MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin

PubMed Central

Di Gregoli, Karina; Mohamad Anuar, Nur Najmi; Bianco, Rosaria; White, Stephen J.; Newby, Andrew C.; George, Sarah J.

2017-01-01

Rationale: Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with many cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm stability are poorly understood. Objective: To investigate whether miR-181b regulates tissue inhibitor of metalloproteinase-3 expression and affects atherosclerosis and aneurysms. Methods and Results: Here, we demonstrate that miR-181b was overexpressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms and correlated with decreased expression of predicted miR-181b targets, tissue inhibitor of metalloproteinase-3, and elastin. Using the well-characterized mouse atherosclerosis models of Apoe−/− and Ldlr−/−, we observed that in vivo administration of locked nucleic acid anti-miR-181b retarded both the development and the progression of atherosclerotic plaques. Systemic delivery of anti-miR-181b in angiotensin II–infused Apoe−/− and Ldlr−/− mice attenuated aneurysm formation and progression within the ascending, thoracic, and abdominal aorta. Moreover, miR-181b inhibition greatly increased elastin and collagen expression, promoting a fibrotic response and subsequent stabilization of existing plaques and aneurysms. We determined that miR-181b negatively regulates macrophage tissue inhibitor of metalloproteinase-3 expression and vascular smooth muscle cell elastin production, both important factors in maintaining atherosclerotic plaque and aneurysm stability. Validation studies in Timp3−/− mice confirmed that the beneficial effects afforded by miR-181b inhibition are largely tissue inhibitor of metalloproteinase-3 dependent, while also revealing an additional protective effect through elevating elastin synthesis. Conclusions: Our findings suggest that the management of miR-181b and its target genes provides therapeutic potential for limiting the progression of atherosclerosis and aneurysms and protecting them from rupture. PMID:27756793

MicroRNA-181b Controls Atherosclerosis and Aneurysms Through Regulation of TIMP-3 and Elastin.

PubMed

Di Gregoli, Karina; Mohamad Anuar, Nur Najmi; Bianco, Rosaria; White, Stephen J; Newby, Andrew C; George, Sarah J; Johnson, Jason L

2017-01-06

Atherosclerosis and aneurysms are leading causes of mortality worldwide. MicroRNAs (miRs) are key determinants of gene and protein expression, and atypical miR expression has been associated with many cardiovascular diseases; although their contributory role to atherosclerotic plaque and abdominal aortic aneurysm stability are poorly understood. To investigate whether miR-181b regulates tissue inhibitor of metalloproteinase-3 expression and affects atherosclerosis and aneurysms. Here, we demonstrate that miR-181b was overexpressed in symptomatic human atherosclerotic plaques and abdominal aortic aneurysms and correlated with decreased expression of predicted miR-181b targets, tissue inhibitor of metalloproteinase-3, and elastin. Using the well-characterized mouse atherosclerosis models of Apoe - /- and Ldlr -/- , we observed that in vivo administration of locked nucleic acid anti-miR-181b retarded both the development and the progression of atherosclerotic plaques. Systemic delivery of anti-miR-181b in angiotensin II-infused Apoe -/- and Ldlr -/- mice attenuated aneurysm formation and progression within the ascending, thoracic, and abdominal aorta. Moreover, miR-181b inhibition greatly increased elastin and collagen expression, promoting a fibrotic response and subsequent stabilization of existing plaques and aneurysms. We determined that miR-181b negatively regulates macrophage tissue inhibitor of metalloproteinase-3 expression and vascular smooth muscle cell elastin production, both important factors in maintaining atherosclerotic plaque and aneurysm stability. Validation studies in Timp3 -/- mice confirmed that the beneficial effects afforded by miR-181b inhibition are largely tissue inhibitor of metalloproteinase-3 dependent, while also revealing an additional protective effect through elevating elastin synthesis. Our findings suggest that the management of miR-181b and its target genes provides therapeutic potential for limiting the progression of atherosclerosis and aneurysms and protecting them from rupture. © 2016 The Authors.

Silencing miR-181a produces neuroprotection against hippocampus neuron cell apoptosis post-status epilepticus in a rat model and in children with temporal lobe epilepsy.

PubMed

Ren, L; Zhu, R; Li, X

2016-02-22

Epilepsy is one of the most frequent neurological disorders. Recently, the regulation of microRNAs was found to be associated with epilepsy, but the molecular mechanism by which microRNA influences epilepsy process remains to be unveiled and the development of microRNA-based therapy requires more intensive research. In this study, five microRNAs with potential relevance to epilepsy were initially chosen: miR-132, miR-146a, miR-181a, miR-34a, and miR-124. Twenty-five children who were patients with epilepsy were selected as subjects to obtain tissue samples for the study. The miRNA-181a, which represented the most increased fold-changes in clinical samples, were then selected for further function study in mouse model. The temporal lobe epilepsy (TLE) model, along with lithium-pilocarpine-induced status epilepticus (SE), was established in Sprague-Dawley rats. The antagomir of miR-181a was used to determine the role of miR-181a in cell apoptosis. Analyses were conducted to determine the expression levels of miR-181a, neuronal apoptosis in post-SE, and activated caspase-3. We found evidence of significant time dependent up-regulation of miR-181a amongst post-SE rats and TLE on 24 h (4.47 ± 0.35), 7 days (4.85 ± 0.53), and 2 weeks (5.66 ± 0.64). Experiments with the miR-181a antagomir showed that this particular miRNA led to the inhibition of the protein expression of caspase-3, and was up-regulated in the course of seizure-induced neuronal apoptosis. This study provided evidence that targeting miR-181a leads to a neuroprotective response and is linked to an increase in the activation of the caspase-3 protein. These findings suggest that miR-181a may serve as a promising therapeutic target for epilepsy.

MicroRNA-30d and microRNA-181a regulate HOXA11 expression in the uterosacral ligaments and are overexpressed in pelvic organ prolapse

PubMed Central

Jeon, Myung Jae; Kim, Eun Jae; Lee, Maria; Kim, Hoguen; Choi, Jong Rak; Chae, Hee Dong; Moon, Yeo Jung; Kim, Sei Kwang; Bai, Sang Wook

2015-01-01

The balanced turnover of collagen is necessary to maintain the mechanical strength of pelvic supportive connective tissues. Homeobox (HOX) A11 is a key transcriptional factor that controls collagen metabolism and homoeostasis in the uterosacral ligaments (USLs), and the deficient HOXA11 signalling may contribute to alterations in the biochemical strength of the USLs, leading to pelvic organ prolapse (POP). However, it is unknown how HOXA11 transcripts are regulated in the USLs. In this study, we found that microRNA (miRNA)-30d and 181a were overexpressed in women with POP, and their expression was inversely correlated with HOXA11 mRNA levels. The overexpression of miR-30d or 181a suppressed HOXA11 mRNA and protein levels in 293T cells, whereas the knockdown of these miRNAs enhanced HOXA11 levels and collagen production. Cotransfection of a luciferase reporter plasmid containing the 3′-untranslated region of HOXA11 with miR-30d or 181a mimic resulted in decreased relative luciferase activity. Conversely, cotransfection with anti-miR-30d or 181a increased luciferase activity. Taken together, these results indicate that both miR-30d and 181a are important posttranscriptional regulators of HOXA11 in the USLs and could be a potential therapeutic target for POP. PMID:25630974

Investigating the Impact of Asp181 Point Mutations on Interactions between PTP1B and Phosphotyrosine Substrate

NASA Astrophysics Data System (ADS)

Liu, Mengyuan; Wang, Lushan; Sun, Xun; Zhao, Xian

2014-05-01

Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of insulin and leptin signaling, which suggests that it is an attractive therapeutic target in type II diabetes and obesity. The aim of this research is to explore residues which interact with phosphotyrosine substrate can be affected by D181 point mutations and lead to increased substrate binding. To achieve this goal, molecular dynamics simulations were performed on wild type (WT) and two mutated PTP1B/substrate complexes. The cross-correlation and principal component analyses show that point mutations can affect the motions of some residues in the active site of PTP1B. Moreover, the hydrogen bond and energy decomposition analyses indicate that apart from residue 181, point mutations have influence on the interactions of substrate with several residues in the active site of PTP1B.

Blood lead concentrations in mallards from Delevan and Colusa National Wildlife Refuges

USGS Publications Warehouse

Mauser, David M.; Rocke, Tonie E.; Mensik, John G.; Brand, Christopher J.

1990-01-01

Blood samples were taken from 181 (108 adult drakes and 73 individuals of mixed age and sex) mallards, Anas platyrhynchos , from Colusa and Delevan National Wildlife Refuges during late winter and summer of 1987. The percentage of birds with elevated lead concentration was 28.7 for late winter and 16.4 for late summer. For summer trapped birds, a significantly greater proportion of males than females contained elevated lead levels. These findings indicate that lead poisoning may be a year-round event in certain areas of the Sacramento Valley.

Upregulation of miR-181c contributes to chemoresistance in pancreatic cancer by inactivating the Hippo signaling pathway.

PubMed

Chen, Meiyuan; Wang, Min; Xu, Simiao; Guo, Xingjun; Jiang, Jianxin

2015-12-29

The Hippo signaling pathway plays a crucial role in regulating tissue homeostasis, organ size, tumorigenesis and cancer chemoresistance when deregulated. Physiologically, the Hippo core kinase cassette that consists of mamma-lian STE20-like protein kinase 1/2 (MST1/2), and large tumour suppressor 1/2 (LATS1/2), together with the adaptor proteins Salvador homologue 1 (SAV1) and MOB kinase activator 1 (MOB1), tightly restricts the activities of homologous oncoproteins Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) to low levels. However, how the Hippo kinase cassette core components are simultaneously inhibited, to exhibit constitutively inactivated Hippo signaling and activated YAP/TAZ in cancer remains puzzling. Herein, we reported that miR-181c directly repressed MST1, LATS2, MOB1 and SAV1 expression in human pancreatic cancer cells. Overexpression of miR-181c induced hyperactivation of the YAP/TAZ and enhanced expression of the Hippo signaling downstream genes CTGF, BIRC5 and BLC2L1, leading to pancreatic cancer cell survival and chemoresistance in vitro and in vivo. Importantly, high miR-181c levels were significantly correlated with Hippo signaling inactivation in pancreatic cancer samples, and predicted a poor patient overall survival. These findings provide a novel mechanism for Hippo signaling inactivation in cancer, indicating not only a potentially pivotal role for miR-181c in the progression of pancreatic cancer, but also may represent a new therapeutic target and prognostic marker.

Psychiatric epidemiologic study of occupational lead exposure

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

Parkinson, D.K.; Ryan, C.; Bromet, E.J.

1986-02-01

The association of occupational lead exposure with neuropsychiatric functioning was evaluated using data collected in 1982 in eastern Pennsylvania from 288 lead-exposed workers and 181 nonexposed subjects. Both current and cumulative exposure indices were used. After controlling for age, education, and income, few meaningful differences between exposed and control workers were found on either neuropsychologic or psychosocial variables. Dose-response analyses indicated that among lead-exposed workers, cumulative and current exposure were unrelated to neuropsychologic performance. The only meaningful associations occurred between exposure and level of conflict in interpersonal relationships. The results thus give evidence against hypotheses suggesting adverse neuropsychologic effects.

21 CFR 181.22 - Certain substances employed in the manufacture of food-packaging materials.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Certain substances employed in the manufacture of... INGREDIENTS Specific Prior-Sanctioned Food Ingredients § 181.22 Certain substances employed in the manufacture....23, 181.24, 181.25, 181.26, 181.27, 181.28, 181.29, and 181.30 in the manufacture of packaging...

Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier

PubMed Central

Tominaga, Naoomi; Kosaka, Nobuyoshi; Ono, Makiko; Katsuda, Takeshi; Yoshioka, Yusuke; Tamura, Kenji; Lötvall, Jan; Nakagama, Hitoshi; Ochiya, Takahiro

2015-01-01

Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood–brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell–cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the destruction of BBB through the abnormal localization of actin via the downregulation of its target gene, PDPK1. PDPK1 degradation by miR-181c leads to the downregulation of phosphorylated cofilin and the resultant activated cofilin-induced modulation of actin dynamics. Furthermore, we demonstrate that systemic injection of brain metastatic cancer cell-derived EVs promoted brain metastasis of breast cancer cell lines and are preferentially incorporated into the brain in vivo. Taken together, these results indicate a novel mechanism of brain metastasis mediated by EVs that triggers the destruction of BBB. PMID:25828099

The membrane fusion enigma: SNAREs, Sec1/Munc18 proteins, and their accomplices--guilty as charged?

PubMed

Rizo, Josep; Südhof, Thomas C

2012-01-01

Neurotransmitter release is governed by proteins that have homo-logs in most types of intracellular membrane fusion, including the Sec1/Munc18 protein Munc18-1 and the SNARE proteins syntaxin-1, synaptobrevin/VAMP, and SNAP-25. The SNAREs initiate fusion by forming tight SNARE complexes that bring the vesicle and plasma membranes together. SNARE maintenance in a functional state depends on two chaperone systems (Hsc70/αCSP/SGT and synuclein); defects in these systems lead to neurodegeneration. Munc18-1 binds to an autoinhibitory closed conformation of syntaxin-1, gating formation of SNARE complexes, and also binds to SNARE complexes, which likely underlies the crucial function of Munc18-1 in membrane fusion by an as-yet unclear mechanism. Syntaxin-1 opening is mediated by Munc13s through their MUN domain, which is homologous to diverse tethering factors and may also have a general role in fusion. MUN domain activity is likely modulated in diverse presynaptic plasticity processes that depend on Ca(2+) and RIM proteins, among others.

Characterization of Three Vasopressin Receptor 2 Variants: An Apparent Polymorphism (V266A) and Two Loss-of-Function Mutations (R181C and M311V)

PubMed Central

Armstrong, Stephen P.; Seeber, Ruth M.; Ayoub, Mohammed Akli; Feldman, Brian J.; Pfleger, Kevin D. G.

2013-01-01

Arginine vasopressin (AVP) is released from the posterior pituitary and controls water homeostasis. AVP binding to vasopressin V2 receptors (V2Rs) located on kidney collecting duct epithelial cells triggers activation of Gs proteins, leading to increased cAMP levels, trafficking of aquaporin-2 water channels, and consequent increased water permeability and antidiuresis. Typically, loss-of-function V2R mutations cause nephrogenic diabetes insipidus (NDI), whereas gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Here we provide further characterization of two mutant V2Rs, R181C and M311V, reported to cause complete and partial NDI respectively, together with a V266A variant, in a patient diagnosed with NSIAD. Our data in HEK293FT cells revealed that for cAMP accumulation, AVP was about 500- or 30-fold less potent at the R181C and M311V mutants than at the wild-type receptor respectively (and about 4000- and 60-fold in COS7 cells respectively). However, in contrast to wild type V2R, the R181C mutant failed to increase inositol phosphate production, while with the M311V mutant, AVP exhibited only partial agonism in addition to a 37-fold potency decrease. Similar responses were detected in a BRET assay for β-arrestin recruitment, with the R181C receptor unresponsive to AVP, and partial agonism with a 23-fold decrease in potency observed with M311V in both HEK293FT and COS7 cells. Notably, the V266A V2R appeared functionally identical to the wild-type receptor in all assays tested, including cAMP and inositol phosphate accumulation, β-arrestin interaction, and in a BRET assay of receptor ubiquitination. Each receptor was expressed at comparable levels. Hence, the M311V V2R retains greater activity than the R181C mutant, consistent with the milder phenotype of NDI associated with this mutant. Notably, the R181C mutant appears to be a Gs protein-biased receptor incapable of signaling to inositol phosphate or recruiting β-arrestin. The etiology of NSIAD in the patient with V266A V2R remains unknown. PMID:23762448

Characterization of three vasopressin receptor 2 variants: an apparent polymorphism (V266A) and two loss-of-function mutations (R181C and M311V).

PubMed

Armstrong, Stephen P; Seeber, Ruth M; Ayoub, Mohammed Akli; Feldman, Brian J; Pfleger, Kevin D G

2013-01-01

Arginine vasopressin (AVP) is released from the posterior pituitary and controls water homeostasis. AVP binding to vasopressin V2 receptors (V2Rs) located on kidney collecting duct epithelial cells triggers activation of Gs proteins, leading to increased cAMP levels, trafficking of aquaporin-2 water channels, and consequent increased water permeability and antidiuresis. Typically, loss-of-function V2R mutations cause nephrogenic diabetes insipidus (NDI), whereas gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis (NSIAD). Here we provide further characterization of two mutant V2Rs, R181C and M311V, reported to cause complete and partial NDI respectively, together with a V266A variant, in a patient diagnosed with NSIAD. Our data in HEK293FT cells revealed that for cAMP accumulation, AVP was about 500- or 30-fold less potent at the R181C and M311V mutants than at the wild-type receptor respectively (and about 4000- and 60-fold in COS7 cells respectively). However, in contrast to wild type V2R, the R181C mutant failed to increase inositol phosphate production, while with the M311V mutant, AVP exhibited only partial agonism in addition to a 37-fold potency decrease. Similar responses were detected in a BRET assay for β-arrestin recruitment, with the R181C receptor unresponsive to AVP, and partial agonism with a 23-fold decrease in potency observed with M311V in both HEK293FT and COS7 cells. Notably, the V266A V2R appeared functionally identical to the wild-type receptor in all assays tested, including cAMP and inositol phosphate accumulation, β-arrestin interaction, and in a BRET assay of receptor ubiquitination. Each receptor was expressed at comparable levels. Hence, the M311V V2R retains greater activity than the R181C mutant, consistent with the milder phenotype of NDI associated with this mutant. Notably, the R181C mutant appears to be a Gs protein-biased receptor incapable of signaling to inositol phosphate or recruiting β-arrestin. The etiology of NSIAD in the patient with V266A V2R remains unknown.

miR-181a shows tumor suppressive effect against oral squamous cell carcinoma cells by downregulating K-ras

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

Shin, Ki-Hyuk, E-mail: kshin@dentistry.ucla.edu; Dental Research Institute, University of California, Los Angeles, CA 90095; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095

2011-01-28

Research highlights: {yields} MicroRNA-181a (miR-181a) was frequently downregulated in oral squamous cell carcinoma (OSCC). {yields} Overexpression of miR-181a suppressed OSCC growth. {yields} K-ras is a novel target of miR-181a. {yields} Decreased miR-181a expression is attributed to its lower promoter activity in OSCC. -- Abstract: MicroRNAs (miRNAs) are epigenetic regulators of gene expression, and their deregulation plays an important role in human cancer, including oral squamous cell carcinoma (OSCC). Recently, we found that miRNA-181a (miR-181a) was upregulated during replicative senescence of normal human oral keratinocytes. Since senescence is considered as a tumor suppressive mechanism, we thus investigated the expression and biologicalmore » role of miR-181a in OSCC. We found that miR-181a was frequently downregulated in OSCC. Ectopic expression of miR-181a suppressed proliferation and anchorage independent growth ability of OSCC. Moreover, miR-181a dramatically reduces the growth of OSCC on three dimensional organotypic raft culture. We also identified K-ras as a novel target of miR-181a. miR-181a decreased K-ras protein level as well as the luciferase activity of reporter vectors containing the 3'-untranslated region of K-ras gene. Finally, we defined a minimal regulatory region of miR-181a and found a positive correlation between its promoter activity and the level of miR-181a expression. In conclusion, miR-181a may function as an OSCC suppressor by targeting on K-ras oncogene. Thus, miR-181a should be considered for therapeutic application for OSCC.« less

miR-181b Promotes hepatic stellate cells proliferation by targeting p27 and is elevated in the serum of cirrhosis patients

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

Wang, Baocan; Li, Wenxi; Guo, Kun

2012-04-27

Highlights: Black-Right-Pointing-Pointer miR-181a and miR-181b, especially, miR-181b could be induced by transforming growth factor-beta 1 (TGF-{beta}1) in hepatic stellate cells. Black-Right-Pointing-Pointer miR-181b could promote HSC-T6 cell proliferation by directly targeting the negative cell regulator-p27 in HSC-T6 cell. Black-Right-Pointing-Pointer miR-181b was identified as potential serum diagnostic marker for liver cirrhosis patients. -- Abstract: MicroRNAs, as a kind of negative gene regulators, were demonstrated to be involved in many types of diseases. In this study, we found that transforming growth factor-beta 1 could induce the expression of miR-181a and miR-181b, and miR-181b increased in the much higher folds than miR-181a. Because ofmore » the important role of transforming growth factor-beta 1 in HSC activation and liver cirrhosis, we investigate the effect of miR-181a and miR-181b on HSC proliferation. The results showed that miR-181b could promote HSC-T6 cell proliferation by regulating cell cycle. Further study showed p27, the cell cycle regulator, was the direct target of miR-181b in HSC-T6 cell. But miR-181a had no effects on HSC-T6 cell proliferation and cell cycle, and did not target p27. Interestingly, miR-181b is elevated significantly in serum of liver cirrhosis cases comparing to that of normal persons, whereas miR-181a expression was in the similar level with that of normal persons. These results suggested that miR-181b could be induced by TGF-{beta}1 and promote the growth of HSCs by directly targeting p27. The elevation of miR-181b in serum suggested that it may be potential diagnostic biomarkers for cirrhosis. As for miR-181a, it may work in TGF-{beta}1 pathway by a currently unknown mechanism.« less

Fatty acid anilides: in vivo formation and relevance to toxic oil syndrome.

PubMed

Kaphalia, B S; Khan, M F; Ansari, G A

1999-01-01

Toxic oil syndrome (TOS), a multisystemic epidemic outbreak in 1981 in Spain, was caused by the ingestion of a cooking oil mixture containing rapeseed oil denatured with aniline. The mechanisms and causative agents responsible for the TOS are still not known. Although primary lesions observed in TOS patients could not be reproduced experimentally, the levels of fatty acid anilides (FAAs) and aniline in TOS-related cooking oil were considered proximate markers of TOS. Aniline, available from free aniline and FAAs ingested with TOS-related cooking oil, and its reconjugation with endogenous fatty acids could be an early event leading to TOS. Therefore, the present study was undertaken to determine the formation of FAAs following an oral dose of 2 mmol/kg aniline hydrochloride (AH) via gavage in rats. Here, 16:0, 18:0, 18:1, 18:2, 18:3, and 20:4 FAAs were analyzed in the whole blood, brown fat, liver, and pancreas at 0 (control), 0.25, 0.5, 1, 3, 6, 12, 24, and 48 hours. Generally, 16:0 and 18:1 FAAs were detected in the whole blood, brown fat, and liver of AH-treated rats with highest mean levels at 0.25 or 0.5 hour, except 3 hours for the whole blood. Only 16:0 FAA was detectable in the pancreas of AH-treated animals. The 18:0 FAA was also detected frequently in the liver while other FAAs were either in trace amounts or not detectable in the tissues analyzed in the present study. Overall, highest formation of the 16:0 FAA was found in the liver followed by pancreas and of 18:1 FAA in the whole blood and brown fat. These results indicate a rapid formation and further metabolism and disposition of FAAs in rat model and support our previous findings that 18:1 and 16:0 fatty acids are better substrates for the conjugation with aniline. Surprisingly, a small or trace amount of a few FAAs also detected in the tissues of control rats indicates their endogenous biosynthesis and/or presence. Results of 18:1 fatty acid incubation and aniline in the presence of fatty acid ethyl ester synthase, purified to homogeneity from rat liver microsome, suggest that formation of FAAs is catalyzed by an enzyme involved in the conjugation of fatty acids with xenobiotic alcohols. Because the FAAs are known to exert a wide range of toxicity in experimental animals and primary cell cultures, in vivo formation of FAAs could be an early event leading to TOS.

Environmental Lead (Pb) Exposure Versus Fatty Acid Content in Blood and Milk of the Mother and in the Blood of Newborn Children.

PubMed

Baranowska-Bosiacka, Irena; Kosińska, Ida; Jamioł, Dominika; Gutowska, Izabela; Prokopowicz, Adam; Rębacz-Maron, Ewa; Goschorska, Marta; Olszowski, Tomasz; Chlubek, Dariusz

2016-04-01

Significant progress in understanding the effects of the neurotoxic action of lead (Pb) in young organisms had led to reduction of "safe" level in the blood (Pb-B) to 5 μg/dL in children and pregnant women. Prolonged exposure to relatively low levels of Pb, generally asymptomatic and subclinical (i.e., microintoxication), is currently the dominant form of environmental poisoning, and its negative effects on health may appear after many years, e.g., secondary contamination from Pb bone deposits released in pregnancy. Therefore, the aim of this study was to investigate the effect of environmental exposure (urban areas) of mothers to Pb, on its levels in their milk and blood and in the blood of newborns. Moreover, the aim was to determine the fatty acid profile in the mothers' blood and milk and in the blood of newborns. We also wanted to find if infant birth weight depends on Pb blood levels, as well as on Pb and fatty acid levels in the blood and milk of the mothers. Finally, we examined if the mothers' weight and body mass index (BMI) before pregnancy influenced the concentration of Pb and fatty acid profile in the blood and milk of mothers and in the blood of their children. Analysis of fatty acids elaidic (C18:1, 9t), oleic (C18:1, 9c), vaccenic (C18:1, 11t), cis-vaccenic (C18:1, 11c), linoleic (C18:2, cis), γ-linolenic (C18:3, n-6), α-linolenic (C18:3, n-3), arachidonic (C20:4, n-6), eicosapentaenoic (C20:5, n-3), and docosahexaenoic (C22:6, n-3) was conducted by gas chromatography. The concentration of Pb in the whole blood and milk were determined by atomic absorption spectrometry with graphite furnace atomization and Zeeman correction. Our study established a significant and strong correlation between the content of Pb in the blood of the mother and the child. This supports the assumption that the transport of Pb through the placenta is neither regulated nor selective. Environmental maternal exposure to lead resulting in Pb-B levels considered safe for pregnant women had no effect on infant birth weight, the concentration of fatty acids in the blood and milk of mothers, or in the blood of newborns. Mothers' weight and BMI before pregnancy had no effect on the concentration of Pb and studied fatty acid profile.

Indolyl aryl sulfones (IASs): development of highly potent NNRTIs active against wt-HIV-1 and clinically relevant drug resistant mutants.

PubMed

Silvestri, Romano; Artico, Marino

2005-01-01

Indolyl aryl sulfones (IASs) are a potent class of NNRTIs developed from L-737,126, a lead agent discovered by Merck AG. IAS derivatives are endowed with inhibitory activities against wt HIV-1 in the low nanomolar concentration range. Introduction of two methyl groups at positions 3 and 5 of the phenyl ring of the aryl sulfonyl moiety furnished IAS derivatives such as 5-chloro- or 5-bromo-3-[(3,5-dimethylphenyl)sulfonyl]indole-2-carboxyamide, which showed very potent and selective anti-HIV-1 activity against some mutants carrying NNRTI resistant mutations at positions 103 and 181 of the reverse transcriptase. IAS derivatives bearing 2-hydroxyethylcarboxyamide or 2-hydroxyethylcarboxyhydrazide groups at position 2 of the indole nucleus were more active than L-737,126 against the K103N-Y181C double mutant. A great improvement of antiviral activity against wt HIV-1 and resistant mutants was obtained by coupling 1-3 simple amino acids, such as glycine and alanine, in sequence, with the 3-[(3,5-dimethylphenyl)sulfonyl]-1H-indole-2-carbonyl moiety. The transformation of the chain terminus into amide or hydrazide, produced short peptides with high selectivity and potent activity against wt HIV-1, and the viral mutants Y181C, K103N-Y181C and EFV(R). IAS having two halogen atoms at the indole showed potent inhibitory activity against the Y181C and the EFV(R) resistant mutant strains. In particular, the introduction of a fluorine atom at position 4 of the indole ring notably contributed to improve the antiviral activities against both wt and the related resistant mutants. 5-Nitro-IASs were highly active against wt HIV-1 and exhibited low cytotoxicity. Experimental data highlighted the class IAS derivatives as promising candidates for clinical trials.

Three centuries of heavy metal pollution in Paris (France) recorded by urban speleothems.

PubMed

Pons-Branchu, Edwige; Ayrault, Sophie; Roy-Barman, Matthieu; Bordier, Louise; Borst, Wolfgang; Branchu, Philippe; Douville, Eric; Dumont, Emmanuel

2015-06-15

The first record of urban speleothems used to reconstruct the history of heavy metal pollution of shallow groundwaters is presented. Two speleothems grew during the last 300 years in an underground aqueduct in the north-eastern part of Paris. They display high Pb, Mn V, Cu, Cd and Al concentrations since 1900 due to the urbanization of the site which triggered anthropogenic contamination of the water feeding the speleothems. Surprisingly, these heavy metal concentrations are also high in the oldest part. This early pollution could come from the use of Parisian waste as fertilizers in the orchards and vineyards cultivated above the aqueduct before urbanization. Lead isotopes were measured in these carbonates as well as in lead artifacts from the 17th-18th centuries ((206)Pb/(207)Pb=1.180+/-0.003). The mean (206)Pb/(207)Pb ratio, for one of the speleothems is 1.181+/-0.003 unvarying with time. These lead signatures are close to those of coal and old lead from northern European mines, lower than the natural background signature. It confirms that the high metal concentrations found come from anthropogenic pollution. Conversely, the lead isotopic composition of the second speleothem presents two temporal trends: for the oldest levels, the mean value (1.183+/-0.003) is similar to the first speleothem. For the youngest part, a lower value (1.172+/-0.005) is recorded, evidencing the contribution of a new lead source at the beginning of the industrial revolution. Pb isotopes were also measured in recent samples from a nearby superficial site. The first sample is a recent (AD 1975+/-15 years) deposit ((206)Pb/(207)Pb=1.148+/-0.003), and the second, a thin subactual layer ((206)Pb/(207)Pb=1.181+/-0.002). These data are compatible with the adding of anthropogenic sources (leaded gasoline and industrial lead from Rio Tinto ore). Copyright © 2015 Elsevier B.V. All rights reserved.

19 CFR 181.122 - Disclosure to government authorities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Disclosure to government authorities. 181.122 Section 181.122 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... Information § 181.122 Disclosure to government authorities. Nothing in § 181.121 of this part shall preclude...

Phenotypic and genotypic characterization of influenza virus mutants selected with the sialidase fusion protein DAS181

PubMed Central

Triana-Baltzer, Gallen B.; Sanders, Rebecca L.; Hedlund, Maria; Jensen, Kellie A.; Aschenbrenner, Laura M.; Larson, Jeffrey L.; Fang, Fang

2011-01-01

Background Influenza viruses (IFVs) frequently achieve resistance to antiviral drugs, necessitating the development of compounds with novel mechanisms of action. DAS181 (Fludase®), a sialidase fusion protein, may have a reduced potential for generating drug resistance due to its novel host-targeting mechanism of action. Methods IFV strains B/Maryland/1/59 and A/Victoria/3/75 (H3N2) were subjected to >30 passages under increasing selective pressure with DAS181. The DAS181-selected IFV isolates were characterized in vitro and in mice. Results Despite extensive passaging, DAS181-selected viruses exhibited a very low level of resistance to DAS181, which ranged between 3- and 18-fold increase in EC50. DAS181-selected viruses displayed an attenuated phenotype in vitro, as exhibited by slower growth, smaller plaque size and increased particle to pfu ratios relative to wild-type virus. Further, the DAS181 resistance phenotype was unstable and was substantially reversed over time upon DAS181 withdrawal. In mice, the DAS181-selected viruses exhibited no greater virulence than their wild-type counterparts. Genotypic and phenotypic analysis of DAS181-selected viruses revealed mutations in the haemagglutinin (HA) and neuraminidase (NA) molecules and also changes in HA and NA function. Conclusions Results indicate that resistance to DAS181 is minimal and unstable. The DAS181-selected IFV isolates exhibit reduced fitness in vitro, likely due to altered HA and NA functions. PMID:21097900

Sphingosine in plants--more riddles from the Sphinx?

PubMed

Islam, M Nurul; Jacquemot, Marie-Pierre; Coursol, Sylvie; Ng, Carl K-Y

2012-01-01

• Sphingolipids are emerging as important mediators of cellular and developmental processes in plants, and advances in lipidomics have yielded a wealth of information on the composition of plant sphingolipidomes. Studies using Arabidopsis thaliana showed that the dihydroxy long-chain base (LCB) is desaturated at carbon position 8 (d18:1(Δ8)). This raised important questions on the role(s) of sphingosine (d18:1(Δ4)) and sphingosine-1-phosphate (d18:1(Δ4)-P) in plants, as these LCBs appear to be absent in A. thaliana. • Here, we surveyed 21 species from various phylogenetic groups to ascertain the position of desaturation of the d18:1 LCB, in order to gain further insights into the prevalence of d18:1(Δ4) and d18:1(Δ8) in plants. • Our results showed that d18:1(Δ8) is common in gymnosperms, whereas d18:1(Δ4) is widespread within nonseed land plants and the Poales, suggesting that d18:1(Δ4) is evolutionarily more ancient than d18:1(Δ8) in Viridiplantae. Additionally, phylogenetic analysis indicated that the sphingolipid Δ4-desaturases from Viridiplantae form a monophyletic group, with Angiosperm sequences falling into two distinct clades, the Eudicots and the Poales. • We propose that efforts to elucidate the role(s) of d18:1(Δ4) and d18:1(Δ4)-P should focus on genetically tractable Viridiplantae species where the d18:1 LCB is desaturated at carbon position 4. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

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

Xia, Ying; Gao, Yan, E-mail: gaoyanhdhos@126.com

Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (largemore » tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.« less

Protease Inhibition by Oleic Acid Transfer From Chronic Wound Dressings to Albumin

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

Edwards, J. V.; Howley, Phyllis; Davis, Rachel M.

High elastase and cathepsin G activities have been observed in chronic wounds. These levels can inhibit healing through degradation of growth factors, cytokines, and extracellular matrix proteins. Oleic acid (18:1) is a non-toxic elastase inhibitor with some potential for redressing the imbalance of elastase activity found in chronic wounds. Cotton wound dressing material was characterized as a transfer carrier for affinity uptake of 18:1 by albumin under conditions mimicking chronic wounds. 18:1-treated cotton was examined for its ability to bind and release the fatty acid in the presence of albumin. The mechanism of 18:1 uptake from cotton and binding bymore » albumin was examined with both intact dressings and cotton fiber-designed chromatography. Raman spectra of the albumin-18:1 complexes under liquid-liquid equilibrium conditions revealed fully saturated albumin-18:1 complexes with a 1:1 weight ratio of albumin:18:1. Cotton chromatography under liquid-solid equilibrium conditions revealed oleic acid transfer from cotton to albumin at 27 mole equivalents of 18:1 per mole albumin. Cotton was contrasted with hydrogel, and hydrocolloid wound dressing for its comparative ability to lower elastase activity. Each dressing material evaluated was found to release 18:1 in the presence of albumin with significant inhibition of elastase activity. The 18:1-formulated wound dressings lowered elastase activity in a dose dependent manner in the order cotton gauze > hydrogel > hydrocolloid. In contrast the cationic serine protease Cathepsin G was inihibited by 18:1 within a narrow range of 18:1-cotton formulations. Four per cent Albumin solutions were most effective in binding cotton bound-18:1. However, 2% albumin was sufficient to transfer quantities of 18:1 necessary to achieve a significant elastase-lowering effect. Formulations with 128 mg 18:1/g cotton gauze had equivalent elastase lowering with 1 - 4% albumin. 18:1 bound to cotton wound dressings may have promise in the selective lowering of cationic serine protease activity useful in topical application for chronic inflammatory pathogenesis.« less

46 CFR 181.610 - Fire bucket.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PROTECTION EQUIPMENT Additional Equipment § 181.610 Fire bucket. A vessel not required to have a power driven fire pump by § 181.300 must have at least three 9.5 liter (21/2 gallon) buckets, with an attached... 46 Shipping 7 2011-10-01 2011-10-01 false Fire bucket. 181.610 Section 181.610 Shipping COAST...

46 CFR 181.610 - Fire bucket.

Code of Federal Regulations, 2012 CFR

2012-10-01

... PROTECTION EQUIPMENT Additional Equipment § 181.610 Fire bucket. A vessel not required to have a power driven fire pump by § 181.300 must have at least three 9.5 liter (21/2 gallon) buckets, with an attached... 46 Shipping 7 2012-10-01 2012-10-01 false Fire bucket. 181.610 Section 181.610 Shipping COAST...

46 CFR 181.610 - Fire bucket.

Code of Federal Regulations, 2014 CFR

2014-10-01

... PROTECTION EQUIPMENT Additional Equipment § 181.610 Fire bucket. A vessel not required to have a power driven fire pump by § 181.300 must have at least three 9.5 liter (21/2 gallon) buckets, with an attached... 46 Shipping 7 2014-10-01 2014-10-01 false Fire bucket. 181.610 Section 181.610 Shipping COAST...

46 CFR 181.610 - Fire bucket.

Code of Federal Regulations, 2013 CFR

2013-10-01

... PROTECTION EQUIPMENT Additional Equipment § 181.610 Fire bucket. A vessel not required to have a power driven fire pump by § 181.300 must have at least three 9.5 liter (21/2 gallon) buckets, with an attached... 46 Shipping 7 2013-10-01 2013-10-01 false Fire bucket. 181.610 Section 181.610 Shipping COAST...

UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in Caenorhabditis elegans

PubMed Central

Park, Seungmee; Bin, Na-Ryum; Wong, Raymond; Sitarska, Ewa; Sugita, Kyoko; Ma, Ke; Algouneh, Arash; Turlova, Ekaterina; Wang, Siyan; Siriya, Pranay; Kalia, Lorraine; Feng, Zhong-Ping; Monnier, Philippe P.; Zhen, Mei; Gao, Shangbang

2017-01-01

Munc18-1/UNC-18 is believed to prime SNARE-mediated membrane fusion, yet the underlying mechanisms remain enigmatic. Here, we examine how potential gain-of-function mutations of Munc18-1/UNC-18 affect locomotory behavior and synaptic transmission, and how Munc18-1-mediated priming is related to Munc13-1/UNC-13 and Tomosyn/TOM-1, positive and negative SNARE regulators, respectively. We show that a Munc18-1(P335A)/UNC-18(P334A) mutation leads to significantly increased locomotory activity and acetylcholine release in Caenorhabditis elegans, as well as enhanced synaptic neurotransmission in cultured mammalian neurons. Importantly, similar to tom-1 null mutants, unc-18(P334A) mutants partially bypass the requirement of UNC-13. Moreover, unc-18(P334A) and tom-1 null mutations confer a strong synergy in suppressing the phenotypes of unc-13 mutants. Through biochemical experiments, we demonstrate that Munc18-1(P335A) exhibits enhanced activity in SNARE complex formation as well as in binding to the preformed SNARE complex, and partially bypasses the Munc13-1 requirement in liposome fusion assays. Our results indicate that Munc18-1/UNC-18 primes vesicle fusion downstream of Munc13-1/UNC-13 by templating SNARE complex assembly and acts antagonistically with Tomosyn/TOM-1. SIGNIFICANCE STATEMENT At presynaptic sites, SNARE-mediated membrane fusion is tightly regulated by several key proteins including Munc18/UNC-18, Munc13/UNC-13, and Tomosyn/TOM-1. However, how these proteins interact with each other to achieve the precise regulation of neurotransmitter release remains largely unclear. Using Caenorhabditis elegans as an in vivo model, we found that a gain-of-function mutant of UNC-18 increases locomotory activity and synaptic acetylcholine release, that it partially bypasses the requirement of UNC-13 for release, and that this bypass is synergistically augmented by the lack of TOM-1. We also elucidated the biochemical basis for the gain-of-function caused by this mutation. Thus, our study provides novel mechanistic insights into how Munc18/UNC-18 primes synaptic vesicle release and how this protein interacts functionally with Munc13/UNC-13 and Tomosyn/TOM-1. PMID:28821673

Self-Assembled Multivalent (SAMul) Polyanion Binding-Impact of Hydrophobic Modifications in the Micellar Core on DNA and Heparin Binding at the Peripheral Cationic Ligands.

PubMed

Albanyan, Buthaina; Laurini, Erik; Posocco, Paola; Pricl, Sabrina; Smith, David K

2017-05-05

This paper reports a small family of cationic surfactants designed to bind polyanions such as DNA and heparin. Each molecule has the same hydrophilic cationic ligand and a hydrophobic aliphatic group with eighteen carbon atoms with one, two, or three alkene groups within the hydrophobic chain (C18-1, C18-2 and C18-3). Dynamic light scattering indicates that more alkenes lead to geometric distortion, giving rise to larger self-assembled multivalent (SAMul) nanostructures. Mallard Blue and Ethidium Bromide dye displacement assays demonstrate that heparin and DNA have markedly different binding preferences, with heparin binding most effectively to C18-1, and DNA to C18-3, even though the molecular structural differences of these SAMul systems are buried in the hydrophobic core. Multiscale modelling suggests that adaptive heparin maximises enthalpically favourable interactions with C18-1, while shape-persistent DNA forms a similar number of interactions with each ligand display, but with slightly less entropic cost for binding to C18-3-fundamental thermodynamic differences in SAMul binding of heparin or DNA. This study therefore provides unique insight into electrostatic molecular recognition between highly charged nanoscale surfaces in biologically relevant systems. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Environmental lead and childhood blood lead levels in US children: NHANES, 1999-2006.

PubMed

Benson, Stacey M; Talbott, Evelyn O; Brink, LuAnn L; Wu, Candace; Sharma, Ravi K; Marsh, Gary M

2017-03-04

Although blood lead levels in the United States have fallen dramatically since 1980, there remain subgroups of children with high blood lead levels. We assessed the relationship between environmental lead sources and blood lead levels in children ages 1 to 5 years from the National Health and Nutrition Examination Survey (NHANES), 1999-2006. Modeled ambient air lead levels and industrial lead releases at the census-tract level were assigned to each child's residence with adjustment for confounding factors. Of 3,223 children, 272 (8.4%) had blood lead levels ≥ 5 ug/dL. Industrial releases (2,252 vs 1,696 lbs/mi 2 ) and ambient air lead levels (2.28 vs 1.75 ng/m 3 ) were greater in exposed versus unexposed children. For every 10,000 lb/mi 2 increase in inverse distance squared weighted exposure, there was a 1.13% increase (95% CI: 0.45%, 1.81%) in blood lead (p = .001).

Characterization of cis- and trans-octadecenoic acid positional isomers in edible fat and oil using gas chromatography-flame ionisation detector equipped with highly polar ionic liquid capillary column.

PubMed

Yoshinaga, Kazuaki; Asanuma, Masaharu; Mizobe, Hoyo; Kojima, Koichi; Nagai, Toshiharu; Beppu, Fumiaki; Gotoh, Naohiro

2014-10-01

In this study, the characterisation of all cis- and trans-octadecenoic acid (C18:1) positional isomers in partially hydrogenated vegetable oil (PHVO) and milk fat, which contain several cis- and trans-C18:1 positional isomers, was achieved by gas chromatography-flame ionisation detector equipped with a highly polar ionic liquid capillary column (SLB-IL111). Prior to analysis, the cis- and trans-C18:1 fractions in PHVO and milk fat were separated using a silver-ion cartridge. The resolution of all cis-C18:1 positional isomers was successfully accomplished at the optimal isothermal column temperature of 120 °C. Similarly, the positional isomers of trans-C18:1, except for trans-6-C18:1 and trans-7-C18:1, were separated at 120 °C. The resolution of trans-6-C18:1 and trans-7-C18:1 isomers was made possible by increasing the column temperature to 160 °C. This analytical method is suitable for determining the cis- and trans-C18:1 positional isomers in edible fats and oils. Copyright © 2014 Elsevier Ltd. All rights reserved.

Upregulation of miR-181a suppresses the formation of glioblastoma stem cells by targeting the Notch2 oncogene and correlates with good prognosis in patients with glioblastoma multiforme

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

Huang, Shi-Xiong; Zhao, Zhong-Yan; Weng, Guo-Hu

Glioblastoma stem-like cells (GSCs) are responsible for the initiation and progression of glioblastoma multiforme (GBM), and microRNAs (miRNAs) play an important role in this disease. However, the mechanisms underlying the role of miRNAs in the stemness of GSCs have not been completely elucidated. We previously showed that miR-181a is downregulated in GBM and may predict prognosis in patients with this disease. Here, we demonstrate that the upregulation of miR-181a suppressed GSC formation and inhibited GBM tumorigenesis by targeting the Notch2 oncogene. We found that miR-181a was downregulated in GSCs derived from human glioblastoma U87MG and U373MG cells. The high expressionmore » of miR-181a inhibited the levels of stemness-related markers CD133 and BMI1, attenuated sphere proliferation, promoted cell apoptosis, and reduced the tumorigenicity of GSCs. MiR-181a decreased the expression of Notch2 by targeting the 3’-untranslated region of its mRNA. Notch2 overexpression inhibited the effects of miR-181a downregulation on GSCs, and was negatively correlated with miR-181a expression. Moreover, high Notch2 expression together with low miR-181a expression was correlated with a shorter median overall survival for GBM patients. Together, these data show that miR-181a may play an essential role in GSC formation and GBM progression by targeting Notch2, suggesting that Notch2 and miR-181a have potential prognostic value as tumor biomarkers in GBM patients. - Highlights: • MiR-181a suppressed GSC formation and GBM tumorigenesis by targeting Notch2. • Notch2 and miR-181a expression were correlated with OS for GBM patients. • Notch2 and miR-181a have potential prognostic value in GBM patients.« less

40 CFR 464.15 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

....0095 Oil and grease (for alternate monitoring) 0.363 0.121 (c) Die Casting Operations. PSES Pollutant... Total phenols 0.0074 0.0026 TTO 0.0308 0.01 Oil and grease (for alternate monitoring) 0.259 0.0864 (d...) 8.48 4.63 Lead (T) 8.7 4.3 Zinc (T) 12.6 4.74 TTO 18.1 5.91 Oil and grease (for alternate monitoring...

40 CFR 436.181 - Specialized definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Specialized definitions. 436.181 Section 436.181 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS MINERAL MINING AND PROCESSING POINT SOURCE CATEGORY Phosphate Rock Subcategory § 436.181...

22 CFR 181.3 - Determinations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Determinations. 181.3 Section 181.3 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL AGREEMENTS COORDINATION, REPORTING AND PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.3 Determinations. (a) Whether any undertaking, document, or set of documents...

A meta-analysis of observational studies of the association between chronic occupational exposure to lead and amyotrophic lateral sclerosis.

PubMed

Wang, Ming-Dong; Gomes, James; Cashman, Neil R; Little, Julian; Krewski, Daniel

2014-12-01

The association between occupational exposure to lead and amyotrophic lateral sclerosis (ALS) was examined through systematic review and meta-analyses of relevant epidemiological studies and reported according to PRISMA guidelines. Relevant studies were searched in multiple bibliographic databases through September 2013; additional articles were tracked through PubMed until submission. All records were screened in DistillerSR, and the data extracted from included articles were synthesized with meta-analysis. The risk of developing ALS among individuals with a history of exposure to lead was almost doubled (odds ratio, 1.81; 95% confidence interval, 1.39 to 2.36) on the basis of nine included case-control studies with specific lead exposure information, with no apparent heterogeneity across included studies (I = 14%). The attributable risk of ALS because of exposure to lead was estimated to be 5%. Previous exposure to lead may be a risk factor for ALS.

22 CFR 181.6 - Documentation and certification.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Documentation and certification. 181.6 Section 181.6 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL AGREEMENTS COORDINATION, REPORTING AND PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.6 Documentation and certification. (a) Transmittals of concluded...

5 CFR 550.181 - Coverage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Coverage. 550.181 Section 550.181 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) Premium Pay Law Enforcement Availability Pay § 550.181 Coverage. (a) Each employee meeting the definition...

5 CFR 550.181 - Coverage.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Coverage. 550.181 Section 550.181 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) Premium Pay Law Enforcement Availability Pay § 550.181 Coverage. (a) Each employee meeting the definition...

5 CFR 550.181 - Coverage.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Coverage. 550.181 Section 550.181 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) Premium Pay Law Enforcement Availability Pay § 550.181 Coverage. (a) Each employee meeting the definition...

5 CFR 550.181 - Coverage.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Coverage. 550.181 Section 550.181 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) Premium Pay Law Enforcement Availability Pay § 550.181 Coverage. (a) Each employee meeting the definition...

5 CFR 550.181 - Coverage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Coverage. 550.181 Section 550.181 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PAY ADMINISTRATION (GENERAL) Premium Pay Law Enforcement Availability Pay § 550.181 Coverage. (a) Each employee meeting the definition...

49 CFR 37.181 - Applicability dates.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Applicability dates. 37.181 Section 37.181 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Over-the-Road Buses (OTRBs) § 37.181 Applicability dates. This subpart applies to all...

49 CFR 37.181 - Applicability dates.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 1 2011-10-01 2011-10-01 false Applicability dates. 37.181 Section 37.181 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Over-the-Road Buses (OTRBs) § 37.181 Applicability dates. This subpart applies to all...

50 CFR 216.181 - Effective dates.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Effective dates. 216.181 Section 216.181 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION... Frequency Active (SURTASS LFA sonar) Sonar § 216.181 Effective dates. Regulations in this subpart are...

MicroRNA-181a promotes docetaxel resistance in prostate cancer cells.

PubMed

Armstrong, Cameron M; Liu, Chengfei; Lou, Wei; Lombard, Alan P; Evans, Christopher P; Gao, Allen C

2017-06-01

Docetaxel is one of the primary drugs used for treating castration resistant prostate cancer (CRPC). Unfortunately, over time patients invariably develop resistance to docetaxel therapy and their disease will continue to progress. The mechanisms by which resistance develops are still incompletely understood. This study seeks to determine the involvement of miRNAs, specifically miR-181a, in docetaxel resistance in CRPC. Real-time PCR was used to measure miR-181a expression in parental and docetaxel resistant C4-2B and DU145 cells (TaxR and DU145-DTXR). miR-181a expression was modulated in parental or docetaxel resistant cells by transfecting them with miR-181a mimics or antisense, respectively. Following transfection, cell number was determined after 48 h with or without docetaxel. Cross resistance to cabazitaxel induced by miR-181a was also determined. Western blots were used to determine ABCB1 protein expression and rhodamine assays used to assess activity. Phospho-p53 expression was assessed by Western blot and apoptosis was measured by ELISA in C4-2B TaxR and PC3 cells with inhibited or overexpressed miR-181a expression with or without docetaxel. miR-181a is significantly overexpressed in TaxR and DU145-DTXR cells compared to parental cells. Overexpression of miR-181a in parental cells confers docetaxel and cabazitaxel resistance and knockdown of miR-181a in TaxR cells re-sensitizes them to treatment with both docetaxel and cabazitaxel. miR-181a was not observed to impact ABCB1 expression or activity, a protein which was previously demonstrated to be highly involved in docetaxel resistance. Knockdown of miR-181a in TaxR cells induced phospho-p53 expression. Furthermore, miR-181a knockdown alone induced apoptosis in TaxR cells which could be further enhanced by the addition of DTX. Overexpression of mir-181a in prostate cancer cells contributes to their resistance to docetaxel and cabazitaxel and inhibition of mir-181a expression can restore treatment response. This is due, in part, to modulation of p53 phosphorylation and apoptosis. © 2017 Wiley Periodicals, Inc.

25 CFR 181.1 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Purpose. 181.1 Section 181.1 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN HIGHWAY SAFETY PROGRAM § 181.1 Purpose. This... projects are designed to reduce traffic crashes, reduce impaired driving crashes, increase occupant...

25 CFR 181.1 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true Purpose. 181.1 Section 181.1 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN HIGHWAY SAFETY PROGRAM § 181.1 Purpose. This... projects are designed to reduce traffic crashes, reduce impaired driving crashes, increase occupant...

25 CFR 181.1 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Purpose. 181.1 Section 181.1 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN HIGHWAY SAFETY PROGRAM § 181.1 Purpose. This... projects are designed to reduce traffic crashes, reduce impaired driving crashes, increase occupant...

25 CFR 181.1 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Purpose. 181.1 Section 181.1 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN HIGHWAY SAFETY PROGRAM § 181.1 Purpose. This... projects are designed to reduce traffic crashes, reduce impaired driving crashes, increase occupant...

25 CFR 181.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Purpose. 181.1 Section 181.1 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN HIGHWAY SAFETY PROGRAM § 181.1 Purpose. This... projects are designed to reduce traffic crashes, reduce impaired driving crashes, increase occupant...

10 CFR 60.181 - Violations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Violations. 60.181 Section 60.181 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES Violations § 60.181 Violations. (a) The Commission may obtain an injunction or other court order to prevent a...

46 CFR 181.520 - Installation and location.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Installation and location. 181.520 Section 181.520... TONS) FIRE PROTECTION EQUIPMENT Portable Fire Extinguishers § 181.520 Installation and location... the space being protected. The installation and location must be to the satisfaction of the Officer in...

19 CFR 181.91 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Applicability. 181.91 Section 181.91 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY... provisions of this subpart whenever the requested ruling involves a subject matter specified in § 181.92(b)(6...

19 CFR 181.91 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Applicability. 181.91 Section 181.91 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY... provisions of this subpart whenever the requested ruling involves a subject matter specified in § 181.92(b)(6...

19 CFR 181.91 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Applicability. 181.91 Section 181.91 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY... provisions of this subpart whenever the requested ruling involves a subject matter specified in § 181.92(b)(6...

19 CFR 181.91 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Applicability. 181.91 Section 181.91 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY... provisions of this subpart whenever the requested ruling involves a subject matter specified in § 181.92(b)(6...

19 CFR 181.91 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Applicability. 181.91 Section 181.91 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY... provisions of this subpart whenever the requested ruling involves a subject matter specified in § 181.92(b)(6...

46 CFR 181.400 - Where required.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Where required. 181.400 Section 181.400 Shipping COAST... PROTECTION EQUIPMENT Fixed Fire Extinguishing and Detecting Systems § 181.400 Where required. (a) The... cubic meters (6,000 cubic feet); (2) A pre-engineered fixed gas fire extinguishing system must be in...

21 CFR 820.181 - Device master record.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Device master record. 820.181 Section 820.181 Food... DEVICES QUALITY SYSTEM REGULATION Records § 820.181 Device master record. Each manufacturer shall maintain device master records (DMR's). Each manufacturer shall ensure that each DMR is prepared and approved in...

21 CFR 820.181 - Device master record.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Device master record. 820.181 Section 820.181 Food... DEVICES QUALITY SYSTEM REGULATION Records § 820.181 Device master record. Each manufacturer shall maintain device master records (DMR's). Each manufacturer shall ensure that each DMR is prepared and approved in...

22 CFR 181.5 - Twenty-day rule for concluded agreements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Twenty-day rule for concluded agreements. 181.5 Section 181.5 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL AGREEMENTS COORDINATION, REPORTING AND PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.5 Twenty-day rule for concluded agreements. (a) Any agency...

21 CFR 133.181 - Provolone cheese.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Provolone cheese. 133.181 Section 133.181 Food and... CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.181 Provolone cheese. (a) Description. (1) Provolone, a pasta filata or stretched curd-type...

21 CFR 133.181 - Provolone cheese.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Provolone cheese. 133.181 Section 133.181 Food and... CONSUMPTION CHEESES AND RELATED CHEESE PRODUCTS Requirements for Specific Standardized Cheese and Related Products § 133.181 Provolone cheese. (a) Description. (1) Provolone, a pasta filata or stretched curd-type...

7 CFR 28.181 - Review of cotton classification.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Review of cotton classification. 28.181 Section 28.181... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Classification for Foreign Growth Cotton § 28.181 Review of cotton classification. A review of any classification or comparison made pursuant to this subpart...

7 CFR 28.181 - Review of cotton classification.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Review of cotton classification. 28.181 Section 28.181... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Classification for Foreign Growth Cotton § 28.181 Review of cotton classification. A review of any classification or comparison made pursuant to this subpart...

7 CFR 28.181 - Review of cotton classification.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Review of cotton classification. 28.181 Section 28.181... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Classification for Foreign Growth Cotton § 28.181 Review of cotton classification. A review of any classification or comparison made pursuant to this subpart...

7 CFR 28.181 - Review of cotton classification.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Review of cotton classification. 28.181 Section 28.181... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Classification for Foreign Growth Cotton § 28.181 Review of cotton classification. A review of any classification or comparison made pursuant to this subpart...

7 CFR 28.181 - Review of cotton classification.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Review of cotton classification. 28.181 Section 28.181... REGULATIONS COTTON CLASSING, TESTING, AND STANDARDS Classification for Foreign Growth Cotton § 28.181 Review of cotton classification. A review of any classification or comparison made pursuant to this subpart...

14 CFR 23.181 - Dynamic stability.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Dynamic stability. 23.181 Section 23.181... STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Flight Stability § 23.181 Dynamic... that the function of a stability augmentation system, reference § 23.672, is needed to meet the flight...

46 CFR 181.300 - Fire pumps.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Fire pumps. 181.300 Section 181.300 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) FIRE PROTECTION EQUIPMENT Fire Main System § 181.300 Fire pumps. (a) A self priming, power driven fire pump must be...

9 CFR 319.181 - Cheesefurters and similar products.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Cheesefurters and similar products. 319.181 Section 319.181 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Cooked Sausage § 319.181...

9 CFR 319.181 - Cheesefurters and similar products.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Cheesefurters and similar products. 319.181 Section 319.181 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... INSPECTION AND CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Cooked Sausage § 319.181...

21 CFR 181.1 - General.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false General. 181.1 Section 181.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PRIOR-SANCTIONED FOOD INGREDIENTS General Provisions § 181.1 General. (a) An ingredient whose use in food or food packaging is...

46 CFR 181.610 - Fire bucket.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Fire bucket. 181.610 Section 181.610 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) FIRE PROTECTION EQUIPMENT Additional Equipment § 181.610 Fire bucket. A vessel not required to have a power driven...

46 CFR 181.300 - Fire pumps.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Fire pumps. 181.300 Section 181.300 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) FIRE PROTECTION EQUIPMENT Fire Main System § 181.300 Fire pumps. (a) A self priming, power driven fire pump must be...

19 CFR 122.181 - Definition of Customs security area.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 1 2014-04-01 2014-04-01 false Definition of Customs security area. 122.181 Section 122.181 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Access to Customs Security Areas § 122.181 Definition of...

19 CFR 122.181 - Definition of Customs security area.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 1 2011-04-01 2011-04-01 false Definition of Customs security area. 122.181 Section 122.181 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Access to Customs Security Areas § 122.181 Definition of...

19 CFR 122.181 - Definition of Customs security area.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 1 2012-04-01 2012-04-01 false Definition of Customs security area. 122.181 Section 122.181 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Access to Customs Security Areas § 122.181 Definition of...

19 CFR 122.181 - Definition of Customs security area.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 1 2013-04-01 2013-04-01 false Definition of Customs security area. 122.181 Section 122.181 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Access to Customs Security Areas § 122.181 Definition of...

19 CFR 181.101 - Publication of decisions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Publication of decisions. 181.101 Section 181.101 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) NORTH AMERICAN FREE TRADE AGREEMENT Advance Ruling Procedures § 181.101 Publication of...

1 CFR 18.1 - Original and copies required.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 1 General Provisions 1 2014-01-01 2012-01-01 true Original and copies required. 18.1 Section 18.1... PROCESSING OF DOCUMENTS PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.1 Original and copies... two duplicate originals or certified copies. 1 However, if the document is printed or processed on...

1 CFR 18.1 - Original and copies required.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 1 General Provisions 1 2013-01-01 2012-01-01 true Original and copies required. 18.1 Section 18.1... PROCESSING OF DOCUMENTS PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.1 Original and copies... two duplicate originals or certified copies. 1 However, if the document is printed or processed on...

1 CFR 18.1 - Original and copies required.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 1 General Provisions 1 2012-01-01 2012-01-01 false Original and copies required. 18.1 Section 18.1... PROCESSING OF DOCUMENTS PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.1 Original and copies... two duplicate originals or certified copies. 1 However, if the document is printed or processed on...

40 CFR 464.15 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 0.029 0.0095 Oil and grease (for alternate monitoring) 0.363 0.121 (c) Die Casting Operations. PSES... Total phenols 0.0074 0.0026 TTO 0.0308 0.01 Oil and grease (for alternate monitoring) 0.259 0.0864 (d...) 8.48 4.63 Lead (T) 8.7 4.3 Zinc (T) 12.6 4.74 TTO 18.1 5.91 Oil and grease (for alternate monitoring...

40 CFR 464.15 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 0.029 0.0095 Oil and grease (for alternate monitoring) 0.363 0.121 (c) Die Casting Operations. PSES... Total phenols 0.0074 0.0026 TTO 0.0308 0.01 Oil and grease (for alternate monitoring) 0.259 0.0864 (d...) 8.48 4.63 Lead (T) 8.7 4.3 Zinc (T) 12.6 4.74 TTO 18.1 5.91 Oil and grease (for alternate monitoring...

40 CFR 464.15 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 0.029 0.0095 Oil and grease (for alternate monitoring) 0.363 0.121 (c) Die Casting Operations. PSES... Total phenols 0.0074 0.0026 TTO 0.0308 0.01 Oil and grease (for alternate monitoring) 0.259 0.0864 (d...) 8.48 4.63 Lead (T) 8.7 4.3 Zinc (T) 12.6 4.74 TTO 18.1 5.91 Oil and grease (for alternate monitoring...

Telecommunications Services Required by Distributed and Interconnected Office Centers.

DTIC Science & Technology

1980-07-20

systems and communications management systems which are on the market . It is expected that these systems and the capabilities they offer will be available...saw the possibilities of marketing the service, but was delayed in its implementation because the high capacity communication network to support the...Jersey 07666. [181 Washburn, C, Unfolding Electronic Mail Market Leads to Integrated Info Systems, Communications News, November 1979, page 56. /191

[The function and application of animal microRNA-181].

PubMed

Chang, Yang; Mu, Weitao; Man, Chaolai

2014-02-01

MicroRNAs (miRNAs) are a type of non-coding RNAs which are short (17-25nt) and highly conservative in evolution. They can regulate gene expression by preventing target mRNA translation or inducing degradation via oligonucleotides complementary to target mRNA. Here, we briefly summarize the functions and regulatory mechanisms of microRNA-181 (miR-181) in cell proliferation, apoptosis and differentiation, and discuss the miR-181-mediated regulation of immune response in lymphocyte proliferation and differentiation, autoimmunity, inflammation and virus infection. Also, we analyze the functions of miR-181 in tumorigenesis, tumor development, diagnosis, treatment and prognosis. Finally, we discuss the application prospects of miR-181. The functional studies of miR-181 family members have important significance in understanding the mechanisms of biological events, pathogenesis of diseases, and finding new ways to diagnose and treat related diseases.

19 CFR 181.131 - Rules of origin.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Rules of origin. 181.131 Section 181.131 Customs... (CONTINUED) NORTH AMERICAN FREE TRADE AGREEMENT Rules of Origin § 181.131 Rules of origin. (a) The regulations effective October 1, 1995, implementing the rules of origin provisions of General Note 12, HTSUS...

46 CFR 108.181 - Ventilation for enclosed spaces.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Ventilation for enclosed spaces. 108.181 Section 108.181... AND EQUIPMENT Construction and Arrangement Ventilation § 108.181 Ventilation for enclosed spaces. (a) Each enclosed space must be vented or ventilated. (b) There must be a means to close each vent or...

46 CFR 108.181 - Ventilation for enclosed spaces.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Ventilation for enclosed spaces. 108.181 Section 108.181... AND EQUIPMENT Construction and Arrangement Ventilation § 108.181 Ventilation for enclosed spaces. (a) Each enclosed space must be vented or ventilated. (b) There must be a means to close each vent or...

46 CFR 108.181 - Ventilation for enclosed spaces.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Ventilation for enclosed spaces. 108.181 Section 108.181... AND EQUIPMENT Construction and Arrangement Ventilation § 108.181 Ventilation for enclosed spaces. (a) Each enclosed space must be vented or ventilated. (b) There must be a means to close each vent or...

46 CFR 108.181 - Ventilation for enclosed spaces.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Ventilation for enclosed spaces. 108.181 Section 108.181... AND EQUIPMENT Construction and Arrangement Ventilation § 108.181 Ventilation for enclosed spaces. (a) Each enclosed space must be vented or ventilated. (b) There must be a means to close each vent or...

46 CFR 108.181 - Ventilation for enclosed spaces.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Ventilation for enclosed spaces. 108.181 Section 108.181... AND EQUIPMENT Construction and Arrangement Ventilation § 108.181 Ventilation for enclosed spaces. (a) Each enclosed space must be vented or ventilated. (b) There must be a means to close each vent or...

46 CFR 181.320 - Fire hoses and nozzles.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Fire hoses and nozzles. 181.320 Section 181.320 Shipping...) FIRE PROTECTION EQUIPMENT Fire Main System § 181.320 Fire hoses and nozzles. (a) A fire hose with a... cargo decks, where no protection is provided, hoses may be temporarily removed during heavy weather or...

46 CFR 181.320 - Fire hoses and nozzles.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Fire hoses and nozzles. 181.320 Section 181.320 Shipping...) FIRE PROTECTION EQUIPMENT Fire Main System § 181.320 Fire hoses and nozzles. (a) A fire hose with a... cargo decks, where no protection is provided, hoses may be temporarily removed during heavy weather or...

46 CFR 181.320 - Fire hoses and nozzles.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Fire hoses and nozzles. 181.320 Section 181.320 Shipping...) FIRE PROTECTION EQUIPMENT Fire Main System § 181.320 Fire hoses and nozzles. (a) A fire hose with a... cargo decks, where no protection is provided, hoses may be temporarily removed during heavy weather or...

46 CFR 181.320 - Fire hoses and nozzles.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Fire hoses and nozzles. 181.320 Section 181.320 Shipping...) FIRE PROTECTION EQUIPMENT Fire Main System § 181.320 Fire hoses and nozzles. (a) A fire hose with a... cargo decks, where no protection is provided, hoses may be temporarily removed during heavy weather or...

46 CFR 181.600 - Fire axe.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Fire axe. 181.600 Section 181.600 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) FIRE PROTECTION EQUIPMENT Additional Equipment § 181.600 Fire axe. A vessel of more than 19.8 meters (65 feet) in length...

46 CFR 201.181 - General matters.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 8 2011-10-01 2011-10-01 false General matters. 201.181 Section 201.181 Shipping... PROCEDURE Judicial Standards of Practice (Rule 19) § 201.181 General matters. (a) In general, the functions... after notice and opportunity for hearing, or in the case of other matters from the time of notice by the...

46 CFR 201.181 - General matters.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 8 2012-10-01 2012-10-01 false General matters. 201.181 Section 201.181 Shipping... PROCEDURE Judicial Standards of Practice (Rule 19) § 201.181 General matters. (a) In general, the functions... after notice and opportunity for hearing, or in the case of other matters from the time of notice by the...

46 CFR 201.181 - General matters.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false General matters. 201.181 Section 201.181 Shipping... PROCEDURE Judicial Standards of Practice (Rule 19) § 201.181 General matters. (a) In general, the functions... after notice and opportunity for hearing, or in the case of other matters from the time of notice by the...

46 CFR 201.181 - General matters.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 8 2013-10-01 2013-10-01 false General matters. 201.181 Section 201.181 Shipping... PROCEDURE Judicial Standards of Practice (Rule 19) § 201.181 General matters. (a) In general, the functions... after notice and opportunity for hearing, or in the case of other matters from the time of notice by the...

46 CFR 201.181 - General matters.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 8 2014-10-01 2014-10-01 false General matters. 201.181 Section 201.181 Shipping... PROCEDURE Judicial Standards of Practice (Rule 19) § 201.181 General matters. (a) In general, the functions... after notice and opportunity for hearing, or in the case of other matters from the time of notice by the...

29 CFR 18.1 - Scope of rules.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 1 2010-07-01 2010-07-01 true Scope of rules. 18.1 Section 18.1 Labor Office of the Secretary of Labor RULES OF PRACTICE AND PROCEDURE FOR ADMINISTRATIVE HEARINGS BEFORE THE OFFICE OF ADMINISTRATIVE LAW JUDGES General § 18.1 Scope of rules. (a) General application. These rules of practice are...

12 CFR 225.181 - Conformance Period for Banking Entities Engaged in Prohibited Proprietary Trading or Private Fund...

Code of Federal Regulations, 2013 CFR

2013-01-01

... in Prohibited Proprietary Trading or Private Fund Activities. 225.181 Section 225.181 Banks and... Trading and Relationships With Hedge Funds and Private Equity Funds § 225.181 Conformance Period for Banking Entities Engaged in Prohibited Proprietary Trading or Private Fund Activities. (a) Conformance...

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

Zou, Chengcheng; Chen, Juan; Chen, Ke

The hepatitis B virus (HBV) is responsible for most of hepatocellular carcinoma (HCC). However, whether HBV plays an important role during hepatocarcinogenesis through effecting miRNAs remains unknown. Here, we reported that HBV up-regulated microRNA-181a (miR-181a) by enhancing its promoter activity. Simultaneously, we found that miR-181a inhibited apoptosis in vitro and promoted tumor cell growth in vivo. TNF receptor superfamily member 6 (Fas) was further identified as a target of miR-181a. We also found that Fas could reverse the apoptosis-inhibition effect induced by miR-181a. Moreover, HBV could inhibit cell apoptosis by down-regulating Fas expression, which could be reversed by miR-181a inhibitor.more » Our data demonstrated that HBV suppressed apoptosis of hepatoma cells by up-regulating miR-181a expression and down-regulating Fas expression, which may provide a new understanding of the mechanism in HBV-related HCC pathogenesis. - Highlights: • HBV could up-regulate miR-181a expression by interacting with nt−800 to +240 in its promoter region in HCC cell lines. • HBV could down-regulate Fas expression and suppress apoptosis of hepatoma cells, which could be reversed by miR-181a inhibitor. • Up-regulation of miR-181a promoted proliferation of hepatoma cells and repressed apoptosis, which could be reversed by Fas. • Our study provides a new understanding of the mechanism in HBV-related HCC pathogenesis.« less

Micro-RNA-181a suppresses progestin-promoted breast cancer cell growth.

PubMed

Gu, Muqing; Wang, Lijuan; Yang, Chun; Li, Xue; Jia, Chanwei; Croteau, Stephane; Ruan, Xiangyan; Hardy, Pierre

2018-08-01

Recent investigations have indicated that hormone therapy may increase the risk of breast cancer (BC), and the addition of synthetic progestins may play a critical role in this. Several studies have pointed out the important role of progesterone receptor membrane component 1 (PGRMC1) in the development of BC, especially with hormone therapy using progestins. Although the deregulation of microRNA-181a (miR-181a) is often associated with human BC, the effect of miR-181a on PGRMC1 expression during hormone therapy has not been investigated. Cell viability assay and apoptosis assay were performed to investigate the pro-BC effect of progestin (norethisterone, NET) and anti-BC effect of miR-181a on MCF-7 cells. Quantitative RT-PCR and Western blot analysis were used to evaluate gene expressions in the NET-treated MCF-7 cells. NET dose-dependently increased BC cell viability and this effect was accompanied by increased expression of PGRMC1. Overexpression of miR-181a strongly reduced the cell viability of MCF-7 cells, mainly through increased apoptosis, which was evidenced by substantially increased gene expression of pro-apoptosis factors such as BAX and CASPASE 9 in miR-181a overexpressed cells. Importantly, miR-181a abrogated NET-stimulated cell viability and PGRMC1 expression. We provide evidence that miR-181a promotes MCF-7 cell apoptosis. Moreover, miR-181a suppressed NET-provoked cell viability and PGRMC1 expression in MCF-7 cells. These data may suggest a therapeutic strategy of using miR-181a to reduce BC risk in progestin hormone replacement therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

miR-181c-BRK1 axis plays a key role in actin cytoskeleton-dependent T cell function.

PubMed

Lim, Shok Ping; Ioannou, Nikolaos; Ramsay, Alan G; Darling, David; Gäken, Joop; Mufti, Ghulam J

2018-05-01

MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a diverse range of cellular processes. The miR-181 family is important in T cell development, proliferation, and activation. In this study, we have identified BRK1 as a potential target of miR-181c using a dual selection functional assay and have showed that miR-181c regulates BRK1 by translational inhibition. Given the importance of miR-181 in T cell function and the potential role of BRK1 in the involvement of WAVE2 complex and actin polymerization in T cells, we therefore investigated the influence of miR-181c-BRK1 axis in T cell function. Stimulation of PBMC derived CD3 + T cells resulted in reduced miR-181c expression and up-regulation of BRK1 protein expression, suggesting that miR-181c-BRK1 axis is important in T cell activation. We further showed that overexpression of miR-181c or suppression of BRK1 resulted in inhibition of T cell activation and actin polymerization coupled with defective lamellipodia generation and immunological synapse formation. Additionally, we found that BRK1 silencing led to reduced expressions of other proteins in the WAVE2 complex, suggesting that the impairment of T cell actin dynamics was a result of the instability of the WAVE2 complex following BRK1 depletion. Collectively, we demonstrated that miR-181c reduces BRK1 protein expression level and highlighted the important role of miR-181c-BRK1 axis in T cell activation and actin polymerization-mediated T cell functions. ©2018 Society for Leukocyte Biology.

miR-181b regulates vascular stiffness age dependently in part by regulating TGF-β signaling

PubMed Central

Hori, Daijiro; Dunkerly-Eyring, Brittany; Nomura, Yohei; Biswas, Debjit; Steppan, Jochen; Henao-Mejia, Jorge; Adachi, Hideo; Santhanam, Lakshmi; Berkowitz, Dan E.; Steenbergen, Charles; Flavell, Richard A.

2017-01-01

Background Endothelial dysfunction and arterial stiffening play major roles in cardiovascular diseases. The critical role for the miR-181 family in vascular inflammation has been documented. Here we tested whether the miR-181 family can influence the pathogenesis of hypertension and vascular stiffening. Methods and results qPCR data showed a significant decrease in miR-181b expression in the aorta of the older mice. Eight miR-181a1/b1-/- mice and wild types (C57BL6J:WT) were followed weekly for pulse wave velocity (PWV) and blood pressure measurements. After 20 weeks, the mice were tested for endothelial function and aortic modulus. There was a progressive increase in PWV and higher systolic blood pressure in miR-181a1/b1-/- mice compared with WTs. At 21 weeks, aortic modulus was significantly greater in the miR-181a1/b1-/- group, and serum TGF-β was found to be elevated at this time. A luciferase reporter assay confirmed miR-181b targets TGF-βi (TGF-β induced) in the aortic VSMCs. In contrast, wire myography revealed unaltered endothelial function along with higher nitric oxide production in the miR-181a1/b1-/- group. Cultured VECs and VSMCs from the mouse aorta showed more secreted TGF-β in VSMCs of the miR-181a1/b1-/- group; whereas, no change was observed from VECs. Circulating levels of angiotensin II were similar in both groups. Treatment with losartan (0.6 g/L) prevented the increase in PWV, blood pressure, and vascular stiffness in miR-181a1/b1-/- mice. Immunohistochemistry and western blot for p-SMAD2/3 validated the inhibitory effect of losartan on TGF-β signaling in miR-181a1/b1-/- mice. Conclusions Decreased miR-181b with aging plays a critical role in ECM remodeling by removing the brake on the TGF-β, pSMAD2/3 pathway. PMID:28323879

miR-181b regulates vascular stiffness age dependently in part by regulating TGF-β signaling.

PubMed

Hori, Daijiro; Dunkerly-Eyring, Brittany; Nomura, Yohei; Biswas, Debjit; Steppan, Jochen; Henao-Mejia, Jorge; Adachi, Hideo; Santhanam, Lakshmi; Berkowitz, Dan E; Steenbergen, Charles; Flavell, Richard A; Das, Samarjit

2017-01-01

Endothelial dysfunction and arterial stiffening play major roles in cardiovascular diseases. The critical role for the miR-181 family in vascular inflammation has been documented. Here we tested whether the miR-181 family can influence the pathogenesis of hypertension and vascular stiffening. qPCR data showed a significant decrease in miR-181b expression in the aorta of the older mice. Eight miR-181a1/b1-/- mice and wild types (C57BL6J:WT) were followed weekly for pulse wave velocity (PWV) and blood pressure measurements. After 20 weeks, the mice were tested for endothelial function and aortic modulus. There was a progressive increase in PWV and higher systolic blood pressure in miR-181a1/b1-/- mice compared with WTs. At 21 weeks, aortic modulus was significantly greater in the miR-181a1/b1-/- group, and serum TGF-β was found to be elevated at this time. A luciferase reporter assay confirmed miR-181b targets TGF-βi (TGF-β induced) in the aortic VSMCs. In contrast, wire myography revealed unaltered endothelial function along with higher nitric oxide production in the miR-181a1/b1-/- group. Cultured VECs and VSMCs from the mouse aorta showed more secreted TGF-β in VSMCs of the miR-181a1/b1-/- group; whereas, no change was observed from VECs. Circulating levels of angiotensin II were similar in both groups. Treatment with losartan (0.6 g/L) prevented the increase in PWV, blood pressure, and vascular stiffness in miR-181a1/b1-/- mice. Immunohistochemistry and western blot for p-SMAD2/3 validated the inhibitory effect of losartan on TGF-β signaling in miR-181a1/b1-/- mice. Decreased miR-181b with aging plays a critical role in ECM remodeling by removing the brake on the TGF-β, pSMAD2/3 pathway.

21 CFR 181.22 - Certain substances employed in the manufacture of food-packaging materials.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Certain substances employed in the manufacture of food-packaging materials. 181.22 Section 181.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... Food Ingredients § 181.22 Certain substances employed in the manufacture of food-packaging materials...

21 CFR 181.22 - Certain substances employed in the manufacture of food-packaging materials.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Certain substances employed in the manufacture of food-packaging materials. 181.22 Section 181.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... INGREDIENTS Specific Prior-Sanctioned Food Ingredients § 181.22 Certain substances employed in the manufacture...

21 CFR 181.22 - Certain substances employed in the manufacture of food-packaging materials.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Certain substances employed in the manufacture of food-packaging materials. 181.22 Section 181.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... INGREDIENTS Specific Prior-Sanctioned Food Ingredients § 181.22 Certain substances employed in the manufacture...

46 CFR 181.320 - Fire hoses and nozzles.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Fire hoses and nozzles. 181.320 Section 181.320 Shipping...) FIRE PROTECTION EQUIPMENT Fire Main System § 181.320 Fire hoses and nozzles. (a) A fire hose with a nozzle must be attached to each fire hydrant at all times. For fire hydrants located on open decks or...

25 CFR 181.6 - How are applicants informed of the results?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false How are applicants informed of the results? 181.6 Section 181.6 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN HIGHWAY SAFETY PROGRAM § 181.6 How are applicants informed of the results? BIA will send a letter to all...

25 CFR 181.6 - How are applicants informed of the results?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false How are applicants informed of the results? 181.6 Section 181.6 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN HIGHWAY SAFETY PROGRAM § 181.6 How are applicants informed of the results? BIA will send a letter to all...

25 CFR 181.6 - How are applicants informed of the results?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false How are applicants informed of the results? 181.6 Section 181.6 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN HIGHWAY SAFETY PROGRAM § 181.6 How are applicants informed of the results? BIA will send a letter to all...

14 CFR 91.181 - Course to be flown.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Course to be flown. 91.181 Section 91.181... § 91.181 Course to be flown. Unless otherwise authorized by ATC, no person may operate an aircraft... airway. (b) On any other route, along the direct course between the navigational aids or fixes defining...

14 CFR 91.181 - Course to be flown.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Course to be flown. 91.181 Section 91.181... § 91.181 Course to be flown. Unless otherwise authorized by ATC, no person may operate an aircraft... airway. (b) On any other route, along the direct course between the navigational aids or fixes defining...

14 CFR 91.181 - Course to be flown.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Course to be flown. 91.181 Section 91.181... § 91.181 Course to be flown. Unless otherwise authorized by ATC, no person may operate an aircraft... airway. (b) On any other route, along the direct course between the navigational aids or fixes defining...

14 CFR 91.181 - Course to be flown.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Course to be flown. 91.181 Section 91.181... § 91.181 Course to be flown. Unless otherwise authorized by ATC, no person may operate an aircraft... airway. (b) On any other route, along the direct course between the navigational aids or fixes defining...

14 CFR 91.181 - Course to be flown.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Course to be flown. 91.181 Section 91.181... § 91.181 Course to be flown. Unless otherwise authorized by ATC, no person may operate an aircraft... airway. (b) On any other route, along the direct course between the navigational aids or fixes defining...

42 CFR 440.181 - Home and community-based services for individuals age 65 or older.

Code of Federal Regulations, 2010 CFR

2010-10-01

... age 65 or older. 440.181 Section 440.181 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES... Definitions § 440.181 Home and community-based services for individuals age 65 or older. (a) Description of services— Home and community-based services for individuals age 65 or older means services, not otherwise...

miR-181a promotes G1/S transition and cell proliferation in pediatric acute myeloid leukemia by targeting ATM.

PubMed

Liu, Xiaodan; Liao, Wang; Peng, Hongxia; Luo, Xuequn; Luo, Ziyan; Jiang, Hua; Xu, Ling

2016-01-01

Abnormal expression of miRNAs is intimately related to a variety of human cancers. The purpose of this study is to confirm the expression of miR-181a and elucidate its physiological function and mechanism in pediatric acute myeloid leukemia (AML). Pediatric AML patients and healthy controls were enrolled, and the expression of miR-181a and ataxia telangiectasia mutated (ATM) in tissues were examined using quantitative PCR. Moreover, cell proliferation and cell cycle were evaluated in several cell lines (HL60, NB4 and K562) by using flow cytometry after transfected with miR-181a mimics and inhibitors, or ATM siRNA and control siRNA. Finally, ATM as the potential target protein of miR-181a was examined. We found that miR-181a was significantly increased in pediatric AML, which showed an inverse association with ATM expression. Overexpressed miR-181a in cell lines significantly enhanced cell proliferation, as well as increased the ratio of S-phase cells by miR-181a mimics transfection in vitro. Luciferase activity of the reporter construct identified ATM as the direct molecular target of miR-181a. ATM siRNA transfection significantly enhanced cell proliferation and increased the ratio of S-phase cells in vitro. The results revealed novel mechanism through which miR-181a regulates G1/S transition and cell proliferation in pediatric AML by regulating the tumor suppressor ATM, providing insights into the molecular mechanism in pediatric AML.

Applied anatomy of small branches of the portal vein in transverse groove of hepatic hilum.

PubMed

Yan, Pei-ning; Tan, Wei-feng; Yang, Xin-wei; Zhang, Chuan-sen; Jiang, Xiao-qing

2014-12-01

The objective of this study was to provide the morphological details on small branches of the portal vein in transverse groove of hepatic hilum. According to the surgery significance, the small branches of portal vein in transverse groove of hepatic hilum were named as "Short hepatic portal veins (SHPVs)". SHPVs were minutely dissected in 30 adult cadaveric livers. The number, diameter, length, origin points, and entering liver sites of SHPVs were explored and measured. There were 181 SHPVs in 30 liver specimens, including 46% (83/181) from the left portal vein, 31% (56/181) from the bifurcation, and 23% (42/181) from the right portal vein. At the entering liver sites of SHPVs, 22% (40/181) supplied for segment IV, 9% (17/181) for segment V, 4% (7/181) for segment VI, 23% (41/181) for segment VII, and 42% (76/181) for segment I (caudate lobe). There were 6.0 ± 2.4 branches per liver specimen with range 3-12. The mean diameter of SHPVs was 2.25 ± 0.89 mm. The average length of SHPVs was 4.86 ± 2.12 mm. SHPVs widely existed in each liver specimen. The detailed anatomical study of SHPVs could be useful to avoid damaging the short portal branches during hepatic operations, such as isolated or combined caudate lobectomy.

Oleic acid-dependent modulation of Nitric oxide associated 1 protein levels regulates nitric oxide-mediated defense signaling in Arabidopsis

USDA-ARS?s Scientific Manuscript database

The conserved cellular metabolites nitric oxide (NO) and oleic acid (18:1) are well-known regulators of disease physiologies in diverse organism. We show that NO production in plants is regulated via 18:1. Reduction in 18:1 levels, via a genetic mutation in the 18:1-synthesizing gene SUPPRESSOR OF S...

30 CFR 206.181 - How do I establish processing costs for dual accounting purposes when I do not process the gas?

Code of Federal Regulations, 2010 CFR

2010-07-01

... accounting purposes when I do not process the gas? 206.181 Section 206.181 Mineral Resources MINERALS... Processing Allowances § 206.181 How do I establish processing costs for dual accounting purposes when I do not process the gas? Where accounting for comparison (dual accounting) is required for gas production...

26 CFR 1.181-0T - Table of contents (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Table of contents (temporary). 1.181-0T Section...-0T Table of contents (temporary). This section lists the table of contents for §§ 1.181-1T through 1... deduction allowed. § 1.181-2TElection (temporary). (a) Time and manner of making election. (b) Election by...

Plasma phospho-tau181 increases with Alzheimer's disease clinical severity and is associated with tau- and amyloid-positron emission tomography.

PubMed

Mielke, Michelle M; Hagen, Clinton E; Xu, Jing; Chai, Xiyun; Vemuri, Prashanthi; Lowe, Val J; Airey, David C; Knopman, David S; Roberts, Rosebud O; Machulda, Mary M; Jack, Clifford R; Petersen, Ronald C; Dage, Jeffrey L

2018-04-04

We examined and compared plasma phospho-tau181 (pTau181) and total tau: (1) across the Alzheimer's disease (AD) clinical spectrum; (2) in relation to brain amyloid β (Aβ) positron emission tomography (PET), tau PET, and cortical thickness; and (3) as a screening tool for elevated brain Aβ. Participants included 172 cognitively unimpaired, 57 mild cognitively impaired, and 40 AD dementia patients with concurrent Aβ PET (Pittsburgh compound B), tau PET (AV1451), magnetic resonance imaging, plasma total tau, and pTau181. Plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aβ and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aβ than total tau and was as good as, or better than, the combination of age and apolipoprotein E (APOE). Plasma pTau181 may have utility as a biomarker of AD pathophysiology and as a noninvasive screener for elevated brain Aβ. Copyright © 2018. Published by Elsevier Inc.

Examination of the persistency of milk fatty acid composition responses to fish oil and sunflower oil in the diet of dairy cows.

PubMed

Shingfield, K J; Reynolds, C K; Hervás, G; Griinari, J M; Grandison, A S; Beever, D E

2006-02-01

Based on the potential benefits of cis-9, trans-11 conjugated linoleic acid (CLA) for human health, there is a need to develop effective strategies for enhancing milk fat CLA concentrations. Levels of cis-9, trans-11 CLA in milk can be increased by supplements of fish oil (FO) and sunflower oil (SO), but there is considerable variation in the response. Part of this variance may reflect time-dependent ruminal adaptations to high levels of lipid in the diet, which lead to alterations in the formation of specific biohydrogenation intermediates. To test this hypothesis, 16 late lactation Holstein-British Friesian cows were used in a repeated measures randomized block design to examine milk fatty acid composition responses to FO and SO in the diet over a 28-d period. Cows were allocated at random to corn silage-based rations (8 per treatment) containing 0 (control) or 45 g of oil supplement/kg of dry matter consisting (1:2; wt/wt) of FO and SO (FSO), and milk composition was determined on alternate days from d 1. Compared with the control, the FSO diet decreased mean dry matter intake (21.1 vs. 17.9 kg/d), milk fat (47.7 vs. 32.6 g/kg), and protein content (36.1 vs. 33.3 g/kg), but had no effect on milk yield (27.1 vs. 26.4 kg/d). Reductions in milk fat content relative to the FSO diet were associated with increases in milk trans-10 18:1, trans-10, cis-12 CLA, and trans-9, cis-11 CLA concentrations (r(2) = 0.74, 0.57, and 0.80, respectively). Compared with the control, the FSO diet reduced milk 4:0 to 18:0 and cis 18:1 content and increased trans 18:1, trans 18:2, cis-9, trans-11 CLA, 20:5 n-3, and 22:6 n-3 concentrations. The FSO diet caused a rapid elevation in milk cis-9, trans-11 CLA content, reaching a maximum of 5.37 g/100 g of fatty acids on d 5, but these increases were transient, declining to 2.35 g/100 g of fatty acids by d 15. They remained relatively constant thereafter. Even though concentrations of trans-11 18:1 followed the same pattern of temporal changes as cis-9, trans-11 CLA, the total trans 18:1 content of FSO milk was unchanged because of the concomitant increases in the concentration of other isomers (Delta(4-10) and Delta(12-15)), predominantely trans-10 18:1. In conclusion, supplementing diets with FSO enhances milk fat cis-9, trans-11 CLA content, but the high level of enrichment declines because of changes in ruminal biohydrogenation that result in trans-10 replacing trans-11 as the major 18:1 biohydrogenation intermediate formed in the rumen.

BASEOPS Default Profiles for Civil Aircraft

DTIC Science & Technology

1989-09-01

CXMPOSITE GA JET ............................. A-53 LEXR35 GATES LEAR 35/ TFE731 ......................... A-54 LEAR25 GATES LEAR 25/CJ610...BUS JET YES 54 LEAR35 GATES LEAR 35/ TFE731 JGA TF7312 895 INM54 LEARJET-35 YES 55 LEAR25 GATES LEAR 25/CJ610 JGA CJ610 893 INM55 LEARJET 25 YES 56...180 180 180 180 0 0 0 54 LEAR35 GATES LEAR 35/ TFE731 JGA 23 TF7312 38 181 181 181 181 181 0 0 55 LEAR25 GATES LEAR 25/CJ610 JGA 22 CJ610 39 182 182

Clinical pharmacology of AMG 181, a gut-specific human anti-α4β7 monoclonal antibody, for treating inflammatory bowel diseases

PubMed Central

Pan, Wei-Jian; Köck, Kathleen; Rees, William A; Sullivan, Barbara A; Evangelista, Christine M; Yen, Mark; Andrews, Jane M; Radford-Smith, Graham L; Prince, Peter J; Reynhardt, Kaz O; Doherty, David R; Patel, Sonal K; Krill, Christine D; Zhou, Kefei; Shen, Jing; Smith, Lynn E; Gow, Jason M; Lee, Jonathan; Treacy, Anthony M; Yu, Zhigang; Platt, Virginia M; Borie, Dominic C

2014-01-01

Aims AMG 181 pharmacokinetics/pharmacodynamics (PK/PD), safety, tolerability and effects after single subcutaneous (s.c.) or intravenous (i.v.) administration were evaluated in a randomized, double-blind, placebo-controlled study. Methods Healthy male subjects (n= 68) received a single dose of AMG 181 or placebo at 0.7, 2.1, 7, 21, 70 mg s.c. (or i.v.), 210 mg s.c. (or i.v.), 420 mg i.v. or placebo. Four ulcerative colitis (UC) subjects (n= 4, male : female 2:2) received 210 mg AMG 181 or placebo s.c. (3:1). AMG 181 concentration, anti-AMG 181-antibody (ADA), α4β7 receptor occupancy (RO), target cell counts, serum C-reactive protein, fecal biomarkers and Mayo score were measured. Subjects were followed 3–9 months after dose. Results Following s.c. dosing, AMG 181 was absorbed with a median tmax ranging between 2–10 days and a bioavailability between 82% and 99%. Cmax and AUC increased dose-proportionally and approximately dose-proportionally, respectively, within the 70–210 mg s.c. and 70–420 mg i.v. ranges. The linear β-phase t1/2 was 31 (range 20–48) days. Target-mediated disposition occurred at serum AMG 181 concentrations of less than 1 μg ml−1. The PD effect on α4β7 RO showed an EC50 of 0.01 μg ml−1. Lymphocytes, eosinophils, CD4+ T cells and subset counts were unchanged. AMG 181-treated UC subjects were in remission with mucosal healing at weeks 6, 12 and/or 28. The placebo-treated UC subject experienced colitis flare at week 6. No ADA or AMG 181 treatment-related serious adverse events were observed. Conclusions AMG 181 has PK/PD, safety, and effect profiles suitable for further testing in subjects with inflammatory bowel diseases. PMID:24803302

A Meta-Analysis of Observational Studies of the Association Between Chronic Occupational Exposure to Lead and Amyotrophic Lateral Sclerosis

PubMed Central

Gomes, James; Cashman, Neil R.; Little, Julian; Krewski, Daniel

2014-01-01

Objective: The association between occupational exposure to lead and amyotrophic lateral sclerosis (ALS) was examined through systematic review and meta-analyses of relevant epidemiological studies and reported according to PRISMA guidelines. Methods: Relevant studies were searched in multiple bibliographic databases through September 2013; additional articles were tracked through PubMed until submission. All records were screened in DistillerSR, and the data extracted from included articles were synthesized with meta-analysis. Results: The risk of developing ALS among individuals with a history of exposure to lead was almost doubled (odds ratio, 1.81; 95% confidence interval, 1.39 to 2.36) on the basis of nine included case-control studies with specific lead exposure information, with no apparent heterogeneity across included studies (I2 = 14%). The attributable risk of ALS because of exposure to lead was estimated to be 5%. Conclusions: Previous exposure to lead may be a risk factor for ALS. PMID:25479292

miR-181a Targets RGS16 to Promote Chondrosarcoma Growth, Angiogenesis, and Metastasis.

PubMed

Sun, Xiaojuan; Charbonneau, Cherie; Wei, Lei; Chen, Qian; Terek, Richard M

2015-09-01

Chondrosarcoma is the most common primary malignant bone tumor in adults, has no effective systemic treatment, and patients with this disease have poor survival. Altered expression of microRNA (miR) is involved in tumorigenesis; however, its role in chondrosarcoma is undetermined. miR-181a is overexpressed in high-grade chondrosarcoma, is upregulated by hypoxia, and increases VEGF expression. Here, the purpose was to determine the mechanism of miR-181a regulation of VEGF, determine whether miR-181a overexpression promotes tumor progression, and to evaluate an antagomir-based approach for chondrosarcoma treatment. Therapeutic inhibition of miR-181a decreased expression of VEGF and MMP1 in vitro, and angiogenesis, MMP1 activity, tumor growth, and lung metastasis, all by more than 50%, in a xenograft mouse model. A target of miR-181a is a regulator of G-protein signaling 16 (RGS16), a negative regulator of CXC chemokine receptor 4 (CXCR4) signaling. CXCR4 signaling is increased in chondrosarcoma, its expression is also increased by hypoxia, and is associated with angiogenesis and metastasis; however, receptor blockade is only partially effective. RGS16 expression is restored after miR-181a inhibition and partially accounts for the antiangiogenic and antimetastatic effects of miR-181a inhibition. These data establish miR-181a as an oncomiR that promotes chondrosarcoma progression through a new mechanism involving enhancement of CXCR4 signaling by inhibition of RGS16. Targeting miR-181a can inhibit tumor angiogenesis, growth, and metastasis, thus suggesting the possibility of antagomir-based therapy in chondrosarcoma. ©2015 American Association for Cancer Research.

MiR-181a-5p is downregulated in hepatocellular carcinoma and suppresses motility, invasion and branching-morphogenesis by directly targeting c-Met.

PubMed

Korhan, Peyda; Erdal, Esra; Atabey, Neşe

2014-08-08

c-Met receptor tyrosine kinase has been regarded as a promising therapeutic target for hepatocellular carcinoma (HCC). Recently, microRNAs (miRNAs) have been shown as a novel mechanism to control c-Met expression in cancer. In this study, we investigate the potential contribution of miR-181a-5p dysregulation to the biology of c-Met overexpression in HCC. Herein, we found an inverse expression pattern between miR-181a-5p and c-Met expression in normal, cirrhotic and HCC liver tissues. Luciferase assay confirmed that miR-181a-5p binding to the 3'-UTR of c-Met downregulated the expression of c-Met in HCC cells. Overexpression of miR-181a-5p suppressed both HGF-independent and -dependent activation of c-Met and consequently diminished branching-morphogenesis and invasion. Combined treatment with miR-181a-5p and c-Met inhibitor led to a further inhibition of c-Met-driven cellular activities. Knockdown of miR-181a-5p promoted HGF-independent/-dependent signaling of c-Met and accelerated migration, invasion and branching-morphogenesis. In conclusion, our results demonstrated for the first time that c-Met is a functional target gene of miR-181a-5p and the loss of miR-181a-5p expression led to the activation of c-Met-mediated oncogenic signaling in hepatocarcinogenesis. These findings display a novel molecular mechanism of c-Met regulation in HCC and strategies to increase miR-181a5p level might be an alternative approach for the enhancement of the inhibitory effects of c-Met inhibitors. Copyright © 2014 Elsevier Inc. All rights reserved.

miR-181a Targets RGS16 to Promote Chondrosarcoma Growth, Angiogenesis, and Metastasis

PubMed Central

Sun, Xiaojuan; Charbonneau, Cherie; Wei, Lei; Chen, Qian; Terek, Richard M.

2015-01-01

Chondrosarcoma is the most common primary malignant bone tumor in adults, has no effective systemic treatment, and patients with this disease have poor survival. Altered expression of microRNA (miR) is involved in tumorigenesis, however its role in chondrosarcoma is undetermined. MicroRNA-181a is overexpressed in high grade chondrosarcoma, is upregulated by hypoxia, and increases VEGF expression. Here, the purpose was to determine the mechanism of miR-181a regulation of VEGF, determine if miR-181a overexpression promotes tumor progression, and to evaluate an antagomir-based approach for chondrosarcoma treatment. Therapeutic inhibition of miR-181a decreased expression of VEGF and MMP1 in vitro, and angiogenesis, MMP1 activity, tumor growth, and lung metastasis, all by more than 50%, in a xenograft mouse model. A target of miR-181a is regulator of G-protein signaling 16 (RGS16), a negative regulator of CXC chemokine receptor 4 (CXCR4) signaling. CXCR4 signaling is increased in chondrosarcoma, its expression is also increased by hypoxia, and is associated with angiogenesis and metastasis, however, receptor blockade is only partially effective. RGS16 expression is restored after miR-181a inhibition and partially accounts for the anti-angiogenic and anti-metastatic effects of miR-181a inhibition. These data establish miR-181a as an oncomiR that promotes chondrosarcoma progression through a new mechanism involving enhancement of CXCR4 signaling by inhibition of RGS16. PMID:26013170

49 CFR 40.181 - What does the second laboratory do with the split specimen when it is tested to reconfirm a...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 1 2013-10-01 2013-10-01 false What does the second laboratory do with the split specimen when it is tested to reconfirm a substituted test result? 40.181 Section 40.181 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Split Specimen Tests § 40.181...

MicroRNA-181 promotes synaptogenesis and attenuates axonal outgrowth in cortical neurons

PubMed Central

Kos, Aron; Olde Loohuis, Nikkie; Meinhardt, Julia; van Bokhoven, Hans; Kaplan, Barry B; Martens, Gerard; Aschrafi, Armaz

2016-01-01

MicroRNAs (miRs) are non-coding gene transcripts abundantly expressed in both the developing and adult mammalian brain. They act as important modulators of complex gene regulatory networks during neuronal development and plasticity. miR-181c is highly abundant in cerebellar cortex and its expression is increased in autism patients as well as in an animal model of autism. To systematically identify putative targets of miR-181c, we repressed this miR in growing cortical neurons and found over 70 differentially expressed target genes using transcriptome profiling. Pathway analysis showed that the miR-181c-modulated genes converge on signaling cascades relevant to neurite and synapse developmental processes. To experimentally examine the significance of these data, we inhibited miR-181c during rat cortical neuronal maturation in vitro; this loss-of miR-181c function resulted in enhanced neurite sprouting and reduced synaptogenesis. Collectively, our findings suggest that miR-181c is a modulator of gene networks associated with cortical neuronal maturation. PMID:27017280

Native presynaptic metabotropic glutamate receptor 4 (mGluR4) interacts with exocytosis proteins in rat cerebellum.

PubMed

Ramos, Cathy; Chardonnet, Solenne; Marchand, Christophe H; Decottignies, Paulette; Ango, Fabrice; Daniel, Hervé; Le Maréchal, Pierre

2012-06-08

The eight pre- or/and post-synaptic metabotropic glutamatergic receptors (mGluRs) modulate rapid excitatory transmission sustained by ionotropic receptors. They are classified in three families according to their percentage of sequence identity and their pharmacological properties. mGluR4 belongs to group III and is mainly localized presynaptically. Activation of group III mGluRs leads to depression of excitatory transmission, a process that is exclusively provided by mGluR4 at parallel fiber-Purkinje cell synapse in rodent cerebellum. This function relies at least partly on an inhibition of presynaptic calcium influx, which controls glutamate release. To improve the understanding of molecular mechanisms of the mGluR4 depressant effect, we decided to identify the proteins interacting with this receptor. Immunoprecipitations using anti-mGluR4 antibodies were performed with cerebellar extracts. 183 putative partners that co-immunoprecipitated with anti-mGluR4 antibodies were identified and classified according to their cellular functions. It appears that native mGluR4 interacts with several exocytosis proteins such as Munc18-1, synapsins, and syntaxin. In addition, native mGluR4 was retained on a Sepharose column covalently grafted with recombinant Munc18-1, and immunohistochemistry experiments showed that Munc18-1 and mGluR4 colocalized at plasma membrane in HEK293 cells, observations in favor of an interaction between the two proteins. Finally, affinity chromatography experiments using peptides corresponding to the cytoplasmic domains of mGluR4 confirmed the interaction observed between mGluR4 and a selection of exocytosis proteins, including Munc18-1. These results could give indications to explain how mGluR4 can modulate glutamate release at parallel fiber-Purkinje cell synapses in the cerebellum in addition to the inhibition of presynaptic calcium influx.

DNA mutagenic activity and capacity for HIV-1 restriction of the cytidine deaminase APOBEC3G depend on whether DNA or RNA binds to tyrosine 315

PubMed Central

Polevoda, Bogdan; Joseph, Rebecca; Friedman, Alan E.; Bennett, Ryan P.; Greiner, Rebecca; De Zoysa, Thareendra; Stewart, Ryan A.; Smith, Harold C.

2017-01-01

APOBEC3G (A3G) belongs to the AID/APOBEC protein family of cytidine deaminases (CDA) that bind to nucleic acids. A3G mutates the HIV genome by deamination of dC to dU, leading to accumulation of virus-inactivating mutations. Binding to cellular RNAs inhibits A3G binding to substrate single-stranded (ss) DNA and CDA activity. Bulk RNA and substrate ssDNA bind to the same three A3G tryptic peptides (amino acids 181–194, 314–320, and 345–374) that form parts of a continuously exposed protein surface extending from the catalytic domain in the C terminus of A3G to its N terminus. We show here that the A3G tyrosines 181 and 315 directly cross-linked ssDNA. Binding experiments showed that a Y315A mutation alone significantly reduced A3G binding to both ssDNA and RNA, whereas Y181A and Y182A mutations only moderately affected A3G nucleic acid binding. Consistent with these findings, the Y315A mutant exhibited little to no deaminase activity in an Escherichia coli DNA mutator reporter, whereas Y181A and Y182A mutants retained ∼50% of wild-type A3G activity. The Y315A mutant also showed a markedly reduced ability to assemble into viral particles and had reduced antiviral activity. In uninfected cells, the impaired RNA-binding capacity of Y315A was evident by a shift of A3G from high-molecular-mass ribonucleoprotein complexes to low-molecular-mass complexes. We conclude that Tyr-315 is essential for coordinating ssDNA interaction with or entry to the deaminase domain and hypothesize that RNA bound to Tyr-315 may be sufficient to competitively inhibit ssDNA deaminase-dependent antiviral activity. PMID:28381554

Effects of MRP8, LPS, and lenalidomide on the expressions of TNF-α , brain-enriched, and inflammation-related microRNAs in the primary astrocyte culture.

PubMed

Omran, Ahmed; Ashhab, Muhammad Usman; Gan, Na; Kong, Huimin; Peng, Jing; Yin, Fei

2013-01-01

Astrocytes are now recognized as a heterogeneous class of cells with many important and diverse functions in healthy and diseased central nervous system (CNS). MicroRNAs (miRNAs) are small, noncoding RNAs which may have key roles in astrocytes activation in response to various stimuli. We performed quantitative real-time PCR (qPCR) to detect changes in the expressions of brain-enriched miRNAs (124, 134, 9, 132, and 138), inflammation-related miRNAs (146a, 21, 181a, 221, and 222), and tumor necrosis factor alpha (TNF- α ) in the rat primary astrocyte cultures after stimulation with myeloid-related protein 8 (MRP8) and lipopolysaccharides (LPS). Further, we inhibited the expression of TNF- α in the astrocytes by using TNF- α inhibitor (lenalidomide) and tested for the first time the effect of this inhibition on the expressions of the same tested miRNAs. Stimulation of the astrocytes with MRP8 or LPS leads to significant upregulation of miRNAs (124, 134, 9, 132, 146a, 21, 181a, 221, and 222), while miRNA-138 was downregulated. TNF- α inhibition with lenalidomide leads to opposite expressions of the tested miRNAs. These miRNAs may play an important role in activation of the astrocytes and may be a novel target for cell-specific therapeutic interventions in multiple CNS diseases.

26 CFR 1.181-4T - Special rules (temporary).

Code of Federal Regulations, 2011 CFR

2011-04-01

... to § 1.181-2T(d). (2) Principal photography not commencing prior to January 1, 2009. If a taxpayer claims a deduction under section 181 with respect to a production for which principal photography does...

26 CFR 1.181-4T - Special rules (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... to § 1.181-2T(d). (2) Principal photography not commencing prior to January 1, 2009. If a taxpayer claims a deduction under section 181 with respect to a production for which principal photography does...

Quantification of plasma phosphorylated tau to use as a biomarker for brain Alzheimer pathology: pilot case-control studies including patients with Alzheimer's disease and down syndrome.

PubMed

Tatebe, Harutsugu; Kasai, Takashi; Ohmichi, Takuma; Kishi, Yusuke; Kakeya, Tomoshi; Waragai, Masaaki; Kondo, Masaki; Allsop, David; Tokuda, Takahiko

2017-09-04

There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer's disease (AD) pathology. This study is aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181) is informative in the diagnosis of AD. We have developed a novel ultrasensitive immunoassay to quantify plasma p-tau181, and measured the levels of plasma p-tau181 in three cohorts. In the first cohort composed of 20 AD patients and 15 age-matched controls, the plasma levels of p-tau181 were significantly higher in the AD patients than those in the controls (0.171 ± 0.166 pg/ml in AD versus 0.0405 ± 0.0756 pg/ml in controls, p = 0.0039). The percentage of the subjects whose levels of plasma p-tau181 exceeded the cut-off value (0.0921 pg/ml) was significantly higher in the AD group compared with the control group (60% in AD versus 16.7% in controls, p = 0.0090). In the second cohort composed of 20 patients with Down syndrome (DS) and 22 age-matched controls, the plasma concentrations of p-tau181 were significantly higher in the DS group (0.767 ± 1.26 pg/ml in DS versus 0.0415 ± 0.0710 pg/ml in controls, p = 0.0313). There was a significant correlation between the plasma levels of p-tau181 and age in the DS group (R 2  = 0.4451, p = 0.0013). All of the DS individuals showing an extremely high concentration of plasma p-tau181 (> 1.0 pg/ml) were older than the age of 40. In the third cohort composed of 8 AD patients and 3 patients with other neurological diseases, the levels of plasma p-tau181 significantly correlated with those of CSF p-tau181 (R 2  = 0.4525, p = 0.023). We report for the first time quantitative data on the plasma levels of p-tau181 in controls and patients with AD and DS, and these data suggest that the plasma p-tau181 is a promising blood biomarker for brain AD pathology. This exploratory pilot study warrants further large-scale and well-controlled studies to validate the usefulness of plasma p-tau181 as an urgently needed surrogate marker for the diagnosis and disease progression of AD.

40 CFR 436.181 - Specialized definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Specialized definitions. 436.181 Section 436.181 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) MINERAL MINING AND PROCESSING POINT SOURCE CATEGORY Phosphate Rock...

40 CFR 436.181 - Specialized definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Specialized definitions. 436.181 Section 436.181 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) MINERAL MINING AND PROCESSING POINT SOURCE CATEGORY Phosphate Rock...

40 CFR 436.181 - Specialized definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Specialized definitions. 436.181 Section 436.181 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) MINERAL MINING AND PROCESSING POINT SOURCE CATEGORY Phosphate Rock...

10 CFR 26.181 - Purpose.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Purpose. 26.181 Section 26.181 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Determining Fitness-for-Duty Policy Violations and Determining Fitness... FFD policy and for making a determination of fitness. ...

10 CFR 26.181 - Purpose.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Purpose. 26.181 Section 26.181 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Determining Fitness-for-Duty Policy Violations and Determining Fitness... FFD policy and for making a determination of fitness. ...

10 CFR 26.181 - Purpose.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Purpose. 26.181 Section 26.181 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Determining Fitness-for-Duty Policy Violations and Determining Fitness... FFD policy and for making a determination of fitness. ...

10 CFR 26.181 - Purpose.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Purpose. 26.181 Section 26.181 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Determining Fitness-for-Duty Policy Violations and Determining Fitness... FFD policy and for making a determination of fitness. ...

10 CFR 26.181 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Purpose. 26.181 Section 26.181 Energy NUCLEAR REGULATORY COMMISSION FITNESS FOR DUTY PROGRAMS Determining Fitness-for-Duty Policy Violations and Determining Fitness... FFD policy and for making a determination of fitness. ...

[Effect of anthropotechnogenic chemical factors on formation of somatotypes in children and adolescents of school age].

PubMed

Iudin, G V; Osipova, M I; Eremin, G A; Stroĭkova, S B

2003-01-01

This research was done to study the dynamics of a process of constitutional types formation in 163 schoolboys and 181 schoolgirls, who live and study in various regions of the city of Ivanovo which are characterized by a different degree of environmental pollution with heavy metal salts and lead in particular. To define the constitutional types, the method of V.G. Shtefko and A.D. Ostrovsky (1929) was used. It was demonstrated that environmental pollution with heavy metal salts, the absorbed dose of which 3 times exceeded the maximum permissible dose, lead to the delay of somatotype differentiation in children and adolescents, which was more pronounced in schoolboys than in schoolgirls.

40 CFR 51.903 - How do the classification and attainment date provisions in section 181 of subpart 2 of the CAA...

Code of Federal Regulations, 2010 CFR

2010-07-01

... attainment date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? 51... date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? (a) In accordance with section 181(a)(1) of the CAA, each area subject to § 51.902(a) shall be classified by...

40 CFR 51.903 - How do the classification and attainment date provisions in section 181 of subpart 2 of the CAA...

Code of Federal Regulations, 2012 CFR

2012-07-01

... attainment date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? 51... date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? (a) In accordance with section 181(a)(1) of the CAA, each area subject to § 51.902(a) shall be classified by...

40 CFR 51.903 - How do the classification and attainment date provisions in section 181 of subpart 2 of the CAA...

Code of Federal Regulations, 2013 CFR

2013-07-01

... attainment date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? 51... date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? (a) In accordance with section 181(a)(1) of the CAA, each area subject to § 51.902(a) shall be classified by...

40 CFR 51.903 - How do the classification and attainment date provisions in section 181 of subpart 2 of the CAA...

Code of Federal Regulations, 2011 CFR

2011-07-01

... attainment date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? 51... date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? (a) In accordance with section 181(a)(1) of the CAA, each area subject to § 51.902(a) shall be classified by...

40 CFR 51.903 - How do the classification and attainment date provisions in section 181 of subpart 2 of the CAA...

Code of Federal Regulations, 2014 CFR

2014-07-01

... attainment date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? 51... date provisions in section 181 of subpart 2 of the CAA apply to areas subject to § 51.902(a)? (a) In accordance with section 181(a)(1) of the CAA, each area subject to § 51.902(a) shall be classified by...

Involvement of microRNA-181a and Bim in a rat model of retinal ischemia-reperfusion injury.

PubMed

He, Yu; Liu, Jin-Nan; Zhang, Jun-Jun; Fan, Wei

2016-01-01

To investigate the changes in the expression of microRNA-181a (miR-181a) and Bim in a rat model of retinal ischemia-reperfusion (RIR), to explore their target relationship in RIR and their involvement in regulating apoptosis of retinal ganglion cells (RGCs). Target gene prediction for miR-181a was performed with the aid of bioinformatics and Bim was identified as a potential target gene of miR-181a. A rat model of RIR was created by increasing the intraocular pressure. RGCs in the flatmounted retinas were labeled with Brn3, a marker for alive RGCs, by immunofluorescent staining. The changes in the number of RGCs after RIR were recorded. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to determine the expression level of miR-181a in the retina. Bim/Brn3 double immunofluorescence was used to detect the localization of Bim. The expression of Bim in the retina was determined with the aids of Western blot and qRT-PCR. Compared with the negative control group, the density of RGCs was significantly lower in the ischemia/reperfusion (I/R)-24h and I/R-72h groups (P<0.001). The expression level of miR-181a started to decrease at 0h after RIR, and further decreased at 24h and 72h compared with the negative control group (P<0.001). Bim was significantly upregulated at 12h after RIR (P<0.05) and reached peak at 24, 72h compared with the negative control group (P<0.01). Pearson correlation analysis showed that the expression level of Bim was negatively correlated with the expression level of miR-181a and the density of RGCs. Bim may be a potential target gene of miR-181a. Both miR-181a and Bim are involved in RGCs death in RIR. RIR may promote RGCs apoptosis in the retina via downregulation of miR-181a and its inhibition on Bim expression.

Miscibility, chain packing, and hydration of 1-palmitoyl-2-oleoyl phosphatidylcholine and other lipids in surface phases.

PubMed

Smaby, J M; Brockman, H L

1985-11-01

The miscibility of 1-palmitoyl-2-oleoyl phosphatidylcholine with triolein, 1,2-diolein, 1,3-diolein, 1(3)-monoolein, oleyl alcohol, methyl oleate, oleic acid, and oleyl cyanide (18:1 lipids) was studied at the argon-water interface. The isothermal phase diagrams for the mixtures at 24 degrees were characterized by two compositional regions. At the limit of miscibility with lower mol fractions of 18:1 lipid, the surface pressure was composition-independent, but above a mixture-specific stoichiometry, surface pressure at the limit of miscibility was composition-dependent. From the two-dimensional phase rule, it was determined that at low mol fractions of 18:1 lipids, the surface consisted of phospholipid and a preferred packing array or complex of phospholipid and 18:1 lipid, whereas, above the stoichiometry of the complex, the surface phase consisted of complex and excess 18:1 lipids. In both regions of the phase diagram, mixing along the phase boundary was apparently ideal allowing application of an equation of state described earlier (J. M. Smaby and H. L. Brockman, 1984, Biochemistry, 23:3312-3316). From such analysis, apparent partial molecular areas and hydrations for phospholipid, complex, and 18:1 lipid were obtained. Comparison of these calculated parameters for the complexed and uncomplexed states shows that the aliphatic moieties behave independently of polar head group. The transition of each 18:1 chain to the complexed state involves the loss of about one interfacial water molecule and its corresponding area. For 18:1 lipids with more than one chain another two water molecules per additional chain are present in both states but contribute little to molecular area. In contrast to 18:1 lipids, the phospholipid area and hydration change little upon complexation. The uniformity of chain packing and hydration behavior among 18:1 lipid species contrasts with complex stoichiometries that vary from 0.04 to 0.65. This suggests that the stoichiometry of the preferred packing array is determined by interactions involving the more polar moieties of the 18:1 lipids and the phospholipid.

Milk fatty acids as possible biomarkers to early diagnose elevated concentrations of blood plasma nonesterified fatty acids in dairy cows.

PubMed

Jorjong, S; van Knegsel, A T M; Verwaeren, J; Lahoz, M Val; Bruckmaier, R M; De Baets, B; Kemp, B; Fievez, V

2014-11-01

Most cows encounter a state of negative energy balance during the periparturient period, which may lead to metabolic disorders and impaired fertility. The aim of this study was to assess the potential of milk fatty acids as diagnostic tools of detrimental levels of blood plasma nonesterified fatty acids (NEFA), defined as NEFA concentrations beyond 0.6 mmol/L, in a data set of 92 early lactating cows fed a glucogenic or lipogenic diet and subjected to 0-, 30-, or 60-d dry period before parturition. Milk was collected in wk 2, 3, 4, and 8 (n = 368) and blood was sampled weekly from wk 2 to 8 after parturition. Milk was analyzed for milk fatty acids and blood plasma for NEFA. Data were classified as "at risk of detrimental blood plasma NEFA" (NEFA ≥ 0.6 mmol/L) and "not at risk of detrimental blood plasma NEFA" (NEFA <0.6 mmol/L). Concentrations of 45 milk fatty acids and milk fat C18:1 cis-9-to-C15:0 ratio were subjected to a discriminant analysis. Milk fat C18:1 cis-9 revealed the most discriminating variable to identify detrimental blood plasma NEFA. A false positive rate of 10% allowed us to diagnose 46% of the detrimental blood plasma NEFA cases based on a milk fat C18:1 cis-9 concentration of at least 230 g/kg of milk fatty acids. Additionally, it was assessed whether the milk fat C18:1 cis-9 concentrations of wk 2 could be used as an early warning for detrimental blood plasma NEFA risk during the first 8 wk in lactation. Cows with at least 240 g/kg of C18:1 cis-9 in milk fat had about 50% chance to encounter blood plasma NEFA values of 0.6 mmol/L or more during the first 8 wk of lactation, with a false positive rate of 11.4%. Profit simulations were based on costs for cows suffering from detrimental blood plasma NEFA, and costs for preventive treatment based on daily dosing of propylene glycol for 3 wk. Given the relatively low incidence rate (8% of all observations), continuous monitoring of milk fatty acids during the first 8 wk of lactation to diagnose detrimental blood plasma NEFA does not seem cost effective. On the contrary, milk fat C18:1 cis-9 of the second lactation week could be an early warning of cows at risk of detrimental blood NEFA. In this case, selective treatment may be cost effective. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Reciprocal activation between STAT3 and miR-181b regulates the proliferation of esophageal cancer stem-like cells via the CYLD pathway.

PubMed

Xu, Dan-Dan; Zhou, Peng-Jun; Wang, Ying; Zhang, Li; Fu, Wu-Yu; Ruan, Bi-Bo; Xu, Hai-Peng; Hu, Chao-Zhi; Tian, Lu; Qin, Jin-Hong; Wang, Sheng; Wang, Xiao; Li, Yi-Cheng; Liu, Qiu-Ying; Ren, Zhe; Zhang, Rong; Wang, Yi-Fei

2016-05-17

Recent studies have suggested that cancer cells contain subpopulations that can initiate tumor growth, self-renew, and maintain tumor cell growth. However, for esophageal cancer cells, the relationship between STAT3, microRNAs and cancer stem cells remains unclear. Serum-free culture was used to enrich esophageal cancer stem-like cells (ECSLC). Flow cytometry determined the proportion of ECSLC. qPCR were performed to examine expression level of stemness factors, mesenchymal markers, ATP-binding cassette (ABC) transporters, STAT3, miR-181b, CYLD. Western blot were performed to analyze the expression of STAT3, p-STAT3 and CYLD (cylindromatosis). BALB/c mice xenograft studies were conducted to evaluate the tumorigenicity of enriched ECSLC. Sphere formation assay and colony formation assays were employed to analyze the relationship between STAT3 and miR-181b. Luciferase assays were used to evaluate activity which CYLD is a target of miR-181b. Sphere formation cells (SFCs) with properties of ECSLC were enriched. Enriched SFCs in serum-free suspension culture exhibited cancer stem-like cell properties and increased single-positive CD44 + CD24-, stemness factor, mesenchymal marker expression ABC transporters and tumorigenicity in vivo compared with the parental cells. Additionally, we found that reciprocal activation between STAT3 and miR-181b regulated SFCs proliferation. Moreover, STAT3 directly activated miR-181b transcription in SFCs and miR-181b then potentiated p-STAT3 activity. Luciferase assays indicated that CYLD was a direct and functional target of miR-181b. The mutual regulation between STAT3 and miR-181b in SFCs was required for proliferation and apoptosis resistance. STAT3 and miR-181b control each other's expression in a positive feedback loop that regulates SFCs via CYLD pathway. These findings maybe is helpful for targeting ECSLC and providing approach for esophageal cancer treatments.

27 CFR 479.181 - Penalties.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Penalties. 479.181 Section 479.181 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN OTHER FIREARMS...

27 CFR 479.181 - Penalties.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Penalties. 479.181 Section 479.181 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN OTHER FIREARMS...

27 CFR 479.181 - Penalties.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Penalties. 479.181 Section 479.181 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN OTHER FIREARMS...

27 CFR 479.181 - Penalties.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Penalties. 479.181 Section 479.181 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN OTHER FIREARMS...

27 CFR 479.181 - Penalties.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Penalties. 479.181 Section 479.181 Alcohol, Tobacco Products, and Firearms BUREAU OF ALCOHOL, TOBACCO, FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE FIREARMS AND AMMUNITION MACHINE GUNS, DESTRUCTIVE DEVICES, AND CERTAIN OTHER FIREARMS...

First Report of an ST410 OXA-181 and CTX-M-15 Coproducing Escherichia coli Clone in Italy: A Whole-Genome Sequence Characterization.

PubMed

Piazza, Aurora; Comandatore, Francesco; Romeri, Francesca; Pagani, Cristina; Floriano, Anna Maria; Ridolfo, Annalisa; Antona, Carlo; Brilli, Matteo; Mattioni Marchetti, Vittoria; Bandi, Claudio; Gismondo, Maria Rita; Rimoldi, Sara Giordana

2018-02-23

We investigated an Italian OXA-181-producing Escherichia coli clinical isolate (ECS1_14) by whole-genome sequencing. The strain coharbored bla CTX-M-15 , bla CMY-2 , and qnrS1 genes; it belonged to ST410(Achtman)/ST692(Pasteur) and phylogroup A. The bla OXA-181 gene was harbored on a plasmid highly similar (99% identity) to the pOXA181_EC14828 plasmid, recently reported in China.

A Safety Evaluation of DAS181, a Sialidase Fusion Protein, in Rodents

PubMed Central

Larson, Jeffrey L.; Kang, Seong-Kwi; Choi, Bo In; Hedlund, Maria; Aschenbrenner, Laura M.; Cecil, Beth; Machado, GloriaMay; Nieder, Matthew; Fang, Fang

2011-01-01

DAS181 is a novel inhaled drug candidate blocking influenza virus (IFV) and parainfluenza virus (PIV) infections through removal of sialic acid receptors from epithelial surface of the respiratory tract. To support clinical development, a 28-day Good Laboratory Practices inhalation toxicology study was conducted in Sprague-Dawley rats. In this study, achieved average daily doses based on exposure concentrations were 0.47, 0.90, 1.55, and 3.00 mg/kg/day of DAS181 in a dry powder formulation. DAS181 was well tolerated at all dose levels, and there were no significant toxicological findings. DAS181 administration did not affect animal body weight, food consumption, clinical signs, ophthalmology, respiratory parameters, or organ weight. Gross pathology evaluations were unremarkable. Histological examination of the lungs was devoid of pulmonary tissue damage, and findings were limited to mild and transient changes indicative of exposure and clearance of a foreign protein. DAS181 did not show any cytotoxic effects on human and animal primary cells, including hepatocytes, skeletal muscle cells, osteoblasts, or respiratory epithelial cells. DAS181 did not cause direct or indirect hemolysis. A laboratory abnormality observed in the 28-day toxicology study was mild and transient anemia in male rats at the 3.00 mg/kg dose, which is an expected outcome of enhanced clearance of desialylated red blood cells resulting from systemic exposure with DAS181. Another laboratory observation was a transient dose-dependent elevation in alkaline phosphatase (ALP), which can be attributed to reduced ALP clearance resulting from increased protein desialylation due to DAS181 systemic exposure. These laboratory parameters returned to normal at the end of the recovery period. PMID:21572096

21 CFR 181.23 - Antimycotics.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Antimycotics. Substances classified as antimycotics, when migrating from food-packaging material shall include... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Antimycotics. 181.23 Section 181.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.24 - Antioxidants.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Antioxidants. Substances classified as antioxidants, when migrating from food-packaging material (limit of... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Antioxidants. 181.24 Section 181.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.23 - Antimycotics.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Antimycotics. Substances classified as antimycotics, when migrating from food-packaging material shall include... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Antimycotics. 181.23 Section 181.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.24 - Antioxidants.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Antioxidants. Substances classified as antioxidants, when migrating from food-packaging material (limit of... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Antioxidants. 181.24 Section 181.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.25 - Driers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Driers. Substances classified as driers, when migrating from food-packaging material shall include... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Driers. 181.25 Section 181.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.25 - Driers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Driers. Substances classified as driers, when migrating from food-packaging material shall include... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Driers. 181.25 Section 181.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.24 - Antioxidants.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Antioxidants. Substances classified as antioxidants, when migrating from food-packaging material (limit of... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Antioxidants. 181.24 Section 181.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.23 - Antimycotics.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Antimycotics. Substances classified as antimycotics, when migrating from food-packaging material shall include... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Antimycotics. 181.23 Section 181.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.25 - Driers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... migrating from food-packaging material shall include: Cobalt caprylate. Cobalt linoleate. Cobalt naphthenate... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Driers. 181.25 Section 181.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PRIOR-SANCTIONED FOOD...

21 CFR 181.23 - Antimycotics.

Code of Federal Regulations, 2014 CFR

2014-04-01

... antimycotics, when migrating from food-packaging material shall include: Calcium propionate. Methylparaben... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Antimycotics. 181.23 Section 181.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PRIOR-SANCTIONED FOOD...

21 CFR 181.23 - Antimycotics.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Antimycotics. Substances classified as antimycotics, when migrating from food-packaging material shall include... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Antimycotics. 181.23 Section 181.23 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.25 - Driers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Driers. Substances classified as driers, when migrating from food-packaging material shall include... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Driers. 181.25 Section 181.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.25 - Driers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Driers. Substances classified as driers, when migrating from food-packaging material shall include... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Driers. 181.25 Section 181.25 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.24 - Antioxidants.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Antioxidants. Substances classified as antioxidants, when migrating from food-packaging material (limit of... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Antioxidants. 181.24 Section 181.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

19 CFR 181.122 - Disclosure to government authorities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Disclosure to government authorities. 181.122 Section 181.122 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... responsible for the administration and enforcement of determinations of origin and of customs and revenue...

19 CFR 181.122 - Disclosure to government authorities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Disclosure to government authorities. 181.122 Section 181.122 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... responsible for the administration and enforcement of determinations of origin and of customs and revenue...

19 CFR 181.122 - Disclosure to government authorities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Disclosure to government authorities. 181.122 Section 181.122 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... responsible for the administration and enforcement of determinations of origin and of customs and revenue...

14 CFR 23.181 - Dynamic stability.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Dynamic stability. 23.181 Section 23.181 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS... force required to maintain speeds differing from the trim speed by at least plus and minus 15 percent is...

10 CFR 60.181 - Violations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Violations. 60.181 Section 60.181 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES... violation of the provisions of— (1) The Atomic Energy Act of 1954, as amended; (2) Title II of the Energy...

10 CFR 60.181 - Violations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Violations. 60.181 Section 60.181 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES... violation of the provisions of— (1) The Atomic Energy Act of 1954, as amended; (2) Title II of the Energy...

10 CFR 60.181 - Violations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Violations. 60.181 Section 60.181 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES... violation of the provisions of— (1) The Atomic Energy Act of 1954, as amended; (2) Title II of the Energy...

10 CFR 60.181 - Violations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Violations. 60.181 Section 60.181 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES IN GEOLOGIC REPOSITORIES... violation of the provisions of— (1) The Atomic Energy Act of 1954, as amended; (2) Title II of the Energy...

33 CFR 181.25 - Hull identification number format.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Hull identification number format... (CONTINUED) BOATING SAFETY MANUFACTURER REQUIREMENTS Identification of Boats § 181.25 Hull identification number format. Each of the hull identification numbers required by § 181.23 must consist of twelve...

21 CFR 181.28 - Release agents.

Code of Federal Regulations, 2014 CFR

2014-04-01

... classified as release agents, when migrating from food-packaging material shall include: Dimethylpolysiloxane... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Release agents. 181.28 Section 181.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PRIOR-SANCTIONED...

42 CFR 456.181 - Reports of evaluations and plans of care.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Reports of evaluations and plans of care. 456.181 Section 456.181 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Utilization Control: Mental Hospitals...

19 CFR 181.116 - Petition regarding adverse marking decision.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Petition regarding adverse marking decision. 181.116 Section 181.116 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... merchandise which was the subject of the adverse marking decision may file a petition with Customs requesting...

19 CFR 181.116 - Petition regarding adverse marking decision.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Petition regarding adverse marking decision. 181.116 Section 181.116 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... merchandise which was the subject of the adverse marking decision may file a petition with Customs requesting...

19 CFR 181.116 - Petition regarding adverse marking decision.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Petition regarding adverse marking decision. 181.116 Section 181.116 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... merchandise which was the subject of the adverse marking decision may file a petition with Customs requesting...

37 CFR 2.181 - Term of original registrations and renewals.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Term of original registrations and renewals. 2.181 Section 2.181 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND... of original registrations and renewals. (a)(1) Subject to the provisions of section 8 of the Act...

21 CFR 181.1 - General.

Code of Federal Regulations, 2011 CFR

2011-04-01

... ingredient whose use in food or food packaging is subject to a prior sanction or approval within the meaning... 21 Food and Drugs 3 2011-04-01 2011-04-01 false General. 181.1 Section 181.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.1 - General.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ingredient whose use in food or food packaging is subject to a prior sanction or approval within the meaning... 21 Food and Drugs 3 2010-04-01 2009-04-01 true General. 181.1 Section 181.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.28 - Release agents.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Release agents. Substances classified as release agents, when migrating from food-packaging material shall... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Release agents. 181.28 Section 181.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

29 CFR 1915.181 - Electrical circuits and distribution boards.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 7 2010-07-01 2010-07-01 false Electrical circuits and distribution boards. 1915.181... Electrical Machinery § 1915.181 Electrical circuits and distribution boards. (a) The provisions of this... employee is permitted to work on an electrical circuit, except when the circuit must remain energized for...

21 CFR 181.28 - Release agents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Release agents. 181.28 Section 181.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN... Release agents. Substances classified as release agents, when migrating from food-packaging material shall...

25 CFR 181.4 - How do I obtain an application?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false How do I obtain an application? 181.4 Section 181.4 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN HIGHWAY SAFETY PROGRAM... 2003, Albuquerque, New Mexico 87103. Each application package contains the necessary information...

21 CFR 181.32 - Acrylonitrile copolymers and resins.

Code of Federal Regulations, 2012 CFR

2012-04-01

... acrylonitrile monomer extraction for finished food-contact articles, determined by using the method of analysis... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Acrylonitrile copolymers and resins. 181.32 Section 181.32 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 181.32 - Acrylonitrile copolymers and resins.

Code of Federal Regulations, 2013 CFR

2013-04-01

... acrylonitrile monomer extraction for finished food-contact articles, determined by using the method of analysis... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Acrylonitrile copolymers and resins. 181.32 Section 181.32 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 181.32 - Acrylonitrile copolymers and resins.

Code of Federal Regulations, 2014 CFR

2014-04-01

... finished food-contact articles, determined by using the method of analysis titled “Gas-Solid... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Acrylonitrile copolymers and resins. 181.32 Section 181.32 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

14 CFR 125.181 - Induction system ice prevention.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Induction system ice prevention. 125.181... Requirements § 125.181 Induction system ice prevention. A means for preventing the malfunctioning of each engine due to ice accumulation in the engine air induction system must be provided for each airplane. ...

14 CFR 125.181 - Induction system ice prevention.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Induction system ice prevention. 125.181... Requirements § 125.181 Induction system ice prevention. A means for preventing the malfunctioning of each engine due to ice accumulation in the engine air induction system must be provided for each airplane. ...

14 CFR 125.181 - Induction system ice prevention.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Induction system ice prevention. 125.181... Requirements § 125.181 Induction system ice prevention. A means for preventing the malfunctioning of each engine due to ice accumulation in the engine air induction system must be provided for each airplane. ...

14 CFR 125.181 - Induction system ice prevention.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Induction system ice prevention. 125.181... Requirements § 125.181 Induction system ice prevention. A means for preventing the malfunctioning of each engine due to ice accumulation in the engine air induction system must be provided for each airplane. ...

14 CFR 125.181 - Induction system ice prevention.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Induction system ice prevention. 125.181... Requirements § 125.181 Induction system ice prevention. A means for preventing the malfunctioning of each engine due to ice accumulation in the engine air induction system must be provided for each airplane. ...

21 CFR 181.1 - General.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ingredient whose use in food or food packaging is subject to a prior sanction or approval within the meaning... 21 Food and Drugs 3 2013-04-01 2013-04-01 false General. 181.1 Section 181.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.24 - Antioxidants.

Code of Federal Regulations, 2014 CFR

2014-04-01

... antioxidants, when migrating from food-packaging material (limit of addition to food, 0.005 percent) shall... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Antioxidants. 181.24 Section 181.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PRIOR-SANCTIONED FOOD...

21 CFR 181.1 - General.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ingredient whose use in food or food packaging is subject to a prior sanction or approval within the meaning... 21 Food and Drugs 3 2012-04-01 2012-04-01 false General. 181.1 Section 181.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.28 - Release agents.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Release agents. Substances classified as release agents, when migrating from food-packaging material shall... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Release agents. 181.28 Section 181.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 181.28 - Release agents.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Release agents. Substances classified as release agents, when migrating from food-packaging material shall... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Release agents. 181.28 Section 181.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN...

21 CFR 169.181 - Vanilla-vanillin flavoring.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Vanilla-vanillin flavoring. 169.181 Section 169... Dressings and Flavorings § 169.181 Vanilla-vanillin flavoring. (a) Vanilla-vanillin flavoring conforms to... ingredients prescribed for vanilla-vanillin extract by § 169.180, except that its content of ethyl alcohol is...

21 CFR 169.181 - Vanilla-vanillin flavoring.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Vanilla-vanillin flavoring. 169.181 Section 169... Dressings and Flavorings § 169.181 Vanilla-vanillin flavoring. (a) Vanilla-vanillin flavoring conforms to... ingredients prescribed for vanilla-vanillin extract by § 169.180, except that its content of ethyl alcohol is...

21 CFR 169.181 - Vanilla-vanillin flavoring.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Vanilla-vanillin flavoring. 169.181 Section 169... Dressings and Flavorings § 169.181 Vanilla-vanillin flavoring. (a) Vanilla-vanillin flavoring conforms to... ingredients prescribed for vanilla-vanillin extract by § 169.180, except that its content of ethyl alcohol is...

21 CFR 169.181 - Vanilla-vanillin flavoring.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Vanilla-vanillin flavoring. 169.181 Section 169... Dressings and Flavorings § 169.181 Vanilla-vanillin flavoring. (a) Vanilla-vanillin flavoring conforms to... ingredients prescribed for vanilla-vanillin extract by § 169.180, except that its content of ethyl alcohol is...

21 CFR 169.181 - Vanilla-vanillin flavoring.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Vanilla-vanillin flavoring. 169.181 Section 169... Dressings and Flavorings § 169.181 Vanilla-vanillin flavoring. (a) Vanilla-vanillin flavoring conforms to... ingredients prescribed for vanilla-vanillin extract by § 169.180, except that its content of ethyl alcohol is...

19 CFR 181.12 - Maintenance and availability of records.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Maintenance and availability of records. 181.12 Section 181.12 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... or in automated record storage devices (for example, magnetic discs and tapes) if associated computer...

19 CFR 181.12 - Maintenance and availability of records.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Maintenance and availability of records. 181.12 Section 181.12 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... or in automated record storage devices (for example, magnetic discs and tapes) if associated computer...

19 CFR 181.12 - Maintenance and availability of records.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Maintenance and availability of records. 181.12 Section 181.12 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... or in automated record storage devices (for example, magnetic discs and tapes) if associated computer...

19 CFR 181.12 - Maintenance and availability of records.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Maintenance and availability of records. 181.12 Section 181.12 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... or in automated record storage devices (for example, magnetic discs and tapes) if associated computer...

19 CFR 181.62 - Commercial samples of negligible value.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Commercial samples of negligible value. 181.62... Returned After Repair or Alteration § 181.62 Commercial samples of negligible value. (a) General. Commercial samples of negligible value imported from Canada or Mexico may qualify for duty-free entry under...

19 CFR 181.115 - Intervention in importer's protest.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Intervention in importer's protest. 181.115... Marking Decisions § 181.115 Intervention in importer's protest. (a) Conditional right to intervene. An...'s protest. Such intervention shall not affect any time limits applicable to the protest or delay...

19 CFR 181.115 - Intervention in importer's protest.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Intervention in importer's protest. 181.115... Marking Decisions § 181.115 Intervention in importer's protest. (a) Conditional right to intervene. An...'s protest. Such intervention shall not affect any time limits applicable to the protest or delay...

19 CFR 181.115 - Intervention in importer's protest.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Intervention in importer's protest. 181.115... Marking Decisions § 181.115 Intervention in importer's protest. (a) Conditional right to intervene. An...'s protest. Such intervention shall not affect any time limits applicable to the protest or delay...

19 CFR 181.115 - Intervention in importer's protest.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Intervention in importer's protest. 181.115... Marking Decisions § 181.115 Intervention in importer's protest. (a) Conditional right to intervene. An...'s protest. Such intervention shall not affect any time limits applicable to the protest or delay...

19 CFR 181.115 - Intervention in importer's protest.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Intervention in importer's protest. 181.115... Marking Decisions § 181.115 Intervention in importer's protest. (a) Conditional right to intervene. An...'s protest. Such intervention shall not affect any time limits applicable to the protest or delay...

33 CFR 181.35 - Removal of numbers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Removal of numbers. 181.35...) BOATING SAFETY MANUFACTURER REQUIREMENTS Identification of Boats § 181.35 Removal of numbers. No person may remove or alter a number required by this subpart unless authorized by the Commandant, U.S. Coast...

33 CFR 181.35 - Removal of numbers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Removal of numbers. 181.35...) BOATING SAFETY MANUFACTURER REQUIREMENTS Identification of Boats § 181.35 Removal of numbers. No person may remove or alter a number required by this subpart unless authorized by the Commandant, U.S. Coast...

78 FR 11626 - Foreign-Trade Zone 181-Akron/Canton, OH, Authorization of Production Activity, Cimbar Performance...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-19

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [B-73-2012] Foreign-Trade Zone 181--Akron/Canton, OH, Authorization of Production Activity, Cimbar Performance Minerals, (Barium Sulfate Grinding), Wellsville, OH On October 10, 2012, the Northeast Ohio Trade & Economic Consortium, grantee of FTZ 181...

37 CFR 1.81 - Drawings required in patent application.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Drawings required in patent application. 1.81 Section 1.81 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions The Drawings...

37 CFR 1.81 - Drawings required in patent application.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Drawings required in patent application. 1.81 Section 1.81 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions The Drawings...

37 CFR 1.81 - Drawings required in patent application.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Drawings required in patent application. 1.81 Section 1.81 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions The Drawings...

Phosphorylation at Ser-181 of oncogenic KRAS is required for tumor growth.

PubMed

Barceló, Carles; Paco, Noelia; Morell, Mireia; Alvarez-Moya, Blanca; Bota-Rabassedas, Neus; Jaumot, Montserrat; Vilardell, Felip; Capella, Gabriel; Agell, Neus

2014-02-15

KRAS phosphorylation has been reported recently to modulate the activity of mutant KRAS protein in vitro. In this study, we defined S181 as a specific phosphorylation site required to license the oncogenic function of mutant KRAS in vivo. The phosphomutant S181A failed to induce tumors in mice, whereas the phosphomimetic mutant S181D exhibited an enhanced tumor formation capacity, compared with the wild-type KRAS protein. Reduced growth of tumors composed of cells expressing the nonphosphorylatable KRAS S181A mutant was correlated with increased apoptosis. Conversely, increased growth of tumors composed of cells expressing the phosphomimetic KRAS S181D mutant was correlated with increased activation of AKT and ERK, two major downstream effectors of KRAS. Pharmacologic treatment with PKC inhibitors impaired tumor growth associated with reduced levels of phosphorylated KRAS and reduced effector activation. In a panel of human tumor cell lines expressing various KRAS isoforms, we showed that KRAS phosphorylation was essential for survival and tumorigenic activity. Furthermore, we identified phosphorylated KRAS in a panel of primary human pancreatic tumors. Taken together, our findings establish that KRAS requires S181 phosphorylation to manifest its oncogenic properties, implying that its inhibition represents a relevant target to attack KRAS-driven tumors. ©2013 AACR.

A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune type 1 diabetes

PubMed Central

Serr, Isabelle; Scherm, Martin G.; Zahm, Adam M.; Schug, Jonathan; Flynn, Victoria K.; Hippich, Markus; Kälin, Stefanie; Becker, Maike; Achenbach, Peter; Nikolaev, Alexei; Gerlach, Katharina; Liebsch, Nicole; Loretz, Brigitta; Lehr, Claus-Michael; Kirchner, Benedikt; Spornraft, Melanie; Haase, Bettina; Segars, James; Küper, Christoph; Palmisano, Ralf; Waisman, Ari; Willis, Richard A.; Kim, Wan-Uk; Weigmann, Benno; Kaestner, Klaus H.; Ziegler, Anette-Gabriele; Daniel, Carolin

2018-01-01

Molecular checkpoints that trigger the onset of islet autoimmunity or progression to human type 1 diabetes (T1D) are incompletely understood. Using T cells from children at an early stage of islet autoimmunity without clinical T1D, we find that a microRNA181a (miRNA181a)–mediated increase in signal strength of stimulation and costimulation links nuclear factor of activated T cells 5 (NFAT5) with impaired tolerance induction and autoimmune activation. We show that enhancing miRNA181a activity increases NFAT5 expression while inhibiting FOXP3+ regulatory T cell (Treg) induction in vitro. Accordingly, Treg induction is improved using T cells from NFAT5 knockout (NFAT5ko) animals, whereas altering miRNA181a activity does not affect Treg induction in NFAT5ko T cells. Moreover, high costimulatory signals result in phosphoinositide 3-kinase (PI3K)–mediated NFAT5, which interferes with FoxP3+ Treg induction. Blocking miRNA181a or NFAT5 increases Treg induction in murine and humanized models and reduces murine islet autoimmunity in vivo. These findings suggest targeting miRNA181a and/or NFAT5 signaling for the development of innovative personalized medicines to limit islet autoimmunity. PMID:29298866

General Electric Company Hanford Works, Project C-431-A Production Facility-Section A, design report

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

Colburn, R.T.

1951-03-29

The 100-C project is to be located adjacent to the present 100-B Area. It is planned to build an addition to the present 181-B river pump house using the same elevations for pump settings, intakes, and floors as for the present pump house, thus maintaining the same suction conditions and flood protection as B Area. The 105 Building will be located on higher ground than B Area and therefore, protection against possible flood damage is assured. This report is divided into the following sections: (1) general description of project; (2) addition to existing river pump house; (3) raw water linesmore » from 181-B addition to 183-C lead house; (4) the 183-C filter plant; (5) 190-C process pump house; (6) power house addition; (7) high tanks; (8) retention basins; (9) outside streamlines; (10) primary substation; (11) outside underground lines; (12) outside electric lines; (13) roads, railroads, walks, fences; (14) structural design of all buildings; and (15) architectural design of all buildings.« less

Fatty acid composition of cooked chicken meat and chicken meat products as influenced by price range at retail.

PubMed

Gibbs, Rachael A; Rymer, Caroline; Givens, D I

2013-06-01

The primary objective was to determine fatty acid composition of skinless chicken breast and leg meat portions and chicken burgers and nuggets from the economy price range, standard price range (both conventional intensive rearing) and the organic range from four leading supermarkets. Few significant differences in the SFA, MUFA and PUFA composition of breast and leg meat portions were found among price ranges, and supermarket had no effect. No significant differences in fatty acid concentrations of economy and standard chicken burgers were found, whereas economy chicken nuggets had higher C16:1, C18:1 cis, C18:1 trans and C18:3 n-3 concentrations than had standard ones. Overall, processed chicken products had much higher fat contents and SFA than had whole meat. Long chain n-3 fatty acids had considerably lower concentrations in processed products than in whole meat. Overall there was no evidence that organic chicken breast or leg meat had a more favourable fatty acid composition than had meat from conventionally reared birds. Copyright © 2012 Elsevier Ltd. All rights reserved.

Analysis of globotriaosylceramide (Gb3) isoforms/analogs in unfractionated leukocytes, B lymphocytes and monocytes from Fabry patients using ultra-high performance liquid chromatography/tandem mass spectrometry.

PubMed

Toupin, Amanda; Lavoie, Pamela; Arthus, Marie-Françoise; Abaoui, Mona; Boutin, Michel; Fortier, Carole; Ménard, Claudia; Bichet, Daniel G; Auray-Blais, Christiane

2018-07-26

Fabry disease is an X-linked lysosomal storage disorder with marked variability in the phenotype and genotype. Glycosphingolipids such as globotriaosylceramide (Gb 3 ) isoforms/analogs, globotriaosylsphingosine (lyso-Gb 3 ) and analogs, and galabiosylceramide (Ga 2 ) isoforms/analogs may accumulate in biological fluids and different organs. The aims of this study were to: 1) develop/validate a novel UHPLC-MS/MS method for relative quantitation of Gb 3 in leukocytes (unfractionated white blood cells), B lymphocytes and monocytes; 2) evaluate these biomarkers in a cohort of Fabry patients and healthy controls; and 3) assess correlations between these biomarkers, treatment and genotype. Whole blood, plasma and urine samples from 21 Fabry patients and 20 healthy controls were analyzed. Samples were purified by liquid-liquid extraction and analyzed by UHPLC-MS/MS in positive electrospray ionization. Methylated Gb 3 isoforms were detected, showing that a methylation process occurs at the cellular level. Our results show that there were no significant differences in the distribution of the different Gb 3 isoforms/analogs in blood cells between Fabry patients and healthy controls. In leukocyte, Gb 3 [(d18:1)(C14:0)], Gb 3 [(d18:1)(C16:0)], Gb 3 [(d18:1)(C16:0)]Me, Gb 3 [(d18:1)(C16:1)], Gb 3 [(d18:1)(C18:0)], Gb 3 [(d18:1)(C18:1)], Gb 3 [(d18:1)(C20:1)], Gb 3 [(d18:1)(C24:2)], Gb 3 [(d18:1)(C26:1)] and total Gb 3 allowed good discrimination between male Fabry patients and male controls, patients having higher biomarker levels than controls. Regarding B lymphocytes and monocytes, the same tendency was observed without reaching statistical significance. A positive concordance between mutation types and biomarker levels in white blood cells was established. Our results might provide a deeper mechanistic comprehension of the underlying biochemical processes of Gb 3 biomarkers in white blood cells of Fabry patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Childhood Lead Poisoning: Conservative Estimates of the Social and Economic Benefits of Lead Hazard Control

PubMed Central

Gould, Elise

2009-01-01

Background This study is a cost–benefit analysis that quantifies the social and economic benefits to household lead paint hazard control compared with the investments needed to minimize exposure to these hazards. Objectives This research updates estimates of elevated blood lead levels among a cohort of children ≤ 6 years of age and compiles recent research to determine a range of the costs of lead paint hazard control ($1–$11 billion) and the benefits of reduction attributed to each cohort for health care ($11–$53 billion), lifetime earnings ($165–$233 billion), tax revenue ($25–$35 billion), special education ($30–$146 million), attention deficit–hyperactivity disorder ($267 million), and the direct costs of crime ($1.7 billion). Results Each dollar invested in lead paint hazard control results in a return of $17–$221 or a net savings of $181–269 billion. Conclusions There are substantial returns to investing in lead hazard control, particularly targeted at early intervention in communities most likely at risk. Given the high societal costs of inaction, lead hazard control appears to be well worth the price. PMID:19654928

19 CFR 181.92 - Definitions and general NAFTA advance ruling practice.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Definitions and general NAFTA advance ruling practice. 181.92 Section 181.92 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... National Commodity Specialist Division or by such other office as designated by the Commissioner of Customs...

19 CFR 181.92 - Definitions and general NAFTA advance ruling practice.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Definitions and general NAFTA advance ruling practice. 181.92 Section 181.92 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... National Commodity Specialist Division or by such other office as designated by the Commissioner of Customs...

19 CFR 181.95 - Oral discussion of issues.

Code of Federal Regulations, 2013 CFR

2013-04-01

... in the Customs file in the matter a written record setting forth any and all additional information... 19 Customs Duties 2 2013-04-01 2013-04-01 false Oral discussion of issues. 181.95 Section 181.95 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE...

19 CFR 181.95 - Oral discussion of issues.

Code of Federal Regulations, 2014 CFR

2014-04-01

... in the Customs file in the matter a written record setting forth any and all additional information... 19 Customs Duties 2 2014-04-01 2014-04-01 false Oral discussion of issues. 181.95 Section 181.95 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE...

19 CFR 181.95 - Oral discussion of issues.

Code of Federal Regulations, 2012 CFR

2012-04-01

... in the Customs file in the matter a written record setting forth any and all additional information... 19 Customs Duties 2 2012-04-01 2012-04-01 false Oral discussion of issues. 181.95 Section 181.95 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE...

19 CFR 181.95 - Oral discussion of issues.

Code of Federal Regulations, 2011 CFR

2011-04-01

... in the Customs file in the matter a written record setting forth any and all additional information... 19 Customs Duties 2 2011-04-01 2011-04-01 false Oral discussion of issues. 181.95 Section 181.95 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE...

50 CFR 218.181 - Permissible methods of taking.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Permissible methods of taking. 218.181... Center Panama City Division § 218.181 Permissible methods of taking. (a) Under Letters of Authorization... activities identified in § 218.180(c) is limited to the following species, by the indicated method of take...

25 CFR 224.181 - Who may appeal Departmental decisions or inaction under this part?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Who may appeal Departmental decisions or inaction under this part? 224.181 Section 224.181 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS TRIBAL ENERGY RESOURCE AGREEMENTS UNDER THE INDIAN TRIBAL ENERGY DEVELOPMENT AND SELF...

25 CFR 224.181 - Who may appeal Departmental decisions or inaction under this part?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Who may appeal Departmental decisions or inaction under this part? 224.181 Section 224.181 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS TRIBAL ENERGY RESOURCE AGREEMENTS UNDER THE INDIAN TRIBAL ENERGY DEVELOPMENT AND SELF...

26 CFR 1.181-6T - Effective date (temporary).

Code of Federal Regulations, 2011 CFR

2011-04-01

... first day of principal photography for which occurs on or after February 9, 2007, and before January 1...-between animation” in place of “principal photography”. Productions involving both animation and live-action photography may use either standard. (2) The applicability of §§ 1.181-1T through 1.181-5T expires...

26 CFR 1.181-6 - Effective/applicability date.

Code of Federal Regulations, 2014 CFR

2014-04-01

....181-1 through 1.181-5 apply to productions the first day of principal photography for which occurs on... principal photography or in-between animation occurs on or after December 7, 2012. (b) Pre-effective date... applies and for which the first day of principal photography (or in-between animation) occurred before...

26 CFR 1.181-6 - Effective/applicability date.

Code of Federal Regulations, 2013 CFR

2013-04-01

....181-1 through 1.181-5 apply to productions the first day of principal photography for which occurs on... principal photography or in-between animation occurs on or after December 7, 2012. (b) Pre-effective date... applies and for which the first day of principal photography (or in-between animation) occurred before...

21 CFR 181.26 - Drying oils as components of finished resins.

Code of Federal Regulations, 2011 CFR

2011-04-01

... classified as drying oils, when migrating from food-packaging material (as components of finished resins... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Drying oils as components of finished resins. 181.26 Section 181.26 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 181.22 - Certain substances employed in the manufacture of food-packaging materials.

Code of Federal Regulations, 2011 CFR

2011-04-01

... food-packaging materials. 181.22 Section 181.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... of food-packaging materials. Prior to the enactment of the food additives amendment to the Federal... manufacturing practice for food-packaging materials includes the restriction that the quantity of any of these...

21 CFR 181.26 - Drying oils as components of finished resins.

Code of Federal Regulations, 2010 CFR

2010-04-01

... classified as drying oils, when migrating from food-packaging material (as components of finished resins... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Drying oils as components of finished resins. 181.26 Section 181.26 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

22 CFR 181.9 - Internet Web site publication.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Internet Web site publication. 181.9 Section... PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.9 Internet Web site publication. The Office of the Assistant... responsible for making publicly available on the Internet Web site of the Department of State each treaty or...

22 CFR 181.9 - Internet Web site publication.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Internet Web site publication. 181.9 Section... PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.9 Internet Web site publication. The Office of the Assistant... responsible for making publicly available on the Internet Web site of the Department of State each treaty or...

22 CFR 181.9 - Internet Web site publication.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Internet Web site publication. 181.9 Section... PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.9 Internet Web site publication. The Office of the Assistant... responsible for making publicly available on the Internet Web site of the Department of State each treaty or...

26 CFR 1.181-6T - Effective date (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... first day of principal photography for which occurs on or after February 9, 2007, and before January 1...-between animation” in place of “principal photography”. Productions involving both animation and live-action photography may use either standard. (2) The applicability of §§ 1.181-1T through 1.181-5T expires...

26 CFR 1.181-1T - Deduction for qualified film and television production costs (temporary).

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Deduction for qualified film and television... Individuals and Corporations (continued) § 1.181-1T Deduction for qualified film and television production... provides definitions and rules concerning qualified film and television productions. Section 1.181-4...

21 CFR 181.33 - Sodium nitrate and potassium nitrate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium nitrate and potassium nitrate. 181.33...-Sanctioned Food Ingredients § 181.33 Sodium nitrate and potassium nitrate. Sodium nitrate and potassium nitrate are subject to prior sanctions issued by the U.S. Department of Agriculture for use as sources of...

21 CFR 181.33 - Sodium nitrate and potassium nitrate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium nitrate and potassium nitrate. 181.33...-Sanctioned Food Ingredients § 181.33 Sodium nitrate and potassium nitrate. Sodium nitrate and potassium nitrate are subject to prior sanctions issued by the U.S. Department of Agriculture for use as sources of...

21 CFR 181.34 - Sodium nitrite and potassium nitrite.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium nitrite and potassium nitrite. 181.34...-Sanctioned Food Ingredients § 181.34 Sodium nitrite and potassium nitrite. Sodium nitrite and potassium nitrite are subject to prior sanctions issued by the U.S. Department of Agriculture for use as color...

21 CFR 181.34 - Sodium nitrite and potassium nitrite.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium nitrite and potassium nitrite. 181.34...-Sanctioned Food Ingredients § 181.34 Sodium nitrite and potassium nitrite. Sodium nitrite and potassium nitrite are subject to prior sanctions issued by the U.S. Department of Agriculture for use as color...

19 CFR 181.13 - Failure to comply with requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... warrant where an exporter or a producer in the United States fails to comply with any requirement of this... 19 Customs Duties 2 2010-04-01 2010-04-01 false Failure to comply with requirements. 181.13 Section 181.13 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY...

21 CFR 181.33 - Sodium nitrate and potassium nitrate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium nitrate and potassium nitrate. 181.33...-Sanctioned Food Ingredients § 181.33 Sodium nitrate and potassium nitrate. Sodium nitrate and potassium... nitrite, with or without sodium or potassium nitrite, in the production of cured red meat products and...

21 CFR 181.34 - Sodium nitrite and potassium nitrite.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium nitrite and potassium nitrite. 181.34...-Sanctioned Food Ingredients § 181.34 Sodium nitrite and potassium nitrite. Sodium nitrite and potassium... fixatives and preservative agents, with or without sodium or potassium nitrate, in the curing of red meat...

21 CFR 181.33 - Sodium nitrate and potassium nitrate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium nitrate and potassium nitrate. 181.33...-Sanctioned Food Ingredients § 181.33 Sodium nitrate and potassium nitrate. Sodium nitrate and potassium... nitrite, with or without sodium or potassium nitrite, in the production of cured red meat products and...

22 CFR 181.9 - Internet Web site publication.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Internet Web site publication. 181.9 Section... PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.9 Internet Web site publication. The Office of the Assistant... responsible for making publicly available on the Internet Web site of the Department of State each treaty or...

22 CFR 181.9 - Internet Web site publication.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Internet Web site publication. 181.9 Section... PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.9 Internet Web site publication. The Office of the Assistant... responsible for making publicly available on the Internet Web site of the Department of State each treaty or...

19 CFR 122.181 - Definition of Customs security area.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 1 2010-04-01 2010-04-01 false Definition of Customs security area. 122.181...; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Access to Customs Security Areas § 122.181 Definition of Customs security area. For purposes of this section, the term “Customs security area” means the Federal...

21 CFR 181.26 - Drying oils as components of finished resins.

Code of Federal Regulations, 2013 CFR

2013-04-01

... classified as drying oils, when migrating from food-packaging material (as components of finished resins... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Drying oils as components of finished resins. 181.26 Section 181.26 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 181.26 - Drying oils as components of finished resins.

Code of Federal Regulations, 2014 CFR

2014-04-01

... food-packaging material (as components of finished resins) shall include: Chinawood oil (tung oil... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Drying oils as components of finished resins. 181.26 Section 181.26 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 181.26 - Drying oils as components of finished resins.

Code of Federal Regulations, 2012 CFR

2012-04-01

... classified as drying oils, when migrating from food-packaging material (as components of finished resins... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Drying oils as components of finished resins. 181.26 Section 181.26 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 181.34 - Sodium nitrite and potassium nitrite.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium nitrite and potassium nitrite. 181.34...-Sanctioned Food Ingredients § 181.34 Sodium nitrite and potassium nitrite. Sodium nitrite and potassium... fixatives and preservative agents, with or without sodium or potassium nitrate, in the curing of red meat...

33 CFR 181.17 - Label numbers and letters.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Label numbers and letters. 181.17...) BOATING SAFETY MANUFACTURER REQUIREMENTS Manufacturer Certification of Compliance § 181.17 Label numbers and letters. Letters and numbers on each label must: (a) Be no less than one-eighth of an inch in...

33 CFR 181.17 - Label numbers and letters.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Label numbers and letters. 181.17...) BOATING SAFETY MANUFACTURER REQUIREMENTS Manufacturer Certification of Compliance § 181.17 Label numbers and letters. Letters and numbers on each label must: (a) Be no less than one-eighth of an inch in...

19 CFR 181.94 - Nonconforming requests for advance rulings.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Nonconforming requests for advance rulings. 181.94...; DEPARTMENT OF THE TREASURY (CONTINUED) NORTH AMERICAN FREE TRADE AGREEMENT Advance Ruling Procedures § 181.94 Nonconforming requests for advance rulings. A person submitting a request for an advance ruling that does not...

19 CFR 181.97 - Withdrawal of NAFTA advance ruling requests.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Withdrawal of NAFTA advance ruling requests. 181...; DEPARTMENT OF THE TREASURY (CONTINUED) NORTH AMERICAN FREE TRADE AGREEMENT Advance Ruling Procedures § 181.97 Withdrawal of NAFTA advance ruling requests. Any request for an advance ruling may be withdrawn by the person...

Expression of microRNA-181 determines response to treatment with azacitidine and predicts survival in elderly patients with acute myeloid leukaemia.

PubMed

Butrym, Aleksandra; Rybka, Justyna; Baczyńska, Dagmara; Poręba, Rafał; Mazur, Grzegorz; Kuliczkowski, Kazimierz

2016-10-01

MicroRNAs (miRs) are small non-coding RNAs that play important roles in cell differentiation and survival. Abnormal expression of miRs has been demonstrated in numerous types of cancer, including acute myeloid leukaemia (AML). The aim of the present study was to evaluate miR-181 expression at diagnosis and following the completion of chemotherapy in AML patients, with regard to clinical response and outcome, particularly in patients treated with azacitidine. miR-181 expression was analysed using reverse transcription-quantitative polymerase chain reaction in 95 bone marrow specimens from newly diagnosed AML patients and in 20 healthy subjects for comparison. The results revealed upregulated miR-181 expression in the total cohort of AML patients, which was correlated with longer survival. However, in a subset of older AML patients treated with azacitidine, low miR-181 expression at diagnosis was a predictor for complete remission and prolonged survival. The findings indicated that miR-181 has an important role in AML and determines response to azacitidine treatment in older AML patients.

Expression of microRNA-181 determines response to treatment with azacitidine and predicts survival in elderly patients with acute myeloid leukaemia

PubMed Central

Butrym, Aleksandra; Rybka, Justyna; Baczyńska, Dagmara; Poręba, Rafał; Mazur, Grzegorz; Kuliczkowski, Kazimierz

2016-01-01

MicroRNAs (miRs) are small non-coding RNAs that play important roles in cell differentiation and survival. Abnormal expression of miRs has been demonstrated in numerous types of cancer, including acute myeloid leukaemia (AML). The aim of the present study was to evaluate miR-181 expression at diagnosis and following the completion of chemotherapy in AML patients, with regard to clinical response and outcome, particularly in patients treated with azacitidine. miR-181 expression was analysed using reverse transcription-quantitative polymerase chain reaction in 95 bone marrow specimens from newly diagnosed AML patients and in 20 healthy subjects for comparison. The results revealed upregulated miR-181 expression in the total cohort of AML patients, which was correlated with longer survival. However, in a subset of older AML patients treated with azacitidine, low miR-181 expression at diagnosis was a predictor for complete remission and prolonged survival. The findings indicated that miR-181 has an important role in AML and determines response to azacitidine treatment in older AML patients. PMID:27698792

Deregulation of microRNA-181c in cerebrospinal fluid of patients with clinically isolated syndrome is associated with early conversion to relapsing-remitting multiple sclerosis.

PubMed

Ahlbrecht, Jonas; Martino, Filippo; Pul, Refik; Skripuletz, Thomas; Sühs, Kurt-Wolfram; Schauerte, Celina; Yildiz, Özlem; Trebst, Corinna; Tasto, Lars; Thum, Sabrina; Pfanne, Angelika; Roesler, Romy; Lauda, Florian; Hecker, Michael; Zettl, Uwe K; Tumani, Hayrettin; Thum, Thomas; Stangel, Martin

2016-08-01

MiRNA-181c, miRNA-633 and miRNA-922 have been reported to be deregulated in multiple sclerosis. To investigate the association between miRNA-181c, miRNA-633 and miRNA-922 and conversion from clinically isolated syndrome (CIS) to relapsing-remitting multiple sclerosis (RRMS); and to compare microRNAs in cerebrospinal fluid (CSF) and serum with regard to dysfunction of the blood-CSF barrier. CSF and serum miRNA-181c, miRNA-633 and miRNA-922 were retrospectively determined by quantitative real-time polymerase chain reaction in CIS patients with (CIS-RRMS) and without (CIS-CIS) conversion to RRMS within 1 year. Thirty of 58 CIS patients developed RRMS. Cerebrospinal fluid miRNA-922, serum miRNA-922 and cerebrospinal fluid miRNA-181c were significantly higher in CIS-RRMS compared to CIS-CIS (P=0.027, P=0.048, P=0.029, respectively). High levels of cerebrospinal fluid miRNA-181c were independently associated with conversion from CIS to RRMS in multivariate Cox regression analysis (hazard ratio 2.99, 95% confidence interval 1.41-6.34, P=0.005). A combination of high cerebrospinal fluid miRNA-181c, younger age and more than nine lesions on magnetic resonance imaging showed the highest specificity (96%) and positive predictive value (94%) for conversion from CIS to RRMS. MiRNA-181c was higher in serum than in cerebrospinal fluid (P <0.001), while miRNA-633 and miRNA-922 were no different in cerebrospinal fluid and serum. Cerebrospinal fluid/serum albumin quotients did not correlate with microRNAs in cerebrospinal fluid (all P>0.711). Cerebrospinal fluid miRNA-181c might serve as a biomarker for early conversion to RRMS. Moreover, our data suggest an intrathecal origin of microRNAs detected in the cerebrospinal fluid. © The Author(s), 2015.

CSF Aβ1-42, but not p-Tau181, differentiates aMCI from SCI.

PubMed

Rizzi, Liara; Maria Portal, Marcelle; Batista, Carlos Eduardo Alves; Missiaggia, Luciane; Roriz-Cruz, Matheus

2018-01-01

Individuals with amnestic mild cognitive impairment (aMCI) are at a high risk to develop Alzheimer's disease (AD). We compared CSF levels of biomarkers of amyloidosis (Aβ 1-42 ) and neurodegeneration (p-Tau 181 ) in individuals with aMCI and with subjective cognitive impairment (SCI) in order to ascertain diagnostic accuracy and predict the odds ratio associated with aMCI. We collected CSF of individuals clinically diagnosed with aMCI (33) and SCI (12) of a memory clinic of Southern Brazil. Levels of Aβ 1-42 and p-Tau 181 were measured by immunoenzymatic assay. Participants also underwent neuropsychological testing including the verbal memory test subscore of the Consortium to Establish a Registry for Alzheimer's Disease (VM-CERAD). CSF concentration of Aβ 1-42 was significantly lower (p: .007) and p-Tau 181 /Aβ 1-42 ratio higher (p: .014) in aMCI individuals than in SCI. However, isolate p-Tau 181 levels were not associated with aMCI (p: .166). There was a statistically significant association between Aβ 1-42 and p-Tau 181 (R 2 : 0.177; β: -4.43; p: .017). ROC AUC of CSF Aβ 1-42 was 0.768 and of the p-Tau 181 /Aβ 1-42 ratio equals 0.742. Individuals with Aβ 1-42  < 823 pg/mL levels were 6.0 times more likely to be diagnosed with aMCI (p: .019), with a 68.9% accuracy. Those with p-Tau 181 /Aβ 1-42 ratio > 0.071 were at 4.6 increased odds to have aMCI (p: .043), with a 64.5% accuracy. VM-CERAD was significantly lower in aMCI than among SCI (p: .041). CSF Aβ 1-42 , but not p-Tau 181, level was significantly associated with aMCI. Copyright © 2017 Elsevier B.V. All rights reserved.

Oleic acid levels regulated by glycerolipid metabolism modulate defense gene expression in Arabidopsis

PubMed Central

Kachroo, Aardra; Venugopal, Srivathsa C.; Lapchyk, Ludmila; Falcone, Deane; Hildebrand, David; Kachroo, Pradeep

2004-01-01

Stearoyl-acyl-carrier-protein-desaturase-mediated conversion of stearic acid (18:0) to oleic acid (18:1) is a key step, which regulates levels of unsaturated fatty acids in cells. We previously showed that stearoyl-acyl-carrier-protein-desaturase mutants ssi2/fab2 carrying a loss-of-function mutation in the plastidial glycerol-3-phosphate (G3P) acyltransferase (act1) have elevated 18:1 levels and are restored in their altered defense signaling. Because G3P is required for the acylation of 18:1 by G3P acyltransferase, it was predicted that reduction of G3P levels should increase 18:1 levels and thereby revert ssi2-triggered phenotypes. Here we show that a mutation in G3P dehydrogenase restores both salicylic acid- and jasmonic acid-mediated phenotypes of ssi2 plants. The G3P dehydrogenase gene was identified by map-based cloning of the ssi2 suppressor mutant rdc8 (gly1-3) and confirmed by epistatic analysis of ssi2 with gly1-1. Restoration of ssi2-triggered phenotypes by the gly1-3 mutation was age-dependent and correlated with the levels of 18:1. Regeneration of G3P pools by glycerol application in ssi2 and ssi2 gly1-3 plants caused a marked reduction in the 18:1 levels, which rendered these plants hypersensitive to glycerol. This hypersensitivity in ssi2 was rescued by the act1 mutation. Furthermore, overexpression of the ACT1 gene resulted in enhanced sensitivity to glycerol. Glycerol application also lowered the 18:1 content in SSI2 plants and converted these into ssi2-mimics. Our results show that 18:1 levels in plastids are regulated by means of acylation with G3P, and a balance between G3P and 18:1 is critical for the regulation of salicylic acid- and jasmonic acid-mediated signaling pathways. PMID:15044700

26 CFR 1.181-6T - Effective/applicability dates (temporary).

Code of Federal Regulations, 2012 CFR

2012-04-01

... paragraph (b) of this section, § 1.181-1T applies to productions, the first day of principal photography for... animation” in place of “principal photography.” Productions involving both animation and live-action photography may use either standard. (2) The applicability of § 1.181-1T expires on October 17, 2014. (b...

27 CFR 24.181 - Use of sugar.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Use of sugar. 24.181... OF THE TREASURY LIQUORS WINE Production of Wine § 24.181 Use of sugar. Only sugar, as defined in § 24.10, may be used in the production of standard wine. The quantity of sugar used will be determined...

27 CFR 24.181 - Use of sugar.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Use of sugar. 24.181... OF THE TREASURY LIQUORS WINE Production of Wine § 24.181 Use of sugar. Only sugar, as defined in § 24.10, may be used in the production of standard wine. The quantity of sugar used will be determined...

15 CFR 18.1 - Purpose of these rules.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 18.1 Commerce and Foreign Trade Office of the Secretary of Commerce ATTORNEY'S FEES AND OTHER EXPENSES General Provisions § 18.1 Purpose of these rules. The Equal Access to Justice Act, 5 U.S.C. 504 (called “the Act” in this part), provides for the award of attorney fees and other expenses to eligible...

27 CFR 24.181 - Use of sugar.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Use of sugar. 24.181... OF THE TREASURY ALCOHOL WINE Production of Wine § 24.181 Use of sugar. Only sugar, as defined in § 24.10, may be used in the production of standard wine. The quantity of sugar used will be determined...

27 CFR 24.181 - Use of sugar.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Use of sugar. 24.181... OF THE TREASURY ALCOHOL WINE Production of Wine § 24.181 Use of sugar. Only sugar, as defined in § 24.10, may be used in the production of standard wine. The quantity of sugar used will be determined...

27 CFR 24.181 - Use of sugar.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Use of sugar. 24.181... OF THE TREASURY LIQUORS WINE Production of Wine § 24.181 Use of sugar. Only sugar, as defined in § 24.10, may be used in the production of standard wine. The quantity of sugar used will be determined...

34 CFR 403.181 - What are the cost-sharing requirements applicable to the basic programs?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 34 Education 3 2013-07-01 2013-07-01 false What are the cost-sharing requirements applicable to the basic programs? 403.181 Section 403.181 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND...

34 CFR 403.181 - What are the cost-sharing requirements applicable to the basic programs?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false What are the cost-sharing requirements applicable to the basic programs? 403.181 Section 403.181 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND...

34 CFR 403.181 - What are the cost-sharing requirements applicable to the basic programs?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 34 Education 3 2012-07-01 2012-07-01 false What are the cost-sharing requirements applicable to the basic programs? 403.181 Section 403.181 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND...

34 CFR 403.181 - What are the cost-sharing requirements applicable to the basic programs?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 3 2014-07-01 2014-07-01 false What are the cost-sharing requirements applicable to the basic programs? 403.181 Section 403.181 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND...

34 CFR 403.181 - What are the cost-sharing requirements applicable to the basic programs?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 3 2011-07-01 2011-07-01 false What are the cost-sharing requirements applicable to the basic programs? 403.181 Section 403.181 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND...

Thyroid hormone negatively regulates CDX2 and SOAT2 mRNA expression via induction of miRNA-181d in hepatic cells

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

Yap, Chui Sun; Sinha, Rohit Anthony; Ota, Sho

2013-11-01

Highlights: •Thyroid hormone induces miR-181d expression in human hepatic cells and mouse livers. •Thyroid hormone downregulates CDX2 and SOAT2 (or ACAT2) via miR-181d. •miR-181d reduces cholesterol output from human hepatic cells. -- Abstract: Thyroid hormones (THs) regulate transcription of many metabolic genes in the liver through its nuclear receptors (TRs). Although the molecular mechanisms for positive regulation of hepatic genes by TH are well understood, much less is known about TH-mediated negative regulation. Recently, several nuclear hormone receptors were shown to downregulate gene expression via miRNAs. To further examine the potential role of miRNAs in TH-mediated negative regulation, we usedmore » a miRNA microarray to identify miRNAs that were directly regulated by TH in a human hepatic cell line. In our screen, we discovered that miRNA-181d is a novel hepatic miRNA that was regulated by TH in hepatic cell culture and in vivo. Furthermore, we identified and characterized two novel TH-regulated target genes that were downstream of miR-181d signaling: caudal type homeobox 2 (CDX2) and sterol O-acyltransferase 2 (SOAT2 or ACAT2). CDX2, a known positive regulator of hepatocyte differentiation, was regulated by miR-181d and directly activated SOAT2 gene expression. Since SOAT2 is an enzyme that generates cholesteryl esters that are packaged into lipoproteins, our results suggest miR-181d plays a significant role in the negative regulation of key metabolic genes by TH in the liver.« less

MicroRNA-181c targets Bcl-2 and regulates mitochondrial morphology in myocardial cells

PubMed Central

Wang, Hongjiang; Li, Jing; Chi, Hongjie; Zhang, Fan; Zhu, Xiaoming; Cai, Jun; Yang, Xinchun

2015-01-01

Apoptosis is an important mechanism for the development of heart failure. Mitochondria are central to the execution of apoptosis in the intrinsic pathway. The main regulator of mitochondrial pathway of apoptosis is Bcl-2 family which includes pro- and anti-apoptotic proteins. MicroRNAs are small noncoding RNA molecules that regulate gene expression by inhibiting mRNA translation and/or inducing mRNA degradation. It has been proposed that microRNAs play critical roles in the cardiovascular physiology and pathogenesis of cardiovascular diseases. Our previous study has found that microRNA-181c, a miRNA expressed in the myocardial cells, plays an important role in the development of heart failure. With bioinformatics analysis, we predicted that miR-181c could target the 3′ untranslated region of Bcl-2, one of the anti-apoptotic members of the Bcl-2 family. Thus, we have suggested that miR-181c was involved in regulation of Bcl-2. In this study, we investigated this hypothesis using the Dual-Luciferase Reporter Assay System. Cultured myocardial cells were transfected with the mimic or inhibitor of miR-181c. We found that the level of miR-181c was inversely correlated with the Bcl-2 protein level and that transfection of myocardial cells with the mimic or inhibitor of miR-181c resulted in significant changes in the levels of caspases, Bcl-2 and cytochrome C in these cells. The increased level of Bcl-2 caused by the decrease in miR-181c protected mitochondrial morphology from the tumour necrosis factor alpha-induced apoptosis. PMID:25898913

19 CFR 181.98 - Situations in which no NAFTA advance ruling may be issued.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Situations in which no NAFTA advance ruling may be issued. 181.98 Section 181.98 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... subpart. No advance ruling letter will be issued in regard to a completed transaction. (b) Pending matters...

19 CFR 181.98 - Situations in which no NAFTA advance ruling may be issued.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Situations in which no NAFTA advance ruling may be issued. 181.98 Section 181.98 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... subpart. No advance ruling letter will be issued in regard to a completed transaction. (b) Pending matters...

19 CFR 181.98 - Situations in which no NAFTA advance ruling may be issued.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Situations in which no NAFTA advance ruling may be issued. 181.98 Section 181.98 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... subpart. No advance ruling letter will be issued in regard to a completed transaction. (b) Pending matters...

19 CFR 181.98 - Situations in which no NAFTA advance ruling may be issued.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Situations in which no NAFTA advance ruling may be issued. 181.98 Section 181.98 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND... subpart. No advance ruling letter will be issued in regard to a completed transaction. (b) Pending matters...

19 CFR 181.64 - Goods re-entered after repair or alteration in Canada or Mexico.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Canada or Mexico. 181.64 Section 181.64 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF... in Canada or Mexico. (a) General. This section sets forth the rules which apply for purposes of... Mexico as provided for in subheadings 9802.00.40 and 9802.00.50, HTSUS. Goods returned after having been...

20 CFR 220.181 - The month in which the Board will find that the annuitant is no longer disabled.

Code of Federal Regulations, 2010 CFR

2010-04-01

... the annuitant is no longer disabled. 220.181 Section 220.181 Employees' Benefits RAILROAD RETIREMENT... will find that the annuitant is no longer disabled. If the evidence shows that the annuitant is no longer disabled, the Board will find that his or her disability ended in the earliest of the following...

20 CFR 220.181 - The month in which the Board will find that the annuitant is no longer disabled.

Code of Federal Regulations, 2014 CFR

2014-04-01

... the annuitant is no longer disabled. 220.181 Section 220.181 Employees' Benefits RAILROAD RETIREMENT... will find that the annuitant is no longer disabled. If the evidence shows that the annuitant is no longer disabled, the Board will find that his or her disability ended in the earliest of the following...

20 CFR 220.181 - The month in which the Board will find that the annuitant is no longer disabled.

Code of Federal Regulations, 2013 CFR

2013-04-01

... the annuitant is no longer disabled. 220.181 Section 220.181 Employees' Benefits RAILROAD RETIREMENT... will find that the annuitant is no longer disabled. If the evidence shows that the annuitant is no longer disabled, the Board will find that his or her disability ended in the earliest of the following...

20 CFR 220.181 - The month in which the Board will find that the annuitant is no longer disabled.

Code of Federal Regulations, 2012 CFR

2012-04-01

... the annuitant is no longer disabled. 220.181 Section 220.181 Employees' Benefits RAILROAD RETIREMENT... will find that the annuitant is no longer disabled. If the evidence shows that the annuitant is no longer disabled, the Board will find that his or her disability ended in the earliest of the following...

20 CFR 220.181 - The month in which the Board will find that the annuitant is no longer disabled.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the annuitant is no longer disabled. 220.181 Section 220.181 Employees' Benefits RAILROAD RETIREMENT... will find that the annuitant is no longer disabled. If the evidence shows that the annuitant is no longer disabled, the Board will find that his or her disability ended in the earliest of the following...

30 CFR 250.181 - When may the Secretary cancel my lease and when am I compensated for cancellation?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false When may the Secretary cancel my lease and when am I compensated for cancellation? 250.181 Section 250.181 Mineral Resources BUREAU OF OCEAN ENERGY...), property, any mineral deposits (in areas leased or not leased), or the marine, coastal, or human...

Draft Genome Sequence of Lactobacillus paracasei DmW181, a Bacterium Isolated from Wild Drosophila.

PubMed

Hammer, Austin J; Walters, Amber; Carroll, Courtney; Newell, Peter D; Chaston, John M

2017-07-06

The draft genome sequence of Lactobacillus paracasei DmW181, an anaerobic bacterium isolate from wild Drosophila flies, is reported here. Strain DmW181 possesses genes for sialic acid and mannose metabolism. The assembled genome is 3,201,429 bp, with 3,454 predicted genes. Copyright © 2017 Hammer et al.

34 CFR 222.181 - What eligibility requirements must an LEA meet to apply for a modernization grant under the...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false What eligibility requirements must an LEA meet to apply for a modernization grant under the fourth priority? 222.181 Section 222.181 Education Regulations of the Offices of the Department of Education OFFICE OF ELEMENTARY AND SECONDARY EDUCATION, DEPARTMENT OF...

26 CFR 1.181-1T - Deduction for qualified film and television production costs (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Deduction for qualified film and television... and Corporations (continued) § 1.181-1T Deduction for qualified film and television production costs... film or television production (as defined in § 1.181-3T(b)) that the owner reasonably expects will be...

Normal Molecular Specification and Neurodegenerative Disease-Like Death of Spinal Neurons Lacking the SNARE-Associated Synaptic Protein Munc18-1.

PubMed

Law, Chris; Schaan Profes, Marcos; Levesque, Martin; Kaltschmidt, Julia A; Verhage, Matthijs; Kania, Artur

2016-01-13

The role of synaptic activity during early formation of neural circuits is a topic of some debate; genetic ablation of neurotransmitter release by deletion of the Munc18-1 gene provides an excellent model to answer the question of whether such activity is required for early circuit formation. Previous analysis of Munc18-1(-/-) mouse mutants documented their grossly normal nervous system, but its molecular differentiation has not been assessed. Munc18-1 deletion in mice also results in widespread neurodegeneration that remains poorly characterized. In this study, we demonstrate that the early stages of spinal motor circuit formation, including motor neuron specification, axon growth and pathfinding, and mRNA expression, are unaffected in Munc18-1(-/-) mice, demonstrating that synaptic activity is dispensable for early nervous system development. Furthermore, we show that the neurodegeneration caused by Munc18-1 loss is cell autonomous, consistent with apparently normal expression of several neurotrophic factors and normal GDNF signaling. Consistent with cell-autonomous degeneration, we demonstrate defects in the trafficking of the synaptic proteins Syntaxin1a and PSD-95 and the TrkB and DCC receptors in Munc18-1(-/-) neurons; these defects do not appear to cause ER stress, suggesting other mechanisms for degeneration. Finally, we demonstrate pathological similarities to Alzheimer's disease, such as altered Tau phosphorylation, neurofibrillary tangles, and accumulation of insoluble protein plaques. Together, our results shed new light upon the neurodegeneration observed in Munc18-1(-/-) mice and argue that this phenomenon shares parallels with neurodegenerative diseases. In this work, we demonstrate the absence of a requirement for regulated neurotransmitter release in the assembly of early neuronal circuits by assaying transcriptional identity, axon growth and guidance, and mRNA expression in Munc18-1-null mice. Furthermore, we characterize the neurodegeneration observed in Munc18-1 mutants and demonstrate that this cell-autonomous process does not appear to be a result of defects in growth factor signaling or ER stress caused by protein trafficking defects. However, we find the presence of various pathological hallmarks of Alzheimer's disease that suggest parallels between the degeneration in these mutants and neurodegenerative conditions. Copyright © 2016 the authors 0270-6474/16/360562-16$15.00/0.

Nitro-fatty acid metabolome: saturation, desaturation, beta-oxidation, and protein adduction.

PubMed

Rudolph, Volker; Schopfer, Francisco J; Khoo, Nicholas K H; Rudolph, Tanja K; Cole, Marsha P; Woodcock, Steven R; Bonacci, Gustavo; Groeger, Alison L; Golin-Bisello, Franca; Chen, Chen-Shan; Baker, Paul R S; Freeman, Bruce A

2009-01-16

Nitrated derivatives of fatty acids (NO2-FA) are pluripotent cell-signaling mediators that display anti-inflammatory properties. Current understanding of NO2-FA signal transduction lacks insight into how or if NO2-FA are modified or metabolized upon formation or administration in vivo. Here the disposition and metabolism of nitro-9-cis-octadecenoic (18:1-NO2) acid was investigated in plasma and liver after intravenous injection in mice. High performance liquid chromatography-tandem mass spectrometry analysis showed that no 18:1-NO2 or metabolites were detected under basal conditions, whereas administered 18:1-NO2 is rapidly adducted to plasma thiol-containing proteins and glutathione. NO2-FA are also metabolized via beta-oxidation, with high performance liquid chromatography-tandem mass spectrometry analysis of liver lipid extracts of treated mice revealing nitro-7-cis-hexadecenoic acid, nitro-5-cis-tetradecenoic acid, and nitro-3-cis-dodecenoic acid and corresponding coenzyme A derivatives of 18:1-NO2 as metabolites. Additionally, a significant proportion of 18:1-NO2 and its metabolites are converted to nitroalkane derivatives by saturation of the double bond, and to a lesser extent are desaturated to diene derivatives. There was no evidence of the formation of nitrohydroxyl or conjugated ketone derivatives in organs of interest, metabolites expected upon 18:1-NO2 hydration or nitric oxide (*NO) release. Plasma samples from treated mice had significant extents of protein-adducted 18:1-NO2 detected by exchange to added beta-mercaptoethanol. This, coupled with the observation of 18:1-NO2 release from glutathione-18:1-NO2 adducts, supports that reversible and exchangeable NO2-FA-thiol adducts occur under biological conditions. After administration of [3H]18:1-NO2, 64% of net radiolabel was recovered 90 min later in plasma (0.2%), liver (18%), kidney (2%), adipose tissue (2%), muscle (31%), urine (6%), and other tissue compartments, and may include metabolites not yet identified. In aggregate, these findings show that electrophilic FA nitroalkene derivatives (a) acquire an extended half-life by undergoing reversible and exchangeable electrophilic reactions with nucleophilic targets and (b) are metabolized predominantly via saturation of the double bond and beta-oxidation reactions that terminate at the site of acyl-chain nitration.

Nitro-fatty Acid Metabolome: Saturation, Desaturation, β-Oxidation, and Protein Adduction*

PubMed Central

Rudolph, Volker; Schopfer, Francisco J.; Khoo, Nicholas K. H.; Rudolph, Tanja K.; Cole, Marsha P.; Woodcock, Steven R.; Bonacci, Gustavo; Groeger, Alison L.; Golin-Bisello, Franca; Chen, Chen-Shan; Baker, Paul R. S.; Freeman, Bruce A.

2009-01-01

Nitrated derivatives of fatty acids (NO2-FA) are pluripotent cell-signaling mediators that display anti-inflammatory properties. Current understanding of NO2-FA signal transduction lacks insight into how or if NO2-FA are modified or metabolized upon formation or administration in vivo. Here the disposition and metabolism of nitro-9-cis-octadecenoic (18:1-NO2) acid was investigated in plasma and liver after intravenous injection in mice. High performance liquid chromatography-tandem mass spectrometry analysis showed that no 18:1-NO2 or metabolites were detected under basal conditions, whereas administered 18:1-NO2 is rapidly adducted to plasma thiol-containing proteins and glutathione. NO2-FA are also metabolized via β-oxidation, with high performance liquid chromatography-tandem mass spectrometry analysis of liver lipid extracts of treated mice revealing nitro-7-cis-hexadecenoic acid, nitro-5-cis-tetradecenoic acid, and nitro-3-cis-dodecenoic acid and corresponding coenzyme A derivatives of 18:1-NO2 as metabolites. Additionally, a significant proportion of 18:1-NO2 and its metabolites are converted to nitroalkane derivatives by saturation of the double bond, and to a lesser extent are desaturated to diene derivatives. There was no evidence of the formation of nitrohydroxyl or conjugated ketone derivatives in organs of interest, metabolites expected upon 18:1-NO2 hydration or nitric oxide (•NO) release. Plasma samples from treated mice had significant extents of protein-adducted 18:1-NO2 detected by exchange to added β-mercaptoethanol. This, coupled with the observation of 18:1-NO2 release from glutathione-18:1-NO2 adducts, supports that reversible and exchangeable NO2-FA-thiol adducts occur under biological conditions. After administration of [3H]18:1-NO2, 64% of net radiolabel was recovered 90 min later in plasma (0.2%), liver (18%), kidney (2%), adipose tissue (2%), muscle (31%), urine (6%), and other tissue compartments, and may include metabolites not yet identified. In aggregate, these findings show that electrophilic FA nitroalkene derivatives (a) acquire an extended half-life by undergoing reversible and exchangeable electrophilic reactions with nucleophilic targets and (b) are metabolized predominantly via saturation of the double bond and β-oxidation reactions that terminate at the site of acyl-chain nitration. PMID:19015269

30 CFR 219.417 - How will MMS disburse qualified OCS revenues to the coastal political subdivisions if, during any...

Code of Federal Regulations, 2010 CFR

2010-07-01

... in the 181 Area in the Eastern Gulf of Mexico Planning Area? 219.417 Section 219.417 Mineral... no applicable leased tracts in the 181 Area in the Eastern Gulf of Mexico Planning Area? If, during any fiscal year, there are no applicable leased tracts in the 181 Area in the Eastern Gulf of Mexico...

30 CFR 550.181 - When may the Secretary cancel my lease and when am I compensated for cancellation?

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 2 2013-07-01 2013-07-01 false When may the Secretary cancel my lease and when am I compensated for cancellation? 550.181 Section 550.181 Mineral Resources BUREAU OF OCEAN ENERGY... deposits (in areas leased or not leased), or the marine, coastal, or human environment; (b) The threat of...

30 CFR 550.181 - When may the Secretary cancel my lease and when am I compensated for cancellation?

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 2 2012-07-01 2012-07-01 false When may the Secretary cancel my lease and when am I compensated for cancellation? 550.181 Section 550.181 Mineral Resources BUREAU OF OCEAN ENERGY... deposits (in areas leased or not leased), or the marine, coastal, or human environment; (b) The threat of...

30 CFR 550.181 - When may the Secretary cancel my lease and when am I compensated for cancellation?

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 2 2014-07-01 2014-07-01 false When may the Secretary cancel my lease and when am I compensated for cancellation? 550.181 Section 550.181 Mineral Resources BUREAU OF OCEAN ENERGY... deposits (in areas leased or not leased), or the marine, coastal, or human environment; (b) The threat of...

34 CFR 222.181 - What eligibility requirements must an LEA meet to apply for a modernization grant under the...

Code of Federal Regulations, 2011 CFR

2011-07-01

... value of real property available to be taxed for school purposes that is below its State average; and (d... 34 Education 1 2011-07-01 2011-07-01 false What eligibility requirements must an LEA meet to apply for a modernization grant under the fourth priority? 222.181 Section 222.181 Education Regulations of...

Decision Aiding and Coordination in Decision-Making Organizations.

DTIC Science & Technology

1988-01-01

30111 211100 30131 281 150 90 131 231 100 40 9 151 241 90 30151 241 90 30181 331 150 90 161 261 100 40 10 181 271 90 30 181 271 90 30231 381 150 90 181...check mark is present, the delayed execution will take place. I’, Hm ~One: function: Used to specify that the execution is implemented one firing at a

25 CFR 1000.181 - How does the Tribe/Consortium initiate the negotiation of a successor AFA?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 2 2010-04-01 2010-04-01 false How does the Tribe/Consortium initiate the negotiation of a successor AFA? 1000.181 Section 1000.181 Indians OFFICE OF THE ASSISTANT SECRETARY, INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ANNUAL FUNDING AGREEMENTS UNDER THE TRIBAL SELF-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATIO...

BDNF-TrkB Signaling Coupled to nPKCε and cPKCβI Modulate the Phosphorylation of the Exocytotic Protein Munc18-1 During Synaptic Activity at the Neuromuscular Junction

PubMed Central

Simó, Anna; Just-Borràs, Laia; Cilleros-Mañé, Víctor; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A.; Tomàs, Josep

2018-01-01

Munc18-1, a neuron-specific member of the Sec1/Munc18 family, is involved in neurotransmitter release by binding tightly to syntaxin. Munc18-1 is phosphorylated by PKC on Ser-306 and Ser-313 in vitro which reduces the amount of Munc18-1 able to bind syntaxin. We have previously identified that PKC is involved in neurotransmitter release when continuous electrical stimulation imposes a moderate activity on the NMJ and that muscle contraction through TrkB has an important impact on presynaptic PKC isoforms levels, specifically cPKCβI and nPKCε. Therefore, the present study was designed to understand how Munc18-1 phosphorylation is affected by (1) synaptic activity at the neuromuscular junction, (2) nPKCε and cPKCβI isoforms activity, (3) muscle contraction per se, and (4) the BDNF/TrkB signaling in a neuromuscular activity-dependent manner. We performed immunohistochemistry and confocal techniques to evidence the presynaptic location of Munc18-1 in the rat diaphragm muscle. To study synaptic activity, we stimulated the phrenic nerve (1 Hz, 30 min) with or without contraction (abolished by μ-conotoxin GIIIB). Specific inhibitory reagents were used to block nPKCε and cPKCβI activity and to modulate the tropomyosin receptor kinase B (TrkB). Main results obtained from Western blot experiments showed that phosphorylation of Munc18-1 at Ser-313 increases in response to a signaling mechanism initiated by synaptic activity and directly mediated by nPKCε. Otherwise, cPKCβI and TrkB activities work together to prevent this synaptic activity–induced Munc18-1 phosphorylation by a negative regulation of cPKCβI over nPKCε. Therefore, a balance between the activities of these PKC isoforms could be a relevant cue in the regulation of the exocytotic apparatus. The results also demonstrate that muscle contraction prevents the synaptic activity–induced Munc18-1 phosphorylation through a mechanism that opposes the TrkB/cPKCβI/nPKCε signaling. PMID:29946239

BDNF-TrkB Signaling Coupled to nPKCε and cPKCβI Modulate the Phosphorylation of the Exocytotic Protein Munc18-1 During Synaptic Activity at the Neuromuscular Junction.

PubMed

Simó, Anna; Just-Borràs, Laia; Cilleros-Mañé, Víctor; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Garcia, Neus; Lanuza, Maria A; Tomàs, Josep

2018-01-01

Munc18-1, a neuron-specific member of the Sec1/Munc18 family, is involved in neurotransmitter release by binding tightly to syntaxin. Munc18-1 is phosphorylated by PKC on Ser-306 and Ser-313 in vitro which reduces the amount of Munc18-1 able to bind syntaxin. We have previously identified that PKC is involved in neurotransmitter release when continuous electrical stimulation imposes a moderate activity on the NMJ and that muscle contraction through TrkB has an important impact on presynaptic PKC isoforms levels, specifically cPKCβI and nPKCε. Therefore, the present study was designed to understand how Munc18-1 phosphorylation is affected by (1) synaptic activity at the neuromuscular junction, (2) nPKCε and cPKCβI isoforms activity, (3) muscle contraction per se , and (4) the BDNF/TrkB signaling in a neuromuscular activity-dependent manner. We performed immunohistochemistry and confocal techniques to evidence the presynaptic location of Munc18-1 in the rat diaphragm muscle. To study synaptic activity, we stimulated the phrenic nerve (1 Hz, 30 min) with or without contraction (abolished by μ-conotoxin GIIIB). Specific inhibitory reagents were used to block nPKCε and cPKCβI activity and to modulate the tropomyosin receptor kinase B (TrkB). Main results obtained from Western blot experiments showed that phosphorylation of Munc18-1 at Ser-313 increases in response to a signaling mechanism initiated by synaptic activity and directly mediated by nPKCε. Otherwise, cPKCβI and TrkB activities work together to prevent this synaptic activity-induced Munc18-1 phosphorylation by a negative regulation of cPKCβI over nPKCε. Therefore, a balance between the activities of these PKC isoforms could be a relevant cue in the regulation of the exocytotic apparatus. The results also demonstrate that muscle contraction prevents the synaptic activity-induced Munc18-1 phosphorylation through a mechanism that opposes the TrkB/cPKCβI/nPKCε signaling.

Munc18-1-regulated stage-wise SNARE assembly underlying synaptic exocytosis.

PubMed

Ma, Lu; Rebane, Aleksander A; Yang, Guangcan; Xi, Zhiqun; Kang, Yuhao; Gao, Ying; Zhang, Yongli

2015-12-23

Synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins couple their stage-wise folding/assembly to rapid exocytosis of neurotransmitters in a Munc18-1-dependent manner. The functions of the different assembly stages in exocytosis and the role of Munc18-1 in SNARE assembly are not well understood. Using optical tweezers, we observed four distinct stages of assembly in SNARE N-terminal, middle, C-terminal, and linker domains (or NTD, MD, CTD, and LD, respectively). We found that SNARE layer mutations differentially affect SNARE assembly. Comparison of their effects on SNARE assembly and on exocytosis reveals that NTD and CTD are responsible for vesicle docking and fusion, respectively, whereas MD regulates SNARE assembly and fusion. Munc18-1 initiates SNARE assembly and structures t-SNARE C-terminus independent of syntaxin N-terminal regulatory domain (NRD) and stabilizes the half-zippered SNARE complex dependent upon the NRD. Our observations demonstrate distinct functions of SNARE domains whose assembly is intimately chaperoned by Munc18-1.

Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

PubMed Central

Urigüen, L; Gil-Pisa, I; Munarriz-Cuezva, E; Berrocoso, E; Pascau, J; Soto-Montenegro, M L; Gutiérrez-Adán, A; Pintado, B; Madrigal, J L M; Castro, E; Sánchez-Blázquez, P; Ortega, J E; Guerrero, M J; Ferrer-Alcon, M; García-Sevilla, J A; Micó, J A; Desco, M; Leza, J C; Pazos, Á; Garzón, J; Meana, J J

2013-01-01

Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D1 receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia. The animal could provide valuable insights into phenotypic aspects of this psychiatric disorder. PMID:23340504

CA-125 AUC as a predictor for epithelial ovarian cancer relapse.

PubMed

Mano, António; Falcão, Amílcar; Godinho, Isabel; Santos, Jorge; Leitão, Fátima; de Oliveira, Carlos; Caramona, Margarida

2008-01-01

The aim of the present work was to evaluate the usefulness of CA-125 normalized in time area under the curve (CA-125 AUC) to signalise epithelial ovarian cancer relapse. Data from a hundred and eleven patients were submitted to two different approaches based on CA-125 AUC increase values to predict patient relapse. In Criterion A total CA-125 AUC normalized in time value (AUC(i)) was compared with the immediately previous one (AUC(i-1)) using the formulae AUC(i) > or = F * AUC(i-1) (several F values were tested) to find the appropriate close related increment associated to patient relapse. In Criterion B total CA-125 AUC normalised in time was calculated and several cut-off values were correlated with patient relapse prediction capacity. In Criterion A the best accuracy was achieved with a factor (F) of 1.25 (increment of 25% from the previous status), while in Criterion B the best accuracies were achieved with cut-offs of 25, 50, 75 and 100 IU/mL. The mean lead time to relapse achieved with Criterion A was 181 days, while with Criterion B they were, respectively, 131, 111, 63 and 11 days. Based on our results we believe that conjugation and sequential application of both criteria in patient relapse detection should be highly advisable. CA-125 AUC rapid burst in asymptomatic patients should be firstly evaluated using Criterion A with a high accuracy (0.85) and with a substantial mean lead time to relapse (181 days). If a negative answer was obtained then Criterion B should performed to confirm the absence of relapse.

GSK3 inhibitors CHIR99021 and 6-bromoindirubin-3′-oxime inhibit microRNA maturation in mouse embryonic stem cells

PubMed Central

Wu, Yongyan; Liu, Fayang; Liu, Yingying; Liu, Xiaolei; Ai, Zhiying; Guo, Zekun; Zhang, Yong

2015-01-01

Wnt/β-catenin signalling plays a prominent role in maintaining self-renewal and pluripotency of mouse embryonic stem cells (mESCs). microRNAs (miRNAs) have critical roles in maintaining pluripotency and directing reprogramming. To investigate the effect of GSK3 inhibitors on miRNA expression, we analysed the miRNA expression profile of J1 mESCs in the absence or presence of CHIR99021 (CHIR) or 6-bromoindirubin-3′-oxime (BIO) by small RNA deep-sequencing. The results demonstrate that CHIR and BIO decrease mature miRNAs of most miRNA species, 90.4% and 98.1% of the differentially expressed miRNAs in BIO and CHIR treated cells were downregulated respectively. CHIR and BIO treatment leads to a slight upregulation of the primary transcripts of the miR-302–367 cluster and miR-181 family of miRNAs, these miRNAs are activated by Wnt/β-catenin signalling. However, the precursor and mature form of the miR-302–367 cluster and miR-181 family of miRNAs are downregulated by CHIR, suggesting CHIR inhibits maturation of primary miRNA. Western blot analysis shows that BIO and CHIR treatment leads to a reduction of the RNase III enzyme Drosha in the nucleus. These data suggest that BIO and CHIR inhibit miRNA maturation by disturbing nuclear localisation of Drosha. Results also show that BIO and CHIR induce miR-211 expression in J1 mESCs. PMID:25727520

26 CFR 31.3121(b)(18)-1 - Services performed by a resident of the Republic of the Philippines while temporarily in Guam.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Republic of the Philippines while temporarily in Guam. 31.3121(b)(18)-1 Section 31.3121(b)(18)-1 Internal... performed by a resident of the Republic of the Philippines while temporarily in Guam. (a) Services performed after 1960 by a resident of the Republic of the Philippines while in Guam on a temporary basis as a...

Down-regulation of miR-181a can reduce heat stress damage in PBMCs of Holstein cows.

PubMed

Chen, Kun-Lin; Fu, Yuan-Yuan; Shi, Min-Yan; Li, Hui-Xia

2016-09-01

Heat stress can weaken the immune system and even increase livestock's susceptibility to disease. MicroRNA (miR) is short non-coding RNA that functions in post-transcriptional regulation of gene expression and some phenotypes. Our recent study found that miR-181a is highly expressed in the serum of heat-stressed Holstein cows, but the potential function of miR-181a is still not clarified. In this study, peripheral blood mononuclear cells (PBMCs), isolated from Holstein cows' peripheral blood, were used to investigate the effects of miR-181a inhibitor on heat stress damage. Our results showed that significant apoptosis and oxidative damage were induced by heat stress in PBMCs. However, with apoptosis, the levels of reactive oxygen species (ROS) and content of malondialdehyde (MDA) were reduced, while the content of glutathione (GSH) and the activity of superoxide dismutase (SOD) were increased even under heat stress conditions after transfecting miR-181a inhibitors to PBMCs. Meanwhile, mRNA expression of bax and caspase-3 was significantly decreased, but mRNA expression of bcl-2 was increased in transfected PBMCs. In conclusion, our results demonstrated that down-regulation of miR-181a can reduce heat stress damage in PBMCs of Holstein cows.

Acid Response of Bifidobacterium longum subsp. longum BBMN68 Is Accompanied by Modification of the Cell Membrane Fatty Acid Composition.

PubMed

Liu, Songling; Ren, Fazheng; Jiang, Jingli; Zhao, Liang

2016-07-28

The acid response of Bifidobacterium longum subsp. longum BBMN68 has been studied in our previous study. The fab gene, which is supposed to be involved in membrane fatty acid biosynthesis, was demonstrated to be induced in acid response. In order to investigate the relationship between acid response and cell membrane fatty acid composition, the acid adaptation of BBMN68 was assessed and the membrane fatty acid composition at different adaptation conditions was identified. Indeed, the fatty acid composition was influenced by acid adaptation. Our results showed that the effective acid adaptations were accompanied with decrease in the unsaturated to saturated fatty acids ratio (UFA/SFA) and increase in cyclopropane fatty acid (CFA) content, which corresponded to previous studies. Moreover, both effective and non-effective acid adaptation conditions resulted in decrease in the C18:1 cis-9/C18:1 trans-9 ratio, indicating that the C18:1 cis-9/C18:1 trans-9 ratio is associated with acid tolerance response but not with acid adaptation response. Taken together, this study indicated that the UFA/SFA and CFA content of BBMN68 were involved in acid adaptation and the C18:1 cis-9/C18:1 trans-9 ratio was involved in acid tolerance response.

Stereochemistry of C18 monounsaturated cork suberin acids determined by spectroscopic techniques including (1) H-NMR multiplet analysis of olefinic protons.

PubMed

Santos, Sara; Graça, José

2014-01-01

Suberin is a biopolyester responsible for the protection of secondary plant tissues, and yet its molecular structure remains unknown. The C18:1 ω-hydroxyacid and the C18:1 α,ω-diacid are major monomers in the suberin structure, but the configuration of the double bond remains to be elucidated. To unequivocally define the configuration of the C18:1 suberin acids. Pure C18:1 ω-hydroxyacid and C18:1 α,ω-diacid, isolated from cork suberin, and two structurally very close C18:1 model compounds of known stereochemistry, methyl oleate and methyl elaidate, were analysed by NMR spectroscopy, Fourier transform infrared (FTIR) and Raman spectroscopy, and GC-MS. The GC-MS analysis showed that both acids were present in cork suberin as only one geometric isomer. The analysis of dimethyloxazoline (DMOX) and picolinyl derivatives proved the double bond position to be at C-9. The FTIR spectra were concordant with a cis-configuration for both suberin acids, but their unambiguous stereochemical assignment came from the NMR analysis: (i) the chemical shifts of the allylic (13) C carbons were shielded comparatively to the trans model compound, and (ii) the complex multiplets of the olefinic protons could be simulated only with (3) JHH and long-range (4) JHH coupling constants typical of a cis geometry. The two C18:1 suberin acids in cork are (Z)-18-hydroxyoctadec-9-enoic acid and (Z)-octadec-9-enedoic acid. Copyright © 2013 John Wiley & Sons, Ltd.

Inhibition of gentamicin binding to rat renal brush-border membrane by megalin ligands and basic peptides.

PubMed

Nagai, Junya; Saito, Masaki; Adachi, Yoshinori; Yumoto, Ryoko; Takano, Mikihisa

2006-05-01

Our previous studies showed that coadministration of cytochrome c and a 20-residue basic peptide, N-WASP181-200 (NISHTKEKKKGKAKKKRLTK, pI=10.87) inhibits renal accumulation of gentamicin. In this study, we examined effects of ligands of megalin, an endocytic receptor involved in renal uptake of gentamicin, and basic peptides including N-WASP180-200 and its mutant peptides on gentamicin binding to isolated rat renal brush-border membrane (BBM). Gentamicin binding to BBM was inhibited by megalin ligands, basic peptide fragments of cytochrome c, and N-WASP181-200 in a concentration-dependent manner. Klotz plot analysis showed that N-WASP181-200 inhibited the binding of gentamicin in a competitive manner. By substituting glycines for lysines in N-WASP181-200 at positions 9 and 15, the inhibitory effect on gentamicin binding to BBM was reduced, which may be related to a decrease in the alpha-helix content in the peptide. Gentamicin binding to BBM treated with trypsin, in which megalin completely disappeared, was significantly but not completely decreased compared with the native BBM. In addition, treatment of BBM with trypsin led to a decrease in the inhibitory effect of N-WASP181-200 on gentamicin binding. These observations support that megalin ligands and basic peptides including N-WASP181-200 decrease renal accumulation of gentamicin by inhibiting its binding to BBM of proximal tubule cells, partly interacting with megalin. In addition, the alpha-helix conformation may play an important role in the inhibitory effect of N-WASP181-200 on the binding of gentamicin to BBM.

Molecular dynamics and Monte Carlo simulations for protein-ligand binding and inhibitor design.

PubMed

Cole, Daniel J; Tirado-Rives, Julian; Jorgensen, William L

2015-05-01

Non-nucleoside inhibitors of HIV reverse transcriptase are an important component of treatment against HIV infection. Novel inhibitors are sought that increase potency against variants that contain the Tyr181Cys mutation. Molecular dynamics based free energy perturbation simulations have been run to study factors that contribute to protein-ligand binding, and the results are compared with those from previous Monte Carlo based simulations and activity data. Predictions of protein-ligand binding modes are very consistent for the two simulation methods; the accord is attributed to the use of an enhanced sampling protocol. The Tyr181Cys binding pocket supports large, hydrophobic substituents, which is in good agreement with experiment. Although some discrepancies exist between the results of the two simulation methods and experiment, free energy perturbation simulations can be used to rapidly test small molecules for gains in binding affinity. Free energy perturbation methods show promise in providing fast, reliable and accurate data that can be used to complement experiment in lead optimization projects. This article is part of a Special Issue entitled "Recent developments of molecular dynamics". Copyright © 2014 Elsevier B.V. All rights reserved.

The reduced serum free triiodothyronine and increased dorsal hippocampal SNAP-25 and Munc18-1 had existed in middle-aged CD-1 mice with mild spatial cognitive impairment.

PubMed

Cao, Lei; Jiang, Wei; Wang, Fang; Yang, Qi-Gang; Wang, Chao; Chen, Yong-Ping; Chen, Gui-Hai

2013-12-02

Changes of synaptic proteins in highlighted brain regions and decreased serum thyroid hormones (THs) have been implied in age-related learning and memory decline. Previously, we showed significant pairwise correlations among markedly impaired spatial learning and memory ability, decreased serum free triiodothyronine (FT3) and increased hippocampal SNAP-25 and Munc18-1 in old Kunming mice. However, whether these changes and the correlations occur in middle-age mice remains unclear. Since this age is one of the best stages to study age-related cognitive decline, we explored the spatial learning and memory ability, serum THs, cerebral SNAP-25 and Munc18-1 levels and their relationships of middle-aged mice in this study. The learning and memory abilities of 35 CD-1 mice (19 mice aged 6 months and 16 mice aged 12 months) were measured with a radial six-arm water maze (RAWM). The SNAP-25 and Munc18-1 levels were semi-quantified by Western blotting and the serum THs were detected by radioimmunoassay. The results showed the middle-aged mice had decreased serum FT3, increased dorsal hippocampal (DH) SNAP-25 and Munc18-1, and many or long number of errors and latency in both learning and memory phases of the RAWM. The Pearson's correlation test showed that the DH SANP-25 and Munc18-1 levels were positively correlated with the number of errors and latency in learning phases of the RAWM. Meanwhile, the DH SANP-25 and Munc18-1 levels negatively correlated with the serum FT3 level. These results suggested that reduced FT3 with increased DH SNAP-25 and Munc18-1 levels might be involved in the spatial learning ability decline in the middle-aged mice. © 2013 Elsevier B.V. All rights reserved.

MiR-181b targets Six2 and inhibits the proliferation of metanephric mesenchymal cells in vitro

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

Lyu, Zhongshi; Mao, Zhaomin; Wang, Honglian

2013-11-01

Highlights: •We do bio-informatics websites to analysis of Six2 3′UTR. •MiR181b is a putative miRNA which can targets Six2 3′UTR. •MiR-181b binding site in the 3′UTR of Six2 is functional. •MiR-181b suppresses MK3 cells cell proliferation by targeting Six2. -- Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that down-regulate gene expression by binding to target mRNA for cleavage or translational repression, and play important regulatory roles in renal development. Despite increasing genes have been predicted to be miRNA targets by bioinformatic analysis during kidney development, few of them have been verified by experiment. The objective of our study is tomore » identify the miRNAs targeting Six2, a critical transcription factor that maintains the mesenchymal progenitor pool via self-renewal (proliferation) during renal development. We initially analyzed the 3′UTR of Six2 and found 37 binding sites targeted by 50 putative miRNAs in the 3′UTR of Six2. Among the 50 miRNAs, miR-181b is the miRNAs predicted by the three used websites. In our study, the results of luciferase reporter assay, realtime-PCR and Western blot demonstrated that miR-181b directly targeted on the 3′UTR of Six2 and down-regulate the expression of Six2 at mRNA and protein levels. Furthermore, EdU proliferation assay along with the Six2 rescue strategy showed that miR-181b suppresses the proliferation of metanephric mesenchymal by targeting Six2 in part. In our research, we concluded that by targeting the transcription factor gene Six2, miR-181b inhibits the proliferation of metanephric mesenchymal cells in vitro and might play an important role in the formation of nephrons.« less

21 CFR 181.27 - Plasticizers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... CONSUMPTION (CONTINUED) PRIOR-SANCTIONED FOOD INGREDIENTS Specific Prior-Sanctioned Food Ingredients § 181.27... oxygen, minimum, 6.0 percent). Ethylphthalyl ethyl glycolate. Glycerol monooleate. Monoisopropyl citrate...

40 CFR 51.1103 - Application of classification and attainment date provisions in CAA section 181 of subpart 2 to...

Code of Federal Regulations, 2012 CFR

2012-07-01

... attainment date provisions in CAA section 181 of subpart 2 to areas subject to § 51.1102(a). 51.1103 Section... attainment date provisions in CAA section 181 of subpart 2 to areas subject to § 51.1102(a). (a) In... Ozone NAAQS (0.075 ppm) for Areas Subject to Section 51.1102(a) Area class 8-hour design value(ppm ozone...

40 CFR 51.1103 - Application of classification and attainment date provisions in CAA section 181 of subpart 2 to...

Code of Federal Regulations, 2014 CFR

2014-07-01

... attainment date provisions in CAA section 181 of subpart 2 to areas subject to § 51.1102(a). 51.1103 Section... attainment date provisions in CAA section 181 of subpart 2 to areas subject to § 51.1102(a). (a) In... Ozone NAAQS (0.075 ppm) for Areas Subject to Section 51.1102(a) Area class 8-hour design value(ppm ozone...

40 CFR 51.1103 - Application of classification and attainment date provisions in CAA section 181 of subpart 2 to...

Code of Federal Regulations, 2013 CFR

2013-07-01

... attainment date provisions in CAA section 181 of subpart 2 to areas subject to § 51.1102(a). 51.1103 Section... attainment date provisions in CAA section 181 of subpart 2 to areas subject to § 51.1102(a). (a) In... Ozone NAAQS (0.075 ppm) for Areas Subject to Section 51.1102(a) Area class 8-hour design value(ppm ozone...

Neuropsychiatric Symptoms and Alzheimer's Disease Biomarkers Predict Driving Decline: Brief Report.

PubMed

Babulal, Ganesh M; Stout, Sarah H; Head, Denise; Holtzman, David M; Fagan, Anne M; Morris, John C; Roe, Catherine M

2017-01-01

We examined whether neuropsychiatric symptoms (NPS) interact with cerebrospinal fluid (CSF) biomarkers (amyloid-β42 [Aβ42], tau, phosphorylated tau181 [ptau181], tau/Aβ42, and ptau181/Aβ42) of Alzheimer's disease pathology to predict driving decline among cognitively-normal older adults (N = 116) aged ≥65. Cox proportional hazards models examined time to receiving a rating of marginal or fail on the driving test. Age, education, and gender were adjusted in the models. Participants with more abnormal CSF (Aβ42, tau/Aβ42, ptau181/Aβ42) and NPS were faster to receive a marginal/fail on the road test compared to those without NPS. NPS interact with abnormal CSF biomarkers to impact driving performance among cognitively-normal older adults.

Fragment distribution in 78,86Kr+181Ta reactions

NASA Astrophysics Data System (ADS)

Zhang, Dong-Hong; Zhang, Feng-Shou

2018-05-01

Within the framework of the isospin-dependent quantum molecular dynamics model, along with the GEMINI model, the 86Kr+181Ta reaction at 80, 120 and 160 MeV/nucleon and the 78Kr+181Ta reaction at 160 MeV/nucleon are studied, and the production cross sections of the generated fragments are calculated. More inter-mediate and large mass fragments can be produced in the reactions with a large range of impact parameter. The production cross sections of nuclei such as the isotopes of Si and P generally decrease with increasing incident energy. Isotopes near the neutron drip line are produced more in the neutron-rich system 86Kr+181Ta. Supported by Youth Research Foundation of Shanxi Datong University (2016Q10)

Evidence for lysine acetylation in the coat protein of a polerovirus.

PubMed

Cilia, Michelle; Johnson, Richard; Sweeney, Michelle; DeBlasio, Stacy L; Bruce, James E; MacCoss, Michael J; Gray, Stewart M

2014-10-01

Virions of the RPV strain of Cereal yellow dwarf virus-RPV were purified from infected oat tissue and analysed by MS. Two conserved residues, K147 and K181, in the virus coat protein, were confidently identified to contain epsilon-N-acetyl groups. While no functional data are available for K147, K181 lies within an interfacial region critical for virion assembly and stability. The signature immonium ion at m/z 126.0919 demonstrated the presence of N-acetyllysine, and the sequence fragment ions enabled an unambiguous assignment of the epsilon-N-acetyl modification on K181. We hypothesize that selection favours acetylation of K181 in a fraction of coat protein monomers to stabilize the capsid by promoting intermonomer salt bridge formation.

Chlamydia abortus Pmp18.1 Induces IL-1β Secretion by TLR4 Activation through the MyD88, NF-κB, and Caspase-1 Signaling Pathways

PubMed Central

Pan, Qing; Zhang, Qiang; Chu, Jun; Pais, Roshan; Liu, Shanshan; He, Cheng; Eko, Francis O.

2017-01-01

The polymorphic membrane protein D (Pmp18D) is a 160-kDa outer membrane protein that is conserved and plays an important role in Chlamydia abortus pathogenesis. We have identified an N-terminal fragment of Pmp18D (designated Pmp18.1) as a possible subunit vaccine antigen. In this study, we evaluated the vaccine potential of Pmp18.1 by investigating its ability to induce innate immune responses in dendritic cells and the signaling pathway(s) involved in rPmp18.1-induced IL-1β secretion. We next investigated the immunomodulatory impact of VCG, in comparison with the more established Th1-promoting adjuvants, CpG and FL, on rPmp18.1-mediated innate immune activation. Finally, the effect of siRNA targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in DCs on IL-1β cytokine secretion was also investigated. Bone marrow-derived dendritic cells (BMDCs) were stimulated with rPmp18.1 in the presence or absence of VCG or CpG or FL and the magnitude of cytokines produced was assessed using a multiplex cytokine ELISA assay. Expression of costimulatory molecules and Toll-like receptors (TLRs) was analyzed by flow cytometry. Quantitation of intracellular levels of myeloid differentiation factor 88 (MyD88), nuclear factor kappa beta (NF-κB p50/p65), and Caspase-1 was evaluated by Western immunoblotting analysis while NF-κB p65 nuclear translocation was assessed by confocal microscopy. The results showed DC stimulation with rPmp18.1 provoked the secretion of proinflammatory cytokines and upregulated expression of TLRs and co-stimulatory molecules associated with DC maturation. These responses were significantly (p ≤ 0.001) enhanced by VCG but not CpG or FL. In addition, rPmp18.1 activated the expression of MyD88, NF-κB p50, and Caspase-1 as well as the nuclear expression of NF-κB p65 in treated DCs. Furthermore, targeting TLR4, MyD88, NF-κB p50, and Caspase-1 mRNA in BMDCs with siRNA significantly reduced their expression levels, resulting in decreased IL-1β cytokine secretion, strongly suggesting their involvement in the rPmp18.1-induced IL-1β cytokine secretion. Taken together, these results indicate that C. abortus Pmp18.1 induces IL-1β secretion by TLR4 activation through the MyD88, NF-κB as well as the Caspase-1 signaling pathways and may be a potential C. abortus vaccine candidate. The vaccine potential of Pmp18.1 will subsequently be evaluated in an appropriate animal model, using VCG as an immunomodulator, following immunization and challenge. PMID:29326885

Nucleic Acid Amplification Testing and Sequencing Combined with Acid-Fast Staining in Needle Biopsy Lung Tissues for the Diagnosis of Smear-Negative Pulmonary Tuberculosis.

PubMed

Jiang, Faming; Huang, Weiwei; Wang, Ye; Tian, Panwen; Chen, Xuerong; Liang, Zongan

2016-01-01

Smear-negative pulmonary tuberculosis (PTB) is common and difficult to diagnose. In this study, we investigated the diagnostic value of nucleic acid amplification testing and sequencing combined with acid-fast bacteria (AFB) staining of needle biopsy lung tissues for patients with suspected smear-negative PTB. Patients with suspected smear-negative PTB who underwent percutaneous transthoracic needle biopsy between May 1, 2012, and June 30, 2015, were enrolled in this retrospective study. Patients with AFB in sputum smears were excluded. All lung biopsy specimens were fixed in formalin, embedded in paraffin, and subjected to acid-fast staining and tuberculous polymerase chain reaction (TB-PCR). For patients with positive AFB and negative TB-PCR results in lung tissues, probe assays and 16S rRNA sequencing were used for identification of nontuberculous mycobacteria (NTM). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of PCR and AFB staining were calculated separately and in combination. Among the 220 eligible patients, 133 were diagnosed with TB (men/women: 76/57; age range: 17-80 years, confirmed TB: 9, probable TB: 124). Forty-eight patients who were diagnosed with other specific diseases were assigned as negative controls, and 39 patients with indeterminate final diagnosis were excluded from statistical analysis. The sensitivity, specificity, PPV, NPV, and accuracy of histological AFB (HAFB) for the diagnosis of smear-negative were 61.7% (82/133), 100% (48/48), 100% (82/82), 48.5% (48/181), and 71.8% (130/181), respectively. The sensitivity, specificity, PPV, and NPV of histological PCR were 89.5% (119/133), 95.8% (46/48), 98.3% (119/121), and 76.7% (46/60), respectively, demonstrating that histological PCR had significantly higher accuracy (91.2% [165/181]) than histological acid-fast staining (71.8% [130/181]), P < 0.001. Parallel testing of histological AFB staining and PCR showed the sensitivity, specificity, PPV, NPV, and accuracy to be 94.0% (125/133), 95.8% (46/48), 98.4% (125/127), 85.2% (46/54), and 94.5% (171/181), respectively. Among patients with positive AFB and negative PCR results in lung tissue specimens, two were diagnosed with NTM infections (Mycobacterium avium-intracellulare complex and Mycobacterium kansasii). Nucleic acid amplification testing combined with acid-fast staining in lung biopsy tissues can lead to early and accurate diagnosis in patients with smear-negative pulmonary tuberculosis. For patients with positive histological AFB and negative tuberculous PCR results in lung tissue, NTM infection should be suspected and could be identified by specific probe assays or 16S rRNA sequencing.

MitomiRs in human inflamm-aging: a hypothesis involving miR-181a, miR-34a and miR-146a.

PubMed

Rippo, Maria Rita; Olivieri, Fabiola; Monsurrò, Vladia; Prattichizzo, Francesco; Albertini, Maria Cristina; Procopio, Antonio Domenico

2014-08-01

Mitochondria are intimately involved in the aging process. The decline of autophagic clearance during aging affects the equilibrium between mitochondrial fusion and fission, leading to a build-up of dysfunctional mitochondria, oxidative stress, chronic low-grade inflammation, and increased apoptosis rates, the main hallmarks of aging. Current research suggests that a large number of microRNAs (miRs or miRNAs) are differentially expressed during cell aging. Other lines of evidence indicate that several miRs likely share in "inflamm-aging", an aging-related state characterized by systemic chronic inflammation that in turn provides a biological background favoring susceptibility to age-related diseases and disabilities. Interestingly, miRs can modulate mitochondrial activity, and a discrete miR set has recently been identified in mitochondria of different species and cell types (mitomiRs). Here we show that some mitomiRs (let7b, mir-146a, -133b, -106a, -19b, -20a, -34a, -181a and -221) are also among the miRs primarily involved in cell aging and in inflamm-aging. Of note, Ingenuity Pathway Analysis (IPA) of aging-related mitomiR targets has disclosed a number of resident mitochondrial proteins playing large roles in energy metabolism, mitochondrial transport and apoptosis. Among these, Bcl-2 family members--which are critically involved in maintaining mitochondrial integrity--may play a role in controlling mitochondrial function and dysfunction during cellular aging, also considering that Bcl-2, the master member of the family, is an anti-oxidant and anti-apoptotic factor and regulates mitochondrial fission/fusion and autophagy. This intriguing hypothesis is supported by several observations: i) in endothelial cells undergoing replicative senescence (HUVECs), a well-established model of cell senescence, miR-146a, miR-34a, and miR-181a are over-expressed whereas their target Bcl-2 is down-regulated; ii) IPA of the miR-146a, miR-34a and miR-181a network shows that they are closely linked to each other, to Bcl-2 and to mitochondria; and iii) miR-146a, miR-34a, and miR-181a are involved in important cell functions (growth, proliferation, death, survival, maintenance) and age-related diseases (cancer, skeletal and muscle disorders, neurological, cardiovascular and metabolic diseases). In conclusion several aging-related mitomiRs may play a direct role in controlling mitochondrial function by regulating mitochondrial protein expression. Their modulation could thus mediate the loss of mitochondrial integrity and function in aging cells, inducing or contributing to the inflammatory response and to age-related diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

22 CFR 18.1 - Scope.

Code of Federal Regulations, 2010 CFR

2010-04-01

... § 18.1 Scope. This part contains rules governing disciplinary action against a former officer or... employment conflict of interest prohibitions. Such disciplinary action may include prohibition from practice...

Effects of protonation state of Asp181 and position of active site water molecules on the conformation of PTP1B.

PubMed

Ozcan, Ahmet; Olmez, Elif Ozkirimli; Alakent, Burak

2013-05-01

In protein tyrosine phosphatase 1B (PTP1B), the flexible WPD loop adopts a closed conformation (WPDclosed ) in the active state of PTP1B, bringing the catalytic Asp181 close to the active site pocket, while WPD loop is in an open conformation (WPDopen ) in the inactive state. Previous studies showed that Asp181 may be protonated at physiological pH, and ordered water molecules exist in the active site. In the current study, molecular dynamics simulations are employed at different Asp181 protonation states and initial positions of active site water molecules, and compared with the existing crystallographic data of PTP1B. In WPDclosed conformation, the active site is found to maintain its conformation only in the protonated state of Asp181 in both free and liganded states, while Asp181 is likely to be deprotonated in WPDopen conformation. When the active site water molecule network that is a part of the free WPDclosed crystal structure is disrupted, intermediate WPD loop conformations, similar to that in the PTPRR crystal structure, are sampled in the MD simulations. In liganded PTP1B, one active site water molecule is found to be important for facilitating the orientation of Cys215 and the phosphate ion, thus may play a role in the reaction. In conclusion, conformational stability of WPD loop, and possibly catalytic activity of PTP1B, is significantly affected by the protonation state of Asp181 and position of active site water molecules, showing that these aspects should be taken into consideration both in MD simulations and inhibitor design. Copyright © 2013 Wiley Periodicals, Inc.

Clofibric acid increases the formation of oleic acid in endoplasmic reticulum of the liver of rats.

PubMed

Hirose, Akihiko; Yamazaki, Tohru; Sakamoto, Takeshi; Sunaga, Katsuyoshi; Tsuda, Tadashi; Mitsumoto, Atsushi; Kudo, Naomi; Kawashima, Yoichi

2011-01-01

The effects of 2-(4-chlorophenoxy)-2-methylpropionic acid (clofibric acid) on the formation of oleic acid (18:1) from stearic acid (18:0) and utilization of the 18:1 formed for phosphatidylcholine (PC) formation in endoplasmic reticulum in the liver of rats were studied in vivo. [¹⁴C]18:0 was intravenously injected into control Wistar male rats and rats that had been fed on a diet containing 0.5% (w/w) clofibric acid for 7 days; and the distribution of radiolabeled fatty acids among subcellular organelles, microsomes, peroxisomes, and mitochondria, was estimated on the basis of correction utilizing the yields from homogenates of marker enzymes for these organelles. The radioactivity was mostly localized in microsomes and the radiolabeled fatty acids present in microsomes were significantly increased by the treatment of rats with clofibric acid. The formation of radiolabeled 18:1 in microsomes markedly increased and incorporations of the formed [¹⁴C]18:1 into PC and phosphatidylethanolamine in microsomes were augmented in response to clofibric acid. The [¹⁴C]18:1 incorporated into PC was mostly located at the C-2 position, but not the C-1 position, of PC, and the radioactivity in 18:1 at the C-2 position of PC was strikingly increased by clofibric acid. These results obtained from the in vivo experiments directly link the findings that clofibric acid treatment induces microsomal stearoyl-CoA desaturase and 1-acylglycerophosphocholine acyltransferase in the liver and the findings that the treatment with the drug elevated absolute mass and mass proportion of 18:1 at the C-2 position, but not the C-1 position, of PC in the liver together.

MiRNA-181d Expression Significantly Affects Treatment Responses to Carmustine Wafer Implantation.

PubMed

Sippl, Christoph; Ketter, Ralf; Bohr, Lisa; Kim, Yoo Jin; List, Markus; Oertel, Joachim; Urbschat, Steffi

2018-05-26

Standard therapeutic protocols for glioblastoma, the most aggressive type of brain cancer, include surgery followed by chemoradiotherapy. Additionally, carmustine-eluting wafers can be implanted locally into the resection cavity. To evaluate microRNA (miRNA)-181d as a prognostic marker of responses to carmustine wafer implantation. A total of 80 glioblastoma patients (40/group) were included in a matched pair analysis. One group (carmustine wafer group) received concomitant chemoradiotherapy with carmustine wafer implantation (Stupp protocol). The second group (control group) received only concomitant chemoradiotherapy. All tumor specimens were subjected to evaluations of miRNA-181d expression, results were correlated with further individual clinical data. The Cancer Genome Atlas (TCGA) dataset of 149 patients was used as an independent cohort to validate the results. Patients in the carmustine wafer group with low miRNA-181d expression had significantly longer overall (hazard ratio [HR], 35.03, [95% confidence interval (CI): 3.50-350.23], P = .002) and progression-free survival (HR, 20.23, [95% CI: 2.19-186.86], P = .008) than patients of the same group with a high miRNA-181d expression. These correlations were not observed in the control group. The nonsignificance in the control group was confirmed in the independent TCGA dataset. The carmustine wafer group patients with low miRNA-181d expression also had a significantly longer progression-free (P = .049) and overall survival (OS) (P = .034), compared with control group patients. Gross total resection correlated significantly with longer OS (P = .023). MiRNA-181d expression significantly affects treatment responses to carmustine wafer implantation.

40 CFR 464.22 - Effluent limitations guidelines representing the degree of effluent reduction attainable by the...

Code of Federal Regulations, 2013 CFR

2013-07-01

....399 TSS 1.52 0.598 pH (1) (1) 1 Within the range of 7.0 to 10.0 at all times. Maximum for any 1 day....39 0.0088 Zinc (T) 1.14 0.43 0.0108 Oil and grease 30 10 0.199 TSS 38 15 0.399 pH (3) (3) (3) 1 kg....506 Lead (T) 0.952 0.47 Zinc (T) 1.37 0.518 Oil and grease 36.2 12.1 TSS 45.8 18.1 pH (1) (1) 1 Within...

Reliability Evaluation of Low Power Schottky Clamped Microcircuits.

DTIC Science & Technology

1980-02-01

Temperature 52 15. 54LS191: ICC Versus Temperature 53 16. 54LS181: ICC Versus Temperature 54 17. High Temperature ...Response, Vendor A, 54LS181 56 18. High Temperature Response, Vendor B, 54LS181 57 19. High Temperature Response, Vendor A, 54LS191 58 20. High ... Temperature Response, Vendor B, 54LS191 59 21. High Temperature Response, Vendor A, 54LS251 60 3 LIST OF FIGURES (continued) Figure No. Title Page 22. High

Harnessing endogenous miR-181a to segregate transgenic antigen receptor expression in developing versus post-thymic T cells in murine hematopoietic chimeras.

PubMed

Papapetrou, Eirini P; Kovalovsky, Damian; Beloeil, Laurent; Sant'angelo, Derek; Sadelain, Michel

2009-01-01

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression by targeting complementary sequences, referred to as miRNA recognition elements (MREs), typically located in the 3' untranslated region of mRNAs. miR-181a is highly expressed in developing thymocytes and markedly downregulated in post-thymic T cells. We investigated whether endogenous miR-181a can be harnessed to segregate expression of chimeric antigen receptors (CARs) and TCRs between developing and mature T cells. Lentiviral-encoded antigen receptors were tagged with a miR-181a-specific MRE and transduced into mouse BM cells that were used to generate hematopoietic chimeras. Expression of a CAR specific for human CD19 (hCD19) was selectively suppressed in late double-negative and double-positive thymocytes, coinciding with the peak in endogenous miR-181a expression. Receptor expression was fully restored in post-thymic resting and activated T cells, affording protection against a subsequent challenge with hCD19+ tumors. Hematopoietic mouse chimeras engrafted with a conalbumin-specific TCR prone to thymic clonal deletion acquired peptide-specific T cell responsiveness only when the vector-encoded TCR transcript was similarly engineered to be subject to regulation by miR-181a. These results demonstrate the potential of miRNA-regulated transgene expression in stem cell-based therapies, including cancer immunotherapy.

Sequence-based screening for self-sufficient P450 monooxygenase from a metagenome library.

PubMed

Kim, B S; Kim, S Y; Park, J; Park, W; Hwang, K Y; Yoon, Y J; Oh, W K; Kim, B Y; Ahn, J S

2007-05-01

Cytochrome P450 monooxygenases (CYPs) are useful catalysts for oxidation reactions. Self-sufficient CYPs harbour a reductive domain covalently connected to a P450 domain and are known for their robust catalytic activity with great potential as biocatalysts. In an effort to expand genetic sources of self-sufficient CYPs, we devised a sequence-based screening system to identify them in a soil metagenome. We constructed a soil metagenome library and performed sequence-based screening for self-sufficient CYP genes. A new CYP gene, syk181, was identified from the metagenome library. Phylogenetic analysis revealed that SYK181 formed a distinct phylogenic line with 46% amino-acid-sequence identity to CYP102A1 which has been extensively studied as a fatty acid hydroxylase. The heterologously expressed SYK181 showed significant hydroxylase activity towards naphthalene and phenanthrene as well as towards fatty acids. Sequence-based screening of metagenome libraries is expected to be a useful approach for searching self-sufficient CYP genes. The translated product of syk181 shows self-sufficient hydroxylase activity towards fatty acids and aromatic compounds. SYK181 is the first self-sufficient CYP obtained directly from a metagenome library. The genetic and biochemical information on SYK181 are expected to be helpful for engineering self-sufficient CYPs with broader catalytic activities towards various substrates, which would be useful for bioconversion of natural products and biodegradation of organic chemicals.

Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer.

PubMed

Bisso, Andrea; Faleschini, Michela; Zampa, Federico; Capaci, Valeria; De Santa, Jacopo; Santarpia, Libero; Piazza, Silvano; Cappelletti, Vera; Daidone, Mariagrazia; Agami, Reuven; Del Sal, Giannino

2013-06-01

Breast cancer is a heterogeneous tumor type characterized by a complex spectrum of molecular aberrations, resulting in a diverse array of malignant features and clinical outcomes. Deciphering the molecular mechanisms that fuel breast cancer development and act as determinants of aggressiveness is a primary need to improve patient management. Among other alterations, aberrant expression of microRNAs has been found in breast cancer and other human tumors, where they act as either oncogenes or tumor suppressors by virtue of their ability to finely modulate gene expression at the post-transcriptional level. In this study, we describe a new role for miR-181a/b as negative regulators of the DNA damage response in breast cancer, impacting on the expression and activity of the stress-sensor kinase ataxia telangiectasia mutated (ATM). We report that miR-181a and miR-181b were overexpressed in more aggressive breast cancers, and their expression correlates inversely with ATM levels. Moreover we demonstrate that deregulated expression of miR-181a/b determines the sensitivity of triple-negative breast cancer cells to the poly-ADP-ribose-polymerase1 (PARP1) inhibition. These evidences suggest that monitoring the expression of miR-181a/b could be helpful in tailoring more effective treatments based on inhibition of PARP1 in breast and other tumor types.

Retinal Photoisomerization in Rhodopsin: Electrostatic and Steric Catalysis

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

Tomasello, Gaia; Altoe, Piero; Stenta, Marco

2007-12-26

Excited state QM(CASPT2//CASSCF)/MM(GAFF) calculations, by our recently developed code COBRAMM (Computations at Bologna Relating Ab-initio and Molecular Mechanic Methods), were carried out in rhodopsin to investigate on the steric and electrostatic effects in retinal photoisomerization catalysis due to the {beta}-ionone ring and glutammate 181 (GLU 181), respectively. The excited state photoisomerization channel has been mapped and a new christallographyc structure (2.2 Aa resolution) has been used for this purpose. Two different set-ups have been used to evaluate the electrostatic effects of GLU 181 (which is very close to the central double bond of the chromophore): the first with a neutralmore » GLU 181 (as commonly accepted), the second with a negatively charged (i.e. deprotonated) GLU 181 (as very recent experimental findings seem to suggest). On the other hand, {beta}-ionone ring steric effects were evaluated by calculating the photoisomerization path of a modified chromophore, where the ring double bond has been saturated. Spectroscopic properties were calculated and compared with the available experimental data.« less

27 CFR 18.1 - Scope.

Code of Federal Regulations, 2013 CFR

2013-04-01

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19 CFR 181.132 - Disassembly.

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14 CFR 61.181 - Applicability.

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2010-01-01

... Instructors With a Sport Pilot Rating § 61.181 Applicability. This subpart prescribes the requirements for the... sport pilot rating), the conditions under which those certificates and ratings are necessary, and the...

Altered expression of miR-181a-5p and miR-23a-3p is associated with obesity and TNFα-induced insulin resistance.

PubMed

Lozano-Bartolomé, Javier; Llauradó, Gemma; Otin, Manel Portero; Altuna-Coy, Antonio; Rojo-Martínez, Gemma; Vendrell, Joan; Jorba, Rosa; Rodríguez-Gallego, Esther; Chacón, Matilde R

2018-02-01

The proinflammatory cytokine TNFα is a key player in insulin resistance (IR). While several miRNAs are believed to be involved in the development of adipose tissue (AT) IR, the role of miRNAs in the association between inflammation and IR is poorly understood. To investigate the expression profile of miR-181a-5p and miR-23a-3p in obesity and to study their role in TNFα-induced IR in adipocytes. Two separate cohorts were employed. Cohort 1 was used for AT expression studies and included 28 subjects with BMI<30 and 30 subjects with BMI≥30. Cohort 2 was used for circulating serum miRNA studies and included 101 subjects with 4-years follow-up (48 cases and 53 controls). miR-181a-5p and miR-23a-3p expression was assessed in subcutaneous (SAT) and visceral (VAT) AT. Functional analysis was performed in adipocytes utilizing miRNA mimics and inhibitors. Key molecules of the insulin pathway, AKT, PTEN, AS160 and S6K, were analyzed. Expression of miR-181a-5p and miR-23a-3p was reduced in AT from obese and diabetic subjects and was inversely correlated to adiposity and HOMA-IR. Overexpression of miR-181a-5p and miR-23a-3p in adipocytes upregulated insulin-stimulated AKT activation and reduced TNFα-induced IR, regulating PTEN and S6K expression. Serum levels of miR-181a-5p were reduced in cases vs controls at baseline, pointing towards its prognostic value. Variable importance in projection scores revealed miR-181a-5p had more impact in the model than insulin or glucose at 120 minutes. miR-181a-5p and miR-23a-3p may prevent TNFα-induced IR in adipocytes through modulation of PTEN and S6K expression. Copyright © 2018 Endocrine Society

Prevalence of etravirine-associated mutations in clinical samples with resistance to nevirapine and efavirenz.

PubMed

Llibre, J M; Santos, J R; Puig, T; Moltó, J; Ruiz, L; Paredes, R; Clotet, B

2008-11-01

To evaluate the expected activity of etravirine in clinical samples, according to mutational patterns associated with decreased virological response (VR). We identified 1586 routine clinical samples with resistance-associated mutations (RAMs) to nevirapine and efavirenz (K103N 60%, Y181C 37%, G190A 27%, V108I 13%). Concerning in vitro identified etravirine mutations, samples with F227C, Y181I, M230L or L100I plus K103N plus Y181C were considered highly resistant. Samples with two RAMs plus Y181C or V179D or K101E or Y188L were considered intermediate. The prevalence of 13 RAMs recently associated with decreased VR to etravirine in the DUET clinical trials was also investigated. Most samples (69%) harboured more than one IAS-USA RAM to first-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs): 42% harboured two RAMs, 21% three RAMs and 6% four or more RAMs. The prevalence of 13 specific etravirine RAMs was V179F 0.12%, G190S 3.9%, Y181V 0.1%, V106I 2.6%, V179D 1.6%, K101P 2.0%, K101E 10.1%, Y181C 36.9%, A98G 5.9%, V90I 6.9%, Y181I 3.6%, G190A 27% and L100I 9.1%. The five RAMs with the most impact on VR (V179F/D, G190S, Y181V and V106I) occurred less often. Overall, 8.2% of the samples had three or more etravirine RAMs and only 1.1% had four or more. In addition, patterns of RAMs previously associated with intermediate etravirine resistance were present in 26.2% of the samples, whereas 4.85% displayed patterns of high-degree resistance. For RAMs associated with decreased VR, etravirine resistance in routine clinical samples was lower than previously reported. High-degree resistance was uncommon, even in patients with resistance to first-generation NNRTIs, whereas low-to-intermediate etravirine resistance was more common.

26 CFR 1.181-4 - Special rules.

Code of Federal Regulations, 2014 CFR

2014-04-01

... before computing gain or loss from the disposition. (2) Principal photography not commencing prior to the... for which principal photography does not commence prior to the date of expiration of section 181, the...

26 CFR 1.181-4 - Special rules.

Code of Federal Regulations, 2012 CFR

2012-04-01

... before computing gain or loss from the disposition. (2) Principal photography not commencing prior to the... for which principal photography does not commence prior to the date of expiration of section 181, the...

26 CFR 1.181-4 - Special rules.

Code of Federal Regulations, 2013 CFR

2013-04-01

... before computing gain or loss from the disposition. (2) Principal photography not commencing prior to the... for which principal photography does not commence prior to the date of expiration of section 181, the...

28 CFR 0.181 - Requirements for orders.

Code of Federal Regulations, 2010 CFR

2010-07-01

... the Attorney General § 0.181 Requirements for orders. Each order prepared for issuance by or approval of the Attorney General shall be given a suitable title, shall contain a clear and concise statement...

Identification of pre-clinical Alzheimer’s disease by a profile of pathogenic proteins in neurally-derived blood exosomes: a case-control study

PubMed Central

Fiandaca, Massimo S.; Kapogiannis, Dimitrios; Mapstone, Mark; Boxer, Adam; Eitan, Erez; Schwartz, Janice B.; Abner, Erin L.; Petersen, Ronald C.; Federoff, Howard J.; Miller, Bruce L.; Goetzl, Edward J.

2014-01-01

Background Proteins pathogenic in Alzheimer’s disease (AD) were extracted from neurally-derived blood exosomes and quantified to develop biomarkers for staging of sporadic AD. Methods Blood exosomes obtained at one time-point from patients with AD (n=57) or frontotemporal dementia (FTD) (n=16), and at two time-points from others (n=24) when cognitively normal and one-ten years later when diagnosed with AD were enriched for neural sources by immunoabsorption. AD-pathogenic exosomal proteins were extracted and quantified by ELISAs. Results Mean exosomal levels of total Tau, P-T181-tau, P-S396-tau and Aβ1-42 for AD and levels of P-T181-tau and Aβ1-42 for FTD were significantly higher than for case-controls. Stepwise discriminant modeling incorporated P-T181-tau, P-S396-tau and Aβ1-42 in AD, but only P-T181-tau in FTD. Classification of 96.4% of AD patients and 87.5% of FTD patients was correct. In 24 AD patients, exosomal levels of P-S396-tau, P-T181-tau and Aβ1-42 were significantly higher than for controls both one to ten years before and when diagnosed with AD. Conclusions Levels of P-S396-tau, P-T181-tau and Aβ1-42 in extracts of neurally-derived blood exosomes predict development of AD up to 10 years prior to clinical onset. PMID:25130657

Is vaccenic acid (18:1t n-7) associated with an increased incidence of hip fracture? An explanation for the calcium paradox.

PubMed

Hamazaki, Kei; Suzuki, Nobuo; Kitamura, Kei-Ichiro; Hattori, Atsuhiko; Nagasawa, Tetsuro; Itomura, Miho; Hamazaki, Tomohito

2016-06-01

High calcium intake may increase hip fracture (HF) incidence. This phenomenon, known as the calcium paradox, might be explained by vaccenic acid (18:1t n-7, VA), the highly specific trans fatty acid (TFA) present in dairy products. First, we ecologically investigated the relationship between 18:1 TFA intake and HF incidence using data from 12 to 13 European countries collected before 2000; then we measured the effects of VA and elaidic acid (18:1t n-9, EA) on osteoblasts from goldfish scales (tissues very similar to mammalian bone), with alkaline phosphatase as a marker; and finally we measured the effect of VA on mRNA expression in the scales for the major bone proteins type I collagen and osteocalcin. HF incidence was significantly correlated with 18:1 TFA intake in men (r=0.57) and women (r=0.65). Incubation with 1μmol/L VA and EA for 48h significantly decreased alkaline phosphatase activity by 25% and 21%, respectively. Incubation of scales with 10μmol/L VA for 48h significantly decreased mRNA expression for type I collagen and osteocalcin (by about 50%). In conclusion, VA may be causatively related to HF and could explain the calcium paradox. It may be prudent to reduce 18:1 TFA intake, irrespective of trans positions, to prevent HF. Copyright © 2016 Elsevier Ltd. All rights reserved.

Regulation by carbohydrate and clofibric acid of palmitoyl-CoA chain elongation in the liver of rats.

PubMed

Kudo, Naomi; Toyama, Tomoaki; Mitsumoto, Atsushi; Kawashima, Yoichi

2003-05-01

Regulation of palmitoyl-CoA chain elongation (PCE) and its contribution to oleic acid formation were investigated in rat liver in comparison with stearoyl-CoA desaturase (SCD). Hepatic PCE activity was induced by the administration of 20% wt/vol glucose or fructose in the drinking water of normal rats. In streptozotocin-induced diabetic rats, the activities of both PCE and SCD were suppressed, and fructose, but not glucose, feeding caused an increase in the activities of both enzymes. Treatment of normal rats with clofibric acid in combination with carbohydrate further increased PCE, but not SCD, activity. FA analysis of hepatic lipids revealed that the proportion of oleic acid (18:1 n-9) increased upon administration of carbohydrate or clofibric acid. The treatment of rats with clofibric acid in combination with carbohydrate greatly increased the proportion of 18:1 n-9. A significant correlation was observed between PCE activity and the hepatic proportion of 18:1 n-9 (r2 = 0.874, P < 0.01), whereas the relationship between SCD activity and the proportion of 18:1 n-9 was not significant (r2 = 0.552, P > 0.05). Taken together, these results suggest that carbohydrate induces PCE as well as SCD activity to increase the hepatic 18:1 content in rat liver, and the increased PCE activity seems to be responsible for the further increase in 18:1 n-9 when carbohydrate is administered in combination with clofibric acid.

Association of matrix metalloproteinase-7 (-181A/G) promoter polymorphism in chronic pancreatitis.

PubMed

Manjari, K Sri; Jyothy, A; Kumar, P Shravan; Prabhakar, B; Nallari, Pratibha; Venkateshwari, A

2014-11-01

Chronic pancreatitis is progressive and irreversible destruction of the pancreas. Matrix metalloproteinase-7 (MMP-7) is a secreted matrilysin, which contributes to angiogenesis and breakdown of basement membranes of pancreatic tissues. The present study was aimed to investigate the association of MMP-7 -181A/G (rs11568818) gene promoter polymorphism in patients with chronic pancreatitis. A total of 100 chronic pancreatitis patients and 150 unrelated healthy individuals were included in this case control study. The genotyping of the MMP-7 gene (- 181 A/G) (rs11568818) was carried out based on PCR-RFLP. The serum levels of MMP-7 were determined by ELISA. Association between genotypes and chronic pancreatitis was examined by odds ratio (OR) with 95% confidence interval (CI). The frequencies of the genotypes in promoter of MMP-7 were AA 49 per cent, AG 25 per cent and GG 26 per cent in chronic pancreatitis patients and AA 53 per cent, AG 38 per cent and GG 9 per cent in control subjects. Frequency of MMP-7 -181GG genotype and - 181G allele was significantly associated with chronic pancreatitis compared to healthy subjects [OR = 1.58 (95% CI: 1.06 -2.36), p =0.019]. There was no significant difference in the serum MMP-7 levels in the patients compared to control subjects. The present study revealed a significant association of MMP-7 -181A/G (rs11568818) GG genotype with chronic pancreatitis patients, indicating its possible association with the disease.

Short communication: Genetic study of methane production predicted from milk fat composition in dairy cows.

PubMed

van Engelen, S; Bovenhuis, H; Dijkstra, J; van Arendonk, J A M; Visker, M H P W

2015-11-01

Dairy cows produce enteric methane, a greenhouse gas with 25 times the global warming potential of CO2. Breeding could make a permanent, cumulative, and long-term contribution to methane reduction. Due to a lack of accurate, repeatable, individual methane measurements needed for breeding, indicators of methane production based on milk fatty acids have been proposed. The aim of the present study was to quantify the genetic variation for predicted methane yields. The milk fat composition of 1,905 first-lactation Dutch Holstein-Friesian cows was used to investigate 3 different predicted methane yields (g/kg of DMI): Methane1, Methane2, and Methane3. Methane1 was based on the milk fat proportions of C17:0anteiso, C18:1 rans-10+11, C18:1 cis-11, and C18:1 cis-13 (R(2)=0.73). Methane2 was based on C4:0, C18:0, C18:1 trans-10+11, and C18:1 cis-11 (R(2)=0.70). Methane3 was based on C4:0, C6:0, and C18:1 trans-10+11 (R(2)=0.63). Predicted methane yields were demonstrated to be heritable traits, with heritabilities between 0.12 and 0.44. Breeding can, thus, be used to decrease methane production predicted based on milk fatty acids. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

OXA-181 Beta Lactamase is not a Major Mediator of Carbapenem Resistance in Enterobacteriaceae

PubMed Central

Shanthi, M.; Sekar, Uma; K., Arunagiri; Bramhne, Hemant Goverdhandas

2013-01-01

Background: Detection of carbapenem hydrolyzing class D beta lactamase OXA-181, (a variant of OXA-48) in Enterobacteriaceae, is important, to institute appropriate therapy and to initiate preventive measures. This study was done to determine the presence of OXA 48 and its derivative OXA-181 in Enterobacteriaceae of pathogenic significance. Material and Methods: One hundred and eleven non–repetitive Enterobacteriaceae isolates which were resistant to any of the cephalosporin subclasses III and which exhibited reduced susceptibility to carbapenems were included in the study. Minimum inhibitory concentrations (MICs) to imipenem and meropenem was determined by broth microdilution. Production of carbapenamase was screened by Modified Hodge test (MHT). Polymerase Chain Reaction (PCR) was done to detect the presence of bla OXA-181 and bla OXA-48 .Coexistence of other carbapenemase encoding genes, namely, NDM-1, VIM, IMP and KPC were also looked for, by PCR. Results: Of all the isolates which were tested, only 2 (1.8%) revealed the presence of OXA-181 and OXA-48. These were Klebsiella pneumoniae and Citrobacter freundii. MICs of imipenem and meropenem for Klebsiella pneumoniae were 128mg/l and 64 mg/l and for Citrobacter freundii, they were 32mg/l and 16mg/l respectively. MHT was positive in both isolates. Conclusion: Production of OXA-48 / OXA-181 is not a major mechanism of carbapenem resistance. PCR is the gold standard for its routine identification in clinical microbiology laboratory. PMID:24179916

Association of Cerebrospinal Fluid β-Amyloid 1-42, T-tau, P-tau181, and α-Synuclein Levels With Clinical Features of Drug-Naive Patients With Early Parkinson Disease

PubMed Central

Kang, Ju-Hee; Irwin, David J.; Chen-Plotkin, Alice S.; Siderowf, Andrew; Caspell, Chelsea; Coffey, Christopher S.; Waligórska, Teresa; Taylor, Peggy; Pan, Sarah; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Simuni, Tanya; Tanner, Caroline M.; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Mollenhauer, Brit; Trojanowski, John Q.; Shaw, Leslie M.

2014-01-01

Importance We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1–42 (Aβ1–42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. Objective To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1–42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau181], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson’s Progression Markers Initiative (PPMI) study. Design, Setting, and Participants Cross-sectional study of the initial 102 research volunteers (63 patients with PD and 39 healthy controls) of the PPMI cohort. Main Outcomes and Measures The CSF biomarkers were measured by INNO-BIA AlzBio3 immunoassay (Aβ1–42, T-tau, and P-tau181; Innogenetics Inc) or by enzyme-linked immunosorbent assay (α-synuclein). Clinical features including diagnosis, demographic characteristics, motor, neuropsychiatric, and cognitive assessments, and DaTscan were systematically assessed according to the PPMI study protocol. Results Slightly, but significantly, lower levels of Aβ1–42, T-tau, P-tau181, α-synuclein, and T-tau/Aβ1–42 were seen in subjects with PD compared with healthy controls but with a marked overlap between groups. Using multivariate regression analysis, we found that lower Aβ1–42 and P-tau181 levels were associated with PD diagnosis and that decreased CSF T-tau and α-synuclein were associated with increased motor severity. Notably, when we classified patients with PD by their motor phenotypes, lower CSF Aβ1–42 and P-tau181 concentrations were associated with the postural instability–gait disturbance–dominant phenotype but not with the tremor-dominant or intermediate phenotype. Finally, we found a significant correlation of the levels of α-synuclein with the levels of T-tau and P-tau181. Conclusions and Relevance In this first report of CSF biomarkers in PPMI study subjects, we found that measures of CSF Aβ1–42, T-tau, P-tau181, and α-synuclein have prognostic and diagnostic potential in early-stage PD. Further investigations using the entire PPMI cohort will test the predictive performance of CSF biomarkers for PD progression. PMID:23979011

Interferon-alpha/beta deficiency greatly exacerbates arthritogenic disease in mice infected with wild-type chikungunya virus but not with the cell culture-adapted live-attenuated 181/25 vaccine candidate

PubMed Central

Gardner, Christina L.; Burke, Crystal W.; Higgs, Stephen T.; Klimstra, William B.; Ryman, Kate D.

2012-01-01

In humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthalgia/arthritis associated with joint swelling. We report a new CHIKV disease model in adult mice that distinguishes the wild-type CHIKV-LR strain from the live-attenuated vaccine strain (CHIKV-181/25). Although eight-week old normal mice inoculated in the hind footpad developed no hind limb swelling with either virus, CHIKV-LR replicated in musculoskeletal tissues and caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated and contralateral limbs and dramatic inflammatory lesions, while CHIKV-181/25 vaccine and another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR and CHIKV-181/25 replication equally in dendritic cells in vitro whereas macrophages were refractory to infection independently of STAT1-mediated IFN responses. Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent. PMID:22305131

Functional single nucleotide polymorphisms of matrix metalloproteinase 7 and 12 genes in idiopathic recurrent spontaneous abortion.

PubMed

Barišić, Anita; Pereza, Nina; Hodžić, Alenka; Kapović, Miljenko; Peterlin, Borut; Ostojić, Saša

2017-03-01

The aim of this study was to investigate the potential association of matrix metalloproteinase 7 (MMP7) -181 A/G and MMP12 -82 A/G functional single nucleotide polymorphisms (SNP) with idiopathic recurrent spontaneous abortion (IRSA) in Slovenian reproductive couples. A case-control study was conducted on 149 couples with 3 or more consecutive idiopathic spontaneous pregnancy loses and 149 women and men with at least 2 live births and no history of pregnancy complications. Genotyping of MMP7 -181 A/G and MMP12 -82 A/G SNPs was performed using polymerase chain reaction and restriction fragment length polymorphism methods. There were no statistically significant differences in the distribution of MMP7 -181 A/G and MMP12 -82 A/G genotype, allele, or haplotype frequencies between IRSA patients and controls, as well as patients' primary and secondary IRSA. We also found no association of MMP7 -181 A/G and MMP12 -82 A/G genotypes, alleles, and haplotypes with IRSA. We found no evidence to support the association between IRSA and MMP7 -181 A/G and MMP12 -82 A/G SNPs in Slovenian reproductive couples.

[Research on sexually transmitted infections in asymptomatic heterosexual males whose partners have cervical intraepithelial neoplasia].

PubMed

Varela, José A; Otero, Luis; Junquera, Maria Luisa; Melón, Santiago; del Valle, Asunción; Vázquez, Fernando

2006-06-01

Human papillomaviruses (HPV) are the etiological agents of genital warts and of cervical intraepithelial neoplasia (CIN), and they are sexually transmitted. The aim of this study is to determine the prevalence of sexually transmitted infections (STI) in asymptomatic heterosexual males who consult their physicians seeking advice after their partners have been diagnosed with CIN. 181 asymptomatic males whose partners were women diagnosed with CIN were studied at the STI unit in Gijón over a five-year period (1999-2003). The same diagnostic protocol was used in all cases: clinical exam, genitoscopy and the taking of samples for bacterial, fungus and Trichomonas cultures, as well as samples for the genomic detection of Chlamydia, and syphilis, HIV and viral hepatitis serology. 101 infections were diagnosed in 85 patients (47 %). By order of greatest prevalence, these were: urethritis from Ureaplasma urealyticum (35/181; 19.3 %), genital warts (31/181; 17.1 %), Haemophilus spp. (12 de 181; 6.6 %) and mycotic balanoposthitis (10/181; 5.5 %). The prevalence of STI in the partners of women with CIN is high, and in these cases it is necessary to establish STI detection and control programs in both members of the couple.

Publications - GMC 181 | Alaska Division of Geological & Geophysical

Science.gov Websites

DGGS GMC 181 Publication Details Title: Geologic logs and core assays of 14 nickel, copper, and cobalt information. Bibliographic Reference Inspiration Development Company, 1991, Geologic logs and core assays of

Replacement of Tyrosine 181 by Phenylalanine in Gentisate 1,2-Dioxygenase I from Pseudomonas alcaligenes NCIMB 9867 Enhances Catalytic Activities

PubMed Central

Tan, Chew Ling; Yeo, Chew Chieng; Khoo, Hoon Eng; Poh, Chit Laa

2005-01-01

xlnE, encoding gentisate 1,2-dioxygenase (EC 1.13.11.4), from Pseudomonas alcaligenes (P25X) was mutagenized by site-directed mutagenesis. The mutant enzyme, Y181F, demonstrated 4-, 3-, 6-, and 16-fold increases in relative activity towards gentisate and 3-fluoro-, 4-methyl-, and 3-methylgentisate, respectively. The specific mutation conferred a 13-fold higher catalytic efficiency (kcat/Km) on Y181F towards 3-methylgentisate than that of the wild-type enzyme. PMID:16237038

Alzheimer Disease Biomarkers and Driving in Clinically Normal Older Adults: Role of Spatial Navigation Abilities.

PubMed

Allison, Samantha; Babulal, Ganesh M; Stout, Sarah H; Barco, Peggy P; Carr, David B; Fagan, Anne M; Morris, John C; Roe, Catherine M; Head, Denise

2018-01-01

Older adults experience impaired driving performance, and modify their driving habits, including limiting amount and spatial extent of travel. Alzheimer disease (AD)-related pathology, as well as spatial navigation difficulties, may influence driving performance and driving behaviors in clinically normal older adults. We examined whether AD biomarkers [cerebrospinal fluid (CSF) concentrations of Aβ42, tau, and ptau181] were associated with lower self-reported spatial navigation abilities, and whether navigation abilities mediated the relationship of AD biomarkers with driving performance and extent. Clinically normal older adults (n=112; aged 65+) completed an on-road driving test, the Santa Barbara Sense of Direction scale (self-report measure of spatial navigation ability), and the Driving Habits Questionnaire for an estimate of driving extent (composite of driving exposure and driving space). All participants had a lumbar puncture to obtain CSF. CSF Aβ42, but not tau or ptau181, was associated with self-reported navigation ability. Lower self-reported navigation was associated with reduced driving extent, but not driving errors. Self-reported navigation mediated the relationship between CSF Aβ42 and driving extent. Findings suggest that cerebral amyloid deposition is associated with lower perceived ability to navigate the environment, which may lead older adults with AD pathology to limit their driving extent.

Impact of selective use of breast MRI on surgical decision-making in women with newly diagnosed operable breast cancer.

PubMed

Brennan, Meagan E; McKessar, Merran; Snook, Kylie; Burgess, Ian; Spillane, Andrew J

2017-04-01

This study evaluated the impact of breast MRI on surgical planning in selected cases of breast malignancy (invasive cancer or DCIS). MRI was used when there was ambiguity on clinical and/or conventional imaging assessment. Consecutive women with breast malignancy undergoing breast MRI were included. Clinical, mammogram and ultrasound findings and surgical plan before and after MRI were recorded. MRI findings and histopathology results were documented and the impact of MRI on treatment planning was evaluated. MRI was performed in 181/1416 (12.8%) cases (invasive cancer 155/1219 (12.7%), DCIS 26/197 (13.2%)). Indications for MRI were: clinically dense breast tissue difficult to assess (n = 66; 36.5%), discordant clinical/conventional imaging assessment (n = 61; 33.7%), invasive lobular carcinoma in clinically dense breast tissue (n = 22; 12.2%), palpable/mass-forming DCIS (n = 11; 6.1%); other (n = 19; 10.5%). The recall rate for assessment of additional lesions was 35% (63/181). Additional biopsy-proven malignancy was found in 11/29 (37.9%) ipsilateral breast recalls and 8/34 (23.5%) contralateral breast recalls. MRI detected contralateral malignancy (unsuspected on conventional imaging) in 5/179 (2.8%). The additional information from MRI changed management in 69/181 (38.1%), with more unilateral surgery (wider excision or mastectomy) in 53/181 (29.3%), change to bilateral surgery in 12/181 (6.6%), less surgery in 4/181 (2.2%). Clinical examination estimated histological size within 20 mm in 57%, conventional imaging in 55% and MRI in 71%. MRI was most likely to show concordance with histopathology in the 'discordant assessment' and 'invasive lobular' groups and less likely for 'challenging clinically dense breast tissue.' MRI changed management in 69/181 (38.1%). Copyright © 2017 Elsevier Ltd. All rights reserved.

21 CFR 820.181 - Device master record.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DEVICES QUALITY SYSTEM REGULATION Records § 820.181 Device master record. Each manufacturer shall maintain... following information: (a) Device specifications including appropriate drawings, composition, formulation... specifications; (c) Quality assurance procedures and specifications including acceptance criteria and the quality...

21 CFR 820.181 - Device master record.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DEVICES QUALITY SYSTEM REGULATION Records § 820.181 Device master record. Each manufacturer shall maintain... following information: (a) Device specifications including appropriate drawings, composition, formulation... specifications; (c) Quality assurance procedures and specifications including acceptance criteria and the quality...

21 CFR 820.181 - Device master record.

Code of Federal Regulations, 2011 CFR

2011-04-01

... DEVICES QUALITY SYSTEM REGULATION Records § 820.181 Device master record. Each manufacturer shall maintain... following information: (a) Device specifications including appropriate drawings, composition, formulation... specifications; (c) Quality assurance procedures and specifications including acceptance criteria and the quality...

77 FR 72923 - Deduction for Qualified Film and Television Production Costs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-07

..., Office of Associate Chief Counsel (Income Tax and Accounting). However, other personnel from the IRS and... provides rules for making the election under section 181. Section 1.181-3 provides definitions and rules...

Analysis of TP53 gene expression and p53 level of human hypopharyngeal FaDu (HTB-43) head and neck cancer cell line after microRNA-181a inhibition.

PubMed

Cheah, Y K; Cheng, R W; Yeap, S K; Khoo, C H; See, H S

2014-03-17

The identification of new biomarkers for early detection of highly recurrent head and neck cancer is urgently needed. MicroRNAs (miRNAs) are small and non-coding RNAs that regulate cancer-related gene expression, such as tumor protein 53 (TP53) gene expression. This study was carried out to analyze TP53 gene expression using real-time PCR and to determine changes in intracellular p53 level by flow cytometry after downregulation of miRNA-181a miRNA inhibitor in the FaDu cell line. TP53 gene expression showed a 3-fold increment and the p53 protein level was also increased in the miRNA-181a-treated cells. In conclusion, miRNA-181a binds to the TP53 gene and inhibits its expression, decreasing the synthesis of p53.

Zr-based bulk metallic glass as a cylinder material for high pressure apparatuses

DOE PAGES

Komatsu, Kazuki; Munakata, Koji; Matsubayashi, Kazuyuki; ...

2015-05-12

Zirconium-based bulk metallic glass (Zr-based BMG) has outstanding properties as a cylinder mate- rial for piston-cylinder high pressure apparatuses and is especially useful for neutron scattering. The piston-cylinder consisting of a Zr-based BMG cylinder with outer/inner diameters of 8.8/2.5 mm sustains pressures up to 1.81 GPa and ruptured at 2.0 GPa, with pressure values determined by the superconduct- ing temperature of lead. The neutron attenuation of Zr-based BMG is similar to that of TiZr null-scattering alloy and more transparent than that of CuBe alloy. No contamination of sharp Bragg reflections is observed in the neutron diffraction pattern for Zr-based BMG.more » The magnetic susceptibility of Zr-based BMG is similar to that of CuBe alloy; this leads to a potential application for measurements of magnetic properties under pressure.« less

Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation

PubMed Central

Frucht, Corey S.; Uduman, Mohamed; Duke, Jamie L.; Kleinstein, Steven H.; Santos-Sacchi, Joseph; Navaratnam, Dhasakumar S.

2010-01-01

Background Auditory hair cells spontaneously regenerate following injury in birds but not mammals. A better understanding of the molecular events underlying hair cell regeneration in birds may allow for identification and eventually manipulation of relevant pathways in mammals to stimulate regeneration and restore hearing in deaf patients. Methodology/Principal Findings Gene expression was profiled in forskolin treated (i.e., proliferating) and quiescent control auditory epithelia of post-hatch chicks using an Affymetrix whole-genome chicken array after 24 (n = 6), 48 (n = 6), and 72 (n = 12) hours in culture. In the forskolin-treated epithelia there was significant (p<0.05; >two-fold change) upregulation of many genes thought to be relevant to cell cycle control and inner ear development. Gene set enrichment analysis was performed on the data and identified myriad microRNAs that are likely to be upregulated in the regenerating tissue, including microRNA181a (miR181a), which is known to mediate proliferation in other systems. Functional experiments showed that miR181a overexpression is sufficient to stimulate proliferation within the basilar papilla, as assayed by BrdU incorporation. Further, some of the newly produced cells express the early hair cell marker myosin VI, suggesting that miR181a transfection can result in the production of new hair cells. Conclusions/Significance These studies have identified a single microRNA, miR181a, that can cause proliferation in the chicken auditory epithelium with production of new hair cells. PMID:20634979

Asian-American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study.

PubMed

Berumen, J; Ordoñez, R M; Lazcano, E; Salmeron, J; Galvan, S C; Estrada, R A; Yunes, E; Garcia-Carranca, A; Gonzalez-Lira, G; Madrigal-de la Campa, A

2001-09-05

Human papillomavirus 16 (HPV16) has a number of variants, each with a different geographic distribution and some that are associated more often with invasive neoplasias. We investigated whether the high incidence of cervical cancer in Mexico (50 cases per 100 000 women) may be associated with a high prevalence of oncogenic HPV16 variants. Cervical samples were collected from 181 case patients with cervical cancer and from 181 age-matched control subjects, all from Mexico City. HPV16 was detected with an E6/E7 gene-specific polymerase chain reaction, and variant HPV classes and subclasses were identified by sequencing regions of the E6 and L1/MY genes. Clinical data and data on tumor characteristics were also collected. All statistical tests were two-sided. HPV16 was detected in cervical scrapes from 50.8% (92 of 181) of case patients and from 11% (20 of 181) of control subjects. All HPV16-positive samples, except one, contained European (E) or Asian-American (AA) variants. AA and E variants were found statistically significantly more often in case patients (AA = 23.2% [42 of 181]; E = 27.1% [49 of 181]) than in control subjects (AA = 1.1% [two of 181]; E = 10% [18 of 181]) (P<.001 for case versus control subjects for either E or AA variants, chi2 test). However, the frequency of AA variants was 21 times higher in cancer patients than in control subjects, whereas that ratio for E variants was only 2.7 (P =.006, chi2 test). The odds ratio (OR) for cervical cancer associated with AA variants (OR = 27.0; 95% confidence interval [CI] = 6.4 to 113.7) was higher than that associated with E variants (OR = 3.4; 95% CI = 1.9 to 6.0). AA-positive case patients (46.2 +/- 12.5 years [mean +/- standard deviation]) were 7.7 years younger than E-positive case patients (53.9 +/- 12.2 years) (P =.004, Student's t test). AA variants were associated with squamous cell carcinomas and adenocarcinomas, but E variants were associated with only squamous cell carcinomas (P =.014, Fisher's exact test). The high frequency of HPV16 AA variants, which appear to be more oncogenic than E variants, might contribute to the high incidence of cervical cancer in Mexico.

Modified osteo-odonto-keratoprosthesis for treatment of corneal blindness: long-term anatomical and functional outcomes in 181 cases.

PubMed

Falcinelli, Giancarlo; Falsini, Benedetto; Taloni, Maurizio; Colliardo, Paolo; Falcinelli, Giovanni

2005-10-01

To evaluate long-term anatomical and functional outcomes of a modified osteo-odonto-keratoprosthesis (OOKP) technique for treatment of corneal blindness from various etiologies. Two-hundred three patients (224 eyes) underwent modified OOKP surgery between 1973 and 1999. Of the original cohort, 181 patients (98 men and 83 women; mean [SD], age 54.3 [15] years) in whom a standardized 2-step surgical procedure was performed were included in the study. Preoperative diagnoses were dry eye (n = 70) due to ocular pemphigoid (n = 39), Sjögren syndrome (n = 11), trachoma (n = 8), Lyell syndrome (n = 6), Stevens-Johnson syndrome (n = 4), and graft-vs-host disease (n = 1) and congenital lid coloboma (n = 1), severe corneal burns (n = 68), bullous keratopathy (n = 13), keratitis sequelae (n = 15), and bullous keratopathy secondary to antiglaucoma surgery (n = 15). Several innovations were made to the original Strampelli technique. Median follow-up duration was 12 years (range, 1-25 years). Anatomical complications leading to OOKP loss were found in 11 (6.07%) of 181 patients. Survival analysis estimated that 18 years after surgery, the probability of retaining an intact OOKP was 85% (95% confidence interval, 79.3%-90.7%). Pooling patient groups, mean (SD) best postoperative visual acuity was 0.76 (0.34). Mean (SD) final acuity at the end of follow-up declined slightly (0.69 [0.39]) but significantly (P<.01). In individual diagnostic groups, mean acuity decline reached statistical significance (P<.05) only in the pemphigoid (1 line), trachoma (1 line), and bullous keratopathy secondary to antiglaucoma surgery (2 lines) groups. Survival analysis estimated that 18 years after surgery, the probability of retaining best postoperative visual acuity (within 2 lines) was mean (SD) 55.5% (12.9%). Modified OOKP surgery for corneal blindness of different etiologies may provide, in the long-term, anatomically stable corneal prosthesis as well as an effective, rehabilitating recovery in visual acuity.

Biofilm formation and binding specificities of CFA/I, CFA/II and CS2 adhesions of enterotoxigenic Escherichia coli and Cfae-R181A mutant.

PubMed

Liaqat, Iram; Sakellaris, Harry

2012-07-01

Enterotoxigenic Escherichia coli (ETEC) strains are leading causes of childhood diarrhea in developing countries. Adhesion is the first step in pathogenesis of ETEC infections and ETEC pili designated colonization factor antigens (CFAs) are believed to be important in the biofim formation, colonization and host cell adhesions. As a first step, we have determined the biofilm capability of ETEC expressing various types of pili (CFA/I, CfaE-R181A mutant/CfaE tip mutant, CFA/II and CS2). Further, enzyme-linked immunosorbent assay (ELISA) assay were developed to compare the binding specificity of CFA/I, CFA/II (CS1 - CS3) and CS2 of ETEC, using extracted pili and piliated bacteria. CFA/II strain (E24377a) as well as extracted pili exhibited significantly higher binding both in biofilm and ELISA assays compared to non piliated wild type E24377a, CFA/I and CS2 strains. This indicates that co-expression of two or more CS2 in same strain is more efficient in increasing adherence. Significant decrease in binding specificity of DH5αF'lacI (q)/∆cotD (CS2) strain and MC4100/pEU2124 (CfaE-R181A) mutant strain indicated the important contribution of tip proteins in adherence assays. However, CS2 tip mutant strain (DH5αF'lacI (q)/pEU5881) showed that this specific residue may not be important as adhesions in these strains. In summary, our data suggest that pili, their minor subunits are important for biofilm formation and adherence mechanisms. Overall, the functional reactivity of strains co expressing various antigens, particularly minor subunit antigen observed in this study suggest that fewer antibodies may be required to elicit immunity to ETEC expressing a wider array of related pili.

Identification and distribution of sulfate reducing bacteria and sulphur-oxidising bacteria in northern South China Sea

NASA Astrophysics Data System (ADS)

Mao, S.; Zhu, X.; Guan, H.; Wu, D.; Wu, N.

2015-12-01

Fatty acids are one of the major components in modern marine sediments. It is well known that the saturated short-chain FAs were typically to be from vascular plants, algae, bacteria, and other sources, while the saturated long-chain FAs are the major components found in leaf waxes, suberin, and cutin in terrestrial higher plants. So the lipid biomarkers of fatty acids in Site 4B from Shenhu Area, northern South China Sea were investigated in Recent research supported from the 973 Program (2009CB219506), and the resources of branched fatty acids and monounsaturated fatty acids were mainly discussed. The results reveal that i/a15:0, i/a17:0, 16:1ω5, 18:1ω9 and 10me16:0 are derived from sulfate reducing bacteria (SRB), while 16:1ω7t/c and 18:1ω7 are originated from sulphur-oxidising bacteria (SOB). The biomakers of methanotrophs such as 16:1ω6/8 and 18:1ω6/8 were not detected in the sediments which coincide with more positive carbon isotope values of the fatty acids in the sediments. The stable relationship between SRB and SOB below 97cm in the sediments reflects the relative stable oxidative and reductive depositional environment which may be connected with the sulphur cycle in the sediments, that is carried out as sulfate is reduced to sulfide, and then sulfide is oxidized to sulfate and elemental sulfur, at last elemental sulfur is disproportionated to sulfide and sulfate. The frequently changed relationship of SRB and SOB above 97cm in the sediments indicates intensely changing oxidative and reductive sedimental environment, that may related with diapir structure around Site 4B, which also brings about hydrocarbon seepage leading to increasing biomass at 97cm.

Cerebrospinal Fluid Biomarkers of Neurodegeneration Are Decreased or Normal in Narcolepsy.

PubMed

Jørgen Jennum, Poul; Østergaard Pedersen, Lars; Czarna Bahl, Justyna Maria; Modvig, Signe; Fog, Karina; Holm, Anja; Rahbek Kornum, Birgitte; Gammeltoft, Steen

2017-01-01

To investigate whether cerebrospinal fluid (CSF) biomarkers of neurodegeneration are altered in narcolepsy in order to evaluate whether the hypocretin deficiency and abnormal sleep-wake pattern in narcolepsy leads to neurodegeneration. Twenty-one patients with central hypersomnia (10 type 1 narcolepsy, 5 type 2 narcolepsy, and 6 idiopathic hypersomnia cases), aged 33 years on average and with a disease duration of 2-29 years, and 12 healthy controls underwent CSF analyses of the levels of β-amyloid, total tau protein (T-tau), phosphorylated tau protein (P-tau181), α-synuclein, neurofilament light chain (NF-L), and chitinase 3-like protein-1 (CHI3L1). Levels of β-amyloid were lower in patients with type 1 narcolepsy (375.4 ± 143.5 pg/mL) and type 2 narcolepsy (455.9 ± 65.0 pg/mL) compared to controls (697.9 ± 167.3 pg/mL, p < .05). Furthermore, in patients with type 1 narcolepsy, levels of T-tau (79.0 ± 27.5 pg/mL) and P-tau181 (19.1 ± 4.3 pg/mL) were lower than in controls (162.2 ± 49.9 pg/mL and 33.8 ± 9.2 pg/mL, p < .05). Levels of α-synuclein, NF-L, and CHI3L1 in CSF from narcolepsy patients were similar to those of healthy individuals. Six CSF biomarkers of neurodegeneration were decreased or normal in narcolepsy indicating that taupathy, synucleinopathy, and immunopathy are not prevalent in narcolepsy patients with a disease duration of 2-29 years. Lower CSF levels of β-amyloid, T-tau protein, and P-tau181 in narcolepsy may indicate that hypocretin deficiency and an abnormal sleep-wake pattern alter the turnover of these proteins in the central nervous system. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

19 CFR 181.121 - Maintenance of confidentiality.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 181.121 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) NORTH AMERICAN FREE TRADE AGREEMENT Confidentiality of Business... possession of confidential business information collected pursuant to this part shall, in accordance with...

19 CFR 181.122 - Disclosure to government authorities.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 181.122 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY (CONTINUED) NORTH AMERICAN FREE TRADE AGREEMENT Confidentiality of Business... the disclosure of confidential business information to governmental authorities in the United States...

Plasmodium falciparum: differing effects of non-esterified fatty acids and phospholipids on intraerythrocytic growth in serum-free medium.

PubMed

Asahi, Hiroko; Izumiyama, Shinji; Tolba, Mohammed Essa Marghany; Kwansa-Bentum, Bethel

2011-03-01

Different combinations of non-esterified fatty acids (NEFA) had variable effects on intraerythrocytic growth of Plasmodium falciparum. All stages of the parasite cultured in medium supplemented with cis-9-octadecenoic acid (C18:1-cis-9), hexadecanoic acid (C16:0), phospholipids (Pld) and bovine albumin free of NEFA were similar to those grown in complete growth medium. Three typical growth patterns indicating suppressed schizogony (SS), suppressed formation of merozoites (SMF), and inhibited invasion of merozoites (IMI) resulted from culture in other combinations of lipids. Unsaturated or saturated NEFA with longer or shorter carbon chains than C18:1-cis-9 or C16:0, higher degree of unsaturation, and trans-forms mainly resulted in SS and SMF effects. However, IMI or partial IMI was observed with tetradecanoic acid or octadecanoic acid enriched with C18:1-cis-9, and cis-9-hexadecenoic acid plus C16:0. Isoforms of C18:1-cis-9 also mainly resulted in partial IMI. SMF also occurred with C18:1-cis-9 plus C16:0 in the absence of Pld. Thus different NEFA exerted distinct roles in erythrocytic growth of the parasite by sustaining development at different stages. Copyright © 2010 Elsevier Inc. All rights reserved.

21 CFR 145.181 - Artificially sweetened canned pineapple.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Section 145.181 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CANNED FRUITS Requirements for Specific Standardized Canned Fruits... is water artificially sweetened with saccharin, sodium saccharin, or a combination of both. Such...

1 CFR 18.1 - Original and copies required.

Code of Federal Regulations, 2011 CFR

2011-01-01

... General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION, TRANSMITTAL, AND PROCESSING OF DOCUMENTS PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.1 Original and copies... computer processed data are urged to consult with the Office of the Federal Register staff about possible...

1 CFR 18.1 - Original and copies required.

Code of Federal Regulations, 2010 CFR

2010-01-01

... General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER PREPARATION, TRANSMITTAL, AND PROCESSING OF DOCUMENTS PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.1 Original and copies... computer processed data are urged to consult with the Office of the Federal Register staff about possible...

Inducing effect of clofibric acid on stearoyl-CoA desaturase in intestinal mucosa of rats.

PubMed

Yamazaki, Tohru; Kadokura, Makiko; Mutoh, Yuki; Sakamoto, Takeshi; Okazaki, Mari; Mitsumoto, Atsushi; Kawashima, Yoichi; Kudo, Naomi

2014-12-01

Fibrates have been reported to elevate the hepatic proportion of oleic acid (18:1n-9) through inducing stearoyl-CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of clofibric acid on the fatty acid profile, particularly monounsaturated fatty acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5% (w/w) clofibric acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n-9 was significantly increased, whereas those of palmitoleic (16:1n-7) and cis-vaccenic (18:1n-7) acids were not changed. Upon the treatment with clofibric acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty acid elongase (Elovl) 6 was up-regulated, but that of Elovl5 was unaffected. Fat-free diet feeding for 28 days increased the proportions of 16:1n-7 and 18:1n-7, but did not effectively change that of 18:1n-9, in intestinal mucosa. Fat-free diet feeding up-regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by clofibric acid and a fat-free diet and suggest that up-regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n-9 in intestinal mucosa.

Dual microRNA Screens Reveal That the Immune-Responsive miR-181 Promotes Henipavirus Entry and Cell-Cell Fusion

PubMed Central

Foo, Chwan Hong; Rootes, Christina L.; Marsh, Glenn A.; Gould, Cathryn M.; Klein, Reuben; Riddell, Sarah J.; Middleton, Deborah; Simpson, Kaylene J.; Bean, Andrew G. D.; Stewart, Cameron R.

2016-01-01

Hendra and Nipah viruses (family Paramyxoviridae, genus Henipavirus) are bat-borne viruses that cause fatal disease in humans and a range of other mammalian species. Gaining a deeper understanding of host pathways exploited by henipaviruses for infection may identify targets for new anti-viral therapies. Here we have performed genome-wide high-throughput agonist and antagonist screens at biosafety level 4 to identify host-encoded microRNAs (miRNAs) impacting henipavirus infection in human cells. Members of the miR-181 and miR-17~93 families strongly promoted Hendra virus infection. miR-181 also promoted Nipah virus infection, but did not affect infection by paramyxoviruses from other genera, indicating specificity in the virus-host interaction. Infection promotion was primarily mediated via the ability of miR-181 to significantly enhance henipavirus-induced membrane fusion. Cell signalling receptors of ephrins, namely EphA5 and EphA7, were identified as novel negative regulators of henipavirus fusion. The expression of these receptors, as well as EphB4, were suppressed by miR-181 overexpression, suggesting that simultaneous inhibition of several Ephs by the miRNA contributes to enhanced infection and fusion. Immune-responsive miR-181 levels was also up-regulated in the biofluids of ferrets and horses infected with Hendra virus, suggesting that the host innate immune response may promote henipavirus spread and exacerbate disease severity. This study is the first genome-wide screen of miRNAs influencing infection by a clinically significant mononegavirus and nominates select miRNAs as targets for future anti-viral therapy development. PMID:27783670

LncRNA CASC2 Interacts With miR-181a to Modulate Glioma Growth and Resistance to TMZ Through PTEN Pathway.

PubMed

Liao, Yiwei; Shen, Liangfang; Zhao, Haiting; Liu, Qing; Fu, Jun; Guo, Yong; Peng, Renjun; Cheng, Lei

2017-07-01

Temozolomide (TMZ)-based chemotherapy is a standard strategy for glioma, while chemoresistance remains a major therapeutic challenge. Recent evidence highlights the crucial regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. However, the roles and regulatory mechanisms of lncRNA cancer susceptibility candidate 2 (CASC2), in glioma tumorigenesis and chemoresistance are poorly understood. In this study, CASC2 expression was down-regulated in glioma tissues and cell lines, and was related to a clinicopathologic features and shorter survival time. Exogenous CACS2 alone was sufficient to inhibit glioma cells' proliferation and amplified TMZ-induced repression of cell proliferation, while CACS2 knockdown could reverse this process. CACS2 overexpression could sensitize TMZ-resistant glioma cells to TMZ, while CACS2 knockdown exerted the opposite function. Moreover, CASC2 could inhibit the miR-181a expression by direct targeting in TMZ-resistant glioma cells. CASC2 up-regulated PTEN protein and down-regulated p-AKT protein through regulating miR-181a, and the effect of CASC2 on PTEN and p-AKT could be partially restored by miR-181a. With TMZ-resistant glioma tissues, miR-181a was up-regulated while PTEN was down-regulated. Taken together, these observations suggest CASC2 up-regulates PTEN through direct inhibiting miR-181a and plays an important role in glioma sensitivity to TMZ and may serve as a potential target for cancer diagnosis and treatment. J. Cell. Biochem. 118: 1889-1899, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

33 CFR 181.29 - Hull identification number display.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Hull identification number... SECURITY (CONTINUED) BOATING SAFETY MANUFACTURER REQUIREMENTS Identification of Boats § 181.29 Hull identification number display. Two identical hull identification numbers are required to be displayed on each...

33 CFR 181.23 - Hull identification numbers required.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Hull identification numbers... SECURITY (CONTINUED) BOATING SAFETY MANUFACTURER REQUIREMENTS Identification of Boats § 181.23 Hull... identify each boat produced or imported with two hull identification numbers that meet the requirements of...

Steered Molecular Dynamics for Investigating the Interactions Between Insulin Receptor Tyrosine Kinase (IRK) and Variants of Protein Tyrosine Phosphatase 1B (PTP1B).

PubMed

Nguyen, Hung; Do, Nhat; Phan, Tuyn; Pham, Tri

2018-02-01

The aim of this study is to use steered molecular dynamics to investigate the dissociation process between IRK and PTP1Bs for wild type and five mutants (consisting of p.D181E, p.D181A, p.Q262A, p.D181A-Y46F, and p.D181A-Q262A). The gained results are observed not only the unbinding mechanism of IRK-PTP1B complexes came from pulling force profile, number of hydrogen bonds, and interaction energy between IRK and PTP1Bs but also described PTP1B's point mutations could variably change its binding affinity towards IRK. Additionally, the binding free energy calculated by Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) is also revealed that electrostatic energy and polar solvation energy mainly made up the binding free energy of PTP1B-IRK complexes.

The effect of lead exposure on fatty acid composition in mouse brain analyzed using pseudo-catalytic derivatization.

PubMed

Jung, Jong-Min; Lee, Jechan; Kim, Ki-Hyun; Jang, In Geon; Song, Jae Gwang; Kang, Kyeongjin; Tack, Filip M G; Oh, Jeong-Ik; Kwon, Eilhann E; Kim, Hyung-Wook

2017-03-01

We performed toxicological study of mice exposed to lead by quantifying fatty acids in brain of the mice. This study suggests that the introduced analytical method had an extremely high tolerance against impurities such as water and extractives; thus, it led to the enhanced resolution in visualizing the spectrum of fatty acid profiles in animal brain. Furthermore, one of the biggest technical advantages achieved in this study was the quantitation of fatty acid methyl ester profiles of mouse brain using a trace amount of sample (e.g., 100 μL mixture). Methanol was screened as the most effective extraction solvent for mouse brain. The behavioral test of the mice before and after lead exposure was conducted to see the effect of lead exposure on fatty acid composition of the mice' brain. The lead exposure led to changes in disease-related behavior of the mice. Also, the lead exposure induced significant alterations of fatty acid profile (C16:0, C 18:0, and C 18:1) in brain of the mice, implicated in pathology of psychiatric diseases. The alteration of fatty acid profile of brain of the mice suggests that the derivatizing technique can be applicable to most research fields associated with the environmental neurotoxins with better resolution in a short time, as compared to the current protocols for lipid analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation.

PubMed

Gerstmeier, Jana; Newcomer, Marcia E; Dennhardt, Sophie; Romp, Erik; Fischer, Jana; Werz, Oliver; Garscha, Ulrike

2016-05-01

Leukotrienes (LTs) are proinflammatory lipid mediators formed from arachidonic acid in a 2-step reaction catalyzed by 5-lipoxygenase (5-LOX) requiring the formation of 5-HPETE [5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid] and its subsequent transformation to LTA4 5-LOX is thought to receive arachidonic acid from the nuclear membrane-embedded 5-LOX-activating protein (FLAP). The crystal structure of 5-LOX revealed an active site concealed by F177 and Y181 (FY cork). We examined the influence of the FY cork on 5-LOX activity and membrane binding in HEK293 cells in the absence and presence of FLAP. Uncapping the 5-LOX active site by mutation of F177 and/or Y181 to alanine (5-LOX-F177A, 5-LOX-Y181A, 5-LOX-F177/Y181A) resulted in delayed and diminished 5-LOX membrane association in A23187-stimulated cells. For 5-LOX-F177A and 5-LOX-F177/Y181A, formation of 5-LOX products was dramatically reduced relative to 5-LOX-wild type (wt). Strikingly, coexpression of FLAP in A23187-activated HEK293 cells effectively restored formation of 5-H(p)ETE (5-hydroxy- and 5-peroxy-6-trans-8,11,14-cis-eicosatetraenoic acid) by these same 5-LOX mutants (≈60-70% 5-LOX-wt levels) but not of LTA4 hydrolysis products. Yet 5-LOX-Y181A generated 5-H(p)ETE at levels comparable to 5-LOX-wt but reduced LTA4 hydrolysis products. Coexpression of FLAP partially restored LTA4 hydrolysis product formation by 5-LOX-Y181A. Together, the data suggest that the concealed FY cork impacts membrane association and that FLAP may help shield an uncapped active site.-Gerstmeier, J., Newcomer, M. E., Dennhardt, S., Romp, E., Fischer, J., Werz, O., Garscha, U. 5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation. © FASEB.

Oscillator strengths of the Si II 181 nanometer resonance multiplet

NASA Technical Reports Server (NTRS)

Bergeson, S. D.; Lawler, J. E.

1993-01-01

We report Si II experimental log (gf)-values of -2.38(4) for the 180.801 nm line, of -2.18(4) for the 181.693 nm line, and of -3.29(5) for the 181.745 nm line, where the number in parentheses is the uncertainty in the last digit. The overall uncertainties (about 10 percent) include the 1 sigma random uncertainty (about 6 percent) and an estimate of the systematic uncertainty. The oscillator strengths are determined by combining branching fractions and radiative lifetimes. The branching fractions are measured using standard spectroradiometry on an optically thin source; the radiative lifetimes are measured using time-resolved laser-induced fluorescence.

181. Photocopy of Photograph, Twin Falls Canal Company. Photographer and ...

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

181. Photocopy of Photograph, Twin Falls Canal Company. Photographer and date unknown. POINT SPILL, TWIN FALLS COUNTY; SOUTH VIEW. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

22 CFR 181.2 - Criteria.

Code of Federal Regulations, 2010 CFR

2010-04-01

... binding, are not international agreements. An example of the latter is the Final Act of the Helsinki... by the law of any foreign state, are not international agreements for these purposes. For example, a.... Determinations are made pursuant to § 181.3. Examples of arrangements that may constitute international...

22 CFR 181.2 - Criteria.

Code of Federal Regulations, 2014 CFR

2014-04-01

... binding, are not international agreements. An example of the latter is the Final Act of the Helsinki... by the law of any foreign state, are not international agreements for these purposes. For example, a.... Determinations are made pursuant to § 181.3. Examples of arrangements that may constitute international...

22 CFR 181.2 - Criteria.

Code of Federal Regulations, 2011 CFR

2011-04-01

... binding, are not international agreements. An example of the latter is the Final Act of the Helsinki... by the law of any foreign state, are not international agreements for these purposes. For example, a.... Determinations are made pursuant to § 181.3. Examples of arrangements that may constitute international...

22 CFR 181.2 - Criteria.

Code of Federal Regulations, 2013 CFR

2013-04-01

... binding, are not international agreements. An example of the latter is the Final Act of the Helsinki... by the law of any foreign state, are not international agreements for these purposes. For example, a.... Determinations are made pursuant to § 181.3. Examples of arrangements that may constitute international...

22 CFR 181.2 - Criteria.

Code of Federal Regulations, 2012 CFR

2012-04-01

... binding, are not international agreements. An example of the latter is the Final Act of the Helsinki... by the law of any foreign state, are not international agreements for these purposes. For example, a.... Determinations are made pursuant to § 181.3. Examples of arrangements that may constitute international...

46 CFR 181.425 - Galley hood fire extinguishing systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

...), or other standard specified by the Commandant, and must be listed by an independent laboratory... 181.425 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS... UL 710 (incorporated by reference, see 46 CFR 175.600) or other standard specified by the Commandant...

47 CFR 36.181 - Material and supplies-Account 1220.

Code of Federal Regulations, 2010 CFR

2010-10-01

... JURISDICTIONAL SEPARATIONS PROCEDURES; STANDARD PROCEDURES FOR SEPARATING TELECOMMUNICATIONS PROPERTY COSTS... Material and Supplies and Cash Working Capital § 36.181 Material and supplies—Account 1220. (a) The amount included in Account 1220 is apportioned among the operations on the basis of the apportionment of the cost...

12 CFR 18.1 - Purpose and OMB control number.

Code of Federal Regulations, 2013 CFR

2013-01-01

... statement with narrative information management deems important. The availability of this information is... AND OTHER INFORMATION BY NATIONAL BANKS § 18.1 Purpose and OMB control number. (a) Purpose. The... public confidence in the national banking system. (b) OMB control number. The collection of information...

12 CFR 18.1 - Purpose and OMB control number.

Code of Federal Regulations, 2011 CFR

2011-01-01

... statement with narrative information management deems important. The availability of this information is... AND OTHER INFORMATION BY NATIONAL BANKS § 18.1 Purpose and OMB control number. (a) Purpose. The... public confidence in the national banking system. (b) OMB control number. The collection of information...

12 CFR 18.1 - Purpose and OMB control number.

Code of Federal Regulations, 2014 CFR

2014-01-01

... statement with narrative information management deems important. The availability of this information is... AND OTHER INFORMATION BY NATIONAL BANKS § 18.1 Purpose and OMB control number. (a) Purpose. The... public confidence in the national banking system. (b) OMB control number. The collection of information...

12 CFR 18.1 - Purpose and OMB control number.

Code of Federal Regulations, 2012 CFR

2012-01-01

... statement with narrative information management deems important. The availability of this information is... AND OTHER INFORMATION BY NATIONAL BANKS § 18.1 Purpose and OMB control number. (a) Purpose. The... public confidence in the national banking system. (b) OMB control number. The collection of information...

27 CFR 17.181 - Exportation of medicinal preparations and flavoring extracts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Exportation of medicinal... USED IN MANUFACTURING NONBEVERAGE PRODUCTS Miscellaneous Provisions § 17.181 Exportation of medicinal preparations and flavoring extracts. Medicinal preparations and flavoring extracts, approved for drawback under...

15 CFR 922.181 - Boundary.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the east side of Lanai; to the waters seaward of the three nautical mile limit north of Kahoolawe, to... MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands Humpback Whale National Marine Sanctuary § 922.181 Boundary. (a) Except for excluded areas described in paragraph (b) of this section, the Hawaiian Islands...

15 CFR 922.181 - Boundary.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the east side of Lanai; to the waters seaward of the three nautical mile limit north of Kahoolawe, to... MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands Humpback Whale National Marine Sanctuary § 922.181 Boundary. (a) Except for excluded areas described in paragraph (b) of this section, the Hawaiian Islands...

15 CFR 922.181 - Boundary.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the east side of Lanai; to the waters seaward of the three nautical mile limit north of Kahoolawe, to... MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands Humpback Whale National Marine Sanctuary § 922.181 Boundary. (a) Except for excluded areas described in paragraph (b) of this section, the Hawaiian Islands...

15 CFR 922.181 - Boundary.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the east side of Lanai; to the waters seaward of the three nautical mile limit north of Kahoolawe, to... MARINE SANCTUARY PROGRAM REGULATIONS Hawaiian Islands Humpback Whale National Marine Sanctuary § 922.181 Boundary. (a) Except for excluded areas described in paragraph (b) of this section, the Hawaiian Islands...

Dietary lead: effects on hepatic fatty acid composition in chicks.

PubMed

Donaldson, W E; Leeming, T K

1984-03-30

Arbor Acre broiler chicks were fed diets containing 0, 500, 750, 1000, 2000, or 4000 ppm lead (as Pb acetate X 3 H2O) from day-old through 21 days of age. There were 8 groups of 10 male chicks per lead level. Eight chicks from each dietary lead level were killed at 21 days, and hepatic fatty acid composition was determined for each chick by gas-liquid chromatography. Increasing dietary lead levels decreased the concentrations of 16:1 and 18:1 fatty acids (first No. = No. carbons; second No. = No. double bonds) and increased the concentrations of 18:0 and 20:4. The concentration of 18:2 fatty acids did not differ significantly from control values for any level of lead. However, the ratio 18:2/20:4 declined from a control value of 3.3 to approximately 2 for all lead treatments. The ratio of saturated/monoenoic fatty acids increased with dietary lead levels above 1000 ppm. In a second experiment 10 male broiler chicks per treatment were fed either a control diet or the control diet plus 2000 ppm lead, 60 ppm cadmium, 500 ppm mercury, or 10 ppm selenium (as Pb acetate X 3 H2O, CdSO4, HgCl2, or Na2SeO3, respectively) for 21 days. Six chicks from each group were killed at 21 days, and hepatic fatty acid composition was determined for each chick. In comparison to control, the ratio 18:2/20:4 was lowered by lead but unaffected by cadmium, mercury, and selenium. The data suggest that lead may increase tissue peroxidation (as noted by other workers) via a relative increase of 20:4 fatty acid and that a decrease of hepatic ratio 18:2/20:4 may be a specific sign of lead toxicity.

49 CFR 572.181 - General description.

Code of Federal Regulations, 2012 CFR

2012-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES 2re Side Impact Crash Test Dummy, 50th Percentile Adult Male § 572.181 General description. (a) The ES-2re Side Impact Crash Test... (PADI) of the ES-2re Side Impact Crash Test Dummy, February 2008, incorporated by reference, see § 572...

49 CFR 572.181 - General description.

Code of Federal Regulations, 2013 CFR

2013-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES ES-2re Side Impact Crash Test Dummy, 50th Percentile Adult Male § 572.181 General description. (a) The ES-2re Side Impact Crash... (PADI) of the ES-2re Side Impact Crash Test Dummy, February 2008, incorporated by reference, see § 572...

49 CFR 572.181 - General description.

Code of Federal Regulations, 2014 CFR

2014-10-01

... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) ANTHROPOMORPHIC TEST DEVICES ES-2re Side Impact Crash Test Dummy, 50th Percentile Adult Male § 572.181 General description. (a) The ES-2re Side Impact Crash... (PADI) of the ES-2re Side Impact Crash Test Dummy, February 2008, incorporated by reference, see § 572...

37 CFR 1.81 - Drawings required in patent application.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Drawings required in patent..., DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions The Drawings § 1.81 Drawings required in patent application. (a) The applicant for a patent is required to furnish...

USE OF THE AERODYNAMIC PARTICLE SIZER TO MEASURE PM-COARSE

EPA Science Inventory

The aerodynamic particle sizer (APS 3321, TSI, Inc.) measures particle size distributions from 0.5 µm to 20 µm by determining the time-of-flight of individual particles in an accelerating flow field. A complete particle size distribution may be determined in a matter of s...

18 CFR 367.1810 - Account 181, Unamortized debt expense.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Account 181, Unamortized debt expense. 367.1810 Section 367.1810 Conservation of Power and Water Resources FEDERAL ENERGY..., FEDERAL POWER ACT AND NATURAL GAS ACT UNIFORM SYSTEM OF ACCOUNTS FOR CENTRALIZED SERVICE COMPANIES SUBJECT...

49 CFR 572.181 - General description.

Code of Federal Regulations, 2011 CFR

2011-10-01

... assembly Drawing number Head Assembly 175-1000 Neck Assembly Test/Cert 175-2000 Neck Bracket Including..., dated February 2008. (c) Weights of body segments (head, neck, upper and lower torso, arms and upper and... the convenience of the user, the added and revised text is set forth as follows: § 572.181 General...

33 CFR 181.703 - Information pamphlet: Contents.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Information pamphlet: Contents... § 181.703 Information pamphlet: Contents. Unless otherwise specified in this subpart, each information pamphlet must contain the information specified in sections 33, 34 and 35 of UL 1123. [CGD 93-055, 61 FR...

78 FR 14015 - Medical Devices; Exemption From Premarket Notification; Class II Devices; Powered Patient Transport

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-04

... for Safety--Collateral Standard: Electromagnetic Compatibility--Requirements and Tests,'' and ASME A18.1 ``Safety Standard for Platform Lifts and Stairway Chair Lifts'') must validate electromagnetic...: Electromagnetic Compatibility--Requirements and Tests,'' and ASME A18.1 ``Safety Standard for Platform Lifts and...

19 CFR 181.75 - Issuance of origin determination.

Code of Federal Regulations, 2010 CFR

2010-04-01

... origin verification initiated under § 181.72(a) of this part in regard to a good imported into the United... the origin verification, Customs shall provide the exporter or producer whose good is the subject of the verification with a written determination of whether the good qualifies as an originating good...

33 CFR 181.31 - Manufacturer identification code assignment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... SECURITY (CONTINUED) BOATING SAFETY MANUFACTURER REQUIREMENTS Identification of Boats § 181.31 Manufacturer... manufacturer's name and U.S. address along with the general types and lengths of boats that will be manufactured. (b) For boats manufactured outside of the jurisdiction of the United States, a U.S. importer must...

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2011-04-01 2010-04-01 true Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

22 CFR 181.1 - Purpose and application.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., will not give rise to a cause of action, and will not affect any public or private rights established... Foreign Relations DEPARTMENT OF STATE INTERNATIONAL AGREEMENTS COORDINATION, REPORTING AND PUBLICATION OF INTERNATIONAL AGREEMENTS § 181.1 Purpose and application. (a) The purpose of this part is to implement the...

27 CFR 31.181 - Requirements for retail dealers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Requirements for retail... BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL ALCOHOL BEVERAGE DEALERS Records and Reports Retail Dealer's Records § 31.181 Requirements for retail dealers. (a) Records of receipt. All retail dealers must keep at...

27 CFR 31.181 - Requirements for retail dealers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Requirements for retail... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS ALCOHOL BEVERAGE DEALERS Records and Reports Retail Dealer's Records § 31.181 Requirements for retail dealers. (a) Records of receipt. All retail dealers must keep at...

27 CFR 31.181 - Requirements for retail dealers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Requirements for retail... BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL ALCOHOL BEVERAGE DEALERS Records and Reports Retail Dealer's Records § 31.181 Requirements for retail dealers. (a) Records of receipt. All retail dealers must keep at...

27 CFR 31.181 - Requirements for retail dealers.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Requirements for retail... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS ALCOHOL BEVERAGE DEALERS Records and Reports Retail Dealer's Records § 31.181 Requirements for retail dealers. (a) Records of receipt. All retail dealers must keep at...

27 CFR 31.181 - Requirements for retail dealers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Requirements for retail... BUREAU, DEPARTMENT OF THE TREASURY LIQUORS ALCOHOL BEVERAGE DEALERS Records and Reports Retail Dealer's Records § 31.181 Requirements for retail dealers. (a) Records of receipt. All retail dealers must keep at...

33 CFR 181.23 - Hull identification numbers required.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Hull identification numbers... identification numbers required. (a) A manufacturer must identify each boat produced or imported with primary and secondary hull identification numbers permanently affixed in accordance with § 181.29 of this subpart. (b) A...

33 CFR 181.23 - Hull identification numbers required.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Hull identification numbers... identification numbers required. (a) A manufacturer must identify each boat produced or imported with primary and secondary hull identification numbers permanently affixed in accordance with § 181.29 of this subpart. (b) A...

181. Photographic copy of original construction drawing dated March 28, ...

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

181. Photographic copy of original construction drawing dated March 28, 1932 (from Record Group 115, Denver Branch of the National Archives, Denver). VOLUME CHANGE IN MASS CONCRETE; OWYHEE DAM CONCRETE RESEARCH FOR HOOVER DAM; LOCATION OF TERMINAL BOARDS AND CONDUCTS. - Owyhee Dam, Across Owyhee River, Nyssa, Malheur County, OR

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2010-04-01 2010-04-01 false Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2013-04-01 2013-04-01 false Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2014-04-01 2014-04-01 false Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

27 CFR 555.181 - Reporting of plastic explosives.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 3 2012-04-01 2010-04-01 true Reporting of plastic..., FIREARMS, AND EXPLOSIVES, DEPARTMENT OF JUSTICE EXPLOSIVES COMMERCE IN EXPLOSIVES Marking of Plastic Explosives § 555.181 Reporting of plastic explosives. All persons, other than an agency of the United States...

Indolyl aryl sulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: role of two halogen atoms at the indole ring in developing new analogues with improved antiviral activity.

PubMed

Regina, Giuseppe La; Coluccia, Antonio; Piscitelli, Francesco; Bergamini, Alberto; Sinistro, Anna; Cavazza, Antonella; Maga, Giovanni; Samuele, Alberta; Zanoli, Samantha; Novellino, Ettore; Artico, Marino; Silvestri, Romano

2007-10-04

Indolyl aryl sulfones bearing the 4,5-difluoro (10) or 5-chloro-4-fluoro (16) substitution pattern at the indole ring were potent inhibitors of HIV-1 WT and the NNRTI-resistant strains Y181C and K103N-Y181C. These compounds were highly effective against the 112 and the AB1 strains in lymphocytes and inhibited at nanomolar concentration the multiplication of the IIIBBa-L strain in macrophages. Compound 16 was exceptionally potent against RT WT and RTs carrying the K103N, Y181I, and L100I mutations.

181. Photocopy of drawing (1973 architectural drawing by the Space ...

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

181. Photocopy of drawing (1973 architectural drawing by the Space and Missile Test Center, VAFB, USAF) SITE PLAN, SECTIONS, AND DETAILS FOR THE FUEL TANK RETAINING WALL, SHEET 27A OF 53 - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA

26 CFR 1.181-1 - Deduction for qualified film and television production costs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... amount of aggregate production costs that may be claimed as a deduction for a post-amendment production... provides special rules, including rules for recapture of the deduction. Section 1.181-5 provides examples... paid or incurred in connection with obtaining financing for the production (for example, premiums paid...

19 CFR 181.100 - Effect of NAFTA advance ruling letters; modification and revocation.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., may be applied to entries for consumption and warehouse withdrawals for consumption which are... qualifies for duty-free treatment under § 181.64 of this part when the good re-enters the United States... be applied to entries or warehouse withdrawals for consumption which were made prior to the effective...

19 CFR 181.100 - Effect of NAFTA advance ruling letters; modification and revocation.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., may be applied to entries for consumption and warehouse withdrawals for consumption which are... qualifies for duty-free treatment under § 181.64 of this part when the good re-enters the United States... be applied to entries or warehouse withdrawals for consumption which were made prior to the effective...

19 CFR 181.100 - Effect of NAFTA advance ruling letters; modification and revocation.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., may be applied to entries for consumption and warehouse withdrawals for consumption which are... qualifies for duty-free treatment under § 181.64 of this part when the good re-enters the United States... be applied to entries or warehouse withdrawals for consumption which were made prior to the effective...

77 FR 31496 - Approval and Promulgation of Air Quality Implementation Plans; Massachusetts and New Hampshire...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-29

...(b)(2)(A) of the Clean Air Act (CAA), that the Boston-Lawrence-Worcester (Eastern Massachusetts...) proposing its determination under section 181(b)(2) that the Boston-Lawrence- Worcester (Eastern... section 181(b)(2)(A), that the Boston-Lawrence- Worcester (Eastern Massachusetts) moderate 1997 eight-hour...

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

46 CFR 181.450 - Independent modular smoke detecting units.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Independent modular smoke detecting units. 181.450... Independent modular smoke detecting units. (a) An independent modular smoke detecting unit must: (1) Meet UL 217 (incorporated by reference, see 46 CFR 175.600) and be listed as a “Single Station Smoke detector...

14 CFR 121.181 - Airplanes: Reciprocating engine-powered: En route limitations: One engine inoperative.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Airplanes: Reciprocating engine-powered: En... OPERATIONS Airplane Performance Operating Limitations § 121.181 Airplanes: Reciprocating engine-powered: En... person operating a reciprocating engine powered airplane may take off that airplane at a weight, allowing...

14 CFR 121.181 - Airplanes: Reciprocating engine-powered: En route limitations: One engine inoperative.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Airplanes: Reciprocating engine-powered: En... OPERATIONS Airplane Performance Operating Limitations § 121.181 Airplanes: Reciprocating engine-powered: En... person operating a reciprocating engine powered airplane may take off that airplane at a weight, allowing...

14 CFR 121.181 - Airplanes: Reciprocating engine-powered: En route limitations: One engine inoperative.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Airplanes: Reciprocating engine-powered: En... OPERATIONS Airplane Performance Operating Limitations § 121.181 Airplanes: Reciprocating engine-powered: En... person operating a reciprocating engine powered airplane may take off that airplane at a weight, allowing...

14 CFR 121.181 - Airplanes: Reciprocating engine-powered: En route limitations: One engine inoperative.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Airplanes: Reciprocating engine-powered: En... OPERATIONS Airplane Performance Operating Limitations § 121.181 Airplanes: Reciprocating engine-powered: En... person operating a reciprocating engine powered airplane may take off that airplane at a weight, allowing...

19 CFR 181.45 - Goods eligible for full drawback.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-Deferral Programs § 181.45 Goods eligible for full drawback. (a) Goods originating in Canada or Mexico. A... originating good is: (1) Subsequently exported to Canada or Mexico; (2) Used as a material in the production of another good that is subsequently exported to Canada or Mexico; or (3) Substituted by a good of...

19 CFR 181.45 - Goods eligible for full drawback.

Code of Federal Regulations, 2011 CFR

2011-04-01

...-Deferral Programs § 181.45 Goods eligible for full drawback. (a) Goods originating in Canada or Mexico. A... originating good is: (1) Subsequently exported to Canada or Mexico; (2) Used as a material in the production of another good that is subsequently exported to Canada or Mexico; or (3) Substituted by a good of...

21 CFR 181.33 - Sodium nitrate and potassium nitrate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium nitrate and potassium nitrate. 181.33... nitrate and potassium nitrate. Sodium nitrate and potassium nitrate are subject to prior sanctions issued... potassium nitrite, in the production of cured red meat products and cured poultry products. [48 FR 1705, Jan...

13 CFR 120.181 - Status of Lenders and CDCs.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Status of Lenders and CDCs. 120....181 Status of Lenders and CDCs. Lenders, CDCs and their contractors are independent contractors that... wrongful action taken by a Lender, CDC or an employee, agent, or contractor of a Lender or CDC. [72 FR...