Integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} effectors p130Cas, Src and talin regulate carcinoma invasion and chemoresistance

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

Sansing, Hope A.; Sarkeshik, Ali; Yates, John R.

2011-03-11

Research highlights: {yields} Proteomics of clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta}, {alpha}{sub 6}{beta} receptors in oral carcinoma. {yields} p130Cas, Dek, Src and talin regulate oral carcinoma invasion. {yields} p130Cas, talin, Src and zyxin regulate oral carcinoma resistance to cisplatin. -- Abstract: Ligand engagement by integrins induces receptor clustering and formation of complexes at the integrin cytoplasmic face that controls cell signaling and cytoskeletal dynamics critical for adhesion-dependent processes. This study searches for a subset of integrin effectors that coordinates both tumor cell invasion and resistance to the chemotherapeutic drug cisplatin in oral carcinomas. Candidate integrin effectors were identified in a proteomicsmore » screen of proteins recruited to clustered integrin {alpha}{beta}1, {alpha}{sub v}{beta} or {alpha}{sub 6}{beta} receptors in oral carcinomas. Proteins with diverse functions including microtubule and actin binding proteins, and factors involved in trafficking, transcription and translation were identified in oral carcinoma integrin complexes. Knockdown of effectors in the oral carcinoma HN12 cells revealed that p130Cas, Dek, Src and talin were required for invasion through Matrigel. Disruption of talin or p130Cas by RNA interference increased resistance to cisplatin, whereas targeting Dek, Src or zyxin reduced HN12 resistance to cisplatin. Analysis of the spreading of HN12 cells on collagen I and laminin I revealed that a decrease in p130Cas or talin expression inhibited spreading on both matrices. Interestingly, a reduction in zyxin expression enhanced spreading on laminin I and inhibited spreading on collagen I. Reduction of Dek, Src, talin or zyxin expression reduced HN12 proliferation by 30%. Proliferation was not affected by a reduction in p130Cas expression. We conclude that p130Cas, Src and talin function in both oral carcinoma invasion and resistance to cisplatin.« less

lin-4 and the NRDE pathway are required to activate a transgenic lin-4 reporter but not the endogenous lin-4 locus in C. elegans.

PubMed

Jiao, Alan L; Foster, Daniel J; Dixon, Julia; Slack, Frank J

2018-01-01

As the founding member of the microRNA (miRNA) gene family, insights into lin-4 regulation and function have laid a conceptual foundation for countless miRNA-related studies that followed. We previously showed that a transcriptional lin-4 reporter in C. elegans was positively regulated by a lin-4-complementary element (LCE), and by lin-4 itself. In this study, we sought to (1) identify additional factors required for lin-4 reporter expression, and (2) validate the endogenous relevance of a potential positive autoregulatory mechanism of lin-4 expression. We report that all four core nuclear RNAi factors (nrde-1, nrde-2, nrde-3 and nrde-4), positively regulate lin-4 reporter expression. In contrast, endogenous lin-4 levels were largely unaffected in nrde-2;nrde-3 mutants. Further, an endogenous LCE deletion generated by CRISPR-Cas9 revealed that the LCE was also not necessary for the activity of the endogenous lin-4 promoter. Finally, mutations in mature lin-4 did not reduce primary lin-4 transcript levels. Taken together, these data indicate that under growth conditions that reveal effects at the transgenic locus, a direct, positive autoregulatory mechanism of lin-4 expression does not occur in the context of the endogenous lin-4 locus.

In vitro expansion of Lin+ and Lin- mononuclear cells from human peripheral blood

NASA Astrophysics Data System (ADS)

Norhaiza, H. Siti; Rohaya, M. A. W.; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul

2013-11-01

Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin-) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs) were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin+) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin- cell population. The ability of Lin+ and Lin- to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin+ and Lin- were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin+ mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin- stem cells were not able to survive in proliferation medium however, addition of cytokines into the proliferation medium support Lin

In vivo quantitative analysis of Talin turnover in response to force

PubMed Central

Hákonardóttir, Guðlaug Katrín; López-Ceballos, Pablo; Herrera-Reyes, Alejandra Donají; Das, Raibatak; Coombs, Daniel; Tanentzapf, Guy

2015-01-01

Cell adhesion to the extracellular matrix (ECM) allows cells to form and maintain three-dimensional tissue architecture. Cell–ECM adhesions are stabilized upon exposure to mechanical force. In this study, we used quantitative imaging and mathematical modeling to gain mechanistic insight into how integrin-based adhesions respond to increased and decreased mechanical forces. A critical means of regulating integrin-based adhesion is provided by modulating the turnover of integrin and its adhesion complex (integrin adhesion complex [IAC]). The turnover of the IAC component Talin, a known mechanosensor, was analyzed using fluorescence recovery after photobleaching. Experiments were carried out in live, intact flies in genetic backgrounds that increased or decreased the force applied on sites of adhesion. This analysis showed that when force is elevated, the rate of assembly of new adhesions increases such that cell–ECM adhesion is stabilized. Moreover, under conditions of decreased force, the overall rate of turnover, but not the proportion of adhesion complex components undergoing turnover, increases. Using point mutations, we identify the key functional domains of Talin that mediate its response to force. Finally, by fitting a mathematical model to the data, we uncover the mechanisms that mediate the stabilization of ECM-based adhesion during development. PMID:26446844

Nitric oxide inhibits calpain-mediated proteolysis of talin in skeletal muscle cells

NASA Technical Reports Server (NTRS)

Koh, T. J.; Tidball, J. G.

2000-01-01

We tested the hypothesis that nitric oxide can inhibit cytoskeletal breakdown in skeletal muscle cells by inhibiting calpain cleavage of talin. The nitric oxide donor sodium nitroprusside prevented many of the effects of calcium ionophore on C(2)C(12) muscle cells, including preventing talin proteolysis and release into the cytosol and reducing loss of vinculin, cell detachment, and loss of cellular protein. These results indicate that nitric oxide inhibition of calpain protected the cells from ionophore-induced proteolysis. Calpain inhibitor I and a cell-permeable calpastatin peptide also protected the cells from proteolysis, confirming that ionophore-induced proteolysis was primarily calpain mediated. The activity of m-calpain in a casein zymogram was inhibited by sodium nitroprusside, and this inhibition was reversed by dithiothreitol. Previous incubation with the active site-targeted calpain inhibitor I prevented most of the sodium nitroprusside-induced inhibition of m-calpain activity. These data suggest that nitric oxide inhibited m-calpain activity via S-nitrosylation of the active site cysteine. The results of this study indicate that nitric oxide produced endogenously by skeletal muscle and other cell types has the potential to inhibit m-calpain activity and cytoskeletal proteolysis.

Cell Adhesion-dependent Serine 85 Phosphorylation of Paxillin Modulates Focal Adhesion Formation and Haptotactic Migration via Association with the C-terminal Tail Domain of Talin*

PubMed Central

Kwak, Tae Kyoung; Lee, Mi-Sook; Ryu, Jihye; Choi, Yoon-Ju; Kang, Minkyung; Jeong, Doyoung; Lee, Jung Weon

2012-01-01

Integrin-mediated adhesion to extracellular matrix proteins is dynamically regulated during morphological changes and cell migration. Upon cell adhesion, protein-protein interactions among molecules at focal adhesions (FAs) play major roles in the regulation of cell morphogenesis and migration. Although tyrosine phosphorylation of paxillin is critically involved in adhesion-mediated signaling, the significance of paxillin phosphorylation at Ser-85 and the mechanism by which it regulates cell migration remain unclear. In this study, we examined how Ser-85 phosphorylation of paxillin affects FA formation and cell migration. We found that paxillin phosphorylation at Ser-85 occurred during HeLa cell adhesion to collagen I and was concomitant with tyrosine phosphorylation of both focal adhesion kinase and talin. However, the non-phosphorylatable S85A mutant of paxillin impaired cell spreading, FA turnover, and migration toward collagen I but not toward serum. Furthermore, whereas the (presumably indirect) interaction between paxillin and the C-terminal tail of talin led to dynamic FAs at the cell boundary, S85A paxillin did not bind talin and caused stabilized FAs in the central region of cells. Together, these observations suggest that cell adhesion-dependent Ser-85 phosphorylation of paxillin is important for its interaction with talin and regulation of dynamic FAs and cell migration. PMID:22761432

In vitro expansion of Lin{sup +} and Lin{sup −} mononuclear cells from human peripheral blood

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

Norhaiza, H. Siti; Zarina, Z. A. Intan; Hisham, Z. A. Shahrul

2013-11-27

Haematopoietic stem cells (HSCs) are used in the therapy of blood disorders due to the ability of these cells to reconstitute haematopoietic lineage cells when transplanted into myeloablative recipients. However, substantial number of cells is required in order for the reconstitution to take place. Since HSCs present in low frequency, larger number of donor is required to accommodate the demand of transplantable HSCs. Therefore, in vitro expansion of HSCs will have profound impact on clinical purposes. The aim of this study was to expand lineage negative (Lin{sup −}) stem cells from human peripheral blood. Total peripheral blood mononuclear cells (PBMNCs)more » were fractionated from human blood by density gradient centrifugation. Subsequently, PBMNCs were subjected to magnetic assisted cell sorter (MACS) which depletes lineage positive (Lin{sup +}) mononuclear cells expressing lineage positive markers such as CD2, CD3, CD11b, CD14, CD15, CD16, CD19, CD56, CD123, and CD235a to obtained Lin{sup −} cell population. The ability of Lin{sup +} and Lin{sup −} to survive in vitro was explored by culturing both cell populations in complete medium consisting of Alpha-Minimal Essential Medium (AMEM) +10% (v/v) Newborn Calf Serum (NBCS)+ 2% (v/v) pen/strep. In another experiment, Lin{sup +} and Lin{sup −} were cultured with complete medium supplemented with 10ng/mL of the following growth factors: stem cell factor (SCF), interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF), 2IU/mL of Erythropoietin (Epo) and 20ng/mL of IL-6. Three samples were monitored in static culture for 22 days. The expansion potential was assessed by the number of total viable cells, counted by trypan blue exclusion assay. It was found that Lin{sup +} mononuclear cells were not able to survive either in normal proliferation medium or proliferation medium supplemented with cytokines. Similarly, Lin{sup −} stem cells were not able to survive in proliferation medium

The Lin28 Expression in Stallion Testes.

PubMed

Lee, Geumhui; Jung, Heejun; Yoon, Minjung

2016-01-01

The molecular markers for specific germ cell stages can be utilized for identifying, monitoring, and separating a particular stage of germ cells. The RNA-binding protein Lin28 is expressed in gonocytes of human fetal testes. The Lin28 expression is restricted to a very small population of spermatogonial cells in human, mice, and monkey. The main objective of this study was to investigate the expression pattern of Lin28 in stallion testes at different reproductive stages. Based on the presence or absence of full spermatogenesis and lumina in seminiferous tubules, the testicular samples were categorized into two reproductive stages pre-pubertal and post-pubertal. We performed a reverse transcription polymerase chain reaction to confirm the presence of Lin28 mRNA in the testicular tissues and a western blot analysis to verify the cross-reactivity of rabbit Lin28 antibody with horse testicular tissue. For immunohistochemistry, Lin28 (rabbit anti-human), GATA4 (goat anti-human) or DAZL (goat anti-human) antibodies were used. The results of RT-PCR confirmed the expression of Lin28 mRNA in the stallion testes. The western blot analysis showed that the expression of 28 kDa Lin28 protein was localized in the cytoplasm of spermatogonia at both reproductive stages. The numbers of Lin28-positive germ cells per 1000 Sertoli cells in pre- and post-pubertal stages were 253 ± 8.66 and 29.67 ± 2.18, respectively. At both reproductive stages, all Lin28 positive cells showed no co-stained with GATA4 antibody, whereas only some of the Lin28-positive germ cells showed co-staining with DAZL antibody. The results from whole-mount staining showed that the Lin28 expression was limited to Asingle (As) and Apaired (Apr) spermatogonia. In conclusion, Lin28 might be utilized as a molecular marker for undifferentiated spermatogonial stem cells when used with DAZL antibody.

The Lin28 Expression in Stallion Testes

PubMed Central

Yoon, Minjung

2016-01-01

The molecular markers for specific germ cell stages can be utilized for identifying, monitoring, and separating a particular stage of germ cells. The RNA-binding protein Lin28 is expressed in gonocytes of human fetal testes. The Lin28 expression is restricted to a very small population of spermatogonial cells in human, mice, and monkey. The main objective of this study was to investigate the expression pattern of Lin28 in stallion testes at different reproductive stages. Based on the presence or absence of full spermatogenesis and lumina in seminiferous tubules, the testicular samples were categorized into two reproductive stages pre-pubertal and post-pubertal. We performed a reverse transcription polymerase chain reaction to confirm the presence of Lin28 mRNA in the testicular tissues and a western blot analysis to verify the cross-reactivity of rabbit Lin28 antibody with horse testicular tissue. For immunohistochemistry, Lin28 (rabbit anti-human), GATA4 (goat anti-human) or DAZL (goat anti-human) antibodies were used. The results of RT-PCR confirmed the expression of Lin28 mRNA in the stallion testes. The western blot analysis showed that the expression of 28 kDa Lin28 protein was localized in the cytoplasm of spermatogonia at both reproductive stages. The numbers of Lin28-positive germ cells per 1000 Sertoli cells in pre- and post-pubertal stages were 253 ± 8.66 and 29.67 ± 2.18, respectively. At both reproductive stages, all Lin28 positive cells showed no co-stained with GATA4 antibody, whereas only some of the Lin28-positive germ cells showed co-staining with DAZL antibody. The results from whole-mount staining showed that the Lin28 expression was limited to Asingle (As) and Apaired (Apr) spermatogonia. In conclusion, Lin28 might be utilized as a molecular marker for undifferentiated spermatogonial stem cells when used with DAZL antibody. PMID:27798668

MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma

PubMed Central

Beckers, Anneleen; Van Peer, Gert; Carter, Daniel R.; Gartlgruber, Moritz; Herrmann, Carl; Agarwal, Saurabh; Helsmoortel, Hetty H.; Althoff, Kristina; Molenaar, Jan J.; Cheung, Belamy B.; Schulte, Johannes H.; Benoit, Yves; Shohet, Jason M.; Westermann, Frank; Marshall, Glenn M.; Vandesompele, Jo; De Preter, Katleen; Speleman, Frank

2016-01-01

LIN28B has been identified as an oncogene in various tumor entities, including neuroblastoma, a childhood cancer that originates from neural crest-derived cells, and is characterized by amplification of the MYCN oncogene. Recently, elevated LIN28B expression levels were shown to contribute to neuroblastoma tumorigenesis via let-7 dependent de-repression of MYCN. However, additional insight in the regulation of LIN28B in neuroblastoma is lacking. Therefore, we have performed a comprehensive analysis of the regulation of LIN28B in neuroblastoma, with a specific focus on the contribution of miRNAs. We show that MYCN regulates LIN28B expression in neuroblastoma tumors via two distinct parallel mechanisms. First, through an unbiased LIN28B-3′UTR reporter screen, we found that miR-26a-5p and miR-26b-5p regulate LIN28B expression. Next, we demonstrated that MYCN indirectly affects the expression of miR-26a-5p, and hence regulates LIN28B, therefor establishing a MYCN-miR-26a-5p-LIN28B regulatory axis. Second, we provide evidence that MYCN regulates LIN28B expression via interaction with the LIN28B promotor, establishing a direct MYCN-LIN28B regulatory axis. We believe that these findings mark LIN28B as an important effector of the MYCN oncogenic phenotype and underlines the importance of MYCN-regulated miRNAs in establishing the MYCN-driven oncogenic process. PMID:26123663

Bartonella henselae engages inside-out and outside-in signaling by integrin β1 and talin1 during invasome-mediated bacterial uptake.

PubMed

Truttmann, Matthias C; Misselwitz, Benjamin; Huser, Sonja; Hardt, Wolf-Dietrich; Critchley, David R; Dehio, Christoph

2011-11-01

The VirB/D4 type IV secretion system (T4SS) of the bacterial pathogen Bartonella henselae (Bhe) translocates seven effector proteins (BepA-BepG) into human cells that subvert host cellular functions. Two redundant pathways dependent on BepG or the combination of BepC and BepF trigger the formation of a bacterial uptake structure termed the invasome. Invasome formation is a multi-step process consisting of bacterial adherence, effector translocation, aggregation of bacteria on the cell surface and engulfment, and eventually, complete internalization of the bacterial aggregate occurs in an F-actin-dependent manner. In the present study, we show that Bhe-triggered invasome formation depends on integrin-β1-mediated signaling cascades that enable assembly of the F-actin invasome structure. We demonstrate that Bhe interacts with integrin β1 in a fibronectin- and VirB/D4 T4SS-independent manner and that activated integrin β1 is essential for both effector translocation and the actin rearrangements leading to invasome formation. Furthermore, we show that talin1, but not talin2, is required for inside-out activation of integrin β1 during invasome formation. Finally, integrin-β1-mediated outside-in signaling by FAK, Src, paxillin and vinculin is necessary for invasome formation. This is the first example of a bacterial entry process that fully exploits the bi-directional signaling capacity of integrin receptors in a talin1-specific manner.

Ground-state geometries and stability of impurity doped clusters: LinBe and LinMg (n=1-12)

NASA Astrophysics Data System (ADS)

Deshpande, M.; Dhavale, A.; Zope, R. R.; Chacko, S.; Kanhere, D. G.

2000-12-01

We have investigated the ground-state geometries of LinBe and LinMg (n=1-12) clusters using ab initio molecular dynamics. These divalent impurities Be and Mg induce different geometries and follow a different growth path for n>5. LinMg clusters are significantly different from the host geometries while LinBe clusters can be approximately viewed as Be occupying an interstitial site in the host. Our results indicate that Be gets trapped inside the Li cage, while Mg remains on the surface of the cluster. Mg-induced geometries become three-dimensional earlier at n=4 as compared to the Be system. In spite of a distinct arrangement of atoms in both cases the character of the wave functions in the d manifold is remarkably similar. In both cases an eight valence electron system has been found to be the most stable, in conformity with the spherical jellium model.

Weighted Lin-Wang Tests for Crossing Hazards

PubMed Central

Koziol, James A.; Jia, Zhenyu

2014-01-01

Lin and Wang have introduced a quadratic version of the logrank test, appropriate for situations in which the underlying survival distributions may cross. In this note, we generalize the Lin-Wang procedure to incorporate weights and investigate the performance of Lin and Wang's test and weighted versions in various scenarios. We find that weighting does increase statistical power in certain situations; however, none of the procedures was dominant under every scenario. PMID:24795776

Lin28a regulates germ cell pool size and fertility

PubMed Central

Shinoda, Gen; de Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Moss, Eric G.; Daley, George Q.

2013-01-01

Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. PMID:23378032

Bacterial diversity and real-time PCR based assessment of linA and linB gene distribution at hexachlorocyclohexane contaminated sites.

PubMed

Lal, Devi; Jindal, Swati; Kumari, Hansi; Jit, Simran; Nigam, Aeshna; Sharma, Pooja; Kumari, Kirti; Lal, Rup

2015-03-01

The disposal of hexachlorocyclohexane (HCH) muck has created large number of HCH dumpsites all over the world from where the harmful HCH isomers are leaking into the environment. Bacteria have evolved at such contaminated sites that have the ability to degrade HCH. Degradation of various HCH isomers in bacterial strains is mediated primarily by two genes: linA and linB which encode dehydrochlorinase and haloalkane dehalogenase respectively. In this study we explored one such highly contaminated HCH dumpsite located in Lucknow, Uttar Pradesh, India. To assess the biostimulation potential of the contaminated site, microbial diversity study and real-time PCR based quantification of lin genes was carried out. The soil samples from dumpsite and surrounding areas were found to be highly contaminated with HCH residue levels as high as 1.8 × 10(5)  mg kg(-1). The residues were detected in areas upto 13 km from the dumpsite. Sphingomonads, Chromohalobacter, and Marinobacter were the dominant genera present at the dump-site. Role of Sphingomonads in HCH degradation has been well documented. The highest copy numbers of linA and linB genes as determined using real-time PCR were 6.2 × 10(4) and 5.3 × 10(5), respectively, were found in sample from the dump site. The presence of Sphingomonads, linA, and linB genes from HCH contaminated soil indicates the presence of indigenous bacterial communities capable of HCH degradation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Lin28/let-7 axis regulates glucose metabolism

PubMed Central

Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

2012-01-01

SUMMARY The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by blocking let-7 biogenesis. In studies of the Lin28/let-7 pathway, we discovered unexpected roles in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, whereas muscle-specific loss of Lin28a and overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance. These phenomena occurred in part through let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. The mTOR inhibitor rapamycin abrogated the enhanced glucose uptake and insulin-sensitivity conferred by Lin28a in vitro and in vivo. In addition, we found that let-7 targets were enriched for genes that contain SNPs associated with type 2 diabetes and fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. PMID:21962509

The NCU Lu-Lin Observatory Survived the Taiwan 921 Earthquake

NASA Astrophysics Data System (ADS)

Tsay, W. S.; Chang, K. H.; Li, H. H.

1999-12-01

The NCU (National Central University) Lu-Lin Observatory is located at Mt. Front Lu-Lin, 120o 52' 25" E and 23o 28' 07" N, a 2862-m peak in the Yu-Shan National Park. The construction of Lu-Lin Observatory was finished in January 1999. Fortunately the Lu-Lin Observatory survived the Taiwan 921 Earthquake that was 7.3 on the Ritcher scale. We are proud of the design of Lu-Lin Observatory adopted H-beam and steel wall even the center of earthquake was only 40 km away. The initial study of Lu-Lin site was started since late 1989. Later on, a three-year project was founded by the National Science Council , which supported the development of a modern seeing monitor for this site survey study from 1990 through 1993. The average seeing of Lu-Lin site is about 1.39 arc-second with average 200 clear nights annually. The sky background of this site is 20.72 mag/arcsec2 in V band and 21.22 mag/arcsec2 in B band. The Lu-Lin observatory is developed for both research and education activity. A homemade 76-cm Super Light Telescope (SLT) and three TAOS's 50-cm robotic telescopes will be the two major research facilities. This work is supported by the National Science Council of Taiwan.

Lin28 sustains early renal progenitors and induces Wilms tumor

PubMed Central

Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S.; Zhu, Hao; Perez-Atayde, Antonio R.; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q.

2014-01-01

Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis. PMID:24732380

Antagonism of LIN-17/Frizzled and LIN-18/Ryk in nematode vulva induction reveals evolutionary alterations in core developmental pathways.

PubMed

Wang, Xiaoyue; Sommer, Ralf J

2011-07-01

Most diversity in animals and plants results from the modification of already existing structures. Many organ systems, for example, are permanently modified during evolution to create developmental and morphological diversity, but little is known about the evolution of the underlying developmental mechanisms. The theory of developmental systems drift proposes that the development of conserved morphological structures can involve large-scale modifications in their regulatory mechanisms. We test this hypothesis by comparing vulva induction in two genetically tractable nematodes, Caenorhabditis elegans and Pristionchus pacificus. Previous work indicated that the vulva is induced by epidermal growth factor (EGF)/RAS and WNT signaling in Caenorhabditis and Pristionchus, respectively. Here, we show that the evolution of vulva induction involves major molecular alterations and that this shift of signaling pathways involves a novel wiring of WNT signaling and the acquisition of novel domains in otherwise conserved receptors in Pristionchus vulva induction. First, Ppa-LIN-17/Frizzled acts as an antagonist of WNT signaling and suppresses the ligand Ppa-EGL-20 by ligand sequestration. Second, Ppa-LIN-18/Ryk transmits WNT signaling and requires inhibitory SH3 domain binding motifs, unknown from Cel-LIN-18/Ryk. Third, Ppa-LIN-18/Ryk signaling involves Axin and β-catenin and Ppa-axl-1/Axin is epistatic to Ppa-lin-18/Ryk. These results confirm developmental system drift as an important theory for the evolution of organ systems and they highlight the significance of protein modularity in signal transduction and the dynamics of signaling networks.

Selective blockade of microRNA processing by Lin-28

PubMed Central

Viswanathan, Srinivas R.; Daley, George Q.; Gregory, Richard I.

2012-01-01

MicroRNAs (miRNAs) play critical roles in development, and dysregulation of miRNA expression has been observed in human malignancies. Recent evidence suggests that the processing of several primary miRNA transcripts (pri-miRNAs) is blocked post-transcriptionally in embryonic stem (ES) cells, embryonal carcinoma (EC) cells, and primary tumors. Here we show that Lin-28, a developmentally regulated RNA-binding protein, selectively blocks the processing of pri-let-7 miRNAs in embryonic cells. Using in vitro and in vivo studies, we demonstrate that Lin-28 is necessary and sufficient for blocking Microprocessor-mediated cleavage of pri-let-7 miRNAs. Our results identify Lin-28 as a negative regulator of miRNA biogenesis and suggest that Lin-28 may play a central role in blocking miRNA-mediated differentiation in stem cells and certain cancers. PMID:18292307

Antagonism of LIN-17/Frizzled and LIN-18/Ryk in Nematode Vulva Induction Reveals Evolutionary Alterations in Core Developmental Pathways

PubMed Central

Wang, Xiaoyue; Sommer, Ralf J.

2011-01-01

Most diversity in animals and plants results from the modification of already existing structures. Many organ systems, for example, are permanently modified during evolution to create developmental and morphological diversity, but little is known about the evolution of the underlying developmental mechanisms. The theory of developmental systems drift proposes that the development of conserved morphological structures can involve large-scale modifications in their regulatory mechanisms. We test this hypothesis by comparing vulva induction in two genetically tractable nematodes, Caenorhabditis elegans and Pristionchus pacificus. Previous work indicated that the vulva is induced by epidermal growth factor (EGF)/RAS and WNT signaling in Caenorhabditis and Pristionchus, respectively. Here, we show that the evolution of vulva induction involves major molecular alterations and that this shift of signaling pathways involves a novel wiring of WNT signaling and the acquisition of novel domains in otherwise conserved receptors in Pristionchus vulva induction. First, Ppa-LIN-17/Frizzled acts as an antagonist of WNT signaling and suppresses the ligand Ppa-EGL-20 by ligand sequestration. Second, Ppa-LIN-18/Ryk transmits WNT signaling and requires inhibitory SH3 domain binding motifs, unknown from Cel-LIN-18/Ryk. Third, Ppa-LIN-18/Ryk signaling involves Axin and β-catenin and Ppa-axl-1/Axin is epistatic to Ppa-lin-18/Ryk. These results confirm developmental system drift as an important theory for the evolution of organ systems and they highlight the significance of protein modularity in signal transduction and the dynamics of signaling networks. PMID:21814488

Dynamic gene expression of Lin-28 during embryonic development in mouse and chicken.

PubMed

Yokoyama, Shigetoshi; Hashimoto, Megumi; Shimizu, Hirohito; Ueno-Kudoh, Hiroe; Uchibe, Kenta; Kimura, Ichiro; Asahara, Hiroshi

2008-02-01

The Caenorhabditis elegans heterochronic gene lin-28 regulates developmental timing in the nematode trunk. We report the dynamic expression patterns of Lin-28 homologues in mouse and chick embryos. Whole mount in situ hybridization revealed specific and intriguing expression patterns of Lin-28 in the developing mouse and chick limb bud. Mouse Lin-28 expression was detected in both the forelimb and hindlimb at E9.5, but disappeared from the forelimb at E10.5, and finally from the forelimb and hindlimb at E11.5. Chicken Lin-28, which was first detected in the limb primordium at stage 15/16, was also downregulated as the stage proceeded. The amino acid sequences of mouse and chicken Lin-28 genes are highly conserved and the similar expression patterns of Lin-28 during limb development in mouse and chicken suggest that this heterochronic gene is also conserved during vertebrate limb development.

Multiple transcription factors directly regulate Hox gene lin-39 expression in ventral hypodermal cells of the C. elegans embryo and larva, including the hypodermal fate regulators LIN-26 and ELT-6.

PubMed

Liu, Wan-Ju; Reece-Hoyes, John S; Walhout, Albertha J M; Eisenmann, David M

2014-05-13

Hox genes encode master regulators of regional fate specification during early metazoan development. Much is known about the initiation and regulation of Hox gene expression in Drosophila and vertebrates, but less is known in the non-arthropod invertebrate model system, C. elegans. The C. elegans Hox gene lin-39 is required for correct fate specification in the midbody region, including the Vulval Precursor Cells (VPCs). To better understand lin-39 regulation and function, we aimed to identify transcription factors necessary for lin-39 expression in the VPCs, and in particular sought factors that initiate lin-39 expression in the embryo. We used the yeast one-hybrid (Y1H) method to screen for factors that bound to 13 fragments from the lin-39 region: twelve fragments contained sequences conserved between C. elegans and two other nematode species, while one fragment was known to drive reporter gene expression in the early embryo in cells that generate the VPCs. Sixteen transcription factors that bind to eight lin-39 genomic fragments were identified in yeast, and we characterized several factors by verifying their physical interactions in vitro, and showing that reduction of their function leads to alterations in lin-39 levels and lin-39::GFP reporter expression in vivo. Three factors, the orphan nuclear hormone receptor NHR-43, the hypodermal fate regulator LIN-26, and the GATA factor ELT-6 positively regulate lin-39 expression in the embryonic precursors to the VPCs. In particular, ELT-6 interacts with an enhancer that drives GFP expression in the early embryo, and the ELT-6 site we identified is necessary for proper embryonic expression. These three factors, along with the factors ZTF-17, BED-3 and TBX-9, also positively regulate lin-39 expression in the larval VPCs. These results significantly expand the number of factors known to directly bind and regulate lin-39 expression, identify the first factors required for lin-39 expression in the embryo, and hint at a

A Network of Genes Antagonistic to the LIN-35 Retinoblastoma Protein of Caenorhabditis elegans

PubMed Central

Polley, Stanley R. G.; Fay, David S.

2012-01-01

The Caenorhabditis elegans pRb ortholog, LIN-35, functions in a wide range of cellular and developmental processes. This includes a role of LIN-35 in nutrient utilization by the intestine, which it carries out redundantly with SLR-2, a zinc-finger protein. This and other redundant functions of LIN-35 were identified in genetic screens for mutations that display synthetic phenotypes in conjunction with loss of lin-35. To explore the intestinal role of LIN-35, we conducted a genome-wide RNA-interference-feeding screen for suppressors of lin-35; slr-2 early larval arrest. Of the 26 suppressors identified, 17 fall into three functional classes: (1) ribosome biogenesis genes, (2) mitochondrial prohibitins, and (3) chromatin regulators. Further characterization indicates that different categories of suppressors act through distinct molecular mechanisms. We also tested lin-35; slr-2 suppressors, as well as suppressors of the synthetic multivulval phenotype, to determine the spectrum of lin-35-synthetic phenotypes that could be suppressed following inhibition of these genes. We identified 19 genes, most of which are evolutionarily conserved, that can suppress multiple unrelated lin-35-synthetic phenotypes. Our study reveals a network of genes broadly antagonistic to LIN-35 as well as genes specific to the role of LIN-35 in intestinal and vulval development. Suppressors of multiple lin-35 phenotypes may be candidate targets for anticancer therapies. Moreover, screening for suppressors of phenotypically distinct synthetic interactions, which share a common altered gene, may prove to be a novel and effective approach for identifying genes whose activities are most directly relevant to the core functions of the shared gene. PMID:22542970

Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism

PubMed Central

Shinoda, Gen; Shyh-Chang, Ng; de Soysa, T. Yvanka; Zhu, Hao; Seligson, Marc T.; Shah, Samar P.; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P.; Gregory, Richard I.; Asara, John M.; Cantley, Lewis C.; Moss, Eric G.; Daley, George Q.

2013-01-01

LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO can be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. PMID:23666760

Lin28 induces resistance to anti-androgens via promotion of AR splice variant generation.

PubMed

Tummala, Ramakumar; Nadiminty, Nagalakshmi; Lou, Wei; Evans, Christopher P; Gao, Allen C

2016-04-01

Prostate cancer (PCa) is androgen-dependent initially and progresses to a castration-resistant state after androgen deprivation therapy. Treatment options for castration-resistant PCa include the potent second-generation anti-androgen enzalutamide or CYP17A1 inhibitor abiraterone. Recent clinical observations point to the development of resistance to these therapies which may be mediated by constitutively active alternative splice variants of the androgen receptor (AR). Sensitivity of LNCaP cells overexpressing Lin28 (LN-Lin28) to enzalutamide, abiraterone, or bicalutamide was compared to that of control LN-neo cells using cell growth assays, proliferation assays using MTT, anchorage-dependent clonogenic ability assays and soft agar assays. Ability of LN-Lin28 cells to maintain AR activation after treatment with enzalutamide, abiraterone, or bicalutamide was tested using immunofluorescence, Western blotting, ChIP assays, and qRT-PCR. Importance of Lin28 in enzalutamide resistance was assessed by the downregulation of Lin28 expression in C4-2B and 22Rv1 cells chronically treated with enzalutamide. Requirement for sustained AR signaling in LN-Lin28 cells was examined by the downregulation of either full length AR or AR-V7 using siRNA. We show that Lin28 promotes the development of resistance to currently used targeted therapeutics by enhancing the expression of AR splice variants such as AR-V7. PCa cells overexpressing Lin28 exhibit resistance to treatment with enzalutamide, abiraterone, or bicalutamide. Downregulation of Lin28 resensitizes enzalutamide-resistant PCa cells to enzalutamide treatment. We also show that the upregulation of splicing factors such as hnRNPA1 by Lin28 may mediate the enhanced generation of AR splice variants in Lin28-expressing cells. Our findings suggest that Lin28 plays a key role in the acquisition of resistance to AR-targeted therapies by PCa cells and establish the importance of Lin28 in PCa progression. © 2015 Wiley Periodicals, Inc.

Dynamics of Multiple lin Gene Expression in Sphingomonas paucimobilis B90A in Response to Different Hexachlorocyclohexane Isomers

PubMed Central

Suar, Mrutyunjay; van der Meer, Jan Roelof; Lawlor, Kirsten; Holliger, Christof; Lal, Rup

2004-01-01

Sphingomonas paucimobilis B90A is able to degrade the α-, β-, γ-, and δ-isomers of hexachlorocyclohexane (HCH). It contains the genes linA, linB, linC, linD, linE, and linR, which have been implicated in HCH degradation. In this study, dynamic expression of the lin genes was measured in chemostat-grown S. paucimobilis B90A by RNA dot blot hybridization and real-time reverse transcriptase PCR upon exposure to a pulse of different HCH isomers. Irrespective of the addition of HCH, linA, linB, and linC were all expressed constitutively. In contrast, linD and linE were induced with α-HCH (2 mg/liter) and γ-HCH (7 mg/liter). A sharp increase in mRNA levels for linD and linE was observed from 10 to 45 min after the addition of α- or γ-HCH. Induction of linD and linE was not detectable upon the addition of 0.7 mg of γ-HCH per liter, although the compound was degraded by the cells. The addition of β-HCH (5 mg/liter) or δ-HCH (20 mg/liter) did not lead to linE and linD induction, despite the fact that 50% of the compounds were degraded. This suggests that degradation of β- and δ-HCH proceeds by a different pathway than that of α- and γ-HCH. PMID:15528530

A role for Lin-28 in growth and metamorphosis in Drosophila melanogaster.

PubMed

González-Itier, Sergio; Contreras, Esteban G; Larraín, Juan; Glavic, Álvaro; Faunes, Fernando

2018-06-13

Insect metamorphosis has been a classic model to understand the role of hormones in growth and timing of developmental transitions. In addition to hormones, transitions in some species are regulated by genetic programs, such as the heterochronic gene network discovered in C. elegans. However, the functional link between hormones and heterochronic genes is not clear. The heterochronic gene lin-28 is involved in the maintenance of stem cells, growth and developmental timing in vertebrates. In this work, we used gain-of-function and loss-of-function experiments to study the role of Lin-28 in larval growth and the timing of metamorphosis of Drosophila melanogaster. During the late third instar stage, Lin-28 is mainly expressed in neurons of the central nervous system and in the intestine. Loss-of-function lin-28 mutant larvae are smaller and the larval-to-pupal transition is accelerated. This faster transition correlates with increased levels of ecdysone direct target genes such as Broad-Complex (BR-C) and Ecdysone Receptor (EcR). Overexpression of Lin-28 does not affect the timing of pupariation but most animals are not able to eclose, suggesting defects in metamorphosis. Overexpression of human Lin-28 results in delayed pupariation and the death of animals during metamorphosis. Altogether, these results suggest that Lin-28 is involved in the control of growth during larval development and in the timing and progression of metamorphosis. Copyright © 2017. Published by Elsevier B.V.

LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans

PubMed Central

Tu, Ho-Chou; Schwitalla, Sarah; Qian, Zhirong; LaPier, Grace S.; Yermalovich, Alena; Ku, Yuan-Chieh; Chen, Shann-Ching; Viswanathan, Srinivas R.; Zhu, Hao; Nishihara, Reiko; Inamura, Kentaro; Kim, Sun A.; Morikawa, Teppei; Mima, Kosuke; Sukawa, Yasutaka; Yang, Juhong; Meredith, Gavin; Fuchs, Charles S.; Ogino, Shuji

2015-01-01

Colorectal cancer (CRC) remains a major contributor to cancer-related mortality. LIN28A and LIN28B are highly related RNA-binding protein paralogs that regulate biogenesis of let-7 microRNAs and influence development, metabolism, tissue regeneration, and oncogenesis. Here we demonstrate that overexpression of either LIN28 paralog cooperates with the Wnt pathway to promote invasive intestinal adenocarcinoma in murine models. When LIN28 alone is induced genetically, half of the resulting tumors harbor Ctnnb1 (β-catenin) mutation. When overexpressed in ApcMin/+ mice, LIN28 accelerates tumor formation and enhances proliferation and invasiveness. In conditional genetic models, enforced expression of a LIN28-resistant form of the let-7 microRNA reduces LIN28-induced tumor burden, while silencing of LIN28 expression reduces tumor volume and increases tumor differentiation, indicating that LIN28 contributes to tumor maintenance. We detected aberrant expression of LIN28A and/or LIN28B in 38% of a large series of human CRC samples (n = 595), where LIN28 expression levels were associated with invasive tumor growth. Our late-stage CRC murine models and analysis of primary human tumors demonstrate prominent roles for both LIN28 paralogs in promoting CRC growth and progression and implicate the LIN28/let-7 pathway as a therapeutic target. PMID:25956904

Lin Receives 2010 Natural Hazards Focus Group Award for Graduate Research

NASA Astrophysics Data System (ADS)

2010-11-01

Ning Lin has been awarded the Natural Hazards Focus Group Award for Graduate Research, given annually to a recent Ph.D. recipient for outstanding contributions to natural hazards research. Lin's thesis is entitled “Multi-hazard risk analysis related to hurricanes.” She is scheduled to present an invited talk in the Extreme Natural Events: Modeling, Prediction, and Mitigation session (NH20) during the 2010 AGU Fall Meeting, held 13-17 December in San Francisco, Calif. Lin will be formally presented with the award at the Natural Hazards focus group reception on 14 December 2010.

Let-7 miRNA Precursors Co-express with LIN28B in Cervical Cells.

PubMed

Zamora-Contreras, Aida Margarita; Alvarez-Salas, Luis Marat

2018-01-01

The let-7 microRNAs (miRNAs) are frequently dysregulated in carcinogenic processes, including cervical cancer. LIN28 proteins regulate let-7 biogenesis by binding to conserved sequences within the pre-miRNA structure. Nevertheless, recent research has shown that some let-7 miRNAs may escape LIN28 regulation. Correlate pre-let-7 miRNAs and LIN28B levels in cervical cell lines with different malignancy and HPV content. Pre-let-7 levels were determined by RTqPCR. LIN28B and other let-7 targets were analyzed by immunoblot. In silico tools were used to correlate let-7 and LIN28B expression and to analyze prelet- 7 sequences and structures. Lin28B protein was detected in all tested cell lines although it was more expressed in tumor cell lines. High levels of pre-let-7c/f-1 and pre-miR-98 were present in almost all cell lines regardless malignancy and LIN28B expression. Pre-let-7g/i were mainly expressed in tumor cell lines, pre-let-7e and pre-let-7-a3 were absent in all cell lines and pre-let-7a-2 showed indistinct expression. LIN28B showed positive correlation with pre-let-7i/g/f-1 and pre-miR-98 in tumor cell lines, suggesting escape from regulation. Sequence alignment and analysis of pre-let-7 miRNAs showed distinctive structural features within the preE region that may influence the ideal pre-let-7 structuring for LIN28B interaction. Short preE-stems were present in pre-let-7 that may escape LIN28B regulation, but long preEstems were mostly associated with high-level pre-let-7 miRNAs. The observed differences of pre-let-7 levels in cervical cell lines may be the result of alternative preE structuring affecting interaction with LIN28B thus resulting in differential let-7 regulation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models

PubMed Central

Nguyen, Liem H.; Robinton, Daisy A.; Seligson, Marc; Wu, Linwei; Li, Lin; Rakheja, Dinesh; Comerford, Sarah; Ramezani, Saleh; Sun, Xiankai; Parikh, Monisha; Yang, Erin; Powers, John T.; Shinoda, Gen; Shah, Samar; Hammer, Robert; Daley, George Q.; Zhu, Hao

2014-01-01

SUMMARY Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Thus, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance. PMID:25117712

Lin-28 binds IGF-2 mRNA and participates in skeletal myogenesis by increasing translation efficiency.

PubMed

Polesskaya, Anna; Cuvellier, Sylvain; Naguibneva, Irina; Duquet, Arnaud; Moss, Eric G; Harel-Bellan, Annick

2007-05-01

Lin-28 is a highly conserved, RNA-binding, microRNA-regulated protein that is involved in regulation of developmental timing in Caenorhabditis elegans. In mammals, Lin-28 is stage-specifically expressed in embryonic muscle, neurons, and epithelia, as well as in embryonic carcinoma cells, but is suppressed in most adult tissues, with the notable exception of skeletal and cardiac muscle. The specific function and mechanism of action of Lin-28 are not well understood. Here we used loss-of-function and gain-of-function assays in cultured myoblasts to show that expression of Lin-28 is essential for skeletal muscle differentiation in mice. In order to elucidate the specific function of Lin-28, we used a combination of biochemical and functional assays, which revealed that, in differentiating myoblasts, Lin-28 binds to the polysomes and increases the efficiency of protein synthesis. An important target of Lin-28 is IGF-2, a crucial growth and differentiation factor for muscle tissue. Interaction of Lin-28 with translation initiation complexes in skeletal myoblasts and in the embryonic carcinoma cell line P19 was confirmed by localization of Lin-28 to the stress granules, temporary structures that contain stalled mRNA-protein translation complexes. Our results unravel novel mechanisms of translational regulation in skeletal muscle and suggest that Lin-28 performs the role of "translational enhancer" in embryonic and adult cells and tissues.

The heterochronic gene Lin28 regulates amphibian metamorphosis through disturbance of thyroid hormone function.

PubMed

Faunes, Fernando; Gundermann, Daniel G; Muñoz, Rosana; Bruno, Renzo; Larraín, Juan

2017-05-15

Metamorphosis is a classic example of developmental transition, which involves important morphological and physiological changes that prepare the organism for the adult life. It has been very well established that amphibian metamorphosis is mainly controlled by Thyroid Hormone (TH). Here, we show that the heterochronic gene Lin28 is downregulated during Xenopus laevis metamorphosis. Lin28 overexpression before activation of TH signaling delays metamorphosis and inhibits the expression of TH target genes. The delay in metamorphosis is rescued by incubation with exogenous TH, indicating that Lin28 works upstream or parallel to TH. High-throughput analyses performed before any delay on metamorphosis or change in TH signaling showed that overexpression of Lin28 reduces transcript levels of several hormones secreted by the pituitary, including the Thyroid-Stimulating Hormone (TSH), and regulates the expression of proteins involved in TH transport, metabolism and signaling, showing that Lin28 disrupts TH function at different levels. Our data demonstrates that the role of Lin28 in controlling developmental transitions is evolutionary conserved and establishes a functional interaction between Lin28 and thyroid hormone function introducing a new regulatory step in perinatal development with implications for our understanding of endocrine disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Lin4Neuro: a customized Linux distribution ready for neuroimaging analysis

PubMed Central

2011-01-01

Background A variety of neuroimaging software packages have been released from various laboratories worldwide, and many researchers use these packages in combination. Though most of these software packages are freely available, some people find them difficult to install and configure because they are mostly based on UNIX-like operating systems. We developed a live USB-bootable Linux package named "Lin4Neuro." This system includes popular neuroimaging analysis tools. The user interface is customized so that even Windows users can use it intuitively. Results The boot time of this system was only around 40 seconds. We performed a benchmark test of inhomogeneity correction on 10 subjects of three-dimensional T1-weighted MRI scans. The processing speed of USB-booted Lin4Neuro was as fast as that of the package installed on the hard disk drive. We also installed Lin4Neuro on a virtualization software package that emulates the Linux environment on a Windows-based operation system. Although the processing speed was slower than that under other conditions, it remained comparable. Conclusions With Lin4Neuro in one's hand, one can access neuroimaging software packages easily, and immediately focus on analyzing data. Lin4Neuro can be a good primer for beginners of neuroimaging analysis or students who are interested in neuroimaging analysis. It also provides a practical means of sharing analysis environments across sites. PMID:21266047

Lin4Neuro: a customized Linux distribution ready for neuroimaging analysis.

PubMed

Nemoto, Kiyotaka; Dan, Ippeita; Rorden, Christopher; Ohnishi, Takashi; Tsuzuki, Daisuke; Okamoto, Masako; Yamashita, Fumio; Asada, Takashi

2011-01-25

A variety of neuroimaging software packages have been released from various laboratories worldwide, and many researchers use these packages in combination. Though most of these software packages are freely available, some people find them difficult to install and configure because they are mostly based on UNIX-like operating systems. We developed a live USB-bootable Linux package named "Lin4Neuro." This system includes popular neuroimaging analysis tools. The user interface is customized so that even Windows users can use it intuitively. The boot time of this system was only around 40 seconds. We performed a benchmark test of inhomogeneity correction on 10 subjects of three-dimensional T1-weighted MRI scans. The processing speed of USB-booted Lin4Neuro was as fast as that of the package installed on the hard disk drive. We also installed Lin4Neuro on a virtualization software package that emulates the Linux environment on a Windows-based operation system. Although the processing speed was slower than that under other conditions, it remained comparable. With Lin4Neuro in one's hand, one can access neuroimaging software packages easily, and immediately focus on analyzing data. Lin4Neuro can be a good primer for beginners of neuroimaging analysis or students who are interested in neuroimaging analysis. It also provides a practical means of sharing analysis environments across sites.

Lin28 Mediates Cancer Chemotherapy Resistance via Regulation of miRNA Signaling.

PubMed

Xu, Chaoyang; Xie, Shuduo; Song, Chunjiao; Huang, Liming; Jiang, Zhinong

2014-06-01

Chemotherapy resistance is one of the major obstacles limiting the success of cancer drug treatment. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to P-Glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. Lin28 is a highly conserved RNA-binding protein, it consists of a cold shock domain and retroviral-type (CCHC) zinc finger motifs. In previous preclinical and clinical studies, positive Lin28 expression in cancer cells was correlated with decreased sensitivity to chemotherapy. And Lin28 could mediate cancer chemotherapy resistance via regulation of miR107 and Let-7 MiRNA. This article reviews current knowledge on predictive value of Lin28 in response to chemotherapy. Better understanding of its role may facilitate patient's selection of therapeutic regimen and lead to optimal clinical outcome.

Importance of the pluripotency factor LIN28 in the mammalian nucleolus during early embryonic development.

PubMed

Vogt, Edgar J; Meglicki, Maciej; Hartung, Kristina Ilka; Borsuk, Ewa; Behr, Rüdiger

2012-12-01

The maternal nucleolus is required for proper activation of the embryonic genome (EGA) and early embryonic development. Nucleologenesis is characterized by the transformation of a nucleolar precursor body (NPB) to a mature nucleolus during preimplantation development. However, the function of NPBs and the involved molecular factors are unknown. We uncover a novel role for the pluripotency factor LIN28, the biological significance of which was previously demonstrated in the reprogramming of human somatic cells to induced pluripotent stem (iPS) cells. Here, we show that LIN28 accumulates at the NPB and the mature nucleolus in mouse preimplantation embryos and embryonic stem cells (ESCs), where it colocalizes with the nucleolar marker B23 (nucleophosmin 1). LIN28 has nucleolar localization in non-human primate (NHP) preimplantation embryos, but is cytoplasmic in NHP ESCs. Lin28 transcripts show a striking decline before mouse EGA, whereas LIN28 protein localizes to NPBs at the time of EGA. Following knockdown with a Lin28 morpholino, the majority of embryos arrest between the 2- and 4-cell stages and never develop to morula or blastocyst. Lin28 morpholino-injected embryos arrested at the 2-cell stage were not enriched with nucleophosmin at presumptive NPB sites, indicating that functional NPBs were not assembled. Based on these results, we propose that LIN28 is an essential factor of nucleologenesis during early embryonic development.

Clinicopathological Characteristics of Patients with Gastric Cancer according to the Expression of LIN28A.

PubMed

Park, Chan Hyuk; Lee, Jung Hwa; Lee, Na Keum; Lee, Yong Chan; Lee, Sang Kil

2016-09-15

Although LIN28A is known to potentially play a role in the oncogenesis of various cancers, whether LIN28A expression is a predictor of poor prognosis in patients with gastric cancer has not been fully explored. We sought to evaluate clinicopathological characteristics according to the expression of LIN28A in numerous gastric cancer tissue samples. LIN28A expression was evaluated by immunohistochemical (IHC) analysis of a tissue microarray comprising 288 gastric cancer tissues and 288 adjacent normal tissues. Clinicopathological characteristics, including overall survival, were compared according to LIN28A expression. The IHC staining score was lower for the cancer tissues than the normal tissues (p<0.001). However, no significant differences were observed in the clinicopathological characteristics between the low and high LIN28A expression groups. In addition, the 5-year overall survival rate did not differ between the two groups: 75.3% (95% confidence interval [CI], 69.3% to 81.7%) versus 71.6% (95% CI, 63.3% to 80.9%) for low versus high expression, respectively. The expression of LIN28A did not appear to play a distinct role in predicting the clinicopathological characteristics of patients with gastric cancer. In addition, LIN28A expression was not an independently associated factor for overall survival in patients with gastric cancer.

Reciprocal Expression of lin-41 and the microRNAs let-7 and mir-125 During Mouse Embryogenesis

PubMed Central

Schulman, Betsy R. Maller; Esquela-Kerscher, Aurora; Slack, Frank J.

2008-01-01

In C. elegans, heterochronic genes control the timing of cell fate determination during development. Two heterochronic genes, let-7 and lin-4, encode microRNAs (miRNAs) that down-regulate a third heterochronic gene lin-41 by binding to complementary sites in its 3’UTR. let-7 and lin-4 are conserved in mammals. Here we report the cloning and sequencing of mammalian lin-41 orthologs. We find that mouse and human lin-41 genes contain predicted conserved complementary sites for let-7 and the lin-4 ortholog, mir-125, in their 3’UTRs. Mouse lin-41 (Mlin-41) is temporally expressed in developing mouse embryos, most dramatically in the limb buds. Mlin-41 is down-regulated during mid-embryogenesis at the time when mouse let-7c and mir-125 RNA levels are up-regulated. Our results suggest that mammalian lin-41 is temporally regulated by miRNAs in order to direct key developmental events such as limb formation. PMID:16247770

LIN28 phosphorylation by MAPK/ERK couples signaling to the post-transcriptional control of pluripotency

PubMed Central

Tsanov, Kaloyan M.; Pearson, Daniel S.; Wu, Zhaoting; Han, Areum; Triboulet, Robinson; Seligson, Marc T.; Powers, John T.; Osborne, Jihan K.; Kane, Susan; Gygi, Steven P.; Gregory, Richard I.; Daley, George Q.

2016-01-01

Signaling and post-transcriptional gene control are both critical for the regulation of pluripotency1,2, yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein (RBP), has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA (miRNA) biogenesis and direct modulation of mRNA translation3. Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells (PSCs), which increases its levels via post-translational stabilization. LIN28 phosphorylation had little impact on let-7 but enhanced LIN28’s effect on its direct mRNA targets, revealing a mechanism that uncouples LIN28’s let-7-dependent and independent activities. We have linked this mechanism to the induction of pluripotency by somatic cell reprogramming and the transition from naïve to primed pluripotency. Collectively, our findings indicate that MAPK/ERK directly impacts LIN28, defining an axis that connects signaling, post-transcriptional gene control, and cell fate regulation. PMID:27992407

LinAir: A multi-element discrete vortex Weissinger aerodynamic prediction method

NASA Technical Reports Server (NTRS)

Durston, Donald A.

1993-01-01

LinAir is a vortex lattice aerodynamic prediction method similar to Weissinger's extended lifting-line theory, except that the circulation around a wing is represented by discrete horseshoe vortices, not a continuous distribution of vorticity. The program calculates subsonic longitudinal and lateral/directional aerodynamic forces and moments for arbitrary aircraft geometries. It was originally written by Dr. Ilan Kroo of Stanford University, and subsequently modified by the author to simplify modeling of complex configurations. The Polhamus leading-edge suction analogy was added by the author to extend the range of applicability of LinAir to low aspect ratio (i.e., fighter-type) configurations. A brief discussion of the theory of LinAir is presented, and details on how to run the program are given along with some comparisons with experimental data to validate the code. Example input and output files are given in the appendices to aid in understanding the program and its use. This version of LinAir runs in the VAX/VMS, Cray UNICOS, and Silicon Graphics Iris workstation environments at the time of this writing.

Identification and Characterization of Genes That Interact with Lin-12 in Caenorhabditis Elegans

PubMed Central

Tax, F. E.; Thomas, J. H.; Ferguson, E. L.; Horvitz, H. R.

1997-01-01

We identified and characterized 14 extragenic mutations that suppressed the dominant egg-laying defect of certain lin-12 gain-of-function mutations. These suppressors defined seven genes: sup-17, lag-2, sel-4, sel-5, sel-6, sel-7 and sel-8. Mutations in six of the genes are recessive suppressors, whereas the two mutations that define the seventh gene, lag-2, are semi-dominant suppressors. These suppressor mutations were able to suppress other lin-12 gain-of-function mutations. The suppressor mutations arose at a very low frequency per gene, 10-50 times below the typical loss-of-function mutation frequency. The suppressor mutations in sup-17 and lag-2 were shown to be rare non-null alleles, and we present evidence that null mutations in these two genes cause lethality. Temperature-shift studies for two suppressor genes, sup-17 and lag-2, suggest that both genes act at approximately the same time as lin-12 in specifying a cell fate. Suppressor alleles of six of these genes enhanced a temperature-sensitive loss-of-function allele of glp-1, a gene related to lin-12 in structure and function. Our analysis of these suppressors suggests that the majority of these genes are part of a shared lin-12/glp-1 signal transduction pathway, or act to regulate the expression or stability of lin-12 and glp-1. PMID:9409830

Stepwise assembly of multiple Lin28 proteins on the terminal loop of let-7 miRNA precursors

PubMed Central

Desjardins, Alexandre; Bouvette, Jonathan; Legault, Pascale

2014-01-01

Lin28 inhibits the biogenesis of let-7 miRNAs through direct interactions with let-7 precursors. Previous studies have described seemingly inconsistent Lin28 binding sites on pre-let-7 RNAs. Here, we reconcile these data by examining the binding mechanism of Lin28 to the terminal loop of pre-let-7g (TL-let-7g) using biochemical and biophysical methods. First, we investigate Lin28 binding to TL-let-7g variants and short RNA fragments and identify three independent binding sites for Lin28 on TL-let-7g. We then determine that Lin28 assembles in a stepwise manner on TL-let-7g to form a stable 1:3 complex. We show that the cold-shock domain (CSD) of Lin28 is responsible for remodelling the terminal loop of TL-let-7g, whereas the NCp7-like domain facilitates the initial binding of Lin28 to TL-let-7g. This stable binding of multiple Lin28 molecules to the terminal loop of pre-let-7g extends to other precursors of the let-7 family, but not to other pre-miRNAs tested. We propose a model for stepwise assembly of the 1:1, 1:2 and 1:3 pre-let-7g/Lin28 complexes. Stepwise multimerization of Lin28 on pre-let-7 is required for maximum inhibition of Dicer cleavage for a least one member of the let-7 family and may be important for orchestrating the activity of the several factors that regulate let-7 biogenesis. PMID:24452802

From lin-benzoguanines to lin-benzohypoxanthines as ligands for Zymomonas mobilis tRNA-guanine transglycosylase: replacement of protein-ligand hydrogen bonding by importing water clusters.

PubMed

Barandun, Luzi Jakob; Immekus, Florian; Kohler, Philipp C; Tonazzi, Sandro; Wagner, Björn; Wendelspiess, Severin; Ritschel, Tina; Heine, Andreas; Kansy, Manfred; Klebe, Gerhard; Diederich, François

2012-07-23

The foodborne illness shigellosis is caused by Shigella bacteria that secrete the highly cytotoxic Shiga toxin, which is also formed by the closely related enterohemorrhagic Escherichia coli (EHEC). It has been shown that tRNA-guanine transglycosylase (TGT) is essential for the pathogenicity of Shigella flexneri. Herein, the molecular recognition properties of a guanine binding pocket in Zymomonas mobilis TGT are investigated with a series of lin-benzohypoxanthine- and lin-benzoguanine-based inhibitors that bear substituents to occupy either the ribose-33 or the ribose-34 pocket. The three inhibitor scaffolds differ by the substituent at C(6) being H, NH(2), or NH-alkyl. These differences lead to major changes in the inhibition constants, pK(a) values, and binding modes. Compared to the lin-benzoguanines, with an exocyclic NH(2) at C(6), the lin-benzohypoxanthines without an exocyclic NH(2) group have a weaker affinity as several ionic protein-ligand hydrogen bonds are lost. X-ray cocrystal structure analysis reveals that a new water cluster is imported into the space vacated by the lacking NH(2) group and by a conformational shift of the side chain of catalytic Asp102. In the presence of an N-alkyl group at C(6) in lin-benzoguanine ligands, this water cluster is largely maintained but replacement of one of the water molecules in the cluster leads to a substantial loss in binding affinity. This study provides new insight into the role of water clusters at enzyme active sites and their challenging substitution by ligand parts, a topic of general interest in contemporary structure-based drug design. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Dynamic Attitude Measurement System Based on LINS

PubMed Central

Li, Hanzhou; Pan, Quan; Wang, Xiaoxu; Zhang, Juanni; Li, Jiang; Jiang, Xiangjun

2014-01-01

A dynamic attitude measurement system (DAMS) is developed based on a laser inertial navigation system (LINS). Three factors of the dynamic attitude measurement error using LINS are analyzed: dynamic error, time synchronization and phase lag. An optimal coning errors compensation algorithm is used to reduce coning errors, and two-axis wobbling verification experiments are presented in the paper. The tests indicate that the attitude accuracy is improved 2-fold by the algorithm. In order to decrease coning errors further, the attitude updating frequency is improved from 200 Hz to 2000 Hz. At the same time, a novel finite impulse response (FIR) filter with three notches is designed to filter the dither frequency of the ring laser gyro (RLG). The comparison tests suggest that the new filter is five times more effective than the old one. The paper indicates that phase-frequency characteristics of FIR filter and first-order holder of navigation computer constitute the main sources of phase lag in LINS. A formula to calculate the LINS attitude phase lag is introduced in the paper. The expressions of dynamic attitude errors induced by phase lag are derived. The paper proposes a novel synchronization mechanism that is able to simultaneously solve the problems of dynamic test synchronization and phase compensation. A single-axis turntable and a laser interferometer are applied to verify the synchronization mechanism. The experiments results show that the theoretically calculated values of phase lag and attitude error induced by phase lag can both match perfectly with testing data. The block diagram of DAMS and physical photos are presented in the paper. The final experiments demonstrate that the real-time attitude measurement accuracy of DAMS can reach up to 20″ (1σ) and the synchronization error is less than 0.2 ms on the condition of three axes wobbling for 10 min. PMID:25177802

Lin28a protects against postinfarction myocardial remodeling and dysfunction through Sirt1 activation and autophagy enhancement.

PubMed

Hao, Yuanyuan; Lu, Qun; Yang, Guodong; Ma, Aiqun

2016-10-28

Myocardial remodeling and cardiac dysfunction prevention may represent a therapeutic approach to reduce mortality in patients with myocardial infarction (MI). We investigated the effects of Lin28a in experimental MI models, as well as the mechanisms underlying these effects. Left anterior descending (LAD) coronary artery ligation was used to construct an MI-induced injury model. Neonatal cardiomyocytes were isolated and cultured to investigate the mechanisms underlying the protective effects of Lin28a against MI-induced injury. Lin28a significantly inhibited left ventricular remodeling and cardiac dysfunction after MI, as demonstrated via echocardiography and hemodynamic measurements. Lin28a reduced cardiac enzyme and inflammatory marker release in mice subjected to MI-induced injury. The mechanisms underlying the protective effects of Lin28a against MI-induced injury were associated with autophagy enhancements and apoptosis inhibition. Consistent with these findings, Lin28a knockdown aggravated cardiac remodeling and dysfunction after MI-induced injury. Lin28a knockdown also inhibited cardiomyocyte autophagy and increased cardiomyocyte apoptosis in mice subjected to MI-induced injury. Interestingly, Sirt1 knockdown abolished the protective effects of Lin28a against cardiac remodeling and dysfunction after MI, and Lin28a failed to increase the numbers of GFP-LC3-positive punctae and decrease aggresome and p62 accumulation in Sirt1-knockdown neonatal cardiomyocytes subjected to hypoxia-induced injury. Lin28a inhibits cardiac remodeling, improves cardiac function, and reduces cardiac enzyme and inflammatory marker release after MI. Lin28a also up-regulates cardiomyocyte autophagy and inhibits cardiomyocyte apoptosis through Sirt1 activation. Copyright © 2016 Elsevier Inc. All rights reserved.

Bistable switch in let-7 miRNA biogenesis pathway involving Lin28.

PubMed

Shi, Fei; Yu, Wenbao; Wang, Xia

2014-10-21

miRNAs are small noncoding RNAs capable of regulating gene expression at the post-transcriptional level. A growing body of evidence demonstrated that let-7 family of miRNAs, as one of the highly conserved miRNAs, plays an important role in cell differentiation and development, as well as tumor suppressor function depending on their levels of expression. To explore the physiological significance of let-7 in regulating cell fate decisions, we present a coarse grained model of let-7 biogenesis network, in which let-7 and its regulator Lin28 inhibit mutually. The dynamics of this minimal network architecture indicates that, as the concentration of Lin28 increases, the system undergoes a transition from monostability to a bistability and then to a one-way switch with increasing strength of positive feedback of let-7, while in the absence of Lin28 inhibition, the system loses bistability. Moreover, the ratio of degradation rates of let-7 and Lin28 is critical for the switching sensitivity and resistance to stimulus fluctuations. These findings may highlight why let-7 is required for normal gene expression in the context of embryonic development and oncogenesis, which will facilitate the development of approaches to exploit this regulatory pathway by manipulating Lin28/let-7 axis for novel treatments of human diseases.

LIN9, a Subunit of the DREAM Complex, Regulates Mitotic Gene Expression and Proliferation of Embryonic Stem Cells

PubMed Central

Esterlechner, Jasmina; Reichert, Nina; Iltzsche, Fabian; Krause, Michael; Finkernagel, Florian; Gaubatz, Stefan

2013-01-01

The DREAM complex plays an important role in regulation of gene expression during the cell cycle. We have previously shown that the DREAM subunit LIN9 is required for early embryonic development and for the maintenance of the inner cell mass in vitro. In this study we examined the effect of knocking down LIN9 on ESCs. We demonstrate that depletion of LIN9 alters the cell cycle distribution of ESCs and results in an accumulation of cells in G2 and M and in an increase of polyploid cells. Genome-wide expression studies showed that the depletion of LIN9 results in downregulation of mitotic genes and in upregulation of differentiation-specific genes. ChIP-on chip experiments showed that mitotic genes are direct targets of LIN9 while lineage specific markers are regulated indirectly. Importantly, depletion of LIN9 does not alter the expression of pluripotency markers SOX2, OCT4 and Nanog and LIN9 depleted ESCs retain alkaline phosphatase activity. We conclude that LIN9 is essential for proliferation and genome stability of ESCs by activating genes with important functions in mitosis and cytokinesis. PMID:23667535

Regulation of C. elegans L4 cuticle collagen genes by the heterochronic protein LIN-29.

PubMed

Abete-Luzi, Patricia; Eisenmann, David M

2018-05-01

The cuticle, the outer covering of the nematode C. elegans, is synthesized five times during the worm's life by the underlying hypodermis. Cuticle collagens, the major cuticle component, are encoded by a large family of col genes and, interestingly, many of these genes express predominantly at a single developmental stage. This temporal preference motivated us to investigate the mechanisms underlying col gene expression and here we focus on a subset of col genes expressed in the L4 stage. We identified minimal promoter regions of <300 bp for col-38, col-49, and col-63. In these regions, we predicted cis-regulatory sequences and evaluated their function in vivo via mutagenesis of a col-38p::yfp reporter. We used RNAi to study the requirement for candidate transcription regulators ELT-1 and ELT-3, LIN-29, and the LIN-29 co-factor MAB-10, and found LIN-29 to be necessary for the expression of four L4-specific genes (col-38, col-49, col-63, and col-138). Temporal misexpression of LIN-29 was also sufficient to activate these genes at a different developmental stage. The LIN-29 DNA-binding domain bound the col-38, col-49, and col-63 minimal promoters in vitro. For col-38 we showed that the LIN-29 sites necessary for reporter expression in vivo are also bound in vitro: this is the first identification of specific binding sites for LIN-29 necessary for in vivo target gene expression. © 2018 Wiley Periodicals, Inc.

Germline Genetic Variants Disturbing the Let-7/LIN28 Double-Negative Feedback Loop Alter Breast Cancer Susceptibility

PubMed Central

Fan, Lei; Li, Ji-Yu; Yang, Chen; Huang, A-Ji; Shao, Zhi-Ming

2011-01-01

Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7/LIN28 loop and breast cancer risk. We initially demonstrated that the T/C variants of rs3811463, a single nucleotide polymorphism (SNP) located near the let-7 binding site in LIN28, could lead to differential regulation of LIN28 by let-7. Specifically, the C allele of rs3811463 weakened let-7–induced repression of LIN28 mRNA, resulting in increased production of LIN28 protein, which could in turn down-regulate the level of mature let-7. This effect was then validated at the tissue level in that the normal breast tissue of individuals with the rs3811463-TC genotype expressed significantly lower levels of let-7 and higher levels of LIN28 protein than those individuals with the rs3811463-TT genotype. Because previous in vitro and ex vivo experiments have consistently suggested that LIN28 could promote cellular transformation, we then systematically evaluated the relationship between rs3811463 as well as other common LIN28 SNPs and the risk of breast cancer in a stepwise manner. The first hospital-based association study (n = 2,300) demonstrated that two SNPs were significantly associated with breast cancer risk, one of which was rs3811463, while the other was rs6697410. The C allele of the rs3811463 SNP corresponded to an increased risk of breast cancer with an odds ratio (OR) of 1.25 (P = 0.0091), which was successfully replicated in a second independent study (n = 1,156) with community-based controls. The combined P-value of the two studies was 8.0×10−5. Taken together, our study demonstrates that host genetic variants could disturb the regulation of the let-7/LIN28 double-negative feedback loop and alter breast cancer risk. PMID:21912531

LIN-39/Hox triggers cell division and represses EFF-1/fusogen-dependent vulval cell fusion

PubMed Central

Shemer, Gidi; Podbilewicz, Benjamin

2002-01-01

General mechanisms by which Hox genes establish cell fates are known. However, a few Hox effectors mediating cell behaviors have been identified. Here we found the first effector of LIN-39/HoxD4/Dfd in Caenorhabditis elegans. In specific vulval precursor cells (VPCs), LIN-39 represses early and late expression of EFF-1, a membrane protein essential for cell fusion. Repression of eff-1 is also achieved by the activity of CEH-20/Exd/Pbx, a known cofactor of Hox proteins. Unfused VPCs in lin-39(−);eff-1(−) double mutants fail to divide but migrate, executing vulval fates. Thus, lin-39 is essential for inhibition of EFF-1-dependent cell fusion and stimulation of cell proliferation during vulva formation. Supplemental material is available at http://www.genesdev.org. PMID:12502736

RNA binding protein Lin28B confers gastric cancer cells stemness via directly binding to NRP-1.

PubMed

Wang, Xiaocong; Hu, Huihua; Liu, Hebo

2018-05-19

This work aims to explore the roles and related mechanisms of RNA binding protein Lin28B in gastric cancer cells stemness. We found that Lin28B expression was negatively correlated with the overall survival (OS) of gastric cancer patients, and significantly increased in gastric cancer cells compared with that in gastric epithelial cells. Lin28B overexpression increased spheroid formation, expression of gastric cancer stemness-related markers, and decreased cisplatin sensitivity in gastric cancer cells. Mechanistically, Lin28B could directly bind to NRP-1 3'UTR, thus increasing NRP-1 mRNA stability and expression, and activate the downstream Wnt/β-catenin signaling. Knockdown of NRP-1 or treatment with Wnt/β-catenin antagonist could rescue the promotive effects of Lin28B on gastric cancer stemness. Thus, thes results indicate that Lin28B could facilitate gastric cancer stemness via directly binding to NRP-1 3'UTR and activating the downstream Wnt/β-catenin signaling. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The DREAM complex through its subunit Lin37 cooperates with Rb to initiate quiescence

PubMed Central

Mages, Christina FS; Wintsche, Axel; Bernhart, Stephan H

2017-01-01

The retinoblastoma Rb protein is an important factor controlling the cell cycle. Yet, mammalian cells carrying Rb deletions are still able to arrest under growth-limiting conditions. The Rb-related proteins p107 and p130, which are components of the DREAM complex, had been suggested to be responsible for a continued ability to arrest by inhibiting E2f activity and by recruiting chromatin-modifying enzymes. Here, we show that p130 and p107 are not sufficient for DREAM-dependent repression. We identify the MuvB protein Lin37 as an essential factor for DREAM function. Cells not expressing Lin37 proliferate normally, but DREAM completely loses its ability to repress genes in G0/G1 while all remaining subunits, including p130/p107, still bind to target gene promoters. Furthermore, cells lacking both Rb and Lin37 are incapable of exiting the cell cycle. Thus, Lin37 is an essential component of DREAM that cooperates with Rb to induce quiescence. PMID:28920576

Mechanisms of Lin28-Mediated miRNA and mRNA Regulation—A Structural and Functional Perspective

PubMed Central

Mayr, Florian; Heinemann, Udo

2013-01-01

Lin28 is an essential RNA-binding protein that is ubiquitously expressed in embryonic stem cells. Its physiological function has been linked to the regulation of differentiation, development, and oncogenesis as well as glucose metabolism. Lin28 mediates these pleiotropic functions by inhibiting let-7 miRNA biogenesis and by modulating the translation of target mRNAs. Both activities strongly depend on Lin28’s RNA-binding domains (RBDs), an N-terminal cold-shock domain (CSD) and a C-terminal Zn-knuckle domain (ZKD). Recent biochemical and structural studies revealed the mechanisms of how Lin28 controls let-7 biogenesis. Lin28 binds to the terminal loop of pri- and pre-let-7 miRNA and represses their processing by Drosha and Dicer. Several biochemical and structural studies showed that the specificity of this interaction is mainly mediated by the ZKD with a conserved GGAGA or GGAGA-like motif. Further RNA crosslinking and immunoprecipitation coupled to high-throughput sequencing (CLIP-seq) studies confirmed this binding motif and uncovered a large number of new mRNA binding sites. Here we review exciting recent progress in our understanding of how Lin28 binds structurally diverse RNAs and fulfills its pleiotropic functions. PMID:23939427

Clinical application of Lin's biopsy grasper for intrauterine targeted biopsy and polypectomy during office hysteroscopy.

PubMed

Cheng, Hsin-Yi; Lin, Bao-Liang; Tseng, Jen-Yu; Ueno, Kazunori; Nakada, Sakura

2018-06-01

Hysteroscopy has widely been used for diagnosis of the uterine cavity; however, target biopsy has often been difficult in part to the inherent limitations of ancillary instruments. Lin's biopsy grasper was specifically designed to work in conjunction with a flexible hysteroscope to obtain intrauterine biopsy under transabdominal sonography. Herein, we share our clinical experience in the management of endometrial abnormalities with the use of Lin's biopsy grasper during office-based hysteroscopy. From February 2006 to November 2016, the use of Lin's biopsy grasper for tissue biopsy was attempted on 126 cases. We retrospectively recorded and analyzed the patients' preoperative characteristics and biopsy outcomes to demonstrate the feasibility and efficacy of Lin's biopsy grasper. Out of the one hundred and twenty-six enrolled patients, satisfactory targeted biopsies were achieved; including high diagnostic rate (92.1%, with 116 cases confirmed histologically) and adequate tissue retrieval (77.8%, with 98 cases obtaining optimal specimen volume). All patients tolerated the procedure without analgesics or anesthesia. Diagnostic flexible hysteroscopy combined with the use of Lin's biopsy grasper has proven to be an effective tool for intrauterine evaluation and obtaining tissue sample. Copyright © 2018. Published by Elsevier B.V.

Lin28-let7 Modulates Radiosensitivity of Human Cancer Cells With Activation of K-Ras

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

Oh, Jee-Sun.; Kim, Jae-Jin; Byun, Ju-Yeon

2010-01-15

Purpose: To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling. Methods and Materials: A549 lung carcinoma cells and ASPC1 pancreatic cancer cells possessing K-RAS mutation were transfected with pre-let7a microRNA or Lin28 siRNA, respectively. Clonogenic assay, quantitative reverse transcription polymerase chain reaction, and Western analysis were performed. The effects of Lin28 on SQ20B cells having wild-type K-RAS, and a normal fibroblast were also assessed. Results: The overexpression of let-7a decreased expression of K-Ras and radiosensitized A549 cells. Inhibition of Lin28, a repressor of let-7, attenuated K-Ras expression andmore » radiosensitized A549 and ASPC1 cells. Neither SQ20B cells expressing wild-type K-RAS nor HDF, the normal human fibroblasts, were radiosensitized by this approach. Conclusions: The Lin28-let7 regulatory network may be a potentially useful therapeutic target for overcoming the radioresistance of human cancers having activated K-Ras signaling.« less

Metabolomics of hexachlorocyclohexane (HCH) transformation: ratio of LinA to LinB determines metabolic fate of HCH isomers.

PubMed

Geueke, Birgit; Garg, Nidhi; Ghosh, Sneha; Fleischmann, Thomas; Holliger, Christof; Lal, Rup; Kohler, Hans-Peter E

2013-04-01

Although the production and use of technical hexachlorocyclohexane (HCH) and lindane (the purified insecticidal isomer γ-HCH) are prohibited in most countries, residual concentrations still constitute an immense environmental burden. Many studies describe the mineralization of γ-HCH by bacterial strains under aerobic conditions. However, the metabolic fate of the other HCH isomers is not well known. In this study, we investigated the transformation of α-, β-, γ-, δ-, ε-HCH, and a heptachlorocyclohexane isomer in the presence of varying ratios of the two enzymes that initiate γ-HCH degradation, a dehydrochlorinase (LinA) and a haloalkane dehalogenase (LinB). Each substrate yielded a unique metabolic profile that was strongly dependent on the enzyme ratio. Comparison of these results to those of in vivo experiments with different bacterial isolates showed that HCH transformation in the tested strains was highly optimized towards productive metabolism of γ-HCH and that under these conditions other HCH-isomers were metabolized to mixtures of dehydrochlorinated and hydroxylated side-products. In view of these results, bioremediation efforts need very careful planning and toxicities of accumulating metabolites need to be evaluated. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Biodegradation of γ-hexachlorocyclohexane by transgenic hairy root cultures of Cucurbita moschata that accumulate recombinant bacterial LinA.

PubMed

Nanasato, Yoshihiko; Namiki, Sayuri; Oshima, Masao; Moriuchi, Ryota; Konagaya, Ken-Ichi; Seike, Nobuyasu; Otani, Takashi; Nagata, Yuji; Tsuda, Masataka; Tabei, Yutaka

2016-09-01

γ-HCH was successfully degraded using LinA-expressed transgenic hairy root cultures of Cucurbita moschata . Fusing an endoplasmic reticulum-targeting signal peptide to LinA was essential for stable accumulation in the hairy roots. The pesticide γ-hexachlorocyclohexane (γ-HCH) is a persistent organic pollutant (POP) that raises public health and environmental pollution concerns worldwide. Although several isolates of γ-HCH-degrading bacteria are available, inoculating them directly into γ-HCH-contaminated soil is ineffective because of the bacterial survival rate. Cucurbita species incorporate significant amounts of POPs from soils compared with other plant species. Here, we describe a novel bioremediation strategy that combines the bacterial degradation of γ-HCH and the efficient uptake of γ-HCH by Cucurbita species. We produced transgenic hairy root cultures of Cucurbita moschata that expressed recombinant bacterial linA, isolated from the bacterium Sphingobium japonicum UT26. The LinA protein was accumulated stably in the hairy root cultures by fusing an endoplasmic reticulum (ER)-targeting signal peptide to LinA. Then, we demonstrated that the cultures degraded more than 90 % of γ-HCH (1 ppm) overnight and produced the γ-HCH metabolite 1,2,4-trichlorobenzene, indicating that LinA degraded γ-HCH. These results indicate that the gene linA has high potential for phytoremediation of environmental γ-HCH.

The role of lin-22, a hairy/enhancer of split homolog, in patterning the peripheral nervous system of C. elegans.

PubMed

Wrischnik, L A; Kenyon, C J

1997-08-01

In C. elegans, six lateral epidermal stem cells, the seam cells V1-V6, are located in a row along the anterior-posterior (A/P) body axis. Anterior seam cells (V1-V4) undergo a fairly simple sequence of stem cell divisions and generate only epidermal cells. Posterior seam cells (V5 and V6) undergo a more complicated sequence of cell divisions that include additional rounds of stem cell proliferation and the production of neural as well as epidermal cells. In the wild type, activity of the gene lin-22 allows V1-V4 to generate their normal epidermal lineages rather than V5-like lineages. lin-22 activity is also required to prevent additional neurons from being produced by one branch of the V5 lineage. We find that the lin-22 gene exhibits homology to the Drosophila gene hairy, and that lin-22 activity represses neural development within the V5 lineage by blocking expression of the posterior-specific Hox gene mab-5 in specific cells. In addition, in order to prevent anterior V cells from generating V5-like lineages, wild-type lin-22 gene activity must inhibit (directly or indirectly) at least five downstream regulatory gene activities. In anterior body regions, lin-22(+) inhibits expression of the Hox gene mab-5. It also inhibits the activity of the achaete-scute homolog lin-32 and an unidentified gene that we postulate regulates stem cell division. Each of these three genes is required for the expression of a different piece of the ectopic V5-like lineages generated in lin-22 mutants. In addition, lin-22 activity prevents two other Hox genes, lin-39 and egl-5, from acquiring new activities within their normal domains of function along the A/P body axis. Some, but not all, of the patterning activities of lin-22 in C. elegans resemble those of hairy in Drosophila.

Coordinated Regulation of Intestinal Functions in C. elegans by LIN-35/Rb and SLR-2

PubMed Central

Kirienko, Natalia V.; McEnerney, John D. K.; Fay, David S.

2008-01-01

LIN-35 is the sole C. elegans representative of the pocket protein family, which includes the mammalian Retinoblastoma protein pRb and its paralogs p107 and p130. In addition to having a well-established and central role in cell cycle regulation, pocket proteins have been increasingly implicated in the control of critical and diverse developmental and cellular processes. To gain a greater understanding of the roles of pocket proteins during development, we have characterized a synthetic genetic interaction between lin-35 and slr-2, which we show encodes a C2H2-type Zn-finger protein. Whereas animals harboring single mutations in lin-35 or slr-2 are viable and fertile, lin-35; slr-2 double mutants arrest uniformly in early larval development without obvious morphological defects. Using a combination of approaches including transcriptome profiling, mosaic analysis, starvation assays, and expression analysis, we demonstrate that both LIN-35 and SLR-2 act in the intestine to regulate the expression of many genes required for normal nutrient utilization. These findings represent a novel role for pRb family members in the maintenance of organ function. Our studies also shed light on the mechanistic basis of genetic redundancy among transcriptional regulators and suggest that synthetic interactions may result from the synergistic misregulation of one or more common targets. PMID:18437219

[Professor LIN Guohua's experience of gold implantation at acupoint for rheumatoid arthritis].

PubMed

Li, Jingjing; Pei, Wenya

2015-12-01

Based on the pathogenesis and symptom of rheumatoid arthritis (RA), professor LIN Guohua's unique opinion and method for RA in clinical treatment are summarized and analyzed. In the opinion of Professor Lin, RA is considered as "Jinbi" and "Gubi" in TCM, which is caused by deficient root with superficial excess. Based on the symptoms of RA, attention should be focused on lung-kidney diagnosis and treatment, and gold and catgut implantation at acupoint can be mutually combined, which is aimed to provide a special and effective method for clinical treatment of RA.

The Lin28/Let-7 System in Early Human Embryonic Tissue and Ectopic Pregnancy

PubMed Central

Steffani, Liliana; Martínez, Sebastián; Monterde, Mercedes; Ferri, Blanca; Núñez, Maria Jose; AinhoaRomero-Espinós; Zamora, Omar; Gurrea, Marta; Sangiao-Alvarellos, Susana; Vega, Olivia; Simón, Carlos; Pellicer, Antonio; Tena-Sempere, Manuel

2014-01-01

Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7–9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans. PMID:24498170

Drosophila Lin-52 Acts in Opposition to Repressive Components of the Myb-MuvB/dREAM Complex

PubMed Central

Lewis, Peter W.; Sahoo, Debashis; Geng, Cuiyun; Bell, Maren

2012-01-01

The Drosophila melanogaster Myb-MuvB/dREAM complex (MMB/dREAM) participates in both the activation and repression of developmentally regulated genes and origins of DNA replication. Mutants in MMB subunits exhibit diverse phenotypes, including lethality, eye defects, reduced fecundity, and sterility. Here, we used P-element excision to generate mutations in lin-52, which encodes the smallest subunit of the MMB/dREAM complex. lin-52 is required for viability, as null mutants die prior to pupariation. The generation of somatic and germ line mutant clones indicates that lin-52 is required for adult eye development and for early embryogenesis via maternal effects. Interestingly, the maternal-effect embryonic lethality, larval lethality, and adult eye defects could be suppressed by mutations in other subunits of the MMB/dREAM complex. These results suggest that a partial MMB/dREAM complex is responsible for the lethality and eye defects of lin-52 mutants. Furthermore, these findings support a model in which the Lin-52 and Myb proteins counteract the repressive activities of the other members of the MMB/dREAM complex at specific genomic loci in a developmentally controlled manner. PMID:22688510

Overexpression of Lin28 inhibits the proliferation, migration and cell cycle progression and induces apoptosis of BGC-823 gastric cancer cells.

PubMed

Song, Hu; Xu, Wei; Song, Jun; Liang, Yong; Fu, Wei; Zhu, Xiao-Cheng; Li, Chao; Peng, Jun-Sheng; Zheng, Jun-Nian

2015-02-01

Lin28 plays important roles in the development, maintenance of pluripotency and progression of various types of cancers. Lin28 represses the biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Oncogenic regulation of let-7 microRNAs has been demonstrated in several human malignancies, yet their correlation with Lin28 has not yet been studied in gastric cancer. Therefore, in the present study, we explored the possible mechanisms involved in the effects by Lin28 on the proliferation, migration, cell cycle arrest and apoptosis in gastric cancer cells via alteration of let-7 miRNA. The expression levels of Lin28 and let-7 were detected by real-time PCR in gastric cancer cell lines in vitro. Lin28 was overexpressed in the BGC-823 cells via lentiviral transfection, and let-7 expression was assessed. Cell proliferation and migration capabilities were investigated by MTT and Transwell assays, while cell cycle distribution and the apoptosis rate were detected using flow cytometry. The expression of Lin28 was moderately expressed in the GES cells while underexpressed in the BGC-823, SGC-7901 and HGC-27 cells. Let-7a miRNA was highly expressed in the GES, BGC-823, SGC-7901 and HGC-27 cells. Overexpression of Lin28 was inversely correlated with the downregulated expression of let-7a, and markedly suppressed the proliferation, migration, cell cycle progression and induced apoptosis in the BGC-823 cells. These findings demonstrated that overexpression of Lin28 can suppress the biological behavior of gastric cancer in vitro, and let-7 miRNA may play an important role in the process. We suggest that Lin28 may be a candidate predictor or an anticancer therapeutic target for gastric cancer patients.

The ubiquitin ligase LIN41/TRIM71 targets p53 to antagonize cell death and differentiation pathways during stem cell differentiation

PubMed Central

Nguyen, Duong Thi Thuy; Richter, Daniel; Michel, Geert; Mitschka, Sibylle; Kolanus, Waldemar; Cuevas, Elisa; Gregory Wulczyn, F

2017-01-01

Rapidity and specificity are characteristic features of proteolysis mediated by the ubiquitin-proteasome system. Therefore, the UPS is ideally suited for the remodeling of the embryonic stem cell proteome during the transition from pluripotent to differentiated states and its inverse, the generation of inducible pluripotent stem cells. The Trim-NHL family member LIN41 is among the first E3 ubiquitin ligases to be linked to stem cell pluripotency and reprogramming. Initially discovered in C. elegans as a downstream target of the let-7 miRNA, LIN41 is now recognized as a critical regulator of stem cell fates as well as the timing of neurogenesis. Despite being indispensable for embryonic development and neural tube closure in mice, the underlying mechanisms for LIN41 function in these processes are poorly understood. To better understand the specific contributions of the E3 ligase activity for the stem cell functions of LIN41, we characterized global changes in ubiquitin or ubiquitin-like modifications using Lin41-inducible mouse embryonic stem cells. The tumor suppressor protein p53 was among the five most strongly affected proteins in cells undergoing neural differentiation in response to LIN41 induction. We show that LIN41 interacts with p53, controls its abundance by ubiquitination and antagonizes p53-dependent pro-apoptotic and pro-differentiation responses. In vivo, the lack of LIN41 is associated with upregulation of Grhl3 and widespread caspase-3 activation, two downstream effectors of p53 with essential roles in neural tube closure. As Lin41-deficient mice display neural tube closure defects, we conclude that LIN41 is critical for the regulation of p53 functions in cell fate specification and survival during early brain development. PMID:28430184

Lin28a uses distinct mechanisms of binding to RNA and affects miRNA levels positively and negatively.

PubMed

Nowak, Jakub Stanislaw; Hobor, Fruzsina; Downie Ruiz Velasco, Angela; Choudhury, Nila Roy; Heikel, Gregory; Kerr, Alastair; Ramos, Andres; Michlewski, Gracjan

2017-03-01

Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3'-5' exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production. Finally, we show that the constitutive expression of untagged Lin28a during neuronal differentiation in vitro positively and negatively affects numerous other miRNAs. Our findings shed light on the role of Lin28a in differentiating cells and on the ways in which one RNA-binding protein can perform multiple roles in the regulation of RNA processing. © 2017 Nowak et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Genome packaging in EL and Lin68, two giant phiKZ-like bacteriophages of P. aeruginosa

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

Sokolova, O.S., E-mail: sokolova@mail.bio.msu.ru; A.V. Shoubnikov Institute of Crystallography RAS, Moscow; Shaburova, O.V.

A unique feature of the Pseudomonas aeruginosa giant phage phiKZ is its way of genome packaging onto a spool-like protein structure, the inner body. Until recently, no similar structures have been detected in other phages. We have studied DNA packaging in P. aeruginosa phages EL and Lin68 using cryo-electron microscopy and revealed the presence of inner bodies. The shape and positioning of the inner body and the density of the DNA packaging in EL are different from those found in phiKZ and Lin68. This internal organization explains how the shorter EL genome is packed into a large EL capsid, whichmore » has the same external dimensions as the capsids of phiKZ and Lin68. The similarity in the structural organization in EL and other phiKZ-like phages indicates that EL is phylogenetically related to other phiKZ-like phages, and, despite the lack of detectable DNA homology, EL, phiKZ, and Lin68 descend from a common ancestor. - Highlights: • We performed a comparative structural study of giant P. aeruginosa phages: EL, Lin68 and phiKZ. • We revealed that the inner body is a common feature in giant phages. • The phage genome size correlates with the overall dimensions of the inner body.« less

75 FR 842 - Action Affecting Export Privileges: Hailin Lin

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-06

... DEPARTMENT OF COMMERCE Bureau of Industry and Security Action Affecting Export Privileges: Hailin... Regulations. Charges 112-12415: CFR 764.2(h)--Taking Action With Intent To Evade the Regulations In connection... through on or about September 30, 2004, Lin took actions with intent to evade the provisions of the...

Efficient method to create integration-free, virus-free, Myc and Lin28-free human induced pluripotent stem cells from adherent cells.

PubMed

Kamath, Anant; Ternes, Sara; McGowan, Stephen; English, Anthony; Mallampalli, Rama; Moy, Alan B

2017-08-01

Nonviral induced pluripotent stem cell (IPSC) reprogramming is not efficient without the oncogenes, Myc and Lin28 . We describe a robust Myc and Lin28 -free IPSC reprogramming approach using reprogramming molecules. IPSC colony formation was compared in the presence and absence of Myc and Lin28 by the mixture of reprogramming molecules and episomal vectors. While more colonies were observed in cultures transfected with the aforementioned oncogenes, the Myc and Lin28 -free method achieved the same reprogramming efficiency as reports that used these oncogenes. Further, all colonies were fully reprogrammed based on expression of SSEA4, even in the absence of Myc and Lin28 . This approach satisfies an important regulatory pathway for developing IPSC cell therapies with lower clinical risk.

LIN28 expression in malignant germ cell tumors down-regulates let-7 and increases oncogene levels

PubMed Central

Murray, Matthew J.; Saini, Harpreet K.; Siegler, Charlotte A.; Hanning, Jennifer E.; Barker, Emily M.; van Dongen, Stijn; Ward, Dawn M.; Raby, Katie L.; Groves, Ian J.; Scarpini, Cinzia G.; Pett, Mark R.; Thornton, Claire M.; Enright, Anton J.; Nicholson, James C.; Coleman, Nicholas

2013-01-01

Despite their clinico-pathologic heterogeneity, malignant germ-cell-tumors (GCTs) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of down-regulation of the let-7 family of tumor-suppressor microRNAs in malignant-GCTs. Microarray results from pediatric and adult samples (n=45) showed that LIN28, the negative-regulator of let-7 biogenesis, was abundant in malignant-GCTs, regardless of patient age, tumor site or histologic subtype. Indeed, a strong negative-correlation existed between LIN28 and let-7 levels in specimens with matched datasets. Low let-7 levels were biologically significant, since the sequence complementary to the 2-7nt common let-7 seed ‘GAGGUA’ was enriched in the 3′untranslated regions of mRNAs up-regulated in pediatric and adult malignant-GCTs, compared with normal gonads (a mixture of germ cells and somatic cells). We identified 27 mRNA targets of let-7 that were up-regulated in malignant-GCT cells, confirming significant negative-correlations with let-7 levels. Among 16 mRNAs examined in a largely independent set of specimens by qRT-PCR, we defined negative-associations with let-7e levels for six oncogenes, including MYCN, AURKB, CCNF, RRM2, MKI67 and C12orf5 (when including normal control tissues). Importantly, LIN28 depletion in malignant-GCT cells restored let-7 levels and repressed all of these oncogenic let-7 mRNA targets, with LIN28 levels correlating with cell proliferation and MYCN levels. Conversely, ectopic expression of let-7e was sufficient to reduce proliferation and down-regulate MYCN, AURKB and LIN28, the latter via a double-negative feedback loop. We concluded that the LIN28/let-7 pathway has a critical pathobiological role in malignant-GCTs and therefore offers a promising target for therapeutic intervention. PMID:23774216

Developmental regulation of myeloerythroid progenitor function by the Lin28b–let-7–Hmga2 axis

PubMed Central

Rowe, R. Grant; Wang, Leo D.; Coma, Silvia; Pearson, Daniel S.; Nguyen, Phi T.; Wagers, Amy J.

2016-01-01

For appropriate development, tissue and organ system morphogenesis and maturation must occur in synchrony with the overall developmental requirements of the host. Mistiming of such developmental events often results in disease. The hematopoietic system matures from the fetal state, characterized by robust erythrocytic output that supports prenatal growth in the hypoxic intrauterine environment, to the postnatal state wherein granulocytes predominate to provide innate immunity. Regulation of the developmental timing of these myeloerythroid states is not well understood. In this study, we find that expression of the heterochronic factor Lin28b decreases in common myeloid progenitors during hematopoietic maturation to adulthood in mice. This decrease in Lin28b coincides with accumulation of mature let-7 microRNAs, whose biogenesis is regulated by Lin28 proteins. We find that inhibition of let-7 in the adult hematopoietic system recapitulates fetal erythroid-dominant hematopoiesis. Conversely, deletion of Lin28b or ectopic activation of let-7 microRNAs in the fetal state induces a shift toward adult-like myeloid-dominant output. Furthermore, we identify Hmga2 as an effector of this genetic switch. These studies provide the first detailed analysis of the roles of endogenous Lin28b and let-7 in the timing of hematopoietic states during development. PMID:27401346

Genome packaging in EL and Lin68, two giant phiKZ-like bacteriophages of P. aeruginosa.

PubMed

Sokolova, O S; Shaburova, O V; Pechnikova, E V; Shaytan, A K; Krylov, S V; Kiselev, N A; Krylov, V N

2014-11-01

A unique feature of the Pseudomonas aeruginosa giant phage phiKZ is its way of genome packaging onto a spool-like protein structure, the inner body. Until recently, no similar structures have been detected in other phages. We have studied DNA packaging in P. aeruginosa phages EL and Lin68 using cryo-electron microscopy and revealed the presence of inner bodies. The shape and positioning of the inner body and the density of the DNA packaging in EL are different from those found in phiKZ and Lin68. This internal organization explains how the shorter EL genome is packed into a large EL capsid, which has the same external dimensions as the capsids of phiKZ and Lin68. The similarity in the structural organization in EL and other phiKZ-like phages indicates that EL is phylogenetically related to other phiKZ-like phages, and, despite the lack of detectable DNA homology, EL, phiKZ, and Lin68 descend from a common ancestor. Copyright © 2014 Elsevier Inc. All rights reserved.

A role for Lin28 in primordial germ cell development and germ cell malignancy

PubMed Central

West, Jason A.; Viswanathan, Srinivas R.; Yabuuchi, Akiko; Cunniff, Kerianne; Takeuchi, Ayumu; Park, In-Hyun; Sero, Julia E.; Zhu, Hao; Perez-Atayde, Antonio; Frazier, A. Lindsay; Surani, M. Azim; Daley, George Q.

2009-01-01

The rarity and inaccessibility of the earliest primordial germ cells (PGCs) in the mouse embryo thwarts efforts to investigate molecular mechanisms of germ cell specification. Stella marks the minute founder population of the germ lineage1,2. Here we differentiate mouse embryonic stem cells (ESCs) carrying a Stella transgenic reporter into putative PGCs in vitro. The Stella+ cells possess a transcriptional profile similar to embryo-derived PGCs, and like their counterparts in vivo, lose imprints in a time-dependent manner. Using inhibitory RNAs to screen candidate genes for effects on the development of Stella+ cells in vitro, we discovered that Lin28, a negative regulator of let-7 microRNA processing3-6, is essential for proper PGC development. We further show that Blimp1, a let-7 target and a master regulator of PGC specification7-9, can rescue the effect of Lin28-deficiency during PGC development, thereby establishing a mechanism of action for Lin28 during PGC specification. Over-expression of Lin28 promotes formation of Stella+ cells in vitro and PGCs in chimeric embryos, and is associated with human germ cell tumours. The differentiation of putative PGCs from ESCs in vitro recapitulates the early stages of gamete development in vivo, and provides an accessible system for discovering novel genes involved in germ cell development and malignancy. PMID:19578360

H19/let-7/LIN28 reciprocal negative regulatory circuit promotes breast cancer stem cell maintenance

PubMed Central

Peng, Fei; Li, Ting-Ting; Wang, Kai-Li; Xiao, Guo-Qing; Wang, Ju-Hong; Zhao, Hai-Dong; Kang, Zhi-Jie; Fan, Wen-Jun; Zhu, Li-Li; Li, Mei; Cui, Bai; Zheng, Fei-Meng; Wang, Hong-Jiang; Lam, Eric W-F; Wang, Bo; Xu, Jie; Liu, Quentin

2017-01-01

Long noncoding RNA-H19 (H19), an imprinted oncofetal gene, has a central role in carcinogenesis. Hitherto, the mechanism by which H19 regulates cancer stem cells, remains elusive. Here we show that breast cancer stem cells (BCSCs) express high levels of H19, and ectopic overexpression of H19 significantly promotes breast cancer cell clonogenicity, migration and mammosphere-forming ability. Conversely, silencing of H19 represses these BCSC properties. In concordance, knockdown of H19 markedly inhibits tumor growth and suppresses tumorigenesis in nude mice. Mechanistically, we found that H19 functions as a competing endogenous RNA to sponge miRNA let-7, leading to an increase in expression of a let-7 target, the core pluripotency factor LIN28, which is enriched in BCSC populations and breast patient samples. Intriguingly, this gain of LIN28 expression can also feedback to reverse the H19 loss-mediated suppression of BCSC properties. Our data also reveal that LIN28 blocks mature let-7 production and, thereby, de-represses H19 expression in breast cancer cells. Appropriately, H19 and LIN28 expression exhibits strong correlations in primary breast carcinomas. Collectively, these findings reveal that lncRNA H19, miRNA let-7 and transcriptional factor LIN28 form a double-negative feedback loop, which has a critical role in the maintenance of BCSCs. Consequently, disrupting this pathway provides a novel therapeutic strategy for breast cancer. PMID:28102845

Analyzing Lie symmetry and constructing conservation laws for time-fractional Benny-Lin equation

NASA Astrophysics Data System (ADS)

Rashidi, Saeede; Hejazi, S. Reza

This paper investigates the invariance properties of the time fractional Benny-Lin equation with Riemann-Liouville and Caputo derivatives. This equation can be reduced to the Kawahara equation, fifth-order Kdv equation, the Kuramoto-Sivashinsky equation and Navier-Stokes equation. By using the Lie group analysis method of fractional differential equations (FDEs), we derive Lie symmetries for the Benny-Lin equation. Conservation laws for this equation are obtained with the aid of the concept of nonlinear self-adjointness and the fractional generalization of the Noether’s operators. Furthermore, by means of the invariant subspace method, exact solutions of the equation are also constructed.

Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation.

PubMed

Choudhury, Nila Roy; Nowak, Jakub S; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H; Michlewski, Gracjan

2014-11-20

RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity.

77 FR 18862 - Zhiwei Lin, M.D.; Decision and Order

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-28

... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-54] Zhiwei Lin, M.D.; Decision and Order On September 19, 2011, Administrative Law Judge (ALJ) Timothy D. Wing issued the....C. 824, of the CSA. Calvin Ramsey, 76 FR 20034, 20036 (2011) (other citations omitted); Brenton D...

The ceilometer inter-comparison campaign CeiLinEx2015

NASA Astrophysics Data System (ADS)

Mattis, Ina; Begbie, Robert; Boyouk, Neda; Bravo-Aranda, Juan Antonio; Brettle, Mike; Cermak, Jan; Drouin, Marc-Antoine; Geiß, Alexander; Görsdorf, Ulrich; Haefele, Alexander; Haeffelin, Martial; Hervo, Maxime; Komínková, Kateřina; Leinweber, Ronny; Müller, Gerhard; Münkel, Christoph; Pattantyús-Ábrahám, Margit; Pönitz, Kornelia; Wagner, Frank; Wiegner, Matthias

2016-04-01

Ceilometers are well established instruments for the detection of cloud base heights. Since about 2000, modern ceilometer types (mainly CHM15k, CL51, and CL31) are used also for investigations of the top height of the planetary boundary layer and for quantitative retrievals of vertical profiles of backscatter coefficients. In the framework of the European projects E-PROFILE and TOPROF, tools for the exchange of ceilometer data among European meteorological services, as well as calibration and visualization procedures are developed and established. Unfortunately, the national networks are equipped with instruments of different generations and different manufacturers. In order to quantify and reduce those inhomogeneities, the ceilometer inter-comparison experiment CeiLinEx2015 was performed between June and September 2015 at the Meteorological Observatory Lindenberg, Germany. We tested six different instrument types: LD40, CL31, CL51, CHM15k, CHM15kx, and CS135. Each instrument type was represented by two instruments to estimate the instrument-to-instrument variability and the influence of different firmware versions. Two Raman lidars (RAMSES and RALPH), operated by German Meteorological Service (DWD) are used as reference instruments. Further ancillary data are available, e.g., hourly eye observations, four radio soundings per day, and AERONET sun photometer observations. Beside the typical vertically pointing measurement scheme, we performed special measurements with horizontal pointing direction or blocked receiver telescope. During the experiment, we could collect measurements under very different meteorological situations: Several clear nights allow for Rayleigh-Calibration (see Hervo and CeiLinEx2015 team [EGU2016-4785]), a strong event of Sahara dust intrusion can be used to study the behaviour of the instruments in presence of large, non-spherical particles (like volcanic ash). Further investigations focus, e.g., on the detection of very low cloud base

The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

PubMed

McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

2017-07-07

The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Altered expression of talin 1 in peripheral immune cells points to a significant role of the innate immune system in spontaneous autoimmune uveitis.

PubMed

Degroote, Roxane L; Hauck, Stefanie M; Kremmer, Elisabeth; Amann, Barbara; Ueffing, Marius; Deeg, Cornelia A

2012-07-19

The molecular mechanism which enables activated immune cells to cross the blood-retinal barrier in spontaneous autoimmune uveitis is yet to be unraveled. Equine recurrent uveitis is the only spontaneous animal model allowing us to investigate the autoimmune mediated transformation of leukocytes in the course of this sight threatening disease. Hypothesizing that peripheral blood immune cells change their protein expression pattern in spontaneous autoimmune uveitis, we used DIGE to detect proteins with altered abundance comparing peripheral immune cells of healthy and ERU diseased horses. Among others, we found a significant downregulation of talin 1 in peripheral blood granulocytes of ERU specimen, pointing to changes in β integrin activation and indicating a significant role of the innate immune system in spontaneous autoimmune diseases. Copyright © 2012. Published by Elsevier B.V.

Knockdown of miR-128a induces Lin28a expression and reverts myeloid differentiation blockage in acute myeloid leukemia

PubMed Central

De Luca, Luciana; Trino, Stefania; Laurenzana, Ilaria; Tagliaferri, Daniela; Falco, Geppino; Grieco, Vitina; Bianchino, Gabriella; Nozza, Filomena; Campia, Valentina; D'Alessio, Francesca; La Rocca, Francesco; Caivano, Antonella; Villani, Oreste; Cilloni, Daniela; Musto, Pellegrino; Del Vecchio, Luigi

2017-01-01

Lin28A is a highly conserved RNA-binding protein that concurs to control the balance between stemness and differentiation in several tissue lineages. Here, we report the role of miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia (AML), a genetically heterogeneous disease characterized by abnormally controlled proliferation of myeloid progenitor cells accompanied by partial or total inability to undergo terminal differentiation. First, we found Lin28A underexpressed in blast cells from AML patients and AML cell lines as compared with CD34+ normal precursors. In vitro transfection of Lin28A in NPM1-mutated OCI-AML3 cell line significantly triggered cell-cycle arrest and myeloid differentiation, with increased expression of macrophage associate genes (EGR2, ZFP36 and ANXA1). Furthermore, miR-128a, a negative regulator of Lin28A, was found overexpressed in AML cells compared with normal precursors, especially in acute promyelocytic leukemia (APL) and in ‘AML with maturation’ (according to 2016 WHO classification of myeloid neoplasms and acute leukemia). Its forced overexpression by lentiviral infection in OCI-AML3 downregulated Lin28A with ensuing repression of macrophage-oriented differentiation. Finally, knockdown of miR-128a in OCI-AML3 and in APL/AML leukemic cells (by transfection and lentiviral infection, respectively) induced myeloid cell differentiation and increased expression of Lin28A, EGR2, ZFP36 and ANXA1, reverting myeloid differentiation blockage. In conclusion, our findings revealed a new mechanism for AML differentiation blockage, suggesting new strategies for AML therapy based upon miR-128a inhibition. PMID:28569789

Trim25 Is an RNA-Specific Activator of Lin28a/TuT4-Mediated Uridylation

PubMed Central

Choudhury, Nila Roy; Nowak, Jakub S.; Zuo, Juan; Rappsilber, Juri; Spoel, Steven H.; Michlewski, Gracjan

2014-01-01

Summary RNA binding proteins have thousands of cellular RNA targets and often exhibit opposite or passive molecular functions. Lin28a is a conserved RNA binding protein involved in pluripotency and tumorigenesis that was previously shown to trigger TuT4-mediated pre-let-7 uridylation, inhibiting its processing and targeting it for degradation. Surprisingly, despite binding to other pre-microRNAs (pre-miRNAs), only pre-let-7 is efficiently uridylated by TuT4. Thus, we hypothesized the existence of substrate-specific cofactors that stimulate Lin28a-mediated pre-let-7 uridylation or restrict its functionality on non-let-7 pre-miRNAs. Through RNA pull-downs coupled with quantitative mass spectrometry, we identified the E3 ligase Trim25 as an RNA-specific cofactor for Lin28a/TuT4-mediated uridylation. We show that Trim25 binds to the conserved terminal loop (CTL) of pre-let-7 and activates TuT4, allowing for more efficient Lin28a-mediated uridylation. These findings reveal that protein-modifying enzymes, only recently shown to bind RNA, can guide the function of canonical ribonucleoprotein (RNP) complexes in cis, thereby providing an additional level of specificity. PMID:25457611

Overexpression of Lin28b in Neural Stem Cells is Insufficient for Brain Tumor Formation, but Induces Pathological Lobulation of the Developing Cerebellum.

PubMed

Wefers, Annika K; Lindner, Sven; Schulte, Johannes H; Schüller, Ulrich

2017-02-01

LIN28B is a homologue of the RNA-binding protein LIN28A and regulates gene expression during development and carcinogenesis. It is strongly upregulated in a variety of brain tumors, such as medulloblastoma, embryonal tumor with multilayered rosettes (ETMR), atypical teratoid/rhabdoid tumor (AT/RT), or glioblastoma, but the effect of an in vivo overexpression of LIN28B on the developing central nervous system is unknown. We generated transgenic mice that either overexpressed Lin28b in Math1-positive cerebellar granule neuron precursors or in a broad range of Nestin-positive neural precursors. Sections of the cerebellar vermis from adult Math1-Cre::lsl-Lin28b mice had an additional subfissure in lobule IV. Vermes from p0 and p7 Nestin-Cre::lsl-Lin28b mice appeared normal, but we found a pronounced vermal hypersublobulation at p15 and p21 in these mice. Also, the external granule cell layer (EGL) was thicker at p15 than in controls, contained more proliferating cells, and persisted up to p21. Consistently, some Pax6- and NeuN-positive cells were present in the EGL of Nestin-Cre::lsl-Lin28b mice even at p21, and we detected more NeuN-positive granule neuron precursors in the molecular layer (ML) as compared to control. Finally, we found some residual Pax2-positive precursors of inhibitory interneurons in the ML of Nestin-Cre::lsl-Lin28b mice at p21, which have already disappeared in controls. We conclude that while overexpression of LIN28B in Nestin-positive cells does not lead to tumor formation, it results in a protracted development of granule cells and inhibitory interneurons and leads to a hypersublobulation of the cerebellar vermis.

[Analysis of acid rain characteristics of Lin'an Regional Background Station using long-term observation data].

PubMed

Li, Zheng-Quan; Ma, Hao; Mao, Yu-Ding; Feng, Tao

2014-02-01

Using long-term observation data of acid rain at Lin'an Regional Background Station (Lin'an RBS), this paper studied the interannual and monthly variations of acid rain, the reasons for the variations, and the relationships between acid rain and meteorological factors. The results showed that interannual variation of acid rain at Lin'an RBS had a general increasing trend in which there were two obvious intensifying processes and two distinct weakening processes, during the period ranging from 1985 to 2012. In last two decades, the monthly variation of acid rain at Lin'an RBS indicated that rain acidity and frequency of severe acid rain were increasing but the frequency of weak acid rain was decreasing when moving towards bilateral side months of July. Acid rain occurrence was affected by rainfall intensity, wind speed and wind direction. High frequency of severe acid rain and low frequency of weak acid rain were on days with drizzle, but high frequency of weak acid rain and low frequency of severe acid rain occurred on rainstorm days. With wind speed upgrading, the frequency of acid rain and the proportion of severe acid rain were declining, the pH value of precipitation was reducing too. Another character is that daily dominant wind direction of weak acid rain majorly converged in S-W section ,however that of severe acid rain was more likely distributed in N-E section. The monthly variation of acid rain at Lin'an RBS was mainly attributed to precipitation variation, the increasing and decreasing of monthly incoming wind from SSE-WSW and NWN-ENE sections of wind direction. The interannual variation of acid rain could be due to the effects of energy consumption raising and significant green policies conducted in Zhejiang, Jiangsu and Shanghai.

A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis.

PubMed

Hartin, Samantha N; Hudson, Martin L; Yingling, Curtis; Ackley, Brian D

2015-01-01

The C. elegans proteins PTP-3/LAR-RPTP and SDN-1/Syndecan are conserved cell adhesion molecules. Loss-of-function (LOF) mutations in either ptp-3 or sdn-1 result in low penetrance embryonic developmental defects. Work from other systems has shown that syndecans can function as ligands for LAR receptors in vivo. We used double mutant analysis to test whether ptp-3 and sdn-1 function in a linear genetic pathway during C. elegans embryogenesis. We found animals with LOF in both sdn-1 and ptp-3 exhibited a highly penetrant synthetic lethality (SynLet), with only a small percentage of animals surviving to adulthood. Analysis of the survivors demonstrated that these animals had a synergistic increase in the penetrance of embryonic developmental defects. Together, these data strongly suggested PTP-3 and SDN-1 function in parallel during embryogenesis. We subsequently used RNAi to knockdown ~3,600 genes predicted to encode secreted and/or transmembrane molecules to identify genes that interacted with ptp-3 or sdn-1. We found that the Wnt ligand, lin-44, was SynLet with sdn-1, but not ptp-3. We used 4-dimensional time-lapse analysis to characterize the interaction between lin-44 and sdn-1. We found evidence that loss of lin-44 caused defects in the polarization and migration of endodermal precursors during gastrulation, a previously undescribed role for lin-44 that is strongly enhanced by the loss of sdn-1. PTP-3 and SDN-1 function in compensatory pathways during C. elegans embryonic and larval development, as simultaneous loss of both genes has dire consequences for organismal survival. The Wnt ligand lin-44 contributes to the early stages of gastrulation in parallel to sdn-1, but in a genetic pathway with ptp-3. Overall, the SynLet phenotype provides a robust platform to identify ptp-3 and sdn-1 interacting genes, as well as other genes that function in development, yet might be missed in traditional forward genetic screens.

A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis

PubMed Central

Hartin, Samantha N.; Hudson, Martin L.; Yingling, Curtis; Ackley, Brian D.

2015-01-01

Background The C. elegans proteins PTP-3/LAR-RPTP and SDN-1/Syndecan are conserved cell adhesion molecules. Loss-of-function (LOF) mutations in either ptp-3 or sdn-1 result in low penetrance embryonic developmental defects. Work from other systems has shown that syndecans can function as ligands for LAR receptors in vivo. We used double mutant analysis to test whether ptp-3 and sdn-1 function in a linear genetic pathway during C. elegans embryogenesis. Results We found animals with LOF in both sdn-1 and ptp-3 exhibited a highly penetrant synthetic lethality (SynLet), with only a small percentage of animals surviving to adulthood. Analysis of the survivors demonstrated that these animals had a synergistic increase in the penetrance of embryonic developmental defects. Together, these data strongly suggested PTP-3 and SDN-1 function in parallel during embryogenesis. We subsequently used RNAi to knockdown ~3,600 genes predicted to encode secreted and/or transmembrane molecules to identify genes that interacted with ptp-3 or sdn-1. We found that the Wnt ligand, lin-44, was SynLet with sdn-1, but not ptp-3. We used 4-dimensional time-lapse analysis to characterize the interaction between lin-44 and sdn-1. We found evidence that loss of lin-44 caused defects in the polarization and migration of endodermal precursors during gastrulation, a previously undescribed role for lin-44 that is strongly enhanced by the loss of sdn-1. Conclusions PTP-3 and SDN-1 function in compensatory pathways during C. elegans embryonic and larval development, as simultaneous loss of both genes has dire consequences for organismal survival. The Wnt ligand lin-44 contributes to the early stages of gastrulation in parallel to sdn-1, but in a genetic pathway with ptp-3. Overall, the SynLet phenotype provides a robust platform to identify ptp-3 and sdn-1 interacting genes, as well as other genes that function in development, yet might be missed in traditional forward genetic screens. PMID:25938228

Primordial dwarfism gene maintains Lin28 expression to safeguard embryonic stem cells from premature differentiation.

PubMed

Dai, Qian; Luan, Guangxin; Deng, Li; Lei, Tingjun; Kang, Han; Song, Xu; Zhang, Yujun; Xiao, Zhi-Xiong; Li, Qintong

2014-05-08

Primordial dwarfism (PD) is characterized by global growth failure, both during embryogenesis and postnatally. Loss-of-function germline mutations in La ribonucleoprotein domain family, member 7 (LAPR7) have recently been linked to PD. Paradoxically, LARP7 deficiency was previously assumed to be associated with increased cell growth and proliferation via activation of positive transcription elongation factor b (P-TEFb). Here, we show that Larp7 deficiency likely does not significantly increase P-TEFb activity. We further discover that Larp7 knockdown does not affect pluripotency but instead primes embryonic stem cells (ESCs) for differentiation via downregulation of Lin28, a positive regulator of organismal growth. Mechanistically, we show that Larp7 interacts with a poly(A) polymerase Star-PAP to maintain Lin28 mRNA stability. We propose that proper regulation of Lin28 and PTEFb is essential for embryonic cells to achieve a sufficient number of cell divisions prior to differentiation and ultimately to maintain proper organismal size. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

DPL-1 DP, LIN-35 Rb and EFL-1 E2F act with the MCD-1 zinc-finger protein to promote programmed cell death in Caenorhabditis elegans.

PubMed

Reddien, Peter W; Andersen, Erik C; Huang, Michael C; Horvitz, H Robert

2007-04-01

The genes egl-1, ced-9, ced-4, and ced-3 play major roles in programmed cell death in Caenorhabditis elegans. To identify genes that have more subtle activities, we sought mutations that confer strong cell-death defects in a genetically sensitized mutant background. Specifically, we screened for mutations that enhance the cell-death defects caused by a partial loss-of-function allele of the ced-3 caspase gene. We identified mutations in two genes not previously known to affect cell death, dpl-1 and mcd-1 (modifier of cell death). dpl-1 encodes the C. elegans homolog of DP, the human E2F-heterodimerization partner. By testing genes known to interact with dpl-1, we identified roles in cell death for four additional genes: efl-1 E2F, lin-35 Rb, lin-37 Mip40, and lin-52 dLin52. mcd-1 encodes a novel protein that contains one zinc finger and that is synthetically required with lin-35 Rb for animal viability. dpl-1 and mcd-1 act with efl-1 E2F and lin-35 Rb to promote programmed cell death and do so by regulating the killing process rather than by affecting the decision between survival and death. We propose that the DPL-1 DP, MCD-1 zinc finger, EFL-1 E2F, LIN-35 Rb, LIN-37 Mip40, and LIN-52 dLin52 proteins act together in transcriptional regulation to promote programmed cell death.

LIN28A enhances the therapeutic potential of cultured neural stem cells in a Parkinson's disease model.

PubMed

Rhee, Yong-Hee; Kim, Tae-Ho; Jo, A-Young; Chang, Mi-Yoon; Park, Chang-Hwan; Kim, Sang-Mi; Song, Jae-Jin; Oh, Sang-Min; Yi, Sang-Hoon; Kim, Hyeon Ho; You, Bo-Hyun; Nam, Jin-Wu; Lee, Sang-Hun

2016-10-01

The original properties of tissue-specific stem cells, regardless of their tissue origins, are inevitably altered during in vitro culturing, lessening the clinical and research utility of stem cell cultures. Specifically, neural stem cells derived from the ventral midbrain lose their dopamine neurogenic potential, ventral midbrain-specific phenotypes, and repair capacity during in vitro cell expansion, all of which are critical concerns in using the cultured neural stem cells in therapeutic approaches for Parkinson's disease. In this study, we observed that the culture-dependent changes of neural stem cells derived from the ventral midbrain coincided with loss of RNA-binding protein LIN28A expression. When LIN28A expression was forced and sustained during neural stem cell expansion using an inducible expression-vector system, loss of dopamine neurogenic potential and midbrain phenotypes after long-term culturing was blocked. Furthermore, dopamine neurons that differentiated from neural stem cells exhibited remarkable survival and resistance against toxic insults. The observed effects were not due to a direct action of LIN28A on the differentiated dopamine neurons, but rather its action on precursor neural stem cells as exogene expression was switched off in the differentiating/differentiated cultures. Remarkable and reproducible behavioural recovery was shown in all Parkinson's disease rats grafted with neural stem cells expanded with LIN28A expression, along with extensive engraftment of dopamine neurons expressing mature neuronal and midbrain-specific markers. These findings suggest that LIN28A expression during stem cell expansion could be used to prepare therapeutically competent donor cells. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Using Lin's method to solve Bykov's problems

NASA Astrophysics Data System (ADS)

Knobloch, Jürgen; Lamb, Jeroen S. W.; Webster, Kevin N.

2014-10-01

We consider nonwandering dynamics near heteroclinic cycles between two hyperbolic equilibria. The constituting heteroclinic connections are assumed to be such that one of them is transverse and isolated. Such heteroclinic cycles are associated with the termination of a branch of homoclinic solutions, and called T-points in this context. We study codimension-two T-points and their unfoldings in Rn. In our consideration we distinguish between cases with real and complex leading eigenvalues of the equilibria. In doing so we establish Lin's method as a unified approach to (re)gain and extend results of Bykov's seminal studies and related works. To a large extent our approach reduces the study to the discussion of intersections of lines and spirals in the plane. Case (RR): Under open conditions on the eigenvalues, there exist open sets in parameter space for which there exist periodic orbits close to the heteroclinic cycle. In addition, there exist two one-parameter families of homoclinic orbits to each of the saddle points p1 and p2.See Theorem 2.1 and Proposition 2.2 for precise statements and Fig. 2 for bifurcation diagrams. Cases (RC) and (CC): At the bifurcation point μ=0 and for each N≥2, there exists an invariant set S0N close to the heteroclinic cycle on which the first return map is topologically conjugated to a full shift on N symbols. For any fixed N≥2, the invariant set SμN persists for |μ| sufficiently small.In addition, there exist infinitely many transversal and non-transversal heteroclinic orbits connecting the saddle points p1 and p2 in a neighbourhood of μ=0, as well as infinitely many one-parameter families of homoclinic orbits to each of the saddle points.For full statements of the results see Theorem 2.3 and Propositions 2.4, 2.5 and Fig. 3 for bifurcation diagrams. The dynamics near T-points has been studied previously by Bykov [6-10], Glendinning and Sparrow [20], Kokubu [27,28] and Labouriau and Rodrigues [30,31,38]. See also the surveys

Lin28B promotes Müller glial cell de-differentiation and proliferation in the regenerative rat retinas

PubMed Central

Tao, Zui; Zhao, Chen; Jian, Qian; Gillies, Mark; Xu, Haiwei; Yin, Zheng Qin

2016-01-01

Retinal regeneration and repair are severely impeded in higher mammalian animals. Although Müller cells can be activated and show some characteristics of progenitor cells when injured or under pathological conditions, they quickly form gliosis scars. Unfortunately, the basic mechanisms that impede retinal regeneration remain unknown. We studied retinas from Royal College of Surgeon (RCS) rats and found that let-7 family molecules, let-7e and let-7i, were significantly overexpressed in Müller cells of degenerative retinas. It demonstrated that down-regulation of the RNA binding protein Lin28B was one of the key factors leading to the overexpression of let-7e and let-7i. Lin28B ectopic expression in the Müller cells suppressed overexpression of let-7e and let-7i, stimulated and mobilized Müller glia de-differentiation, proliferation, promoted neuronal commitment, and inhibited glial fate acquisition of de-differentiated Müller cells. ERG recordings revealed that the amplitudes of a-wave and b-wave were improved significantly after Lin28B was delivered into the subretinal space of RCS rats. In summary, down-regulation of Lin28B as well as up-regulation of let-7e and let-7i may be the main factors that impede Müller cell de-differentiation and proliferation in the retina of RCS rats. PMID:27384999

Blocking neutrophil integrin activation prevents ischemia-reperfusion injury.

PubMed

Yago, Tadayuki; Petrich, Brian G; Zhang, Nan; Liu, Zhenghui; Shao, Bojing; Ginsberg, Mark H; McEver, Rodger P

2015-07-27

Neutrophil recruitment, mediated by β2 integrins, combats pyogenic infections but also plays a key role in ischemia-reperfusion injury and other inflammatory disorders. Talin induces allosteric rearrangements in integrins that increase affinity for ligands (activation). Talin also links integrins to actin and other proteins that enable formation of adhesions. Structural studies have identified a talin1 mutant (L325R) that perturbs activation without impairing talin's capacity to link integrins to actin and other proteins. Here, we found that mice engineered to express only talin1(L325R) in myeloid cells were protected from renal ischemia-reperfusion injury. Dissection of neutrophil function in vitro and in vivo revealed that talin1(L325R) neutrophils had markedly impaired chemokine-induced, β2 integrin-mediated arrest, spreading, and migration. Surprisingly, talin1(L325R) neutrophils exhibited normal selectin-induced, β2 integrin-mediated slow rolling, in sharp contrast to the defective slow rolling of neutrophils lacking talin1 or expressing a talin1 mutant (W359A) that blocks talin interaction with integrins. These studies reveal the importance of talin-mediated activation of integrins for renal ischemia-reperfusion injury. They further show that neutrophil arrest requires talin recruitment to and activation of integrins. However, although neutrophil slow rolling requires talin recruitment to integrins, talin-mediated integrin activation is dispensable. © 2015 Yago et al.

Blocking neutrophil integrin activation prevents ischemia–reperfusion injury

PubMed Central

Yago, Tadayuki; Petrich, Brian G.; Zhang, Nan; Liu, Zhenghui; Shao, Bojing; Ginsberg, Mark H.

2015-01-01

Neutrophil recruitment, mediated by β2 integrins, combats pyogenic infections but also plays a key role in ischemia–reperfusion injury and other inflammatory disorders. Talin induces allosteric rearrangements in integrins that increase affinity for ligands (activation). Talin also links integrins to actin and other proteins that enable formation of adhesions. Structural studies have identified a talin1 mutant (L325R) that perturbs activation without impairing talin’s capacity to link integrins to actin and other proteins. Here, we found that mice engineered to express only talin1(L325R) in myeloid cells were protected from renal ischemia–reperfusion injury. Dissection of neutrophil function in vitro and in vivo revealed that talin1(L325R) neutrophils had markedly impaired chemokine-induced, β2 integrin–mediated arrest, spreading, and migration. Surprisingly, talin1(L325R) neutrophils exhibited normal selectin-induced, β2 integrin–mediated slow rolling, in sharp contrast to the defective slow rolling of neutrophils lacking talin1 or expressing a talin1 mutant (W359A) that blocks talin interaction with integrins. These studies reveal the importance of talin-mediated activation of integrins for renal ischemia–reperfusion injury. They further show that neutrophil arrest requires talin recruitment to and activation of integrins. However, although neutrophil slow rolling requires talin recruitment to integrins, talin-mediated integrin activation is dispensable. PMID:26169939

A computational study of the dechlorination of β-hexachlorocyclohexane (β-HCH) catalyzed by the haloalkane dehalogenase LinB.

PubMed

Manna, Rabindra Nath; Dybala-Defratyka, Agnieszka

2014-11-15

LinB, a haloalkane dehalogenase from Sphingomonas paucimobilis UT26, is known to metabolize halohydrocarbons to halide ions and the respective alcohols. Its broad substrate specificity allowed its consideration for bioremediation. Herein, we have shown its catalytic action toward β-hexachlorocyclohexane (β-HCH) - an example of large-size substrates that can be accommodated in its active site. We have analyzed the capability of combined QM/MM schemes to describe in detail the SN2 dechlorination reaction between β-HCH and Asp108 in the active site of LinB. Free energy surfaces have been calculated using one and two dimensional potentials of mean force (PMF) obtained at the PM3/MM (MM=amberff99SB, TIP3P) level of theory. The overestimated energetic barriers by the PM3 Hamiltonian were corrected using a DFT functional (M06-2X). The resulted activation energies (16 and 19 kcal mol(-1) from 1D and 2D-PMF profiles, respectively) for the dechlorination reaction of β-HCH in the active site of LinB enzyme are in qualitative agreement with the experimentally determined value of 17 kcal mol(-1). The binding of β-HCH to the active site of LinB has been compared to the binding of smaller 1-chlorobutane (1-CB) and larger δ-hexabromocyclododecane (δ-HBCD). Copyright © 2014 Elsevier Inc. All rights reserved.

The gga-let-7 family post-transcriptionally regulates TGFBR1 and LIN28B during the differentiation process in early chick development.

PubMed

Lee, Sang In; Jeon, Mi-Hyang; Kim, Jeom Sun; Jeon, Ik-Soo; Byun, Sung June

2015-12-01

Early chick embryogenesis is governed by a complex mechanism involving transcriptional and post-transcriptional regulation, although how post-transcriptional processes influence the balance between pluripotency and differentiation during early chick development have not been previously investigated. Here, we characterized the microRNA (miRNA) signature associated with differentiation in the chick embryo, and found that as expression of the gga-let-7 family increases through early development, expression of their direct targets, TGFBR1 and LIN28B, decreases; indeed, gga-let-7a-5p and gga-let-7b miRNAs directly bind to TGFBR1 and LIN28B transcripts. Our data further indicate that TGFBR1 and LIN28B maintain pluripotency by regulating POUV, NANOG, and CRIPTO. Therefore, gga-let-7 miRNAs act as post-transcriptional regulators of differentiation in blastodermal cells by repressing the expression of the TGFBR1 and LIN28B, which intrinsically controls blastodermal cell differentiation in early chick development. © 2015 Wiley Periodicals, Inc.

The Value of SCMC in SLA: Comments on Lin, Huang & Liou (2013)

ERIC Educational Resources Information Center

Taylor, Alan M.

2014-01-01

Meta-analytic methods are often used to determine the effectiveness of certain treatments across studies. However, we are often unaware of how a meta-analysis can provide value to researchers and practitioners. This paper offers a brief commentary on a meta-analysis conducted by Lin, Huang and Liou (2013) in LLT, providing further statistical…

LIN-23, an E3 Ubiquitin Ligase Component, Is Required for the Repression of CDC-25.2 Activity during Intestinal Development in Caenorhabditis elegans.

PubMed

Son, Miseol; Kawasaki, Ichiro; Oh, Bong-Kyeong; Shim, Yhong-Hee

2016-11-30

Caenorhabditis elegans ( C. elegans ) utilizes two different cell-cycle modes, binucleations during the L1 larval stage and endoreduplications at four larval moltings, for its postembryonic intestinal development. Previous genetic studies indicated that CDC-25.2 is specifically required for binucleations at the L1 larval stage and is repressed before endoreduplications. Furthermore, LIN-23, the C. elegans β-TrCP ortholog, appears to function as a repressor of CDC-25.2 to prevent excess intestinal divisions. We previously reported that intestinal hyperplasia in lin-23(e1883) mutants was effectively suppressed by the RNAi depletion of cdc-25.2 . Nevertheless, LIN-23 targeting CDC-25.2 for ubiquitination as a component of E3 ubiquitin ligase has not yet been tested. In this study, LIN-23 is shown to be the major E3 ubiquitin ligase component, recognizing CDC-25.2 to repress their activities for proper transition of cell-cycle modes during the C. elegans postembryonic intestinal development. In addition, for the first time that LIN-23 physically interacts with both CDC-25.1 and CDC-25.2 and facilitates ubiquitination for timely regulation of their activities during the intestinal development.

ChiLin: a comprehensive ChIP-seq and DNase-seq quality control and analysis pipeline.

PubMed

Qin, Qian; Mei, Shenglin; Wu, Qiu; Sun, Hanfei; Li, Lewyn; Taing, Len; Chen, Sujun; Li, Fugen; Liu, Tao; Zang, Chongzhi; Xu, Han; Chen, Yiwen; Meyer, Clifford A; Zhang, Yong; Brown, Myles; Long, Henry W; Liu, X Shirley

2016-10-03

Transcription factor binding, histone modification, and chromatin accessibility studies are important approaches to understanding the biology of gene regulation. ChIP-seq and DNase-seq have become the standard techniques for studying protein-DNA interactions and chromatin accessibility respectively, and comprehensive quality control (QC) and analysis tools are critical to extracting the most value from these assay types. Although many analysis and QC tools have been reported, few combine ChIP-seq and DNase-seq data analysis and quality control in a unified framework with a comprehensive and unbiased reference of data quality metrics. ChiLin is a computational pipeline that automates the quality control and data analyses of ChIP-seq and DNase-seq data. It is developed using a flexible and modular software framework that can be easily extended and modified. ChiLin is ideal for batch processing of many datasets and is well suited for large collaborative projects involving ChIP-seq and DNase-seq from different designs. ChiLin generates comprehensive quality control reports that include comparisons with historical data derived from over 23,677 public ChIP-seq and DNase-seq samples (11,265 datasets) from eight literature-based classified categories. To the best of our knowledge, this atlas represents the most comprehensive ChIP-seq and DNase-seq related quality metric resource currently available. These historical metrics provide useful heuristic quality references for experiment across all commonly used assay types. Using representative datasets, we demonstrate the versatility of the pipeline by applying it to different assay types of ChIP-seq data. The pipeline software is available open source at https://github.com/cfce/chilin . ChiLin is a scalable and powerful tool to process large batches of ChIP-seq and DNase-seq datasets. The analysis output and quality metrics have been structured into user-friendly directories and reports. We have successfully compiled 23

Mitotic Vulnerability in Triple-Negative Breast Cancer Associated with LIN9 Is Targetable with BET Inhibitors.

PubMed

Sahni, Jennifer M; Gayle, Sylvia S; Webb, Bryan M; Weber-Bonk, Kristen L; Seachrist, Darcie D; Singh, Salendra; Sizemore, Steven T; Restrepo, Nicole A; Bebek, Gurkan; Scacheri, Peter C; Varadan, Vinay; Summers, Matthew K; Keri, Ruth A

2017-10-01

Triple-negative breast cancers (TNBC) are highly aggressive, lack FDA-approved targeted therapies, and frequently recur, making the discovery of novel therapeutic targets for this disease imperative. Our previous analysis of the molecular mechanisms of action of bromodomain and extraterminal protein inhibitors (BETi) in TNBC revealed these drugs cause multinucleation, indicating BET proteins are essential for efficient mitosis and cytokinesis. Here, using live cell imaging, we show that BET inhibition prolonged mitotic progression and induced mitotic cell death, both of which are indicative of mitotic catastrophe. Mechanistically, the mitosis regulator LIN9 was a direct target of BET proteins that mediated the effects of BET proteins on mitosis in TNBC. Although BETi have been proposed to function by dismantling super-enhancers (SE), the LIN9 gene lacks an SE but was amplified or overexpressed in the majority of TNBCs. In addition, its mRNA expression predicted poor outcome across breast cancer subtypes. Together, these results provide a mechanism for cancer selectivity of BETi that extends beyond modulation of SE-associated genes and suggest that cancers dependent upon LIN9 overexpression may be particularly vulnerable to BETi. Cancer Res; 77(19); 5395-408. ©2017 AACR . ©2017 American Association for Cancer Research.

Safety and Feasibility of Lin- Cells Administration to ALS Patients: A Novel View on Humoral Factors and miRNA Profiles.

PubMed

Sobuś, Anna; Baumert, Bartłomiej; Litwińska, Zofia; Gołąb-Janowska, Monika; Stępniewski, Jacek; Kotowski, Maciej; Pius-Sadowska, Ewa; Kawa, Miłosz P; Gródecka-Szwajkiewicz, Dorota; Peregud-Pogorzelski, Jarosław; Dulak, Józef; Nowacki, Przemysław; Machaliński, Bogusław

2018-04-27

Therapeutic options for amyotrophic lateral sclerosis (ALS) are still limited. Great hopes, however, are placed in growth factors that show neuroprotective abilities (e.g., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF)) and in the immune modulating features, in particular, the anti-inflammatory effects. In our study we aimed to investigate whether a bone marrow-derived lineage-negative (Lin-) cells population, after autologous application into cerebrospinal fluid (CSF), is able to produce noticeable concentrations of trophic factors and inflammatory-related proteins and thus influence the clinical course of ALS. To our knowledge, the evaluation of Lin- cells transplantation for ALS treatment has not been previously reported. Early hematopoietic Lin- cells were isolated from twelve ALS patients’ bone marrow, and later, the suspension of cells was administered into the subarachnoid space by lumbar puncture. Concentrations of selected proteins in the CSF and plasma were quantified by multiplex fluorescent bead-based immunoassays at different timepoints post-transplantation. We also chose microRNAs (miRNAs) related to muscle biology (miRNA-1, miRNA-133a, and miRNA-206) and angiogenesis and inflammation (miRNA-155 and miRNA-378) and tested, for the first time, their expression profiles in the CSF and plasma of ALS patients after Lin- cells transplantation. The injection of bone marrow cells resulted in decreased concentration of selected inflammatory proteins (C3) after Lin- cells injection, particularly in patients who had a better clinical outcome. Moreover, several analyzed miRNAs have changed expression levels in the CSF and plasma of ALS patients subsequent to Lin- cells administration. Interestingly, the expression of miR-206 increased in ALS patients, while miR-378 decreased both in the CSF and plasma one month after the cells’ injection. We propose that autologous lineage

Long-term results of endoscopic sympathetic block using the Lin-Telaranta classification.

PubMed

Rantanen, Tuomo; Telaranta, Timo

2013-10-01

Endoscopic thoracic sympathectomy has been used successfully in the treatment of blushing, excessive sweating, and social phobia. However, the adverse effects of endoscopic thoracic sympathectomy are more severe and frequent than the adverse effects of endoscopic sympathetic block (ESB). The use of different blocking levels for different indications in ESB according to the Lin-Telaranta classification further decreases the postoperative adverse effects. However, there are few data on the long-term results of ESB performed using the Lin-Telaranta classification. Ninety-five patients (55 men, 40 women) were interviewed by before the surgery using our routine questionnaire, and the same questionnaire was answered postoperatively by the patients. In addition, a long-term follow-up questionnaire was sent to all patients whose address was known. Forty-seven patients (24 men, 23 women) answered to this questionnaire. The Davidson brief social phobia scale and the Liebowitz quality of life scale were used. Patients were divided to 3 categories: category 1, patients with sweating problems; category 2, patients with blushing; and category 3, and patients with symptoms other than sweating or blushing. Among patients in category 1, social phobia decreased from 12.43 to 6.71 (p = 0.004), in category 2 from 13.97 to 7.69 (p < 0.001), and in category 3 from 13.18 to 9.64 (p = 0.007) during long-term follow-up. Among patients with severe sweating problems preoperatively, sweating decreased from 2.50 to 1.29 (p = 0.003) among patients in category 1 and from 1.86 to 1.16 (p < 0.001) among patients in category 2. Among patients with unbearable blushing, blushing decreased from 4 to 1.80 (p < 0.001). Patients got a clear help from ESB performed using the Lin-Telaranta classification to treat blushing, excessive sweating, and social phobia with and without physical symptoms. In addition, compensatory sweating increased only slightly.

Therapeutic Inhibitors of LIN28/let-7 Pathway in Ovarian Cancer

DTIC Science & Technology

2015-09-01

generate loss of function lines (siRNA and the CrispR /Cas9 system). Task 4. Determine oncogenic properties associated with TUTase and LIN28B loss in...of-function cell lines to complement our already generated shRNA lines, we are developing handson experience with CrispR /Cas9 technology to...generate stable cell lines where our genes of interest will be inactivated. The advantage of the CrispR /Cas9 method is that stable lines can be

COMBINED ENDOCRINE EFFECTS OF IN UTERO EXPOSURE TO THE ANTIANDROGENS BUTYLBENZYL PHTHALATE (BBP) AND LINURON (LIN) ON FETAL TESTOSTERONE (T) SYNTHESIS AND REPRODUCTIVE TRACT DEVELOPMENT

EPA Science Inventory

COMBINED ENDOCRINE EFFECTS OF IN UTERO EXPOSURE TO THE ANTIANDROGENS BUTYLBENZYL PHTHALATE (BBP) AND LINURON (Lin) ON FETAL TESTOSTERONE (T) SYNTHESIS AND REPRODUCTIVE TRACT DEVELOPMENT
Parks LG , Hotchkiss AK, Ostby J, Lambright C and Gray LE, Jr.

Lin and BBP are toxic...

H3K9me2/3 Binding of the MBT Domain Protein LIN-61 Is Essential for Caenorhabditis elegans Vulva Development

PubMed Central

Koester-Eiserfunke, Nora; Fischle, Wolfgang

2011-01-01

MBT domain proteins are involved in developmental processes and tumorigenesis. In vitro binding and mutagenesis studies have shown that individual MBT domains within clustered MBT repeat regions bind mono- and dimethylated histone lysine residues with little to no sequence specificity but discriminate against the tri- and unmethylated states. However, the exact function of promiscuous histone methyl-lysine binding in the biology of MBT domain proteins has not been elucidated. Here, we show that the Caenorhabditis elegans four MBT domain protein LIN-61, in contrast to other MBT repeat factors, specifically interacts with histone H3 when methylated on lysine 9, displaying a strong preference for di- and trimethylated states (H3K9me2/3). Although the fourth MBT repeat is implicated in this interaction, H3K9me2/3 binding minimally requires MBT repeats two to four. Further, mutagenesis of residues conserved with other methyl-lysine binding MBT regions in the fourth MBT repeat does not abolish interaction, implicating a distinct binding mode. In vivo, H3K9me2/3 interaction of LIN-61 is required for C. elegans vulva development within the synMuvB pathway. Mutant LIN-61 proteins deficient in H3K9me2/3 binding fail to rescue lin-61 synMuvB function. Also, previously identified point mutant synMuvB alleles are deficient in H3K9me2/3 interaction although these target residues that are outside of the fourth MBT repeat. Interestingly, lin-61 genetically interacts with two other synMuvB genes, hpl-2, an HP1 homologous H3K9me2/3 binding factor, and met-2, a SETDB1 homologous H3K9 methyl transferase (H3K9MT), in determining C. elegans vulva development and fertility. Besides identifying the first sequence specific and di-/trimethylation binding MBT domain protein, our studies imply complex multi-domain regulation of ligand interaction of MBT domains. Our results also introduce a mechanistic link between LIN-61 function and biology, and they establish interplay of the H3K9me2

Lin28a is a putative factor in regulating cancer stem cell-like properties in side population cells of oral squamous cell carcinoma

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

Hayashi, S.; Tanaka, J.; Okada, S.

Cancer stem cells (CSCs) are among the target cells of cancer therapy because they are uniquely involved in both cancer progression and sensitivity to chemotherapeutic agents. We identified side population (SP) cells, which are known to be an enriched population of CSC, in five oral squamous cell carcinoma (OSCC) cells (SCC9, SCC25, TOSCC7, TOSCC17, and TOSCC23). The percentages of SP cells ranged from 0% to 3.3%, with TOSCC23 cells showing the highest percentages of SP cells (3.3% of the total cell population). The SP cells isolated from TOSCC23 cells also showed greater cell proliferation and invasion compared to non-SP (MP)more » cells. Therefore, our initial findings suggested that SP cells were enriched for CSC-like cells. Furthermore, DNA microarray analysis revealed that the expression of cell proliferation-related and anti-apoptotic genes was greater in SP cells compared to MP cells. We focused on Lin28a, which showed the highest expression (approximately 22-fold) among the upregulated genes. The overexpression of Lin28a in TOSCC23 cells increased their proliferation, colony formation, and invasion. These findings suggest that Lin28a is an appropriate CSC target molecule for OSCC treatment - Highlights: ► Lin28a is a SP cell-specific factor in oral squamous cell carcinoma (OSCC) cells. ► SP cells in OSCC cells show cancer stem cell-like properties. ► Lin28a regulates OSCC proliferative and invasive activities.« less

[Characteristics of atmospheric CO2 concentration and variation of carbon source & sink at Lin'an regional background station].

PubMed

Pu, Jing-Jiao; Xu, Hong-Hui; Kang, Li-Li; Ma, Qian-Li

2011-08-01

Characteristics of Atmospheric CO2 concentration obtained by Flask measurements were analyzed at Lin'an regional background station from August 2006 to July 2009. According to the simulation results of carbon tracking model, the impact of carbon sources and sinks on CO2 concentration was evaluated in Yangtze River Delta. The results revealed that atmospheric CO2 concentrations at Lin'an regional background station were between 368.3 x 10(-6) and 414.8 x 10(-6). The CO2 concentration varied as seasons change, with maximum in winter and minimum in summer; the annual difference was about 20.5 x 10(-6). The long-term trend of CO2 concentration showed rapid growth year by year; the average growth rate was about 3.2 x 10(-6)/a. CO2 flux of Yangtze River Delta was mainly contributed by fossil fuel burning, terrestrial biosphere exchange and ocean exchange, while the contribution of fire emission was small. CO2 flux from fossil fuel burning played an important role in carbon source; terrestrial biosphere and ocean were important carbon sinks in this area. Seasonal variations of CO2 concentration at Lin'an regional background station were consistent with CO2 fluxes from fossil fuel burning and terrestrial biosphere exchange.

The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family

PubMed Central

Busch, Bianca; Bley, Nadine; Müller, Simon; Glaß, Markus; Misiak, Danny; Lederer, Marcell; Vetter, Martina; Strauß, Hans-Georg; Thomssen, Christoph; Hüttelmaier, Stefan

2016-01-01

The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the let-7 targets HMGA2, LIN28B and IGF2BP1 to form a let-7 antagonizing self-promoting oncogenic triangle. Surprisingly, 3′-end processing of IGF2BP1 mRNAs is unaltered in aggressive cancers and tumor-derived cells although IGF2BP1 synthesis was proposed to escape let-7 attack by APA-dependent (alternative polyadenylation) 3′ UTR shortening. However, the expression of the triangle factors is inversely correlated with let-7 levels and promoted by LIN28B impairing let-7 biogenesis. Moreover, IGF2BP1 enhances the expression of all triangle factors by recruiting the respective mRNAs in mRNPs lacking AGO proteins and let-7 miRNAs. This indicates that the downregulation of let-7, largely facilitated by LIN28B upregulation, and the protection of let-7 target mRNAs by IGF2BP1-directed shielding in mRNPs synergize in enhancing the expression of triangle factors. The oncogenic potential of this triangle was confirmed in ovarian cancer (OC)-derived ES-2 cells transduced with let-7 targeting decoys. In these, the depletion of HMGA2 only diminishes tumor cell growth under permissive conditions. The depletion of LIN28B and more prominently IGF2BP1 severely impairs tumor cell viability, self-renewal and 2D as well as 3D migration. In conclusion, this suggests the targeting of the HMGA2-LIN28B-IGF2BP1 triangle as a promising strategy in cancer treatment. PMID:26917013

The oncogenic triangle of HMGA2, LIN28B and IGF2BP1 antagonizes tumor-suppressive actions of the let-7 family.

PubMed

Busch, Bianca; Bley, Nadine; Müller, Simon; Glaß, Markus; Misiak, Danny; Lederer, Marcell; Vetter, Martina; Strauß, Hans-Georg; Thomssen, Christoph; Hüttelmaier, Stefan

2016-05-05

The tumor-suppressive let-7 microRNA family targets various oncogene-encoding mRNAs. We identify the let-7 targets HMGA2, LIN28B and IGF2BP1 to form a let-7 antagonizing self-promoting oncogenic triangle. Surprisingly, 3'-end processing of IGF2BP1 mRNAs is unaltered in aggressive cancers and tumor-derived cells although IGF2BP1 synthesis was proposed to escape let-7 attack by APA-dependent (alternative polyadenylation) 3' UTR shortening. However, the expression of the triangle factors is inversely correlated with let-7 levels and promoted by LIN28B impairing let-7 biogenesis. Moreover, IGF2BP1 enhances the expression of all triangle factors by recruiting the respective mRNAs in mRNPs lacking AGO proteins and let-7 miRNAs. This indicates that the downregulation of let-7, largely facilitated by LIN28B upregulation, and the protection of let-7 target mRNAs by IGF2BP1-directed shielding in mRNPs synergize in enhancing the expression of triangle factors. The oncogenic potential of this triangle was confirmed in ovarian cancer (OC)-derived ES-2 cells transduced with let-7 targeting decoys. In these, the depletion of HMGA2 only diminishes tumor cell growth under permissive conditions. The depletion of LIN28B and more prominently IGF2BP1 severely impairs tumor cell viability, self-renewal and 2D as well as 3D migration. In conclusion, this suggests the targeting of the HMGA2-LIN28B-IGF2BP1 triangle as a promising strategy in cancer treatment. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Functional study of risk loci of stem cell-associated gene lin-28B and associations with disease survival outcomes in epithelial ovarian cancer.

PubMed

Lu, Lingeng; Katsaros, Dionyssios; Mayne, Susan T; Risch, Harvey A; Benedetto, Chiara; Canuto, Emilie Marion; Yu, Herbert

2012-11-01

Several single-nucleotide polymorphisms (SNPs) of the stem cell-associated gene lin-28B have been identified in association with ovarian cancer and ovarian cancer-related risk factors. However, whether these SNPs are functional or might be potential biomarkers for ovarian cancer prognosis remains unknown. The purposes of this study were to investigate the functional relevance of the identified lin-28B SNPs, as well as the associations of genotype and phenotype with epithelial ovarian cancer (EOC) survival. We analyzed five SNPs and mRNA levels of lin-28B in 211 primary EOC tissues using Taqman(®) SNP genotyping assays and SYBR green-based real-time PCR, respectively. The RNA secondary structures at the region of a genome-wide association-identified intronic rs314276 were analyzed theoretically with mfold and experimentally with circular dichroism spectroscopy. We found that rs314276 was a cis-acting expression quantitative trait locus (eQTL) in both additive and dominant models, while rs7759938 and rs314277 were significant or of borderline significance in dominant models only. The rs314276 variant significantly affects RNA secondary structure. No SNPs alone were associated with patient survival. However, we found that among patients initially responding to chemotherapy, those with higher lin-28B expression had higher mortality risk (hazard ratio =3.27, 95% confidence interval: 1.63-6.56) and relapse risk (hazard ratio = 2.53, 95% confidence interval: 1.41-4.54) than those with lower expression, and these associations remained in multivariate analyses. These results suggest that rs314276 alters RNA secondary structure and thereby influences gene expression, and that lin-28B is a cancer stem cell-associated marker, which may be a pharmaceutical target in the management of EOC.

LIN-12/Notch signaling instructs postsynaptic muscle arm development by regulating UNC-40/DCC and MADD-2 in Caenorhabditis elegans

PubMed Central

Li, Pengpeng; Collins, Kevin M; Koelle, Michael R; Shen, Kang

2013-01-01

The diverse cell types and the precise synaptic connectivity between them are the cardinal features of the nervous system. Little is known about how cell fate diversification is linked to synaptic target choices. Here we investigate how presynaptic neurons select one type of muscles, vm2, as a synaptic target and form synapses on its dendritic spine-like muscle arms. We found that the Notch-Delta pathway was required to distinguish target from non-target muscles. APX-1/Delta acts in surrounding cells including the non-target vm1 to activate LIN-12/Notch in the target vm2. LIN-12 functions cell-autonomously to up-regulate the expression of UNC-40/DCC and MADD-2 in vm2, which in turn function together to promote muscle arm formation and guidance. Ectopic expression of UNC-40/DCC in non-target vm1 muscle is sufficient to induce muscle arm extension from these cells. Therefore, the LIN-12/Notch signaling specifies target selection by selectively up-regulating guidance molecules and forming muscle arms in target cells. DOI: http://dx.doi.org/10.7554/eLife.00378.001 PMID:23539368

Crystal structures of MW1337R and lin2004: Representatives of a novel protein family that adopt a four-helical bundle fold

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

Kozbial, Piotr; Xu, Qingping; Chiu, Hsiu-Ju

2009-08-28

To extend the structural coverage of proteins with unknown functions, we targeted a novel protein family (Pfam accession number PF08807, DUF1798) for which we proposed and determined the structures of two representative members. The MW1337R gene of Staphylococcus aureus subsp. aureus Rosenbach (Wood 46) encodes a protein with a molecular weight of 13.8 kDa (residues 1-116) and a calculated isoelectric point of 5.15. The lin2004 gene of the nonspore-forming bacterium Listeria innocua Clip11262 encodes a protein with a molecular weight of 14.6 kDa (residues 1-121) and a calculated isoelectric point of 5.45. MW1337R and lin2004, as well as their homologs,more » which, so far, have been found only in Bacillus, Staphylococcus, Listeria, and related genera (Geobacillus, Exiguobacterium, and Oceanobacillus), have unknown functions and are annotated as hypothetical proteins. The genomic contexts of MW1337R and lin2004 are similar and conserved in related species. In prokaryotic genomes, most often, functionally interacting proteins are coded by genes, which are colocated in conserved operons. Proteins from the same operon as MW1337R and lin2004 either have unknown functions (i.e., belong to DUF1273, Pfam accession number PF06908) or are similar to ypsB from Bacillus subtilis. The function of ypsB is unclear, although it has a strong similarity to the N-terminal region of DivIVA, which was characterized as a bifunctional protein with distinct roles during vegetative growth and sporulation. In addition, members of the DUF1273 family display distant sequence similarity with the DprA/Smf protein, which acts downstream of the DNA uptake machinery, possibly in conjunction with RecA. The RecA activities in Bacillus subtilis are modulated by RecU Holliday-junction resolvase. In all analyzed cases, the gene coding for RecU is in the vicinity of MW1337R, lin2004, or their orthologs, but on a different operon located in the complementary DNA strand. Here, we report the crystal

A Novel Method to Increase LinLog CMOS Sensors’ Performance in High Dynamic Range Scenarios

PubMed Central

Martínez-Sánchez, Antonio; Fernández, Carlos; Navarro, Pedro J.; Iborra, Andrés

2011-01-01

Images from high dynamic range (HDR) scenes must be obtained with minimum loss of information. For this purpose it is necessary to take full advantage of the quantification levels provided by the CCD/CMOS image sensor. LinLog CMOS sensors satisfy the above demand by offering an adjustable response curve that combines linear and logarithmic responses. This paper presents a novel method to quickly adjust the parameters that control the response curve of a LinLog CMOS image sensor. We propose to use an Adaptive Proportional-Integral-Derivative controller to adjust the exposure time of the sensor, together with control algorithms based on the saturation level and the entropy of the images. With this method the sensor’s maximum dynamic range (120 dB) can be used to acquire good quality images from HDR scenes with fast, automatic adaptation to scene conditions. Adaptation to a new scene is rapid, with a sensor response adjustment of less than eight frames when working in real time video mode. At least 67% of the scene entropy can be retained with this method. PMID:22164083

A novel method to increase LinLog CMOS sensors' performance in high dynamic range scenarios.

PubMed

Martínez-Sánchez, Antonio; Fernández, Carlos; Navarro, Pedro J; Iborra, Andrés

2011-01-01

Images from high dynamic range (HDR) scenes must be obtained with minimum loss of information. For this purpose it is necessary to take full advantage of the quantification levels provided by the CCD/CMOS image sensor. LinLog CMOS sensors satisfy the above demand by offering an adjustable response curve that combines linear and logarithmic responses. This paper presents a novel method to quickly adjust the parameters that control the response curve of a LinLog CMOS image sensor. We propose to use an Adaptive Proportional-Integral-Derivative controller to adjust the exposure time of the sensor, together with control algorithms based on the saturation level and the entropy of the images. With this method the sensor's maximum dynamic range (120 dB) can be used to acquire good quality images from HDR scenes with fast, automatic adaptation to scene conditions. Adaptation to a new scene is rapid, with a sensor response adjustment of less than eight frames when working in real time video mode. At least 67% of the scene entropy can be retained with this method.

A laser desorption ionization/matrix-assisted laser desorption ionization target system applicable for three distinct types of instruments (LinTOF/curved field RTOF, LinTOF/RTOF and QqRTOF) with different performance characteristics from three vendors.

PubMed

Rados, Edita; Pittenauer, Ernst; Frank, Johannes; Varmuza, Kurt; Allmaier, Günter

2018-04-30

We have developed a target system which enables the use of only one target (i.e. target preparation set) for three different laser desorption ionization (LDI)/matrix-assisted laser desorption ionization (MALDI) mass spectrometric instruments. The focus was on analysing small biomolecules with LDI for future use of the system for the study of meteorite samples (carbonaceous chondrites) using devices with different mass spectrometric performance characteristics. Three compounds were selected due to their potential presence in meteoritic chondrites: tryptophan, 2-deoxy-d-ribose and triphenylene. They were prepared (with and without MALDI matrix, i.e. MALDI and LDI) and analysed with three different mass spectrometers (LinTOF/curved field RTOF, LinTOF/RTOF and QqRTOF). The ion sources of two of the instruments were run at high vacuum, and one at intermediate pressure. Two devices used a laser wavelength of 355 nm and one a wavelength of 337 nm. The developed target system operated smoothly with all devices. Tryptophan, 2-deoxy-d-ribose and triphenylene showed similar desorption/ionization behaviour for all instruments using the LDI mode. Interestingly, protonated tryptophan could be observed only with the LinTOF/curved field RTOF device in LDI and MALDI mode, while sodiated molecules were observed with all three instruments (in both ion modes). Deprotonated tryptophan was almost completely obscured by matrix ions in the MALDI mode whereas LDI yielded abundant deprotonated molecules. The presented target system allowed successful analyses of the three compounds using instruments from different vendors with only one preparation showing different analyser performance characteristics. The elemental composition with the QqRTOF analyser and the high-energy 20 keV collision-induced dissociation fragmentation will be important in identifying unknown compounds in chondrites. © 2018 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.

Building a Rapid Learning Health Care System for Oncology: Why CancerLinQ Collects Identifiable Health Information to Achieve Its Vision.

PubMed

Shah, Alaap; Stewart, Andrew K; Kolacevski, Andrej; Michels, Dina; Miller, Robert

2016-03-01

The ever-increasing volume of scientific discoveries, clinical knowledge, novel diagnostic tools, and treatment options juxtaposed with rising costs in health care challenge physicians to identify, prioritize, and use new information rapidly to deliver efficient and high-quality care to a growing and aging patient population. CancerLinQ, a rapid learning health care system in oncology, is an initiative of the American Society of Clinical Oncology and its Institute for Quality that addresses these challenges by collecting information from the electronic health records of large numbers of patients with cancer. CancerLinQ is first and foremost a quality measurement and reporting system through which oncologists can harness the depth and power of their patients' clinical records and other data to assess, monitor, and improve the care they deliver. However, in light of privacy and security concerns with regard to collection, use, and disclosure of patient information, this article addresses the need to collect protected health information as defined under the Health Insurance Portability and Accountability Act of 1996 to drive rapid learning through CancerLinQ. © 2016 by American Society of Clinical Oncology.

Kinetics and stereochemistry of LinB-catalyzed δ-HBCD transformation: Comparison of in vitro and in silico results.

PubMed

Heeb, Norbert V; Mazenauer, Manuel; Wyss, Simon; Geueke, Birgit; Kohler, Hans-Peter E; Lienemann, Peter

2018-05-12

LinB is a haloalkane dehalogenase found in Sphingobium indicum B90A, an aerobic bacterium isolated from contaminated soils of hexachlorocyclohexane (HCH) dumpsites. We showed that this enzyme also converts hexabromocyclododecanes (HBCDs). Here we give new insights in the kinetics and stereochemistry of the enzymatic transformation of δ-HBCD, which resulted in the formation of two pentabromocyclododecanols (PBCDols) as first- (P 1δ , P 2δ ) and two tetrabromocyclododecadiols (TBCDdiols) as second-generation products (T 1δ , T 2δ ). Enzymatic transformations of δ-HBCD, α 1 -PBCDol, one of the transformation products, and α 2 -PBCDol, its enantiomer, were studied and modeled with Michaelis-Menten (MM) kinetics. Respective MM-parameters K M , v max , k cat /K M indicated that δ-HBCD is the best LinB substrate followed by α 2 - and α 1 -PBCDol. The stereochemistry of these transformations was modeled in silico, investigating respective enzyme-substrate (ES) and enzyme-product (EP) complexes. One of the four predicted ES-complexes led to the PBCDol product P 1δ , identical to α 2 -PBCDol with the 1R,2R,5S,6R,9R,10S-configuration. An S N 2-like substitution of bromine at C6 of δ-HBCD by Asp-108 of LinB and subsequent hydrolysis of the alkyl-enzyme led to α 2 -PBCDol. Modeling results further indicate that backside attacks at C1, C9 and C10 are reasonable too, selectively binding leaving bromide ions in a halide pocket found in LinB. Docking with α 2 -PBCDol, also allowed productive enzyme binding. A TBCD-1,5-diol with the 1S,2S,5R,6R,9S,10R-configuration is the predicted second-generation product T 1δ . In conclusion, in vitro- and in silico findings now allow a detailed description of step-wise enzymatic dehalohydroxylation reactions of δ-HBCD to specific PBCDols and TBCDdiols at Å-resolution and predictions of their stereochemistry. Copyright © 2018 Elsevier Ltd. All rights reserved.

Mitotic Spindle Positioning in the EMS Cell of Caenorhabditis elegans Requires LET-99 and LIN-5/NuMA.

PubMed

Liro, Małgorzata J; Rose, Lesilee S

2016-11-01

Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types, a cortically localized complex consisting of Gα, GPR-1/2, and LIN-5 (Gαi/Pins/Mud, Gαi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle. The conserved PAR polarity proteins are known to regulate both cytoplasmic asymmetry and spindle positioning in many cases. However, spindle positioning also occurs in response to cell signaling cues that appear to be PAR-independent. In the four-cell Caenorhabditis elegans embryo, Wnt and Mes-1/Src-1 signaling pathways act partially redundantly to align the spindle on the anterior/posterior axis of the endomesodermal (EMS) precursor cell. It is unclear how those extrinsic signals individually contribute to spindle positioning and whether either pathway acts via conserved spindle positioning regulators. Here, we genetically test the involvement of Gα, LIN-5, and their negative regulator LET-99, in transducing EMS spindle positioning polarity cues. We also examined whether the C. elegans ortholog of another spindle positioning regulator, DLG-1, is required. We show that LET-99 acts in the Mes-1/Src-1 pathway for spindle positioning. LIN-5 is also required for EMS spindle positioning, possibly through a Gα- and DLG-1-independent mechanism. Copyright © 2016 by the Genetics Society of America.

Mitotic Spindle Positioning in the EMS Cell of Caenorhabditis elegans Requires LET-99 and LIN-5/NuMA

PubMed Central

Liro, Małgorzata J.; Rose, Lesilee S.

2016-01-01

Asymmetric divisions produce daughter cells with different fates, and thus are critical for animal development. During asymmetric divisions, the mitotic spindle must be positioned on a polarized axis to ensure the differential segregation of cell fate determinants into the daughter cells. In many cell types, a cortically localized complex consisting of Gα, GPR-1/2, and LIN-5 (Gαi/Pins/Mud, Gαi/LGN/NuMA) mediates the recruitment of dynactin/dynein, which exerts pulling forces on astral microtubules to physically position the spindle. The conserved PAR polarity proteins are known to regulate both cytoplasmic asymmetry and spindle positioning in many cases. However, spindle positioning also occurs in response to cell signaling cues that appear to be PAR-independent. In the four-cell Caenorhabditis elegans embryo, Wnt and Mes-1/Src-1 signaling pathways act partially redundantly to align the spindle on the anterior/posterior axis of the endomesodermal (EMS) precursor cell. It is unclear how those extrinsic signals individually contribute to spindle positioning and whether either pathway acts via conserved spindle positioning regulators. Here, we genetically test the involvement of Gα, LIN-5, and their negative regulator LET-99, in transducing EMS spindle positioning polarity cues. We also examined whether the C. elegans ortholog of another spindle positioning regulator, DLG-1, is required. We show that LET-99 acts in the Mes-1/Src-1 pathway for spindle positioning. LIN-5 is also required for EMS spindle positioning, possibly through a Gα- and DLG-1-independent mechanism. PMID:27672093

Lin- CD34hi CD117int/hi FcεRI+ cells in human blood constitute a rare population of mast cell progenitors.

PubMed

Dahlin, Joakim S; Malinovschi, Andrei; Öhrvik, Helena; Sandelin, Martin; Janson, Christer; Alving, Kjell; Hallgren, Jenny

2016-01-28

Mast cells are rare tissue-resident immune cells that are involved in allergic reactions, and their numbers are increased in the lungs of asthmatics. Murine lung mast cells arise from committed bone marrow-derived progenitors that enter the blood circulation, migrate through the pulmonary endothelium, and mature in the tissue. In humans, mast cells can be cultured from multipotent CD34(+) progenitor cells. However, a population of distinct precursor cells that give rise to mast cells has remained undiscovered. To our knowledge, this is the first report of human lineage-negative (Lin(-)) CD34(hi) CD117(int/hi) FcεRI(+) progenitor cells, which represented only 0.0053% of the isolated blood cells in healthy individuals. These cells expressed integrin β7 and developed a mast cell-like phenotype, although with a slow cell division capacity in vitro. Isolated Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells had an immature mast cell-like appearance and expressed high levels of many mast cell-related genes as compared with human blood basophils in whole-transcriptome microarray analyses. Furthermore, serglycin, tryptase, and carboxypeptidase A messenger RNA transcripts were detected by quantitative reverse transcription-polymerase chain reaction. Altogether, we propose that the Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood cells are closely related to human tissue mast cells and likely constitute an immediate precursor population, which can give rise to predominantly mast cells. Furthermore, asthmatics with reduced lung function had a higher frequency of Lin(-) CD34(hi) CD117(int/hi) FcεRI(+) blood mast cell progenitors than asthmatics with normal lung function. © 2016 by The American Society of Hematology.

Initial results on computational performance of Intel Many Integrated Core (MIC) architecture: implementation of the Weather and Research Forecasting (WRF) Purdue-Lin microphysics scheme

NASA Astrophysics Data System (ADS)

Mielikainen, Jarno; Huang, Bormin; Huang, Allen H.

2014-10-01

Purdue-Lin scheme is a relatively sophisticated microphysics scheme in the Weather Research and Forecasting (WRF) model. The scheme includes six classes of hydro meteors: water vapor, cloud water, raid, cloud ice, snow and graupel. The scheme is very suitable for massively parallel computation as there are no interactions among horizontal grid points. In this paper, we accelerate the Purdue Lin scheme using Intel Many Integrated Core Architecture (MIC) hardware. The Intel Xeon Phi is a high performance coprocessor consists of up to 61 cores. The Xeon Phi is connected to a CPU via the PCI Express (PICe) bus. In this paper, we will discuss in detail the code optimization issues encountered while tuning the Purdue-Lin microphysics Fortran code for Xeon Phi. In particularly, getting a good performance required utilizing multiple cores, the wide vector operations and make efficient use of memory. The results show that the optimizations improved performance of the original code on Xeon Phi 5110P by a factor of 4.2x. Furthermore, the same optimizations improved performance on Intel Xeon E5-2603 CPU by a factor of 1.2x compared to the original code.

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

PubMed Central

Lee, Chih-Yung Sean; Lu, Tu

2017-01-01

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin. PMID:29111977

Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B.

PubMed

Lee, Chih-Yung Sean; Lu, Tu; Seydoux, Geraldine

2017-11-07

Nanos RNA-binding proteins are required for germline development in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of primordial germ cells (PGCs) lacking the nanos homologs nos-1 and nos-2 in C. elegans. nos-1nos-2 PGCs fail to silence hundreds of transcripts normally expressed in oocytes. We find that this misregulation is due to both delayed turnover of maternal transcripts and inappropriate transcriptional activation. The latter appears to be an indirect consequence of delayed turnover of the maternally-inherited transcription factor LIN-15B, a synMuvB class transcription factor known to antagonize PRC2 activity. PRC2 is required for chromatin reprogramming in the germline, and the transcriptome of PGCs lacking PRC2 resembles that of nos-1nos-2 PGCs. Loss of maternal LIN-15B restores fertility to nos-1nos-2 mutants. These findings suggest that Nanos promotes germ cell fate by downregulating maternal RNAs and proteins that would otherwise interfere with PRC2-dependent reprogramming of PGC chromatin.

A new nuclide transport model in soil in the GENII-LIN health physics code

NASA Astrophysics Data System (ADS)

Teodori, F.

2017-11-01

The nuclide soil transfer model, originally included in the GENII-LIN software system, was intended for residual contamination from long term activities and from waste form degradation. Short life nuclides were supposed absent or at equilibrium with long life parents. Here we present an enhanced soil transport model, where short life nuclide contributions are correctly accounted. This improvement extends the code capabilities to handle incidental release of contaminant to soil, by evaluating exposure since the very beginning of the contamination event, before the radioactive decay chain equilibrium is reached.

Recovery of CD45(-)/Lin(-)/SSEA-4(+) very small embryonic-like stem cells by cord blood bank standard operating procedures.

PubMed

Chang, Yu-Jen; Tien, Kuei-Erh; Wen, Cheng-Hao; Hsieh, Tzu-Bou; Hwang, Shiaw-Min

2014-04-01

Very small embryonic-like (VSEL) stem cells are a rare cell population present in bone marrow, cord blood and other tissues that displays a distinct small cell size and the ability to give rise to cells of the three germ layers. VSEL stem cells were reported to be discarded in the red blood cell fraction by Ficoll-Paque density gradient centrifugation during the processing of bone marrow and cord blood specimens. However, most cord blood banks do not include density gradient centrifugation in their procedures while red blood cells are removed by Hespan sedimentation following the Cord Blood Transplantation Study cord blood bank standard operating procedures (COBLT SOP). To clarify the retention of VSEL stem cells, we investigated the recovery of VSEL stem cells following COBLT SOP guidelines. The recovery of CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells of umbilical cord blood was examined by flow cytometry before and after COBLT SOP processing, and relative expression of pluripotent genes was analyzed by quantitative polymerase chain reaction. CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells were mostly recovered in the final products following COBLT SOP guidelines. The expression of pluripotent genes could be maintained at >80% in products after hetastarch (Hespan; B. Braun Medical Inc., Irvine, CA, USA) processing. The rare sub-population of CD45(-)/Lin(-)/SSEA-4(+) VSEL stem cells survived after Hespan sedimentation. This finding suggests that umbilical cord blood units cryopreserved by COBLT SOP in cord blood banks should retain most VSEL stem cells present in the un-processed specimens. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

[Heavy metal pollution characteristics and ecological risk analysis for soil in Phyllostachys praecox stands of Lin'an].

PubMed

Fang, Xiao-bo; Shi, Han; Liao, Xin-feng; Lou, Zhong; Zhou, Lyu-yan; Yu, Hai-xia; Yao, Lin; Sun, Li-ping

2015-06-01

An investigation was carried out in an attempt to reveal the characteristics of heavy metals contamination in the soils of Phyllostachys praecox forest in Lin' an. Based on the concentrations of Hg, As, Cu, Pb, Zn, Cd, Cr, Ni, Co and Mn in 160 topsoil samples, the pollution status and ecological risks of heavy metals in the soils were assessed by single factor pollution index, Nemerow integrated pollution index and Hankanson potential ecological risk index. The spatial variability of heavy metal concentrations in the soils closely related to the distribution of traffic, industrial and livestock pollution sources. The average concentrations of Hg, As, Cu, Pb, Zn, Cd, Cr, Ni, Co and Mn in the soils were 0.16, 7.41, 34.36, 87.98, 103.98, 0.26, 59.12, 29.56, 11.44 and 350.26 mg · kg(-1), respectively. Pb, Cd, Zn and Cu concentrations were as 2.89, 1.70, 1.12 and 1.12 times as the background values of soil in Zhejiang Province, respectively. But their concentrations were all lower than the threshold values of the National Environmental Quality Standard for Soil (GB 15618-1995). The average single factor pollution index revealed that the level of heavy metal pollution in the soils was in order of Pb>Cd>Cu= Zn>Hg>As>Ni>Co>Cr>Mn. Pb pollution was of moderate level while Cd, Cu and Zn pollutions were slight. There was no soil pollution caused by the other heavy metals. However, the Nemerow integrated pollution index showed that all the 160 soil samples were contaminated by heavy metals to a certain extent. Among total 160 soil samples, slight pollution level, moderate pollution level and heavy pollution level accounted for 55.6%, 29.4% and 15.0%, respectively. The average single factor potential ecological risk index (Er(i)) implied that the potential ecological risk related to Cd reached moderate level, while the others were of slight level. Furthermore, Cd and Hg showed higher potential ecological risk indices which reached up to 256.82 and 187.33 respectively

Actomyosin-dependent formation of the mechanosensitive talin–vinculin complex reinforces actin anchoring

PubMed Central

Ciobanasu, Corina; Faivre, Bruno; Le Clainche, Christophe

2014-01-01

The force generated by the actomyosin cytoskeleton controls focal adhesion dynamics during cell migration. This process is thought to involve the mechanical unfolding of talin to expose cryptic vinculin-binding sites. However, the ability of the actomyosin cytoskeleton to directly control the formation of a talin–vinculin complex and the resulting activity of the complex are not known. Here we develop a microscopy assay with pure proteins in which the self-assembly of actomyosin cables controls the association of vinculin to a talin-micropatterned surface in a reversible manner. Quantifications indicate that talin refolding is limited by vinculin dissociation and modulated by the actomyosin network stability. Finally, we show that the activation of vinculin by stretched talin induces a positive feedback that reinforces the actin–talin–vinculin association. This in vitro reconstitution reveals the mechanism by which a key molecular switch senses and controls the connection between adhesion complexes and the actomyosin cytoskeleton. PMID:24452080

RNA-Binding Protein L1TD1 Interacts with LIN28 via RNA and is Required for Human Embryonic Stem Cell Self-Renewal and Cancer Cell Proliferation

PubMed Central

Närvä, Elisa; Rahkonen, Nelly; Emani, Maheswara Reddy; Lund, Riikka; Pursiheimo, Huha-Pekka; Nästi, Juuso; Autio, Reija; Rasool, Omid; Denessiouk, Konstantin; Lähdesmäki, Harri; Rao, Anjana; Lahesmaa, Ritta

2012-01-01

Human embryonic stem cells (hESC) have a unique capacity to self-renew and differentiate into all the cell types found in human body. Although the transcriptional regulators of pluripotency are well studied, the role of cytoplasmic regulators is still poorly characterized. Here, we report a new stem cell-specific RNA-binding protein L1TD1 (ECAT11, FLJ10884) required for hESC self-renewal and cancer cell proliferation. Depletion of L1TD1 results in immediate downregulation of OCT4 and NANOG. Furthermore, we demonstrate that OCT4, SOX2, and NANOG all bind to the promoter of L1TD1. Moreover, L1TD1 is highly expressed in seminomas, and depletion of L1TD1 in these cancer cells influences self-renewal and proliferation. We show that L1TD1 colocalizes and interacts with LIN28 via RNA and directly with RNA helicase A (RHA). LIN28 has been reported to regulate translation of OCT4 in complex with RHA. Thus, we hypothesize that L1TD1 is part of the L1TD1-RHA-LIN28 complex that could influence levels of OCT4. Our results strongly suggest that L1TD1 has an important role in the regulation of stemness. PMID:22162396

Expression and associations of TRAF1, BMI-1, ALDH1, and Lin28B in oral squamous cell carcinoma.

PubMed

Wu, Tian-Fu; Li, Yi-Cun; Ma, Si-Rui; Bing-Liu; Zhang, Wen-Feng; Sun, Zhi-Jun

2017-04-01

Tumor necrosis factor receptor-associated factor 1, an adaptor protein of tumor necrosis factor 2, is involved in classical nuclear factor (NF)-κB activation and lymphocyte recruitment. However, less is known about the expression and association of tumor necrosis factor receptor-associated factor 1 with cancer stem cell markers in oral squamous cell carcinoma. This study aimed to investigate the expression of tumor necrosis factor receptor-associated factor 1 and stem cell characteristic markers (lin28 homolog B, B cell-specific Moloney murine leukemia virus integration site 1, and aldehyde dehydrogenase 1) in oral squamous cell carcinoma and analyze their relations. Paraffin-embedded tissues of 78 oral squamous cell carcinomas, 39 normal oral mucosa, and 12 oral dysplasia tissues were employed in tissue microarrays, and the expression of tumor necrosis factor receptor-associated factor 1, B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B was measured by immunohistostaining and digital pathological analysis. The expression of tumor necrosis factor receptor-associated factor 1 was higher in the oral squamous cell carcinoma group as compared with the expression in the oral mucosa (p < 0.01) and oral dysplasia (p < 0.001) groups. In addition, the expression of tumor necrosis factor receptor-associated factor 1 was associated with those of B cell-specific Moloney murine leukemia virus integration site 1, aldehyde dehydrogenase 1, and lin28 homolog B (p = 0.032, r 2  = 0.109; p < 0.0001, r 2  = 0.64; and p < 0.001, r 2  = 0.16) in oral squamous cell carcinoma. The patient survival rate was lower in the highly expressed tumor necrosis factor receptor-associated factor 1 group, although the difference was not significant. The clustering analysis showed that tumor necrosis factor receptor-associated factor 1 was most related to aldehyde dehydrogenase 1. These findings suggest

A new measurement of the 6Li(n, α)t cross section at MeV energies using a 252Cf fission chamber and 6Li scintillators

NASA Astrophysics Data System (ADS)

Kirsch, Leo E.; Devlin, M.; Mosby, S. M.; Gomez, J. A.

2017-12-01

A new measurement is presented of the 6Li(n, α)t cross section from 245 keV to 10 MeV using a 252Cf fission chamber with 6LiI(Eu) and Cs2LiYCl6:Ce (CLYC) scintillators which act as both target and detector. Neutron energies are determined from the time of flight (TOF) method using the signals from spontaneous fission and reaction product recoil. Simulations of neutron downscatter in the crystals and fission chamber bring 6Li(n, α)t cross section values measured with the 6LiI(Eu) into agreement with previous experiments and evaluations, except for two resonances at 4.2 and 6.5 MeV introduced by ENDF/B-VII.1. Suspected neutron transport modeling issues cause the cross section values obtained with CLYC to be discrepant above 2 MeV.

A lncRNA fine tunes the dynamics of a cell state transition involving Lin28, let-7 and de novo DNA methylation

PubMed Central

Li, Meng Amy; Amaral, Paulo P; Cheung, Priscilla; Bergmann, Jan H; Kinoshita, Masaki; Kalkan, Tüzer; Ralser, Meryem; Robson, Sam; von Meyenn, Ferdinand; Paramor, Maike; Yang, Fengtang; Chen, Caifu; Nichols, Jennifer; Spector, David L; Kouzarides, Tony; He, Lin; Smith, Austin

2017-01-01

Execution of pluripotency requires progression from the naïve status represented by mouse embryonic stem cells (ESCs) to a state capacitated for lineage specification. This transition is coordinated at multiple levels. Non-coding RNAs may contribute to this regulatory orchestra. We identified a rodent-specific long non-coding RNA (lncRNA) linc1281, hereafter Ephemeron (Eprn), that modulates the dynamics of exit from naïve pluripotency. Eprn deletion delays the extinction of ESC identity, an effect associated with perduring Nanog expression. In the absence of Eprn, Lin28a expression is reduced which results in persistence of let-7 microRNAs, and the up-regulation of de novo methyltransferases Dnmt3a/b is delayed. Dnmt3a/b deletion retards ES cell transition, correlating with delayed Nanog promoter methylation and phenocopying loss of Eprn or Lin28a. The connection from lncRNA to miRNA and DNA methylation facilitates the acute extinction of naïve pluripotency, a pre-requisite for rapid progression from preimplantation epiblast to gastrulation in rodents. Eprn illustrates how lncRNAs may introduce species-specific network modulations. DOI: http://dx.doi.org/10.7554/eLife.23468.001 PMID:28820723

Evidence of cation vacancy induced room temperature ferromagnetism in Li-N codoped ZnO thin films

NASA Astrophysics Data System (ADS)

Zhang, B. Y.; Yao, B.; Li, Y. F.; Liu, A. M.; Zhang, Z. Z.; Li, B. H.; Xing, G. Z.; Wu, T.; Qin, X. B.; Zhao, D. X.; Shan, C. X.; Shen, D. Z.

2011-10-01

Room temperature ferromagnetism (RTFM) was observed in Li-N codoped ZnO thin films [ZnO:(Li, N)] fabricated by plasma-assisted molecular beam epitaxy, and p-type ZnO:(Li, N) shows the strongest RTFM. Positron annihilation spectroscopy and low temperature photoluminescence measurements indicate that the RTFM in ZnO:(Li, N) is attributed to the defect complex related to VZn, such as VZn and Lii-NO-VZn complex, well supported by first-principles calculations. The incorporation of NO can stabilize and enhance the RTFM of ZnO:(Li, N) by combining with Lii to form Lii-NO complex, which restrains the compensation of Lii for VZn and makes the ZnO:(Li, N) conduct in p-type.

Crystal Structure of Haloalkane Dehalogenase LinB from Sphingomonas paucimobilis UT26 at 0.95 Å Resolution: Dynamics of Catalytic Residues

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

Oakley, Aaron J.; Klvana, Martin; Otyepka, Michal

We present the structure of LinB, a 33-kDa haloalkane dehalogenase from Sphingomonas paucimobilis UT26, at 0.95 {angstrom} resolution. The data have allowed us to directly observe the anisotropic motions of the catalytic residues. In particular, the side-chain of the catalytic nucleophile, Asp108, displays a high degree of disorder. It has been modeled in two conformations, one similar to that observed previously (conformation A) and one strained (conformation B) that approached the catalytic base (His272). The strain in conformation B was mainly in the C{sub {alpha}}-C{sub {beta}}-C{sub {gamma}} angle (126{sup o}) that deviated by 13.4{sup o} from the 'ideal' bond anglemore » of 112.6{sup o}. On the basis of these observations, we propose a role for the charge state of the catalytic histidine in determining the geometry of the catalytic residues. We hypothesized that double-protonation of the catalytic base (His272) reduces the distance between the side-chain of this residue and that of the Asp108. The results of molecular dynamics simulations were consistent with the structural data showing that protonation of the His272 side-chain nitrogen atoms does indeed reduce the distance between the side-chains of the residues in question, although the simulations failed to demonstrate the same degree of strain in the Asp108 C{sub {alpha}}-C{sub {beta}}-C{sub {gamma}} angle. Instead, the changes in the molecular dynamics structures were distributed over several bond and dihedral angles. Quantum mechanics calculations on LinB with 1-chloro-2,2-dimethylpropane as a substrate were performed to determine which active site conformations and protonation states were most likely to result in catalysis. It was shown that His272 singly protonated at N{sub {delta}1} and Asp108 in conformation A gave the most exothermic reaction ({Delta}H = -22 kcal/mol). With His272 doubly protonated at N{sub {delta}1} and N{sub {epsilon}2}, the reactions were only slightly exothermic or were

Regio- and Enantioselective Sequential Dehalogenation of rac-1,3-Dibromobutane by Haloalkane Dehalogenase LinB.

PubMed

Gross, Johannes; Prokop, Zbyněk; Janssen, Dick; Faber, Kurt; Hall, Mélanie

2016-08-03

The hydrolytic dehalogenation of rac-1,3-dibromobutane catalyzed by the haloalkane dehalogenase LinB from Sphingobium japonicum UT26 proceeds in a sequential fashion: initial formation of intermediate haloalcohols followed by a second hydrolytic step to produce the final diol. Detailed investigation of the course of the reaction revealed favored nucleophilic displacement of the sec-halogen in the first hydrolytic event with pronounced R enantioselectivity. The second hydrolysis step proceeded with a regioselectivity switch at the primary position, with preference for the S enantiomer. Because of complex competition between all eight possible reactions, intermediate haloalcohols formed with moderate to good ee ((S)-4-bromobutan-2-ol: up to 87 %). Similarly, (S)-butane-1,3-diol was formed at a maximum ee of 35 % before full hydrolysis furnished the racemic diol product. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solving quantum optimal control problems using Clebsch variables and Lin constraints

NASA Astrophysics Data System (ADS)

Delgado-Téllez, M.; Ibort, A.; Rodríguez de la Peña, T.

2018-01-01

Clebsch variables (and Lin constraints) are applied to the study of a class of optimal control problems for affine-controlled quantum systems. The optimal control problem will be modelled with controls defined on an auxiliary space where the dynamical group of the system acts freely. The reciprocity between both theories: the classical theory defined by the objective functional and the quantum system, is established by using a suitable version of Lagrange’s multipliers theorem and a geometrical interpretation of the constraints of the system as defining a subspace of horizontal curves in an associated bundle. It is shown how the solutions of the variational problem defined by the objective functional determine solutions of the quantum problem. Then a new way of obtaining explicit solutions for a family of optimal control problems for affine-controlled quantum systems (finite or infinite dimensional) is obtained. One of its main advantages, is the the use of Clebsch variables allows to compute such solutions from solutions of invariant problems that can often be computed explicitly. This procedure can be presented as an algorithm that can be applied to a large class of systems. Finally, some simple examples, spin control, a simple quantum Hamiltonian with an ‘Elroy beanie’ type classical model and a controlled one-dimensional quantum harmonic oscillator, illustrating the main features of the theory, will be discussed.

Cell type-specific recruitment of Drosophila Lin-7 to distinct MAGUK-based protein complexes defines novel roles for Sdt and Dlg-S97.

PubMed

Bachmann, André; Timmer, Marco; Sierralta, Jimena; Pietrini, Grazia; Gundelfinger, Eckart D; Knust, Elisabeth; Thomas, Ulrich

2004-04-15

Stardust (Sdt) and Discs-Large (Dlg) are membrane-associated guanylate kinases (MAGUKs) involved in the organization of supramolecular protein complexes at distinct epithelial membrane compartments in Drosophila. Loss of either Sdt or Dlg affects epithelial development with severe effects on apico-basal polarity. Moreover, Dlg is required for the structural and functional integrity of synaptic junctions. Recent biochemical and cell culture studies have revealed that various mammalian MAGUKs can interact with mLin-7/Veli/MALS, a small PDZ-domain protein. To substantiate these findings for their in vivo significance with regard to Sdt- and Dlg-based protein complexes, we analyzed the subcellular distribution of Drosophila Lin-7 (DLin-7) and performed genetic and biochemical assays to characterize its interaction with either of the two MAGUKs. In epithelia, Sdt mediates the recruitment of DLin-7 to the subapical region, while at larval neuromuscular junctions, a particular isoform of Dlg, Dlg-S97, is required for postsynaptic localization of DLin-7. Ectopic expression of Dlg-S97 in epithelia, however, was not sufficient to induce a redistribution of DLin-7. These results imply that the recruitment of DLin-7 to MAGUK-based protein complexes is defined by cell-type specific mechanisms and that DLin-7 acts downstream of Sdt in epithelia and downstream of Dlg at synapses.

Plant Type Selection for Reclamation of Sarcheshmeh Copper Mine Using Fuzzy-Topsis Approach / Wybór Gatunków Roślin Do Wykorzystania W Projekcie Rekultywacji Terenów Kopalni Miedzi Sarcheshmeh Z Wykorzystaniem Metod Logiki Rozmytej Topsis

NASA Astrophysics Data System (ADS)

Ebrahimabadi, Arash; Alavi, Iraj

2013-09-01

Plant species selection is a multi-criteria evaluation decision and has a strategic importance for many companies. The conventional methods for plant species selection are inadequate for dealing with the imprecise or vague nature of linguistic assessment. To overcome this difficulty, fuzzy multi-criteria decision-making methods are proposed. The aim of this study is to use the fuzzy technique for order preference by similarity to ideal solution (F.TOPSIS) methods for the selection of plant species in mine reclamation plan. Plant type selection and planting to protect the environment and the reclamation of the mine are some of the most important solutions. Therefore, the objective of the current research study is to choose the proper plant types for reclamation of Sarcheshmeh Copper Mine using Fuzzy-topsis method. In this regard, primarily, surrounding area of Sarcheshmeh copper mine, one of the world's 10 biggest copper mine which is located near Kerman city of Iran, are surveyed, to choose the best plant type for reclamation of disturbance area. With this respect, based on reclamation plan, primary criteria were consisted of kinds of post mining land use, climate, and nature of soil. Comparison matrixes were then obtained based on experts' opinion and plant types were subsequently prioritized using the Fuzzy Topsis method. Secondary factors considered through the analysis were as follows: perspective of the region, resistance against disease and insects, strength and method of growth, availability to plant type, economic efficiency, protection of soil, storing water, and prevention of pollution. Finally, suitable plant types in the mining perimeter were prioritized as: Amygdalus scoparia, Tamarix, Pistachio Wild, Ephedra, Astragalus, Salsola, respectively. Wybór gatunków roślin jest decyzją podejmowaną w oparciu o wiele kryteriów i stanowi poważne wyzwanie strategiczne dla wielu firm. Konwencjonalne metody wyboru gatunków roślin okazują si

Rate and extent of pH decline affect proteolysis of cytoskeletal proteins and water-holding capacity in pork.

PubMed

Bee, Giuseppe; Anderson, Abbey L; Lonergan, Steven M; Huff-Lonergan, Elisabeth

2007-06-01

The objective of this study was to determine the extent to which early postmortem (PM) pH decline influences proteolysis of the intermediate filament protein desmin, the costameric proteins vinculin and talin and autolysis of μ-calpain in the longissimus muscle (LM) of pigs from two genetic lines. Based on the LM 3h pH (H=3h pH of LM>6.0; L=3h pH of LM pH<5.7) PM, 10 carcasses per line and pH group were selected. The average 3h pH within pH group was 6.23 (H) and 5.44 (L). The LM samples were collected 24, 48, 72, and 120h PM and percent drip loss was measured after 1, 2, and 4d of storage. Samples collected at 24, 48, 72, and 120h PM were used to monitor desmin, vinculin, and talin degradation and samples collected at 24h PM were used to determine the extent of μ-calpain autolysis by immunoblotting. Higher (P<0.01) pH values at 45min, 6h, and 24h PM and lower (P<0.01) drip losses after 1, 2, and 4d of storage were recorded in the H-compared to the L-group. Abundance of the 76kDa μ-calpain autolysis product was greater (P<0.01), proteolysis of talin at all measured time points and proteolysis of desmin after 24 and 48h PM was greater (P⩽0.03) in the H-group than in the L-group. The current findings indicate activation rate of μ-calpain may be associated with proteolysis of desmin and talin and could play a role in the development of drip loss. The rate of early PM pH decline can partly explain the variation of desmin and talin degradation by affecting the activation of μ-calpain.

Formation of positive cluster ions Li(n) Br (n = 2-7) and ionization energies studied by thermal ionization mass spectrometry.

PubMed

Veličković, S R; Đustebek, J B; Veljković, F M; Veljković, M V

2012-05-01

Clusters of the type Li(n)X (X = halides) can be considered as potential building blocks of cluster-assembly materials. In this work, Li(n)Br (n = 2-7) clusters were obtained by a thermal ionization source of modified design and selected by a magnetic sector mass spectrometer. Positive ions of the Li(n)Br (n = 4-7) cluster were detected for the first time. The order of ion intensities was Li(2)Br(+) > Li(4)Br(+) > Li(5)Br(+) > Li(6)Br(+) > Li(3)Br(+). The ionization energies (IEs) were measured and found to be 3.95 ± 0.20 eV for Li(2)Br, 3.92 ± 0.20 eV for Li(3)Br, 3.93 ± 0.20 eV for Li(4)Br, 4.08 ± 0.20 eV for Li(5)Br, 4.14 ± 0.20 eV for Li(6)Br and 4.19 ± 0.20 eV for Li(7)Br. All of these clusters have a much lower ionization potential than that of the lithium atom, so they belong to the superalkali class. The IEs of Li(n)Br (n = 2-4) are slightly lower than those in the corresponding small Li(n) or Li(n)H clusters, whereas the IEs of Li(n)Br are very similar to those of Li(n) or Li(n)H for n = 5 and 6. The thermal ionization source of modified design is an important means for simultaneously obtaining and measuring the IEs of Li(n)Br (n = 2-7) clusters (because their ions are hermodynamically stable with respect to the loss of lithium atoms in the gas phase) and increasingly contributes toward the development of clusters for practical applications. Copyright © 2012 John Wiley & Sons, Ltd.

Digital cultural heritage and its applications: case studies of Digital Mogao Grottos and Chi Lin Nunnery reconstruction

NASA Astrophysics Data System (ADS)

Li, Deren; Du, Zhiqiang; Zhu, Yixuan; Wang, Tingsong

2009-09-01

Considerable damage has been done to the cultural heritage sites around the world ranging from natural erosion to artificial destruction. With the development of information sciences, frontier technologies are actively introduced to help protect cultural heritage sites. The new concept of a Digital Cultural Heritage has been presented for culture protection and is gradually becoming an efficient method to solve or to remit various difficult problems. This paper puts forward a digitalization method for cultural heritage sites which rationally integrates and utilizes multiform surveying measurements. These techniques have been successfully implemented into two projects, namely the Digital Mogao Grottos and the Chi Lin Nunnery reconstruction. Our results prove that the concept of and the techniques utilized in Digital Cultural Heritage can not only contribute to research, preservation, management, interpretation, and representation of cultural heritages but can also help resolve the conflicts between tourism and protection.

Digital cultural heritage and its applications: case studies of Digital Mogao Grottos and Chi Lin Nunnery reconstruction

NASA Astrophysics Data System (ADS)

Li, Deren; Du, Zhiqiang; Zhu, Yixuan; Wang, Tingsong

2010-11-01

Considerable damage has been done to the cultural heritage sites around the world ranging from natural erosion to artificial destruction. With the development of information sciences, frontier technologies are actively introduced to help protect cultural heritage sites. The new concept of a Digital Cultural Heritage has been presented for culture protection and is gradually becoming an efficient method to solve or to remit various difficult problems. This paper puts forward a digitalization method for cultural heritage sites which rationally integrates and utilizes multiform surveying measurements. These techniques have been successfully implemented into two projects, namely the Digital Mogao Grottos and the Chi Lin Nunnery reconstruction. Our results prove that the concept of and the techniques utilized in Digital Cultural Heritage can not only contribute to research, preservation, management, interpretation, and representation of cultural heritages but can also help resolve the conflicts between tourism and protection.

The Integrin Receptor in Biologically Relevant Bilayers: Insights from Molecular Dynamics Simulations.

PubMed

Kalli, Antreas C; Rog, Tomasz; Vattulainen, Ilpo; Campbell, Iain D; Sansom, Mark S P

2017-08-01

Integrins are heterodimeric (αβ) cell surface receptors that are potential therapeutic targets for a number of diseases. Despite the existence of structural data for all parts of integrins, the structure of the complete integrin receptor is still not available. We have used available structural data to construct a model of the complete integrin receptor in complex with talin F2-F3 domain. It has been shown that the interactions of integrins with their lipid environment are crucial for their function but details of the integrin/lipid interactions remain elusive. In this study an integrin/talin complex was inserted in biologically relevant bilayers that resemble the cell plasma membrane containing zwitterionic and charged phospholipids, cholesterol and sphingolipids to study the dynamics of the integrin receptor and its effect on bilayer structure and dynamics. The results of this study demonstrate the dynamic nature of the integrin receptor and suggest that the presence of the integrin receptor alters the lipid organization between the two leaflets of the bilayer. In particular, our results suggest elevated density of cholesterol and of phosphatidylserine lipids around the integrin/talin complex and a slowing down of lipids in an annulus of ~30 Å around the protein due to interactions between the lipids and the integrin/talin F2-F3 complex. This may in part regulate the interactions of integrins with other related proteins or integrin clustering thus facilitating signal transduction across cell membranes.

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

PubMed Central

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

2011-01-01

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

In vitro and in vivo antimicrobial activities of seeds of Caesalpinia bonduc (Lin.) Roxb.

PubMed

Arif, Tasleem; Mandal, T K; Kumar, Naresh; Bhosale, J D; Hole, Archana; Sharma, G L; Padhi, M M; Lavekar, G S; Dabur, Rajesh

2009-05-04

Caesalpinia bonduc (Lin.) Roxb. is a known drug in Ayurveda to treat various diseases specifically tumors, cysts and cystic fibrosis (CF). The aim of this study was to assess in vitro as well as in vivo antimicrobial activity of Caesalpinia bonduc seeds. The in vitro antimicrobial activities of seed coat and seed kernel extracts were investigated by microbroth dilution assay. In vivo activities of hydro-alcoholic extracts were investigated in rat models of chronic Pseudomonas aeruginosa pneumonia mimicking that in patients with cystic fibrosis. Various extracts of plant seeds exhibited in vitro antimicrobial activities in a range of 22-350 microg/ml. The extracts also showed activity against methicillin resistant (MR) Staphylococcus aureus and ampicillin resistant (AR) Pseudomonas aeruginosa as in the sensitive strains. In rat model of chronic Pseudomonas aeruginosa pneumonia, hydro-alcoholic extracts of Caesalpinia bonduc seed kernel (CBSK) and Caesalpinia bonduc seed coat (CBSC) were injected subcutaneously in the test groups of animals. The control groups were treated with cortisone and saline. Two weeks after challenge with Pseudomonas aeruginosa, the CBSK treated animals showed a significant bacterial clearance from the lungs (P<0.04) and less severe incidence of lung abscess (P<0.05). Results showed that Caesalpinia bonduc may have the potential to be promising natural medicine, with other forms of treatments, for CF patients with chronic Pseudomonas aeruginosa lung infections.

Coordinated Mechanosensitivity of Membrane Rafts and Focal Adhesions

PubMed Central

Fuentes, Daniela E.; Butler, Peter J.

2013-01-01

Endothelial cells sense mechanical forces of blood flow through mechanisms that involve focal adhesions (FAs). The mechanosensitive pathways that originate from FA-associated integrin activation may involve membrane rafts, small cholesterol- and sphigolipid-rich domains that are either immobilized, by virtue of their attachment to the cytoskeleton, or highly mobile in the plane of the plasma membrane. In this study, we fluorescently labeled non-mobile and mobile populations of GM1, a ganglioside associated with lipid rafts, and transfected cells with the red fluorescent protein-(RFP-) talin, an indicator of integrin activation at FAs, in order to determine the kinetics and sequential order of raft and talin mechanosensitivity. Cells were imaged under confocal microscopy during mechanical manipulation of a FA induced by a fibronectin (FN)-functionalized nanoelectrode with feedback control of position. First, FA deformation led to long range deformation of immobile rafts followed by active recoil of a subpopulation of displaced rafts. Second, initial adhesion between the FN-probe and the cell induced rapid accumulation of GM1 at the probe site with a time constant of 1.7 s. Talin accumulated approximately 20 s later with a time constant of 0.6 s. Third, a 1 μm deformation of the FA lead to immediate (0.3 s) increase in GM1 fluorescence and a later (6 s) increase in talin. Fourth, long term deformation of FAs led to continual GM1 accumulation at the probe site that was reversed upon removal of the deformation. These results demonstrate that rafts are directly mechanosensitive and that raft mobility may enable the earliest events related to FA mechanosensing and reinforcement upon force application. PMID:23487555

Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness

PubMed Central

Meller, Julia; Rogozin, Igor B.; Poliakov, Eugenia; Meller, Nahum; Bedanov-Pack, Mark; Plow, Edward F.; Qin, Jun; Podrez, Eugene A.; Byzova, Tatiana V.

2015-01-01

Kindlins are integrin-interacting proteins essential for integrin-mediated cell adhesiveness. In this study, we focused on the evolutionary origin and functional specialization of kindlins as a part of the evolutionary adaptation of cell adhesive machinery. Database searches revealed that many members of the integrin machinery (including talin and integrins) existed before kindlin emergence in evolution. Among the analyzed species, all metazoan lineages—but none of the premetazoans—had at least one kindlin-encoding gene, whereas talin was present in several premetazoan lineages. Kindlin appears to originate from a duplication of the sequence encoding the N-terminal fragment of talin (the talin head domain) with a subsequent insertion of the PH domain of separate origin. Sequence analysis identified a member of the actin filament–associated protein 1 (AFAP1) superfamily as the most likely origin of the kindlin PH domain. The functional divergence between kindlin paralogues was assessed using the sequence swap (chimera) approach. Comparison of kindlin 2 (K2)/kindlin 3 (K3) chimeras revealed that the F2 subdomain, in particular its C-terminal part, is crucial for the differential functional properties of K2 and K3. The presence of this segment enables K2 but not K3 to localize to focal adhesions. Sequence analysis of the C-terminal part of the F2 subdomain of K3 suggests that insertion of a variable glycine-rich sequence in vertebrates contributed to the loss of constitutive K3 targeting to focal adhesions. Thus emergence and subsequent functional specialization of kindlins allowed multicellular organisms to develop additional tissue-specific adaptations of cell adhesiveness. PMID:25540429

[Deciphering the argots of the names of materia medica and its dosage in the Yi lin kou pu liu zhi mi shu (A Secret Medical Book of Six Therapies in Rhymes of Medical Professionals)].

PubMed

Zhou, Jian; Lin, Shiyi; Liu, Shijue

2014-11-01

Yi lin kou pu liu zhi mi shu (A Secret Medical Book of Six Therapies in Rhymes of Medical Professionals) was additionally compiled, supplemented and annotated by Zhou Sheng, a famous doctor of the Qing Dynasty, based on Yi lin kou pu (Rhymes of Medical Professionals) which was composed by Lu Qi. The book contains four volumes in total, dealing mainly with the miscellaneous diseases of internal medicine, as well as external medicine, gynecology, and pediatrics etc. The syndrome differentiation and treatment, prescriptions and medications in this book has its own characteristic with rather high academic value and practical significance. There were 20 drug names were deciphered by the argots, for instance, "you che" was the argot of golden thread, and "wu yue (May)" was the argot of medicinal evodia fruit, etc. In addition, the argots were often used to decipher numerals and quantifiers, for example, "su, qi, zi, qi, man" referring to 1, 2, 3, 4, 5 respectively, and "huo, pu, xiang, feng, lai" referring to 6, 7, 8, 9, 10 respectively, and "qing","zhong","xi" referring to qian, liang and fen respectively. Hence, deciphering of these argots could help to understand and apply these prescriptions correctly.

Quality by design: optimization of a liquid filled pH-responsive macroparticles using Draper-Lin composite design.

PubMed

Rafati, Hasan; Talebpour, Zahra; Adlnasab, Laleh; Ebrahimi, Samad Nejad

2009-07-01

In this study, pH responsive macroparticles incorporating peppermint oil (PO) were prepared using a simple emulsification/polymer precipitation technique. The formulations were examined for their properties and the desired quality was then achieved using a quality by design (QBD) approach. For this purpose, a Draper-Lin small composite design study was employed in order to investigate the effect of four independent variables, including the PO to water ratio, the concentration of pH sensitive polymer (hydroxypropyl methylcellulose phthalate), acid and plasticizer concentrations, on the encapsulation efficiency and PO loading. The analysis of variance showed that the polymer concentration was the most important variable on encapsulation efficiency (p < 0.05). The multiple regression analysis of the results led to equations that adequately described the influence of the independent variables on the selected responses. Furthermore, the desirability function was employed as an effective tool for transforming each response separately and encompassing all of these responses in an overall desirability function for global optimization of the encapsulation process. The optimized macroparticles were predicted to yield 93.4% encapsulation efficiency and 72.8% PO loading, which were remarkably close to the experimental values of 89.2% and 69.5%, consequently.

The mutational landscape of MYCN, Lin28b and ALK F1174L driven murine neuroblastoma mimics human disease.

PubMed

De Wilde, Bram; Beckers, Anneleen; Lindner, Sven; Kristina, Althoff; De Preter, Katleen; Depuydt, Pauline; Mestdagh, Pieter; Sante, Tom; Lefever, Steve; Hertwig, Falk; Peng, Zhiyu; Shi, Le-Ming; Lee, Sangkyun; Vandermarliere, Elien; Martens, Lennart; Menten, Björn; Schramm, Alexander; Fischer, Matthias; Schulte, Johannes; Vandesompele, Jo; Speleman, Frank

2018-02-02

Genetically engineered mouse models have proven to be essential tools for unraveling fundamental aspects of cancer biology and for testing novel therapeutic strategies. To optimally serve these goals, it is essential that the mouse model faithfully recapitulates the human disease. Recently, novel mouse models for neuroblastoma have been developed. Here, we report on the further genomic characterization through exome sequencing and DNA copy number analysis of four of the currently available murine neuroblastoma model systems ( ALK, Th- MYCN, Dbh- MYCN and Lin28b ). The murine tumors revealed a low number of genomic alterations - in keeping with human neuroblastoma - and a positive correlation of the number of genetic lesions with the time to onset of tumor formation was observed. Gene copy number alterations are the hallmark of both murine and human disease and frequently affect syntenic genomic regions. Despite low mutational load, the genes mutated in murine disease were found to be enriched for genes mutated in human disease. Taken together, our study further supports the validity of the tested mouse models for mechanistic and preclinical studies of human neuroblastoma.

Two different roles of purified CD45+c-Kit+Sca-1+Lin- cells after transplantation in muscles.

PubMed

Yoshimoto, Momoko; Chang, Hsi; Shiota, Mitsutaka; Kobayashi, Hirohiko; Umeda, Katsutsugu; Kawakami, Atsushi; Heike, Toshio; Nakahata, Tatsutoshi

2005-05-01

Recent studies have indicated that bone marrow cells can regenerate damaged muscles and that they can adopt phenotypes of other cells by cell fusion. Our direct visualization system gave evidence of massive muscle regeneration by green fluorescent protein (GFP)-labeled CD45+c-Kit+Sca-1+Lin- cells (KSL cells), and we investigated the role of KSL cells in muscle regeneration after transplantation with or without lethal irradiation. In the early phase, GFP signals were clearly observed in all the muscles of only irradiated mice. Transverse cryostat sections showed GFP+myosin+ muscle fibers, along with numerous GFP+ hematopoietic cells in damaged muscle. These phenomena were temporary, and GFP signals had dramatically reduced 30 days after transplantation. After 6 months, GFP+ fibers could hardly be detected, but GFP+c-Met+ mononuclear cells were located beneath the basal lamina where satellite cells usually exist in both conditioned mice. Immunostaining of isolated single fibers revealed GFP+PAX7+, GFP+MyoD+, and GFP+Myf5+ satellite-like cells on the fibers. Single-fiber cultures from these mice showed proliferation of GFP+ fibers. These results indicate two different roles of KSL cells: one leading to regeneration of damaged muscles in the early phase and the other to conversion into satellite cells in the late phase.

A model for the Lin-Shu type density-wave structure of our Galaxy: Line-of-sight and transverse-longitudinal velocities of 242 optically visible open clusters

NASA Astrophysics Data System (ADS)

Griv, E.; Jiang, I.-G.

2015-02-01

In this paper, the fourth in a series, we examine again one of the implications of the Lin-Shu density-wave theory, specifically, the noncircular systematic motion of the Galactic objects. Our previous investigation is extended by analyzing simultaneously both the line-of-sight and transversal velocities of a sample of open clusters for which velocities, distances and ages are available. The ordinary equations of the Oort-Lindblad theory of galactic differential rotation are used. The minor effects caused by the two-dimensional tightly-wound density waves are also taken into account. The published data of 242 currently known optically visible clusters having distances r<3 kpc from the Sun and -200 < z <200 pc from the Galactic plane, and ages 2 × 108 < t < 2 × 109 yr are collected from Dias et al. (2014), excluding extremely far, high-velocity, young and old objects in our fitting. The most noteworthy result is the fact that the parameters of Lin-Shu type density waves estimated from two independent line-of-sight and transversal along the Galactic longitude velocities are nearly equal. We argue that the resemblance of these Galactic wave structures is so remarkable that no doubt is felt as to the theory's truth with respect to these data. The results obtained allow us to conclude that several low-m trailing density-wave patterns with different number of spiral arms m (say, m=1, 2, 3, and 4), pitch angles (about 5o, 8o, 11o, and 14o, respectively) and amplitudes of the perturbed gravitational potential may coexist in the Galaxy. The latter suggests the asymmetric multiarm, not well-organized (``flocculent'') spiral structure of the system. In memory of Professors Alexei M. Fridman (1940-2010) and Chi Yuan (1937-2008)

Source apportionment of PM2.5 at the Lin'an regional background site in China with three receptor models

NASA Astrophysics Data System (ADS)

Deng, Junjun; Zhang, Yanru; Qiu, Yuqing; Zhang, Hongliang; Du, Wenjiao; Xu, Lingling; Hong, Youwei; Chen, Yanting; Chen, Jinsheng

2018-04-01

Source apportionment of fine particulate matter (PM2.5) were conducted at the Lin'an Regional Atmospheric Background Station (LA) in the Yangtze River Delta (YRD) region in China from July 2014 to April 2015 with three receptor models including principal component analysis combining multiple linear regression (PCA-MLR), UNMIX and Positive Matrix Factorization (PMF). The model performance, source identification and source contribution of the three models were analyzed and inter-compared. Source apportionment of PM2.5 was also conducted with the receptor models. Good correlations between the reconstructed and measured concentrations of PM2.5 and its major chemical species were obtained for all models. PMF resolved almost all masses of PM2.5, while PCA-MLR and UNMIX explained about 80%. Five, four and seven sources were identified by PCA-MLR, UNMIX and PMF, respectively. Combustion, secondary source, marine source, dust and industrial activities were identified by all the three receptor models. Combustion source and secondary source were the major sources, and totally contributed over 60% to PM2.5. The PMF model had a better performance on separating the different combustion sources. These findings improve the understanding of PM2.5 sources in background region.

Differential Processing of let-7a Precursors Influences RRM2 Expression and Chemosensitivity in Pancreatic Cancer: Role of LIN-28 and SET Oncoprotein

PubMed Central

Bhutia, Yangzom Doma; Hung, Sau Wai; Krentz, Madeline; Patel, Dimal; Lovin, Dylan; Manoharan, Radhika; Thomson, J. Michael; Govindarajan, Rajgopal

2013-01-01

Overexpression of ribonucleotide reductase subunit M2 (RRM2), involved in deoxyribonucleotide synthesis, drives the chemoresistance of pancreatic cancer to nucleoside analogs (e.g., gemcitabine). While silencing RRM2 by synthetic means has shown promise in reducing chemoresistance, targeting endogenous molecules, especially microRNAs (miRNAs), to advance chemotherapeutic outcomes has been poorly explored. Based on computational predictions, we hypothesized that the let-7 tumor suppressor miRNAs will inhibit RRM2-mediated gemcitabine chemoresistance in pancreatic cancer. Reduced expression of the majority of let-7 miRNAs with an inverse relationship to RRM2 expression was identified in innately gemcitabine-resistant pancreatic cancer cell lines. Direct binding of let-7 miRNAs to the 3′ UTR of RRM2 transcripts identified post-transcriptional regulation of RRM2 influencing gemcitabine chemosensitivity. Intriguingly, overexpression of human precursor-let-7 miRNAs led to differential RRM2 expression and chemosensitivity responses in a poorly differentiated pancreatic cancer cell line, MIA PaCa-2. Defective processing of let-7a precursors to mature forms, in part, explained the discrepancies observed with let-7a expressional outcomes. Consistently, the ratios of mature to precursor let-7a were progressively reduced in gemcitabine-sensitive L3.6pl and Capan-1 cell lines induced to acquire gemcitabine resistance. Besides known regulators of let-7 biogenesis (e.g., LIN-28), short hairpin RNA library screening identified several novel RNA binding proteins, including the SET oncoprotein, to differentially impact let-7 biogenesis and chemosensitivity in gemcitabine-sensitive versus -resistant pancreatic cancer cells. Further, LIN-28 and SET knockdown in the cells led to profound reductions in cellular proliferation and colony-formation capacities. Finally, defective processing of let-7a precursors with a positive correlation to RRM2 overexpression was identified in patient

Méthode de prédétermination des caractéristiques électromagnétiques de machines á bobinage global à commutation de flux. Application à un actionneur linéaire

NASA Astrophysics Data System (ADS)

Prevond, L.; Ben Ahmed, A.; Multon, B.; Lucidarme, J.

1997-06-01

This paper presents a predetermination method of Permanent Magnet (P.M.) multicellular flux switching machines. The non-linear characteristic of the ferromagnetic material is integrated in this method which combines analytical and numerical calculus. This study permits to make a fast parametrical analysis to define optimal parameters of a flux switching cell such as magnetic shear stress and flux concentration factor as function of magnetomotive force. The demagnetisation limit is introduced by a finite element calculus applied. The comparison of the theoritical results and experimental one gives a good correlation. Cet article présente une méthode de prédétermination des caractéristiques de machines multicellulaires (bobinage global) à commutation de flux (aimants permanents) en tenant compte de la non linéarité des matériaux ferromagnétiques. Cette méthode allie le calcul numérique par éléments finis et le calcul analytique. Cette étude nous a permis, d'une part, d'effectuer une analyse paramétrique intrinsèque et, d'autre part, de définir les paramètres optimaux de la cellule à commutation de flux. La notion de désaimantation est introduite en calculant le champ démagnétisant dans l'aimant. Les calculs effectués, dans le cas d'un actionneur linéaire à cômmutation de flux, montrent une bonne corrélation avec les essais directs.

Integrative genomic analyses identify LIN28 and OLIG2 as markers of survival and metastatic potential in childhood central nervous system primitive neuro-ectodermal brain tumours

PubMed Central

Picard, Daniel; Miller, Suzanne; Hawkins, Cynthia E; Bouffet, Eric; Rogers, Hazel A; Chan, Tiffany SY; Kim, Seung-Ki; Ra, Young-Shin; Fangusaro, Jason; Korshunov, Andrey; Toledano, Helen; Nakamura, Hideo; Hayden, James T; Chan, Jennifer; Lafay-Cousin, Lucie; Hu, Ping X; Fan, Xing; Muraszko, Karin M; Pomeroy, Scott L; Lau, Ching C; Ng, Ho-Keung; Jones, Chris; Meter, Timothy Van; Clifford, Steven C; Eberhart, Charles; Gajjar, Amar; Pfister, Stefan M; Grundy, Richard G; Huang, Annie

2013-01-01

Background Childhood Central Nervous System Primitive Neuro-Ectodermal brain Tumours (CNS-PNETs) are highly aggressive brain tumours for which molecular features and best therapeutic strategy remains unknown. We interrogated a large cohort of these rare tumours in order to identify molecular markers that will enhance clinical management of CNS-PNET. Methods Transcriptional and copy number profiles from primary hemispheric CNS-PNETs were examined using clustering, gene and pathways enrichment analyses to discover tumour sub-groups and group-specific molecular markers. Immuno-histochemical and/or gene expression analyses were used to validate and examine the clinical significance of novel sub-group markers in 123 primary CNS-PNETs. Findings Three molecular sub-groups of CNS-PNETs distinguished by primitive neural (Group 1), oligo-neural (Group 2) and mesenchymal lineage (Group 3) gene expression signature were identified. Tumour sub-groups exhibited differential expression of cell lineage markers, LIN28 and OLIG2, and correlated with distinct demographics, survival and metastatic incidence. Group 1 tumours affected primarily younger females; male: female ratios were respectively 0.61 (median age 2.9 years; 95% CI: 2.4–5.2; p≤ 0.005), 1.25 (median age 7.9 years; 95% CI: 6–9.7) and 1.63 (median age 5.9 years; 95% CI: 4.9–7.8) for group 1, 2 and 3 patients. Overall outcome was poorest in group 1 patients which had a median survival of 0.8 years (95% CI: 0.47–1.2; p=0.019) as compared to 1.8 years (95% CI: 1.4–2.3) and 4.3 years; (95% CI: 0.82–7.8) respectively for group 2 and 3 patients. Group 3 tumours had the highest incidence of metastases at diagnosis; M0: M+ ratio were respectively 0.9 and 3.9 for group 3, versus group 1 and 2 tumours combined (p=0.037). Interpretation LIN28 and OLIG2 represent highly promising, novel diagnostic and prognostic molecular markers for CNS PNET that warrants further evaluation in prospective clinical trials. PMID:22691720

Uterine molecular changes for non-invasive embryonic attachment in the marsupials Macropus eugenii (Macropodidae) and Trichosurus vulpecula (Phalangeridae).

PubMed

Laird, Melanie K; Dargan, Jessica R; Paterson, Lillian; Murphy, Christopher R; McAllan, Bronwyn M; Shaw, Geoff; Renfree, Marilyn B; Thompson, Michael B

2017-10-01

Pregnancy in mammals requires remodeling of the uterus to become receptive to the implanting embryo. Remarkably similar morphological changes to the uterine epithelium occur in both eutherian and marsupial mammals, irrespective of placental type. Nevertheless, molecular differences in uterine remodeling indicate that the marsupial uterus employs maternal defences, including molecular reinforcement of the uterine epithelium, to regulate embryonic invasion. Non-invasive (epitheliochorial) embryonic attachment in marsupials likely evolved secondarily from invasive attachment, so uterine defences in these species may prevent embryonic invasion. We tested this hypothesis by identifying localization patterns of Talin, a key basal anchoring molecule, in the uterine epithelium during pregnancy in the tammar wallaby (Macropus eugenii; Macropodidae) and the brush tail possum (Trichosurus vulpecula; Phalangeridae). Embryonic attachment is non-invasive in both species, yet Talin undergoes a clear distributional change during pregnancy in M. eugenii, including recruitment to the base of the uterine epithelium just before attachment, that closely resembles that of invasive implantation in the marsupial species Sminthopsis crassicaudata. Basal localization occurs throughout pregnancy in T. vulpecula, although, as for M. eugenii, this pattern is most specific prior to attachment. Such molecular reinforcement of the uterine epithelium for non-invasive embryonic attachment in marsupials supports the hypothesis that less-invasive and non-invasive embryonic attachment in marsupials may have evolved via accrual of maternal defences. Recruitment of basal molecules, including Talin, to the uterine epithelium may have played a key role in this transition. © 2017 Wiley Periodicals, Inc.

An update on finances and financial support for medical students in Yong Loo Lin School of Medicine

PubMed Central

Sayampanathan, Andrew Arjun; Tan, Yeong Tze Wilnard; Fong, Jie Ming Nigel; Koh, Yun Qing; Ng, Chew Lip; Mohan, Niraj; Jang, Jin Hao Justin; Tambyah, Paul Anantharajah

2017-01-01

INTRODUCTION Increasing financial challenges have resulted in great debt among medical graduates worldwide. In Singapore, more scholarships and bursaries have been disbursed in recent years to support students who are financially challenged. We aimed to study the financial status of medical students in National University of Singapore (NUS) Yong Loo Lin School of Medicine (i.e. NUS Medicine), Singapore, and the financial support available to them. METHODS A cross-sectional quantitative study was performed. Surveys were distributed and completed by medical students of NUS Medicine. Information regarding household income, financial assistance, monthly allowance and expense, and concurrent occupations was collected. We compared our findings with the results of a similar study performed in 2007 and national income data. RESULTS A total of 956 (66.2%) out of 1,445 medical students completed the survey. 19.5% and 58.5% of respondents came from households with monthly incomes < SGD 3,000 and > SGD 7,000, respectively. 20.6% of students had loans, 18.9% had scholarships and bursaries, and 14.4% worked to support themselves. CONCLUSION Medical school fees have risen by more than 50% over the past ten years. Our study found that there were increases in the proportion of students from both the lower- and higher-income segments, with proportionally fewer students from the middle-income segment. A large number of students were working and/or had some form of financial support. More should be done to meet the needs of financially challenged medical students to ensure equal access to quality medical education. PMID:27516114

Interactions with the actin cytoskeleton are required for cell wall localization of barley stripe mosaic virus TGB proteins

USDA-ARS?s Scientific Manuscript database

The host cytoskeleton and membrane system are the main routes by which plant viruses move within or between cells. Barley stripe mosaic virus (BSMV) -induced actin filament thickening was visualized in the cytoskeleton of agroinfiltrated Nicotiana benthamiana epidermal cells expressing DsRed:Talin. ...

Cloning of a CACTA transposon-like insertion in intron I of tomato invertase Lin5 gene and identification of transposase-like sequences of Solanaceae species.

PubMed

Proels, Reinhard K; Roitsch, Thomas

2006-03-01

Very few CACTA transposon-like sequences have been described in Solanaceae species. Sequence information has been restricted to partial transposase (TPase)-like fragments, and no target gene of CACTA-like transposon insertion has been described in tomato to date. In this manuscript, we report on a CACTA transposon-like insertion in intron I of tomato (Lycopersicon esculentum) invertase gene Lin5 and TPase-like sequences of several Solanaceae species. Consensus primers deduced from the TPase region of the tomato CACTA transposon-like element allowed the amplification of similar sequences from various Solanaceae species of different subfamilies including Solaneae (Solanum tuberosum), Cestreae (Nicotiana tabacum) and Datureae (Datura stramonium). This demonstrates the ubiquitous presence of CACTA-like elements in Solanaceae genomes. The obtained partial sequences are highly conserved, and allow further detection and detailed analysis of CACTA-like transposons throughout Solanaceae species. CACTA-like transposon sequences make possible the evaluation of their use for genome analysis, functional studies of genes and the evolutionary relationships between plant species.

Deficiency of Suppressor Enhancer Lin12 1 Like (SEL1L) in Mice Leads to Systemic Endoplasmic Reticulum Stress and Embryonic Lethality*

PubMed Central

Francisco, Adam B.; Singh, Rajni; Li, Shuai; Vani, Anish K.; Yang, Liu; Munroe, Robert J.; Diaferia, Giuseppe; Cardano, Marina; Biunno, Ida; Qi, Ling; Schimenti, John C.; Long, Qiaoming

2010-01-01

Stress in the endoplasmic reticulum (ER) plays an important causal role in the pathogenesis of several chronic diseases such as Alzheimer, Parkinson, and diabetes mellitus. Insight into the genetic determinants responsible for ER homeostasis will greatly facilitate the development of therapeutic strategies for the treatment of these debilitating diseases. Suppressor enhancer Lin12 1 like (SEL1L) is an ER membrane protein and was thought to be involved in the quality control of secreted proteins. Here we show that the mice homozygous mutant for SEL1L were embryonic lethal. Electron microscopy studies revealed a severely dilated ER in the fetal liver of mutant embryos, indicative of alteration in ER homeostasis. Consistent with this, several ER stress responsive genes were significantly up-regulated in the mutant embryos. Mouse embryonic fibroblast cells deficient in SEL1L exhibited activated unfolded protein response at the basal state, impaired ER-associated protein degradation, and reduced protein secretion. Furthermore, markedly increased apoptosis was observed in the forebrain and dorsal root ganglions of mutant embryos. Taken together, our results demonstrate an essential role for SEL1L in protein quality control during mouse embryonic development. PMID:20197277

Deficiency of suppressor enhancer Lin12 1 like (SEL1L) in mice leads to systemic endoplasmic reticulum stress and embryonic lethality.

PubMed

Francisco, Adam B; Singh, Rajni; Li, Shuai; Vani, Anish K; Yang, Liu; Munroe, Robert J; Diaferia, Giuseppe; Cardano, Marina; Biunno, Ida; Qi, Ling; Schimenti, John C; Long, Qiaoming

2010-04-30

Stress in the endoplasmic reticulum (ER) plays an important causal role in the pathogenesis of several chronic diseases such as Alzheimer, Parkinson, and diabetes mellitus. Insight into the genetic determinants responsible for ER homeostasis will greatly facilitate the development of therapeutic strategies for the treatment of these debilitating diseases. Suppressor enhancer Lin12 1 like (SEL1L) is an ER membrane protein and was thought to be involved in the quality control of secreted proteins. Here we show that the mice homozygous mutant for SEL1L were embryonic lethal. Electron microscopy studies revealed a severely dilated ER in the fetal liver of mutant embryos, indicative of alteration in ER homeostasis. Consistent with this, several ER stress responsive genes were significantly up-regulated in the mutant embryos. Mouse embryonic fibroblast cells deficient in SEL1L exhibited activated unfolded protein response at the basal state, impaired ER-associated protein degradation, and reduced protein secretion. Furthermore, markedly increased apoptosis was observed in the forebrain and dorsal root ganglions of mutant embryos. Taken together, our results demonstrate an essential role for SEL1L in protein quality control during mouse embryonic development.

Lithology identification of aquifers from geophysical well logs and fuzzy logic analysis: Shui-Lin Area, Taiwan

NASA Astrophysics Data System (ADS)

Hsieh, Bieng-Zih; Lewis, Charles; Lin, Zsay-Shing

2005-04-01

The purpose of this study is to construct a fuzzy lithology system from well logs to identify formation lithology of a groundwater aquifer system in order to better apply conventional well logging interpretation in hydro-geologic studies because well log responses of aquifers are sometimes different from those of conventional oil and gas reservoirs. The input variables for this system are the gamma-ray log reading, the separation between the spherically focused resistivity and the deep very-enhanced resistivity curves, and the borehole compensated sonic log reading. The output variable is groundwater formation lithology. All linguistic variables are based on five linguistic terms with a trapezoidal membership function. In this study, 50 data sets are clustered into 40 training sets and 10 testing sets for constructing the fuzzy lithology system and validating the ability of system prediction, respectively. The rule-based database containing 12 fuzzy lithology rules is developed from the training data sets, and the rule strength is weighted. A Madani inference system and the bisector of area defuzzification method are used for fuzzy inference and defuzzification. The success of training performance and the prediction ability were both 90%, with the calculated correlation of training and testing equal to 0.925 and 0.928, respectively. Well logs and core data from a clastic aquifer (depths 100-198 m) in the Shui-Lin area of west-central Taiwan are used for testing the system's construction. Comparison of results from core analysis, well logging and the fuzzy lithology system indicates that even though the well logging method can easily define a permeable sand formation, distinguishing between silts and sands and determining grain size variation in sands is more subjective. These shortcomings can be improved by a fuzzy lithology system that is able to yield more objective decisions than some conventional methods of log interpretation.

Heterodimerization with the β1 subunit directs the α2 subunit of nitric oxide-sensitive guanylyl cyclase to calcium-insensitive cell-cell contacts in HEK293 cells: Interaction with Lin7a.

PubMed

Hochheiser, Julia; Haase, Tobias; Busker, Mareike; Sömmer, Anne; Kreienkamp, Hans-Jürgen; Behrends, Sönke

2016-12-15

Nitric oxide-sensitive guanylyl cyclase is a heterodimeric enzyme consisting of an α and a β subunit. Two different α subunits (α 1 and α 2 ) give rise to two heterodimeric enzymes α 1 /β 1 and α 2 /β 1 . Both coexist in a wide range of tissues including blood vessels and the lung, but expression of the α 2 /β 1 form is generally much lower and approaches levels similar to the α 1 /β 1 form in the brain only. In the present paper, we show that the α 2 /β 1 form interacts with Lin7a in mouse brain synaptosomes based on co-precipitation analysis. In HEK293 cells, we found that the overexpressed α 2 /β 1 form, but not the α 1 /β 1 form is directed to calcium-insensitive cell-cell contacts. The isolated PDZ binding motif of an amino-terminally truncated α 2 subunit was sufficient for cell-cell contact localization. For the full length α 2 subunit with the PDZ binding motif this was only the case in the heterodimer configuration with the β 1 subunit, but not as isolated α 2 subunit. We conclude that the PDZ binding motif of the α 2 subunit is only accessible in the heterodimer conformation of the mature nitric oxide-sensitive enzyme. Interaction with Lin7a, a small scaffold protein important for synaptic function and cell polarity, can direct this complex to nectin based cell-cell contacts via MPP3 in HEK293 cells. We conclude that heterodimerization is a prerequisite for further protein-protein interactions that direct the α 2 /β 1 form to strategic sites of the cell membrane with adjacent neighbouring cells. Drugs increasing the nitric oxide-sensitivity of this specific form may be particularly effective. Copyright © 2016 Elsevier Inc. All rights reserved.

MIB-1 Is Required for Spermatogenesis and Facilitates LIN-12 and GLP-1 Activity in Caenorhabditis elegans.

PubMed

Ratliff, Miriam; Hill-Harfe, Katherine L; Gleason, Elizabeth J; Ling, Huiping; Kroft, Tim L; L'Hernault, Steven W

2018-05-01

Covalent attachment of ubiquitin to substrate proteins changes their function or marks them for proteolysis, and the specificity of ubiquitin attachment is mediated by the numerous E3 ligases encoded by animals. Mind Bomb is an essential E3 ligase during Notch pathway signaling in insects and vertebrates. While Caenorhabditis elegans encodes a Mind Bomb homolog ( mib-1 ), it has never been recovered in the extensive Notch suppressor/enhancer screens that have identified numerous pathway components. Here, we show that C. elegans mib-1 null mutants have a spermatogenesis-defective phenotype that results in a heterogeneous mixture of arrested spermatocytes, defective spermatids, and motility-impaired spermatozoa. mib-1 mutants also have chromosome segregation defects during meiosis, molecular null mutants are intrinsically temperature-sensitive, and many mib-1 spermatids contain large amounts of tubulin. These phenotypic features are similar to the endogenous RNA intereference (RNAi) mutants, but mib-1 mutants do not affect RNAi. MIB-1 protein is expressed throughout the germ line with peak expression in spermatocytes followed by segregation into the residual body during spermatid formation. C. elegans mib-1 expression, while upregulated during spermatogenesis, also occurs somatically, including in vulva precursor cells. Here, we show that mib-1 mutants suppress both lin-12 and glp-1 ( C. elegans Notch) gain-of-function mutants, restoring anchor cell formation and a functional vulva to the former and partly restoring oocyte production to the latter. However, suppressed hermaphrodites are only observed when grown at 25°, and they are self-sterile. This probably explains why mib-1 was not previously recovered as a Notch pathway component in suppressor/enhancer selection experiments. Copyright © 2018 by the Genetics Society of America.

Iodine Deficiency in a Study Population of Norwegian Pregnant Women-Results from the Little in Norway Study (LiN).

PubMed

Dahl, Lisbeth; Wik Markhus, Maria; Sanchez, Perla Vanessa Roldan; Moe, Vibeke; Smith, Lars; Meltzer, Helle Margrete; Kjellevold, Marian

2018-04-20

Iodine sufficiency is particularly important in pregnancy, where median urinary iodine concentration (UIC) in the range of 150⁻250 µg/L indicates adequate iodine status. The aims of this study were to determine UIC and assess if dietary and maternal characteristics influence the iodine status in pregnant Norwegian women. The study comprises a cross-sectional population-based prospective cohort of pregnant women (Little in Norway (LiN)). Median UIC in 954 urine samples was 85 µg/L and 78.4% of the samples ( n = 748) were ≤150 µg/L. 23.2% ( n = 221) of the samples were ≤50 µg/L and 5.2% ( n = 50) were above the requirements of iodine intake (>250 µg/L). Frequent iodine-supplement users ( n = 144) had significantly higher UIC (120 µg/L) than non-frequent users (75 µg/L). Frequent milk and dairy product consumers (4⁻9 portions/day) had significantly higher UIC (99 µg/L) than women consuming 0⁻1 portion/day (57 µg/L) or 2⁻3 portions/day (83 µg/L). Women living in mid-Norway ( n = 255) had lowest UIC (72 µg/L). In conclusion, this study shows that the diet of the pregnant women did not necessarily secure a sufficient iodine intake. There is an urgent need for public health strategies to secure adequate iodine nutrition among pregnant women in Norway.

Mechanical Signal Transduction in Countermeasures to Muscle Atrophy

NASA Technical Reports Server (NTRS)

Tidball, James G.; Chu, Amy (Technical Monitor)

2002-01-01

We have shown that modifications in muscle use result in changes in the expression and activity of calpains and nitric oxide synthase (NOS). Although muscle unloading for 10 days produced no change in the concentrations of calpain 1 or 2 and no change in calpain activation, muscle reloading produced a 90% increase in calpain 2 concentration. We developed an in vitro model to test our hypothesis that nitric oxide can inhibit cytoskeletal breakdown in skeletal muscle cells by inhibiting calpain cleavage of talin. Talin was selected because it is a well-characterized calpain substrate and it is codistributed with calpain in muscle cells. We found that intermittant loading during hindlimb suspension that is sufficient to prevent muscle mass loss that occurs during muscle unloading is also sufficient to prevent the decrease in NOS expression that normally occurs during hindlimb unloading. These findings indicate that therapeutics directed toward regulating the calpain/calpastatin system may be beneficial in preventing muscle mass loss in muscle injury, unloading and disease.

A Hydrological Tomography Collocated with Time-varying Gravimetry for Hydrogeology -An Example in Yun-Lin Alluvial Plain and Ming-Ju Basin in Taiwan

NASA Astrophysics Data System (ADS)

Chen, K. H.; Cheng, C. C.; Hwang, C.

2016-12-01

A new inversion technique featured by the collocation of hydrological modeling and gravimetry observation is presented in this report. Initially this study started from a project attempting to build a sequence of hydrodynamic models of ground water system, which was applied to identify the supplement areas of alluvial plains and basins along the west coast of Taiwan. To calibrate the decent hydro-geological parameters for the modeling, geological evolution were carefully investigated and absolute gravity observations, along with other on-site hydrological monitoring data were specially introduced. It was discovered in the data processing that the time-varying gravimetrical data are highly sensitive to certain boundary conditions in the hydrodynamic model, which are correspondent with respective geological features. A new inversion technique coined by the term "hydrological tomography" is therefore developed by reversing the boundary condition into the unknowns to be solved. An example of accurate estimate for water storage and precipitation infiltration of a costal alluvial plain Yun-Lin is presented. In the mean time, the study of an anticline structure of the upstream basin Ming-Ju is also presented to demonstrate how a geological formation is outlined when the gravimetrical data and hydrodynamic model are re-directed into an inversion.

Force-activatable coating enables high-resolution cellular force imaging directly on regular cell culture surfaces.

PubMed

Sarkar, Anwesha; Zhao, Yuanchang; Wang, Yongliang; Wang, Xuefeng

2018-06-25

Integrin-transmitted cellular forces are crucial mechanical signals regulating a vast range of cell functions. Although various methods have been developed to visualize and quantify cellular forces at the cell-matrix interface, a method with high performance and low technical barrier is still in demand. Here we developed a force-activatable coating (FAC), which can be simply coated on regular cell culture apparatus' surfaces by physical adsorption, and turn these surfaces to force reporting platforms that enable cellular force mapping directly by fluorescence imaging. The FAC molecule consists of an adhesive domain for surface coating and a force-reporting domain which can be activated to fluoresce by integrin molecular tension. The tension threshold required for FAC activation is tunable in 10-60 piconewton (pN), allowing the selective imaging of cellular force contributed by integrin tension at different force levels. We tested the performance of two FACs with tension thresholds of 12 and 54 pN (nominal values), respectively, on both glass and polystyrene surfaces. Cellular forces were successfully mapped by fluorescence imaging on all the surfaces. FAC-coated surfaces also enable co-imaging of cellular forces and cell structures in both live cells and immunostained cells, therefore opening a new avenue for the study of the interplay of force and structure. We demonstrated the co-imaging of integrin tension and talin clustering in live cells, and concluded that talin clustering always occurs before the generation of integrin tension above 54 pN, reinforcing the notion that talin is an important adaptor protein for integrin tension transmission. Overall, FAC provides a highly convenient approach that is accessible to general biological laboratories for the study of cellular forces with high sensitivity and resolution, thus holding the potential to greatly boost the research of cell mechanobiology.

The RING finger/B-box factor TAM-1 and a retinoblastoma-like protein LIN-35 modulate context-dependent gene silencing in Caenorhabditis elegans.

PubMed

Hsieh, J; Liu, J; Kostas, S A; Chang, C; Sternberg, P W; Fire, A

1999-11-15

Context-dependent gene silencing is used by many organisms to stably modulate gene activity for large chromosomal regions. We have used tandem array transgenes as a model substrate in a screen for Caenorhabditis elegans mutants that affect context-dependent gene silencing in somatic tissues. This screen yielded multiple alleles of a previously uncharacterized gene, designated tam-1 (for tandem-array-modifier). Loss-of-function mutations in tam-1 led to a dramatic reduction in the activity of numerous highly repeated transgenes. These effects were apparently context dependent, as nonrepetitive transgenes retained activity in a tam-1 mutant background. In addition to the dramatic alterations in transgene activity, tam-1 mutants showed modest alterations in expression of a subset of endogenous cellular genes. These effects include genetic interactions that place tam-1 into a group called the class B synMuv genes (for a Synthetic Multivulva phenotype); this family plays a negative role in the regulation of RAS pathway activity in C. elegans. Loss-of-function mutants in other members of the class-B synMuv family, including lin-35, which encodes a protein similar to the tumor suppressor Rb, exhibit a hypersilencing in somatic transgenes similar to that of tam-1 mutants. Molecular analysis reveals that tam-1 encodes a broadly expressed nuclear protein with RING finger and B-box motifs.

A Cross-Grade Study Validating the Evolutionary Pathway of Student Mental Models in Electric Circuits

ERIC Educational Resources Information Center

Lin, Jing-Wen

2017-01-01

Cross-grade studies are valuable for the development of sequential curriculum. However such studies are time and resource intensive and fail to provide a clear representation to integrate different levels of representational complexity. Lin (Lin, 2006; Lin & Chiu, 2006; Lin, Chiu, & Hsu, 2006) proposed a cladistics approach in conceptual…

Characterization of two Listeria innocua chitinases of different sizes that were expressed in Escherichia coli.

PubMed

Honda, Shotaro; Wakita, Satoshi; Sugahara, Yasusato; Kawakita, Masao; Oyama, Fumitaka; Sakaguchi, Masayoshi

2016-09-01

Two putative chitinase genes, lin0153 and lin1996, from the nonpathogenic bacterium Listeria innocua were expressed in Escherichia coli, and the gene products were characterized. The genes were close homologs of chitinases from the pathogenic bacterium Listeria monocytogenes, in which chitinases and chitin-binding proteins play important roles in pathogenesis in mice-infection models. The purified recombinant enzymes that are different in size, LinChi78 (lin0153 product) and LinChi35 (lin1996 product)-with molecular masses of 82 and 38 kDa, including vector-derived additional sequences, respectively-exhibited optimum catalytic activity under neutral and acidic conditions at 50 °C, respectively, and were stable over broad pH (4-11) and temperature (4-40 °C) ranges. LinChi35 displayed higher k cat and K M values for 4-nitrophenyl N,N-diacetyl-β-D-chitobioside [4NP-(GlcNAc)2] than LinChi78. Both enzymes produced primarily dimers from colloidal chitin as a substrate. However, LinChi78 and LinChi35 could hydrolyze oligomeric substrates in a processive exo- and nonprocessive endo-manner, respectively, and showed different reactivity toward oligomeric substrates. Both enzymes could bind chitin beads but were different in their binding ability toward crystalline α-chitin and cellulose. The structure-function relationships of these chitinases are discussed in reference to other bacterial chitinases.

The N terminus of SKAP55 enables T cell adhesion to TCR and integrin ligands via distinct mechanisms

PubMed Central

Ophir, Michael J.; Liu, Beiyun C.

2013-01-01

The T cell receptor (TCR) triggers the assembly of “SLP-76 microclusters,” which mediate signals required for T cell activation. In addition to regulating integrin activation, we show that Src kinase–associated phosphoprotein of 55 kD (SKAP55) is required for microcluster persistence and movement, junctional stabilization, and integrin-independent adhesion via the TCR. These functions require the dimerization of SKAP55 and its interaction with the adaptor adhesion and degranulation-promoting adaptor protein (ADAP). A “tandem dimer” containing two ADAP-binding SKAP55 Src homology 3 (SH3) domains stabilized SLP-76 microclusters and promoted T cell adhesion via the TCR, but could not support adhesion to integrin ligands. Finally, the SKAP55 dimerization motif (DM) enabled the coimmunoprecipitation of the Rap1-dependent integrin regulator Rap1-GTP–interacting adaptor molecule (RIAM), the recruitment of talin into TCR-induced adhesive junctions, and “inside-out” signaling to β1 integrins. Our data indicate that SKAP55 dimers stabilize SLP-76 microclusters, couple SLP-76 to the force-generating systems responsible for microcluster movement, and enable adhesion via the TCR by mechanisms independent of RIAM, talin, and β1 integrins. PMID:24368808

Selectins and chemokines use shared and distinct signals to activate β2 integrins in neutrophils

PubMed Central

Yago, Tadayuki; Zhang, Nan; Zhao, Liang; Abrams, Charles S.

2018-01-01

Rolling neutrophils receive signals while engaging P- and E-selectin and chemokines on inflamed endothelium. Selectin signaling activates β2 integrins to slow rolling velocities. Chemokine signaling activates β2 integrins to cause arrest. Despite extensive study, key aspects of these signaling cascades remain unresolved. Using complementary in vitro and in vivo assays, we found that selectin and chemokine signals in neutrophils triggered Rap1a-dependent and phosphatidylinositol-4-phosphate 5-kinase γ (PIP5Kγ90)–dependent pathways that induce integrin-dependent slow rolling and arrest. Interruption of both pathways, but not either pathway alone, blocked talin-1 recruitment to and activation of integrins. An isoform of PIP5Kγ90 lacking the talin-binding domain (PIP5Kγ87) could not activate integrins. Chemokines, but not selectins, used phosphatidylinositol-4,5-bisphosphate 3-kinase γ (PI3Kγ) in cooperation with Rap1a to mediate integrin-dependent slow rolling (at low chemokine concentrations), as well as arrest (at high chemokine concentrations). High levels of chemokines activated β2 integrins without selectin signals. When chemokines were limiting, they synergized with selectins to activate β2 integrins. PMID:29592875

Selectins and chemokines use shared and distinct signals to activate β2 integrins in neutrophils.

PubMed

Yago, Tadayuki; Zhang, Nan; Zhao, Liang; Abrams, Charles S; McEver, Rodger P

2018-04-10

Rolling neutrophils receive signals while engaging P- and E-selectin and chemokines on inflamed endothelium. Selectin signaling activates β2 integrins to slow rolling velocities. Chemokine signaling activates β2 integrins to cause arrest. Despite extensive study, key aspects of these signaling cascades remain unresolved. Using complementary in vitro and in vivo assays, we found that selectin and chemokine signals in neutrophils triggered Rap1a-dependent and phosphatidylinositol-4-phosphate 5-kinase γ (PIP5Kγ90)-dependent pathways that induce integrin-dependent slow rolling and arrest. Interruption of both pathways, but not either pathway alone, blocked talin-1 recruitment to and activation of integrins. An isoform of PIP5Kγ90 lacking the talin-binding domain (PIP5Kγ87) could not activate integrins. Chemokines, but not selectins, used phosphatidylinositol-4,5-bisphosphate 3-kinase γ (PI3Kγ) in cooperation with Rap1a to mediate integrin-dependent slow rolling (at low chemokine concentrations), as well as arrest (at high chemokine concentrations). High levels of chemokines activated β2 integrins without selectin signals. When chemokines were limiting, they synergized with selectins to activate β2 integrins. © 2018 by The American Society of Hematology.

Smurf1 inhibits integrin activation by controlling Kindlin-2 ubiquitination and degradation

PubMed Central

Wei, Xiaofan; Wang, Xiang; Zhan, Jun; Chen, Yuhan; Fang, Weigang; Zhang, Lingqiang

2017-01-01

Integrin activation is an indispensable step for various integrin-mediated biological functions. Kindlin-2 is known to coactivate integrins with Talin; however, molecules that restrict integrin activation are elusive. Here, we demonstrate that the E3 ubiquitin ligase Smurf1 controls the amount of Kindlin-2 protein in cells and hinders integrin activation. Smurf1 interacts with and promotes Kindlin-2 ubiquitination and degradation. Smurf1 selectively mediates degradation of Kindlin-2 but not Talin, leading to inhibition of αIIbβ3 integrin activation in Chinese hamster ovary cells and β1 integrin activation in fibroblasts. Enhanced activation of β1 integrin was found in Smurf1-knockout mouse embryonic fibroblasts, which correlates with an increase in Kindlin-2 protein levels. Similarly, a reciprocal relationship between Smurf1 and Kindlin-2 protein levels is found in tissues from colon cancer patients, suggesting that Smurf1 mediates Kindlin-2 degradation in vivo. Collectively, we demonstrate that Smurf1 acts as a brake for integrin activation by controlling Kindlin-2 protein levels, a new mechanism that permits precise modulation of integrin-mediated cellular functions. PMID:28408404

Lin Simpson | NREL

Science.gov Websites

technology areas that included: nanotechnology, nanomaterials, thin-film photovoltaics, thin-film processing , and program management. This includes extensive experience in nanotechnology, materials science

A single mutation in a tunnel to the active site changes the mechanism and kinetics of product release in haloalkane dehalogenase LinB.

PubMed

Biedermannová, Lada; Prokop, Zbyněk; Gora, Artur; Chovancová, Eva; Kovács, Mihály; Damborsky, Jiří; Wade, Rebecca C

2012-08-17

Many enzymes have buried active sites. The properties of the tunnels connecting the active site with bulk solvent affect ligand binding and unbinding and also the catalytic properties. Here, we investigate ligand passage in the haloalkane dehalogenase enzyme LinB and the effect of replacing leucine by a bulky tryptophan at a tunnel-lining position. Transient kinetic experiments show that the mutation significantly slows down the rate of product release. Moreover, the mechanism of bromide ion release is changed from a one-step process in the wild type enzyme to a two-step process in the mutant. The rate constant of bromide ion release corresponds to the overall steady-state turnover rate constant, suggesting that product release became the rate-limiting step of catalysis in the mutant. We explain the experimental findings by investigating the molecular details of the process computationally. Analysis of trajectories from molecular dynamics simulations with a tunnel detection software reveals differences in the tunnels available for ligand egress. Corresponding differences are seen in simulations of product egress using a specialized enhanced sampling technique. The differences in the free energy barriers for egress of a bromide ion obtained using potential of mean force calculations are in good agreement with the differences in rates obtained from the transient kinetic experiments. Interactions of the bromide ion with the introduced tryptophan are shown to affect the free energy barrier for its passage. The study demonstrates how the mechanism of an enzymatic catalytic cycle and reaction kinetics can be engineered by modification of protein tunnels.

Temporal variation and source identification of black carbon at Lin'an and Longfengshan regional background stations in China

NASA Astrophysics Data System (ADS)

Cheng, Siyang; Wang, Yaqiang; An, Xingqin

2017-12-01

Black carbon (BC) is a component of fine particulate matter (PM2.5), associated with climate, weather, air quality, and people's health. However, studies on temporal variation of atmospheric BC concentration at background stations in China and its source area identification are lacking. In this paper, we use 2-yr BC observations from two background stations, Lin'an (LAN) and Longfengshan (LFS), to perform the investigation. The results show that the mean diurnal variation of BC has two significant peaks at LAN while different characteristics are found in the BC variation at LFS, which are probably caused by the difference in emission source contributions. Seasonal variation of monthly BC shows double peaks at LAN but a single peak at LFS. The annual mean concentrations of BC at LAN and LFS decrease by 1.63 and 0.26 μg m-3 from 2009 to 2010, respectively. The annual background concentration of BC at LAN is twice higher than that at LFS. The major source of the LAN BC is industrial emission while the source of the LFS BC is residential emission. Based on transport climatology on a 7-day timescale, LAN and LFS stations are sensitive to surface emissions respectively in belt or approximately circular area, which are dominated by summer monsoon or colder land air flows in Northwest China. In addition, we statistically analyze the BC source regions by using BC observation and FLEXible PARTicle dispersion model (FLEXPART) simulation. In summer, the source regions of BC are distributed in the northwest and south of LAN and the southwest of LFS. Low BC concentration is closely related to air mass from the sea. In winter, the source regions of BC are concentrated in the west and south of LAN and the northeast of the threshold area of s tot at LFS. The cold air mass in the northwest plays an important role in the purification of atmospheric BC. On a yearly scale, sources of BC are approximately from five provinces in the northwest/southeast of LAN and the west of LFS. These

Biochemistry of Microbial Degradation of Hexachlorocyclohexane and Prospects for Bioremediation

PubMed Central

Lal, Rup; Pandey, Gunjan; Sharma, Pooja; Kumari, Kirti; Malhotra, Shweta; Pandey, Rinku; Raina, Vishakha; Kohler, Hans-Peter E.; Holliger, Christof; Jackson, Colin; Oakeshott, John G.

2010-01-01

Summary: Lindane, the γ-isomer of hexachlorocyclohexane (HCH), is a potent insecticide. Purified lindane or unpurified mixtures of this and α-, β-, and δ-isomers of HCH were widely used as commercial insecticides in the last half of the 20th century. Large dumps of unused HCH isomers now constitute a major hazard because of their long residence times in soil and high nontarget toxicities. The major pathway for the aerobic degradation of HCH isomers in soil is the Lin pathway, and variants of this pathway will degrade all four of the HCH isomers although only slowly. Sequence differences in the primary LinA and LinB enzymes in the pathway play a key role in determining their ability to degrade the different isomers. LinA is a dehydrochlorinase, but little is known of its biochemistry. LinB is a hydrolytic dechlorinase that has been heterologously expressed and crystallized, and there is some understanding of the sequence-structure-function relationships underlying its substrate specificity and kinetics, although there are also some significant anomalies. The kinetics of some LinB variants are reported to be slow even for their preferred isomers. It is important to develop a better understanding of the biochemistries of the LinA and LinB variants and to use that knowledge to build better variants, because field trials of some bioremediation strategies based on the Lin pathway have yielded promising results but would not yet achieve economic levels of remediation. PMID:20197499

miR-188 promotes senescence of lineage-negative bone marrow cells by targeting MAP3K3 expression.

PubMed

Zheng, Yue; Liu, Hua; Kong, Ye

2017-08-01

Lineage-negative bone marrow cells (lin-BMCs) have reparative potential for overcoming endothelial dysfunction and reducing cardiovascular risk. Here, we found that miR-188 is upregulated and mitogen-activated protein kinase kinase kinase 3 (MAP3K3) is downregulated in aged lin-BMCs, whereas their expression is reversed in young lin-BMCs. We identified and confirmed MAP3K3 as a direct target of miR-188. MiR-188 overexpression or MAP3K3 silencing in young lin-BMCs increases p16 and p21 expression, enhances cell senescence, and decreases the ability for cell proliferation, migration, and tube formation. Conversely, miR-188 suppression in aged lin-BMCs yields the opposite results. We further found that MAP3K3 is involved in miR-188-induced promotion of lin-BMC senescence. All data reveal that miR-188 induces lin-BMC senescence by targeting MAP3K3 expression, thus, providing new theoretical basis for the prevention and treatment of cardiovascular diseases. © 2017 Federation of European Biochemical Societies.

Taxonomic notes on the armored spiders of the families Pacullidae and Tetrablemmidae (Arachnida, Araneae) from Singapore.

PubMed

Lin, Yucheng; Koh, Joseph K H; Koponen, Seppo; Li, Shuqiang

2017-01-01

Eight species of armored spiders belonging to two families, Pacullidae Simon, 1894 and Tetrablemmidae O. Pickard-Cambridge, 1873, are reported from Singapore. Five species are documented as new to science: Paculla bukittimahensis Lin & Li, sp. n. (male and female), Paculla globosa Lin & Li, sp. n. (male and female), Ablemma malacca Lin & Li, sp. n. (male and female), Singaporemma lenachanae Lin & Li, sp. n. (male and female), and Sulaimania brevis Lin & Li, sp. n. (male). The three known species are Brignoliella besutensis Lin, Li & Jäger, 2012, Brignoliella michaeli Lehtinen, 1981, and Singaporemma singulare Shear, 1978, of which the female of Brignoliella besutensis is described for the first time. For comparison, types of Singaporemma adjacens Lehtinen, 1981 from Vietnam, Singaporemma halongense Lehtinen, 1981 from Vietnam, Singaporemma singulare from Singapore and Sulaimania vigelandi Lehtinen, 1981 from Malaysia are studied and photographed.

Taxonomic notes on the armored spiders of the families Pacullidae and Tetrablemmidae (Arachnida, Araneae) from Singapore

PubMed Central

Lin, Yucheng; Koh, Joseph K. H.; Koponen, Seppo; Li, Shuqiang

2017-01-01

Abstract Eight species of armored spiders belonging to two families, Pacullidae Simon, 1894 and Tetrablemmidae O. Pickard-Cambridge, 1873, are reported from Singapore. Five species are documented as new to science: Paculla bukittimahensis Lin & Li, sp. n. (male and female), Paculla globosa Lin & Li, sp. n. (male and female), Ablemma malacca Lin & Li, sp. n. (male and female), Singaporemma lenachanae Lin & Li, sp. n. (male and female), and Sulaimania brevis Lin & Li, sp. n. (male). The three known species are Brignoliella besutensis Lin, Li & Jäger, 2012, Brignoliella michaeli Lehtinen, 1981, and Singaporemma singulare Shear, 1978, of which the female of Brignoliella besutensis is described for the first time. For comparison, types of Singaporemma adjacens Lehtinen, 1981 from Vietnam, Singaporemma halongense Lehtinen, 1981 from Vietnam, Singaporemma singulare from Singapore and Sulaimania vigelandi Lehtinen, 1981 from Malaysia are studied and photographed. PMID:28769602

Morphological adaptation and protein modulation of myotendinous junction following moderate aerobic training.

PubMed

Curzi, Davide; Baldassarri, Valentina; De Matteis, Rita; Salamanna, Francesca; Bolotta, Alessandra; Frizziero, Antonio; Fini, Milena; Marini, Marina; Falcieri, Elisabetta

2015-04-01

Myotendinous junction is the muscle-tendon interface through which the contractile force can be transferred from myofibrils to the tendon extracellular matrix. At the ultrastructural level, aerobic training can modify the distal myotendinous junction of rat gastrocnemius, increasing the contact area between tissues. The aim of this work is to investigate the correlation between morphological changes and protein modulation of the myotendinous junction following moderate training. For this reason, talin, vinculin and type IV collagen amount and spatial distribution were investigated by immunohistochemistry and confocal microscopy. The images were then digitally analyzed by evaluating fluorescence intensity. Morphometric analysis revealed a significant increased thickening of muscle basal lamina in the trained group (53.1 ± 0.4 nm) with respect to the control group (43.9 ± 0.3 nm), and morphological observation showed the presence of an electron-dense area in the exercised muscles, close to the myotendinous junction. Protein concentrations appeared significantly increased in the trained group (talin +22.2%; vinculin +22.8% and type IV collagen +11.8%) with respect to the control group. Therefore, our findings suggest that moderate aerobic training induces/causes morphological changes at the myotendinous junction, correlated to the synthesis of structural proteins of the muscular basal lamina and of the cytoskeleton.

Remote Field Eddy Curent Signal Modeling for the Gap Measurement of Neighboring Tubes

NASA Astrophysics Data System (ADS)

Jung, H. K.; Lee, D. H.; Lee, Y. S.

2005-04-01

The fuel channels in the Canadian Deuterium Uranium (CANDU) reactor consist of the coaxial pressure tube (PT) and the calandria tube (CT). The Liquid injection nozzle (LIN) is cross aligned with the fuel channel to control the reactor by injecting poison. For a safe operation, the gap between the LIN and CT should be maintained in order to prevent a contact of the neighboring tubes. The remote field eddy current (RFEC) method was applied to measure the gap between a nonmagnetic Zircaloy-2 liquid injection nozzle (LIN) and a Zircaloy-2 calandria tube. Under the condition of inserting the RFEC probe into the coaxial tubes and of crossing a LIN above or under the CT, the modeling of a LIN signal is needed to check the possibility of a gap measurement. The Volume Integral Code S/W which covers the axi-symmetric 3D configuration has been very rarely applied to obtain a LIN signal. This problem was solved by assuming a LIN as a flaw which can be described as a complete 3D object. This simulated LIN signal was verified by performing the laboratory experiment. The gap between the LIN and CT can be correlated with the amplitude of the LIN signals in the voltage plane. Typical noises in the fuel channel were the relative constriction, the change in the pressure tube diameter (fill-factor), thickness variation, and so on. These noise signals were simulated by using the modeling and were analyzed by considering their dependency on the phase angle and amplitude of the voltage plane in order to separate the gap signal from them. It could be concluded that the voltage plane analysis of the simulated RFEC signals were effective for obtaining the gap measurement of the neighboring tube.

Hematopoietic stem cells found in lineage-positive subsets in the bone marrow of 5-fluorouracil-treated mice.

PubMed

Nishi, N; Osawa, M; Ishikawa, R; Nishikawa, M; Tsumura, H; Inoue, H; Sudo, T

1995-09-01

It is known that treatment of mice with 5-fluorouracil (5-FU, 150 mg/kg) confers radioprotection. To investigate this effect, we performed bone marrow transplantation (BMT) using C57BL/6-Ly5 congenic mice treated with 5-FU five days prior to experiments. The mononuclear cells (MNC) in 5-FU-treated bone marrow (BM) were 10 times more radioprotective than those in untreated BM. Moreover, the number of BM MNC expressing c-kit on their surface from 5-FU-treated mice was markedly decreased relative to those from untreated controls. These results showed that the surface characteristics of cells that contributed to this radio-protective effect differ from those of stem cells as reported recently. BM MNC of mice treated with 5-FU were separated on the basis of expression of the lineage-specific antigens (Lin), c-kit, and Ly6A/E. When injected into lethally irradiated mice, 1,000 Lin+ and Lin-c-kit+Ly6A/E+ cells showed radioprotective effects such that 100% and 60% survived, respectively. Flow cytometric analysis 165 days after BMT showed that 88.8% and 65.1% of peripheral blood (PB) in mice transplanted with Lin+ and Lin-c-kit+Ly6A/E+ was derived from donor mice, respectively. After six months, donor-derived Lin-c-kit+Ly6A/E+ cells which showed radioprotective effects on a secondary irradiated host were detected from mice transplanted with Lin+ cells from 5-FU-treated mice. Taken together, these findings demonstrated that stem cells expressing Lin+ present in the BM of mice treated with 5-FU other than Lin-c-kit+Ly6A/E+ cells and these Lin+ cells play an important role in the recovery of myeloablative mice.

Selection based on CD133 and high aldehyde dehydrogenase activity isolates long-term reconstituting human hematopoietic stem cells

PubMed Central

Hess, David A.; Wirthlin, Louisa; Craft, Timothy P.; Herrbrich, Phillip E.; Hohm, Sarah A.; Lahey, Ryan; Eades, William C.; Creer, Michael H.; Nolta, Jan A.

2006-01-01

The development of novel cell-based therapies requires understanding of distinct human hematopoietic stem and progenitor cell populations. We recently isolated reconstituting hematopoietic stem cells (HSCs) by lineage depletion and purification based on high aldehyde dehydrogenase activity (ALDHhiLin- cells). Here, we further dissected the ALDHhi-Lin- population by selection for CD133, a surface molecule expressed on progenitors from hematopoietic, endothelial, and neural lineages. ALDHhiCD133+Lin- cells were primarily CD34+, but also included CD34-CD38-CD133+ cells, a phenotype previously associated with repopulating function. Both ALDHhiCD133-Lin- and ALDHhiCD133+Lin- cells demonstrated distinct clonogenic progenitor function in vitro, whereas only the ALDHhiCD133+Lin- population seeded the murine bone marrow 48 hours after transplantation. Significant human cell repopulation was observed only in NOD/SCID and NOD/SCID β2M-null mice that received transplants of ALDHhiCD133+Lin- cells. Limiting dilution analysis demonstrated a 10-fold increase in the frequency of NOD/SCID repopulating cells compared with CD133+Lin- cells, suggesting that high ALDH activity further purified cells with repopulating function. Transplanted ALDHhiCD133+Lin- cells also maintained primitive hematopoietic phenotypes (CD34+CD38-) and demonstrated enhanced repopulating function in recipients of serial, secondary transplants. Cell selection based on ALDH activity and CD133 expression provides a novel purification of HSCs with long-term repopulating function and may be considered an alternative to CD34 cell selection for stem cell therapies. PMID:16269619

The pedagogical value of a student-run community-based experiential learning project: The Yong Loo Lin School of Medicine Public Health Screening.

PubMed

Wee, Liang En; Yeo, Wei Xin; Tay, Clifton M; Lee, Jeannette J M; Koh, Gerald C H

2010-09-01

We assessed the pedagogical value of a student-led community-based experiential learning project called the Public Health Screening (PHS) run by medical and nursing students of the National University of Singapore's Yong Loo Lin School of Medicine (NUS YLLSoM). We conducted a cross-sectional study using a self-administered anonymised questionnaire on medical and nursing students who participated in PHS using the Fund for the Improvement of Postsecondary Education (FIPSE) Survey Instrument. Participants also gave an overall score for their learning experience at the PHS. The participation rate was 93.1% (576/619) for medical students and 100% (37/37) for nursing students. All participants gave the PHS learning experience a high rating (median = 8 out of maximum of 10, inter-quartile range, 7 to 9). A majority of participants felt that PHS had helped them to improve across all domains surveyed. For medical students, those in preclinical years and females were independently more likely to feel that PHS had helped them to improve in communication skills, teamwork, ability to identify social issues, taking action, and gaining and applying their knowledge than those in clinical years and males. Improved ability to interact with patients (β=1.64, 95%CI, 1.01-2.27), appreciation of challenges to healthcare faced by Singaporeans from lower income groups (β=0.93, 95%CI, 0.49-1.37), thinking of others (β=0.70, 95%CI, 0.04-1.37) and tolerance of different people (β =0.63, 95%CI, 0.17-1.10) were strongly associated with the overall rating score. PHS was a positive learning experience in a wide range of domains for all students involved. This suggests that student-organised community-based experiential learning projects have potential educational value for both medical and nursing students.

Planning by Using Digital Technology in the Reconstruction of Cultural Heritage Sites - a Case Study of Qiong-Lin Settlement in Kinmen Area

NASA Astrophysics Data System (ADS)

Yang, W. B.; Ye, Y. N.

2017-08-01

ICOMOS Florence Declaration in 2014, encourages an in-depth reflection on human values through cultural heritage and landscapes, which emphasizes the importance of historical heritage sites, in order to achieve the application of cultural heritage records through the public participation, sharing new technology platform and facilitation tools for knowledge diffusion, for instance. Nikos adopted digitized intangible cultural heritage within i-Treasures project to create a novel digital platform in 2016. Nowadays, the display platform developed based on geographic information system has been gradually accepted and widely used to distribute cultural heritage information, aiming to combine geography, time, events, issues, trends with the interactive maps to show the context of data changes from the consideration of planarity; for example, Burnaby City in Canada has cooperated with the Columbia University to create a navigation platform for guidance of tangible cultural heritage based on story maps in order to provide public recognition function. In this study, Qiong-Lin Settlement in Kinmen Area was taken as an example to illustrate the developing process of an overall planning framework for reappearing the glory of historic settlements of cultural heritage sites with digital technology, which included tangible and intangible cultural heritage preservation and transmission planning, community participation and digital navigation programs. The digital technology with the GIS-based digital platform can provide more diverse and interesting information while using an intuitive, graphical user story mapping interface. So that tangible cultural heritage can be effectively understood, interpreted and preserved with the value-added methods, and also intangible cultural heritage can be continuously transmitted to establish a complete system of cultural heritage preservation. The main contents include several navigation technologies, such as 3D laser scanning, UAV images

Silicon Nanotips and Related Nano-Systems Involving Fluid and Carrier Transport and Their Micro-Devices for Power and Sensing Applications

DTIC Science & Technology

2011-05-10

Methanol’, Chien-Cheng Li, Ran-Jin Lin, Hong-Ping Lin, Ching-Chun Chang, Yu - Kai Lin, Li-Chyong Chen*, Kuei-Hsien Chen*, Chem. Comm. 47, 1473 (2011). (5...CuO-ZnO Inverse Opals as High-performance Methanol Microreformer’, Yan-Gu Lin, Yu -Kuei Hsu, San-Yuan Chen, Li-Chyong Chen* and Kuei-Hsien Chen*, J...Chun Lo, Hsin-I Hsiung, Surojit Chattopadhyay*, Hsieh -Cheng Han, Chia-Fu Chen*, Jih Perng Leu, Kuei-Hsien Chen and Li-Chyong Chen*, Biosens

BRMS1 Suppresses Breast Cancer Metastasis to Bone via Its Regulation of microRNA-125b and Downstream Attenuation of TNF-Alpha and HER2 Signaling Pathways

DTIC Science & Technology

2014-04-01

cytoskeleton genes and genes regulating focal adhesion assembly, such as a5 integrin, Tenascin C, Talin-1, Profilin 1, and Actinin [35]. Intravital ...and allowed to adhere for time indicated, at which point cells were fixed and stainedwith crystal violet. Representative images for times 5, 10, 15...matrix milieu and imaged by time-lapse microscopy for 1 h or fixed and stained with crystal violet at times indicated. As shown in Figure 1C and

Comparative genomic analysis of nine Sphingobium strains: Insights into their evolution and hexachlorocyclohexane (HCH) degradation pathways

DOE PAGES

Verma, Helianthous; Kumar, Roshan; Oldach, Phoebe; ...

2014-11-23

Background: Sphingobium spp. are efficient degraders of a wide range of chlorinated and aromatic hydrocarbons. In particular, strains which harbour the lin pathway genes mediating the degradation of hexachlorocyclohexane (HCH) isomers are of interest due to the widespread persistence of this contaminant. Here, we examined the evolution and diversification of the lin pathway under the selective pressure of HCH, by comparing the draft genomes of six newly-sequenced Sphingobium spp. (strains LL03, DS20, IP26, HDIPO4, P25 and RL3) isolated from HCH dumpsites, with three existing genomes ( S. indicum B90A, S. japonicum UT26S and Sphingobium sp. SYK6). Results: Efficient HCH degradersmore » phylogenetically clustered in a closely related group comprising of UT26S, B90A, HDIPO4 and IP26, where HDIPO4 and IP26 were classified as subspecies with ANI value >98%. Less than 10% of the total gene content was shared among all nine strains, but among the eight HCH-associated strains, that is all except SYK6, the shared gene content jumped to nearly 25%. Genes associated with nitrogen stress response and two-component systems were found to be enriched. The strains also housed many xenobiotic degradation pathways other than HCH, despite the absence of these xenobiotics from isolation sources. In addition, these strains, although non-motile, but posses flagellar assembly genes. While strains HDIPO4 and IP26 contained the complete set of lin genes, DS20 was entirely devoid of lin genes (except linKLMN) whereas, LL03, P25 and RL3 were identified as lin deficient strains, as they housed incomplete lin pathways. Further, in HDIPO4, linA was found as a hybrid of two natural variants i.e., linA1 and linA2 known for their different enantioselectivity. In conclusion, the bacteria isolated from HCH dumpsites provide a natural testing ground to study variations in the lin system and their effects on degradation efficacy. Further, the diversity in the lin gene sequences and copy number

Comparison of the complete genome sequences of four γ-hexachlorocyclohexane-degrading bacterial strains: insights into the evolution of bacteria able to degrade a recalcitrant man-made pesticide.

PubMed

Tabata, Michiro; Ohhata, Satoshi; Nikawadori, Yuki; Kishida, Kouhei; Sato, Takuya; Kawasumi, Toru; Kato, Hiromi; Ohtsubo, Yoshiyuki; Tsuda, Masataka; Nagata, Yuji

2016-12-01

γ-Hexachlorocyclohexane (γ-HCH) is a recalcitrant man-made chlorinated pesticide. Here, the complete genome sequences of four γ-HCH-degrading sphingomonad strains, which are most unlikely to have been derived from one ancestral γ-HCH degrader, were compared. Together with several experimental data, we showed that (i) all the four strains carry almost identical linA to linE genes for the conversion of γ-HCH to maleylacetate (designated "specific" lin genes), (ii) considerably different genes are used for the metabolism of maleylacetate in one of the four strains, and (iii) the linKLMN genes for the putative ABC transporter necessary for γ-HCH utilization exhibit structural divergence, which reflects the phylogenetic relationship of their hosts. Replicon organization and location of the lin genes in the four genomes are significantly different with one another, and that most of the specific lin genes are located on multiple sphingomonad-unique plasmids. Copies of IS6100, the most abundant insertion sequence in the four strains, are often located in close proximity to the specific lin genes. Analysis of the footprints of target duplication upon IS6100 transposition and the experimental detection of IS6100 transposition strongly suggested that the IS6100 transposition has caused dynamic genome rearrangements and the diversification of lin-flanking regions in the four strains. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

An AGEF-1/Arf GTPase/AP-1 Ensemble Antagonizes LET-23 EGFR Basolateral Localization and Signaling during C. elegans Vulva Induction

PubMed Central

Skorobogata, Olga; Escobar-Restrepo, Juan M.; Rocheleau, Christian E.

2014-01-01

LET-23 Epidermal Growth Factor Receptor (EGFR) signaling specifies the vulval cell fates during C. elegans larval development. LET-23 EGFR localization on the basolateral membrane of the vulval precursor cells (VPCs) is required to engage the LIN-3 EGF-like inductive signal. The LIN-2 Cask/LIN-7 Veli/LIN-10 Mint (LIN-2/7/10) complex binds LET-23 EGFR, is required for its basolateral membrane localization, and therefore, vulva induction. Besides the LIN-2/7/10 complex, the trafficking pathways that regulate LET-23 EGFR localization have not been defined. Here we identify vh4, a hypomorphic allele of agef-1, as a strong suppressor of the lin-2 mutant Vulvaless (Vul) phenotype. AGEF-1 is homologous to the mammalian BIG1 and BIG2 Arf GTPase guanine nucleotide exchange factors (GEFs), which regulate secretory traffic between the Trans-Golgi network, endosomes and the plasma membrane via activation of Arf GTPases and recruitment of the AP-1 clathrin adaptor complex. Consistent with a role in trafficking we show that AGEF-1 is required for protein secretion and that AGEF-1 and the AP-1 complex regulate endosome size in coelomocytes. The AP-1 complex has previously been implicated in negative regulation of LET-23 EGFR, however the mechanism was not known. Our genetic data indicate that AGEF-1 is a strong negative regulator of LET-23 EGFR signaling that functions in the VPCs at the level of the receptor. In line with AGEF-1 being an Arf GEF, we identify the ARF-1.2 and ARF-3 GTPases as also negatively regulating signaling. We find that the agef-1(vh4) mutation results in increased LET-23 EGFR on the basolateral membrane in both wild-type and lin-2 mutant animals. Furthermore, unc-101(RNAi), a component of the AP-1 complex, increased LET-23 EGFR on the basolateral membrane in lin-2 and agef-1(vh4); lin-2 mutant animals. Thus, an AGEF-1/Arf GTPase/AP-1 ensemble functions opposite the LIN-2/7/10 complex to antagonize LET-23 EGFR basolateral membrane localization and signaling

An AGEF-1/Arf GTPase/AP-1 ensemble antagonizes LET-23 EGFR basolateral localization and signaling during C. elegans vulva induction.

PubMed

Skorobogata, Olga; Escobar-Restrepo, Juan M; Rocheleau, Christian E

2014-10-01

LET-23 Epidermal Growth Factor Receptor (EGFR) signaling specifies the vulval cell fates during C. elegans larval development. LET-23 EGFR localization on the basolateral membrane of the vulval precursor cells (VPCs) is required to engage the LIN-3 EGF-like inductive signal. The LIN-2 Cask/LIN-7 Veli/LIN-10 Mint (LIN-2/7/10) complex binds LET-23 EGFR, is required for its basolateral membrane localization, and therefore, vulva induction. Besides the LIN-2/7/10 complex, the trafficking pathways that regulate LET-23 EGFR localization have not been defined. Here we identify vh4, a hypomorphic allele of agef-1, as a strong suppressor of the lin-2 mutant Vulvaless (Vul) phenotype. AGEF-1 is homologous to the mammalian BIG1 and BIG2 Arf GTPase guanine nucleotide exchange factors (GEFs), which regulate secretory traffic between the Trans-Golgi network, endosomes and the plasma membrane via activation of Arf GTPases and recruitment of the AP-1 clathrin adaptor complex. Consistent with a role in trafficking we show that AGEF-1 is required for protein secretion and that AGEF-1 and the AP-1 complex regulate endosome size in coelomocytes. The AP-1 complex has previously been implicated in negative regulation of LET-23 EGFR, however the mechanism was not known. Our genetic data indicate that AGEF-1 is a strong negative regulator of LET-23 EGFR signaling that functions in the VPCs at the level of the receptor. In line with AGEF-1 being an Arf GEF, we identify the ARF-1.2 and ARF-3 GTPases as also negatively regulating signaling. We find that the agef-1(vh4) mutation results in increased LET-23 EGFR on the basolateral membrane in both wild-type and lin-2 mutant animals. Furthermore, unc-101(RNAi), a component of the AP-1 complex, increased LET-23 EGFR on the basolateral membrane in lin-2 and agef-1(vh4); lin-2 mutant animals. Thus, an AGEF-1/Arf GTPase/AP-1 ensemble functions opposite the LIN-2/7/10 complex to antagonize LET-23 EGFR basolateral membrane localization and signaling.

Smart Methods for Linezolid Determination in the Presence of Alkaline and Oxidative Degradation Products Utilizing Their Overlapped Spectral Bands

NASA Astrophysics Data System (ADS)

Abd El-Monem Hegazy, M.; Shaaban Eissa, M.; Abd El-Sattar, O. I.; Abd El-Kawy, M. M.

2014-09-01

Linezolid (LIN) is considered the first available oxazolidinone antibacterial agent. It is susceptible to hydrolysis and oxidation. Five simple, accurate, sensitive and validated UV spectrophotometric methods were developed for LIN determination in the presence of its alkaline (ALK) and oxidative (OXD) degradation products in bulk powder and pharmaceutical formulation. Method A is a second derivative one (D2) in which LIN is determined at 240.9 nm. Method B is a pH-induced differential derivative one where LIN is determined using the fourth derivative (D4) of the difference spectra (ΔA) at 285.3 nm. Methods C, D, and E are manipulating ratio spectra, where C is the double divisor-ratio difference spectrophotometric one (DD-RD) in which LIN was determined by calculating the amplitude difference at 243.7 and 267.6 nm of the ratio spectra. Method D is the double divisor-first derivative of ratio spectra (DD-DD1) in which LIN was determined at 270.2 nm. Method E is a mean centering of ratio spectra one (MCR) in which LIN was determined at 318.0 nm. The developed methods have been validated according to ICH guidelines. The results were statistically compared to that of a reported HPLC method and there was no significant difference regarding both accuracy and precision.

Caenorhabditis elegans histone deacetylase hda-1 is required for morphogenesis of the vulva and LIN-12/Notch-mediated specification of uterine cell fates.

PubMed

Ranawade, Ayush Vasant; Cumbo, Philip; Gupta, Bhagwati P

2013-08-07

Chromatin modification genes play crucial roles in development and disease. In Caenorhabditis elegans, the class I histone deacetylase family member hda-1, a component of the nucleosome remodeling and deacetylation complex, has been shown to control cell proliferation. We recovered hda-1 in an RNA interference screen for genes involved in the morphogenesis of the egg-laying system. We found that hda-1 mutants have abnormal vulva morphology and vulval-uterine connections (i.e., no uterine-seam cell). We characterized the vulval defects by using cell fate-specific markers and found that hda-1 is necessary for the specification of all seven vulval cell types. The analysis of the vulval-uterine connection defect revealed that hda-1 is required for the differentiation of the gonadal anchor cell (AC), which in turn induces ventral uterine granddaughters to adopt π fates, leading to the formation of the uterine-seam cell. Consistent with these results, hda-1 is expressed in the vulva and AC. A search for hda-1 target genes revealed that fos-1 (fos proto-oncogene family) acts downstream of hda-1 in vulval cells, whereas egl-43 (evi1 proto-oncogene family) and nhr-67 (tailless homolog, NHR family) mediate hda-1 function in the AC. Furthermore, we showed that AC expression of hda-1 plays a crucial role in the regulation of the lin-12/Notch ligand lag-2 to specify π cell fates. These results demonstrate the pivotal role of hda-1 in the formation of the vulva and the vulval-uterine connection. Given that hda-1 homologs are conserved across the phyla, our findings are likely to provide a better understanding of HDAC1 function in development and disease.

Caenorhabditis elegans Histone Deacetylase hda-1 Is Required for Morphogenesis of the Vulva and LIN-12/Notch-Mediated Specification of Uterine Cell Fates

PubMed Central

Ranawade, Ayush Vasant; Cumbo, Philip; Gupta, Bhagwati P.

2013-01-01

Chromatin modification genes play crucial roles in development and disease. In Caenorhabditis elegans, the class I histone deacetylase family member hda-1, a component of the nucleosome remodeling and deacetylation complex, has been shown to control cell proliferation. We recovered hda-1 in an RNA interference screen for genes involved in the morphogenesis of the egg-laying system. We found that hda-1 mutants have abnormal vulva morphology and vulval-uterine connections (i.e., no uterine-seam cell). We characterized the vulval defects by using cell fate-specific markers and found that hda-1 is necessary for the specification of all seven vulval cell types. The analysis of the vulval-uterine connection defect revealed that hda-1 is required for the differentiation of the gonadal anchor cell (AC), which in turn induces ventral uterine granddaughters to adopt π fates, leading to the formation of the uterine-seam cell. Consistent with these results, hda-1 is expressed in the vulva and AC. A search for hda-1 target genes revealed that fos-1 (fos proto-oncogene family) acts downstream of hda-1 in vulval cells, whereas egl-43 (evi1 proto-oncogene family) and nhr-67 (tailless homolog, NHR family) mediate hda-1 function in the AC. Furthermore, we showed that AC expression of hda-1 plays a crucial role in the regulation of the lin-12/Notch ligand lag-2 to specify π cell fates. These results demonstrate the pivotal role of hda-1 in the formation of the vulva and the vulval-uterine connection. Given that hda-1 homologs are conserved across the phyla, our findings are likely to provide a better understanding of HDAC1 function in development and disease. PMID:23797102

Significance of lobular intraepithelial neoplasia at margins of breast conservation specimens: a report of 38 cases and literature review

PubMed Central

2010-01-01

Background Presence of lobular intraepithelial neoplasia (LIN) is not routinely reported as part of margin assessment in breast conservation therapy (BCT) as in ductal carcinoma in situ (DCIS). With new emerging evidence of LIN as possible precursor lesion, the hypothesis is that LIN at the margin may increase the risk of local recurrence with BCT. The aim is to determine whether there is an increase incidence of recurrence when LIN is found at surgical margins on BCT. Methods We retrospectively reviewed a total of 1,334 BCT at a single institution in a 10 year period. Inclusion criteria are positive margin with LIN from primary BCT containing invasive and/or in situ carcinoma with comparison to the negative control group who had similar diseases with negative margin for LIN. Results We identified 38 cases (2.8%) with LIN either lobular carcinoma in situ/atypical lobular hyperplasia (LCIS/ALH) at a margin on initial BCT with 36% recurrence rate. Of the 38 cases: 5 (13%) were lost to follow-up, 12 (32%) had no further procedures performed and 21 (55%) had re-excision. Out of 21 patients who had re-excisions, 12 (57%) had residual invasive carcinoma or DCIS, three (14%) had pleomorphic LCIS and 4 (19%) showed residual classic type LCIS. 71% had significant residual disease (local recurrence) and 29% had no residual disease. A negative control group consisted of 38 cases. We found two patients with bone or brain metastasis and one local recurrence. Clinical follow up periods range from 1 to 109 months. Conclusions LIN found at a margin on BCT showed a significant recurrent ipsilateral disease. Our study supports the view that LIN seen at the margin may play a role in recurrence. PMID:20727142

A Collection of Selected Papers from the Third All-China Electroemissions Technology Conference 21-25 May 1990 (Selected Pages)

DTIC Science & Technology

1991-03-21

FIM and Ni-Cr Alloy Microstructures (Ren 9:10 D3 Research on AP-FIM and Element Distribution in Ni-Al Alloy ( Sun Jia(unclear)yan and Ren Dagang...Accumulated Si02(unclear) Thin Membrane Research (Jing J h a sun Qing) ........................ 11:30 E9 Percolation Mechanisms of Electrical...Tunnel Structures ( Sun Chengjie, Liu Kelin, and Gao Zhonglin) ............. . 48 10:10 Break 10:30 F6 Research on a New Type of Noncry-taline Semiconductor

BRMS1 Suppresses Breast Cancer Metastasis to Bone via Its Regulation of MicroRNA-125b and Downstream Attenuation of TNF-alpha and HER2 Signaling Pathways

DTIC Science & Technology

2013-10-01

genes regulating focal adhesion assembly, such as a5 integrin, Tenascin C, Talin-1, Profilin 1, and Actinin [35]. Intravital microscopy had shown...adhere for time indicated, at which point cells were fixed and stainedwith crystal violet. Representative images for times 5, 10, 15, 30, and 60 min... imaged by time-lapse microscopy for 1 h or fixed and stained with crystal violet at times indicated. As shown in Figure 1C and quantified in Figure 1D

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

Zhao, Chen; Tao, Zui; Xue, Langyue

In lower-order vertebrates, Müller glia exhibit characteristics of retinal progenitor cells, while in higher vertebrates, such as mammals, the regenerative capacity of Müller glia is limited. Recently, we reported that Lin28b promoted the trans-differentiation of Müller cells to rod photoreceptor and bipolar cells in the retina of retinitis pigmentosa rat model, whereas it is unclear whether Lin28b can stimulate the reprogramming of Müller glia in vitro for transplantation into a damaged retina. In the present study, Long-Evens rat Müller glia were infected with Adeno-Lin28b or Adeno-GFP. Over-expression of Lin28b in isolated rat Müller glia resulted in the suppression of GFAP expression,more » enhancement of cell proliferation and a significant increase of the expression of retinal progenitor markers 5 days after infection. Moreover, Lin28b caused a significant reduction of the Let-7 family of microRNAs. Following sub-retinal space transplantation, Müller glia-derived retinal progenitors improved b-wave amplification of 30d Royal College of Surgeons retinitis pigmentosa model (RCS-P+) rats, as detected by electroretinography (ERG) recordings. Taken together, these data suggest that the up-regulation of Lin28b expression facilitated the reprogramming of Müller cells toward characteristics of retinal progenitors. - Highlights: • Lin28b reprograms Müller glia to retinal progenitors. • Let-7 micrRNAs are suppressed by Lin28b. • Transplantation of reprogrammed Müller glia restores retinal function.« less

Development of the Lupus Interactive Navigator as an Empowering Web-Based eHealth Tool to Facilitate Lupus Management: Users Perspectives on Usability and Acceptability.

PubMed

Neville, Carolyn; Da Costa, Deborah; Rochon, Murray; Peschken, Christine A; Pineau, Christian A; Bernatsky, Sasha; Keeling, Stephanie; Avina-Zubieta, Antonio; Lye, Elizabeth; Eng, Davy; Fortin, Paul R

2016-05-30

Systemic Lupus Erythematosus (SLE) is a serious, complex, and chronic illness. Similar to most other chronic illness states, there is great interest in helping persons with SLE engage in their disease management. The objectives of this study were to (1) develop the Lupus Interactive Navigator (LIN), a web-based self-management program for persons with SLE, and (2) test the LIN for usability and acceptability. The LIN development platform was based on the results of preliminary comprehensive needs assessments and adapted from the Oncology Interactive Navigator, a web-based tool developed for persons with cancer. Medical researchers, writers, designers, and programmers worked with clinical experts and persons with SLE to develop content for the LIN. Usability and acceptability of the LIN was tested on individuals with SLE meeting American College of Rheumatology criteria, who were recruited from five Canadian SLE clinics. Participants were provided with access to the LIN and were asked to use it over a two-week period. Following the testing period, participants were contacted for a 30-minute telephone interview to assess usability and acceptability. The content for the LIN was subdivided into six primary information topics with interview videos featuring rheumatologists, allied health professionals, and persons with SLE. Usability and acceptability of the LIN was tested on 43 females with SLE. Of these, 37 (86%) completed telephone interviews. The average age was 43.6 (SD 15.9) years and disease duration averaged 14.1 (SD 10.8) years. Median time spent on LIN was 16.3 (interquartile range [IQR]:13.7, 53.5) minutes and median number of sessions was 2 (IQR: 1, 3). Overall, Likert ratings (0=strongly disagree; 7=strongly agree) of website usability and content were very high, with 75% scoring >6 out of 7 on all items. All participants agreed that LIN was easy to use, would recommend it to others with SLE, and would refer to it for future questions about SLE. Very high

Taxonomic review of the plant bug subfamily Isometopinae for Taiwan and Japanese Southwest Islands, with descriptions of new taxa (Hemiptera: Heteroptera: Miridae: Isometopinae).

PubMed

Yasunaga, Tomohide; Yamada, Kazutaka; Tsai, Jing-Fu

2017-12-19

The fauna of plant bug subfamily Isometopinae in Taiwan and Japanese Southwest (Nansei) Islands is reviewed. Twenty-five species are recognized, including two new species of Myiomma Puton, M. austroccidens sp. nov. and M. kentingense sp. nov., which are herein diagnosed and described. In addition, Isometopus yehi Lin, 2004 is synonymized with I. bipunctatus Lin; Isometopidea yangi Lin is transferred to Kohnometopus; and a substitute name, Alcecoris linyangorum, is proposed for A. formosanus (Lin Yang) (= a junior secondary homonym of Alcecoris formosanus Lin). An annotated checklist, with updated distributional record and biological information, is provided for all treated taxa. A new tribe Sophianini is proposed for two genera, Alcecoris and Sophianus, characterized principally by the conspicuously modified antennal structures. An additional new species, Alcecoris cochlearatus sp. nov., found during examination of related Oriental specimens, is described from the Malay Peninsula.

Focal adhesion kinase is required for actin polymerization and remodeling of the cytoskeleton during sperm capacitation

PubMed Central

Roa-Espitia, Ana L.; Hernández-Rendón, Eva R.; Baltiérrez-Hoyos, Rafael; Muñoz-Gotera, Rafaela J.; Cote-Vélez, Antonieta; Jiménez, Irma; González-Márquez, Humberto

2016-01-01

ABSTRACT Several focal adhesion proteins are known to cooperate with integrins to link the extracellular matrix to the actin cytoskeleton; as a result, many intracellular signaling pathways are activated and several focal adhesion complexes are formed. However, how these proteins function in mammalian spermatozoa remains unknown. We confirm the presence of focal adhesion proteins in guinea pig spermatozoa, and we explore their role during capacitation and the acrosome reaction, and their relationship with the actin cytoskeleton. Our results suggest the presence of a focal adhesion complex formed by β1-integrin, focal adhesion kinase (FAK), paxillin, vinculin, talin, and α-actinin in the acrosomal region. Inhibition of FAK during capacitation affected the protein tyrosine phosphorylation associated with capacitation that occurs within the first few minutes of capacitation, which caused the acrosome reaction to become increasingly Ca2+ dependent and inhibited the polymerization of actin. The integration of vinculin and talin into the complex, and the activation of FAK and paxillin during capacitation, suggests that the complex assembles at this time. We identify that vinculin and α-actinin increase their interaction with F-actin while it remodels during capacitation, and that during capacitation focal adhesion complexes are structured. FAK contributes to acrosome integrity, likely by regulating the polymerization and the remodeling of the actin cytoskeleton. PMID:27402964

Diamagnetic levitation causes changes in the morphology, cytoskeleton, and focal adhesion proteins expression in osteocytes.

PubMed

Qian, A R; Wang, L; Gao, X; Zhang, W; Hu, L F; Han, J; Li, J B; Di, S M; Shang, Peng

2012-01-01

Diamagnetic levitation technology is a novel simulated weightless technique and has recently been applied in life-science research. We have developed a superconducting magnet platform with large gradient high magnetic field (LG-HMF), which can provide three apparent gravity levels, namely, μg (diamagnetic levitation), 1g, and 2g for diamagnetic materials. In this study, the effects of LG-HMF on the activity, morphology, and cytoskeleton (actin filament, microtubules, and vimentin intermediate filaments) in osteocyte - like cell line MLO-Y4 were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) methods, hematoxylin-eosin (HE) staining, and laser scanning confocal microscopy (LSCM), respectively. The changes induced by LG-HMF in distribution and expression of focal adhesion (FA) proteins, including vinculin, paxillin, and talin in MLO-Y4 were determined by LSCM and Western blotting. The results showed that LG-HMF produced by superconducting magnet had no lethal effects on MLO-Y4. Compared to control, diamagnetic levitation (μg) affected MLO-Y4 morphology, nucleus size, cytoskeleton architecture, and FA proteins distribution and expression. The study indicates that osteocytes are sensitive to altered gravity and FA proteins (vinculin, paxillin, and talin) may be involved in osteocyte mechanosensation. The diamagnetic levitation may be a novel ground-based space-gravity simulator and can be used for biological experiment at cellular level. © 2011 IEEE

Stress Survival Islet 2, Predominantly Present in Listeria monocytogenes Strains of Sequence Type 121, Is Involved in the Alkaline and Oxidative Stress Responses

PubMed Central

Harter, Eva; Wagner, Eva Maria; Zaiser, Andreas; Halecker, Sabrina; Wagner, Martin

2017-01-01

ABSTRACT The foodborne pathogen Listeria monocytogenes is able to survive a variety of stress conditions leading to the colonization of different niches like the food processing environment. This study focuses on the hypervariable genetic hot spot lmo0443 to lmo0449 haboring three inserts: the stress survival islet 1 (SSI-1), the single-gene insert LMOf2365_0481, and two homologous genes of the nonpathogenic species Listeria innocua: lin0464, coding for a putative transcriptional regulator, and lin0465, encoding an intracellular PfpI protease. Our prevalence study revealed a different distribution of the inserts between human and food-associated isolates. The lin0464-lin0465 insert was predominantly found in food-associated strains of sequence type 121 (ST121). Functional characterization of this insert showed that the putative PfpI protease Lin0465 is involved in alkaline and oxidative stress responses but not in acidic, gastric, heat, cold, osmotic, and antibiotic stresses. In parallel, deletion of lin0464 decreased survival under alkaline and oxidative stresses. The expression of both genes increased significantly under oxidative stress conditions independently of the alternative sigma factor σB. Furthermore, we showed that the expression of the protease gene lin0465 is regulated by the transcription factor lin0464 under stress conditions, suggesting that lin0464 and lin0465 form a functional unit. In conclusion, we identified a novel stress survival islet 2 (SSI-2), predominantly present in L. monocytogenes ST121 strains, beneficial for survival under alkaline and oxidative stresses, potentially supporting adaptation and persistence of L. monocytogenes in food processing environments. IMPORTANCE Listeria monocytogenes strains of ST121 are known to persist for months and even years in food processing environments, thereby increasing the risk of food contamination and listeriosis. However, the molecular mechanism underlying this remarkable niche

Stress Survival Islet 2, Predominantly Present in Listeria monocytogenes Strains of Sequence Type 121, Is Involved in the Alkaline and Oxidative Stress Responses.

PubMed

Harter, Eva; Wagner, Eva Maria; Zaiser, Andreas; Halecker, Sabrina; Wagner, Martin; Rychli, Kathrin

2017-08-15

The foodborne pathogen Listeria monocytogenes is able to survive a variety of stress conditions leading to the colonization of different niches like the food processing environment. This study focuses on the hypervariable genetic hot spot lmo0443 to lmo0449 haboring three inserts: the stress survival islet 1 (SSI-1), the single-gene insert LMOf2365_0481 , and two homologous genes of the nonpathogenic species Listeria innocua : lin0464 , coding for a putative transcriptional regulator, and lin0465 , encoding an intracellular PfpI protease. Our prevalence study revealed a different distribution of the inserts between human and food-associated isolates. The lin0464-lin0465 insert was predominantly found in food-associated strains of sequence type 121 (ST121). Functional characterization of this insert showed that the putative PfpI protease Lin0465 is involved in alkaline and oxidative stress responses but not in acidic, gastric, heat, cold, osmotic, and antibiotic stresses. In parallel, deletion of lin0464 decreased survival under alkaline and oxidative stresses. The expression of both genes increased significantly under oxidative stress conditions independently of the alternative sigma factor σ B Furthermore, we showed that the expression of the protease gene lin0465 is regulated by the transcription factor lin0464 under stress conditions, suggesting that lin0464 and lin0465 form a functional unit. In conclusion, we identified a novel stress survival islet 2 (SSI-2), predominantly present in L. monocytogenes ST121 strains, beneficial for survival under alkaline and oxidative stresses, potentially supporting adaptation and persistence of L. monocytogenes in food processing environments. IMPORTANCE Listeria monocytogenes strains of ST121 are known to persist for months and even years in food processing environments, thereby increasing the risk of food contamination and listeriosis. However, the molecular mechanism underlying this remarkable niche-specific adaptation

Beta-cyclodextrin enhanced gastroprotective effect of (-)-linalool, a monoterpene present in rosewood essential oil, in gastric lesion models.

PubMed

da Silva, Francilene Vieira; de Barros Fernandes, Hélio; Oliveira, Irisdalva Sousa; Viana, Ana Flávia Seraine Custódio; da Costa, Douglas Soares; Lopes, Miriam Teresa Paz; de Lira, Kamila Lopes; Quintans-Júnior, Lucindo José; de Sousa, Adriano Antunes; de Cássia Meneses Oliveira, Rita

2016-11-01

(-)-Linalool is a monoterpene constituent of many essential oils. This particular monoterpene has both anti-inflammatory and antimicrobial activity. Moreover, this compound has been shown to be antinociceptive. However, the poor chemical stability and short half-life prevents the clinical application of (-)-linalool and many other essential oils. Important to the topic of this study, β-cyclodextrin (β-CD) has been used to increase the solubility, stability, and pharmacological effects of numerous lipophilic compounds in vivo. In this study, the gastroprotective activities of (-)-linalool (LIN) and linalool incorporated into inclusion complex containing β-cyclodextrin (LIN-βCD) were evaluated using models of acute and chronic gastric ulcers in rodents. LIN and LIN-βCD showed strong gastroprotective activity (p < 0.001). The LIN-βCD complex revealed that the gastroprotective effect was significantly improved compared with LIN uncomplexed, suggesting that this improvement is related to increased solubility and stability. Taking together the potentiation of the antioxidant profile of this monoterpene, our results suggest that β-CD may represent an important tool for improved gastroprotective activity of (-)-linalool and other water-insoluble compounds.

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

PubMed Central

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

2013-01-01

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

Thin Film Thermoelectric Metal-Organic Framework with High Seebeck Coefficient and Low Thermal Conductivity. Supporting Information

DTIC Science & Technology

2015-04-28

François Léonard, Vitalie Stavila, Michael E. Foster, Catalin D. Spataru, Reese E. Jones, Brian M. Foley, Patrick E. Hopkins, Mark D. Allendorf, A. Alec...Léonard, Vitalie Stavila, Michael E. Foster, Catalin D. Spataru, Reese E. Jones, Brian M. Foley, Patrick E. Hopkins, Mark D. Allendorf, and A. Alec Talin...Kristopher J. Erickson, François Léonard, Vitalie Stavila, Michael E. Foster, Catalin D. Spataru, Reese E. Jones, Brian M. Foley, Patrick E. Hopkins, Mark D

An Analysis of Navy Nurse Corps Accession Sources

DTIC Science & Technology

2014-03-01

1 I. INTRODUCTION A. BACKGROUND Since 1998, the United States has experienced a nationwide nursing shortage (Juraschek, Zhang, Ranganathan ...supply of RNs in the civilian workforce (Juraschek, Zhang, Ranganathan , & Lin, 2012). A study by Juraschek, Zhang, Ranganathan , & Lin (2012...Postgraduate School, Monterey, CA. Retrieved from www.dtic.mil/cgi- bin/GetTRDoc?AD=ADA344570 Juraschek, S. P., Zhang, X., Ranganathan , V. K., & Lin, V

Evolutionary plasticity of the NHL domain underlies distinct solutions to RNA recognition.

PubMed

Kumari, Pooja; Aeschimann, Florian; Gaidatzis, Dimos; Keusch, Jeremy J; Ghosh, Pritha; Neagu, Anca; Pachulska-Wieczorek, Katarzyna; Bujnicki, Janusz M; Gut, Heinz; Großhans, Helge; Ciosk, Rafal

2018-04-19

RNA-binding proteins regulate all aspects of RNA metabolism. Their association with RNA is mediated by RNA-binding domains, of which many remain uncharacterized. A recently reported example is the NHL domain, found in prominent regulators of cellular plasticity like the C. elegans LIN-41. Here we employ an integrative approach to dissect the RNA specificity of LIN-41. Using computational analysis, structural biology, and in vivo studies in worms and human cells, we find that a positively charged pocket, specific to the NHL domain of LIN-41 and its homologs (collectively LIN41), recognizes a stem-loop RNA element, whose shape determines the binding specificity. Surprisingly, the mechanism of RNA recognition by LIN41 is drastically different from that of its more distant relative, the fly Brat. Our phylogenetic analysis suggests that this reflects a rapid evolution of the domain, presenting an interesting example of a conserved protein fold that acquired completely different solutions to RNA recognition.

RNA interference can target pre-mRNA: consequences for gene expression in a Caenorhabditis elegans operon.

PubMed Central

Bosher, J M; Dufourcq, P; Sookhareea, S; Labouesse, M

1999-01-01

In nematodes, flies, trypanosomes, and planarians, introduction of double-stranded RNA results in sequence-specific inactivation of gene function, a process termed RNA interference (RNAi). We demonstrate that RNAi against the Caenorhabditis elegans gene lir-1, which is part of the lir-1/lin-26 operon, induced phenotypes very different from a newly isolated lir-1 null mutation. Specifically, lir-1(RNAi) induced embryonic lethality reminiscent of moderately strong lin-26 alleles, whereas the lir-1 null mutant was viable. We show that the lir-1(RNAi) phenotypes resulted from a severe loss of lin-26 gene expression. In addition, we found that RNAi directed against lir-1 or lin-26 introns induced similar phenotypes, so we conclude that lir-1(RNAi) targets the lir-1/lin-26 pre-mRNA. This provides direct evidence that RNA interference can prevent gene expression by targeting nuclear transcripts. Our results highlight that caution may be necessary when interpreting RNA interference without the benefit of mutant alleles. PMID:10545456

The let-7 microRNA target gene, Mlin41/Trim71 is required for mouse embryonic survival and neural tube closure

PubMed Central

Schulman, Betsy R. Maller; Liang, Xianping; Stahlhut, Carlos; DelConte, Casey; Stefani, Giovanni; Slack, Frank J.

2010-01-01

In the nematode Caenorhabditis elegans, the let-7 microRNA (miRNA) controls the timing of key developmental events and terminal differentiation in part by directly regulating lin-41. C. elegans lin-41 mutants display precocious cell cycle exit and terminal differentiation of epidermal skin cells. lin-41 orthologues are found in more complex organisms including both mice and humans, but their roles are not known. We generated Mlin41 mouse mutants to ascertain a functional role for Mlin41. Strong loss of function Mlin41 gene-trap mutants demonstrated a striking neural tube closure defect during development, and embryonic lethality. Like C. elegans lin-41, Mlin41 also appears to be regulated by the let-7 and mir-125 miRNAs. Since Mlin41 is required for neural tube closure and survival it points to human lin-41 (HLIN41/TRIM71) as a potential human development and disease gene. PMID:19098426

Ku-band system design study and TDRSS interface analysis

NASA Technical Reports Server (NTRS)

Lindsey, W. C.; Mckenzie, T. M.; Choi, H. J.; Tsang, C. S.; An, S. H.

1983-01-01

The capabilities of the Shuttle/TDRSS link simulation program (LinCsim) were expanded to account for radio frequency interference (RFI) effects on the Shuttle S-band links, the channel models were updated to reflect the RFI related hardware changes, the ESTL hardware modeling of the TDRS communication payload was reviewed and evaluated, in LinCsim the Shuttle/TDRSS signal acquisition was modeled, LinCsim was upgraded, and possible Shuttle on-orbit navigation techniques was evaluated.

Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans.

PubMed

Carpentier, André C; Frisch, Frédérique; Brassard, Pascal; Lavoie, François; Bourbonnais, Annie; Cyr, Denis; Giguère, Robert; Baillargeon, Jean-Patrice

2007-03-01

Insulin increases plasma nonesterified fatty acid (NEFA) clearance in humans, but whether this is independent of change in plasma NEFA appearance is currently unknown. Nine nondiabetic men (age: 28+/-3 yr, body mass index: 27.2+/-1.7 kg/m2) underwent euglycemic clamps to maintain low (LINS) vs. high (HINS) physiological insulin levels for 6 h. An intravenous infusion of heparin+Intralipid (HI) was performed during 4 of the 6 h of the clamps (in the last 4 h at LINS and in the first 4 h at HINS), whereas saline infusion (SAL) was administered in the remaining 2 h to modulate plasma NEFA levels independently of plasma insulin levels. Four experimental conditions were obtained in each individual: LINS with saline (LINS/SAL) and with HI infusion (LINS/HI) and HINS with saline (HINS/SAL) and with HI infusion (HINS/HI). Plasma palmitate appearance during HINS/SAL was lower than during the three other experimental conditions (P<0.05). In contrast, plasma linoleate appearance, as expected, was increased by HI independently of insulin level (P<0.02). Plasma palmitate clearance during HINS/SAL was higher than LINS/SAL and LINS/HI (P<0.008), and this increase was blunted during HINS/HI. We observed a linear decrease in plasma palmitate clearance with increasing plasma NEFA appearance independent of insulin levels. Plasma NEFA levels increased exponentially with increase in plasma NEFA appearance. We conclude that insulin stimulates plasma NEFA clearance by reducing the endogenous appearance rate of NEFA. The relationship between plasma NEFA level and appearance rate is nonlinear.

C. elegans microRNAs.

PubMed

Vella, Monica C; Slack, Frank J

2005-09-21

MicroRNAs (miRNAs) are small, non-coding regulatory RNAs found in many phyla that control such diverse events as development, metabolism, cell fate and cell death. They have also been implicated in human cancers. The C. elegans genome encodes hundreds of miRNAs, including the founding members of the miRNA family lin-4 and let-7. Despite the abundance of C. elegans miRNAs, few miRNA targets are known and little is known about the mechanism by which they function. However, C. elegans research continues to push the boundaries of discovery in this area. lin-4 and let-7 are the best understood miRNAs. They control the timing of adult cell fate determination in hypodermal cells by binding to partially complementary sites in the mRNA of key developmental regulators to repress protein expression. For example, lin-4 is predicted to bind to seven sites in the lin-14 3' untranslated region (UTR) to repress LIN-14, while let-7 is predicted to bind two let-7 complementary sites in the lin-41 3' UTR to down-regulate LIN-41. Two other miRNAs, lsy-6 and mir-273, control left-right asymmetry in neural development, and also target key developmental regulators for repression. Approximately one third of the C. elegans miRNAs are differentially expressed during development indicating a major role for miRNAs in C. elegans development. Given the remarkable conservation of developmental mechanism across phylogeny, many of the principles of miRNAs discovered in C. elegans are likely to be applicable to higher animals.

The influence of BDNF on human umbilical cord blood stem/progenitor cells: implications for stem cell-based therapy of neurodegenerative disorders.

PubMed

Paczkowska, Edyta; Łuczkowska, Karolina; Piecyk, Katarzyna; Rogińska, Dorota; Pius-Sadowska, Ewa; Ustianowski, Przemysław; Cecerska, Elżbieta; Dołęgowska, Barbara; Celewicz, Zbigniew; Machaliński, Bogusław

2015-01-01

Umbilical cord blood (UCB)-derived stem/progenitor cells (SPCs) have demonstrated the potential to improve neurologic function in different experimental models. SPCs can survive after transplantation in the neural microenvironment and indu ce neuroprotection, endogenous neurogenesis by secreting a broad repertoire of trophic and immunomodulatory cytokines. In this study, the influence of brain-derived neurotrophic factor (BDNF) pre-treatment was comprehensively evaluated in a UCB-derived lineage-negative (Lin-) SPC population. UCB-derived Lin- cells were evaluated with respect to the expression of (i) neuronal markers using immunofluorescence staining and (ii) specific (TrkB) receptors for BDNF using flow cytometry. Next, after BDNF pre-treatment, Lin- cells were extensively assessed with respect to apoptosis using Western blotting and proliferation via BrdU incorporation. Furthermore, NT-3 expression levels in Lin- cells using RQ PCR and antioxidative enzyme activities were assessed. We demonstrated neuronal markers as well as TrkB expression in Lin- cells and the activation of the TrkB receptor by BDNF. BDNF pre-treatment diminished apoptosis in Lin- cells and influenced the proliferation of these cells. We observed significant changes in antioxidants as well as in the increased expression of NT-3 in Lin- cells following BDNF exposure. Complex global miRNA and mRNA profiling analyses using microarray technology and GSEA revealed the differential regulation of genes involved in the proliferation, gene expression, biosynthetic processes, translation, and protein targeting. Our results support the hypothesis that pre-treatment of stem/progenitor cells could be beneficial and may be used as an auxiliary strategy for improving the properties of SPCs.

The generation of centripetal force when walking in a circle: insight from the distribution of ground reaction forces recorded by plantar insoles.

PubMed

Turcato, Anna Maria; Godi, Marco; Giordano, Andrea; Schieppati, Marco; Nardone, Antonio

2015-01-09

Turning involves complex reorientation of the body and is accompanied by asymmetric motion of the lower limbs. We investigated the distribution of the forces under the two feet, and its relation to the trajectory features and body medio-lateral displacement during curved walking. Twenty-six healthy young participants walked under three different randomized conditions: in a straight line (LIN), in a circular clockwise path and in a circular counter-clockwise path. Both feet were instrumented with Pedar-X insoles. An accelerometer was fixed to the trunk to measure the medio-lateral inclination of the body. We analyzed walking speed, stance duration as a percent of gait cycle (%GC), the vertical component of the ground reaction force (vGRF) of both feet during the entire stance, and trunk inclination. Gait speed was faster during LIN than curved walking, but not affected by the direction of the curved trajectory. Trunk inclination was negligible during LIN, while the trunk was inclined toward the center of the path during curved trajectories. Stance duration of LIN foot and foot inside the curved trajectory (Foot-In) was longer than for foot outside the trajectory (Foot-Out). vGRF at heel strike was larger in LIN than in curved walking. At mid-stance, vGRF for both Foot-In and Foot-Out was higher than for LIN foot. At toe off, vGRF for both Foot-In and Foot-Out was lower than for LIN foot; in addition, Foot-In had lower vGRF than Foot-Out. During curved walking, a greater loading of the lateral heel occurred for Foot-Out than Foot-In and LIN foot. On the contrary, a smaller lateral loading of the heel was found for Foot-In than LIN foot. At the metatarsal heads, an opposite behaviour was seen, since lateral loading decreased for Foot-Out and increased for Foot-In. The lower gait speed during curved walking is shaped by the control of trunk inclination and the production of asymmetric loading of heel and metatarsal heads, hence by the different contribution of the feet

Ang II-AT2R increases mesenchymal stem cell migration by signaling through the FAK and RhoA/Cdc42 pathways in vitro.

PubMed

Xu, Xiu-Ping; He, Hong-Li; Hu, Shu-Ling; Han, Ji-Bin; Huang, Li-Li; Xu, Jing-Yuan; Xie, Jian-Feng; Liu, Ai-Ran; Yang, Yi; Qiu, Hai-Bo

2017-07-12

Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury and are possibly attracted by inflammatory factors. As a proinflammatory mediator, angiotensin II (Ang II) reportedly enhances the migration of various cell types by signaling via the Ang II receptor in vitro. However, few studies have focused on the effects of Ang II on MSC migration and the underlying mechanisms. Human bone marrow MSCs migration was measured using wound healing and Boyden chamber migration assays after treatments with different concentrations of Ang II, an AT1R antagonist (Losartan), and/or an AT2R antagonist (PD-123319). To exclude the effect of proliferation on MSC migration, we measured MSC proliferation after stimulation with the same concentration of Ang II. Additionally, we employed the focal adhesion kinase (FAK) inhibitor PF-573228, RhoA inhibitor C3 transferase, Rac1 inhibitor NSC23766, or Cdc42 inhibitor ML141 to investigate the role of cell adhesion proteins and the Rho-GTPase protein family (RhoA, Rac1, and Cdc42) in Ang II-mediated MSC migration. Cell adhesion proteins (FAK, Talin, and Vinculin) were detected by western blot analysis. The Rho-GTPase family protein activities were assessed by G-LISA and F-actin levels, which reflect actin cytoskeletal organization, were detected by using immunofluorescence. Human bone marrow MSCs constitutively expressed AT1R and AT2R. Additionally, Ang II increased MSC migration in an AT2R-dependent manner. Notably, Ang II-enhanced migration was not mediated by Ang II-mediated cell proliferation. Interestingly, Ang II-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased Talin and Vinculin expression. Moreover, RhoA and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. Furthermore, FAK, Talin, and Vinculin activation and F-actin reorganization in response to Ang II were prevented by PD-123319 but

CD44-mediated activation of α5β1-integrin, cortactin and paxillin signaling underpins adhesion of basal-like breast cancer cells to endothelium and Fibronectin-enriched matrices

PubMed Central

McFarlane, Suzanne; McFarlane, Cheryl; Montgomery, Nicola; Hill, Ashleigh; Waugh, David J.J.

2015-01-01

CD44 expression is elevated in basal-like breast cancer (BLBC) tissue, and correlates with increased efficiency of distant metastasis in patients and experimental models. We sought to characterize mechanisms underpinning CD44-promoted adhesion of BLBC cells to vascular endothelial monolayers and extracellular matrix (ECM) substrates. Stimulation with hyaluronan (HA), the native ligand for CD44, increased expression and activation of β1-integrin receptors, and increased α5-integrin subunit expression. Adhesion assays confirmed that CD44-signalling potentiated BLBC cell adhesion to endothelium and Fibronectin in an α5B1-integrin-dependent mechanism. Co-immunoprecipitation experiments confirmed HA-promoted association of CD44 with talin and the β1-integrin chain in BLBC cells. Knockdown of talin inhibited CD44 complexing with β1-integrin and repressed HA-induced, CD44-mediated activation of β1-integrin receptors. Immunoblotting confirmed that HA induced rapid phosphorylation of cortactin and paxillin, through a CD44-dependent and β1-integrin-dependent mechanism. Knockdown of CD44, cortactin or paxillin independently attenuated the adhesion of BL-BCa cells to endothelial monolayers and Fibronectin. Accordingly, we conclude that CD44 induced, integrin-mediated signaling not only underpins efficient adhesion of BLBC cells to BMECs to facilitate extravasation but initiates their adhesion to Fibronectin, enabling penetrant cancer cells to adhere more efficiently to underlying Fibronectin-enriched matrix present within the metastatic niche. PMID:26447611

Platelets lacking PIP5KIγ have normal integrin activation but impaired cytoskeletal-membrane integrity and adhesion

PubMed Central

Wang, Yanfeng; Zhao, Liang; Suzuki, Aae; Lian, Lurong; Min, Sang H.; Wang, Ziqian; Litvinov, Rustem I.; Stalker, Timothy J.; Yago, Tadayuki; Klopocki, Arkadiusz G.; Schmidtke, David W.; Yin, Helen; Choi, John K.; McEver, Rodger P.; Weisel, John W.; Hartwig, John H.; Abrams, Charles S.

2013-01-01

Three isoforms of phosphatidylinositol-4-phosphate 5-kinase (PIP5KIα, PIP5KIβ, and PIP5KIγ) can each catalyze the final step in the synthesis of phosphatidylinositol-4,5-bisphosphate (PIP2), which in turn can be either converted to second messengers or bind directly to and thereby regulate proteins such as talin. A widely quoted model speculates that only p90, a longer splice form of platelet-specific PIP5KIγ, but not the shorter p87 PIP5KIγ, regulates the ligand-binding activity of integrins via talin. However, when we used mice genetically engineered to lack only p90 PIP5KIγ, we found that p90 PIP5KIγ is not critical for integrin activation or platelet adhesion on collagen. However, p90 PIP5KIγ-null platelets do have impaired anchoring of their integrins to the underlying cytoskeleton. Platelets lacking both the p90 and p87 PIP5KIγ isoforms had normal integrin activation and actin dynamics, but impaired anchoring of their integrins to the cytoskeleton. Most importantly, they formed weak shear-resistant adhesions ex vivo and unstable vascular occlusions in vivo. Together, our studies demonstrate that, although PIP5KIγ is essential for normal platelet function, individual isoforms of PIP5KIγ fulfill unique roles for the integrin-dependent integrity of the membrane cytoskeleton and for the stabilization of platelet adhesion. PMID:23372168

Comparison of the Gene Expression Profiles of Human Hematopoietic Stem Cells between Humans and a Humanized Xenograft Model.

PubMed

Matsuzawa, Hideyuki; Matsushita, Hiromichi; Yahata, Takashi; Tanaka, Masayuki; Ando, Kiyoshi

2017-04-20

The aim of this study is to evaluate the feasibility of NOD/Shi-scid-IL2Rγ null (NOG) mice transplanted with human CD34 + /CD38 - /Lin -/low hematopoietic cells from cord blood (CB) as an experimental model of the gene expression in human hematopoiesis. We compared the gene expressions of human CD34 + /CD38 - /Lin -/low cells from human bone marrow (BM) and in xenograft models. The microarray data revealed that 25 KEGG pathways were extracted from the comparison of human CD34 + /CD38 - /Lin -/low HSCs between CB and BM, and that 17 of them--which were mostly related to cellular survival, RNA metabolism and lymphoid development--were shared with the xenograft model. When the probes that were commonly altered in CD34 + /CD38 - /Lin -/low cells from both human and xenograft BM were analyzed, most of them, including the genes related hypoxia, hematopoietic differentiation, epigenetic modification, translation initiation, and RNA degradation, were downregulated. These alterations of gene expression suggest a reduced differentiation capacity and likely include key alterations of gene expression for settlement of CB CD34 + /CD38 - /Lin -/low cells in BM. Our findings demonstrate that the xenograft model of human CB CD34 + /CD38 - /Lin -/low cells using NOG mice was useful, at least in part, for the evaluation of the gene expression profile of human hematopoietic stem cells.

Characterization and Targeting of the Aldehyde Dehydrogenase Subpopulation in Ovarian Cancer

DTIC Science & Technology

2011-07-01

2006. † 21. Han LY, Landen CN, Trevino JG, Halder J, Lin YG, Kamat AA, Kim TJ, Merritt WM, Coleman RL, Gershenson DM, Shakespeare WC, Wang Y...Kamat AA, Lin YG, MerritWM, Shakespeare WC, Sawyer TK, Gallick G, Sood AK. Src as a novel therapeutic target in ovarian carcinoma. Proceedings of...Landen CN, Li Y, Kamat AA, Lin YG, Merritt WM, Pena-Armaiz G, Shakespeare WC, Sawyer TK, Coleman RL, Gallick GE, Sood AK. IL-8 and VEGF as biomarkers

Evolution of New cis-Regulatory Motifs Required for Cell-Specific Gene Expression in Caenorhabditis

PubMed Central

Félix, Marie-Anne

2016-01-01

Patterning of C. elegans vulval cell fates relies on inductive signaling. In this induction event, a single cell, the gonadal anchor cell, secretes LIN-3/EGF and induces three out of six competent precursor cells to acquire a vulval fate. We previously showed that this developmental system is robust to a four-fold variation in lin-3/EGF genetic dose. Here using single-molecule FISH, we find that the mean level of expression of lin-3 in the anchor cell is remarkably conserved. No change in lin-3 expression level could be detected among C. elegans wild isolates and only a low level of change—less than 30%—in the Caenorhabditis genus and in Oscheius tipulae. In C. elegans, lin-3 expression in the anchor cell is known to require three transcription factor binding sites, specifically two E-boxes and a nuclear-hormone-receptor (NHR) binding site. Mutation of any of these three elements in C. elegans results in a dramatic decrease in lin-3 expression. Yet only a single E-box is found in the Drosophilae supergroup of Caenorhabditis species, including C. angaria, while the NHR-binding site likely only evolved at the base of the Elegans group. We find that a transgene from C. angaria bearing a single E-box is sufficient for normal expression in C. elegans. Even a short 58 bp cis-regulatory fragment from C. angaria with this single E-box is able to replace the three transcription factor binding sites at the endogenous C. elegans lin-3 locus, resulting in the wild-type expression level. Thus, regulatory evolution occurring in cis within a 58 bp lin-3 fragment, results in a strict requirement for the NHR binding site and a second E-box in C. elegans. This single-cell, single-molecule, quantitative and functional evo-devo study demonstrates that conserved expression levels can hide extensive change in cis-regulatory site requirements and highlights the evolution of new cis-regulatory elements required for cell-specific gene expression. PMID:27588814

[Pollution characteristics and ecological risk assessment of heavy metals in surface sediments of Qingshan Reservoir in Lin' an City, Zhejiang Province of East China].

PubMed

Zhang, Fen; Yang, Chang-Ming; Pan, Rui-Jie

2013-09-01

A total of 8 representative surface sediment sampling sites were collected from the Qingshan Reservoir in Lin'an City of Zhejiang Province to investigate the differences in the total concentrations of As, Cr, Cu, Ni, Mn, Pb, and Zn among the sampling sites. The different forms of the heavy metals, i. e., acid soluble, easily reducible, easily oxidizable, and residual, were determined by BCR sequential extraction method, and the pollution degrees and potential ecological risk, of the heavy metals in the surface sediments at different sampling sites of the Reservoir were assessed by using geo-accumulation index (I(geo)) and Hakanson potential ecological risk index. There existed obvious spatial differences in the total concentrations of the heavy metals in the surface sediments of the Reservoir. The sampling sites nearby the estuaries of the tributaries flowing through downtowns and heavy industrial parks to the Reservoir had obviously higher heavy metals concentrations in surface sediments, as compared to the other sampling sites. In the sediments, Mn was mainly in acid extractable form, Cu and Pb were mainly in reducible form, and As was mainly in residual form. The surface sediments at the sampling sites nearby the estuaries of the tributaries flowing through downtowns to the Reservoir had higher proportions of acid extractable and reducibles forms of the heavy metals, which would have definite potential toxic risk to aquatic organisms. Among the 7 heavy metals in the surface sediments, As showed the highest pollution degree, followed by Cu, Ni, Mn, Pb, and Zn, which were at moderate pollution degree, while Cr was at non-pollution degree, with relatively low potential ecological risk. Through the comparison of the sampling sites, it was observed that the surface sediments at the sites nearby the estuaries of Jinxi River and Hengxi River flowing through downtowns and heavy industrial parks to the Reservoir showed obviously higher heavy metals pollution degree and

Microstructure Development in Polymers.

DTIC Science & Technology

1981-05-12

J. S. Lin, R. W. Hendricks, J. Petermann , and R. M. Gohil, J. Polymer Sci., Polym. Phys. Ed., 19, 609 (1981). 8. J. Petermann , J. M. Schultz, R. M...Gohil, R. W. Hendricks, and J. S. Lin, submitted to Polymer. 9. J. Rau, R. M. Gohil, J. Petermann , and J. M. Schultz, Colloid & Polymer Sci., 259, 241...1981). 10. J. Petermann , J. M. Schultz, R. W. Hendricks, and J. S. Lin, J. Mater. Sci., 16, 265 (1981). 11. K. M. Gupte, Ph.D. Dissertation, Univ. of

Contributions of mRNA abundance, ribosome loading, and post- or peri-translational effects to temporal repression of C. elegans heterochronic miRNA targets

PubMed Central

Stadler, Michael; Artiles, Karen; Pak, Julia; Fire, Andrew

2012-01-01

miRNAs are post-transcriptional regulators of gene activity that reduce protein accumulation from target mRNAs. Elucidating precise molecular effects that animal miRNAs have on target transcripts has proven complex, with varied evidence indicating that miRNA regulation may produce different molecular outcomes in different species, systems, and/or physiological conditions. Here we use high-throughput ribosome profiling to analyze detailed translational parameters for five well-studied targets of miRNAs that regulate C. elegans developmental timing. For two targets of the miRNA lin-4 (lin-14 and lin-28), functional down-regulation was associated with decreases in both overall mRNA abundance and ribosome loading; however, these changes were of substantially smaller magnitude than corresponding changes observed in protein abundance. For three functional targets of the let-7 miRNA family for which down-regulation is critical in temporal progression of the animal (daf-12, hbl-1, and lin-41), we observed only modest changes in mRNA abundance and ribosome loading. lin-41 provides a striking example in that populations of ribosome-protected fragments from this gene remained essentially unchanged during the L3–L4 time interval when lin-41 activity is substantially down-regulated by let-7. Spectra of ribosomal positions were also examined for the five lin-4 and let-7 target mRNAs as a function of developmental time, with no indication of miRNA-induced ribosomal drop-off or significant pauses in translation. These data are consistent with models in which physiological regulation by this set of C. elegans miRNAs derives from combinatorial effects including suppressed recruitment/activation of translational machinery, compromised stability of target messages, and post- or peri-translational effects on lifetimes of polypeptide products. PMID:22855835

RNA-Seq in the discovery of a sparsely expressed scent-determining monoterpene synthase in lavender (Lavandula).

PubMed

Adal, Ayelign M; Sarker, Lukman S; Malli, Radesh P N; Liang, Ping; Mahmoud, Soheil S

2018-06-09

Using RNA-Seq, we cloned and characterized a unique monoterpene synthase responsible for the formation of a scent-determining S-linalool constituent of lavender oils from Lavandula × intermedia. Several species of Lavandula produce essential oils (EOs) consisting mainly of monoterpenes including linalool, one of the most abundant and scent-determining oil constituents. Although R-linalool dominates the EOs of lavenders, varying amounts (depending on the species) of the S-linalool enantiomer can also be found in these plants. Despite its relatively low abundance, S-linalool contributes a sweet, pleasant scent and is an important constituent of lavender EOs. While several terpene synthase genes including R-linalool synthase have been cloned from lavenders many important terpene synthases including S-linalool synthase have not been described from these plants. In this study, we employed RNA-Seq and other complementary sequencing data to clone and functionally characterize the sparsely expressed S-linalool synthase cDNA (LiS-LINS) from Lavandula × intermedia. Recombinant LiS-LINS catalyzed the conversion of the universal monoterpene precursor geranyl diphosphate to S-linalool as the sole product. Intriguingly, LiS-LINS exhibited very low (~ 30%) sequence similarity to other Lavandula terpene synthases, including R-linalool synthase. However, the predicted 3D structure of this protein, including the composition and arrangement of amino acids at the active site, is highly homologous to known terpene synthase proteins. LiS-LINS transcripts were detected in flowers, but were much less abundant than those corresponding to LiR-LINS, paralleling enantiomeric composition of linalool in L. × intermedia oils. These data indicate that production of S-linalool is at least partially controlled at the level of transcription from LiS-LINS. The cloned LiS-LINS cDNA may be used to enhance oil composition in lavenders and other plants through metabolic engineering.

Classifying chemical mode of action using gene networks and machine learning: a case study with the herbicide linuron.

PubMed

Ornostay, Anna; Cowie, Andrew M; Hindle, Matthew; Baker, Christopher J O; Martyniuk, Christopher J

2013-12-01

The herbicide linuron (LIN) is an endocrine disruptor with an anti-androgenic mode of action. The objectives of this study were to (1) improve knowledge of androgen and anti-androgen signaling in the teleostean ovary and to (2) assess the ability of gene networks and machine learning to classify LIN as an anti-androgen using transcriptomic data. Ovarian explants from vitellogenic fathead minnows (FHMs) were exposed to three concentrations of either 5α-dihydrotestosterone (DHT), flutamide (FLUT), or LIN for 12h. Ovaries exposed to DHT showed a significant increase in 17β-estradiol (E2) production while FLUT and LIN had no effect on E2. To improve understanding of androgen receptor signaling in the ovary, a reciprocal gene expression network was constructed for DHT and FLUT using pathway analysis and these data suggested that steroid metabolism, translation, and DNA replication are processes regulated through AR signaling in the ovary. Sub-network enrichment analysis revealed that FLUT and LIN shared more regulated gene networks in common compared to DHT. Using transcriptomic datasets from different fish species, machine learning algorithms classified LIN successfully with other anti-androgens. This study advances knowledge regarding molecular signaling cascades in the ovary that are responsive to androgens and anti-androgens and provides proof of concept that gene network analysis and machine learning can classify priority chemicals using experimental transcriptomic data collected from different fish species. © 2013.

A mutation in a coproporphyrinogen III oxidase gene confers growth inhibition, enhanced powdery mildew resistance and powdery mildew-induced cell death in Arabidopsis.

PubMed

Guo, Chuan-yu; Wu, Guang-heng; Xing, Jin; Li, Wen-qi; Tang, Ding-zhong; Cui, Bai-ming

2013-05-01

A gene encoding a coproporphyrinogen III oxidase mediates disease resistance in plants by the salicylic acid pathway. A number of genes that regulate powdery mildew resistance have been identified in Arabidopsis, such as ENHANCED DISEASE RESISTANCE 1 to 3 (EDR1 to 3). To further study the molecular interactions between the powdery mildew pathogen and Arabidopsis, we isolated and characterized a mutant that exhibited enhanced resistance to powdery mildew. The mutant also showed dramatic powdery mildew-induced cell death as well as growth defects and early senescence in the absence of pathogens. We identified the affected gene by map-based cloning and found that the gene encodes a coproporphyrinogen III oxidase, a key enzyme in the tetrapyrrole biosynthesis pathway, previously known as LESION INITIATION 2 (LIN2). Therefore, we designated the mutant lin2-2. Further studies revealed that the lin2-2 mutant also displayed enhanced resistance to Hyaloperonospora arabidopsidis (H.a.) Noco2. Genetic analysis showed that the lin2-2-mediated disease resistance and spontaneous cell death were dependent on PHYTOALEXIN DEFICIENT 4 (PAD4), SALICYLIC ACID INDUCTION-DEFICIENT 2 (SID2), and NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), which are all involved in salicylic acid signaling. Furthermore, the relative expression levels of defense-related genes were induced after powdery mildew infection in the lin2-2 mutant. These data indicated that LIN2 plays an important role in cell death control and defense responses in plants.

Mobilization of Peripheral Blood Stem Cells and Changes in the Concentration of Plasma Factors Influencing their Movement in Patients with Panic Disorder.

PubMed

Jabłoński, Marcin; Mazur, Jolanta Kucharska; Tarnowski, Maciej; Dołęgowska, Barbara; Pędziwiatr, Daniel; Kubiś, Ewa; Budkowska, Marta; Sałata, Daria; Wysiecka, Justyna Pełka; Kazimierczak, Arkadiusz; Reginia, Artur; Ratajczak, Mariusz Z; Samochowiec, Jerzy

2017-04-01

In this paper we examined whether stem cells and factors responsible for their movement may serve as new biological markers of anxiety disorders. The study was carried out on a group of 30 patients diagnosed with panic disorder (examined before and after treatment), compared to 30 healthy individuals forming the control group. We examined the number of circulating HSCs (hematopoetic stem cells) (Lin-/CD45 +/CD34 +) and HSCs (Lin-/CD45 +/AC133 +), the number of circulating VSELs (very small embryonic-like stem cells) (Lin-/CD45-/CD34 +) and VSELs (Lin-/CD45-/AC133 +), as well as the concentration of complement components: C3a, C5a and C5b-9, SDF-1 (stromal derived factor) and S1P (sphingosine-1-phosphate). Significantly lower levels of HSCs (Lin-/CD45 +/AC133 +) have been demonstrated in the patient group compared to the control group both before and after treatment. The level of VSELs (Lin-/CD45-/CD133 +) was significantly lower in the patient group before treatment as compared to the patient group after treatment.The levels of factors responsible for stem cell movement were significantly lower in the patient group compared to the control group before and after treatment. It was concluded that the study of stem cells and factors associated with their movement can be useful in the diagnostics of panic disorder, as well as differentiating between psychotic and anxiety disorders.

Ability of circulating human hematopoietic lineage negative cells to support hematopoiesis.

PubMed

Peris, Pilar; Roforth, Matthew M; Nicks, Kristy M; Fraser, Daniel; Fujita, Koji; Jilka, Robert L; Khosla, Sundeep; McGregor, Ulrike

2015-01-01

Hematopoietic stem cell (HSC) self-renewal is regulated by osteoblast and/or endothelial cells within the hematopoietic niche. However, the true identity of the supporting cells and the nature of the secreted factors remain uncertain. We developed a novel mouse model and analyzed whether circulating human peripheral hematopoietic lineage negative/AP+ (lin-/AP+) cells support hematopoiesis in vivo. Thus, immunocompromised (Rag) mice expressing thymidine kinase (Tk) under the control of the 3.6Col1α1 promoter (Tk-Rag) were treated with ganciclovir, resulting in osteoblast progenitor cell ablation and subsequent loss of hematopoiesis (evaluated by measuring mouse Ter119+ erythroid cells). Following hematopoietic cell depletion, human bone marrow-derived marrow stromal cells (MSCs) or lin-/AP+ cells were infused into Tk-Rag mice and compared with saline infusions. Ganciclovir significantly reduced (7.4-fold) Ter119+ cells in the bone marrow of Tk-Rag mice compared to saline injections. Infusion of either MSCs or lin-/AP+ cells into ganciclovir-treated mice resulted in a 3.3-fold and 2.7-fold increase (P < 0.01), respectively, in Ter119+ cells compared to mice receiving saline. Relative to lin-/AP- cells, lin-/AP+ cells expressed high levels of mesenchymal, endothelial, and hematopoiesis supporting genes. Thus, human peripheral blood lin-/AP+ cells represent a novel cell type capable of supporting hematopoiesis in a manner comparable to MSCs. © 2014 Wiley Periodicals, Inc.

Carboxy-terminal truncation activates glp-1 protein to specify vulval fates in Caenorhabditis elegans.

PubMed

Mango, S E; Maine, E M; Kimble, J

1991-08-29

The glp-1 and lin-12 genes encode homologous transmembrane proteins that may act as receptors for cell interactions during development. The glp-1 product is required for induction of germ-line proliferation and for embryogenesis. By contrast, lin-12 mediates somatic cell interactions, including those between the precursor cells that form the vulval hypodermis (VPCs). Here we analyse an unusual allele of glp-1, glp-1(q35), which displays a semidominant multivulva phenotype (Muv), as well as the typical recessive, loss-of-function Glp phenotypes (sterility and embryonic lethality). We find that the effects of glp-1(q35) on VPC development mimic those of dominant lin-12 mutations, even in the absence of lin-12 activity. The glp-1(q35) gene bears a nonsense mutation predicted to eliminate the 122 C-terminal amino acids, including a ProGluSerThr (PEST) sequence thought to destabilize proteins. We suggest that the carboxy terminus bears a negative regulatory domain which normally inactivates glp-1 in the VPCs. We propose that inappropriate glp-1(q35) activity can substitute for lin-12 to determine vulval fate, perhaps by driving the VPCs to proliferate.

Linear Discriminant Analysis on a Spreadsheet.

ERIC Educational Resources Information Center

Busbey, Arthur Bresnahan III

1989-01-01

Described is a software package, "Trapeze," within which a routine called LinDis can be used. Discussed are teaching methods, the linear discriminant model and equations, the LinDis worksheet, and an example. The set up for this routine is included. (CW)

Platelet Proteomic Analysis Revealed Differential Pattern of Cytoskeletal- and Immune-Related Proteins at Early Stages of Alzheimer's Disease.

PubMed

González-Sánchez, Marta; Díaz, Teresa; Pascual, Consuelo; Antequera, Desiree; Herrero-San Martín, Alejandro; Llamas-Velasco, Sara; Villarejo-Galende, Alberto; Bartolome, Fernando; Carro, Eva

2018-03-30

Platelets are considered a good model system to study a number of elements associated with neuronal pathways as they share biochemical similarities. Platelets represent the major source of amyloid-β (Aβ) in blood contributing to the Aβ accumulation in the brain parenchyma and vasculature. Peripheral blood platelet alterations including cytoskeletal abnormalities, abnormal cytoplasmic calcium fluxes or increased oxidative stress levels have been related to Alzheimer's disease (AD) pathology. Therefore, platelets can be considered a peripheral model to study metabolic mechanisms occurring in AD. To investigate peripheral molecular alterations, we examined platelet protein expression in a cohort of 164 subjects, including mild cognitive impairment (MCI), and AD patients, and healthy aged-matched controls. A two-dimensional difference gel electrophoresis (2D-DIGE) discovery phase revealed significant differences between patients and controls in five proteins: talin, vinculin, moesin, complement C3b and Rho GDP, which are known to be involved in cytoskeletal regulation including focal adhesions, inflammation and immune functions. Western blot analysis verified that talin was found to be increased in mild and moderate AD groups versus control, while the other three were found to be decreased. We also analysed amyloid precursor protein (APP), amyloid-β 1-40 (Aβ 40 ) and 1-42 (Aβ 42 ) levels in platelets from the same groups of subjects. Upregulation of platelet APP and Aβ peptides was found in AD patients compared to controls. These findings complement and expand previous reports concerning the morphological and functional alterations in AD platelets, and provide more insights into possible mechanisms that participate in the multifactorial and systemic damage in AD.

cDNA microarray reveals the alterations of cytoskeleton-related genes in osteoblast under high magneto-gravitational environment.

PubMed

Qian, Airong; Di, Shengmeng; Gao, Xiang; Zhang, Wei; Tian, Zongcheng; Li, Jingbao; Hu, Lifang; Yang, Pengfei; Yin, Dachuan; Shang, Peng

2009-07-01

The diamagnetic levitation as a novel ground-based model for simulating a reduced gravity environment has been widely applied in many fields. In this study, a special designed superconducting magnet, which can produce three apparent gravity levels (0, 1, and 2 g), namely high magneto-gravitational environment (HMGE), was used to simulate space gravity environment. The effects of HMGE on osteoblast gene expression profile were investigated by microarray. Genes sensitive to diamagnetic levitation environment (0 g), gravity changes, and high magnetic field changes were sorted on the basis of typical cell functions. Cytoskeleton, as an intracellular load-bearing structure, plays an important role in gravity perception. Therefore, 13 cytoskeleton-related genes were chosen according to the results of microarray analysis, and the expressions of these genes were found to be altered under HMGE by real-time PCR. Based on the PCR results, the expressions of WASF2 (WAS protein family, member 2), WIPF1 (WAS/WASL interacting protein family, member 1), paxillin, and talin 1 were further identified by western blot assay. Results indicated that WASF2 and WIPF1 were more sensitive to altered gravity levels, and talin 1 and paxillin were sensitive to both magnetic field and gravity changes. Our findings demonstrated that HMGE can affect osteoblast gene expression profile and cytoskeleton-related genes expression. The identification of mechanosensitive genes may enhance our understandings to the mechanism of bone loss induced by microgravity and may provide some potential targets for preventing and treating bone loss or osteoporosis.

Green fluorescent protein fusions to Arabidopsis fimbrin 1 for spatio-temporal imaging of F-actin dynamics in roots.

PubMed

Wang, Yuh-Shuh; Motes, Christy M; Mohamalawari, Deepti R; Blancaflor, Elison B

2004-10-01

The visualization of green fluorescent protein (GFP) fusions with microtubule or actin filament (F-actin) binding proteins has provided new insights into the function of the cytoskeleton during plant development. For studies on actin, GFP fusions to talin have been the most generally used reporters. Although GFP-Talin has allowed in vivo F-actin imaging in a variety of plant cells, its utility in monitoring F-actin in stably transformed plants is limited particularly in developing roots where interesting actin dependent cell processes are occurring. In this study, we created a variety of GFP fusions to Arabidopsis Fimbrin 1 (AtFim1) to explore their utility for in vivo F-actin imaging in root cells and to better understand the actin binding properties of AtFim1 in living plant cells. Translational fusions of GFP to full-length AtFim1 or to some truncated variants of AtFim1 showed filamentous labeling in transient expression assays. One truncated fimbrin-GFP fusion was capable of labeling distinct filaments in stably transformed Arabidopsis roots. The filaments decorated by this construct were highly dynamic in growing root hairs and elongating root cells and were sensitive to actin disrupting drugs. Therefore, the fimbrin-GFP reporters we describe in this study provide additional tools for studying the actin cytoskeleton during root cell development. Moreover, the localization of AtFim1-GFP offers insights into the regulation of actin organization in developing roots by this class of actin cross-linking proteins. Copyright 2004 Wiley-Liss, Inc.

Transforming properties of the Huntingtin interacting protein 1/ platelet-derived growth factor beta receptor fusion protein.

PubMed

Ross, T S; Gilliland, D G

1999-08-06

We have previously reported that the Huntingtin interacting protein 1 (HIP1) gene is fused to the platelet-derived growth factor beta receptor (PDGFbetaR) gene in a patient with chronic myelomonocytic leukemia. We now show that HIP1/PDGFbetaR oligomerizes, is constitutively tyrosine-phosphorylated, and transforms the murine hematopoietic cell line, Ba/F3, to interleukin-3-independent growth. A kinase-inactive mutant is neither tyrosine-phosphorylated nor able to transform Ba/F3 cells. Oligomerization and kinase activation required the 55-amino acid carboxyl-terminal TALIN homology region but not the leucine zipper domain. Tyrosine phosphorylation of a 130-kDa protein and STAT5 correlates with transformation in cells expressing HIP1/PDGFbetaR and related mutants. A deletion mutant fusion protein that contains only the TALIN homology region of HIP1 fused to PDGFbetaR is incapable of transforming Ba/F3 cells and does not tyrosine-phosphorylate p130 or STAT5, although it is itself constitutively tyrosine-phosphorylated. We have also analyzed cells expressing Tyr --> Phe mutants of HIP1/PDGFbetaR in the known PDGFbetaR SH2 docking sites and report that none of these sites are necessary for STAT5 activation, p130 phosphorylation, or Ba/F3 transformation. The correlation of factor-independent growth of hematopoietic cells with p130 and STAT5 phosphorylation/activation in both the HIP1/PDGFbetaR Tyr --> Phe and deletion mutational variants suggests that both STAT5 and p130 are important for transformation mediated by HIP1/PDGFbetaR.

acn-1, a C. elegans homologue of ACE, genetically interacts with the let-7 microRNA and other heterochronic genes.

PubMed

Metheetrairut, Chanatip; Ahuja, Yuri; Slack, Frank J

2017-10-02

The heterochronic pathway in C. elegans controls the relative timing of cell fate decisions during post-embryonic development. It includes a network of microRNAs (miRNAs), such as let-7, and protein-coding genes, such as the stemness factors, LIN-28 and LIN-41. Here we identified the acn-1 gene, a homologue of mammalian angiotensin-converting enzyme (ACE), as a new suppressor of the stem cell developmental defects of let-7 mutants. Since acn-1 null mutants die during early larval development, we used RNAi to characterize the role of acn-1 in C. elegans seam cell development, and determined its interaction with heterochronic factors, including let-7 and its downstream interactors - lin-41, hbl-1, and apl-1. We demonstrate that although RNAi knockdown of acn-1 is insufficient to cause heterochronic defects on its own, loss of acn-1 suppresses the retarded phenotypes of let-7 mutants and enhances the precocious phenotypes of hbl-1, though not lin-41, mutants. Conversely, the pattern of acn-1 expression, which oscillates during larval development, is disrupted by lin-41 mutants but not by hbl-1 mutants. Finally, we show that acn-1(RNAi) enhances the let-7-suppressing phenotypes caused by loss of apl-1, a homologue of the Alzheimer's disease-causing amyloid precursor protein (APP), while significantly disrupting the expression of apl-1 during the L4 larval stage. In conclusion, acn-1 interacts with heterochronic genes and appears to function downstream of let-7 and its target genes, including lin-41 and apl-1.

A Proposal for a Genome Similarity-Based Taxonomy for Plant-Pathogenic Bacteria that Is Sufficiently Precise to Reflect Phylogeny, Host Range, and Outbreak Affiliation Applied to Pseudomonas syringae sensu lato as a Proof of Concept.

PubMed

Vinatzer, Boris A; Weisberg, Alexandra J; Monteil, Caroline L; Elmarakeby, Haitham A; Sheppard, Samuel K; Heath, Lenwood S

2017-01-01

Taxonomy of plant pathogenic bacteria is challenging because pathogens of different crops often belong to the same named species but current taxonomy does not provide names for bacteria below the subspecies level. The introduction of the host range-based pathovar system in the 1980s provided a temporary solution to this problem but has many limitations. The affordability of genome sequencing now provides the opportunity for developing a new genome-based taxonomic framework. We already proposed to name individual bacterial isolates based on pairwise genome similarity. Here, we expand on this idea and propose to use genome similarity-based codes, which we now call life identification numbers (LINs), to describe and name bacterial taxa. Using 93 genomes of Pseudomonas syringae sensu lato, LINs were compared with a P. syringae genome tree whereby the assigned LINs were found to be informative of a majority of phylogenetic relationships. LINs also reflected host range and outbreak association for strains of P. syringae pathovar actinidiae, a pathovar for which many genome sequences are available. We conclude that LINs could provide the basis for a new taxonomic framework to address the shortcomings of the current pathovar system and to complement the current taxonomic system of bacteria in general.

Microring Resonators Vertically Coupled to Buried Heterostructure Bus Waveguides

DTIC Science & Technology

2005-06-01

Seung June Choi, Kostadin Djordjev, Sang Jun Choi, P. Daniel Dapkus, Fellow, IEEE, Wilson Lin, Giora Griffel , Ray Menna, and John Connolly Abstract—The...Department of Electrical Engineering-Electrophysics, University of Southern California, Los Angeles, CA 90089 USA. W. Lin, G. Griffel , R. Menna, and J

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

PubMed Central

Powers, John T; Tsanov, Kaloyan M; Pearson, Daniel S; Roels, Frederik; Spina, Catherine S; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Theiβen, Jessica; Tu, Ho-Chou; Han, Areum; Kurek, Kyle C; LaPier, Grace S; Osborne, Jihan K; Ross, Samantha J; Cesana, Marcella; Collins, James J; Berthold, Frank; Daley, George Q

2016-01-01

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumor suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. However, here we show that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN mRNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN-amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma pathogenesis with broad implications for cancer pathogenesis. PMID:27383785

The POU transcription factor UNC-86 controls the timing and ventral guidance of C. elegans axon growth

PubMed Central

Olsson-Carter, Katherine; Slack, Frank J.

2012-01-01

The in vivo mechanisms that coordinate the timing of axon growth and guidance are not well understood. In the C. elegans hermaphrodite specific neurons, the lin-4 microRNA controls the stage of axon initiation independent of the UNC-40 and SAX-3 ventral guidance receptors. lin-4 loss-of-function mutants exhibit marked delays in axon outgrowth, while lin-4 overexpression, leads to precocious growth in the L3. Here we show that loss of the POU transcription factor UNC-86 not only results in penetrant ventral axon growth defects in the HSNs, but also causes processes to extend in the L1, three stages earlier than wild-type. This temporal shift is not dependent on UNC-40 or SAX-3, and does not require the presence of lin-4. We propose that unc-86(lf) HSN axons are misguided due to the temporal decoupling of axon initiation and ventral guidance responses. PMID:21656875

Vertical spatial sensitivity and exploration depth of low-induction-number electromagnetic-induction instruments

USGS Publications Warehouse

Callegary, J.B.; Ferré, T.P.A.; Groom, R.W.

2007-01-01

Vertical spatial sensitivity and effective depth of exploration (d e) of low-induction-number (LIN) instruments over a layered soil were evaluated using a complete numerical solution to Maxwell's equations. Previous studies using approximate mathematical solutions predicted a vertical spatial sensitivity for instruments operating under LIN conditions that, for a given transmitter-receiver coil separation (s), coil orientation, and transmitter frequency, should depend solely on depth below the land surface. When not operating under LIN conditions, vertical spatial sensitivity and de also depend on apparent soil electrical conductivity (??a) and therefore the induction number (??). In this new evaluation, we determined the range of ??a and ?? values for which the LIN conditions hold and how de changes when they do not. Two-layer soil models were simulated with both horizontal (HCP) and vertical (VCP) coplanar coil orientations. Soil layers were given electrical conductivity values ranging from 0.1 to 200 mS m-1. As expected, de decreased as ??a increased. Only the least electrically conductive soil produced the de expected when operating under LIN conditions. For the VCP orientation, this was 1.6s, decreasing to 0.8s in the most electrically conductive soil. For the HCP orientation, de decreased from 0.76s to 0.51s. Differences between this and previous studies are attributed to inadequate representation of skin-depth effect and scattering at interfaces between layers. When using LIN instruments to identify depth to water tables, interfaces between soil layers, and variations in salt or moisture content, it is important to consider the dependence of de on ??a. ?? Soil Science Society of America.

Comparison of Two Methods for Calculating the Frictional Properties of Articular Cartilage Using a Simple Pendulum and Intact Mouse Knee Joints

PubMed Central

Drewniak, Elizabeth I.; Jay, Gregory D.; Fleming, Braden C.; Crisco, Joseph J.

2009-01-01

In attempts to better understand the etiology of osteoarthritis, a debilitating joint disease that results in the degeneration of articular cartilage in synovial joints, researchers have focused on joint tribology, the study of joint friction, lubrication, and wear. Several different approaches have been used to investigate the frictional properties of articular cartilage. In this study, we examined two analysis methods for calculating the coefficient of friction (μ) using a simple pendulum system and BL6 murine knee joints (n=10) as the fulcrum. A Stanton linear decay model (Lin μ) and an exponential model that accounts for viscous damping (Exp μ) were fit to the decaying pendulum oscillations. Root mean square error (RMSE), asymptotic standard error (ASE), and coefficient of variation (CV) were calculated to evaluate the fit and measurement precision of each model. This investigation demonstrated that while Lin μ was more repeatable, based on CV (5.0% for Lin μ; 18% for Exp μ), Exp μ provided a better fitting model, based on RMSE (0.165° for Exp μ; 0.391° for Lin μ) and ASE (0.033 for Exp μ; 0.185 for Lin μ), and had a significantly lower coefficient of friction value (0.022±0.007 for Exp μ; 0.042±0.016 for Lin μ) (p=0.001). This study details the use of a simple pendulum for examining cartilage properties in situ that will have applications investigating cartilage mechanics in a variety of species. The Exp μ model provided a more accurate fit to the experimental data for predicting the frictional properties of intact joints in pendulum systems. PMID:19632680

Loss of the Mammalian DREAM Complex Deregulates Chondrocyte Proliferation

PubMed Central

Forristal, Chantal; Henley, Shauna A.; MacDonald, James I.; Bush, Jason R.; Ort, Carley; Passos, Daniel T.; Talluri, Srikanth; Ishak, Charles A.; Thwaites, Michael J.; Norley, Chris J.; Litovchick, Larisa; DeCaprio, James A.; DiMattia, Gabriel; Holdsworth, David W.; Beier, Frank

2014-01-01

Mammalian DREAM is a conserved protein complex that functions in cellular quiescence. DREAM contains an E2F, a retinoblastoma (RB)-family protein, and the MuvB core (LIN9, LIN37, LIN52, LIN54, and RBBP4). In mammals, MuvB can alternatively bind to BMYB to form a complex that promotes mitotic gene expression. Because BMYB-MuvB is essential for proliferation, loss-of-function approaches to study MuvB have generated limited insight into DREAM function. Here, we report a gene-targeted mouse model that is uniquely deficient for DREAM complex assembly. We have targeted p107 (Rbl1) to prevent MuvB binding and combined it with deficiency for p130 (Rbl2). Our data demonstrate that cells from these mice preferentially assemble BMYB-MuvB complexes and fail to repress transcription. DREAM-deficient mice show defects in endochondral bone formation and die shortly after birth. Micro-computed tomography and histology demonstrate that in the absence of DREAM, chondrocytes fail to arrest proliferation. Since DREAM requires DYRK1A (dual-specificity tyrosine phosphorylation-regulated protein kinase 1A) phosphorylation of LIN52 for assembly, we utilized an embryonic bone culture system and pharmacologic inhibition of (DYRK) kinase to demonstrate a similar defect in endochondral bone growth. This reveals that assembly of mammalian DREAM is required to induce cell cycle exit in chondrocytes. PMID:24710275

Implementation of Structures in the CMS:Part 1, Rubble Mound

DTIC Science & Technology

2013-08-01

Lin, C. Lu, and A. T. Shak . 2011. Evaluation of Breakwaters and Sedimentation at Dana Point Harbor, CA. In Proceedings of Coastal Sediments 2011...08-13. Vicksburg, MS: US Army Engineer Research and Development Center. ERDC/CHL CHETN-IV-93 August 2013 9 Lu, C., A. T. Shak , H. Li, and L. Lin

Staff Directory | Argonne National Laboratory

Science.gov Websites

Engineer essam@anl.gov Jeff Elam Elam, Jeffrey Senior Chemist/Group Leader - Atomic Layer Deposition jelam of Greg Krumdick Krumdick, Greg Manager, Materials Engineering and Research Facility (MERF), Group Postdoctoral Appointee qi.li@anl.gov Photo of Yupo Lin Lin, YuPo Group Leader, Chemical and Biological

Prevalence and determinants of anaemia among children aged 0-59 months in a rural region of Armenia: a case-control study.

PubMed

Demirchyan, Anahit; Petrosyan, Varduhi; Sargsyan, Viktoria; Hekimian, Kim

2016-05-01

Despite the trend of increasing prevalence of childhood anaemia in Armenia, no studies exploring its risk factors have been conducted in the country. The present study aimed to investigate the prevalence and determinants of childhood anaemia in rural Armenia. Blood Hb level was measured among a representative sample of children using the HemoCue Hb201+ analyser. The revealed cases with anaemia were compared with randomly selected non-anaemic controls. Mothers of cases and controls were interviewed. Logistic and linear regression models were fitted to identify the risk factors of anaemia and low Hb level, respectively. Talin communities, Aragatsotn Province, Armenia. Children under 5 years of age in Talin region. Of the 729 studied children, 32·4% were anaemic with 14·7% having moderate/severe anaemia. Infants were the most affected group with 51·1% being anaemic before 6 months and 67·9% at 6-12 months of age. Fitted regression models identified the following predictors of anaemia: younger age, male gender, shorter birth length, anaemia during pregnancy, lower meal frequency per day, lack of meat in the diet, using dung cakes for heating and living in a community that received an incomplete set of nutrition interventions. The study identified several modifiable risk factors that could be targeted to reduce childhood anaemia in rural Armenia and, possibly, in rural areas in other low-/middle-income countries. The suggested interventions include prevention and treatment of anaemia during pregnancy, provision of adequate complementary feeding to children with inclusion of meat in their daily diet and reduction of their exposure to biomass fuel smoke.

Selective inhibition of prostaglandin E2 receptors EP2 and EP4 inhibits adhesion of human endometriotic epithelial and stromal cells through suppression of integrin-mediated mechanisms.

PubMed

Lee, JeHoon; Banu, Sakhila K; Burghardt, Robert C; Starzinski-Powitz, Anna; Arosh, Joe A

2013-03-01

Endometriosis is a chronic gynecological disease of reproductive age women characterized by the presence of functional endometrial tissues outside the uterine cavity. Interactions between the endometriotic cells and the peritoneal extracellular matrix proteins (ECM) are crucial mechanisms that allow adhesion of the endometriotic cells into peritoneal mesothelia. Prostaglandin E2 (PGE2) plays an important role in the pathogenesis of endometriosis. In previous studies, we have reported that selective inhibition of PGE2 receptors PTGER2 and PTGER4 decreases survival and invasion of human endometriotic epithelial and stromal cells through multiple mechanisms. Results of the present study indicates that selective inhibition of PTGER2- and PTGER4-mediated PGE2 signaling 1) decreases the expression and/or activity of specific integrin receptor subunits Itgb1 (beta1) and Itgb3 (beta3) but not Itgb5 (beta5), Itga1 (alpha1), Itga2 (alpha2), Itga5 (alpha5), and Itgav (alphav); 2) decreases integrin-signaling components focal adhesion kinase or protein kinase 2 (PTK2) and talin proteins; 3) inhibits interactions between Itgb1/Itgb3 subunits, PTK2, and talin and PTGER2/PTGER4 proteins through beta-arrestin-1 and Src kinase protein complex in human endometriotic epithelial cells 12Z and stromal cells 22B; and 4) decreases adhesion of 12Z and 22B cells to ECM collagen I, collagen IV, fibronectin, and vitronectin in a substrate-specific manner. These novel findings provide an important molecular framework for further evaluation of selective inhibition of PTGER2 and PTGER4 as potential nonsteroidal therapy to expand the spectrum of currently available treatment options for endometriosis in child-bearing age women.

Biodegradation of gamma-hexachlorocyclohexane (lindane) and alpha-hexachlorocyclohexane in water and a soil slurry by a Pandoraea species.

PubMed

Okeke, Benedict C; Siddique, Tariq; Arbestain, Marta Camps; Frankenberger, William T

2002-04-24

Isomers of 1,2,3,4,5,6-hexachlorocyclohexane (HCH) were some of the most widely used pesticides. Despite reduction in their production and use, HCH isomers present a serious environmental hazard. In this study, two bacterial isolates (LIN-1 and LIN-3) that can grow on gamma-HCH as a sole source of carbon and energy were isolated from an enrichment culture. In liquid cultures of LIN-1 and LIN-3, 25.0 and 45.5% removal of gamma-HCH, respectively, were achieved in 2 weeks. LIN-3 was identified as Pandoraea sp. by 16S rRNA gene sequence analysis (99% identity). Pandoraea sp. substantially degraded both gamma- and alpha-HCH isomers at concentrations of 10-200 mg L(-1) in liquid cultures. After 8 weeks of incubation in liquid culture, 89.9 and 93.3% of the gamma- and alpha-HCH isomers declined, respectively, at an initial concentration of 150 mg L(-1). In soil slurry cultures of Pandoraea sp., simulating a soil slurry phase bioremediation treatment, substantial decreases in the levels of the HCH isomers were observed at concentrations of 50-200 mg L(-1). After 9 weeks, 59.6 and 53.3% biodegradations of gamma- and alpha-HCH isomers, respectively, were achieved at 150 mg L(-1). Using two 23-mer oligonucloetide primers targeting the 330 bp region of the 16S rRNA gene of Pandoraea sp., an approximately 330 bp PCR product was successfully amplified from DNA templates prepared from bacterial colonies and soil slurry culture. This system provides a direct and rapid PCR-based molecular tool for tracking Pandoraea sp. strain LIN-3 in water and soils. These results have implied implications for the treatment of soils and water contaminated with HCH isomers.

Photonic-Networks-on-Chip for High Performance Radiation Survivable Multi-Core Processor Systems

DTIC Science & Technology

2013-12-01

Loss Spectra” Proceedings of SPIE 8255, (2012) and in a journal publication: M. T. Crowley, D. Murrell, N. Patel, M. Breivik , C.-Y. Lin, Y. Li, B.-O...Crowley, D. Murrell, N. Patel, M. Breivik , C.-Y. Lin, Y. Li, B.-O. Fimland and L. F. Lester, "Analytical Modeling of the Temperature Performance of

Deficiency of a membrane skeletal protein, 4.1G, results in myelin abnormalities in the peripheral nervous system.

PubMed

Saitoh, Yurika; Ohno, Nobuhiko; Yamauchi, Junji; Sakamoto, Takeharu; Terada, Nobuo

2017-12-01

We previously demonstrated that a membrane skeletal molecular complex, 4.1G-membrane palmitoylated protein 6 (MPP6)-cell adhesion molecule 4, is incorporated in Schwann cells in the peripheral nervous system (PNS). In this study, we evaluated motor activity and myelin ultrastructures in 4.1G-deficient (-/-) mice. When suspended by the tail, aged 4.1G -/- mice displayed spastic leg extension, especially after overwork. Motor-conduction velocity in 4.1G -/- mice was slower than that in wild-type mice. Using electron microscopy, 4.1G -/- mice exhibited myelin abnormalities: myelin was thicker in internodes, and attachment of myelin tips was distorted in some paranodes. In addition, we found a novel function of 4.1G for sorting a scaffold protein, Lin7, due to disappearance of the immunolocalization and reduction of the production of Lin7c and Lin7a in 4.1G -/- sciatic nerves, as well as the interaction of MPP6 and Lin7 with immunoprecipitation. Thus, we herein propose 4.1G functions as a signal for proper formation of myelin in PNS.

Can linear superiorization be useful for linear optimization problems?

NASA Astrophysics Data System (ADS)

Censor, Yair

2017-04-01

Linear superiorization (LinSup) considers linear programming problems but instead of attempting to solve them with linear optimization methods it employs perturbation resilient feasibility-seeking algorithms and steers them toward reduced (not necessarily minimal) target function values. The two questions that we set out to explore experimentally are: (i) does LinSup provide a feasible point whose linear target function value is lower than that obtained by running the same feasibility-seeking algorithm without superiorization under identical conditions? (ii) How does LinSup fare in comparison with the Simplex method for solving linear programming problems? Based on our computational experiments presented here, the answers to these two questions are: ‘yes’ and ‘very well’, respectively.

Granulocyte-colony stimulating factor and stem cell factor are the crucial factors in long-term culture of human primitive hematopoietic cells supported by a murine stromal cell line.

PubMed

Nishi, N; Ishikawa, R; Inoue, H; Nishikawa, M; Kakeda, M; Yoneya, T; Tsumura, H; Ohashi, H; Yamaguchi, Y; Motoki, K; Sudo, T; Mori, K J

1996-09-01

The findings that murine marrow stromal cell line MS-5 supported the proliferation of human lineage-negative (Lin-) CD34+CD38- bone marrow cells in long-term culture have been reported. In this study, we analyzed this proliferating activity of MS-5-conditioned medium (CM) on human primitive hematopoietic cells. When Lin-CD34+CD38- cells of normal human cord blood cells were co-cultured with MS-5, colony forming cells (CFCs) were maintained over 7 weeks in vitro. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by using membrane filter (0.45 micron) was negligible for this activity. This indicated that the activity of MS-5 on human primitive hematopoietic cells is a soluble factor(s) secreted from MS-5, which is not induced by the contact between MS-5 and Lin-CD34+CD38- cells. We tried to purify this soluble activity. An active material with a molecular weight of about 150 kDa, determined by gel filtration chromatography, solely supported the growth of Lin-CD34+CD38- cells and Mo7e, a human megakaryocytic cell line. This activity not only reacted with anti-mouse stem cell factor (mSCF) antibody on Western blots, but it was also neutralized in the presence of anti-mSCF antibody. Another active material with a molecular weight of about 20-30 kDa synergized with mSCF to stimulate the growth of Lin-CD34+CD38- cells but failed to do so alone, although this synergy was inhibited in the presence of soluble mouse granulocyte-colony stimulating factor (mG-CSF) receptor, which is a chimeric protein consisting of the extracellular domain of mG-CSF receptor and the Fe region of human IgG1. In addition, the latter molecule supported the growth of the G-CSF dependent cell line FD/GR3, which is a murine myeloid leukemia cell line, FDC-P2, transfected with mG-CSF receptor cDNA. Adding of anti-mSCF antibody and soluble mG-CSF receptor to the culture completely abrogated the activity of MS-5-CM. Recombinant (r) mSCF and rmG-CSF had synergistic activity on the growth of Lin

Physical Science Rocks! Outreach for Elementary Students

ERIC Educational Resources Information Center

McKone, Kevin

2010-01-01

Students at Copiah-Lincoln Community College (Co-Lin) have been hesitant to take courses in the physical sciences, mostly because of a lack of exposure to them in K-12 or a bad experience in this area. The college is addressing this need by exposing students to the physical sciences early on in their education. The science division at Co-Lin has…

Wide area Hyperspectral Motion Imaging

DTIC Science & Technology

2017-02-03

LEXINGTON, MASSACHUSETTS 02420-9108 (781) 981-1343 3 February 2017 TO: FROM: Dr. Joseph Lin (joseph.lin@ll.mit.edu), Advanced Imager ...Technology SUBJECT: Wide-area Hyperspectral Motion Imaging Introduction Wide-area motion imaging (WAMI) has received increased attention in...fielded imaging spectrometers use either dispersive or interferometric techniques. A dispersive spectrometer uses a grating or prism to disperse the

Geographic extension of an uneven-aged, multi-species matrix growth model for northern hardwood forests

Treesearch

Audra E. Kolbe; Joseph Buongiorno; Michael Vasievich

1999-01-01

The objective of this study was to update and extend the geographic range of a forest growth model for northern hardwoods, developed previously with data from the fourth Wisconsin inventory (Lin et al., 1996. Ecol. Model., 91: 193-211.). To this end, Lin's model was recalibrated with data from the recent fifth inventory of Wisconsin and Michigan, and with the...

Effects of acerola fruit extract on sensory and shelf-life of salted beef patties from grinds differing in fatty acid composition.

PubMed

Realini, C E; Guàrdia, M D; Díaz, I; García-Regueiro, J A; Arnau, J

2015-01-01

The effects of added acerola fruit extract on sensory and shelf-life of beef patties were evaluated. Ground beef was obtained from young bulls fed one of four diets (CON: control, LIN: linseed, CLA: conjugated linoleic acid, LINCLA: LIN plus CLA). Pre-salted (1.8% w/w) beef patties (7.7% fat) with (0.15% w/w) or without acerola were packed in modified atmosphere (80%O2:20%CO2) and displayed in a retail case for 8days. There were no interactions between diet and antioxidant treatments. LIN and/or CLA had no effect on color and lipid stability during display. However, LIN increased n-3 fatty acids in beef and tended to increase intensity of rancid flavor. Addition of acerola extended shelf-life by at least 3 days by improving color and lipid stability and a decreased trend in intensity of rancid flavor of patties without affecting microbial counts. Thus, the use of acerola as a natural antioxidant can be considered an effective method to retard color and lipid oxidation in beef patties. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional relevance of “seed” and “non-seed” sequences in microRNA-mediated promotion of C. elegans developmental progression

PubMed Central

Zhang, Huibin; Artiles, Karen L.; Fire, Andrew Z.

2015-01-01

The founding heterochronic microRNAs, lin-4 and let-7, together with their validated targets and well-characterized phenotypes in C. elegans, offer an opportunity to test functionality of microRNAs in a developmental context. In this study, we defined sequence requirements at the microRNA level for these two microRNAs, evaluating lin-4 and let-7 mutant microRNAs for their ability to support temporal development under conditions where the wild-type lin-4 and let-7 gene products are absent. For lin-4, we found a strong requirement for seed sequences, with function drastically affected by several central mutations in the seed sequence, while rescue was retained by a set of mutations peripheral to the seed. let-7 rescuing activity was retained to a surprising degree by a variety of central seed mutations, while several non-seed mutant effects support potential noncanonical contributions to let-7 function. Taken together, this work illustrates both the functional partnership between seed and non-seed sequences in mediating C. elegans temporal development and a diversity among microRNA effectors in the contributions of seed and non-seed regions to activity. PMID:26385508

Pushing the Material Limits in High Kappa Dielectrics on High Carrier Mobility Semiconductors for Science/Technology Beyond Si CMOS and More

DTIC Science & Technology

2014-01-28

In0.53Ga0.47As, with an Al2O3 cap, were employed as a gate dielectric. 15. SUBJECT TERMS CMOS, Magneto-optical imaging , Nanotechnology, Indium Gallium ...2012. 2. “ Thermodynamic stability of MBE-HfO2 on In0.53Ga0.47As”, T. D. Lin, P. Chang, W. C. Lee, M. L. Huang, C. A. Lin, J. Kwo, and M. Hong

ONR Tokyo Scientific Bulletin. Volume 5, Number 3, July-September 1980,

DTIC Science & Technology

1980-09-01

engineering Director NATIONAL TAIWAN UNIVERSITY, TAIPEI - Department of Agricultural Chemistry Chen. Yuh-Lin Pesticide chemistry Professor Lin. Liang-Ping...3-1, Hongo, Bynkyo-ku Tokyo 113 August 9- The 5th International Congress Kyoto, Japan Rikagaku Kenkyusho September 3 of Pesticide Chemistry, IUPAC 2-1...to those who request them. The meeting emphasized two timely subjects, inhalation injuries and fluid therapy. Papers presented were: Basil A. Pruitt

Orbiter global positioning system design and Ku-band problems investigation, exhibit B, revision 1

NASA Technical Reports Server (NTRS)

Chie, C. M.; Braun, W. R.

1981-01-01

The LinCom effort in supporting the JSC study of the use of the Global Positioning System (GPS) on the space shuttle and in Ku-band problem investigation is documented. LinCom was tasked to evaluate system implementation, performance, and integration aspects of the shuttle GPS and to provide independent technical assessment of reports submitted to JSC regarding integration studies, system studies and navigation analyses.

Epidemiology of Toxocara canis in the dog population from two areas of different socioeconomic status, Greater Buenos Aires, Argentina.

PubMed

Rubel, D; Zunino, G; Santillán, G; Wisnivesky, C

2003-07-29

Toxocara canis infection in dogs is a public health problem in most countries, although it has been poorly documented in many of them. The main objective of the present work was to investigate the epidemiology of infection in the canine populations from two areas of Buenos Aires of different socioeconomic status and urban conditions: a middle-income neighbourhood (MIN) and a low-income neighbourhood (LIN). This study evaluated the prevalence of infection in dogs by parasitological and serological techniques in both areas, and described the relationship between the infection and different epidemiological variables for each neighbourhood. A cross-sectional study was carried out after a house-to-house census was completed. During August 1999, a sample of households was selected at random (nMIN=53 and nPA=52). In each house, one dog was randomly chosen for the collection of fresh faeces and blood. The dog owners were interviewed utilising a questionnaire about dogs on sex, recent anthelmintic treatment, degree of confinement, control by the dog's owner (whether the dog goes out of the house accompanied or not, leashed or unleashed), defecation site, defecation substratum and number of dogs in the house. The diagnostic techniques were concentration-sedimentation formalin/ether method and ELISA test. The parasitological prevalences in dogs were 9% (5/53) in MIN and 19% (10/52) in LIN, and serological prevalences were 22% (2/9) in MIN and 40% (15/37) in LIN. In MIN, the patent infection of males was significantly higher than that of females. In LIN, puppies less than 1 year old were the most prevalent age class. Our serological results showed that the positivity of adult dogs was more frequent in LIN than in MIN. The density of puppies with patent infection was seven times higher in LIN than in MIN, when combining coprological analysis and the estimated age structure obtained by the census.

The effect of Bcr-Abl protein tyrosine kinase on maturation and proliferation of primitive haematopoietic cells.

PubMed Central

Buckle, A. M.; Mottram, R.; Pierce, A.; Lucas, G. S.; Russell, N.; Miyan, J. A.; Whetton, A. D.

2000-01-01

BACKGROUND: Chronic Myeloid Leukaemia (CML) is characterised by the chromosomal translocation resulting in expression of the Bcr-Abl protein tyrosine kinase (PTK) in early stem cells and their progeny. However the precise nature of Bcr-Abl effects in primitive CML stem cells remains a matter of active debate. MATERIALS AND METHODS: Extremely primitive Bcr-Abl fusion positive cells were purified from patients with CML using multiparameter flow cytometric analysis of CD34, Thy, and lineage marker (Lin) expression, plus rhodamine-123 (Rh-123) brightness. Progenitor cells of increasing maturity were examined for cycling status by flow cytometry and their proliferative status directly correlated with cell phenotype. The activation status of a key transcription factor, signal transducers and activators of transcription (STAT-5), was also analyzed by immunocytochemistry. RESULTS: The most primitive stem cells currently defined (CD34+Lin-Thy+ Rh-1231o) were present as a lower proportion of the stem cell compartment (CD34+Lin-) of CML patients at presentation than of normal individuals (2.3% +/- 0.4 compared with 5.1% +/- 0.6 respectively). Conversely there was a significantly higher proportion of the more mature cells (CD34+Lin-Thy-Rh-123 hi) in CML patients than in normal individuals (79.3 +/- 1.8 compared with 70.9 +/- 3.3). No primitive subpopulation of CML CD34+Lin- cells was cycling to a significantly greater degree than cells from normal donors, in fact, late progenitor cells (CD34+Lin+) were cycling significantly less in CML samples than normal samples. STAT5, however, was observed to be activated in CML cells. CONCLUSIONS: We conclude that no subpopulation of CML stem cells displays significantly increased cell cycling. Thus, increased cycling cannot be a direct consequence of Bcr-Abl PTK acquisition in highly enriched stem cells from patients with CML. In vivo CML need not be considered a disease of unbridled stem cell proliferation, but a subtle defect in the

Extremely low frequency electromagnetic fields promote mesenchymal stem cell migration by increasing intracellular Ca2+ and activating the FAK/Rho GTPases signaling pathways in vitro.

PubMed

Zhang, Yingchi; Yan, Jiyuan; Xu, Haoran; Yang, Yong; Li, Wenkai; Wu, Hua; Liu, Chaoxu

2018-05-21

The ability of mesenchymal stem cells (MSCs) to migrate to the desired tissues or lesions is crucial for stem cell-based regenerative medicine and tissue engineering. Optimal therapeutics for promoting MSC migration are expected to become an effective means for tissue regeneration. Electromagnetic fields (EMF), as a noninvasive therapy, can cause a lot of biological changes in MSCs. However, whether EMF can promote MSC migration has not yet been reported. We evaluated the effects of EMF on cell migration in human bone marrow-derived MSCs. With the use of Helmholtz coils and an EMF stimulator, 7.5, 15, 30, 50, and 70 Hz/1 mT EMF was generated. Additionally, we employed the L-type calcium channel blocker verapamil and the focal adhesion kinase (FAK) inhibitor PF-573228 to investigate the role of intracellular calcium content, cell adhesion proteins, and the Rho GTPase protein family (RhoA, Rac1, and Cdc42) in EMF-mediated MSC migration. Cell adhesion proteins (FAK, talin, and vinculin) were detected by Western blot analysis. The Rho GTPase protein family activities were assessed by G-LISA, and F-actin levels, which reflect actin cytoskeletal organization, were detected using immunofluorescence. All the 7.5, 15, 30, 50, and 70 Hz/1 mT EMF promoted MSC migration. EMF increased MSC migration in an intracellular calcium-dependent manner. Notably, EMF-enhanced migration was mediated by FAK activation, which was critical for the formation of focal contacts, as evidenced by increased talin and vinculin expression. Moreover, RhoA, Rac1, and Cdc42 were activated by FAK to increase cytoskeletal organization, thus promoting cell contraction. EMF promoted MSC migration by increasing intracellular calcium and activating the FAK/Rho GTPase signaling pathways. This study provides insights into the mechanisms of MSC migration and will enable the rational design of targeted therapies to improve MSC engraftment.

Ultrastructural and biochemical localization of N-RAP at the interface between myofibrils and intercalated disks in the mouse heart.

PubMed

Zhang, J Q; Elzey, B; Williams, G; Lu, S; Law, D J; Horowits, R

2001-12-11

N-RAP is a recently discovered muscle-specific protein found at cardiac intercalated disks. Double immunogold labeling of mouse cardiac muscle reveals that vinculin is located immediately adjacent to the fascia adherens region of the intercalated disk membrane, while N-RAP extends approximately 100 nm further toward the interior of the cell. We partially purified cardiac intercalated disks using low- and high-salt extractions followed by density gradient centrifugation. Immunoblots show that this preparation is highly enriched in desmin and junctional proteins, including N-RAP, talin, vinculin, beta1-integrin, N-cadherin, and connexin 43. Electron microscopy and immunolabeling demonstrate that N-RAP and vinculin are associated with the large fragments of intercalated disks that are present in this preparation, which also contains numerous membrane vesicles. Detergent treatment of the partially purified intercalated disks removed the membrane vesicles and extracted vinculin and beta1-integrin. Further separation on a sucrose gradient removed residual actin and myosin and yielded a fraction morphologically similar to fasciae adherentes that was highly enriched in N-RAP, N-cadherin, connexin 43, talin, desmin, and alpha-actinin. The finding that N-RAP copurifies with detergent-extracted intercalated disk fragments even though beta-integrin and vinculin have been completely removed suggests that N-RAP association with the adherens junction region is mediated by the cadherin system. Consistent with this hypothesis, we found that recombinant N-RAP fragments bind alpha-actinin in a gel overlay assay. In addition, immunofluorescence shows that N-RAP remains bound at the ends of isolated, detergent-treated cardiac myofibrils. These results demonstrate that N-RAP remains tightly bound to myofibrils and fasciae adherentes during biochemical purification and may be a key constituent in the mechanical link between these two structures.

MAXI observation of a long X-ray burst from SAX J1712.6-3739

NASA Astrophysics Data System (ADS)

Iwakiri, W.; Negoro, H.; Serino, M.; in't Zand, J.; Kawai, N.; Nakajima, M.; Sakamaki, A.; Maruyama, W.; Mihara, T.; Nakahira, S.; Yatabe, F.; Takao, Y.; Matsuoka, M.; Sakamoto, T.; Sugita, S.; Kawakubo, Y.; Hashimoto, T.; Yoshida, A.; Sugizaki, M.; Tachibana, Y.; Morita, K.; Ueno, S.; Tomida, H.; Ishikawa, M.; Sugawara, Y.; Isobe, N.; Shimomukai, R.; Ueda, Y.; Tanimoto, A.; Morita, T.; Yamada, S.; Tsuboi, Y.; Sasaki, R.; Kawai, H.; Sato, T.; Tsunemi, H.; Yoneyama, T.; Yamauchi, M.; Hidaka, K.; Iwahori, S.; Kawamuro, T.; Yamaoka, K.; Shidatsu, M.

2018-05-01

We analyzed the MAXI observation of the long type-I X-ray burst from SAX J1712.6-3739 reported by Lin & Yu (ATel #11623, 2018). MAXI observed the region of SAX J1712.6-3739 during 09:25:38 to 09:26:58 UT May 8th 2018 which is about 8 minutes after the peak observed with Swift/BAT (at 09:18:12 UT according to Lin & Yu 2018).

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2015-08-01

1 AD_________________ Award Number: W81XWH-10-1-0558 TITLE: Characterizing and Targeting Replication Stress Response Defects in Breast Cancer ...PRINCIPAL INVESTIGATOR: Shiaw-Yih Lin, Ph.D. CONTRACTING ORGANIZATION: University of Texas M. D. Anderson Cancer Center Houston, TX 77030 REPORT...Response Defects in Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Betty Diamond 5d. PROJECT NUMBER Chun-Jen Lin, Hui Dai

General and Robust Strategies for Multifunctional Organic-Inorganic Nanocompositesvia Direct Growth of Monodisperse Nanocrystals Intimately and Permanently Connected with Polymers

DTIC Science & Technology

2016-04-21

Nanocrystals Intimately and Permanently Connected with Polymers Zhiqun Lin GEORGIA TECH RESEARCH CORPORATION Final Report 04/21/2016 DISTRIBUTION A...Connected with Polymers 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA9550-13-1-0101 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Lin, Zhiqun 5d. PROJECT...and properties, which are intimately and permanently capped by polymers on their surface (i.e., forming organic-inorganic nanocomposites), by

Combined Biology and Bioinformatics Approaches to Breast Cancer

DTIC Science & Technology

2007-10-01

Figure 1-9 B. Bibliography of publications and meeting abstracts: Papers: 1). Ning Wang, Kevin Lin, Zhongxian Lu, Kaye Starr Lam, Xiaoman Xu...Oncogene， 2006, 25(20): 2920-2930. 3). Zhengquan Yu, Kevin Lin，Ambica Bhandari, Joel Spencer, Xiaoman Xu, Ning Wang，Zhongxian Lu，Gordon N Gill...and interacts functionally with LMO4. Developmental Biology, 2006, 299(1):122-36. Abstracts: 1). Zhongxian Lu, Ning Wang, Kevin K. Lin, Kaye Starr

FY08 In-House Laboratory Independent Research (ILIR) and Independent Applied Research (IAR) Annual Reports

DTIC Science & Technology

2009-01-01

body (SUBOFF) in rotation, NSWCCD-50- TR-2008/030. Carneal, J., S. Percival, A. Etebari, P. Atsavapranee, T. Farabee, M. Goody, Optical bubble...Coursekeeping Funding Year: Third Principal Investigator: Dr. Ray-Qing Lin, Code: 5500, NSWC Carderock Phone: 301-227-3945, E-mail Address...accepted for publications Lin, R-Q., and W. Kuang, , Solid- body motion in fully nonlinear ship motion model, submitted to J. Marine Science and

Lower Oncogenic Potential of Human Mesenchymal Stem Cells Derived from Cord Blood Compared to Induced Pluripotent Stem Cells

PubMed Central

Foroutan, T.; Najmi, M.; Kazemi, N.; Hasanlou, M.; Pedram, A.

2015-01-01

Background: In regenerative medicine, use of each of the mesenchymal stem cells derived from bone marrow, cord blood, and adipose tissue, has several cons and pros. Mesenchymal stem cells derived from cord blood have been considered the best source for precursor transplantation. Direct reprogramming of a somatic cell into induced pluripotent stem cells by over-expression of 6 transcription factors Oct4, Sox2, Klf4, lin28, Nanog, and c-Myc has great potential for regenerative medicine, eliminating the ethical issues of embryonic stem cells and the rejection problems of using non-autologous cells. Objective: To compare reprogramming and pluripotent markers OCT4, Sox-2, c-Myc, Klf4, Nanog, and lin28 in mesenchymal stem cells derived from cord blood and induced pluripotent stem cells. Methods: We analyzed the expression level of OCT4, Sox-2, c-Myc, Klf4, Nanog and lin28 genes in human mesenchymal stem cells derived from cord blood and induced pluripotent stem cells by cell culture and RT-PCR. Results: The expression level of pluripotent genes OCT4 and Sox-2, Nanog and lin28 in mesenchymal stem cells derived from cord blood were significantly higher than those in induced pluripotent stem cells. In contrast to OCT-4A and Sox-2, Nanog and lin28, the expression level of oncogenic factors c-Myc and Klf4 were significantly higher in induced pluripotent stem cells than in mesenchymal stem cells derived from cord blood. Conclusion: It could be concluded that mesenchymal stem cells derived from human cord blood have lower oncogenic potential compared to induced pluripotent stem cells. PMID:26306155

Effects of anti-androgens cyproterone acetate, linuron, vinclozolin, and p,p'-DDE on the reproductive organs of the copepod Acartia tonsa.

PubMed

Watermann, Burkard T; Albanis, Triantafyllos A; Galassi, Silvana; Gnass, Katarina; Kusk, Kresten O; Sakkas, Vasilios A; Wollenberger, Leah

2016-11-09

The study was performed to detect the effects of anti-androgenic compounds on the reproduction. In this paper alterations observed in the marine calanoid copepod Acartia tonsa exposed to environmental concentrations of cyproterone acetate (CPA), linuron (LIN), vinclozolin (VIN), and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) for 21 days covering a full life cycle are described. Histological alterations were studied with a focus on reproductive organs, gonad and accessory sexual glands. Exposure to ≥1.2 µg L(-1) CPA caused degeneration of spermatocytes and deformation of the spermatophore in males. In a single male exposed to 33 µg L(-1) CPA, an ovotestis was observed. In CPA exposed females, enhancement of oogenesis, increase in apoptosis and a decrease in proliferation occurred. Exposure of males to ≥12 µg L(-1) LIN caused degenerative effects in spermatogonia, spermatocytes and spermatids, and at 4.7 µg L(-1) LIN, the spermatophore wall displayed an irregular formation. In LIN exposed females, no such structural alterations were found; however, the proliferation index was reduced at 29 µg L(-1) LIN. At an exposure concentration of ≥100 µg L(-1) VIN, distinct areas in male gonad were stimulated, whereas others displayed a disturbed spermatogenesis and a deformed spermatophore wall. In VIN exposed female A. tonsa, no effects were observed. Male A. tonsa exposed to p,p'-DDE displayed an impairment of spermatogenesis in all stages with increased degrees of apoptosis. In p,p'-DDE-exposed females, a statistical significant increase of the proliferation index and an intensification of oogenesis were observed at 0.0088 µg L(-1).

RLE (Research Laboratory of Electronics) Progress Report Number 130

DTIC Science & Technology

1988-07-01

Ippen, James G. Fujimoto, Wei-Zhu Lin, Beat Zysset, Robert W. Schoenlein, 4 Michael J. Lagasse The investigation of transient carrier dynamics in GaAs...G. Fujimoto, Wei-Zhu Lin, Reginald Birngruber, Beat Zysset, Robert W. Schoenleln Working in collaboration with researchers at the Massachusetts Eye... Binaural Hearing National Institutes of Health (Grant 5 RO 1 NS 10916) H. Steven Colburn, Nathaniel 1. Durlach, Patrick M. Zurek 17 Brooklyn College14 141

Draft Genome Sequence of a Hexachlorocyclohexane-Degrading Bacterium, Sphingobium baderi Strain LL03T

PubMed Central

Kaur, Jasvinder; Verma, Helianthous; Tripathi, Charu; Khurana, J. P.

2013-01-01

Sphingobium baderi strain LL03T was isolated from hexachlorocyclohexane (HCH)-contaminated soil from Spolana, Czech Republic. Strain LL03T is a mutant that is deficient in linB and linC (genes that encode hexachlorocyclohexane haloalkane dehalogenase and dehydrogenase, respectively). The draft genome sequence of LL03T (~4.85 Mb) consists of 92 contigs and 4,914 coding sequences, with a G+C content of 63.5%. PMID:24051322

Transient Non Lin Deformation in Fractured Rock

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

Sartori, Enrico

1998-10-14

MATLOC is a nonlinear, transient, two-dimensional (planer and axisymmetric), thermal stress, finite-element code designed to determine the deformation within a fractured rock mass. The mass is modeled as a nonlinear anistropic elastic material which can exhibit stress-dependent bi-linear locking behavior.

Interactive and Continuous Collision Detection for Avatars in Virtual Environments

DTIC Science & Technology

2007-01-01

Box 12211 Research Triangle Park, NC 27709-2211 15. SUBJECT TERMS collision detection Young Kim, Stephane Redon, Ming Lin, Dinesh Manocha, Jim...Redon1 Young J. Kim2 Ming C. Lin1 Dinesh Manocha1 Jim Templeman3 1 University of North Carolina at Chapel Hill 2 Ewha University, Korea 3 Naval...An offset spline approximation for plane cubic splines. Computer-Aided Design, 15(5):297– 299, 1983. [20] S. Kumar and D. Manocha. Efficient

International Conference on Superlattices, Microstructures and Microdevices (3rd) Held in Chicago, Illinois on August 17-20, 1987.

DTIC Science & Technology

1987-08-20

contributed) A. Scherer, P. S. 0. Lin, P. Grobbe, Tp6 electron Impact Ionization from GaAs J. Harbison, L. Schiavone , Bell imntibued) quantum well...molecular beam epitaxy. 20 :’% .•% , *U.%.*. Mp 4 eVV % % Semiconductor Microcrystallites in Porous Glass and Their Applications in Optics .1%• John C. Luong...A. Scherer, P.S.D. Lin, P. Grabbe, J. Harbison, L. Schiavone .v/- Bell Communications Research Red Bank, NJ 07701 Recent advances in electron beam

A Computational Wireless Network Backplane: Performance in a Distributed Speaker Identification Application Postprint

DTIC Science & Technology

2008-12-01

AUTHOR(S) H.T. Kung, Chit-Kwan Lin, Chia-Yung Su, Dario Vlah, John Grieco, Mark Huggins, and Bruce Suter 5d. PROJECT NUMBER WCNA 5e. TASK NUMBER...APPLICATION H. T. Kung, Chit-Kwan Lin, Chia-Yung Su, Dario Vlah John Grieco†, Mark Huggins‡, Bruce Suter† Harvard University Air Force Research Lab†, Oasis...contributing its C7 processors used in our wireless testbed. REFERENCES [1] R. North, N. Browne, and L. Schiavone , “Joint tactical radio system - connecting

Single Microwave-Photon Detector using an Artificial Lambda-type Three-Level System

DTIC Science & Technology

2016-01-11

Single microwave-photon detector using an artificial Λ-type three- level system Kunihiro Inomata,1∗†, Zhirong Lin,1†, Kazuki Koshino,2, William D...three- level system Kunihiro Inomata,1∗† Zhirong Lin,1† Kazuki Koshino,2 William D. Oliver,3,4 Jaw-Shen Tsai,1 Tsuyoshi Yamamoto,5 Yasunobu Nakamura...single-microwave-photon detector based on the deterministic switching in an artificial Λ-type three- level system implemented using the dressed states of a

Understanding Selective Downregulation of c-Myc Expression through Inhibition of General Transcription Regulators in Multiple Myeloma

DTIC Science & Technology

2014-06-01

AUTHOR(S) 5d. PROJECT NUMBER Dr. Charles Lin 5e. TASK NUMBER E-Mail: Charles_lin@dfci.harvard.edu 5f. WORK UNIT NUMBER 7...landscape of Multiple Myeloma (MM), this project has endeavored to provide an explanatory mechanism for how treatment with inhibitors of chromatin...category: 1472-1), BRD4 (Epitomics, category: 5716-1) or b-actin ( Sigma , clone AC-15, A5441). Data Analysis All ChIP-seq data sets were aligned using

Spectroscopic Investigation of the Argon Metastable State Through Optical Emission From Pulsed Argon Discharge

DTIC Science & Technology

2010-07-01

a multielectron atom from occupying the same stationary state. This is expressed in the Pauli exclusion principle as the rule that no two electrons...ed. (John Wiley and Sons Inc., ADDRESS, 1971). 54 [20] R. O. Jung , J. B. Boffard, L. W. Anderson, and C. C. Lin, Physical Review A (Atomic, Molecular...Physics 41, 065206 (2008). [34] J. B. Boffard, R. O. Jung , C. C. Lin, and A. E. Wendt, Plasma Sources Science and Technology 18, 035017 (2009). [35

Wobbled electronic properties of lithium clusters: Deterministic approach through first principles

NASA Astrophysics Data System (ADS)

Kushwaha, Anoop Kumar; Nayak, Saroj Kumar

2018-03-01

The innate tendency to form dendritic growth promoted through cluster formation leading to the failure of a Li-ion battery system have drawn significant attention of the researchers towards the effective destabilization of the cluster growth through selective implementation of electrolytic media such as acetonitrile (MeCN). In the present work, using first principles density functional theory and continuum dielectric model, we have investigated the origin of oscillatory nature of binding energy per atom of Lin (n ≤ 8) under the influence of MeCN. In the gas phase, we found that static mean polarizability is strongly correlated with binding energy and shows oscillatory nature with cluster size due to the open shell of Lin cluster. However, in acetonitrile medium, the binding energy has been correlated with electrostatic Lin -MeCN interaction and it has been found that both of them possess wobbled behavior characterized by the cluster size.

CD4 T-cell cytokines synergize to induce proliferation of malignant and nonmalignant innate intraepithelial lymphocytes.

PubMed

Kooy-Winkelaar, Yvonne M C; Bouwer, Dagmar; Janssen, George M C; Thompson, Allan; Brugman, Martijn H; Schmitz, Frederike; de Ru, Arnoud H; van Gils, Tom; Bouma, Gerd; van Rood, Jon J; van Veelen, Peter A; Mearin, M Luisa; Mulder, Chris J; Koning, Frits; van Bergen, Jeroen

2017-02-07

Refractory celiac disease type II (RCDII) is a severe complication of celiac disease (CD) characterized by the presence of an enlarged clonal population of innate intraepithelial lymphocytes (IELs) lacking classical B-, T-, and natural killer (NK)-cell lineage markers (Lin - IELs) in the duodenum. In ∼50% of patients with RCDII, these Lin - IELs develop into a lymphoma for which no effective treatment is available. Current evidence indicates that the survival and expansion of these malignant Lin - IELs is driven by epithelial cell-derived IL-15. Like CD, RCDII is strongly associated with HLA-DQ2, suggesting the involvement of HLA-DQ2-restricted gluten-specific CD4 + T cells. We now show that gluten-specific CD4 + T cells isolated from CD duodenal biopsy specimens produce cytokines able to trigger proliferation of malignant Lin - IEL lines as powerfully as IL-15. Furthermore, we identify TNF, IL-2, and IL-21 as CD4 + T-cell cytokines that synergistically mediate this effect. Like IL-15, these cytokines were found to increase the phosphorylation of STAT5 and Akt and transcription of antiapoptotic mediator bcl-x L Several small-molecule inhibitors targeting the JAK/STAT pathway blocked proliferation elicited by IL-2 and IL-15, but only an inhibitor targeting the PI3K/Akt/mTOR pathway blocked proliferation induced by IL-15 as well as the CD4 + T-cell cytokines. Confirming and extending these findings, TNF, IL-2, and IL-21 also synergistically triggered the proliferation of freshly isolated Lin - IELs and CD3 - CD56 + IELs (NK-IELs) from RCDII as well as non-RCDII duodenal biopsy specimens. These data provide evidence implicating CD4 + T-cell cytokines in the pathogenesis of RCDII. More broadly, they suggest that adaptive immune responses can contribute to innate IEL activation during mucosal inflammation.

Morphological parameters of flat epithelial atypia (FEA) in stereotactic vacuum-assisted needle core biopsies do not predict the presence of malignancy on subsequent surgical excision.

PubMed

Bianchi, Simonetta; Bendinelli, Benedetta; Castellano, Isabella; Piubello, Quirino; Renne, Giuseppe; Cattani, Maria Grazia; Di Stefano, Domenica; Carrillo, Giovanna; Laurino, Licia; Bersiga, Alessandra; Giardina, Carmela; Dante, Stefania; Di Loreto, Carla; Quero, Carmela; Antonacci, Concetta Maria; Palli, Domenico

2012-10-01

Flat epithelial atypia (FEA) may represent the earliest precursor of low-grade breast cancer and often coexists with more advanced atypical proliferative breast lesions such as atypical ductal hyperplasia (ADH) and lobular intraepithelial neoplasia (LIN). The present study aims to investigate the association between morphological parameters of FEA and presence of malignancy at surgical excision (SE) and the clinical significance of the association of FEA with ADH and/or LIN. This study included 589 cases of stereotactic 11-gauge vacuum-assisted needle core biopsy (VANCB), reporting a diagnosis of FEA, ADH or LIN with subsequent SE from 14 pathology departments in Italy. Available slides were reviewed, with 114 (19.4 %) showing a malignant outcome at SE. Among the 190 cases of pure FEA, no statistically significant association emerged between clinical-pathological parameters of FEA and risk of malignancy. Logistic regression analyses showed an increased risk of malignancy according to the extension of ADH among the 275 cases of FEA associated with ADH (p = 0.004) and among the 34 cases of FEA associated with ADH and LIN (p = 0.02). In the whole series, a statistically significant increased malignancy risk emerged according to mammographic R1-R3/R4-R5 categories (OR = 1.56; p = 0.04), extension (OR = 1.24; p = 0.04) and grade (OR = 1.94; p = 0.004) of cytological atypia of FEA. The presence of ADH was associated with an increased malignancy risk (OR = 2.85; p < 0.0001). Our data confirm the frequent association of FEA with ADH and/or LIN. A diagnosis of pure FEA on VANCB carries a 9.5 % risk of concurrent malignancy and thus warrants follow-up excision because none of the clinical-pathological parameters predicts which cases will present carcinoma on SE.

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

PubMed

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

2016-08-01

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

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

PubMed Central

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

2016-01-01

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

Integrative taxonomy of Leptonetela spiders (Araneae, Leptonetidae), with descriptions of 46 new species

PubMed Central

Wang, Chun-Xia; Xu, Xin; Li, Shu-Qiang

2017-01-01

Extreme environments, such as subterranean habitats, are suspected to be responsible for morphologically inseparable cryptic or sibling species and can bias biodiversity assessment. A DNA barcode is a short, standardized DNA sequence used for taxonomic purposes and has the potential to lessen the challenges presented by a biotic inventory. Here, we investigate the diversity of the genus Leptonetela Kratochvíl, 1978 that is endemic to karst systems in Eurasia using DNA barcoding. We analyzed 624 specimens using one mitochondrial gene fragment (COI). The results show that DNA barcoding is an efficient and rapid species identification method in this genus. DNA barcoding gap and automatic barcode gap discovery (ABGD) analyses indicated the existence of 90 species, a result consistent with previous taxonomic hypotheses, and supported the existence of extreme male pedipalpal tibial spine and median apophysis polymorphism in Leptonetela species, with direct implications for the taxonomy of the group and its diversity. Based on the molecular and morphological evidence, we delimit and diagnose 90 Leptonetela species, including the type species Leptonetela kanellisi(Deeleman-Reinhold, 1971). Forty-six of them are previously undescribed. The female of Leptonetela zhai Wang & Li, 2011 is reported for the first time. Leptonetela tianxinensis (Tong & Li, 2008) comb. nov. is transferred from the genus Leptoneta Simon, 1872;the genus Guineta Lin & Li, 2010 syn. nov. is a junior synonym of Leptonetela; Leptonetela gigachela(Lin & Li, 2010) comb. nov. is transferred from Guineta. The genus Sinoneta Lin & Li, 2010 syn. nov. is a junior synonym of Leptonetela; Leptonetela notabilis(Lin & Li, 2010) comb. nov. and Leptonetela sexdigiti(Lin & Li, 2010) comb. nov. are transferred from Sinoneta; Leptonetela sanchahe Wang & Li nom. nov. is proposed as a replacement name for Sinoneta palmata(Chen et al, 2010) because Leptonetela palmata is preoccupied. PMID:29280363

Integrative taxonomy of Leptonetela spiders (Araneae, Leptonetidae), with descriptions of 46 new species.

PubMed

Wang, Chun-Xia; Xu, Xin; Li, Shu-Qiang

2017-11-18

Extreme environments, such as subterranean habitats, are suspected to be responsible for morphologically inseparable cryptic or sibling species and can bias biodiversity assessment. A DNA barcode is a short, standardized DNA sequence used for taxonomic purposes and has the potential to lessen the challenges presented by a biotic inventory. Here, we investigate the diversity of the genus Leptonetela Kratochvíl, 1978 that is endemic to karst systems in Eurasia using DNA barcoding. We analyzed 624 specimens using one mitochondrial gene fragment ( COI ). The results show that DNA barcoding is an efficient and rapid species identification method in this genus. DNA barcoding gap and automatic barcode gap discovery (ABGD) analyses indicated the existence of 90 species, a result consistent with previous taxonomic hypotheses, and supported the existence of extreme male pedipalpal tibial spine and median apophysis polymorphism in Leptonetela species, with direct implications for the taxonomy of the group and its diversity. Based on the molecular and morphological evidence, we delimit and diagnose 90 Leptonetela species, including the type species Leptonetela kanellisi (Deeleman-Reinhold, 1971). Forty-six of them are previously undescribed. The female of Leptonetela zhai Wang & Li, 2011 is reported for the first time. Leptonetela tianxinensis (Tong & Li, 2008) comb. nov. is transferred from the genus Leptoneta Simon, 1872; the genus Guineta Lin & Li, 2010 syn. nov. is a junior synonym of Leptonetela; Leptonetela gigachela (Lin & Li, 2010) comb. nov. is transferred from Guineta . The genus Sinoneta Lin & Li, 2010 syn. nov. is a junior synonym of Leptonetela ; Leptonetela notabilis (Lin & Li, 2010) comb. nov. and Leptonetela sexdigiti (Lin & Li, 2010) comb. nov. are transferred from Sinoneta ; Leptonetela sanchahe Wang & Li nom. nov. is proposed as a replacement name for Sinoneta palmata (Chen et al., 2010) because Leptonetela palmata is preoccupied.

Renorming c0 and closed, bounded, convex sets with fixed point property for affine nonexpansive mappings

NASA Astrophysics Data System (ADS)

Nezir, Veysel; Mustafa, Nizami

2017-04-01

In 2008, P.K. Lin provided the first example of a nonreflexive space that can be renormed to have fixed point property for nonexpansive mappings. This space was the Banach space of absolutely summable sequences l1 and researchers aim to generalize this to c0, Banach space of null sequences. Before P.K. Lin's intriguing result, in 1979, Goebel and Kuczumow showed that there is a large class of non-weak* compact closed, bounded, convex subsets of l1 with fixed point property for nonexpansive mappings. Then, P.K. Lin inspired by Goebel and Kuczumow's ideas to give his result. Similarly to P.K. Lin's study, Hernández-Linares worked on L1 and in his Ph.D. thesis, supervisored under Maria Japón, showed that L1 can be renormed to have fixed point property for affine nonexpansive mappings. Then, related questions for c0 have been considered by researchers. Recently, Nezir constructed several equivalent norms on c0 and showed that there are non-weakly compact closed, bounded, convex subsets of c0 with fixed point property for affine nonexpansive mappings. In this study, we construct a family of equivalent norms containing those developed by Nezir as well and show that there exists a large class of non-weakly compact closed, bounded, convex subsets of c0 with fixed point property for affine nonexpansive mappings.

First-principles calculated decomposition pathways for LiBH4 nanoclusters

PubMed Central

Huang, Zhi-Quan; Chen, Wei-Chih; Chuang, Feng-Chuan; Majzoub, Eric H.; Ozoliņš, Vidvuds

2016-01-01

We analyze thermodynamic stability and decomposition pathways of LiBH4 nanoclusters using grand-canonical free-energy minimization based on total energies and vibrational frequencies obtained from density-functional theory (DFT) calculations. We consider (LiBH4)n nanoclusters with n = 2 to 12 as reactants, while the possible products include (Li)n, (B)n, (LiB)n, (LiH)n, and Li2BnHn; off-stoichiometric LinBnHm (m ≤ 4n) clusters were considered for n = 2, 3, and 6. Cluster ground-state configurations have been predicted using prototype electrostatic ground-state (PEGS) and genetic algorithm (GA) based structural optimizations. Free-energy calculations show hydrogen release pathways markedly differ from those in bulk LiBH4. While experiments have found that the bulk material decomposes into LiH and B, with Li2B12H12 as a kinetically inhibited intermediate phase, (LiBH4)n nanoclusters with n ≤ 12 are predicted to decompose into mixed LinBn clusters via a series of intermediate clusters of LinBnHm (m ≤ 4n). The calculated pressure-composition isotherms and temperature-pressure isobars exhibit sloping plateaus due to finite size effects on reaction thermodynamics. Generally, decomposition temperatures of free-standing clusters are found to increase with decreasing cluster size due to thermodynamic destabilization of reaction products. PMID:27189731

In vitro long-term culture of human primitive hematopoietic cells supported by murine stromal cell line MS-5.

PubMed

Nishi, N; Ishikawa, R; Inoue, H; Nishikawa, M; Yoneya, T; Kakeda, M; Tsumura, H; Ohashi, H; Mori, K J

1997-04-01

When Lin-CD34+CD38- cells from normal human cord blood were cocultured with MS-5, colony forming cells were maintained for over 8 weeks. Prevention of contact between MS-5 and Lin-CD34+CD38- cells by using a membrane filter was negligible for this activity, indicating that the activity of MS-5 on human primitive hematopoietic cells may be due to soluble factor(s) secreted from MS-5. We tried to purify this activity by a [3H]TdR incorporation assay. The activity was found in 150 kD fraction and was neutralized with anti-mSCF (stem cell factor) antibody. Another 20-30 kD fraction synergized with mSCF to stimulate the growth of Lin-CD34+CD38- cells but failed alone. This fraction supported the growth of the G-CSF (granulocyte-colony stimulating factor)-dependent cell line FD/GR3, FDC-P2 transfected with mG-CSF receptor cDNA. This synergy was canceled in the presence of soluble mG-CSF receptor. Addition of anti-mSCF antibody and soluble mG-CSF receptor to the culture completely abrogated the activity of MS-5-culture supernatant. These results indicate the activity of MS-5 on Lin-CD34+CD38- cells is due to synergistic effect of mSCF and mG-CSF.

Comparison between Two Linear Supervised Learning Machines' Methods with Principle Component Based Methods for the Spectrofluorimetric Determination of Agomelatine and Its Degradants.

PubMed

Elkhoudary, Mahmoud M; Naguib, Ibrahim A; Abdel Salam, Randa A; Hadad, Ghada M

2017-05-01

Four accurate, sensitive and reliable stability indicating chemometric methods were developed for the quantitative determination of Agomelatine (AGM) whether in pure form or in pharmaceutical formulations. Two supervised learning machines' methods; linear artificial neural networks (PC-linANN) preceded by principle component analysis and linear support vector regression (linSVR), were compared with two principle component based methods; principle component regression (PCR) as well as partial least squares (PLS) for the spectrofluorimetric determination of AGM and its degradants. The results showed the benefits behind using linear learning machines' methods and the inherent merits of their algorithms in handling overlapped noisy spectral data especially during the challenging determination of AGM alkaline and acidic degradants (DG1 and DG2). Relative mean squared error of prediction (RMSEP) for the proposed models in the determination of AGM were 1.68, 1.72, 0.68 and 0.22 for PCR, PLS, SVR and PC-linANN; respectively. The results showed the superiority of supervised learning machines' methods over principle component based methods. Besides, the results suggested that linANN is the method of choice for determination of components in low amounts with similar overlapped spectra and narrow linearity range. Comparison between the proposed chemometric models and a reported HPLC method revealed the comparable performance and quantification power of the proposed models.

The expression of the Alzheimer’s Amyloid Precursor Protein-like gene is regulated by developmental timing microRNAs and their targets in Caenorhabditis elegans

PubMed Central

Niwa, Ryusuke; Zhou, Feng; Li, Chris; Slack, Frank J.

2008-01-01

Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by the accumulation of dense plaques in the brain, resulting in progressive dementia. A major plaque component is the β-amyloid peptide, which is a cleavage product of the amyloid precursor protein (APP). Studies of dominant inheritable familial AD support the hypothesis that APP is critical for AD development. On the other hand, the pathogenesis of amyloid plaque deposition in AD is thought to be the result of age-related changes with unknown mechanisms. Here we show that the Caenorhabditis elegans homolog of APP, APP-like-1 (apl-1), functions with and is under the control of molecules regulating developmental progression. In C. elegans, the timing of cell fate determination is controlled by the heterochronic genes, including let-7 microRNAs. C. elegans apl-1 shows significant genetic interactions with let-7 family microRNAs and let-7-targeted heterochronic genes, hbl-1, lin-41 and lin-42. apl-1 expression is upregulated during the last larval stage in hypodermal seam cells which is transcriptionally regulated by hbl-1, lin-41 and lin-42. Moreover, the levels of the apl-1 transcription are modulated by the activity of let-7 family microRNAs. Our works places apl-1 in a developmental timing pathway and may provide new insights into the time-dependent progression of AD. PMID:18262516

Fatigue Crack Initiation.

DTIC Science & Technology

1991-01-01

here adopted. McCommon and Rosenberg [3] and MacCone et al . [4] showed that metals are subject to failure at temperatures as low as 1.7’K. This indicates...by Meke and Blochwitz [ 11 ] and Mughrabi [ 12] in their studies of persistent slip bands. Following the clue, which the observations on extrusions...compression as developed by Cooley and Lin, 1986 [33]. Lin et al ., 1987 [34]. Displacement component normal to the free surface is taken as a measure

[Research on partial least squares for determination of impurities in the presence of high concentration of matrix by ICP-AES].

PubMed

Wang, Yan-peng; Gong, Qi; Yu, Sheng-rong; Liu, You-yan

2012-04-01

A method for detecting trace impurities in high concentration matrix by ICP-AES based on partial least squares (PLS) was established. The research showed that PLS could effectively correct the interference caused by high level of matrix concentration error and could withstand higher concentrations of matrix than multicomponent spectral fitting (MSF). When the mass ratios of matrix to impurities were from 1 000 : 1 to 20 000 : 1, the recoveries of standard addition were between 95% and 105% by PLS. For the system in which interference effect has nonlinear correlation with the matrix concentrations, the prediction accuracy of normal PLS method was poor, but it can be improved greatly by using LIN-PPLS, which was based on matrix transformation of sample concentration. The contents of Co, Pb and Ga in stream sediment (GBW07312) were detected by MSF, PLS and LIN-PPLS respectively. The results showed that the prediction accuracy of LIN-PPLS was better than PLS, and the prediction accuracy of PLS was better than MSF.

Chaperone Function in Androgen-Independent Prostate Cancer

DTIC Science & Technology

2012-05-01

differentiation. Proc Natl Acad Sci U S A 92, 11081-11085. Yong, W., Yang, Z., Periyasamy, S., Chen, H., Yucel, S., Li, W., Lin, L. Y., Wolf , I. M., Cohn, M...Biol Chem 282, 5026-5036. Yong, W., Yang, Z., Periyasamy, S., Chen, H., Yucel, S., Li, W., Lin, L. Y., Wolf , I. M., Cohn, M. J., Baskin, L. S., et... Reintroduction of AR into PC-3 cells activates the endogenous FKBP51 gene, an observation that is consistent with AR regulation of FKBP51 expression

Automatic Registration of Scanned Satellite Imagery with a Digital Map Data Base.

DTIC Science & Technology

1980-11-01

define the corresponding map window (mW)(procedure TRANSFORMWINDOW MAP A-- S4S Araofms Cpo iin et Serc Area deiatl compAr tal _______________ T...to a LIST-item). LIN: = ( ® code 2621431 ; ® pointer LA to the line list, © pointer PRI; pointer PR2), LIST: = ( Q pointer PL to a LIN-item; n pointer...items where PL -pointers are replaced by a code for the beginning (the number 262140 in our case) and end (the number 26241). Figure 3.2 illustra- tes a

Characterizing and Targeting Replication Stress Response Defects in Breast Cancer

DTIC Science & Technology

2014-08-01

NUMBER Shiaw-Yih Lin , Chun-Jen Lin, Lili Gong, Hui Dai, Ju-Seog Lee 5e. TASK NUMBER E-Mail: sylin@mdanderson.org The University of...the mammary fat pads of female nude mice. We closely monitored tumor formation in the mice. Notably, tumors began to form in 3 of 10 mice injected...and two independent TUSC4-knockdown MCF-10A cell lines (TUSC4 #1 and TUSC4 #4) were injected per mouse into mammary fat pads of 6-week-old female nude

S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans.

PubMed

Cascella, Roberta; Evangelisti, Elisa; Zampagni, Mariagioia; Becatti, Matteo; D'Adamio, Giampiero; Goti, Andrea; Liguri, Gianfranco; Fiorillo, Claudia; Cecchi, Cristina

2014-08-01

Oxidative stress has a prominent role in life-span regulation of living organisms. One of the endogenous free radical scavenger systems is associated with glutathione (GSH), the most abundant nonprotein thiol in mammalian cells, acting as a major reducing agent and in antioxidant defense by maintaining a tight control over redox status. We have recently designed a series of novel S-acyl-GSH derivatives capable of preventing amyloid oxidative stress and cholinergic dysfunction in Alzheimer disease models, upon an increase in GSH intake. In this study we show that the longevity of the wild-type N2 Caenorhabditis elegans strain was significantly enhanced by dietary supplementation with linolenoyl-SG (lin-SG) thioester with respect to the ethyl ester of GSH, linolenic acid, or vitamin E. RNA interference analysis and activity inhibition assay indicate that life-span extension was mediated by the upregulation of Sir-2.1, a NAD-dependent histone deacetylase ortholog of mammalian SIRT1. In particular, lin-SG-mediated overexpression of Sir-2.1 appears to be related to the Daf-16 (FoxO) pathway. Moreover, the lin-SG derivative protects N2 worms from the paralysis and oxidative stress induced by Aβ/H2O2 exposure. Overall, our findings put forward lin-SG thioester as an antioxidant supplement triggering sirtuin upregulation, thus opening new future perspectives for healthy aging or delayed onset of oxidative-related diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Germ-line induction of the Caenorhabditis elegans vulva

PubMed Central

Thompson, Beth E.; Lamont, Liana B.; Kimble, Judith

2006-01-01

Development of the Caenorhabditis elegans vulva serves as a paradigm for intercellular signaling during animal development. In wild-type animals, the somatic gonadal anchor cell generates the LIN-3/EGF ligand to induce vulval fates in the underlying hypodermis, whereas FBF, FOG-1, and FOG-3 control germ-line development. Here we report that FBF functions redundantly with FOG-1 and FOG-3 to control vulval induction: animals lacking FBF and either FOG-1 or FOG-3 have multiple vulvae, the Muv phenotype. The fog; fbf Muv phenotype is generated by aberrant induction of vulval precursor cells (VPCs): in wild-type animals, three VPCs are induced to form a single vulva, but, in fog; fbf mutants, four or five VPCs are typically induced, resulting in ectopic vulvae. Laser ablation experiments and mosaic analyses demonstrate that the germ line is critical for the fog; fbf Muv phenotype. Consistent with that site of action, we detect FBF and FOG-1 in the germ line but not in the VPCs. The simplest interpretation is that FOG-1, FOG-3, and FBF act in the germ line to influence vulval fates. The LIN-3/EGF ligand may be the germ-line signal to the VPCs: the fog; fbf Muv phenotype depends on LIN-3 activity, and the lin-3 3′ UTR possesses an FBF binding element. Our findings reveal new insights into germ line-to-soma signals and the role of PUF proteins in animal development. PMID:16407099

Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and -dependent manners under hypoxic culture.

PubMed

Takizawa, Naoki; Okubo, Naoto; Kamo, Masaharu; Chosa, Naoyuki; Mikami, Toshinari; Suzuki, Keita; Yokota, Seiji; Ibi, Miho; Ohtsuka, Masato; Taira, Masayuki; Yaegashi, Takashi; Ishisaki, Akira; Kyakumoto, Seiko

2017-09-15

Immunosuppressive/anti-inflammatory macrophage (Mφ), M2-Mφ that expressed the typical M2-Mφs marker, CD206, and anti-inflammatory cytokine, interleukin (IL)-10, is beneficial and expected tool for the cytotherapy against inflammatory diseases. Here, we demonstrated that bone marrow-derived lineage-positive (Lin+) blood cells proliferated and differentiated into M2-Mφs by cooperation with the bone marrow-derived mesenchymal stem cells (MSCs) under hypoxic condition: MSCs not only promoted proliferation of undifferentiated M2-Mφs, pre-M2-Mφs, in the Lin+ fraction via a proliferative effect of the MSCs-secreted macrophage colony-stimulating factor, but also promoted M2-Mφ polarization of the pre-M2-Mφs through cell-to-cell contact with the pre-M2-Mφs. Intriguingly, an inhibitor for intercellular adhesion molecule (ICAM)-1 receptor/lymphocyte function-associated antigen (LFA)-1, Rwj50271, partially suppressed expression of CD206 in the Lin+ blood cells but an inhibitor for VCAM-1 receptor/VLA-4, BIO5192, did not, suggesting that the cell-to-cell adhesion through LFA-1 on pre-M2-Mφs and ICAM-1 on MSCs was supposed to promoted the M2-Mφ polarization. Thus, the co-culture system consisting of bone marrow-derived Lin+ blood cells and MSCs under hypoxic condition was a beneficial supplier of a number of M2-Mφs, which could be clinically applicable to inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Space Shuttle/TDRSS communication and tracking systems analysis

NASA Astrophysics Data System (ADS)

Lindsey, W. C.; Chie, C. M.; Cideciyan, R.; Dessouky, K.; Su, Y. T.; Tsang, C. S.

1986-04-01

In order to evaluate the technical and operational problem areas and provide a recommendation, the enhancements to the Tracking and Data Delay Satellite System (TDRSS) and Shuttle must be evaluated through simulation and analysis. These enhancement techniques must first be characterized, then modeled mathematically, and finally updated into LinCsim (analytical simulation package). The LinCsim package can then be used as an evaluation tool. Three areas of potential enhancements were identified: shuttle payload accommodations, TDRSS SSA and KSA services, and shuttle tracking system and navigation sensors. Recommendations for each area were discussed.

Eavesdropping on the improved three-party quantum secret sharing protocol

NASA Astrophysics Data System (ADS)

Gao, Gan

2011-02-01

Lin et al. [Song Lin, Fei Gao, Qiao-yan Wen, Fu-chen Zhu, Opt. Commun. 281 (2008) 4553] pointed out that the multiparty quantum secret sharing protocol [Zhan-jun Zhang, Gan Gao, Xin Wang, Lian-fang Han, Shou-hua Shi, Opt. Commun. 269 (2007) 418] is not secure and proposed an improved three-party quantum secret sharing protocol. In this paper, we study the security of the improved three-party quantum secret sharing protocol and find that it is still not secure. Finally, a further improved three-party quantum secret sharing protocol is proposed.

Space Shuttle/TDRSS communication and tracking systems analysis

NASA Technical Reports Server (NTRS)

Lindsey, W. C.; Chie, C. M.; Cideciyan, R.; Dessouky, K.; Su, Y. T.; Tsang, C. S.

1986-01-01

In order to evaluate the technical and operational problem areas and provide a recommendation, the enhancements to the Tracking and Data Delay Satellite System (TDRSS) and Shuttle must be evaluated through simulation and analysis. These enhancement techniques must first be characterized, then modeled mathematically, and finally updated into LinCsim (analytical simulation package). The LinCsim package can then be used as an evaluation tool. Three areas of potential enhancements were identified: shuttle payload accommodations, TDRSS SSA and KSA services, and shuttle tracking system and navigation sensors. Recommendations for each area were discussed.

Chaperone Function in Androgen-Independent Prostate Cancer

DTIC Science & Technology

2010-05-01

funding). To address this need, I have located a collaborator (Dr. Scott Lucia) at the University of Colorado who should be able to perform the IHC on his...Periyasamy, S., Chen, H., Yucel, S., Li, W., Lin, L. Y., Wolf , I. M., Cohn, M. J., Baskin, L. S., et al. (2007a). Essential role for Co-chaperone...Yucel, S., Li, W., Lin, L. Y., Wolf , I. M., Cohn, M. J., Baskin, L. S., et al. (2007b). Essential role for Co-chaperone Fkbp52 but not Fkbp51 in

Modulating Leukemia-Initiating Cell Quiescence to Improve Leukemia Treatment

DTIC Science & Technology

2015-09-01

T- cells and in innate immunity (Lacorazza et al., 2002). It controls the proliferation and homing of CD8+ T- cells via the Kruppel-like factors...Lin2Sca12IL7R2Kit1FccRII/ IIIhighCD34high), megakaryocyte-erythroid progenitor cell (MEP) (Lin2Sca12IL7R2Kit1FccRII/IIIlowCD34low), and common lymphoid ...to this model, the first wave gives rise exclusively to innate immune B cells in early embryonic life and may be derived from progenitor cells

Dynamique d'un oscillateur photoréfractif : instabilités et analogie avec la loi de Curie-Weiss

NASA Astrophysics Data System (ADS)

Mathey, P.; Odoulov, S. G.; Rytz, D.

2002-06-01

La dynamique et l'état stationnaire du faisceau issu d'une cavité oscillante comprenant un cristal non-linéaire de titanate de baryum utilisé en tant que miroir à conjugaison de phase sont étudiés. Le paramètre du système étant le gain du milieu non-linéaire, les dépendances de l'intensité de l'oscillation et de l'inverse du temps de réponse sont similaires aux lois de Curie en physique du solide.

Normal and abnormal secretion by haemopoietic cells

PubMed Central

STINCHCOMBE, JANE C; GRIFFITHS, GILLIAN M

2001-01-01

The secretory lysosomes found in haemopoietic cells provide a very efficient mechanism for delivering the effector proteins of many immune cells in response to antigen recognition. Although secretion shows some similarities to the secretion of specialized granules in other secretory cell types, some aspects of secretory lysosome release appear to be unique to melanocytes and cells of the haemopoietic lineage. Mast cells and platelets have provided excellent models for studying secretion, but recent advances in characterizing the immunological synapse allow a very fine dissection of the secretory process in T lymphocytes. These studies show that secretory lysosomes are secreted from the centre of the talin ring at the synapse. Proper secretion requires a series of Rab and cytoskeletal elements which play critical roles in the specialized secretion of lysosomes in haemopoietic cells. PMID:11380687

TES is a novel focal adhesion protein with a role in cell spreading.

PubMed

Coutts, Amanda S; MacKenzie, Elaine; Griffith, Elen; Black, Donald M

2003-03-01

Previously, we identified TES as a novel candidate tumour suppressor gene that mapped to human chromosome 7q31.1. In this report we demonstrate that the TES protein is localised at focal adhesions, actin stress fibres and areas of cell-cell contact. TES has three C-terminal LIM domains that appear to be important for focal adhesion targeting. Additionally, the N-terminal region is important for targeting TES to actin stress fibres. Yeast two-hybrid and biochemical analyses yielded interactions with several focal adhesion and/or cytoskeletal proteins including mena, zyxin and talin. The fact that TES localises to regions of cell adhesion suggests that it functions in events related to cell motility and adhesion. In support of this, we demonstrate that fibroblasts stably overexpressing TES have an increased ability to spread on fibronectin.

First Jurassic grasshopper (Insecta, Caelifera) from China.

PubMed

Gu, Jun-Jie; Yue, Yanli; Shi, Fuming; Tian, He; Ren, Dong

2016-09-20

Orthoptera is divided into two suborders, the Ensifera (katydids, crickets and mole crickets) and the Caelifera (grasshoppers and pygmy mole crickets). The earliest definitive caeliferans are those found in the Triassic (Bethoux & Ross 2005). The extinct caeliferan families, such as Locustopsidae and Locustavidae, may prove to be stem groups to some of the modern superfamilies (Grimaldi & Engel 2005). Locustopsidae is known from the Late Triassic or Early Jurassic to Late Cretaceous, consisting of two subfamilies (Gorochov et al. 2006). They are recorded from Europe, England, Russia, central Asia, China, Egypt, North America, Brazil and Australia. Up to now, Late Mesozoic fossil deposits of China has been reported plenty taxa of orthopterids, e.g. ensiferans, phasmatodeans, grylloblattids (Cui et al. 2012; Gu et al. 2010; Gu et al. 2012a; Gu et al. 2012b; Ren et al. 2012; Wang et al. 2014); but, with few caeliferans records, only four species, Pseudoacrida costata Lin 1982, Mesolocustopsis sinica Hong 1990, Tachacris stenosis Lin 1977 and T. turgis Lin 1980, were reported from the Early Cretaceous of Ningxia, Shandong, Yunnan and Zhejiang of China.

Three-dimensional sensitivity distribution and sample volume of low-induction-number electromagnetic-induction instruments

USGS Publications Warehouse

Callegary, J.B.; Ferré, T.P.A.; Groom, R.W.

2012-01-01

There is an ongoing effort to improve the understanding of the correlation of soil properties with apparent soil electrical conductivity as measured by low-induction-number electromagnetic-induction (LIN FEM) instruments. At a minimum, the dimensions of LIN FEM instruments' sample volume, the spatial distribution of sensitivity within that volume, and implications for surveying and analyses must be clearly defined and discussed. Therefore, a series of numerical simulations was done in which a conductive perturbation was moved systematically through homogeneous soil to elucidate the three-dimensional sample volume of LIN FEM instruments. For a small perturbation with electrical conductivity similar to that of the soil, instrument response is a measure of local sensitivity (LS). Our results indicate that LS depends strongly on the orientation of the instrument's transmitter and receiver coils and includes regions of both positive and negative LS. Integration of the absolute value of LS from highest to lowest was used to contour cumulative sensitivity (CS). The 90% CS contour was used to define the sample volume. For both horizontal and vertical coplanar coil orientations, the longest dimension of the sample volume was at the surface along the main instrument axis with a length of about four times the intercoil spacing (s) with maximum thicknesses of about 1 and 0.3 s, respectively. The imaged distribution of spatial sensitivity within the sample volume is highly complex and should be considered in conjunction with the expected scale of heterogeneity before the use and interpretation of LIN FEM for mapping and profiling. ?? Soil Science Society of America.

Linear relationship between increasing amounts of extruded linseed in dairy cow diet and milk fatty acid composition and butter properties.

PubMed

Hurtaud, C; Faucon, F; Couvreur, S; Peyraud, J-L

2010-04-01

The aim of this experiment was to compare the effects of increasing amounts of extruded linseed in dairy cow diet on milk fat yield, milk fatty acid (FA) composition, milk fat globule size, and butter properties. Thirty-six Prim'Holstein cows at 104 d in milk were sorted into 3 groups by milk production and milk fat globule size. Three diets were assigned: a total mixed ration (control) consisting of corn silage (70%) and concentrate (30%), or a supplemented ration based on the control ration but where part of the concentrate energy was replaced on a dry matter basis by 2.1% (LIN1) or 4.3% (LIN2) extruded linseed. The increased amounts of extruded linseed linearly decreased milk fat content and milk fat globule size and linearly increased the percentage of milk unsaturated FA, specifically alpha-linolenic acid and trans FA. Extruded linseed had no significant effect on butter color or on the sensory properties of butters, with only butter texture in the mouth improved. The LIN2 treatment induced a net improvement of milk nutritional properties but also created problems with transforming the cream into butter. The butters obtained were highly spreadable and melt-in-the-mouth, with no pronounced deficiency in taste. The LIN1 treatment appeared to offer a good tradeoff of improved milk FA profile and little effect on butter-making while still offering butters with improved functional properties. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Experimental Modal Analysis and Dynamic Component Synthesis. Volume 2. Measurement Techniques for Experimental Modal Analysis

DTIC Science & Technology

1987-12-01

A- -- HZ LIN 3.0 . Be-I. •,% •4’ 20.. 0-p -4 -0 30a 4a j0 O0 100a 10 4140 iSo 130 20C. 2210 140 M* LIN g•" %g Figur 19. Cyli Avergin (N4,M 0 -3- 40...shows that the degree of nonlinearity of a structure varies according to the characteristics of the system. That is, welded structures will usually...exhibit a linear response; where a riveted or spot welded structure exhibits a very nonlinear response [52]. As an example of a nonlinear system

Structures spatiales localisées dans un oscillateur paramétrique optique (OPO)

NASA Astrophysics Data System (ADS)

Coulibaly, S.; Durniak, C.; Taki, M.

2004-11-01

La prise en compte du caractère non uniforme du pompage optique dans l'étude linéaire et faiblement non linéaire d'un OPO dégénéré (DOPO) a permis de mettre en évidence la discrétisation du seuil et l'existence de structures spatiales localisées de type Hermite-Gauss. L'évolution spatio-temporelle du signal en sortie est quant à elle gouvernée par l'équation de Ginzburg-Landau réelle dont les coefficients dépendent des variables d'espace.

Mississippi River: Study of Alternatives for Rehabilitation of Lock and Dam Number 1. Minneapolis, Minnesota. Volume 2. Appendix A. Alternative Plans of Rehabilitation.

DTIC Science & Technology

1976-04-01

25,00 oo4 L.S I 1 00 L.S 15 000 L.t. 1 0SIOOO L.S. is 1 3,00l 2 00 ,o000 c.Y. 3.00 27 000 9.000 C.V. 3 27 000 9000 c .. 3.00 - . rZ 27000 N 00...34_ __ 75.00 _45( 6 ea. 75.00 ___ _ 5 6 ea. .0L0 _450 6 0g. .00.~ * 1.00 1s 180 lin.ft. 1.00 190 180 lin.ft. 1.00 ISO 1e0 180 1 .ft. 1.80 1" * 0.30 ___ _ 1 500

Tensin stabilizes integrin adhesive contacts in Drosophila.

PubMed

Torgler, Catherine N; Narasimha, Maithreyi; Knox, Andrea L; Zervas, Christos G; Vernon, Matthew C; Brown, Nicholas H

2004-03-01

We report the functional characterization of the Drosophila ortholog of tensin, a protein implicated in linking integrins to the cytoskeleton and signaling pathways. A tensin null was generated and is viable with wing blisters, a phenotype characteristic of loss of integrin adhesion. In tensin mutants, mechanical abrasion is required during wing expansion to cause wing blisters, suggesting that tensin strengthens integrin adhesion. The localization of tensin requires integrins, talin, and integrin-linked kinase. The N-terminal domain and C-terminal PTB domain of tensin provide essential recruitment signals. The intervening SH2 domain is not localized on its own. We suggest a model where tensin is recruited to sites of integrin adhesion via its PTB and N-terminal domains, localizing the SH2 domain so that it can interact with phosphotyrosine-containing proteins, which stabilize the integrin link to the cytoskeleton.

Decreased expression of cell adhesion genes in cancer stem-like cells isolated from primary oral squamous cell carcinomas.

PubMed

Mishra, Amrendra; Sriram, Harshini; Chandarana, Pinal; Tanavde, Vivek; Kumar, Rekha V; Gopinath, Ashok; Govindarajan, Raman; Ramaswamy, S; Sadasivam, Subhashini

2018-05-01

The goal of this study was to isolate cancer stem-like cells marked by high expression of CD44, a putative cancer stem cell marker, from primary oral squamous cell carcinomas and identify distinctive gene expression patterns in these cells. From 1 October 2013 to 4 September 2015, 76 stage III-IV primary oral squamous cell carcinoma of the gingivobuccal sulcus were resected. In all, 13 tumours were analysed by immunohistochemistry to visualise CD44-expressing cells. Expression of CD44 within The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma RNA-sequencing data was also assessed. Seventy resected tumours were dissociated into single cells and stained with antibodies to CD44 as well as CD45 and CD31 (together referred as Lineage/Lin). From 45 of these, CD44 + Lin - and CD44 - Lin - subpopulations were successfully isolated using fluorescence-activated cell sorting, and good-quality RNA was obtained from 14 such sorted pairs. Libraries from five pairs were sequenced and the results analysed using bioinformatics tools. Reverse transcription quantitative polymerase chain reaction was performed to experimentally validate the differential expression of selected candidate genes identified from the transcriptome sequencing in the same 5 and an additional 9 tumours. CD44 was expressed on the surface of poorly differentiated tumour cells, and within the The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma samples, its messenger RNA levels were higher in tumours compared to normal. Transcriptomics revealed that 102 genes were upregulated and 85 genes were downregulated in CD44 + Lin - compared to CD44 - Lin - cells in at least 3 of the 5 tumours sequenced. The upregulated genes included those involved in immune regulation, while the downregulated genes were enriched for genes involved in cell adhesion. Decreased expression of PCDH18, MGP, SPARCL1 and KRTDAP was confirmed by reverse transcription quantitative polymerase chain reaction. Lower expression of

On the downscaling of actual evapotranspiration maps based on combination of MODIS and landsat-based actual evapotranspiration estimates

USGS Publications Warehouse

Singh, Ramesh K.; Senay, Gabriel B.; Velpuri, Naga Manohar; Bohms, Stefanie; Verdin, James P.

2014-01-01

 Downscaling is one of the important ways of utilizing the combined benefits of the high temporal resolution of Moderate Resolution Imaging Spectroradiometer (MODIS) images and fine spatial resolution of Landsat images. We have evaluated the output regression with intercept method and developed the Linear with Zero Intercept (LinZI) method for downscaling MODIS-based monthly actual evapotranspiration (AET) maps to the Landsat-scale monthly AET maps for the Colorado River Basin for 2010. We used the 8-day MODIS land surface temperature product (MOD11A2) and 328 cloud-free Landsat images for computing AET maps and downscaling. The regression with intercept method does have limitations in downscaling if the slope and intercept are computed over a large area. A good agreement was obtained between downscaled monthly AET using the LinZI method and the eddy covariance measurements from seven flux sites within the Colorado River Basin. The mean bias ranged from −16 mm (underestimation) to 22 mm (overestimation) per month, and the coefficient of determination varied from 0.52 to 0.88. Some discrepancies between measured and downscaled monthly AET at two flux sites were found to be due to the prevailing flux footprint. A reasonable comparison was also obtained between downscaled monthly AET using LinZI method and the gridded FLUXNET dataset. The downscaled monthly AET nicely captured the temporal variation in sampled land cover classes. The proposed LinZI method can be used at finer temporal resolution (such as 8 days) with further evaluation. The proposed downscaling method will be very useful in advancing the application of remotely sensed images in water resources planning and management.

Identification and agreement of first turn point by mathematical analysis applied to heart rate, carbon dioxide output and electromyography.

PubMed

Zamunér, Antonio R; Catai, Aparecida M; Martins, Luiz E B; Sakabe, Daniel I; Da Silva, Ester

2013-01-01

The second heart rate (HR) turn point has been extensively studied, however there are few studies determining the first HR turn point. Also, the use of mathematical and statistical models for determining changes in dynamic characteristics of physiological variables during an incremental cardiopulmonary test has been suggested. To determine the first turn point by analysis of HR, surface electromyography (sEMG), and carbon dioxide output (VCO2) using two mathematical models and to compare the results to those of the visual method. Ten sedentary middle-aged men (53.9 ± 3.2 years old) were submitted to cardiopulmonary exercise testing on an electromagnetic cycle ergometer until exhaustion. Ventilatory variables, HR, and sEMG of the vastus lateralis were obtained in real time. Three methods were used to determine the first turn point: 1) visual analysis based on loss of parallelism between VCO2 and oxygen uptake (VO2); 2) the linear-linear model, based on fitting the curves to the set of VCO2 data (Lin-LinVCO2); 3) a bi-segmental linear regression of Hinkley's algorithm applied to HR (HMM-HR), VCO2 (HMM-VCO2), and sEMG data (HMM-RMS). There were no differences between workload, HR, and ventilatory variable values at the first ventilatory turn point as determined by the five studied parameters (p>0.05). The Bland-Altman plot showed an even distribution of the visual analysis method with Lin-LinVCO2, HMM-HR, HMM-VCO2, and HMM-RMS. The proposed mathematical models were effective in determining the first turn point since they detected the linear pattern change and the deflection point of VCO2, HR responses, and sEMG.

Identification and agreement of first turn point by mathematical analysis applied to heart rate, carbon dioxide output and electromyography

PubMed Central

Zamunér, Antonio R.; Catai, Aparecida M.; Martins, Luiz E. B.; Sakabe, Daniel I.; Silva, Ester Da

2013-01-01

Background The second heart rate (HR) turn point has been extensively studied, however there are few studies determining the first HR turn point. Also, the use of mathematical and statistical models for determining changes in dynamic characteristics of physiological variables during an incremental cardiopulmonary test has been suggested. Objectives To determine the first turn point by analysis of HR, surface electromyography (sEMG), and carbon dioxide output () using two mathematical models and to compare the results to those of the visual method. Method Ten sedentary middle-aged men (53.9±3.2 years old) were submitted to cardiopulmonary exercise testing on an electromagnetic cycle ergometer until exhaustion. Ventilatory variables, HR, and sEMG of the vastus lateralis were obtained in real time. Three methods were used to determine the first turn point: 1) visual analysis based on loss of parallelism between and oxygen uptake (); 2) the linear-linear model, based on fitting the curves to the set of data (Lin-Lin ); 3) a bi-segmental linear regression of Hinkley' s algorithm applied to HR (HMM-HR), (HMM- ), and sEMG data (HMM-RMS). Results There were no differences between workload, HR, and ventilatory variable values at the first ventilatory turn point as determined by the five studied parameters (p>0.05). The Bland-Altman plot showed an even distribution of the visual analysis method with Lin-Lin , HMM-HR, HMM-CO2, and HMM-RMS. Conclusion The proposed mathematical models were effective in determining the first turn point since they detected the linear pattern change and the deflection point of , HR responses, and sEMG. PMID:24346296

Linear and Non-Linear Piezoresistance Coefficients in Cubic Semiconductors. I. Theoretical Formulations

NASA Astrophysics Data System (ADS)

Durand, S.; Tellier, C. R.

1996-02-01

This paper constitutes the first part of a work devoted to applications of piezoresistance effects in germanium and silicon semiconductors. In this part, emphasis is placed on a formal explanation of non-linear effects. We propose a brief phenomenological description based on the multi-valleys model of semiconductors before to adopt a macroscopic tensorial model from which general analytical expressions for primed non-linear piezoresistance coefficients are derived. Graphical representations of linear and non-linear piezoresistance coefficients allows us to characterize the influence of the two angles of cut and of directions of alignment. The second part will primarily deal with specific applications for piezoresistive sensors. Cette publication constitue la première partie d'un travail consacré aux applications des effets piézorésistifs dans les semiconducteurs germanium et silicium. Cette partie traite essentiellement de la modélisation des effets non-linéaires. Après une description phénoménologique à partir du modèle de bande des semiconducteurs nous développons un modèle tensoriel macroscopique et nous proposons des équations générales analytiques exprimant les coefficients piézorésistifs non-linéaires dans des repères tournés. Des représentations graphiques des variations des coefficients piézorésistifs linéaires et non-linéaires permettent une pré-caractérisation de l'influence des angles de coupes et des directions d'alignement avant l'étude d'applications spécifiques qui feront l'objet de la deuxième partie.

Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors.

PubMed

Kyoizumi, Seishi; Kubo, Yoshiko; Misumi, Munechika; Kajimura, Junko; Yoshida, Kengo; Hayashi, Tomonori; Imai, Kazue; Ohishi, Waka; Nakachi, Kei; Young, Lauren F; Shieh, Jae-Hung; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

2016-01-01

It is not yet known whether hematopoietic stem and progenitor cells (HSPCs) are compromised in the aging population of atomic bomb (A-bomb) survivors after their exposure nearly 70 years ago. To address this, we evaluated age- and radiation-related changes in different subtypes of circulating HSPCs among the CD34-positive/lineage marker-negative (CD34(+)Lin(-)) cell population in 231 Hiroshima A-bomb survivors. We enumerated functional HSPC subtypes, including: cobblestone area-forming cells; long-term culture-initiating cells; erythroid burst-forming units; granulocyte and macrophage colony-forming units; and T-cell and natural killer cell progenitors using cell culture. We obtained the count of each HSPC subtype per unit volume of blood and the proportion of each HSPC subtype in CD34(+)Lin(-) cells to represent the lineage commitment trend. Multivariate analyses, using sex, age and radiation dose as variables, showed significantly decreased counts with age in the total CD34(+)Lin(-) cell population and all HSPC subtypes. As for the proportion, only T-cell progenitors decreased significantly with age, suggesting that the commitment to the T-cell lineage in HSPCs continuously declines with age throughout the lifetime. However, neither the CD34(+)Lin(-) cell population, nor HSPC subtypes showed significant radiation-induced dose-dependent changes in counts or proportions. Moreover, the correlations of the proportions among HSPC subtypes in the survivors properly revealed the hierarchy of lineage commitments. Taken together, our findings suggest that many years after exposure to radiation and with advancing age, the number and function of HSPCs in living survivors as a whole may have recovered to normal levels.

Streptomyces sp. is a powerful biotechnological tool for the biodegradation of HCH isomers: biochemical and molecular basis.

PubMed

Cuozzo, S A; Sineli, P E; Davila Costa, J; Tortella, G

2018-08-01

Actinobacteria are well-known degraders of toxic materials that have the ability to tolerate and remove organochloride pesticides; thus, they are used for bioremediation. The biodegradation of organochlorines by actinobacteria has been demonstrated in pure and mixed cultures with the concomitant production of metabolic intermediates including γ-pentachlorocyclohexene (γ-PCCH); 1,3,4,6-tetrachloro-1,4-cyclohexadiene (1,4-TCDN); 1,2-dichlorobenzene (1,2-DCB), 1,3-dichlorobenzene (1,3-DCB), or 1,4-dichlorobenzene (1,4-DCB); 1,2,3-trichlorobenzene (1,2,3-TCB), 1,2,4-trichlorobenzene (1,2,4-TCB), or 1,3,5-trichlorobenzene (1,3,5-TCB); 1,3-DCB; and 1,2-DCB. Chromatography coupled to mass spectrometric detection, especially GC-MS, is typically used to determine HCH-isomer metabolites. The important enzymes involved in HCH isomer degradation metabolic pathways include hexachlorocyclohexane dehydrochlorinase (LinA), haloalkane dehalogenase (LinB), and alcohol dehydrogenase (LinC). The metabolic versatility of these enzymes is known. Advances have been made in the identification of actinobacterial haloalkane dehydrogenase, which is encoded by linB. This knowledge will permit future improvements in biodegradation processes using Actinobacteria. The enzymatic and genetic characterizations of the molecular mechanisms involved in these processes have not been fully elucidated, necessitating further studies. New advances in this area suggest promising results. The scope of this paper encompasses the following: (i) the aerobic degradation pathways of hexachlorocyclohexane (HCH) isomers; (ii) the important genes and enzymes involved in the metabolic pathways of HCH isomer degradation; and (iii) the identification and quantification of intermediate metabolites through gas chromatography coupled to mass spectrometry (GC-MS).

Accelerated functional recovery after skeletal muscle ischemia-reperfusion injury using freshly isolated bone marrow cells.

PubMed

Corona, Benjamin T; Rathbone, Christopher R

2014-05-01

Relatively little information exists regarding the usefulness of bone marrow-derived cells for skeletal muscle ischemia-reperfusion injury (I/R), especially when compared with I/R that occurs in other tissues. The objectives of this study were to evaluate the ability of freshly isolated bone marrow cells to home to injured skeletal muscle and to determine their effects on muscle regeneration. Freshly isolated lineage-depleted bone marrow cells (Lin(-) BMCs) were injected intravenously 2 d after I/R. Bioluminescent imaging was used to evaluate cell localization for up to 28 d after injury. Muscle function, the percentage of fibers with centrally located nuclei, and the capillary-to-fiber ratio were evaluated 14 d after delivery of either saline (Saline) or saline containing Lin(-) BMCs (Lin(-) BMCs). Bioluminescence was higher in the injured leg than the contralateral control leg for up to 7 d after injection (P < 0.05) suggestive of cell homing to the injured skeletal muscle. Fourteen days after injury, there was a significant improvement in maximal tetanic torque (40% versus 22% deficit; P < 0.05), a faster rate of force production (+dP/dt) (123.6 versus 94.5 Nmm/S; P < 0.05), and a reduction in the percentage of fibers containing centrally located nuclei (40 versus 17%; P < 0.05), but no change in the capillary-to-fiber ratio in the Lin(-) BMC as compared with the Saline group. The homing of freshly isolated BMCs to injured skeletal muscle after I/R is associated with an increase in functional outcomes. Published by Elsevier Inc.

Synthetic mRNA devices that detect endogenous proteins and distinguish mammalian cells.

PubMed

Kawasaki, Shunsuke; Fujita, Yoshihiko; Nagaike, Takashi; Tomita, Kozo; Saito, Hirohide

2017-07-07

Synthetic biology has great potential for future therapeutic applications including autonomous cell programming through the detection of protein signals and the production of desired outputs. Synthetic RNA devices are promising for this purpose. However, the number of available devices is limited due to the difficulty in the detection of endogenous proteins within a cell. Here, we show a strategy to construct synthetic mRNA devices that detect endogenous proteins in living cells, control translation and distinguish cell types. We engineered protein-binding aptamers that have increased stability in the secondary structures of their active conformation. The designed devices can efficiently respond to target proteins including human LIN28A and U1A proteins, while the original aptamers failed to do so. Moreover, mRNA delivery of an LIN28A-responsive device into human induced pluripotent stem cells (hiPSCs) revealed that we can distinguish living hiPSCs and differentiated cells by quantifying endogenous LIN28A protein expression level. Thus, our endogenous protein-driven RNA devices determine live-cell states and program mammalian cells based on intracellular protein information. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis

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

Faehnle, Christopher R.; Walleshauser, Jack; Joshua-Tor, Leemor

2017-07-03

The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-interacting module (LIM) is indispensable for oligoU. A TUT7 CM structure trapped in the monoU activity staterevealed a duplex-RNA-binding pocket that orients group II pre-let-7 hairpins tomore » favor monoU addition. Conversely, the switch to oligoU requires the ZK domain of Lin28 to drive the formation of a stable ternary complex between pre-let-7 and the inactive LIM. Finally, ZK2 of TUT4(7) aids oligoU addition by engaging the growing oligoU tail through uracil-specific interactions.« less

Multiple HOM-C gene interactions specify cell fates in the nematode central nervous system.

PubMed

Salser, S J; Loer, C M; Kenyon, C

1993-09-01

Intricate patterns of overlapping HOM-C gene expression along the A/P axis have been observed in many organisms; however, the significance of these patterns in establishing the ultimate fates of individual cells is not well understood. We have examined the expression of the Caenorhabditis elegans Antennapedia homolog mab-5 and its role in specifying cell fates in the posterior of the ventral nerve cord. We find that the pattern of fates specified by mab-5 not only depends on mab-5 expression but also on post-translational interactions with the neighboring HOM-C gene lin-39 and a second, inferred gene activity. Where mab-5 expression overlaps with lin-39 activity, they can interact in two different ways depending on the cell type: They can either effectively neutralize one another where they are both expressed or lin-39 can predominate over mab-5. As observed for Antennapedia in Drosophila, expression of mab-5 itself is repressed by the next most posterior HOM-C gene, egl-5. Thus, a surprising diversity in HOM-C regulatory mechanisms exists within a small set of cells even in a simple organism.

Wnt Ligands Differentially Regulate Toxicity and Translocation of Graphene Oxide through Different Mechanisms in Caenorhabditis elegans

NASA Astrophysics Data System (ADS)

Zhi, Lingtong; Ren, Mingxia; Qu, Man; Zhang, Hanyu; Wang, Dayong

2016-12-01

In this study, we investigated the possible involvement of Wnt signals in the control of graphene oxide (GO) toxicity using the in vivo assay system of Caenorhabditis elegans. In nematodes, the Wnt ligands, CWN-1, CWN-2, and LIN-44, were found to be involved in the control of GO toxicity. Mutation of cwn-1 or lin-44 gene induced a resistant property to GO toxicity and resulted in the decreased accumulation of GO in the body of nematodes, whereas mutation of cwn-2 gene induces a susceptible property to GO toxicity and an enhanced accumulation of GO in the body of nematodes. Genetic interaction assays demonstrated that mutation of cwn-1 or lin-44 was able to suppress the susceptibility to GO toxicity shown in the cwn-2 mutants. Loss-of-function mutations in all three of these Wnt ligand genes resulted in the resistance of nematodes to GO toxicity. Moreover, the Wnt ligands might differentially regulate the toxicity and translocation of GO through different mechanisms. These findings could be important in understanding the function of Wnt signals in the regulation of toxicity from environmental nanomaterials.

Conservation in the involvement of heterochronic genes and hormones during developmental transitions.

PubMed

Faunes, Fernando; Larraín, Juan

2016-08-01

Developmental transitions include molting in some invertebrates and the metamorphosis of insects and amphibians. While the study of Caenorhabditis elegans larval transitions was crucial to determine the genetic control of these transitions, Drosophila melanogaster and Xenopus laevis have been classic models to study the role of hormones in metamorphosis. Here we review how heterochronic genes (lin-4, let-7, lin-28, lin-41), hormones (dafachronic acid, ecdysone, thyroid hormone) and the environment regulate developmental transitions. Recent evidence suggests that some heterochronic genes also regulate transitions in higher organisms that they are controlled by hormones involved in metamorphosis. We also discuss evidence demonstrating that heterochronic genes and hormones regulate the proliferation and differentiation of embryonic and neural stem cells. We propose the hypothesis that developmental transitions are regulated by an evolutionary conserved mechanism in which heterochronic genes and hormones interact to control stem/progenitor cells proliferation, cell cycle exit, quiescence and differentiation and determine the proper timing of developmental transitions. Finally, we discuss the relevance of these studies to understand post-embryonic development, puberty and regeneration in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification and isolation from either adult human bone marrow or G-CSF-mobilized peripheral blood of CD34(+)/CD133(+)/CXCR4(+)/ Lin(-)CD45(-) cells, featuring morphological, molecular, and phenotypic characteristics of very small embryonic-like (VSEL) stem cells.

PubMed

Sovalat, Hanna; Scrofani, Maurice; Eidenschenk, Antoinette; Pasquet, Stéphanie; Rimelen, Valérie; Hénon, Philippe

2011-04-01

Recently, we demonstrated that normal human bone marrow (hBM)-derived CD34(+) cells, released into the peripheral blood after granulocyte colony-stimulating factor mobilization, contain cell subpopulations committed along endothelial and cardiac differentiation pathways. These subpopulations could play a key role in the regeneration of post-ischemic myocardial lesion after their direct intracardiac delivery. We hypothesized that these relevant cells might be issued from very small embryonic-like stem cells deposited in the BM during ontogenesis and reside lifelong in the adult BM, and that they could be mobilized into peripheral blood by granulocyte colony-stimulating factor. Samples of normal hBM and leukapheresis products harvested from cancer patients after granulocyte colony-stimulating factor mobilization were analyzed and sorted by multiparameter flow cytometry strategy. Immunofluorescence and reverse transcription quantitative polymerase chain reaction assays were performed to analyze the expression of typical pluripotent stem cells markers. A population of CD34(+)/CD133(+)/CXCR4(+)/Lin(-) CD45(-) immature cells was first isolated from the hBM or from leukapheresis products. Among this population, very small (2-5 μm) cells expressing Oct-4, Nanog, and stage-specific embryonic antigen-4 at protein and messenger RNA levels were identified. Our study supports the hypothesis that very small embryonic-like stem cells constitute a "mobile" pool of primitive/pluripotent stem cells that could be released from the BM into the peripheral blood under the influence of various physiological or pathological stimuli. In order to fully support that hBM- and leukapheresis product-derived very small embryonic-like stem cells are actually pluripotent, we are currently testing their ability to differentiate in vitro into cells from all three germ layers. Copyright © 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Identification of key factors regulating self-renewal and differentiation in EML hematopoietic precursor cells by RNA-sequencing analysis.

PubMed

Zong, Shan; Deng, Shuyun; Chen, Kenian; Wu, Jia Qian

2014-11-11

Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo.

Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors

PubMed Central

Breece, Elizabeth; Paciotti, Brian; Nordahl, Christine Wu; Ozonoff, Sally; Van de Water, Judy A.; Rogers, Sally J.; Amaral, David; Ashwood, Paul

2012-01-01

The pathophysiology of Autism Spectrum Disorder (ASD) is not yet known; however, studies suggest that dysfunction of the immune system affects many children with ASD. Increasing evidence points to dysfunction of the innate immune system including activation of microglia and perivascular macrophages, increases in inflammatory cytokines/chemokines in brain tissue and CSF, and abnormal peripheral monocyte cell function. Dendritic cells are major players in innate immunity and have important functions in the phagocytosis of pathogens or debris, antigen presentation, activation of naïve T cells, induction of tolerance and cytokine/chemokine production. In this study, we assessed circulating frequencies of myeloid dendritic cells (defined as Lin-1−BDCA1+CD11c+ and Lin-1−BDCA3+CD123−) and plasmacytoid dendritic cells (Lin-1− BDCA2+CD123+ or Lin-1−BDCA4+ CD11c−) in 57 children with ASD, and 29 typically developing controls of the same age, all of who were enrolled as part of the Autism Phenome Project (APP). The frequencies of dendritic cells and associations with behavioral assessment and MRI measurements of amygdala volume were compared in the same participants. The frequencies of myeloid dendritic cells were significantly increased in children with ASD compared to typically developing controls (p < 0.03). Elevated frequencies of myeloid dendritic cells were positively associated with abnormal right and left amygdala enlargement, severity of gastrointestinal symptoms and increased repetitive behaviors. The frequencies of plasmacytoid dendritic cells were also associated with amygdala volumes as well as developmental regression in children with ASD. Dendritic cells play key roles in modulating immune responses and differences in frequencies or functions of these cells may result in immune dysfunction in children with ASD. These data further implicate innate immune cells in the complex pathophysiology of ASD. PMID:23063420

Effect of colorectal cancer on the number of normal stem cells circulating in peripheral blood.

PubMed

Marlicz, Wojciech; Sielatycka, Katarzyna; Serwin, Karol; Kubis, Ewa; Tkacz, Marta; Głuszko, Rafał; Białek, Andrzej; Starzyńska, Teresa; Ratajczak, Mariusz Z

2016-12-01

Bone marrow (BM) residing stem cells are mobilized from their BM niches into peripheral blood (PB) in several pathological situations including tissue organ injury and systemic inflammation. We recently reported that the number of BM-derived stem cells (SCs) increases in patients with pancreatic and stomach cancer. Accordingly, we observed higher numbers of circulating very small embryonic/epiblast‑like stem cells (VSELs) and mesenchymal stem cells (MSCs) that were associated with the activation of pro-mobilizing complement cascade and an elevated level of sphingosine-1 phosphate (S1P) in PB plasma. We wondered if a similar correlation occurs in patients with colorectal cancer (CRC). A total of 46 patients were enrolled in this study: 17 with CRC, 18 with benign colonic adenomas (BCA) and 11 healthy individuals. By employing fluorescence-activated cell sorting (FACS) we evaluated the number of BM-derived SCs circulating in PB: i) CD34+/Lin-/CD45- and CD133-/Lin-/CD45- VSELs; ii) CD45-/CD105+/CD90+/CD29+ MSCs; iii) CD45-/CD34+/CD133+/KDR+ endothelial progenitor cells (EPCs); and iv) CD133+/Lin-/CD45+ or CD34+/Lin-/CD45+ cells enriched for hematopoietic stem/progenitor cells (HSPCs). In parallel, we measured in the PB parameters regulating the egress of SCs from BM into PB. In contrast to pancreatic and gastric cancer patients, CRC subjects presented neither an increase in the number of circulating SCs nor the activation of pro-mobilizing factors such as complement, coagulation and fibrinolytic cascade, circulating stromal derived factor 1 (SDF‑1), vascular endothelial growth factor (VEGF) and intestinal permeability marker (zonulin). In conclusion, mobilization of SCs in cancer patients depends on the type of malignancy and its ability to activate pro-mobilization cascades.

Formal ontology for natural language processing and the integration of biomedical databases.

PubMed

Simon, Jonathan; Dos Santos, Mariana; Fielding, James; Smith, Barry

2006-01-01

The central hypothesis underlying this communication is that the methodology and conceptual rigor of a philosophically inspired formal ontology can bring significant benefits in the development and maintenance of application ontologies [A. Flett, M. Dos Santos, W. Ceusters, Some Ontology Engineering Procedures and their Supporting Technologies, EKAW2002, 2003]. This hypothesis has been tested in the collaboration between Language and Computing (L&C), a company specializing in software for supporting natural language processing especially in the medical field, and the Institute for Formal Ontology and Medical Information Science (IFOMIS), an academic research institution concerned with the theoretical foundations of ontology. In the course of this collaboration L&C's ontology, LinKBase, which is designed to integrate and support reasoning across a plurality of external databases, has been subjected to a thorough auditing on the basis of the principles underlying IFOMIS's Basic Formal Ontology (BFO) [B. Smith, Basic Formal Ontology, 2002. http://ontology.buffalo.edu/bfo]. The goal is to transform a large terminology-based ontology into one with the ability to support reasoning applications. Our general procedure has been the implementation of a meta-ontological definition space in which the definitions of all the concepts and relations in LinKBase are standardized in the framework of first-order logic. In this paper we describe how this principles-based standardization has led to a greater degree of internal coherence of the LinKBase structure, and how it has facilitated the construction of mappings between external databases using LinKBase as translation hub. We argue that the collaboration here described represents a new phase in the quest to solve the so-called "Tower of Babel" problem of ontology integration [F. Montayne, J. Flanagan, Formal Ontology: The Foundation for Natural Language Processing, 2003. http://www.landcglobal.com/].

Identification of Key Factors Regulating Self-renewal and Differentiation in EML Hematopoietic Precursor Cells by RNA-sequencing Analysis

PubMed Central

Chen, Kenian; Wu, Jia Qian

2014-01-01

Hematopoietic stem cells (HSCs) are used clinically for transplantation treatment to rebuild a patient's hematopoietic system in many diseases such as leukemia and lymphoma. Elucidating the mechanisms controlling HSCs self-renewal and differentiation is important for application of HSCs for research and clinical uses. However, it is not possible to obtain large quantity of HSCs due to their inability to proliferate in vitro. To overcome this hurdle, we used a mouse bone marrow derived cell line, the EML (Erythroid, Myeloid, and Lymphocytic) cell line, as a model system for this study. RNA-sequencing (RNA-Seq) has been increasingly used to replace microarray for gene expression studies. We report here a detailed method of using RNA-Seq technology to investigate the potential key factors in regulation of EML cell self-renewal and differentiation. The protocol provided in this paper is divided into three parts. The first part explains how to culture EML cells and separate Lin-CD34+ and Lin-CD34- cells. The second part of the protocol offers detailed procedures for total RNA preparation and the subsequent library construction for high-throughput sequencing. The last part describes the method for RNA-Seq data analysis and explains how to use the data to identify differentially expressed transcription factors between Lin-CD34+ and Lin-CD34- cells. The most significantly differentially expressed transcription factors were identified to be the potential key regulators controlling EML cell self-renewal and differentiation. In the discussion section of this paper, we highlight the key steps for successful performance of this experiment. In summary, this paper offers a method of using RNA-Seq technology to identify potential regulators of self-renewal and differentiation in EML cells. The key factors identified are subjected to downstream functional analysis in vitro and in vivo. PMID:25407807

Tomato ovary-to-fruit transition is characterized by a spatial shift of mRNAs for cell wall invertase and its inhibitor with the encoded proteins localized to sieve elements.

PubMed

Palmer, William M; Ru, Lei; Jin, Ye; Patrick, John W; Ruan, Yong-Ling

2015-02-01

Central to understanding fruit development is to elucidate the processes mediating a successful transition from pre-pollination ovaries to newly set fruit, a key step in establishing fruit yield potential. In tomato, cell wall invertase (CWIN) LIN5 and its inhibitor INH1 are essential for fruit growth. However, the molecular and cellular basis by which they exert their roles in ovary-to-fruit transition remains unknown. To address this issue, we conducted a study focusing on ovaries and fruitlets at 2 days before and 2 days after anthesis, respectively. In situ hybridization analyses revealed that LIN5 and INH1 exhibited a dispersed expression in ovaries compared with their phloem-specific expression in fruitlets. Remarkably, LIN5 and INH1 proteins were immunologically co-localized to cell walls of sieve elements (SEs) in ovaries immediately prior to anthesis and in young fruitlets, but were undetectable in provascular bundles of younger ovaries. A burst in CWIN activity occurred during ovary-to-fruit transition. Interestingly, the ovaries, but not the fruitlets, exhibited high expression of a defective invertase, SldeCWIN1, an ortholog of which is known to enhance inhibition of INH on CWIN activity in tobacco. Imaging of a fluorescent symplasmic tracer indicated an apoplasmic phloem unloading pathway operated in ovaries, contrary to the previously observed symplasmic unloading pathway in fruit pericarp. These new data indicate that (1) a phloem-specific patterning of the CWIN and INH mRNAs is induced during ovary-to-fruit transition, and (2) LIN5 protein functions specifically in walls of SEs and increases its activity during ovary-to-fruit transition, probably to facilitate phloem unloading and to generate a glucose signal positively regulating cell division, hence fruit set. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

A 25-Gbps high-sensitivity optical receiver with 10-Gbps photodiode using inductive input coupling for optical interconnects

NASA Astrophysics Data System (ADS)

Oku, Hideki; Narita, Kiyomi; Shiraishi, Takashi; Ide, Satoshi; Tanaka, Kazuhiro

2012-01-01

A 25-Gbps high-sensitivity optical receiver with a 10-Gbps photodiode (PD) using inductive input coupling has been demonstrated for optical interconnects. We introduced the inductive input coupling technique to achieve the 25-Gbps optical receiver using a 10-Gbps PD. We implemented an input inductor (Lin) between the PD and trans-impedance amplifier (TIA), and optimized inductance to enhance the bandwidth and reduce the input referred noise current through simulation with the RF PD-model. Near the resonance frequency of the tank circuit formed by PD capacitance, Lin, and TIA input capacitance, the PD photo-current through Lin into the TIA is enhanced. This resonance has the effects of enhancing the bandwidth at TIA input and reducing the input equivalent value of the noise current from TIA. We fabricated the 25-Gbps optical receiver with the 10-Gbps PD using an inductive input coupling technique. Due to the application of an inductor, the receiver bandwidth is enhanced from 10 GHz to 14.2 GHz. Thanks to this wide-band and low-noise performance, we were able to improve the sensitivity at an error rate of 1E-12 from non-error-free to -6.5 dBm. These results indicate that our technique is promising for cost-effective optical interconnects.

Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number

PubMed Central

Katsanos, Dimitris; Koneru, Sneha L.; Mestek Boukhibar, Lamia; Gritti, Nicola; Ghose, Ritobrata; Appleford, Peter J.; Doitsidou, Maria; Woollard, Alison; van Zon, Jeroen S.; Poole, Richard J.

2017-01-01

Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens. PMID:29108019

An integrated global regulatory network of hematopoietic precursor cell self-renewal and differentiation.

PubMed

You, Yanan; Cuevas-Diaz Duran, Raquel; Jiang, Lihua; Dong, Xiaomin; Zong, Shan; Snyder, Michael; Wu, Jia Qian

2018-06-12

Systematic study of the regulatory mechanisms of Hematopoietic Stem Cell and Progenitor Cell (HSPC) self-renewal is fundamentally important for understanding hematopoiesis and for manipulating HSPCs for therapeutic purposes. Previously, we have characterized gene expression and identified important transcription factors (TFs) regulating the switch between self-renewal and differentiation in a multipotent Hematopoietic Progenitor Cell (HPC) line, EML (Erythroid, Myeloid, and Lymphoid) cells. Herein, we report binding maps for additional TFs (SOX4 and STAT3) by using chromatin immunoprecipitation (ChIP)-Sequencing, to address the underlying mechanisms regulating self-renewal properties of lineage-CD34+ subpopulation (Lin-CD34+ EML cells). Furthermore, we applied the Assay for Transposase Accessible Chromatin (ATAC)-Sequencing to globally identify the open chromatin regions associated with TF binding in the self-renewing Lin-CD34+ EML cells. Mass spectrometry (MS) was also used to quantify protein relative expression levels. Finally, by integrating the protein-protein interaction database, we built an expanded transcriptional regulatory and interaction network. We found that MAPK (Mitogen-activated protein kinase) pathway and TGF-β/SMAD signaling pathway components were highly enriched among the binding targets of these TFs in Lin-CD34+ EML cells. The present study integrates regulatory information at multiple levels to paint a more comprehensive picture of the HSPC self-renewal mechanisms.

Wnt signaling induces vulva development in the nematode Pristionchus pacificus.

PubMed

Tian, Huiyu; Schlager, Benjamin; Xiao, Hua; Sommer, Ralf J

2008-01-22

The Caenorhabditis elegans vulva is induced by a member of the epidermal growth factor (EGF) family that is expressed in the gonadal anchor cell, representing a prime example of signaling processes in animal development. Comparative studies indicated that vulva induction has changed rapidly during evolution. However, nothing was known about the molecular mechanisms underlying these differences. By analyzing deletion mutants in five Wnt pathway genes, we show that Wnt signaling induces vulva formation in Pristionchus pacificus. A Ppa-bar-1/beta-catenin deletion is completely vulvaless. Several Wnt ligands and receptors act redundantly in vulva induction, and Ppa-egl-20/Wnt; Ppa-mom-2/Wnt; Ppa-lin-18/Ryk triple mutants are strongly vulvaless. Wnt ligands are differentially expressed in the somatic gonad, the anchor cell, and the posterior body region, respectively. In contrast, previous studies indicated that Ppa-lin-17, one of the Frizzled-type receptors, has a negative role in vulva formation. We found that mutations in Ppa-bar-1 and Ppa-egl-20 suppress the phenotype of Ppa-lin-17. Thus, an unexpected complexity of Wnt signaling is involved in vulva induction and vulva repression in P. pacificus. This study provides the first molecular identification of the inductive vulva signal in a nematode other than Caenorhabditis.

Matrix remodeling between cells and cellular interactions with collagen bundle

NASA Astrophysics Data System (ADS)

Kim, Jihan; Sun, Bo

When cells are surrounded by complex environment, they continuously probe and interact with it by applying cellular traction forces. As cells apply traction forces, they can sense rigidity of their local environment and remodel the matrix microstructure simultaneously. Previous study shows that single human carcinoma cell (MDA-MB-231) remodeled its surrounding extracellular matrix (ECM) and the matrix remodeling was reversible. In this study we examined the matrix microstructure between cells and cellular interaction between them using quantitative confocal microscopy. The result shows that the matrix microstructure is the most significantly remodeled between cells consisting of aligned, and densified collagen fibers (collagen bundle)., the result shows that collagen bundle is irreversible and significantly change micromechanics of ECM around the bundle. We further examined cellular interaction with collagen bundle by analyzing dynamics of actin and talin formation along with the direction of bundle. Lastly, we analyzed dynamics of cellular protrusion and migrating direction of cells along the bundle.

Phosphatidylinositol Phosphate 5-Kinase Iγi2 in Association with Src Controls Anchorage-independent Growth of Tumor Cells*

PubMed Central

Thapa, Narendra; Choi, Suyong; Hedman, Andrew; Tan, Xiaojun; Anderson, Richard A.

2013-01-01

A fundamental property of tumor cells is to defy anoikis, cell death caused by a lack of cell-matrix interaction, and grow in an anchorage-independent manner. How tumor cells organize signaling molecules at the plasma membrane to sustain oncogenic signals in the absence of cell-matrix interactions remains poorly understood. Here, we describe a role for phosphatidylinositol 4-phosphate 5-kinase (PIPK) Iγi2 in controlling anchorage-independent growth of tumor cells in coordination with the proto-oncogene Src. PIPKIγi2 regulated Src activation downstream of growth factor receptors and integrins. PIPKIγi2 directly interacted with the C-terminal tail of Src and regulated its subcellular localization in concert with talin, a cytoskeletal protein targeted to focal adhesions. Co-expression of PIPKIγi2 and Src synergistically induced the anchorage-independent growth of nonmalignant cells. This study uncovers a novel mechanism where a phosphoinositide-synthesizing enzyme, PIPKIγi2, functions with the proto-oncogene Src, to regulate oncogenic signaling. PMID:24151076

HIP1 exhibits an early recruitment and a late stage function in the maturation of coated pits.

PubMed

Gottfried, Irit; Ehrlich, Marcelo; Ashery, Uri

2009-09-01

Huntingtin interacting protein 1 (HIP1) is an accessory protein of the clathrin-mediated endocytosis (CME) pathway, yet its precise role and the step at which it becomes involved are unclear. We employed live-cell imaging techniques to focus on the early steps of CME and characterize HIP1 dynamics. We show that HIP1 is highly colocalized with clathrin at the plasma membrane and shares similar dynamics with a subpopulation of clathrin assemblies. Employing transferrin receptor fused to pHluorin, we distinguished between open pits to which HIP1 localizes and newly internalized vesicles that are devoid of HIP1. Moreover, shRNA knockdown of clathrin compromised HIP1 membranal localization, unlike the reported behavior of Sla2p. HIP1 fragment, lacking its ANTH and Talin-like domains, inhibits internalization of transferrin, but retains colocalization with membranal clathrin assemblies. These data demonstrate HIP1's role in pits maturation and formation of the coated vesicle, and its strong dependence on clathrin for membranal localization.

Soluble factor(s) from bone marrow cells can rescue lethally irradiated mice by protecting endogenous hematopoietic stem cells.

PubMed

Zhao, Yi; Zhan, Yuxia; Burke, Kathleen A; Anderson, W French

2005-04-01

Ionizing radiation-induced myeloablation can be rescued via bone marrow transplantation (BMT) or administration of cytokines if given within 2 hours after radiation exposure. There is no evidence for the existence of soluble factors that can rescue an animal after a lethal dose of radiation when administered several hours postradiation. We established a system that could test the possibility for the existence of soluble factors that could be used more than 2 hours postirradiation to rescue animals. Animals with an implanted TheraCyte immunoisolation device (TID) received lethal-dose radiation and then normal bone marrow Lin- cells were loaded into the device (thereby preventing direct interaction between donor and recipient cells). Animal survival was evaluated and stem cell activity was tested with secondary bone marrow transplantation and flow cytometry analysis. Donor cell gene expression of five antiapoptotic cytokines was examined. Bone marrow Lin- cells rescued lethally irradiated animals via soluble factor(s). Bone marrow cells from the rescued animals can rescue and repopulate secondary lethally irradiated animals. Within the first 6 hours post-lethal-dose radiation, there is no significant change of gene expression of the known radioprotective factors TPO, SCF, IL-3, Flt-3 ligand, and SDF-1. Hematopoietic stem cells can be protected in lethally irradiated animals by soluble factors produced by bone marrow Lin- cells.

Shuttle inhibition by chemical adsorption of lithium polysulfides in B and N co-doped graphene for Li-S batteries.

PubMed

Li, Fen; Su, Yan; Zhao, Jijun

2016-09-14

The advance of lithium sulfur batteries is now greatly restricted by the fast capacity fading induced by shuttle effect. Using first-principles calculations, various vacancies, N doping, and B,N co-doping in graphene sheets have been systematically explored for lithium polysufides entrapped in Li-S batteries. The LiS, LiC, LiN and SB bonds and Hirshfeld charges in the Li 2 S 6 adsorbed defective graphene systems have been analyzed to understand the intrinsic mechanism of retaining lithium polysulfides in these systems. Total and local densities of states analyses elucidate the strongest adsorption sites among the N and B-N co-doped graphene systems. The overall electrochemical performance of Li-S batteries varies with the types of defects in graphene. Among the defective graphene systems, only the reconstructed pyrrole-like vacancy is effective for retaining lithium polysulfides. N doping induces a strong LiN interaction in the defective graphene systems, in which the pyrrolic N rather than the pyridinic N plays a dominant role in trapping of lithium polysulfides. The shuttle effect can be further depressed via pyrrolic B,N co-doped defective graphene materials, especially the G-B-N-hex system with extremely strong adsorption of lithium polysulfides (4-5 eV), and simultaneous contribution from the strong LiN and SB interactions.

Ly6CHi Blood Monocyte/Macrophage Drive Chronic Inflammation and Impair Wound Healing in Diabetes Mellitus.

PubMed

Kimball, Andrew; Schaller, Matthew; Joshi, Amrita; Davis, Frank M; denDekker, Aaron; Boniakowski, Anna; Bermick, Jennifer; Obi, Andrea; Moore, Bethany; Henke, Peter K; Kunkel, Steve L; Gallagher, Katherine A

2018-05-01

Wound monocyte-derived macrophage plasticity controls the initiation and resolution of inflammation that is critical for proper healing, however, in diabetes mellitus, the resolution of inflammation fails to occur. In diabetic wounds, the kinetics of blood monocyte recruitment and the mechanisms that control in vivo monocyte/macrophage differentiation remain unknown. Here, we characterized the kinetics and function of Ly6C Hi [Lin - (CD3 - CD19 - NK1.1 - Ter-119 - ) Ly6G - CD11b + ] and Ly6C Lo [Lin - (CD3 - CD19 - NK1.1 - Ter-119 - ) Ly6G - CD11b + ] monocyte/macrophage subsets in normal and diabetic wounds. Using flow-sorted tdTomato -labeled Ly6C Hi monocyte/macrophages, we show Ly6C Hi cells transition to a Ly6C Lo phenotype in normal wounds, whereas in diabetic wounds, there is a late, second influx of Ly6C Hi cells that fail transition to Ly6C Lo . The second wave of Ly6C Hi cells in diabetic wounds corresponded to a spike in MCP-1 (monocyte chemoattractant protein-1) and selective administration of anti-MCP-1 reversed the second Ly6C Hi influx and improved wound healing. To examine the in vivo phenotype of wound monocyte/macrophages, RNA-seq-based transcriptome profiling was performed on flow-sorted Ly6C Hi [Lin - Ly6G - CD11b + ] and Ly6C Lo [Lin - Ly6G - CD11b + ] cells from normal and diabetic wounds. Gene transcriptome profiling of diabetic wound Ly6C Hi cells demonstrated differences in proinflammatory and profibrotic genes compared with controls. Collectively, these data identify kinetic and functional differences in diabetic wound monocyte/macrophages and demonstrate that selective targeting of CD11b + Ly6C Hi monocyte/macrophages is a viable therapeutic strategy for inflammation in diabetic wounds. © 2018 American Heart Association, Inc.

Physically-based Assessment of Tropical Cyclone Damage and Economic Losses

NASA Astrophysics Data System (ADS)

Lin, N.

2012-12-01

Estimating damage and economic losses caused by tropical cyclones (TC) is a topic of considerable research interest in many scientific fields, including meteorology, structural and coastal engineering, and actuarial sciences. One approach is based on the empirical relationship between TC characteristics and loss data. Another is to model the physical mechanism of TC-induced damage. In this talk we discuss about the physically-based approach to predict TC damage and losses due to extreme wind and storm surge. We first present an integrated vulnerability model, which, for the first time, explicitly models the essential mechanisms causing wind damage to residential areas during storm passage, including windborne-debris impact and the pressure-debris interaction that may lead, in a chain reaction, to structural failures (Lin and Vanmarcke 2010; Lin et al. 2010a). This model can be used to predict the economic losses in a residential neighborhood (with hundreds of buildings) during a specific TC (Yau et al. 2011) or applied jointly with a TC risk model (e.g., Emanuel et al 2008) to estimate the expected losses over long time periods. Then we present a TC storm surge risk model that has been applied to New York City (Lin et al. 2010b; Lin et al. 2012; Aerts et al. 2012), Miami-Dade County, Florida (Klima et al. 2011), Galveston, Texas (Lickley, 2012), and other coastal areas around the world (e.g., Tampa, Florida; Persian Gulf; Darwin, Australia; Shanghai, China). These physically-based models are applicable to various coastal areas and have the capability to account for the change of the climate and coastal exposure over time. We also point out that, although made computationally efficient for risk assessment, these models are not suitable for regional or global analysis, which has been a focus of the empirically-based economic analysis (e.g., Hsiang and Narita 2012). A future research direction is to simplify the physically-based models, possibly through

Metagenome-assembled genomes of deep-branching magnetotactic bacteria in the Nitrospirae phylum

NASA Astrophysics Data System (ADS)

Zhang, W.; He, M.; Gu, L.; Tang, X.; Pan, Y.; Lin, W.

2017-12-01

Magnetotactic bacteria (MTB) are aquatic microorganisms that synthesize intracellular magnetic nanoparticles composed of magnetite and/or greigite. MTB have thus far been identified in the phyla of Proteobacteria, Nitrospirae, Omnitrophica, Latescibacteria and Planctomycetes (Lin et al., 2017b). Among these organisms, MTB belonging to the Nitrospirae phylum are of great interest because of the formation of hundreds of magnetite magnetosomes in a single cell and of the great potential for iron, sulfur, nitrogen, and carbon cycling in natural environments. However, due to the lack of genomic information, our current knowledge on magnetotactic Nitrospirae remains very limited. In the present study, we have identified and characterized two novel populations of uncultivated MTB from freshwater lakes in Shaanxi province, China. 16S rRNA gene-based analyses revealed that they belonged to two different clusters in the Nitrospirae. The draft population genomes of these two Nitrospirae MTB were successfully recovered through genome-resolved metagenomics, both of which containing nearly complete magnetosome gene clusters (MGCs) responsible for magnetosome biomineralization and organization. In consistent with our previous study (Lin et al., 2017a), we found that the gene content and gene organization of the MGCs in the Nitrospirae MTB were highly conserved, indicating that Nitrospirae gene clusters represent one of the ancestral types of MGCs. The population genome sequences suggest that magnetotactic Nitrospirae are capable of CO2 fixtion through Wood-Ljungdahl pathway. They may also reduce sulfate and nitrate/nitrite through sulfate reduction pathway and denitrification pathway, respectively. Our genomic analyses revealed the potential metabolic capability of the Nitrospirae MTB and shed light on their ecology, evolution and biomineralization mechanism. References: Lin W, Paterson GA, Zhu Q, Wang Y, Kopylova E, Li Y, Knight R, Bazylinski DA, Zhu R, Kirschvink JL, Pan Y

A Muskingum-based methodology for river discharge estimation and rating curve development under significant lateral inflow conditions

NASA Astrophysics Data System (ADS)

Barbetta, Silvia; Moramarco, Tommaso; Perumal, Muthiah

2017-11-01

Quite often the discharge at a site is estimated using the rating curve developed for that site and its development requires river flow measurements, which are costly, tedious and dangerous during severe floods. To circumvent the conventional rating curve development approach, Perumal et al. in 2007 and 2010 applied the Variable Parameter Muskingum Stage-hydrograph (VPMS) routing method for developing stage-discharge relationships especially at those ungauged river sites where stage measurements and details of section geometry are available, but discharge measurements are not made. The VPMS method enables to estimate rating curves at ungauged river sites with acceptable accuracy. But the application of the method is subjected to the limitation of negligible presence of lateral flow within the routing reach. To overcome this limitation, this study proposes an extension of the VPMS method, henceforth, known herein as the VPMS-Lin method, for enabling the streamflow assessment even when significant lateral inflow occurs along the river reach considered for routing. The lateral inflow is estimated through the continuity equation expressed in the characteristic form as advocated by Barbetta et al. in 2012. The VPMS-Lin, is tested on two rivers characterized by different geometric and hydraulic properties: 1) a 50 km reach of the Tiber River in (central Italy) and 2) a 73 km reach of the Godavari River in the peninsular India. The study demonstrates that both the upstream and downstream discharge hydrographs are well reproduced, with a root mean square error equal on average to about 35 and 1700 m3 s-1 for the Tiber River and the Godavari River case studies, respectively. Moreover, simulation studies carried out on a river stretch of the Tiber River using the one-dimensional hydraulic model MIKE11 and the VPMS-Lin models demonstrate the accuracy of the VMPS-Lin model, which besides enabling the estimation of streamflow, also enables the estimation of reach averaged

Various types of stem cells, including a population of very small embryonic-like stem cells, are mobilized into peripheral blood in patients with Crohn's disease.

PubMed

Marlicz, Wojciech; Zuba-Surma, Ewa; Kucia, Magda; Blogowski, Wojciech; Starzynska, Teresa; Ratajczak, Mariusz Z

2012-09-01

Developmentally early cells, including hematopoietic stem progenitor cells (HSPCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs), are mobilized into peripheral blood (PB) in response to tissue/organ injury. We sought to determine whether these cells are mobilized into PB in patients with Crohn's disease (CD). Twenty-five patients with active CD, 20 patients in clinical remission, and 25 age-matched controls were recruited and PB samples harvested. The circulating CD133+/Lin-/CD45+ and CD34+/Lin-/CD45+ cells enriched for HSPCs, CD105+/STRO-1+/CD45- cells enriched for MSCs, CD34+/KDR+/CD31+/CD45-cells enriched for EPCs, and small CXCR4+CD34+CD133+ subsets of Lin-CD45- cells that correspond to the population of VSELs were counted by fluorescence-activated cell sorting (FACS) and evaluated by direct immunofluorescence staining for pluripotency embryonic markers and by reverse-transcription polymerase chain reaction (RT-PCR) for expression of messenger (m)RNAs for a panel of genes expressed in intestine epithelial stem cells. The serum concentration of factors involved in stem cell trafficking, such as stromal derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) were measured by enzyme-linked immunosorbent assay (ELISA). Our data indicate that cells expressing markers for MSCs, EPCs, and small Oct-4+Nanog+SSEA-4+CXCR4+lin-CD45- VSELs are mobilized into PB in CD. The mobilized cells also expressed at the mRNA level genes playing a role in development and regeneration of gastrointestinal epithelium. All these changes were accompanied by increased serum concentrations of VEGF and HGF. CD triggers the mobilization of MSCs, EPCs, and VSELs, while the significance and precise role of these mobilized cells in repair of damaged intestine requires further study. Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.

The 3-D aftershock distribution of three recent M5~5.5 earthquakes in the Anza region,California

NASA Astrophysics Data System (ADS)

Zhang, Q.; Wdowinski, S.; Lin, G.

2011-12-01

The San Jacinto fault zone (SJFZ) exhibits the highest level of seismicity compared to other regions in southern California. On average, it produces four earthquakes per day, most of them at depth of 10-17 km. Over the past decade, an increasing seismic activity occurred in the Anza region, which included three M5~5.5 events and their aftershock sequences. These events occurred in 2001, 2005, and 2010. In this research we map the 3-D distribution of these three events to evaluate their rupture geometry and better understand the unusual deep seismic pattern along the SJFZ, which was termed "deep creep" (Wdowinski, 2009). We relocated 97,562 events from 1981 to 2011 in Anza region by applying the Source-Specific Station Term (SSST) method (Lin et al., 2006) and used an accurate 1-D velocity model derived from 3-D model of Lin et al (2007) and used In order to separate the aftershock sequence from background seismicity, we characterized each of the three aftershock sequences using Omori's law. Preliminary results show that all three sequences had a similar geometry of deep elongated aftershock distribution. Most aftershocks occurred at depth of 10-17 km and extended over a 70 km long segments of the SJFZ, centered at the mainshock hypocenters. A comparative study of other M5~5.5 mainshocks and their aftershock sequences in southern California reveals very different geometrical pattern, suggesting that the three Anza M5~5.5 events are unique and can be indicative of "deep creep" deformation processes. Reference 1.Lin, G.and Shearer,P.M.,2006, The COMPLOC earthquake location package,Seism. Res. Lett.77, pp.440-444. 2.Lin, G. and Shearer, P.M., Hauksson, E., and Thurber C.H.,2007, A three-dimensional crustal seismic velocity model for southern California from a composite event method,J. Geophys.Res.112, B12306, doi: 10.1029/ 2007JB004977. 3.Wdowinski, S. ,2009, Deep creep as a cause for the excess seismicity along the San Jacinto fault, Nat. Geosci.,doi:10.1038/NGEO684.

78 FR 33437 - Notice of Lodging of Proposed Consent Decree Under the Comprehensive Environmental Response...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-04

...), for costs of past response actions in connection with the release of hazardous substances at the Lin....htm . We will provide a paper copy of the Consent Decree upon written request and payment of...

Outdoor fitness routine

MedlinePlus

... on a sport you enjoy, such as bicycling, hiking, jogging, rowing, tennis, or Frisbee. Make chores a ... L, Lin BB, Gaston KJ, Fuller RA. The benefits of natural environments for physical activity. Sports Med . ...

Long-term effect of linseed plus nitrate fed to dairy cows on enteric methane emission and nitrate and nitrite residuals in milk.

PubMed

Guyader, J; Doreau, M; Morgavi, D P; Gérard, C; Loncke, C; Martin, C

2016-07-01

A previous study showed the additive methane (CH4)-mitigating effect of nitrate and linseed fed to non-lactating cows. Before practical application, the use of this new strategy in dairy cows requires further investigation in terms of persistency of methanogenesis reduction and absence of residuals in milk products. The objective of this experiment was to study the long-term effect of linseed plus nitrate on enteric CH4 emission and performance in dairy cows. We also assessed the effect of this feeding strategy on the presence of nitrate residuals in milk products, total tract digestibility, nitrogen (N) balance and rumen fermentation. A total of 16 lactating Holstein cows were allocated to two groups in a randomised design conducted in parallel for 17 weeks. Diets were on a dry matter (DM) basis: (1) control (54% maize silage, 6% hay and 40% concentrate; CON) or (2) control plus 3.5% added fat from linseed and 1.8% nitrate (LIN+NIT). Diets were equivalent in terms of CP (16%), starch (28%) and NDF (33%), and were offered twice daily. Cows were fed ad libitum, except during weeks 5, 16 and 17 in which feed was restricted to 95% of dry matter intake (DMI) to ensure complete consumption of meals during measurement periods. Milk production and DMI were measured weekly. Nitrate and nitrite concentrations in milk and milk products were determined monthly. Daily CH4 emission was quantified in open circuit respiration chambers (weeks 5 and 16). Total tract apparent digestibility, N balance and rumen fermentation parameters were determined in week 17. Daily DMI tended to be lower with LIN+NIT from week 4 to 16 (-5.1 kg/day on average). The LIN+NIT diet decreased milk production during 6 non-consecutive weeks (-2.5 kg/day on average). Nitrate or nitrite residuals were not detected in milk and associated products. The LIN+NIT diet reduced CH4 emission to a similar extent at the beginning and end of the trial (-47%, g/day; -30%, g/kg DMI; -33%, g/kg fat- and protein

Fracture structures of active Nojima fault, Japan, revealed by borehole televiewer imaging

NASA Astrophysics Data System (ADS)

Nishiwaki, T.; Lin, A.

2017-12-01

Most large intraplate earthquakes occur as slip on mature active faults, any investigation of the seismic faulting process and assessment of seismic hazards require an understanding of the nature of active fault damage zones as seismogenic source. In this study, we focus on the fracture structures of the Nojima Fault (NF) that triggered the 1995 Kobe Mw 7.2 earthquake using ultrasonic borehole televiewer (BHTV) images from a borehole wall. The borehole used in this study was drilled throughout the NF at 1000 m in depth by a science project of Drilling into Fault Damage Zone(DFDZ) in 2016 (Lin, 2016; Miyawaki et al., 2016). In the depth of <230 m of the borehole, the rocks are composed of weak consolidated sandstone and conglomerate of the Plio-Pleistocene Osaka-Group and mudstone and sandstone of the Miocene Kobe Group. The basement rock in the depth of >230 m consist of pre-Neogene granitic rock. Based on the observations of cores and analysis of the BHTV images, the main fault plane was identified at a depth of 529.3 m with a 15 cm thick fault gouge zone and a damage zone of 100 m wide developed in the both sides of the main fault plane. Analysis of the BHTV images shows that the fractures are concentrated in two groups: N45°E (Group-1), parallel to the general trend of the NF, and another strikes N70°E (Group-2), oblique to the fault with an angle of 20°. It is well known that Riedel shear structures are common within strike-slip fault zones. Previous studies show that the NF is a right-lateral strike-slip fault with a minor thrust component, and that the fault damage zone is characterized by Riedel shear structures dominated by Y shears (main faults), R shears and P foliations (Lin, 2001). We interpret that the fractures of Group (1) correspond to Y Riedel fault shears, and those of Group (2) are R shears. Such Riedel shear structures indicate that the NF is a right-lateral strike-slip fault which is activated under a regional stress field oriented to the

Convective and microphysics parameterization impact on simulating heavy rainfall in Semarang (case study on February 12th, 2015)

NASA Astrophysics Data System (ADS)

Faridatussafura, Nurzaka; Wandala, Agie

2018-05-01

The meteorological model WRF-ARW version 3.8.1 is used for simulating the heavy rainfall in Semarang that occurred on February 12th, 2015. Two different convective schemes and two different microphysics scheme in a nested configuration were chosen. The sensitivity of those schemes in capturing the extreme weather event has been tested. GFS data were used for the initial and boundary condition. Verification on the twenty-four hours accumulated rainfall using GSMaPsatellite data shows that Kain-Fritsch convective scheme and Lin microphysics scheme is the best combination scheme among the others. The combination also gives the highest success ratio value in placing high intensity rainfall area. Based on the ROC diagram, KF-Lin shows the best performance in detecting high intensity rainfall. However, the combination still has high bias value.

Ligand regulation of a constitutively dimeric EGF receptor

NASA Astrophysics Data System (ADS)

Freed, Daniel M.; Alvarado, Diego; Lemmon, Mark A.

2015-06-01

Ligand-induced receptor dimerization has traditionally been viewed as the key event in transmembrane signalling by epidermal growth factor receptors (EGFRs). Here we show that the Caenorhabditis elegans EGFR orthologue LET-23 is constitutively dimeric, yet responds to its ligand LIN-3 without changing oligomerization state. SAXS and mutational analyses further reveal that the preformed dimer of the LET-23 extracellular region is mediated by its domain II dimerization arm and resembles other EGFR extracellular dimers seen in structural studies. Binding of LIN-3 induces only minor structural rearrangements in the LET-23 dimer to promote signalling. Our results therefore argue that EGFR can be regulated by allosteric changes within an existing receptor dimer--resembling signalling by insulin receptor family members, which share similar extracellular domain compositions but form covalent dimers.

On the classification of elliptic foliations induced by real quadratic fields with center

NASA Astrophysics Data System (ADS)

Puchuri, Liliana; Bueno, Orestes

2016-12-01

Related to the study of Hilbert's infinitesimal problem, is the problem of determining the existence and estimating the number of limit cycles of the linear perturbation of Hamiltonian fields. A classification of the elliptic foliations in the projective plane induced by the fields obtained by quadratic fields with center was already studied by several authors. In this work, we devise a unified proof of the classification of elliptic foliations induced by quadratic fields with center. This technique involves using a formula due to Cerveau & Lins Neto to calculate the genus of the generic fiber of a first integral of foliations of these kinds. Furthermore, we show that these foliations induce several examples of linear families of foliations which are not bimeromorphically equivalent to certain remarkable examples given by Lins Neto.

Your Endocrine System (For Kids)

MedlinePlus

... by a wild animal — or even your brother! Insulin Is Essential Your pancreas (say: PAN-kree-us) ... your belly. The pancreas makes several hormones, including insulin (say: IN-suh-lin), which helps glucose (say: ...

Society of Reproductive Surgeons

MedlinePlus

... true credit should go to the many capable original reviewers, particularly Meike Uhler, Dan Williams, Paul Lin, ... a decade. I’ve tried to acknowledge these original authors through phrasing such as “Literature reviewed originally ...

Developmental Test of the Honeywell Laser Inertial Navigation System (LINS)

DTIC Science & Technology

1975-11-01

The ISA contains three Systron Donner 4841F-10 single axis accelerometers and three Honeywell GG1300- AEOI laser gyros in an orthogonal strapdown...DIAG.1,kM AN.D PHYSICAL CHARACTERISTICS The GG1300- AEOI laser gyro, shown schematically in Figure 2, has the following performance goals which were

Potassium urine test

MedlinePlus

... in the clinical evaluation of electrolyte, water, and acid-base disorders. In: Alpern RJ, Orson WM, Caplan M, ... Lin S-H, Halperin ML. Interpretation of electrolyte and acid-base parameters in blood and urine. In: Skorecki K, ...

Young Children's Mathematics References during Free Play in Family Childcare Settings

ERIC Educational Resources Information Center

Hendershot, Shawnee M.; Berghout Austin, Ann M.; Blevins-Knabe, Belinda; Ota, Carrie

2016-01-01

Very little is known about children's discussion of mathematics topics during unstructured play. Ginsburg, Lin, Ness, and Seo [2003. Young American and Chinese children's everyday mathematical activity. Mathematical Thinking and Learning, 5(4), 235-258. Retrieved from…

The Bro1-Domain Protein, EGO-2, Promotes Notch Signaling in Caenorhabditis elegans

PubMed Central

Liu, Ying; Maine, Eleanor M.

2007-01-01

In Caenorhabditis elegans, as in other animals, Notch-type signaling mediates numerous inductive events during development. The mechanism of Notch-type signaling involves proteolytic cleavage of the receptor and subsequent transport of the receptor intracellular domain to the nucleus, where it acts as a transcriptional regulator. Notch-type signaling activity is modulated by post-translational modifications and endocytosis of ligand and receptor. We previously identified the ego-2 (enhancer of glp-1) gene as a positive regulator of germline proliferation that interacts genetically with the GLP-1/Notch signaling pathway in the germline. Here, we show that ego-2 positively regulates signaling in various tissues via both GLP-1 and the second C. elegans Notch-type receptor, LIN-12. ego-2 activity also promotes aspects of development not known to require GLP-1 or LIN-12. The EGO-2 protein contains a Bro1 domain, which is known in other systems to localize to certain endosomal compartments. EGO-2 activity in the soma promotes GLP-1 signaling in the germline, consistent with a role for EGO-2 in production of active ligand. Another C. elegans Bro1-domain protein, ALX-1, is known to interact physically with LIN-12/Notch. We document a complex phenotypic interaction between ego-2 and alx-1, consistent with their relationship being antagonistic with respect to some developmental processes and agonistic with respect to others. PMID:17603118

Validity of a portable glucose, total cholesterol, and triglycerides multi-analyzer in adults.

PubMed

Coqueiro, Raildo da Silva; Santos, Mateus Carmo; Neto, João de Souza Leal; Queiroz, Bruno Morbeck de; Brügger, Nelson Augusto Jardim; Barbosa, Aline Rodrigues

2014-07-01

This study investigated the accuracy and precision of the Accutrend Plus system to determine blood glucose, total cholesterol, and plasma triglycerides in adults and evaluated its efficiency in measuring these blood variables. The sample consisted of 53 subjects (≥ 18 years). For blood variable laboratory determination, venous blood samples were collected and processed in a Labmax 240 analyzer. To measure blood variables with the Accutrend Plus system, samples of capillary blood were collected. In the analysis, the following tests were included: Wilcoxon and Student's t-tests for paired samples, Lin's concordance coefficient, Bland-Altman method, receiver operating characteristic curve, McNemar test, and k statistics. The results show that the Accutrend Plus system provided significantly higher values (p ≤ .05) of glucose and triglycerides but not of total cholesterol (p > .05) as compared to the values determined in the laboratory. However, the system showed good reproducibility (Lin's coefficient: glucose = .958, triglycerides = .992, total cholesterol = .940) and high concordance with the laboratory method (Lin's coefficient: glucose = .952, triglycerides = .990, total cholesterol = .944) and high sensitivity (glucose = 80.0%, triglycerides = 90.5%, total cholesterol = 84.4%) and specificity (glucose = 100.0%, triglycerides = 96.9%, total cholesterol = 95.2%) in the discrimination of high values of the three blood variables analyzed. It could be concluded that despite the tendency to overestimate glucose and triglyceride levels, a portable multi-analyzer is a valid alternative for the monitoring of metabolic disorders and cardiovascular risk factors. © The Author(s) 2013.

Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO2 transport.

PubMed

Hsu, Kate; Lee, Ting-Ying; Periasamy, Ammasi; Kao, Fu-Jen; Li, Li-Tzu; Lin, Chuang-Yu; Lin, Hui-Ju; Lin, Marie

2017-10-01

Human CO 2 respiration requires rapid conversion between CO 2 and HCO 3 - Carbonic anhydrase II facilitates this reversible reaction inside red blood cells, and band 3 [anion exchanger 1 (AE1)] provides a passage for HCO 3 - flux across the cell membrane. These 2 proteins are core components of the CO 2 transport metabolon. Intracellular H 2 O is necessary for CO 2 /HCO 3 - conversion. However, abundantly expressed aquaporin 1 (AQP1) in erythrocytes is thought not to be part of band 3 complexes or the CO 2 transport metabolon. To solve this conundrum, we used Förster resonance energy transfer (FRET) measured by fluorescence lifetime imaging (FLIM-FRET) and identified interaction between aquaporin-1 and band 3 at a distance of 8 nm, within the range of dipole-dipole interaction. Notably, their interaction was adaptable to membrane tonicity changes. This suggests that the function of AQP1 in tonicity response could be coupled or correlated to its function in band 3-mediated CO 2 /HCO 3 - exchange. By demonstrating AQP1 as a mobile component of the CO 2 transport metabolon, our results uncover a potential role of water channel in blood CO 2 transport and respiration.-Hsu, K., Lee, T.-Y., Periasamy, A., Kao, F.-J., Li, L.-T., Lin, C.-Y., Lin, H.-J., Lin, M. Adaptable interaction between aquaporin-1 and band 3 reveals a potential role of water channel in blood CO 2 transport. © FASEB.

New alkenyl derivative from Piper malacophyllum and analogues: Antiparasitic activity against Trypanosoma cruzi and Leishmania infantum.

PubMed

Varela, Marina T; Lima, Marta L; Galuppo, Mariana K; Tempone, Andre G; de Oliveira, Alberto; Lago, João Henrique G; Fernandes, João Paulo S

2017-11-01

Alkylphenols isolated from Piper malacophyllum (Piperaceae), gibbilimbols A and B, showed interesting activity against the parasites Trypanosoma cruzi and Leishmania infantum. In continuation to our previous work, a new natural product from the essential oil of the leaves of P. malacophyllum was isolated, the 5-[(3E)-oct-3-en-1-il]-1,3-benzodioxole, and also a new set of five compounds was prepared. The antiparasitic activity of the natural product was evaluated in vitro against these parasites, indicating potential against the promastigote/trypomastigote/amastigote forms (IC 50 32-83 μm) of the parasites and low toxicity (CC 50  > 200 μm) to mammalian cells. The results obtained to the synthetic compounds indicated that the new derivatives maintained the promising antiparasitic activity, but the cytotoxicity was considerably lowered. The amine derivative LINS03011 displayed the most potent IC 50 values (13.3 and 16.7 μm) against amastigotes of T. cruzi and L. infantum, respectively, indicating comparable activity to the phenolic prototype LINS03003, with threefold decreased (CC 50 73.5 μm) cytotoxicity, leading the selectivity index (SI) towards the parasites up to 24.5. In counterpart, LINS03011 has not shown membrane disruptor activity in SYTOX Green model. In summary, this new set showed the hydroxyl is not essential for the antiparasitic activity, and its substitution could decrease the toxicity to mammalian cells. © 2017 John Wiley & Sons A/S.

Genetics Home Reference: branchio-oculo-facial syndrome

MedlinePlus

... Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): ... Zori RT, Burch MN, Clemens M, Mulliken JB, Smith R, Lin AE. TFAP2A mutations result in branchio- ...

Estimating monotonic rates from biological data using local linear regression.

PubMed

Olito, Colin; White, Craig R; Marshall, Dustin J; Barneche, Diego R

2017-03-01

Accessing many fundamental questions in biology begins with empirical estimation of simple monotonic rates of underlying biological processes. Across a variety of disciplines, ranging from physiology to biogeochemistry, these rates are routinely estimated from non-linear and noisy time series data using linear regression and ad hoc manual truncation of non-linearities. Here, we introduce the R package LoLinR, a flexible toolkit to implement local linear regression techniques to objectively and reproducibly estimate monotonic biological rates from non-linear time series data, and demonstrate possible applications using metabolic rate data. LoLinR provides methods to easily and reliably estimate monotonic rates from time series data in a way that is statistically robust, facilitates reproducible research and is applicable to a wide variety of research disciplines in the biological sciences. © 2017. Published by The Company of Biologists Ltd.

Computation of Optimal Actuator/Sensor Locations

DTIC Science & Technology

2013-12-26

weighting matrices Q = I and R = 0.01, and a minimum variance LQ-cost (with V = I ), a plot of the L2 norm of the control signal versus actuator...0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 0.05 0.1 0.15 0.2 0.25 actuator location lin ea r− qu ad ra tic c os t ( re la tiv e) Q = I , R = 100 Q... I , R = 1 Q = I , R = 0.01 Q = I , R = 0.0001 (a) 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 actuator location lin

Response to "The Iris Hypothesis: A Negative or Positive Cloud Feedback?"

NASA Technical Reports Server (NTRS)

Chou, Ming-Dah; Lindzen, Richard S.; Hou, Arthur Y.; Lau, William K. M. (Technical Monitor)

2001-01-01

Based on radiance measurements of Japan's Geostationary Meteorological Satellite, Lindzen et al. found that the high-level cloud cover averaged over the tropical western Pacific decreases with increasing sea surface temperature. They further found that the response of high-level clouds to the sea surface temperature had an effect of reducing the magnitude of climate change, which is referred as a negative climate feedback. Lin et al. reassessed the results found by Lindzen et al. by analyzing the radiation and clouds derived from the Tropical Rainfall Measuring Mission Clouds and the Earth's Radiant Energy System measurements. They found a weak positive feedback between high-level clouds and the surface temperature. We have found that the approach taken by Lin et al. to estimating the albedo and the outgoing longwave radiation is incorrect and that the inferred climate sensitivity is unreliable.

Observations of H1743-322 with the Sardinia Radio Telescope: upper limits

NASA Astrophysics Data System (ADS)

Egron, E.; Bachetti, M.; Pellizzoni, A.; Trois, A.; Iacolina, M. N.; Pilia, M.; Loru, S.; Navarrini, A.; Ballhausen, R.; Corbel, S.; Eikmann, W.; Fuerst, F.; Grinberg, V.; Kreykenbohm, I.; Marongiu, M.; Nowak, M.; Possenti, A.; Pottschmidt, K.; Rodriguez, J.; Wilms, J.

2016-03-01

A new outburst of the Galactic black hole low-mass X-ray binary H1743-322 was reported on 2016 February 28 using Swift/BAT (Lin et al., ATel #8751), less than a year after its previous outburst (#7652).

IRON PRECIPITATION AND ARSENIC ATTENUATION - ASSESSMENT OF ARSENIC NATURAL ATTENUATION OF THE SUBSURFACE USING A GEOCHEMICAL MODEL (PHREEQC)

EPA Science Inventory

Laboratory experiments show that amorphous and poorly crystallized ferric iron hydroxides have much greater capacity to attenuate arsenic compared to clays and other aluminosilicate minerals. Studies (e.g., Lin and Qvarfort, 1996) showed that a sudden change in geochemical condit...

Comprehensive Space-Object Characterization using Spectrally Compressive Polarimetric Sensing

DTIC Science & Technology

2015-04-08

90o, 45o, and 135o polarization channels for lin- ear polarization state estimation. This linear polarimetry would satisfy several applications without...persive element. This technique eliminates mechanical movements that hinder conventional polarimetry . The experimental results show clear spatial

77 FR 28880 - Ocean Transportation Intermediary License Applicants

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-16

... (NVO & OFF), 332 Hindry Avenue, Inglewood, CA 90301, Officers: Edison Chen, Manager (Qualifying Individual), Wei-Nung (Janus) Lin, Member/Manager/CEO, Application Type: QI Change/Trade Name Change. Lone... 77032, Officer: Albert E. Garcia, President/Manager/Member (Qualifying Individual), Application Type...

Immunocytochemistry and Image Analysis of Beta-Catenin Redistribution in Normal Human Colon Cell Cultures Treated with Disinfection By-Products.

EPA Science Inventory

Epidemiological studies have shown an association between the consumption of chlorinated drinking water and increased risk for colon cancer. <l>In vivo studies proved that rodents exposed to chlorination disinfection byproducts (DBPs) developed aberrant crypt foci (ACF) in t...

Tri-Level Optimization Algorithms for Solving Defender-Attacker-Defender Network Models

DTIC Science & Technology

2016-06-01

ed.). New York: Springer. Brimberg, J., Hansen, P., Lin, K., Mladenović, N., & Breton, M. (2003). An Oil Pipeline Design Problem. Operations...H. (2012). Critical infrastructure protection: The vulnerability conundrum. Telematics and informatics , 29(1), 56–65. Retrieved from http

A modeling framework for characterizing near-road air pollutant concentration at community scales

EPA Science Inventory

In this study, we combine information from transportation network, traffic emissions, and dispersion model to develop a framework to inform exposure estimates for traffic-related air pollutants (TRAPs) with a high spatial resolution. A Research LINE source dispersion model (R-LIN...

Development of an in vitro toxicological test system based on zebrafish (Danio rerio) sperm analysis.

PubMed

Kollár, Tímea; Kása, Eszter; Ferincz, Árpád; Urbányi, Béla; Csenki-Bakos, Zsolt; Horváth, Ákos

2018-05-01

The effect of seven heavy metals on the motility parameter of zebrafish sperm was tested in order to develop an in vitro toxicological test system as an alternative to live animal testing. In vitro test systems are currently preferred in ecotoxicology due to their practical and ethical advantages and fish sperm can be a suitable model. A number of studies had been carried out previously on this topic, but the described methods had not been standardized in numerous aspects (donor species, measured endpoint, etc.). In this study, heavy metals (mercury, arsenic, chromium, zinc, nickel, copper, cadmium) were used as reference toxicants with known toxicity to develop a standardized fish sperm in vitro assay. The tested concentrations were determined based on preliminary range finding tests. The endpoints were progressive motility (PMOT, %), curvilinear velocity (VCL, μm/s), and linearity (LIN, %) measured by a computer-assisted sperm analysis (CASA) system. According to our results, PMOT was the most sensitive of the three investigated parameters: dose-response curves were observed for each metal at relatively low concentrations. VCL values were less sensitive: higher concentrations were needed to observe changes. Of the three parameters, LIN was the least affected: dose-response relationship was observed only in the case of mercury (e.g., lowest observed effect concentration (LOEC) of Hg at 120 min: 1 mg/L for PMOT, 2.5 mg/L for VCL, 5 mg/L for LIN; LOEC of Cu at 120 min: 1 mg/L for PMOT, 5 mg/L for VCL, any for LIN). The order of toxicity as determined by PMOT was as follows: Hg 2+  > As 3+  > Cd 2+  > Cu 2+  > Zn 2+  > Cr 3+  > Ni 2+ . In conclusion, we found that PMOT of zebrafish sperm was an accurate and fast bioindicator of heavy metal load. Sperm analysis can be adopted to estimate the possible toxic effects of various chemicals in vitro. Future investigations should concentrate on the applicability of this assay to other

Production of polyol oils from soybean oil by bioprocess: results of microbial screening and identification of positive cultures

USDA-ARS?s Scientific Manuscript database

Recently we reported methods for microbial screening and production of polyol oils from soybean oil through bioprocessing (Hou and Lin, 2013). Soy-polyol oils (oxygenated acylglycerols) are important starting materials for the manufacture of polymers such as polyurethane. Currently, they are produce...

76 FR 43347 - Notice Pursuant to the National Cooperative Research and Production Act of 1993; Network Centric...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-20

... circumstances. Specifically, Wakelight Technologies, Inc., Honolulu, HI; LinQuest Corporation, Los Angeles, CA; and Computer Sciences Corporation, Rockville, MD, have withdrawn as parties to this venture. In... activity of the group research project. Membership in this group research project remains open, and NCOIC...

Feasibility Study of a Novel Diet-Based Intervention for Prostate Cancer

DTIC Science & Technology

2010-09-01

broccoli and cabbage. Isothiocyanates induce expression of cytoprotective phase 2 enzymes in multiple prostate tumor cell lines (26, 31) promote...83-90. 29. Caruso AJ, Yegnasubramanian S, Lin X, Kesler TW, Nelson WG. Hot water extracts from broccoli sprouts trigger induction of carcinogen

Observational test of empirical magnetopause location models using geosynchronous satellite data

NASA Astrophysics Data System (ADS)

Park, Eunsu; Moon, Y.-J.; Lee, Kangjin

2016-11-01

In this study, we identify 123 geosynchronous magnetopause crossings using geosynchronous satellite observation data from 1996 to 2010 as well as make an observational test of magnetopause location models using the identified events. For this, we consider three models: Petrinec and Russell (1996), Shue et al. (1998), and Lin et al. (2010). To evaluate the models, we estimate a probability of detection (PoD) and a critical success index (CSI) as a function of year. To examine the effect of solar cycle phase, we consider three different time periods: (1) ascending phase (1996-1999), (2) maximum phase (2000-2002), and (3) descending phase (2003-2008). Major results from this study are as follows. First, the PoD values of all models range from 0.4 to 0.8 for the most of years. Second, the PoD values of Lin et al. (2010) are noticeably higher than those of the other models. Third, the CSI values of all models range from 0.1 to 0.3, and those of Shue et al. (1998) are slightly higher than those of the other models. Fourth, the predicted magnetopause radii based on Lin et al.(2010) well match the observed ones within 1 Earth radius, while those on Shue et al. (1998) overestimate the observed ones by about 2 Earth radii. Fifth, the PoD and critical success index (CSI) values of all the models are better for the solar maximum phase than those for the other phases, implying that the models are more optimized for the phase.

Dauer larva quiescence alters the circuitry of microRNA pathways regulating cell fate progression in C. elegans.

PubMed

Karp, Xantha; Ambros, Victor

2012-06-01

In C. elegans larvae, the execution of stage-specific developmental events is controlled by heterochronic genes, which include those encoding a set of transcription factors and the microRNAs that regulate the timing of their expression. Under adverse environmental conditions, developing larvae enter a stress-resistant, quiescent stage called 'dauer'. Dauer larvae are characterized by the arrest of all progenitor cell lineages at a stage equivalent to the end of the second larval stage (L2). If dauer larvae encounter conditions favorable for resumption of reproductive growth, they recover and complete development normally, indicating that post-dauer larvae possess mechanisms to accommodate an indefinite period of interrupted development. For cells to progress to L3 cell fate, the transcription factor Hunchback-like-1 (HBL-1) must be downregulated. Here, we describe a quiescence-induced shift in the repertoire of microRNAs that regulate HBL-1. During continuous development, HBL-1 downregulation (and consequent cell fate progression) relies chiefly on three let-7 family microRNAs, whereas after quiescence, HBL-1 is downregulated primarily by the lin-4 microRNA in combination with an altered set of let-7 family microRNAs. We propose that this shift in microRNA regulation of HBL-1 expression involves an enhancement of the activity of lin-4 and let-7 microRNAs by miRISC modulatory proteins, including NHL-2 and LIN-46. These results illustrate how the employment of alternative genetic regulatory pathways can provide for the robust progression of progenitor cell fates in the face of temporary developmental quiescence.

Evaluation of concordance among three cardiac output measurement techniques in adult patients during cardiovascular surgery postoperative care.

PubMed

Muñoz, L; Velandia, A; Reyes, L E; Arevalo-Rodríguez, I; Mejía, C; Asprilla, D; Uribe, D V; Arevalo, J J

2017-12-01

The standard method for cardiac output measuring is thermodilution although it is an invasive technique. Transesophageal Echocardiography (TEE) offers a dynamic and functional alternative to thermodilution. Analyze concordance between two TEE methods and thermodilution for cardiac output assessment. Observational concordance study in cardiovascular surgery patients that required pulmonary artery catheter. TEE cardiac output measurement at both mitral annulus (MA) and left ventricle outflow tract (LVOT) were performed. Results were compared with thermodilution. Correlation was evaluated by Lin's concordance correlation coefficient and Bland-Altman analysis. Statistical analysis was undertaken in STATA 13.0. Twenty-five patients were enrolled. Fifty two percent of patients were male, median age and ejection fraction was 63 years and 35% respectively. Median thermodilution, LVOT and MA -measured cardiac output was 3.25 L/min, 3.46 L/min and 8.4 L/min respectively. Different values between thermodilution and MA measurements were found (Lin concordance=0.071; Confidence Interval 95%=-0.009 to 0.151; Spearman's correlation=0.22) as values between thermodilution and LVOT (Lin concordance=0.232; Confidence Interval 95%=-0.12 a 0.537; Spearman's correlation 0.28). Bland-Altman analysis showed greater difference between MA measurements and thermodilution (DM=-0.408; Bland-Altman Limits=-0.809 to -0.007), than the other echocardiographic findings (DM=0.007; Bland-Altman Limits=-0.441 to 0.428). Results from cardiac output measurement by doppler and 2D-TEE on both MA and LVOT do not correlate with those obtained by thermodilution. Copyright © 2017 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Detecting inflammation in inflammatory bowel disease - how does ultrasound compare to magnetic resonance enterography using standardised scoring systems?

PubMed

Barber, Joy L; Zambrano-Perez, Alexsandra; Olsen, Øystein E; Kiparissi, Fevronia; Baycheva, Mila; Knaflez, Daniela; Shah, Neil; Watson, Tom A

2018-06-01

Magnetic resonance enterography (MRE) is the current gold standard for imaging in inflammatory bowel disease, but ultrasound (US) is a potential alternative. To determine whether US is as good as MRE for the detecting inflamed bowel, using a combined consensus score as the reference standard. We conducted a retrospective cohort study in children and adolescents <18 years with inflammatory bowel disease (IBD) at a tertiary and quaternary centre. We included children who underwent MRE and US within 4 weeks. We scored MRE using the London score and US using a score adapted from the METRIC (MR Enterography or Ultrasound in Crohn's Disease) trial. Four gastroenterologists assessed an independent clinical consensus score. A combined consensus score using the imaging and clinical scores was agreed upon and used as the reference standard to compare MRE with US. We included 53 children. At a whole-patient level, MRE scores were 2% higher than US scores. We used Lin coefficient to assess inter-observer variability. The repeatability of MRE scores was poor (Lin 0.6). Agreement for US scoring was substantial (Lin 0.95). There was a significant positive correlation between MRE and clinical consensus scores (Spearman's rho = 0.598, P=0.0053) and US and clinical consensus scores (Spearman's rho = 0.657, P=0.0016). US detects as much clinically significant bowel disease as MRE. It is possible that MRE overestimates the presence of disease when using a scoring system. This study demonstrates the feasibility of using a clinical consensus reference standard in paediatric IBD imaging studies.

Structural mechanisms of DREAM complex assembly and regulation

PubMed Central

Guiley, Keelan Z.; Liban, Tyler J.; Felthousen, Jessica G.; Ramanan, Parameshwaran

2015-01-01

The DREAM complex represses cell cycle genes during quiescence through scaffolding MuvB proteins with E2F4/5 and the Rb tumor suppressor paralog p107 or p130. Upon cell cycle entry, MuvB dissociates from p107/p130 and recruits B-Myb and FoxM1 for up-regulating mitotic gene expression. To understand the biochemical mechanisms underpinning DREAM function and regulation, we investigated the structural basis for DREAM assembly. We identified a sequence in the MuvB component LIN52 that binds directly to the pocket domains of p107 and p130 when phosphorylated on the DYRK1A kinase site S28. A crystal structure of the LIN52–p107 complex reveals that LIN52 uses a suboptimal LxSxExL sequence together with the phosphate at nearby S28 to bind the LxCxE cleft of the pocket domain with high affinity. The structure explains the specificity for p107/p130 over Rb in the DREAM complex and how the complex is disrupted by viral oncoproteins. Based on insights from the structure, we addressed how DREAM is disassembled upon cell cycle entry. We found that p130 and B-Myb can both bind the core MuvB complex simultaneously but that cyclin-dependent kinase phosphorylation of p130 weakens its association. Together, our data inform a novel target interface for studying MuvB and p130 function and the design of inhibitors that prevent tumor escape in quiescence. PMID:25917549

An analysis toolbox to explore mesenchymal migration heterogeneity reveals adaptive switching between distinct modes

PubMed Central

Shafqat-Abbasi, Hamdah; Kowalewski, Jacob M; Kiss, Alexa; Gong, Xiaowei; Hernandez-Varas, Pablo; Berge, Ulrich; Jafari-Mamaghani, Mehrdad; Lock, John G; Strömblad, Staffan

2016-01-01

Mesenchymal (lamellipodial) migration is heterogeneous, although whether this reflects progressive variability or discrete, 'switchable' migration modalities, remains unclear. We present an analytical toolbox, based on quantitative single-cell imaging data, to interrogate this heterogeneity. Integrating supervised behavioral classification with multivariate analyses of cell motion, membrane dynamics, cell-matrix adhesion status and F-actin organization, this toolbox here enables the detection and characterization of two quantitatively distinct mesenchymal migration modes, termed 'Continuous' and 'Discontinuous'. Quantitative mode comparisons reveal differences in cell motion, spatiotemporal coordination of membrane protrusion/retraction, and how cells within each mode reorganize with changed cell speed. These modes thus represent distinctive migratory strategies. Additional analyses illuminate the macromolecular- and cellular-scale effects of molecular targeting (fibronectin, talin, ROCK), including 'adaptive switching' between Continuous (favored at high adhesion/full contraction) and Discontinuous (low adhesion/inhibited contraction) modes. Overall, this analytical toolbox now facilitates the exploration of both spontaneous and adaptive heterogeneity in mesenchymal migration. DOI: http://dx.doi.org/10.7554/eLife.11384.001 PMID:26821527

Exome Sequencing of a Pedigree Reveals S339L Mutation in the TLN2 Gene as a Cause of Fifth Finger Camptodactyly.

PubMed

Deng, Hao; Deng, Sheng; Xu, Hongbo; Deng, Han-Xiang; Chen, Yulan; Yuan, Lamei; Deng, Xiong; Yang, Shengbo; Guan, Liping; Zhang, Jianguo; Yuan, Hong; Guo, Yi

2016-01-01

Camptodactyly is a digit deformity characterized by permanent flexion contracture of one or both fifth fingers at the proximal interphalangeal joints. Though over 60 distinct types of syndromic camptodactyly have been described, only one disease locus (3q11.2-q13.12) for nonsyndromic camptodactyly has been identified. To identify the genetic defect for camptodactyly in a four-generation Chinese Han family, exome and Sanger sequencings were conducted and a missense variant, c.1016C>T (p.S339L), in the talin 2 gene (TLN2) was identified. The variant co-segregated with disease in the family and was not observed in 12 unaffected family members or 1,000 normal controls, suggesting that p.S339L is a pathogenic mutation. Two asymptomatic carriers in the family indicated incomplete penetrance or more complicated compensated mechanism. Most of p.S339L carriers also have relatively benign cardiac phenotypes. Expression of wild and mutant TLN2 in HEK293 cells suggested the predominant localization in cytoplasm. Our data suggest a potential molecular link between TLN2 and camptodactyly pathogenesis.

Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions

PubMed Central

Swaminathan, Vinay; Kalappurakkal, Joseph Mathew; Moore, Travis I.; Koga, Nobuyasu; Baker, David A.; Oldenbourg, Rudolf; Tani, Tomomi; Springer, Timothy A.; Waterman, Clare M.

2017-01-01

Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization- or contractility-driven “retrograde flow” of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge. Here, polarization-sensitive fluorescence microscopy of GFP-αVβ3 integrins in fibroblasts shows that integrins are coaligned in a specific orientation within focal adhesions (FAs) in a manner dependent on binding immobilized ligand and a talin-mediated linkage to the F-actin cytoskeleton. These findings, together with Rosetta modeling, suggest that integrins in FA are coaligned and may be highly tilted by cytoskeletal forces. Thus, the F-actin cytoskeleton sculpts an anisotropic molecular scaffold in FAs, and this feature may underlie the ability of migrating cells to sense directional extracellular cues. PMID:29073038

DIRECT-DEPOSITION INFRARED SPECTROMETRY WITH GAS AND SUPERCRITICAL FLUID CHROMATOGRAPHY

EPA Science Inventory

A direct-deposition Fourier transform infrared (FT-IR) system has been evaluated for applicability to gas chromatography (GC) and supercritical fluid chromatography (SFC) of environmental analytes. A 100-um i.d. fused-silica transfer line was used for GC, and a 50-um transfer lin...

Intramuscular variation in fresh ham muscle color

USDA-ARS?s Scientific Manuscript database

This experiment was conducted to characterize a defect involving pale muscle tissue in the superficial, ventral portion of ham muscles, resulting in two-toned appearance of cured ham products. Biceps femoris muscles (n = 200), representing 3 production systems, were obtained from the ham-boning lin...

The Virtual Liver Project: Modeling Tissue Response To Chemicals Through Multiscale Simulation

EPA Science Inventory

The US EPA Virtual Liver Project is aimed at simulating the risk of toxic effects from environmental chemicals in silico. The computational systems model of organ injury due to chronic chemical exposure is based on: (i) the dynamics of perturbed molecular pathways, (ii) their lin...

Concrete Durability: A Multibillion-Dollar Opportunity

DTIC Science & Technology

1987-01-01

Fum -Containing Products 79 MDF Materials 85 Fiber-Reinforced Materials 85 Modified - Sulfur Concretes 87 References 88 APPENDIX: BIOGRAPHICAL SKETCHES...construction. MODIFIED - SULFUR CONCRETES Molten sulfur-sand grouts have been used for many years in the constructLin of acid vats because of their

Climate change and the meteorological drivers of PM air pollution: Understanding U.S. particulate matter concentrations in a changing climate

EPA Science Inventory

Particulate matter (PM) air pollution is a serious public health issue for the United States. While there is a growing body of evidence that climate change will partially counter the effectiveness of future precursor emission reductions to reduce ozone (O3) air pollution, the lin...

JPRS Report, China, Quishi Seeking Truth, Nubmer 10, 16 November 1988

DTIC Science & Technology

1989-02-28

neurophysiology , neurology, lin- guistics, artificial intelligence, and various other types of modern science and technology. The subject’s...only makes the book more attractive to read, but also stimulates deep thought in readers by which they obtain useful enlighten - ment. Let us see how

Relationship Between Sea Surface Salinity from L-Band Radiometer and Optical Features in the East China Sea

DTIC Science & Technology

2014-01-01

7330-14-2132. REFERENCE [1] Guo, Z., Lin, T., Zhang, G., et al., "The sedimentary fluxes of polycyclic aromatic hydrocarbons in the Yangtze ...Total Light Absorption in Optically Complex Waters, a Case Study in Yangtze Estuary and Adjacent Coast," Advances in Computational Environment

Budgeted Interactive Learning

DTIC Science & Technology

2017-06-15

the methodology of reducing the online-algorithm-selecting problem as a contextual bandit problem, which is yet another interactive learning...KH2016a] Kuan-Hao Huang and Hsuan-Tien Lin. Linear upper confidence bound algorithm for contextual bandit problem with piled rewards. In Proceedings

Counter Piracy: A Repeated Game with Asymmetric Information

DTIC Science & Technology

2009-09-01

Christopher D. Marsh Approved by: Kyle Y. Lin Thesis Advisor Timothy H. Chung Second Reader Robert F. Dell Chairman, Department of...encourage Malaysia and Indonesia to work with the Singapore Navy in coordinated patrols of the region. Increased cooperation in the region includes the

First report of bacterial blight of sugar beet caused by Pseudomonas syringae pv. aptata in Georgia, USA

USDA-ARS?s Scientific Manuscript database

Sugarbeet [Beta vulgaris L.] is not currently a commercial crop in Georgia, but experimental plantings as a winter rotational crop are promising in terms of yield and industrial sugar production. A disease outbreak of suspected bacterial origin occurred in some plots of sugarbeet [experimental lin...

THE CELLULAR METABOLISM AND SYSTEMIC TOXICITY OF ARSENIC

EPA Science Inventory

Abstract

Toxic Consequences of the Metabolism of Arsenic. David J. Thomas, Miroslav Styblo, and Shan Lin. (2001). Toxicol. Appl. Pharmacol. 000, xxx-yyy.
Although it has been known for decades that humans and many other species metabolize inorganic arsenic to methyl ...

Ancrage des vortex dans les supraconducteurs Description phénoménologique de la réponse linéaire d'un de vortex ancré

NASA Astrophysics Data System (ADS)

Lütke-Entrup, N.; Plaçais, B.; Mathieu, P.; Simon, Y.

Vortices pinning in supraconductors In this article we report on the investigation of the dynamics of vortices based on the high frequency linear response. We present a serie of measurements of the complex penetration depth in the mixed state in a variety of samples, including conventional materials (Nb, V, PbIn), the non-conventional heavy fermion UPt3, and the high-T_c cuprate YBaCuO. We have explored a large frequency range (1 kHz 10 MHz) so as to cover the cross-over from the quasi-static response, which is dominated by elastic interactions between vortices and sample defects, to the high-frequency regime, which is governed by viscous damping due to vortex friction against the host crystal. For a quantitative description of the frequency spectrum we start from a phenomenological theory which makes a rigorous distinction between vortex lines, along a vortex field omega, and magnetic field lines B. It predicts a second electrodynamical mode, which is linked to the vortex line tension and has a rather short range. We show that, in the limit of small vortex oscillations, amplitude and phase of the linear response are governed by an additional boundary condition for the vortex lattice at the sample surface ; it takes the form of a slipping condition with a characteristic length that depends on the surface roughness. The frequency spectrum deduced from this mechanism is clearly different from the Campbell spectrum, which is the common signature of all bulk pinning mechanisms. Our results on samples of PbIn, Nb, V, and YBaCuO entirely confirm our model, including some non-intuitive size effects which appear at low frequency when the sample becomes transparent to the flux flow mode. However, our measurements in the B and C phases of UPt3 reveal and important contribution of the bulk to the vortex pinning. Ce travail porte sur l'étude de l'ancrage des vortex par la réponse linéaire haute fréquence. Nous présentons une série de mesures de la profondeur de p

JPRS Report, Science & Technology, USSR: Life Sciences.

DTIC Science & Technology

1988-03-16

healthy persons. The materials used were the results of neuropsychological studies of 40 subjects who received a synthetic leu-enkephalin ana- logue...Medical Sciences, Moscow] [Abstract] In order to determine the role of " hunger centers" in the implementation of the effects of enkepha- lin-like

77 FR 59002 - Performance Review Board

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-25

... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5665-N-01] Performance Review Board.... Kinney, Jean Lin Pao, and Susan J. Shuback as members of the Departmental Performance Review Board. The... INFORMATION CONTACT: Persons desiring any further information about the Performance Review Board and its...

Propulsion and Power Rapid Response Research and Development (R&D) Support. Delivery Order 0010: Propulsion and Power Student and Faculty Research and Technical Report

DTIC Science & Technology

2009-01-01

using spray cooling in recent years (Chow et al. 1997, Mudawar , 2001, Rini et al. 2002, Lin and Ponnappan, 2003 & and references there in) and various...19. I. Mudawar (2001), Assessment of high heat-flux thermal management schemes, IEEE Transactions on Components and Packaging Technologies, 24

Multi-Nozzle Spray Cooling in a Closed Loop (POSTPRINT)

DTIC Science & Technology

2011-03-01

characteristics and critical heat flux (CHF) at cooling surfaces (Sehmbey et al., 1992, Mudawar and Estes, 1996, Rini et al., 2002, Lin and Ponnappan, 2003...surface characteristics in evaporative spray cooling, Journal of Thermophysics and heat Transfer, 1992, Vol. 6, pp. 505-512. 3. Mudawar , I., and

Genetics Home Reference: familial paroxysmal kinesigenic dyskinesia

MedlinePlus

... gene mutations, which reduce the amount of PRRT2 protein, lead to abnormal neuronal signaling. Altered neuronal activity could underlie the ... YF, Zhang QJ, Li HF, Lin Y, Murong SX, Xu J, Wang N, Wu ZY. Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal ...

Draft Genome Sequence of Sphingobium quisquiliarum Strain P25T, a Novel Hexachlorocyclohexane (HCH)-Degrading Bacterium Isolated from an HCH Dumpsite

PubMed Central

Kumar Singh, Amit; Sangwan, Naseer; Sharma, Anukriti; Gupta, Vipin; Khurana, J. P.

2013-01-01

Here, we report the draft genome sequence (4.2 Mb) of Sphingobium quisquiliarum strain P25T, a natural lin (genes involved in degradation of hexachlorocyclohexane [HCH] isomers) variant genotype, isolated from a heavily contaminated (450 mg HCH/g of soil) HCH dumpsite. PMID:24029763

Assessing Higher-Order Thinking Using a Networked Portfolio System with Peer Assessment

ERIC Educational Resources Information Center

Liu, Eric Zhi-Feng; Zhuo, Yi-Chin; Yuan, Shyan-Ming

2004-01-01

In the past, the quantitative evidences of portfolio assessment have been explored under online instruction. Liu, Lin, and Yuan provide a long-term measure of peer-self, peer-instructor and self-instructor correlation coefficients under networked innovative assessment procedures. Analytical results indicated that undergraduate students could…

ALTERNATIVES FOR REDUCING INSECTICIDES ON COTTON AND CORN: ECONOMIC AND ENVIRONMENTAL IMPACT - SUPPLEMENT 1: DETAILED DATA FOR STATIC AND LINEAR ANALYSIS OF ALTERNATIVES FOR REDUCING INSECTICIDES ON COTTON AND CORN

EPA Science Inventory

The report lists the expected insect control costs and insecticide use per acre for each insect control method on corn and cotton in each region discussed in Alternatives for Reducing Insecticides on Cotton and Corn: Economic and Environmental Impact. All the runs used in the lin...

LACK OF EXPRESSION OF EGF AND TGF-ALPHA IN THE FETAL MOUSE ALTERS FORMATION OF PROSTATIC EPITHELIAL BUDS AND INFLUENCES THE RESPONSE TO TCDD

EPA Science Inventory

Lack of Expression of EGF and TGF in the Fetal Mouse Alters Formation of Prostatic Epithelial Buds and Responsiveness to TCDD-Induced Impairment of Prostatic Bud Formation.

Barbara D. Abbott, Tien-Min Lin, Nathan T. Rasmussen, Robert W. Moore,
Ralph M. Albrecht, Judi...

Petroleum exploration contribution to the structural history of Golfe du Lin

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

Curnelle, R.

1988-08-01

Petroleum exploration has strongly contributed to the knowledge of the post-Hercynian structural history of the Golfe du Lion. It shows three stages: (1) Pyrenean orogenesis which started in the Late Cretaceous and culminated during the Eocene (40-75 Ma), (2) Oligocene rifting associated with the oceanic accretion of the Provencal basin, and (3) post-Messinian deformations due to salt tectonics. Pyrenean deformation of the area seems to have been controlled by its Hercynian inheritance: the major transcurrent faults of the Cevenole belt, Nimes, and the Durance. They favored displacement of the deformation in a northeasterly direction along the fault corridors, inside whichmore » the overthrust units were put into place. These east-west-oriented structures show northward vergence. The Pyrenean axial zone in this downthrown part of the belt consist of progressively more northerly units offset by transverse faults. The Oligocene rifting is represented by a series of horsts and deeply subsiding grabens linked to preexisting major faults. The horst are deeply eroded and the Mesozoic carbonates are karstified. The extension of the Messinian evaporitic deposits known throughout the Mediterranean basin is located north of the shallower deep-water well. The gravitational deformation of the salt is expressed by a large number of listric faults which originate in the salt bodies. The sedimentary sequence ends with a thick discordant, erosional, undeformed Pliocene-Quaternary series.« less

Therapeutic Inhibitors of LIN28/let-7 Pathway in Ovarian Cancer

DTIC Science & Technology

2015-09-01

of-function cell lines to complement our already generated shRNA lines, we are developing handson experience with CrispR /Cas9 technology to...generate stable cell lines where our genes of interest will be inactivated. The advantage of the CrispR /Cas9 method is that stable lines can be...ovarian cancer cell lines using two distinct RNAi methods, shRNA and siRNA. We plan to explore the feasibility of using the CrispR /Cas9 system to

Topics in Library Technology: Labeling Techniques *

PubMed Central

Truelson, Stanley D.

1966-01-01

Labels which do not fit on the spines of books should be placed on the upper rather than lower left corner of the front cover, because the upper corner becomes visible first when a volume is tilted from the shelf. None of the past methods of marking call numbers on the spines or covers of books—direct hand lettering by pen, brush, or stylus; affixing cold release characters; embossing by hot type; or gluing labels which are handlettered, typed, or printed—nor even present automatic data processing systems have offered all the advantages of the relatively new Se-Lin labeling system: legibility, reasonable speed of application, automatic protective covering, permanent bonding, and no need for a skilled letterer. Labels seem unaesthetic to some librarians, but their advantages outweigh this consideration. When only one or a few copies of the same call number are required, Se-Lin is the best system now available for libraries marking over 1,000 books a year. PMID:5901359

The occurrence of ice production in slightly supercooled Arctic stratiform clouds as observed by ground-based remote sensors at the ARM NSA site

NASA Astrophysics Data System (ADS)

Zhang, Damao; Wang, Zhien; Luo, Tao; Yin, Yan; Flynn, Connor

2017-03-01

Ice particle formation in slightly supercooled stratiform clouds is not well documented or understood. In this study, 4 years of combined lidar depolarization and radar reflectivity (Ze) measurements are analyzed to distinguish between cold drizzle and ice crystal formations in slightly supercooled Arctic stratiform clouds over the Atmospheric Radiation Measurement Program Climate Research Facility North Slope of Alaska Utqiaġvik ("Barrow") site. Ice particles are detected and statistically shown to be responsible for the strong precipitation in slightly supercooled Arctic stratiform clouds at cloud top temperatures as high as -4°C. For ice precipitating Arctic stratiform clouds, the lidar particulate linear depolarization ratio (δpar_lin) correlates well with radar Ze at each temperature range, but the δpar_lin-Ze relationship varies with temperature ranges. In addition, lidar depolarization and radar Ze observations of ice generation characteristics in Arctic stratiform clouds are consistent with laboratory-measured temperature-dependent ice growth habits.

[Comment on “Teaching evolution, the Kansas School Board of Education, and the democratization of science”] The causes of anti-science views

NASA Astrophysics Data System (ADS)

White, R. Stephen

Johnny Wei-Bing Lin recently suggested (Eos, August 2, 2000) that the action of the Kansas State Board of Education to exclude questions about evolution by natural selection and “Big Bang” cosmology from required state tests, was driven primarily by the populism of science—the belief that the judgment of everyday men and women in matters deemed scientific is better than that of the trained scientists. In his view, inadequate public science education is only a secondary reason.Lin and Baylor University theologian Barry Harvey [2000] have argued that science is now under siege by populism, and that the ruling of the Kansas Board is but one example. To combat this populism, he urges a wider dialogue between scientists and historians, philosophers and theologians, so that we understand better the limits of our work and discover ways of being more precise and logical. Such discussions may be necessary, but they are not sufficient.

Spreading-vanishing dichotomy in a diffusive logistic model with a free boundary, II

NASA Astrophysics Data System (ADS)

Du, Yihong; Guo, Zongming

We study the diffusive logistic equation with a free boundary in higher space dimensions and heterogeneous environment. Such a model may be used to describe the spreading of a new or invasive species, with the free boundary representing the expanding front. For simplicity, we assume that the environment and the solution are radially symmetric. In the special case of one space dimension and homogeneous environment, this free boundary problem was investigated in Du and Lin (2010) [10]. We prove that the spreading-vanishing dichotomy established in Du and Lin (2010) [10] still holds in the more general and ecologically realistic setting considered here. Moreover, when spreading occurs, we obtain best possible upper and lower bounds for the spreading speed of the expanding front. When the environment is asymptotically homogeneous at infinity, these two bounds coincide. Our results indicate that the asymptotic spreading speed determined by this model does not depend on the spatial dimension.

A comparative in silico linear B-cell epitope prediction and characterization for South American and African Trypanosoma vivax strains.

PubMed

Guedes, Rafael Lucas Muniz; Rodrigues, Carla Monadeli Filgueira; Coatnoan, Nicolas; Cosson, Alain; Cadioli, Fabiano Antonio; Garcia, Herakles Antonio; Gerber, Alexandra Lehmkuhl; Machado, Rosangela Zacarias; Minoprio, Paola Marcella Camargo; Teixeira, Marta Maria Geraldes; de Vasconcelos, Ana Tereza Ribeiro

2018-02-27

Trypanosoma vivax is a parasite widespread across Africa and South America. Immunological methods using recombinant antigens have been developed aiming at specific and sensitive detection of infections caused by T. vivax. Here, we sequenced for the first time the transcriptome of a virulent T. vivax strain (Lins), isolated from an outbreak of severe disease in South America (Brazil) and performed a computational integrated analysis of genome, transcriptome and in silico predictions to identify and characterize putative linear B-cell epitopes from African and South American T. vivax. A total of 2278, 3936 and 4062 linear B-cell epitopes were respectively characterized for the transcriptomes of T. vivax LIEM-176 (Venezuela), T. vivax IL1392 (Nigeria) and T. vivax Lins (Brazil) and 4684 for the genome of T. vivax Y486 (Nigeria). The results presented are a valuable theoretical source that may pave the way for highly sensitive and specific diagnostic tools. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

CDC-25.2, a C. elegans ortholog of cdc25, is essential for the progression of intestinal divisions.

PubMed

Lee, Yong-Uk; Son, Miseol; Kim, Jiyoung; Shim, Yhong-Hee; Kawasaki, Ichiro

2016-01-01

Intestinal divisions in Caenorhabditis elegans take place in 3 stages: (1) cell divisions during embryogenesis, (2) binucleations at the L1 stage, and (3) endoreduplications at the end of each larval stage. Here, we report that CDC-25.2, a C. elegans ortholog of Cdc25, is required for these specialized division cycles between the 16E cell stage and the onset of endoreduplication. Results of our genetic analyses suggest that CDC-25.2 regulates intestinal cell divisions and binucleations by counteracting WEE-1.3 and by activating the CDK-1/CYB-1 complex. CDC-25.2 activity is then repressed by LIN-23 E3 ubiquitin ligase before the onset of intestinal endoreduplication, and this repression is maintained by LIN-35, the C. elegans ortholog of Retinoblastoma (Rb). These findings indicate that timely regulation of CDC-25.2 activity is essential for the progression of specialized division cycles and development of the C. elegans intestine.

CDC-25.2, a C. elegans ortholog of cdc25, is essential for the progression of intestinal divisions

PubMed Central

Lee, Yong-Uk; Son, Miseol; Kim, Jiyoung; Shim, Yhong-Hee; Kawasaki, Ichiro

2016-01-01

ABSTRACT Intestinal divisions in Caenorhabditis elegans take place in 3 stages: (1) cell divisions during embryogenesis, (2) binucleations at the L1 stage, and (3) endoreduplications at the end of each larval stage. Here, we report that CDC-25.2, a C. elegans ortholog of Cdc25, is required for these specialized division cycles between the 16E cell stage and the onset of endoreduplication. Results of our genetic analyses suggest that CDC-25.2 regulates intestinal cell divisions and binucleations by counteracting WEE-1.3 and by activating the CDK-1/CYB-1 complex. CDC-25.2 activity is then repressed by LIN-23 E3 ubiquitin ligase before the onset of intestinal endoreduplication, and this repression is maintained by LIN-35, the C. elegans ortholog of Retinoblastoma (Rb). These findings indicate that timely regulation of CDC-25.2 activity is essential for the progression of specialized division cycles and development of the C. elegans intestine. PMID:27104746

Rainfall Threshold Assessment Corresponding to the Maximum Allowable Turbidity for Source Water.

PubMed

Fan, Shu-Kai S; Kuan, Wen-Hui; Fan, Chihhao; Chen, Chiu-Yang

2016-12-01

  This study aims to assess the upstream rainfall thresholds corresponding to the maximum allowable turbidity of source water, using monitoring data and artificial neural network computation. The Taipei Water Source Domain was selected as the study area, and the upstream rainfall records were collected for statistical analysis. Using analysis of variance (ANOVA), the cumulative rainfall records of one-day Ping-lin, two-day Ping-lin, two-day Tong-hou, one-day Guie-shan, and one-day Tai-ping (rainfall in the previous 24 or 48 hours at the named weather stations) were found to be the five most significant parameters for downstream turbidity development. An artificial neural network model was constructed to predict the downstream turbidity in the area investigated. The observed and model-calculated turbidity data were applied to assess the rainfall thresholds in the studied area. By setting preselected turbidity criteria, the upstream rainfall thresholds for these statistically determined rain gauge stations were calculated.

Frequency domain electromagnetic induction survey in the intertidal zone: Limitations of low-induction-number and depth of exploration

NASA Astrophysics Data System (ADS)

Delefortrie, Samuël; Saey, Timothy; Van De Vijver, Ellen; De Smedt, Philippe; Missiaen, Tine; Demerre, Ine; Van Meirvenne, Marc

2014-01-01

Subsurface investigation in the Belgian intertidal zone is severely complicated due to high heterogeneity and tides. Near-surface geophysical techniques can offer assistance since they allow fast surveying and collection of high spatial density data and frequency domain electromagnetic induction (EMI) was chosen for archaeological prospection on the Belgian shore. However, in the intertidal zone the effects of extreme salinity compromise validity of low-induction-number (LIN) approximated EMI data. In this paper, the effects of incursion of seawater on multi-receiver EMI data are investigated by means of survey results, field observations, cone penetration tests and in-situ electrical conductivity measurements. The consequences of LIN approximation breakdown were researched. Reduced depth of investigation of the quadrature-phase (Qu) response and a complex interpretation of the in-phase response were confirmed. Nonetheless, a high signal-to-noise ratio of the Qu response and viable data with regard to shallow subsurface investigation were also evidenced, allowing subsurface investigation in the intertidal zone.

Million city traveling salesman problem solution by divide and conquer clustering with adaptive resonance neural networks.

PubMed

Mulder, Samuel A; Wunsch, Donald C

2003-01-01

The Traveling Salesman Problem (TSP) is a very hard optimization problem in the field of operations research. It has been shown to be NP-complete, and is an often-used benchmark for new optimization techniques. One of the main challenges with this problem is that standard, non-AI heuristic approaches such as the Lin-Kernighan algorithm (LK) and the chained LK variant are currently very effective and in wide use for the common fully connected, Euclidean variant that is considered here. This paper presents an algorithm that uses adaptive resonance theory (ART) in combination with a variation of the Lin-Kernighan local optimization algorithm to solve very large instances of the TSP. The primary advantage of this algorithm over traditional LK and chained-LK approaches is the increased scalability and parallelism allowed by the divide-and-conquer clustering paradigm. Tours obtained by the algorithm are lower quality, but scaling is much better and there is a high potential for increasing performance using parallel hardware.

Heterogeneous Sensor Webs for Automated Target Recognition and Tracking in Urban Terrain

DTIC Science & Technology

2012-04-09

Seto, E. Martin , A. Yang, P. Yan, R. Gravina, I. Lin, C. Wang, M. Roy, V. Shia, R. Bajcsy, “Opportunistic strategies for lightweight signal...processing for body sensor networks,” PETRAE , 2010. 10. Dheeraj Singaraju, Roberto Tron, Ehsan Elhamifar, Allen Yang, and Shankar Sastry. On the Lagrangian

Berkeley Lab - Materials Sciences Division

Science.gov Websites

Chemical and Mechanical Properties of Surfaces, Interfaces and Nanostructures Inorganic-Organic (2016). top Inorganic-Organic Nanocomposites Program Leader: Ting Xu Co-PI's: A. Paul Alivisatos, Yi Liu , Miquel Salmeron, Lin-Wang Wang The organic/inorganic nanocomposite program aims to design and synthesize

Experimental Study of Super-Resolution Using a Compressive Sensing Architecture

DTIC Science & Technology

2015-03-01

Intelligence 24(9), 1167–1183 (2002). [3] Lin, Z. and Shum, H.-Y., “Fundamental limits of reconstruction-based superresolution algorithms under local...IEEE Transactions on 52, 1289–1306 (April 2006). [9] Marcia, R. and Willett, R., “Compressive coded aperture superresolution image reconstruction,” in

Synthesis and characterization of phosphonates from methyl linoleate and vegetable oils

USDA-ARS?s Scientific Manuscript database

Phosphonates were synthesized on a medium scale (~200 g) from three lipids: methyl linoleate (MeLin), high-oleic sunflower oil (HOSO), and soybean oil (SBO), and three dialkyl phosphites: methyl, ethyl, and n-butyl, using radical initiator. A staged addition of the lipid and the initiator was needed...

Molecular Machine-Based Active Plasmonics

DTIC Science & Technology

2011-07-21

C. S. Lin, M. Lu, T. Gao, T.J. Huang), J. Appl. Phys. 2010, 108, 043514. 33. Ordered Au nanodisk and nanohole arrays: fabrication and applications...Stoddart), J. Am. Chem. Soc. 2011, 133, 4538–4547. 41. Frequency-addressed tunable transmission in optically thin metallic nanohole arrays with

U.S. EPA, Pesticide Product Label, , 01/04/1972

EPA Pesticide Factsheets

2011-04-14

... If brea~:lin;: has ~.t()~r-'PrJl start al sees \\.'ic1,m, If ~,\\,'l!lc .. ... p!T 11 DO h, shun;: dil'llf\\l.· ... tt·,,,~l- l'II;.hdr.:;r atf£ cfu<..in· (,'[li.· r riP I 't ,,~,.t "Y rll ...

Mapping and validation of quantitative trait loci associated with concentrations of 16 elements in unmilled rice grain

USDA-ARS?s Scientific Manuscript database

In this study, quantitative trait loci (QTLs) affecting the concentrations of 16 elements in whole, unmilled rice (Oryza sativa L.) grain were identified. Two rice mapping populations, the ‘Lemont’ x ‘TeQing’ recombinant inbred lines (LT-RILs), and the TeQing-into-Lemont backcross introgression lin...

Identification of Genes That Enhance the Nutritional Value of Rice

USDA-ARS?s Scientific Manuscript database

Consumers in developed countries such as the U.S. are willing to pay premium prices for food products having enhanced nutritional value. Grocery stores contain a myriad of calcium fortified foods ranging from orange juice to margarine to frozen waffles. Cereal aisles and bottled water aisles are lin...

JPRS Report, China.

DTIC Science & Technology

1989-04-04

According to the rules, the Chinese Communists put one Vice-Premier in charge of agriculture. Prior to the Cultural Revolution Deng Zihui and Tan...livelihood and forfeited their careers to fan the sparks of Chinese democracy. After the arrest of Wei Jingsheng, Lu Lin [6424 2651] took over the

U.S. EPA, Pesticide Product Label, BONIDE TOMATO-PEPPER-VEGETABLE SPRAY, 09/07/1983

EPA Pesticide Factsheets

2011-04-13

I ~ " r \\ (Lahel Prart) , op'·'lin·· \\·:it', rOL". or "0.1. 'In not .~11(,,: loo·;{' ,irt to cov('r h.\\ it. ':n~~ci!'it; .lirL'l.-"ri,lll": for ro\\.~l.(\\t ~:o~\\llt'r~. :10 not appl~' hy ...

PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

EPA Science Inventory

PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

Miroslav Styblo1,2,*, Zuzana Drobna1, Felecia S. Walton1, Ilona Jaspers1,2, Shan Lin3,
Stephen B. Waters3, David J. Thomas4

1Department of Pediatrics, 2Center for Environmental Medicine an...

Genetics Home Reference: polymicrogyria

MedlinePlus

... Guerrini R, Katz N, Kimonis V, Lin JP, Lynch DR, Mohammed SN, Massey RF, McDonald M, Rogers RC, Splitt M, Stevens CA, Tischkowitz MD, Stoodley N, Leventer RJ, Pilz DT, Dobyns WB. Polymicrogyria and deletion 22q11.2 syndrome: window to the etiology of a common cortical ...

Arabidopsis genotypes resistant and susceptible to diamondback moth (Lepidoptera: Putellidea): No net effects on insect growth

USDA-ARS?s Scientific Manuscript database

Plutella xylostella (L.), diamondback moth (DBM) is a destructive pest of the Brassicaceae including Arabidopsis thaliana (L.) Heynhold. Ecotypes of Arabidopsis vary in the amounts of leaf area consumed when fed on by DBM, which has been used as a measure of resistance to DBM. Recombinant inbred lin...

Biomechanical and Biochemical Cellular Response Due to Shock Waves

DTIC Science & Technology

2008-12-01

112, 1183-1195. Yen, C.-F., 2008, US Army Reserach Laboratory. Zhong, P., I. Cioanta, F. H. Cocks, and G. M. Preminger, 1997: Inertial cavitation...2940-2950. Zhong, P., H. F. Lin, X. F. Xi, S. L. Zhu, and E. S. Bhogte, 1999: Shock wave-inertial microbubble interaction: Methodology

A NOVEL S-ADENOSYL-L-METHIONINE: ARSENIC (III) METHYLTRANSFERASE FROM RAT LIVER CYTOSOL

EPA Science Inventory

A Novel S-Adenosyl-L-methionine: Arsenic(III) Methyltransferase from Rat Liver Cytosol
Shan Lin, Qing Shi, F. Brent Nix, Miroslav Styblo, Melinda A. Beck, Karen M. Herbin-Davis, Larry L. Hall, Josef B. Simeonsson, and David J. Thomas
S-adenosyl-L-methionine (AdoMet): ar...

U.S. EPA, Pesticide Product Label, , 06/21/1976

EPA Pesticide Factsheets

2011-04-19

... If ,;wLIn,· 1.jU:llil'ty "I' !lltlk, "J.!:g whitt'S, gPlatlt1 solution. or if thl'>;" an' 'wt j\\:td;tl'I,', dril,k !:ll'l,!t' 'Ill.llltlt]., "f \\\\:tt. ...

Categorical likelihood method for combining NDVI and elevation information for cotton precision agricultural applications

USDA-ARS?s Scientific Manuscript database

This presentation investigates an algorithm to fuse the Normalized Difference Vegetation Index (NDVI) with LiDAR elevation data to produce a map useful for the site-specific scouting and pest management (Willers et al. 1999; 2005; 2009) of the cotton insect pests, the tarnished plant bug (Lygus lin...

Cirrus Simulations of CRYSTAL-FACE 23 July 2002 Case

NASA Technical Reports Server (NTRS)

Starr, David; Lin, Ruei-Fong; Demoz, Belay; Lare, Andrew

2004-01-01

A key objective of the Cirrus Regional Study of Tropical Anvils and Cirrus Layers - Florida Area Cirrus Experiment (CRYSTAL-FACE) is to understand relationships between the properties of tropical convective cloud systems and the properties and lifecycle of the extended cirrus anvils they produce. We report here on a case study of 23 July 2002 where a sequence of convective storms over central Florida produced an extensive anvil outflow. Our approach is to use a suitably-initialized cloud- system simulation with MM5 (Starr et al., companion paper in this volume) to define initial conditions and time-dependent forcing for a simulation of anvil evolution using a two-dimensional fine-resolution (100 m) cirrus cloud model that explicitly accounts for details of cirrus microphysical development (bin or spectra model) and fully interactive radiative processes. The cirrus model follows Lin (1997). The microphysical components are described in Lin et al. (2004) - see Lin et a1 (this volume). Meteorological conditions and observations for the 23 July case are described in Starr et al. (this volume). The goals of the present study are to evaluate how well we can simulate a cirrus anvil lifecycle, to evaluate the importance of various physical processes that operate within the anvil, and to evaluate the importance of environmental conditions in regulating anvil lifecycle. CRYSTAL-FACE produced a number of excellent case studies of anvil systems that will allow environmental factors, such as static stability or wind shear in the upper troposphere, to be examined. In the present study, we strive to assess the importance of propagating gravity waves, likely produced by the deep convection itself, and radiative processes, to anvil lifecycle and characteristics.

Fracture induced mobilization and incorporation of bone marrow-derived endothelial progenitor cells for bone healing.

PubMed

Matsumoto, Tomoyuki; Mifune, Yutaka; Kawamoto, Atsuhiko; Kuroda, Ryosuke; Shoji, Taro; Iwasaki, Hiroto; Suzuki, Takahiro; Oyamada, Akira; Horii, Miki; Yokoyama, Ayumi; Nishimura, Hiromi; Lee, Sang Yang; Miwa, Masahiko; Doita, Minoru; Kurosaka, Masahiro; Asahara, Takayuki

2008-04-01

We recently reported that systemic administration of peripheral blood (PB) CD34+ cells, an endothelial progenitor cell (EPC)-enriched population, contributed to fracture healing via vasculogenesis/angiogenesis. However, pathophysiological role of EPCs in fracture healing process has not been fully clarified. Therefore, we investigated the hypothesis whether mobilization and incorporation of bone marrow (BM)-derived EPCs may play a pivotal role in appropriate fracture healing. Serial examinations of Laser doppler perfusion imaging and histological capillary density revealed that neovascularization activity at the fracture site peaked at day 7 post-fracture, the early phase of endochondral ossifification. Fluorescence-activated cell sorting (FACS) analysis demonstrated that the frequency of BM cKit+Sca1+Lineage- (Lin-) cells and PB Sca1+Lin- cells, which are EPC-enriched fractions, significantly increased post-fracture. The Sca1+ EPC-derived vasuculogenesis at the fracture site was confirmed by double immunohistochemistry for CD31 and Sca1. BM transplantation from transgenic donors expressing LacZ transcriptionally regulated by endothelial cell-specific Tie-2 promoter into wild type also provided direct evidence that EPCs contributing to enhanced neovascularization at the fracture site were specifically derived from BM. Animal model of systemic administration of PB Sca1+Lin- Green Fluorescent Protein (GFP)+ cells further confirmed incorporation of the mobilized EPCs into the fracture site for fracture healing. These findings indicate that fracture may induce mobilization of EPCs from BM to PB and recruitment of the mobilized EPCs into fracture sites, thereby augment neovascularization during the process of bone healing. EPCs may play an essential role in fracture healing by promoting a favorable environment through neovascularization in damaged skeletal tissue. (c) 2008 Wiley-Liss, Inc.

Effects of diets containing grape seed, linseed, or both on milk production traits, liver and kidney activities, and immunity of lactating dairy ewes.

PubMed

Nudda, A; Correddu, F; Marzano, A; Battacone, G; Nicolussi, P; Bonelli, P; Pulina, G

2015-02-01

This study aimed to evaluate the effects of the dietary inclusion of grape seed, alone or in combination with linseed, on milk production traits, immune response, and liver and kidney metabolic activity of lactating ewes. Twenty-four Sarda dairy ewes were randomly assigned to 4 dietary treatments consisting of a control diet (CON), a diet containing 300 g/d per head of grape seed (GS), a diet containing 220 g/d per head of extruded linseed (LIN), and a diet containing a mix of 300 g/d per head of grape seed and 220 g/d per head of extruded linseed (MIX). The study lasted 10 wk, with 2 wk of adaptation period and 8 wk of experimental period. Milk yield was measured and samples were collected weekly and analyzed for fat, protein, casein, lactose, pH, milk urea nitrogen, and somatic cell count. Blood samples were collected every 2 wk by jugular vein puncture and analyzed for hematological parameters, for albumin, alkaline phosphatase, bilirubin, creatinine, gamma glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, protein, blood urea nitrogen, and for anti-albumin IgG, IL-6, and lymphocyte T-helper (CD4(+)) and lymphocyte T-cytotoxic (CD8(+)) cells. On d 0, 45, and 60 of the trial, lymphocyte response to phytohemagglutinin was determined in vivo on each animal by measuring skin-fold thickness (SFT) at the site of phytohemagglutinin injection. Humoral response to chicken egg albumin was stimulated by a subcutaneous injection with albumin. Dietary treatments did not affect milk yield and composition. Milk urea nitrogen and lactose were affected by diet × period. Diets did not influence hematological, kidney, and liver parameters, except for blood urea nitrogen, which decreased in LIN and increased in MIX compared with CON and GS. Dietary treatments did not alter CD4(+), CD8(+), and CD4(+)-to-CD8(+) ratio. The SFT was reduced in GS and MIX and increased in LIN compared with CON. The IgG and IL-6 were affected by diet × period. The reduction in Ig

Benchmarking lithium amide versus amine bonding by charge density and energy decomposition analysis arguments.

PubMed

Engelhardt, Felix; Maaß, Christian; Andrada, Diego M; Herbst-Irmer, Regine; Stalke, Dietmar

2018-03-28

Lithium amides are versatile C-H metallation reagents with vast industrial demand because of their high basicity combined with their weak nucleophilicity, and they are applied in kilotons worldwide annually. The nuclearity of lithium amides, however, modifies and steers reactivity, region- and stereo-selectivity and product diversification in organic syntheses. In this regard, it is vital to understand Li-N bonding as it causes the aggregation of lithium amides to form cubes or ladders from the polar Li-N covalent metal amide bond along the ring stacking and laddering principle. Deaggregation, however, is more governed by the Li←N donor bond to form amine adducts. The geometry of the solid state structures already suggests that there is σ- and π-contribution to the covalent bond. To quantify the mutual influence, we investigated [{(Me 2 NCH 2 ) 2 (C 4 H 2 N)}Li] 2 ( 1 ) by means of experimental charge density calculations based on the quantum theory of atoms in molecules (QTAIM) and DFT calculations using energy decomposition analysis (EDA). This new approach allows for the grading of electrostatic Li + N - , covalent Li-N and donating Li←N bonding, and provides a way to modify traditional widely-used heuristic concepts such as the -I and +I inductive effects. The electron density ρ ( r ) and its second derivative, the Laplacian ∇ 2 ρ ( r ), mirror the various types of bonding. Most remarkably, from the topological descriptors, there is no clear separation of the lithium amide bonds from the lithium amine donor bonds. The computed natural partial charges for lithium are only +0.58, indicating an optimal density supply from the four nitrogen atoms, while the Wiberg bond orders of about 0.14 au suggest very weak bonding. The interaction energy between the two pincer molecules, (C 4 H 2 N) 2 2- , with the Li 2 2+ moiety is very strong ( ca. -628 kcal mol -1 ), followed by the bond dissociation energy (-420.9 kcal mol -1 ). Partitioning the interaction energy

A kinetic formulation of piezoresistance in N-type silicon: Application to non-linear effects

NASA Astrophysics Data System (ADS)

Charbonnieras, A. R.; Tellier, C. R.

1999-07-01

This paper is devoted to the theoretical study of the influence of the temperature and of the doping on the piezoresistance of N-type silicon. In the first step the fractional change in the resistivity caused by stresses is calculated in the framework of a multivalley model using a kinetic transport formulation based on the Boltzmann transport equation. In the second step shifts in the minima of the conduction band and the resulting shift of the Fermi level are expressed in terms of deformation potentials and of stresses. General expressions for the fundamental linear, π_{11} and π_{12}, and non-linear, π_{111}, π_{112}, π_{122} and π_{123}, piezoresistance coefficients are then derived. Plots of the non-linear piezoresistance coefficients against the reduced shift of the Fermi level or against temperature allow us to characterize the influence of doping and temperature. Finally some attempts are made to estimate the non-linearity for heavily doped semiconductor gauges. Cette publication est consacrée à l'étude théorique de l'influence de la température et du dopage sur la piezorésistivité du silicium type N. Dans une première étape nous adoptons le modèle de vallées et nous utilisons une formulation cinétique du transport électronique faisant appel à l'équation de transport de Boltzmann pour calculer la variation de la résistivité du semiconducteur sous contrainte. Dans la deuxième étape nous exprimons les déplacements des minima de la bande de conduction et du niveau de Fermi en termes de potentiels de déformation et de contraintes. Nous proposons ensuite des expressions générales pour les coefficients piezorésistifs fondamentaux linéaires, π_{11} et π_{12}, et non-linéaires, π_{111}, π_{112}, π_{122} et π_{123}. Des représentations graphiques des variations des coefficients non-linéaires permettent de caractériser l'influence du dopage et de la température. Enfin nous fournissons une première pré-estimation des effets

Adult cardiac stem cells are multipotent and robustly myogenic: c-kit expression is necessary but not sufficient for their identification.

PubMed

Vicinanza, Carla; Aquila, Iolanda; Scalise, Mariangela; Cristiano, Francesca; Marino, Fabiola; Cianflone, Eleonora; Mancuso, Teresa; Marotta, Pina; Sacco, Walter; Lewis, Fiona C; Couch, Liam; Shone, Victoria; Gritti, Giulia; Torella, Annalaura; Smith, Andrew J; Terracciano, Cesare Mn; Britti, Domenico; Veltri, Pierangelo; Indolfi, Ciro; Nadal-Ginard, Bernardo; Ellison-Hughes, Georgina M; Torella, Daniele

2017-12-01

Multipotent adult resident cardiac stem cells (CSCs) were first identified by the expression of c-kit, the stem cell factor receptor. However, in the adult myocardium c-kit alone cannot distinguish CSCs from other c-kit-expressing (c-kit pos ) cells. The adult heart indeed contains a heterogeneous mixture of c-kit pos cells, mainly composed of mast and endothelial/progenitor cells. This heterogeneity of cardiac c-kit pos cells has generated confusion and controversy about the existence and role of CSCs in the adult heart. Here, to unravel CSC identity within the heterogeneous c-kit-expressing cardiac cell population, c-kit pos cardiac cells were separated through CD45-positive or -negative sorting followed by c-kit pos sorting. The blood/endothelial lineage-committed (Lineage pos ) CD45 pos c-kit pos cardiac cells were compared to CD45 neg (Lineage neg /Lin neg ) c-kit pos cardiac cells for stemness and myogenic properties in vitro and in vivo. The majority (~90%) of the resident c-kit pos cardiac cells are blood/endothelial lineage-committed CD45 pos CD31 pos c-kit pos cells. In contrast, the Lin neg CD45 neg c-kit pos cardiac cell cohort, which represents ⩽10% of the total c-kit pos cells, contain all the cardiac cells with the properties of adult multipotent CSCs. These characteristics are absent from the c-kit neg and the blood/endothelial lineage-committed c-kit pos cardiac cells. Single Lin neg c-kit pos cell-derived clones, which represent only 1-2% of total c-kit pos myocardial cells, when stimulated with TGF-β/Wnt molecules, acquire full transcriptome and protein expression, sarcomere organisation, spontaneous contraction and electrophysiological properties of differentiated cardiomyocytes (CMs). Genetically tagged cloned progeny of one Lin neg c-kit pos cell when injected into the infarcted myocardium, results in significant regeneration of new CMs, arterioles and capillaries, derived from the injected cells. The CSC's myogenic regenerative capacity is

Accuracy of the HumaSensplus point-of-care uric acid meter using capillary blood obtained by fingertip puncture.

PubMed

Fabre, Stéphanie; Clerson, Pierre; Launay, Jean-Marie; Gautier, Jean-François; Vidal-Trecan, Tiphaine; Riveline, Jean-Pierre; Platt, Adam; Abrahamsson, Anna; Miner, Jeffrey N; Hughes, Glen; Richette, Pascal; Bardin, Thomas

2018-05-02

The uric acid (UA) level in patients with gout is a key factor in disease management and is typically measured in the laboratory using plasma samples obtained after venous puncture. This study aimed to assess the reliability of immediate UA measurement with capillary blood samples obtained by fingertip puncture with the HumaSens plus point-of-care meter. UA levels were measured using both the HumaSens plus meter in the clinic and the routine plasma UA method in the biochemistry laboratory of 238 consenting diabetic patients. HumaSens plus capillary and routine plasma UA measurements were compared by linear regression, Bland-Altman plots, intraclass correlation coefficient (ICC), and Lin's concordance coefficient. Values outside the dynamic range of the meter, low (LO) or high (HI), were analyzed separately. The best capillary UA thresholds for detecting hyperuricemia were determined by receiver operating characteristic (ROC) curves. The impact of potential confounding factors (demographic and biological parameters/treatments) was assessed. Capillary and routine plasma UA levels were compared to reference plasma UA measurements by liquid chromatography-mass spectrometry (LC-MS) for a subgroup of 67 patients. In total, 205 patients had capillary and routine plasma UA measurements available. ICC was 0.90 (95% confidence interval (CI) 0.87-0.92), Lin's coefficient was 0.91 (0.88-0.93), and the Bland-Altman plot showed good agreement over all tested values. Overall, 17 patients showed values outside the dynamic range. LO values were concordant with plasma values, but HI values were considered uninterpretable. Capillary UA thresholds of 299 and 340 μmol/l gave the best results for detecting hyperuricemia (corresponding to routine plasma UA thresholds of 300 and 360 μmol/l, respectively). No significant confounding factor was found among those tested, except for hematocrit; however, this had a negligible influence on the assay reliability. When capillary and routine

Detecting Nonadditivity in Single-Facet Generalizability Theory Applications: Tukey's Test

ERIC Educational Resources Information Center

Lin, Chih-Kai; Zhang, Jinming

2018-01-01

Under the generalizability-theory (G-theory) framework, the estimation precision of variance components (VCs) is of significant importance in that they serve as the foundation of estimating reliability. Zhang and Lin advanced the discussion of nonadditivity in data from a theoretical perspective and showed the adverse effects of nonadditivity on…

WaveNet: A Web-Based Metocean Data Access, Processing and Analysis Tool; Part 5 - WW3 Database

DTIC Science & Technology

2015-02-01

Program ( CDIP ); and Part 4 for the Great Lakes Observing System/Coastal Forecasting System (GLOS/GLCFS). Using step-by-step instructions, this Part 5...Demirbilek, Z., L. Lin, and D. Wilson. 2014a. WaveNet: A web-based metocean data access, processing, and analysis tool; part 3– CDIP database

Synthesis and characterization of phosphonates from methyl linoleate and vegetable oils

USDA-ARS?s Scientific Manuscript database

Phosphonates were synthesized on a medium scale (~200 g) from three lipids: methyl linoleate (MeLin), high-oleic sunflower oil (HOSO) and soybean oil (SBO), and three dialkyl phosphites: methyl, ethyl and n-butyl, using a radical initiator. A staged addition of the lipid and the initiator to the dia...

Benchmarking the State of Kosrae's Education Management Information System. REL 2017-174

ERIC Educational Resources Information Center

Kendall, John S.; Dandapani, Nitara; Cicchinelli, Louis F.

2016-01-01

A quality data management system, such as an education management information system (EMIS), a state longitudinal data system, or a data warehouse, is key to ensuring that education policy, planning, and strategy decisions are grounded in accurate information (Data Quality Campaign, 2010; Mohamed, Kadir, May-Lin, Rahman, & Arshad, 2009;…

Benchmarking the State of Chuuk's Education Management Information System. REL 2017-176

ERIC Educational Resources Information Center

Kendall, John S.; Dandapani, Nitara; Cicchinelli, Louis F.

2016-01-01

A quality data management system, such as an education management information system (EMIS), a state longitudinal data system, or a data warehouse, is key to ensuring that education policy, planning, and strategy decisions are grounded in accurate information (Data Quality Campaign, 2010; Mohamed, Kadir, May-Lin, Rahman, & Arshad, 2009;…

Benchmarking the State of Pohnpei's Education Management Information System. REL 2017-175

ERIC Educational Resources Information Center

Kendall, John S.; Dandapani, Nitara; Cicchinelli, Louis F.

2016-01-01

A quality data management system, such as an education management information system (EMIS), a state longitudinal data system, or a data warehouse, is key to ensuring that education policy, planning, and strategy decisions are grounded in accurate information (Data Quality Campaign, 2010; Mohamed, Kadir, May-Lin, Rahman, & Arshad, 2009;…

An Observational Study of a Prefrontal Convective Rainband Using Tamex Single-and Dual-Doppler Data

DTIC Science & Technology

1991-01-01

integration from the surface. Other Doppler studies, e.g., Chong and Testud (1983), Lin et al. 37 (1986), etc, also showed similiar results. 4.3 Variational...Atmos. Sci., 39, 258- 279. Chong, M., and J. Testud , 1983: Three-Dimensional Wind Field Analysis from Dual-Doppler Radar Data. Part III: The Boundary

Synthesis and characterization of phosphonates from methyl linoleate and vegetable oils

USDA-ARS?s Scientific Manuscript database

Phosphonates were synthesized on a medium scale (~200 g) from three lipids–methyl linoleate (MeLin), high-oleic sunflower oil (HOSO) and soybean oil (SBO), and three dialkyl phosphites–methyl, ethyl and n-butyl, using a radical initiator. A staged addition of the lipid and the initiator was used to ...

Proceedings of the Annual Meeting of the Association for Education in Journalism and Mass Communication (85th, Miami, Florida, August 5-8, 2002). International Communication Division.

ERIC Educational Resources Information Center

2002

The International Communication Division of the proceedings contains the following 18 papers: "Spy or Scapegoat: A News Framing Study of the 'New York Times'' Coverage of the Wen Ho Lee Case" (Jia Lin & Junhao Hong); "Individual Perceptions of International Correspondents in the Middle East: An Obstacle to Fair News?" (Dina…

U.S. EPA, Pesticide Product Label, ULTRA-FRESH AF-5, 10/21/1983

EPA Pesticide Factsheets

2011-04-19

... It tlI'Gathtl''1 i. • u"tcult. 91"" • .uYlJrn. Cell. ,.hydO:'oIA. Jt .. ... tOl leal. I., in tho p' ••• nc. ~f .... t.tu.o. tlin-. .. ...

The Oral History of Evaluation: The Professional Development of Robert Stake

ERIC Educational Resources Information Center

Miller, Robin Lin; King, Jean A.; Mark, Melvin M.; Caracelli, Valerie

2016-01-01

Over the past 14 years, AEA's Oral History Project Team (Robin Lin Miller, Jean A. King, Valerie Caracelli, and Melvin M. Mark) has conducted interviews with individuals who have made signal contributions to evaluation theory and practice, tracing their professional development and contextualizing their work within the social and political…

Assessment of Nanobiotechnology-Targeted siRNA Designed to Inhibit NF-KappaB Classical and Alternative Signaling in Breast Tumor Macrophages

DTIC Science & Technology

2014-07-01

Venkataraman R, Crowder SW, Jung DK, Yu SS, Feaster TK, Giorgio TD, Hong CC, Baudenbacher FJ, Hatzopoulos AK and Sung HJ: Combinatorial Electrospun Matrices...Diabetic Complications, Journal of the American Society of Nephrology : JASN, 2009, 20, 2503-2512. 37. E. Y. Lin, J. G. Jones, P. Li, L. Zhu, K. D

Cancer Health Disparities Research: Where have we been and where should we go? | Division of Cancer Prevention

Cancer.gov

Speaker | Scarlett Lin Gomez, PhD, MPH will present the next CPFP Colloquia lecture entitled, "Cancer Health Disparities Research: Where have we been and where should we go?" Date: May 15, 2018; Time: 11:00 am - 12:00 pm; Location: NCI Shady Grove campus, Conference Room: 2W-910/912.

FlyEyes: A CCD-Based Wavefront Sensor for PUEO, the CFHT Curvature AO System

DTIC Science & Technology

2010-09-28

Charles Cuillandre, Kevin K.Y. Ho, Marc Baril , Tom Benedict, Jeff Ward, Jim Thomas, Derrick Salmon, Chueh-Jen Lin, Shiang-Yu Wang, Gerry Luppino...sensor for PUEO, the CFHT curvature AO system Olivier Lai, Jean-Charles Cuillandre , Kevin K.Y. Ho, lVIarc Baril , Tom Benedict, Jeff ’Varel, Jim Thomas

Multi-Chambered Treatment Train (MCTT) For Treating Stormwater Runoff From Highly Polluted Source Areas

EPA Science Inventory

A full-scaled Multi-Chambered Treatment Train (MCTT) stormwater treatment system was tested in Taiwan during the spring and summer of 2007. The MCTT was installed in a parking lot in Ping-Lin, Northern Taiwan. The site is 85% impervious and has a drainage area to the MCTT unit of...

Intervention and Rescue: Arguments for Representational Constraints on Syntactic Dependencies

ERIC Educational Resources Information Center

Shields, Rebecca

2009-01-01

This thesis presents arguments for a representational analysis of certain locality constraints on movement. I look at two types of locality effects: Negative Intervention effects in English (Beck 1996, 2006, Pesetsky 2000), and Relativized Minimality effects with adverb scrambling in Russian, Japanese, and Korean (Rizzi 1990, 2001, Li, Lin &…

Envisioning a Career in Science, Technology, Engineering and Mathematics: Some Challenges and Possibilities

ERIC Educational Resources Information Center

Sharkawy, Azza

2015-01-01

In "How High School Students Envision Their STEM Career Pathways", Lin Zhang and Michael Barnett attempt to shed light on the problem of underrepresented students (e.g., Aboriginals, Hispanics, African Americans, urban, females) in STEM higher education and related careers by exploring, in general terms, five high school students' career…

76 FR 76411 - Ocean Transportation Intermediary License; Applicants

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-07

... at (202) 523-5843 or by email at [email protected] . Bluesea Logistics Corporation (NVO), 327 Elizabeth Avenue, Apt. A, Monterey Park, CA 91755-2044, Officers: Li Lin, General Manager/Sec/CFO, (Qualifying..., Application Type: Name Change. Didi Logistics Inc (NVO & OFF), 2380 SW 80th Court, Miami, FL 33155, Officers...

Analysis of Investigational Drugs in Biological Fluids - Method Development and Routine Assay

DTIC Science & Technology

1994-08-14

Principles of Internal Medicine, Tenth edition. Edited by Petersdorf, R.G.; Adams , R.P.; Braunwald, E.; Isselbacher K.J.; Martin, J.B.; and Wilson, J.D...artelinic acid in blood plasma by high-performance liquid chromatography. 1. Chromatogr., 1989, 495, 167-77. 60Lin ET, Benet LZ, Upton RA, Levai F

The Effects of a Modified Learning Strategy on the Multiple Step Mathematical Word Problem Solving Ability of Middle School Students with High-Functioning Autism or Asperger's Syndrome

ERIC Educational Resources Information Center

Schaefer Whitby, Peggy J.

2009-01-01

Children with HFA/AS are outperformed by their neuro-typical peers on mathematical problem solving skills even though they have average-to-above-average intelligence (Dickerson Mayes & Calhoun, 2003b); have average-to-above-average computation skills (Chiang & Lin, 2007); and, are educated in the general education setting (Twenty Eighth…

Identification of molecular species of polyol oils produced from soybean oil by Pseudomonas aeruginosa e03-12 nrrl b-59991

USDA-ARS?s Scientific Manuscript database

The objective of this study is to develop a bioprocess for the production of polyol oils directly from soybean oil. We reported earlier methods for microbial screening and production of polyol oils from soybean oil (Hou and Lin, 2013). The polyol oil produced by Acinetobacter haemolyticus A01-35 (NR...

76 FR 66361 - Quarterly Publication of Individuals, Who Have Chosen To Expatriate, as Required by Section 6039G

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

... THOMAS YUL BAER JULIAN JULIUS BAGGETT SUSAN BANKES FLORA JUNE BARBALACO STEPHEN BATES LIAM ROBERT BAXTER... THOMAS GRIMM CHRISTOPH GRIMM KATJA GULINO SAYAN HABIB OK YO HACKETT PAMELA D. J. HALL NATALIE JUDITH HAMI... KEUNG LI LYDIA KWAN LIEBMANN BRAD HUNTER LIM LILLAN YUXIAN LIM VIVIAN YUJING LIN CHARLYN LINCKE THOMAS...

Production of polyol oils from soybean oil by bioprocess and Philippines edible medicinal wild mushrooms

USDA-ARS?s Scientific Manuscript database

We have been trying to develop a bioprocess for the production of polyol oils directly from soybean oil. We reported earlier the polyol products produced from soybean oil by Acinetobacter haemolyticus A01-35 (NRRL B-59985) (Hou and Lin, 2013). The objective of this study is to identify the chemical ...

Proceedings of the Annual Meeting of the Association for Education in Journalism and Mass Communication (75th, Montreal, Quebec, Canada, August 5-8, 1992). Part X: Health, Science, and the Environment.

ERIC Educational Resources Information Center

Association for Education in Journalism and Mass Communication.

The Health, Science, and the Environment section of these proceedings contains the following seven papers: "Columbus, Mars, and the Changing Images and Ideologies of Exploration: A Critical Examination" (Lin Bin and August T. Horvath); "Prime Time TV Portrayals of Sex, 'Safe Sex' and AIDS: A Longitudinal Analysis" (Dennis T.…

The Case for Pedagogical Action Research in Psychology Learning and Teaching

ERIC Educational Resources Information Center

Norton, Lin

2014-01-01

It is just over 12 years since "Psychology Teaching Review"'s first Special Issue on action research psychology. In the guest editorial for that issue Lin Norton suggested that pedagogical action research can be controversial, and that for some academic psychologists it appears to be more than curriculum development rather than…

ALTERED SENSITIVITY OF THE MOUSE FETUS TO IMPAIRED PROSTATIC BUD FORMATION BY DIOXIN: INFLUENCE OF GENETIC BACKGROUND AND NULL EXPRESSION OF TGF-ALFA AND EGF

EPA Science Inventory

Altered sensitivity of the mouse fetus to impaired prostatic bud formation by dioxin: Influence of genetic background and null expression of TGF and EGF.
Rasmussen, N.T., Lin T-M., Fenton, S.E., Abbott, B.D. and R.E. Peterson.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)...

Changing Workplace.

ERIC Educational Resources Information Center

1998

This document contains four papers from a symposium on the changing workplace and its relationship to human resource development (HRD). In "Globalization, Immigration and Quality of Life Dynamics for Reverse Brain Drains" (Ben-Chieh Liu, Maw Lin Lee, Hau-Lien), the factors responsible for the brain drain from Taiwan to the United States…

Collaborative Learning: A Critical Success Factor in Distance Education.

ERIC Educational Resources Information Center

Levin, David S.; Ben-Jacob, Marion G.

This paper discusses the use of new technologies for distance learning-- including interactive video, computers, and the Internet-- at Mercy College (New York) and DePaul University (Illinois). The description of a course on discrete mathematics that is taught using the Mercy College Long-distance Instructional Network (MerLIN) focuses on the use…

Using Group-Based Learning in Higher Education. Teaching and Learning in Higher Education Series.

ERIC Educational Resources Information Center

Thorley, Lin, Ed.; Gregory, Roy, Ed.

The 26 papers in this collection from a British conference first provide an overview of group-based learning in higher education, offer a range of examples, and identify issues and trends. Chapters include: (1) "Introduction" (Roy Gregory and Lin Thorley); (2) "An Overview from Higher Education" (Diana M. R. Tribe); (3)…

Translating Methods of Shakespeare in China

ERIC Educational Resources Information Center

Sun, Yanna

2009-01-01

Shakespeare was not known to the Chinese until Lin Zexu's (1785-1850) translation of Hugh Murray's (1789-1845) "Cyclopedia of Geography" (1836). Afterwards Shakespeare in China saw many complicated changes, from being regarded as a story-teller to being fully received as a seasoned playwright and poet, and his plays were rendered into…