant to recruitment are presented. Barriers to Chinese student recruitment are then discussed. Successful, employed, international graduates validate…

  14. Recruiting and Retaining Summer Staff.

    Science.gov (United States)

    Crossen, Brian; Yerkes, Rita

    1998-01-01

    Recruiting of camp staff is challenged by economic and workplace restructuring, including business downsizing, part-time and temporary employment patterns, and generational attitude changes. Strategies for hiring and retaining staff include knowing what college-age workers want, marketing benefits, adopting new business strategies, and empowering…

  15. Do recruitment ties affect wages?

    DEFF Research Database (Denmark)

    Larsen, Anna Folke; Rand, John; Torm, Nina Elisabeth

    This paper examines the extent to which recruitment ties affect individual wage outcomes in small and medium scale manufacturing firms. Based on a unique matched employer-employee dataset from Vietnam we find that there is a significant positive wage premium associated with obtaining a job through...

  16. Training and Recruitment of Judges in Germany

    Directory of Open Access Journals (Sweden)

    Johannes Riedel

    2013-10-01

    Full Text Available Training of German judges is part of general legal education which is the same for all regulated legal professions (judges, prosecutors, practising lawyers, lawyers in administration and private employment. This uniform qualification is acquired by passing two exams administered by the state, i.e. the Länder (not the Federation, the first exam after university studies and the second exam after state-organized practical training. The paper gives an overview of this system of legal education. Germany, as a rule, has career judges. Courts of first and second instance are administered by the Länder, therefore the Länder judicial administrations are also responsible for recruitment of young career judges. General criteria for appointment to any public office are laid down in the German constitution (Grundgesetz. Apart from this, selection proceedings differ in detail, although elaborate lists of criteria (employee profiles, competence profiles are widely used. Professional competence is judged with emphasis on exam results; personal competence and social competence are assessed in interviews with appointment commissions or staff managers of ministries of justice. The paper provides details of these proceedings and also gives the author’s personal experience with recruitment proceedings in the Court of Appeal district of Cologne.

  17. Tumor vasculature is regulated by FGF/FGFR signaling-mediated angiogenesis and bone marrow-derived cell recruitment: this mechanism is inhibited by SSR128129E, the first allosteric antagonist of FGFRs.

    Science.gov (United States)

    Fons, Pierre; Gueguen-Dorbes, Geneviève; Herault, Jean-Pascal; Geronimi, Fabien; Tuyaret, Joël; Frédérique, Dol; Schaeffer, Paul; Volle-Challier, Cécile; Herbert, Jean-Marc; Bono, Françoise

    2015-01-01

    Tumor angiogenesis is accompanied by vasculogenesis, which is involved in the differentiation and mobilization of human bone marrow cells. In order to further characterize the role of vasculogenesis in the tumor growth process, the effects of FGF2 on the differentiation of human bone marrow AC133(+) cells (BM-AC133(+)) into vascular precursors were studied in vitro. FGF2, like VEGFA, induced progenitor cell differentiation into cell types with endothelial cell characteristics. SSR128129E, a newly discovered specific FGFR antagonist acting by allosteric interaction with FGFR, abrogated FGF2-induced endothelial cell differentiation, showing that FGFR signaling is essential during this process. To assess the involvement of the FGF/FRGR signaling in vivo, the pre-clinical model of Lewis lung carcinoma (LL2) in mice was used. Subcutaneous injection of LL2 cells into mice induced an increase of circulating EPCs from peripheral blood associated with tumor growth and an increase of intra-tumoral vascular index. Treatment with the FGFR antagonist SSR128129E strongly decreased LL2 tumor growth as well as the intra-tumoral vascular index (41% and 50% decrease vs. vehicle-treated mice respectively, P FGFR pathway by SSR128129E reduces EPC recruitment during angiogenesis-dependent tumor growth. In this context, circulating EPCs could be a reliable surrogate marker for tumor growth and angiogenic activity.

  18. A recruiting failure turned success

    Directory of Open Access Journals (Sweden)

    Smith Roger

    2008-03-01

    Full Text Available Abstract Background This paper describes an attempt that was made to recruit child-bearing women into a nutrition-based research study and the knowledge that was gained when this approach was unsuccessful. The Assessment Before Children Develop Obesity Study was a cross-sectional survey which planned to follow-up women and children who had previously been, or were currently enrolled in the Mathematical Model of Pregnancy Study. Methods Ethics approval was sought and obtained over an eight month period. After just six weeks it was obvious that our research objectives were not achievable because of an inadequate response rate (10%. This led to a review of the recruiting methodology as well as all written materials provided to potential participants. Advice was sought from those with expertise in the design of large public health campaigns and literature was consulted to refine our recruitment strategy. Results In subsequent redevelopment, the Assessment Before Children Develop Obesity Study was merged with the Mathematical Model of Pregnancy Study to become what is now known as the Women and Their Children's Health Study. Consent rates improved from 10% and 35% in the Assessment Before Children Develop Obesity and Mathematical Model of Pregnancy studies respectively, to 61% in the Women and Their Children's Health Study (chi square test, p Conclusion By sharing our experience we aim to assist other researcher in avoiding the same pitfalls and offer effective strategies for improving response rates.

  19. 48 CFR 252.209-7005 - Reserve Officer Training Corps and military recruiting on campus.

    Science.gov (United States)

    2010-10-01

    ...: Reserve Officer Training Corps and Military Recruiting on Campus (JAN 2000) (a) Definition. “Institution... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Reserve Officer Training Corps and military recruiting on campus. 252.209-7005 Section 252.209-7005 Federal...

  20. Brand Caliphate and recruitment between the genders

    OpenAIRE

    Monroe, Brandi Lynn Evans

    2016-01-01

    Approved for public release; distribution is unlimited Since the declaration of the Islamic State (IS) in 2014, men and women have been recruited to join the Caliphate in numbers surpassing those recruited by al Qaida. This variance in recruitment volume is likely attributable to the online propaganda campaign, Brand Caliphate. This thesis looks at the recruitment of women and asks if Brand Caliphate specifically targets females with its messaging, and if so, is the messaging effective? Ba...

  1. ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage

    OpenAIRE

    Cornelia G. Spruijt; Martijn S. Luijsterburg; Roberta Menafra; Rik G.H. Lindeboom; Pascal W.T.C. Jansen; Raghu Ram Edupuganti; Marijke P. Baltissen; Wouter W. Wiegant; Moritz C. Voelker-Albert; Filomena Matarese; Anneloes Mensinga; Ina Poser; Harmjan R. Vos; Hendrik G. Stunnenberg; Haico van Attikum

    2016-01-01

    NuRD (nucleosome remodeling and histone deacetylase) is a versatile multi-protein complex with roles in transcription regulation and the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The MYND domain of ZMYND8 directly interacts with PPPLΦ motifs in the NuRD subunit GATAD2A. Both GATAD2A and GATAD2B exclusively form homodimers and define mutually exclusive NuRD subcomplexes. ZMYND8 and NuRD share a large number of genome-w...

  2. Gender bias in academic recruitment

    DEFF Research Database (Denmark)

    Abramo, Giovanni; D’Angelo, Ciriaco Andrea; Rosati, Francesco

    2016-01-01

    It is well known that women are underrepresented in the academic systems of many countries. Gender discrimination is one of the factors that could contribute to this phenomenon. This study considers a recent national academic recruitment campaign in Italy, examining whether women are subject...... to more or less bias than men. The findings show that no gender-related differences occur among the candidates who benefit from positive bias, while among those candidates affected by negative bias, the incidence of women is lower than that of men. Among the factors that determine success in a competition...

  3. Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions.

    Science.gov (United States)

    Sawant, Kirti V; Poluri, Krishna Mohan; Dutta, Amit K; Sepuru, Krishna Mohan; Troshkina, Anna; Garofalo, Roberto P; Rajarathnam, Krishna

    2016-09-14

    The chemokine CXCL1/MGSA plays a pivotal role in the host immune response by recruiting and activating neutrophils for microbial killing at the tissue site. CXCL1 exists reversibly as monomers and dimers, and mediates its function by binding glycosaminoglycans (GAG) and CXCR2 receptor. We recently showed that both monomers and dimers are potent CXCR2 agonists, the dimer is the high-affinity GAG ligand, lysine and arginine residues located in two non-overlapping domains mediate GAG interactions, and there is extensive overlap between GAG and receptor-binding domains. To understand how these structural properties influence in vivo function, we characterized peritoneal neutrophil recruitment of a trapped monomer and trapped dimer and a panel of WT lysine/arginine to alanine mutants. Monomers and dimers were active, but WT was more active indicating synergistic interactions promote recruitment. Mutants from both domains showed reduced GAG heparin binding affinities and reduced neutrophil recruitment, providing compelling evidence that both GAG-binding domains mediate in vivo trafficking. Further, mutant of a residue that is involved in both GAG binding and receptor signaling showed the highest reduction in recruitment. We conclude that GAG interactions and receptor activity of CXCL1 monomers and dimers are fine-tuned to regulate neutrophil trafficking for successful resolution of tissue injury.

  4. Childhood poverty and recruitment of adult emotion regulatory neurocircuitry.

    Science.gov (United States)

    Liberzon, Israel; Ma, Sean T; Okada, Go; Ho, S Shaun; Swain, James E; Evans, Gary W

    2015-11-01

    One in five American children grows up in poverty. Childhood poverty has far-reaching adverse impacts on cognitive, social and emotional development. Altered development of neurocircuits, subserving emotion regulation, is one possible pathway for childhood poverty's ill effects. Children exposed to poverty were followed into young adulthood and then studied using functional brain imaging with an implicit emotion regulation task focused. Implicit emotion regulation involved attention shifting and appraisal components. Early poverty reduced left dorsolateral prefrontal cortex recruitment in the context of emotional regulation. Furthermore, this emotion regulation associated brain activation mediated the effects of poverty on adult task performance. Moreover, childhood poverty also predicted enhanced insula and reduced hippocampal activation, following exposure to acute stress. These results demonstrate that childhood poverty can alter adult emotion regulation neurocircuitry, revealing specific brain mechanisms that may underlie long-term effects of social inequalities on health. The role of poverty-related emotion regulatory neurocircuitry appears to be particularly salient during stressful conditions.

  5. Platelets in leucocyte recruitment and function.

    Science.gov (United States)

    Rossaint, Jan; Zarbock, Alexander

    2015-08-01

    Platelets have a longstanding recognition as an essential cellular component of the coagulation system. However, substantial research over the last decade has added another important aspect to platelet function in that they are also an integral part of the innate immune system. Complex organisms are facing a constant threat of infections by invading pathogens, and they have developed a sophisticated and elegant measure to combat this threat, namely the immune system. Leucocyte recruitment to sites of infections is an essential step at the forefront of the immune response. Platelets have been shown to be involved in several steps of this process and they are an integrated connecting element among haemostasis, host defence, and additional immunological functions (e.g. neutrophil extracellular traps formation). However, the immune system also requires a tight regulation, as an overshooting immune response carries the risk of harming the host itself. This review aims at highlighting the unique features and molecular mechanisms that allow for the interactions of platelets and leucocytes and the regulation of this process. Furthermore, this article identifies the functional relevance of these events for the immune response.

  6. Neuroepithelial transforming gene 1 (Net1) binds to caspase activation and recruitment domain (CARD)- and membrane-associated guanylate kinase-like domain-containing (CARMA) proteins and regulates nuclear factor κB activation.

    Science.gov (United States)

    Vessichelli, Mariangela; Ferravante, Angela; Zotti, Tiziana; Reale, Carla; Scudiero, Ivan; Picariello, Gianluca; Vito, Pasquale; Stilo, Romania

    2012-04-20

    The molecular complexes containing CARMA proteins have been recently identified as a key components in the signal transduction pathways that regulate activation of nuclear factor κB (NF-κB) transcription factor. Here, we used immunoprecipitation coupled with mass spectrometry to identify cellular binding partners of CARMA proteins. Our data indicate that the Rho guanine nucleotide exchange factor Net1 binds to CARMA1 and CARMA3 in resting and activated cells. Net1 expression induces NF-κB activation and cooperates with BCL10 and CARMA proteins in inducing NF-κB activity. Conversely, shRNA-mediated abrogation of Net1 results in impaired NF-κB activation following stimuli that require correct CARMA-BCL10-MALT1 complex formation and functioning. Microarray expression data are consistent with a positive role for Net1 on NF-κB activation. Thus, this study identifies Net1 as a CARMA-interacting molecule and brings important information on the molecular mechanisms that control NF-κB transcriptional activity.

  7. Neuroepithelial Transforming Gene 1 (Net1) Binds to Caspase Activation and Recruitment Domain (CARD)- and Membrane-associated Guanylate Kinase-like Domain-containing (CARMA) Proteins and Regulates Nuclear Factor κB Activation*

    Science.gov (United States)

    Vessichelli, Mariangela; Ferravante, Angela; Zotti, Tiziana; Reale, Carla; Scudiero, Ivan; Picariello, Gianluca; Vito, Pasquale; Stilo, Romania

    2012-01-01

    The molecular complexes containing CARMA proteins have been recently identified as a key components in the signal transduction pathways that regulate activation of nuclear factor κB (NF-κB) transcription factor. Here, we used immunoprecipitation coupled with mass spectrometry to identify cellular binding partners of CARMA proteins. Our data indicate that the Rho guanine nucleotide exchange factor Net1 binds to CARMA1 and CARMA3 in resting and activated cells. Net1 expression induces NF-κB activation and cooperates with BCL10 and CARMA proteins in inducing NF-κB activity. Conversely, shRNA-mediated abrogation of Net1 results in impaired NF-κB activation following stimuli that require correct CARMA-BCL10-MALT1 complex formation and functioning. Microarray expression data are consistent with a positive role for Net1 on NF-κB activation. Thus, this study identifies Net1 as a CARMA-interacting molecule and brings important information on the molecular mechanisms that control NF-κB transcriptional activity. PMID:22343628

  8. Gender bias in academic recruitment

    DEFF Research Database (Denmark)

    Abramo, Giovanni; D’Angelo, Ciriaco Andrea; Rosati, Francesco

    2016-01-01

    It is well known that women are underrepresented in the academic systems of many countries. Gender discrimination is one of the factors that could contribute to this phenomenon. This study considers a recent national academic recruitment campaign in Italy, examining whether women are subject...... to more or less bias than men. The findings show that no gender-related differences occur among the candidates who benefit from positive bias, while among those candidates affected by negative bias, the incidence of women is lower than that of men. Among the factors that determine success in a competition...... for an academic position, the number of the applicant’s career years in the same university as the committee members assumes greater weight for male candidates than for females. Being of the same gender as the committee president is also a factor that assumes greater weight for male applicants. On the other hand...

  9. The Challenge of Recruiting Control Groups

    DEFF Research Database (Denmark)

    O'Connor, Maja

    2011-01-01

      Recruitment of a large and reliable control group is a challenge in psychological survey based research. The effect of recruitment styles and age on response-rate, data quality, and individual differences were investigated in a control group for a postal survey of elderly bereaved people. This ...... incentive had the highest response-rate (51%), good data quality, and no sampling bias in individual differences. This method can be highly recommended in future control group recruitment....

  10. Recruiting Diverse Smokers: Enrollment Yields and Cost

    Science.gov (United States)

    Brodar, Kaitlyn E.; Hall, Marissa G.; Butler, Eboneé N.; Parada, Humberto; Stein-Seroussi, Al; Hanley, Sean; Brewer, Noel T.

    2016-01-01

    To help tobacco control research better include vulnerable populations, we sought to identify effective ways to recruit diverse smokers. In 2014–2015, we recruited 2149 adult cigarette smokers in California and North Carolina, United States, to participate in a randomized trial of pictorial cigarette pack warnings. The most effective means of recruiting smokers were the classified advertising website Craigslist (28% of participants), word of mouth (23%), Facebook (16%), and flyers or postcards (14%). Low-income and African American smokers were more likely to respond to interpersonal contact (including staff in-person recruitment and word of mouth) than were high-income and non-African American smokers (all p < 0.05). Hispanic and gay, lesbian, and bisexual smokers were more likely to be recruited by Craigslist than non-Hispanic and straight smokers (both p < 0.05). Of the recruitment methods requiring cost, the cheapest was Craigslist ($3–7 per smoker). The most expensive methods were newspaper ads in California ($375 per smoker) and staff in-person recruiting in North Carolina ($180 per smoker). Successfully recruiting diverse smokers requires using multiple methods including interpersonal, online, and other media. Craigslist and word of mouth are especially useful and low-cost ways to recruit diverse smokers. PMID:27999280

  11. Recruiting Diverse Smokers: Enrollment Yields and Cost

    Directory of Open Access Journals (Sweden)

    Kaitlyn E. Brodar

    2016-12-01

    Full Text Available To help tobacco control research better include vulnerable populations, we sought to identify effective ways to recruit diverse smokers. In 2014–2015, we recruited 2149 adult cigarette smokers in California and North Carolina, United States, to participate in a randomized trial of pictorial cigarette pack warnings. The most effective means of recruiting smokers were the classified advertising website Craigslist (28% of participants, word of mouth (23%, Facebook (16%, and flyers or postcards (14%. Low-income and African American smokers were more likely to respond to interpersonal contact (including staff in-person recruitment and word of mouth than were high-income and non-African American smokers (all p < 0.05. Hispanic and gay, lesbian, and bisexual smokers were more likely to be recruited by Craigslist than non-Hispanic and straight smokers (both p < 0.05. Of the recruitment methods requiring cost, the cheapest was Craigslist ($3–7 per smoker. The most expensive methods were newspaper ads in California ($375 per smoker and staff in-person recruiting in North Carolina ($180 per smoker. Successfully recruiting diverse smokers requires using multiple methods including interpersonal, online, and other media. Craigslist and word of mouth are especially useful and low-cost ways to recruit diverse smokers.

  12. Recruiting Diverse Smokers: Enrollment Yields and Cost.

    Science.gov (United States)

    Brodar, Kaitlyn E; Hall, Marissa G; Butler, Eboneé N; Parada, Humberto; Stein-Seroussi, Al; Hanley, Sean; Brewer, Noel T

    2016-12-16

    To help tobacco control research better include vulnerable populations, we sought to identify effective ways to recruit diverse smokers. In 2014-2015, we recruited 2149 adult cigarette smokers in California and North Carolina, United States, to participate in a randomized trial of pictorial cigarette pack warnings. The most effective means of recruiting smokers were the classified advertising website Craigslist (28% of participants), word of mouth (23%), Facebook (16%), and flyers or postcards (14%). Low-income and African American smokers were more likely to respond to interpersonal contact (including staff in-person recruitment and word of mouth) than were high-income and non-African American smokers (all p < 0.05). Hispanic and gay, lesbian, and bisexual smokers were more likely to be recruited by Craigslist than non-Hispanic and straight smokers (both p < 0.05). Of the recruitment methods requiring cost, the cheapest was Craigslist ($3-7 per smoker). The most expensive methods were newspaper ads in California ($375 per smoker) and staff in-person recruiting in North Carolina ($180 per smoker). Successfully recruiting diverse smokers requires using multiple methods including interpersonal, online, and other media. Craigslist and word of mouth are especially useful and low-cost ways to recruit diverse smokers.

  13. An activation-recruitment scheme for use in muscle modeling.

    Science.gov (United States)

    Hawkins, D A; Hull, M L

    1992-12-01

    The derivation of a new activation-recruitment scheme and the results of a study designed to test its validity are presented. The activation scheme utilizes input data of processed surface EMG signals, muscle composition, muscle architecture, and experimentally determined activation coefficients. In the derivation, the relationship between muscle activation and muscle fiber recruitment was considered. In the experimental study, triceps muscle force was determined for isometric elbow extension tasks varying in intensity from 10 to 100% of a maximum voluntary contraction (MVC) using both a muscle model that incorporates the activation scheme, and inverse dynamics techniques. The forces calculated using the two methods were compared statistically. The modeled triceps force was not significantly different from the experimental results determined using inverse dynamics techniques for average activation levels greater than 25% of MVC, but was significantly different for activation levels less than 25% of MVC. These results lend support for use of the activation-recruitment scheme for moderate to large activation levels, and suggest that factors in addition to fiber recruitment play a role in force regulation at lower activation levels.

  14. Amplitude recruitment of cochlear potential

    Institute of Scientific and Technical Information of China (English)

    LI Xingqi; SUN Wei; SUN Jianhe; YU Ning; JIANG Sichang

    2001-01-01

    Intracellular recordings were made from outer hair cells (OHC) and the cochlear microphonics (CM) were recorded from scala media (SM) in three turn of guinea pig cochlea,the compound action potential (CAP) were recorded at the round window (RW) before and after the animal were exposed to white noise. The results suggest that the nonlinear properties with “saduration” of Input/output (I/O) function of OHC AC recepter potential and CM were founded; the nonlinear properties with “Low”, “Platean” and “high” of CAP also were investigated. After explosion, the threshold shift of CAP has about 10 dB. The I/O of OHC responses and CM were changed in a linearizing (i.e., nonlinearity loss), the “platean” of I/O CAP disappeared and the growth rate of CAP amplitude were larger than before explosion. The response amplitude recruitment of OHC appears to result from reduction in gain (i.e., hearing loss); It was due to the nonlinear growth function of OHC receptor potentials was changed in linearzing that the basilar membrance motion was changed in linearizing. Since intensity coding in the inner ear depends on an interactions of nonlinear basilar membrance and nerve fibers. So that it must lead to a linearizing of CAP as input responses.

  15. When is normative recruitment legitimate?

    Directory of Open Access Journals (Sweden)

    Lars Øystein Ursin

    2008-11-01

    Full Text Available Rosamond Rhodes and John Harris have both recently argued that we all have a general moral duty to participate in medical research. However, neither Rhodes' nor Harris' arguments in support of this obligation stand up to scrutiny, and severe and convincing criticism has been levelled against their case. Still, to refute their arguments is not to refute the conclusion. There seems to be some truth in the view that when people are asked to take part in medical research, their choice is not completely morally neutral. In this article, we argue that the proper question to ask is when, rather than if, a certain moral duty to volunteer for medical research can be appealed to. To answer this question, we need a denser description of relevant research projects and their context rather than just describing medical research in general. Drawing on our study of participants in the Norwegian HUNT biobank, we use the normative implications of the Norwegian concept «dugnad» as an analogy to discuss the requirement of providing neutral information to potential biobank participants in order to promote their free and informed decision as to whether or not to take part. We suggest that normative recruitment is not just a question of principles and ethics. It is also a question of research design and the creation of the common good in the community where the research takes place.http://dx.doi.org/10.5324/eip.v2i2.1697

  16. Biotic interactions at hydrothermal vents: Recruitment inhibition by the mussel Bathymodiolus thermophilus

    Science.gov (United States)

    Lenihan, H. S.; Mills, S. W.; Mullineaux, L. S.; Peterson, C. H.; Fisher, C. R.; Micheli, F.

    2008-12-01

    The structure and dynamics of marine communities are regulated in part by variation in recruitment. As in other ecosystems, recruitment at deep-sea hydrothermal vents is controlled by the interplay of propagule supply and behavior, gradients in physical-chemical conditions, and biotic interactions during pre- and post-settlement periods. Recent research along the East Pacific Rise indicates that inhibition of recently settled larvae by mobile predators (mainly limpets) influences patterns of recruitment and subsequent community succession. We conducted a manipulative experiment at the same sites (˜2510 m water depth) to test whether high-density assemblages of the mussel Bathymodiolus thermophilus also inhibit recruitment. In a preliminary study, recruitment of vent invertebrates within the faunal zone dominated by B. thermophilus was strikingly different at two sites, East Wall and Worm Hole. East Wall had high densities of mussels but very low total recruitment. In contrast, Worm Hole had few mussels but high recruitment. Using the submersible Alvin, we transplanted a large number of mussels from East Wall to Worm Hole and quantified recruitment on basalt blocks placed in three treatments: (1) naturally high densities of mussels at East Wall; (2) naturally low densities of mussels at Worm Hole; and (3) high densities of transplanted mussels at Worm Hole. After 11 months, a total of 24 taxa had recruited to the basalt blocks. Recruitment was 44-60% lower in the transplanted high-density mussel patch at Worm Hole and the natural high-density patch at East Wall than within the natural low-density patch at Worm Hole. Biotic processes that may have caused the pattern of recruitment observed included predation of larvae via water filtration by mussels, larval avoidance of superior competitors, interference competition, and enhanced predation by species within the mussel-bed community. Our results indicate that biotic interactions affecting recruitment must be

  17. Recruiting leaders: an analysis of leadership advertisements

    NARCIS (Netherlands)

    den Hartog, D.N.; Caley, A.; Dewe, P.

    2007-01-01

    Recruiting the right leaders is an important challenge for organisations. How do organisations find these leaders? This article looks at the recruitment of leaders through advertisements. We address to what extent the 'vocabulary of leadership' originating in influential leadership theories is activ

  18. School Board Member Recruitment in Ontario.

    Science.gov (United States)

    Cistone, Peter J.

    Employing a process model of political recruitment, this study investigated the relative impact of a school district's social, economic, and political structure on school board member recruitment. The process data were collected by means of structured interviews with neophyte school board members in a stratified sample of school boards in the…

  19. 48 CFR 209.470 - Reserve Officer Training Corps and military recruiting on campus.

    Science.gov (United States)

    2010-10-01

    ... QUALIFICATIONS Debarment, Suspension, and Ineligibility 209.470 Reserve Officer Training Corps and military... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Reserve Officer Training Corps and military recruiting on campus. 209.470 Section 209.470 Federal Acquisition Regulations...

  20. 48 CFR 3009.470 - Reserve Officer Training Corps and military recruiting on campus.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Reserve Officer Training Corps and military recruiting on campus. 3009.470 Section 3009.470 Federal Acquisition Regulations... PLANNING CONTRACTOR QUALIFICATIONS Debarment, Suspension, and Ineligibility 3009.470 Reserve...

  1. Nursery function of coastal temperate benthic habitats: New insight from the bivalve recruitment perspective

    Science.gov (United States)

    Barbier, Pierrick; Meziane, Tarik; Forêt, Martin; Tremblay, Réjean; Robert, René; Olivier, Frédéric

    2017-03-01

    Marine habitat function has been typically investigated in terms of biogeochemical regulation but rarely in terms of population renewal, which is mainly controlled by recruitment dynamics. The recruitment phase is crucial for organisms with a bentho-pelagic life cycle, such as bivalves, and it regulates the population renewal success. This study provides new insight on the role of temperate benthic habitats on bivalve recruitment, as a function of nursery areas. Six dominant benthic habitats of the Chausey archipelago (Normandy, France) were studied. In each habitat, bivalve recruit assemblages were described at the end of two reproductive seasons. Furthermore, Ostrea edulis juveniles were immerged on each habitat during two months to compare growth performances and feeding status, estimated by fatty acid composition. Recruit assemblages differ from each habitat according to sediment grain-size composition and bathymetrical levels. Subtidal habitats, and especially Crepidula fornicata banks and Glycymeris glycymeris coarse sands, supported the highest species abundance and richness of recruits. All O. edulis juveniles fed on the same trophic resources but digestive glands of juveniles from C. fornicata banks were more concentrated in total fatty acids than those from subtidal G. glycymeris coarse sands and maerl banks. Our results depict the key role of subtidal and structured habitats, composed of ecosystem engineers, in enhancing bivalve recruitment and extending the bivalve population renewal. This study suggests that the crucial role of these habitats as bivalve nurseries must be integrated in management perspectives.

  2. Improving healthcare recruitment: the jupiter medical center experience.

    Science.gov (United States)

    Uomo, Paul Dell; Schwieters, Jill

    2009-04-01

    Hospitals that want to improve their recruitment efforts should: Make recruitment a priority within the organization. Take steps to reduce high vacancy rates and turnover among first-year employees. Develop a recruitment marketing plan for key positions. Establish human resources metrics to track costs and effectiveness of recruiting efforts. Enhance the recruitment process for hiring managers and job candidates.

  3. Longleaf Pine Survival, Growth, and Recruitment Experiment

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This experiment was to determine mean survivorship, growth rate, and recruitment rate of longleaf pine seedlings planted on different soil types on the refuge. Open...

  4. Land crabs as key drivers in tropical coastal forest recruitment

    Science.gov (United States)

    Lindquist, E.S.; Krauss, K.W.; Green, P.T.; O'Dowd, D. J.; Sherman, P.M.; Smith, T. J.

    2009-01-01

    Plant populations are regulated by a diverse assortment of abiotic and biotic factors that influence seed dispersal and viability, and seedling establishment and growth at the microsite. Rarely does one animal guild exert as significant an influence on different plant assemblages as land crabs. We review three tropical coastal ecosystems-mangroves, island maritime forests, and mainland coastal terrestrial forests-where land crabs directly influence forest composition by limiting tree establishment and recruitment. Land crabs differentially prey on seeds, propagules and seedlings along nutrient, chemical and physical environmental gradients. In all of these ecosystems, but especially mangroves, abiotic gradients are well studied, strong and influence plant species distributions. However, we suggest that crab predation has primacy over many of these environmental factors by acting as the first limiting factor of tropical tree recruitment to drive the potential structural and compositional organisation of coastal forests. We show that the influence of crabs varies relative to tidal gradient, shoreline distance, canopy position, time, season, tree species and fruiting periodicity. Crabs also facilitate forest growth and development through such activities as excavation of burrows, creation of soil mounds, aeration of soils, removal of leaf litter into burrows and creation of carbon-rich soil microhabitats. For all three systems, land crabs influence the distribution, density and size-class structure of tree populations. Indeed, crabs are among the major drivers of tree recruitment in tropical coastal forest ecosystems, and their conservation should be included in management plans of these forests. ?? 2009 Cambridge Philosophical Society.

  5. Ruled by Ubiquitylation: A New Order for Polycomb Recruitment

    Directory of Open Access Journals (Sweden)

    Yuri B. Schwartz

    2014-07-01

    Full Text Available Polycomb complexes are found in most cells, but they must be targeted to specific genes in specific cell types in order to regulate pluripotency and differentiation. The recruitment of Polycomb complexes to specific targets has been widely thought to occur in two steps: first, one complex, PRC2, produces histone H3 lysine 27 (H3K27 trimethylation at a specific gene, and then the PRC1 complex is recruited by its ability to bind to H3K27me3. Now, three new articles turn this model upside-down by showing that binding of a variant PRC1 complex and subsequent H2A ubiquitylation of surrounding chromatin is sufficient to trigger the recruitment of PRC2 and H3K27 trimethylation. These studies also show that ubiquitylated H2A is directly sensed by PRC2 and that ablation of PRC1-mediated H2A ubiquitylation impairs genome-wide PRC2 binding and disrupts mouse development.

  6. Increased inflammatory properties of adipose tissue macrophages recruited during diet-induced obesity.

    Science.gov (United States)

    Lumeng, Carey N; Deyoung, Stephanie M; Bodzin, Jennifer L; Saltiel, Alan R

    2007-01-01

    Although recent studies show that adipose tissue macrophages (ATMs) participate in the inflammatory changes in obesity and contribute to insulin resistance, the properties of these cells are not well understood. We hypothesized that ATMs recruited to adipose tissue during a high-fat diet have unique inflammatory properties compared with resident tissue ATMs. Using a dye (PKH26) to pulse label ATMs in vivo, we purified macrophages recruited to white adipose tissue during a high-fat diet. Comparison of gene expression in recruited and resident ATMs using real-time RT-PCR and cDNA microarrays showed that recruited ATMs overexpress genes important in macrophage migration and phagocytosis, including interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and C-C chemokine receptor 2 (CCR2). Many of these genes were not induced in ATMs from high-fat diet-fed CCR2 knockout mice, supporting the importance of CCR2 in regulating recruitment of inflammatory ATMs during obesity. Additionally, expression of Apoe was decreased, whereas genes important in lipid metabolism, such as Pparg, Adfp, Srepf1, and Apob48r, were increased in the recruited macrophages. In agreement with this, ATMs from obese mice had increased lipid content compared with those from lean mice. These studies demonstrate that recruited ATMs in obese animals represent a subclass of macrophages with unique properties.

  7. Targeting cell cycle regulators in hematologic malignancies

    Directory of Open Access Journals (Sweden)

    Eiman eAleem

    2015-04-01

    Full Text Available Hematologic malignancies represent the fourth most frequently diagnosed cancer in economically developed countries. In hematologic malignancies normal hematopoiesis is interrupted by uncontrolled growth of a genetically altered stem or progenitor cell (HSPC that maintains its ability of self-renewal. Cyclin-dependent kinases (CDKs not only regulate the mammalian cell cycle, but also influence other vital cellular processes, such as stem cell renewal, differentiation, transcription, epigenetic regulation, apoptosis, and DNA repair. Chromosomal translocations, amplification, overexpression and altered CDK activities have been described in different types of human cancer, which have made them attractive targets for pharmacological inhibition. Mouse models deficient for one or more CDKs have significantly contributed to our current understanding of the physiological functions of CDKs, as well as their roles in human cancer. The present review focuses on selected cell cycle kinases with recent emerging key functions in hematopoiesis and in hematopoietic malignancies, such as CDK6 and its role in MLL-rearranged leukemia and acute lymphocytic leukemia, CDK1 and its regulator WEE-1 in acute myeloid leukemia, and cyclin C/CDK8/CDK19 complexes in T-cell acute lymphocytic leukemia. The knowledge gained from gene knockout experiments in mice of these kinases is also summarized. An overview of compounds targeting these kinases, which are currently in clinical development in various solid tumors and hematopoietic malignances, is presented. These include the CDK4/CDK6 inhibitors (palbociclib, LEE011, LY2835219, pan-CDK inhibitors that target CDK1 (dinaciclib, flavopiridol, AT7519, TG02, P276-00, terampeprocol and RGB 286638 as well as the WEE-1 kinase inhibitor, MK-1775. The advantage of combination therapy of cell cycle inhibitors with conventional chemotherapeutic agents used in the treatment of AML, such as cytarabine, is discussed.

  8. Structural Basis of CDK4 Inhibition by p18INK4

    Science.gov (United States)

    2000-05-01

    marmor @wistar.upenn.edu 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSORING / MONITORING AGENCY REPORT NUMBER U.S. Army Medical...protein complexes in bacteria. There are sev- PA 19104. Fax: (215) 898-0381. E-mail: marmor @wistar.upenn.edu. eral factors that make the pRM1/pET

  9. Transcriptional Regulation of the p16 Tumor Suppressor Gene.

    Science.gov (United States)

    Kotake, Yojiro; Naemura, Madoka; Murasaki, Chihiro; Inoue, Yasutoshi; Okamoto, Haruna

    2015-08-01

    The p16 tumor suppressor gene encodes a specific inhibitor of cyclin-dependent kinase (CDK) 4 and 6 and is found altered in a wide range of human cancers. p16 plays a pivotal role in tumor suppressor networks through inducing cellular senescence that acts as a barrier to cellular transformation by oncogenic signals. p16 protein is relatively stable and its expression is primary regulated by transcriptional control. Polycomb group (PcG) proteins associate with the p16 locus in a long non-coding RNA, ANRIL-dependent manner, leading to repression of p16 transcription. YB1, a transcription factor, also represses the p16 transcription through direct association with its promoter region. Conversely, the transcription factors Ets1/2 and histone H3K4 methyltransferase MLL1 directly bind to the p16 locus and mediate p16 induction during replicative and premature senescence. In the present review, we discuss the molecular mechanisms by which these factors regulate p16 transcription.

  10. Hfe deficiency impairs pulmonary neutrophil recruitment in response to inflammation.

    Directory of Open Access Journals (Sweden)

    Karolina Benesova

    Full Text Available Regulation of iron homeostasis and the inflammatory response are tightly linked to protect the host from infection. Here we investigate how imbalanced systemic iron homeostasis in a murine disease model of hereditary hemochromatosis (Hfe(-/- mice affects the inflammatory responses of the lung. We induced acute pulmonary inflammation in Hfe(-/- and wild-type mice by intratracheal instillation of 20 µg of lipopolysaccharide (LPS and analyzed local and systemic inflammatory responses and iron-related parameters. We show that in Hfe(-/- mice neutrophil recruitment to the bronchoalveolar space is attenuated compared to wild-type mice although circulating neutrophil numbers in the bloodstream were elevated to similar levels in Hfe(-/- and wild-type mice. The underlying molecular mechanisms are likely multifactorial and include elevated systemic iron levels, alveolar macrophage iron deficiency and/or hitherto unexplored functions of Hfe in resident pulmonary cell types. As a consequence, pulmonary cytokine expression is out of balance and neutrophils fail to be recruited efficiently to the bronchoalveolar compartment, a process required to protect the host from infections. In conclusion, our findings suggest a novel role for Hfe and/or imbalanced iron homeostasis in the regulation of the inflammatory response in the lung and hereditary hemochromatosis.

  11. Comparison of the recruitment process when appointing officials in Iceland before and after the economic collapse

    Directory of Open Access Journals (Sweden)

    Gylfi Dalmann Aðalsteinsson

    2014-12-01

    Full Text Available This research examines the recruitment process prior to appointment of officials during the period of 2004 to 2012. This research investigates wheather a change has occurred in the recruiting process following the economic collapse in the fall of 2008. It is intended to provide insight into the official recruiting process. In all there were 68 appointments during the research period, 40 before the economic collapse and 28 after the collapse, which met the criteria of 13th paragraph in 22nd article of employment laws, no. 70/1996. Content analysis, which is a combination of qualitative and quantitative research methods, was used for processing and analyzing the data. The study investigates whether the job advertisements fulfill the criteria about job advertisments like they appear in regulations no. 464/1996 about job advertisements. Whether job advertisements for vacant jobs were published in Lögbirtingablaðið (Iceland’s Legal Publication Journal, whether the application deadline were according to 7th article og the employment laws, whether special recruiting committees were used for professional support and finally the length of the recruitment process. The main results of this research indicate that there has been improvement in the recruiting process during the chosen research period. Following the economic collapse the execution of job advertisements have improved as the publication of job advertisements in Lögbirtingablaðið was in most cases complied with laws and regulations. The application deadline was more often correctly indicated after the collapse, and special recruiting committees were more often used than the law stipulated. The recruitment process has however become longer after the economic collapse.

  12. Does habitat complexity influence fish recruitment?

    Directory of Open Access Journals (Sweden)

    A. CHEMINÉE

    2014-06-01

    Full Text Available Human activities facilitate coastal habitat transformation and homogenization. The spread of marine invasive species is one example. This in turn may influence fish recruitment and the subsequent replenishment of adult assemblages. We tested habitat complexity effect on fish (Teleostei recruitment by experimentally manipulating meadows of the habitat-forming invasive macroalga Caulerpa taxifolia (Chlorophyta. Among the fourteen fish species recorded during the experiment, only two labrids (Coris julis and Symphodus ocellatus settled in abundance among these meadows. Patterns in the abundance of these juveniles suggested that reduced tri-dimensional meadow complexity may reduce habitat quality and result in altered habitat choices and / or differential mortality of juveniles, therefore reducing fish recruitment and likely the abundance of adults.

  13. Sales Training for Army Recruiter Success: Modeling the Sales Strategies and Skills of Excellent Recruiters

    Science.gov (United States)

    1987-11-01

    strategies used by excellent Army recruiters. Neurolinguistic programming (NLP) was used as the protocol for modeling performance and acquiring...Behavioral and Social Sciences 3001 Eisenhower Avenue, Alexandria, VA 22333-5600 10. PROGRAM ELEMENT. PROJECT. TASK ARE* 4 WORK UNIT...Modeling ’Expert knowledge,, Neurolinguistics Knowledge engineering; Recruiting Sales, &’ Sales cycle Sales skills Sales strategies 20

  14. Ecological factors affecting Rainbow Smelt recruitment in the main basin of Lake Huron, 1976-2010

    Science.gov (United States)

    O'Brien, Timothy P.; Taylor, William W.; Roseman, Edward F.; Madenjian, Charles P.; Riley, Stephen C.

    2014-01-01

    Rainbow Smelt Osmerus mordax are native to northeastern Atlantic and Pacific–Arctic drainages and have been widely introduced throughout North America. In the Great Lakes region, Rainbow Smelt are known predators and competitors of native fish and a primary prey species in pelagic food webs. Despite their widespread distribution, importance as a prey species, and potential to negatively interact with native fish species, there is limited information concerning stock–recruitment relationships for Rainbow Smelt. To better understand recruitment mechanisms, we evaluated potential ecological factors determining recruitment dynamics for Rainbow Smelt in Lake Huron using data from bottom trawl catches. We specifically evaluated influence of stock size, environmental factors (water temperature, lake levels, and precipitation), and salmonine predation on the production of age-0 recruits from 1976 to 2010. Rainbow Smelt recruitment was negatively related to stock size exceeding 10 kg/ha, indicating that compensatory, density-dependent mortality from cannibalism or intraspecific competition was an important factor related to the production of age-0 recruits. Recruitment was positively related to spring precipitation suggesting that the amount of stream-spawning habitat as determined by precipitation was important for the production of strong Rainbow Smelt recruitment. Additionally, density of age-0 Rainbow Smelt was positively related to Lake Trout Salvelinus namaycush abundance. However, spawning stock biomass of Rainbow Smelt, which declined substantially from 1989 to 2010, was negatively associated with Lake Trout catch per effort suggesting predation was an important factor related to the decline of age-2 and older Rainbow Smelt in Lake Huron. As such, we found that recruitment of Rainbow Smelt in Lake Huron was regulated by competition with or cannibalism by older conspecifics, spring precipitation influencing stream spawning habitats, and predation by Lake Trout on

  15. REST-mediated recruitment of polycomb repressor complexes in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Nikolaj Dietrich

    Full Text Available Polycomb Repressive Complex (PRC 1 and PRC2 regulate genes involved in differentiation and development. However, the mechanism for how PRC1 and PRC2 are recruited to genes in mammalian cells is unclear. Here we present evidence for an interaction between the transcription factor REST, PRC1, and PRC2 and show that RNF2 and REST co-regulate a number of neuronal genes in human teratocarcinoma cells (NT2-D1. Using NT2-D1 cells as a model of neuronal differentiation, we furthermore showed that retinoic-acid stimulation led to displacement of PRC1 at REST binding sites, reduced H3K27Me3, and increased gene expression. Genome-wide analysis of Polycomb binding in Rest⁻/⁻ and Eed⁻/⁻ mouse embryonic stem (mES cells showed that Rest was required for PRC1 recruitment to a subset of Polycomb regulated neuronal genes. Furthermore, we found that PRC1 can be recruited to Rest binding sites independently of CpG islands and the H3K27Me3 mark. Surprisingly, PRC2 was frequently increased around Rest binding sites located in CpG-rich regions in the Rest⁻/⁻ mES cells, indicating a more complex interplay where Rest also can limit PRC2 recruitment. Therefore, we propose that Rest has context-dependent functions for PRC1- and PRC2- recruitment, which allows this transcription factor to act both as a recruiter of Polycomb as well as a limiting factor for PRC2 recruitment at CpG islands.

  16. Computational social network modeling of terrorist recruitment.

    Energy Technology Data Exchange (ETDEWEB)

    Berry, Nina M.; Turnley, Jessica Glicken (Sandia National Laboratories, Albuquerque, NM); Smrcka, Julianne D. (Sandia National Laboratories, Albuquerque, NM); Ko, Teresa H.; Moy, Timothy David (Sandia National Laboratories, Albuquerque, NM); Wu, Benjamin C.

    2004-10-01

    The Seldon terrorist model represents a multi-disciplinary approach to developing organization software for the study of terrorist recruitment and group formation. The need to incorporate aspects of social science added a significant contribution to the vision of the resulting Seldon toolkit. The unique addition of and abstract agent category provided a means for capturing social concepts like cliques, mosque, etc. in a manner that represents their social conceptualization and not simply as a physical or economical institution. This paper provides an overview of the Seldon terrorist model developed to study the formation of cliques, which are used as the major recruitment entity for terrorist organizations.

  17. Human telomerase: biogenesis, trafficking, recruitment, and activation.

    Science.gov (United States)

    Schmidt, Jens C; Cech, Thomas R

    2015-06-01

    Telomerase is the ribonucleoprotein enzyme that catalyzes the extension of telomeric DNA in eukaryotes. Recent work has begun to reveal key aspects of the assembly of the human telomerase complex, its intracellular trafficking involving Cajal bodies, and its recruitment to telomeres. Once telomerase has been recruited to the telomere, it appears to undergo a separate activation step, which may include an increase in its repeat addition processivity. This review covers human telomerase biogenesis, trafficking, and activation, comparing key aspects with the analogous events in other species.

  18. D-type Cyclins are important downstream effectors of cytokine signaling that regulate the proliferation of normal and neoplastic mammary epithelial cells.

    Science.gov (United States)

    Zhang, Qian; Sakamoto, Kazuhito; Wagner, Kay-Uwe

    2014-01-25

    In response to the ligand-mediated activation of cytokine receptors, cells decide whether to proliferate or to undergo differentiation. D-type Cyclins (Cyclin D1, D2, or D3) and their associated Cyclin-dependent kinases (CDK4, CDK6) connect signals from cytokines to the cell cycle machinery, and they propel cells through the G1 restriction point and into the S phase, after which growth factor stimulation is no longer essential to complete cell division. D-type Cyclins are upregulated in many human malignancies including breast cancer to promote an uncontrolled proliferation of cancer cells. After summarizing important aspects of the cytokine-mediated transcriptional regulation and the posttranslational modification of D-type Cyclins, this review will highlight the physiological significance of these cell cycle regulators during normal mammary gland development as well as the initiation and promotion of breast cancer. Although the vast majority of published reports focus almost exclusively on the role of Cyclin D1 in breast cancer, we summarize here previous and recent findings that demonstrate an important contribution of the remaining two members of this Cyclin family, in particular Cyclin D3, for the growth of ErbB2-associated breast cancer cells in humans and in mouse models. New data from genetically engineered models as well as the pharmacological inhibition of CDK4/6 suggest that targeting the combined functions of D-type Cyclins could be a suitable strategy for the treatment of ErbB2-positive and potentially other types of breast cancer.

  19. Using PR Tools to Boost Recruitment.

    Science.gov (United States)

    Rabbino, Irma L.

    1979-01-01

    Public relations and admissions are shown to be related. It is not necessary to use exotic PR tools to recruit students. Some suggestions include: the magic of marketing; national, local and hometown media; publications; filmstrips or cassettes; fairs and festivals; public service; and logo buttons, decals, etc. (MLW)

  20. Discrimination in Recruitment: An Empirical Analysis.

    Science.gov (United States)

    Newman, Jerry M.

    1978-01-01

    To investigate whether recruitment practices of companies with affirmative action programs discriminated against Blacks or resulted in reverse discrimination, qualifications and race of fictitious job applicants were manipulated on resumes sent to a sample of employers. Responses strongly indicate discrimination, with Black applicants favored…

  1. 34 CFR 106.23 - Recruitment.

    Science.gov (United States)

    2010-07-01

    ... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE..., schools or entities which admit as students only or predominantly members of one sex, if such actions have... 34 Education 1 2010-07-01 2010-07-01 false Recruitment. 106.23 Section 106.23...

  2. 20 CFR 656.21 - Supervised recruitment.

    Science.gov (United States)

    2010-04-01

    ... advertising for the job opportunity by placing an advertisement in a newspaper of general circulation or in a... workers from which the employer must recruit for U.S. workers in addition to the advertising described in...-related reason for rejecting the U.S. workers. For the purpose of this paragraph (e)(4), a U.S. worker...

  3. Recruiting Middle School Students into Nursing

    Science.gov (United States)

    Matutina, Robin E.

    2008-01-01

    The purpose of this literature review is to illustrate the importance of initiating nursing recruitment during the middle school years. Data sources included citations from the years 1989 to 2006. The study focused on middle school students 9 to 13 years of age in Grades 6 to 8. One survey compared middle school students' perceptions of an ideal…

  4. Recruiting and Retention, A Force Planning Dilemma

    Science.gov (United States)

    2007-11-02

    military relations, military history, and military sociology must be incorporated in the curriculum. JROTC comprises a critical element of the marketing mix for...factored into the marketing mix . Using commercial telemarketing practices to generate leads from centrally produced lists of potential recruits, and

  5. Violent Video Games Recruit American Youth

    Science.gov (United States)

    Lugo, William

    2006-01-01

    An expert on the sociology of video games highlights the power of this medium to popularize violence among children. But few are aware that some of the most technologically potent products are violent war games now being produced at taxpayer expense. These are provided free as a recruiting tool by the United States military. The author contends…

  6. Recruiting and Advising Challenges in Actuarial Science

    Science.gov (United States)

    Case, Bettye Anne; Guan, Yuanying Michelle; Paris, Stephen

    2014-01-01

    Some challenges to increasing actuarial science program size through recruiting broadly among potential students are identified. Possible solutions depend on the structures and culture of the school. Up to three student cohorts may result from partition of potential students by the levels of academic progress before program entry: students…

  7. Recruiting New Populations to the Library Profession.

    Science.gov (United States)

    Jennings, Kriza A.

    1993-01-01

    Discussion of the effects of cultural diversity on academic libraries and library and information science education examines the impact of demographics on affirmative action recruitment in business and higher education; effects of demographic trends on library and information science professions; faculty attitudes; and library and information…

  8. Recruitment and Retention with a Spin

    Science.gov (United States)

    Lindgren, Rita; Hixson, Carla Braun

    2010-01-01

    Strategic planning and innovation at Bismarck State College (BSC) found common ground in the college's goal to recruit and retain employees in an environment of low unemployment and strong competition for skilled employees. BSC's strategic plan for 2007-09 included the objective "to increase retention of employees." One of the strategies…

  9. CERN is still recruiting - Pass it on!

    CERN Multimedia

    2001-01-01

    This year there are still 70 limited duration staff vacancies to fill. Although the Web is proving a very effective way of attracting candidates, CERN people can play their part in the recruitment drive. To find out how you can help, read on. Despite the electronic era, word-of-mouth communication is still doing a good job! Over the last year about 23% of staff applicants found out about our vacancies through personal contacts. The article published last year in the Bulletin (10.4.and 24.4.2000) about recruitment at CERN had a very good initial response from people ready to spread the word about recruitment programmes in schools, universities and at conferences. As the article pointed out, it is still really important for CERN personnel to feel involved in this process. EST Division is now preparing its own initiative to send their engineers and technicians back to their schools in different Member States to attract candidates. We invite you once again to join in with this effort. The recruitment office is re...

  10. Computational social dynamic modeling of group recruitment.

    Energy Technology Data Exchange (ETDEWEB)

    Berry, Nina M.; Lee, Marinna; Pickett, Marc; Turnley, Jessica Glicken (Sandia National Laboratories, Albuquerque, NM); Smrcka, Julianne D. (Sandia National Laboratories, Albuquerque, NM); Ko, Teresa H.; Moy, Timothy David (Sandia National Laboratories, Albuquerque, NM); Wu, Benjamin C.

    2004-01-01

    The Seldon software toolkit combines concepts from agent-based modeling and social science to create a computationally social dynamic model for group recruitment. The underlying recruitment model is based on a unique three-level hybrid agent-based architecture that contains simple agents (level one), abstract agents (level two), and cognitive agents (level three). This uniqueness of this architecture begins with abstract agents that permit the model to include social concepts (gang) or institutional concepts (school) into a typical software simulation environment. The future addition of cognitive agents to the recruitment model will provide a unique entity that does not exist in any agent-based modeling toolkits to date. We use social networks to provide an integrated mesh within and between the different levels. This Java based toolkit is used to analyze different social concepts based on initialization input from the user. The input alters a set of parameters used to influence the values associated with the simple agents, abstract agents, and the interactions (simple agent-simple agent or simple agent-abstract agent) between these entities. The results of phase-1 Seldon toolkit provide insight into how certain social concepts apply to different scenario development for inner city gang recruitment.

  11. Evaluation of Smoking Interventions in Recruit Training

    Science.gov (United States)

    1987-12-23

    These measures vere administered during the first week of training. Smokin Histo Questionnaire. The smoking history questionnaire was administered at...encourages) how the Navy, company comsanders, and other recruits felt about the use of tobacco products. Veekly Assessments of Smokin Behavior. This short

  12. Does Education Reform Make Recruiting More Difficult?

    Science.gov (United States)

    2005-10-01

    Virginia 1986ac Idaho 2006c New Mexico 1990c Washington 2007c Indiana 2000c New York 1985ac 67 Appendix A Other (state-level) data and sources We...Analysis of Eval- uation of Homeschool and ChalleNGe Program Recruits, Jan 2004 (CNA Research Memorandum D0009351.A2) [36] Janice H. Laurence. Education

  13. Implicit Assumptions in High Potentials Recruitment

    Science.gov (United States)

    Posthumus, Jan; Bozer, Gil; Santora, Joseph C.

    2016-01-01

    Purpose: Professionals of human resources (HR) use different criteria in practice than they verbalize. Thus, the aim of this research was to identify the implicit criteria used for the selection of high-potential employees in recruitment and development settings in the pharmaceutical industry. Design/methodology/approach: A semi-structured…

  14. 48 CFR 3052.209-71 - Reserve Officer Training Corps and military recruiting on campus.

    Science.gov (United States)

    2010-10-01

    ... following clause: Reserve Officer Training Corps and Military Recruiting on Campus (DEC 2003) (a... military department from maintaining, establishing, or operating a unit of the Senior Reserve Officer... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Reserve Officer...

  15. Social networks and regional recruitment of foreign labour: Firm recruitment methods and spatial sorting in Denmark

    DEFF Research Database (Denmark)

    Schmidt, Torben Dall; Jensen, Peter Sandholt

    2012-01-01

    This paper tests the hypothesis that social networks are crucial for regional recruitment and inflows of foreign labour. New survey data on 971 firms located in Region Southern Denmark show that the predominant recruitment method of foreign labour was through networks. Danish municipal data from...... 1997–2006 furthermore reveal spatial sorting since initial shares of employees with a foreign background out of total regional employment predict foreign labour inflow rates to regional employment. Thus, social networks appear crucial for the recruitment and inflows of foreign labour, suggesting...

  16. Compensatory effects of recruitment and survival when amphibian populations are perturbed by disease

    Science.gov (United States)

    Muths, E.; Scherer, R. D.; Pilliod, D.S.

    2011-01-01

    The need to increase our understanding of factors that regulate animal population dynamics has been catalysed by recent, observed declines in wildlife populations worldwide. Reliable estimates of demographic parameters are critical for addressing basic and applied ecological questions and understanding the response of parameters to perturbations (e.g. disease, habitat loss, climate change). However, to fully assess the impact of perturbation on population dynamics, all parameters contributing to the response of the target population must be estimated. We applied the reverse-time model of Pradel in Program mark to 6years of capture-recapture data from two populations of Anaxyrus boreas (boreal toad) populations, one with disease and one without. We then assessed a priori hypotheses about differences in survival and recruitment relative to local environmental conditions and the presence of disease. We further explored the relative contribution of survival probability and recruitment rate to population growth and investigated how shifts in these parameters can alter population dynamics when a population is perturbed. High recruitment rates (0??41) are probably compensating for low survival probability (range 0??51-0??54) in the population challenged by an emerging pathogen, resulting in a relatively slow rate of decline. In contrast, the population with no evidence of disease had high survival probability (range 0??75-0??78) but lower recruitment rates (0??25). Synthesis and applications.We suggest that the relationship between survival and recruitment may be compensatory, providing evidence that populations challenged with disease are not necessarily doomed to extinction. A better understanding of these interactions may help to explain, and be used to predict, population regulation and persistence for wildlife threatened with disease. Further, reliable estimates of population parameters such as recruitment and survival can guide the formulation and implementation of

  17. Fragile x mental retardation protein regulates proliferation and differentiation of adult neural stem/progenitor cells.

    Directory of Open Access Journals (Sweden)

    Yuping Luo

    2010-04-01

    Full Text Available Fragile X syndrome (FXS, the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP. FMRP is an RNA-binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs. We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3beta. Dysregulation of GSK3beta led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis.

  18. Recruitment in a changing environment: the 2000s North Sea herring recruitment failure

    DEFF Research Database (Denmark)

    Payne, Mark; Hatfield, E.M.C.; Dickey-Collas, M.;

    2009-01-01

    Environmentally induced change appears to be impacting the recruitment of North Sea herring (Clupea harengus). Despite simultaneously having a large adult population, historically low exploitation, and Marine Stewardship Council accreditation (implying sustainability), there have been an unpreced...

  19. Branchial Cilia and Sperm Flagella Recruit Distinct Axonemal Components

    Science.gov (United States)

    Konno, Alu; Shiba, Kogiku; Cai, Chunhua; Inaba, Kazuo

    2015-01-01

    Eukaryotic cilia and flagella have highly conserved 9 + 2 structures. They are functionally diverged to play cell-type-specific roles even in a multicellular organism. Although their structural components are therefore believed to be common, few studies have investigated the molecular diversity of the protein components of the cilia and flagella in a single organism. Here we carried out a proteomic analysis and compared protein components between branchial cilia and sperm flagella in a marine invertebrate chordate, Ciona intestinalis. Distinct feature of protein recruitment in branchial cilia and sperm flagella has been clarified; (1) Isoforms of α- and β-tubulins as well as those of actins are distinctly used in branchial cilia or sperm flagella. (2) Structural components, such as dynein docking complex, tektins and an outer dense fiber protein, are used differently by the cilia and flagella. (3) Sperm flagella are specialized for the cAMP- and Ca2+-dependent regulation of outer arm dynein and for energy metabolism by glycolytic enzymes. Our present study clearly demonstrates that flagellar or ciliary proteins are properly recruited according to their function and stability, despite their apparent structural resemblance and conservation. PMID:25962172

  20. Branchial cilia and sperm flagella recruit distinct axonemal components.

    Directory of Open Access Journals (Sweden)

    Alu Konno

    Full Text Available Eukaryotic cilia and flagella have highly conserved 9 + 2 structures. They are functionally diverged to play cell-type-specific roles even in a multicellular organism. Although their structural components are therefore believed to be common, few studies have investigated the molecular diversity of the protein components of the cilia and flagella in a single organism. Here we carried out a proteomic analysis and compared protein components between branchial cilia and sperm flagella in a marine invertebrate chordate, Ciona intestinalis. Distinct feature of protein recruitment in branchial cilia and sperm flagella has been clarified; (1 Isoforms of α- and β-tubulins as well as those of actins are distinctly used in branchial cilia or sperm flagella. (2 Structural components, such as dynein docking complex, tektins and an outer dense fiber protein, are used differently by the cilia and flagella. (3 Sperm flagella are specialized for the cAMP- and Ca2+-dependent regulation of outer arm dynein and for energy metabolism by glycolytic enzymes. Our present study clearly demonstrates that flagellar or ciliary proteins are properly recruited according to their function and stability, despite their apparent structural resemblance and conservation.

  1. Generational Theory: Implications for Recruiting the Millennials

    Science.gov (United States)

    2006-03-10

    their existing attitudes about serving in the military. The following sections will discuss these topics. The Influences . Andrew Wilcox, in completing...and Boomers in the Officer Corps, Monograph (Carlisle Barracks: U.S. Army War College, October 2000), 6. 38 Ibid. 39 Andrew G. Wilcox, Recruiting the...51 Jay A. Conger , Winning ‘Em Over: A New Model for Managing in the Age of Persuasion (New York: Simon & Schuster, 1998), 27. 52 Zemke, Raines

  2. Assessing a Science Graduate School Recruitment Symposium

    Science.gov (United States)

    González-Espada, Wilson; Díaz-Muñoz, Greetchen; Feliú-Mójer, Mónica; Flores-Otero, Jacqueline; Fortis-Santiago, Yaihara; Guerrero-Medina, Giovanna; López-Casillas, Marcos; Colón-Ramos, Daniel A.; Fernández-Repollet, Emma

    2015-01-01

    Ciencia Puerto Rico, a non-profit organization dedicated to promoting science, research and scientific education among Latinos, organized an educational symposium to provide college science majors the tools, opportunities and advice to pursue graduate degrees and succeed in the STEM disciplines. In this article we share our experiences and lessons learned, for others interested in developing large-scale events to recruit underrepresented minorities to STEM and in evaluating the effectiveness of these efforts. PMID:26770074

  3. Finding Lawrence recruiting talent for unconventional warfare

    OpenAIRE

    Mourouzis, Michael G.

    2011-01-01

    Approved for public release; distribution is unlimited. From Francis Marion's guerrilla war against the British to advising the resistance against the Nazis and Japanese, the United States has depended on unconventional warfare (UW) as a component of national defense. Today, the U.S. Army Special Forces (SF) is the premiere unconventional warfare unit in the U.S. military. With a smaller Army and increasing missions, SF must expand its recruiting efforts. This thesis analyzes the recruitme...

  4. Occupational Medicine Model and Asthma Military Recruitment.

    Science.gov (United States)

    Brooks, Stuart M

    2015-11-01

    Medical evidence hints that asymptomatic recruits with a history of childhood asthma, quiescent since their 13th birthday, are still at risk for adverse changes in their clinical status following unfavorable environmental exposures during military deployment or combat. Asthmatic persons, claiming none or few symptoms, may still manifest airflow obstruction and display biomarkers of airway inflammation even when they are relatively asymptomatic and experience few if any respiratory complaints. The occupational medicine model offers a credible foundation for acknowledging the importance of personal susceptibility in the pathogenesis of military-associated asthma. It is appropriate to re-explore the current military standard for recruits with asymptomatic childhood asthma (≥12 months) not prescribed antiasthma medications. Raising the acceptance age for these recruits may be a consideration. Unfortunately, there is no effectual screening test that recognizes such susceptible soldiers at risk for future asthma attacks. Nevertheless, there is general support for evidence-based, scientifically valid medical screening that judges fitness for military service. Screening tests comprising asthma biomarkers and genetic indices may better verify vulnerable soldiers destined to suffer future asthma reactivation.

  5. 78 FR 1256 - Guam Military Base Realignment Contractor Recruitment Standards

    Science.gov (United States)

    2013-01-08

    ... (Department) Employment and Training Administration (ETA) is issuing this notice to announce recruitment... Recruitment Support Activities Separate from the Contractor Recruitment Standards, ETA will facilitate a... outreach to its workforce investment system. ETA will do the following: Develop and issue a Training...

  6. Recruiter-Applicant Differences in Perceptions of Extrinsic Rewards.

    Science.gov (United States)

    David, Kermit R., Jr.; And Others

    1991-01-01

    Examined how accurate recruiters would be in estimating relative preferences of college seniors for important category of extrinsic rewards. Compared preferences of 602 graduating college seniors for 11 extrinsic rewards with preference estimates of 486 recruiters. Recruiters underestimated importance of medical and life insurance, pension plans,…

  7. E-recruiting Platforms: Features that Influence the Efficiency of Online Recruitment Systems

    Directory of Open Access Journals (Sweden)

    Ondina ROSOIU

    2016-01-01

    Full Text Available Twenty active e-recruitment platform users took part in this study for discovering the most asked for features in a web based hiring process. The respondents were chosen based on their history on such recruitment platforms. With the help of our Internet users we narrowed down the number of platforms, to research for outstanding features and tool efficiency, to five most impressive ones (e-jobs, hipo, bestjobs, LinkedIn, Freelancer. The results were as useful as we expected when we proposed an investigation related to the future of web recruiting platforms. They underlined in a specific manner that most of such web platform users need to have a professional and fully functional environment where they can list their accomplishments and experience and receive direct feedback from employers or employees. The study also shows in detail how much and why do users like to have certain functionalities when they are searching for a new job.

  8. Recruitment strategies should not be randomly selected: empirically improving recruitment success and diversity in developmental psychology research.

    Science.gov (United States)

    Sugden, Nicole A; Moulson, Margaret C

    2015-01-01

    Psychological and developmental research have been critiqued for the lack of diversity of research samples. Because differences in culture, race, and ethnicity can influence participant behavior, limited diversity limits the generalizability of the findings. These differences may also impact how participants behave in response to recruitment attempts, which suggests that recruitment itself may be leveraged to increase sample diversity. The goal of the current study was to determine what factors, within a recruitment interaction, could be leveraged to increase success and diversity when recruiting families with children for developmental research. Study 1 found three factors influenced success: (1) recruitment was more successful when other potential participants were also interested (i.e., recruiters were busy), (2) recruiters of particular races were more successful than recruiters of other races, and (3) differences in success were related to what the recruiter said to engage the potential participant (i.e., the script). The latter two factors interacted, suggesting some recruiters were using less optimal scripts. To improve success rates, study 2 randomly assigned scripts to recruiters and encouraged them to recruit more vigorously during busy periods. Study 2 found that two factors influenced success: (1) some scripts were more successful than others and (2) we were more successful at recruiting non-White potential participants than White participants. These two interacted, with some scripts being more successful with White and other scripts being more successful with non-White families. This intervention significantly increased recruitment success rate by 8.1% and the overall number of families recruited by 15.3%. These findings reveal that empirically evaluating and tailoring recruitment efforts based on the most successful strategies is effective in boosting diversity through increased participation of children from non-White families.

  9. Pin1 promotes GR transactivation by enhancing recruitment to target genes.

    Science.gov (United States)

    Poolman, Toryn M; Farrow, Stuart N; Matthews, Laura; Loudon, Andrew S; Ray, David W

    2013-10-01

    The glucocorticoid receptor (GR) is a ligand activated transcription factor, serving to regulate both energy metabolism and immune functions. Factors that influence cellular sensitivity to glucocorticoids (GC) are therefore of great interest. The N-terminal of the GR contains numerous potential proline-directed phosphorylation sites, some of which can regulate GR transactivation. Unrestricted proline isomerisation can be inhibited by adjacent serine phosphorylation and requires a prolyl isomerise, Pin1. Pin1 therefore determines the functional outcome of proline-directed kinases acting on the GR, as cis/trans isomers are distinct pools with different interacting proteins. We show that Pin1 mediates GR transactivation, but not GR trans-repression. Two N-terminal GR serines, S203 and S211, are targets for Pin1 potentiation of GR transactivation, establishing a direct link between Pin1 and the GR. We also demonstrate GC-activated co-recruitment of GR and Pin1 to the GILZ gene promoter. The Pin1 effect required both its WW and catalytic domains, and GR recruitment to its GRE was Pin1-dependent. Therefore, Pin1 is a selective regulator of GR transactivation, acting through N-terminal phospho-serine residues to regulate GR recruitment to its target sites in the genome. As Pin1 is dysregulated in disease states, this interaction may contribute to altered GC action in inflammatory conditions.

  10. RECRUITMENT AND PROFESSIONAL TRAINING OF CIVIL SERVANTS

    Directory of Open Access Journals (Sweden)

    Roxana Cristina RADU

    2014-06-01

    Full Text Available An ever increasing feature of public office is the way in which the recruitment and training of civil servants are controlled by legislation. Civil servants are a basic component of public administration but they are also important for labor law because civil service relations have the characteristics of an employment relationship and also specific features resulting from the rules of public law. The relevant expression of the interferences between public and private law for civil servants is recruitment and training. The originality of this article lies in the multidisciplinary character, combining elements of labor law, administrative law and human resources management, character reflected in the bibliography used. Another merit of this study is that the authors correlated the provisions of various laws: Constitution, Labor Code, Law no. 161/2003 on the transparency in exercising public dignities and public functions, Government Ordinance no. 137/2000 regarding the prevention and sanction of all discrimination forms, Government Ordinance no. 129/2000 concerning adults’ professional training.

  11. Analysis of Recruit Attrition from the Navy’s Delayed Entry Program and Recruit Training Command

    Science.gov (United States)

    2007-12-01

    Matrix is depicted below in Figure 1. 3 Jennie W. Wenger and April K. Hodari, Final Analysis of Evaluation of Homeschool and...J. W. and Hodari, A. K., Final Analysis of Evaluation of Homeschool and ChalleNGe Program Recruits. Alexandria, VA: CNA Corporation, 2004. Wirt, J

  12. Staff retention and recruitment: "one great department".

    Science.gov (United States)

    Casady, Wanda M; Dowd, Terry A

    2002-01-01

    The projected demand for healthcare workers during the next ten years has been the impetus for many organizations to develop more creative strategies to ensure adequate staffing levels in the future. In order to keep pace with service demands, the diagnostic imaging department at Valley Lutheran Medical Center (VLMC) in Mesa, Ariz., has been growing as well. Since November of 1999, the number of core FTEs increased from 54.5 to 96. As a result, efforts to retain the current employees became just as critical as efforts to recruit staff for the new positions that were created to support the expanded services. In February 2001, an AHRA seminar was held in Phoenix, which included a day-long session called "Workforce 2001: Recruitment, Selection, Retention of Quality Employees." The presenter, Clint Maun, C.S.P., emphasized the need to provide "passionate orientation" for new employees, encouraged team-based selection of new employees, and reminded the audience that new employees decide within the first three days whether or not they will stay with an organization, regardless of how long it actually takes to leave. Maun also described to the group a model for creating team effort called "One Great Unit" (OGU), which uses a "12-Week Plan" for engaging staff. For the diagnostic imaging department at VLMC, this concept was remodeled so that, instead of focusing on one modality (unit) in the department, the focus was on the whole department. The first step to creating "One Great Department" was to establish an Oversight Committee that would help define the focus of the 12-Week Teams. Five, front-line employees were recruited who represented a cross-section of the imaging department. To assist in the implementation, the director of learning and innovation at VLMC agreed to facilitate the first two meetings. The first 12-Week Team was called together in May 2001. The operational objective addressed was "improving communication inter- and intra-departmentally." Each member

  13. Wuzhi tablet (Schisandra Sphenanthera extract) protects against acetaminophen-induced hepatotoxicity by inhibition of CYP-mediated bioactivation and regulation of NRF2-ARE and p53/p21 pathways.

    Science.gov (United States)

    Fan, Xiaomei; Jiang, Yiming; Wang, Ying; Tan, Huasen; Zeng, Hang; Wang, Yongtao; Chen, Pan; Qu, Aijuan; Gonzalez, Frank J; Huang, Min; Bi, Huichang

    2014-12-01

    Schisandra sphenanthera is widely used as a tonic and restorative in many countries to enhance the function of liver and other organs. Wuzhi tablet (WZ) is a preparation of an ethanol extract of Schisandra sphenanthera. Our previous study demonstrated that WZ exerted a protective effect toward acetaminophen (APAP)-induced hepatotoxicity. However, the molecular mechanisms of this protection remain unclear. This study aimed to determine what molecular pathways contributed to the hepatoprotective effects of WZ against APAP toxicity. Administration of WZ 3 days before APAP treatment significantly attenuated APAP hepatotoxicity in a dose-dependent manner and reduced APAP-induced JNK activation. Treatment with WZ resulted in potent inhibition of CYP2E1, CYP3A11, and CYP1A2 activities and then caused significant inhibition of the formation of the oxidized APAP metabolite N-acetyl-p-benzoquinone imine-reduced glutathione. The expression of NRF2 was increased after APAP and/or WZ treatment, whereas KEAP1 levels were decreased. The protein expression of NRF2 target genes including Gclc, Gclm, Ho-1, and Nqo1 was significantly increased by WZ treatment. Furthermore, APAP increased the levels of p53 and its downstream gene p21 to trigger cell cycle arrest and apoptosis, whereas WZ pretreatment could inhibit p53/p21 signaling to induce cell proliferation-associated proteins including cyclin D1, CDK4, PCNA, and ALR to promote hepatocyte proliferation. This study demonstrated that WZ prevented APAP-induced liver injury by inhibition of cytochrome P450-mediated APAP bioactivation, activation of the NRF2-antioxidant response element pathway to induce detoxification and antioxidation, and regulation of the p53, p21, cyclin D1, CDK4, PCNA, and ALR to facilitate liver regeneration after APAP-induced liver injury.

  14. Recruitment and Retention of LGBTIQ Astronomers

    Science.gov (United States)

    Dixon, William Van Dyke

    2012-01-01

    While lesbian, gay, bisexual, transgender, intersex, or questioning (LGBTIQ) astronomers face many of the same workplace challenges as women and racial/ethnic minorities, from implicit bias to overt discrimination, other challenges are unique to this group. An obvious example is the absence at many institutions of health insurance and other benefits for the same-sex domestic partners of their employees. More subtle is the psychological toll paid by LGBTIQ astronomers who remain "in the closet," self-censoring every statement about their personal lives. Paradoxically, the culture of the physical sciences, in which sexuality, gender identity, and gender expression are considered irrelevant, can discourage their discussion, further isolating LGBTIQ researchers. Addressing these challenges is not just a matter of fairness; it is an essential tool in the recruitment and retention of the brightest researchers and in assuring their productivity. We will discuss these issues and what individuals and departments can to make their institutions more welcoming to their LGBTIQ colleagues.

  15. Using Distributed Applications in Personal Recruitment Management

    Directory of Open Access Journals (Sweden)

    Marian Pompiliu CRISTESCU

    2012-01-01

    Full Text Available In any company, no matter the dimensions, a very important aspect is the selection of human resources and establishing a constant correspondence between the particularities of the job opened and candidate’s profile. Especially in big companies, engaged in big projects, and which must be performed in a fast rhythm, the recruitment process is in a continuum progress, due to the demand rhythm, the work force mobility and to assuring a diversify knowledge data base. Experience has shown that a selection made in advance in the candidates CV’s who apply for a scientific position, before programming the technical interview with them, is a real time saving for both the employers and the candidates.

  16. Actin and dynamin recruitment and the lack thereof at exo- and endocytotic sites in PC12 cells.

    Science.gov (United States)

    Felmy, Felix

    2009-06-01

    Protein recruitment during endocytosis is well characterized in fibroblasts. Since fibroblasts do not engage in regulated exocytosis, only information about protein recruitment during constitutive endocytosis is provided. Furthermore, the cortical actin of fibroblasts is characterized by stress fibers rather than a thick cortical meshwork. A cell model, which differs in these features, could provide insight into the heterogeneity of protein recruitment to constitutive and exocytosis coupled endocytotic areas. Therefore, this study investigates the sequence of protein recruitment in PC12 cells, a well documented exocytotic cell model with thick actin cortex. Using real time total-internal-reflection fluorescence microscopy it was found that at the plasma membrane steady, but not transient, dynamin-1-EGFP or -mCherry fluorescence spots that rapidly dimmed coincided with markers for constitutive endocytotic such as clathrin-LC-dsRed and transferrin-receptor-pHluorin. Clathrin-LC-dsRed and dynamin-1-EGFP were further used to determine the temporal sequence of protein recruitment to areas of constitutive endocytosis. mCherry- and EGFP-beta-actin, Arp-3-EGFP and EGFP-mAbp1 were slowly recruited before the dynamin-1-mCherry fluorescence dimmed, but their fluorescence peaked after the loss of clathrin-LC-dsRed commenced. Furthermore, mCherry-beta-actin fluorescence increased before exocytosis, indicating redistribution prior to release. Also, no average dynamin-1-mCherry recruitment was observed within 50 s to regions of exocytosis marked by NPY-mGFP. This indicates that the temporal-spatial coupling between regulated exo-and endocytosis is rather limited in PC12 cells. Furthermore, the time course of the protein recruitment to constitutive endocytotic sites might depend on the subcellular morphology such as the size of the actin cortex.

  17. Tir Is Essential for the Recruitment of Tks5 to Enteropathogenic Escherichia coli Pedestals.

    Directory of Open Access Journals (Sweden)

    Helene H Jensen

    Full Text Available Enteropathogenic Escherichia coli (EPEC is a bacterial pathogen that infects the epithelial lining of the small intestine and causes diarrhea. Upon attachment to the intestinal epithelium, EPEC uses a Type III Secretion System to inject its own high affinity receptor Translocated intimin receptor (Tir into the host cell. Tir facilitates tight adhesion and recruitment of actin-regulating proteins leading to formation of an actin pedestal beneath the infecting bacterium. The pedestal has several similarities with podosomes, which are basolateral actin-rich extensions found in some migrating animal cells. Formation of podosomes is dependent upon the early podosome-specific scavenger protein Tks5, which is involved in actin recruitment. Although Tks5 is expressed in epithelial cells, and podosomes and EPEC pedestals share many components in their structure and mechanism of formation, the potential role of Tks5 in EPEC infections has not been studied. The aim of this study was to determine the subcellular localization of Tks5 in epithelial cells and to investigate if Tks5 is recruited to the EPEC pedestal. In an epithelial MDCK cell line stably expressing Tks5-EGFP, Tks5 localized to actin bundles. Upon infection, EPEC recruited Tks5-EGFP. Tir, but not Tir phosphorylation was essential for the recruitment. Time-lapse microscopy revealed that Tks5-EGFP was recruited instantly upon EPEC attachment to host cells, simultaneously with actin and N-WASp. EPEC infection of cells expressing a ΔPX-Tks5 deletion version of Tks5 showed that EPEC was able to both infect and form pedestals when the PX domain was deleted from Tks5. Future investigations will clarify the role of Tks5 in EPEC infection and pedestal formation.

  18. REST-mediated recruitment of polycomb repressor complexes in mammalian cells

    DEFF Research Database (Denmark)

    Dietrich, Nikolaj; Lerdrup, Mads; Landt, Eskild;

    2012-01-01

    , and increased gene expression. Genome-wide analysis of Polycomb binding in Rest¿/¿ and Eed¿/¿ mouse embryonic stem (mES) cells showed that Rest was required for PRC1 recruitment to a subset of Polycomb regulated neuronal genes. Furthermore, we found that PRC1 can be recruited to Rest binding sites independently......, and PRC2 and show that RNF2 and REST co-regulate a number of neuronal genes in human teratocarcinoma cells (NT2-D1). Using NT2-D1 cells as a model of neuronal differentiation, we furthermore showed that retinoic-acid stimulation led to displacement of PRC1 at REST binding sites, reduced H3K27Me3......Polycomb Repressive Complex (PRC) 1 and PRC2 regulate genes involved in differentiation and development. However, the mechanism for how PRC1 and PRC2 are recruited to genes in mammalian cells is unclear. Here we present evidence for an interaction between the transcription factor REST, PRC1...

  19. Compliance with donor age recommendations in oocyte donor recruitment advertisements in the USA.

    Science.gov (United States)

    Alberta, Hillary B; Berry, Roberta M; Levine, Aaron D

    2013-04-01

    IVF using donated oocytes offers benefits to many infertile patients, yet the technique also raises a number of ethical concerns, including worries about potential physical and psychological risks to oocyte donors. In the USA, oversight of oocyte donation consists of a combination of federal and state regulations and self-regulatory guidelines promulgated by the American Society for Reproductive Medicine. This study assesses compliance with one of these self-regulatory guidelines - specifically, ASRM's preferred minimum age for donors of 21. To assess compliance, 539 oocyte donor recruitment advertisements from two recruitment channels (Craigslist and college newspapers) were collected and evaluated. Of these, 61% in the Craigslist dataset and 43% in the college newspaper dataset listed minimum ages between 18 and 20, which is inconsistent with ASRM's preferred minimum age recommendation of 21. Advertisements placed by oocyte donor recruitment agencies were more likely than advertisements placed by clinics to specify minimum ages between 18 and 20. These results indicate that ASRM should evaluate and consider revising its donor age guidelines. IVF using donated human eggs can help many patients who have difficulty having children. However, the technique also raises ethical concerns, including concerns about potential physical and psychological harms to egg donors. In the USA, oversight of egg donation relies on a combination of federal and state regulation and professional self-regulation. Governmental regulations address only limited aspects of egg donation, such as the potential spread of infectious diseases and the reporting of success rates, leaving voluntary guidelines developed by an association of medical professionals to address most issues, including ethical concerns raised by the practice. One of these voluntary guidelines recommends that egg donors should be at least 21 years of age. In this article, we analysed 539 egg donor recruitment advertisements

  20. Using marketing theory to inform strategies for recruitment: a recruitment optimisation model and the txt2stop experience

    Science.gov (United States)

    2014-01-01

    Background Recruitment is a major challenge for many trials; just over half reach their targets and almost a third resort to grant extensions. The economic and societal implications of this shortcoming are significant. Yet, we have a limited understanding of the processes that increase the probability that recruitment targets will be achieved. Accordingly, there is an urgent need to bring analytical rigour to the task of improving recruitment, thereby increasing the likelihood that trials reach their recruitment targets. This paper presents a conceptual framework that can be used to improve recruitment to clinical trials. Methods Using a case-study approach, we reviewed the range of initiatives that had been undertaken to improve recruitment in the txt2stop trial using qualitative (semi-structured interviews with the principal investigator) and quantitative (recruitment) data analysis. Later, the txt2stop recruitment practices were compared to a previous model of marketing a trial and to key constructs in social marketing theory. Results Post hoc, we developed a recruitment optimisation model to serve as a conceptual framework to improve recruitment to clinical trials. A core premise of the model is that improving recruitment needs to be an iterative, learning process. The model describes three essential activities: i) recruitment phase monitoring, ii) marketing research, and iii) the evaluation of current performance. We describe the initiatives undertaken by the txt2stop trial and the results achieved, as an example of the use of the model. Conclusions Further research should explore the impact of adopting the recruitment optimisation model when applied to other trials. PMID:24886627

  1. Recruiting Older Youths: Insights from a New Survey of Army Recruits

    Science.gov (United States)

    2014-01-01

    in col- lege or trade school or working. This older group is the least important for the Marine Corps, since 67 percent of its new recruits seem to...each eligible youth and one of his or her parents received hour-long personal interviews. In addition, during the screen - ing process, an extensive...1 � 0 � 46/ c. Adventure ........................................................................... 1 � 0 � 47/ d. Work

  2. Improving Recruiting of the 6th Recruiting Brigade Through Statistical Analysis and Efficiency Measures

    Science.gov (United States)

    2014-12-01

    commentary/2013/10/16/op-ed-why-ending- volunteer-service-next-fight-military-equalityPost. 11 Ibid. 12 Kathy Roth -Douquet and Frank Schaefer, AWOL...Spreadsheet Modeling & Decision Analysis, 4th ed. ( Mason , OH: Thomson South-Western, 2004), 107. 27 U.S. Army Recruiting Command, G7/9 - Marketing, Education...2009. http://www.defense.gov/news/ newsarticle.aspx?id=53310. Ragsdale, Cliff T. Spreadsheet Modeling & Decision Analysis. 4th ed. Mason , OH

  3. Stress Fracture of the Proximal Fibula in Military Recruits

    OpenAIRE

    Hong, Seoung Hwan; Chu, In Tak

    2009-01-01

    Background We wanted to report on stress fracture of the proximal fibula and to suggest the pathomechanism of this fracture. Methods Between April 2004 through April 2005, the military recruits who complained of leg pain during the 6 weeks basic training in the Republic of Korea Marine Corps education and training group were evaluated according to their clinical manifestations and plain radiographs. Results Twelve recruits of 635 recruits who complained leg pain were diagnosed as having fibul...

  4. Learning communities: the link to recruitment and retention.

    Science.gov (United States)

    Bassi, Sherry; Polifroni, E Carol

    2005-01-01

    The professional learning community is a strategy to help staff development educators address recruitment and retention and organizational culture. The purpose of this article is to analyze the concept of learning communities and discuss their potential to increase the recruitment and retention of new graduate nurses and returning practitioners to the nursing profession. Incorporating learning communities into the healthcare organization will decrease the number of nurses leaving nursing, foster retention, and thus, enhance recruitment.

  5. A Simulation of the Bonus Incentive Recruiter Model (BIRM).

    Science.gov (United States)

    1995-09-01

    of the Bonus Incentive Recruiter Model ( BIRM ) and to provide estimates of the BIRM’s effects on recruiting. Since this incentive structure has not been...field tested, it is critical for USAREC to accurately understand the possible outcomes, advantages, and shortcomings if the BIRM were implemented...effects of the utility, cost and production functions. The simulation found that USAREC should meet the Army’s manpower goals with the BIRM and the cost should be less than hiring additional recruiters.

  6. A simulation of the Bonus Incentive Recruiter Model (BIRM)

    OpenAIRE

    Piper, Samuel T.

    1995-01-01

    The purpose of this thesis is to provide the United States Army Recruiting Command (USAREC) with background material for developing the bonus table of the Bonus Incentive Recruiter Model (BIRM) and to provide estimates of the BIRM's effects on recruiting. Since this incentive structure has not been field tested, it is critical for USAREC to accurately understand the possible outcomes, advantages, and shortcomings if the BIRM were implemented. The first part of this thesis describes a method f...

  7. Recruit--An Ontology Based Information Retrieval System for Clinical Trials Recruitment.

    Science.gov (United States)

    Patrão, Diogo F C; Oleynik, Michel; Massicano, Felipe; Morassi Sasso, Ariane

    2015-01-01

    Clinical trials are studies designed to assess whether a new intervention is better than the current alternatives. However, most of them fail to recruit participants on schedule. It is hard to use Electronic Health Record (EHR) data to find eligible patients, therefore studies rely on manual assessment, which is time consuming, inefficient and requires specialized training. In this work we describe the design and development of an information retrieval system with the objective of finding eligible patients for cancer trials. The Recruit system has been in use at A. C. Camargo Cancer Center since August/2014 and contains data from more than 500,000 patients and 9 databases. It uses ontologies to integrate data from several sources and represent medical knowledge, which helps enhance results. One can search both in structured data and inside free text reports. The preliminary quality assessments shows excellent recall rates. Recruit proved to be an useful tool for researchers and its modular design could be applied to other clinical conditions and hospitals.

  8. Substrate temperature constrains recruitment and trail following behavior in ants.

    Science.gov (United States)

    van Oudenhove, Louise; Boulay, Raphaël; Lenoir, Alain; Bernstein, Carlos; Cerda, Xim

    2012-06-01

    In many ant species, foragers use pheromones to communicate the location of resources to nestmates. Mass-recruiting species deposit long-lasting anonymous chemical trails, while group-recruiting species use temporary chemical trails. We studied how high temperature influenced the foraging behavior of a mass-recruiting species (Tapinoma nigerrimum) and a group-recruiting species (Aphaenogaster senilis) through pheromone decay. First, under controlled laboratory conditions, we examined the effect of temperature on the trail pheromone of both species. A substrate, simulating soil, marked with gaster extract was heated for 10 min. at 25°, 35°, 45°, or 55 °C and offered to workers in a choice test. Heating gaster extract reduced the trail following behavior of the mass-recruiters significantly more than that of the group-recruiters. Second, analyses of the chemicals present on the substrate indicated that most T. nigerrimum gaster secretions vanished at 25 °C, and only iridodials persisted up to 55 °C. By contrast, A. senilis secretions were less volatile and resisted better to elevated temperatures to some extent. However, at 55 °C, the only chemicals that persisted were nonadecene and nonadecane. Overall, our results suggest that the foraging behavior of the group-recruiting species A. senilis is less affected by pheromone evaporation than that of the mass-recruiting species T. nigerrimum. This group-recruiting species might, thus, be particularly adapted to environments with fluctuating temperatures.

  9. Spotlight on CERN : Recruitment and professions at CERN

    CERN Multimedia

    CERN video productions

    2010-01-01

    Spotlight on CERN No. 3 Recruitment and professions at CERN Welcome to the Globe of Science and Innovation for this third edition of "Spotlight on CERN". When one thinks about professions at CERN, what springs to mind? Physicists? Engineers? In fact, the smooth operation of the Organisation relies on a diversity of professions and this in itself, poses a real challenge in terms of recruitment in CERN member states. Today, to tell us more about this challenge and about CERN professions in general, we welcome James Purvis, Head of the HR Recruitment, Programmes and Monitoring group, and Lore Taillieu, leader of the group's Recruitment section.

  10. Do larval supply and recruitment vary among chemosynthetic environments of the deep sea?

    Directory of Open Access Journals (Sweden)

    Anna Metaxas

    Full Text Available BACKGROUND: The biological communities that inhabit chemosynthetic environments exist in an ephemeral and patchily distributed habitat with unique physicochemical properties that lead to high endemicity. Consequently, the maintenance and recovery from perturbation of the populations in these habitats is, arguably, mainly regulated by larval supply and recruitment. METHODOLOGY/PRINCIPAL FINDINGS: WE USE DATA FROM THE PUBLISHED SCIENTIFIC LITERATURE TO: (1 compare the magnitudes of and variability in larval supply and settlement and recruitment at hydrothermal vents, seeps, and whale, wood and kelp falls; (2 explore factors that affect these life history processes, when information is available; and (3 explore taxonomic affinities in the recruit assemblages of the different chemosynthetic habitats, using multivariate statistical techniques. Larval supply at vents can vary across segments by several orders of magnitude for gastropods; for bivalves, supply is similar at vents on different segments, and at cold seeps. The limited information on larval development suggests that dispersal potential may be highest for molluscs from cold seeps, intermediate for siboglinids at vents and lowest for the whale-bone siboglinid Osedax. Settlement is poorly studied and only at vents and seeps, but tends to be highest near an active source of emanating fluid in both habitats. Rate of recruitment at vents is more variable among studies within a segment than among segments. Across different chemosynthetic habitats, recruitment rate of bivalves is much more variable than that of gastropods and polychaetes. Total recruitment rate ranges only between 0.1 and 1 ind dm(-2 d(-1 across all chemosynthetic habitats, falling above rates in the non-reducing deep sea. The recruit assemblages at vents, seeps and kelp falls have lower taxonomic breadth, and include more families and genera that have many species more closely related to each other than those at whale and wood

  11. NK cells promote neutrophil recruitment in the brain during sepsis-induced neuroinflammation

    Science.gov (United States)

    He, Hao; Geng, Tingting; Chen, Piyun; Wang, Meixiang; Hu, Jingxia; Kang, Li; Song, Wengang; Tang, Hua

    2016-01-01

    Sepsis could affect the central nervous system and thus induces neuroinflammation, which subsequently leads to brain damage or dysfunction. However, the mechanisms of generation of neuroinflammation during sepsis remain poorly understood. By administration of lipopolysaccharides (LPS) in mice to mimic sepsis, we found that shortly after opening the blood–brain barrier, conventional CD11b+CD27+ NK subset migrated into the brain followed by subsequent neutrophil infiltration. Interestingly, depletion of NK cells prior to LPS treatment severely impaired neutrophil recruitment in the inflamed brain. By in vivo recruitment assay, we found that brain-infiltrated NK cells displayed chemotactic activity to neutrophils, which depended on the higher expression of chemokines such as CXCL2. Moreover, microglia were also responsible for neutrophil recruitment, and their chemotactic activity was significantly impaired by ablation of NK cells. Furthermore, depletion of NK cells could significantly ameliorate depression-like behavior in LPS-treated mice. These data indicated a NK cell-regulated neutrophil recruitment in the blamed brain, which also could be seen on another sepsis model, cecal ligation and puncture. So, our findings revealed an important scenario in the generation of sepsis-induced neuroinflammation. PMID:27270556

  12. SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.

    Science.gov (United States)

    Toiber, Debra; Erdel, Fabian; Bouazoune, Karim; Silberman, Dafne M; Zhong, Lei; Mulligan, Peter; Sebastian, Carlos; Cosentino, Claudia; Martinez-Pastor, Barbara; Giacosa, Sofia; D'Urso, Agustina; Näär, Anders M; Kingston, Robert; Rippe, Karsten; Mostoslavsky, Raul

    2013-08-22

    DNA damage is linked to multiple human diseases, such as cancer, neurodegeneration, and aging. Little is known about the role of chromatin accessibility in DNA repair. Here, we find that the deacetylase sirtuin 6 (SIRT6) is one of the earliest factors recruited to double-strand breaks (DSBs). SIRT6 recruits the chromatin remodeler SNF2H to DSBs and focally deacetylates histone H3K56. Lack of SIRT6 and SNF2H impairs chromatin remodeling, increasing sensitivity to genotoxic damage and recruitment of downstream factors such as 53BP1 and breast cancer 1 (BRCA1). Remarkably, SIRT6-deficient mice exhibit lower levels of chromatin-associated SNF2H in specific tissues, a phenotype accompanied by DNA damage. We demonstrate that SIRT6 is critical for recruitment of a chromatin remodeler as an early step in the DNA damage response, indicating that proper unfolding of chromatin plays a rate-limiting role. We present a unique crosstalk between a histone modifier and a chromatin remodeler, regulating a coordinated response to prevent DNA damage.

  13. Cellular and molecular choreography of neutrophil recruitment to sites of sterile inflammation.

    Science.gov (United States)

    McDonald, Braedon; Kubes, Paul

    2011-11-01

    Liberation of damage-associated molecular patterns (DAMPs) following tissue injury and necrotic cell death leads to the induction of sterile inflammation. A hallmark of acute inflammation is the recruitment of neutrophils to injured tissues. This review focuses on the journey of neutrophils to sites of sterile inflammation and the cellular and molecular mechanisms that choreograph this complex voyage. We review the pathway of leukocyte recruitment, with emphasis on recent additions to our understanding of intravascular neutrophil migration. The contributions of various tissue-resident sentinel cell populations to the detection of danger signals (DAMPs) and coordination of neutrophil recruitment and migration are discussed. In addition, we highlight recent data on the control of neutrophil chemotaxis towards sites of sterile inflammation, including new insight into the temporal and spatial regulation of chemoattractant guidance signals that direct cell migration. Given that inappropriate neutrophilic inflammation is a cornerstone in the pathogenesis of many diseases, a complete understanding of the choreography of neutrophil recruitment to sites of sterile inflammation may uncover new avenues for therapeutic interventions to treat inflammatory pathologies.

  14. Recruiting Minority Students to the Geosciences

    Science.gov (United States)

    Marchese, P.; Cotten, D. E.; Cheung, T. D.; Johnson, L. P.; Austin, S.; Tremberger, G.; Bluestone, C.

    2007-05-01

    Queensborough Community College (QCC) and Medgar Evers College (MEC) of the City University of New York have been actively involved in recruiting primarily minority students to the Geosciences by involving students in research and by incorporating innovative and proven pedagogical methods into the classroom. Students at both colleges have been actively involved in doing research in Space and Earth Science. Students work during the summer under the mentorship of CUNY faculty conducting experiments and analyzing data. At the end of the summer students present findings at various science meetings. In the lecture room, the method of instruction was modified to emphasize active learning. Educational materials and pedagogical methods developed at QCC and other 4 year colleges was introduced to the predominantly minority student body at QCC and MEC. Many of these students did poorly at pre-college schools where lecture based learning is the chief method of instruction. It is not unexpected that many of them are having difficulty if the method of instruction has not changed at the postsecondary level. The intent of introducing active learning was to have students develop an appreciation of science, and have an increased understanding of relevant scientific principles. As a result of these activities student scores increased as compared to student scores in a more affluent college. Students also demonstrated increased conceptual understanding of the material, had higher self- efficacy scores, and seemed to enjoy the class better. Lower scoring students demonstrated the greatest benefit, while the better students had little (or no) changes.

  15. Islamist groups in the UK and recruitment

    Directory of Open Access Journals (Sweden)

    Mohammed Ilyas

    2013-09-01

    Full Text Available Since 2001 and 7/7 the search to find out why and how Muslims born in Europe join political and violence orientated Islamist groups has occupied policy makers and social scientist. The search has produced explanations that suggest social grievance, Islam and physiological problems are the motivations for why some Muslims join and act on behalf of Islamist groups in the UK. However, the approaches tend not to focus the role emotions generated from events that involve Muslim suffering play in some individuals becoming interested in acquiring and acting upon them. These events are often experienced variously by Muslims living in Europe through the media and are used by Islamist groups as resources to recruit. Consequently, this paper is based on interviews carried out with Islamists in the UK and tentatively discusses two process that take into account the emotional effect of events that concern Muslims in order to make sense of how some Muslims become compelled to acquire extreme ideas, act upon extreme ideas (independently or behalf of a group or join Islamist groups.

  16. Elevated Temperature and Allelopathy Impact Coral Recruitment.

    Science.gov (United States)

    Ritson-Williams, Raphael; Ross, Cliff; Paul, Valerie J

    2016-01-01

    As climate change continues to alter seawater temperature and chemistry on a global scale, coral reefs show multiple signs of degradation. One natural process that could facilitate the recovery of reef ecosystems is coral recruitment, which can be influenced by the benthic organisms in a local habitat. We experimentally tested both a global stressor (increased seawater temperature) and a local stressor (exposure to microcolin A, a natural product from a common marine benthic cyanobacterium) to determine how these stressors impacted coral larval sublethal stress, survival and settlement. Larvae of Porites astreoides had the same survival and settlement as the controls after exposure to increased temperature alone, but elevated temperature did cause oxidative stress. When exposed to natural concentrations of microcolin A, larval survival and settlement were significantly reduced. When larvae were exposed to these two stressors sequentially there was no interactive effect; but when exposed to both stressors simultaneously, there was a synergistic reduction in larval survival and an increase in oxidative stress more than in either stressor treatment alone. Increased seawater temperatures made larvae more susceptible to a concurrent local stressor disrupting a key process of coral reef recovery and resilience. These results highlight the importance of understanding how interactive stressors of varying spatial scales can impact coral demographics.

  17. Ant-like task allocation and recruitment in cooperative robots.

    Science.gov (United States)

    Krieger, M J; Billeter, J B; Keller, L

    2000-08-31

    One of the greatest challenges in robotics is to create machines that are able to interact with unpredictable environments in real time. A possible solution may be to use swarms of robots behaving in a self-organized manner, similar to workers in an ant colony. Efficient mechanisms of division of labour, in particular series-parallel operation and transfer of information among group members, are key components of the tremendous ecological success of ants. Here we show that the general principles regulating division of labour in ant colonies indeed allow the design of flexible, robust and effective robotic systems. Groups of robots using ant-inspired algorithms of decentralized control techniques foraged more efficiently and maintained higher levels of group energy than single robots. But the benefits of group living decreased in larger groups, most probably because of interference during foraging. Intriguingly, a similar relationship between group size and efficiency has been documented in social insects. Moreover, when food items were clustered, groups where robots could recruit other robots in an ant-like manner were more efficient than groups without information transfer, suggesting that group dynamics of swarms of robots may follow rules similar to those governing social insects.

  18. Descending control of nociception: Specificity, recruitment and plasticity.

    Science.gov (United States)

    Heinricher, M M; Tavares, I; Leith, J L; Lumb, B M

    2009-04-01

    The dorsal horn of the spinal cord is the location of the first synapse in pain pathways, and as such, offers a very powerful target for regulation of nociceptive transmission by both local segmental and supraspinal mechanisms. Descending control of spinal nociception originates from many brain regions and plays a critical role in determining the experience of both acute and chronic pain. The earlier concept of descending control as an "analgesia system" is now being replaced with a more nuanced model in which pain input is prioritized relative to other competing behavioral needs and homeostatic demands. Descending control arises from a number of supraspinal sites, including the midline periaqueductal gray-rostral ventromedial medulla (PAG-RVM) system, and the more lateral and caudal dorsal reticular nucleus (DRt) and ventrolateral medulla (VLM). Inhibitory control from the PAG-RVM system preferentially suppresses nociceptive inputs mediated by C-fibers, preserving sensory-discriminative information conveyed by more rapidly conducting A-fibers. Analysis of the circuitry within the RVM reveals that the neural basis for bidirectional control from the midline system is two populations of neurons, ON-cells and OFF-cells, that are differentially recruited by higher structures important in fear, illness and psychological stress to enhance or inhibit pain. Dynamic shifts in the balance between pain inhibiting and facilitating outflows from the brainstem play a role in setting the gain of nociceptive processing as dictated by behavioral priorities, but are also likely to contribute to pathological pain states.

  19. 34 CFR 611.12 - What additional selection criteria are used for an application proposing teacher recruitment...

    Science.gov (United States)

    2010-07-01

    ... application proposing teacher recruitment activities? 611.12 Section 611.12 Education Regulations of the... EDUCATION TEACHER QUALITY ENHANCEMENT GRANTS PROGRAM State Grants Program § 611.12 What additional selection... teacher preparation and an effective support system during their first three years of teaching....

  20. Stromal interaction molecule 1 regulates growth, cell cycle, and apoptosis of human tongue squamous carcinoma cells.

    Science.gov (United States)

    Cui, Xiaobo; Song, Laixiao; Bai, Yunfei; Wang, Yaping; Wang, Boqian; Wang, Wei

    2017-04-30

    Oral tongue squamous cell carcinoma (OTSCC) is the most common type of oral carcinomas. However, the molecular mechanism by which OTSCC developed is not fully identified. Stromal interaction molecule 1 (STIM1) is a transmembrane protein, mainly located in the endoplasmic reticulum (ER). STIM1 is involved in several types of cancers. Here, we report that STIM1 contributes to the development of human OTSCC. We knocked down STIM1 in OTSCC cell line Tca-8113 with lentivirus-mediated shRNA and found that STIM1 knockdown repressed the proliferation of Tca-8113 cells. In addition, we also showed that STIM1 deficiency reduced colony number of Tca-8113 cells. Knockdown of STIM1 repressed cells to enter M phase of cell cycle and induced cellular apoptosis. Furthermore, we performed microarray and bioinformatics analysis and found that STIM1 was associated with p53 and MAPK pathways, which may contribute to the effects of STIM1 on cell growth, cell cycle, and apoptosis. Finally, we confirmed that STIM1 controlled the expression of MDM2, cyclin-dependent kinase 4 (CDK4), and growth arrest and DNA damage inducible α (GADD45A) in OTSCC cells. In conclusion, we provide evidence that STIM1 contributes to the development of OTSCC partially through regulating p53 and MAPK pathways to promote cell cycle and survival.

  1. Telomerase recruitment requires both TCAB1 and Cajal bodies independently.

    Science.gov (United States)

    Stern, J Lewis; Zyner, Katherine G; Pickett, Hilda A; Cohen, Scott B; Bryan, Tracy M

    2012-07-01

    The ability of most cancer cells to grow indefinitely relies on the enzyme telomerase and its recruitment to telomeres. In human cells, recruitment depends on the Cajal body RNA chaperone TCAB1 binding to the RNA subunit of telomerase (hTR) and is also thought to rely on an N-terminal domain of the catalytic subunit, hTERT. We demonstrate that coilin, an essential structural component of Cajal bodies, is required for endogenous telomerase recruitment to telomeres but that overexpression of telomerase can compensate for Cajal body absence. In contrast, recruitment of telomerase was sensitive to levels of TCAB1, and this was not rescued by overexpression of telomerase. Thus, although Cajal bodies are important for recruitment, TCAB1 has an additional role in this process that is independent of these structures. TCAB1 itself localizes to telomeres in a telomerase-dependent but Cajal body-independent manner. We identify a point mutation in hTERT that largely abolishes recruitment yet does not affect association of telomerase with TCAB1, suggesting that this region mediates recruitment by an independent mechanism. Our results demonstrate that telomerase has multiple independent requirements for recruitment to telomeres and that the function of TCAB1 is to directly transport telomerase to telomeres.

  2. Recruiting Effective Math Teachers: Evidence from New York City

    Science.gov (United States)

    Boyd, Donald; Grossman, Pamela; Hammerness, Karen; Lankford, Hamilton; Loeb, Susanna; Ronfeldt, Matthew; Wyckoff, James

    2012-01-01

    For well over a decade school districts across the United States have struggled to recruit and retain effective mathematics teachers. In response to the need for qualified math teachers and the difficulty of directly recruiting individuals who have already completed the math content required for qualification, some districts, including Baltimore,…

  3. Understanding Student Recruitment in Mainland China: A Case Study

    Science.gov (United States)

    Spinks, John A.; Wong, Isabella Y. S.

    2010-01-01

    While China continues to be perhaps the most important student recruitment region for many leading international universities, changes in this market, resulting in more regional mobility of students, are fast becoming apparent. This, the increasing penetration and efforts of the traditional recruiting institutions and the entry of new universities…

  4. Inhibition of coral recruitment by macroalgae and cyanobacteria

    Science.gov (United States)

    Kuffner, I.B.; Walters, L.J.; Becerro, M.A.; Paul, V.J.; Ritson-Williams, R.; Beach, K.S.

    2006-01-01

    Coral recruitment is a key process in the maintenance and recovery of coral reef ecosystems. While intense competition between coral and algae is often assumed on reefs that have undergone phase shifts from coral to algal dominance, data examining the competitive interactions involved, particularly during the larval and immediate post-settlement stage, are scarce. Using a series of field and outdoor seawater table experiments, we tested the hypothesis that common species of macroalgae and cyanobacteria inhibit coral recruitment. We examined the effects of Lyngbya spp., Dictyota spp., Lobophora variegata (J. V. Lamouroux) Womersley, and Chondrophycus poiteaui (J. V. Lamouroux) Nam (formerly Laurencia poiteaui) on the recruitment success of Porites astreoides larvae. All species but C. poiteaui caused either recruitment inhibition or avoidance behavior in P. astreoides larvae, while L. confervoides and D. menstrualis significantly increased mortality rates of P. astreoides recruits. We also tested the effect of some of these macrophytes on larvae of the gorgonian octocoral Briareum asbestinum. Exposure to Lyngbya majuscula reduced survival and recruitment in the octocoral larvae. Our results provide evidence that algae and cyanobacteria use tactics beyond space occupation to inhibit coral recruitment. On reefs experiencing phase shifts or temporary algal blooms, the restocking of adult coral populations may be slowed due to recruitment inhibition, thereby perpetuating reduced coral cover and limiting coral community recovery. ?? Inter-Research 2006.

  5. Differential Recruitment of Distinct Amygdalar Nuclei across Appetitive Associative Learning

    Science.gov (United States)

    Cole, Sindy; Powell, Daniel J.; Petrovich, Gorica D.

    2013-01-01

    The amygdala is important for reward-associated learning, but how distinct cell groups within this heterogeneous structure are recruited during appetitive learning is unclear. Here we used Fos induction to map the functional amygdalar circuitry recruited during early and late training sessions of Pavlovian appetitive conditioning. We found that a…

  6. An Analysis of the Incidence of Recruiter Irregularities

    Science.gov (United States)

    2010-01-01

    provided data and answered our questions about the incidence of recruiter irregularities. The people are Ted Disney at the U.S. Army Recruiting...are more likely to ultimately be substantiated. The Army and the Navy, in contrast, have fairly expansive inter- nal reporting requirements that

  7. The Four ‘Ps’ of Hospitality Recruiting

    Directory of Open Access Journals (Sweden)

    John D. Murtha

    2013-07-01

    Full Text Available When recruiting from university programs, there is a consensus among hospitality professionals about the qualities that make candidates achieve success in our industry. These can be categorized as preparation, presentation, purpose, and passion. The Four ‘Ps’ represent a useful assessment system for recruiters, and candidates should be aware that these categories are being considered.

  8. Recruitment and Retention of Latino Children in a Lifestyle Intervention

    Science.gov (United States)

    Guzman, Angelica; Richardson, Irma M.; Gesell, Sabina; Barkin, Shari L.

    2009-01-01

    Objective: To describe promising recruitment and retention strategies for transient Latino populations, assisting investigators who work with this population in their research design and implementation. Methods: Strategies in recruitment and retention from a year-long intervention in children and their families are described. Results: Of the 159…

  9. Recruitment of Native American Parents: Ideas for Practice.

    Science.gov (United States)

    Goodluck, Charlotte

    Recruitment of Native Americans to be foster or adoptive parents for Native American children involves careful planning, preparation, and work. In addition to making standard administrative decisions and maintaining required records, social workers must be sensitive to the attitudes, lifestyle, and culture of Native Americans recruited as adoptive…

  10. The Recruitment Problem in Psychiatry: A Critical Commentary

    Science.gov (United States)

    Stampfer, Hans

    2011-01-01

    The continuing shortfall in recruitment to Psychiatry is examined with suggestions for affirmative action. Recruitment may improve in the near future because of the high demand for psychiatrists, the incentives offered, greater competition for other specialties and a pool of international graduates willing to work in Psychiatry. There remains the…

  11. Reflecting on E-Recruiting Research Using Grounded Theory

    NARCIS (Netherlands)

    Wolfswinkel, Joost; Furtmüller, Elfi; Wilderom, Celeste

    2010-01-01

    This paper presents a systematic review of the e-Recruiting literature through a grounded theory lens. The large number of publications and the increasing diversity of publications on e-Recruiting research, as the most studied area within e-HRM (Electronic Human Resource Management), calls for a syn

  12. Virtual HRM: A Case of e-Recruitment

    DEFF Research Database (Denmark)

    Holm, Anna

    2009-01-01

    -recruitment should be understood as means of automating the process of recruitment, or rather be treated as a more complex organisational concept.  To clarify this issue the paper discusses the phenomenon from the open-system organisational perspective of virtual organising. The paper draws on the results...

  13. Selection, Training, and Utilization of Navy Recruit Training Command Officers.

    Science.gov (United States)

    1980-05-01

    Severe Weather Extremes of Heat and Cold Cardiopulmonary Resuscitation (CPR) Orientation The Heimlich Maneuver Common Recruit Injuries and Complaints...TOPIC 7. DIVISION OFFICER EMERGENCY PROCEDURES Severe Weather Extremes of Hot and Cold Cardiopulmonary Resuscitation (CPR) Orientation The Heimlich ... Maneuver Common Recruit Injuries/Complaints Medical Plan Fire Epidemic Incidents Which May Result in Extensive News Coverage Psychiatric Disorders Suicide

  14. The Four ‘Ps’ of Hospitality Recruiting

    OpenAIRE

    John D. Murtha

    2013-01-01

    When recruiting from university programs, there is a consensus among hospitality professionals about the qualities that make candidates achieve success in our industry. These can be categorized as preparation, presentation, purpose, and passion. The Four ‘Ps’ represent a useful assessment system for recruiters, and candidates should be aware that these categories are being considered.

  15. Recruiting Vietnamese students to Kymenlaakso University of Applied Science

    OpenAIRE

    2010-01-01

    ABSTRACT KYMENLAAKSO UNIVERSITY OF APPLIED SCIENCES International Marketing, Kouvola NGUYEN THI THU THAO Recruiting Vietnamese students to Kymenlaakso University of Applied Sciences Bachelor’s Thesis 54 pages + 4 appendices Supervisor Ulla Puustelli, MSc (Econ.) June 200 Key words Vietnamese students, recruiting, education, culture, communication The main subject of the project is to create a theoretical research of impacts of culture, communication, educa...

  16. A New Hire Looks at the Recruiter's Role

    Science.gov (United States)

    Zider, Robert B.

    1971-01-01

    This article is a followup to one by M. C. Kidd, in this issue. The recruiter of technical personnel must be part psychologist, part engineer, and part accountant, keeping in mind the kind of investment each prospect represents. He must be specific, comprehensive, and more sales" oriented than the nontechnical recruiter. (Author/CJ)

  17. Recruitment Practices Change, but Issues Remain the Same

    Science.gov (United States)

    Hugo, Esther

    2012-01-01

    What the author found most surprising about Richard Haines' survey on 1974 recruitment practices was that the major issues are still relevant. His main points about recruitment, college and counselor interaction, and the need for better information still resonate as the profession consistently calls for clarity and transparency in the college…

  18. 77 FR 3503 - Guam Military Base Realignment Contractor Recruitment Standards

    Science.gov (United States)

    2012-01-24

    ...: Notice. SUMMARY: The U.S. Department of Labor's (Department) Employment and Training Administration (ETA.... Departmental Recruitment Support Activities Separate from the Contractor Recruitment Standards, ETA will..., including outreach to its workforce investment system. ETA will do the following: Develop and issue...

  19. Limits to meritocracy? Gender in academic recruitment and promotion processes

    DEFF Research Database (Denmark)

    Nielsen, Mathias Wullum

    2015-01-01

    According to the literature, women researchers are sometimes at a disadvantage in academic recruitment due to insufficient network ties and subtle gender biases among evaluators. But how exactly do highly formal recruitment procedures allow space for mobilizing informal, potentially gendered, net...

  20. In situ tissue regeneration: chemoattractants for endogenous stem cell recruitment.

    Science.gov (United States)

    Vanden Berg-Foels, Wendy S

    2014-02-01

    Tissue engineering uses cells, signaling molecules, and/or biomaterials to regenerate injured or diseased tissues. Ex vivo expanded mesenchymal stem cells (MSC) have long been a cornerstone of regeneration therapies; however, drawbacks that include altered signaling responses and reduced homing capacity have prompted investigation of regeneration based on endogenous MSC recruitment. Recent successful proof-of-concept studies have further motivated endogenous MSC recruitment-based approaches. Stem cell migration is required for morphogenesis and organogenesis during development and for tissue maintenance and injury repair in adults. A biomimetic approach to in situ tissue regeneration by endogenous MSC requires the orchestration of three main stages: MSC recruitment, MSC differentiation, and neotissue maturation. The first stage must result in recruitment of a sufficient number of MSC, capable of effecting regeneration, to the injured or diseased tissue. One of the challenges for engineering endogenous MSC recruitment is the selection of effective chemoattractant(s). The objective of this review is to synthesize and evaluate evidence of recruitment efficacy by reported chemoattractants, including growth factors, chemokines, and other more recently appreciated MSC chemoattractants. The influence of MSC tissue sources, cell culture methods, and the in vitro and in vivo environments is discussed. This growing body of knowledge will serve as a basis for the rational design of regenerative therapies based on endogenous MSC recruitment. Successful endogenous MSC recruitment is the first step of successful tissue regeneration.

  1. Recruiting Transcultural Qualitative Research Participants: A Conceptual Model

    Directory of Open Access Journals (Sweden)

    Phyllis Eide

    2005-06-01

    Full Text Available Working with diverse populations poses many challenges to the qualitative researcher who is a member of the dominant culture. Traditional methods of recruitment and selection (such as flyers and advertisements are often unproductive, leading to missed contributions from potential participants who were not recruited and researcher frustration. In this article, the authors explore recruitment issues related to the concept of personal knowing based on experiences with Aboriginal Hawai'ian and Micronesian populations, wherein knowing and being known are crucial to successful recruitment of participants. They present a conceptual model that incorporates key concepts of knowing the other, cultural context, and trust to guide other qualitative transcultural researchers. They also describe challenges, implications, and concrete suggestions for recruitment of participants.

  2. CFTR RECRUITMENT TO PHAGOSOMES IN NEUTROPHILS

    OpenAIRE

    Zhou, Yun; Song, Kejing; Painter, Richard G.; Aiken, Martha; Reiser, Jakob; Stanton, Bruce A.; Nauseef, William M.; Wang, Guoshun

    2013-01-01

    Optimal microbicidal activity of human polymorphonuclear leukocytes (PMN) relies on generation of toxic agents such as hypochlorous acid (HOCl) in phagosomes. HOCl formation requires H2O2 produced by the NADPH oxidase, myeloperoxidase derived from azurophilic granules, and chloride ion. Chloride transport from cytoplasm into phagosomes requires chloride channels which include cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. However, the phagosomal...

  3. Desirable cytolytic immune effector cell recruitment by interleukin-15 dendritic cells.

    Science.gov (United States)

    Van Acker, Heleen H; Beretta, Ottavio; Anguille, Sébastien; Caluwé, Lien De; Papagna, Angela; Van den Bergh, Johan M; Willemen, Yannick; Goossens, Herman; Berneman, Zwi N; Van Tendeloo, Viggo F; Smits, Evelien L; Foti, Maria; Lion, Eva

    2017-01-13

    Success of dendritic cell (DC) therapy in treating malignancies is depending on the DC capacity to attract immune effector cells, considering their reciprocal crosstalk is partially regulated by cell-contact-dependent mechanisms. Although critical for therapeutic efficacy, immune cell recruitment is a largely overlooked aspect regarding optimization of DC vaccination. In this paper we have made a head-to-head comparison of interleukin (IL)-15-cultured DCs and conventional IL-4-cultured DCs with regard to their proficiency in the recruitment of (innate) immune effector cells. Here, we demonstrate that IL-4 DCs are suboptimal in attracting effector lymphocytes, while IL15 DCs provide a favorable chemokine milieu for recruiting CD8+ T cells, natural killer (NK) cells and gamma delta (γδ) T cells. Gene expression analysis revealed that IL-15 DCs exhibit a high expression of chemokines involved in antitumor immune effector cell attraction, while IL-4 DCs display a more immunoregulatory profile characterized by the expression of Th2 and regulatory T cell-attracting chemokines. This is confirmed by functional data indicating an enhanced recruitment of granzyme B+ effector lymphocytes by IL-15 DCs, as compared to IL-4 DCs, and subsequent superior killing of tumor cells by the migrated lymphocytes. Elevated CCL4 gene expression in IL-15 DCs and lowered CCR5 expression on both migrated γδ T cells and NK cells, led to validation of increased CCL4 secretion by IL15 DCs. Moreover, neutralization of CCR5 prior to migration resulted in an important inhibition of γδ T cell and NK cell recruitment by IL-15 DCs. These findings further underscore the strong immunotherapeutic potential of IL-15 DCs.

  4. Recruitment and retention of participants for an international type 1 diabetes prevention trial

    DEFF Research Database (Denmark)

    Franciscus, Margaret; Nucci, Anita; Bradley, Brenda;

    2014-01-01

    for long-term follow-up assessments. PURPOSE: Our purpose is to summarize the recruitment and retention strategies used to conduct TRIGR from the perspective of the study coordinators. METHODS: TRIGR was designed to test whether weaning to formula containing hydrolyzed versus intact cow's milk protein...... would be efficacious in decreasing risk for development of T1D-associated autoantibodies and T1D among infants identified to be at increased risk for T1D based on their human leukocyte antigen (HLA) profile and family history. Multiple strategies tailored to local issues were required to enroll...... privacy regulations mid-trial. The majority of participants were recruited from primary care antenatal clinics located near the study centers and from a general hospital or pediatric center that was affiliated with a TRIGR Study center. Internet and magazine advertisements were found to be useful...

  5. IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Serkan I. Göktuna

    2014-06-01

    Full Text Available The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC therapy.

  6. Pseudomonas aeruginosa airway infection recruits and modulates neutrophilic myeloid-derived suppressor cells

    Directory of Open Access Journals (Sweden)

    Hasan Halit Öz

    2016-11-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that causes infections mainly in patients with cystic fibrosis (CF lung disease. Despite innate and adaptive immune responses upon infection, P. aeruginosa is capable of efficiently escaping host defenses, but the underlying immune mechanisms remain poorly understood. Myeloid-derived suppressor cells (MDSCs are innate immune cells that are functionally characterized by their potential to suppress T- and natural killer (NK-cell responses. Here we demonstrate, using an airway in vivo infection model, that P. aeruginosa recruits and activates neutrophilic MDSCs, which functionally suppress T-cell responses. We further show that the CF gene defect (cystic fibrosis transmembrane conductance regulator, CFTR modulates the functionality, but not the recruitment or generation of neutrophilic MDSCs. Collectively, we define a mechanism by which P. aeruginosa airway infection undermines host immunity by modulating neutrophilic MDSCs in vivo.

  7. Effects of hydrology on red mangrove recruits

    Science.gov (United States)

    Doyle, Thomas W.

    2003-01-01

    growth of the red mangrove, Rhizophora mangle (fig. 1). Red mangrove propagules (recruits) of select sizes and genotypes (i.e., genetically similar groups) were planted both in greenhouses and in the field. Seedling growth was monitored in both studies on a quarterly basis for over a year; measurements included shoot growth, seedling height, and a final harvest of plant biomass.

  8. 8-Br-cAMP up-regulates antioncogene expression in human retinoblastoma HXO-Rb44 cells%8-Br-cAMP可上调人视网膜母细胞瘤HX O-Rb44细胞抑癌基因的表达

    Institute of Scientific and Technical Information of China (English)

    邓新国; 郭希让; 吴景兰; 田小莉; 庞广仁; 马丰侠

    2000-01-01

    目的探讨8-B r-Camp对人视网膜母细胞瘤HXO-Rb44细胞抑癌基因表达的效应.方法应用RNA斑点印迹技术检测细胞p16、p21wafl、wp53、mp53和 Rb的Mrna,应用免疫组化斑点印迹技术检测细胞P16、P21wafl 、PRb、cdk2、cdk4和PCNA蛋白质表达的免疫反应性(IR).结果在斑点印迹标本上,人HXO-Rb44细胞p16、p21wafl、wp53及Rb 的Mrna信号和P16-IR、P21wafl-IR及PRb-IR均是实验组高于对照组,P<0.05~0.01,而mp53mRNA信号、PCNA-I R、cdk2-IR和cdk4-IR均是实验组低于对照组,P<0.05~0.01 .结论 8-Br-Camp上调人HXO-Rb44细胞p16、p21wafl、wp 53、Rb抑癌基因的表达及P16、P21wafl、PRb蛋白的表达, 并下调mp53mRNA、PCNA-IR、cdk2-IR和cdk4-IR的表达,提示8-Br-Camp可通过阻抑细胞周期进展相关基因的表达而抑制人HXO- Rb44细胞的生长增殖.%It is kno wn that 8-Br-cAMP is one of selective bi nding site analogues for cAMP RIIα to af fect cell growth through regulation of g ene expression.The p16,p21wafl,p53 a nd Rb are antioncogenes which affect cel l growth through control of cell cycle.T he aim of this study is to investigate t he 8-Br-cAMP effect on the expression of antioncogenes in human HXO-Rb44 cells. Methods Cultured HXO-Rb44 cells in RPMI -1 640 medium were divided into two aliquot s.8-Br-cAMP (2×10-5mol/L) was added i nto one aliquot for 24h as the experime ntal group(EG),the another aliquot witho ut 8-Br-cAMP as the control group(CG).Af ter 24h,the cell suspension was dropped onto the nitrocellulose membrane.The mR NA of p16,p21wafl,wild type(w)p53,mut ant type(m) p53 and Rb were used respec tively with biotin-labeled cDNA probes b y intact cell RNA dot blot.The immunorea ctivity(IR) of P16,P21wafl,PRb,PCN A,cdk2 and cdk4 were detected respecti vely with specific monoclonal antibodies on dot blot.ResultsThe mRNA dot blot s ignals of mp53 and protein dot blot of cdk2-IR,cdk4-IR and PCNA-IR in EG were weaker than those in CG(P<0.05~0.01). W hile

  9. Recruitment difficulties in a primary care cluster randomised trial: investigating factors contributing to general practitioners' recruitment of patients

    Directory of Open Access Journals (Sweden)

    McKenzie Joanne E

    2011-03-01

    Full Text Available Abstract Background Recruitment of patients by health professionals is reported as one of the most challenging steps when undertaking studies in primary care settings. Numerous investigations of the barriers to patient recruitment in trials which recruit patients to receive an intervention have been published. However, we are not aware of any studies that have reported on the recruitment barriers as perceived by health professionals to recruiting patients into cluster randomised trials where patients do not directly receive an intervention. This particular subtype of cluster trial is commonly termed a professional-cluster trial. The aim of this study was to investigate factors that contributed to general practitioners recruitment of patients in a professional-cluster trial which evaluated the effectiveness of an intervention to increase general practitioners adherence to a clinical practice guideline for acute low-back pain. Method General practitioners enrolled in the study were posted a questionnaire, consisting of quantitative items and an open-ended question, to assess possible reasons for poor patient recruitment. Descriptive statistics were used to summarise quantitative items and responses to the open-ended question were coded into categories. Results Seventy-nine general practitioners completed at least one item (79/94 = 84%, representing 68 practices (85% practice response rate, and 44 provided a response to the open-ended question. General practitioners recalled inviting a median of two patients with acute low-back pain to participate in the trial over a seven-month period; they reported that they intended to recruit patients, but forgot to approach patients to participate; and they did not perceive that patients had a strong interest or disinterest in participating. Additional open-ended comments were generally consistent with the quantitative data. Conclusion A number of barriers to the recruitment of patients with acute low

  10. Internet recruitment and e-mail interviews in qualitative studies.

    Science.gov (United States)

    Hamilton, Rebekah J; Bowers, Barbara J

    2006-07-01

    In 2004, 111 million adults accessed the Internet looking for health and medical information. Qualitative researchers can apply long-standing principles of recruitment and interviewing to the Internet. The purpose of this article is to examine the theoretical and methodological aspects of Internet recruitment and e-mail interviewing. The authors address issues of appropriateness, adequacy, representativeness, sample bias, data fraud, flexibility and consistency in interviewing, timing, elimination of the need for transcription, oral versus written communication, reliability and validity, and ethical concerns. They include some practical suggestions on a research design for a qualitative study employing both Internet recruitment and e-mail interviewing.

  11. The Stat3/GR interaction code: predictive value of direct/indirect DNA recruitment for transcription outcome.

    Science.gov (United States)

    Langlais, David; Couture, Catherine; Balsalobre, Aurélio; Drouin, Jacques

    2012-07-13

    Transcription factor recruitment to genomic sites of action is primarily due to direct protein:DNA interactions. The subsequent recruitment of coregulatory complexes leads to either transcriptional activation or repression. In contrast to this canonical scheme, some transcription factors, such as the glucocorticoid receptor (GR), behave as transcriptional repressors when recruited to target genes through protein tethering. We have investigated the genome-wide prevalence of tethering between GR and Stat3 and found nonreciprocal interactions, namely that GR tethering to DNA-bound Stat3 results in transcriptional repression, whereas Stat3 tethering to GR results in synergism. Further, other schemes of GR and Stat3 corecruitment to regulatory modules result in transcriptional synergism, including neighboring and composite binding sites. The results indicate extensive transcriptional interactions between Stat3 and GR; further, they provide a genome-wide assessment of transcriptional regulation by tethering and a molecular basis for integration of signals mediated by GR and Stats in health and disease.

  12. Antigen-induced recruitment of eosinophils: importance of CD4+ T cells, IL5, and mast cells.

    Science.gov (United States)

    Hom, J T; Estridge, T

    1994-12-01

    Eosinophils of sensitized mice readily recruit to the site of antigen challenge. In the present study, experiments were performed to determine the involvement of different cell types in the antigen-induced recruitment of eosinophils. We demonstrated that a single treatment with anti-L3T4 monoclonal antibody (mAb) on the day of allergen challenge significantly decreased antigen-induced recruitment of eosinophils. Treatments with anti-L3T4 mAb during the sensitization period also caused a substantial reduction in the migration of eosinophils into the site of challenge with antigen. Thus, it appears that both stages of eosinophil recruitment, sensitization and antigen-challenge, are dependent upon the presence of L3T4+ T cells. Moreover, while treatments with anti-IL5 mAb blocked eosinophil migration, anti-IL2 mAb failed to alter the antigen-induced recruitment of eosinophils. In addition, significant numbers of eosinophils from the mast-cell-deficient mice were found to migrate into the peritoneal cavities upon allergen challenge. Eosinophil migration was also observed in several mouse strains of different H-2 haplotypes. The present findings suggest that CD4+ T cells and IL5 but not IL2 may play important roles in modulating the recruitment of eosinophils. Moreover, the involvement of mast cells does not appear to be essential for eosinophil migration. Finally, the development of antigen-induced recruitment of eosinophils is probably not under the immunogenetic regulation by genes within the H-2 complex.

  13. Facebook targeted advertisement for research recruitment: A primer for nurse researchers.

    Science.gov (United States)

    Carter-Harris, Lisa

    2016-11-01

    Recruiting participants for research studies can be challenging and costly. Innovative recruitment methods are needed. Facebook targeted advertisement offers a low-cost alternative to traditional methods that has been successfully used in research study recruitment. This primer offers nurse researchers a method utilizing social media as a recruitment tool and details Facebook targeted advertisement for research recruitment.

  14. Cilia Control Vascular Mural Cell Recruitment in Vertebrates

    Directory of Open Access Journals (Sweden)

    Xiaowen Chen

    2017-01-01

    Full Text Available Vascular mural cells (vMCs are essential components of the vertebrate vascular system, controlling blood vessel maturation and homeostasis. Discrete molecular mechanisms have been associated with vMC development and differentiation. The function of hemodynamic forces in controlling vMC recruitment is unclear. Using transgenic lines marking developing vMCs in zebrafish embryos, we find that vMCs are recruited by arterial-fated vessels and that the process is flow dependent. We take advantage of tissue-specific CRISPR gene targeting to demonstrate that hemodynamic-dependent Notch activation and the ensuing arterial genetic program is driven by endothelial primary cilia. We also identify zebrafish foxc1b as a cilia-dependent Notch-specific target that is required within endothelial cells to drive vMC recruitment. In summary, we have identified a hemodynamic-dependent mechanism in the developing vasculature that controls vMC recruitment.

  15. Recruitment and Employment of the Water Pollution Control Specialist.

    Science.gov (United States)

    Sherrard, J. H.; Sherrard, F. A.

    1979-01-01

    Presented are the basic principles of personnel recruitment and employment for the water pollution control field. Attention is given to determination of staffing requirements, effective planning, labor sources, affirmative action, and staffing policies. (CS)

  16. Fast and flexible: argentine ants recruit from nearby trails.

    Science.gov (United States)

    Flanagan, Tatiana P; Pinter-Wollman, Noa M; Moses, Melanie E; Gordon, Deborah M

    2013-01-01

    Argentine ants (Linepithema humile) live in groups of nests connected by trails to each other and to stable food sources. In a field study, we investigated whether some ants recruit directly from established, persistent trails to food sources, thus accelerating food collection. Our results indicate that Argentine ants recruit nestmates to food directly from persistent trails, and that the exponential increase in the arrival rate of ants at baits is faster than would be possible if recruited ants traveled from distant nests. Once ants find a new food source, they walk back and forth between the bait and sometimes share food by trophallaxis with nestmates on the trail. Recruiting ants from nearby persistent trails creates a dynamic circuit, like those found in other distributed systems, which facilitates a quick response to changes in available resources.

  17. Fast and flexible: argentine ants recruit from nearby trails.

    Directory of Open Access Journals (Sweden)

    Tatiana P Flanagan

    Full Text Available Argentine ants (Linepithema humile live in groups of nests connected by trails to each other and to stable food sources. In a field study, we investigated whether some ants recruit directly from established, persistent trails to food sources, thus accelerating food collection. Our results indicate that Argentine ants recruit nestmates to food directly from persistent trails, and that the exponential increase in the arrival rate of ants at baits is faster than would be possible if recruited ants traveled from distant nests. Once ants find a new food source, they walk back and forth between the bait and sometimes share food by trophallaxis with nestmates on the trail. Recruiting ants from nearby persistent trails creates a dynamic circuit, like those found in other distributed systems, which facilitates a quick response to changes in available resources.

  18. Recruiting, Selecting and Developing Executive Personnel in Capital Resource Management.

    Science.gov (United States)

    Nusbaum, Ned A.

    1984-01-01

    Obtaining qualified persons for capital resource management positions requires school districts and colleges to adopt nondiscriminatory selection and hiring policies. Guidelines are offered for the recruitment process, administering the selection process, and inhouse personnel development. (MLF)

  19. Racial athletic stereotype confirmation in college football recruiting.

    Science.gov (United States)

    Thomas, Grant; Good, Jessica J; Gross, Alexi R

    2015-01-01

    The present study tested real-world racial stereotype use in the context of college athletic recruiting. Stereotype confirmation suggests that observers use stereotypes as hypotheses and interpret relevant evidence in a biased way that confirms their stereotypes. Shifting standards suggest that the evaluative standard to which we hold a target changes as a function of their group membership. We examined whether stereotype confirmation and shifting standards effects would be seen in college football coaches during recruiting. College football coaches evaluated a Black or White player on several attributes and made both zero- and non-zero-sum allocations. Results suggested that coaches used the evidence presented to develop biased subjective evaluations of the players based on race while still maintaining equivalent objective evaluations. Coaches also allocated greater overall resources to the Black recruit than the White recruit.

  20. Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies

    NARCIS (Netherlands)

    Schipper-Krom, S.; Juenemann, K.; Jansen, A.H.; Wiemhoefer, A.; van den Nieuwendijk, R.; Smith, D.L.; Hink, M.A.; Bates, G.P.; Overkleeft, H.; Ovaa, H.; Reits, E.

    2014-01-01

    Neurodegenerative disorders such as Huntington's disease are hallmarked by neuronal intracellular inclusion body formation. Whether proteasomes are irreversibly recruited into inclusion bodies in these protein misfolding disorders is a controversial subject. In addition, it has been proposed that th

  1. Exploring recruitment and selection trends in the Eastern Cape

    Directory of Open Access Journals (Sweden)

    Gerrit J. Louw

    2013-01-01

    Full Text Available Orientation: The recruitment, selection and development of suitable candidates are crucial strategic functions to ensure the competitiveness of corporate and public sector organisations. Research purpose: The purpose of the study was to determine whether targeted organisations have a clear recruitment and selection policy by means of a preliminary exploratory study. In addition to this, the objective was the need to establish the various techniques or methods in use to recruit and select candidates for vacant posts. Motivation for the study: To develop a better understanding of the trends in the application of recruitment and selection methods within the Eastern Cape. Research design, approach and method: This study has a non-experimental design. Methodological processes followed a qualitative and quantitative mixed approach. Structured interviews were used to collect data followed by a descriptive statistical analysis, summary and interpretation of results. Main findings: Whereas newspaper advertising and recruitment agencies are the most popular recruitment methods, the application blank and interviews were mostly preferred for selection purposes. Although assessment centres and psychological assessments were also regarded as popular selection methods, assessment centres were; however, the most prominent selection method to follow of the above two mentioned selection methods. Practical/managerial implications: The research findings could provide corporate leaders and their human resource functionaries with a theoretical pointer relative to recruitment and selection trends within the Province which could guide more effective skills attraction and selection decisions. Contribution/value-add: The study provided valuable strategic information to improve on organisational competiveness via effective recruitment and selection processes. In addition, training and educational programmes could eventually fill the needs and gaps identified in

  2. Dietary Intake and Stress Fractures Among Elite Male Combat Recruits

    Science.gov (United States)

    2012-03-13

    8217 anthropometric measurements, nutritional habits , iron indices, and serum calcium were collected on induction and again after 4 months. Blood samples...meat, and fish; 4) bread and baked products; 5) starches and legumes; 6) fruit; 7) vegetables; 8) snacks and cookies; and 9) beverages. Subjects...recruits The recruits had 3 main meals and 3 snacks a day. Breakfast (7–8 am, about 2 h after awakening), which included porridge, bread, 1–2 eggs, cream

  3. Multi-Agent System for Recruiting Patients for Clinical Trials

    Science.gov (United States)

    2014-05-01

    Multi - Agent System for Recruiting Patients for Clinical Trials Samhar Mahmoud King’s College London London, UK samhar.mahmoud@kcl.ac.uk Gareth Tyson...TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Multi - Agent System for Recruiting Patients for Clinical Trials 5a...methodology [15] was proposed to guide the process of de- veloping a multi - agent system from analysis to design. For brevity, we focus here on one

  4. Child welfare employee recruitment and retention: an organizational culture perspective.

    Science.gov (United States)

    Agbényiga, DeBrenna LaFa

    2009-01-01

    Drawing data from an organizational culture study, this cross-sectional study investigates the effect of organizational culture on child welfare employee recruitment and retention (N=92). Findings from quantitative analyses of the organizational culture inventory suggest that constructive culture style in child welfare organizations, especially humanistic-encouraging and self-actualizing culture norms, highly predict recruitment through employees' perception of "fit" and satisfaction as a member of the organization. Limitations, future research, and relevant implications are discussed.

  5. Recruitment of coastal fishes and oceanographic variability in central California

    Science.gov (United States)

    Wilson, J. R.; Broitman, B. R.; Caselle, J. E.; Wendt, D. E.

    2008-09-01

    Recruitment of pelagic larval fishes to the nearshore environment is dependent on a suite of biological and physical processes operating at many spatial and temporal scales. Nearshore circulation processes associated with coastal upwelling are widely upheld as major determinants of year class strength for many rockfishes ( Sebastes spp.), but the mechanism by which these processes drive recruitment is largely unknown. We used Standard Monitoring Units for the Recruitment of Fishes (SMURFs) to monitor recruitment of two rockfish complexes ( Sebastes spp.) and cabezon ( Scorpaenichthys marmoratus) from March to September of 2004 and 2005 at 3 sites along the central California coast. We examined the relationship between recruitment of these fishes and measurements of oceanographic variability associated with upwelling dynamics, including in situ water temperature, AVHRR sea surface temperature, the Bakun upwelling index, and an index of alongshore surface water transport. We found that rockfish comprising the KCGB complex ( Sebastes atrovirens, Sebastes caurinus, Sebastes carnatus, Sebastes chrysomelas) recruit during early summer, while fishes of the BYO complex ( Sebastes melanops, Sebastes flavidus, Sebastes serranoides), as well as cabezon recruit during late summer. Our results provide limited support for an association between the arrival of juvenile pelagic rockfish and cabezon to the nearshore environment and physical processes related to upwelling and relaxation. Beyond the limitations of our bimonthly sampling scheme, the lack of a clear pattern may be related to the near absence of upwelling-relaxation cycles along this stretch of coast during these two study periods. Moreover, the settlement and recruitment of nearshore fishes may be closely tied to processes occurring earlier in the larval stage.

  6. RECRUITMENT AND SELECTION IS AN EXERCISE IN DISCRIMINATION

    Directory of Open Access Journals (Sweden)

    Dragan Čizmić

    2013-12-01

    Full Text Available Throughout the course of this work it is examined how the ways in which both, the law of the land and the morals held by a company, can improve the process of choosing an employee. It also identified the principles of recruitment and selection which should be applied and discuss their effect upon a potential recruit. It looked into the ways in which these considerations benefit both the employer and the employee.

  7. Sexual Recruitment in Zostera marina: Progress toward a Predictive Model.

    Science.gov (United States)

    Furman, Bradley T; Peterson, Bradley J

    2015-01-01

    Ecophysiological stress and physical disturbance are capable of structuring meadows through a combination of direct biomass removal and recruitment limitation; however, predicting these effects at landscape scales has rarely been successful. To model environmental influence on sexual recruitment in perennial Zostera marina, we selected a sub-tidal, light-replete study site with seasonal extremes in temperature and wave energy. During an 8-year observation period, areal coverage increased from 4.8 to 42.7%. Gains were stepwise in pattern, attributable to annual recruitment of patches followed by centrifugal growth and coalescence. Recruitment varied from 13 to 4,894 patches per year. Using a multiple linear regression approach, we examined the association between patch appearance and relative wave energy, atmospheric condition and water temperature. Two models were developed, one appropriate for the dispersal of naked seeds, and another for rafted flowers. Results indicated that both modes of sexual recruitment varied as functions of wind, temperature, rainfall and wave energy, with a regime shift in wind-wave energy corresponding to periods of rapid colonization within our site. Temporal correlations between sexual recruitment and time-lagged climatic summaries highlighted floral induction, seed bank and small patch development as periods of vulnerability. Given global losses in seagrass coverage, regions of recovery and re-colonization will become increasingly important. Lacking landscape-scale process models for seagrass recruitment, temporally explicit statistical approaches presented here could be used to forecast colonization trajectories and to provide managers with real-time estimates of future meadow performance; i.e., when to expect a good year in terms of seagrass expansion. To facilitate use as forecasting tools, we did not use statistical composites or normalized variables as our predictors. This study, therefore, represents a first step toward linking

  8. Sexual Recruitment in Zostera marina: Progress toward a Predictive Model.

    Directory of Open Access Journals (Sweden)

    Bradley T Furman

    Full Text Available Ecophysiological stress and physical disturbance are capable of structuring meadows through a combination of direct biomass removal and recruitment limitation; however, predicting these effects at landscape scales has rarely been successful. To model environmental influence on sexual recruitment in perennial Zostera marina, we selected a sub-tidal, light-replete study site with seasonal extremes in temperature and wave energy. During an 8-year observation period, areal coverage increased from 4.8 to 42.7%. Gains were stepwise in pattern, attributable to annual recruitment of patches followed by centrifugal growth and coalescence. Recruitment varied from 13 to 4,894 patches per year. Using a multiple linear regression approach, we examined the association between patch appearance and relative wave energy, atmospheric condition and water temperature. Two models were developed, one appropriate for the dispersal of naked seeds, and another for rafted flowers. Results indicated that both modes of sexual recruitment varied as functions of wind, temperature, rainfall and wave energy, with a regime shift in wind-wave energy corresponding to periods of rapid colonization within our site. Temporal correlations between sexual recruitment and time-lagged climatic summaries highlighted floral induction, seed bank and small patch development as periods of vulnerability. Given global losses in seagrass coverage, regions of recovery and re-colonization will become increasingly important. Lacking landscape-scale process models for seagrass recruitment, temporally explicit statistical approaches presented here could be used to forecast colonization trajectories and to provide managers with real-time estimates of future meadow performance; i.e., when to expect a good year in terms of seagrass expansion. To facilitate use as forecasting tools, we did not use statistical composites or normalized variables as our predictors. This study, therefore, represents a first

  9. Disclosure of investigators' recruitment performance in multicenter clinical trials

    DEFF Research Database (Denmark)

    Dal-Ré, Rafael; Moher, David; Gluud, Christian;

    2011-01-01

    Rafael Dal-Ré and colleagues argue that the recruitment targets and performance of all site investigators in multi-centre clinical trials should be disclosed in trial registration sites before a trial starts, and when it ends.......Rafael Dal-Ré and colleagues argue that the recruitment targets and performance of all site investigators in multi-centre clinical trials should be disclosed in trial registration sites before a trial starts, and when it ends....

  10. Recruitment and Retention of Patients into Emergency Medicine Clinical Trials

    OpenAIRE

    Cofield,Stacey; Conwit, Robin; Barsan, William; Quinn, James

    2010-01-01

    The emergency medicine and pre-hospital environments are unlike any other clinical environments and require special consideration to allow the successful implementation of clinical trials. This article reviews the specific issues involved in Emergency Medicine Clinical Trials (EMCT), and provides strategies from emergency medicine and non-emergency medicine trials to maximize recruitment and retention. While the evidence supporting some of these strategies is deficient, addressing recruitment...

  11. The synaptic recruitment of lipid rafts is dependent on CD19-PI3K module and cytoskeleton remodeling molecules.

    Science.gov (United States)

    Xu, Liling; Auzins, Arturs; Sun, Xiaolin; Xu, Yinsheng; Harnischfeger, Fiona; Lu, Yun; Li, Zhanguo; Chen, Ying-Hua; Zheng, Wenjie; Liu, Wanli

    2015-08-01

    Sphingolipid- and cholesterol-rich lipid raft microdomains are important in the initiation of BCR signaling. Although it is known that lipid rafts promote the coclustering of BCR and Lyn kinase microclusters within the B cell IS, the molecular mechanism of the recruitment of lipid rafts into the B cell IS is not understood completely. Here, we report that the synaptic recruitment of lipid rafts is dependent on the cytoskeleton-remodeling proteins, RhoA and Vav. Such an event is also efficiently regulated by motor proteins, myosin IIA and dynein. Further evidence suggests the synaptic recruitment of lipid rafts is, by principle, an event triggered by BCR signaling molecules and second messenger molecules. BCR-activating coreceptor CD19 potently enhances such an event depending on its cytoplasmic Tyr421 and Tyr482 residues. The enhancing function of the CD19-PI3K module in synaptic recruitment of lipid rafts is also confirmed in human peripheral blood B cells. Thus, these results improve our understanding of the molecular mechanism of the recruitment of lipid raft microdomains in B cell IS.

  12. Omega-3 Fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment.

    Directory of Open Access Journals (Sweden)

    Samantha P Tull

    2009-08-01

    Full Text Available Inflammation is a physiological response to tissue trauma or infection, but leukocytes, which are the effector cells of the inflammatory process, have powerful tissue remodelling capabilities. Thus, to ensure their precise localisation, passage of leukocytes from the blood into inflamed tissue is tightly regulated. Recruitment of blood borne neutrophils to the tissue stroma occurs during early inflammation. In this process, peptide agonists of the chemokine family are assumed to provide a chemotactic stimulus capable of supporting the migration of neutrophils across vascular endothelial cells, through the basement membrane of the vessel wall, and out into the tissue stroma. Here, we show that, although an initial chemokine stimulus is essential for the recruitment of flowing neutrophils by endothelial cells stimulated with the inflammatory cytokine tumour necrosis factor-alpha, transit of the endothelial monolayer is regulated by an additional and downstream stimulus. This signal is supplied by the metabolism of the omega-6-polyunsaturated fatty acid (n-6-PUFA, arachidonic acid, into the eicosanoid prostaglandin-D(2 (PGD(2 by cyclooxygenase (COX enzymes. This new step in the neutrophil recruitment process was revealed when the dietary n-3-PUFA, eicosapentaenoic acid (EPA, was utilised as an alternative substrate for COX enzymes, leading to the generation of PGD(3. This alternative series eicosanoid inhibited the migration of neutrophils across endothelial cells by antagonising the PGD(2 receptor. Here, we describe a new step in the neutrophil recruitment process that relies upon a lipid-mediated signal to regulate the migration of neutrophils across endothelial cells. PGD(2 signalling is subordinate to the chemokine-mediated activation of neutrophils, but without the sequential delivery of this signal, neutrophils fail to penetrate the endothelial cell monolayer. Importantly, the ability of the dietary n-3-PUFA, EPA, to inhibit this process not

  13. Recruitment of Older Adults: Success May Be in the Details

    Science.gov (United States)

    McHenry, Judith C.; Insel, Kathleen C.; Einstein, Gilles O.; Vidrine, Amy N.; Koerner, Kari M.; Morrow, Daniel G.

    2015-01-01

    Purpose: Describe recruitment strategies used in a randomized clinical trial of a behavioral prospective memory intervention to improve medication adherence for older adults taking antihypertensive medication. Results: Recruitment strategies represent 4 themes: accessing an appropriate population, communication and trust-building, providing comfort and security, and expressing gratitude. Recruitment activities resulted in 276 participants with a mean age of 76.32 years, and study enrollment included 207 women, 69 men, and 54 persons representing ethnic minorities. Recruitment success was linked to cultivating relationships with community-based organizations, face-to-face contact with potential study participants, and providing service (e.g., blood pressure checks) as an access point to eligible participants. Seventy-two percent of potential participants who completed a follow-up call and met eligibility criteria were enrolled in the study. The attrition rate was 14.34%. Implications: The projected increase in the number of older adults intensifies the need to study interventions that improve health outcomes. The challenge is to recruit sufficient numbers of participants who are also representative of older adults to test these interventions. Failing to recruit a sufficient and representative sample can compromise statistical power and the generalizability of study findings. PMID:22899424

  14. Review on hard coral recruitment (Cnidaria: Scleractinia in Colombia

    Directory of Open Access Journals (Sweden)

    Luisa F. Dueñas

    2011-12-01

    Full Text Available Recruitment, defined and measured as the incorporation of new individuals (i.e. coral juveniles into a population, is a fundamentalprocess for ecologists, evolutionists and conservationists due to its direct effect on population structure and function. Because most coralpopulations are self-feeding, a breakdown in recruitment would lead to local extinction. Recruitment indirectly affects both renewal andmaintenance of existing and future coral communities, coral reef biodiversity (bottom-up effect and therefore coral reef resilience. This process has been used as an indirect measure of individual reproductive success (fitness and is the final stage of larval dispersal leading to population connectivity. As a result, recruitment has been proposed as an indicator of coral-reef health in marine protected areas, as well as a central aspect of the decision-making process concerning management and conservation. The creation of management plans to promote impact mitigation, rehabilitation and conservation of the Colombian coral reefs is a necessity that requires firstly, a review and integration of existing literature on scleractinian coral recruitment in Colombia and secondly, larger scale field studies. This motivated us to summarize and analyze all existing information on coral recruitment to determine the state of knowledge, isolate patterns, identify gaps, and suggest future lines of research.

  15. Strategies for Successful Recruitment of Pregnant Patients Into Clinical Trials.

    Science.gov (United States)

    Sutton, Elizabeth F; Cain, Loren E; Vallo, Porsha M; Redman, Leanne M

    2017-03-01

    Clinical research in the pregnant population allows for delivery of quality, evidence-based care in obstetrics. However, in recent years, the field of obstetrics has faced severe challenges in the recruitment of the pregnant population into clinical trials, a struggle also shared by several other medical disciplines. We candidly describe our failure to recruit a healthy population of overweight and obese pregnant women in their first trimester. We were then able to glean unsuccessful and successful recruitment approaches and improve our recruitment effort by autopsy of failed strategies and with guidance from a survey disseminated to improve our understanding of community feelings about participating in research while pregnant. These "lessons learned" taught us that active recruitment within this population is a necessity; that is, direct (face-to-face discussions at obstetric appointments) compared with indirect (flyers and general emails) modalities and that prenatal care provider support of the proposed research study is vital to a patient's willingness to participate. By implementation of "lessons learned," we describe how we successfully recruited a similar pregnant population 1 year later. The Clinical Trials related to our article are as follows: 1) Expecting Success: NCT01610752, https://clinicaltrials.gov/ct2/show/NCT01610752; 2) MomEE: NCT01954342, https://clinicaltrials.gov/ct2/show/NCT01954342; and 3) Participate While Pregnant Survey: NCT02699632, https://clinicaltrials.gov/ct2/show/NCT02699632.

  16. The Transcriptional Repressive Activity of KRAB Zinc Finger Proteins Does Not Correlate with Their Ability to Recruit TRIM28

    Science.gov (United States)

    Murphy, Kristin E.; Shylo, Natalia A.; Alexander, Katherine A.; Churchill, Angela J.; Copperman, Cecilia; García-García, María J.

    2016-01-01

    KRAB domain Zinc finger proteins are one of the most abundant families of transcriptional regulators in higher vertebrates. The prevailing view is that KRAB domain proteins function as potent transcriptional repressors by recruiting TRIM28 and promoting heterochromatin spreading. However, the extent to which all KRAB domain proteins are TRIM28-dependent transcriptional repressors is currently unclear. Our studies on mouse ZFP568 revealed that TRIM28 recruitment by KRAB domain proteins is not sufficient to warrant transcriptional repressive activity. By using luciferase reporter assays and yeast two-hybrid experiments, we tested the ability of ZFP568 and other mouse KRAB domain proteins to repress transcription and bind TRIM28. We found that some mouse KRAB domain proteins are poor transcriptional repressors despite their ability to recruit TRIM28, while others showed strong KRAB-dependent transcriptional repression, but no TRIM28 binding. Together, our results show that the transcriptional repressive activity of KRAB-ZNF proteins does not correlate with their ability to recruit TRIM28, and provide evidence that KRAB domains can regulate transcription in a TRIM28-independent fashion. Our findings challenge the current understanding of the molecular mechanisms used by KRAB domain proteins to control gene expression and highlight that a high percentage of KRAB domain proteins in the mouse genome differ from the consensus KRAB sequence at amino acid residues that are critical for TRIM28 binding and/or repressive activity. PMID:27658112

  17. Between hearth and labor market: the recruitment of peasant women in the Andes.

    Science.gov (United States)

    Radcliffe, S A

    1990-01-01

    To cover subsistence requirements, peasant women from the Peruvian Andes increasingly are being forced to engage in income-generating activities, including domestic service, marketing, manufacturing, and herding. In many cases, recruitment into waged labor involves migration from rural communities. Case studies of the placement of peasant women in external labor markets illustrate the complex micro- and macro-level factors that determine the mix of productive and reproductive labor. The sexual division of labor in the domestic economy and community is the critical in regulating the length of absence of peasant women from the home, the types of jobs taken, and the migratory destination. In 1 such case study, 56 women from the village of Kallarayan (all of whom had migrated at some point) were interviewed during 13 months of fieldwork in 1984-85. There is no paid employment in Kallarayan, so 14% of the village's population is involved in migration to urban areas or commercial agricultural areas in jungle valleys at any point. Male migration is high in the 11-40-year age group, but becomes seasonal once men marry. Female migrants tend to remain away from the village for longer periods, but are almost exclusively single. Recruitment of peasant women into paid labor is achieved by 5 types of agents: family, godparents and friends, authority figures, recruiting agents, and employers. Peasant girls under 15 years of age tend to be allocated to external labor markets (largely domestic services) by parents and godparents; after 15 years, however, when children are considered to reach adulthood, there is a shift toward self-motivated migration or recruitment by employers and agents. The eldest daughter typically enters migration at age 14 years and sacrifices her education, while younger siblings remain in the home longer. In all but the poorest families, female migration for waged labor ends with marriage.

  18. Zebrafish cyclin Dx is required for development of motor neuron progenitors, and its expression is regulated by hypoxia-inducible factor 2α.

    Science.gov (United States)

    Lien, Huang-Wei; Yuan, Rey-Yue; Chou, Chih-Ming; Chen, Yi-Chung; Hung, Chin-Chun; Hu, Chin-Hwa; Hwang, Sheng-Ping L; Hwang, Pung-Pung; Shen, Chia-Ning; Chen, Chih-Lung; Cheng, Chia-Hsiung; Huang, Chang-Jen

    2016-06-21

    Cyclins play a central role in cell-cycle regulation; in mammals, the D family of cyclins consists of cyclin D1, D2, and D3. In Xenopus, only homologs of cyclins D1 and D2 have been reported, while a novel cyclin, cyclin Dx (ccndx), was found to be required for the maintenance of motor neuron progenitors during embryogenesis. It remains unknown whether zebrafish possess cyclin D3 or cyclin Dx. In this study, we identified a zebrafish ccndx gene encoding a protein which can form a complex with Cdk4. Through whole-mount in situ hybridization, we observed that zccndx mRNA is expressed in the motor neurons of hindbrain and spinal cord during development. Analysis of a 4-kb promoter sequence of the zccndx gene revealed the presence of HRE sites, which can be regulated by HIF2α. Morpholino knockdown of zebrafish Hif2α and cyclin Dx resulted in the abolishment of isl1 and oligo2 expression in the precursors of motor neurons, and also disrupted axon growth. Overexpression of cyclin Dx mRNA in Hif2α morphants partially rescued zccndx expression. Taken together, our data indicate that zebrafish cyclin Dx plays a role in maintaining the precursors of motor neurons.

  19. Honokiol, a phytochemical from the Magnolia plant, inhibits photocarcinogenesis by targeting UVB-induced inflammatory mediators and cell cycle regulators: development of topical formulation.

    Science.gov (United States)

    Vaid, Mudit; Sharma, Som D; Katiyar, Santosh K

    2010-11-01

    To develop newer and more effective chemopreventive agents for skin cancer, we assessed the effect of honokiol, a phytochemical from the Magnolia plant, on ultraviolet (UV) radiation-induced skin tumorigenesis using the SKH-1 hairless mouse model. Topical treatment of mice with honokiol in a hydrophilic cream-based topical formulation before or after UVB (180 mJ/cm(2)) irradiation resulted in a significant protection against photocarcinogenesis in terms of tumor multiplicity (28-60%, P skin samples from the tumor-bearing mice were analyzed for inflammatory mediators, cell cycle regulators and survival signals using immunostaining, western blotting and enzyme-linked immunosorbent assay. Treatment with honokiol significantly inhibited UVB-induced expression of cyclooxygenase-2, prostaglandin E(2) (P skin as well as in skin tumors. Western blot analysis revealed that honokiol: (i) inhibited the levels of cyclins D1, D2 and E and associated cyclin-dependent kinases (CDKs)2, CDK4 and CDK6, (ii) upregulated Cip/p21 and Kip/p27 and (iii) inhibited the levels of phosphatidylinositol 3-kinase and the phosphorylation of Akt at Ser(473) in UVB-induced skin tumors. Together, our results indicate that honokiol holds promise for the prevention of UVB-induced skin cancer by targeting inflammatory mediators, cell cycle regulators and cell survival signals in UVB-exposed skin.

  20. Cdk1 Phosphorylates Drosophila Sas-4 to Recruit Polo to Daughter Centrioles and Convert Them to Centrosomes.

    Science.gov (United States)

    Novak, Zsofia A; Wainman, Alan; Gartenmann, Lisa; Raff, Jordan W

    2016-06-20

    Centrosomes and cilia are organized by a centriole pair comprising an older mother and a younger daughter. Centriole numbers are tightly regulated, and daughter centrioles (which assemble in S phase) cannot themselves duplicate or organize centrosomes until they have passed through mitosis. It is unclear how this mitotic "centriole conversion" is regulated, but it requires Plk1/Polo kinase. Here we show that in flies, Cdk1 phosphorylates the conserved centriole protein Sas-4 during mitosis. This creates a Polo-docking site that helps recruit Polo to daughter centrioles and is required for the subsequent recruitment of Asterless (Asl), a protein essential for centriole duplication and mitotic centrosome assembly. Point mutations in Sas-4 that prevent Cdk1 phosphorylation or Polo docking do not block centriole disengagement during mitosis, but block efficient centriole conversion and lead to embryonic lethality. These observations can explain why daughter centrioles have to pass through mitosis before they can duplicate and organize a centrosome.

  1. Effect of adaptability of field army recruits to psychological education

    Directory of Open Access Journals (Sweden)

    Meng-xue ZHAO

    2015-07-01

    Full Text Available Objective To explore the effect of psychological education adaptability on the mental quality and mental health of recruits of field army units. Methods A total number of 1244 recruits who joined the army in 2012 were tested with Mental Quality Questionnaire of Armyman (MQQA, Symptom Checklist 90 (SCL-90, Self-rating Anxiety Scale (SAS, Selfrating Depression Scale (SDS, State-Trait Anxiety Inventory (STAI, and self-compiled questionnaire for adaptability psychological education. 568 recruits received adaptability psychological education for 10 times (sessions in the experimental group, and 676 in the control group did not receive the education. Results After intervention, each dimension score of experimental and control groups on MQQA significantly increased (P0.05. Psychological education showed a significant effect on improving mental quality (P0.05. After education, the anxiety, depression, state-trait anxiety scores of the two groups reduced significantly (P<0.001; compared with the control group, the anxious emotion was effectively relieved by psychological education in experimental group (P<0.001. The recruits in the experimental group showed significant difference in 30 subjective evaluation items between before- and after-education periods (P<0.001. Conclusions The adaptability psychological education has a significant effect on promoting the mental quality, mental health, emotional state and positive cognition of the recruits in field army units. DOI: 10.11855/j.issn.0577-7402.2015.06.15

  2. Dietary intake and stress fractures among elite male combat recruits

    Directory of Open Access Journals (Sweden)

    Moran Daniel S

    2012-03-01

    Full Text Available Abstract Background Appropriate and sufficient dietary intake is one of the main requirements for maintaining fitness and health. Inadequate energy intake may have a negative impact on physical performance which may result in injuries among physically active populations. The purpose of this research was to evaluate a possible relationship between dietary intake and stress fracture occurrence among combat recruits during basic training (BT. Methods Data was collected from 74 combat recruits (18.2 ± 0.6 yrs in the Israeli Defense Forces. Data analyses included changes in anthropometric measures, dietary intake, blood iron and calcium levels. Measurements were taken on entry to 4-month BT and at the end of BT. The occurrence of stress reaction injury was followed prospectively during the entire 6-month training period. Results Twelve recruits were diagnosed with stress fracture in the tibia or femur (SF group. Sixty two recruits completed BT without stress fractures (NSF. Calcium and vitamin D intakes reported on induction day were lower in the SF group compared to the NSF group-38.9% for calcium (589 ± 92 and 964 ± 373 mg·d-1, respectively, p -1, respectively, p Conclusions The development of stress fractures in young recruits during combat BT was associated with dietary deficiency before induction and during BT of mainly vitamin D and calcium. For the purpose of intervention, the fact that the main deficiency is before induction will need special consideration.

  3. TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment.

    Science.gov (United States)

    Orinska, Zane; Bulanova, Elena; Budagian, Vadim; Metz, Martin; Maurer, Marcus; Bulfone-Paus, Silvia

    2005-08-01

    Mast cells play an important role in host defense against various pathogens, but their role in viral infection has not been clarified in detail. dsRNA, synthesized by various types of viruses and mimicked by polyinosinic-polycytidylic acid (poly(I:C)) is recognized by Toll-like receptor 3 (TLR3). In this study, we demonstrate that poly(I:C) injection in vivo potently stimulates peritoneal mast cells to up-regulate a number of different costimulatory molecules. Therefore, we examined the expression and the functional significance of TLR3 activation in mast cells. Mast cells express TLR3 on the cell surface and intracellularly. After stimulation of mast cells with poly(I:C) and Newcastle disease virus (NDV), TLR3 is phosphorylated and the expression of key antiviral response cytokines (interferon beta, ISG15) and chemokines (IP10, RANTES) is upregulated. Interestingly, mast cells activated via TLR3-poly(I:C) potently stimulate CD8+ T-cell recruitment. Indeed, mast-cell-deficient mice (KitW/KitW-v) given an intraperitoneal injection of poly(I:C) show a decreased CD8+ T-cell recruitment, whereas granulocytes normally migrate to the peritoneal cavity. Mast-cell reconstitution of KitW/KitW-v mice normalizes the CD8+ T-cell influx. Thus, mast cells stimulated through engagement of TLR3 are potent regulators of CD8+ T-cell activities in vitro and in vivo.

  4. Heterogeneity in IRB policies with regard to disclosures about payment for participation in recruitment materials.

    Science.gov (United States)

    Wright, Megan S; Robertson, Christopher T

    2014-01-01

    Although the Federal Common Rule requires that informed consent documents include all material information, it does not specify the content of materials used to recruit human subjects. In particular, there is no federal regulation relating to how payment for research participation is to be advertised. Rather, the FDA has issued guidance, advising researchers not to emphasize payment information. In order to determine how IRBs have interpreted this guidance, we coded the policies of the top 100 institutions by receipt of NIH funding, in order to determine whether they require, permit, or forbid researchers to disclose the amount of compensation in their recruitment materials. We found that the vast majority of institutions implicitly or explicitly permit such disclosures; however, there are a significant number of IRBs at each extreme, some discouraging or forbidding with others encouraging or mandating such disclosures. Such heterogeneity in local regulations suggests that IRB discretion may be imposing costs on human subjects and the scientific enterprise that outweigh the benefits. We suggest that this heterogeneity should be resolved towards a national consensus on permissibility.

  5. Dynamic recruitment of active proteasomes into polyglutamine initiated inclusion bodies.

    Science.gov (United States)

    Schipper-Krom, Sabine; Juenemann, Katrin; Jansen, Anne H; Wiemhoefer, Anne; van den Nieuwendijk, Rianne; Smith, Donna L; Hink, Mark A; Bates, Gillian P; Overkleeft, Hermen; Ovaa, Huib; Reits, Eric

    2014-01-01

    Neurodegenerative disorders such as Huntington's disease are hallmarked by neuronal intracellular inclusion body formation. Whether proteasomes are irreversibly recruited into inclusion bodies in these protein misfolding disorders is a controversial subject. In addition, it has been proposed that the proteasomes may become clogged by the aggregated protein fragments, leading to impairment of the ubiquitin-proteasome system. Here, we show by fluorescence pulse-chase experiments in living cells that proteasomes are dynamically and reversibly recruited into inclusion bodies. As these recruited proteasomes remain catalytically active and accessible to substrates, our results challenge the concept of proteasome sequestration and impairment in Huntington's disease, and support the reported absence of proteasome impairment in mouse models of Huntington's disease.

  6. The Dynamics of Protest Recruitment through an Online Network

    CERN Document Server

    Gonzalez-Bailon, Sandra; Rivero, Alejandro; Moreno, Yamir

    2011-01-01

    The recent wave of mobilizations in the Arab world and across Western countries has generated much discussion on how digital media is connected to the diffusion of protests. We examine that connection using data from the surge of mobilizations that took place in Spain in May 2011. We study recruitment patterns in the Twitter network and find evidence of social influence and complex contagion. We identify the network position of early participants (i.e. the leaders of the recruitment process) and of the users who acted as seeds of message cascades (i.e. the spreaders of information). We find that early participants cannot be characterized by a typical topological position but spreaders tend to me more central to the network. These findings shed light on the connection between online networks, social contagion, and collective dynamics, and offer an empirical test to the recruitment mechanisms theorized in formal models of collective action.

  7. Institutional Context and E-recruitment Practices of Danish Organisations

    DEFF Research Database (Denmark)

    Holm, Anna B.

    2014-01-01

    on interpretive methods and the inductive analysis of data. The data were collected from a number of sources, such as exploratory interviews, observations, websites and other secondary material from 2008-2013. Findings - The findings indicate that recruitment practices are strongly influenced by changes stemming......Purpose - Up to now, there has been little research on the impact of the external environment on recruitment practices of organizations, and in part it lags behind practice. This paper attempts to rectify this by studying recent changes in recruitment practices of Danish organizations...... transformed and reviewed its practices to a great extent due to the changes in how individuals search for employment and expect to be hired. Research limitations/implications - The empirical part of this study is limited to Denmark, and its economic, social, and cultural domains, yet the research design can...

  8. Potential applications of immunoassays in studies of flatfish recruitment

    Science.gov (United States)

    Feller, Robert J.

    The fisheries recruitment-stock problem, a lack of correlation between measures of reproductive output of the parent stock and recruitment to the fishery, has several potential biotic and abiotic causes. Immunoassays may be useful in examining several aspects of this and several other problems in flatfish ecology: stock identification, parasitism and disease, and trophic interactions. Given stage-specific antisera capable of recognozing antigenic moieties of, for instance, eggs, larvae, or newly-settled juveniles, it is possible to screen stomach contents of many putative predators ( e.g., shrimp or crabs) rapidly for the presence and amounts of platfish prey. This trophic application of immunological methods has great promise for measuring loss of potential recruits to predation. All immunoassays are limited by the quality of antisera used and the researcher's ability to interpret quantitative data in an ecologically meaningful way. Key references for applications of immunoassays in fish-related questions are provided with recommendations for their utilization.

  9. Does a code make a difference – assessing the English code of practice on international recruitment

    Directory of Open Access Journals (Sweden)

    Mensah Kwadwo

    2009-04-01

    global code: without a clear link between explicit objectives of a code, and relevant monitoring capacity, it is not possible to judge the actual impact of a code. A second message for policy-makers is that attempts to use a single country code in other countries where there are a multiplicity of independent, private-sector health care employers, or where there is a federated political and regulatory structure, will be a much more challenging and complex issue than in England, which has one major public sector health care employer and one national point of entry for regulated health professionals. Finally, there is a message about the importance of the "visibility" of any recruitment code – for policy-makers, employers and potential recruits. The Department of Health Code has a good level of recognition in the National Health Service, but would benefit from better dissemination in low-income countries, particularly in Africa, together with further consultation on the appropriateness of its provisions in specific countries. To achieve high visibility and recognition of any global code will be a much bigger challenge.

  10. Cancer epidemiology and patient recruitment for hadron therapy.

    Science.gov (United States)

    Engels, H; Wambersie, A

    1999-06-01

    Patient recruitment is an important issue in the feasibility study of a hadron therapy programme such as Med-AUSTRON. Data on cancer incidence in Europe, Austria, and neighbouring countries are reviewed for the most frequent tumors suitable for charged particle therapy. From these data, the numbers of potential patients suitable for MED-AUSTRON are derived for each tumor site by applying the coefficients proposed in the EULIMA-1992 feasibility study. Whatever the assumptions made, a sufficient and adequate recruitment for MED-AUSTRON can be expected. However, an appropriate referring system has to be established within Austria and also in the neighbouring countries.

  11. Desert ants achieve reliable recruitment across noisy interactions.

    Science.gov (United States)

    Razin, Nitzan; Eckmann, Jean-Pierre; Feinerman, Ofer

    2013-05-06

    We study how desert ants, Cataglyphis niger, a species that lacks pheromone-based recruitment mechanisms, inform each other about the presence of food. Our results are based on automated tracking that allows us to collect a large database of ant trajectories and interactions. We find that interactions affect an ant's speed within the nest. Fast ants tend to slow down, whereas slow ones increase their speed when encountering a faster ant. Faster ants tend to exit the nest more frequently than slower ones. So, if an ant gains enough speed through encounters with others, then she tends to leave the nest and look for food. On the other hand, we find that the probability for her to leave the nest depends only on her speed, but not on whether she had recently interacted with a recruiter that has found the food. This suggests a recruitment system in which ants communicate their state by very simple interactions. Based on this assumption, we estimate the information-theoretical channel capacity of the ants' pairwise interactions. We find that the response to the speed of an interacting nest-mate is very noisy. The question is then how random interactions with ants within the nest can be distinguished from those interactions with a recruiter who has found food. Our measurements and model suggest that this distinction does not depend on reliable communication but on behavioural differences between ants that have found the food and those that have not. Recruiters retain high speeds throughout the experiment, regardless of the ants they interact with; non-recruiters communicate with a limited number of nest-mates and adjust their speed following these interactions. These simple rules lead to the formation of a bistable switch on the level of the group that allows the distinction between recruitment and random noise in the nest. A consequence of the mechanism we propose is a negative effect of ant density on exit rates and recruitment success. This is, indeed, confirmed by our

  12. Leadership strategies in transport team recruitment and retention.

    Science.gov (United States)

    Caron, Stephen

    2011-01-01

    The goal of the pediatric registered nurse-registered respiratory therapist (RN-RRT) transport team is to safely transport the pediatric patients requiring transport to a tertiary facility. Attrition of RN-RRT team members threatened the future existence of this invaluable service. This research project examined recruitment and retention practices through use of an interview with a manager of a successful transport organization and a world café with key stakeholders involved in pediatric transport. Main findings included the impact of education, leadership and teamwork in addressing strategies to improve recruitment and retention practices of the RN-RRT transport team.

  13. Optimal counterterrorism and the recruitment effect of large terrorist attacks

    DEFF Research Database (Denmark)

    Jensen, Thomas

    2011-01-01

    We analyze a simple dynamic model of the interaction between terrorists and authorities. Our primary aim is to study optimal counterterrorism and its consequences when large terrorist attacks lead to a temporary increase in terrorist recruitment. First, we show that an increase in counterterrorism...... makes it more likely that terrorist cells plan small rather than large attacks and therefore may increase the probability of a successful attack. Analyzing optimal counterterrorism we see that the recruitment effect makes authorities increase the level of counterterrorism after large attacks. Therefore...

  14. Recruitment of ethnic minorities for public health research

    DEFF Research Database (Denmark)

    Nielsen, Annemette Ljungdalh; Jervelund, Signe Smith; Villadsen, Sarah Fredsted

    2017-01-01

    Aims: This paper examines the importance of recruitment site in relation to the recruitment of ethnic minorities into health research. It presents a synthesis of experiences drawn from six interlinked Danish studies which applied different methods and used healthcare facilities and educational...... study designs also depended on the possibility of singling out specific locations with a high proportion of the relevant ethnic minority target population. Conclusions:The findings, though based on a small number of cases, indicate that health professionals and healthcare institutions, despite...

  15. Transforming Personnel Accessions: Recruiting in the E-Business World

    Science.gov (United States)

    2002-04-09

    Geoff Helt of the Red McCombs School of Business at The University of Texas. Additionally, Professor Helt granted me permission to use any of the...to recruit qualified persons for the Active Army and the US Army Reserve (USAR).1 This research looks at many different aspects and opinions of the new...digital divide clearly impacts any transformation to an eBusiness, eEnterprise, and eCommerce etc. model for recruiting. This research will not assume the

  16. Osteoblast recruitment routes in human cancellous bone remodeling

    DEFF Research Database (Denmark)

    Kristensen, Helene B; Levin Andersen, Thomas; Marcussen, Niels

    2014-01-01

    It is commonly proposed that bone forming osteoblasts recruited during bone remodeling originate from bone marrow perivascular cells, bone remodeling compartment canopy cells, or bone lining cells. However, an assessment of osteoblast recruitment during adult human cancellous bone remodeling......-terminal peptide versus osterix, and (ii) canopy cell densities, found to decline with age, and canopy-capillary contacts above eroded surfaces correlated positively with osteoblast density on bone-forming surfaces. Furthermore, we showed that bone remodeling compartment canopies arise from a mesenchymal envelope...

  17. Recruitment and Retention of Patients into Emergency Medicine Clinical Trials

    Science.gov (United States)

    Cofield, Stacey; Conwit, Robin; Barsan, William; Quinn, James

    2010-01-01

    The emergency medicine and pre-hospital environments are unlike any other clinical environments and require special consideration to allow the successful implementation of clinical trials. This article reviews the specific issues involved in Emergency Medicine Clinical Trials (EMCT), and provides strategies from emergency medicine and non-emergency medicine trials to maximize recruitment and retention. While the evidence supporting some of these strategies is deficient, addressing recruitment and retention issues with specific strategies will help researchers deal with these issues in their funding applications and in turn develop the necessary infrastructure to participate in emergency medicine clinical trials. PMID:21040112

  18. Complexity and simplification in understanding recruitment in benthic populations

    KAUST Repository

    Pineda, Jesús

    2008-11-13

    Research of complex systems and problems, entities with many dependencies, is often reductionist. The reductionist approach splits systems or problems into different components, and then addresses these components one by one. This approach has been used in the study of recruitment and population dynamics of marine benthic (bottom-dwelling) species. Another approach examines benthic population dynamics by looking at a small set of processes. This approach is statistical or model-oriented. Simplified approaches identify "macroecological" patterns or attempt to identify and model the essential, "first-order" elements of the system. The complexity of the recruitment and population dynamics problems stems from the number of processes that can potentially influence benthic populations, including (1) larval pool dynamics, (2) larval transport, (3) settlement, and (4) post-settlement biotic and abiotic processes, and larval production. Moreover, these processes are non-linear, some interact, and they may operate on disparate scales. This contribution discusses reductionist and simplified approaches to study benthic recruitment and population dynamics of bottom-dwelling marine invertebrates. We first address complexity in two processes known to influence recruitment, larval transport, and post-settlement survival to reproduction, and discuss the difficulty in understanding recruitment by looking at relevant processes individually and in isolation. We then address the simplified approach, which reduces the number of processes and makes the problem manageable. We discuss how simplifications and "broad-brush first-order approaches" may muddle our understanding of recruitment. Lack of empirical determination of the fundamental processes often results in mistaken inferences, and processes and parameters used in some models can bias our view of processes influencing recruitment. We conclude with a discussion on how to reconcile complex and simplified approaches. Although it

  19. Expected Time To Recruitment In A Two Grade Manpower System

    Directory of Open Access Journals (Sweden)

    J.SRIDHARAN,

    2014-02-01

    Full Text Available In this paper a two graded organization is considered in which depletion of manpower occurs due to its policy decisions. Three mathematical models are constructed by assuming the loss of man-hours and the inter-decision times form an order statistics. Mean and variance of time to recruitment are obtained using an univariate recruitment policy based on shock model approach and the analytical results are numerically illustrated by assuming different distributions for the thresholds. The influence of the nodal parameters on the system characteristics is studied and relevant conclusions are presented.

  20. Investigating the effect of recruitment variability on length-based recruitment indices for antarctic krill using an individual-based population dynamics model.

    Directory of Open Access Journals (Sweden)

    Stéphane Thanassekos

    Full Text Available Antarctic krill (Euphausia superba; herein krill is monitored as part of an on-going fisheries observer program that collects length-frequency data. A krill feedback management programme is currently being developed, and as part of this development, the utility of data-derived indices describing population level processes is being assessed. To date, however, little work has been carried out on the selection of optimum recruitment indices and it has not been possible to assess the performance of length-based recruitment indices across a range of recruitment variability. Neither has there been an assessment of uncertainty in the relationship between an index and the actual level of recruitment. Thus, until now, it has not been possible to take into account recruitment index uncertainty in krill stock management or when investigating relationships between recruitment and environmental drivers. Using length-frequency samples from a simulated population - where recruitment is known - the performance of six potential length-based recruitment indices is assessed, by exploring the index-to-recruitment relationship under increasing levels of recruitment variability (from ±10% to ±100% around a mean annual recruitment. The annual minimum of the proportion of individuals smaller than 40 mm (F40 min, % was selected because it had the most robust index-to-recruitment relationship across differing levels of recruitment variability. The relationship was curvilinear and best described by a power law. Model uncertainty was described using the 95% prediction intervals, which were used to calculate coverage probabilities and assess model performance. Despite being the optimum recruitment index, the performance of F40 min degraded under high (>50% recruitment variability. Due to the persistence of cohorts in the population over several years, the inclusion of F40 min values from preceding years in the relationship used to estimate recruitment in a given year

  1. Investigating the effect of recruitment variability on length-based recruitment indices for antarctic krill using an individual-based population dynamics model.

    Science.gov (United States)

    Thanassekos, Stéphane; Cox, Martin J; Reid, Keith

    2014-01-01

    Antarctic krill (Euphausia superba; herein krill) is monitored as part of an on-going fisheries observer program that collects length-frequency data. A krill feedback management programme is currently being developed, and as part of this development, the utility of data-derived indices describing population level processes is being assessed. To date, however, little work has been carried out on the selection of optimum recruitment indices and it has not been possible to assess the performance of length-based recruitment indices across a range of recruitment variability. Neither has there been an assessment of uncertainty in the relationship between an index and the actual level of recruitment. Thus, until now, it has not been possible to take into account recruitment index uncertainty in krill stock management or when investigating relationships between recruitment and environmental drivers. Using length-frequency samples from a simulated population - where recruitment is known - the performance of six potential length-based recruitment indices is assessed, by exploring the index-to-recruitment relationship under increasing levels of recruitment variability (from ±10% to ±100% around a mean annual recruitment). The annual minimum of the proportion of individuals smaller than 40 mm (F40 min, %) was selected because it had the most robust index-to-recruitment relationship across differing levels of recruitment variability. The relationship was curvilinear and best described by a power law. Model uncertainty was described using the 95% prediction intervals, which were used to calculate coverage probabilities and assess model performance. Despite being the optimum recruitment index, the performance of F40 min degraded under high (>50%) recruitment variability. Due to the persistence of cohorts in the population over several years, the inclusion of F40 min values from preceding years in the relationship used to estimate recruitment in a given year improved its

  2. ZEB2 mediates multiple pathways regulating cell proliferation, migration, invasion, and apoptosis in glioma.

    Directory of Open Access Journals (Sweden)

    Songtao Qi

    Full Text Available BACKGROUND: The aim of the present study was to analyze the expression of Zinc finger E-box Binding homeobox 2 (ZEB2 in glioma and to explore the molecular mechanisms of ZEB2 that regulate cell proliferation, migration, invasion, and apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Expression of ZEB2 in 90 clinicopathologically characterized glioma patients was analyzed by immunohistochemistry. Furthermore, siRNA targeting ZEB2 was transfected into U251 and U87 glioma cell lines in vitro and proliferation, migration, invasion, and apoptosis were examined separately by MTT assay, Transwell chamber assay, flow cytometry, and western blot. RESULTS: The expression level of ZEB2 protein was significantly increased in glioma tissues compared to normal brain tissues (P<0.001. In addition, high levels of ZEB2 protein were positively correlated with pathology grade classification (P = 0.024 of glioma patients. Knockdown of ZEB2 by siRNA suppressed cell proliferation, migration and invasion, as well as induced cell apoptosis in glioma cells. Furthermore, ZEB2 downregulation was accompanied by decreased expression of CDK4/6, Cyclin D1, Cyclin E, E2F1, and c-myc, while p15 and p21 were upregulated. Lowered expression of ZEB2 enhanced E-cadherin levels but also inhibited β-Catenin, Vimentin, N-cadherin, and Snail expression. Several apoptosis-related regulators such as Caspase-3, Caspase-6, Caspase-9, and Cleaved-PARP were activated while PARP was inhibited after ZEB2 siRNA treatment. CONCLUSION: Overexpression of ZEB2 is an unfavorable factor that may facilitate glioma progression. Knockdown ZEB2 expression by siRNA suppressed cell proliferation, migration, invasion and promoted cell apoptosis in glioma cells.

  3. 某部新兵集训期心理状况与情绪调节方式及认知偏向的关系%Relationship of mental status with emotion regulation and cognitive bias in a troop of recruits during training

    Institute of Scientific and Technical Information of China (English)

    陈秀秀; 左昕; 彭李; 于永菊; 刘波涛; 边晨; 李敏

    2016-01-01

    目的 研究某部新兵集训2个月时应激水平、情绪体验特点与情绪调节方式和认知偏向的关系.方法 采用心理应激自评问卷(psychological stress self-evaluation test,PSET)、正性负性情感量表(positive and negative affect scale,PANAS)、情绪调节方式问卷(emotion regulation scale,ERS)和正性负性认知偏向量表(attention to positive and negative inventory scale,APNIS)对某部集训期新兵1 600人进行整群抽样调查.结果 ①某部新兵心理应激T分为(50.04±10.00).不同文化程度新兵心理应激水平差异有统计学意义(F =3.25,P<0.05).②心理应激高分组在负性情绪、负性认知偏向和表达抑制上均显著高于心理应激低分组(P<0.01),在正性情绪、正性认知偏向和认知重评上显著低于低分组(P<0.01).③总体心理应激水平与正性情绪、正性认知偏向和认知重评呈显著负相关(r值分别为-0.49、-0.32、-0.21,P<0.01);与负性情绪、负性认知偏向和表达抑制呈显著正相关(r值分别为0.48、0.34、0.12,P<0.01).④正性情绪、负性情绪、负性认知偏向和正性认知偏向可有效预测心理应激水平,总解释率为37.6%.⑤认知重评在正性情绪与心理应激水平之间起调节作用.结论 新兵的心理应激水平与情绪体验特点、情绪调节方式之间密切相关.

  4. SUMO: regulating the regulator

    Directory of Open Access Journals (Sweden)

    Bossis Guillaume

    2006-06-01

    Full Text Available Abstract Post-translational modifiers of the SUMO (Small Ubiquitin-related Modifier family have emerged as key regulators of protein function and fate. While the past few years have seen an enormous increase in knowledge on SUMO enzymes, substrates, and consequences of modification, regulation of SUMO conjugation is far from being understood. This brief review will provide an overview on recent advances concerning (i the interplay between sumoylation and other post-translational modifications at the level of individual targets and (ii global regulation of SUMO conjugation and deconjugation.

  5. The role of social media in recruiting for clinical trials in pregnancy.

    Directory of Open Access Journals (Sweden)

    Mahvash Shere

    Full Text Available Recruitment of women in the periconceptional period to clinical studies using traditional advertising through medical establishments is difficult and slow. Given the widespread use of the internet as a source for medical information and research, we analyze the impact of social media in the second phase of an ongoing randomized, open-label clinical trial among pregnant women. This study aims to assess the effectiveness of social media as a recruitment tool through the comparison of diverse recruitment techniques in two different phases of the trial.Recruitment in Phase 1 of the study consisted solely of traditional healthcare-based sources. This was compared to Phase 2 of the study where traditional recruitment was continued and expanded, while social media was used as a supplementary source. Yearly recruitment and recruitment rates in the two phases were compared using the Mann Whitney U test. The contributions of each recruitment source to overall recruitment were analyzed, and the impact of potential confounders on recruitment rate was evaluated using a multiple regression and Interrupted Time Series Analysis.In the first phase of the study, with over 56 months of recruitment using traditional sources, 35 women were enrolled in the study, resulting in a mean rate of ±0.62 recruits/month. In the 6 months implementing recruitment through social media, 45 women were recruited, for a 12-fold higher rate of ±7.5 recruits/month. Attrition rates remained constant, suggesting that social media had a positive impact on recruitment. The Interrupted Time Series Analysis detected a significant difference in recruitment after the intervention of social media (p<0.0001 with an evident increase in the number of recruits observed after the use of social media.Clinicians and scientists recruiting for clinical studies should learn how to use online social media platforms to improve recruitment rates, thus increasing recruitment efficiency and cost-effectiveness.

  6. Recruitment of African American and Latino Adolescent Couples in Romantic Relationships: Lessons Learned

    Science.gov (United States)

    Rivera, Angelic; Watnick, Dana; Bauman, Laurie J.

    2011-01-01

    Background: There is considerable literature on effective engagement strategies for recruiting adolescents individually for health research studies, but literature on recruiting adolescent couples is new an minimal. Purpose: This paper describes the recruitment strategies used for Teen Connections (TC), a longitudinal study that recruited 139…

  7. Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression

    NARCIS (Netherlands)

    Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

    2015-01-01

    AIMS: Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte recruit

  8. Recruiting New Teachers: Campaign Response 1988-1992. Executive Summary.

    Science.gov (United States)

    Harris, Louis

    This study evaluated the impact of a public service advertising campaign conducted for Recruiting New Teachers, Inc (RNT). The study surveyed a national sample of 2,750 individuals who called the RNT toll-free number mentioned in public service advertising and returned information about their educational background and teaching interests. The…

  9. Study Healthy Ageing and Intellectual Disabilities: Recruitment and Design

    Science.gov (United States)

    Hilgenkamp, Thessa I. M.; Bastiaanse, Luc P.; Hermans, Heidi; Penning, Corine; van Wijck, Ruud; Evenhuis, Heleen M.

    2011-01-01

    Problems encountered in epidemiologic health research in older adults with intellectual disabilities (ID) are how to recruit a large-scale sample of participants and how to measure a range of health variables in such a group. This cross-sectional study into healthy ageing started with founding a consort of three large care providers with a total…

  10. Mechanism of neutrophil recruitment to the lung after pulmonary contusion.

    Science.gov (United States)

    Hoth, J Jason; Wells, Jonathan D; Hiltbold, Elizabeth M; McCall, Charles E; Yoza, Barbara K

    2011-06-01

    Blunt chest trauma resulting in pulmonary contusion is a common but poorly understood injury. We previously demonstrated that lung contusion activates localized and systemic innate immune mechanisms and recruits neutrophils to the injured lung. We hypothesized that the innate immune and inflammatory activation of neutrophils may figure prominently in the response to lung injury. To investigate this, we used a model of pulmonary contusion in the mouse that is similar to that observed clinically in humans and evaluated postinjury lung function and pulmonary neutrophil recruitment. Comparisons were made between injured mice with and without neutrophil depletion. We further examined the role of chemokines and adhesion receptors in neutrophil recruitment to the injured lung. We found that lung injury and resultant physiological dysfunction after contusion were dependent on the presence of neutrophils in the alveolar space. We show that CXCL1, CXCL2/3, and CXCR2 are involved in neutrophil recruitment to the lung after injury and that intercellular adhesion molecule 1 is locally expressed and actively participates in this process. Injured gp91-deficient mice showed improved lung function, indicating that oxidant production by neutrophil NADPH oxidase mediates lung dysfunction after contusion. These data suggest that both neutrophil presence and function are required for lung injury after lung contusion.

  11. Biofilm recruitment of Vibrio cholerae by matrix proteolysis.

    Science.gov (United States)

    Duperthuy, Marylise; Uhlin, Bernt Eric; Wai, Sun Nyunt

    2015-11-01

    The appearance of bacterial biofilms involves secretion of polysaccharides and proteins that form an extracellular matrix embedding the bacteria. Proteases have also been observed, but their role has remained unclear. Smith and co-workers have now found that proteolysis can contribute to further recruitment of bacteria to Vibrio cholerae biofilms.

  12. Factors Affecting Recruitment into Child and Adolescent Psychiatry Training

    Science.gov (United States)

    Shaw, Jon A.; Lewis, John E.; Katyal, Shalini

    2010-01-01

    Objective: The authors studied the factors affecting the recruitment into child and adolescent psychiatry training in the United States. Methods: Medical students (n = 154) and general and child and adolescent psychiatry residents (n = 111) completed a questionnaire to evaluate career choice in child psychiatry (n = 265). Results: Compared with…

  13. Internet College Recruiting and Marketing: Web Promotion, Techniques and Law.

    Science.gov (United States)

    Mentz, George; Whiteside, Richard

    2003-01-01

    After using online recruiting techniques, researching Internet marketing, and consulting companies regarding search engine ranking, the authors made many observations about the evolution of the Internet as a tool for educating students and targeting enrollment for new admission. Article presents recommendations for using Internet to promote online…

  14. HEFCE Staff Recruitment Incentives: Consultation on "Golden Hellos".

    Science.gov (United States)

    Higher Education Funding Council for England, Bristol.

    This "consultation" notifies interested parties of the plans by the Higher Education Funding Council for England (HEFCE) to introduce recruitment incentives for teaching staff in higher education, also known as "golden hellos." These are being introduced from 2003-2004 to encourage new entrants to teaching in higher education in subject areas…

  15. Similarity Attracts: An Analysis of Recruitment Decisions in Academia

    Science.gov (United States)

    Roebken, Heinke

    2010-01-01

    The finding and the recruiting of scientists have been a long-standing issue in higher education. Due to the dearth of reliable evidence on scholarly potential at an early stage of a scientist's career, the hiring department often has to look for alternative assessment criteria. Drawing on the similarity-attraction theory, it is hypothesized that…

  16. 76 FR 12418 - Recruitment Notice for the Taxpayer Advocacy Panel

    Science.gov (United States)

    2011-03-07

    ... Internal Revenue Service Recruitment Notice for the Taxpayer Advocacy Panel AGENCY: Internal Revenue... Advocacy Panel (TAP) Members. DATES: March 14, 2011 through April 29, 2011. FOR FURTHER INFORMATION CONTACT... nation's tax agency by applying to be members of the Taxpayer Advocacy Panel (TAP). The mission of...

  17. Buoyed by Divestment Victories, Activists Protest CIA Recruiting.

    Science.gov (United States)

    Greene, Elizabeth

    1987-01-01

    Inspired by victories in the South African divestment movement and fueled by the Iran-Contra affair, student activists are intensifying the perennial crusade to ban Central Intelligence Agency (CIA) recruiters from campuses, but other students dislike the interference and the CIA says that job-seekers are increasing. (MSE)

  18. Recruiting and Selecting Principals. ERIC Digest Series Number EA27.

    Science.gov (United States)

    Klauke, Amy

    This ERIC Digest is an overview of the process of recruiting and selecting principals. Criteria for selecting a principal should include problem analysis, organizational ability, decisiveness, effective communication skills, and stress tolerance, along with personal qualities such as dedication, creativity, and enthusiasm. Innovative steps that…

  19. Minority Recruitment and Retention for Universities: Bilingual Special Education Faculty

    Science.gov (United States)

    Brice, Alejandro E.

    2012-01-01

    Recruitment and retention of minority faculty in bilingual special education is a perilous task. Research has shown that minority faculty/teachers are able to provide emotional support, mentor students, serve as role models, create a positive climate, provide diverse views, increase collaboration among faculty and teachers, and work with…

  20. Student Recruitment and Relationship Marketing--Convergence or Contortion?

    Science.gov (United States)

    Beneke, J.

    2011-01-01

    This article investigates the intersection of student recruitment and relationship marketing in the public high education sector. They key objectives of this analysis are to understand if a strategic fit exists and whether South African institutions are indeed embracing the principles of relationship marketing in order to optimise their student…

  1. Resilience and Critical Stock Size in a Stochastic Recruitment Model

    NARCIS (Netherlands)

    Grasman, J.; Huiskes, M.J.

    2001-01-01

    A stochastic model for fish recruitment is fitted to data after performing an age-structured stock assessment. The main aim is to investigate the relation between safe levels of spawning stock size and fish stock resilience. Resilience indicators, such as stock recovery time and the frequency that a

  2. Transparency in Academic Recruitment: A Problematic Tool for Gender Equality?

    NARCIS (Netherlands)

    Brink, M.C.L. van den; Benschop, Y.W.M.; Jansen, W.H.M.

    2010-01-01

    Gender research has made a call for more transparency and accountability in academic recruitment and selection in order to overcome the inequality practices that have led to an underrepresentation of women among full professors. This paper provides insight into the multiple ways in which the notions

  3. Conceptual Change as an Agent for Teacher Recruitment

    Science.gov (United States)

    Swanson, Peter

    2011-01-01

    The purpose of this study was to recruit undergraduate students into language teaching by investigating students' perceptions of second-language learning and becoming a foreign language (FL) teacher in a rural context. The investigator used two quantitative surveys and qualitative interviews with undergraduates in second- and third-semester FL…

  4. Dilemmas of a Newly Recruited Academic Qualified Professor: A Case

    Science.gov (United States)

    Agrawal, Anand

    2015-01-01

    This case describes the situation of a newly recruited academic professor who volunteered to teach a course on Research Methods to first-term MBA students in a practitioner-oriented case method Business School. Research Methods is a unique course due to its relevance not only in business but also across all graduate programs. Instructional and…

  5. 45 CFR 1170.42 - Admissions and recruitment.

    Science.gov (United States)

    2010-10-01

    ... impairs sensory, manual, or speaking skills, the test results accurately reflect the applicant's aptitude... subjected to discrimination in admission or recruitment by a recipient to which this subpart applies. (b... make use of any test or criterion for admission that has a disproportionate, adverse effect...

  6. 7 CFR 15b.30 - Admissions and recruitment.

    Science.gov (United States)

    2010-01-01

    ... handicap that impairs sensory, manual, or speaking skills, the test results accurately reflect the... be subjected to discrimination in admission or recruitment by a recipient to which this subpart... admitted; (2) May not make use of any test or criterion for admission that has a disproportionate,...

  7. 22 CFR 142.42 - Admissions and recruitment.

    Science.gov (United States)

    2010-04-01

    ... who has a handicap that impairs sensory, manual, or speaking skills, the test results accurately... denied admission or be subjected to discrimination in admission or recruitment by a recipient to which... persons who may be admitted; (2) May not make use of any test or criterion for admission that has...

  8. 22 CFR 217.42 - Admissions and recruitment.

    Science.gov (United States)

    2010-04-01

    ... applicant who has a handicap that impairs sensory, manual, or speaking skills, the test results accurately... denied admission or be subjected to discrimination in admission or recruitment by a recipient to which... who may be admitted; (2) May not make use of any test or criterion for admission that has...

  9. 45 CFR 84.42 - Admissions and recruitment.

    Science.gov (United States)

    2010-10-01

    ... administered to an applicant who has a handicap that impairs sensory, manual, or speaking skills, the test... basis of handicap, be denied admission or be subjected to discrimination in admission or recruitment by... proportion of handicapped persons who may be admitted; (2) May not make use of any test or criterion...

  10. Recruiting and Retaining Army Nurses: An Annotated Bibliography

    Science.gov (United States)

    1988-12-01

    rather than active duty). Also, identify ways in which nursing organizations could assist DOD in recruiting, develop videos of current nursing... nursing organizations . Slewitzke, Connie L., Vail, James D., and McMarlin, Susan A., US Army Reserve and National Guard Survey: An Analysis of Factors

  11. 75 FR 9028 - Recruitment Notice for the Taxpayer Advocacy Panel

    Science.gov (United States)

    2010-02-26

    ... improving IRS service and customer satisfaction. The TAP serves as an advisory body to the Secretary of the... Internal Revenue Service Recruitment Notice for the Taxpayer Advocacy Panel AGENCY: Internal Revenue... the Treasury and the Internal Revenue Service (IRS) are inviting individuals to help improve...

  12. 77 FR 13390 - Recruitment Notice for the Taxpayer Advocacy Panel

    Science.gov (United States)

    2012-03-06

    ... improving IRS service and customer satisfaction. The TAP serves as an advisory body to the Secretary of the... Internal Revenue Service Recruitment Notice for the Taxpayer Advocacy Panel AGENCY: Internal Revenue... the Treasury and the Internal Revenue Service (IRS) are inviting individuals to help improve...

  13. Study healthy ageing and intellectual disabilities : Recruitment and design

    NARCIS (Netherlands)

    Hilgenkamp, Thessa I. M.; Bastiaanse, Luc P.; Hermans, Heidi; Penning, Corine; van Wijck, Ruud; Evenhuis, Heleen M.

    2011-01-01

    Problems encountered in epidemiologic health research in older adults with intellectual disabilities (ID) are how to recruit a large-scale sample of participants and how to measure a range of health variables in such a group. This cross-sectional study into healthy ageing started with founding a con

  14. Hemispheric Differences in the Recruitment of Semantic Processing Mechanisms

    Science.gov (United States)

    Kandhadai, Padmapriya; Federmeier, Kara D.

    2010-01-01

    This study examined how the two cerebral hemispheres recruit semantic processing mechanisms by combining event-related potential measures and visual half-field methods in a word priming paradigm in which semantic strength and predictability were manipulated using lexically associated word pairs. Activation patterns on the late positive complex…

  15. Recruiting Diverse Students and Enabling Them to Succeed in STEM

    Science.gov (United States)

    Tremmel, Michael J.; Pre-Major in Astronomy Program

    2015-01-01

    Improving the diversity within the rapidly growing fields of science, technology, engineering, and mathematics (STEM) has become a forefront issue facing collegiate departments today. It is well known that there are large gaps in the participation and performance of minorities, women, and low-income students within these fields and that special attention must be paid in order to close this gap. Since 2005, the Pre-Major in Astronomy Program (Pre-MAP) at the University of Washington (UW) Department of Astronomy has made a concentrated effort to recruit and retain underrepresented undergraduates in STEM, at which it has been very successful. Of course, recruiting these students can be a challenge, as is creating a curriculum and atmosphere that enables undergraduates to successfully participate in real astronomy research during their first or second year at a four-year college. Pre-MAP recruits a significant population of minorities and women into the program. The structure of the seminar is intended to not only provide necessary skills and experience, but also create a collaborative and supportive atmosphere among each cohort. I will discuss the recruitment practices of Pre-MAP as well as the structure of the seminar and how it addresses the goal of early participation and success in STEM research and course work.The intent of this talk is to share our methods so that more programs like Pre-MAP can be adopted successfully in other institutions.

  16. An interim analysis of recruitment to the COLOFOL trial

    DEFF Research Database (Denmark)

    Wille-Jørgensen, Peer; Laurberg, S.; Pahlman, L.

    2009-01-01

    Objective To analyse the ongoing process of recruiting patients into a multicenter randomized trial on follow-up after curative surgery for colorectal cancer. The trial is registered in Clinical Trials Registration. Method Prospective registration of all operated patients as well as inclusions (c...

  17. Recruitment Evaluation of a Preschooler Obesity-Prevention Intervention

    Science.gov (United States)

    Skouteris, Helen; Hill, Briony; McCabe, Marita; Swinburn, Boyd; Sacher, Paul; Chadwick, Paul

    2014-01-01

    The aim of this paper was to compare the recruitment strategies of two recent studies that focused on the parental influences on childhood obesity during the preschool years. The first study was a randomised controlled trial (RCT) of the Mind, Exercise, Nutrition?…?Do It! 2-4 obesity prevention programme and the second was a longitudinal cohort…

  18. Recruitment to Physics and Mathematics Teaching: A Personality Problem?

    Science.gov (United States)

    Smithers, Alan; Hill, Susan

    1989-01-01

    Results of a British study indicate that, among potential applicants (N=177), a small demand exists for a proposed science education degree program. Findings suggest that recruitment of science and math teachers may be hampered because the satisfactions provided by teaching are unlike those sought by science and math specialists. (IAH)

  19. Essential Elements for Recruitment and Retention: Generation Y

    Science.gov (United States)

    Luscombe, Jenna; Lewis, Ioni; Biggs, Herbert C.

    2013-01-01

    Purpose: Generation Y (Gen Y) is the newest and largest generation entering the workforce. Gen Y may differ from previous generations in work-related characteristics which may have recruitment and retention repercussions. Currently, limited theoretically-based research exists regarding Gen Y's work expectations and goals in relation to…

  20. University and Course Choice: Implications for Positioning, Recruitment and Marketing

    Science.gov (United States)

    Maringe, Felix

    2006-01-01

    Purpose: Higher education environments have become increasingly competitive and institutions have to compete for students in the recruitment markets. With the introduction of student fees, it is hypothesised that potential applicants to HE will increasingly become consumerist. The research upon which this paper was based was aimed at finding out…

  1. The Recruiting Game: Community Colleges Step up to the Plate.

    Science.gov (United States)

    Bus, Ken

    This paper offers advice for ways in which community colleges can approach the challenge of recruiting international students. Community colleges are enjoying a new popularity with overseas students, even though other higher education programs are showing slow growth for this group. According to the paper, it is becoming more common to find…

  2. Why Minority Recruiting Is Alive and Well in Texas.

    Science.gov (United States)

    Selingo, Jeffrey

    1999-01-01

    Capitalizing on the ban on affirmative action in college admissions in Texas, a number of out-of-state colleges are aggressively recruiting in that state and offering generous financial aid packages. Oklahoma was one of the first states to do so. For many students, financial aid makes the difference in college attendance. (MSE)

  3. Waterlogging and canopy interact to control species recruitment in floodplains

    NARCIS (Netherlands)

    Kotowski, Wiktor; Beauchard, Olivier; Opdekamp, Wout; Meire, Patrick; van Diggelen, Rudy

    2010-01-01

    P>1. The extent to which seedling recruitment contributes to local functional diversity depends on the environmental filters operating in a plant community. Classical community assembly models assume that habitat constraints and competition act like hierarchical filters with habitat filtering as the

  4. Military Recruit Training: An Arena for Stress Coping Skills.

    Science.gov (United States)

    1981-03-27

    negative effect on veterans who are manifesting "delayed stress reactions." The common themes of the post-combat syndrome are guilt and self-punishment...task demands and responding to the drill instructor 31 stands in contrast to how recruits respond to the haircut (electric clipper shavings) that they

  5. HEFCE Staff Recruitment Incentives: Consultation on "Golden Hellos".

    Science.gov (United States)

    Higher Education Funding Council for England, Bristol.

    This "consultation" notifies interested parties of the plans by the Higher Education Funding Council for England (HEFCE) to introduce recruitment incentives for teaching staff in higher education, also known as "golden hellos." These are being introduced from 2003-2004 to encourage new entrants to teaching in higher education…

  6. Paid and unpaid benefits. Strategies for nurse recruitment and retention.

    Science.gov (United States)

    Klemm, R; Schreiber, E J

    1992-03-01

    One of the biggest problems facing hospital administrators is the recruitment and retention of nursing staff. The authors examine how a sampling of hospitals are meeting this challenge and describe important tangible and intangible benefits that can curb nursing turnover. This study defines ways to boost employee morale and cut administrative costs.

  7. Building Authenticity in Social Media Tools to Recruit Postsecondary Students

    Science.gov (United States)

    Sandlin, Jean Kelso; Peña, Edlyn Vallejo

    2014-01-01

    An increasing number of institutions utilize social media tools, including student-written blogs, on their admission websites in an effort to enhance authenticity in their recruitment marketing materials. This study offers a framework for understanding what contributes to prospective college students' perceptions of social media authenticity…

  8. 41 CFR 60-20.2 - Recruitment and advertisement.

    Science.gov (United States)

    2010-07-01

    ... advertisement. 60-20.2 Section 60-20.2 Public Contracts and Property Management Other Provisions Relating to... OF LABOR 20-SEX DISCRIMINATION GUIDELINES § 60-20.2 Recruitment and advertisement. (a) Employers... occupation qualification. (b) Advertisement in newspapers and other media for employment must not express...

  9. Recruiting Languages and Lifeworlds for Border-Crossing Compositions

    Science.gov (United States)

    Skerrett, Allison; Bomer, Randy

    2013-01-01

    In this article, we show how two transnational youth, with the instructional support of their teacher, recruited their languages and lifeworlds, particularly their border-crossing experiences, as tools for engaging with school-based literacy practices. We analyze literary texts that the students composed, showing how the students' uses of…

  10. High School Profiles: Application of HTML for Recruitment Decision Making

    Science.gov (United States)

    Johnson, Iryna Y.

    2008-01-01

    Because high school graduates are many colleges' primary target population, information on high school students' performance and sociodemographic characteristics becomes important for the recruitment process. This article introduces an HTML application (referred to here as the High School Profile) that arranges high school information and makes…

  11. An Integrated Approach to Recruiting and Retaining Appalachian Engineering Students

    Science.gov (United States)

    Winn, Gary; Hensel, Robin; Curtis, Reagan; Taylor, Lydotta M.; Cilento, Gene

    2012-01-01

    Recruiting and retaining Appalachian engineering students is difficult for a variety of ecological and cultural reasons. At West Virginia University an NSF STEP grant has allowed the development of specific interventions to evolve from an ecological model we describe here. The interventions include web-based, realistic engineering design exercises…

  12. Workers in Agribusiness: Profile, Images, Recruitment, Mobility, and Occupations.

    Science.gov (United States)

    Taylor, Lee, Ed.; Leagans, J. Paul, Ed.

    Designed and conducted by a team of professors and research associates at New York State College of Agriculture, this study focuses on five primary areas of concern: (1) profile of firms and workers, (2) images of agribusiness work, (3) recruitment, (4) occupational mobility, and (5) agribusiness occupations and projections. Findings reveal that…

  13. Protein misfolding specifies recruitment to cytoplasmic inclusion bodies.

    Science.gov (United States)

    Bersuker, Kirill; Brandeis, Michael; Kopito, Ron R

    2016-04-25

    Inclusion bodies (IBs) containing aggregated disease-associated proteins and polyubiquitin (poly-Ub) conjugates are universal histopathological features of neurodegenerative diseases. Ub has been proposed to target proteins to IBs for degradation via autophagy, but the mechanisms that govern recruitment of ubiquitylated proteins to IBs are not well understood. In this paper, we use conditionally destabilized reporters that undergo misfolding and ubiquitylation upon removal of a stabilizing ligand to examine the role of Ub conjugation in targeting proteins to IBs that are composed of an N-terminal fragment of mutant huntingtin, the causative protein of Huntington's disease. We show that reporters are excluded from IBs in the presence of the stabilizing ligand but are recruited to IBs after ligand washout. However, we find that Ub conjugation is not necessary to target reporters to IBs. We also report that forced Ub conjugation by the Ub fusion degradation pathway is not sufficient for recruitment to IBs. Finally, we find that reporters and Ub conjugates are stable at IBs. These data indicate that compromised folding states, rather than conjugation to Ub, can specify recruitment to IBs.

  14. Leadership Success in Schools: Planning, Recruitment, and Socialization

    Science.gov (United States)

    Normore, Anthony H.

    2004-01-01

    This article presents findings from an exploratory study that compared and contrasted leadership succession planning in two large Ontario school districts with focus on three themes: (a) leadership succession planning, (b) recruitment and selection, and (c) professional and organizational socialization of school administrators. Among the findings…

  15. Roles of lung epithelium in neutrophil recruitment during pneumococcal pneumonia.

    Science.gov (United States)

    Yamamoto, Kazuko; Ahyi, Ayele-Nati N; Pepper-Cunningham, Zachary A; Ferrari, Joseph D; Wilson, Andrew A; Jones, Matthew R; Quinton, Lee J; Mizgerd, Joseph P

    2014-02-01

    Epithelial cells line the respiratory tract and interface with the external world. Epithelial cells contribute to pulmonary inflammation, but specific epithelial roles have proven difficult to define. To discover unique epithelial activities that influence immunity during infection, we generated mice with nuclear factor-κB RelA mutated throughout all epithelial cells of the lung and coupled this approach with epithelial cell isolation from infected and uninfected lungs for cell-specific analyses of gene induction. The RelA mutant mice appeared normal basally, but in response to pneumococcus in the lungs they were unable to rapidly recruit neutrophils to the air spaces. Epithelial cells expressed multiple neutrophil-stimulating cytokines during pneumonia, all of which depended on RelA. Cytokine expression by nonepithelial cells was unaltered by the epithelial mutation of RelA. Epithelial cells were the predominant sources of CXCL5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), whereas nonepithelial cells were major sources for other neutrophil-activating cytokines. Epithelial RelA mutation decreased whole lung levels of CXCL5 and GM-CSF during pneumococcal pneumonia, whereas lung levels of other neutrophil-recruiting factors were unaffected. Defective neutrophil recruitment in epithelial mutant mice could be rescued by administration of CXCL5 or GM-CSF. These results reveal a specialized immune function for the pulmonary epithelium, the induction of CXCL5 and GM-CSF, to accelerate neutrophil recruitment in the infected lung.

  16. Personnel Recruitment and Retention in Rural America: A Growing Problem.

    Science.gov (United States)

    Helge, Doris I.; Marrs, Lawrence W.

    1982-01-01

    The article presents successful strategies based on A. Maslow's hierarchy for recruiting special education personnel for rural school systems. Techniques for selling a district to prospective teachers and administrators are discussed and suggestions for integrating newcomers are covered. (Author/SB)

  17. An Analytic Strategy To Assist Institutional Recruitment and Marketing Efforts.

    Science.gov (United States)

    DesJardins, Stephen L.

    2002-01-01

    Fit a statistical model to historical college enrollment data, testing whether the model could accurately predict enrollment out-of-sample, and used the results to segment admitted students into groups so that different recruitment and marketing interventions could be applied to encourage enrollment. (EV)

  18. Invited commentary: recruiting for epidemiologic studies using social media.

    Science.gov (United States)

    Allsworth, Jenifer E

    2015-05-15

    Social media-based recruitment for epidemiologic studies has the potential to expand the demographic and geographic reach of investigators and identify potential participants more cost-effectively than traditional approaches. In fact, social media are particularly appealing for their ability to engage traditionally "hard-to-reach" populations, including young adults and low-income populations. Despite their great promise as a tool for epidemiologists, social media-based recruitment approaches do not currently compare favorably with gold-standard probability-based sampling approaches. Sparse data on the demographic characteristics of social media users, patterns of social media use, and appropriate sampling frames limit our ability to implement probability-based sampling strategies. In a well-conducted study, Harris et al. (Am J Epidemiol. 2015;181(10):737-746) examined the cost-effectiveness of social media-based recruitment (advertisements and promotion) in the Contraceptive Use, Pregnancy Intention, and Decisions (CUPID) Study, a cohort study of 3,799 young adult Australian women, and the approximate representativeness of the CUPID cohort. Implications for social media-based recruitment strategies for cohort assembly, data accuracy, implementation, and human subjects concerns are discussed.

  19. Leukocytes require ADAM10 but not ADAM17 for their migration and inflammatory recruitment into the alveolar space.

    Science.gov (United States)

    Pruessmeyer, Jessica; Hess, Franz Martin; Alert, Henriette; Groth, Esther; Pasqualon, Tobias; Schwarz, Nicole; Nyamoya, Stella; Kollert, Jos; van der Vorst, Emiel; Donners, Marjo; Martin, Christian; Uhlig, Stefan; Saftig, Paul; Dreymueller, Daniela; Ludwig, Andreas

    2014-06-26

    Inflammation is a key process in various diseases, characterized by leukocyte recruitment to the inflammatory site. This study investigates the role of a disintegrin and a metalloproteinase (ADAM) 10 and ADAM17 for leukocyte migration in vitro and in a murine model of acute pulmonary inflammation. Inhibition experiments or RNA knockdown indicated that monocytic THP-1 cells and primary human neutrophils require ADAM10 but not ADAM17 for efficient chemokine-induced cell migration. Signaling and adhesion events that are linked to cell migration such as p38 and ρ GTPase-family activation, F-actin polymerization, adhesion to fibronectin, and up-regulation of α5 integrin were also dependent on ADAM10 but not ADAM17. This was confirmed with leukocytes isolated from mice lacking either ADAM10 or ADAM17 in all hematopoietic cells (vav 1 guanine nucleotide exchange factor [Vav]-Adam10(-/-) or Vav-Adam17(-/-) mice). In lipopolysaccharide-induced acute pulmonary inflammation, alveolar recruitment of neutrophils and monocytes was transiently increased in Vav-Adam17(-/-) but steadily reduced in Vav-Adam10(-/-) mice. This deficit in alveolar leukocyte recruitment was also observed in LysM-Adam10(-/-) mice lacking ADAM10 in myeloid cells and correlated with protection against edema formation. Thus, with regard to leukocyte migration, leukocyte-expressed ADAM10 but not ADAM17 displays proinflammatory activities and may therefore serve as a target to limit inflammatory cell recruitment.

  20. Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.

    KAUST Repository

    Foley, Joseph W

    2013-10-20

    BACKGROUND: High-occupancy target (HOT) regions are compact genome loci occupied by many different transcription factors (TFs). HOT regions were initially defined in invertebrate model organisms, and we here show that they are a ubiquitous feature of the human gene-regulation landscape. RESULTS: We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs. The sequence motif associated with any given TF\\'s direct DNA binding is somewhat predictive of its empirical occupancy, but a great deal of occupancy occurs at sites without the TF\\'s motif, implying indirect recruitment by another TF whose motif is present. CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.

  1. Integrin-beta3 clusters recruit clathrin-mediated endocytic machinery in the absence of traction force

    Science.gov (United States)

    Yu, Cheng-han; Rafiq, Nisha Bte Mohd; Cao, Fakun; Zhou, Yuhuan; Krishnasamy, Anitha; Biswas, Kabir Hassan; Ravasio, Andrea; Chen, Zhongwen; Wang, Yu-Hsiu; Kawauchi, Keiko; Jones, Gareth E.; Sheetz, Michael P.

    2015-01-01

    The turnover of integrin receptors is critical for cell migration and adhesion dynamics. Here we find that force development at integrins regulates adaptor protein recruitment and endocytosis. Using mobile RGD (Arg-Gly-Asp) ligands on supported lipid membranes (RGD membranes) and rigid RGD ligands on glass (RGD-glass), we find that matrix force-dependent integrin signals block endocytosis. Dab2, an adaptor protein of clathrin-mediated endocytosis, is not recruited to activated integrin-beta3 clusters on RGD-glass; however, it is recruited to integrin-mediated adhesions on RGD membranes. Further, when force generation is inhibited on RGD-glass, Dab2 binds to integrin-beta3 clusters. Dab2 binding to integrin-beta3 excludes other adhesion-related adaptor proteins, such as talin. The clathrin-mediated endocytic machinery combines with Dab2 to facilitate the endocytosis of RGD-integrin-beta3 clusters. From these observations, we propose that loss of traction force on ligand-bound integrin-beta3 causes recruitment of Dab2/clathrin, resulting in endocytosis of integrins. PMID:26507506

  2. Recruitment of Factor H as a Novel Complement Evasion Strategy for Blood-Stage Plasmodium falciparum Infection.

    Science.gov (United States)

    Kennedy, Alexander T; Schmidt, Christoph Q; Thompson, Jennifer K; Weiss, Greta E; Taechalertpaisarn, Tana; Gilson, Paul R; Barlow, Paul N; Crabb, Brendan S; Cowman, Alan F; Tham, Wai-Hong

    2016-02-01

    The human complement system is the frontline defense mechanism against invading pathogens. The coexistence of humans and microbes throughout evolution has produced ingenious molecular mechanisms by which microorganisms escape complement attack. A common evasion strategy used by diverse pathogens is the hijacking of soluble human complement regulators to their surfaces to afford protection from complement activation. One such host regulator is factor H (FH), which acts as a negative regulator of complement to protect host tissues from aberrant complement activation. In this report, we show that Plasmodium falciparum merozoites, the invasive form of the malaria parasites, actively recruit FH and its alternative spliced form FH-like protein 1 when exposed to human serum. We have mapped the binding site in FH that recognizes merozoites and identified Pf92, a member of the six-cysteine family of Plasmodium surface proteins, as its direct interaction partner. When bound to merozoites, FH retains cofactor activity, a key function that allows it to downregulate the alternative pathway of complement. In P. falciparum parasites that lack Pf92, we observed changes in the pattern of C3b cleavage that are consistent with decreased regulation of complement activation. These results also show that recruitment of FH affords P. falciparum merozoites protection from complement-mediated lysis. Our study provides new insights on mechanisms of immune evasion of malaria parasites and highlights the important function of surface coat proteins in the interplay between complement regulation and successful infection of the host.

  3. Methodological approaches to staff recruitment at labour market

    Directory of Open Access Journals (Sweden)

    V.V. Bozhkova

    2016-12-01

    Full Text Available The aim of article. The purpose of the article is to improve and formalize methodological approaches to staff recruitment at labour markets. The results of the analysis. The integral result of the study is the following. The author systematized the main problems of the staff recruitment according to the subjects of the employment process (or their place of origin: 1 on the part of the applicants: - inflated / deflated self-esteem; - incorrect understanding of their own capabilities, abilities and aptitudes; - incorrect assessment of their own physical and mental health; - incorrect formulation of expectations from the new position (inflated, deflated or inadequate; - willful false responses in the survey (in order to get a better position; - inaccurate responses in the survey (due to misunderstanding of the nature of questions; - popular or prestigious professions preference, but not those to which the applicant has more talent; - providing inaccurate personal information (false or willful; 2 on the part of employers: - wrong definition of the criteria list to be met by applicants; - inflated requirements to applicants; - the best quality choice among applicants, but not employees for teamwork; 3 on the part of Heads of Labour Markets (as well as employment agencies: - lack of adequate supervision of Labour Market specialists activity (i.e., the quality level in the staff recruitment for specific employers orders; - lack of motivation to improve the skill level of subordinates; 4 on the part of experts on recruitment: - recruitment of the best available applicants, rather than looking for the applicants who fully meet the requirements; - not precise understanding of the requirements for applicants; - the use of inappropriate methods for the applicants recruitment. Such systematization of major problems can determine the direction of management decisions aimed at improving the process of recruitment more accurately. The essential characteristics

  4. Assessment of Nutritional Status and Fatigue Among Army Recruits During the Army Common Recruit Training Course: Part A: Catering Services and Diet

    Science.gov (United States)

    2005-06-01

    request and 18% were “not suited to be a soldier” [3]. A lower limb injury was sustained in 21% (276) of the recruits, with tibial fracture or... periostitis accounting for 36% of these injuries. Injured recruits were ten times less likely to complete recruit training. Such attrition costs thousands

  5. Evaluating outcome-correlated recruitment and geographic recruitment bias in a respondent-driven sample of people who inject drugs in Tijuana, Mexico

    OpenAIRE

    Rudolph, Abby E; Gaines, Tommi L.; Lozada, Remedios; Vera, Alicia; Brouwer, Kimberly C.

    2014-01-01

    Respondent-driven sampling’s (RDS) widespread use and reliance on untested assumptions suggests a need for new exploratory/diagnostic tests. We assessed geographic recruitment bias and outcome-correlated recruitment among 1048 RDS-recruited people who inject drugs (Tijuana, Mexico).

  6. Desktop software to identify patients eligible for recruitment into a clinical trial: using SARMA to recruit to the ROAD feasibility trial

    Directory of Open Access Journals (Sweden)

    Shaun Treweek

    2010-03-01

    Conclusion An automated recruitment tool can support primary care trials in Scotland and has the potential to support recruitment in other jurisdictions. It offers a low-cost supplement to other trial recruitment methods and is likely to have a much lower screen failure rate than blanket approaches such as mailshots and newspaper campaigns.

  7. Molecular insights into seed dispersal mutualisms driving plant population recruitment

    Science.gov (United States)

    García, Cristina; Grivet, Delphine

    2011-11-01

    Most plant species require mutualistic interactions with animals to fulfil their demographic cycle. In this regard frugivory (i.e., the intake of fruits by animals) enhances natural regeneration by mobilizing a large amount of seeds from source trees to deposition sites across the landscape. By doing so, frugivores move propagules, and the genotypes they harbour creating the spatial, ecological, and genetic environment under which subsequent recruitment proceeds. Recruitment patterns can be envisioned as the result of two density- and distance-dependent processes: seed dispersal and seed/seedling survival (the Janzen-Connell model). Population genetic studies add another layer of complexity for understanding the fate of dispersed propagules: the genetic relatedness among neighbouring seeds within a seed clump, a major outcome of frugivore activity, modifies their chances of germinating and surviving. Yet, we virtually ignore how the spatial distribution of maternal progenies and recruitment patterns relate with each other in frugivore-generated seed rains. Here we focus on the critical role of frugivore-mediated seed dispersal in shaping the spatial distribution of maternal progenies in the seed rain. We first examine which genetic mechanisms underlying recruitment are influenced by the spatial distribution of maternal progenies. Next, we examine those studies depicting the spatial distribution of maternal progenies in a frugivore-generated seed rain. In doing so, we briefly review the most suitable analytical approaches applied to track the contribution of fruiting trees to the seed rain based on molecular data. Then we look more specifically at the role of distinct frugivore guilds in determining maternal genetic correlations and their expected consequences for recruitment patterns. Finally we posit some general conclusions and suggest future research directions that would provide a more comprehensive understanding of the ecological and evolutionary consequences

  8. Visual change detection recruits auditory cortices in early deafness.

    Science.gov (United States)

    Bottari, Davide; Heimler, Benedetta; Caclin, Anne; Dalmolin, Anna; Giard, Marie-Hélène; Pavani, Francesco

    2014-07-01

    Although cross-modal recruitment of early sensory areas in deafness and blindness is well established, the constraints and limits of these plastic changes remain to be understood. In the case of human deafness, for instance, it is known that visual, tactile or visuo-tactile stimuli can elicit a response within the auditory cortices. Nonetheless, both the timing of these evoked responses and the functional contribution of cross-modally recruited areas remain to be ascertained. In the present study, we examined to what extent auditory cortices of deaf humans participate in high-order visual processes, such as visual change detection. By measuring visual ERPs, in particular the visual MisMatch Negativity (vMMN), and performing source localization, we show that individuals with early deafness (N=12) recruit the auditory cortices when a change in motion direction during shape deformation occurs in a continuous visual motion stream. Remarkably this "auditory" response for visual events emerged with the same timing as the visual MMN in hearing controls (N=12), between 150 and 300 ms after the visual change. Furthermore, the recruitment of auditory cortices for visual change detection in early deaf was paired with a reduction of response within the visual system, indicating a shift from visual to auditory cortices of part of the computational process. The present study suggests that the deafened auditory cortices participate at extracting and storing the visual information and at comparing on-line the upcoming visual events, thus indicating that cross-modally recruited auditory cortices can reach this level of computation.

  9. Mediator coordinates PIC assembly with recruitment of CHD1.

    Science.gov (United States)

    Lin, Justin J; Lehmann, Lynn W; Bonora, Giancarlo; Sridharan, Rupa; Vashisht, Ajay A; Tran, Nancy; Plath, Kathrin; Wohlschlegel, James A; Carey, Michael

    2011-10-15

    Murine Chd1 (chromodomain helicase DNA-binding protein 1), a chromodomain-containing chromatin remodeling protein, is necessary for embryonic stem (ES) cell pluripotency. Chd1 binds to nucleosomes trimethylated at histone 3 Lys 4 (H3K4me3) near the beginning of active genes but not to bivalent domains also containing H3K27me3. To address the mechanism of this specificity, we reproduced H3K4me3- and CHD1-stimulated gene activation in HeLa extracts. Multidimensional protein identification technology (MuDPIT) and immunoblot analyses of purified preinitiation complexes (PICs) revealed the recruitment of CHD1 to naive chromatin but enhancement on H3K4me3 chromatin. Studies in depleted extracts showed that the Mediator coactivator complex, which controls PIC assembly, is also necessary for CHD1 recruitment. MuDPIT analyses of CHD1-associated proteins support the recruitment data and reveal numerous components of the PIC, including Mediator. In vivo, CHD1 and Mediator are recruited to an inducible gene, and genome-wide binding of the two proteins correlates well with active gene transcription in mouse ES cells. Finally, coimmunoprecipitation of CHD1 and Mediator from cell extracts can be ablated by shRNA knockdown of a specific Mediator subunit. Our data support a model in which the Mediator coordinates PIC assembly along with the recruitment of CHD1. The combined action of the PIC and H3K4me3 provides specificity in targeting CHD1 to active genes.

  10. Recruitment barriers in a randomized controlled trial from the physicians' perspective – A postal survey

    Directory of Open Access Journals (Sweden)

    Karrer Werner

    2009-03-01

    Full Text Available Abstract Background The feasibility of randomized trials often depends on successful patient recruitment. Although numerous recruitment barriers have been identified it is unclear which of them complicate recruitment most. Also, most surveys have focused on the patients' perspective of recruitment barriers whereas the perspective of recruiting physicians has received less attention. Therefore, our aim was to conduct a postal survey among recruiting physicians of a multi-center trial to weigh barriers according to their impact on recruitment. Methods We identified any potential recruitment barriers from the literature and from our own experience with a multi-center trial of respiratory rehabilitation in patients with chronic obstructive pulmonary disease. We developed and pilot-tested a self-administered questionnaire where recruiting physicians were asked to express their agreement with statements about recruitment barriers on a Likert-type scale from 1 (full agreement with statement = very substantial recruitment barrier to 7 (no agreement with statement = no recruitment barrier. Results 38 of 55 recruiting physicians returned questionnaires (69% response rate, of which 35 could be analyzed (64% useable response rate. Recruiting physicians reported that "time constraints" (median agreement of 3, interquartile range 2–5 had the most negative impact on recruitment followed by "difficulties including identified eligible patients" (median agreement of 5, IQR 3–6. Other barriers such as "trial design barriers", "lack of access to treatment", "individual barriers of recruiting physicians" or "insufficient training of recruiting physicians" were perceived to have little or no impact on patient recruitment. Conclusion Physicians perceived time constraints as the most relevant recruitment barrier in a randomized trial. To overcome recruitment barriers interventions, that are affordable for both industry- and investigator-driven trials, need to be

  11. Cold-Inducible RNA-Binding Protein Bypasses Replicative Senescence in Primary Cells through Extracellular Signal-Regulated Kinase 1 and 2 Activation▿ †

    Science.gov (United States)

    Artero-Castro, Ana; Callejas, Francisco B.; Castellvi, Josep; Kondoh, Hiroshi; Carnero, Amancio; Fernández-Marcos, Pablo J.; Serrano, Manuel; Ramón y Cajal, Santiago; Lleonart, Matilde E.

    2009-01-01

    Embryonic stem cells are immortalized cells whose proliferation rate is comparable to that of carcinogenic cells. To study the expression of embryonic stem cell genes in primary cells, genetic screening was performed by infecting mouse embryonic fibroblasts (MEFs) with a cDNA library from embryonic stem cells. Cold-inducible RNA-binding protein (CIRP) was identified due to its ability to bypass replicative senescence in primary cells. CIRP enhanced extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation, and treatment with an MEK inhibitor decreased the proliferation caused by CIRP. In contrast to CIRP upregulation, CIRP downregulation decreased cell proliferation and resulted in inhibition of phosphorylated ERK1/2 inhibition. This is the first evidence that ERK1/2 activation, through the same mechanism as that described for a Val12 mutant K-ras to induce premature senescence, is able to bypass senescence in the absence of p16INK4a, p21WAF1, and p19ARF upregulation. Moreover, these results show that CIRP functions by stimulating general protein synthesis with the involvement of the S6 and 4E-BP1 proteins. The overall effect is an increase in kinase activity of the cyclin D1-CDK4 complex, which is in accordance with the proliferative capacity of CIRP MEFs. Interestingly, CIRP mRNA and protein were upregulated in a subgroup of cancer patients, a finding that may be of relevance for cancer research. PMID:19158277

  12. Neutrophil-derived CCL3 is essential for the rapid recruitment of dendritic cells to the site of Leishmania major inoculation in resistant mice.

    Directory of Open Access Journals (Sweden)

    Mélanie Charmoy

    2010-02-01

    Full Text Available Neutrophils are rapidly and massively recruited to sites of microbial infection, where they can influence the recruitment of dendritic cells. Here, we have analyzed the role of neutrophil released chemokines in the early recruitment of dendritic cells (DCs in an experimental model of Leishmania major infection. We show in vitro, as well as during infection, that the parasite induced the expression of CCL3 selectively in neutrophils from L. major resistant mice. Neutrophil-secreted CCL3 was critical in chemotaxis of immature DCs, an effect lost upon CCL3 neutralisation. Depletion of neutrophils prior to infection, as well as pharmacological or genetic inhibition of CCL3, resulted in a significant decrease in DC recruitment at the site of parasite inoculation. Decreased DC recruitment in CCL3(-/- mice was corrected by the transfer of wild type neutrophils at the time of infection. The early release of CCL3 by neutrophils was further shown to have a transient impact on the development of a protective immune response. Altogether, we identified a novel role for neutrophil-secreted CCL3 in the first wave of DC recruitment to the site of infection with L. major, suggesting that the selective release of neutrophil-secreted chemokines may regulate the development of immune response to pathogens.

  13. Cypermethrin Induces Macrophages Death through Cell Cycle Arrest and Oxidative Stress-Mediated JNK/ERK Signaling Regulated Apoptosis

    Directory of Open Access Journals (Sweden)

    Fang Huang

    2016-06-01

    Full Text Available Cypermethrin is one of the most highly effective synthetic pyrethroid insecticides. The toxicity of cypermethrin to the reproductive and nervous systems has been well studied. However, little is known about the toxic effect of cypermethrin on immune cells such as macrophages. Here, we investigated the cytotoxicity of cypermethrin on macrophages and the underlying molecular mechanisms. We found that cypermethrin reduced cell viability and induced apoptosis in RAW 264.7 cells. Cypermethrin also increased reactive oxygen species (ROS production and DNA damage in a dose-dependent manner. Moreover, cypermethrin-induced G1 cell cycle arrest was associated with an enhanced expression of p21, wild-type p53, and down-regulation of cyclin D1, cyclin E and CDK4. In addition, cypermethrin treatment activated MAPK signal pathways by inducing c-Jun N-terminal kinase (JNK and extracellular regulated protein kinases 1/2 ERK1/2 phosphorylation, and increased the cleaved poly ADP-ribose polymerase (PARP. Further, pretreatment with antioxidant N-acetylcysteine (NAC effectively abrogated cypermethrin-induced cell cytotoxicity, G1 cell cycle arrest, DNA damage, PARP activity, and JNK and ERK1/2 activation. The specific JNK inhibitor (SP600125 and ERK1/2 inhibitor (PD98059 effectively reversed the phosphorylation level of JNK and ERK1/2, and attenuated the apoptosis. Taken together, these data suggested that cypermethrin caused immune cell death via inducing cell cycle arrest and apoptosis regulated by ROS-mediated JNK/ERK pathway.

  14. Mangiferin Facilitates Islet Regeneration and β-Cell Proliferation through Upregulation of Cell Cycle and β-Cell Regeneration Regulators

    Science.gov (United States)

    Wang, Hai-Lian; Li, Chun-Yang; Zhang, Bin; Liu, Yuan-De; Lu, Bang-Min; Shi, Zheng; An, Na; Zhao, Liang-Kai; Zhang, Jing-Jing; Bao, Jin-Ku; Wang, Yi

    2014-01-01

    Mangiferin, a xanthonoid found in plants including mangoes and iris unguicularis, was suggested in previous studies to have anti-hyperglycemic function, though the underlying mechanisms are largely unknown. This study was designed to determine the therapeutic effect of mangiferin by the regeneration of β-cells in mice following 70% partial pancreatectomy (PPx), and to explore the mechanisms of mangiferin-induced β-cell proliferation. For this purpose, adult C57BL/6J mice after 7–14 days post-PPx, or a sham operation were subjected to mangiferin (30 and 90 mg/kg body weight) or control solvent injection. Mangiferin-treated mice exhibited an improved glycemia and glucose tolerance, increased serum insulin levels, enhanced β-cell hyperplasia, elevated β-cell proliferation and reduced β-cell apoptosis. Further dissection at the molecular level showed several key regulators of cell cycle, such as cyclin D1, D2 and cyclin-dependent kinase 4 (Cdk4) were significantly up-regulated in mangiferin-treated mice. In addition, critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (PDX-1), neurogenin 3 (Ngn3), glucose transporter 2 (GLUT-2), Forkhead box protein O1 (Foxo-1), and glucokinase (GCK), were found to be promoted by mangiferin at both the mRNA and protein expression level. Thus, mangiferin administration markedly facilitates β-cell proliferation and islet regeneration, likely by regulating essential genes in the cell cycle and the process of islet regeneration. These effects therefore suggest that mangiferin bears a therapeutic potential in preventing and/or treating the diabetes. PMID:24853132

  15. Mangiferin Facilitates Islet Regeneration and β-Cell Proliferation through Upregulation of Cell Cycle and β-Cell Regeneration Regulators

    Directory of Open Access Journals (Sweden)

    Hai-Lian Wang

    2014-05-01

    Full Text Available Mangiferin, a xanthonoid found in plants including mangoes and iris unguicularis, was suggested in previous studies to have anti-hyperglycemic function, though the underlying mechanisms are largely unknown. This study was designed to determine the therapeutic effect of mangiferin by the regeneration of β-cells in mice following 70% partial pancreatectomy (PPx, and to explore the mechanisms of mangiferin-induced β-cell proliferation. For this purpose, adult C57BL/6J mice after 7–14 days post-PPx, or a sham operation were subjected to mangiferin (30 and 90 mg/kg body weight or control solvent injection. Mangiferin-treated mice exhibited an improved glycemia and glucose tolerance, increased serum insulin levels, enhanced β-cell hyperplasia, elevated β-cell proliferation and reduced β-cell apoptosis. Further dissection at the molecular level showed several key regulators of cell cycle, such as cyclin D1, D2 and cyclin-dependent kinase 4 (Cdk4 were significantly up-regulated in mangiferin-treated mice. In addition, critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (PDX-1, neurogenin 3 (Ngn3, glucose transporter 2 (GLUT-2, Forkhead box protein O1 (Foxo-1, and glucokinase (GCK, were found to be promoted by mangiferin at both the mRNA and protein expression level. Thus, mangiferin administration markedly facilitates β-cell proliferation and islet regeneration, likely by regulating essential genes in the cell cycle and the process of islet regeneration. These effects therefore suggest that mangiferin bears a therapeutic potential in preventing and/or treating the diabetes.

  16. The mobilization and recruitment of c-kit+ cells contribute to wound healing after surgery.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Takemoto

    Full Text Available Delayed wound healing is a serious clinical problem in patients after surgery. A recent study has demonstrated that bone marrow-derived c-kit-positive (c-kit(+ cells play important roles in repairing and regenerating various tissues and organs. To examine the hypothesis that surgical injury induces the mobilization and recruitment of c-kit+ cells to accelerate wound healing. Mice were subjected to a left pneumonectomy. The mobilization of c-kit+ cells was monitored after surgery. Using green fluorescent protein (GFP(+ bone marrow-transplanted chimera mice, we investigated further whether the mobilized c-kit+ cells were recruited to effect wound healing in a skin puncture model. The group with left pneumonectomies increased the c-kit(+ and CD34(+ stem cells in peripheral blood 24 h after surgery. At 3 days after surgery, the skin wound size was observed to be significantly smaller, and the number of bone marrow-derived GFP(+ cells and GFP(+/c-kit+ cells in the wound tissue was significantly greater in mice that had received pneumonectomies, as compared with those that had received a sham operation. Furthermore, some of these GFP(+ cells were positively expressed specific markers of macrophages (F4/80, endothelial cells (CD31, and myofibroblasts (αSMA. The administration of AMD3100, an antagonist of a stromal-cell derived factor (SDF-1/CXCR4 signaling pathway, reduced the number of GFP(+ cells in wound tissue and completely negated the accelerated wound healing. Surgical injury induces the mobilization and recruitment of c-kit+ cells to contribute to wound healing. Regulating c-kit+ cells may provide a new approach that accelerates wound healing after surgery.

  17. Local IL-17A potentiates early neutrophil recruitment to the respiratory tract during severe RSV infection.

    Directory of Open Access Journals (Sweden)

    Arie Jan Stoppelenburg

    Full Text Available Respiratory syncytial virus (RSV bronchiolitis triggers a strong innate immune response characterized by excessive neutrophil infiltration which contributes to RSV induced pathology. The cytokine IL-17A enhances neutrophil infiltration into virus infected lungs. IL-17A is however best known as an effector of adaptive immune responses. The role of IL-17A in early immune modulation in RSV infection is unknown. We aimed to elucidate whether local IL-17A facilitates the innate neutrophil infiltration into RSV infected lungs prior to adaptive immunity. To this end, we studied IL-17A production in newborns that were hospitalized for severe RSV bronchiolitis. In tracheal aspirates we measured IL-17A concentration and neutrophil counts. We utilized cultured human epithelial cells to test if IL-17A regulates RSV infection-induced IL-8 release as mediator of neutrophil recruitment. In mice we investigated the cell types that are responsible for early innate IL-17A production during RSV infection. Using IL-17A neutralizing antibodies we tested if IL-17A is responsible for innate neutrophil infiltration in mice. Our data show that increased IL-17A production in newborn RSV patient lungs correlates with subsequent neutrophil counts recruited to the lungs. IL-17A potentiates RSV-induced production of the neutrophil-attracting chemokine IL-8 by airway epithelial cells in vitro. Various lung-resident lymphocytes produced IL-17A during early RSV infection in Balb/c mice, of which a local population of CD4 T cells stood out as the predominant RSV-induced cell type. By removing IL-17A during early RSV infection in mice we showed that IL-17A is responsible for enhanced innate neutrophil infiltration in vivo. Using patient material, in vitro studies, and an animal model of RSV infection, we thus show that early local IL-17A production in the airways during RSV bronchiolitis facilitates neutrophil recruitment with pathologic consequences to infant lungs.

  18. Neotuberostemonine attenuates bleomycin-induced pulmonary fibrosis by suppressing the recruitment and activation of macrophages.

    Science.gov (United States)

    Xiang, Juan; Cheng, Si; Feng, Tianlong; Wu, Yan; Xie, Weina; Zhang, Mian; Xu, Xianghong; Zhang, Chaofeng

    2016-07-01

    Neotuberostemonine (NTS) is one of the main antitussive alkaloids in the root of Stemona tuberosa Lour. This study aimed to investigate the effects of NTS on bleomycin (BLM)-induced pulmonary fibrosis in mice and the underlying mechanism. After BLM administration, NTS were orally administered to mice at 20 and 40mg/kg per day from days 8 to 21, with nintedanib as a positive control. The effect of NTS on BLM-induced mice was assessed via histopathological examination by HE and Masson's trichrome staining, TGF-β1 level and macrophage recruitment by immunohistochemical staining, expression of profibrotic media and M1/M2 polarization by western blot. RAW 264.7 cells were used to evaluate whether NTS (1, 10, 100μM) directly affected macrophages. The results revealed that NTS treatment significantly ameliorated lung histopathological changes and decreased inflammatory cell counts in the bronchoalveolar lavage fluid. The over-expression of collagen, α-SMA and TGF-β1 was reduced by NTS. Furthermore, NTS markedly lowered the expression of MMP-2 and TIMP-1 while raised the expression of MMP-9. A further analysis showed that NTS was able to decrease the recruitment of macrophages and to inhibit the M2 polarization in mice lung tissues. The experiment in vitro showed that NTS significantly reduced the arginase-1 (marker for M2) expression in a dose-dependent manner but down-regulated the iNOS (marker for M1) expression only at 100μM. In conclusion, our study demonstrated for the first time that NTS has a significant protective effect on BLM-induced pulmonary fibrosis through suppressing the recruitment and M2 polarization of macrophages.

  19. Recruitment Strategies for Geoscience Majors: Conceptual Framework and Practical Suggestions

    Science.gov (United States)

    Richardson, R. M.; Eyles, C.; Ormand, C. J.

    2009-12-01

    One characteristic of strong geoscience departments is that they recruit and retain quality students. In a survey to over 900 geoscience departments in the US and Canada several years ago nearly 90% of respondents indicated that recruiting and retaining students was important. Two years ago we offered a pre-GSA workshop on recruiting and retaining students that attracted over 30 participants from over 20 different institutions, from liberal arts colleges to state universities to research intensive universities. Since then we have sought additional feedback from a presentation to the AGU Heads & Chairs at a Fall AGU meeting, and most recently from a workshop on strengthening geoscience programs in June 2009. In all of these settings, a number of themes and concrete strategies have emerged. Key themes included strategies internal to the department/institution; strategies that reach beyond the department/institution; determining how scalable/transferable strategies that work in one setting are to your own setting; identifying measures of success; and developing or improving on an existing action plan specific to your departmental/institutional setting. The full results of all of these efforts to distill best practices in recruiting students will be shared at the Fall AGU meeting, but some of the best practices for strategies local to the department/institution include: 1) focusing on introductory classes (having the faculty who are most successful in that setting teach them, having one faculty member make a common presentation to all classes about what one can do with a geoscience major, offering topical seminars, etc.); 2) informing students of career opportunities (inviting alumni back to talk to students, using AGI resources, etc.,); 3) creating common space for students to work, study, and be a community; 4) inviting all students earning an ‘A’ (or ‘B’) in introductory classes to a departmental event just for them; and 5) creating a field trip for incoming

  20. Recruiting older people to a randomised controlled dietary intervention trial - how hard can it be?

    Directory of Open Access Journals (Sweden)

    Pockley A Graham

    2010-02-01

    Full Text Available Abstract Background The success of a human intervention trial depends upon the ability to recruit eligible volunteers. Many trials fail because of unrealistic recruitment targets and flawed recruitment strategies. In order to predict recruitment rates accurately, researchers need information on the relative success of various recruitment strategies. Few published trials include such information and the number of participants screened or approached is not always cited. Methods This paper will describe in detail the recruitment strategies employed to identify older adults for recruitment to a 6-month randomised controlled dietary intervention trial which aimed to explore the relationship between diet and immune function (The FIT study. The number of people approached and recruited, and the reasons for exclusion, will be discussed. Results Two hundred and seventeen participants were recruited to the trial. A total of 7,482 letters were sent to potential recruits using names and addresses that had been supplied by local Family (General Practices. Eight hundred and forty three potential recruits replied to all methods of recruitment (528 from GP letters and 315 from other methods. The eligibility of those who replied was determined using a screening telephone interview, 217 of whom were found to be suitable and agreed to take part in the study. Conclusion The study demonstrates the application of multiple recruitment methods to successfully recruit older people to a randomised controlled trial. The most successful recruitment method was by contacting potential recruits by letter on NHS headed note paper using contacts provided from General Practices. Ninety percent of recruitment was achieved using this method. Adequate recruitment is fundamental to the success of a research project, and appropriate strategies must therefore be adopted in order to identify eligible individuals and achieve recruitment targets. Trial registration number ISRCTN45031464.

  1. Basic Analysis of Problems and Countermeasures for Enterprises during Recruitment%浅析企业招聘中存在的问题及对策

    Institute of Scientific and Technical Information of China (English)

    赵广军

    2015-01-01

    Recruitment is an important part of human resource management in enterprises. Talented personnel have already become the most valuable assets for enterprises. The human resources department is tasked with the important responsibility of selecting employees for an enterprise. Not only is recruitment an important stage in acquiring talented personnel for an enterprise, the results of recruitment impacts the operating efficiency of the enterprise, or even affects the enterprise’s ability to continue to develop. In order to effectively recruit for an enterprise, first, the concept of en-terprise recruitment must be altered;second, the basic work of recruitment must be strengthened;third, overall recruitment staff quality must be in-creased;and finally, the system must be formulated and the recruitment process must be regulated.%招聘是企业人力资源管理的重要内容,人才已成为企业最宝贵的财富,人力资源部门承担着为企业选人的重要职责。招聘不仅是企业获取人才的重要环节,而且招聘的效果还影响企业运营的效率,关系到企业的持续发展。做好企业招聘工作,一要转变企业招聘观念;二要加强招聘基础工作建设;三要提高招聘人员的综合素质;四要制定制度,规范招聘流程。

  2. Employee Motivation, Recruitment Practices and Banks Performance in Nigeria

    Directory of Open Access Journals (Sweden)

    Adeola Mukarramah Modupe

    2016-12-01

    Full Text Available Many organisations recognizes the use of human resource as a major influence to their success. And with today’s competitive environment, it is imperative for organisations to find ways to be more effective and efficient in utilizing their resources so as to improve their general performance. Hence, there is need to recruit and retain highly qualified and motivated employees in order to remain competitive in the unstable environment. This study evaluates the relationship between recruitment practices, employee motivation and their impact on organisational performance focusing on the Nigerian banking industry, with a view to investigating factors that motivate employees of Nigerian banks and the methods banks adopt to motivate their employees. The study also assesses recruitment and selection methods used by Nigerian banks to select effective employees. The study is a cross-sectional in time and the primary data collected from a conveniently selected sample of 60 employees each of the seven selected banks. Face-to-face survey and interview was carried out in order to achieve the research objectives and back up theoretical findings. Using correlation and thematic analysis, the results indicated that there was a strong positive relationship between employee motivation, recruitment practices and organisational performance. Findings from the analysis identified that bank employees are mostly extrinsically motivated; although intrinsic factors also motivate them, it is not as motivating as extrinsic factors. The banks also provide more of extrinsic motivators to increase the performance of their employees. The banks make use of various methods of employee selection, by dividing the methods into stages. In addition, recruiting is mostly undertaken through recruitment agencies or advert placements. The study provides future recommendations that banks in Nigeria should be firmer in their selection processes; this will allow them to identify unsuitable

  3. MAL Is a Regulator of the Recruitment of Myelin Protein PLP to Membrane Microdomains

    NARCIS (Netherlands)

    Bijlard, Marjolein; de Jonge, Jenny C.; Klunder, Bert; Nomden, Anita; Hoekstra, Dick; Baron, Wia

    2016-01-01

    In oligodendrocytes (OLGs), an indirect, transcytotic pathway is mediating transport of de novo synthesized PLP, a major myelin specific protein, from the apical-like plasma membrane to the specialized basolateral-like myelin membrane to prevent its premature compaction. MAL is a well-known regulato

  4. Leptin recruits Creb-regulated transcriptional coactivator 1 to improve hyperglycemia in insulin-deficient diabetes

    Directory of Open Access Journals (Sweden)

    Geun Hyang Kim

    2015-03-01

    Conclusions: Our study reveals that Crtc1 functions as a conduit for leptin's glucoregulatory actions in insulin-dependent diabetes. This study also highlights a new role for Crtc1 in modulating peripheral glucose metabolism.

  5. Determining the requirements for e-selection in a small recruitment company - using the regulative cycle

    NARCIS (Netherlands)

    Bondarouk, T.V.; Ruel, H.J.M.; Timmermans, P.; Buragga, K.A.; Zaman, N.

    2013-01-01

    The requirements for e-selection technology to be of practical use for Company T have been investigated. Company T’s main business is in identifying and seconding personnel, especially in the technical sector, and it had been anticipating a shortage in the supply of candidates. This served as the in

  6. F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse.

    Science.gov (United States)

    Pérez-Martínez, Manuel; Gordón-Alonso, Mónica; Cabrero, José Román; Barrero-Villar, Marta; Rey, Mercedes; Mittelbrunn, María; Lamana, Amalia; Morlino, Giulia; Calabia, Carmen; Yamazaki, Hiroyuki; Shirao, Tomoaki; Vázquez, Jesús; González-Amaro, Roberto; Veiga, Esteban; Sánchez-Madrid, Francisco

    2010-04-01

    The adaptive immune response depends on the interaction of T cells and antigen-presenting cells at the immune synapse. Formation of the immune synapse and the subsequent T-cell activation are highly dependent on the actin cytoskeleton. In this work, we describe that T cells express drebrin, a neuronal actin-binding protein. Drebrin colocalizes with the chemokine receptor CXCR4 and F-actin at the peripheral supramolecular activation cluster in the immune synapse. Drebrin interacts with the cytoplasmic tail of CXCR4 and both proteins redistribute to the immune synapse with similar kinetics. Drebrin knockdown in T cells impairs the redistribution of CXCR4 and inhibits actin polymerization at the immune synapse as well as IL-2 production. Our data indicate that drebrin exerts an unexpected and relevant functional role in T cells during the generation of the immune response.

  7. Ordered transcriptional factor recruitment and epigenetic regulation of tnf-alpha in necrotizing acute pancreatitis.

    NARCIS (Netherlands)

    Sandoval, J.; Pereda, J.; Rodriguez, J.L.; Escobar, J.; Hidalgo, J.; Joosten, L.A.B.; Franco, L.; Sastre, J.; Lopez-Rodas, G.

    2010-01-01

    Tauhe expression of the critical initiator cytokine TNF-alpha was strongly upregulated in vivo in acute necrotic pancreatitis (AP) in rodents and in vitro in TNF-alpha activated acinar AR42J cells. Upregulation of tnf-alpha, inos, icam-1 and il-6 occurred both in TNF-alpha receptor 1 and 2 knock-out

  8. Processing of CXCL12 impedes the recruitment of endothelial progenitor cells in diabetic wound healing.

    Science.gov (United States)

    Feng, Guang; Hao, Daifeng; Chai, Jiake

    2014-11-01

    High blood sugar levels result in defective wound healing processes in diabetic patients. Endothelial progenitor cells (EPCs) play an important role in vasculogenesis, and thereby contribute to reconstitution of the microcirculation and healing. This study aimed to determine the possible mechanism by which the numbers of circulating EPCs are regulated in response to tissue wounding. In the streptozotocin-induced diabetic mouse model, we found that phagocytes activated by local inflammatory cytokines in the wound interfere with the mobilization and recruitment of EPCs to the lesion area. Specifically, the activated macrophages inactivate CXCL12, the major chemokine for EPC recruitment, via matrix metalloproteinases (MMPs), and thereby prevent local chemotaxis and subsequent homing of EPCs to the wound. The wound healing process is delayed by local administration of inflammatory cytokines, and its rate is increased by MMP inhibitors. This study indicates that local inhibition of MMPs is beneficial for regeneration of damaged vessels, and may explain poor wound healing in diabetic patients, thus demonstrating its potential utility as a local treatment therapy to promote diabetic wound healing.

  9. Yeast one-hybrid gγ recruitment system for identification of protein lipidation motifs.

    Science.gov (United States)

    Fukuda, Nobuo; Doi, Motomichi; Honda, Shinya

    2013-01-01

    Fatty acids and isoprenoids can be covalently attached to a variety of proteins. These lipid modifications regulate protein structure, localization and function. Here, we describe a yeast one-hybrid approach based on the Gγ recruitment system that is useful for identifying sequence motifs those influence lipid modification to recruit proteins to the plasma membrane. Our approach facilitates the isolation of yeast cells expressing lipid-modified proteins via a simple and easy growth selection assay utilizing G-protein signaling that induces diploid formation. In the current study, we selected the N-terminal sequence of Gα subunits as a model case to investigate dual lipid modification, i.e., myristoylation and palmitoylation, a modification that is widely conserved from yeast to higher eukaryotes. Our results suggest that both lipid modifications are required for restoration of G-protein signaling. Although we could not differentiate between myristoylation and palmitoylation, N-terminal position 7 and 8 play some critical role. Moreover, we tested the preference for specific amino-acid residues at position 7 and 8 using library-based screening. This new approach will be useful to explore protein-lipid associations and to determine the corresponding sequence motifs.

  10. Yeast one-hybrid gγ recruitment system for identification of protein lipidation motifs.

    Directory of Open Access Journals (Sweden)

    Nobuo Fukuda

    Full Text Available Fatty acids and isoprenoids can be covalently attached to a variety of proteins. These lipid modifications regulate protein structure, localization and function. Here, we describe a yeast one-hybrid approach based on the Gγ recruitment system that is useful for identifying sequence motifs those influence lipid modification to recruit proteins to the plasma membrane. Our approach facilitates the isolation of yeast cells expressing lipid-modified proteins via a simple and easy growth selection assay utilizing G-protein signaling that induces diploid formation. In the current study, we selected the N-terminal sequence of Gα subunits as a model case to investigate dual lipid modification, i.e., myristoylation and palmitoylation, a modification that is widely conserved from yeast to higher eukaryotes. Our results suggest that both lipid modifications are required for restoration of G-protein signaling. Although we could not differentiate between myristoylation and palmitoylation, N-terminal position 7 and 8 play some critical role. Moreover, we tested the preference for specific amino-acid residues at position 7 and 8 using library-based screening. This new approach will be useful to explore protein-lipid associations and to determine the corresponding sequence motifs.

  11. Comparing recruitment strategies in a study of acupuncture for chronic back pain

    Directory of Open Access Journals (Sweden)

    Avins Andrew L

    2009-10-01

    Full Text Available Abstract Background Meeting recruitment goals is challenging for many clinical trials conducted in primary care populations. Little is known about how the use of different recruitment strategies affects the types of individuals choosing to participate or the conclusions of the study. Methods A secondary analysis was performed using data from participants recruited to a clinical trial evaluating acupuncture for chronic back pain among primary care patients in a large integrated health care organization. We used two recruitment methods: mailed letters of invitation and an advertisement in the health plan's magazine. For these two recruitment methods, we compared recruitment success (% randomized, treatment completers, drop outs and losses to follow-up, participant characteristics, and primary clinical outcomes. A linear regression model was used to test for interaction between treatment group and recruitment method. Results Participants recruited via mailed letters closely resembled those responding to the advertisement in terms of demographic characteristics, most aspects of their back pain history and current episode and beliefs and expectations about acupuncture. No interaction between method of recruitment and treatment group was seen, suggesting that study outcomes were not affected by recruitment strategy. Conclusion In this trial, the two recruitment strategies yielded similar estimates of treatment effectiveness. However, because this finding may not apply to other recruitment strategies or trial circumstances, trials employing multiple recruitment strategies should evaluate the effect of recruitment strategy on outcome. Trial registration Clinical Trials.gov NCT00065585.

  12. HoxBlinc RNA recruits Set1/MLL complexes to activate Hox gene expression patterns and mesoderm lineage development

    Science.gov (United States)

    Deng, Changwang; Li, Ying; Zhou, Lei; Cho, Joonseok; Patel, Bhavita; Terada, Nao; Li, Yangqiu; Bungert, Jörg; Qiu, Yi; Huang, Suming

    2015-01-01

    Summary Trithorax proteins and long-intergenic noncoding RNAs are critical regulators of embryonic stem cell pluripotency; however, how they cooperatively regulate germ layer mesoderm specification remains elusive. We report here that HoxBlinc RNA first specifies Flk1+ mesoderm and then promotes hematopoietic differentiation through regulating hoxb gene pathways. HoxBlinc binds to the hoxb genes, recruits Setd1a/MLL1 complexes, and mediates long-range chromatin interactions to activate transcription of the hoxb genes. Depletion of HoxBlinc by shRNA-mediated KD or CRISPR-Cas9-mediated genetic deletion inhibits expression of hoxb genes and other factors regulating cardiac/hematopoietic differentiation. Reduced hoxb gene expression is accompanied by decreased recruitment of Set1/MLL1 and H3K4me3 modification, as well as by reduced chromatin loop formation. Re-expression of hoxb2-b4 genes in HoxBlinc-depleted embryoid bodies rescues Flk1+ precursors that undergo hematopoietic differentiation. Thus, HoxBlinc plays an important role in controlling hoxb transcription networks that mediate specification of mesoderm-derived Flk1+ precursors and differentiation of Flk1+ cells into hematopoietic lineages. PMID:26725110

  13. HoxBlinc RNA Recruits Set1/MLL Complexes to Activate Hox Gene Expression Patterns and Mesoderm Lineage Development

    Directory of Open Access Journals (Sweden)

    Changwang Deng

    2016-01-01

    Full Text Available Trithorax proteins and long-intergenic noncoding RNAs are critical regulators of embryonic stem cell pluripotency; however, how they cooperatively regulate germ layer mesoderm specification remains elusive. We report here that HoxBlinc RNA first specifies Flk1+ mesoderm and then promotes hematopoietic differentiation through regulation of hoxb pathways. HoxBlinc binds to the hoxb genes, recruits Setd1a/MLL1 complexes, and mediates long-range chromatin interactions to activate transcription of the hoxb genes. Depletion of HoxBlinc by shRNA-mediated knockdown or CRISPR-Cas9-mediated genetic deletion inhibits expression of hoxb genes and other factors regulating cardiac/hematopoietic differentiation. Reduced hoxb expression is accompanied by decreased recruitment of Set1/MLL1 and H3K4me3 modification, as well as by reduced chromatin loop formation. Re-expression of hoxb2–b4 genes in HoxBlinc-depleted embryoid bodies rescues Flk1+ precursors that undergo hematopoietic differentiation. Thus, HoxBlinc plays an important role in controlling hoxb transcription networks that mediate specification of mesoderm-derived Flk1+ precursors and differentiation of Flk1+ cells into hematopoietic lineages.

  14. Experimental test for facilitation of seedling recruitment by the dominant bunchgrass in a fire-maintained savanna.

    Directory of Open Access Journals (Sweden)

    Gwenllian D Iacona

    Full Text Available Facilitative interactions between neighboring plants can influence community composition, especially in locations where environmental stress is a factor limiting competitive effects. The longleaf pine savanna of the southeastern United States is a threatened and diverse system where seedling recruitment success and understory species richness levels are regulated by the availability of moist microsites. We hypothesized that the dominant bunch grass species (Aristida stricta Michx. would facilitate moist seedling microsites through shading, but that the effect would depend on stress gradients. Here, we examined the environmental properties modified by the presence of wiregrass and tested the importance of increased shade as a potential facilitative mechanism promoting seedling recruitment across spatial and temporal stress gradients. We showed that environmental gradients, season, and experimental water manipulation influence seedling success. Environmental properties were modified by wiregrass proximity in a manner that could facilitate seedling success, but we showed that shade alone does not provide a facilitative benefit to seedlings in this system.

  15. Administrative Circular No. 2 (Rev. 7) - Recruitment, appointment and possible developments regarding the contractual position of staff members

    CERN Multimedia

    2015-01-01

    Administrative Circular No. 2 (Rev. 7), entitled "Recruitment, appointment and possible developments regarding the contractual position of staff members", approved by the Director-General following discussion at the Standing Concertation Committee meeting held on 17 February 2015 is available via the following link: AC No. 2 (Rev.7).   This revised circular cancels and replaces Administrative Circular No. 2 (Rev. 6), entitled "Recruitment, appointment and possible developments regarding the contractual position of staff members" and dated January 2015. The circular was revised in order to implement the amendment to Article R II 1.17 of the Staff Regulations, which introduces the possibility of extending limited-duration (LD) contracts up to a maximum total duration of eight years from the previous duration of five years. The award of indefinite contracts will continue to be subject to the outcome of a competitive process. Department Head Of...

  16. Crossmodal recruitment of the ventral visual stream in congenital blindness

    DEFF Research Database (Denmark)

    Ptito, Maurice; Matteau, Isabelle; Zhi Wang, Arthur

    2012-01-01

    We used functional MRI (fMRI) to test the hypothesis that blind subjects recruit the ventral visual stream during nonhaptic tactile-form recognition. Congenitally blind and blindfolded sighted control subjects were scanned after they had been trained during four consecutive days to perform...... a tactile-form recognition task with the tongue display unit (TDU). Both groups learned the task at the same rate. In line with our hypothesis, the fMRI data showed that during nonhaptic shape recognition, blind subjects activated large portions of the ventral visual stream, including the cuneus, precuneus......, inferotemporal (IT), cortex, lateral occipital tactile vision area (LOtv), and fusiform gyrus. Control subjects activated area LOtv and precuneus but not cuneus, IT and fusiform gyrus. These results indicate that congenitally blind subjects recruit key regions in the ventral visual pathway during nonhaptic...

  17. Reduced recruitment in Hyalella azteca (Saussure, 1858) exposed to copper.

    Science.gov (United States)

    Othman, M Shuhaimi; Pascoe, David

    2002-09-01

    Neonates of the amphipod Hyalella azteca were exposed for a 35-day period in the laboratory to a range of copper concentrations, nominally 18 microg/l, 40 microg/l, 70 microg/l and 260 microg/l. The reproductive status of the population was assessed by recording recruitment, the number of precopulatory pairs and number of gravid females. At the end of the experiment, the body lengths of individuals were measured using image analysis. There was a significant decrease in the final population size of H. azteca with increasing copper concentration and compared with the control. Copper significantly reduced recruitment of juveniles and length composition of the final population and there was also a trend toward reduced precopula number with increasing copper concentrations.

  18. Longitudinal study of magnesium status of Israeli military recruits.

    Science.gov (United States)

    Dolev, E; Burstein, R; Wishnitzer, R; Lubin, F; Chetriet, A; Shefi, M; Deuster, P A

    The following study was conducted to assess the biochemical and nutritional status of new military recruits during 12 weeks of strenuous physical activity. Calorie and magnesium (Mg) intake, energy expenditure, and serum, red blood cell (RBC) and mononuclear cell (MNC) Mg were assessed at the start, after 6 weeks and after 12 weeks of training. The results provide evidence that MNC Mg content decreases, whereas serum Mg increases, under prolonged, strenuous training conditions in previously unconditioned military recruits. Mg dietary intake alone could not account for these changes. It is postulated that this decrease in MNC Mg (from 64.76 +/- 34.99 to 23.81 +/- 15.55 fg/cell), unparalleled by similar changes in serum Mg or RBC Mg, reflects a reduction in exchangeable Mg body stores, and the onset of a Mg deficiency state.

  19. LINKING MARKETING AND HUMAN RESOURCES RECRUITMENT TO OBTAIN ORGANIZATIONAL EFFICIENCY

    Directory of Open Access Journals (Sweden)

    Nicoleta Valentina FLOREA

    2010-01-01

    Full Text Available In times of rapid change and technical change, in a complex and dynamic environment, organizations must strive for superiority, in order to survive and to serve the clients who want more quality and lower price. Corporate leaders and human resources strategists have to take up this challenge of changing work attitudes across the organization. This involves guiding, leading, enabling and motivating people. This article is looking at aligning marketing with recruitment efforts, to obtain organizational performance. Anticipating customers’ needs, the organization develop specific plans of recruitment, selection and retention of those candidates who satisfy these needs at the highest level. Only anticipating and retaining those “right people at the right time”, an organization may obtain success into a global, dynamic and changing environment.

  20. A procedure for distributing recruits in manpower systems

    Directory of Open Access Journals (Sweden)

    Ekhosuehi Virtue U.

    2015-01-01

    Full Text Available In this paper, we treat the following problem: Given a stable Gani-type personflow model and assuming no negative recruitment, what recruitment distribution at the n − step is capable of generating a staff-mix that closely follows the desired structure? We relate the problem to the challenge of universities in Nigeria towards reaching the desired academic staff-mix by rank specified by the National Universities Commission (NUC. We formulate a population-dynamic model consisting of aggregate-fractional flow balance equations within a discrete-time Markov chain framework for the system. We use MATLas a convenient platform to solve the system of equations. The utility of the model is illustrated by means of academic staff flows in a university-faculty setting in Nigeria.

  1. Differential recruitment of executive resources during mind wandering.

    Science.gov (United States)

    Kam, Julia W Y; Handy, Todd C

    2014-05-01

    Recent research has shown that mind wandering recruits executive resources away from the external task towards inner thoughts. No studies however have determined whether executive functions are drawn away in a unitary manner during mind wandering episodes, or whether there is variation in specific functions impacted. Accordingly, we examined whether mind wandering differentially modulates three core executive functions-response inhibition, updating of working memory, and mental set shifting. In three experiments, participants performed one of these three executive function tasks and reported their attentional state as either on-task or mind wandering at random intervals. We found that mind wandering led to poorer performance in the response inhibition and working memory tasks, but not the set-shifting task. These findings suggest that mind wandering does not recruit executive functions in a monolithic manner. Rather, it appears to selectively engage certain executive functions, which may reflect the adaptive maintenance of ongoing task performance.

  2. Ethnic and Gender Discrimination in Recruitment: Experimental Evidence From Finland

    Directory of Open Access Journals (Sweden)

    Karmela Liebkind

    2016-06-01

    Full Text Available We ask (1 how the position of an ethnic (majority or minority group in the local ethnic hierarchy affects the amount of recruitment discrimination faced by applicants from that group, and (2 whether gender discrimination is dependent on occupational gender stereotypes in the same way among ethnic majority and minority applicants. We use the situation testing method for the first time in Finland: In an experimental study (Study 1, 103 dentistry students made recruitment decisions based on the CVs of three bogus applicants from different ethnic groups (Finnish, Austrian and Polish and in a field experiment (Study 2, four test applicants (male and female Finns and Russians with equivalent CVs applied for 1,258 vacant jobs, addressing gender discrimination in relation to occupational gender stereotypes as well as ethnic discrimination. Together these studies cover both skilled (Study 1 and semi-skilled jobs (Study 2 and applicants from ethnic minority groups originating from within as well as outside the EU. Results show that majority group members are more likely to be hired compared to minority members (both Studies and that minority members from a higher status group are more likely to be hired than those from a lower status group (Study 1. Results also show that male applicants from the majority group were discriminated compared to women in occupations characterised as feminine, while Russian men faced recruitment discrimination compared to Russian women independently of the job’s gender stereotype (Study 2. Implications of recruitment discrimination based on ethnicity and gender are discussed.

  3. Mechanism of neutrophil recruitment to the lung after pulmonary contusion

    OpenAIRE

    2011-01-01

    Blunt chest trauma resulting in pulmonary contusion is a common but poorly understood injury. We previously demonstrated that lung contusion activates localized and systemic innate immune mechanisms and recruits neutrophils to the injured lung. We hypothesized that the innate immune and inflammatory activation of neutrophils may figure prominently in the response to lung injury. To investigate this, we used a model of pulmonary contusion in the mouse that is similar to that observed clinicall...

  4. USAR Recruiting and Manpower in the 21st Century

    Science.gov (United States)

    1993-12-01

    Statistical Area Projections of Income, Employment. and Population to the Year 2000," Survey of Current Business , Vol. 70, October 1990. Changes in...a community of adequate public safety or health care. Careful planning between reserve recruiting and community and business leaders should be a...Congressional Budget Office, October 1989, pp 69-73 38 Table 17. Family Income and Enlistment Probability Enlistment Probability Probability Farmily When Youth

  5. Recruiting and Retaining Army Nurses: An Annotated Bibliography, 1990

    Science.gov (United States)

    1990-12-01

    nursing organizations could assist DOD in recruiting, develop videos of current nursing leaders who are also reservists for PR purposes, and encourage...occurred under the leadership of Julia Stinson, the Superintendent from 1919 to 1937. Also discussed is the relationship of the corps to the nursing ... organizations . Slewitzke, Connie L., Vail, James D., and M arlin, Susan A. US Army Reserve and National Guard Survey: An Analysis of Factors Which

  6. Recruiting Campaigns: How Advertising and Training Target the Millennial Generation

    Science.gov (United States)

    2007-12-01

    youth market through advertising and training. Even though recruiting numbers may wane from time to time, the overall messages are parallel to perceived...or nonmilitary service. This thesis demonstrates that USAREC is leveraging its knowledge of the youth market through advertising and training...USAREC can determine its advertising efficacy. By comparing common traits and characteristics with these messages, USAREC can validate its marketing

  7. Recruitment and retention of mental health workers in Ghana.

    Directory of Open Access Journals (Sweden)

    Helen Jack

    Full Text Available INTRODUCTION: The lack of trained mental health workers is a primary contributor to the mental health treatment gap worldwide. Despite the great need to recruit and retain mental health workers in low-income countries, little is known about how these workers perceive their jobs and what drives them to work in mental health care. Using qualitative interviews, we aimed to explore factors motivating mental health workers in order to inform interventions to increase recruitment and retention. METHODS: We conducted 28 in-depth, open-ended interviews with staff in Ghana's three public psychiatric hospitals. We used the snowballing method to recruit participants and the constant comparative method for qualitative data analysis, with multiple members of the research team participating in data coding to enhance the validity and reliability of the analysis. The use of qualitative methods allowed us to understand the range and depth of motivating and demotivating factors. RESULTS: Respondents described many factors that influenced their choice to enter and remain in mental health care. Motivating factors included 1 desire to help patients who are vulnerable and in need, 2 positive day-to-day interactions with patients, 3 intellectual or academic interest in psychiatry or behavior, and 4 good relationships with colleagues. Demotivating factors included 1 lack of resources at the hospital, 2 a rigid supervisory hierarchy, 3 lack of positive or negative feedback on work performance, and 4 few opportunities for career advancement within mental health. CONCLUSIONS: Because many of the factors are related to relationships, these findings suggest that strengthening the interpersonal and team dynamics may be a critical and relatively low cost way to increase worker motivation. The data also allowed us to highlight key areas for resource allocation to improve both recruitment and retention, including risk pay, adequate tools for patient care, improved hospital work

  8. Predictors of Back Injury Among Women Military Recruits

    Science.gov (United States)

    1999-11-01

    infection (by history, physical, or laboratory examination) 4. Ankylosing spondylitis, rheumatoid arthritis or other rheumatoid or connective tissue...Force recruits: a multimillion-dollar epidemic. Seminars in Arthritis & Rheumatism. 1993;22(4):275-279. 8. Fiymoyer J., Mooney V. Current concepts...pain. Baltimore: Williams & Wilkins. 1989. 46. Kendall P, Jenkins J. Exercises for backache: A double-blind controlled trial. Physiotherapy . 1968;54

  9. Whither RDS? An investigation of Respondent Driven Sampling as a method of recruiting mainstream marijuana users

    Directory of Open Access Journals (Sweden)

    Cousineau Marie-Marthe

    2010-07-01

    gathering respondents who are more representative of users in the general population than nonrandom methods of recruitment ordinarily produce. Conclusions Research on marijuana use, and other forms of drug use hidden in the general population of adults, is important for informing and extending harm reduction beyond its current emphasis on 'at-risk' populations. Expanding harm reduction in a normalizing context, through innovative research on users often overlooked, further challenges assumptions about reducing harm through prohibition of drug use and urges consideration of alternative policies such as decriminalization and legal regulation.

  10. The Dilemma of Physician Shortage and International Recruitment in Canada

    Directory of Open Access Journals (Sweden)

    Nazrul Islam

    2014-06-01

    Full Text Available The perception of physician shortage in Canada is widespread. Absolute shortages and relative discrepancies, both specialty-wise and in urban-rural distribution, have been a daunting policy challenge. International Medical Graduates (IMGs have been at the core of mitigating this problem, especially as long as shortage of physicians in rural areas is concerned. Considering such recruitment as historical reality is naïve annotation, but when it is recommended per se, then the indication of interest overweighs the intent of ethically justified solution. Such a recommendation has not only invited policy debate and disagreement, but has also raised serious ethical concerns. Canadian healthcare policy-makers were put into a series of twisting puzzles—recruiting IMGs in mitigating physician shortage was questioned by lack of vision for Canada’s self-sufficiency. In-migration of IMGs was largely attributed to Canada’s point-based physician-friendly immigration system without much emphasizing on IMGs’ home countries’ unfavorable factors and ignoring their basic human rights and choice of livelihood. While policy-makers’ excellence in integrating the already-migrated IMGs into the Canadian healthcare is cautiously appraised, its logical consequence in passively drawing more IMGs is loudly criticised. Even the passive recruitment of IMGs raised the ethical concern of source countries’ (which are often developing countries with already-compromised healthcare system vulnerability. The current paper offers critical insights juxtaposing all these seemingly conflicting ideas and interests within the scope of national and transnational instruments.

  11. Oceanography promotes self-recruitment in a planktonic larval disperser

    Science.gov (United States)

    Teske, Peter R.; Sandoval-Castillo, Jonathan; van Sebille, Erik; Waters, Jonathan; Beheregaray, Luciano B.

    2016-01-01

    The application of high-resolution genetic data has revealed that oceanographic connectivity in marine species with planktonic larvae can be surprisingly limited, even in the absence of major barriers to dispersal. Australia’s southern coast represents a particularly interesting system for studying planktonic larval dispersal, as the hydrodynamic regime of the wide continental shelf has potential to facilitate onshore retention of larvae. We used a seascape genetics approach (the joint analysis of genetic data and oceanographic connectivity simulations) to assess population genetic structure and self-recruitment in a broadcast-spawning marine gastropod that exists as a single meta-population throughout its temperate Australian range. Levels of self-recruitment were surprisingly high, and oceanographic connectivity simulations indicated that this was a result of low-velocity nearshore currents promoting the retention of planktonic larvae in the vicinity of natal sites. Even though the model applied here is comparatively simple and assumes that the dispersal of planktonic larvae is passive, we find that oceanography alone is sufficient to explain the high levels of genetic structure and self-recruitment. Our study contributes to growing evidence that sophisticated larval behaviour is not a prerequisite for larval retention in the nearshore region in planktonic-developing species. PMID:27687507

  12. Yorkie Promotes Transcription by Recruiting a Histone Methyltransferase Complex

    Directory of Open Access Journals (Sweden)

    Hyangyee Oh

    2014-07-01

    Full Text Available Hippo signaling limits organ growth by inhibiting the transcriptional coactivator Yorkie. Despite the key role of Yorkie in both normal and oncogenic growth, the mechanism by which it activates transcription has not been defined. We report that Yorkie binding to chromatin correlates with histone H3K4 methylation and is sufficient to locally increase it. We show that Yorkie can recruit a histone methyltransferase complex through binding between WW domains of Yorkie and PPxY sequence motifs of NcoA6, a subunit of the Trithorax-related (Trr methyltransferase complex. Cell culture and in vivo assays establish that this recruitment of NcoA6 contributes to Yorkie’s ability to activate transcription. Mammalian NcoA6, a subunit of Trr-homologous methyltransferase complexes, can similarly interact with Yorkie’s mammalian homolog YAP. Our results implicate direct recruitment of a histone methyltransferase complex as central to transcriptional activation by Yorkie, linking the control of cell proliferation by Hippo signaling to chromatin modification.

  13. Recruitment of Perisomatic Inhibition during Spontaneous Hippocampal Activity In Vitro.

    Directory of Open Access Journals (Sweden)

    Anna Beyeler

    Full Text Available It was recently shown that perisomatic GABAergic inhibitory postsynaptic potentials (IPSPs originating from basket and chandelier cells can be recorded as population IPSPs from the hippocampal pyramidal layer using extracellular electrodes (eIPSPs. Taking advantage of this approach, we have investigated the recruitment of perisomatic inhibition during spontaneous hippocampal activity in vitro. Combining intracellular and extracellular recordings from pyramidal cells and interneurons, we confirm that inhibitory signals generated by basket cells can be recorded extracellularly, but our results suggest that, during spontaneous activity, eIPSPs are mostly confined to the CA3 rather than CA1 region. CA3 eIPSPs produced the powerful time-locked inhibition of multi-unit activity expected from perisomatic inhibition. Analysis of the temporal dynamics of spike discharges relative to eIPSPs suggests significant but moderate recruitment of excitatory and inhibitory neurons within the CA3 network on a 10 ms time scale, within which neurons recruit each other through recurrent collaterals and trigger powerful feedback inhibition. Such quantified parameters of neuronal interactions in the hippocampal network may serve as a basis for future characterisation of pathological conditions potentially affecting the interactions between excitation and inhibition in this circuit.

  14. Variable recruitment in bundles of miniature pneumatic artificial muscles.

    Science.gov (United States)

    DeLaHunt, Sylvie A; Pillsbury, Thomas E; Wereley, Norman M

    2016-09-13

    The natural compliance and force generation properties of pneumatic artificial muscles (PAMs) allow them to operate like human muscles in anthropomorphic robotic manipulators. Traditionally, manipulators use a single PAM or multiple PAMs actuated in unison in place of a human muscle. However, these standard manipulators can experience significant efficiency losses when operated outside their target performance ranges at low actuation pressures. This study considers the application of a variable recruitment control strategy to a parallel bundle of miniature PAMs as an attempt to mimic the selective recruitment of motor units in a human muscle. Bundles of miniature PAMs are experimentally characterized, their actuation behavior is modeled, and the efficiency gains and losses associated with the application of a variable recruitment control strategy are assessed. This bio-inspired control strategy allows muscle bundles to operate the fewest miniature PAMs necessary to achieve a desired performance objective, improving the muscle bundle's operating efficiency over larger ranges of force generation and displacement. The study also highlights the need for improved PAM fabrication techniques to facilitate the production of identical miniature PAMs for inclusion in muscle bundles.

  15. Recruitment and retention of young adult veteran drinkers using Facebook.

    Science.gov (United States)

    Pedersen, Eric R; Naranjo, Diana; Marshall, Grant N

    2017-01-01

    The objective of this study was to describe the feasibility of using Facebook as a platform to recruit and retain young adult veteran drinkers into an online-alcohol use intervention study. Facebook's wide accessibility and popularity among the age group that comprises the majority of veterans from the conflicts in Iraq and Afghanistan make it a compelling resource through which research can extend its reach to this otherwise hard-to-reach group. We developed a series of Facebook advertisement campaigns to reach veteran drinkers not specifically searching for alcohol treatment. In doing so, we recruited 793 valid veteran participants in approximately two weeks for an advertising cost of $4.53 per obtained participant. The study sample consisted primarily of male veterans, between 19 and 34 years of age, who were drinking at moderate to heavy levels. Although about half of the sample reported mental health comorbidity, few had received any mental health or substance use treatment in the past year. Facebook appears to be a valuable mechanism through which to recruit young veterans with unmet behavioral health needs, although more specific efforts may be needed to engage certain types of veterans after initial study enrollment.

  16. Research recruitment using Facebook advertising: big potential, big challenges.

    Science.gov (United States)

    Kapp, Julie M; Peters, Colleen; Oliver, Debra Parker

    2013-03-01

    To our knowledge, ours is the first study to report on Facebook advertising as an exclusive mechanism for recruiting women ages 35-49 years residing in the USA into a health-related research study. We directed our survey to women ages 35-49 years who resided in the USA exclusively using three Facebook advertisements. Women were then redirected to our survey site. There were 20,568,960 women on Facebook that met the eligibility criteria. The three ads resulted in 899,998 impressions with a reach of 374,225 women. Of the women reached, 280 women (0.075 %) clicked the ad. Of the women who clicked the ad, nine women (3.2 %) proceeded past the introductory page. Social networking, and in particular Facebook, is an innovative venue for recruiting participants for research studies. Challenges include developing an ad to foster interest without biasing the sample, and motivating women who click the ad to complete the survey. There is still much to learn about this potential method of recruitment.

  17. Recruitment and retention of young adult veteran drinkers using Facebook

    Science.gov (United States)

    Pedersen, Eric R.; Naranjo, Diana; Marshall, Grant N.

    2017-01-01

    The objective of this study was to describe the feasibility of using Facebook as a platform to recruit and retain young adult veteran drinkers into an online-alcohol use intervention study. Facebook’s wide accessibility and popularity among the age group that comprises the majority of veterans from the conflicts in Iraq and Afghanistan make it a compelling resource through which research can extend its reach to this otherwise hard-to-reach group. We developed a series of Facebook advertisement campaigns to reach veteran drinkers not specifically searching for alcohol treatment. In doing so, we recruited 793 valid veteran participants in approximately two weeks for an advertising cost of $4.53 per obtained participant. The study sample consisted primarily of male veterans, between 19 and 34 years of age, who were drinking at moderate to heavy levels. Although about half of the sample reported mental health comorbidity, few had received any mental health or substance use treatment in the past year. Facebook appears to be a valuable mechanism through which to recruit young veterans with unmet behavioral health needs, although more specific efforts may be needed to engage certain types of veterans after initial study enrollment. PMID:28249027

  18. The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms.

    Science.gov (United States)

    Fry, Bryan G; Roelants, Kim; Champagne, Donald E; Scheib, Holger; Tyndall, Joel D A; King, Glenn F; Nevalainen, Timo J; Norman, Janette A; Lewis, Richard J; Norton, Raymond S; Renjifo, Camila; de la Vega, Ricardo C Rodríguez

    2009-01-01

    Throughout evolution, numerous proteins have been convergently recruited into the venoms of various animals, including centipedes, cephalopods, cone snails, fish, insects (several independent venom systems), platypus, scorpions, shrews, spiders, toxicoferan reptiles (lizards and snakes), and sea anemones. The protein scaffolds utilized convergently have included AVIT/colipase/prokineticin, CAP, chitinase, cystatin, defensins, hyaluronidase, Kunitz, lectin, lipocalin, natriuretic peptide, peptidase S1, phospholipase A(2), sphingomyelinase D, and SPRY. Many of these same venom protein types have also been convergently recruited for use in the hematophagous gland secretions of invertebrates (e.g., fleas, leeches, kissing bugs, mosquitoes, and ticks) and vertebrates (e.g., vampire bats). Here, we discuss a number of overarching structural, functional, and evolutionary generalities of the protein families from which these toxins have been frequently recruited and propose a revised and expanded working definition for venom. Given the large number of striking similarities between the protein compositions of conventional venoms and hematophagous secretions, we argue that the latter should also fall under the same definition.

  19. ANALYSIS OF INTENTION TO CONTINUE SERVICES AMONG RECRUITED VOLUNTARY SOLDIERS

    Directory of Open Access Journals (Sweden)

    Kuo-Wei Lin

    2012-01-01

    Full Text Available In order to attract more promising young people to join the military and enhance combat capability, Taiwan’s Department of Defense is transforming the nation’s military service system from a draft system, which has been in effect for more than sixty years, to an all-volunteer military force system. The government hopes that the new system not only can recruit promising voluntary soldiers, but that they also continue their military service after the contract expires in order to ensure stability in recruitment sources. This study explores the intention of voluntary soldiers to continue their military service. This study’s questionnaire encompasses five dimensions: Participation motivation, organization commitment, career planning, personality traits and departure tendency. The questionnaires were issued to 350 voluntary soldiers to explore if they intend to continue their service after their contract expires, with a total of 314 effective questionnaires that were recovered and analyzed. The results find that about half of the voluntary soldiers indicate that they do not plan on staying and continuing their service after contract expiration, which will result in understaffing in the military. In order to stabilize the prescribed number of soldiers, the existing recruiting policy and military management system should be re-adjusted.

  20. A Review of Interventions to Recruit and Retain ICT Students

    Directory of Open Access Journals (Sweden)

    Leo A. Siiman

    2014-03-01

    Full Text Available This article reviews and analyses the educational research literature on interventions to increase the recruitment and retention of information and communications technology (ICT students. The results show that three changes in computing pedagogy characterize successful interventions, and consequently offer promising ways to attract and prepare more people for careers in ICT. The most important selection criterion considered when choosing papers to review was that interventions had been tested in practice and their effectiveness measured. Interventions were arranged into two groups: recruitment and retention. Recruitment interventions described initiatives to motivate interest in computing among secondary schools students, whereas retention interventions described efforts to retain students in ICT majors at universities. The three pedagogical approaches that emerged from an analysis of the successful interventions were: (1 visual programming environments to teach introductory programming, (2 inquiry learning activities to engage students in computing, and (3 integration of interdisciplinary knowledge to attract students from diverse disciplines. This review draws attention to innovative teaching practices currently shaping computer science education. Wider adoption of these pedagogical strategies has the potential to significantly increase the number of qualified ICT professionals.