gebhart/patrepeval huggingface dataset:
Syndecan-4–dependent Rac1 regulation determines directional migration in response to the extracellular matrix (2007)

Cell migration in wound healing and disease is critically dependent on integration with the extracellular matrix, but the receptors that couple matrix topography to migratory behavior remain obscure. Using nano-engineered fibronectin surfaces and cell-derived matrices, we identify syndecan-4 as a key signaling receptor determining directional migration. In wild-type fibroblasts, syndecan-4 mediates the matrix-induced protein kinase Calpha (PKCalpha)-dependent activation of Rac1 and localizes Rac1 activity and membrane protrusion to the leading edge of the cell, resulting in persistent migration. In contrast, syndecan-4-null fibroblasts migrate randomly as a result of high delocalized Rac1 activity, whereas cells expressing a syndecan-4 cytodomain mutant deficient in PKCalpha regulation fail to localize active Rac1 to points of matrix engagement and consequently fail to recognize and respond to topographical changes in the matrix.
Oxidative DNA Cleavage by the Antitumor Antibiotic Leinamycin and Simple 1,2-Dithiolan-3-one 1-Oxides:  Evidence for Thiol-Dependent Conversion of Molecular Oxygen to DNA-Cleaving Oxygen Radicals Mediated by Polysulfides (1997)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTOxidative DNA Cleavage by the Antitumor Antibiotic Leinamycin and Simple 1,2-Dithiolan-3-one 1-Oxides: Evidence for Thiol-Dependent Conversion of Molecular Oxygen to DNA-Cleaving Oxygen Radicals Mediated by PolysulfidesKaushik Mitra, Woongki Kim, J. Scott Daniels, and Kent S. GatesView Author Information Departments of Chemistry and Biochemistry University of MissouriColumbia Columbia, Missouri 65211 Cite this: J. Am. Chem. Soc. 1997, 119, 48, 11691–11692Publication Date (Web):December 3, 1997Publication History Received29 April 1997Published online3 December 1997Published inissue 1 December 1997https://pubs.acs.org/doi/10.1021/ja971359zhttps://doi.org/10.1021/ja971359zrapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views505Altmetric-Citations82LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Bond cleavage,Crystal cleavage,Genetics,Oxygen,Thiols Get e-Alerts
Do lampreys have lymphocytes? The Spi evidence (2000)

It is generally accepted that living jawless vertebrates (lampreys and hagfishes) lack the capability of mounting an adaptive immune response. At the same time, however, there are reports describing histological evidence for the presence in agnathan tissues of lymphocytes, the key players in adaptive immunity. The question therefore arises whether the cells identified morphologically as lymphocytes are true lymphocytes in terms of their genetic developmental program. In this study, evidence is provided that the lampreys express a member of the purine box 1 (PU.1)/spleen focus-forming virus integration B (Spi-B) gene family known to be critically and specifically involved in the differentiation of lymphocytes in jawed vertebrates. The lamprey gene is expressed in the lymphocyte-like cells of the digestive tract and inexplicably also in the ovary.
Detection of apoptotic circulating tumor cells in advanced pancreatic cancer following 5-fluorouracil chemotherapy (2011)

The objective of the present study was to evaluate CA19-9 and CK8/18 expression patterns in pancreatic cancer cell lines induced by 5-fluorouracil (5-Fu), and in circulating tumor cells (CTCs) in peripheral blood of patients previously untreated with advanced pancreatic cancer. Furthermore, the goal was to test the relationship of dynamic of CTCs with the effects of the first cycle of chemotherapy. To accomplish this study, CD45 antibody coated beads were used to discard white blood cells in peripheral blood. This was done in combination with CA19-9-Alexa488 and CK8/18-Alexa594 immunofluorescence staining to identify CTCs in circulation from 41 advanced pancreatic cancer patients, before and after chemotherapy. The PL45 pancreatic cancer cell line was incubated with 20 µmmol/L 5-Fu for 12 and 24 hours to induce apoptosis, and the expression patterns of CA19-9 and CK8/18 were measured, and the extent of apoptosis was evaluated. Subsequently, apoptotic cells and CTCs were measured. Of 41 patients with stage III and Ⅳ pancreatic cancer, 80.5% were detected with more than two CTCs in 7.5mL peripheral blood before any therapy and the median number of CTCs was 16.8±16.0 (0-59). After 7 days by the first cycle of 5-Fu chemotherapy, only 29.3% (12/41) of these patients were detected more than two CTCs in 7.5mL peripheral blood and the median number of CTCs was 3.8±7.8 (0-40) (P=0.000). And no CTCs were detected in 20 healthy donors from 7.5mL peripheral blood (P=0.000). Apoptotic CTCs were detected after advanced pancreatic patients were administered the first cycle of chemotherapy. Punctate, granular, and bubble-like morphologies with CA19-9 and CK8/18 staining were found and may reflect apoptosis in pancreatic cancer cells and CTCs. Apoptotic CTCs may indicate the efficacy of chemotherapy in pancreatic cancer patients. However, further studies are required to follow up these findings.
Studies on the Synthesis of Condensed Pyridazine Derivatives. IV. Synthesis and Anxiolytic Activity of 2-Aryl-5,6-dihydro-(1)benzothiepino(5,4-c)pyridazin-3(2H)-ones and Related Compound. (1991)

A series of 2-aryl-5,6-dihydro-(1)benzothiepino[5,4-c]pyridazin-3(2H)- ones and related compounds were synthesized and evaluated for their ability to displace 3H-diazepam from rat brain membranes in vitro, and to prevent bicuculline induced convulsions in mice in vivo. Compounds with a 4'-methoxyphenyl (36) or 4'-chlorophenyl group (37, 39--42) as 2-aryl substituents showed prominent activities in both the in vitro and in vivo tests. Among them, 2-(4'-chlorophenyl)-5,6-dihydro- (37) and 2-(4'-chlorophenyl)-5,6-dihydro-10-fluoro-(1)benzothiepino[5,4-c]+ ++pyridazin- 3(2H)-one 7-oxides (41) showed activity twice as potent as diazepam in an anticonflict test (Vogel type, rats) while exhibiting less muscle relaxation (rotarod test, mice) and augmentation of gamma-aminobutyric acid-induced chloride current (Icl) in isolated frog sensory neurones than diazepam. Compound 37 (Y-23684) was selected from this series as a candidate for further development. The structure-activity relationships are discussed.
Urokinase-Receptor (u-PAR)–An Essential Player in Multiple Games of Cancer: A Review on Its Role in Tumor Progression, Invasion, Metastasis, Proliferation/dormancy, Clinical Outcome and Minimal Residual Disease (2006)

The relevance of the u-PA system in mediating tumor-associated proteolysis, invasion and metastasis, amongst other phenomena associated with tumor progression, has been clearly demonstrated in diverse cancer entities. This review will update on the biological and clinical relevance of the urokinase-receptor (u-PAR). Specifically, the article focuses on the potential importance of u-PAR for the development of minimal residual disease in solid cancer, and in this context reviews the biological relevance of the u-PAR for tumor cell dormancy. Furthermore, transcriptional mechanisms regulating u-PAR in vitro and in vivo, and their potential clinical and therapeutic relevance in gastrointestinal cancers, are elucidated.
Down-regulation of CXCR2 on Neutrophils in Severe Sepsis Is Mediated by Inducible Nitric Oxide Synthase–derived Nitric Oxide (2006)

These results highlight evidences that the failure of neutrophils to migrate to an infection focus during severe sepsis is associated with excessive NO production and NO-dependent regulation of the expression of CXCR2 on the neutrophil surface.
Expression of a mouse brain cDNA encoding novel gamma-aminobutyric acid transporter. (1992)

A nipecotic acid-resistant gamma-aminobutyric acid (GABA) transporter was cloned from a mouse brain cDNA library. The 2.3-kilobase cDNA clone contains an open reading frame of 1842 nucleotides encoding a protein of 614 amino acids. The predicted amino acid sequence indicates it is a member of the gene family of the sodium-dependent neurotransmitter transporters. The new GABA transporter, named GAT2, is highly homologous to the betaine transporter (BGT1) cloned from canine kidney. However, GAT2 expression in the brain distinguished it from BGT1 which was exclusively expressed in the kidney. The transcripts of GAT2 were found in the cerebral cortex, cerebellum, and brainstem as well as in kidney. Expression of GAT2 in Xenopus oocytes revealed a Km of 79 microM for GABA uptake which is about 10-fold higher than that of the high affinity GABA transporter (GAT1). The pharmacology of GAT2 is different from that of GAT1 because of lack of inhibition by guvacine and nipecotic acid and sensitivity to high concentrations of betaine and beta-alanine. GAT2 transports betaine with a Km of about 200 microM, but no significant transport of beta-alanine could be detected. The presence of mRNA encoding GAT2 in parts of the brain suggests it is a neurotransmitter transporter.
NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis (2012)

The NLRP3 inflammasome is a multiprotein complex consisting of three kinds of proteins, NLRP3, ASC, and pro-caspase-1, and plays a role in sensing pathogens and danger signals in the innate immune system. The NLRP3 inflammasome is thought to be involved in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, the mechanism by which the NLRP3 inflammasome induces EAE is not clear. In this study, we found that the NLRP3 inflammasome played a critical role in inducing T-helper cell migration into the CNS. To gain migratory ability, CD4(+) T cells need to be primed by NLRP3 inflammasome-sufficient antigen-presenting cells to up-regulate chemotaxis-related proteins, such as osteopontin, CCR2, and CXCR6. In the presence of the NLRP3 inflammasome, dendritic cells and macrophages also induce chemotactic ability and up-regulate chemotaxis-related proteins, such as α4β1 integrin, CCL7, CCL8, and CXCL16. On the other hand, reduced Th17 cell population size in immunized Nlrp3(-/-) and Asc(-/-) mice is not a determinative factor for their resistance to EAE. As currently applied in clinical interventions of MS, targeting immune cell migration molecules may be an effective approach in treating MS accompanied by NLRP3 inflammasome activation.
An integrated system for planning, navigation and robotic assistance for skull base surgery (2008)

The image-guided cooperatively-controlled robot system can improve the safety and ergonomics of skull base drilling by stabilizing the drill and enforcing virtual fixtures to protect critical neurovascular structures. The next step is to improve the accuracy so that the overcut can be reduced to a more clinically acceptable value of about 1 mm.
Development of an animal model for prostate cancer cell metastasis to adult human bone. (2001)

These data suggest that the tumor cells may induce an osteolytic response to enhance their ability to metastasize to bone. This animal model allows us to study the biologic interaction between prostate cancer cells and human bone and may enhance our understanding of the events associated with prostate cancer metastasis to bone.
Human Mid-Trimester Amniotic Fluid Stem Cells Cultured Under Embryonic Stem Cell Conditions with Valproic Acid Acquire Pluripotent Characteristics (2012)

Human mid-trimester amniotic fluid stem cells (AFSC) have promising applications in regenerative medicine, being broadly multipotent with an intermediate phenotype between embryonic (ES) and mesenchymal stem cells (MSC). Despite this propluripotent phenotype, AFSC are usually cultured in adherence in a serum-based expansion medium, and how expansion in conditions sustaining pluripotency might affect their phenotype remains unknown. We recently showed that early AFSC from first trimester amniotic fluid, which endogenously express Sox2 and Klf4, can be reprogrammed to pluripotency without viral vectors using the histone deacetylase inhibitor valproic acid (VPA). Here, we show that mid-trimester AFSC cultured under MSC conditions contained a subset of cells endogenously expressing telomerase, CD24, OCT4, C-MYC, and SSEA4, but low/null levels of SOX2, NANOG, KLF4, SSEA3, TRA-1-60, and TRA-1-81, with cells unable to form embryoid bodies (EBs) or teratomas. In contrast, AFSC cultured under human ESC conditions were smaller in size, grew faster, formed colonies, upregulated OCT4 and C-MYC, and expressed KLF4 and SOX2, but not NANOG, SSEA3, TRA-1-60, and TRA-1-81. Supplementation with VPA for 5 days further upregulated OCT4, KLF4, and SOX2, and induced expression of NANOG, SSEA3, TRA-1-60, and TRA-1-81, with cells now able to form EBs and teratomas. We conclude that human mid-trimester AFSC, which may be isolated autologously during pregnancy without ethics restriction, can acquire pluripotent characteristics without the use of ectopic factors. Our data suggest that this medium-dependant approach to pluripotent mid-trimester AFSC reflects true reprogramming and not the selection of prepluripotent cells.
Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a general mechanism for BTB/POZ transcriptional repressors: The case of HIC-1 and γFBP-B (1999)

Hypermethylated in cancer (HIC-1), a new candidate tumor suppressor gene located in 17p13.3, encodes a protein with five C(2)H(2) zinc fingers and an N-terminal broad complex, tramtrack, and bric à brac/poxviruses and zinc-finger (BTB/POZ) domain found in actin binding proteins or transcriptional regulators involved in chromatin modeling. In the human B cell lymphoma (BCL-6) and promyelocityc leukemia (PLZF) oncoproteins, this domain mediates transcriptional repression through its ability to recruit a silencing mediator of retinoid and thyroid hormone receptor (SMRT)/nuclear receptor corepressor (N-CoR)-mSin3A-histone deacetylase (HDAC) complex, a mechanism shared with numerous transcription factors. HIC-1 appears unique because it contains a 13-aa insertion acquired late in evolution, because it is not found in its avian homologue, gammaF1-binding protein isoform B (gammaFBP-B), a transcriptional repressor of the gammaF-crystallin gene. This insertion, located in a conserved region involved in the dimerization and scaffolding of the BTB/POZ domain, mainly affects slightly the ability of the HIC-1 and gammaFBP-B BTB/POZ domains to homo- and heterodimerize in vivo, as shown by mammalian two-hybrid experiments. Both the HIC-1 and gammaFBP-B BTB/POZ domains behave as autonomous transcriptional repression domains. However, in striking contrast with BCL-6 and PLZF, both HIC-1 and gammaFBP-B similarly fail to interact with members of the HDAC complexes (SMRT/N-CoR, mSin3A or HDAC-1) in vivo and in vitro. In addition, a general and specific inhibitor of HDACs, trichostatin A, did not alleviate the HIC-1- and gammaFBP-B-mediated transcriptional repression, as previously shown for BCL-6. Taken together, our studies show that the recruitment onto target promoters of an HDAC complex is not a general property of transcriptional repressors containing a conserved BTB/POZ domain.
Studies in vitro on the relative efficacy of current acaricides for Sarcoptes scabiei var. hominis (2000)

Resistance of Sarcoptes scabiei to various topical therapies has been described, but clinical assessment of treatment failure is problematic and in-vitro assays are generally not available. We describe a simple in-vitro analysis used to evaluate the relative efficacy of a range of topical, oral, and herbal treatments available in Australia for the treatment of scabies. S. scabiei var. hominis mites were collected from skin scrapings obtained from 7 crusted scabies patients over a period of 2 years (1997 and 1998). Larvae, nymphal instars, and adult mites were tested within 3 h of collection and continuously exposed to selected commercially available treatment products until death, with the elapsed time recorded. Neem was the only product to show little acaricidal activity. Survival curves indicated that, of the other agents, 5% permethrin (Lyclear) had the slowest killing time, with 35% of mites still alive after 3 h, and 4% still alive after 18-22 h of constant exposure. In contrast, no mites were alive after 3 h exposure to 25% benzyl benzoate (Ascabiol), 1% lindane (Quellada), 5% tea tree oil and 100-8000 ng/g of ivermectin (Equimec). Despite the slower killing time with 5% permethrin, there was no evidence of any mite tolerance in vivo or treatment failure in any patients or contact cases.
Dynamic distribution of the replacement histone variant H3.3 in the mouse oocyte and preimplantation embryos (2006)

Upon fertilization, the gametes undergo a drastic reprogramming that includes changes in DNA methylation and histone modifications. Currently, it is not known whether replacement of the major histones by histone variants is also involved in these processes. Here we have examined the expression and localization of the histone variant H3.3 in early mouse embryogenesis. We show that H3.3 is present in the oocyte as a maternal factor. It is then incorporated preferentially into the male pronucleus before genome activation, pointing towards an asymmetry in histone composition between the two pronuclei. This is in line with the male pronucleus bearing transcriptional activation first. The same distribution was observed when we followed the localisation of a tagged version of H3.3. We detected H3.3 in the nuclei of mouse embryos in all of the stages analysed, from the zygote to the blastocyst stage, suggesting that the epigenetic mechanisms in the early embryo not only involve changes in histone modifications but may also include histone replacement.
New Strategies for the Elimination of Polio from India (2006)

The feasibility of global polio eradication is being questioned as a result of continued transmission in a few localities that act as sources for outbreaks elsewhere. Perhaps the greatest challenge is in India, where transmission has persisted in Uttar Pradesh and Bihar despite high coverage with multiple doses of vaccine. We estimate key parameters governing the seasonal epidemics in these areas and show that high population density and poor sanitation cause persistence by not only facilitating transmission of poliovirus but also severely compromising the efficacy of the trivalent vaccine. We analyze strategies to counteract this and show that switching to monovalent vaccine may finally interrupt virus transmission.
Investigating Cellular Signaling Reactions in Single Attoliter Vesicles (2005)

Understanding cellular signaling mediated by cell surface receptors is key to modern biomedical research and drug development. The discovery of a growing number of potential molecular targets and therapeutic compounds requires downscaling and accelerated functional screening. Receptor-mediated cellular responses are typically investigated on single cells or cell populations. Here, we show how to monitor cellular signaling reactions at a yet unreached miniaturization level. On the basis of our observations, cytochalasin induces mammalian cells to extrude from their plasma membrane submicrometer-sized native vesicles. They comprise functional cell surface receptors correctly exposing their extracellular ligand binding sites on the outer vesicle surface and retaining cytosolic proteins in the vesicle interior. As a prototypical example, ligand binding to the ionotropic 5-HT(3) receptor and subsequent transmembrane Ca(2+) signaling were monitored in single attoliter vesicles. Thus, native vesicles are the smallest autonomous containers capable of performing cellular signaling reactions under physiological conditions. Because a single cell delivers about 50 native vesicles, which can be isolated and addressed as individuals, our concept allows multiple functional analyses of individual cells having a limited availability and opens new vistas for miniaturized bioanalytics.
Interactions of doxycycline with chemotherapeutic agents in human breast adenocarcinoma MDA-MB-231 cells (2009)

Commonly used chemotherapeutic agents for breast cancer treatment include cisplatin, doxorubicin, and paclitaxel. Unfortunately, these effective antiproliferative agents are limited by their toxicities. Previously, we have shown that doxycycline can substantially reduce tumor burden in an animal model of breast cancer bone metastasis. The purpose of this study was to examine the effect of doxycycline in combination with chemotherapy. Human breast adenocarcinoma MDA-MB-231 cells were treated in vitro with each drug individually and in combination with doxycycline. Cell survival was determined using the clonogenic survival assay. Doxycycline in combination with doxorubicin or paclitaxel yielded therapeutic antagonism at all effect levels. Combinatory treatment with cisplatin, however, yielded a biphasic interaction, at low combinatorial doses, the effect was quantified as nearly additive, whereas higher doxycycline-cisplatin doses yielding greater than 50% cell inhibition resulted in synergistic effects. Cell cycle profiles were determined and showed that treatment with doxycycline, cisplatin, and doxorubicin resulted in G1-phase, S-phase, and G2/M-phase arrests, respectively. Upon addition of doxycycline to doxorubicin, the G2/M-arrest characteristic of doxorubicin-only treatment was abrogated, which may account for the observed antagonism. Cells treated with doxycycline and cisplatin showed a further increase in S-phase arrest, also observed with cisplatin alone, which may be responsible for the additive and synergistic effects on cell survival. We clearly show that doxycycline in combination with paclitaxel or doxorubicin treatment resulted in antagonism; however, combining doxycycline with cisplatin led to synergistic interactions at higher effect levels. The increased potency of cisplatin may warrant dose reduction and thus decrease toxicity in vivo.
TOLERANCE OF POLISH NEW CUCUMBER F1 HYBRIDS TO DOWNY MILDEW (PSEUDOPERONOSPORA CUBENSIS BERK & CURT) AND LIMITATION OR ELIMINATION CHEMICAL DISEASE CONTROL. (1994)

ISHS VII International Symposium on Timing Field Production of Vegetables TOLERANCE OF POLISH NEW CUCUMBER F1 HYBRIDS TO DOWNY MILDEW (PSEUDOPERONOSPORA CUBENSIS BERK & CURT) AND LIMITATION OR ELIMINATION CHEMICAL DISEASE CONTROL.