Circulating CD36 is reduced in HNF1A-MODY carriers.

Directory of Open Access Journals (Sweden)

Siobhan Bacon

Full Text Available INTRODUCTION: Premature atherosclerosis is a significant cause of morbidity and mortality in type 2 diabetes mellitus. Maturity onset diabetes of the young (MODY accounts for approximately 2% of all diabetes, with mutations in the transcription factor; hepatocyte nuclear factor 1 alpha (HNF1A accounting for the majority of MODY cases. There is somewhat limited data available on the prevalence of macrovascular disease in HNF1A-MODY carriers with diabetes. Marked insulin resistance and the associated dyslipidaemia are not clinical features of HNF1A-MODY carriers. The scavenger protein CD36 has been shown to play a substantial role in the pathogenesis of atherosclerosis, largely through its interaction with oxidised LDL. Higher levels of monocyte CD36 and plasma CD36(sCD36 are seen to cluster with insulin resistance and diabetes. The aim of this study was to determine levels of sCD36 in participants with HNF1A-MODY diabetes and to compare them with unaffected normoglycaemic family members and participants with type 2 diabetes mellitus. METHODS: We recruited 37 participants with HNF1A-MODY diabetes and compared levels of sCD36 with BMI-matched participants with type 2 diabetes mellitus and normoglycaemic HNF1A-MODY negative family controls. Levels of sCD36 were correlated with phenotypic and biochemical parameters. RESULTS: HNF1A-MODY participants were lean, normotensive, with higher HDL and lower triglyceride levels when compared to controls and participants with type 2 diabetes mellitus. sCD36 was also significantly lower in HNF1A-MODY participants when compared to both the normoglycaemic family controls and to lean participants with type 2 diabetes mellitus. CONCLUSION: In conclusion, sCD36 is significantly lower in lean participants with HNF1A-MODY diabetes when compared to weight-matched normoglycaemic familial HNF1A-MODY negative controls and to lean participants with type 2 diabetes mellitus. Lower levels of this pro-atherogenic marker may

Mutations in HNF1A Result in Marked Alterations of Plasma Glycan Profile

Science.gov (United States)

Thanabalasingham, Gaya; Huffman, Jennifer E.; Kattla, Jayesh J.; Novokmet, Mislav; Rudan, Igor; Gloyn, Anna L.; Hayward, Caroline; Adamczyk, Barbara; Reynolds, Rebecca M.; Muzinic, Ana; Hassanali, Neelam; Pucic, Maja; Bennett, Amanda J.; Essafi, Abdelkader; Polasek, Ozren; Mughal, Saima A.; Redzic, Irma; Primorac, Dragan; Zgaga, Lina; Kolcic, Ivana; Hansen, Torben; Gasperikova, Daniela; Tjora, Erling; Strachan, Mark W.J.; Nielsen, Trine; Stanik, Juraj; Klimes, Iwar; Pedersen, Oluf B.; Njølstad, Pål R.; Wild, Sarah H.; Gyllensten, Ulf; Gornik, Olga; Wilson, James F.; Hastie, Nicholas D.; Campbell, Harry; McCarthy, Mark I.; Rudd, Pauline M.; Owen, Katharine R.; Lauc, Gordan; Wright, Alan F.

2013-01-01

A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-α (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic ≥0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction. PMID:23274891

Repression of HNF1α-mediated transcription by amino-terminal enhancer of split (AES)

Energy Technology Data Exchange (ETDEWEB)

Han, Eun Hee [Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912 (United States); Gorman, Amanda A. [Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY 40536 (United States); Singh, Puja [Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912 (United States); Chi, Young-In, E-mail: ychi@hi.umn.edu [Section of Structural Biology, Hormel Institute, University of Minnesota, Austin, MN 55912 (United States)

2015-12-04

HNF1α (Hepatocyte Nuclear Factor 1α) is one of the master regulators in pancreatic beta-cell development and function, and the mutations in Hnf1α are the most common monogenic causes of diabetes mellitus. As a member of the POU transcription factor family, HNF1α exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge in their functional complex formation. In this study, we identified the Groucho protein AES (Amino-terminal Enhancer of Split) as a HNF1α-specific physical binding partner and functional repressor of HNF1α-mediated transcription, which has a direct link to glucose-stimulated insulin secretion in beta-cells that is impaired in the HNF1α mutation-driven diabetes. - Highlights: • We identified AES as a transcriptional repressor for HNF1α in pancreatic beta-cell. • AES's repressive activity was HNF1α-specific and was not observed with HNF1β. • AES interacts with the transactivation domain of HNF1α. • Small molecules can be designed or discovered to disrupt this interaction and improve insulin secretion and glucose homeostasis.

Repression of HNF1α-mediated transcription by amino-terminal enhancer of split (AES)

International Nuclear Information System (INIS)

Han, Eun Hee; Gorman, Amanda A.; Singh, Puja; Chi, Young-In

2015-01-01

HNF1α (Hepatocyte Nuclear Factor 1α) is one of the master regulators in pancreatic beta-cell development and function, and the mutations in Hnf1α are the most common monogenic causes of diabetes mellitus. As a member of the POU transcription factor family, HNF1α exerts its gene regulatory function through various molecular interactions; however, there is a paucity of knowledge in their functional complex formation. In this study, we identified the Groucho protein AES (Amino-terminal Enhancer of Split) as a HNF1α-specific physical binding partner and functional repressor of HNF1α-mediated transcription, which has a direct link to glucose-stimulated insulin secretion in beta-cells that is impaired in the HNF1α mutation-driven diabetes. - Highlights: • We identified AES as a transcriptional repressor for HNF1α in pancreatic beta-cell. • AES's repressive activity was HNF1α-specific and was not observed with HNF1β. • AES interacts with the transactivation domain of HNF1α. • Small molecules can be designed or discovered to disrupt this interaction and improve insulin secretion and glucose homeostasis.

De novo mutations of GCK, HNF1A and HNF4A may be more frequent in MODY than previously assumed.

Science.gov (United States)

Stanik, Juraj; Dusatkova, Petra; Cinek, Ondrej; Valentinova, Lucia; Huckova, Miroslava; Skopkova, Martina; Dusatkova, Lenka; Stanikova, Daniela; Pura, Mikulas; Klimes, Iwar; Lebl, Jan; Gasperikova, Daniela; Pruhova, Stepanka

2014-03-01

MODY is mainly characterised by an early onset of diabetes and a positive family history of diabetes with an autosomal dominant mode of inheritance. However, de novo mutations have been reported anecdotally. The aim of this study was to systematically revisit a large collection of MODY patients to determine the minimum prevalence of de novo mutations in the most prevalent MODY genes (i.e. GCK, HNF1A, HNF4A). Analysis of 922 patients from two national MODY centres (Slovakia and the Czech Republic) identified 150 probands (16%) who came from pedigrees that did not fulfil the criterion of two generations with diabetes but did fulfil the remaining criteria. The GCK, HNF1A and HNF4A genes were analysed by direct sequencing. Mutations in GCK, HNF1A or HNF4A genes were detected in 58 of 150 individuals. Parents of 28 probands were unavailable for further analysis, and in 19 probands the mutation was inherited from an asymptomatic parent. In 11 probands the mutations arose de novo. In our cohort of MODY patients from two national centres the de novo mutations in GCK, HNF1A and HNF4A were present in 7.3% of the 150 families without a history of diabetes and 1.2% of all of the referrals for MODY testing. This is the largest collection of de novo MODY mutations to date, and our findings indicate a much higher frequency of de novo mutations than previously assumed. Therefore, genetic testing of MODY could be considered for carefully selected individuals without a family history of diabetes.

HNF1 alpha activates the aminopeptidase N promoter in intestinal (Caco-2) cells

DEFF Research Database (Denmark)

Olsen, Jørgen; Laustsen, Lotte; Troelsen, J

1994-01-01

The importance of HNF1 binding proteins for intestinal aminopeptidase N expression was investigated using the Caco-2 cell-line. Aminopeptidase N promoter activity in Caco-2 cells depends on the HNF1 element (positions -85 to -58) and co-transfection with an HNF1 alpha expression vector demonstrates...... a direct activation of the promoter by HNF1 alpha through this element. Electrophoretic mobility shift assays using nuclear extracts from Caco-2 cells show the presence of high amounts of HNF1 binding proteins irrespective of their state of differentiation....

References for HNF-SD-WM-TRD-007, ''System specification for the double-shell tank system: HNF-PROs, CFRs, DOE Orders, WACs''

International Nuclear Information System (INIS)

Shaw, C.P.

1998-01-01

HNF-SD-WM-TRD-O07, System Specification for the Double-Shell Tank System, (hereafter referred to as DST Specification), defines the requirements of the double-shell tank system at the Hanford Site for Phase 1 privatization. Many of the sections in this document reference other documents for design guidance and requirements. Referenced documents include Project Hanford Management Contract (PHMC) procedures (HNF-PROS), Codes of Federal Regulation (CFRs), DOE Orders, and Washington Administrative Codes (WACs). This document provides rationale for the selection and inclusion of HNF-PROS, CFRs, DOE Orders and WACs

Mutations in HNF1A result in marked alterations of plasma glycan profile

DEFF Research Database (Denmark)

Thanabalasingham, Gaya; Huffman, Jennifer E; Kattla, Jayesh J

2013-01-01

A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma...... proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated...... to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-α (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167...

HNF-1B specifically regulates the transcription of the {gamma}a-subunit of the Na{sup +}/K{sup +}-ATPase

Energy Technology Data Exchange (ETDEWEB)

Ferre, Silvia [Department of Physiology, Radboud University Nijmegen Medical Centre (Netherlands); Veenstra, Gert Jan C. [Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen (Netherlands); Bouwmeester, Rianne; Hoenderop, Joost G.J. [Department of Physiology, Radboud University Nijmegen Medical Centre (Netherlands); Bindels, Rene J.M., E-mail: r.bindels@fysiol.umcn.nl [Department of Physiology, Radboud University Nijmegen Medical Centre (Netherlands)

2011-01-07

Research highlights: {yields} Defects in HNF-1B transcription factor affect Mg{sup 2+} handling in the distal kidney. {yields} {gamma}a- and {gamma}b- subunits of the Na{sup +}/K{sup +}-ATPase colocalize in the distal convoluted tubule of the nephron. {yields} HNF-1B specifically activates {gamma}a expression. {yields} HNF-1B mutants have a dominant negative effect on wild type HNF-1B activity. {yields} Defective transcription of {gamma}a may promote renal Mg{sup 2+} wasting. -- Abstract: Hepatocyte nuclear factor-1B (HNF-1B) is a transcription factor involved in embryonic development and tissue-specific gene expression in several organs, including the kidney. Recently heterozygous mutations in the HNF1B gene have been identified in patients with hypomagnesemia due to renal Mg{sup 2+} wasting. Interestingly, ChIP-chip data revealed HNF-1B binding sites in the FXYD2 gene, encoding the {gamma}-subunit of the Na{sup +}/K{sup +}-ATPase. The {gamma}-subunit has been described as one of the molecular players in the renal Mg{sup 2+} reabsorption in the distal convoluted tubule (DCT). Of note, the FXYD2 gene can be alternatively transcribed into two main variants, namely {gamma}a and {gamma}b. In the present study, we demonstrated via two different reporter gene assays that HNF-1B specifically acts as an activator of the {gamma}a-subunit, whereas the {gamma}b-subunit expression was not affected. Moreover, the HNF-1B mutations H69fsdelAC, H324S325fsdelCA, Y352finsA and K156E, previously identified in patients with hypomagnesemia, prevented transcription activation of {gamma}a-subunit via a dominant negative effect on wild type HNF1-B. By immunohistochemistry, it was shown that the {gamma}a- and {gamma}b-subunits colocalize at the basolateral membrane of the DCT segment of mouse kidney. On the basis of these data, we suggest that abnormalities involving the HNF-1B gene may impair the relative abundance of {gamma}a and {gamma}b, thus affecting the transcellular Mg{sup 2

Crystallization of hepatocyte nuclear factor 4α (HNF4α) in complex with the HNF1α promoter element

Energy Technology Data Exchange (ETDEWEB)

Lu, Peng; Liu, Jianguo; Melikishvili, Manana; Fried, Michael G.; Chi, Young-In, E-mail: ychi@uky.edu [Department of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, Lexington, KY 40536 (United States)

2008-04-01

Sample preparation, characterization, crystallization and preliminary X-ray analysis are reported for the HNF4α–DNA binary complex. Hepatocyte nuclear factor 4α (HNF4α) is a member of the nuclear receptor superfamily that plays a central role in organ development and metabolic functions. Mutations on HNF4α cause maturity-onset diabetes of the young (MODY), a dominant monogenic cause of diabetes. In order to understand the molecular mechanism of promoter recognition and the molecular basis of disease-causing mutations, the recombinant HNF4α DNA-binding domain was prepared and used in a study of its binding properties and in crystallization with a 21-mer DNA fragment that contains the promoter element of another MODY gene, HNF1α. The HNF4α protein displays a cooperative and specific DNA-binding activity towards its target gene-recognition elements. Crystals of the complex diffract to 2.0 Å using a synchrotron-radiation source under cryogenic (100 K) conditions and belong to space group C2, with unit-cell parameters a = 121.63, b = 35.43, c = 70.99 Å, β = 119.36°. A molecular-replacement solution has been obtained and structure refinement is in progress. This structure and the binding studies will provide the groundwork for detailed functional and biochemical studies of the MODY mutants.

Crystallization of hepatocyte nuclear factor 4α (HNF4α) in complex with the HNF1α promoter element

International Nuclear Information System (INIS)

Lu, Peng; Liu, Jianguo; Melikishvili, Manana; Fried, Michael G.; Chi, Young-In

2008-01-01

Sample preparation, characterization, crystallization and preliminary X-ray analysis are reported for the HNF4α–DNA binary complex. Hepatocyte nuclear factor 4α (HNF4α) is a member of the nuclear receptor superfamily that plays a central role in organ development and metabolic functions. Mutations on HNF4α cause maturity-onset diabetes of the young (MODY), a dominant monogenic cause of diabetes. In order to understand the molecular mechanism of promoter recognition and the molecular basis of disease-causing mutations, the recombinant HNF4α DNA-binding domain was prepared and used in a study of its binding properties and in crystallization with a 21-mer DNA fragment that contains the promoter element of another MODY gene, HNF1α. The HNF4α protein displays a cooperative and specific DNA-binding activity towards its target gene-recognition elements. Crystals of the complex diffract to 2.0 Å using a synchrotron-radiation source under cryogenic (100 K) conditions and belong to space group C2, with unit-cell parameters a = 121.63, b = 35.43, c = 70.99 Å, β = 119.36°. A molecular-replacement solution has been obtained and structure refinement is in progress. This structure and the binding studies will provide the groundwork for detailed functional and biochemical studies of the MODY mutants

HNF1B mutations associate with hypomagnesemia and renal magnesium wasting

NARCIS (Netherlands)

Adalat, Shazia; Woolf, Adrian S.; Johnstone, Karen A.; Wirsing, Andrea; Harries, Lorna W.; Long, David A.; Hennekam, Raoul C.; Ledermann, Sarah E.; Rees, Lesley; van't Hoff, William; Marks, Stephen D.; Trompeter, Richard S.; Tullus, Kjell; Winyard, Paul J.; Cansick, Janette; Mushtaq, Imran; Dhillon, Harjeeta K.; Bingham, Coralie; Edghill, Emma L.; Shroff, Rukshana; Stanescu, Horia; Ryffel, Gerhart U.; Ellard, Sian; Bockenhauer, Detlef

2009-01-01

Mutations in hepatocyte nuclear factor 1B (HNF1B), which is a transcription factor expressed in tissues including renal epithelia, associate with abnormal renal development. While studying renal phenotypes of children with HNF1B mutations, we identified a teenager who presented with tetany and

HNF - Helmholtz Nano Facility

Directory of Open Access Journals (Sweden)

Wolfgang Albrecht

2017-05-01

Full Text Available The Helmholtz Nano Facility (HNF is a state-of-the-art cleanroom facility. The cleanroom has ~1100 m2 with cleanroom classes of DIN ISO 1-3. HNF operates according to VDI DIN 2083, Good Manufacturing Practice (GMP and aquivalent to Semiconductor Industry Association (SIA standards. HNF is a user facility of Forschungszentrum Jülich and comprises a network of facilities, processes and systems for research, production and characterization of micro- and nanostructures. HNF meets the basic supply of micro- and nanostructures for nanoelectronics, fluidics. micromechanics, biology, neutron and energy science, etc.. The task of HNF is rapid progress in nanostructures and their technology, offering efficient access to infrastructure and equipment. HNF gives access to expertise and provides resources in production, synthesis, characterization and integration of structures, devices and circuits. HNF covers the range from basic research to application oriented research facilitating a broad variety of different materials and different sample sizes.

Functional characterization of the HNF4α isoform (HNF4α8) expressed in pancreatic β-cells

International Nuclear Information System (INIS)

Ihara, Arisa; Yamagata, Kazuya; Nammo, Takao; Miura, Atsuko; Yuan, Ming; Tanaka, Toshiya; Sladek, Frances M.; Matsuzawa, Yuji; Miyagawa, Jun-ichiro; Shimomura, Iichiro

2005-01-01

Mutations in the hepatocyte nuclear factor (HNF) 4α gene cause a form of maturity-onset diabetes of the young (MODY1), which is a monogenic form of type 2 diabetes characterized by impaired insulin secretion by pancreatic β-cells. HNF4α is a transcription factor expressed in the liver, kidney, intestine, and pancreatic islet. Multiple splice variants of the HNF4α gene have been identified and an isoform of HNF4α8, an N-terminal splice variant, is expressed in pancreatic β-cells. However, expression levels of HNF4α protein in pancreatic β-cells and the transcriptional activity of HNF4α8 are not yet understood. In the present study, we investigated the expression of HNF4α in β-cells and examined its functional properties. Western blotting and immunohistochemical analysis revealed that the expression of HNF4α protein in pancreatic islets and INS-1 cells was much lower than in the liver. A reporter gene assay showed that the transactivation potential of HNF4α8 was significantly weaker than that of HNF4α2, which is a major isoform in the liver, suggesting that the total level of HNF4α activity is very weak in pancreatic β-cells. We also showed that the N-terminal A/B region of HNF4α8 possessed no activation function and C-terminal F region negatively regulated the transcriptional activity of HNF4α8. The information presented here would be helpful for the better understanding of MODY1/HNF4α diabetes

Circulating CD36 Is Reduced in HNF1A-MODY Carriers.

LENUS (Irish Health Repository)

Bacon, Siobhan

2013-01-01

Premature atherosclerosis is a significant cause of morbidity and mortality in type 2 diabetes mellitus. Maturity onset diabetes of the young (MODY) accounts for approximately 2% of all diabetes, with mutations in the transcription factor; hepatocyte nuclear factor 1 alpha (HNF1A) accounting for the majority of MODY cases. There is somewhat limited data available on the prevalence of macrovascular disease in HNF1A-MODY carriers with diabetes. Marked insulin resistance and the associated dyslipidaemia are not clinical features of HNF1A-MODY carriers. The scavenger protein CD36 has been shown to play a substantial role in the pathogenesis of atherosclerosis, largely through its interaction with oxidised LDL. Higher levels of monocyte CD36 and plasma CD36(sCD36) are seen to cluster with insulin resistance and diabetes. The aim of this study was to determine levels of sCD36 in participants with HNF1A-MODY diabetes and to compare them with unaffected normoglycaemic family members and participants with type 2 diabetes mellitus.

Intima-media thickness and endothelial dysfunction in GCK and HNF1A-MODY patients.

Science.gov (United States)

Szopa, Magdalena; Osmenda, Grzegorz; Wilk, Grzegorz; Matejko, Bartłomiej; Skupien, Jan; Zapala, Barbara; Młynarski, Wojciech; Guzik, Tomasz; Malecki, Maciej T

2015-03-01

Mutations in the glucokinase (GCK) gene, along with hepatocyte nuclear factor 1A (HNF1A) gene mutations, are the most frequent cause of maturity-onset diabetes of the young (MODY). GCK-MODY patients are typically characterized by a moderate fasting hyperglycemia; however, little is known about atherosclerosis and intermediate-related phenotypes in these subjects. To examine carotid artery intima-media thickness (IMT) and endothelial function assessed by brachial artery flow-mediated dilatation (FMD) in GCK gene mutations carriers and HNF1A-MODY. A total of 64 subjects with GCK gene mutations, and 52 HNF1A gene mutation carriers as well as 53 nondiabetic controls were examined. IMT and FMD were assessed by ultrasonography. Appropriate statistical tests were performed to assess differences between the groups, and multivariate linear regression was done for the association with IMT and FMD. The clinical characteristics of all groups were similar with the mean age at examination of 35.1, 41.1, and 39.5 years for GCK, HNF1A and the control group respectively. The highest mean IMT value was in the HNF1A-MODY group: 7.0±1.4 mm, whereas it reached 6.3±1.4 mm in GCK mutation carriers and 6.3±1.3 mm in controls (P=0.008). After adjustment for possible clinical and biochemical cofounders, IMT remained higher in HNF1A-MODY patients as compared with GCK-MODY patients (P=0.02) and controls (P=0.0003). FMD was significantly lower in HNF1A (9.9±4.6%) and GCK-MODY (11.1±4.6%) patients in comparison with controls (13.9±4.7%; P=0.0001). After adjustment, FMD remained lower in HNF1A-MODY (P=0.0005) and GCK-MODY patients (P=0.01) as compared with controls. Both examined MODY groups demonstrated evidence of endothelial dysfunction. In addition, HNF1-MODY patients seem to be more prone to an early atherosclerotic phenotype. © 2015 European Society of Endocrinology.

Regulation of hepatitis B virus ENI enhancer activity by hepatocyte-enriched transcription factor HNF3.

Science.gov (United States)

Chen, M; Hieng, S; Qian, X; Costa, R; Ou, J H

1994-11-15

Hepatitis B virus (HBV) ENI enhancer can activate the expression of HBV and non-HBV genes in a liver-specific manner. By performing the electrophoretic mobility-shift assays, we demonstrated that the three related, liver-enriched, transcription factors, HNF3 alpha, HNF3 beta, and HNF3 gamma could all bind to the 2c site of HBV ENI enhancer. Mutations introduced in the 2c site to abolish the binding by HNF3 reduced the enhancer activity approximately 15-fold. Moreover, expression of HNF3 antisense sequences to suppress the expression of HNF3 in Huh-7 hepatoma cells led to reduction of the ENI enhancer activity. These results indicate that HNF3 positively regulates the ENI enhancer activity and this regulation is most likely mediated through the 2c site. The requirement of HNF3 for the ENI enhancer activity could explain the liver specificity of this enhancer element.

HNF1B-associated clinical phenotypes: the kidney and beyond.

Science.gov (United States)

Bockenhauer, Detlef; Jaureguiberry, Graciana

2016-05-01

Mutations in HNF1B, the gene encoding hepatocyte nuclear factor 1β are the most commonly identified genetic cause of renal malformations. HNF1B was first identified as a disease gene for diabetes (MODY5) in 1997, and its involvement in renal disease was subsequently noted through clinical observations in pedigrees affected by MODY5. Since then, a whole spectrum of associated phenotypes have been reported, including genital malformations, autism, epilepsy, gout, hypomagnesaemia, primary hyperparathyroidism, liver and intestinal abnormalities and a rare form of kidney cancer. The most commonly identified mutation, in approximately 50 % of patients, is an entire gene deletion occurring in the context of a 17q12 chromosomal microdeletion that also includes several other genes. Some of the associated phenotypes, especially the neurologic ones, appear to occur only in the context of this microdeletion and thus may not be directly linked to HNF1B. Here we review the spectrum of associated phenotypes and discuss potential implications for clinical management.

Studies of the variability of the hepatocyte nuclear factor-1beta (HNF-1beta / TCF2) and the dimerization cofactor of HNF-1 (DcoH / PCBD) genes in relation to type 2 diabetes mellitus and beta-cell function

DEFF Research Database (Denmark)

Ek, J; Grarup, N; Urhammer, S A

2001-01-01

Mutations in the homeodomain-containing transcription factor hepatocyte nuclear factor-1beta (HNF-1beta) are known to cause a rare subtype of maturity-onset diabetes of the young (MODY5), which is associated with early-onset progressive non-diabetic renal dysfunction. To investigate whether...... mutations in HNF-1 are implicated in the pathogenesis of MODY or late-onset diabetes with and without nephropathy in Danish Caucasians we examined the HNF-1beta (TCF2) and the dimerization cofactor of HNF-1 (DCoH, PCBD) genes for mutations in 11 MODY probands, 28 type 2 diabetic patients with nephropathy...... comprising the DCoH gene revealed a previously described A-->G polymorphism located in the 3' untranslated region, which was not investigated further. In conclusion, mutations in HNF-1beta and DCoH are not a major cause of MODY or late onset type 2 diabetes in Danish Caucasian subjects....

Nitric oxide and TGF-β1 inhibit HNF-4α function in HEPG2 cells

International Nuclear Information System (INIS)

Lucas, Susana de; Lopez-Alcorocho, Juan Manuel; Bartolome, Javier; Carreno, Vicente

2004-01-01

This study analyzes if the profibrogenic factors nitric oxide and transforming growth factor-β1 (TGF-β1) affect hepatocyte nuclear factor-4α (HNF-4α) function. For this purpose, HepG2 cells were treated with TGF-β1 or with a nitric oxide donor to determine mRNA levels of coagulation factor VII and HNF-4α. Treatment effect on factor VII gene promoter was assessed by chloramphenicol acetyl-transferase assays in cells transfected with the pFVII-CAT plasmid. HNF-4α binding and protein levels were determined by gel shift assays and Western blot. TGF-β1 and nitric oxide downregulated factor VII mRNA levels by inhibiting its gene promoter activity. This inhibition is caused by a decrease in the DNA binding of HNF-4α. TGF-β1 induces degradation of HNF-4α in the proteasome while nitric oxide provokes nitrosylation of cysteine residues in this factor. TGF-β1 and nitric oxide inhibit HNF-4α activity. These findings may explain the loss of liver functions that occurs during fibrosis progression

Prevalence of Retinopathy in Adult Patients with GCK-MODY and HNF1A-MODY.

Science.gov (United States)

Szopa, M; Wolkow, J; Matejko, B; Skupien, J; Klupa, T; Wybrańska, I; Trznadel-Morawska, I; Kiec-Wilk, B; Borowiec, M; Malecki, M T

2015-10-01

We aimed to assess the prevalence of diabetic retinopathy (DR) in adult patients with GCK-MODY and HNF1A-MODY in Poland and to identify biochemical and clinical risk factors associated with its occurrence.We examined 74 GCK mutation carriers, 51 with diabetes and 23 with prediabetes, respectively, and 63 patients with HNF1A-MODY. Retinal photographs, 12 for each patient, were done by a fundus camera. Signs of DR were graded according to the DR disease severity scale. Statistical tests were performed to assess differences between the groups and logistic regression was done for the association with DR.The mean age at examination was 34.5±14.8 and 39.9±15.2 in the GCK-MODY and HNF1A-MODY groups, respectively. Mild nonproliferative DR (NPDR) was found in one patient with the GCK mutation and likely concomitant type 1 diabetes, whereas DR was diagnosed in 15 HNF1A-MODY patients: 9 with proliferative, 3 with moderate NPDR and 2 with mild NPDR. In univariate logistic regression analysis in the HNF1A-MODY group, significant results were found for diabetes duration, fasting glycemia, HbA1c, arterial hypertension, age at the examination, and eGFR. The strongest independent predictors of DR in HNF1A-MODY were markers of glucose control: HbA1c (OR: 2.05, CL%95: 1.2-3.83, p=0.01) and glucose (p=0.006, OR: 1.40, CL%95: 1.12-1.83) analyzed in 2 separated models. Additionally, arterial hypertension independently predicted DR (OR: 9.06, CL%95: 1.19-98.99, p=0.04) in the model with HbA1c as glycaemic control marker.In conclusion, DR of any degree was not present in our GCK-MODY group, while in spite of young age almost every fourth subject with HNF1A-MODY showed signs of this complication. © Georg Thieme Verlag KG Stuttgart · New York.

Analysis list: Hnf4a [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Hnf4a Digestive tract,Embryo,Gonad,Kidney,Liver,Prostate + mm9 http://dbarchive.bio...sciencedbc.jp/kyushu-u/mm9/target/Hnf4a.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hnf4a.5....tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Hnf4a.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Hnf4...a.Digestive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Hnf4...a.Embryo.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Hnf4a.Gonad.tsv,http://dbar

Identification of HNF4A Mutation p.T130I and HNF1A Mutations p.I27L and p.S487N in a Han Chinese Family with Early-Onset Maternally Inherited Type 2 Diabetes

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Ying Yang

2016-01-01

Full Text Available Maturity-onset diabetes of the young (MODY is characterized by the onset of diabetes before the age of 25 years, positive family history, high genetic predisposition, monogenic mutations, and an autosomal dominant mode of inheritance. Here, we aimed to investigate the mutations and to characterize the phenotypes of a Han Chinese family with early-onset maternally inherited type 2 diabetes. Detailed clinical assessments and genetic screening for mutations in the HNF4α, GCK, HNF-1α, IPF-1, HNF1β, and NEUROD1 genes were carried out in this family. One HNF4A mutation (p.T130I and two HNF1A polymorphisms (p.I27L and p.S487N were identified. Mutation p.T130I was associated with both early-onset and late-onset diabetes and caused downregulated HNF4A expression, whereas HNF1A polymorphisms p.I27L and p.S487N were associated with the age of diagnosis of diabetes. We demonstrated that mutation p.T130I in HNF4A was pathogenic as were the predicted polymorphisms p.I27L and p.S487N in HNF1A by genetic and functional analysis. Our results show that mutations in HNF4A and HNF1A genes might account for this early-onset inherited type 2 diabetes.

Successful maintenance on sulphonylurea therapy and low diabetes complication rates in a HNF1A-MODY cohort.

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Bacon, S; Kyithar, M P; Rizvi, S R; Donnelly, E; McCarthy, A; Burke, M; Colclough, K; Ellard, S; Byrne, M M

2016-07-01

HNF1A gene mutations are the most common cause of maturity-onset diabetes of the young (MODY) in the UK. Persons with HNF1A-MODY display sensitivity to sulphonylurea therapy; however, the long-term efficacy is not established. There is limited literature as to the prevalence of micro- and macrovascular complications in this unique cohort. The aim of this study was to determine the natural progression and clinical management of HNF1A-MODY diabetes in a dedicated MODY clinic. Sixty patients with HNF1A-MODY and a cohort of 60 BMI-, age-, ethnicity- and diabetes duration-matched patients with Type 1 diabetes mellitus participated in the study. All patients were phenotyped in detail. Clinical follow-up of the HNF1A-MODY cohort occurred on a bi-annual basis. Following a genetic diagnosis of MODY, the majority of the cohort treated with sulphonylurea therapy remained insulin independent at 84-month follow-up (80%). The HbA1c in the HNF1A-MODY group treated with sulphonylurea therapy alone improved significantly over the study period [from 49 (44-63) mmol/mol, 6.6 (6.2-7.9)% to 41 (31-50) mmol/mol, 5.9 (5-6.7)%; P = 0.003]. The rate of retinopathy was significantly lower than that noted in the Type 1 diabetes mellitus group (13.6 vs. 50%; P = 0.0001).There was also a lower rate of microalbuminuria and cardiovascular disease in the HNF1A-MODY group compared with the Type 1 diabetes mellitus group. This study demonstrates that the majority of patients with HNF1A-MODY can be maintained successfully on sulphonylurea therapy with good glycaemic control. We note a significantly lower rate of micro- and macrovascular complications than reported previously. The use of appropriate therapy at early stages of the disorder may decrease the incidence of complications. © 2015 Diabetes UK.

Laron Dwarfism and Non-Insulin-Dependent Diabetes Mellitus in the Hnf-1α Knockout Mouse

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Lee, Ying-Hue; Sauer, Brian; Gonzalez, Frank J.

1998-01-01

Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1α) were produced by use of the Cre-loxP recombination system. HNF-1α-null mice are viable but sterile and exhibit a phenotype reminiscent of both Laron-type dwarfism and non-insulin-dependent diabetes mellitus (NIDDM). In contrast to an earlier HNF-1α-null mouse line that had been produced by use of standard gene disruption methodology (M. Pontoglio, J. Barra, M. Hadchouel, A. Doyen, C. Kress, J. P. Bach, C. Babinet, and M. Yaniv, Cell 84:575–585, 1996), these mice exhibited no increased mortality and only minimal renal dysfunction during the first 6 months of development. Both dwarfism and NIDDM are most likely due to the loss of expression of insulin-like growth factor I (IGF-I) and lower levels of insulin, resulting in stunted growth and elevated serum glucose levels, respectively. These results confirm the functional significance of the HNF-1α regulatory elements that had previously been shown to reside in the promoter regions of both the IGF-I and the insulin genes. PMID:9566924

Circulating ghrelin level is higher in HNF1A-MODY and GCK-MODY than in polygenic forms of diabetes mellitus.

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Nowak, Natalia; Hohendorff, Jerzy; Solecka, Iwona; Szopa, Magdalena; Skupien, Jan; Kiec-Wilk, Beata; Mlynarski, Wojciech; Malecki, Maciej T

2015-12-01

Ghrelin is a hormone that regulates appetite. It is likely to be involved in the pathophysiology of varying forms of diabetes. In animal studies, the ghrelin expression was regulated by the hepatocyte nuclear factor 1 alpha (HNF1A). Mutations of the HNF1A gene cause maturity onset diabetes of the young (MODY). We aimed to assess the circulating ghrelin levels in HNF1A-MODY and in other types of diabetes and to evaluate its association with HNF1A mutation status. Our cohort included 46 diabetic HNF1A gene mutation carriers, 55 type 2 diabetes (T2DM) subjects, 42 type 1 diabetes (T1DM) patients, and 31 glucokinase (GCK) gene mutation carriers with diabetes as well as 51 healthy controls. Plasma ghrelin concentration was measured using the immunoenzymatic assay with polyclonal antibody against the C-terminal fragment of its acylated and desacylated forms. Ghrelin concentrations were 0.75 ± 0.32, 0.70 ± 0.21, 0.50 ± 0.20, and 0.40 ± 0.16 ng/ml in patients with HNF1A-MODY, GCK-MODY, T1DM, and T2DM, respectively. The ghrelin levels were higher in HNF1A-MODY and GCK-MODY than in T1DM and T2DM (p MODY groups and common diabetes types remained significant. Analysis by a HNF1A mutation type indicated that ghrelin concentration is similar in patients with different types of sequence differences. Plasma ghrelin level is higher in HNF1A-MODY and GCK-MODY than in the common polygenic forms of diabetes.

Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha.

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Dietrich, Christoph G; Martin, Ina V; Porn, Anne C; Voigt, Sebastian; Gartung, Carsten; Trautwein, Christian; Geier, Andreas

2007-09-01

Fasting induces numerous adaptive changes in metabolism by several central signaling pathways, the most important represented by the HNF4alpha/PGC-1alpha-pathway. Because HNF4alpha has been identified as central regulator of basolateral bile acid transporters and a previous study reports increased basolateral bile acid uptake into the liver during fasting, we hypothesized that HNF4alpha is involved in fasting-induced bile acid uptake via upregulation of basolateral bile acid transporters. In rats, mRNA of Ntcp, Oatp1, and Oatp2 were significantly increased after 48 h of fasting. Protein expression as determined by Western blot showed significant increases for all three transporters 72 h after the onset of fasting. Whereas binding activity of HNF1alpha in electrophoretic mobility shift assays remained unchanged, HNF4alpha binding activity to the Ntcp promoter was increased significantly. In line with this result, we found significantly increased mRNA expression of HNF4alpha and PGC-1alpha. Functional studies in HepG2 cells revealed an increased endogenous NTCP mRNA expression upon cotransfection with either HNF4alpha, PGC-1alpha, or a combination of both. We conclude that upregulation of the basolateral bile acid transporters Ntcp, Oatp1, and Oatp2 in fasted rats is mediated via the HNF4alpha/PGC-1alpha pathway.

Clinical application of ACMG-AMP guidelines in HNF1A and GCK variants in a cohort of MODY families.

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Santana, L S; Caetano, L A; Costa-Riquetto, A D; Quedas, E P S; Nery, M; Collett-Solberg, P; Boguszewski, M C S; Vendramini, M F; Crisostomo, L G; Floh, F O; Zarabia, Z I; Kohara, S K; Guastapaglia, L; Passone, C G B; Sewaybricker, L E; Jorge, A A L; Teles, M G

2017-10-01

Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. GCK -MODY and HNF1A -MODY are the prevalent subtypes. Currently, there is growing concern regarding the correct interpretation of molecular genetic findings. The American College of Medical Genetics and Genomics (ACMG) updated guidelines to interpret and classify molecular variants. This study aimed to determine the prevalence of MODY ( GCK / HNF1A ) in a large cohort of Brazilian families, to report variants related to phenotype, and to classify them according to ACMG guidelines. One hundred and nine probands were investigated, 45% with clinical suspicion of GCK -MODY and 55% with suspicion of HNF1A -MODY. Twenty-five different variants were identified in GCK gene (30 probands-61% of positivity), and 7 variants in HNF1A (10 probands-17% of positivity). Fourteen of them were novel (12- GCK /2- HNF1A ). ACMG guidelines were able to classify a large portion of variants as pathogenic (36%- GCK /86%- HNF1A ) and likely pathogenic (44%- GCK /14%- HNF1A ), with 16% (5/32) as uncertain significance. This allows us to determine the pathogenicity classification more efficiently, and also reinforces the suspected associations with the phenotype among novel variants. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Targeted deficiency of the transcriptional activator Hnf1alpha alters subnuclear positioning of its genomic targets.

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Reini F Luco

2008-05-01

Full Text Available DNA binding transcriptional activators play a central role in gene-selective regulation. In part, this is mediated by targeting local covalent modifications of histone tails. Transcriptional regulation has also been associated with the positioning of genes within the nucleus. We have now examined the role of a transcriptional activator in regulating the positioning of target genes. This was carried out with primary beta-cells and hepatocytes freshly isolated from mice lacking Hnf1alpha, an activator encoded by the most frequently mutated gene in human monogenic diabetes (MODY3. We show that in Hnf1a-/- cells inactive endogenous Hnf1alpha-target genes exhibit increased trimethylated histone H3-Lys27 and reduced methylated H3-Lys4. Inactive Hnf1alpha-targets in Hnf1a-/- cells are also preferentially located in peripheral subnuclear domains enriched in trimethylated H3-Lys27, whereas active targets in wild-type cells are positioned in more central domains enriched in methylated H3-Lys4 and RNA polymerase II. We demonstrate that this differential positioning involves the decondensation of target chromatin, and show that it is spatially restricted rather than a reflection of non-specific changes in the nuclear organization of Hnf1a-deficient cells. This study, therefore, provides genetic evidence that a single transcriptional activator can influence the subnuclear location of its endogenous genomic targets in primary cells, and links activator-dependent changes in local chromatin structure to the spatial organization of the genome. We have also revealed a defect in subnuclear gene positioning in a model of a human transcription factor disease.

An Atypical HNF4A Mutation Which Does Not Conform to the Classic Presentation of HNF4A-MODY

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Andrew J. Spiro

2018-01-01

Full Text Available Objective. To present the case of an atypical Hepatocyte Nuclear Factor 4 Alpha (HNF4A mutation that is not consistent with the classically published presentation of HNF4A-Mature Onset Diabetes of the Young (MODY. Methods. Clinical presentation and literature review. Results. A 43-year-old nonobese man was referred to the endocrinology clinic for evaluation of elevated fasting blood glucose (FBG measurements. Laboratory review revealed prediabetes and hypertriglyceridemia for the previous decade. Testing of autoantibodies for type 1 diabetes was negative. Genetic testing showed an autosomal dominant, heterozygous missense mutation (c.991C>T; p.Arg331Cys in the HNF4A gene, which is correlated with HNF4A-MODY. Phenotypically, patients with an HNF4A-MODY tend to have early-onset diabetes, microvascular complications, low triglyceride levels, increased birth weight, fetal macrosomia, and less commonly neonatal hyperinsulinemic hypoglycemia. The patient did not demonstrate any of these features but instead presented with late-onset diabetes, an elevated triglyceride level, and a normal birth weight. Conclusion. Our patient likely represents an atypical variant of HNF4A-MODY with a milder clinical presentation. Patients with atypical, less-severe presentations of HNF4A-MODY may be largely undiagnosed or misdiagnosed, but identification is important due to implications for treatment, pregnancy, and screening of family members.

Kinetic Stability May Determine the Interaction Dynamics of the Bifunctional Protein DCoH1, the Dimerization Cofactor of the Transcription Factor HNF-1[alpha

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Rho, H.; Jones, C.N.; Rose, R.B. (NCSU)

2010-12-07

The two disparate functions of DCoH1 (dimerization cofactor of HNF-1)/PCD (pterin-4a-carbinolamine dehydratase) are associated with a change in oligomeric state. DCoH dimers enhance the activity of the diabetes-associated transcription factor HNF-1{alpha} (hepatocyte nuclear factor-1{alpha}), while the PCD activity of DCoH1 homotetramers aids in aromatic amino acid metabolism. These complexes compete for the same interface of the DCoH dimer. Formation of the DCoH1/HNF-1{alpha} complex requires cofolding. The homotetramer of the DCoH1 paralogue, DCoH2, interacts with HNF-1{alpha} through simple mixing. To further investigate regulation of DCoH/HNF-1{alpha} complex formation, we measured the stability of the DCoH1 homotetramer through unfolding studies by intrinsic tryptophan fluorescence. DCoH2 unfolding is reversible. Surprisingly, the DCoH1 homotetramer is resistant to guanidine unfolding but refolds at a much lower guanidine concentration. We show that a point mutation at the DCoH1 tetramer interface, Thr 51 Ser, overcomes the dissociation barrier of the homotetramer and increases the interaction with HNF-1{alpha}. The 1.8 {angstrom} resolution crystal structure of DCoH1 T51S shows the presence of an ordered water molecule at the tetramer interface, as in DCoH2, which may destabilize the homotetramer. The equilibrium unfolding data were fit to a two-state model with no apparent intermediate. Folding intermediates were detectable by size exclusion chromatography. For wild-type DCoH1 the intermediates changed with time, suggesting a kinetic origin for the unfolding barrier of the homotetramer. We propose an unfolding pathway in which the tetramer unfolds slowly, but the dimer folds reversibly. Implications for regulation of DCoH1/HNF-1{alpha} complex formation are discussed.

Functional Investigations of HNF1A Identify Rare Variants as Risk Factors for Type 2 Diabetes in the General Population

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Najmi, Laeya Abdoli; Aukrust, Ingvild; Flannick, Jason; Molnes, Janne; Burtt, Noel; Molven, Anders; Groop, Leif; Altshuler, David; Johansson, Stefan; Njølstad, Pål Rasmus

2017-01-01

Variants in HNF1A encoding hepatocyte nuclear factor 1α (HNF-1A) are associated with maturity-onset diabetes of the young form 3 (MODY 3) and type 2 diabetes. We investigated whether functional classification of HNF1A rare coding variants can inform models of diabetes risk prediction in the general population by analyzing the effect of 27 HNF1A variants identified in well-phenotyped populations (n = 4,115). Bioinformatics tools classified 11 variants as likely pathogenic and showed no association with diabetes risk (combined minor allele frequency [MAF] 0.22%; odds ratio [OR] 2.02; 95% CI 0.73–5.60; P = 0.18). However, a different set of 11 variants that reduced HNF-1A transcriptional activity to diabetes in the general population (combined MAF 0.22%; OR 5.04; 95% CI 1.99–12.80; P = 0.0007). Our functional investigations indicate that 0.44% of the population carry HNF1A variants that result in a substantially increased risk for developing diabetes. These results suggest that functional characterization of variants within MODY genes may overcome the limitations of bioinformatics tools for the purposes of presymptomatic diabetes risk prediction in the general population. PMID:27899486

Maturity Onset Diabetes of the Young (MODY) in Tunisia: Low frequencies of GCK and HNF1A mutations.

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Ben Khelifa, S; Martinez, R; Dandana, A; Khochtali, I; Ferchichi, S; Castaño, L

2018-04-20

Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes characterized by autosomal dominant inheritance, an early clinical onset and a primary defect in β-cell function. Mutations in the GCK and HNF1A genes are the most common cause of MODY among Caucasians. The etiology of MODY in Tunisia stills a challenge for researchers. The aim of this study was to screen for mutations in GCK, HNF1A, HNF4A and INS genes in North African Tunisians subjects, in whom the clinical profile was very suggestive of MODY. A total of 23 unrelated patients, with clinical presentation of MODY were tested for mutations in GCK, HNF1A, HNF4A and INS genes, using Denaturing High Performance Liquid Chromatography (DHPLC), Multiplex Ligation-depend Probe Amplification (MLPA) and sequencing analysis. We identified the previously reported mutation c-169C > T in one patient as well as a new mutation c-457C > T in two unrelated patients. No mutations were detected in the HNF1A and INS genes. Despite restrictive clinical criteria used for selecting patients in this study, the most common genes known for MODY do not explain the majority of cases in Tunisians. This suggests that there are others candidate or unidentified genes contributing to the etiology of MODY in Tunisians families. Copyright © 2018 Elsevier B.V. All rights reserved.

Mapping of HNF4alpha target genes in intestinal epithelial cells

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Boyd, Mette; Bressendorff, Simon; Moller, Jette

2009-01-01

ABSTRACT: BACKGROUND: The role of HNF4alpha has been extensively studied in hepatocytes and pancreatic beta-cells, and HNF4alpha is also regarded as key regulator of intestinal epithelial cell differentiation as well. The aim of the present work is to identify novel HNF4alpha target genes....... The HNF4alpha ChIP-chip data was matched with gene expression and histone H3 acetylation status of the promoters in order to identify HNF4alpha binding to actively transcribed genes with an open chromatin structure. RESULTS: 1,541 genes were identified as potential HNF4alpha targets, many of which have...

Chemical processes in the HNF flame

NARCIS (Netherlands)

Ermolin, N.E.; Zarko, V.E.; Keizers, H.L.J.

2006-01-01

Results of modeling the HNF flame structure are presented. From an analysis of literature data on the thermal decomposition and combustion of HNF, it is concluded that the dissociative vaporization of HNF proceeds via the route HNFliq → (N2H4)g + (HC(NO 2)3)g. The flame structure is modeled using a

Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer

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Shen, Hui; Fridley, Brooke L; Song, Honglin

2013-01-01

HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we...... comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs......11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous...

Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene.

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Ewan R Pearson

2007-04-01

Full Text Available Macrosomia is associated with considerable neonatal and maternal morbidity. Factors that predict macrosomia are poorly understood. The increased rate of macrosomia in the offspring of pregnant women with diabetes and in congenital hyperinsulinaemia is mediated by increased foetal insulin secretion. We assessed the in utero and neonatal role of two key regulators of pancreatic insulin secretion by studying birthweight and the incidence of neonatal hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY genes HNF4A (encoding HNF-4alpha and HNF1A/TCF1 (encoding HNF-1alpha, and the effect of pancreatic deletion of Hnf4a on foetal and neonatal insulin secretion in mice.We examined birthweight and hypoglycaemia in 108 patients from families with diabetes due to HNF4A mutations, and 134 patients from families with HNF1A mutations. Birthweight was increased by a median of 790 g in HNF4A-mutation carriers compared to non-mutation family members (p < 0.001; 56% (30/54 of HNF4A-mutation carriers were macrosomic compared with 13% (7/54 of non-mutation family members (p < 0.001. Transient hypoglycaemia was reported in 8/54 infants with heterozygous HNF4A mutations, but was reported in none of 54 non-mutation carriers (p = 0.003. There was documented hyperinsulinaemia in three cases. Birthweight and prevalence of neonatal hypoglycaemia were not increased in HNF1A-mutation carriers. Mice with pancreatic beta-cell deletion of Hnf4a had hyperinsulinaemia in utero and hyperinsulinaemic hypoglycaemia at birth.HNF4A mutations are associated with a considerable increase in birthweight and macrosomia, and are a novel cause of neonatal hypoglycaemia. This study establishes a key role for HNF4A in determining foetal birthweight, and uncovers an unanticipated feature of the natural history of HNF4A-deficient diabetes, with hyperinsulinaemia at birth evolving to decreased insulin secretion and diabetes later in life.

Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer

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Shen, Hui; Fridley, Brooke L.; Song, Honglin; Lawrenson, Kate; Cunningham, Julie M.; Ramus, Susan J.; Cicek, Mine S.; Tyrer, Jonathan; Stram, Douglas; Larson, Melissa C.; Köbel, Martin; Ziogas, Argyrios; Zheng, Wei; Yang, Hannah P.; Wu, Anna H.

2013-01-01

HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide poly...

Determining the role of missense mutations in the POU domain of HNF1A that reduce the DNA-binding affinity: A computational approach.

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Sneha P

Full Text Available Maturity-onset diabetes of the young type 3 (MODY3 is a non-ketotic form of diabetes associated with poor insulin secretion. Over the past years, several studies have reported the association of missense mutations in the Hepatocyte Nuclear Factor 1 Alpha (HNF1A with MODY3. Missense mutations in the POU homeodomain (POUH of HNF1A hinder binding to the DNA, thereby leading to a dysfunctional protein. Missense mutations of the HNF1A were retrieved from public databases and subjected to a three-step computational mutational analysis to identify the underlying mechanism. First, the pathogenicity and stability of the mutations were analyzed to determine whether they alter protein structure and function. Second, the sequence conservation and DNA-binding sites of the mutant positions were assessed; as HNF1A protein is a transcription factor. Finally, the biochemical properties of the biological system were validated using molecular dynamic simulations in Gromacs 4.6.3 package. Two arginine residues (131 and 203 in the HNF1A protein are highly conserved residues and contribute to the function of the protein. Furthermore, the R131W, R131Q, and R203C mutations were predicted to be highly deleterious by in silico tools and showed lower binding affinity with DNA when compared to the native protein using the molecular docking analysis. Triplicate runs of molecular dynamic (MD simulations (50ns revealed smaller changes in patterns of deviation, fluctuation, and compactness, in complexes containing the R131Q and R131W mutations, compared to complexes containing the R203C mutant complex. We observed reduction in the number of intermolecular hydrogen bonds, compactness, and electrostatic potential, as well as the loss of salt bridges, in the R203C mutant complex. Substitution of arginine with cysteine at position 203 decreases the affinity of the protein for DNA, thereby destabilizing the protein. Based on our current findings, the MD approach is an important

Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer

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Harries, Lorna W; Perry, John RB; McCullagh, Paul; Crundwell, Malcolm

2010-01-01

Genome wide association studies (GWAS) have identified several genetic variants that are associated with prostate cancer. Most of these variants, like other GWAS association signals, are located in non-coding regions of potential candidate genes, and thus could act at the level of the mRNA transcript. We measured the expression and isoform usage of seven prostate cancer candidate genes in benign and malignant prostate by real-time PCR, and correlated these factors with cancer status and genotype at the GWAS risk variants. We determined that levels of LMTK2 transcripts in prostate adenocarcinomas were only 32% of those in benign tissues (p = 3.2 × 10 -7 ), and that an independent effect of genotype at variant rs6465657 on LMTK2 expression in benign (n = 39) and malignant tissues (n = 21) was also evident (P = 0.002). We also identified that whilst HNF1B(C) and MSMB2 comprised the predominant isoforms in benign tissues (90% and 98% of total HNF1B or MSMB expression), HNF1B(B) and MSMB1 were predominant in malignant tissue (95% and 96% of total HNF1B or MSMB expression; P = 1.7 × 10 -7 and 4 × 10 -4 respectively), indicating major shifts in isoform usage. Our results indicate that the amount or nature of mRNA transcripts expressed from the LMTK2, HNF1B and MSMB candidate genes is altered in prostate cancer, and provides further evidence for a role for these genes in this disorder. The alterations in isoform usage we detect highlights the potential importance of alternative mRNA processing and moderation of mRNA stability as potentially important disease mechanisms

High-sensitivity C-reactive protein does not improve the differential diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes: A grey zone analysis.

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Bellanné-Chantelot, C; Coste, J; Ciangura, C; Fonfrède, M; Saint-Martin, C; Bouché, C; Sonnet, E; Valéro, R; Lévy, D-J; Dubois-Laforgue, D; Timsit, J

2016-02-01

Low plasma levels of high-sensitivity C-reactive protein (hs-CRP) have been suggested to differentiate hepatocyte nuclear factor 1 alpha-maturity-onset diabetes of the young (HNF1A-MODY) from type 2 diabetes (T2D). Yet, differential diagnosis of HNF1A-MODY and familial young-onset type 2 diabetes (F-YT2D) remains a difficult challenge. Thus, this study assessed the added value of hs-CRP to distinguish between the two conditions. This prospective multicentre study included 143 HNF1A-MODY patients, 310 patients with a clinical history suggestive of HNF1A-MODY, but not confirmed genetically (F-YT2D), and 215 patients with T2D. The ability of models, including clinical characteristics and hs-CRP to predict HNF1A-MODY was analyzed, using the area of the receiver operating characteristic (AUROC) curve, and a grey zone approach was used to evaluate these models in clinical practice. Median hs-CRP values were lower in HNF1A-MODY (0.25mg/L) than in F-YT2D (1.14mg/L) and T2D (1.70mg/L) patients. Clinical parameters were sufficient to differentiate HNF1A-MODY from classical T2D (AUROC: 0.99). AUROC analyses to distinguish HNF1A-MODY from F-YT2D were 0.82 for clinical features and 0.87 after including hs-CRP. For the grey zone analysis, the lower boundary was set to missMODY with F-YT2D, 65% of patients were classified in between these categories - in the zone of diagnostic uncertainty - even after adding hs-CRP to clinical parameters. hs-CRP does not improve the differential diagnosis of HNF1A-MODY and F-YT2D. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Alterations in LMTK2, MSMB and HNF1B gene expression are associated with the development of prostate cancer

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McCullagh Paul

2010-06-01

Full Text Available Abstract Background Genome wide association studies (GWAS have identified several genetic variants that are associated with prostate cancer. Most of these variants, like other GWAS association signals, are located in non-coding regions of potential candidate genes, and thus could act at the level of the mRNA transcript. Methods We measured the expression and isoform usage of seven prostate cancer candidate genes in benign and malignant prostate by real-time PCR, and correlated these factors with cancer status and genotype at the GWAS risk variants. Results We determined that levels of LMTK2 transcripts in prostate adenocarcinomas were only 32% of those in benign tissues (p = 3.2 × 10-7, and that an independent effect of genotype at variant rs6465657 on LMTK2 expression in benign (n = 39 and malignant tissues (n = 21 was also evident (P = 0.002. We also identified that whilst HNF1B(C and MSMB2 comprised the predominant isoforms in benign tissues (90% and 98% of total HNF1B or MSMB expression, HNF1B(B and MSMB1 were predominant in malignant tissue (95% and 96% of total HNF1B or MSMB expression; P = 1.7 × 10-7 and 4 × 10-4 respectively, indicating major shifts in isoform usage. Conclusions Our results indicate that the amount or nature of mRNA transcripts expressed from the LMTK2, HNF1B and MSMB candidate genes is altered in prostate cancer, and provides further evidence for a role for these genes in this disorder. The alterations in isoform usage we detect highlights the potential importance of alternative mRNA processing and moderation of mRNA stability as potentially important disease mechanisms.

Genomics meets glycomics-the first GWAS study of human N-Glycome identifies HNF1α as a master regulator of plasma protein fucosylation.

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Gordan Lauc

2010-12-01

Full Text Available Over half of all proteins are glycosylated, and alterations in glycosylation have been observed in numerous physiological and pathological processes. Attached glycans significantly affect protein function; but, contrary to polypeptides, they are not directly encoded by genes, and the complex processes that regulate their assembly are poorly understood. A novel approach combining genome-wide association and high-throughput glycomics analysis of 2,705 individuals in three population cohorts showed that common variants in the Hepatocyte Nuclear Factor 1α (HNF1α and fucosyltransferase genes FUT6 and FUT8 influence N-glycan levels in human plasma. We show that HNF1α and its downstream target HNF4α regulate the expression of key fucosyltransferase and fucose biosynthesis genes. Moreover, we show that HNF1α is both necessary and sufficient to drive the expression of these genes in hepatic cells. These results reveal a new role for HNF1α as a master transcriptional regulator of multiple stages in the fucosylation process. This mechanism has implications for the regulation of immunity, embryonic development, and protein folding, as well as for our understanding of the molecular mechanisms underlying cancer, coronary heart disease, and metabolic and inflammatory disorders.

Could FISH on buccal smears become a new method of screening in children suspect of HNF1B anomaly?

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Laffargue, Fanny; Bourthoumieu, Sylvie; Bellanné-Chantelot, Christine; Guigonis, Vincent; Yardin, Catherine

2013-02-01

HNF1B gene anomalies include renal development defects associated with cysts and are well known by pediatric nephrologists that ask for molecular analysis of this gene. Two types of genomic rearrangements are reported: mutation and more frequently deletion. Using microsatellites or CGH array the size of the deletion was found to be at least of 1.2 Mb including 15 genes among which HNF1B, leading to the diagnosis of chromosomal microdeletion. Fluorescent In Situ Hybridization (FISH) is a simple routinely performed technique, considered as the referring tool to diagnose microdeletion in genetic practice. We performed interphasic FISH on buccal smears from 6 patients known to have HNF1B deletion to valid our technique and to determine the size of the 17q12 deletion. All the patients were found to present a 17q12 microdeletion. Our results showed that FISH is a rapid, reliable and specific technique to diagnose 17q12 microdeletion and might be performed as non invasive sampling procedure useful in pediatric practice. In conclusion we propose to use interphasic FISH to screen pediatric patients presenting with renal abnormalities possibly linked to HNF1B anomaly. Molecular analysis and MLPA (Multiplex Ligand Probe Analysis) could be performed in cases with normal interphasic FISH to detect a point mutation of the gene or more rarely a single exon deletion. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

miR-34a Inhibits Proliferation and Invasion of Bladder Cancer Cells by Targeting Orphan Nuclear Receptor HNF4G

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Huaibin Sun

2015-01-01

Full Text Available miR-34a is a member of the miR-34 family and acts as a tumor suppressor in bladder cancer. This study explored the regulative role of miR-34a on an orphan nuclear receptor HNF4G, which has a well-confirmed role in bladder tumor growth and invasion. qRT-PCR analysis was applied to measure miR-34a expression in two tumorigenic bladder cancer cell lines 5637 and T24 and one normal human urothelial cell line SV-HUC-1. Luciferase assay was performed to verify the putative binding between miR-34a and HNF4G. The influence of miR-34a-HNF4G axis on cell viability, colony formation, and invasion was assessed with loss- and gain-of-function analysis. This study observed that the miR-34a expressions in 5637 and T24 cells were significantly lower than in SV-HUC-1, while the muscle invasive cell sublines 5637-M and T24-M had even lower miR-34a expression than in the nonmuscle invasive sublines. HNF4G has a 3′-UTR binding site with miR-34a and is a direct downstream target of miR-34a. miR-34a can directly downregulate the expression of HNF4G and thus inhibit tumor cell viability, colony formation, and invasion. Therefore, miR-34a-HNF4G axis is an important pathway modulating cell viability, proliferation, and invasion of bladder cancer cells.

The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4α

International Nuclear Information System (INIS)

Klapper, Maja; Boehme, Mike; Nitz, Inke; Doering, Frank

2007-01-01

The cytosolic human intestinal fatty acid binding protein (hFABP2) is proposed to be involved in intestinal absorption of long-chain fatty acids. The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4α (HNF-4α), involved in regulation of genes of fatty acid metabolism and differentiation. Electromobility shift assays demonstrated that HNF-4α binds at position -324 to -336 within the hFABP2 promoter. Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4α by about 50%. Thus, binding element at position -336/-324 essentially determines the transcriptional activity of promoter and may be important in control of hFABP2 expression by dietary lipids and differentiation. Studying genotype interactions of hFABP2 and HNF-4α, that are both candidate genes for diabetes type 2, may be a powerful approach

The human intestinal fatty acid binding protein (hFABP2) gene is regulated by HNF-4{alpha}

Energy Technology Data Exchange (ETDEWEB)

Klapper, Maja [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Boehme, Mike [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Nitz, Inke [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany); Doering, Frank [Molecular Nutrition, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, Heinrich-Hecht-Platz 10, D-24118 Kiel (Germany)

2007-04-27

The cytosolic human intestinal fatty acid binding protein (hFABP2) is proposed to be involved in intestinal absorption of long-chain fatty acids. The aim of this study was to investigate the regulation of hFABP2 by the endodermal hepatocyte nuclear factor 4{alpha} (HNF-4{alpha}), involved in regulation of genes of fatty acid metabolism and differentiation. Electromobility shift assays demonstrated that HNF-4{alpha} binds at position -324 to -336 within the hFABP2 promoter. Mutation of this HNF-4 binding site abolished the luciferase reporter activity of hFABP2 in postconfluent Caco-2 cells. In HeLa cells, this mutation reduced the activation of the hFABP2 promoter by HNF-4{alpha} by about 50%. Thus, binding element at position -336/-324 essentially determines the transcriptional activity of promoter and may be important in control of hFABP2 expression by dietary lipids and differentiation. Studying genotype interactions of hFABP2 and HNF-4{alpha}, that are both candidate genes for diabetes type 2, may be a powerful approach.

HNF4alpha dysfunction as a molecular rational for cyclosporine induced hypertension.

Science.gov (United States)

Niehof, Monika; Borlak, Jürgen

2011-01-27

Induction of tolerance against grafted organs is achieved by the immunosuppressive agent cyclosporine, a prominent member of the calcineurin inhibitors. Unfortunately, its lifetime use is associated with hypertension and nephrotoxicity. Several mechanism for cyclosporine induced hypertension have been proposed, i.e. activation of the sympathetic nervous system, endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in prostaglandin and nitric oxide, altered cytosolic calcium translocation, and activation of the renin-angiotensin system (RAS). In this regard the molecular basis for undue RAS activation and an increased signaling of the vasoactive oligopeptide angiotensin II (AngII) remain elusive. Notably, angiotensinogen (AGT) is the precursor of AngII and transcriptional regulation of AGT is controlled by the hepatic nuclear factor HNF4alpha. To better understand the molecular events associated with cyclosporine induced hypertension, we investigated the effect of cyclosporine on HNF4alpha expression and activity and searched for novel HNF4alpha target genes among members of the RAS cascade. Using bioinformatic algorithm and EMSA bandshift assays we identified angiotensin II receptor type 1 (AGTR1), angiotensin I converting enzyme (ACE), and angiotensin I converting enzyme 2 (ACE2) as genes targeted by HNF4alpha. Notably, cyclosporine represses HNF4alpha gene and protein expression and its DNA-binding activity at consensus sequences to AGT, AGTR1, ACE, and ACE2. Consequently, the gene expression of AGT, AGTR1, and ACE2 was significantly reduced as evidenced by quantitative real-time RT-PCR. While RAS is composed of a sophisticated interplay between multiple factors we propose a decrease of ACE2 to enforce AngII signaling via AGTR1 to ultimately result in vasoconstriction and hypertension. Taken collectively we demonstrate cyclosporine to repress HNF4alpha activity through calcineurin inhibitor mediated inhibition of nuclear

HNF4alpha dysfunction as a molecular rational for cyclosporine induced hypertension.

Directory of Open Access Journals (Sweden)

Monika Niehof

Full Text Available Induction of tolerance against grafted organs is achieved by the immunosuppressive agent cyclosporine, a prominent member of the calcineurin inhibitors. Unfortunately, its lifetime use is associated with hypertension and nephrotoxicity. Several mechanism for cyclosporine induced hypertension have been proposed, i.e. activation of the sympathetic nervous system, endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in prostaglandin and nitric oxide, altered cytosolic calcium translocation, and activation of the renin-angiotensin system (RAS. In this regard the molecular basis for undue RAS activation and an increased signaling of the vasoactive oligopeptide angiotensin II (AngII remain elusive. Notably, angiotensinogen (AGT is the precursor of AngII and transcriptional regulation of AGT is controlled by the hepatic nuclear factor HNF4alpha. To better understand the molecular events associated with cyclosporine induced hypertension, we investigated the effect of cyclosporine on HNF4alpha expression and activity and searched for novel HNF4alpha target genes among members of the RAS cascade. Using bioinformatic algorithm and EMSA bandshift assays we identified angiotensin II receptor type 1 (AGTR1, angiotensin I converting enzyme (ACE, and angiotensin I converting enzyme 2 (ACE2 as genes targeted by HNF4alpha. Notably, cyclosporine represses HNF4alpha gene and protein expression and its DNA-binding activity at consensus sequences to AGT, AGTR1, ACE, and ACE2. Consequently, the gene expression of AGT, AGTR1, and ACE2 was significantly reduced as evidenced by quantitative real-time RT-PCR. While RAS is composed of a sophisticated interplay between multiple factors we propose a decrease of ACE2 to enforce AngII signaling via AGTR1 to ultimately result in vasoconstriction and hypertension. Taken collectively we demonstrate cyclosporine to repress HNF4alpha activity through calcineurin inhibitor mediated inhibition

Current state of the art of HNF based composite propellants

NARCIS (Netherlands)

Ciucci, A.; Frota, O.; Welland, W.H.M.; Heijden, A.E.D.M. van der; Leeming, B.; Bellerby, J.M.; Brotzu, A.

2004-01-01

The main activities currently performed for the development of HNF-based propellants are presented. The objectives and approach adopted are described. The results obtained on the HNF decomposition mechanism and on the re- and co-crystallisation of HNF with potential propellant ingredients are

Novel P2 promoter-derived HNF4α isoforms with different N-terminus generated by alternate exon insertion

International Nuclear Information System (INIS)

Huang, Jianmin; Levitsky, Lynne L.; Rhoads, David B.

2009-01-01

Hepatocyte nuclear factor 4α (HNF4α) is a critical transcription factor for pancreas and liver development and functions in islet β cells to maintain glucose homeostasis. Mutations in the human HNF4A gene lead to maturity onset diabetes of the young (MODY1) and polymorphisms are associated with increased risk for type 2 diabetes mellitus (T2DM). Expression of six HNF4α variants, three each from two developmentally regulated promoters, has been firmly established. We have now detected a new set of HNF4α variants designated HNF4α10-12 expressed from distal promoter P2. These variants, generated by inclusion of previously undetected exon 1E (human = 222 nt, rodent = 136 nt) following exon 1D have an altered N-terminus but identical remaining reading frame. HNF4α10-α12 are expressed in pancreatic islets (and liver) and exhibit transactivation potentials similar to the corresponding α7-α9 isoforms. DNA-binding analyses implied much higher protein levels of HNF4α10-α12 in liver than expected from the RT-PCR data. Our results provide evidence for a more complex expression pattern of HNF4α than previously appreciated. We recommend inclusion of exon 1E and nearby DNA sequences in screening for HNF4α mutations and polymorphisms in genetic analyses of MODY1 and T2DM.

Novel P2 promoter-derived HNF4{alpha} isoforms with different N-terminus generated by alternate exon insertion

Energy Technology Data Exchange (ETDEWEB)

Huang, Jianmin, E-mail: jmhuang@partners.org [Pediatric Endocrine Unit, MassGeneral Hospital for Children and Harvard Medical School, Boston, Massachusetts, 02114-2696 (United States); Levitsky, Lynne L. [Pediatric Endocrine Unit, MassGeneral Hospital for Children and Harvard Medical School, Boston, Massachusetts, 02114-2696 (United States); Rhoads, David B., E-mail: rhoads@helix.mgh.harvard.edu [Pediatric Endocrine Unit, MassGeneral Hospital for Children and Harvard Medical School, Boston, Massachusetts, 02114-2696 (United States)

2009-04-15

Hepatocyte nuclear factor 4{alpha} (HNF4{alpha}) is a critical transcription factor for pancreas and liver development and functions in islet {beta} cells to maintain glucose homeostasis. Mutations in the human HNF4A gene lead to maturity onset diabetes of the young (MODY1) and polymorphisms are associated with increased risk for type 2 diabetes mellitus (T2DM). Expression of six HNF4{alpha} variants, three each from two developmentally regulated promoters, has been firmly established. We have now detected a new set of HNF4{alpha} variants designated HNF4{alpha}10-12 expressed from distal promoter P2. These variants, generated by inclusion of previously undetected exon 1E (human = 222 nt, rodent = 136 nt) following exon 1D have an altered N-terminus but identical remaining reading frame. HNF4{alpha}10-{alpha}12 are expressed in pancreatic islets (and liver) and exhibit transactivation potentials similar to the corresponding {alpha}7-{alpha}9 isoforms. DNA-binding analyses implied much higher protein levels of HNF4{alpha}10-{alpha}12 in liver than expected from the RT-PCR data. Our results provide evidence for a more complex expression pattern of HNF4{alpha} than previously appreciated. We recommend inclusion of exon 1E and nearby DNA sequences in screening for HNF4{alpha} mutations and polymorphisms in genetic analyses of MODY1 and T2DM.

Assessment of Newly Proposed Clinical Criteria to Identify HNF1A MODY in Patients with an Initial Diagnosis of Type 1 or Type 2 Diabetes Mellitus

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Malgorzata Grzanka

2016-01-01

Full Text Available The most common form of maturity-onset diabetes of the young (MODY is caused by mutations in the hepatocyte nuclear factor 1A (HNF1A gene. However, most HNF1A mutation-carriers are initially misdiagnosed with type 1 (T1DM or type 2 (T2DM diabetes mellitus; hence, they often receive nonoptimal treatment. The aim of our study was to test newly proposed clinical criteria for the identification of HNF1A MODY in patients with a diagnosis of T1DM or T2DM. To achieve this, the following criteria to preselect patients for screening were used: for T1DM: TDIR (total daily insulin requirement > 0.3 IU of insulin/kg and the percentage of basal insulin > 30% of TDIR; for T2DM: sulphonylurea- (SU- based oral treatment (monotherapy or combined with Metformin > 15 years and BMI < 30 kg/m2. We reviewed the clinical data of 140 patients with T1DM and 524 clinically diagnosed with T2DM. On the basis of these criteria, we found a HNF1A mutation in 1 out of 2 individuals with a diagnosis of T1DM and 1 out of 11 selected individuals with a diagnosis of T2DM. We believe that the simplicity of the proposed criteria might prove useful in clinical practice, as an alternative to more time-consuming classical diagnostic techniques.

Assessment of Newly Proposed Clinical Criteria to Identify HNF1A MODY in Patients with an Initial Diagnosis of Type 1 or Type 2 Diabetes Mellitus.

Science.gov (United States)

Grzanka, Malgorzata; Matejko, Bartlomiej; Szopa, Magdalena; Kiec-Wilk, Beata; Malecki, Maciej T; Klupa, Tomasz

2016-01-01

The most common form of maturity-onset diabetes of the young (MODY) is caused by mutations in the hepatocyte nuclear factor 1A (HNF1A) gene. However, most HNF1A mutation-carriers are initially misdiagnosed with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus; hence, they often receive nonoptimal treatment. The aim of our study was to test newly proposed clinical criteria for the identification of HNF1A MODY in patients with a diagnosis of T1DM or T2DM. To achieve this, the following criteria to preselect patients for screening were used: for T1DM: TDIR (total daily insulin requirement) > 0.3 IU of insulin/kg and the percentage of basal insulin > 30% of TDIR; for T2DM: sulphonylurea- (SU-) based oral treatment (monotherapy or combined with Metformin) > 15 years and BMI < 30 kg/m(2). We reviewed the clinical data of 140 patients with T1DM and 524 clinically diagnosed with T2DM. On the basis of these criteria, we found a HNF1A mutation in 1 out of 2 individuals with a diagnosis of T1DM and 1 out of 11 selected individuals with a diagnosis of T2DM. We believe that the simplicity of the proposed criteria might prove useful in clinical practice, as an alternative to more time-consuming classical diagnostic techniques.

Low frequency variants in the exons only encoding isoform A of HNF1A do not contribute to susceptibility to type 2 diabetes.

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Bahram Jafar-Mohammadi

2009-08-01

Full Text Available There is considerable interest in the hypothesis that low frequency, intermediate penetrance variants contribute to the proportion of Type 2 Diabetes (T2D susceptibility not attributable to the common variants uncovered through genome-wide association approaches. Genes previously implicated in monogenic and multifactorial forms of diabetes are obvious candidates in this respect. In this study, we focussed on exons 8-10 of the HNF1A gene since rare, penetrant mutations in these exons (which are only transcribed in selected HNF1A isoforms are associated with a later age of diagnosis of Maturity onset diabetes of the young (MODY than mutations in exons 1-7. The age of diagnosis in the subgroup of HNF1A-MODY individuals with exon 8-10 mutations overlaps with that of early multifactorial T2D, and we set out to test the hypothesis that these exons might also harbour low-frequency coding variants of intermediate penetrance that contribute to risk of multifactorial T2D.We performed targeted capillary resequencing of HNF1A exons 8-10 in 591 European T2D subjects enriched for genetic aetiology on the basis of an early age of diagnosis ( or =1 affected sibling. PCR products were sequenced and compared to the published HNF1A sequence. We identified several variants (rs735396 [IVS9-24T>C], rs1169304 [IVS8+29T>C], c.1768+44C>T [IVS9+44C>T] and rs61953349 [c.1545G>A, p.T515T] but no novel non-synonymous coding variants were detected.We conclude that low frequency, nonsynonymous coding variants in the terminal exons of HNF1A are unlikely to contribute to T2D-susceptibility in European samples. Nevertheless, the rationale for seeking low-frequency causal variants in genes known to contain rare, penetrant mutations remains strong and should motivate efforts to screen other genes in a similar fashion.

P1 promoter-driven HNF4α isoforms are specifically repressed by β-catenin signaling in colorectal cancer cells.

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Babeu, Jean-Philippe; Jones, Christine; Geha, Sameh; Carrier, Julie C; Boudreau, François

2018-06-13

HNF4α is a key nuclear receptor for regulating gene expression in the gut. While both P1 and P2 isoform classes of HNF4α are expressed in colonic epithelium, specific inhibition of P1 isoforms is commonly found in colorectal cancer. Previous studies have suggested that P1 and P2 isoforms may regulate different cellular functions. Despite these advances, it remains unclear whether these isoform classes are functionally divergent in the context of human biology. Here, the consequences of specific inhibition of P1 or P2 isoform expression was measured in a human colorectal cancer cell transcriptome. Results indicate that P1 isoforms were specifically associated with the control of cell metabolism while P2 isoforms globally supported aberrant oncogenic signalization, promoting cancer cell survival and progression. P1 promoter-driven isoform expression was found to be repressed by β-catenin, one of the earliest oncogenic pathways to be activated during colon tumorigenesis. These findings identify a novel cascade by which the expression of P1 isoforms are rapidly shut down in the early stages of colon tumorigenesis, allowing a change in HNF4α-dependent transcriptome thereby promoting colorectal cancer progression. © 2018. Published by The Company of Biologists Ltd.

The spectrum of HNF1A gene mutations in Greek patients with MODY3: relative frequency and identification of seven novel germline mutations.

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Tatsi, Christina; Kanaka-Gantenbein, Christina; Vazeou-Gerassimidi, Adriani; Chrysis, Dionysios; Delis, Dimitrios; Tentolouris, Nikolaos; Dacou-Voutetakis, Catherine; Chrousos, George P; Sertedaki, Amalia

2013-11-01

Maturity-Onset Diabetes of the Young (MODY) is the most common type of monogenic diabetes accounting for 1-2% of the population with diabetes. The relative incidence of HNF1A-MODY (MODY3) is high in European countries; however, data are not available for the Greek population. The aims of this study were to determine the relative frequency of MODY3 in Greece, the type of the mutations observed, and their relation to the phenotype of the patients. Three hundred ninety-five patients were referred to our center because of suspected MODY during a period of 15 yr. The use of Denaturing Gradient Gel Electrophoresis of polymerase chain reaction amplified DNA revealed 72 patients carrying Glucokinase gene mutations (MODY2) and 8 patients carrying HNF1A gene mutations (MODY3). After using strict criteria, 54 patients were selected to be further evaluated by direct sequencing or by multiplex ligation probe amplification (MLPA) for the presence of HNF1A gene mutations. In 16 unrelated patients and 13 of their relatives, 15 mutations were identified in the HNF1A gene. Eight of these mutations were previously reported, whereas seven were novel. Clinical features, such as age of diabetes at diagnosis or severity of hyperglycemia, were not related to the mutation type or location. In our cohort of patients fulfilling strict clinical criteria for MODY, 12% carried an HNF1A gene mutation, suggesting that defects of this gene are responsible for a significant proportion of monogenic diabetes in the Greek population. No clear phenotype-genotype correlations were identified. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of Glomerular Filtration Rate Estimation from Serum Creatinine and Cystatin C in HNF1A-MODY and Other Types of Diabetes

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Magdalena Szopa

2015-01-01

Full Text Available Introduction. We previously showed that in HNF1A-MODY the cystatin C-based glomerular filtration rate (GFR estimate is higher than the creatinine-based estimate. Currently, we aimed to replicate this finding and verify its clinical significance. Methods. The study included 72 patients with HNF1A-MODY, 72 with GCK-MODY, 53 with type 1 diabetes (T1DM, 70 with type 2 diabetes (T2DM, and 65 controls. Serum creatinine and cystatin C levels were measured. GFR was calculated from creatinine and cystatin C using the CKD-EPI creatinine equation (eGRF-cr and CKD-EPI cystatin C equation (eGFR-cys, respectively. Results. Cystatin C levels were lower (p<0.001 in the control (0.70±0.13 mg/L, HNF1A (0.75±0.21, and GCK (0.72±0.16 mg/L groups in comparison to those with either T1DM (0.87±0.15 mg/L or T2DM (0.9±0.23 mg/L. Moreover, eGFR-cys was higher than eGRF-cr in HNF1A-MODY, GCK-MODY, and the controls (p=0.004; p=0.003; p<0.0001. This corresponded to 8.9 mL/min/1.73 m2, 9.7 mL/min/1.73 m2, and 16.9 mL/min/1.73 m2 of difference. Additionally, T1DM patients had higher eGFR-cr than eGFR-cys (11.6 mL/min/1.73 m2; p=0.0004; no difference occurred in T2DM (p=0.91. Conclusions. We confirmed that eGFR-cys values in HNF1A-MODY patients are higher compared to eGFR-cr. Some other differences were also described in diabetic groups. However, none of them appears to be clinically relevant.

A role for coding functional variants in HNF4A in type 2 diabetes susceptibility

DEFF Research Database (Denmark)

Jafar-Mohammadi, B; Groves, C J; Gjesing, A P

2011-01-01

Rare mutations in the gene HNF4A, encoding the transcription factor hepatocyte nuclear factor 4α (HNF-4A), account for ~5% of cases of MODY and more frequent variants in this gene may be involved in multifactorial forms of diabetes. Two low-frequency, non-synonymous variants in HNF4A (V255M, minor...... allele frequency [MAF] ~0.1%; T130I, MAF ~3.0%)-known to influence downstream HNF-4A target gene expression-are of interest, but previous type 2 diabetes association reports were inconclusive. We aimed to evaluate the contribution of these variants to type 2 diabetes susceptibility through large...

HNF1A variant, energy-reduced diets and insulin resistance improvement during weight loss: The POUNDS Lost trial and DIRECT.

Science.gov (United States)

Huang, Tao; Wang, Tiange; Heianza, Yoriko; Sun, Dianjianyi; Ivey, Kerry; Durst, Ronen; Schwarzfuchs, Dan; Stampfer, Meir J; Bray, George A; Sacks, Frank M; Shai, Iris; Qi, Lu

2018-06-01

To determine whether weight-loss diets varying in macronutrients modulate the genetic effect of hepatocyte nuclear factor 1α (HNF1A) rs7957197 on weight loss and improvement of insulin resistance. We analysed the interaction between HNF1A rs7957197 and weight-loss diets with regard to weight loss and insulin resistance improvement among 722 overweight/obese adults from a 2-year randomized weight-loss trial, the POUNDS Lost trial. The findings were replicated in another independent 2-year weight-loss trial, the Dietary Intervention Randomized Controlled Trial (DIRECT), in 280 overweight/obese adults. In the POUNDS Lost trial, we found that a high-fat diet significantly modified the genetic effect of HNF1A on weight loss and reduction in waist circumference (P for interaction = .006 and .005, respectively). Borderline significant interactions for fasting insulin and insulin resistance (P for interaction = .07 and .06, respectively) were observed. We replicated the results in DIRECT. Pooled results showed similar significant interactions with weight loss, waist circumference reduction, and improvement in fasting insulin and insulin resistance (P values for interaction = .001, .005, .02 and .03, respectively). Greater decreases in weight, waist circumference, fasting insulin level and insulin resistance were observed in participants with the T allele compared to those without the T allele in the high-fat diet group (P = .04, .03 and .01, respectively). Our replicable findings provide strong evidence that individuals with the HNF1A rs7957197 T allele might obtain more benefits in weight loss and improvement of insulin resistance by choosing a hypocaloric and high-fat diet. © 2018 John Wiley & Sons Ltd.

Clinical differences between patients with MODY-3, MODY-2 and type 2 diabetes mellitus with I27L polymorphism in the HNF1alpha gene.

Science.gov (United States)

Pinés Corrales, Pedro José; López Garrido, María P; Aznar Rodríguez, Silvia; Louhibi Rubio, Lynda; López Jiménez, Luz M; Lamas Oliveira, Cristina; Alfaro Martínez, Jose J; Lozano García, Jose J; Hernández López, Antonio; Requejo Castillo, Ramón; Escribano Martínez, Julio; Botella Romero, Francisco

2010-01-01

The aim of our study was to describe and evaluate the clinical and metabolic characteristics of patients with MODY-3, MODY-2 or type 2 diabetes who presented I27L polymorphism in the HNF1alpha gene. The study included 31 previously diagnosed subjects under follow-up for MODY-3 (10 subjects from 5 families), MODY-2 (15 subjects from 9 families), or type 2 diabetes (6 subjects) with I27L polymorphism in the HNF1alpha gene. The demographic, clinical, metabolic, and genetic characteristics of all patients were analyzed. No differences were observed in distribution according to sex, age of onset, or form of diagnosis. All patients with MODY-2 or MODY-3 had a family history of diabetes. In contrast, 33.3% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene had no family history of diabetes (p MODY-3 patients, but not required by 100% of MODY-2 patients or 16.7% of patients with type 2 diabetes mellitus and I27L polymorphism in the HNF1alpha gene (p MODY-2, MODY-3 or type 2 diabetes of atypical characteristics, in this case patients who present I27L polymorphism in the HNF1alpha gene. Copyright 2010 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

Serum levels of pancreatic stone protein (PSP/reg1A as an indicator of beta-cell apoptosis suggest an increased apoptosis rate in hepatocyte nuclear factor 1 alpha (HNF1A-MODY carriers from the third decade of life onward

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Bacon Siobhan

2012-07-01

Full Text Available Abstract Background Mutations in the transcription factor hepatocyte nuclear factor-1-alpha (HNF1A result in the commonest type of maturity onset diabetes of the young (MODY. HNF1A-MODY carriers have reduced pancreatic beta cell mass, partially due to an increased rate of apoptosis. To date, it has not been possible to determine when apoptosis is occurring in HNF1A-MODY.We have recently demonstrated that beta cell apoptosis stimulates the expression of the pancreatic stone protein/regenerating (PSP/reg gene in surviving neighbour cells, and that PSP/reg1A protein is subsequently secreted from these cells. The objective of this study was to determine whether serum levels of PSP/reg1A are elevated during disease progression in HNF1A-MODY carriers, and whether it may provide information regarding the onset of beta-cell apoptosis. Methods We analysed serum PSP/reg1A levels and correlated with clinical and biochemical parameters in subjects with HNF1A-MODY, glucokinase (GCK-MODY, and type 1 diabetes mellitus. A control group of normoglycaemic subjects was also analysed. Results PSP/reg1A serum levels were significantly elevated in HNF1A-MODY (n = 37 subjects compared to controls (n = 60 (median = 12.50 ng/ml, IQR = 10.61-17.87 ng/ml versus median = 10.72 ng/ml, IQR = 8.94-12.54 ng/ml, p = 0.0008. PSP/reg1A correlated negatively with insulin levels during OGTT, (rho = −0.40, p = 0.02. Interestingly we noted a significant positive correlation of PSP/reg1A with age of the HNF1A-MODY carriers (rho = 0.40 p = 0.02 with an age of 25 years separating carriers with low and high PSP/reg1A levels. Patients with type 1 diabetes mellitus also had elevated serum levels of PSP/reg1A compared to controls, however this was independent of the duration of diabetes. Conclusion Our data suggest that beta cell apoptosis contributes increasingly to the pathophysiology of HNF1A-MODY in patients 25 years and over

Serum levels of pancreatic stone protein (PSP)/reg1A as an indicator of beta-cell apoptosis suggest an increased apoptosis rate in hepatocyte nuclear factor 1 alpha (HNF1A-MODY) carriers from the third decade of life onward

LENUS (Irish Health Repository)

Bacon, Siobhan

2012-07-18

AbstractBackgroundMutations in the transcription factor hepatocyte nuclear factor-1-alpha (HNF1A) result in the commonest type of maturity onset diabetes of the young (MODY). HNF1A-MODY carriers have reduced pancreatic beta cell mass, partially due to an increased rate of apoptosis. To date, it has not been possible to determine when apoptosis is occurring in HNF1A-MODY.We have recently demonstrated that beta cell apoptosis stimulates the expression of the pancreatic stone protein\\/regenerating (PSP\\/reg) gene in surviving neighbour cells, and that PSP\\/reg1A protein is subsequently secreted from these cells. The objective of this study was to determine whether serum levels of PSP\\/reg1A are elevated during disease progression in HNF1A-MODY carriers, and whether it may provide information regarding the onset of beta-cell apoptosis.MethodsWe analysed serum PSP\\/reg1A levels and correlated with clinical and biochemical parameters in subjects with HNF1A-MODY, glucokinase (GCK-MODY), and type 1 diabetes mellitus. A control group of normoglycaemic subjects was also analysed.ResultsPSP\\/reg1A serum levels were significantly elevated in HNF1A-MODY (n = 37) subjects compared to controls (n = 60) (median = 12.50 ng\\/ml, IQR = 10.61-17.87 ng\\/ml versus median = 10.72 ng\\/ml, IQR = 8.94-12.54 ng\\/ml, p = 0.0008). PSP\\/reg1A correlated negatively with insulin levels during OGTT, (rho = −0.40, p = 0.02). Interestingly we noted a significant positive correlation of PSP\\/reg1A with age of the HNF1A-MODY carriers (rho = 0.40 p = 0.02) with an age of 25 years separating carriers with low and high PSP\\/reg1A levels. Patients with type 1 diabetes mellitus also had elevated serum levels of PSP\\/reg1A compared to controls, however this was independent of the duration of diabetes.ConclusionOur data suggest that beta cell apoptosis contributes increasingly to the pathophysiology of HNF1A-MODY in patients 25 years and

Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus.

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Mrozinska, Sandra; Radkowski, Piotr; Gosiewski, Tomasz; Szopa, Magdalena; Bulanda, Malgorzata; Ludwig-Galezowska, Agnieszka H; Morawska, Iwona; Sroka-Oleksiak, Agnieszka; Matejko, Bartlomiej; Kapusta, Przemyslaw; Salamon, Dominika; Malecki, Maciej T; Wolkow, Pawel; Klupa, Tomasz

2016-01-01

Background . Type 2 diabetes mellitus (T2DM) is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY). Methods . The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A - MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed. Results . There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher ( p = 0.0006) and the amount of Bacteroidetes was lower ( p = 0.0005) in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group ( p = 0.0143). At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group. Conclusions . It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted.

Qualitative Parameters of the Colonic Flora in Patients with HNF1A-MODY Are Different from Those Observed in Type 2 Diabetes Mellitus

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Sandra Mrozinska

2016-01-01

Full Text Available Background. Type 2 diabetes mellitus (T2DM is determined by genetic and environmental factors. There have been many studies on the relationship between the composition of the gastrointestinal bacterial flora, T2DM, and obesity. There are no data, however, on the gut microbiome structure in monogenic forms of the disease including Maturity Onset Diabetes of the Young (MODY. Methods. The aim of the investigation was to compare the qualitative parameters of the colonic flora in patients with HNF1A-MODY and T2DM and healthy individuals. 16S sequencing of bacterial DNA isolated from the collected fecal samples using the MiSeq platform was performed. Results. There were significant between-group differences in the bacterial profile. At the phylum level, the amount of Proteobacteria was higher (p=0.0006 and the amount of Bacteroidetes was lower (p=0.0005 in T2DM group in comparison to the control group. In HNF1A-MODY group, the frequency of Bacteroidetes was lower than in the control group (p=0.0143. At the order level, Turicibacterales was more abundant in HNF1A-MODY group than in T2DM group. Conclusions. It appears that there are differences in the gut microbiome composition between patients with HNF1A-MODY and type 2 diabetes. Further investigation on this matter should be conducted.

Trichloroethylene perturbs HNF4a expression and activity in the developing chick heart.

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Harris, Alondra P; Ismail, Kareem A; Nunez, Martha; Martopullo, Ira; Lencinas, Alejandro; Selmin, Ornella I; Runyan, Raymond B

2018-03-15

Exposure to trichloroethylene (TCE) is linked to formation of congenital heart defects in humans and animals. Prior interactome analysis identified the transcription factor, Hepatocyte Nuclear Factor 4 alpha (HNF4a), as a potential target of TCE exposure. As a role for HNF4a is unknown in the heart, we examined developing avian hearts for HNF4a expression and for sensitivity to TCE and the HNF4a agonist, Benfluorex. In vitro analysis using a HNF4a reporter construct showed both TCE and HFN4a to be antagonists of HNF4a-mediated transcription at the concentrations tested. HNF4a mRNA is expressed transiently in the embryonic heart during valve formation and cardiac development. Embryos were examined for altered gene expression in the presence of TCE or Benfluorex. TCE altered expression of selected mRNAs including HNF4a, TRAF6 and CYP2C45. There was a transition between inhibition and induction of marker gene expression in embryos as TCE concentration increased. Benfluorex was largely inhibitory to selected markers. Echocardiography of exposed embryos showed reduced cardiac function with both TCE and Benfluorex. Cardiac contraction was reduced by 29% and 23%, respectively at 10 ppb. The effects of TCE and Benfluorex on autocrine regulation of HNF4a, selected markers and cardiac function argue for a functional interaction of TCE and HNF4a. Further, the dose-sensitive shift between inhibition and induction of marker expression may explain the nonmonotonic-like dose response observed with TCE exposure in the heart. Copyright © 2018 Elsevier B.V. All rights reserved.

Generation of an induced pluripotent stem cell (iPSC line from a patient with maturity-onset diabetes of the young type 3 (MODY3 carrying a hepatocyte nuclear factor 1-alpha (HNF1A mutation

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Frank Griscelli

2018-05-01

Full Text Available Heterozygous non-synonymous (p.S142F mutation in HNF1A leads to maturity-onset diabetes of the young (MODY type 3, which is a subtype of dominant inherited young-onset non-autoimmune diabetes due to the defect of insulin secretion from pancreatic beta cells. We generated induced pluripotent stem cells (iPSCs from a patient with HNF1A p.S142F mutation. Cells from this patient, which were reprogrammed by non-integrative viral transduction had normal karyotype, harboured the HNF1A p.S142F mutation, expressed pluripotency hallmarks.

A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus.

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Hohendorff, J; Szopa, M; Skupien, J; Kapusta, M; Zapala, B; Platek, T; Mrozinska, S; Parpan, T; Glodzik, W; Ludwig-Galezowska, A; Kiec-Wilk, B; Klupa, T; Malecki, M T

2017-08-01

SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level. There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1A-MODY, GCK-MODY, and T2DM, respectively, p MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was -6.57 ± 7.34 mg/ml (p = 0.04). A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies.

Co-inheritance of HNF1a and GCK mutations in a family with maturity-onset diabetes of the young (MODY): implications for genetic testing.

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López-Garrido, M P; Herranz-Antolín, S; Alija-Merillas, M J; Giralt, P; Escribano, J

2013-09-01

To determine the genetic basis of dominant early-onset diabetes mellitus in two families. Molecular analysis by PCR sequencing of the promoter, the 5' untranslated region (UTR) and exons of both GCK and HNF1A genes was carried out in two families with clinically diagnosed dominant diabetes mellitus. The novel HNF1A c.-154_-160TGGGGGT mutation, located in the 5' UTR, was present in several members of the two families in the heterozygous state. Interestingly, the GCK p.Y61X mutation was also identified in three members of one of the families, and two of them carried both mutations in heterozygosis. To the best of our knowledge, this is the first report of the co-inheritance of GCK and HNF1A mutations and the coexistence of maturity-onset diabetes of the young (MODY) 2, MODY 3 and unusual MODY 2-3 genotypes in the same family. Carriers of both GCK and HNF1A mutations manifested a typical MODY 3 phenotype and showed that the presence of a second mutation in the GCK gene apparently did not modify the clinical outcome, at least at the time of this study. Our data show that co-inheritance of MODY 2 and MODY 3 mutations should be considered, at least in some cases, for accurate genetic testing. © 2012 John Wiley & Sons Ltd.

TET-Catalyzed 5-Hydroxymethylation Precedes HNF4A Promoter Choice during Differentiation of Bipotent Liver Progenitors

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Pierre-Benoit Ancey

2017-07-01

Full Text Available Understanding the processes that govern liver progenitor cell differentiation has important implications for the design of strategies targeting chronic liver diseases, whereby regeneration of liver tissue is critical. Although DNA methylation (5mC and hydroxymethylation (5hmC are highly dynamic during early embryonic development, less is known about their roles at later stages of differentiation. Using an in vitro model of hepatocyte differentiation, we show here that 5hmC precedes the expression of promoter 1 (P1-dependent isoforms of HNF4A, a master transcription factor of hepatocyte identity. 5hmC and HNF4A expression from P1 are dependent on ten-eleven translocation (TET dioxygenases. In turn, the liver pioneer factor FOXA2 is necessary for TET1 binding to the P1 locus. Both FOXA2 and TETs are required for the 5hmC-related switch in HNF4A expression. The epigenetic event identified here may be a key step for the establishment of the hepatocyte program by HNF4A.

Two cases of diabetic ketoacidosis in HNF1A-MODY linked to severe dehydration: is it time to change the diagnostic criteria for MODY?

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Pruhova, Stepanka; Dusatkova, Petra; Neumann, David; Hollay, Erik; Cinek, Ondrej; Lebl, Jan; Sumnik, Zdenek

2013-09-01

Hepatocyte nuclear factor-1A maturity-onset diabetes of the young (HNF1A-MODY) is a monogenic form of diabetes caused by heterozygous mutations in HNF1A. Currently, a history of diabetic ketoacidosis (DKA) is an exclusion criterion for genetic testing for MODY. In this article, we describe two unrelated patients aged 17 and 24 years with severe DKA developed several years after the diagnosis of HNF1A-MODY. Both patients were treated with insulin, but their metabolic control was poor (HbA1c 15%, 140 mmol/mol and 13%, 119 mmol/mol, respectively) due to noncompliance and missed insulin injections. In both patients, DKA followed a course of recurrent vomiting with dehydration and prerenal acute kidney injury. Their glycemia, blood pH, and base excess at admission were 97 mmol/L [1,748 mg/dL], 6.80, and -33 mmol/L (patient 1) and 34 mmol/L [613 mg/dL], 7.03, and -14 mmol/L (patient 2). This anecdotal observation supports the notion that a history of DKA does not exclude MODY.

HNF1B and endometrial cancer risk: results from the PAGE study.

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Veronica Wendy Setiawan

Full Text Available We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC and the Women's Health Initiative (WHI as part of the Population Architecture using Genomics and Epidemiology (PAGE study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931 cases/3,755 controls. The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs per allele and 95% confidence intervals (CIs of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P ≥ 0.21 or between studies (P ≥ 0.70. The OR(per allele was 0.82 (95% CI: 0.75, 0.89; P = 5.63 × 10(-6 for rs4430796 (G allele and 0.79 (95% CI: 0.73, 0.87; P = 3.77 × 10(-7 for rs7501939 (A allele. The associations with the risk of Type I and Type II tumors were similar (P ≥ 0.19. Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors.

Duodenal atresia in 17q12 microdeletion including HNF1B: a new associated malformation in this syndrome.

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Quintero-Rivera, Fabiola; Woo, Jennifer S; Bomberg, Eric M; Wallace, W Dean; Peredo, Jane; Dipple, Katrina M

2014-12-01

Deletions of chromosome 17q12 [OMIM 614527] encompass a wide range of phenotypes, including renal cysts, diabetes mellitus, pancreatic structural abnormalities, genital tract anomalies, developmental delay, learning difficulties, and more recently, autism spectrum disorder and schizophrenia. To date, gastrointestinal malformations have not been fully characterized in this syndrome. In this case report, we describe a four-year-old girl with a 17q12 microdeletion who was born with duodenal atresia, bilateral renal cysts, left kidney dysplasia, a midline cystic structure at the conus medullaris, and dysmorphic features. Both the patient and her affected father were found to have a deletion of 17q12, which encompasses the HNF1B (hepatocyte nuclear factor beta). It is hypothesized that HNF1B may play a role in intestinal differentiation and development. Our clinical report further expands the pre-and post-natal presentation of this rare microdeletion syndrome. © 2014 Wiley Periodicals, Inc.

Exocrine pancreatic function in hepatocyte nuclear factor 1β-maturity-onset diabetes of the young (HNF1B-MODY) is only moderately reduced: compensatory hypersecretion from a hypoplastic pancreas.

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Tjora, E; Wathle, G; Erchinger, F; Engjom, T; Molven, A; Aksnes, L; Haldorsen, I S; Dimcevski, G; Raeder, H; Njølstad, P R

2013-08-01

To examine the exocrine pancreatic function in carriers of the hepatocyte nuclear factor 1β gene (HNF1B) mutation by direct testing. Patients with HNF1B mutations and control subjects were assessed using rapid endoscopic secretin tests and secretin-stimulated magnetic resonance imaging. Seven patients and 25 controls underwent endoscopy, while eight patients and 20 controls had magnetic resonance imaging. Ductal function was assessed according to peak bicarbonate concentrations and acinar function was assessed according to peak digestive enzyme activities in secretin-stimulated duodenal juice. The association of pancreatic exocrine function and diabetes status with pancreatic gland volume was examined. The mean increase in secretin-stimulated duodenal fluid was smaller in patients than controls (4.0 vs 6.4 ml/min; P = 0.003). We found lower ductal function in patients than controls (median peak bicarbonate concentration: 73 vs 116 mEq/L; P function (median peak lipase activity: 6.4 vs 33.5 kU/ml; P = 0.01; median peak elastase activity: 0.056 vs 0.130 U/ml; P = 0.01). Pancreatic fluid volume outputs correlated significantly with pancreatic gland volumes (r² = 0.71, P = 0.008) in patients. The total fluid output to pancreatic gland volume ratios were higher in patients than controls (4.5 vs 1.3 ml/cm³; P = 0.03), suggesting compensatory hypersecretion in the remaining gland. Carriers of the HNF1B mutation have lower exocrine pancreatic function involving both ductal and acinar cells. Compensatory hypersecretion suggests that the small pancreas of HNF1B mutation carriers is attributable to hypoplasia, not atrophy. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Data report for the integrity assessment report HNF-4589

Energy Technology Data Exchange (ETDEWEB)

MCSHANE, D.S.

1999-10-27

The purpose of this document is to compile supporting documentation for the Integrity Assessment Report (HNF 4589) for Tanks 101 and 102 in the 2194 Facility. This approach minimizes the size of the Integrity Assessment Report (IAR) (HNF-4589) and still provide a path to detailed information. This IAR addresses the evaluation of Tanks 101 and 102 and other existing components located in the 219-5 Waste Handling Facility.

Dungeness crab survey for the Southwest Ocean Disposal Site off Grays Harbor, Washington, June 1990

Energy Technology Data Exchange (ETDEWEB)

Higgins, B.J.; Pearson, W.H. (Battelle/Marine Sciences Lab., Sequim, WA (United States))

1991-09-01

As part of the Grays Harbor Navigation Improvement Project, the Seattle District of the US Army Corps of Engineers has begun active use of the Southwest Ocean Disposal Site off Grays Harbor, Washington. This survey was to verify that the location of the area of high crab density observed during site selection surveys has not shifted into the Southeast Ocean Disposal Site. In June 1990, mean densities of juvenile Dungeness crab were 146 crab/ha within the disposal site and 609 crab/ha outside ad north of the disposal site. At nearshore locations outside the disposal site, juvenile crab density was 3275 crab/ha. Despite the low overall abundance, the spatial distribution of crab was such that the high crab densities in 1990 have remained outside the Southwest Ocean Disposal Site. The survey data have confirmed the appropriateness of the initial selection of the disposal site boundaries and indicated no need to move to the second monitoring tier. 8 refs., 9 figs., 2 tabs.

Phenotypic screening of hepatocyte nuclear factor (HNF) 4-γ receptor knockout mice

International Nuclear Information System (INIS)

Gerdin, Anna Karin; Surve, Vikas V.; Joensson, Marie; Bjursell, Mikael; Bjoerkman, Maria; Edenro, Anne; Schuelke, Meint; Saad, Alaa; Bjurstroem, Sivert; Lundgren, Elisabeth Jensen; Snaith, Michael; Fransson-Steen, Ronny; Toernell, Jan; Berg, Anna-Lena; Bohlooly-Y, Mohammad

2006-01-01

Using the mouse as a model organism in pharmaceutical research presents unique advantages as its physiology in many ways resembles the human physiology, it also has a relatively short generation time, low breeding and maintenance costs, and is available in a wide variety of inbred strains. The ability to genetically modify mouse embryonic stem cells to generate mouse models that better mimic human disease is another advantage. In the present study, a comprehensive phenotypic screening protocol is applied to elucidate the phenotype of a novel mouse knockout model of hepatocyte nuclear factor (HNF) 4-γ. HNF4-γ is expressed in the kidneys, gut, pancreas, and testis. First level of the screen is aimed at general health, morphologic appearance, normal cage behaviour, and gross neurological functions. The second level of the screen looks at metabolic characteristics and lung function. The third level of the screen investigates behaviour more in-depth and the fourth level consists of a thorough pathological characterisation, blood chemistry, haematology, and bone marrow analysis. When compared with littermate wild-type mice (HNF4-γ +/+ ), the HNF4-γ knockout (HNF4-γ -/- ) mice had lowered energy expenditure and locomotor activity during night time that resulted in a higher body weight despite having reduced intake of food and water. HNF4-γ -/- mice were less inclined to build nest and were found to spend more time in a passive state during the forced swim test

Direct induction of hepatocyte-like cells from immortalized human bone marrow mesenchymal stem cells by overexpression of HNF4α

International Nuclear Information System (INIS)

Hu, Xiaojun; Xie, Peiyi; Li, Weiqiang; Li, Zhengran; Shan, Hong

2016-01-01

Hepatocytes from human bone marrow-derived mesenchymal stem cells (hBM-MSCs) are expected to be a useful source for cell transplantation. However, relatively low efficiency and repeatability of hepatic differentiation of human BM-MSCs remains an obstacle for clinical translation. Hepatocyte nuclear factor 4 alpha (HNF4α), a critical transcription factor, plays an essential role in the entire process of liver development. In this study, immortalized hBM-MSCs, UE7T-13 cells were transduced with a lentiviral vector containing HNF4α. The typical fibroblast-like morphology of the MSCs changed, and polygonal, epithelioid cells grew out after HNF4α transduction. In hepatocyte culture medium, HNF4α-transduced MSCs (E7-hHNF4α cells) strongly expressed the albumin (ALB), CYP2B6, alpha-1 antitrypsin (AAT), and FOXA2 mRNA and exhibited morphology markedly similar to that of mature hepatocytes. The E7-hHNF4α cells showed hepatic functions such as Indocyanine green (ICG) uptake and release, glycogen storage, urea production and ALB secretion. Approximately 28% of E7-hHNF4α cells expressed both ALB and AAT. Furthermore, these E7-hHNF4α cells via superior mesenteric vein (SMV) injection expressed human ALB in mouse chronic injured liver. In conclusion, this study represents a novel strategy by directly inducing hepatocyte-like cells from MSCs. - Highlights: • We overexpressed HNF4α in immortalized BM-MSCs by lentiviral transduction. • HNF4α-transduced MSCs transdifferentiated into hepatocytes with mature hepatic metabolic functions. • Our study represents a novel strategy by direct induction of hepatocyte-like cells from MSCs.

A novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) gene mutation, presenting with neonatal cholestasis

NARCIS (Netherlands)

de Vries, Aleida G. M.; Bakker-van Waarde, Willie M.; Dassel, Anne C. M.; Losekoot, Monique; Duiker, Evelien W.; Gouw, Annette S. H.; Bodewes, Frank A. J. A.

We report a novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) mutation (heterozygote c.130dup, p.Leu44fs) presenting with transient neonatal cholestasis, subsequently followed by persistent elevation of transaminases, maturity-onset diabetes of the young (MODY) type 3 and

Data report for the integrity assessment report HNF-4589

International Nuclear Information System (INIS)

MCSHANE, D.S.

1999-01-01

Supporting data for the Integrity Assessment Report of Tanks TK-101 and TK-102. The purpose of this document is to compile supporting documentation for the Integrity Assessment Report (HNF 4589) for Tanks 101 and 102 in the 2194 Facility. This approach minimizes the size of the Integrity Assessment Report (IAR) (HNF-4589) and still provide a path to detailed information. This IAR addresses the evaluation of Tanks 101 and 102 and other existing components located in the 219-5 Waste Handling Facility

Long-lasting response to oral therapy in a young male with monogenic diabetes as part of HNF1B-related disease.

Science.gov (United States)

Carrillo, Elena; Lomas, Amparo; Pinés, Pedro J; Lamas, Cristina

2017-01-01

Mutations in hepatocyte nuclear factor 1β gene ( HNF1B ) are responsible for a multisystemic syndrome where monogenic diabetes (classically known as MODY 5) and renal anomalies, mostly cysts, are the most characteristic findings. Urogenital malformations, altered liver function tests, hypomagnesemia or hyperuricemia and gout are also part of the syndrome. Diabetes in these patients usually requires early insulinization. We present the case of a young non-obese male patient with a personal history of renal multicystic dysplasia and a debut of diabetes during adolescence with simple hyperglycemia, negative pancreatic autoimmunity and detectable C-peptide levels. He also presented epididymal and seminal vesicle cysts, hypertransaminasemia, hyperuricemia and low magnesium levels. In the light of these facts we considered the possibility of a HNF1B mutation. The sequencing study of this gene confirmed a heterozygous mutation leading to a truncated and less functional protein. Genetic studies of his relatives were negative; consequently, it was classified as a de novo mutation. In particular, our patient maintained good control of his diabetes on oral antidiabetic agents for a long period of time. He eventually needed insulinization although oral therapy was continued alongside, allowing reduction of prandial insulin requirements. The real prevalence of mutations in HNF1B is probably underestimated owing to a wide phenotypical variability. As endocrinologists, we should consider this possibility in young non-obese diabetic patients with a history of chronic non-diabetic nephropathy, especially in the presence of some of the other characteristic manifestations. HNF1B mutations are a rare cause of monogenic diabetes, often being a part of a multisystemic syndrome.The combination of young-onset diabetes and genitourinary anomalies with slowly progressive nephropathy of non-diabetic origin in non-obese subjects should rise the suspicion of such occurrence. A family history

Mody-3: novel HNF1A mutation and the utility of glucagon-like peptide (GLP)-1 receptor agonist therapy.

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Docena, Maricor K; Faiman, Charles; Stanley, Christine M; Pantalone, Kevin M

2014-02-01

An estimated 1 to 2% of cases of diabetes mellitus have a monogenic basis; however, delayed diagnosis and misdiagnosis as type 1 and 2 diabetes are common. Correctly identifying the molecular basis of an individual's diabetes may significantly alter the management approach to both the patient and his or her relatives. We describe a case of mature onset diabetes of the young (MODY) with sufficient evidence to support the classification of a novel HNF1A (hepatocyte nuclear factor-1-α) mutation as a cause of MODY-3. A 21-year-old Caucasian female presented to our office with a diagnosis of noninsulin-dependent diabetes mellitus (NIDDM) at age 10; glycemia was initially managed with oral antidiabetic (OAD) agents and insulin detemir. The patient reported a strong family history of early-onset NIDDM in both her mother and maternal grandmother, both of whom eventually required insulin therapy to control glycemia. The patient's medical and family history were highly suggestive of maturity-onset diabetes of the young (MODY), and genetic testing was performed. Genetic screening detected a mutation p. Arg200Trp in the HNF1A gene in the patient, her mother, and maternal grandmother, suggesting a diagnosis of MODY-3. This finding resulted in a change of antidiabetic therapy in all 3 patients, including the addition of once-daily liraglutide therapy, which helped improve their glycemic control. Our case report supports the classification of the p. Arg200Trp mutation as a cause of MODY-3. The findings also suggest that glucagon-like peptide-1 (GLP-1) receptor agonist therapy may be of value in managing glycemia in patients with MODY-3.

Long-lasting response to oral therapy in a young male with monogenic diabetes as part of HNF1B-related disease

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Elena Carrillo

2017-06-01

Full Text Available Mutations in hepatocyte nuclear factor 1β gene (HNF1B are responsible for a multisystemic syndrome where monogenic diabetes (classically known as MODY 5 and renal anomalies, mostly cysts, are the most characteristic findings. Urogenital malformations, altered liver function tests, hypomagnesemia or hyperuricemia and gout are also part of the syndrome. Diabetes in these patients usually requires early insulinization. We present the case of a young non-obese male patient with a personal history of renal multicystic dysplasia and a debut of diabetes during adolescence with simple hyperglycemia, negative pancreatic autoimmunity and detectable C-peptide levels. He also presented epididymal and seminal vesicle cysts, hypertransaminasemia, hyperuricemia and low magnesium levels. In the light of these facts we considered the possibility of a HNF1B mutation. The sequencing study of this gene confirmed a heterozygous mutation leading to a truncated and less functional protein. Genetic studies of his relatives were negative; consequently, it was classified as a de novo mutation. In particular, our patient maintained good control of his diabetes on oral antidiabetic agents for a long period of time. He eventually needed insulinization although oral therapy was continued alongside, allowing reduction of prandial insulin requirements. The real prevalence of mutations in HNF1B is probably underestimated owing to a wide phenotypical variability. As endocrinologists, we should consider this possibility in young non-obese diabetic patients with a history of chronic non-diabetic nephropathy, especially in the presence of some of the other characteristic manifestations.

Comparison of Glomerular Filtration Rate Estimation from Serum Creatinine and Cystatin C in HNF1A-MODY and Other Types of Diabetes.

Science.gov (United States)

Szopa, Magdalena; Kapusta, Maria; Matejko, Bartlomiej; Klupa, Tomasz; Koblik, Teresa; Kiec-Wilk, Beata; Borowiec, Maciej; Malecki, Maciej T

2015-01-01

We previously showed that in HNF1A-MODY the cystatin C-based glomerular filtration rate (GFR) estimate is higher than the creatinine-based estimate. Currently, we aimed to replicate this finding and verify its clinical significance. The study included 72 patients with HNF1A-MODY, 72 with GCK-MODY, 53 with type 1 diabetes (T1DM), 70 with type 2 diabetes (T2DM), and 65 controls. Serum creatinine and cystatin C levels were measured. GFR was calculated from creatinine and cystatin C using the CKD-EPI creatinine equation (eGRF-cr) and CKD-EPI cystatin C equation (eGFR-cys), respectively. Cystatin C levels were lower (p MODY, GCK-MODY, and the controls (p = 0.004; p = 0.003; p MODY patients are higher compared to eGFR-cr. Some other differences were also described in diabetic groups. However, none of them appears to be clinically relevant.

Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation

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Olivia Alder

2014-10-01

Full Text Available Summary: Cell fate acquisition is heavily influenced by direct interactions between master regulators and tissue-specific enhancers. However, it remains unclear how lineage-specifying transcription factors, which are often expressed in both progenitor and mature cell populations, influence cell differentiation. Using in vivo mouse liver development as a model, we identified thousands of enhancers that are bound by the master regulators HNF4A and FOXA2 in a differentiation-dependent manner, subject to chromatin remodeling, and associated with differentially expressed target genes. Enhancers exclusively occupied in the embryo were found to be responsive to developmentally regulated TEAD2 and coactivator YAP1. Our data suggest that Hippo signaling may affect hepatocyte differentiation by influencing HNF4A and FOXA2 interactions with temporal enhancers. In summary, transcription factor-enhancer interactions are not only tissue specific but also differentiation dependent, which is an important consideration for researchers studying cancer biology or mammalian development and/or using transformed cell lines. : It is unclear how key transcription factors are critical for both lineage specification during embryonic development and maintenance of a differentiated, adult phenotype. By profiling the enhancer occupancy of the key transcription factors HNF4A and FOXA2 during mouse liver development, Alder et al. have found that YAP1 can influence enhancer interactions and target gene expression levels. Enhancer switching enables HNF4A and FOXA2 to fulfill distinct roles during organ development.

ATR-Hanford site emergency alerting system - 400 Area (F1-F2) and 600 Area (S6-S10)

International Nuclear Information System (INIS)

Whattam, J.W.

1998-01-01

This document provides the results of the acceptance test procedure performed under document number: HNF-2501, Rev 0. This Acceptance Test Procedure has been prepared to demonstrate the Hanford Site Emergency Alerting System functions as required by Specification WHC-S0454, Rev. 1 and project criteria

HNF1 alpha gene coding regions mutations screening, in a Caucasian population clinically characterized as MODY from Argentina.

Science.gov (United States)

Lopez, Ariel Pablo; Foscaldi, Sabrina Andrea; Perez, Maria Silvia; Rodriguez, Martín; Traversa, Mercedes; Puchulu, Félix Miguel; Bergada, Ignacio; Frechtel, Gustavo Daniel

2011-02-01

There are at least six subtypes of Maturity Onset Diabetes of the Young (MODY) with distinctive genetic causes. MODY 3 is caused by mutations in HNF1A gene, an insulin transcription factor, so mutations in this gene are associated with impaired insulin secretion. MODY 3 prevalence differs according to the population analyzed, but it is one of the most frequent subtypes. Therefore, our aims in this work were to find mutations present in the HNF1A gene and provide information on their prevalence. Mutations screening was done in a group of 80 unrelated patients (average age 17.1 years) selected by clinical characterization of MODY, by SSCP electrophoresis followed by sequenciation. We found eight mutations, of which six were novel and four sequence variants, which were all novel. Therefore the prevalence of MODY 3 in this group was 10%. Compared clinical data between the non-MODY 3 patients and the MODY 3 diagnosed patients did not show any significant difference. Eight patients were diagnosed as MODY 3 and new data about the prevalence of that subtype is provided. Our results contribute to reveal novel mutations, providing new data about the prevalence of that subtype. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Prolonged episodes of hypoglycaemia in HNF4A-MODY mutation carriers with IGT. Evidence of persistent hyperinsulinism into early adulthood.

Science.gov (United States)

Bacon, S; Kyithar, M P; Condron, E M; Vizzard, N; Burke, M; Byrne, M M

2016-12-01

HNF4A is an established cause of maturity onset diabetes of the young (MODY). Congenital hyperinsulinism can also be associated with mutations in the HNF4A gene. A dual phenotype is observed in HNF4A-MODY with hyperinsulinaemic hypoglycaemia in the neonatal period progressing to diabetes in adulthood. The nature and timing of the transition remain poorly defined. We performed an observational study to establish changes in glycaemia and insulin secretion over a 6-year period. We investigated glycaemic variability and hypoglycaemia in HNF4A-MODY using a continuous glucose monitoring system (CGMS). An OGTT with measurement of glucose, insulin and C-peptide was performed in HNF4A participants with diabetes mellitus (DM) (n = 14), HNF4A-IGT (n = 7) and age- and BMI-matched MODY negative family members (n = 10). Serial assessment was performed in the HNF4A-IGT cohort. In a subset of HNF4A-MODY mutation carriers (n = 10), CGMS was applied over a 72-h period. There was no deterioration in glycaemic control in the HNF4A-IGT cohort. The fasting glucose-to-insulin ratio was significantly lower in the HNF4A-IGT cohort when compared to the normal control group (0.13 vs. 0.24, p = 0.03). CGMS profiling demonstrated prolonged periods of hypoglycaemia in the HNF4A-IGT group when compared to the HNF4A-DM group (432 vs. 138 min p = 0.04). In a young adult HNF4A-IGT cohort, we demonstrate preserved glucose, insulin and C-peptide secretory responses to oral glucose. Utilising CGMS, prolonged periods of hypoglycaemia are evident despite a median age of 21 years. We propose a prolonged hyperinsulinaemic phase into adulthood is responsible for the notable hypoglycaemic episodes.

HNF-4α regulated miR-122 contributes to development of gluconeogenesis and lipid metabolism disorders in Type 2 diabetic mice and in palmitate-treated HepG2 cells.

Science.gov (United States)

Wei, Shengnan; Zhang, Ming; Yu, Yang; Xue, Huan; Lan, Xiaoxin; Liu, Shuping; Hatch, Grant; Chen, Li

2016-11-15

Hepatocyte Nuclear Factor-4α (HNF-4α) is a key nuclear receptor protein required for liver development. miR-122 is a predominant microRNA expressed in liver and is involved in the regulation of cholesterol and fatty acid metabolism. HNF-4α is know to regulate expression of miR-122 in liver. We examined how HNF-4α regulated gluconeogenesis and lipid metabolism through miR-122 in vivo and in vitro. Expression of miR-122, HNF-4α, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol response elementary binding protein-1 (SREBP-1), fatty acid synthase-1 (FAS-1), carnitine palmitoyltransferase-1 (CPT-1) and acetyl Coenzyme A carboxylase alpha (ACCα) were determined in livers of Type 2 diabetic mice and in insulin resistant palmitate-treated HepG2 cells. CPT-1 and phosphorylated ACCα expression were significantly decreased in livers of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. In contrast, expression of miR-122, HNF-4α, PEPCK, G6Pase, SREBP-1, FAS-1 and ACCα were significantly elevated in liver of Type 2 diabetic mice and in palmitate-treated HepG2 cells compared to controls. Expression of HNF-4α increased whereas siRNA knockdown of HNF-4α decreased miR-122 levels in HepG2 cells compared to controls. In addition, expression of HNF-4α in HepG2 cells increased PEPCK, G6Pase, SREBP-1, FAS-1, ACCα mRNA and protein expression and decreased CPT-1 and p-ACCα mRNA and protein expression compared to controls. Addition of miR-122 inhibitors attenuated the HNF-4α mediated effect on expression of these gluconeogenic and lipid metabolism proteins. The results indicate that HNF-4α regulated miR-122 contributes to development of the gluconeogenic and lipid metabolism alterations observed in Type 2 diabetic mice and in palmitate-treated HepG2 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Behavior of tight-junction, adherens-junction and cell polarity proteins during HNF-4α-induced epithelial polarization

International Nuclear Information System (INIS)

Satohisa, Seiro; Chiba, Hideki; Osanai, Makoto; Ohno, Shigeo; Kojima, Takashi; Saito, Tsuyoshi; Sawada, Norimasa

2005-01-01

We previously reported that expression of tight-junction molecules occludin, claudin-6 and claudin-7, as well as establishment of epithelial polarity, was triggered in mouse F9 cells expressing hepatocyte nuclear factor (HNF)-4α [H. Chiba, T. Gotoh, T. Kojima, S. Satohisa, K. Kikuchi, M. Osanai, N. Sawada. Hepatocyte nuclear factor (HNF)-4α triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells, Exp. Cell Res. 286 (2003) 288-297]. Using these cells, we examined in the present study behavior of tight-junction, adherens-junction and cell polarity proteins and elucidated the molecular mechanism behind HNF-4α-initiated junction formation and epithelial polarization. We herein show that not only ZO-1 and ZO-2, but also ZO-3, junctional adhesion molecule (JAM)-B, JAM-C and cell polarity proteins PAR-3, PAR-6 and atypical protein kinase C (aPKC) accumulate at primordial adherens junctions in undifferentiated F9 cells. In contrast, CRB3, Pals1 and PATJ appeared to exhibit distinct subcellular localization in immature cells. Induced expression of HNF-4α led to translocation of these tight-junction and cell polarity proteins to beltlike tight junctions, where occludin, claudin-6 and claudin-7 were assembled, in differentiated cells. Interestingly, PAR-6, aPKC, CRB3 and Pals1, but not PAR-3 or PATJ, were also concentrated on the apical membranes in differentiated cells. These findings indicate that HNF-4α provokes not only expression of tight-junction adhesion molecules, but also modulation of subcellular distribution of junction and cell polarity proteins, resulting in junction formation and epithelial polarization

CRSMP Potential Harbor Borrow Sites 2012

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California Natural Resource Agency — Harbor locations as identified originally in the California Shoreline Database compiled by Noble Consultants (Jon Moore) for California Department of Boating and...

MED25 is a mediator component of HNF4α-driven transcription leading to insulin secretion in pancreatic beta-cells.

Directory of Open Access Journals (Sweden)

Eun Hee Han

Full Text Available Unique nuclear receptor Hepatocyte Nuclear Factor 4α (HNF4α is an essential transcriptional regulator for early development and proper function of pancreatic ß-cells, and its mutations are monogenic causes of a dominant inherited form of diabetes referred to as Maturity Onset Diabetes of the Young 1 (MODY1. As a gene-specific transcription factor, HNF4α exerts its function through various molecular interactions, but its protein recruiting network has not been fully characterized. Here we report the identification of MED25 as one of the HNF4α binding partners in pancreatic ß-cells leading to insulin secretion which is impaired in MODY patients. MED25 is one of the subunits of the Mediator complex that is required for induction of RNA polymerase II transcription by various transcription factors including nuclear receptors. This HNF4α-MED25 interaction was initially identified by a yeast-two-hybrid method, confirmed by in vivo and in vitro analyses, and proven to be mediated through the MED25-LXXLL motif in a ligand-independent manner. Reporter-gene based transcription assays and siRNA/shRNA-based gene silencing approaches revealed that this interaction is crucial for full activation of HNF4α-mediated transcription, especially expression of target genes implicated in glucose-stimulated insulin secretion. Selected MODY mutations at the LXXLL motif binding pocket disrupt these interactions and cause impaired insulin secretion through a 'loss-of-function' mechanism.

Effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on oxcarbazepine concentrations and therapeutic efficacy in patients with epilepsy.

Science.gov (United States)

Shen, Chunhong; Zhang, Bijun; Liu, Zhirong; Tang, Yelei; Zhang, Yinxi; Wang, Shan; Guo, Yi; Ding, Yao; Wang, Shuang; Ding, Meiping

2017-10-01

The aim of the study is to investigate the effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P<0.05). As for UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

HDL cholesterol as a diagnostic tool for clinical differentiation of GCK-MODY from HNF1A-MODY and type 1 diabetes in children and young adults.

Science.gov (United States)

Fendler, Wojciech; Borowiec, Maciej; Antosik, Karolina; Szadkowska, Agnieszka; Deja, Grazyna; Jarosz-Chobot, Przemyslawa; Mysliwiec, Malgorzata; Wyka, Krystyna; Pietrzak, Iwona; Skupien, Jan; Malecki, Maciej T; Mlynarski, Wojciech

2011-09-01

Confirmation of monogenic diabetes caused by glucokinase mutations (GCK-MODY) allows pharmacogenetic intervention in the form of insulin discontinuation. This is especially important among paediatric and young adult populations where GCK-MODY is most prevalent. The study evaluated the utility of lipid parameters in screening for patients with GCK-MODY. Eighty-nine children with type 1 diabetes and 68 with GCK-MODY were screened for triglyceride (TG), total and HDL cholesterol levels. Standardization against a control group of 171 healthy children was applied to eliminate the effect of development. Clinical applicability and cut-off value were evaluated in all available patients with GCK-MODY (n = 148), hepatocyte nuclear factor 1-alpha-MODY (HNF1A MODY) (n = 37) or type 1 diabetes (n = 221). Lower lipid parameter values were observed in GCK-MODY than in patients with type 1 diabetes. Standard deviation scores were -0·22 ± 2·24 vs 1·31 ± 2·17 for HDL cholesterol (P MODY selection [sensitivity 87%, specificity 54%, negative predictive value (NPV) 86%, positive PV 56%]. A threshold HDL concentration of 1·56 mm offered significantly better diagnostic efficiency than total cholesterol (cut-off value 4·51 mm; NPV 80%; PPV 38%; P MODY and differentiation from T1DM and HNF1A-MODY, regardless of treatment or metabolic control. © 2011 Blackwell Publishing Ltd.

Insertion of liver enriched transcription factor hepatocyte nuclear factor-4 (HNF-4) in a vector which contains simian virus (SV40) promoter

International Nuclear Information System (INIS)

Al-Nbaheen, M.; Pourzand, C.; Tyrrell, R.M.

2006-01-01

One way of targeting gene expression in vivo is to control transcription using a tissue-specific regulatory system. Tissue specific promoters or enhancers are in use in transgenic animals and could be utilized in medical for gene therapy. At present the usual method for selection of a tissue-specific promoter is to identify a gene, which is expressed at unusually high level in the target tissue, and then to use the promoter for this gene to drive expression of another therapeutic gene in the target tissue. This approach is logical but does not always lead to high levels of gene expression. A second approach is to investigate the scope for discovery of synthetic specific promoters using a target tissue. The objective of the work described in this paper was to use both approach to design plasmid DNA expression vectors that would carry liver-specific promoter/enhancer linked to reporter gene (i.e. luciferase). Then transfect these vectors to both liver-derived and non-liver cell lines. This is followed by evaluation of the liver-specificity of each construct by measuring the basal level expression of the reporter gene (i.e. luciferase activity) in both cell lines. Hepatocyte nuclear factor-4 (HNF-4) is liver-enriched transcription factor used to design new synthetic enhancers by inserting a tandem array of 1', 3' or 5' repeats of the HNF-4 binding site upstream of the SV40 promoter linked to the luciferase reporter gene within an Epstein-Barr virus (EBV)-based vector, p 706. The results of transfection revealed that unexpectedly the HNF-4 binding sites in these constructs act as a repressor rather than enhancer of the liver-specific expression of the luciferase gene. (author)

Feedback regulation of bile acid synthesis in human liver: Importance of HNF-4α for regulation of CYP7A1

International Nuclear Information System (INIS)

Abrahamsson, Anna; Gustafsson, Ulf; Ellis, Ewa; Nilsson, Lisa-Mari; Sahlin, Staffan; Bjoerkhem, Ingemar; Einarsson, Curt

2005-01-01

A great number of nuclear factors are involved in the negative feedback mechanism regulating bile acid synthesis. There are two major ways for the negative feedback to effect the synthesis; the SHP-dependent, involving FXR, and the SHP-independent way, affecting HNF-4α. We studied 23 patients with gallstone disease. Eight patients were treated with chenodeoxycholic acid, 7 with cholestyramine prior to operation, and 8 served as controls. Liver biopsies were analyzed with Real-time-PCR. In the cholestyramine-treated group mRNA levels of CYP7A1 were increased about 10-fold. Treatment with CDCA decreased the mRNA levels of CYP7A1 by about 70%. The mRNA levels of CYP8B1, CYP27A1, and CYP7B1 were not significantly altered in the treated groups. The analysis of mRNA levels for HNF-4α showed 64% higher levels in the cholestyramine-treated group compared to the controls. These levels showed positive and highly significant correlation to the levels of mRNA of CYP7A1 when studied in all three groups together. FXR, SHP, and LRH-1/FTF were not significantly affected by the different treatments. Our results indicate that when bile acid synthesis is upregulated by cholestyramine treatment the SHP-independent pathway for controlling CYP7A1 transcription dominates over the SHP-dependent pathway

Yes-associated protein/TEA domain family member and hepatocyte nuclear factor 4-alpha (HNF4α) repress reciprocally to regulate hepatocarcinogenesis in rats and mice.

Science.gov (United States)

Cai, Wang-Yu; Lin, Ling-Yun; Hao, Han; Zhang, Sai-Man; Ma, Fei; Hong, Xin-Xin; Zhang, Hui; Liu, Qing-Feng; Ye, Guo-Dong; Sun, Guang-Bin; Liu, Yun-Jia; Li, Sheng-Nan; Xie, Yuan-Yuan; Cai, Jian-Chun; Li, Bo-An

2017-04-01

Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between Yes-associated protein/TEA domain family member (YAP-TEAD) and hepatocyte nuclear factor 4-alpha (HNF4α) in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells by a ubiquitin proteasome pathway. By contrast, HNF4α was found to directly associate with TEAD4 to compete with YAP1 for binding to TEAD4, thus inhibiting the transcriptional activity of YAP-TEAD and expression of their target genes. Moreover, overexpression of HNF4α was found to significantly compromise YAP-TEAD-induced HCC cell proliferation and stem cell expansion. Finally, we documented the regulatory mechanism between YAP-TEAD and HNF4α in rat and mouse tumor models, which confirmed our in vitro results. There is a double-negative feedback mechanism that controls TEAD-YAP and HNF4α expression in vitro and in vivo, thereby regulating cellular proliferation and differentiation. Given that YAP acts as a dominant oncogene in HCC and plays a crucial role in stem cell homeostasis and tissue regeneration, manipulating the interaction between YAP, TEADs, and HNF4α may provide a new approach for HCC treatment and regenerative medicine. (Hepatology 2017;65:1206-1221). © 2016 by the American Association for the Study of Liver Diseases.

Pearl Harbor, Hawaii 1 arc-second DEM

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National Oceanic and Atmospheric Administration, Department of Commerce — The 1/3-second Pearl Harbor Hawaii Elevation Grid provides bathymetric data in ASCII raster format of 1/3-second resolution in geographic coordinates. This grid is...

[Monogenic form of diabetes mellitus due to HNF4α mutation (MODY-1) - the first case in Hungary].

Science.gov (United States)

Jermendy, György; Balogh, István; Gaál, Zsolt

2016-03-20

The classification of diabetes mellitus in adolescents and young adults is often difficult. The diagnosis of the monogenic form of diabetes may have substantial influence on quality of life, prognosis and the choice of the appropriate treatment of affected patients. Among MODY (maturity-onset of diabetes in the young) MODY-1 is rarely detected, only 13 families were described in 2000, and 103 different mutations in 173 families were known in 2013 worldwide. The authors present the first Hungarian case of a monogenic form of diabetes due to HNF4α mutation (MODY-1). The diabetes of the index patient No. 1 (42-year-old woman with insulin treated diabetes) was diagnosed as gestational diabetes at age of 20 when she was treated with diet only. Later, insulin treatment has been initiated when marked hyperglycaemia was detected during an episode of acute pneumonia at age of 26. The diabetes of the index patient No. 2 (20-year-old daughter of the index patient No. 1, treated also with insulin) was diagnosed as type 2 diabetes at age of 13 and the patient was treated with diet only. Later the classification was modified to type 1 and insulin therapy was initiated at age of 14. The manifestation of diabetes, the familial occurrence and the low dose insulin requirement were suggestive for monogenic diabetes. Using molecular genetic method a mutation (c.869G>A, p.R290H) of HNF4α gene was found and MODY-1 was diagnosed in both cases. Insulin therapy was switched to treatment with low dose sulfanylurea and an excellent glycaemic control was achieved and sustained at follow-up of 1-year. No further positive cases were found during screening of other family members.

Interaction of hepatocyte nuclear factors in transcriptional regulation of tissue specific hormonal expression of human multidrug resistance-associated protein 2 (abcc2)

International Nuclear Information System (INIS)

Qadri, Ishtiaq; Hu, L.-J.; Iwahashi, Mieko; Al-Zuabi, Subhi; Quattrochi, Linda C.; Simon, Francis R.

2009-01-01

Multidrug resistance-associated protein 2 (MRP2) (ABCC2) is an ATP-binding cassette membrane protein located primarily on apical surface of hepatocytes that mediates transport of conjugated xenobiotics and endogenous compounds into bile. MRP2 is highly expressed in hepatocytes, and at lower levels in small intestines, stomach and kidney. Previous reports have characterized mammalian MRP2 promoters, but none have established the molecular mechanism(s) involved in liver enriched expression. This study aims to investigate the mechanism of hepatic MRP2 regulation. A 2130 bp of MRP2 promoter was cloned from PAC-1 clone P108G1-7, to identify putative liver specific/hormone responsive functional DNA binding sites. Using deletion analysis, site specific mutagenesis and co-transfection studies, liver specific expression was determined. MRP2 promoter-LUC constructs were highly expressed in liver cell lines compared to non-liver cells. The region extending from - 3 to+ 458 bp of MRP2 promoter starting from AUG contained the potential binding sites for CAAATT box enhancer binding protein (C/EBP), hepatocytes nuclear factor 1, 3 and 4 (HNF1, HNF3, and HNF4. Only HNF1 and HNF4 co-transfection with MRP2 luciferase increased expression. Site specific mutational analysis of HNF1 binding site indicated an important role for HNF1α. HNF4α induction of MRP2 was independent of HNF1 binding site. C/EBP, HNF3, and HNF6 inhibited HNF1α while HNF4α induced MRP2 luciferase expression and glucocorticoids stimulated MRP2 expression. This study emphasizes the complex regulation of MRP2 with HNF1α and HNF4α playing a central role. The coordinated regulation of xenobiotic transporters and oxidative conjugation may determine the adaptive responses to cellular detoxification processes

A model for steady-state HNF combustion

Energy Technology Data Exchange (ETDEWEB)

Louwers, J.; Gadiot, G.M.H.J.L. [TNO Prins Maurits Lab., Rijswijk (Netherlands); Brewster, M.Q. [Univ. of Illinois, Urbana, IL (United States); Son, S.F. [Los Alamos National Lab., NM (United States)

1997-09-01

A simple model for the combustion of solid monopropellants is presented. The condensed phase is treated by high activation energy asymptotics. The gas phase is treated by two limit cases: high activation energy, and low activation energy. This results in simplification of the gas phase energy equation, making an (approximate) analytical solution possible. The results of the model are compared with experimental results of Hydrazinium Nitroformate (HNF) combustion.

Tech Talk for Social Studies Teachers Lest We Forget: Remembering Pearl Harbor.

Science.gov (United States)

Green, Tim

2001-01-01

Presents an annotated bibliography that provides Web sites about Pearl Harbor (Hawaii). Includes Web sites that cover Pearl Harbor history, a live view of Pearl Harbor, stories from people who remember where they were during the attack, information on the naval station at Pearl Harbor, and a virtual tour of the USS Arizona. (CMK)

Developments on HNF based high performance and green solid propellants

NARCIS (Netherlands)

Keizers, H.L.J.; Heijden, A.E.D.M. van der; Vliet, L.D. van; Welland-Veltmans, W.H.M.; Ciucci, A.

2001-01-01

Worldwide developments are ongoing to develop new and more energetic composite solid propellant formulations for space transportation and military applications. Since the 90's, the use of HNF as a new high performance oxidiser is being reinvestigated. Within European development programmes,

76 FR 20287 - Superfund Site, New Bedford Harbor, New Bedford, MA: Anchorage Ground and Regulated Navigation Area

Science.gov (United States)

2011-04-12

... may lead to the discovery of a significant environmental impact from this proposed rule. List of... engaged in activities associated with remediation efforts in the New Bedford Harbor Superfund Site... activity can be performed without undue risk to environmental remediation efforts. Requests for waivers...

Intrinsic dechlorination of 1,2-dichloroethane at an industrial site

NARCIS (Netherlands)

Bosma, T.N.P.; Aalst-van Leeuwen, M.A. van; Gerritse, J.; Heiningen, E. van; Taat, J.; Pruijn, M.

1998-01-01

Bioremediation strategies for an industrial site located in the Rotterdam Harbor Area, the Netherlands and contaminated with 1,2-dichloroethane (1,2-DCA), are under investigation. The contamination is present in a confined anaerobic aquifer. The objective of the research is to assess the potential

Teaching about Pearl Harbor. Curriculum Enhancement Series #1.

Science.gov (United States)

Shields, Anna Marshall

These materials consist of sample lesson plans for teaching about the Japanese attack on Pearl Harbor on December 7, 1941, in both U.S. and world history classes. The lesson plans challenge students to examine how current attitudes toward the Japanese may be rooted in World War II and Pearl Harbor. Selected bibliographies on Pearl Harbor, World…

Induction of highly functional hepatocytes from human umbilical cord mesenchymal stem cells by HNF4α transduction.

Directory of Open Access Journals (Sweden)

Hualian Hang

Full Text Available To investigate the differentiation potential of human umbilical mesenchymal stem cells (HuMSCs and the key factors that facilitate hepatic differentiation.HuMSCs were induced to become hepatocyte-like cells according to a previously published protocol. The differentiation status of the hepatocyte-like cells was examined by observing the morphological changes under an inverted microscope and by immunofluorescence analysis. Hepatocyte nuclear factor 4 alpha (HNF4α overexpression was achieved by plasmid transfection of the hepatocyte-like cells. The expression of proteins and genes of interest was then examined by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR or real-time RT-PCR methods.Our results demonstrated that HuMSCs can easily be induced into hepatocyte-like cells using a published differentiation protocol. The overexpression of HNF4α in the induced HuMSCs significantly enhanced the expression levels of hepatic-specific proteins and genes. HNF4α overexpression may be associated with liver-enriched transcription factor networks and the Wnt/β-Catenin pathway.The overexpression of HNF4α improves the hepatic differentiation of HuMSCs and is a simple way to improve cellular sources for clinical applications.

Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway.

Science.gov (United States)

Wei, Shengnan; Zhang, Ming; Yu, Yang; Lan, Xiaoxin; Yao, Fan; Yan, Xin; Chen, Li; Hatch, Grant M

2016-01-01

Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122

Incidence of plasmid-linked antibiotic-heavy metal resistant enterics in water-sediment from agricultural and harbor sites

Energy Technology Data Exchange (ETDEWEB)

Mietz, J.A.; Sjorgren, R.E.

1983-01-01

This study assesses the impact of antibiotics used in clinical and veterinary practices on the incidence of antibiotic-heavy metal resistant enterics in fresh water and sediment from agricultural and harbor sample sites. A total of 848 bacterial strains of the family Enterobacteriaceae was isolated from agricultural and lake harbor samples. These were examined for anitbiotic-heavy metal resistance. A select smaller number of these isolates were also examined for the presence of plasmids and ability to transfer antibiotic resistance via conjugation or transformation. More than 85% of the 848 isolates from all four sites were resistant to Pb, Zn, and Co while 5.6% to 16% were resistant to Te and 2.4% to 5.7% to Hg. Of the total isolates tested, 87% were resistant to six or more antibiotics and 74% were also simultaneously resistant to Co, Zn, and Pb. Testing the resistance of the water isolates to antibiotics used solely in animal husbandry-veterinary medicine indicated that 55.6% of the agricultural isolates possessed resistance to these antibiotics while only 31.9% of the isolates from harbor water showed resistance to the same antibiotics. Of 41 ampicillin resistant isolates examined, 16 (39%) were capable of transferring antibiotic-heavy resistance markers via conjugation. From this same group, plasmid DNA preparations were made. Of these latter preparations, 67% transformed recipient E. coli cells while 58% possessed discernible, often multiple plasmids when examined by gel electrophoresis.

Variants of the HNF1α gene: a molecular approach concerning diabetic patients from southern Brazil

Directory of Open Access Journals (Sweden)

Naieli Bonatto

2012-01-01

Full Text Available Maturity Onset Diabetes of the Young (MODY presents monogenic inheritance and mutation factors which have already been identified in six different genes. Given the wide molecular variation present in the hepatocyte nuclear factor-1α gene (HNF1α MODY3, the aimof this study was to amplify and sequence the coding regions of this gene in seven patients from the Campos Gerais region, Paraná State, Brazil, presenting clinical MODY3 features. Besides the synonymous variations, A15A, L17L, Q141Q, G288G and T515T, two missense mutations, I27L and A98V, were also detected. Clinical and laboratory data obtained from patients were compared with the molecular findings, including the I27L polymorphism that was revealed in some overweight/obese diabetic patients of this study, this corroborating with the literature. We found certain DNA variations that could explain the hyperglycemic phenotype of the patients.

An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides.

Science.gov (United States)

Armour, Sean M; Remsberg, Jarrett R; Damle, Manashree; Sidoli, Simone; Ho, Wesley Y; Li, Zhenghui; Garcia, Benjamin A; Lazar, Mitchell A

2017-09-15

The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR-HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by hepatocyte nuclear factor 4α (HNF4α). The HDAC3-PROX1 module controls the expression of a gene program regulating lipid homeostasis, and hepatic-specific ablation of either component increases triglyceride content in liver. These findings underscore the importance of specific combinations of transcription factors and coregulators in the fine tuning of organismal metabolism.HDAC3 is a critical mediator of hepatic lipid metabolism and its loss leads to fatty liver. Here, the authors characterize the liver HDAC3 interactome in vivo, provide evidence that HDAC3 interacts with PROX1, and show that HDAC3 and PROX1 control expression of genes regulating lipid homeostasis.

A common variant within the HNF1B gene is associated with overall survival of multiple myeloma patients

DEFF Research Database (Denmark)

Ríos-Tamayo, Rafael; Lupiañez, Carmen Belén; Campa, Daniele

2016-01-01

Diabetogenic single nucleotide polymorphisms (SNPs) have recently been associated with multiple myeloma (MM) risk but their impact on overall survival (OS) of MM patients has not been analysed yet. In order to investigate the impact of 58 GWAS-identified variants for type 2 diabetes (T2D) on OS...... of patients with MM, we analysed genotyping data of 936 MM patients collected by the International Multiple Myeloma rESEarch (IMMENSE) consortium and an independent set of 700 MM patients recruited by the University Clinic of Heidelberg. A meta-analysis of the cox regression results of the two sets showed...... that rs7501939 located in the HNF1B gene negatively impacted OS (HRRec= 1.44, 95% CI = 1.18-1.76, P = 0.0001). The meta-analysis also showed a noteworthy gender-specific association of the SLC30A8rs13266634 SNP with OS. The presence of each additional copy of the minor allele at rs13266634 was associated...

33 CFR 100.109 - Winter Harbor Lobster Boat Race, Winter Harbor, ME.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Winter Harbor Lobster Boat Race, Winter Harbor, ME. 100.109 Section 100.109 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY REGATTAS AND MARINE PARADES SAFETY OF LIFE ON NAVIGABLE WATERS § 100.109 Winter Harbor...

A novel -192c/g mutation in the proximal P2 promoter of the hepatocyte nuclear factor-4 alpha gene (HNF4A) associates with late-onset diabetes

DEFF Research Database (Denmark)

Ek, Jakob; Hansen, Sara P; Lajer, Maria

2006-01-01

Recently, it has been shown that mutations in the P2 promoter of the hepatocyte nuclear factor (HNF)-4 alpha gene (HNF4A) cause maturity-onset diabetes of the young (MODY), while single nucleotide polymorphisms in this locus are associated with type 2 diabetes. In this study, we examined 1,189 bp...... of the P2 promoter and the associated exon 1D of HNF4A for variations associated with diabetes in 114 patients with type 2 diabetes, 72 MODYX probands, and 85 women with previous gestational diabetes mellitus. A -192c/g mutation was found in five patients. We screened 1,587 diabetic subjects and 4......,812 glucose-tolerant subjects for the -192c/g mutation and identified 5 diabetic and 1 glucose-tolerant mutation carriers (P=0.004). Examination of the families showed that carriers of the -192c/g mutation had a significantly impaired glucose-stimulated insulin release and lower levels of serum total...

Effect of the methionine ligand on the reorganization energy of the type-1 copper site of nitrite Reductase

DEFF Research Database (Denmark)

Farver, Ole; Wijma, Hein J.; MacPherson, Iain

2007-01-01

Copper-containing nitrite reductase harbors a type-1 and a type-2 Cu site. The former acts as the electron acceptor site of the enzyme, and the latter is the site of catalytic action. The effect of the methionine ligand on the reorganization energy of the type-1 site was explored by studying...

Emergence of colistin-resistant Escherichia coli clinical isolates harboring mcr-1 in Vietnam.

Science.gov (United States)

Tada, Tatsuya; Nhung, Pham Hong; Shimada, Kayo; Tsuchiya, Mitsuhiro; Phuong, Doan Mai; Anh, Nguyen Quoc; Ohmagari, Norio; Kirikae, Teruo

2017-10-01

The mcr-1 was first detected on a plasmid in colistin-resistant Escherichia coli from livestock and patients in China. We described here the emergence of colistin-resistant E. coli clinical isolates harboring mcr-1 on the chromosomes in Vietnam. To our knowledge, this is the first report of hospital-acquired E. coli isolates harboring mcr-1 in a medical setting in Vietnam. Copyright © 2017. Published by Elsevier Ltd.

Grays Harbor and Chehalis River Improvements to Navigation Environmental Studies. Wildlife Studies at Proposed Disposal Sites in Grays Harbor, Washington,

Science.gov (United States)

1982-01-01

sltand. T 𔃼~P i’ W 210 three times VtwCerI November IOC’C -nd ~co l.Etls ~ ec!,!zervc-o betxwe H -gF 12 Th -ind hl rway u- 7Plie Sicuobh. E. Cumin -s 1... stress imposed by dredge dsosal ;ictivities on these species. It is difficult to rredict the effects of establishing a salt marsh in Grays Harbor on

Red mangrove (Rhizophora mangle) reproduction and seedling colonization after Hurricane Charley: Comparisons of Charlotte Harbor and Tampa Bay

Science.gov (United States)

Proffitt, C.E.; Milbrandt, E.C.; Travis, S.E.

2006-01-01

Reproductive aspects of life history are known to be important in recovery following disturbance in many plant species although this has not been well studied in mangroves. Hurricane Charley devastated large areas of mangroves in Charlotte Harbor, Florida, in August 2004. We surveyed 6 forests in Charlotte Harbor (2002, 2003, and 2005) and 16 in Tampa Bay, Florida (2001, 2002, 2003, and 2005) for total numbers of reproducing trees and trees heterozygotic for albinism that produce both normal and albino propagules. Tree size (estimated height and diameter at breast height) was also recorded for sentinel heterozygotic trees. Total number of reproducing trees km-1 was used as an index of reproductive output of the population, and deviation from the 3:1 (normal:albino propagules) ratio on heterozygotic trees expected with 100% selfing was used to estimate outcrossing. Numbers of Rhizophora mangle reproducing trees km-1 of shoreline in Charlotte Harbor were reduced by an order of magnitude following Hurricane Charley, while numbers of reproducing trees in Tampa Bay were similar to those of previous years. Reduced reproduction in Charlotte Harbor was accompanied by fewer new recruits in plots on Sanibel and Captiva Islands. Numbers of new recruits after the storm also tended to be fewer in plots where canopy loss was greater. More new recruits occurred in sites that had higher densities of pre-storm Rhizophora seedlings and greater relative dominance by Rhizophora. Outcrossing of sentinel trees was 2.5 times greater in Charlotte Harbor (mean site-1 = 33.6 ?? 6.7%; with 17% of forest sites completely selfing) than in Tampa Bay (mean site-1 = 13.4 ?? 4.7%; with 40% of sites completely selfing), although the implications for seedling recruitment of this difference are not known. ?? 2006 Estuarine Research Federation.

MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2

Energy Technology Data Exchange (ETDEWEB)

Simion, Alexandru; Laudadio, Ilaria; Prevot, Pierre-Paul; Raynaud, Peggy; Lemaigre, Frederic P. [Universite catholique de Louvain, de Duve Institute, 75 Avenue Hippocrate 7529, B-1200 Brussels (Belgium); Jacquemin, Patrick, E-mail: patrick.jacquemin@uclouvain.be [Universite catholique de Louvain, de Duve Institute, 75 Avenue Hippocrate 7529, B-1200 Brussels (Belgium)

2010-01-01

MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate gene expression mainly by binding to the 3'UTR of their target mRNAs. Recent data revealed that microRNAs have an important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show that a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis, and in pancreas and liver at key stages of cell fate determination. Among the microRNAs that are expressed at these stages, miR-495 and miR-218 were predicted to, respectively, target the Onecut (OC) transcription factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2, two important regulators of liver and pancreas development. MiR-495 and miR-218 are dynamically expressed in developing liver and pancreas, and by transient transfection, we show that they target HNF-6 and OC-2 3'UTRs. Moreover, when overexpressed in cultured cells, miR-495 and miR-218 decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results indicate that the expression of regulators of liver and pancreas development is modulated by microRNAs. They also suggest a developmental role for miR-495 and miR-218.

MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2

International Nuclear Information System (INIS)

Simion, Alexandru; Laudadio, Ilaria; Prevot, Pierre-Paul; Raynaud, Peggy; Lemaigre, Frederic P.; Jacquemin, Patrick

2010-01-01

MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate gene expression mainly by binding to the 3'UTR of their target mRNAs. Recent data revealed that microRNAs have an important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show that a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis, and in pancreas and liver at key stages of cell fate determination. Among the microRNAs that are expressed at these stages, miR-495 and miR-218 were predicted to, respectively, target the Onecut (OC) transcription factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2, two important regulators of liver and pancreas development. MiR-495 and miR-218 are dynamically expressed in developing liver and pancreas, and by transient transfection, we show that they target HNF-6 and OC-2 3'UTRs. Moreover, when overexpressed in cultured cells, miR-495 and miR-218 decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results indicate that the expression of regulators of liver and pancreas development is modulated by microRNAs. They also suggest a developmental role for miR-495 and miR-218.

Development of Site-Specific Water Quality Criteria for the Arpa Harbor Wastewater Treatment Plant in Tipalao Bay, Guam

Science.gov (United States)

2016-07-01

flats, estuaries, and coastal creeks. It is usually found within tidally influenced waters , but it may enter freshwater, ascending about 10...based on a dissolved metal concentration endpoint in the receiving body of water . In other words , the translator supports estimations of the fraction of...TECHNICAL REPORT 2068 July 2016 Development of Site-Specific Water Quality Criteria for the Arpa Harbor Wastewater Treatment Plant

Cytoskeletal actin genes function downstream of HNF-3beta in ascidian notochord development.

Science.gov (United States)

Jeffery, W R; Ewing, N; Machula, J; Olsen, C L; Swalla, B J

1998-11-01

We have examined the expression and regulation of cytoskeletal actin genes in ascidians with tailed (Molgula oculata) and tailless larvae (Molgula occulta). Four cDNA clones were isolated representing two pairs of orthologous cytoskeletal actin genes (CA1 and CA2), which encode proteins differing by five amino acids in the tailed and tailless species. The CA1 and CA2 genes are present in one or two copies, although several related genes may also be present in both species. Maternal CA1 and CA2 mRNA is present in small oocytes but transcript levels later decline, suggesting a role in early oogenesis. In the tailed species, embryonic CA1 and CA2 mRNAs first appear in the presumptive mesenchyme and muscle cells during gastrulation, subsequently accumulate in the presumptive notochord cells, and can be detected in these tissues through the tadpole stage. CA1 mRNAs accumulate initially in the same tissues in the tailless species but subsequently disappear, in concert with the arrest of notochord and tail development. In contrast, CA2 mRNAs were not detected in embryos of the tailless species. Fertilization of eggs of the tailless species with sperm of the tailed species, which restores the notochord and the tail, also results in the upregulation of CA1 and CA2 gene expression in hybrid embryos. Antisense oligodeoxynucleotide experiments suggest that CA1 and CA2 expression in the notochord, but not in the muscle cells, is dependent on prior expression of Mocc FHI, an ascidian HNF-3beta-like gene. The expression of the CA1 and CA2 genes in the notochord in the tailed species, downregulation in the tailless species, upregulation in interspecific hybrids, and dependence on HNF-3beta activity is consistent with a role of these genes in development of the ascidian notochord.

NifH- Harboring Bacterial Community Composition Across an Alaskan Permafrost Thaw Gradient

Directory of Open Access Journals (Sweden)

Christopher Ryan Penton

2016-11-01

Full Text Available Since nitrogen (N is often limiting in permafrost soils, we investigated the N2-fixing genetic potential and the inferred taxa harboring those genes by sequencing nifH gene fragments in samples taken along a permafrost thaw gradient in an Alaskan boreal soil. Samples from minimally, moderately and extensively thawed sites were taken to a depth of 79 cm to encompass zones above and below the depth of the water table. NifH reads were translated with frameshift correction and 112,476 sequences were clustered at 5% amino acid dissimilarity resulting in 1,631 OTUs. Sample depth in relation to water table depth was correlated to differences in the NifH sequence classes. NifH sequences most closely related to group I nifH-harboring Alpha- and Beta Proteobacteria were in higher abundance above water table depth while those related to group III nifH-harboring Delta and Gamma Proteobacteria were more abundant below. The most dominant below water table depth NifH sequences, comprising 1/3 of the total, were distantly related to Verrucomicrobia-Opitutaceae. Overall, these results suggest that permafrost thaw alters the class-level composition of N2-fixing communities in the thawed soil layers and that this distinction corresponds to the depth of the water table. These nifH data were also compared to nifH sequences obtained from a study at an Alaskan taiga site, and to those of other geographically distant, non-permafrost sites. The two Alaska sites were differentiated largely by changes in relative abundances of the same OTUs, whereas the non-Alaska sites were differentiated by the lack of many Alaskan OTUs, and the presence of unique halophilic, sulfate- and iron-reducing taxa in the Alaska sites.

Identification of evolutionarily invariant sequences in the protein C gene promoter

NARCIS (Netherlands)

Spek, C. A.; Bertina, R. M.; Reitsma, P. H.

1998-01-01

Recent studies on human protein C gene expression have revealed the presence of three transcription factor binding sites in close proximity to the transcription start site. Binding sites for the liver-enriched hepatocyte nuclear factors 1 and 3 (HNF-1 and HNF-3, respectively) are located immediately

Three-year summary report of biological monitoring at the Southwest Ocean dredged-material disposal site and additional locations off Grays Harbor, Washington, 1990--1992

Energy Technology Data Exchange (ETDEWEB)

Antrim, L.D.; Shreffler, D.K.; Pearson, W.H.; Cullinan, V.I. [Battelle Marine Research Lab., Sequim, WA (United States)

1992-12-01

The Grays Harbor Navigation Improvement Project was initiated to improve navigation by widening and deepening the federal channel at Grays Harbor. Dredged-material disposal sites were selected after an extensive review process that included inter-agency agreements, biological surveys, other laboratory and field studies, and preparation of environmental impact statements The Southwest Site, was designated to receive materials dredged during annual maintenance dredging as well as the initial construction phase of the project. The Southwest Site was located, and the disposal operations designed, primarily to avoid impacts to Dungeness crab. The Final Environmental Impact Statement Supplement for the project incorporated a Site Monitoring Plan in which a tiered approach to disposal site monitoring was recommended. Under Tier I of the Site Monitoring Plan, Dungeness crab densities are monitored to confirm that large aggregations of newly settled Dungeness crab have not moved onto the Southwest Site. Tier 2 entails an increased sampling effort to determine whether a change in disposal operations is needed. Four epibenthic surveys using beam trawls were conducted in 1990, 1991, and 1992 at the Southwest Site and North Reference area, where high crab concentrations were found in the spring of 1985. Survey results during these three years prompted no Tier 2 activities. Epibenthic surveys were also conducted at two nearshore sites where construction of sediment berms has been proposed. This work is summarized in an appendix to this report.

Temporal and spatial variation in harbor seal (Phoca vitulina L.) roar calls from southern Scandinavia

DEFF Research Database (Denmark)

Sabinsky, Puk Faxe; Larsen, Ole Næsbye; Wahlberg, Magnus

2017-01-01

Male harbor seals gather around breeding sites for competitive mating displays. Here, they produce underwater vocalizations possibly to attract females and/or scare off other males. These calls offer prospects for passive acoustic monitoring. Acoustic monitoring requires a good understanding...... of natural variation in calling behavior both temporally and among geographically separate sites. Such variation in call structure and calling patterns were studied in harbor seal vocalizations recorded at three locations in Danish and Swedish waters. There was a strong seasonality in the calls from end...... biological differences when comparing harbor seal roars among recording sites and between years....

Bioaccumulation of polychlorinated biphenyls and organochlorine pesticides in young-of-the-year bluefish (Pomatomus saltatrix) in the vicinity of a Superfund Site in New Bedford Harbor, Massachusetts, and in the adjacent waters.

Science.gov (United States)

Deshpande, Ashok D; Dockum, Bruce W; Cleary, Thomas; Farrington, Cameron; Wieczorek, Daniel

2013-07-15

Spatial gradients of polychlorinated biphenyls (PCBs) and organochlorine pesticides were examined in the young-of-the-year (YOY) bluefish (Pomatomus saltatrix) in the vicinity of a PCB Superfund Site in New Bedford Harbor, Massachusetts, and in the adjacent waters. PCB concentrations in bluefish varied between different locations, and also among fish from a given location. A generally decreasing gradient in PCB concentrations was evident as the bluefish were collected away from the Superfund Site. The average sum of PCB concentrations were highest for bluefish collected in the Upper Harbor between Interstate-195 Bridge and Coggeshall Street Bridge (Upper Harbor), followed by bluefish in Lower Harbor from north of Popes Island Bridge (Lower Harbor), and bluefish from Outer Harbor south of Hurricane Barrier (Outer Harbor). The levels of PCBs in bluefish from Clarks Cove and PCBs in bluefish from Buzzards Bay were similar and lowest among all bluefish specimens analyzed in the present study. Pesticide concentrations were about one order of magnitude or lower than the PCB concentrations, and the gradient of pesticide concentrations generally followed the gradient of PCB concentrations. Some of the commonly detected pesticides in the order of decreasing concentrations included DDTs and metabolites, heptachlor epoxide, endosulfan sulfate, and α-chlordane. Distribution of PCBs and organochlorine pesticides were examined in the tissues of YOY bluefish from Clarks Cove. PCBs and lipids in the brain samples of YOY bluefish were generally numerically greater than PCBs in the liver samples, but these differences were not statistically significant. PCBs and lipids in hypaxial muscle samples were numerically greater than PCBs in epaxial muscle samples, although these two groups of tissues were not statistically different. Despite the higher susceptibility of lighter PCB homologs to geophysical and biogeochemical weathering processes, the relative dominance of lighter homologs

Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β.

Science.gov (United States)

Choi, Yun-Hee; McNally, Brian T; Igarashi, Peter

2013-07-01

Hepatocyte nuclear factor-1β (HNF-1β) is an epithelial tissue-specific transcription factor that regulates gene expression in the kidney, liver, pancreas, intestine, and other organs. Mutations of HNF-1β in humans produce renal cysts and congenital kidney anomalies. Here, we identify the LIM-domain protein zyxin as a novel binding partner of HNF-1β in renal epithelial cells. Zyxin shuttles to the nucleus where it colocalizes with HNF-1β. Immunoprecipitation of zyxin in leptomycin B-treated cells results in coprecipitation of HNF-1β. The protein interaction requires the second LIM domain of zyxin and two distinct domains of HNF-1β. Overexpression of zyxin stimulates the transcriptional activity of HNF-1β, whereas small interfering RNA silencing of zyxin inhibits HNF-1β-dependent transcription. Epidermal growth factor (EGF) induces translocation of zyxin into the nucleus and stimulates HNF-1β-dependent promoter activity. The EGF-mediated nuclear translocation of zyxin requires activation of Akt. Expression of dominant-negative mutant HNF-1β, knockdown of zyxin, or inhibition of Akt inhibits EGF-stimulated cell migration. These findings reveal a novel pathway by which extracellular signals are transmitted to the nucleus to regulate the activity of a transcription factor that is essential for renal epithelial differentiation.

Implementation guide for Hanford Tanks Initiative C-106 heel retrieval contract management HNF-2511

International Nuclear Information System (INIS)

McDaniel, L.B.

1998-01-01

This report is an Implementation Guide for Hanford Tanks Initiative C-106 heel retrieval contract management HNF-2511 to provide a set of uniform instructions for managing the two contractors selected. The primary objective is to produce the necessary deliverables and services for the HTI project within schedule and budget

Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line.

Science.gov (United States)

Takahashi, Shigeru; Matsuura, Naomi; Kurokawa, Takako; Takahashi, Yuji; Miura, Takashi

2002-11-01

We reported previously that the 5'-flanking region (nucleotides -1976 to -1655) of the human haem oxygenase-1 ( hHO-1 ) gene enhances hHO-1 promoter activity in human hepatoma HepG2 cells, but not in HeLa cells [Takahashi, Takahashi, Ito, Nagano, Shibahara and Miura (1999) Biochim. Biophys. Acta 1447, 231-235]. To define more precisely the regulatory elements involved, in the present study we have functionally dissected this region and localized the enhancer to a 50 bp fragment (-1793 to -1744). Site-direct mutagenesis analysis revealed that two regions were responsible for this enhancer activity, i.e. a hepatocyte nuclear factor-4 (HNF-4) homologous region and a GC box motif homologous region. Mutation in either region alone moderately decreased enhancer activity. However, mutations in both regions reduced promoter activity to the basal level. Electrophoretic mobility-shift assays demonstrated that the P5-2 fragment (-1793 to -1744) interacted with at least two nuclear factors, i.e. HNF-4 and Sp1/Sp3. Co-transfection experiments using Drosophila SL2 cells revealed that HNF-4 and Sp1/Sp3 synergistically stimulated the enhancer activity of the P5-2 fragment. These results indicate that co-operation of HNF-4 with Sp1 or Sp3 leads to the activation of hHO-1 gene expression in hepatoma cells.

Waste Analysis Plan for the Low-Level Burial Grounds [CANCELLED] Reissued as HNF-5841

International Nuclear Information System (INIS)

ELLEFSON, M.D.

2000-01-01

Canceled see HNF-5841 Rev 0. This waste analysis plan (WAP) has been prepared for the Low-Level Burial Grounds which are located in the 200 East and West Areas of the Hanford Facility, Richland, Washington. This WAP documents the methods used to characterize, obtain and analyze representative samples of waste managed at this unit

Hanford site transuranic waste sampling plan

International Nuclear Information System (INIS)

GREAGER, T.M.

1999-01-01

This sampling plan (SP) describes the selection of containers for sampling of homogeneous solids and soil/gravel and for visual examination of transuranic and mixed transuranic (collectively referred to as TRU) waste generated at the U.S. Department of Energy (DOE) Hanford Site. The activities described in this SP will be conducted under the Hanford Site TRU Waste Certification Program. This SP is designed to meet the requirements of the Transuranic Waste Characterization Quality Assurance Program Plan (CAO-94-1010) (DOE 1996a) (QAPP), site-specific implementation of which is described in the Hanford Site Transuranic Waste Characterization Program Quality Assurance Project Plan (HNF-2599) (Hanford 1998b) (QAPP). The QAPP defines the quality assurance (QA) requirements and protocols for TRU waste characterization activities at the Hanford Site. In addition, the QAPP identifies responsible organizations, describes required program activities, outlines sampling and analysis strategies, and identifies procedures for characterization activities. The QAPP identifies specific requirements for TRU waste sampling plans. Table 1-1 presents these requirements and indicates sections in this SP where these requirements are addressed

Ecological evaluation of proposed discharge of dredged material from Oakland Harbor into ocean waters (Phase 1 of -42-foot project)

International Nuclear Information System (INIS)

Word, J.Q.; Ward, J.A.; Strand, J.A.; Cullinan, V.I.; Crecelius, E.A.; Steinhauer, W.; Hyland, J.L.

1990-09-01

The US Army Corps of Engineers (USACE), San Francisco District, was authorized by the Water Resources Development Act of 1986 (Public Law 99-662) to deepen and widen the navigation channels of Inner and Outer Oakland Harbor, California, to accommodate modern deep-draft vessels. To help provide the scientific basis for determining whether Oakland Harbor sediments are suitable for offshore disposal, the Battelle/Marine Sciences Laboratory collected sediment cores from 20 stations in Oakland Harbor, evaluated the cores geologically, analyzed sediment for selected contaminants, conducted a series of solid phase toxicity tests with four sensitive marine invertebrates (Macoma nasuta, Nephtys caecoides, Ampelisca abdita, and Rhepoxynius abronius), and assessed the bioaccumulation potential of sediment-associated contaminants in tissues of M. nasuta. Toxicological test results indicate that none of the sediment from the channel-area stations (CH-1 - CH-7), the Merritt Sand samples (MS-1 and MS-2), or the reference sediment sites (PR-C and PR-F) resulted in significant sediment toxicity to the four species tested. Sediment treatments showing no significant sediment toxicity as well as no significant bioaccumulation included CH-5, MS-1, MS-2, PR-coarse, and PR-fine. Stations that showed little or no significant sediment toxicity, but significant bioaccumulation included SS-2-L (PAHs); TS-1-L (Cu, PAHs, PCBs, tributyltin, and DDE); TS-1-U (tributyltin); TS-5-U (PAHs, PCBs, DDE, and tributyltin); SS-1-U (PB, PAHs, and PCBs); SS-5-L (PAHs, PCBs, and DDE); CH-6 and CH-7 (PAHs, PCBs, and DDE); Ch-4 and CH-1 (Cr); and CH-3 (DDE). 28 refs., 31 figs., 75 tabs

Synergistic growth inhibition of cancer cells harboring the RET/PTC1 ...

Indian Academy of Sciences (India)

Synergistic growth inhibition of cancer cells harboring the RET/PTC1 oncogene by staurosporine and rotenone involves enhanced cell death. ANTÓNIO PEDRO GONÇALVES, ARNALDO VIDEIRA, VALDEMAR MÁXIMO and PAULA SOARES. J. Biosci. 36(4), September 2011, 639-648, © Indian Academy of Sciences.

77 FR 19967 - Safety Zone, Port of Dutch Harbor; Dutch Harbor, AK

Science.gov (United States)

2012-04-03

...-AA00 Safety Zone, Port of Dutch Harbor; Dutch Harbor, AK AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast Guard proposes temporary safety zones in the Port of Dutch Harbor... Dutch Harbor, Alaska, and the adjacent territorial sea due to additional vessel traffic associated with...

PCBs and DDE in tree swallow (Tachycineta bicolor) eggs and nestlings from an estuarine PCB superfund site, New Bedford Harbor, MA, U.S.A.

Science.gov (United States)

Jayaraman, Saro; Nacci, Diane E.; Champlin, Denise M.; Pruell, Richard J.; Rocha, Kenneth J.; Custer, Christine M.; Custer, Thomas W.; Cantwell, Mark

2009-01-01

While breeding tree swallows (Tachycineta bicolor) have been used as biomonitors for freshwater sites, we report the first use of this species to assess contaminant bioaccumulation from estuarine breeding grounds into these aerial insectivores. Eggs and nestlings were collected from nest boxes in a polychlorinated biphenyl (PCB) contaminated estuary, the New Bedford Harbor Superfund site (NBH, Massachusetts, USA), and a reference salt marsh, Fox Hill (FH, Jamestown, Rhode Island, USA). Sediments, eggs, and nestlings were compared on a ng g−1 wet weight basis for total PCBs and DDE (1,1-bis-(4-chlorophenyl)-2,2-dichloroethene), metabolite of DDT (1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane). NBH samples contained high concentrations of PCBs compared to FH for sediment (36,500 and 0.2), eggs (11,200 and 323), and nestlings (16,800 and 26). PCB homologue patterns linked tree swallow contamination to NBH sediment. NBH samples were also contaminated with DDE compared to FH for sediment (207 and 0.9) and nestlings (235 and 30) but not for eggs (526 and 488), suggesting both NBH and nonbreeding ground sources for DDE. The relationships between sediment and tree swallow egg and nestling PCBs were similar to those reported for freshwater sites. Like some highly contaminated freshwater sites, NBH PCB bioaccumulation had little apparent effect on reproductive success.

Project W-314 acceptance test report HNF-4651 for HNF-4650 SN-268 encasement leak detection ANA-WT-LDSTA-335 for project W-314

International Nuclear Information System (INIS)

HAMMERS, J.S.

1999-01-01

The purpose of the test was to verify that the AN Tank Farm Encasement Leak Detector components are functionally integrated and operate in accordance with engineering design specifications The Acceptance Test Procedure HNF-4650, SN-268 Encasement Leak Detection ANA-W-LDSTA-335, was conducted between 22 June and 01 July 1999 at the 200E AN Tank Farm. The test has been completed with no open test exceptions The test was conducted prior to final engineering ''as built'' activities being completed this had no impact on the procedure or test results. All components, identified in the procedure, were found to be labeled and identified as written in the procedure

Should the negativity for islet cell autoantibodies be used in a prescreening for genetic testing in maturity-onset diabetes of the young? The case of autoimmunity-associated destruction of pancreatic β-cells in a family of HNF1A-MODY subjects.

Science.gov (United States)

Urbanová, Jana; Rypáčková, Blanka; Kučera, Petr; Anděl, Michal; Heneberg, Petr

2013-01-01

It was recently suggested that routine islet cell autoantibody testing should be performed to discriminate maturity-onset diabetes of the young (MODY) from type 1 diabetes mellitus (T1DM). This is the first report ever to describe the familial manifestation of T1DM autoimmunity in nonobese HNF1A-MODY subjects and the presence of islet antigen-2 (IA-2) antibodies in MODY subjects. Three nonobese subjects in an age range of 14-35 years were diagnosed with HNF1A-MODY (p. Arg159Gln mutation). All the tested subjects had detectable (but varying) levels of islet cell autoantibodies (i.e., antibodies against glutamate decarboxylase or IA-2) in the absence of other T1DM characteristics. They displayed long-term expression of intermediate fasting C-peptide levels, ketoacidosis was absent even in periods of spontaneous insulin withdrawal, and full dependence on externally administered insulin was not detected in any of them although better glycemic control was achieved when insulin was supplemented. The course of the disease was similar to that of the autoantibody-negative HNF1A-MODY subjects. The case questions the selectivity of autoantibodies as a marker of T1DM or late-onset autoimmune diabetes of adulthood (LADA) over MODY and challenges the use of autoantibodies as a universal negative marker of MODY in an effort to decrease the cost of health care, as it may eventually lead to the wrong diagnosis and thus to the incorrect treatment. Further research should involve examination of the autoantibody titers and prevalence in large and geographically diverse cohorts of MODY subjects selected for genetic testing (regardless of their autoantibody titers) as well as determination of the islet cell autoantibody kinetics in the course of MODY onset and progression. Copyright © 2013 S. Karger AG, Basel.

Diffuse glomerular nodular lesions in diabetic pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha, an inheritant diabetic gene in humans.

Directory of Open Access Journals (Sweden)

Satoshi Hara

Full Text Available Glomerular nodular lesions, known as Kimmelstiel-Wilson nodules, are a pathological hallmark of progressive human diabetic nephropathy. We have induced severe diabetes in pigs carrying a dominant-negative mutant hepatocyte nuclear factor 1-alpha (HNF1α P291fsinsC, a maturity-onset diabetes of the young type-3 (MODY3 gene in humans. In this model, glomerular pathology revealed that formation of diffuse glomerular nodules commenced as young as 1 month of age and increased in size and incidence until the age of 10 months, the end of the study period. Immunohistochemistry showed that the nodules consisted of various collagen types (I, III, IV, V and VI with advanced glycation end-product (AGE and Nε-carboxymethyl-lysine (CML deposition, similar to those in human diabetic nodules, except for collagen type I. Transforming growth factor-beta (TGF-β was also expressed exclusively in the nodules. The ultrastructure of the nodules comprised predominant interstitial-type collagen deposition arising from the mesangial matrices. Curiously, these nodules were found predominantly in the deep cortex. However, diabetic pigs failed to show any of the features characteristic of human diabetic nephropathy; e.g., proteinuria, glomerular basement membrane thickening, exudative lesions, mesangiolysis, tubular atrophy, interstitial fibrosis, and vascular hyalinosis. The pigs showed only Armanni-Ebstein lesions, a characteristic tubular manifestation in human diabetes. RT-PCR analysis showed that glomeruli in wild-type pigs did not express endogenous HNF1α and HNF1β, indicating that mutant HNF1α did not directly contribute to glomerular nodular formation in diabetic pigs. In conclusion, pigs harboring the dominant-negative mutant human MODY3 gene showed reproducible and distinct glomerular nodules, possibly due to AGE- and CML-based collagen accumulation. Although the pathology differed in several respects from that of human glomerular nodular lesions, the

Canister storage building compliance assessment SNF project NRC equivalency criteria - HNF-SD-SNF-DB-003

International Nuclear Information System (INIS)

BLACK, D.M.

1999-01-01

This document presents the Project's position on compliance with the SNF Project NRC Equivalency Criteria - HNF-SD-SNF-DE-003, Spent Nuclear Fuel Project Path Forward Additional NRC Requirements. No non-compliances are shown. The compliance statements have been reviewed and approved by DOE. Open items are scheduled to be closed prior to project completion

Identification and functional analysis of novel phosphorylation sites in the RNA surveillance protein Upf1.

Science.gov (United States)

Lasalde, Clarivel; Rivera, Andrea V; León, Alfredo J; González-Feliciano, José A; Estrella, Luis A; Rodríguez-Cruz, Eva N; Correa, María E; Cajigas, Iván J; Bracho, Dina P; Vega, Irving E; Wilkinson, Miles F; González, Carlos I

2014-02-01

One third of inherited genetic diseases are caused by mRNAs harboring premature termination codons as a result of nonsense mutations. These aberrant mRNAs are degraded by the Nonsense-Mediated mRNA Decay (NMD) pathway. A central component of the NMD pathway is Upf1, an RNA-dependent ATPase and helicase. Upf1 is a known phosphorylated protein, but only portions of this large protein have been examined for phosphorylation sites and the functional relevance of its phosphorylation has not been elucidated in Saccharomyces cerevisiae. Using tandem mass spectrometry analyses, we report the identification of 11 putative phosphorylated sites in S. cerevisiae Upf1. Five of these phosphorylated residues are located within the ATPase and helicase domains and are conserved in higher eukaryotes, suggesting a biological significance for their phosphorylation. Indeed, functional analysis demonstrated that a small carboxy-terminal motif harboring at least three phosphorylated amino acids is important for three Upf1 functions: ATPase activity, NMD activity and the ability to promote translation termination efficiency. We provide evidence that two tyrosines within this phospho-motif (Y-738 and Y-742) act redundantly to promote ATP hydrolysis, NMD efficiency and translation termination fidelity.

Increased hepatic FAT/CD36, PTP1B and decreased HNF4A expression contributes to dyslipidemia associated with ethanol-induced liver dysfunction: Rescue effect of ginger extract.

Science.gov (United States)

Shirpoor, Alireza; Heshmati, Elaheh; Kheradmand, Fatemeh; Gharalari, Farzaneh Hosseini; Chodari, Leila; Naderi, Roya; Majd, Farideh Nezami; Samadi, Mahrokh

2018-05-28

The association between chronic alcohol consumption and the development of alcpholic liver disease is a very well known phenomenon, but the precise underlying molecular mediators involved in ethanol-induced liver disease remain elusive. This study aimed to characterize the lipid metabolism alterations and the molecular mediators which are related to lipid metabolism in liver under the heavy ethanol exposure alone or combined with ginger extract. Twenty-four male wistar rats were assigned into three groups, namely control, ethanol, and ginger extract treated ethanol (GETE) groups. Six weeks after the treatment, the ethanol group showed a significant increase in fatty acid translocase (FAT)/CD36, protein tyrosine phosphatase 1B (PTP1B) and decrease hepatocyte nuclear factor 4 Alpha (HNF4A) genes expressions compared to the control group. The ethanol administration also significantly increased plasma LDL, cholesterol, triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group. Moreover, compared to the control group, the ethanol group showed liver histhological changes, such as fibrosis, focal microvesicular steatosis, some apoptotic hepatocytes, spotty necrosis, portal lymphocytic inflammation, mallory-denk bodies, giant mitochondria, piecemeal necrosis. Consumption of ginger extract along with ethanol, partially ameliorated gene expression alteration and histological changes, improved undesirable lipid profile and liver enzymes changes compare to those in the ethanol group. These findings indicate that ethanol-induced liver abnormalities may in part be associated with lipid homeostasis changes mediated by overexpression of FAT/CD36, PTP1B and downexpressionof HNF4A genes. It also show that these effects can be reduced by using ginger extract as an antioxidant and anti-inflammatory agent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Project W-314 acceptance test report HNF-4647 for HNF-4646 241-B pit leak detection ANB-WT-LDSTA-231 for project W-314

International Nuclear Information System (INIS)

HAMMERS, J.S.

1999-01-01

The purpose of the test was to verify that the AN Tank Farm B Pit Leak Detector components are functionally integrated and operate in accordance with engineering design specifications. The Acceptance Test Procedure HNF-4646,241-AN-B-Pit Leak Detection ANB-WT-LDSTA-231 was conducted between 26 June and 02 July 1999 at the 200E AN Tank Farm. The test has been completed with no open test exceptions. The test was conducted prior to final engineering ''as built'' activities being completed this had no impact on the procedure or test results. All components, identified in the procedure were found to be labeled and identified as written in the procedure

Integrated approach to assess ecosystem health in harbor areas.

Science.gov (United States)

Bebianno, M J; Pereira, C G; Rey, F; Cravo, A; Duarte, D; D'Errico, G; Regoli, F

2015-05-01

Harbors are critical environments with strategic economic importance but with potential environmental impact: health assessment criteria are a key issue. An ecosystem health status approach was carried out in Portimão harbor as a case-study. Priority and specific chemical levels in sediments along with their bioavailability in mussels, bioassays and a wide array of biomarkers were integrated in a biomarker index (IBR index) and the overall data in a weight of evidence (WOE) model. Metals, PAHs, PCBs and HCB were not particularly high compared with sediment guidelines and standards for dredging. Bioavailability was evident for Cd, Cu and Zn. Biomarkers proved more sensitive namely changes of antioxidant responses, metallothioneins and vittellogenin-like proteins. IBR index indicated that site 4 was the most impacted area. Assessment of the health status by WOE approach highlighted the importance of integrating sediment chemistry, bioaccumulation, biomarkers and bioassays and revealed that despite some disturbance in the harbor area, there was also an impact of urban effluents from upstream. Environmental quality assessment in harbors. Copyright © 2015 Elsevier B.V. All rights reserved.

Caffeine in Boston Harbor past and present, assessing its utility as a tracer of wastewater contamination in an urban estuary

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Sites throughout Boston Harbor were analyzed for caffeine to assess its utility as a tracer in identifying sources of sanitary wastewater. Caffeine ranged from 15 ng/L in the outer harbor to a high of 185 ng/L in the inner harbor. Inner harbor concentrations were a result of comb...

Selenium and mercury concentrations in harbor seals (Phoca vitulina) from central California: Health implications in an urbanized estuary

Science.gov (United States)

McHuron, Elizabeth A.; Harvey, James T.; Castellini, J. Margaret; Stricker, Craig A.; O'Hara, Todd M.

2014-01-01

We measured total selenium and total mercury concentrations ([TSe] and [THg]) in hair (n = 138) and blood (n = 73) of harbor seals (Phoca vitulina) from California to assess variation by geography and sex, and inferred feeding relationships based on carbon, nitrogen, and sulfur stable isotopes. Harbor seals from Hg-contaminated sites had significantly greater [THg], and lesser [TSe] and TSe:THg molar ratios than seals from a relatively uncontaminated site. Males had significantly greater [THg] than females at all locations. Sulfur stable isotope values explained approximately 25% of the variability in [THg], indicating increased Hg exposure for seals with a greater use of estuarine prey species. Decreased [TSe] in harbor seals from Hg-contaminated regions may indicate a relative Se deficiency to mitigate the toxic effects of Hg. Further investigation into the Se status and the potential negative impact of Hg on harbor seals from Hg-contaminated sites is warranted.

Geoscience rediscovers Phoenicia's buried harbors

Science.gov (United States)

Marriner, Nick; Morhange, Christophe; Doumet-Serhal, Claude; Carbonel, Pierre

2006-01-01

After centuries of archaeological debate, the harbors of Phoenicia's two most important city states, Tyre and Sidon, have been rediscovered, and including new geoarcheological results reveal how, where, and when they evolved after their Bronze Age foundations. The early ports lie beneath their present urban centers, and we have indentified four harbor phases. (1) During the Bronze Age, Tyre and Sidon were characterized by semi-open marine coves that served as protoharbors. (2) Biostratigraphic and lithostratigraphic data indicate the presence of early artificial basins after the first millennium B.C. (3) The harbors reached their apogees during the Greco-Roman and Byzantine periods. (4) Silting up and coastal progradation led to burial of the medieval basins, lost until now.

Calculating background levels for ecological risk parameters in toxic harbor sediment

Science.gov (United States)

Leadon, C.J.; McDonnell, T.R.; Lear, J.; Barclift, D.

2007-01-01

Establishing background levels for biological parameters is necessary in assessing the ecological risks from harbor sediment contaminated with toxic chemicals. For chemicals in sediment, the term contaminated is defined as having concentrations above background and significant human health or ecological risk levels. For biological parameters, a site could be considered contaminated if levels of the parameter are either more or less than the background level, depending on the specific parameter. Biological parameters can include tissue chemical concentrations in ecological receptors, bioassay responses, bioaccumulation levels, and benthic community metrics. Chemical parameters can include sediment concentrations of a variety of potentially toxic chemicals. Indirectly, contaminated harbor sediment can impact shellfish, fish, birds, and marine mammals, and human populations. This paper summarizes the methods used to define background levels for chemical and biological parameters from a survey of ecological risk investigations of marine harbor sediment at California Navy bases. Background levels for regional biological indices used to quantify ecological risks for benthic communities are also described. Generally, background stations are positioned in relatively clean areas exhibiting the same physical and general chemical characteristics as nearby areas with contaminated harbor sediment. The number of background stations and the number of sample replicates per background station depend on the statistical design of the sediment ecological risk investigation, developed through the data quality objective (DQO) process. Biological data from the background stations can be compared to data from a contaminated site by using minimum or maximum background levels or comparative statistics. In Navy ecological risk assessments (ERA's), calculated background levels and appropriate ecological risk screening criteria are used to identify sampling stations and sites with contaminated

Characterization of differential gene expression in adrenocortical tumors harboring beta-catenin (CTNNB1) mutations.

Science.gov (United States)

Durand, Julien; Lampron, Antoine; Mazzuco, Tania L; Chapman, Audrey; Bourdeau, Isabelle

2011-07-01

Mutations of β-catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and adrenocortical carcinomas (ACC). However, the target genes of β-catenin have not yet been identified in adrenocortical tumors. Our objective was to identify genes deregulated in adrenocortical tumors harboring CTNNB1 genetic alterations and nuclear accumulation of β-catenin. Microarray analysis identified a dataset of genes that were differently expressed between AA with CTNNB1 mutations and wild-type (WT) tumors. Within this dataset, the expression profiles of five genes were validated by real time-PCR (RT-PCR) in a cohort of 34 adrenocortical tissues (six AA and one ACC with CTNNB1 mutations, 13 AA and four ACC with WT CTNNB1, and 10 normal adrenal glands) and two human ACC cell lines. We then studied the effects of suppressing β-catenin transcriptional activity with the T-cell factor/β-catenin inhibitors PKF115-584 and PNU74654 on gene expression in H295R and SW13 cells. RT-PCR analysis confirmed the overexpression of ISM1, RALBP1, and PDE2A and the down-regulation of PHYHIP in five of six AA harboring CTNNB1 mutations compared with WT AA (n = 13) and normal adrenal glands (n = 10). RALBP1 and PDE2A overexpression was also confirmed at the protein level by Western blotting analysis in mutated tumors. ENC1 was specifically overexpressed in three of three AA harboring CTNNB1 point mutations. mRNA expression and protein levels of RALBP1, PDE2A, and ENC1 were decreased in a dose-dependent manner in H295R cells after treatment with PKF115-584 or PNU74654. This study identified candidate genes deregulated in CTNNB1-mutated adrenocortical tumors that may lead to a better understanding of the role of the Wnt-β-catenin pathway in adrenocortical tumorigenesis.

Predicting dredging-associated effects to coral reefs in Apra Harbor, Guam - Part 1: Sediment exposure modeling.

Science.gov (United States)

Gailani, Joseph Z; Lackey, Tahirih C; King, David B; Bryant, Duncan; Kim, Sung-Chan; Shafer, Deborah J

2016-03-01

Model studies were conducted to investigate the potential coral reef sediment exposure from dredging associated with proposed development of a deepwater wharf in Apra Harbor, Guam. The Particle Tracking Model (PTM) was applied to quantify the exposure of coral reefs to material suspended by the dredging operations at two alternative sites. Key PTM features include the flexible capability of continuous multiple releases of sediment parcels, control of parcel/substrate interaction, and the ability to efficiently track vast numbers of parcels. This flexibility has facilitated simulating the combined effects of sediment released from clamshell dredging and chiseling within Apra Harbor. Because the rate of material released into the water column by some of the processes is not well understood or known a priori, the modeling approach was to bracket parameters within reasonable ranges to produce a suite of potential results from multiple model runs. Sensitivity analysis to model parameters is used to select the appropriate parameter values for bracketing. Data analysis results include mapping the time series and the maximum values of sedimentation, suspended sediment concentration, and deposition rate. Data were used to quantify various exposure processes that affect coral species in Apra Harbor. The goal of this research is to develop a robust methodology for quantifying and bracketing exposure mechanisms to coral (or other receptors) from dredging operations. These exposure values were utilized in an ecological assessment to predict effects (coral reef impacts) from various dredging scenarios. Copyright © 2015. Published by Elsevier Ltd.

76 FR 33721 - Takes of Marine Mammals Incidental to Specified Activities; Harbor Activities Related to the...

Science.gov (United States)

2011-06-09

..., incidental to conducting Delta Mariner harbor operations for one year. NMFS reviewed the ULA application and... vitulina), and Northern elephant seals (Mirounga angustirostris) hauled out on Small Haul-out Site 1 to... lions; and 43 Northern elephant seals by Level B harassment only. Description of the Specified...

Multiple post-translational modifications in hepatocyte nuclear factor 4α

International Nuclear Information System (INIS)

Yokoyama, Atsushi; Katsura, Shogo; Ito, Ryo; Hashiba, Waka; Sekine, Hiroki; Fujiki, Ryoji; Kato, Shigeaki

2011-01-01

Highlights: → We performed comprehensive PTM analysis for HNF4α protein. → We identified 8 PTMs in HNF4α protein including newly identified PTMs. → Among them, we found acetylation at lysine 458 was one of the prime PTMs for HNF4α function. → Acetylation at lysine 458 was inhibitory for HNF4α transcription function. → This modification fluctuated in response to extracellular condition. -- Abstract: To investigate the role of post-translational modifications (PTMs) in the hepatocyte nuclear factor 4α (HNF4α)-mediated transcription, we took a comprehensive survey of PTMs in HNF4α protein by massspectrometry and identified totally 8 PTM sites including newly identified ubiquitilation and acetylation sites. To assess the impact of identified PTMs in HNF4α-function, we introduced point mutations at the identified PTM sites and, tested transcriptional activity of the HNF4α. Among the point-mutations, an acetylation site at lysine 458 was found significant in the HNF4α-mediated transcriptional control. An acetylation negative mutant at lysine 458 showed an increased transcriptional activity by about 2-fold, while an acetylation mimic mutant had a lowered transcriptional activation. Furthermore, this acetylation appeared to be fluctuated in response to extracellular nutrient conditions. Thus, by applying an comprehensive analysis of PTMs, multiple PTMs were newly identified in HNF4α and unexpected role of an HNF4α acetylation could be uncovered.

U.S. Department of Defense - Pearl Harbor Special

Science.gov (United States)

Hawaii saw that seminal moment in history, and those that were there vividly remember that Sunday morning this noise," he said in an oral history on the Pearl Harbor Survivors' Association Web site. " seeing was an attack. "It didn't mean anything to us until a large group of planes came near the

33 CFR 110.208 - Buffalo Harbor, N.Y.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Buffalo Harbor, N.Y. 110.208 Section 110.208 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.208 Buffalo Harbor, N.Y. (a) The anchorage grounds—(1...

33 CFR 125.15 - Access to waterfront facilities, and port and harbor areas, including vessels and harbor craft...

Science.gov (United States)

2010-07-01

..., and port and harbor areas, including vessels and harbor craft therein. 125.15 Section 125.15....15 Access to waterfront facilities, and port and harbor areas, including vessels and harbor craft....09 to those waterfront facilities, and port and harbor areas, including vessels and harbor craft...

33 CFR 110.238 - Apra Harbor, Guam.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Apra Harbor, Guam. 110.238 Section 110.238 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.238 Apra Harbor, Guam. (a) The anchorage grounds (Datum: WGS...

Navigation Improvement Design Memorandum Number 1, General Design for San Diego Harbor, San Diego County, California. Appendixes.

Science.gov (United States)

1975-02-01

are currently in opposition to spoiling in dredge dispo’sal site "B". To our knowledge , uses planned of this fill would not be water-related...utilized by water- skiers , thereby presenting conflicts with scheduled amphibious training. In addition to conflicts of "joint use", there is a...to time %ater harbor to create a r.ew re- miles south of the base. skiers have interfered with creational beach c.n av- Thcre had b,.a numerous Navy

Preoperational test report, cross-site transfer water flush system (POTP-001)

International Nuclear Information System (INIS)

Parsons, G.L.

1998-01-01

This report documents the results of the testing performed per POTP-001, for the Cross-Site Transfer Water Flush System. (HNF-1552, Rev. 0) The Flush System consists of a 47,000 gallon tank (302C), a 20 hp pump, two 498kW heaters, a caustic addition pump, various valves, instruments, and piping. The purpose of this system is to provide flush water at 140 F, 140gpm, and pH 11-12 for the Cross-Site Transfer System operation

Identification of a functional enhancer variant within the chronic pancreatitis-associated SPINK1 c.101A>G (p.Asn34Ser)-containing haplotype.

Science.gov (United States)

Boulling, Arnaud; Masson, Emmanuelle; Zou, Wen-Bin; Paliwal, Sumit; Wu, Hao; Issarapu, Prachand; Bhaskar, Seema; Génin, Emmanuelle; Cooper, David N; Li, Zhao-Shen; Chandak, Giriraj R; Liao, Zhuan; Chen, Jian-Min; Férec, Claude

2017-08-01

The haplotype harboring the SPINK1 c.101A>G (p.Asn34Ser) variant (also known as rs17107315:T>C) represents the most important heritable risk factor for idiopathic chronic pancreatitis identified to date. The causal variant contained within this risk haplotype has however remained stubbornly elusive. Herein, we set out to resolve this enigma by employing a hypothesis-driven approach. First, we searched for variants in strong linkage disequilibrium (LD) with rs17107315:T>C using HaploReg v4.1. Second, we identified two candidate SNPs by visual inspection of sequences spanning all 25 SNPs found to be in LD with rs17107315:T>C, guided by prior knowledge of pancreas-specific transcription factors and their cognate binding sites. Third, employing a novel cis-regulatory module (CRM)-guided approach to further filter the two candidate SNPs yielded a solitary candidate causal variant. Finally, combining data from phylogenetic conservation and chromatin accessibility, cotransfection transactivation experiments, and population genetic studies, we suggest that rs142703147:C>A, which disrupts a PTF1L-binding site within an evolutionarily conserved HNF1A-PTF1L CRM located ∼4 kb upstream of the SPINK1 promoter, contributes to the aforementioned chronic pancreatitis risk haplotype. Further studies are required not only to improve the characterization of this functional SNP but also to identify other functional components that might contribute to this high-risk haplotype. © 2017 Wiley Periodicals, Inc.

Madaket Harbor, Nantucket, Massachusetts. Water Resources Improvement.

Science.gov (United States)

1977-07-01

will continue to be, important increases in the recreational use of land and water. The harbor area is an important arena for commercial shellfishing...an important arena for commercial shell fishing. The past few years have seen a rather rapid increase in residential land use. Construction has...beamc. Tnis material will be re-deposited,, viaj troio it 1-apfro1inr ox prior location. j, MADAKET HARBOR NANTUCKET, MASSACHUSETTS FEASIBILITY

Production of infectious chimeric hepatitis C virus genotype 2b harboring minimal regions of JFH-1.

Science.gov (United States)

Murayama, Asako; Kato, Takanobu; Akazawa, Daisuke; Sugiyama, Nao; Date, Tomoko; Masaki, Takahiro; Nakamoto, Shingo; Tanaka, Yasuhito; Mizokami, Masashi; Yokosuka, Osamu; Nomoto, Akio; Wakita, Takaji

2012-02-01

To establish a cell culture system for chimeric hepatitis C virus (HCV) genotype 2b, we prepared a chimeric construct harboring the 5' untranslated region (UTR) to the E2 region of the MA strain (genotype 2b) and the region of p7 to the 3' UTR of the JFH-1 strain (genotype 2a). This chimeric RNA (MA/JFH-1.1) replicated and produced infectious virus in Huh7.5.1 cells. Replacement of the 5' UTR of this chimera with that from JFH-1 (MA/JFH-1.2) enhanced virus production, but infectivity remained low. In a long-term follow-up study, we identified a cell culture-adaptive mutation in the core region (R167G) and found that it enhanced virus assembly. We previously reported that the NS3 helicase (N3H) and the region of NS5B to 3' X (N5BX) of JFH-1 enabled replication of the J6CF strain (genotype 2a), which could not replicate in cells. To reduce JFH-1 content in MA/JFH-1.2, we produced a chimeric viral genome for MA harboring the N3H and N5BX regions of JFH-1, combined with a JFH-1 5' UTR replacement and the R167G mutation (MA/N3H+N5BX-JFH1/R167G). This chimeric RNA replicated efficiently, but virus production was low. After the introduction of four additional cell culture-adaptive mutations, MA/N3H+N5BX-JFH1/5am produced infectious virus efficiently. Using this chimeric virus harboring minimal regions of JFH-1, we analyzed interferon sensitivity and found that this chimeric virus was more sensitive to interferon than JFH-1 and another chimeric virus containing more regions from JFH-1 (MA/JFH-1.2/R167G). In conclusion, we established an HCV genotype 2b cell culture system using a chimeric genome harboring minimal regions of JFH-1. This cell culture system may be useful for characterizing genotype 2b viruses and developing antiviral strategies.

Detection of multidrug-resistant Pseudomonas aeruginosa harboring bla GES-1 and bla GES-11 in Recife, Brazil

Directory of Open Access Journals (Sweden)

Valdemir Vicente da Silva Júnior

Full Text Available Abstract INTRODUCTION: Pseudomonas aeruginosa, an important pathogen globally, presents several resistance mechanisms. This study aimed to investigate the presence of bla GES in clinical isolates of Pseudomonas aeruginosa obtained from various clinical specimens from patients admitted to three different hospitals in Recife, Brazil. The Guiana extended spectrum beta-lactamase (GES enzymes are responsible for conferring broad spectrum resistance to beta-lactam drugs, including the carbapenems. METHODS: A total of 100 carbapenem-resistant P. aeruginosa isolates underwent polymerase chain reaction (PCR testing to identify bla GES, bla KPC, bla SPM-1, bla IMP, and bla VIM. Additionally, PCR products positive for bla GES were sequenced. The clonal profiles of these same isolates were then determined by means of enterobacterial repetitive intergenic consensus (ERIC-PCR analysis. RESULTS: PCR analysis revealed that four isolates harbored bla GES; DNA sequencing showed that two harbored bla GES-1 and two bla GES-11. Beta-lactamase genes bla SPM-1, bla IMP, bla VIM, and bla KPC were investigated; none of these genes was detected. Automated susceptibility testing methods (Vitek®2, bioMérieux showed that the bla GES-1-positive isolates were only susceptible to polymyxin B. The patterns obtained with ERIC-PCR methods showed clonal relationship between the two isolates that harbored bla GES-11, whereas different clonal profiles were found in the isolates harboring bla GES-1. CONCLUSIONS: We detected the presence of bacterial isolates positive for two different variants of the enzyme GES in three different hospitals from Recife, Brazil. These enzymes have a great capacity for dissemination among Gram-negative bacteria and confer broad-spectrum resistance to beta-lactam antibiotics and to the carbapenems.

Underwater noise from three types of offshore wind turbines: estimation of impact zones for harbor porpoises and harbor seals.

Science.gov (United States)

Tougaard, Jakob; Henriksen, Oluf Damsgaard; Miller, Lee A

2009-06-01

Underwater noise was recorded from three different types of wind turbines in Denmark and Sweden (Middelgrunden, Vindeby, and Bockstigen-Valar) during normal operation. Wind turbine noise was only measurable above ambient noise at frequencies below 500 Hz. Total sound pressure level was in the range 109-127 dB re 1 microPa rms, measured at distances between 14 and 20 m from the foundations. The 1/3-octave noise levels were compared with audiograms of harbor seals and harbor porpoises. Maximum 1/3-octave levels were in the range 106-126 dB re 1 microPa rms. Maximum range of audibility was estimated under two extreme assumptions on transmission loss (3 and 9 dB per doubling of distance, respectively). Audibility was low for harbor porpoises extending 20-70 m from the foundation, whereas audibility for harbor seals ranged from less than 100 m to several kilometers. Behavioral reactions of porpoises to the noise appear unlikely except if they are very close to the foundations. However, behavioral reactions from seals cannot be excluded up to distances of a few hundred meters. It is unlikely that the noise reaches dangerous levels at any distance from the turbines and the noise is considered incapable of masking acoustic communication by seals and porpoises.

Stabilization and in situ management of radioactive contaminated sediments of Port Hope harbor

International Nuclear Information System (INIS)

Dolinar, G.M.; Killey, R.W.D.; Philipase, K.E.

1991-01-01

This paper presents the findings of laboratory and field studies undertaken to assess the feasibility of in situ management of contaminated sediments in Port Hope harbor. The contaminated sediments stem from historic releases from an adjacent radium and uranium refinery, and uranium, arsenic, and radium are the most abundant contaminants. With improved emission controls, currently accumulating sediments have much lower levels of contamination, and the harbor waters currently meet water quality limits for the contaminants of concern. Within a few years, however, the continuing sedimentation will render the harbor unusable. Field tests have confirmed the dredging will result in incomplete removal of the contaminated sediments and that sediment suspension and the release of pores waters during dredging will produce harbor water contaminant concentrations that would require the treatment of large volumes of water. In addition, no remedial work can start until a site for the dredged material can be found. The local community inquired whether in situ burial of the sediments and abandonment of the harbor would provide safe disposal

Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4{alpha}.

Science.gov (United States)

Hertz, Rachel; Kalderon, Bella; Byk, Tamara; Berman, Ina; Za'tara, Ghadeer; Mayer, Raphael; Bar-Tana, Jacob

2005-07-01

Hepatocyte nuclear factor-4alpha (HNF-4alpha) activity is modulated by natural and xenobiotic fatty acid and fatty acyl-CoA ligands as a function of their chain length, unsaturation, and substitutions. The acyl-CoA site of HNF-4alpha is reported here to consist of the E-F domain, to bind long-chain acyl-CoAs but not the respective free acids, and to catalyze the hydrolysis of bound fatty acyl-CoAs. The free acid pocket, previously reported in the x-ray structure of HNF-4alpha E-domain, entraps fatty acids but excludes acyl-CoAs. The acyl-CoA and free acid sites are distinctive and noncongruent. Free fatty acid products of HNF-4alpha thioesterase may exchange with free acids entrapped in the fatty acid pocket of HNF-4alpha. Cross-talk between the acyl-CoA and free fatty acid binding sites is abrogated by high affinity, nonhydrolyzable acyl-CoA ligands of HNF-4alpha that inhibit its thioesterase activity. Hence, HNF-4alpha transcriptional activity is controlled by its two interrelated acyl ligands and two binding sites interphased in tandem by the thioesterase activity. The acyl-CoA/free-acid and receptor/enzyme duality of HNF-4alpha extends the paradigm of nuclear receptors.

Coastal Harbors Modeling Facility

Data.gov (United States)

Federal Laboratory Consortium — The Coastal Harbors Modeling Facility is used to aid in the planning of harbor development and in the design and layout of breakwaters, absorbers, etc.. The goal is...

Alteration of introns in a hyaluronan synthase 1 (HAS1 minigene convert Pre-mRNA [corrected] splicing to the aberrant pattern in multiple myeloma (MM: MM patients harbor similar changes.

Directory of Open Access Journals (Sweden)

Jitra Kriangkum

Full Text Available Aberrant pre-mRNA splice variants of hyaluronan synthase 1 (HAS1 have been identified in malignant cells from cancer patients. Bioinformatic analysis suggests that intronic sequence changes can underlie aberrant splicing. Deletions and mutations were introduced into HAS1 minigene constructs to identify regions that can influence aberrant intronic splicing, comparing the splicing pattern in transfectants with that in multiple myeloma (MM patients. Introduced genetic variations in introns 3 and 4 of HAS1 as shown here can promote aberrant splicing of the type detected in malignant cells from MM patients. HAS1Vd is a novel intronic splice variant first identified here. HAS1Vb, an intronic splice variant previously identified in patients, skips exon 4 and utilizes the same intron 4 alternative 3'splice site as HAS1Vd. For transfected constructs with unaltered introns 3 and 4, HAS1Vd transcripts are readily detectable, frequently to the exclusion of HAS1Vb. In contrast, in MM patients, HAS1Vb is more frequent than HAS1Vd. In the HAS1 minigene, combining deletion in intron 4 with mutations in intron 3 leads to a shift from HAS1Vd expression to HAS1Vb expression. The upregulation of aberrant splicing, exemplified here by the expression of HAS1Vb, is shown here to be influenced by multiple genetic changes in intronic sequences. For HAS1Vb, this includes enhanced exon 4 skipping and increased usage of alternative 3' splice sites. Thus, the combination of introduced mutations in HAS1 intron3 with introduced deletions in HAS1 intron 4 promoted a shift to an aberrant splicing pattern previously shown to be clinically significant. Most MM patients harbor genetic variations in intron 4, and as shown here, nearly half harbor recurrent mutations in HAS1 intron 3. Our work suggests that aberrant intronic HAS1 splicing in MM patients may rely on intronic HAS1 deletions and mutations that are frequent in MM patients but absent from healthy donors.

33 CFR 80.1450 - Nawiliwili Harbor, Kauai, HI.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Nawiliwili Harbor, Kauai, HI. 80.1450 Section 80.1450 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Islands § 80.1450 Nawiliwili Harbor, Kauai, HI...

33 CFR 80.1470 - Kawaihae Harbor, Hawaii, HI.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Kawaihae Harbor, Hawaii, HI. 80.1470 Section 80.1470 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Islands § 80.1470 Kawaihae Harbor, Hawaii, HI...

33 CFR 80.1460 - Kahului Harbor, Maui, HI.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Kahului Harbor, Maui, HI. 80.1460 Section 80.1460 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Islands § 80.1460 Kahului Harbor, Maui, HI. A line drawn...

33 CFR 80.1480 - Hilo Harbor, Hawaii, HI.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Hilo Harbor, Hawaii, HI. 80.1480 Section 80.1480 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Islands § 80.1480 Hilo Harbor, Hawaii, HI. A line drawn...

Application of probabilistic risk assessment: Evaluating remedial alternatives at the Portland Harbor Superfund Site, Portland, Oregon, USA.

Science.gov (United States)

Ruffle, Betsy; Henderson, James; Murphy-Hagan, Clare; Kirkwood, Gemma; Wolf, Frederick; Edwards, Deborah A

2018-01-01

A probabilistic risk assessment (PRA) was performed to evaluate the range of potential baseline and postremedy health risks to fish consumers at the Portland Harbor Superfund Site (the "Site"). The analysis focused on risks of consuming fish resident to the Site containing polychlorinated biphenyls (PCBs), given that this exposure scenario and contaminant are the primary basis for US Environmental Protection Agency's (USEPA's) selected remedy per the January 2017 Record of Decision (ROD). The PRA used probability distributions fit to the same data sets used in the deterministic baseline human health risk assessment (BHHRA) as well as recent sediment and fish tissue data to evaluate the range and likelihood of current baseline cancer risks and noncancer hazards for anglers. Areas of elevated PCBs in sediment were identified on the basis of a geospatial evaluation of the surface sediment data, and the ranges of risks and hazards associated with pre- and postremedy conditions were calculated. The analysis showed that less active remediation (targeted to areas with the highest concentrations) compared to the remedial alternative selected by USEPA in the ROD can achieve USEPA's interim risk management benchmarks (cancer risk of 10 -4 and noncancer hazard index [HI] of 10) immediately postremediation for the vast majority of subsistence anglers that consume smallmouth bass (SMB) fillet tissue. In addition, the same targeted remedy achieves USEPA's long-term benchmarks (10 -5 and HI of 1) for the majority of recreational anglers. Additional sediment remediation would result in negligible additional risk reduction due to the influence of background. The PRA approach applied here provides a simple but adaptive framework for analysis of risks and remedial options focused on variability in exposures. It can be updated and refined with new data to evaluate and reduce uncertainty, improve understanding of the Site and target populations, and foster informed remedial decision

Current and historic mercury deposition to New Haven Harbor (CT, USA): Implications for industrial coastal environments

International Nuclear Information System (INIS)

Clark, Heather F.; Benoit, Gaboury

2009-01-01

This study quantifies historic and current mercury contamination in New Haven Harbor (New Haven, Connecticut, USA) through the analysis of sediment cores. The mercury concentration measured in surface sediment ranged from 320 to 1640 μg kg -1 with an average of 530 μg kg -1 . The harbor is relatively small in area (6.6 km 2 ) but displays a large range in concentrations, illustrating the important methodological issue that a large number of samples may be necessary to capture the variability in even a small area. Depth profiles of mercury reflect sedimentation over a range of 20 to 200 years and indicate a complex history of contamination. Mercury depth profiles were compared with lead, copper, cadmium, and silver concentrations and the metals generally covary. This trend indicates that the sources of mercury and heavy metals are linked and that regionally specific sources dominate the historic input of metals rather than large-scale atmospheric deposition patterns. Results also show there are large differences in absolute concentrations of metals among sites in the harbor. Differences in the abundance of Fe-rich, fine-grained sediment likely control the level of metals in various parts of the harbor. Proximity to current sources and the long, diverse industrial history of the harbor also influence the distribution pattern. All of the cores can be modeled as mixing between pre-industrial sediments and either one or two pollution endmembers. This study demonstrates the importance of riverine sources in the mass balance of mercury delivered to coastal areas and of watershed management to preserve coastal ecosystems.

Faunal and vegetation monitoring in response to harbor dredging in the Port of Miami

Science.gov (United States)

Daniels, Andre; Stevenson, Rachael; Smith, Erin; Robblee, Michael

2018-04-11

Seagrasses are highly productive ecosystems. A before-after-control-impact (BACI) design was used to examine effects of dredging on seagrasses and the animals that inhabit them. The control site North Biscayne Bay and the affected site Port of Miami had seagrass densities decrease during both the before, Fish and Invertebrate Assessment Network 2006-2011, and after, Faunal Monitoring in Response to Harbor Dredging 2014-2016, studies. Turbidity levels increased at North Biscayne Bay and Port of Miami basins during the Faunal Monitoring in Response to Harbor Dredging study, especially in 2016. Animal populations decreased significantly in North Biscayne Bay and Port of Miami in the Faunal Monitoring in Response to Harbor Dredging study compared to the Fish and Invertebrate Assessment Network study. Predictive modeling shows that numbers of animal populations will likely continue to decrease if the negative trends in seagrass densities continue unabated. There could be effects on several fisheries vital to the south Florida economy. Additional research could determine if animal populations and seagrass densities have rebounded or continued to decrease.

Bacterial Communities in Polluted Seabed Sediments: A Molecular Biology Assay in Leghorn Harbor

Directory of Open Access Journals (Sweden)

Carolina Chiellini

2013-01-01

Full Text Available Seabed sediments of commercial ports are often characterized by high pollution levels. Differences in number and distribution of bacteria in such areas can be related to distribution of pollutants in the port and to sediment conditions. In this study, the bacterial communities of five sites from Leghorn Harbor seabed were characterized, and the main bacterial groups were identified. T-RFLP was used for all samples; two 16S rRNA libraries and in silico digestion of clones were used to identify fingerprint profiles. Library data, phylogenetic analysis, and T-RFLP coupled with in silico digestion of the obtained sequences evidenced the dominance of Proteobacteria and the high percentage of Bacteroidetes in all sites. The approach highlighted similar bacterial communities between samples coming from the five sites, suggesting a modest differentiation among bacterial communities of different harbor seabed sediments and hence the capacity of bacterial communities to adapt to different levels and types of pollution.

Functional defect of truncated hepatocyte nuclear factor-1{alpha} (G554fsX556) associated with maturity-onset diabetes of the young

Energy Technology Data Exchange (ETDEWEB)

Kooptiwut, Suwattanee, E-mail: S_kooptiwut@hotmail.com [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Sujjitjoon, Jatuporn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Plengvidhya, Nattachet [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapapron [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Semprasert, Namoiy [Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Furuta, Hiroto; Nanjo, Kishio [The First Department, Wakayama Medical University (Japan); Banchuin, Napatawn [Department of Immunology and Immunology Graduate Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Yenchitsomanus, Pa-thai [Division of Medical Molecular Biology, Medicine Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Bangkok (Thailand)

2009-05-22

A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1{alpha} (HNF-1{alpha}) encoding a truncated HNF-1{alpha} (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1{alpha} proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1{alpha} could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1{alpha} on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1{alpha} (G554fsX556) on the transactivation of its target-gene promoters would account for the {beta}-cell dysfunction associated with the pathogenesis of MODY.

Functional defect of truncated hepatocyte nuclear factor-1α (G554fsX556) associated with maturity-onset diabetes of the young

International Nuclear Information System (INIS)

Kooptiwut, Suwattanee; Sujjitjoon, Jatuporn; Plengvidhya, Nattachet; Boonyasrisawat, Watip; Chongjaroen, Nalinee; Jungtrakoon, Prapapron; Semprasert, Namoiy; Furuta, Hiroto; Nanjo, Kishio; Banchuin, Napatawn; Yenchitsomanus, Pa-thai

2009-01-01

A novel frameshift mutation attributable to 14-nucleotide insertion in hepatocyte nuclear factor-1α (HNF-1α) encoding a truncated HNF-1α (G554fsX556) with 76-amino acid deletion at its carboxyl terminus was identified in a Thai family with maturity-onset diabetes of the young (MODY). The wild-type and mutant HNF-1α proteins were expressed by in vitro transcription and translation (TNT) assay and by transfection in HeLa cells. The wild-type and mutant HNF-1α could similarly bind to human glucose-transporter 2 (GLUT2) promoter examined by electrophoretic mobility shift assay (EMSA). However, the transactivation activities of mutant HNF-1α on human GLUT2 and rat L-type pyruvate kinase (L-PK) promoters in HeLa cells determined by luciferase reporter assay were reduced to approximately 55-60% of the wild-type protein. These results suggested that the functional defect of novel truncated HNF-1α (G554fsX556) on the transactivation of its target-gene promoters would account for the β-cell dysfunction associated with the pathogenesis of MODY.

Reducing Vulnerability of Ports and Harbors to Earthquake and Tsunami Hazards

Science.gov (United States)

Wood, Nathan J.; Good, James W.; Goodwin, Robert F.

2002-01-01

Recent scientific research suggests the Pacific Northwest could experience catastrophic earthquakes in the near future, both from distant and local sources, posing a significant threat to coastal communities. Damage could result from numerous earthquake-related hazards, such as severe ground shaking, soil liquefaction, landslides, land subsidence/uplift, and tsunami inundation. Because of their geographic location, ports and harbors are especially vulnerable to these hazards. Ports and harbors, however, are important components of many coastal communities, supporting numerous activities critical to the local and regional economy and possibly serving as vital post-event, response-recovery transportation links. A collaborative, multi-year initiative is underway to increase the resiliency of Pacific Northwest ports and harbors to earthquake and tsunami hazards, involving Oregon Sea Grant (OSG), Washington Sea Grant (WSG), the National Oceanic and Atmospheric Administration Coastal Services Center (CSC), and the U.S. Geological Survey Center for Science Policy (CSP). Specific products of this research, planning, and outreach initiative include a regional stakeholder issues and needs assessment, a community-based mitigation planning process, a Geographic Information System (GIS) — based vulnerability assessment methodology, an educational web-site and a regional data archive. This paper summarizes these efforts, including results of two pilot port-harbor community projects, one in Yaquina Bay, Oregon and the other in Sinclair Inlet, Washington. Finally, plans are outlined for outreach to other port and harbor communities in the Pacific Northwest and beyond, using "getting started" workshops and a web-based tutorial.

U2AF1 mutations alter splice site recognition in hematological malignancies.

Science.gov (United States)

Ilagan, Janine O; Ramakrishnan, Aravind; Hayes, Brian; Murphy, Michele E; Zebari, Ahmad S; Bradley, Philip; Bradley, Robert K

2015-01-01

Whole-exome sequencing studies have identified common mutations affecting genes encoding components of the RNA splicing machinery in hematological malignancies. Here, we sought to determine how mutations affecting the 3' splice site recognition factor U2AF1 alter its normal role in RNA splicing. We find that U2AF1 mutations influence the similarity of splicing programs in leukemias, but do not give rise to widespread splicing failure. U2AF1 mutations cause differential splicing of hundreds of genes, affecting biological pathways such as DNA methylation (DNMT3B), X chromosome inactivation (H2AFY), the DNA damage response (ATR, FANCA), and apoptosis (CASP8). We show that U2AF1 mutations alter the preferred 3' splice site motif in patients, in cell culture, and in vitro. Mutations affecting the first and second zinc fingers give rise to different alterations in splice site preference and largely distinct downstream splicing programs. These allele-specific effects are consistent with a computationally predicted model of U2AF1 in complex with RNA. Our findings suggest that U2AF1 mutations contribute to pathogenesis by causing quantitative changes in splicing that affect diverse cellular pathways, and give insight into the normal function of U2AF1's zinc finger domains. © 2015 Ilagan et al.; Published by Cold Spring Harbor Laboratory Press.

Polycyclic aromatic hydrocarbons and trace elements bounded to airborne PM10 in the harbor of Volos, Greece: Implications for the impact of harbor activities

Science.gov (United States)

Manoli, E.; Chelioti-Chatzidimitriou, A.; Karageorgou, K.; Kouras, A.; Voutsa, D.; Samara, C.; Kampanos, I.

2017-10-01

Harbors are often characterized by high levels of air pollutants that are emitted from ship traffic and other harbor activities. In the present study, the concentrations of Polycyclic Aromatic Hydrocarbons (PAHs) and trace elements (As, Cd, Ni, Pb, Cr, Mn, Zn, and Fe) bounded to the inhalable particulate matter PM10 were studied in the harbor of Volos, central Greece, during a 2-year period (2014-2015). Seasonal and daily variations were investigated. Moreover, total carcinogenic and mutagenic activities of PAHs were calculated. The effect of major wind sectors (sea, city, industrial, harbor) was estimated to assess the potential contribution of ship traffic and harbor activities, such as scrap metal handling operations. Results showed that the harbor sector (calm winds ≤ 0.5 m s-1) was associated with the highest concentrations of PM10. The harbor sector was also associated with relatively increased levels of trace elements (As, Fe, Cr, Mn, Ni), however the effect of this sector was lower than the corresponding effect of the industrial wind sector. The sea sector showed only a slight increase in B[a]Py and Σ12PAHs, whereas the highest increasing effect for PAHs and traffic-related elements, such as Pb and Zn, was evidenced for the city sector.

76 FR 8653 - Drawbridge Operation Regulation; Gulf Intracoastal Waterway, New Orleans Harbor, Inner Harbor...

Science.gov (United States)

2011-02-15

... Operation Regulation; Gulf Intracoastal Waterway, New Orleans Harbor, Inner Harbor Navigation Canal, New Orleans, Orleans Parish, LA AGENCY: Coast Guard, DHS. ACTION: Notice of temporary deviation from... Lock), at New Orleans, Orleans Parish, Louisiana. This deviation is necessary to replace all of the...

75 FR 78601 - Drawbridge Operation Regulation; Gulf Intracoastal Waterway, New Orleans Harbor, Inner Harbor...

Science.gov (United States)

2010-12-16

... Operation Regulation; Gulf Intracoastal Waterway, New Orleans Harbor, Inner Harbor Navigation Canal, New Orleans, Orleans Parish, LA AGENCY: Coast Guard, DHS. ACTION: Notice of temporary deviation from... Harvey Lock), at New Orleans, Orleans Parish, Louisiana. This deviation is necessary to adjust the...

New Harbor in Kangerlussuaq, Western Greenland

DEFF Research Database (Denmark)

Stenstad, Jaran Gjerlandj; Eppeland, Kjetil Grødal; Ingeman-Nielsen, Thomas

2015-01-01

transported by rivers from the inland ice to the inner parts of the fjord. These sediment layers reduce the water depth and prevent container- and cruiseships to dock, imposing large additional maintenance costs, and inefficient operability. Through engineering geological field and lab investigations......, a possible new harbor location around 10 km further out the fjord near Hancock Pynt, has been investigated. The onshore area was found to be highly suitable for a harbor support area, where a sub-base thickness of 1.8 m with gravel cover-layer was found adequate for the calculated design loads. Existing...

Extrachromosomal deoxyribonucleic acid in R factor-harboring Enterobacteriaceae

DEFF Research Database (Denmark)

Møller, JK; Bak, AL; Christiansen, C

1976-01-01

Extrachromosomal deoxyribonucleic acid (DNA) from 24 different R factor-harboring Enterobacteriaceae was isolated and characterized by analytical ultracentrifugation and electron microscopy. The R factors represented 15 different patterns of transferable drug resistance found in enterobacteria from...... from 1.700 to 1.720 g/cm3. The majority of the bacteria contained extrachromosomal DNAs of various densities. Three-fourths of the R factors were classified as fi+. The investigation illustrates the extensive variability in the physical characteristics of plasmid DNA from R factor-harboring strains....

Genetic characterization of blaNDM-harboring plasmids in carbapenem-resistant Escherichia coli from Myanmar.

Directory of Open Access Journals (Sweden)

Yo Sugawara

Full Text Available The bacterial enzyme New Delhi metallo-β-lactamase hydrolyzes almost all β-lactam antibiotics, including carbapenems, which are drugs of last resort for severe bacterial infections. The spread of carbapenem-resistant Enterobacteriaceae that carry the New Delhi metallo-β-lactamase gene, blaNDM, poses a serious threat to public health. In this study, we genetically characterized eight carbapenem-resistant Escherichia coli isolates from a tertiary care hospital in Yangon, Myanmar. The eight isolates belonged to five multilocus-sequence types and harbored multiple antimicrobial-resistance genes, resulting in resistance against nearly all of the antimicrobial agents tested, except colistin and fosfomycin. Nine plasmids harboring blaNDM genes were identified from these isolates. Multiple blaNDM genes were found in the distinct Inc-replicon types of the following plasmids: an IncA/C2 plasmid harboring blaNDM-1 (n = 1, IncX3 plasmids harboring blaNDM-4 (n = 2 or blaNDM-7 (n = 1, IncFII plasmids harboring blaNDM-4 (n = 1 or blaNDM-5 (n = 3, and a multireplicon F plasmid harboring blaNDM-5 (n = 1. Comparative analysis highlighted the diversity of the blaNDM-harboring plasmids and their distinct characteristics, which depended on plasmid replicon types. The results indicate circulation of phylogenetically distinct strains of carbapenem-resistant E. coli with various plasmids harboring blaNDM genes in the hospital.

Results of bulk sediment analysis and bioassay testing on selected sediments from Oakland Inner Harbor and Alcatraz disposal site, San Francisco, California

International Nuclear Information System (INIS)

Word, J.Q.; Ward, J.A.; Woodruff, D.L.

1990-09-01

The Battelle/Marine Sciences Laboratory (MSL) was contracted by the US Army Corps of Engineers, San Francisco District, to perform bulk sediment analysis and oyster larvae bioassays (elutriate) on sediments from Inner Oakland Harbor, California. Analysis of sediment characteristics by MSL indicated elevated priority pollutants, PAHs, pesticides, metals, organotins, and oil and grease concentrations, when compared to Alcatraz Island Dredged Material Disposal Site sediment concentrations. Larvae of the Pacific oyster, Crassostrea gigas, were exposed to seawater collected from the Alcatraz Island Site water, and a series of controls using water and sediments collected from Sequim Bay, Washington. Exposure of larvae to the Alcatraz seawater and the 50% and 100% elutriate concentrations from each Oakland sediment resulted in low survival and a high proportion of abnormal larvae compared to Sequim Bay control exposures. MSL identified that field sample collection, preservation, and storage protocols used by Port of Oakland contractors were inconsistent with standard accepted practices. 23 refs., 10 figs., 40 tabs

ФC31 Integrase-Mediated Isolation and Characterization of Novel Safe Harbors for Transgene Expression in the Pig Genome

Science.gov (United States)

Bi, Yanzhen; Hua, Zaidong; Ren, Hongyan; Zhang, Liping; Xiao, Hongwei; Liu, Ximei; Hua, Wenjun; Mei, Shuqi; Molenaar, Adrian; Laible, Götz; Zheng, Xinmin

2018-01-01

Programmable nucleases have allowed the rapid development of gene editing and transgenics, but the technology still suffers from the lack of predefined genetic loci for reliable transgene expression and maintenance. To address this issue, we used ФC31 integrase to navigate the porcine genome and identify the pseudo attP sites suitable as safe harbors for sustained transgene expression. The combined ФC31 integrase mRNA and an enhanced green fluorescence protein (EGFP) reporter donor were microinjected into one-cell zygotes for transgene integration. Among the resulting seven EGFP-positive piglets, two had transgene integrations at pseudo attP sites, located in an intergenic region of chromosome 1 (chr1-attP) and the 6th intron of the TRABD2A gene on chromosome 3 (chr3-attP), respectively. The integration structure was determined by TAIL-PCR and Southern blotting. Primary fibroblast cells were isolated from the two piglets and examined using fluorescence-activated cell sorting (FACS) and enzyme-linked immunosorbent assay (ELISA), which demonstrated that the chr1-attP site was more potent than chr3-attP site in supporting the EGFP expression. Both piglets had green feet under the emission of UV light, and pelleted primary fibroblast cells were green-colored under natural light, corroborating that the two pseudo attP sites are beneficial to transgene expression. The discovery of these two novel safe harbors for robust and durable transgene expression will greatly facilitate the use of transgenic pigs for basic, biomedical and agricultural studies and applications. PMID:29300364

Source characterization using compound composition and stable carbon isotope ratio of PAHs in sediments from lakes, harbor, and shipping waterway

International Nuclear Information System (INIS)

Kim, Moonkoo; Kennicutt, Mahlon C.; Qian, Yaorong

2008-01-01

Molecular compositions and compound specific stable carbon isotope ratios of polycyclic aromatic hydrocarbons (PAH) isolated from sediments were used to characterize possible sources of contamination at an urban lake, a harbor, a shipping waterway, and a relatively undisturbed remote lake in the northwest United States. Total PAH concentrations in urban lake sediments ranged from 66.0 to 16,500 μg g -1 dry wt. with an average of 2600 μg g -1 , which is ∼ 50, 100, and 400 times higher on average than PAH in harbor (48 μg g -1 on average), shipping waterway (26 μg g -1 ), and remote lake (7 μg g -1 ) sediments, respectively. The PAH distribution patterns, methyl phenanthrene/phenanthrene ratios, and a pyrogenic index at the sites suggest a pyrogenic origin for PAHs. Source characterization using principal component analysis and various molecular indices including C2-dibenzothiophenes/C2-phenanthrenes, C3-dibenzothiophenes/C3-phenanthrenes, and C2-chrysenes/C2-phenanthrenes ratios, was able to differentiate PAH deposited in sediments from the four sites. The uniqueness of the source of the sediment PAHs from urban lake was also illustrated by compound specific stable carbon isotope analysis. It was concluded that urban lake sediments are accumulating PAH from sources that are unique from contamination detected at nearby sites in the same watershed

Summary of oceanographic and water–quality measurements in West Falmouth Harbor and Buzzards Bay, Massachusetts, 2009–2010

Science.gov (United States)

Ganju, Neil K.; Dickhudt, Patrick J.; Thomas, Jennifer A.; Borden, Jonathan; Sherwood, Christopher R.; Montgomery, Ellyn T.; Twomey, Erin R.; Martini, Marinna A.

2011-01-01

This data report presents oceanographic and water-quality observations made at six locations in West Falmouth Harbor and Buzzards Bay, Massachusetts, from August 2009 to September 2010. Both Buzzards Bay and West Falmouth Harbor are estuarine embayments; the input of freshwater on the eastern margin of Buzzards Bay adjacent to Cape Cod and West Falmouth Harbor is largely due to groundwater. In West Falmouth Harbor, the groundwater that seeps into the harbor is characterized by relatively high levels of nitrate. This high nitrate load has modified the ecology of the harbor (Howes and others, 2006) and may be a significant source of nitrate to Buzzards Bay during seasons with low biological nitrate uptake. The U.S. Geological Survey undertook these measurements to improve understanding of circulation, residence time, and water quality in the harbor and bay. We set up and monitored multiple sites in both Buzzards Bay and West Falmouth Harbor, measuring depth, water velocity,salinity, pH, dissolved oxygen, chlorophyll-a, and nitrate concentration. In this report we present the processed time-series data at these locations and provide access to the data and metadata. The results will be used to understand circulation mechanisms and verify numerical models of hydrodynamics and biogeochemistry.

In situ assessment of two catfish species (pisces, Ariidae) to evaluate pollution in a harbor

Science.gov (United States)

Neta, Raimunda Nonata Fortes Carvalho; Junior, Audalio Rebelo Torres; Sousa, Débora Batista Pinheiro; de Sousa de Oliveira Mota Andrade, Ticianne; Torres, Hetty Salvino; da Silva Castro, Jonatas; da Silva de Almeida, Zafira; Santos, Débora Martins Silva; Tchaicka, Lígia

2016-12-01

A histopathological and biometric database for the catfish Sciades herzbergii and Bagre bagre from São Luís Island (Harbor area) and Caranguejos Island (reference area) in Brazil is presented. Branchial and hepatic lesions were classified into three reaction patterns: 1) circulatory or inflammatory disturbances; 2) regressive changes; 3) progressive changes. The total length (Lt), standard length (Ls), furcal length (Lf), total weight (Wt), and gonad weight (Wg) of each fish were recorded. As expected, most populations of catfish considered in this study are highly heterogeneous, with lengths and weights deviating from the reference sample. No histopathological lesions were observed in Sciades herzbergii examined at the reference site (Caranguejos Island). In contrast, 90% of the catfish S. herzbergii from sites located in the Harbor Area (São Luís Island) had one or more types of branchial and hepatic lesions. As opposed to what was observed in S. herzbergii, more than 86.33% of Bagre bagre individuals showed histopathological alterations in both areas. The utility of histopathological lesions and biometric data as sensitive indicators of the health of wild catfish populations has been demonstrated. Sciades herzbergii proved to be a better species for biomonitoring because it was able to differentiate one impacted site (Port Area/ São Luís Island) from a region relatively free of contaminants (Reference Area/ Caranguejos Island).

33 CFR 110.27 - Lynn Harbor in Broad Sound, Mass.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lynn Harbor in Broad Sound, Mass. 110.27 Section 110.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.27 Lynn Harbor in Broad Sound, Mass. North of...

33 CFR 117.458 - Inner Harbor Navigation Canal, New Orleans.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Inner Harbor Navigation Canal, New Orleans. 117.458 Section 117.458 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Harbor Navigation Canal, New Orleans. (a) The draws of the SR 46 (St. Claude Avenue) bridge, mile 0.5...

33 CFR 110.87 - Henderson Harbor, N.Y.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Henderson Harbor, N.Y. 110.87... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.87 Henderson Harbor, N.Y. (a) Area A. The area in the... latitude 43°51′08.8″ N, longitude 76°12′08.9″ W, thence to latitude 43°51′09.0″ N, longitude 76°12′19.0″ W...

Remembering Pearl Harbor at 75 Years.

Science.gov (United States)

Liehr, Patricia; Sopcheck, Janet; Milbrath, Gwyneth

2016-12-01

: On December 7, 1941, the Sunday-morning quiet of the U.S. naval base in Pearl Harbor, Hawaii, was shattered by dive-bombing Japanese fighter planes. The planes came in two waves-and when it was all over, more than 2,400 were killed and more than 1,100 were injured.Nurses were stationed at U.S. Naval Hospital Pearl Harbor, Tripler General Hospital (now Tripler Army Medical Center), Hickam Field Hospital, Schofield Barracks Station Hospital, and aboard the USS Solace, and witnessed the devastation. But they also did what nurses do in emergencies-they responded and provided care to those in need. Here are the stories of a few of those nurses.

AB072. Novel mutation in the hepatocyte nuclear factor 1b/maturity-onset diabetes of the young type 5 gene—unreported Vietnamese case

OpenAIRE

Dung, Vu Chi; Thao, Bui Phuong; Ngoc, Can Thi Bich; Khanh, Nguyen Ngoc; Ellard, Sian

2015-01-01

Maturity-onset diabetes of the young type 5 (MODY5), a type of dominantly inherited diabetes mellitus and nephropathy, has been associated with mutations of the hepatocyte nuclear factor-1 (HNF-1β) gene, mostly generating truncated protein. Various phenotypes are related to HNF-1β mutations. Our aim to describe clinical and genetic findings in the unreported Vietnamese case identified with HNF-1β mutations. The proband with kidney failure from 7.5 years of age and diabetes diagnosed at 13.5 y...

Hydraulic modeling of stream channels and structures in Harbor and Crow Hollow Brooks, Meriden, Connecticut

Science.gov (United States)

Weiss, Lawrence A.; Sears, Michael P.; Cervione, Michael A.

1994-01-01

Effects of urbanization have increased the frequency and size of floods along certain reaches of Harbor Brook and Crow Hollow Brook in Meriden, Conn. A floodprofile-modeling study was conducted to model the effects of selected channel and structural modifications on flood elevations and inundated areas. The study covered the reach of Harbor Brook downstream from Interstate 691 and the reach of Crow Hollow Brook downstream from Johnson Avenue. Proposed modifications, which include changes to bank heights, channel geometry, structural geometry, and streambed armoring on Harbor Brook and changes to bank heights on Crow Hollow Brook, significantly lower flood elevations. Results of the modeling indicate a significant reduction of flood elevations for the 10-year, 25-year, 35-year, 50-year, and 100-year flood frequencies using proposed modifications to (1 ) bank heights between Harbor Brook Towers and Interstate 691 on Harbor Brook, and between Centennial Avenue and Johnson Avenue on Crow Hollow Brook; (2) channel geometry between Coe Avenue and Interstate 69 1 on Harbor Brook; (3) bridge and culvert opening geometry between Harbor Brook Towers and Interstate 691 on Harbor Brook; and (4) channel streambed armoring between Harbor Brook Towers and Interstate 691 on Harbor Brook. The proposed modifications were developed without consideration of cost-benefit ratios.

33 CFR 207.610 - St. Lawrence River, Cape Vincent Harbor, N.Y.; use, administration, and navigation of the harbor...

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false St. Lawrence River, Cape Vincent Harbor, N.Y.; use, administration, and navigation of the harbor and U.S. breakwater. 207.610 Section 207... NAVIGATION REGULATIONS § 207.610 St. Lawrence River, Cape Vincent Harbor, N.Y.; use, administration, and...

Regional economic impact assessment: Evaluating remedial alternatives for the Portland Harbor Superfund Site, Portland, Oregon, USA.

Science.gov (United States)

Harrison, David; Coughlin, Conor; Hogan, Dylan; Edwards, Deborah A; Smith, Benjamin C

2018-01-01

The present paper describes a methodology for evaluating impacts of Superfund remedial alternatives on the regional economy in the context of a broader sustainability evaluation. Although economic impact methodology is well established, some applications to Superfund remedial evaluation have created confusion because of seemingly contradictory results. This confusion arises from failure to be explicit about 2 opposing impacts of remediation expenditures: 1) positive regional impacts of spending additional money in the region and 2) negative regional impacts of the need to pay for the expenditures (and thus forgo other expenditures in the region). The present paper provides a template for economic impact assessment that takes both positive and negative impacts into account, thus providing comprehensive estimates of net impacts. The paper also provides a strategy for identifying and estimating major uncertainties in the net impacts. The recommended methodology was applied at the Portland Harbor Superfund Site, located along the Lower Willamette River in Portland, Oregon, USA. The US Environmental Protection Agency (USEPA) developed remedial alternatives that it estimated would cost up to several billion dollars, with construction durations possibly lasting decades. The economic study estimated regional economic impacts-measured in terms of gross regional product (GRP), personal income, population, and employment-for 5 of the USEPA alternatives relative to the "no further action" alternative. Integr Environ Assess Manag 2018;14:32-42. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC). © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

33 CFR 117.753 - Ship Channel, Great Egg Harbor Bay.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Ship Channel, Great Egg Harbor Bay. 117.753 Section 117.753 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements New Jersey § 117.753 Ship Channel, Great Egg Harbor Bay. The draw of the S52 (Ship...

A Carbapenem-Resistant Pseudomonas aeruginosa Isolate Harboring Two Copies of blaIMP-34 Encoding a Metallo-β-Lactamase.

Directory of Open Access Journals (Sweden)

Tatsuya Tada

Full Text Available A carbapenem-resistant strain of Pseudomonas aeruginosa, NCGM1984, was isolated in 2012 from a hospitalized patient in Japan. Immunochromatographic assay showed that the isolate was positive for IMP-type metallo-β-lactamase. Complete genome sequencing revealed that NCGM1984 harbored two copies of blaIMP-34, located at different sites on the chromosome. Each blaIMP-34 was present in the same structures of the class 1 integrons, tnpA(ISPa7-intI1-qacG-blaIMP-34-aac(6'-Ib-qacEdelta1-sul1-orf5-tniBdelta-tniA. The isolate belonged to multilocus sequence typing ST235, one of the international high-risk clones. IMP-34, with an amino acid substitution (Glu126Gly compared with IMP-1, hydrolyzed all β-lactamases tested except aztreonam, and its catalytic activities were similar to IMP-1. This is the first report of a clinical isolate of an IMP-34-producing P. aeruginosa harboring two copies of blaIMP-34 on its chromosome.

33 CFR 165.904 - Lake Michigan at Chicago Harbor & Burnham Park Harbor-Safety and Security Zone.

Science.gov (United States)

2010-07-01

... & Burnham Park Harbor-Safety and Security Zone. 165.904 Section 165.904 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PORTS AND WATERWAYS SAFETY REGULATED NAVIGATION... Guard District § 165.904 Lake Michigan at Chicago Harbor & Burnham Park Harbor—Safety and Security Zone...

33 CFR 80.1490 - Apra Harbor, U.S. Territory of Guam.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Apra Harbor, U.S. Territory of Guam. 80.1490 Section 80.1490 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY INTERNATIONAL NAVIGATION RULES COLREGS DEMARCATION LINES Pacific Islands § 80.1490 Apra Harbor, U...

33 CFR 110.250 - St. Thomas Harbor, Charlotte Amalie, V.I.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false St. Thomas Harbor, Charlotte... SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.250 St. Thomas Harbor, Charlotte Amalie.... Thomas, V.I. of the United States and approaches thereto, including all waters under its jurisdiction, as...

Organic anion and cation SLC22 "drug" transporter (Oat1, Oat3, and Oct1 regulation during development and maturation of the kidney proximal tubule.

Directory of Open Access Journals (Sweden)

Thomas F Gallegos

Full Text Available Proper physiological function in the pre- and post-natal proximal tubule of the kidney depends upon the acquisition of selective permeability, apical-basolateral epithelial polarity and the expression of key transporters, including those involved in metabolite, toxin and drug handling. Particularly important are the SLC22 family of transporters, including the organic anion transporters Oat1 (originally identified as NKT and Oat3 as well as the organic cation transporter Oct1. In ex vivo cultures of metanephric mesenchyme (MM; the embryonic progenitor tissue of the nephron Oat function was evident before completion of nephron segmentation and corresponded with the maturation of tight junctions as measured biochemically by detergent extractability of the tight junction protein, ZO-1. Examination of available time series microarray data sets in the context of development and differentiation of the proximal tubule (derived from both in vivo and in vitro/ex vivo developing nephrons allowed for correlation of gene expression data to biochemically and functionally defined states of development. This bioinformatic analysis yielded a network of genes with connectivity biased toward Hnf4α (but including Hnf1α, hyaluronic acid-CD44, and notch pathways. Intriguingly, the Oat1 and Oat3 genes were found to have strong temporal co-expression with Hnf4α in the cultured MM supporting the notion of some connection between the transporters and this transcription factor. Taken together with the ChIP-qPCR finding that Hnf4α occupies Oat1, Oat3, and Oct1 proximal promoters in the in vivo differentiating rat kidney, the data suggest a network of genes with Hnf4α at its center plays a role in regulating the terminal differentiation and capacity for drug and toxin handling by the nascent proximal tubule of the kidney.

Effects of Harbor Modification on Crescent City, California's Tsunami Vulnerability

Science.gov (United States)

Dengler, Lori; Uslu, Burak

2011-06-01

More damaging tsunamis have impacted Crescent City, California in historic times than any other location on the West Coast of the USA. Crescent City's harbor has undergone significant modification since the early 20th century, including construction of several breakwaters, dredging, and a 200 × 300 m2 small boat basin. In 2006, a M w 8.3 earthquake in the Kuril Islands generated a moderate Pacific-wide tsunami. Crescent City recorded the highest amplitudes of any tide gauge in the Pacific and was the only location to experience structural damage. Strong currents damaged docks and boats within the small boat basin, causing more than US 20 million in damage and replacement costs. We examine how modifications to Crescent City's harbor may have affected its vulnerability to moderate tsunamis such as the 2006 event. A bathymetric grid of the basin was constructed based on US Army Corps of Engineers soundings in 1964 and 1965 before the construction of the small boat basin. The method of splitting tsunamis was used to estimate tsunami water heights and current velocities at several locations in the harbor using both the 1964-1965 grid and the 2006 bathymetric grid for the 2006 Kuril event and a similar-sized source along the Sanriku coast of Japan. Model velocity outputs are compared for the two different bathymetries at the tide gauge location and at six additional computational sites in the harbor. The largest difference between the two grids is at the small boat basin entrance, where the 2006 bathymetry produces currents over three times the strength of the currents produced by the 1965 bathymetry. Peak currents from a Sanriku event are comparable to those produced by the 2006 event, and within the boat basin may have been higher. The modifications of the harbor, and in particular the addition of the small boat basin, appear to have contributed to the high current velocities and resulting damage in 2006 and help to explain why the 1933 M w 8.4-8.7 Sanriku tsunami

Bioaccumulation of chemical warfare agents, energetic materials, and metals in deep-sea shrimp from discarded military munitions sites off Pearl Harbor

Science.gov (United States)

Koide, Shelby; Silva, Jeff A. K.; Dupra, Vilma; Edwards, Margo

2016-06-01

The bioaccumulation of munitions-related chemicals at former military deep-water disposal sites is poorly understood. This paper presents the results of human-food-item biota sampling to assess the potential for bioaccumulation of chemical warfare agents, energetic materials, arsenic, and additional munitions-related metals in deep-sea shrimp tissue samples collected during the Hawai'i Undersea Military Munitions Assessment (HUMMA) project to date. The HUMMA investigation area is located within a former munitions sea-disposal site located south of Pearl Harbor on the island of O'ahu, Hawai'i, designated site Hawaii-05 (HI-05) by the United States Department of Defense. Indigenous deep-sea shrimp (Heterocarpus ensifer) were caught adjacent to discarded military munitions (DMM) and at control sites where munitions were absent. Tissue analysis results showed that chemical warfare agents and their degradation products were not present within the edible portions of these samples at detectable concentrations, and energetic materials and their degradation products were detected in only a few samples at concentrations below the laboratory reporting limits. Likewise, arsenic, copper, and lead concentrations were below the United States Food and Drug Administration's permitted concentrations of metals in marine biota tissue (if defined), and their presence within these samples could not be attributed to the presence of DMM within the study area based on a comparative analysis of munitions-adjacent and control samples collected. Based on this current dataset, it can be concluded that DMM existing within the HUMMA study area is not contributing to the bioaccumulation of munitions-related chemicals for the biota species investigated to date.

Appreciating Site-Specific Qualities in Urban Harbours

DEFF Research Database (Denmark)

Reeh, Henrik

2015-01-01

of observa-tions from Marseille in southern France. After modernization and dislocation of its harbor territories in the early 20th century already, this city is currently taking important steps from industrial urbanism into cultural planning. This transformation allows for new and unprogrammed experiences......When “site-specificity” becomes a central value in city and harbor transformation, it soon proves necessary to address the ways in which scholars and professionals actually determine site-specific qualities in urban fabrics and social life. This paper delves into the above questions by means...

Preliminary assessment of Miramar Petrochemical Harbor as PAH source to Guajará bay (Belém-PA-Brazil surface sediments

Directory of Open Access Journals (Sweden)

Silvana do Socorro Veloso Sodré

Full Text Available Abstract A preliminary study on a petrochemical harbor as a potential source of polycyclic aromatic hydrocarbons (PAH to surface sediments of Guajará bay, located in Belém City, Pará State, Brazil, over the last 10 years is presented here. The 16 priority USEPA PAH were identified and quantified. Surface sediment samples, collected at 5 sites in the bay, near Miramar Petrochemical Harbor (TEMIR, were extracted and analyzed by high performance liquid chromatography with a diode array detector. Total PAH concentration ranged from 533.0 to 3123.3 ng g-1 dry weight with a mean concentration of 1091.9 ng g-1. The most contaminated places were those where muddy sediments were found with highest concentrations of organic matter. The priority PAH with low molecular weight represented 54.4% of the total abundance and indicate that the main source of contamination of the sediments was petrogenic, indicative of the relevant contribution of the petrochemical harbor activity to the input of PAH to Guajará bay. However, pyrolytic PAH coming from fuel combustion, household waste combustion and untreated sewage discharge are also potential contamination sources to this environment.

33 CFR 110.129a - Apra Harbor, Guam. (Datum: WGS 84)

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Apra Harbor, Guam. (Datum: WGS 84) 110.129a Section 110.129a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.129a Apra Harbor, Guam. (Datum: WGS 84) (a...

Rapid movement of wastewater from on-site disposal systems into surface waters in the lower Florida Keys

Science.gov (United States)

Paul, John H.; McLaughlin, Molly R.; Griffin, Dale W.; Lipp, Erin K.; Stokes, Rodger; Rose, Joan B.

2000-01-01

Viral tracer studies have been used previously to study the potential for wastewater contamination of surface marine waters in the Upper and Middle Florida Keys. Two bacteriophages, the marine bacteriophage φHSIC and the Salmonella phage PRD1, were used as tracers in injection well and septic tank studies in Saddlebunch Keys of the Lower Florida Keys and in septic tank studies in Boot Key Harbor, Marathon, of the Middle Keys. In Boot Key Harbor, both phages were detected in a canal adjacent to the seeded septic tank within 3 h 15 min of the end of the seed period. The tracer was then detected at all sampling sites in Boot Key Harbor, including one on the opposite side of U. S. Highway 1 in Florida Bay, and at an Atlantic Ocean beach outside Boot Key Harbor. Rates of migration based on first appearance of the phage ranged from 1.7 to 57.5 m h-1. In Saddlebunch Keys, φHSIC and PRD1 were used to seed a residential septic tank and a commercial injection well. The septic tank tracer was not found in any surface water samples. The injection well tracer was first detected at a site most distant from the seed site, a channel that connected Sugarloaf Sound with the Atlantic Ocean. The rate of tracer migration from the injection well to this channel ranged from 66.8 to 141 m h-1. Both tracer studies showed a rapid movement of wastewater from on-site sewage treatment and disposal systems in a southeasterly direction toward the reef tract and Atlantic Ocean, with preferential movement through tidal channels. These studies indicate that wastewater disposal systems currently in widespread use in the Florida Keys can rapidly contaminate the marine environment.

Project W-314 acceptance test report HNF-4643 for HNF-4642 241-AN-A valve pit manifold valves and position indication for project W-314

International Nuclear Information System (INIS)

HAMMERS, J.S.

1999-01-01

The purpose of the test was to verify that the AN Tank Farm Manifold Valves can be manually manipulated to the required operating position and that the electrical and visual indications accurately reflect that position. Physical locking devices were also verified to function. The Acceptance Test Procedure HNF-4642, 241-AN-A Valve Pit Manifold Valves and Position Indication was conducted between 23 June and 10 August 1999 at the 200E AN Tank Farm. The test has no open test exceptions. The test was conducted prior to final engineering ''as built'' activities being completed, this had an impact on the procedure and test results, ECN 653752 was written to correct the mismatch between the procedure and actual field conditions. P and ID H-14-100941 was changed via ECN-W-314-4C-120. All components, identified in the procedure, were not found to be labeled and identified as written in the procedure, temporary tags were used for operational identification. A retest of valve ANA-WT-V 318 was required because it was removed from its installed position and modified after testing was completed

ABC transporter Cdr1p harbors charged residues in the intracellular loop and nucleotide-binding domain critical for protein trafficking and drug resistance.

Science.gov (United States)

Shah, Abdul Haseeb; Banerjee, Atanu; Rawal, Manpreet Kaur; Saxena, Ajay Kumar; Mondal, Alok Kumar; Prasad, Rajendra

2015-08-01

The ABC transporter Cdr1 protein of Candida albicans, which plays a major role in antifungal resistance, has two transmembrane domains (TMDs) and two nucleotide-binding domains (NBDs). The 12 transmembrane helices of TMDs that are interconnected by extracellular and intracellular loops (ICLs) mainly harbor substrate recognition sites where drugs bind while cytoplasmic NBDs hydrolyze ATP which powers drug efflux. The coupling of ATP hydrolysis to drug transport requires proper communication between NBDs and TMDs typically accomplished by ICLs. This study examines the role of cytoplasmic ICLs of Cdr1p by rationally predicting the critical residues on the basis of their interatomic distances. Among nine pairs that fall within a proximity of trafficking. These results point to a new role for ICL/NBD interacting residues in PDR ABC transporters in protein folding and trafficking. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

77 FR 46285 - Drawbridge Operation Regulation; Inner Harbor Navigational Canal, New Orleans, LA

Science.gov (United States)

2012-08-03

... Operation Regulation; Inner Harbor Navigational Canal, New Orleans, LA AGENCY: Coast Guard, DHS. ACTION... Navigational Canal, mile 3.1, at New Orleans, LA. The deviation is necessary to replace the wire rope lifting... of the US 90 (Danzinger) Bridge across the Inner Harbor Navigational Canal, mile 3.1, at New Orleans...

SNF project's MCO compliance assessment with DOE ''general design criteria,'' order 6430.1A and ''SNF project MCO additional NRC requirements,'' HNF-SD-SNF-DB-005

International Nuclear Information System (INIS)

GOLDMANN, L.H.

1999-01-01

This document is presented to demonstrate the MCOs compliance to the major design criteria invoked on the MCO. This document is broken down into a section for the MCO's evaluation against DOE Order 6430.1A General Design Criteria sixteen divisions and then the evaluation of the MCO against HNF-SD-SNF-DB-005 ''Spent Nuclear Fuel Project Multi-Canister Overpack Additional NRC Requirements.'' The compliance assessment is presented as a matrix in tabular form. The MCO is the primary container for the K-basin's spent nuclear fuel as it leaves the basin pools and through to the 40 year interim storage at the Canister Storage Building (CSB). The MCO and its components interface with; the K basins, shipping cask and transportation system, Cold Vacuum Drying facility individual process bays and equipment, and CSB facility including the MCO handling machine (MHM), the storage tubes, and the MCO work stations where sampling, welding, and inspection of the MCO is performed. As the MCO is the primary boundary for handling, process, and storage, its main goals are to minimize the spread of its radiological contents to the outside of the MCO and provide for nuclear criticality control. The MCO contains personnel radiation shielding only on its upper end, in the form of a shield plug, where the process interfaces are located. Shielding beyond the shield plug is the responsibility of the using facilities. The design of the MCO and its components is depicted in drawings H-2-828040 through H-2-828075. Not every drawing number in the sequence is used. The first drawing number, H-2-828040, is the drawing index for the MCO. The design performance specification for the MCO is HW-S-0426, and was reviewed and approved by the interfacing design authorities, the safety, regulatory, and operations groups, and the local DOE office. The current revision for the design performance specification is revision 5. The designs of the MCO have been reviewed and approved in a similar way and the reports

Physiological studies in aerobic batch cultivations of Saccharomyces cerevisiae strains harboring the MEL1 gene

DEFF Research Database (Denmark)

Østergaard, Simon; Roca, Christophe Francois Aime; Ronnow, B.

2000-01-01

Physiological studies of Saccharomyces cerevisiae strains harboring the MEL1 gene were carried out in aerobic batch cultivations on glucose-galactose mixtures and on the disaccharide melibiose, which is hydrolyzed by the enzyme melibiase (Mel1, EC 3.2.1.22) into a glucose and a galactose moiety...... rates were 2.5-3.3-fold higher on glucose than on galactose for all the strains examined, and hence, ethanol production was pronounced on glucose due to respiro-fermentative metabolism. The T256 strain and the T200 strain having the MEL1 gene inserted in the HXK2 locus and the LEU2 locus, respectively...

77 FR 59551 - Safety Zone, Changes to Original Rule; Boston Harbor's Rock Removal Project, Boston Inner Harbor...

Science.gov (United States)

2012-09-28

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket No. USCG-2012-0767] RIN 1625-AA00 Safety Zone, Changes to Original Rule; Boston Harbor's Rock Removal Project, Boston Inner Harbor... original provisions of that temporary final rule, but adds two additional safety zones necessary for the...

Oral keratinocytes support non-replicative infection and transfer of harbored HIV-1 to permissive cells.

Science.gov (United States)

Vacharaksa, Anjalee; Asrani, Anil C; Gebhard, Kristin H; Fasching, Claudine E; Giacaman, Rodrigo A; Janoff, Edward N; Ross, Karen F; Herzberg, Mark C

2008-07-17

Oral keratinocytes on the mucosal surface are frequently exposed to HIV-1 through contact with infected sexual partners or nursing mothers. To determine the plausibility that oral keratinocytes are primary targets of HIV-1, we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted manner. To study the fate of HIV-1, immortalized oral keratinocytes (OKF6/TERT-2; TERT-2 cells) were characterized for the fate of HIV-specific RNA and DNA. At 6 h post inoculation with X4 or R5-tropic HIV-1, HIV-1gag RNA was detected maximally within TERT-2 cells. Reverse transcriptase activity in TERT-2 cells was confirmed by VSV-G-mediated infection with HIV-NL4-3Deltaenv-EGFP. AZT inhibited EGFP expression in a dose-dependent manner, suggesting that viral replication can be supported if receptors are bypassed. Within 3 h post inoculation, integrated HIV-1 DNA was detected in TERT-2 cell nuclei and persisted after subculture. Multiply spliced and unspliced HIV-1 mRNAs were not detectable up to 72 h post inoculation, suggesting that HIV replication may abort and that infection is non-productive. Within 48 h post inoculation, however, virus harbored by CD4 negative TERT-2 cells trans infected co-cultured peripheral blood mononuclear cells (PBMCs) or MOLT4 cells (CD4+ CCR5+) by direct cell-to-cell transfer or by releasing low levels of infectious virions. Primary tonsil epithelial cells also trans infected HIV-1 to permissive cells in a donor-specific manner. Oral keratinocytes appear, therefore, to support stable non-replicative integration, while harboring and transmitting infectious X4- or R5-tropic HIV-1 to permissive cells for up to 48 h.

Oral keratinocytes support non-replicative infection and transfer of harbored HIV-1 to permissive cells

Directory of Open Access Journals (Sweden)

Giacaman Rodrigo A

2008-07-01

Full Text Available Abstract Background Oral keratinocytes on the mucosal surface are frequently exposed to HIV-1 through contact with infected sexual partners or nursing mothers. To determine the plausibility that oral keratinocytes are primary targets of HIV-1, we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted manner. Results To study the fate of HIV-1, immortalized oral keratinocytes (OKF6/TERT-2; TERT-2 cells were characterized for the fate of HIV-specific RNA and DNA. At 6 h post inoculation with X4 or R5-tropic HIV-1, HIV-1gag RNA was detected maximally within TERT-2 cells. Reverse transcriptase activity in TERT-2 cells was confirmed by VSV-G-mediated infection with HIV-NL4-3Δenv-EGFP. AZT inhibited EGFP expression in a dose-dependent manner, suggesting that viral replication can be supported if receptors are bypassed. Within 3 h post inoculation, integrated HIV-1 DNA was detected in TERT-2 cell nuclei and persisted after subculture. Multiply spliced and unspliced HIV-1 mRNAs were not detectable up to 72 h post inoculation, suggesting that HIV replication may abort and that infection is non-productive. Within 48 h post inoculation, however, virus harbored by CD4 negative TERT-2 cells trans infected co-cultured peripheral blood mononuclear cells (PBMCs or MOLT4 cells (CD4+ CCR5+ by direct cell-to-cell transfer or by releasing low levels of infectious virions. Primary tonsil epithelial cells also trans infected HIV-1 to permissive cells in a donor-specific manner. Conclusion Oral keratinocytes appear, therefore, to support stable non-replicative integration, while harboring and transmitting infectious X4- or R5-tropic HIV-1 to permissive cells for up to 48 h.

Efficient Generation of Functional Hepatocytes From Human Embryonic Stem Cells and Induced Pluripotent Stem Cells by HNF4α Transduction

OpenAIRE

Takayama, Kazuo; Inamura, Mitsuru; Kawabata, Kenji; Katayama, Kazufumi; Higuchi, Maiko; Tashiro, Katsuhisa; Nonaka, Aki; Sakurai, Fuminori; Hayakawa, Takao; Kusuda Furue, Miho; Mizuguchi, Hiroyuki

2012-01-01

Hepatocyte-like cells from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are expected to be a useful source of cells drug discovery. Although we recently reported that hepatic commitment is promoted by transduction of SOX17 and HEX into human ESC- and iPSC-derived cells, these hepatocyte-like cells were not sufficiently mature for drug screening. To promote hepatic maturation, we utilized transduction of the hepatocyte nuclear factor 4α (HNF4α) gene, which is kn...

33 CFR 110.31 - Hull Bay and Allerton Harbor at Hull, Mass.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Hull Bay and Allerton Harbor at Hull, Mass. 110.31 Section 110.31 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.31 Hull Bay and Allerton Harbor at...

Respiratory properties of blood in the harbor porpoise, Phocoena phocoena

DEFF Research Database (Denmark)

Soegaard, Lisette B; Hansen, Marie N; van Elk, Cornelis

2012-01-01

Harbor porpoises are active divers that exchange O(2) and CO(2) with the environment during a fast single breath upon surfacing. We investigated blood O(2)-transporting properties, buffer characteristics, Cl(-) transport via the erythrocyte anion exchanger (AE1), circulating nitric oxide metaboli......Harbor porpoises are active divers that exchange O(2) and CO(2) with the environment during a fast single breath upon surfacing. We investigated blood O(2)-transporting properties, buffer characteristics, Cl(-) transport via the erythrocyte anion exchanger (AE1), circulating nitric oxide....... The true plasma non-bicarbonate buffer value was moderately higher than in terrestrial mammals and increased upon deoxygenation. Plasma bicarbonate was also relatively high, contributing to increase the overall buffer capacity. The apparent Cl(-) permeability of harbor porpoise erythrocytes was similar......, plasma nitrate and hemoglobin-mediated nitrite reduction were elevated compared with mammalian standards, suggesting that increased nitric oxide bioavailability and nitrite-derived nitric oxide could play important roles in diving physiology....

[Pearl Harbor.

Science.gov (United States)

Johnson, Jennifer, Ed.

1992-01-01

This issue of "Loblolly Magazine" was written in observance of the 50th anniversary of the U.S. entrance into World War II. The publication features interviews conducted by East Texas high school students with Clarence Otterman, one of the few survivors of the crew of the USS Arizona, which was bombed during the attack on Pearl Harbor,…

33 CFR 110.235 - Pacific Ocean (Mamala Bay), Honolulu Harbor, Hawaii (Datum: NAD 83).

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Pacific Ocean (Mamala Bay), Honolulu Harbor, Hawaii (Datum: NAD 83). 110.235 Section 110.235 Navigation and Navigable Waters COAST... Pacific Ocean (Mamala Bay), Honolulu Harbor, Hawaii (Datum: NAD 83). (a) The anchorage grounds—(1...

Glucose-Lowering Effects and Low Risk of Hypoglycemia in Patients With Maturity-Onset Diabetes of the Young When Treated With a GLP-1 Receptor Agonist

DEFF Research Database (Denmark)

Ostoft, S. H.; Bagger, J. I.; Hansen, Torben

2014-01-01

OBJECTIVE The most common form of maturity-onset diabetes of the young (MODY), hepatocyte nuclear factor 1 alpha (HNF1A diabetes: MODY3) is often treated with sulfonylureas that confer a high risk of hypoglycemia. We evaluated treatment with GLP-1 receptor agonists (GLP-1RAs) in patients with HNF1A...... diabetes. RESEARCH DESIGN AND METHODS Sixteen patients with HNF1A diabetes (8 women; mean age 39 years [range 23-67 years]; BMI 24.9 +/- 0.5 kg/m(2) [mean +/- SEM]; fasting plasma glucose [FPG] 9.9 +/- 0.9 mmol/L; HbA(1c) 6.4 +/- 0.2% [47 +/- 3 mmol/mol]) received 6 weeks of treatment with a GLP-1RA...

Modeling of Tsunami Currents in Harbors

Science.gov (United States)

Lynett, P. J.

2010-12-01

Extreme events, such as large wind waves and tsunamis, are well recognized as a damaging hazard to port and harbor facilities. Wind wave events, particularly those with long period spectral components or infragravity wave generation, can excite resonance inside harbors leading to both large vertical motions and strong currents. Tsunamis can cause great damage as well. The geometric amplification of these very long waves can create large vertical motions in the interior of a harbor. Additionally, if the tsunami is composed of a train of long waves, which it often is, resonance can be easily excited. These long wave motions create strong currents near the node locations of resonant motions, and when interacting with harbor structures such as breakwaters, can create intense turbulent rotational structures, typical in the form of large eddies or gyres. These gyres have tremendous transport potential, and have been observed to break mooring lines, and even cause ships to be trapped inside the rotation, moving helplessly with the flow until collision, grounding, or dissipation of the eddy (e.g. Okal et al., 2006). This presentation will introduce the traditional theory used to predict wave impacts on harbors, discussing both how these models are practically useful and in what types of situations require a more accurate tool. State-of-the-art numerical models will be introduced, with a focus on recent developments in Boussinesq-type modeling. The Boussinesq equations model can account the dispersive, turbulent and rotational flow properties frequently observed in nature. Also they have the ability to coupling currents and waves and can predict nonlinear wave propagation over uneven bottom from deep (or intermediate) water area to shallow water area. However, during the derivation of a 2D-horizontal equation set, some 3D flow features, such those driven by as the dispersive stresses and the effects of the unresolved small scale 3D turbulence, are excluded. Consequently

ALARA Design Review for the Resumption of the Plutonium Finishing Plant (PFP) Cementation Process Project Activities

CERN Document Server

Dayley, L

2000-01-01

The requirements for the performance of radiological design reviews are codified in 10CFR835, Occupational Radiation Protection. The basic requirements for the performance of ALARA design reviews are presented in the Hanford Site Radiological Control Manual (HSRCM). The HSRCM has established trigger levels requiring radiological reviews of non-routine or complex work activities. These requirements are implemented in site procedures HNF-PRO-1622 and 1623. HNF-PRO-1622 Radiological Design Review Process requires that ''radiological design reviews [be performed] of new facilities and equipment and modifications of existing facilities and equipment''. In addition, HNF-PRO-1623 Radiological Work Planning Process requires a formal ALARA Review for planned activities that are estimated to exceed 1 person-rem total Dose Equivalent (DE). The purpose of this review is to validate that the original design for the PFP Cementation Process ensures that the principles of ALARA (As Low As Reasonably Achievable) were included...

Numerical Modeling of Wave Overtopping of Buffalo Harbor Confined Disposal Facility (CDF4)

Science.gov (United States)

2017-10-01

navigation channel , and harbor complex. Though there are anecdotal claims and debris indicating possible sediment movement, there has been no evidence of...littoral sediments inside the disposal area, into the channel and harbor, and other adjacent areas to the CDF4. 1.4 Study plan 1.4.1 Purpose There...locations. 2.4 Maintenance dredging data The need for maintenance dredging arises from sedimentation in the navigation channels , which impedes

Harbor Seal (Phoca vitulina) Reproductive Advertisement Behavior and the Effects of Vessel Noise

Science.gov (United States)

Matthews, Leanna P.

Harbor seals (Phoca vitulina) are a widely distributed pinniped species that mate underwater. Similar to other aquatically mating pinnipeds, male harbor seals produce vocalizations during the breeding season that function in male-male interactions and possibly as an attractant for females. I investigated multiple aspects of these reproductive advertisement displays in a population of harbor seals in Glacier Bay National Park and Preserve, Alaska. First, I looked at vocal production as a function of environmental variables, including season, daylight, and tidal state. Vocalizations were highly seasonal and detection of these vocalizations peaked in June and July, which correspond with the estimated time of breeding. Vocalizations also varied with light, with the lowest probability of detection during the day and the highest probability of detection at night. The high probability of detection corresponded to when females are known to forage. These results are similar to the vocal behavior of previously studied populations. However, unlike previously studied populations, the detection of harbor seal breeding vocalizations did not vary with tidal state. This is likely due to the location of the hydrophone, as it was not near the haul out and depth was therefore not significantly influenced by changes in tidal height. I also investigated the source levels and call parameters of vocalizations, as well as call rate and territoriality. The average source level of harbor seal breeding vocalizations was 144 dB re 1 ?Pa at 1 m and measurements ranged from 129 to 149 dB re 1 ?Pa. Analysis of call parameters indicated that vocalizations of harbor seals in Glacier Bay were similar in duration to other populations, but were much lower in frequency. During the breeding season, there were two discrete calling areas that likely represent two individual males; the average call rate in these display areas was approximately 1 call per minute. The harbor seal breeding season also

Vibration-based structural health monitoring of harbor caisson structure

Science.gov (United States)

Lee, So-Young; Lee, So-Ra; Kim, Jeong-Tae

2011-04-01

This study presents vibration-based structural health monitoring method in foundation-structure interface of harbor caisson structure. In order to achieve the objective, the following approaches are implemented. Firstly, vibration-based response analysis method is selected and structural health monitoring (SHM) technique is designed for harbor caisson structure. Secondly, the performance of designed SHM technique for harbor structure is examined by FE analysis. Finally, the applicability of designed SHM technique for harbor structure is evaluated by dynamic tests on a lab-scaled caisson structure.

32 CFR 765.6 - Regulations for Pearl Harbor, Hawaii.

Science.gov (United States)

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Regulations for Pearl Harbor, Hawaii. 765.6... RULES RULES APPLICABLE TO THE PUBLIC § 765.6 Regulations for Pearl Harbor, Hawaii. The Commander, U.S. Naval Base, Pearl Harbor, Hawaii, is responsible for prescribing and enforcing such rules and...

Caffeine in an Urbanized Estuary: Past and Present Influence of Wastewater Effluents in Boston Harbor, MA, USA

Science.gov (United States)

Caffeine has been identified by previous research as a potential tracer of sanitary wastewater. To further assess the utility of caffeine as a tracer of wastewater sources, samples from 25 sites throughout Boston Harbor were collected and analyzed for caffeine by LC-MS/MS. Caff...

A 5' splice site enhances the recruitment of basal transcription initiation factors in vivo

DEFF Research Database (Denmark)

Damgaard, Christian Kroun; Kahns, Søren; Lykke-Andersen, Søren

2008-01-01

RNAs, harboring wild-type or various 5′ splice site mutations, we demonstrate a strong positive correlation between splicing efficiency and transcription activity. Interestingly, a 5′ splice site can stimulate transcription even in the absence of splicing. Chromatin immunoprecipitation experiments show enhanced...... a promoter-proximal 5′ splice site via its U1 snRNA interaction can feed back to stimulate transcription initiation by enhancing preinitiation complex assembly....

The effect of a large Danish offshore wind farm on harbor and grey seal haul-out behaviour

DEFF Research Database (Denmark)

Edrén, Susi Manuela Clermont; Andersen, Signe May; Teilmann, Jonas

2010-01-01

This study investigates the effects of the construction and operation of a large Danish offshore wind farm on harbor and gray seal haul-out behavior within a nearby (4 km) seal sanctuary. Time-lapse photography, visual monitoring, and aerial surveys were used to monitor the number of seals on land...... in daylight hours. Seals were monitored during two preconstruction periods (19 June–31 August 2001 and April–August 2002), a construction period of the wind farm (August 2002–December 2003), and a period of operation of the wind farm (December 2003–December 2004). Monthly aerial surveys were conducted...... to estimate the proportion of seals in the sanctuary relative to neighboring haul-out sites. From preconstruction to construction and through the first year of operation the number of harbor seals in the sanctuary increased at the same rate as the number of seals at the neighboring haul-out sites. No long...

The Suez Canal and the petroleum harbors

International Nuclear Information System (INIS)

Anon.

1997-01-01

The Suez Canal is the second longest channel in the world and allows to save 60% of the travel time between the petroleum harbors of the Arabic peninsula and Europe. This short paper gives a summary of the main petroleum harbors activity along the channel from the Red sea to the Mediterranean sea. (J.S.)

Distribution and contamination status of chromium in surface sediments of northern Kaohsiung Harbor, Taiwan.

Science.gov (United States)

Dong, Cheng-Di; Chen, Chiu-Wen; Chen, Chih-Feng

2013-07-01

The distribution, enrichment, accumulation, and potential ecological risk of chromium (Cr) in the surface sediments of northern Kaohsiung Harbor, Taiwan, China were investigated. Sediment samples from ten locations located between the river mouths and harbor entrance of northern Kaohsiung Harbor were collected quarterly in 2011 and characterized for Cr, aluminum, water content, organic matter, total nitrogen, total phosphorous, total grease, and grain size. Results showed that the Cr concentrations varied from 27.0 to 361.9 mg/kg with an average of (113.5 +/- 87.0) mg/kg. High Cr concentration was observed near the Jen-Gen River mouth. The mean Cr concentration was high at 255.5 mg/kg, which was at least 2 to 7 times than that of other sites. This might imply significant Cr contribution from upstream receiving tanneries wastewater into the Jen-Gen River. The spatial distribution of Cr reveals relatively high in the river mouth region, especially in Jen-Gen River, and gradually diminishes toward the harbor entrance region. This indicates that the major sources of Cr pollution from upstream industrial and municipal wastewaters discharged along the river bank; and Cr may drift with sea current and be dispersed into open sea. Moreover, Cr concentrations correlated closely to the physical-chemical properties of the sediments, which suggested the influence of industrial and municipal wastewaters discharged from the neighboring industrial parks and river basins. Results from the enrichment factor and geo-accumulation index analyses imply that the Jen-Gen River sediments can be characterized as moderate enrichment and none to medium accumulation of Cr, respectively. However, results of potential ecological risk index indicate that the sediment has low ecological potential risk. The results can provide valuable information to developing future strategies for the management of river mouth and harbor.

Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

Energy Technology Data Exchange (ETDEWEB)

Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Mostovich, Lyudmila A. [The Institute of Molecular Biology and Biophysics, Timakova str., 2/12, Novosibirsk 630117 (Russian Federation); Pustylnyak, Yuliya A. [Novosibirsk State University, Pirogova str., 2, Novosibirsk 630090 (Russian Federation); Pustylnyak, Vladimir O., E-mail: pustylnyak@ngs.ru [The Institute of Molecular Biology and Biophysics, Timakova str., 2/12, Novosibirsk 630117 (Russian Federation); Novosibirsk State University, Pirogova str., 2, Novosibirsk 630090 (Russian Federation); The Institute International Tomography Center of the Russian Academy of Sciences, Institutskaya str. 3-A, Novosibirsk 630090 (Russian Federation)

2015-10-01

MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α–CAR cross-talk in the regulation of miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α–CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments. - Highlights: • CAR activation decreased the level of miR-122 in mouse livers. • CAR decreases

Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

International Nuclear Information System (INIS)

Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Mostovich, Lyudmila A.; Pustylnyak, Yuliya A.; Pustylnyak, Vladimir O.

2015-01-01

MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α–CAR cross-talk in the regulation of miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α–CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments. - Highlights: • CAR activation decreased the level of miR-122 in mouse livers. • CAR decreases

Wave Climate and Wave Response, 2025 Plan, Kahului Harbor, Maui, Hawaii

National Research Council Canada - National Science Library

Thompson, Edward

2002-01-01

... (wind waves and swell) and long waves (harbor oscillations), was used to evaluate the technical feasibility of three alternative modifications to the harbor, including the Kahului Commercial Harbor 2025 Master Plan...

33 CFR 162.165 - Buffalo and Rochester Harbors, New York.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Buffalo and Rochester Harbors, New York. 162.165 Section 162.165 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... and Rochester Harbors, New York. In Buffalo and Rochester Harbors, no vessel may exceed 6 miles per...

Satellite Monitoring of Boston Harbor Water Quality: Initial Investigations

Science.gov (United States)

Sheldon, P.; Chen, R. F.; Schaaf, C.; Pahlevan, N.; Lee, Z.

2016-02-01

The transformation of Boston Harbor from the "dirtiest in America" to a National Park Area is one of the most remarkable estuarine recoveries in the world. A long-term water quality dataset from 1991 to present exists in Boston Harbor due to a $3. 8 billion lawsuit requiring the harbor clean-up. This project uses discrete water sampling and underway transects with a towed vehicle coordinated with Landsat 7 and Landsat 8 to create surface maps of chlorophyll a (Chl a), dissolved organic matter (CDOM and DOC), total suspended solids (TSS), diffuse attenuation coefficient (Kd_490), and photic depth in Boston Harbor. In addition, 3 buoys have been designed, constructed, and deployed in Boston Harbor that measure Chl a and CDOM fluorescence, optical backscatter, salinity, temperature, and meteorological parameters. We are initially using summer and fall of 2015 to develop atmospheric corrections for conditions in Boston Harbor and develop algorithms for Landsat 8 data to estimate in water photic depth, TSS, Chl a, Kd_490, and CDOM. We will report on initial buoy and cruise data and show 2015 Landsat-derived distributions of water quality parameters. It is our hope that once algorithms for present Landsat imagery can be developed, historical maps of water quality can be constructed using in water data back to 1991.

HIV-1 replication in cell lines harboring INI1/hSNF5 mutations

Directory of Open Access Journals (Sweden)

Wu Xuhong

2006-08-01

Full Text Available Abstract Background INI1/hSNF5 is a cellular protein that directly interacts with HIV-1 integrase (IN. It is specifically incorporated into HIV-1 virions. A dominant negative mutant derived from INI1 inhibits HIV-1 replication. Recent studies indicate that INI1 is associated with pre-integration and reverse transcription complexes that are formed upon viral entry into the target cells. INI1 also is a tumor suppressor, biallelically deleted/mutated in malignant rhabdoid tumors. We have utilized cell lines derived from the rhabdoid tumors, MON and STA-WT1, that harbor either null or truncating mutations of INI1 respectively, to assess the effect of INI1 on HIV-1 replication. Results We found that while HIV-1 virions produced in 293T cells efficiently transduced MON and STA-WT1 cells, HIV-1 particle production was severely reduced in both of these cells. Reintroduction of INI1 into MON and STA-WT1 significantly enhanced the particle production in both cell lines. HIV-1 particles produced in MON cells were reduced for infectivity, while those produced in STA-WT1 were not. Further analysis indicated the presence of INI1 in those virions produced from STA-WT1 but not from those produced from MON cells. HIV-1 produced in MON cells were defective for synthesis of early and late reverse transcription products in the target cells. Furthermore, virions produced in MON cells were defective for exogenous reverse transcriptase activity carried out using exogenous template, primer and substrate. Conclusion Our results suggest that INI1-deficient cells exhibit reduced particle production that can be partly enhanced by re-introduction of INI1. Infectivity of HIV-1 produced in some but not all INI1 defective cells, is affected and this defect may correlate to the lack of INI1 and/or some other proteins in these virions. The block in early events of virion produced from MON cells appears to be at the stage of reverse transcription. These studies suggest that

HIV-1 replication in cell lines harboring INI1/hSNF5 mutations.

Science.gov (United States)

Sorin, Masha; Yung, Eric; Wu, Xuhong; Kalpana, Ganjam V

2006-08-31

INI1/hSNF5 is a cellular protein that directly interacts with HIV-1 integrase (IN). It is specifically incorporated into HIV-1 virions. A dominant negative mutant derived from INI1 inhibits HIV-1 replication. Recent studies indicate that INI1 is associated with pre-integration and reverse transcription complexes that are formed upon viral entry into the target cells. INI1 also is a tumor suppressor, biallelically deleted/mutated in malignant rhabdoid tumors. We have utilized cell lines derived from the rhabdoid tumors, MON and STA-WT1, that harbor either null or truncating mutations of INI1 respectively, to assess the effect of INI1 on HIV-1 replication. We found that while HIV-1 virions produced in 293T cells efficiently transduced MON and STA-WT1 cells, HIV-1 particle production was severely reduced in both of these cells. Reintroduction of INI1 into MON and STA-WT1 significantly enhanced the particle production in both cell lines. HIV-1 particles produced in MON cells were reduced for infectivity, while those produced in STA-WT1 were not. Further analysis indicated the presence of INI1 in those virions produced from STA-WT1 but not from those produced from MON cells. HIV-1 produced in MON cells were defective for synthesis of early and late reverse transcription products in the target cells. Furthermore, virions produced in MON cells were defective for exogenous reverse transcriptase activity carried out using exogenous template, primer and substrate. Our results suggest that INI1-deficient cells exhibit reduced particle production that can be partly enhanced by re-introduction of INI1. Infectivity of HIV-1 produced in some but not all INI1 defective cells, is affected and this defect may correlate to the lack of INI1 and/or some other proteins in these virions. The block in early events of virion produced from MON cells appears to be at the stage of reverse transcription. These studies suggest that presence of INI1 or some other host factor in virions and

Old Harbor Scammon Bay Hydro Feasibility

Energy Technology Data Exchange (ETDEWEB)

Brent Petrie

2007-06-27

The grantee, Alaska Village Electric Cooperative (AVEC), is a non-profit member owned rural electric generation and distribution cooperative. The proposed Project is located near the community of Old Harbor, Alaska. Old Harbor is on the southeastern coast of Kodiak Island, approximately 70 miles southwest of the City of Kodiak and 320 miles southwest of Anchorage. In 1998 sufficient information had been developed to apply for a license to construct the project and the cost was estimated to be $2,445,000 for a 500 KW project on Lagoon Creek. Major features of the project included an eight-foot high diversion dam on Mountain Creek, a desander box, a 9,800-foot long penstock to the powerhouse on Lagoon Creek, and a 5,500-foot long access road. It was also anticipated that the project could provide an additional source of water to Old Harbor. The report details the history and lessons learned in designing and permiting the proposed hydroelectric facility.

High Prevalence of Diabetes-Predisposing Variants in MODY Genes Among Danish Women With Gestational Diabetes Mellitus

DEFF Research Database (Denmark)

Gjesing, Anette Marianne Prior; Rui, Gao; Lauenborg, Jeannet

2017-01-01

Context: Gestational diabetes mellitus (GDM), defined as any degree of glucose intolerance with first recognition during pregnancy, is a heterogeneous form of diabetes characterized by various degrees ofβ-cell dysfunction. Objectives: We aimed to estimate the prevalence of possibly pathogenic...... variants in the maturity-onset diabetes of the young genesGCK,HNF1A,HNF4A,HNF1B, andINSamong women with GDM. Furthermore, we examined the glucose tolerance status in variant carriers vs noncarriers at follow-up. Design Setting and Patients: We sequenced the coding regions and intron/exon boundaries of.......9% (95% confidence interval: 3.5% to 8.4%). At follow-up, 15 out of 135 women with diabetes (11%) were carriers of variants inGCK,HNF1A,HNF4A,HNF1B, orINS. Conclusions: Almost 6% of Danish women with diet-treated GDM have possibly pathogenic variants inGCK,HNF1A,HNF4A,HNF1B, orINS. These women...

Genome-wide analysis of PDX1 target genes in human pancreatic progenitors

Directory of Open Access Journals (Sweden)

Xianming Wang

2018-03-01

Full Text Available Objective: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4. Although the function of Pdx1 is well studied in pre-clinical models during insulin-producing β-cell development and homeostasis, it remains elusive how this TF controls human pancreas development by regulating a downstream transcriptional program. Also, comparative studies of PDX1 binding patterns in pancreatic progenitors and adult β-cells have not been conducted so far. Furthermore, many studies reported the association between single nucleotide polymorphisms (SNPs and T2DM, and it has been shown that islet enhancers are enriched in T2DM-associated SNPs. Whether regions, harboring T2DM-associated SNPs are PDX1 bound and active at the pancreatic progenitor stage has not been reported so far. Methods: In this study, we have generated a novel induced pluripotent stem cell (iPSC line that efficiently differentiates into human pancreatic progenitors (PPs. Furthermore, PDX1 and H3K27ac chromatin immunoprecipitation sequencing (ChIP-seq was used to identify PDX1 transcriptional targets and active enhancer and promoter regions. To address potential differences in the function of PDX1 during development and adulthood, we compared PDX1 binding profiles from PPs and adult islets. Moreover, combining ChIP-seq and GWAS meta-analysis data we identified T2DM-associated SNPs in PDX1 binding sites and active chromatin regions. Results: ChIP-seq for PDX1 revealed a total of 8088 PDX1-bound regions that map to 5664 genes in iPSC-derived PPs. The PDX1 target regions include important pancreatic TFs, such as PDX1 itself, RFX6, HNF1B, and MEIS1, which were activated during the differentiation process as revealed by the active chromatin mark H3K27ac and mRNA expression profiling, suggesting that auto-regulatory feedback regulation

Identification of novel variants in the hepatocyte nuclear factor-1alpha gene in South Indian patients with maturity onset diabetes of young

DEFF Research Database (Denmark)

Radha, V; Ek, J; Anuradha, S

2009-01-01

. There are very few data on MODY mutations from India. OBJECTIVE: The objective was to screen coding and promoter regions of HNF1A gene for mutations in unrelated South Indian subjects in whom a clinical diagnosis of MODY was made. DESIGN: This was an observational cross-sectional study. SETTING: The study...... studies revealed reduced transcriptional activity of the HNF1A promoter for two promoter variants. We also observed cosegregation with diabetes of the Arg263His coding region mutation in eight members of one MODY family, whereas it was absent in nondiabetic subjects of this family. CONCLUSION: This study...... suggests that mutations in the HNF1A gene comprise about 9% of clinically diagnosed MODY subjects in southern India and a novel Arg263His mutation cosegregates with MODY in one family....

A Transcriptional Regulatory Network Containing Nuclear Receptors and Long Noncoding RNAs Controls Basal and Drug-Induced Expression of Cytochrome P450s in HepaRG Cells.

Science.gov (United States)

Chen, Liming; Bao, Yifan; Piekos, Stephanie C; Zhu, Kexin; Zhang, Lirong; Zhong, Xiao-Bo

2018-07-01

Cytochrome P450 (P450) enzymes are responsible for metabolizing drugs. Expression of P450s can directly affect drug metabolism, resulting in various outcomes in therapeutic efficacy and adverse effects. Several nuclear receptors are transcription factors that can regulate expression of P450s at both basal and drug-induced levels. Some long noncoding RNAs (lncRNAs) near a transcription factor are found to participate in the regulatory functions of the transcription factors. The aim of this study is to determine whether there is a transcriptional regulatory network containing nuclear receptors and lncRNAs controlling both basal and drug-induced expression of P450s in HepaRG cells. Small interfering RNAs or small hairpin RNAs were applied to knock down four nuclear receptors [hepatocyte nuclear factor 1 α (HNF1 α ), hepatocyte nuclear factor 4 α (HNF4 α ), pregnane X receptor (PXR), and constitutive androstane receptor (CAR)] as well as two lncRNAs [HNF1 α antisense RNA 1 (HNF1 α -AS1) and HNF4 α antisense RNA 1 (HNF4 α -AS1)] in HepaRG cells with or without treatment of phenobarbital or rifampicin. Expression of eight P450 enzymes was examined in both basal and drug-induced levels. CAR and PXR mainly regulated expression of specific P450s. HNF1 α and HNF4 α affected expression of a wide range of P450s as well as other transcription factors. HNF1 α and HNF4 α controlled the expression of their neighborhood lncRNAs, HNF1 α -AS1 and HNF4 α -AS1, respectively. HNF1 α -AS1 and HNF4 α -AS1 was also involved in the regulation of P450s and transcription factors in diverse manners. Altogether, our study concludes that a transcription regulatory network containing the nuclear receptors and lncRNAs controls both basal and drug-induced expression of P450s in HepaRG cells. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Charleston Harbor, SC, Regional Sediment Management Study: Beneficial Use of Dredged Material through Nearshore Placement

Science.gov (United States)

2017-05-01

Modeling System (CMS) that were developed and applied previously for the Charleston Harbor numerical modeling study (Kashlan 2013) were used in...Particle Tracking Model; Report 1: Model theory, implementation, and example applications. ERDC/CHL TR-6-20. Vicksburg, MS: U.S. Army Engineer Research ...ER D C/ CH L TR -1 7- 7 Regional Sediment Management (RSM) Program Charleston Harbor, SC, Regional Sediment Management Study

Charleston Harbor, SC, Regional Sediment Management Study; Beneficial Use of Dredged Material through Nearshore Placement

Science.gov (United States)

2017-05-01

Modeling System (CMS) that were developed and applied previously for the Charleston Harbor numerical modeling study (Kashlan 2013) were used in...Particle Tracking Model; Report 1: Model theory, implementation, and example applications. ERDC/CHL TR-6-20. Vicksburg, MS: U.S. Army Engineer Research ...ER D C/ CH L TR -1 7- 7 Regional Sediment Management (RSM) Program Charleston Harbor, SC, Regional Sediment Management Study

Ecological evaluation of proposed discharge of dredged material from Oakland Harbor into ocean waters (Phase 3 B of -42-foot project)

Energy Technology Data Exchange (ETDEWEB)

Kohn, N.P.; Ward, J.A.; Mayhew, H.L.; Word, J.Q.; Barrows, E.S.; Goodwin, S.M.; Lefkovitz, L.F. (Battelle/Marine Sciences Lab., Sequim, WA (United States))

1992-06-01

The Water Resources Development Act of 1986 (Public Law 99-662) authorized the US Army Corps of Engineers (USACE) San Francisco District, to deepen and widen the navigational channels of the Oakland Inner and Outer Harbors to accommodate deeper-draft vessels. The USACE is considering several disposal options for the dredged material removed during these channel improvements including open-water disposal. Dredged material proposed for open-water disposal must be evaluated to determine the potential impacts of the disposal activity on the water column and disposal site environments. The USACE requested that Battelle/Marine Sciences Laboratory (MSL) conduct studies to evaluate open-water disposal options for Oakland Harbor sediments. This request developed into the Oakland Harbor Phase III Program. This is Volume 2 of a two-volume report that presents information gathered to determine the suitability of ocean disposal of sediments dredged from Oakland Harbor. This volume contains the Appendixes (A through N), which provide details of the data analyses and full presentation of the data and results.

Tales of some ancient harbors in the Aegean back-arc region: Earthquakes, coastal changes, historical impacts

Science.gov (United States)

Stiros, Stathis; Saltogianni, Vasso

2017-04-01

Tectonically active terrains are characterized by seismic transient ground motions (shaking) and by permanent ground motions in the vicinity of activated faults, with both effects occasionally leaving their signature on human constructions and the landscape. Especially in coastal areas marked by small tidal ranges and normal water salinity, as is the case with most parts of the Eastern Mediterranean, even small-amplitude tectonic motions can be derived from observations on coastal constructions, mainly harbors, but also on spring chambers in nearly arid environments, sewers, etc. Such observations, if coupled with well-dated observations of destructions and repairs and of changes in the occupation style of ancient sites can permit precious information conveyed from archaeology to tectonics/seismology and vice versa. A transect with harbor remains from Rhodes to the Gulf of Corinth and then till the Ionian Islands provides some excellent examples. The military harbor of Rhodes, in an area of long term uplift, a coded report of which seems to be provided by ancient poet Pindar, was subject to seismic subsidence and destruction, but with major international support, it was repaired, till renewed uplift brought it several meters above the water. In the Corinth area, the Kenchreai harbor was abruptly submerged during a major repair of a temple, as revealed by precious stained glass panels, ready to use but abandoned in shallow water beneath ruins, while radiometric dating of the uplift in the western Lechaion harbor, constrains its excavation in swampy environment not in Roman times, but to the period of flourishing of Corinth in circa 600BC and the colonization of Italy. Farther west, the sea-level mark of the harbor of Aigeira, at Mavra Litharia (Derveni/Akrata) indicates 4m uplift since the Roman period, at least partly seismic, correlating with an exposed reef and the abandonment of the repairs of the theatre of Aigeira. Seismic land uplift explains the demise of

Investigation of the marine communities of Midway Harbor and adjacent lagoon, Midway Atoll, Northwest Hawaiian Islands in 1998 (NODC Accession 0001098)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — A survey of the marine communities of Midway Atoll harbor and surrounding lagoon was conducted at 12 sites from September 5 to 9, 1998. The primary focus of these...

Assessement of nonindigenous marine species in harbors and nearby coral reefs on Kauai, Molokai, Maui, and Hawaii, 2002-2003 (NODC Accession 0002270)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Collections and observations in 2002-2003 at harbor and nearby reef sites at Nawilwili and Port Allen, Kauai; Hale O Lono and Kaunakakai, Molokai; Kahului and...

Assessment of nonindigenous marine species in harbors and nearby coral reefs on Kauai, Molokai, Maui, and Hawaii, 2002 - 2003 (NODC Accession 0002270)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Collections and observations in 2002-2003 at harbor and nearby reef sites at Nawilwili and Port Allen, Kauai; Hale O Lono and Kaunakakai, Molokai; Kahului and...

77 FR 45239 - Amendment of Class E Airspace; Bar Harbor, ME

Science.gov (United States)

2012-07-31

...-1366; Airspace Docket No. 11-ANE-13] Amendment of Class E Airspace; Bar Harbor, ME AGENCY: Federal... area at Bar Harbor, ME, as the Surry Non-Directional Radio Beacon (NDB) has been decommissioned and new Standard Instrument Approach Procedures have been developed at Hancock County-Bar Harbor Airport. This...

Final Hanford Site Transuranic (TRU) Waste Characterization QA Project Plan

International Nuclear Information System (INIS)

GREAGER, T.M.

2000-01-01

The Quality Assurance Project Plan (QAPjP) has been prepared for waste characterization activities to be conducted by the Transuranic (TRU) Project at the Hanford Site to meet requirements set forth in the Waste Isolation Pilot Plan (WIPP) Hazardous Waste Facility Permit, 4890139088-TSDF, Attachment B, including Attachments B1 through B6 (WAP) (DOE, 1999a). The QAPjP describes the waste characterization requirements and includes test methods, details of planned waste sampling and analysis, and a description of the waste characterization and verification process. In addition, the QAPjP includes a description of the quality assurance/quality control (QA/QC) requirements for the waste characterization program. Before TRU waste is shipped to the WIPP site by the TRU Project, all applicable requirements of the QAPjP shall be implemented. Additional requirements necessary for transportation to waste disposal at WIPP can be found in the ''Quality Assurance Program Document'' (DOE 1999b) and HNF-2600, ''Hanford Site Transuranic Waste Certification Plan.'' TRU mixed waste contains both TRU radioactive and hazardous components, as defined in the WLPP-WAP. The waste is designated and separately packaged as either contact-handled (CH) or remote-handled (RH), based on the radiological dose rate at the surface of the waste container. RH TRU wastes are not currently shipped to the WIPP facility

77 FR 60109 - Takes of Marine Mammals Incidental to Specified Activities; Harbor Activities Related to the...

Science.gov (United States)

2012-10-02

...; and Northern elephant seals by Level B harassment only. To date, we have issued nine, 1-year... numbers of marine mammals, incidental to conducting Delta Mariner harbor operations for one year. We... California sea lions (Zalophus californianus), Pacific harbor seals (Phoca vitulina), and Northern elephant...

33 CFR 165.1402 - Apra Outer Harbor, Guam-regulated navigation area.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Apra Outer Harbor, Guam-regulated....1402 Apra Outer Harbor, Guam—regulated navigation area. (a) The following is a regulated navigation area—The waters of the Pacific Ocean and Apra Outer Harbor enclosed by a line beginning at latitude 13...

Carboxylesterase 1 Is Regulated by Hepatocyte Nuclear Factor 4α and Protects Against Alcohol- and MCD diet-induced Liver Injury.

Science.gov (United States)

Xu, Jiesi; Xu, Yang; Li, Yuanyuan; Jadhav, Kavita; You, Min; Yin, Liya; Zhang, Yanqiao

2016-04-14

The liver is a major organ that controls hepatic and systemic homeostasis. Dysregulation of liver metabolism may cause liver injury. Previous studies have demonstrated that carboxylesterase 1 (CES1) regulates hepatic triglyceride metabolism and protects against liver steatosis. In the present study, we investigated whether CES1 played a role in the development of alcoholic liver disease (ALD) and methionine and choline-deficient (MCD) diet-induced liver injury. Both hepatocyte nuclear factor 4α (HNF4α) and CES1 were markedly reduced in patients with alcoholic steatohepatitis. Alcohol repressed both HNF4α and CES1 expression in primary hepatocytes. HNF4α regulated CES1 expression by directly binding to the proximal promoter of CES1. Global inactivation of CES1 aggravated alcohol- or MCD diet-induced liver inflammation and liver injury, likely as a result of increased production of acetaldehyde and reactive oxygen species and mitochondrial dysfunctions. Knockdown of hepatic CES1 exacerbated ethanol-induced steatohepatitis. These data indicate that CES1 plays a crucial role in protection against alcohol- or MCD diet-induced liver injury.

Identification and Functional Characterization of P159L Mutation in in a Family with Maturity-Onset Diabetes of the Young 5 (MODY5

Directory of Open Access Journals (Sweden)

Eun Ky Kim

2014-12-01

Full Text Available Mutation in HNF1B, the hepatocyte nuclear factor-1β (HNF-1β gene, results in maturity-onset diabetes of the young (MODY 5, which is characterized by gradual impairment of insulin secretion. However, the functional role of HNF-1β in insulin secretion and glucose metabolism is not fully understood. We identified a family with early-onset diabetes that fulfilled the criteria of MODY. Sanger sequencing revealed that a heterozygous P159L (CCT to CTT in codon 159 in the DNA-binding domain mutation in HNF1B was segregated according to the affected status. To investigate the functional consequences of this HNF1B mutation, we generated a P159L HNF1B construct. The wild-type and mutant HNF1B constructs were transfected into COS-7 cells in the presence of the promoter sequence of human glucose transporter type 2 (GLUT2. The luciferase reporter assay revealed that P159L HNF1B had decreased transcriptional activity compared to wild-type (p < 0.05. Electrophoretic mobility shift assay showed reduced DNA binding activity of P159L HNF1B. In the MIN6 pancreatic β-cell line, overexpression of the P159L mutant was significantly associated with decreased mRNA levels of GLUT2 compared to wild-type (p < 0.05. However, INS expression was not different between the wild-type and mutant HNF1B constructs. These findings suggests that the impaired insulin secretion in this family with the P159L HNF1B mutation may be related to altered GLUT2 expression in β-cells rather than decreased insulin gene expression. In conclusion, we have identified a Korean family with an HNF1B mutation and characterized its effect on the pathogenesis of diabetes.

33 CFR 110.197 - Galveston Harbor, Bolivar Roads Channel, Texas.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Galveston Harbor, Bolivar Roads Channel, Texas. 110.197 Section 110.197 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Roads Channel, Texas. (a)(1) Anchorage area (A). The water bounded by a line connecting the following...

Response to crizotinib in a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant

Science.gov (United States)

Zhao, Zheng; Song, Zhangjun; Wang, Xuwei; Sun, Haifeng; Yang, Xiaomin; Yuan, Yong; Yu, Pan

2017-01-01

ROS1 fusion is a common genetic alteration in non-small-cell lung cancer. Crizotinib, an anaplastic lymphoma kinase inhibitor, shows efficacy in the treatment of lung cancer cases with ROS1 translocation. We report the response to crizotinib of a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant, which was different from the two common SLC34A2-ROS1 fusion types reported in the literature. After crizotinib administration, overall recovery was good in this patient; the primary lesion was successfully treated, the lymph node metastases had disappeared, and the metabolism was normal. PMID:28860822

Cold Spring Harbor symposia on quantitative biology: Volume 49, Recombination at the DNA level

International Nuclear Information System (INIS)

1984-01-01

This volume contains full papers prepared by the participants to the 1984 Cold Springs Harbor Symposia on Quantitative Biology. This year's theme is entitled Recombination at the DNA level. The volume consists of 93 articles grouped into subject areas entitled chromosome mechanics, yeast systems, mammalian homologous recombination, transposons, mu, plant transposons/T4 recombination, topoisomerase, resolvase and gyrase, Escherichia coli general recombination, RecA, repair, leukaryotic enzymes, integration and excision of bacteriophage, site-specific recombination, and recombination in vitro

Mutation in the factor VII hepatocyte nuclear factor 4α-binding site contributes to factor VII deficiency.

Science.gov (United States)

Zheng, Xing-Wu; Kudaravalli, Rama; Russell, Theresa T; DiMichele, Donna M; Gibb, Constance; Russell, J Eric; Margaritis, Paris; Pollak, Eleanor S

2011-10-01

Severe coagulant factor VII (FVII) deficiency in postpubertal dizygotic twin males results from two point mutations in the FVII gene, a promoter region T→C transition at -60 and a His-to-Arg substitution at amino acid 348; both mutations prevent persistence of plasma functional FVII. This report documents longitudinal laboratory measurements from infancy to adulthood of FVII coagulant activity (FVII:C) in the twin FVII-deficient patients; it also details specific biochemical analyses of the -60 T→C mutation. The results revealed FVII:C levels of less than 1% in infancy that remain severely decreased through puberty and into adulthood. In-vitro analyses utilizing hepatocyte nuclear factor 4α (HNF4α) co-transfection and a chromatin immunoprecipitation assay indicate that the -60 T→C mutation severely diminishes functional interaction between the FVII promoter and transcription factor HNF4α. The importance of interaction between the FVII gene and HNF4α in normal FVII expression provides an in-vivo illustration of the regulated expression of an autosomal gene encoding a coagulation protein. The constancy of FVII:C and peripubertal patient symptomatology reported here illustrates androgen-independent expression in contrast to expression with an analogous mutation in the promoter region of the gene encoding coagulation FIX.

Towards an ethics safe harbor for global biomedical research

Science.gov (United States)

Dove, Edward S.; Knoppers, Bartha M.; Zawati, Ma'n H.

2014-01-01

Although increasingly global, data-driven genomics and other ‘omics’-focused research hold great promise for health discoveries, current research ethics review systems around the world challenge potential improvements in human health from such research. To overcome this challenge, we propose a ‘Safe Harbor Framework for International Ethics Equivalency’ that facilitates the harmonization of ethics review of specific types of data-driven international research projects while respecting globally transposable research ethics norms and principles. The Safe Harbor would consist in part of an agency supporting an International Federation for Ethics Review (IFER), formed by a voluntary compact among countries, granting agencies, philanthropies, institutions, and healthcare, patient advocacy, and research organizations. IFER would be both a central ethics review body, and also a forum for review and follow-up of policies concerning ethics norms for international research projects. It would be built on five principle elements: (1) registration, (2) compliance review, (3) recognition, (4) monitoring and enforcement, and (5) public participation. The Safe Harbor would create many benefits for researchers, countries, and the general public, and may eventually have application beyond (gen)omics to other areas of biomedical research that increasingly engage in secondary use of data and present only negligible risks. PMID:27774154

Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma.

Science.gov (United States)

Cai, Shao-Hang; Lu, Shi-Xun; Liu, Li-Li; Zhang, Chris Zhiyi; Yun, Jing-Ping

2017-10-01

Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. A total of 615 HCC specimens were obtained to construct tissue microarrays and perform immunohistochemistry. The relationship between P2-HNF4α and clinical features of HCC patients were analysed. Kaplan-Meier analysis was conducted to assess the prognostic value of P2-HNF4α. The results showed that the expression of P2-HNF4α in HCC was noticeably increased in HCC tissues compared with the nontumourous tissues. In addition, P1-HNF4α expression was negatively correlated with P2-HNF4α expression ( p  = 0.023). High P2-HNF4α expression was significantly associated with poor differentiation of HCC ( p = 0.002) and vascular invasion ( p = 0.017). Kaplan-Meier analysis showed that P2-HNF4α expression was closely correlated with overall survival in the training group ( p = 0.01), validation group ( p = 0.034), and overall group of patients with HCC ( p P2-HNF4α, different from P1-HNF4α, is markedly upregulated and serves as an oncogene-associated protein in HCC. Our study therefore provides a promising biomarker for prognostic prediction and a potential therapeutic target for HCC.

Ground-water status report, Pearl Harbor area, Hawaii, 1978

Science.gov (United States)

Soroos, Ronald L.; Ewart, Charles J.

1979-01-01

Increasing demand for freshwater in Hawaii has placed heavy stress on many of the State 's basal aquifer systems. The most heavily stressed of these systems is the Pearl Harbor on Oahu. The Pearl Harbor basal aquifer supplies as much as 277 million gallons per day. Since early in this century, spring discharge has been declining while pumpage has been increasing. Total ground-water discharge has remained steady despite short-term fluctuations. Some wells show general increases in chloride concentration while others remain steady. Chloride concentrations throughout the area show no apparent increase since 1970. Basal water head maps of the Pearl Harbor area clearly reflect the natural discharge points, which are the springs located along the shore near the center of Pearl Harbor. Basal-water hydrographs show a general decline of about 0.09 foot per year. This implies depletion of storage at a rate of about 25 million gallons per day. (USGS).

Alaska Harbor Seal Glacial Surveys

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Floating glacial ice serves as a haul-out substrate for a significant number (10-15%) of Alaskan harbor seals, and thus surveying tidewater glacial fjords is an...

32 CFR 705.31 - USS Arizona Memorial, Pearl Harbor.

Science.gov (United States)

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false USS Arizona Memorial, Pearl Harbor. 705.31... NAVY REGULATIONS AND OFFICIAL RECORDS PUBLIC AFFAIRS REGULATIONS § 705.31 USS Arizona Memorial, Pearl Harbor. (a) Limited space and the desirability of keeping the Memorial simple and dignified require the...

Evaluation of Proposed Dredged Material Disposal Alternatives for New York/New Jersey Harbor. Phase 1

Science.gov (United States)

1988-08-01

been developed ( Westerdahl and Skogerboe 1981) and is being used x..-’. to predict surface runoff water quality from dredged material as part of the...Islands in New York Harbor," Miscellaneous Paper D-88-3, US Army Engineer Waterways Experiment Station, Vicksburg, MS. Westerdahl , H. E., and Skogerboe

Defense Infrastructure: General and Flag Officer Quarters at Pearl Harbor, Hawaii

National Research Council Canada - National Science Library

2002-01-01

.... We reviewed 17 GFOQs at Pearl Harbor, Hawaii, with budgeted maintenance and repair costs of $1,247,300, to determine whether the Navy had properly classified interior shutter costs as maintenance and repair...

MODY in Ukraine: genes, clinical phenotypes and treatment.

Science.gov (United States)

Globa, Evgenia; Zelinska, Nataliya; Elblova, Lenka; Dusatkova, Petra; Cinek, Ondrej; Lebl, Jan; Colclough, Kevin; Ellard, Sian; Pruhova, Stepanka

2017-10-26

Maturity-onset diabetes of the young (MODY) has not been previously studied in Ukraine. We investigated the genetic etiology in a selected cohort of patients with diabetes diagnosed before 18 years of age, and in their family members. Genetic testing of the most prevalent MODY genes (GCK, HNF1A, HNF4A, HNF1B and INS) was undertaken for 36 families (39 affected individuals) by Sanger or targeted next generation sequencing. A genetic diagnosis of MODY was made in 15/39 affected individuals from 12/36 families (33%). HNF1A and HNF4A MODY were the most common subtypes, accounting for 9/15 of MODY cases. Eight patients with HNF1A or HNF4A MODY and inadequate glycemic control were successfully transferred to sulfonylureas. Median HbA1c decreased from 67 mmol/mol (range 58-69) to 47 mmol/mol (range 43-50) (8.3% [7.5-8.5] to 6.4% [6.1-6.7]) 3 months after transfer (p=0.006). Genetic testing identified pathogenic HNF1A and HNF4A variants as the most common cause of MODY in Ukraine. Transfer to sulfonylureas substantially improved the glycemic control of these patients.

Software configuration plan for the 1,000 CFM portable exhauster's small logic control system

International Nuclear Information System (INIS)

Kaiser, T.D.

1998-01-01

This document describes the formal documentation for maintaining the control system associated with the 1,000 CFM portable exhauster's. The objective of the software configuration control plan is to provide assurances that the portable exhauster's control system will be operable for the duration of 241-C-106 and 241-AY-102 operations (project 320). The design was based upon the criteria documented in the portable exhauster functional design criteria (HNF-SD-WM-DB-035) and procurement specification (HNF-S-0490) for the exhauster interlock systems

33 CFR 117.181 - Oakland Inner Harbor Tidal Canal.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Oakland Inner Harbor Tidal Canal. 117.181 Section 117.181 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY... Tidal Canal. The draws of the Alameda County highway drawbridges at Park Street, mile 5.2; Fruitvale...

76 FR 32071 - Safety Zone; Conneaut Festival Fireworks, Conneaut Harbor, Conneaut, OH

Science.gov (United States)

2011-06-03

...-AA00 Safety Zone; Conneaut Festival Fireworks, Conneaut Harbor, Conneaut, OH AGENCY: Coast Guard, DHS... Conneaut Harbor, Conneaut, OH for the Conneaut Festival Fireworks. This zone is intended to restrict vessels from a portion of Conneaut Harbor, Conneaut, OH during the Conneaut Festival Fireworks on July 3...

A Comprehensive Copper Compliance Strategy: Implementing Regulatory Guidance at Pearl Harbor Naval Shipyard & Intermediate Maintenance Facility

Science.gov (United States)

2007-01-01

species was not listed in the PHLP database (Bishop Museum, 1998). Personal observations by John Zardus (Kewalo Marine Laboratory, Honolulu, Hawaii...Ringwood, 1992). Specimens collected from an open coastal site by the University of Hawaii ( John Zardus ), did not survive the shipment (less than 24... John Ornellas, Randy Kido, and Rich Anderson from Code 106.3. The Shipyard Pearl Harbor Regional Dive Locker, Code 760, provided professional, high

77 FR 27666 - Proposed Amendment of Class E Airspace; Bar Harbor, ME

Science.gov (United States)

2012-05-11

...-1366; Airspace Docket No. 11-ANE-13] Proposed Amendment of Class E Airspace; Bar Harbor, ME AGENCY... action proposes to amend Class E Airspace at Bar Harbor, ME, as the Surry Non-Directional Radio Beacon... Hancock County-Bar Harbor Airport. This action would enhance the safety and airspace management of...

33 CFR 334.1430 - Apra Inner Harbor, Island of Guam; restricted area.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Apra Inner Harbor, Island of Guam... THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.1430 Apra Inner Harbor, Island of Guam; restricted area. (a) The restricted area. The waters within Apra Inner Harbor and...

Harbor seal vibrissa morphology suppresses vortex-induced vibrations

OpenAIRE

Hanke, Wolf; Witte, Mathias; Miersch, Lars; Brede, Martin; Oeffner, Johannes; Michael, Mark; Hanke, Frederike; Leder, Alfred; Dehnhardt, Guido

2010-01-01

Harbor seals (Phoca vitulina) often live in dark and turbid waters, where their mystacial vibrissae, or whiskers, play an important role in orientation. Besides detecting and discriminating objects by direct touch, harbor seals use their whiskers to analyze water movements, for example those generated by prey fish or by conspecifics. Even the weak water movements left behind by objects that have passed by earlier can be sensed and followed accurately (hydrodynamic trail following). While scan...

Assessment of a combination between hard structures and sand nourishment eastern of Damietta harbor using numerical modeling

Directory of Open Access Journals (Sweden)

A.M. Khalifa

2017-12-01

Full Text Available Damietta harbor was constructed in 1982 as an inland harbor with its 15 m depth navigation channel and two jetties acting like an obstacle to not allow sediment deposition in the harbor. On the other hand, they significantly affect the northern coast shoreline and hinder the sediment circulation in Damietta promontory. Satellite images show that new headlands are being implemented in the coastal shores of As-senaneyah. The proposed project consists of implementation of four headlands with length of 160 m, spacing of 400 m and using 150,000 m3 nourishment in those spacing between the hard structures only once during the construction time. Litpack 1D-model is used to predict shoreline responses to number of different five scenarios considered as combination between hard structures such as headlands and sand nourishment. A total number of 32 profiles were used to assess the shoreline changes along Gamasa, Damietta and Ras El-bar resort from 2010 to 2015. This study prevails a high erosion rate of the eastern and western shorelines of the proposed headlands. Nourishment of 200,000 m3/year is found to be a reasonable solution due to simplicity of being attained from Damietta harbor’s annual dredged materials which was reported to be average of 1 million m3/year. Keywords: Numerical modeling, Damietta harbor, Egyptian shoreline changes, Inland harbor

75 FR 42742 - Alaska Village Electric Cooperative; Notice of Environmental Site Review and Scoping Meeting

Science.gov (United States)

2010-07-22

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Project No. 13272-001] Alaska Village Electric Cooperative; Notice of Environmental Site Review and Scoping Meeting July 15, 2010. a. Project No.: 13272-001. b. Name of Project: Old Harbor Hydroelectric Project. c. Location: On Mountain Creek, near the town of Old Harbor, Kodiak Island...

Reference: SITE3SORPS1 [PLACE

Lifescience Database Archive (English)

Full Text Available SITE3SORPS1 Villain P, Clabault G, Mache R, Zhou DX S1F binding site is related to ...but different from the light-responsive GT-1 binding site and differentially represses the spinach rps1 prom

FoxA1 binding to the MMTV LTR modulates chromatin structure and transcription

International Nuclear Information System (INIS)

Holmqvist, Per-Henrik; Belikov, Sergey; Zaret, Kenneth S.; Wrange, Oerjan

2005-01-01

Novel binding sites for the forkhead transcription factor family member Forkhead box A (FoxA), previously referred to as Hepatocyte Nuclear Factor 3 (HNF3), were found within the mouse mammary tumor virus long terminal repeat (MMTV LTR). The effect of FoxA1 on MMTV LTR chromatin structure, and expression was evaluated in Xenopus laevis oocytes. Mutagenesis of either of the two main FoxA binding sites showed that the distal site, -232/-221, conferred FoxA1-dependent partial inhibition of glucocorticoid receptor (GR) driven MMTV transcription. The proximal FoxA binding segment consisted of two individual FoxA sites at -57/-46 and -45/-34, respectively, that mediated an increased basal MMTV transcription. FoxA1 binding altered the chromatin structure of both the inactive- and the hormone-activated MMTV LTR. Hydroxyl radical foot printing revealed FoxA1-mediated changes in the nucleosome arrangement. Micrococcal nuclease digestion showed the hormone-dependent sub-nucleosome complex, containing ∼120 bp of DNA, to be expanded by FoxA1 binding to the proximal segment into a larger complex containing ∼200 bp. The potential function of the FoxA1-mediated expression of the MMTV provirus for maintenance of expression in different tissues is discussed

Ecological evaluation of proposed discharge of dredged material from Oakland Harbor into ocean waters (Phase 3 B of -42-foot project). Volume 2, Appendixes

Energy Technology Data Exchange (ETDEWEB)

Kohn, N.P.; Ward, J.A.; Mayhew, H.L.; Word, J.Q.; Barrows, E.S.; Goodwin, S.M.; Lefkovitz, L.F. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

1992-06-01

The Water Resources Development Act of 1986 (Public Law 99-662) authorized the US Army Corps of Engineers (USACE) San Francisco District, to deepen and widen the navigational channels of the Oakland Inner and Outer Harbors to accommodate deeper-draft vessels. The USACE is considering several disposal options for the dredged material removed during these channel improvements including open-water disposal. Dredged material proposed for open-water disposal must be evaluated to determine the potential impacts of the disposal activity on the water column and disposal site environments. The USACE requested that Battelle/Marine Sciences Laboratory (MSL) conduct studies to evaluate open-water disposal options for Oakland Harbor sediments. This request developed into the Oakland Harbor Phase III Program. This is Volume 2 of a two-volume report that presents information gathered to determine the suitability of ocean disposal of sediments dredged from Oakland Harbor. This volume contains the Appendixes (A through N), which provide details of the data analyses and full presentation of the data and results.

The Hanford Site: An anthology of early histories

Energy Technology Data Exchange (ETDEWEB)

Gerber, M.S.

1993-10-01

This report discusses the following topics: Memories of War: Pearl Harbor and the Genesis of the Hanford Site; safety has always been promoted at the Hanford Site; women have an important place in Hanford Site history; the boom and bust cycle: A 50-year historical overview of the economic impacts of Hanford Site Operations on the Tri-Cities, Washington; Hanford`s early reactors were crucial to the sites`s history; T-Plant made chemical engineering history; the UO{sub 3} plant has a long history of service. PUREX Plant: the Hanford Site`s Historic Workhorse. PUREX Plant Waste Management was a complex challenge; and early Hanford Site codes and jargon.

Influenza A(H10N7) Virus in Dead Harbor Seals, Denmark

DEFF Research Database (Denmark)

Krog, Jesper Schak; Hansen, Mette Sif; Holm, Elisabeth

2015-01-01

Since April 2014, an outbreak of influenza in harbor seals has been ongoing in northern Europe. In Denmark during June-August, 152 harbor seals on the island of Anholt were found dead from severe pneumonia. We detected influenza A(H10N7) virus in 2 of 4 seals examined.......Since April 2014, an outbreak of influenza in harbor seals has been ongoing in northern Europe. In Denmark during June-August, 152 harbor seals on the island of Anholt were found dead from severe pneumonia. We detected influenza A(H10N7) virus in 2 of 4 seals examined....

Emergence of fatal avian influenza in New England harbor seals

Science.gov (United States)

Anthony, S.J.; St. Leger, J. A.; Pugliares, K.; Ip, Hon S.; Chan, J.M.; Carpenter, Z.W.; Navarrete-Macias, I.; Sanchez-Leon, M.; Saliki, J.T.; Pedersen, J.; Karesh, W.; Daszak, P.; Rabadan, R.; Rowles, T.; Lipkin, W.I.

2012-01-01

From September to December 2011, 162 New England harbor seals died in an outbreak of pneumonia. Sequence analysis of postmortem samples revealed the presence of an avian H3N8 influenza A virus, similar to a virus circulating in North American waterfowl since at least 2002 but with mutations that indicate recent adaption to mammalian hosts. These include a D701N mutation in the viral PB2 protein, previously reported in highly pathogenic H5N1 avian influenza viruses infecting people. Lectin staining and agglutination assays indicated the presence of the avian-preferred SAα-2,3 and mammalian SAα-2,6 receptors in seal respiratory tract, and the ability of the virus to agglutinate erythrocytes bearing either the SAα-2,3 or the SAα-2,6 receptor. The emergence of this A/harbor seal/Massachusetts/1/2011 virus may herald the appearance of an H3N8 influenza clade with potential for persistence and cross-species transmission.

Harbor seal vibrissa morphology suppresses vortex-induced vibrations.

Science.gov (United States)

Hanke, Wolf; Witte, Matthias; Miersch, Lars; Brede, Martin; Oeffner, Johannes; Michael, Mark; Hanke, Frederike; Leder, Alfred; Dehnhardt, Guido

2010-08-01

Harbor seals (Phoca vitulina) often live in dark and turbid waters, where their mystacial vibrissae, or whiskers, play an important role in orientation. Besides detecting and discriminating objects by direct touch, harbor seals use their whiskers to analyze water movements, for example those generated by prey fish or by conspecifics. Even the weak water movements left behind by objects that have passed by earlier can be sensed and followed accurately (hydrodynamic trail following). While scanning the water for these hydrodynamic signals at a swimming speed in the order of meters per second, the seal keeps its long and flexible whiskers in an abducted position, largely perpendicular to the swimming direction. Remarkably, the whiskers of harbor seals possess a specialized undulated surface structure, the function of which was, up to now, unknown. Here, we show that this structure effectively changes the vortex street behind the whiskers and reduces the vibrations that would otherwise be induced by the shedding of vortices from the whiskers (vortex-induced vibrations). Using force measurements, flow measurements and numerical simulations, we find that the dynamic forces on harbor seal whiskers are, by at least an order of magnitude, lower than those on sea lion (Zalophus californianus) whiskers, which do not share the undulated structure. The results are discussed in the light of pinniped sensory biology and potential biomimetic applications.

Frequency Domain Response at Pacific Coast Harbors to Major Tsunamis of 2005-2011

Science.gov (United States)

Xing, Xiuying; Kou, Zhiqing; Huang, Ziyi; Lee, Jiin-Jen

2013-06-01

Tsunamis waves caused by submarine earthquake or landslide might contain large wave energy, which could cause significant human loss and property damage locally as well as in distant region. The response of three harbors located at the Pacific coast (i.e. Crescent City Harbor, Los Angeles/Long Beach Port, and San Diego Harbor) to six well-known tsunamis events generated (both near-field and far-field) between 2005 and 2011 are examined and simulated using a hybrid finite element numerical model in frequency domain. The model incorporated the effects of wave refraction, wave diffraction, partial wave reflection from boundaries, entrance and bottom energy dissipation. It can be applied to harbor regions with arbitrary shapes and variable water depth. The computed resonant periods or modes of oscillation for three harbors are in good agreement with the energy spectral analysis of the time series of water surface elevations recorded at tide gauge stations inside three harbors during the six tsunamis events. The computed wave induced currents based on the present model are also in qualitative agreement with some of the reported eye-witness accounts absence of reliable current data. The simulated results show that each harbor responded differently and significantly amplified certain wave period(s) of incident wave trains according to the shape, topography, characteristic dimensions and water depth of the harbor basins.

Using the dioxin receptor-calux in vitro bioassay to screen marine harbor sediments for compounds with a dioxin-like mode of action

NARCIS (Netherlands)

Stronkhorst, J.; Leonards, P.E.G.; Murk, A.J.

2002-01-01

The presence of dioxin-like compounds in sediments from harbors and reference sites along the Dutch coast was investigated using the dioxin receptor–chemically activated luciferase gene expression (DR-CALUX) bioassay. The DR-CALUX response varied between 0.2 and 136 ng/kg dry weight expressed in

Aerial Survey Counts of Harbor Seals in Coastal Alaska (1998-2002)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This dataset supports efforts to estimate the abundance and trends in population size of Alaska harbor seals. Annual surveys of harbor seal populations are...

Aerial Survey Counts of Harbor Seals in Coastal Alaska (2003-2011)

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — This dataset supports efforts to estimate the abundance and trends in population size of Alaska harbor seals. Annual surveys of harbor seal populations are...

78 FR 63381 - Safety Zones; Hawaiian Island Commercial Harbors, HI

Science.gov (United States)

2013-10-24

...; Kaumalapau, Lanai; Kahului, Maui and Kawaihae and Hilo on the Island of Hawaii). The purpose of these safety... the piers faces. (9) All waters of Hilo Harbor, Hawaii immediately adjacent to commercial piers 1 and.... SUMMARY: The Coast Guard is establishing nine (9) permanent safety zones encompassing Hawaii's commercial...

78 FR 18479 - Drawbridge Operation Regulations; Inner Harbor Navigation Canal, New Orleans, LA

Science.gov (United States)

2013-03-27

... Operation Regulations; Inner Harbor Navigation Canal, New Orleans, LA AGENCY: Coast Guard, DHS. ACTION... across the Inner Harbor Navigation Canal, mile 4.6, at New Orleans, Louisiana. This deviation is... Seabrook Highway crossing the Inner Harbor Navigation Canal, mile 4.6, in New Orleans, Louisiana. The...

The Hanford Site: An anthology of early histories

International Nuclear Information System (INIS)

Gerber, M.S.

1993-10-01

This report discusses the following topics: Memories of War: Pearl Harbor and the Genesis of the Hanford Site; safety has always been promoted at the Hanford Site; women have an important place in Hanford Site history; the boom and bust cycle: A 50-year historical overview of the economic impacts of Hanford Site Operations on the Tri-Cities, Washington; Hanford's early reactors were crucial to the sites's history; T-Plant made chemical engineering history; the UO 3 plant has a long history of service. PUREX Plant: the Hanford Site's Historic Workhorse. PUREX Plant Waste Management was a complex challenge; and early Hanford Site codes and jargon

76 FR 50489 - Agency Information Collection Activities: Harbor Maintenance Fee

Science.gov (United States)

2011-08-15

... Activities: Harbor Maintenance Fee AGENCY: U.S. Customs and Border Protection, Department of Homeland... Fee (CBP Forms 349 and 350). This is a proposed extension of an information collection that was... Fee. OMB Number: 1651-0055. Form Number: CBP Forms 349 and 350. Abstract: The Harbor Maintenance Fee...

Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

Science.gov (United States)

Meier, Daniel; Schindler, Detlev

2011-01-01

The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

Fanconi anemia core complex gene promoters harbor conserved transcription regulatory elements.

Directory of Open Access Journals (Sweden)

Daniel Meier

Full Text Available The Fanconi anemia (FA gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS. In the 5' region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 3' regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-β and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs, and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.

Pearl Harbor: lessons for the dam safety community

Energy Technology Data Exchange (ETDEWEB)

Martin, T.E. [AMEC Earth and Environmental Ltd., Burnaby, BC (Canada)

2001-10-01

Every good dam safety program must be based on surveillance and emergency response planning. The same principles apply to the gathering of information for military intelligence and the planning of defence tactics. Lessons learned from failure have spurred the advancement of dam engineering. Dam safety experts can benefit from the inadequacies encountered by the military community, with the most famous occurring on December 7, 1941 in Pearl Harbor. Both intelligence gathering and contingency response planning failed miserably. The data was not properly disseminated, interpreted, analysed. The proper response to the situation was not initiated. Human error and failure to communicate are the two main reasons that explain the debacle. The inquiries into the tragedy at Pearl Harbor provided valuable lessons, related to individual and organizational failures, which the authors shared in this presentation. The relevance to dam safety was made. All Federal Bureau of Investigation (FBI) agents must read the lessons drawn from Pearl Harbor, as they have responsibility for dam safety. 4 refs.

Preclinical Validation of Novel Fluorescently Labeled Compounds to Treat Neurodegenerative Hearing Loss

Science.gov (United States)

2016-10-01

dance at sporting events and concerts, and the aging of a populous generation place 1.1 billion more at risk (Daniel, 2007; Wallhagen et al., 1997...cochlea [Fig. 6(A)]. VOT-33 cells were transfected with Hnf4a shRNA to knock down HNF4a expression and observe the effects of HNF4a deficiency on cell...and cell viability due to Hnf4a knock - down, suggesting that HNF4a may play a role in cochlear neuroblast survival. DISCUSSION We report the first

Isolation, screening, and characterization of surface-active agent-producing, oil-degrading marine bacteria of Mumbai Harbor.

Science.gov (United States)

Mohanram, Rajamani; Jagtap, Chandrakant; Kumar, Pradeep

2016-04-15

Diverse marine bacterial species predominantly found in oil-polluted seawater produce diverse surface-active agents. Surface-active agents produced by bacteria are classified into two groups based on their molecular weights, namely biosurfactants and bioemulsifiers. In this study, surface-active agent-producing, oil-degrading marine bacteria were isolated using a modified Bushnell-Haas medium with high-speed diesel as a carbon source from three oil-polluted sites of Mumbai Harbor. Surface-active agent-producing bacterial strains were screened using nine widely used methods. The nineteen bacterial strains showed positive results for more than four surface-active agent screening methods; further, these strains were characterized using biochemical and nucleic acid sequencing methods. Based on the results, the organisms belonged to the genera Acinetobacter, Alcanivorax, Bacillus, Comamonas, Chryseomicrobium, Halomonas, Marinobacter, Nesterenkonia, Pseudomonas, and Serratia. The present study confirmed the prevalence of surface-active agent-producing bacteria in the oil-polluted waters of Mumbai Harbor. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rhizosphere of rice plants harbor bacteria with multiple plant growth ...

African Journals Online (AJOL)

Rhizosphere of rice plants harbor bacteria with multiple plant growth promoting features. ... 45 (39.46%) isolates were capable of producing siderophore, the range of production being 4.50 to 223.26 μg mg-1 protein. Analysis of molecular diversity was made by amplified ribosomal DNA restriction analysis (ARDRA) and ...

Crystal structure of an affinity-matured prolactin complexed to its dimerized receptor reveals the topology of hormone binding site 2

DEFF Research Database (Denmark)

Broutin, Isabelle; Jomain, Jean-Baptiste; Tallet, Estelle

2010-01-01

We report the first crystal structure of a 1:2 hormone.receptor complex that involves prolactin (PRL) as the ligand, at 3.8-A resolution. Stable ternary complexes were obtained by generating affinity-matured PRL variants harboring an N-terminal tail from ovine placental lactogen, a closely relate...... and prostate cancer.......We report the first crystal structure of a 1:2 hormone.receptor complex that involves prolactin (PRL) as the ligand, at 3.8-A resolution. Stable ternary complexes were obtained by generating affinity-matured PRL variants harboring an N-terminal tail from ovine placental lactogen, a closely related...... PRL receptor (PRLR) ligand. This structure allows one to draw up an exhaustive inventory of the residues involved at the PRL.PRLR site 2 interface, consistent with all previously reported site-directed mutagenesis data. We propose, with this description, an interaction model involving three structural...

Ecological evaluation of proposed dredged material from Richmond Harbor

International Nuclear Information System (INIS)

Pinza, M.R.; Ward, J.A.; Mayhew, H.L.; Word, J.Q.; Niyogi, D.K.; Kohn, N.P.

1992-10-01

During the summer of 1991, Battelle/Marine Sciences Laboratory (MSL) was contracted to conduct sampling and testing of sediments proposed for dredging of Richmond Harbor, California. The MSL collected sediment cores to a depth of -40 ft MLLW (-38 ft + 2 ft overdepth) from 28 (12-in. core) and 30 (4-in. core) stations. The sediment cores were allocated to six composite samples referred to as sediment treatments, which were then subjected to physical, chemical, toxicological, and bioaccumulation testing. Physical and chemical parameters included grain size, total organic carbon (TOC), total volatile solids (TVS), oil and grease, total petroleum hydrocarbons (TPH), polynuclear aromatic hydrocarbons (PAH), chlorinated pesticides, polychlorinated biphenyis (PCBs), priority pollutant metals, and butyltins. The results from the test treatments were compared to results from five reference treatments representative of potential in-bay and offshore disposal sites

Ecological evaluation of proposed dredged material from Richmond Harbor

Energy Technology Data Exchange (ETDEWEB)

Pinza, M R; Ward, J A; Mayhew, H L; Word, J Q; Niyogi, D K; Kohn, N P [Battelle/Marine Sciences Lab., Sequim, WA (United States)

1992-10-01

During the summer of 1991, Battelle/Marine Sciences Laboratory (MSL) was contracted to conduct sampling and testing of sediments proposed for dredging of Richmond Harbor, California. The MSL collected sediment cores to a depth of [minus]40 ft MLLW ([minus]38 ft + 2 ft overdepth) from 28 (12-in. core) and 30 (4-in. core) stations. The sediment cores were allocated to six composite samples referred to as sediment treatments, which were then subjected to physical, chemical, toxicological, and bioaccumulation testing. Physical and chemical parameters included grain size, total organic carbon (TOC), total volatile solids (TVS), oil and grease, total petroleum hydrocarbons (TPH), polynuclear aromatic hydrocarbons (PAH), chlorinated pesticides, polychlorinated biphenyis (PCBs), priority pollutant metals, and butyltins. The results from the test treatments were compared to results from five reference treatments representative of potential in-bay and offshore disposal sites.

Genetics Home Reference: Floating-Harbor syndrome

Science.gov (United States)

... Patton MA, Hurst J, Donnai D, McKeown CM, Cole T, Goodship J. Floating-Harbor syndrome. J Med ... medicine? What is newborn screening? New Pages Lyme disease Fibromyalgia White-Sutton syndrome All New & Updated Pages ...

Regulation of a TGF-β1-CD147 self-sustaining network in the differentiation plasticity of hepatocellular carcinoma cells.

Science.gov (United States)

Wu, J; Lu, M; Li, Y; Shang, Y-K; Wang, S-J; Meng, Y; Wang, Z; Li, Z-S; Chen, H; Chen, Z-N; Bian, H

2016-10-20

Cellular plasticity has an important role in the progression of hepatocellular carcinoma (HCC). In this study, the involvement of a TGF-β1-CD147 self-sustaining network in the regulation of the dedifferentiation progress was fully explored in HCC cell lines, hepatocyte-specific basigin/CD147-knockout mice and human HCC tissues. We demonstrated that TGF-β1 stimulation upregulated CD147 expression and mediated the dedifferentiation of HCC cells, whereas all-trans-retinoic acid induced the downregulation of CD147 and promoted differentiation in HCC cells. Overexpression of CD147 induced the dedifferentiation and enhanced the malignancy of HCC cells, and increased the transcriptional expression of TGF-β1 by activating β-catenin. CD147-induced matrix metalloproteinase (MMP) production activated pro-TGF-β1. The activated TGF-β1 signaling subsequently repressed the HNF4α expression via Smad-Snail1 signaling and enhanced the dedifferentiation progress. Hepatocyte-specific basigin/CD147-knockout mice decreased the susceptibility to N-nitrosodiethylamine-induced tumorigenesis by suppressing TGF-β1-CD147 signaling and inhibiting dedifferentiation in hepatocytes during tumor progression. CD147 was positively correlated with TGF-β1 and negatively correlated with HNF4α in human HCC tissues. Positive CD147 staining and lower HNF4α levels in tumor tissues were significantly associated with poor survival of patients with HCC. The overexpression of HNF4α and Smad7 and the deletion of CD147 by lentiviral vectors jointly reprogrammed the expression profile of hepatocyte markers and attenuated malignant properties including proliferation, cell survival and tumor growth of HCC cells. Our results highlight the important role of the TGF-β1-CD147 self-sustaining network in driving HCC development by regulating differentiation plasticity, which provides a strong basis for further investigations of the differentiation therapy of HCC targeting TGF-β1 and CD147.

A Comparison of Microbial Water Quality and Diversity for Ballast and Tropical Harbor Waters.

Science.gov (United States)

Ng, Charmaine; Le, Thai-Hoang; Goh, Shin Giek; Liang, Liang; Kim, Yiseul; Rose, Joan B; Yew-Hoong, Karina Gin

2015-01-01

Indicator organisms and antibiotic resistance were used as a proxy to measure microbial water quality of ballast tanks of ships, and surface waters in a tropical harbor. The survival of marine bacteria in ballast tanks appeared to diminish over longer water retention time, with a reduction of cell viability observed after a week based on heterotrophic plate counts. Pyrosequencing of 16S rRNA genes showed distinct differences in microbial composition of ballast and harbor waters. The harbor waters had a higher abundance of operational taxonomic units (OTUs) assigned to Cyanobacteria (Synechococcus spp.) and α-proteobacteria (SAR11 members), while marine hydrocarbon degraders such as γ-proteobacteria (Ocenspirillaes spp., Thiotrchales spp.) and Bacteroidetes (Flavobacteriales spp.) dominated the ballast water samples. Screening of indicator organisms found Escherichia coli (E. coli), Enterococcus and Pseudomonas aeruginosa (P. aeruginosa) in two or more of the ballast and harbor water samples tested. Vibrio spp. and Salmonella spp. were detected exclusively in harbor water samples. Using quantitative PCR (qPCR), we screened for 13 antibiotic resistant gene (ARG) targets and found higher abundances of sul1 (4.13-3.44 x 102 copies/mL), dfrA (0.77-1.80 x10 copies/mL) and cfr (2.00-5.21 copies/mL) genes compared to the other ARG targets selected for this survey. These genes encode for resistance to sulfonamides, trimethoprim and chloramphenicol-florfenicol antibiotics, which are also known to persist in sediments of aquaculture farms and coastal environments. Among the ARGs screened, we found significant correlations (Pwater quality survey, quantitatively assessing indicators of antibiotic resistance, potentially pathogenic organisms and a broad-brush description of difference in microbial composition and diversity between open oceans and tropical coastal environments through the use of next generation sequencing technology.

Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma

OpenAIRE

Cai, Shao-hang; Lu, Shi-xun; Liu, Li-li; Zhang, Chris Zhiyi; Yun, Jing-ping

2017-01-01

Background: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. Methods: A total of 615 HCC specimens were obtained to construct tissue microarrays and pe...

76 FR 38153 - California State Nonroad Engine Pollution Control Standards; Commercial Harbor Craft Regulations...

Science.gov (United States)

2011-06-29

... Standards; Commercial Harbor Craft Regulations; Opportunity for Public Hearing and Comment AGENCY... engines on commercial harbor craft. CARB has requested that EPA issue a new authorization under [email protected] . SUPPLEMENTARY INFORMATION: I. California's Commercial Harbor Craft Regulations In a...

CHIRP survey of the submerged harbors of King Herod's Caesarea, offshore Israel - looking for evidence of ancient disasters

Science.gov (United States)

Austin, J. A.; Goodman-Tchernov, B.

2012-12-01

Caesarea Maritima, located on the Israel coast south of Haifa, is an ancient city/harbor site built ~2,000 years ago that continues to produce important insights into both the maritime livelihoods of antiquity and natural/anthropogenic influences on coastal structures/processes. The grandiose, three-basin harbor complex was built by Herod the Great. Today, the inner harbor basin is terrestrial, while the majority of the intermediate/outer harbors lies 1-7 m beneath the sea surface. Explanations for the harbor's destruction have included earthquakes, liquefaction, deterioration from erosion, storm undercutting and tsunami damage. Recently, evidence for tsunami events has been discovered offshore during excavation and coring expeditions, specifically trench exposures and pneumatic hammer cores. Stratigraphic horizons containing tsunamite signatures suggest the occurrence of at least three tsunamis in the past ~3,500 yrs. One may correspond with the catastrophic eruption of Santorini ~1500 BC; another appears to have done significant damage to Caesarea ~115 AD, and a third occurred within the period 5th-7th centuries AD. Extant combined bathymetric/magnetic surveys offshore also show unusual, anomalous features. Excavations in 2003 suggest that these features may be part of an ancient designated anchoring station, and support the existence of underlying man-made terrestrial structures from an earlier period when sea-level was lower. The primary goal of the current survey was to correlate recognized/potential tsunamigenic sediment layers throughout the proximal shelf offshore Caesarea, using extremely high-resolution geophysical images. Such surficial sub-bottom profiling will allow archaeologists to proceed with investigations of recognized anthropogenically-influenced submerged coastal features. The field survey was conducted in August 2011. Seismic data were collected using UTIG's portable Knudsen 320BP CHIRP (2.5-5.5 kHz) profiler, affixed to a metal pole mounted

Congress Investigates: Pearl Harbor and 9/11 Congressional Hearing Exhibits

Science.gov (United States)

Blackerby, Christine

2011-01-01

On the morning of December 7, 1941, Japanese bombers staged a surprise attack on U.S. military forces at Pearl Harbor in Hawaii. Sixty years after the attack on Pearl Harbor, the United States was attacked again. On the morning of September 11, 2001, four commercial airplanes hijacked by 19 terrorists killed nearly 3,000 people when they crashed…

Cold Spring Harbor symposia on quantitative biology. Volume XLVII, Part 1. Structures of DNA

International Nuclear Information System (INIS)

Anon.

1983-01-01

The proceedings for the 47th Annual Cold Spring Harbor Symposia on Quantitative Biology are presented. This symposium focused on the Structure of DNA. Topics presented covered research in the handedness of DNA, conformational analysis, chemically modified DNA, chemical synthesis of DNA, DNA-protein interactions, DNA within nucleosomes, DNA methylation, DNA replication, gyrases and topoisomerases, recombining and mutating DNA, transcription of DNA and its regulation, the organization of genes along DNA, repetitive DNA and pseudogenes, and origins of replication, centromeres, and teleomeres

Composition and variation of sediment bacterial and nirS-harboring bacterial communities at representative sites of the Bohai Gulf coastal zone, China.

Science.gov (United States)

Guan, Xiangyu; Zhu, Lingling; Li, Youxun; Xie, Yuxuan; Zhao, Mingzhang; Luo, Ximing

2014-04-01

With rapid urbanization, anthropogenic activities are increasingly influencing the natural environment of the Bohai Bay. In this study, the composition and variation of bacterial and nirS-harboring bacterial communities in the coastal zone sediments of the Bohai Gulf were analyzed using PCR-based clone libraries. A total of 95 genera were detected in the bacterial communities, with Proteobacteria (72.1 %), Acidobacteria (10.5 %), Firmicutes (1.7 %), Bacteroidetes (1.4 %), Chloroflexi (0.7 %) and Planctomycetes (0.7 %) being the dominated phyla. The NirS sequences were divided into nine Clusters (A-I). Canonical correlation analysis showed that the bacterial or denitrifying communities were correlated with different environmental factors, such as total organic carbon, total nitrogen, ammonium, sulfate, etc. Furthermore, bacterial communities' composition and diversity are influenced by oil exploration, sewage discharge and other anthropogenic activities in the coastal area of the Bohai Sea. Thus, this study provided useful information on further research on regional or global environmental control and restore.

Sedimentation and chronology of heavy metal pollution in Oslo harbor, Norway

International Nuclear Information System (INIS)

Lepland, Aivo; Andersen, Thorbjorn J.; Lepland, Aave; Arp, Hans Peter H.; Alve, Elisabeth; Breedveld, Gijs D.; Rindby, Anders

2010-01-01

Stratigraphic profiles of Cu, Cd and Hg in ten sediment cores from the Oslo harbor, Norway, combined with results of radiometric dating demonstrate that pollution by these metals peaked between 1940 and 1970. Dating results indicate that Hg discharges peaked between 1940 and 1950, Cd reached maximum ca. 1955-1960, and Cu has the highest concentration in sediment interval corresponding to ca. 1970. Geochemical profiles and maxima of Cu, Cd and Hg concentrations can be used as chronostratigraphic markers for sediment cores from the Oslo harbor. Acoustic backscatter and sediment core data indicate that propeller wash affects the seabed in the Oslo harbor. The propeller-induced turbulence causes erosion, and in places exposes and remobilizes contaminated sediments that accumulated in the harbor during previous decades. Such re-exposure of contaminated sediments could be detrimental to local ecosystems and offset remediation efforts, warranting further impact studies and potential mitigation strategies to prevent redistribution.

77 FR 50916 - Safety Zone; Boston Harbor's Rock Removal Project, Boston Inner Harbor, Boston, MA

Science.gov (United States)

2012-08-23

... operation on the navigable waters of Boston Inner Harbor, in the main ship channel near Castle Island. This... operations in support of the U.S. Army Corps of Engineers rock removal project. Entering into, transiting... before the start date of the project. The U.S. Army Corps of Engineers also discussed the rock removal...

33 CFR 110.214 - Los Angeles and Long Beach harbors, California.

Science.gov (United States)

2010-07-01

... Angeles Harbor). A circular area with a radius of 400 yards (approximately 366 meters), centered in... 400 Transportation Corridor. (C) Outer Harbor: The western boundary of Commercial Anchorage B. (2... Thence along a line described as an arc, radius of 460 meters (approximately 1509 feet) centered on 33...

Seasonal monitoring of blue mussel (Mytilus spp.) populations in a harbor area: A focus on responses to environmental factors and chronic contamination.

Science.gov (United States)

Lacroix, C; Duvieilbourg, E; Guillou, N; Guyomarch, J; Bassoulet, C; Moraga, D; Chapalain, G; Auffret, M

2017-08-01

Coastal waters corresponding to macrotidal systems are among the most variable marine biotopes. Sessile animals as bivalve mollusks may however be found forming intertidal beds at high densities, as allowed by full adaptation to local conditions. A better knowledge of adaptive responses to environmental factors is required to foresee possible adverse effects of global change. At the sub-cellular level, transcriptional responses are among the earliest signals of environmental disturbances and they can reveal subtle and meaningful changes in organism exposed to stress. Three blue mussel (Mytilus spp.) populations inhabiting the Bay of Brest (France) in sites exposed to different levels of chronic pollution, from low to moderate, were surveyed upon a seasonal schedule, with special attention to the reproductive cycle. Major seawater parameters were monitored over a full-year in the framework of the S!RANO project, based on an automatic high frequency acquisition system installed aboard a ship of opportunity. The health status of mussels has been assessed by measuring a condition index and gametogenesis has been followed by histology. Selected biological responses to environmental stress were detected using a multimarker approach including expression of genes involved in chemical stress response and energetic metabolism, and cellular immune parameters. Environmental parameters showed deep seasonal variations which differed among sites. Most biological responses followed a seasonal pattern. Late winter and spring corresponded to an active reproduction period in the Bay of Brest. Earlier spawning was observed in harbor areas compared to the oceanic site and an altered physiological state was assumed in commercial harbor mussels during the reproductive period, suggesting that their health is compromised at this time of year. However, no signs of severe chemical stress were detected in both harbor mussel populations, which could reflect adaptive responses to adverse

Influence of the Pearl River estuary and vertical mixing in Victoria Harbor on water quality in relation to eutrophication impacts in Hong Kong waters.

Science.gov (United States)

Yin, Kedong; Harrison, Paul J

2007-06-01

This study presents water quality parameters such as nutrients, phytoplankton biomass and dissolved oxygen based on 11 years of water quality data in Victoria Harbor and examined how the Pearl River estuary discharge in summer and year round sewage discharge influenced these parameters. Nutrients in Victoria Harbor were strongly influenced by both the Pearl River and sewage effluent, as indicated by the high NO(3) inputs from the Pearl River in summer and higher NH(4) and PO(4) in Victoria Harbor than both its sides. N:P ratios were low in the dry season, but increased to >16:1 in the wet season, suggesting that P is potentially the most limiting nutrient in this area during the critical period in the summer. Although there were generally high nutrients, the phytoplankton biomass was not as high as one would expect in Victoria Harbor. In fact, there were high concentrations of chl near the bottom well below the photic zone. Salinity near the bottom was lower in Victoria Harbor than at the two entrances to Victoria Harbor, suggesting strong vertical mixing within Victoria Harbor. Therefore, strong vertical mixing and horizontal advection appear to play an important role in significantly reducing eutrophication impacts in Victoria Harbor. Consequently, dissolved oxygen near the bottom was low in summer, but only occasionally dipped to 2 mgL(-1) despite the high organic loading from sewage effluent.

Hydrophobic organic contaminants in surficial sediments of Baltimore Harbor: Inventories and sources

International Nuclear Information System (INIS)

Ashley, J.T.F.; Baker, J.E.

1999-01-01

The heavily urbanized and industrialized Baltimore Harbor/Patapsco River/Back River system is one of the most highly contaminated regions of the Chesapeake Bay. In June 1996, surficial sediments were collected at 80 sites throughout the subestuarine system, including historically undersampled creek sand embayments. The samples were analyzed for a suite of hydrophobic organic contaminants (HOCs) consisting of 32 polycyclic aromatic hydrocarbons (PAHs) and 113 polychlorinated biphenyl (PCB) congeners. Total PAH and total PCB concentrations ranged from 90 to 46,200 and 8 to 2,150 ng/g dry weight, respectively. There was enormous spatial variability in the concentrations of HOCs, which was not well correlated to grain size or organic carbon content, suggesting nonequilibrium partitioning and/or proximity to sources as important factors explaining the observed spatial variability. High concentrations of both classes of HOCs were localized around major urban stormwater runoff discharges. Elevated PAH concentrations were also centered around the Sparrow's Point Industrial Complex, most likely a result of the pyrolysis of coal during the production of steel. All but 1 of the 80 sites exceeded the effects range-low (ERL) for total PCBs and, of those sites, 40% exceeded the effects range-medium (ERM), suggesting toxicity to marine benthic organisms would frequently occur. Using principal component analysis, differences in PAH signatures were discerned. Higher molecular weight PAHs were enriched in signatures from sediments close to suspected sources (i.e., urban stormwater runoff and steel production complexes) compared to those patterns observed at sites further from outfalls or runoff. Due to varying solubilities and affinities for organic matter of the individual PAHs, partitioning of the heavier weight PAHs may enrich settling particles with high molecular weight PAHs. Lower molecular weight PAHs, having lower affinity for particles, may travel from the source to a

Preliminary site description Forsmark area - version 1.1

International Nuclear Information System (INIS)

2004-03-01

This report presents the interim version (model version 1.1) of the preliminary Site Descriptive Model for Forsmark. The basis for this interim version is quality-assured, geoscientific and ecological field data from Forsmark that were available in the SKB databases SICADA and GIS at April 30, 2003 as well as version 0 of the Site Descriptive Model. The new data acquired during the initial site investigation phase to the date of data freeze 1.1 constitute the basis for the updating of version 0 to version 1.1. These data originate from surface investigations on the candidate area with its regional environment and from drilling and investigations in boreholes. The surface-based data sets were rather extensive whereas the data sets from boreholes were limited to information from one 1,000 m deep cored borehole (KFM01A) and eight 150 to 200 m deep percussion-drilled boreholes in the Forsmark candidate area. Discipline specific models are developed for a selected regional and local model volume and these are then integrated into a site description. The current methodologies for developing the discipline specific models and the integration of these are documented in methodology reports or strategy reports. In the present work, the guidelines given in those reports were followed to the extent possible with the data and information available at the time for data freeze for model version 1.1. Compared with version 0 there are considerable additional features in the version 1.1, especially in the geological description and in the description of the near surface. The geological models of lithology and deformation zones are based on borehole information and much higher resolution surface data. The existence of highly fractured sub-horizontal zones has been verified and these are now part of the model of the deformation zones. A discrete fracture network (DFN) model has also been developed. The rock mechanics model is based on strength information from SFR and an empirical

Littoral cells and harbor dredging along the California coast

Science.gov (United States)

Griggs, Gary B.

1987-02-01

Beach compartments or littoral cells form the framework for our understanding of the sources, transport, and sinks of sand in the nearshore zone. In general, along the California coast, beach sand is derived from rivers or clifferosion, moves alongshore under the influence of the prevailing waver conditions, and ultimately is lost either to a submarine canyon or a dune field. Marinas or harbors built either between or at the upcoast ends of beach compartments have been relatively maintenance-free, because of a lack of significant littoral drift at these locations. On the other hand, those harbors built in the middle reaches or at the downcoast ends of littoral cells have had expensive annual dredging problems, because of the interruption of large volumes of littoral drift. Although engineers have labored for years on various breakwater, jetty, or entrance channel configurations, the actual design utilized is of secondary importance. The critical factors are harbor location within a littoral cell and annual litoral drift volume.

A Polymorphism in Hepatocyte Nuclear Factor 1 Alpha, rs7310409, Is Associated with Left Main Coronary Artery Disease

Directory of Open Access Journals (Sweden)

Rui Liu

2014-01-01

Full Text Available Coronary artery disease is the leading cause of mortality and morbidity in the world. Left main coronary artery disease (LMCAD is a particularly severe phenotypic form of CAD and has a genetic basis. We hypothesized that some inflammation- and hyperhomocysteinemia-related gene polymorphisms may contribute to LMCAD susceptibility in a Chinese population. We studied the association between polymorphisms in the genes hepatocyte nuclear factor 1 alpha (HNF1A; rs7310409, G/A, C-reactive protein (rs1800947 and rs3093059 T/C, methylenetetrahydrofolate reductase (rs1801133, C/T, and methylenetetrahydrofolate dehydrogenase (rs1076991, A/G in 402 LMCAD and 804 more peripheral CAD patients in a Chinese population. Genotyping was performed using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry method. When the HNF1A rs7310409 GG homozygote genotype was used as the reference group, both the individual, GA and AA, and combined GA/AA genotypes were associated with an increased risk of LMCAD. This single nucleotide polymorphism (rs7310409 is strongly associated with plasma CRP levels. In conclusion, the present study provides evidence that the HNF1A rs7310409 G/A functional polymorphism may contribute to the risk of LMCAD.

A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: review of the literature.

Science.gov (United States)

Mirfakhraee, Sasan; Mathews, Dana; Peng, Lan; Woodruff, Stacey; Zigman, Jeffrey M

2013-05-04

Hyperfunctioning nodules of the thyroid are thought to only rarely harbor thyroid cancer, and thus are infrequently biopsied. Here, we present the case of a patient with a hyperfunctioning thyroid nodule harboring thyroid carcinoma and, using MEDLINE literature searches, set out to determine the prevalence of and characteristics of malignant "hot" nodules as a group. Historical, biochemical and radiologic characteristics of the case subjects and their nodules were compared to those in cases of benign hyperfunctioning nodules. A literature review of surgical patients with solitary hyperfunctioning thyroid nodules managed by thyroid resection revealed an estimated 3.1% prevalence of malignancy. A separate literature search uncovered 76 cases of reported malignant hot thyroid nodules, besides the present case. Of these, 78% were female and mean age at time of diagnosis was 47 years. Mean nodule size was 4.13 ± 1.68 cm. Laboratory assessment revealed T3 elevation in 76.5%, T4 elevation in 51.9%, and subclinical hyperthyroidism in 13% of patients. Histological diagnosis was papillary thyroid carcinoma (PTC) in 57.1%, follicular thyroid carcinoma (FTC) in 36.4%, and Hurthle cell carcinoma in 7.8% of patients. Thus, hot thyroid nodules harbor a low but non-trivial rate of malignancy. Compared to individuals with benign hyperfunctioning thyroid nodules, those with malignant hyperfunctioning nodules are younger and more predominantly female. Also, FTC and Hurthle cell carcinoma are found more frequently in hot nodules than in general. We were unable to find any specific characteristics that could be used to distinguish between malignant and benign hot nodules.

Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States

Directory of Open Access Journals (Sweden)

José R. Mediavilla

2016-08-01

Full Text Available Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized.

A Comparison of Microbial Water Quality and Diversity for Ballast and Tropical Harbor Waters.

Directory of Open Access Journals (Sweden)

Charmaine Ng

Full Text Available Indicator organisms and antibiotic resistance were used as a proxy to measure microbial water quality of ballast tanks of ships, and surface waters in a tropical harbor. The survival of marine bacteria in ballast tanks appeared to diminish over longer water retention time, with a reduction of cell viability observed after a week based on heterotrophic plate counts. Pyrosequencing of 16S rRNA genes showed distinct differences in microbial composition of ballast and harbor waters. The harbor waters had a higher abundance of operational taxonomic units (OTUs assigned to Cyanobacteria (Synechococcus spp. and α-proteobacteria (SAR11 members, while marine hydrocarbon degraders such as γ-proteobacteria (Ocenspirillaes spp., Thiotrchales spp. and Bacteroidetes (Flavobacteriales spp. dominated the ballast water samples. Screening of indicator organisms found Escherichia coli (E. coli, Enterococcus and Pseudomonas aeruginosa (P. aeruginosa in two or more of the ballast and harbor water samples tested. Vibrio spp. and Salmonella spp. were detected exclusively in harbor water samples. Using quantitative PCR (qPCR, we screened for 13 antibiotic resistant gene (ARG targets and found higher abundances of sul1 (4.13-3.44 x 102 copies/mL, dfrA (0.77-1.80 x10 copies/mL and cfr (2.00-5.21 copies/mL genes compared to the other ARG targets selected for this survey. These genes encode for resistance to sulfonamides, trimethoprim and chloramphenicol-florfenicol antibiotics, which are also known to persist in sediments of aquaculture farms and coastal environments. Among the ARGs screened, we found significant correlations (P<0.05 between ereA, ermG, cfr and tetO genes to one or more of the indicator organisms detected in this study, which may suggest that these members contribute to the environmental resistome. This study provides a baseline water quality survey, quantitatively assessing indicators of antibiotic resistance, potentially pathogenic organisms and a

A neurological comparative study of the harp seal (Pagophilus groenlandicus) and harbor porpoise (Phocoena phocoena) brain

DEFF Research Database (Denmark)

Walløe, Solveig; Eriksen, Nina; Dabelsteen, Torben

2010-01-01

The cetacean brain is well studied. However, few comparisons have been done with other marine mammals. In this study, we compared the harp seal (Pagophilus groenlandicus) and the harbor porpoise brain (Phocoena phocoena). Stereological methods were applied to compare three areas of interest...... cells, whereas the harp seal have 6.1 × 10(9) neocortical neurons and 17.5 × 10(9) neocortical glial cells. The harbor porpoise have significantly more neurons and glial cells in the auditory cortex than in the visual cortex, whereas the pattern was opposite for the harp seal. These results...... are the first to provide estimates of the number of neurons and glial cells in the neocortex of the harp seal and harbor porpoise brain and offer new data to the comparative field of mammalian brain evolution....

Stakeholder value-linked sustainability assessment: Evaluating remedial alternatives for the Portland Harbor Superfund Site, Portland, Oregon, USA.

Science.gov (United States)

Apitz, Sabine E; Fitzpatrick, Anne G; McNally, Amanda; Harrison, David; Coughlin, Conor; Edwards, Deborah A

2018-01-01

Regulatory decisions on remediation should consider affected communities' needs and values, and how these might be impacted by remedial options; this process requires that diverse stakeholders are able to engage in a transparent consideration of value trade-offs and of the distribution of risks and benefits associated with remedial actions and outcomes. The Stakeholder Values Assessment (SVA) tool was developed to evaluate remedial impacts on environmental quality, economic viability, and social equity in the context of stakeholder values and priorities. Stakeholder values were linked to the pillars of sustainability and also to a range of metrics to evaluate how sediment remediation affects these values. Sediment remedial alternatives proposed by the US Environmental Protection Agency (USEPA) for the Portland Harbor Superfund Site were scored for each metric, based upon data provided in published feasibility study (FS) documents. Metric scores were aggregated to generate scores for each value; these were then aggregated to generate scores for each pillar of sustainability. In parallel, the inferred priorities (in terms of regional remediation, restoration, planning, and development) of diverse stakeholder groups (SGs) were used to evaluate the sensitivity and robustness of the values-based sustainability assessment to diverse SG priorities. This approach, which addresses social indicators of impact and then integrates them with indicators of environmental and economic impacts, goes well beyond the Comprehensive Environmental Response, Compensation and Liability Act's (CERCLA) 9 criteria for evaluating remedial alternatives because it evaluates how remedial alternatives might be ranked in terms of the diverse values and priorities of stakeholders. This approach identified trade-offs and points of potential contention, providing a systematic, semiquantitative, transparent valuation tool that can be used in community engagement. Integr Environ Assess Manag 2018

Pearl Harbor Biological Survey

Science.gov (United States)

1974-08-30

Pearl Harbor also receives Irrigation tailgate waters from the Oahu Sug- ar Company, Industrial waste waters from the Prlmo Brewery , and heated waters...34Observations of the Cell Structure of Salt Fingers", J. Fluid Mech. 41:4, pp 707-719. ~) 3.3-79 ,’:•.-. ^ IV s’V- EFFECTS OF SHIP ACTIVITY Paul L...anticyclonic) death assemblage - in this report, an assemblage (q.v.) of remains (such as shells or bones ) from a naturally occurring association of living

A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians

DEFF Research Database (Denmark)

Anuradha, Shekher; Radha, Venkatesan; Deepa, Raj

2005-01-01

Among Europeans, mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown....... The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1alpha gene in different types of diabetes in Asian Indians....

Ecological evaluation of proposed dredged material from Richmond Harbor Deepening Project and the intensive study of the Turning Basin

Energy Technology Data Exchange (ETDEWEB)

Pinza, M.R.; Mayhew, H.L.; Karle, L.M.; Kohn, N.P.; White, P.J.; Word, J.Q.; Michaels, L.L. [Battelle/Marine Sciences Lab., Sequim, WA (United States)

1995-06-01

Richmond Harbor is on the eastern shoreline of central San Francisco Bay and its access channels and several of the shipping berths are no longer wide or deep enough to accommodate modem deeper-draft vessels. The Water Resources Development Act of 1986 (PL99-662) authorized the US Army Corps of Engineers (USACE), San Francisco District to deepen and widen the navigation channels in Richmond Harbor. Several options for disposal of the material from this dredging project are under consideration by USACE: disposal within San Francisco Bay, at open-ocean disposal sites, or at uplands disposal sites. Purpose of this study was to conduct comprehensive evaluations, including chemical, biological, and bioaccumulation testing of sediments in selected areas of Richmond Harbor. This information was required by the Environmental Protection Agency (EPA) and USACE. Battelle/Marine Sciences Laboratory collected 20 core samples, both 4-in. and 12-in., to a project depth of -40 ft mean lower low water (MLLW) (-38 ft MLLW plus 2 ft of overdepth) using a vibratory-hammer core. These 20 field samples were combined to form five test composites plus an older bay mud (OBM) composite that were analyzed for physical/chemical parameters, biological toxicity, and tissue chemistry. Solid-phase tests were conducted with the amphipod, Rhepoxynius abronius; the clam, Macoma nasuta; and the polychaete worm, Nephtys caecoides. Suspended-particulate-phase (SPP) tests were conducted with the sanddab, Citharichthys stigmaeus; the mysid, Holmesimysis costata; and the bivalve, Mytilus galloprovincialis. Bioaccumulation of contaminants was measured in tissues of Macoma nasuta and Nereis virens. Sediments from one ocean reference sediment, and two in-bay reference sediments, were tested concurrently. Results from analysis of the five test treatments were statistically compared with the reference sediment R-OS in the first five sections of this report.

76 FR 34865 - Safety Zone; Rochester Harbor Festival, Genesee River, Rochester, NY

Science.gov (United States)

2011-06-15

...-AA00 Safety Zone; Rochester Harbor Festival, Genesee River, Rochester, NY AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone on the Genesee River, Rochester, NY for the Rochester Harbor Festival fireworks. This zone is intended to...

33 CFR 334.470 - Cooper River and Charleston Harbor, S.C.; restricted areas.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Cooper River and Charleston....470 Cooper River and Charleston Harbor, S.C.; restricted areas. (a) The restricted areas. (1) Area No. 1 is that portion of the Cooper River beginning near the westerly shore north of Shipyard Creek at...

Chimeric polyomavirus-derived virus-like particles: the immunogenicity of an inserted peptide applied without adjuvant to mice depends on its insertion site and its flanking linker sequence

OpenAIRE

Lawatscheck, R.; Aleksaite, E.; Schenk, J.A.; Micheel, B.; Jandrig, B.; Holland, G.; Sasnauskas, K.; Gedvilaite, A.; Ulrich, R.G.

2007-01-01

We inserted the sequence of the carcinoembryonic antigen-derived T cell epitope CAP-1-6D (CEA) into different positions of the hamster polyomavirus major capsid protein VP1. Independently from additional flanking linkers, yeast-expressed VP1 proteins harboring the CEA insertion between VP1 amino acid residues 80 and 89 (site 1) or 288 and 295 (site 4) or simultaneously at both positions assembled to chimeric virus-like particles (VLPs). BALB/c mice immunized with adjuvant-free VLPs developed ...

Substantial proportion of MODY among multiplex families participating in a Type 1 diabetes prediction programme.

Science.gov (United States)

Petruzelkova, L; Dusatkova, P; Cinek, O; Sumnik, Z; Pruhova, S; Hradsky, O; Vcelakova, J; Lebl, J; Kolouskova, S

2016-12-01

Patients with maturity-onset diabetes of the young (MODY) might be over-represented in families with histories of Type 1 diabetes. Our aim was to re-evaluate families participating in the Czech T1D Prediction Programme (PREDIA.CZ) with at least two members affected with diabetes to assess the proportion of MODY among these families and determine its most significant clinical predictors. Of the 557 families followed up by the PREDIA.CZ, 53 (9.5%) had two or more family members with diabetes. One proband with diabetes from these families was chosen for direct sequencing of the GCK, HNF1A, HNF4A and INS genes. Non-parametric tests and a linear logistic regression model were used to evaluate differences between MODY and non-MODY families. MODY was genetically diagnosed in 24 of the 53 families with multiple occurrences of diabetes (45%). Mutations were detected most frequently in GCK (58%), followed by HNF1A (38%) and INS (4%). MODY families were more likely to have a parent with diabetes and had a higher proportion of females with diabetes than non-MODY families. Higher age (P MODY families already presenting with diabetes. A prediction programme for Type 1 diabetes would provide a useful new source of patients with MODY most likely to benefit from an accurate diagnosis. This identification has implications for patient treatment and disease prognosis. © 2015 Diabetes UK.

76 FR 81904 - Solicitation of New Safe Harbors and Special Fraud Alerts

Science.gov (United States)

2011-12-29

... Medicaid Patient and Program Protection Act of 1987, Public Law 100-93 Sec. 14, the Act, Sec. 1128B(b), 42...-called ``safe harbor'' provisions, specifying various payment and business practices that, although... basis for administrative sanctions. OIG safe harbor provisions have been developed ``to limit the reach...

Prevalence of Panulirus argus Virus 1 (PaV1) and habitation patterns of healthy and diseased Caribbean spiny lobsters in shelter-limited habitats.

Science.gov (United States)

Lozano-Alvarez, Enrique; Briones-Fourzán, Patricia; Ramírez-Estévez, Aurora; Placencia-Sánchez, David; Huchin-Mian, Juan Pablo; Rodríguez-Canul, Rossana

2008-07-07

Caribbean spiny lobsters Panulirus argus are socially gregarious, preferring shelters harboring conspecifics over empty shelters. In laboratory trials, however, healthy lobsters strongly avoided shelters harboring lobsters infected with the highly pathogenic Panulirus argus Virus 1 (PaV1). Because PaV1 is transmitted by contact, this behavior may thwart its spread in wild lobsters. In a field experiment conducted from 1998 to 2002 in a shelter-poor reef lagoon (Puerto Morelos, Mexico), densities of juvenile P. argus increased significantly on sites enhanced with artificial shelters (casitas) but not on control sites. Because PaV1 emerged in this location during 2000, we reexamined these data to assess whether casitas could potentially increase transmission of PaV1. In 2001, PaV1 prevalence was 2.5% and the cohabitation level (percentage of healthy lobsters cohabiting with diseased lobsters) was similar between natural shelters (3.5%) and casitas (2.4 %). The relative lobster densities in casita sites and control sites did not change significantly before (1998-1999) or after (2001-2002) the disease emergence. In late 2006, data from casita sites showed a significant increase in prevalence (10.9%) and cohabitation level (29.4%), but no significant changes in lobster density. In May 2006, casitas were deployed on shelter-poor sites within Chinchorro Bank, 260 km south of Puerto Morelos. In late 2006, prevalence and cohabitation level were 7.4 and 21.7%, respectively. Our results are inconclusive as to whether or not casitas increase PaV1 transmission, but suggest that across shelter-poor habitats, lobsters make a trade-off between avoiding diseased conspecifics and avoiding predation risk.

Functional Genomics for Epithelial-Mesenchymal Transition in Breast Cancer

Science.gov (United States)

2011-10-01

and aromatase activity are high compared to pre-meno- pausal plasma and tissue levels ( Pasqualini et al. 1996). LRH-1 has also been described as an...Hnf3beta, Hnf4alpha, and Hnf1alpha gene promoters. Journal of Biological Chemistry 276 13136–13144. (doi:10.1074/ jbc.M010737200) Pasqualini JR

Polymorphisms A387P in thrombospondin-4 and N700S in thrombospondin-1 perturb calcium binding sites.

Science.gov (United States)

Stenina, Olga I; Ustinov, Valentin; Krukovets, Irene; Marinic, Tina; Topol, Eric J; Plow, Edward F

2005-11-01

Recent genetic studies have associated members of the thrombospondin (TSP) gene family with premature cardiovascular disease. The disease-associated polymorphisms lead to single amino acid changes in TSP-4 (A387P) and TSP-1 (N700S). These substitutions reside in adjacent domains of these highly homologous proteins. Secondary structural predictive programs and the homology of the domains harboring these amino acid substitutions to those in other proteins pointed to potential alterations of putative Ca2+ binding sites that reside in close proximity to the polymorphic amino acids. Since Ca2+ binding is critical for the structure and function of TSP family members, direct evidence for differences in Ca2+ binding by the polymorphic forms was sought. Using synthetic peptides and purified recombinant variant fragments bearing the amino acid substitutions, we measured differences in Tb3+ luminescence as an index of Ca2+ binding. The Tb3+ binding constants placed the TSP-1 region affected by N700S polymorphism among other high-affinity Ca2+ binding sites. The affinity of Ca2+ binding was lower for peptides (3.5-fold) and recombinant fragments (10-fold) containing the S700 vs. the N700 form. In TSP-4, the P387 form acquired an additional Ca2+ binding site absent in the A387 form. The results of our study suggest that both substitutions (A387P in TSP-4 and N700S in TSP-1) alter Ca2+ binding properties. Since these substitutions exert the opposite effects on Ca2+ binding, a decrease in TSP-1 and an increase in TSP-4, the two TSP variants are likely to influence cardiovascular functions in distinct but yet pathogenic ways.

Observations and modeling of tsunami-induced currents in ports and harbors

Science.gov (United States)

Lynett, Patrick J.; Borrero, Jose C.; Weiss, Robert; Son, Sangyoung; Greer, Dougal; Renteria, Willington

2012-04-01

Tsunamis, or "harbor waves" in Japanese, are so-named due to common observations of enhanced wave heights, currents and damage in harbors and ports. However, dynamic currents induced by these waves, while regularly observed and known to cause significant damage, are poorly understood. Observations and modeling of the currents induced by the 2011 Tohoku and 2004 Indian Ocean tsunamis allows us to show that the strongest flows in harbor basins are governed by horizontally sheared and rotational shallow features, such as jets and large eddies. When examining currents in harbors, this conclusion will generally require a simulation approach that both includes the relevant physical processes in the governing equations and uses a numerical scheme that does not artificially damp these features. Without proper representation of the physics associated with these phenomena, predictive models may provide drag force estimates that are an order of magnitude or more in error. The immediate implementation of this type of analysis into tsunami hazard studies can mean the difference between an unaffected port and one in which 300 m long container vessels are detached from their moorings and drift chaotically.

Recreational Boat Harbor, Cedar River, Michigan. Revisions to General Design Memorandum Number 1 and Environmental Impact Statement. Supplement Number 1.

Science.gov (United States)

1980-08-01

26, Tuesday, February 6, 1979. 16. Personal communication with Jim Harter, J.W. Wells State Park Director. 17. Fassett, N.C.; A Manual of Acuatic ...Harbor, Cedar River, Michigan. Pgs. G-37 - q-54. i~ A- A measure of a .h- calact’ a tion to neutrajz hrc-ge, .ons navinc a p. of more than 7. Acuatic ...and ship navigation. Navi- gation aids are often placed on the outermost end of Corps breakwaters and piers. Nekton - Swimming aquatic insects and fish

75 FR 81556 - Solicitation of New Safe Harbors and Special Fraud Alerts

Science.gov (United States)

2010-12-28

... statute (section 1128B(b) of the Social Security Act), as well as developing new OIG Special Fraud Alerts... of New Safe Harbors and Special Fraud Alerts AGENCY: Office of Inspector General (OIG), HHS. ACTION... the public on recommendations for developing new or revised safe harbors and Special Fraud Alerts...

33 CFR 207.580 - Buffalo Harbor, N.Y.; use, administration, and navigation.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Buffalo Harbor, N.Y.; use, administration, and navigation. 207.580 Section 207.580 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE NAVIGATION REGULATIONS § 207.580 Buffalo Harbor, N.Y.; use...

Telemetry data from satellite tags deployed on harbor seals in Cook Inlet, Alaska

Data.gov (United States)

National Oceanic and Atmospheric Administration, Department of Commerce — Between 2004 and 2006 we conducted four harbor seal tagging trips in Cook Inlet during the months of October and May. In total, we captured and released 93 harbor...

Development of Targeted Molecular Therapy for Cancers Harboring BAP1 Mutations

Science.gov (United States)

2016-10-01

study in cultured cells because the loss of BAP1 results in stem cell-like behavior; the cells proliferate slowly, become dedifferentiated and are...result is the inhibition of histone H2A ubiquitination and the accumulation of ubiquitin at the DNA double- strand break sites. The PRC1-mediated...immunodeficiency allows the growth of human cancer cells and cancer stem cells with significant fidelity to the original tumor. b. Actual or anticipated

Preliminary site description. Simpevarp area - version 1.1

International Nuclear Information System (INIS)

Winberg, Anders

2004-08-01

Site characterisation in the Oskarshamn area is currently conducted at two adjoining localities, the Simpevarp and Laxemar subareas. This report presents the interim version (model version Simpevarp 1.1 of S1.1 for short) of the preliminary Site Descriptive Model for the Simpevarp subarea. The basis for this interim version is quality-assured, geoscientific and ecological field data from the Simpevarp subarea (and in part from the Laxemar area) available in the SKB SICADA and GIS data bases as of July 1, 2003 as well as version 0 of the Site Descriptive Model. The new data collected during the initial site investigation phase up till the date of data freeze S1.1 constitute the basis for the update of version 0 to version S1.1. These data include results from surface investigations in the subarea with its regional environment and from drillings and investigations in boreholes. The surface-based data sets were, in a relative sense, extensive compared with data sets from boreholes, were the information largely was limited to information from one c. 1,000 m deep cored borehole (KSH01A), two existing cored boreholes and three c. 200 m deep percussion-drilled boreholes. Discipline-specific models are developed for the selected regional and local model volumes and these models are subsequently integrated into a unified site description. The current methodologies for developing discipline-specific models and their integration are documented in methodology/ strategy reports. In the present work, the procedures and guidelines given in those reports were followed to the extent possible given the data and information available at the time of data freeze for model version S1.1. Compared with version 0 there are considerable additional features in the version S1.1, especially in the geological description and in the description of the near surface. The geological models of lithology and deformation zones are based on borehole information and surface data of much higher

77 FR 76434 - Solicitation of New Safe Harbors and Special Fraud Alerts

Science.gov (United States)

2012-12-28

... statute (section 1128B(b) of the Social Security Act), as well as developing new OIG Special Fraud Alerts... of New Safe Harbors and Special Fraud Alerts AGENCY: Office of Inspector General (OIG), HHS. ACTION... revised safe harbors and Special Fraud Alerts. Please assist us by referencing the file code OIG-121-N...

78 FR 78807 - Solicitation of New Safe Harbors and Special Fraud Alerts

Science.gov (United States)

2013-12-27

... statute (section 1128B(b) of the Social Security Act), as well as developing new OIG Special Fraud Alerts... of New Safe Harbors and Special Fraud Alerts AGENCY: Office of Inspector General (OIG), HHS. ACTION... revised safe harbors and Special Fraud Alerts. Please assist us by referencing the file code OIG-122-N...

33 CFR 165.754 - Safety Zone: San Juan Harbor, San Juan, PR.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Safety Zone: San Juan Harbor, San Juan, PR. 165.754 Section 165.754 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Zone: San Juan Harbor, San Juan, PR. (a) Regulated area. A moving safety zone is established in the...

Application of AE to evaluate deterioration of prt and harbor structures

International Nuclear Information System (INIS)

Matsuyama, Kimitoshi; Ishibashi, Akichika; Fujiwara, Tetsuro; Kanemoto, Yasuhiro; Hamada, Shigenori; Ohtsu, Masayasu

1997-01-01

The degree of concrete deterioration is normally evaluated by uniaxial compression tests of core samples taken from existing concrete structures. The uniaxial compression test can give details on concrete strength, elastic modulus and so forth. By using AE(acoustic emission) technique with uniaxial compression tests, we can get more useful information on interior failures of the core sample. The observation of AE activity was conducted during uniaxial compression tests of concrete specimens and samples. The specimens were cast with 5, 10, 15 and 20% air content. The samples were taken from 2 harbor sites in Japan. Generating behavior of AE was studied quantitatively on the basis of rate process theory. Distribution of pores in the concrete could be measured by the porosimeter. The relation between AE activity in the uniaxial compression test of core samples and concrete property is clarified.

Evaluation of Sediment Contamination in Pearl Harbor

Science.gov (United States)

1992-06-01

ancient Hawaiians, was a large natural inland lagoon. Numerous walled fishponds located inside the harbor were used to cultivate various species of fishes... Ecotoxicology , Commission on Natural Resources, National Academy Press, Washington, D.C., 103 pp. National Research Council, 1989. Contaminated Marine

Crystal structure of the C-terminal domain of the RAP74 subunit of human transcription factor IIF

Energy Technology Data Exchange (ETDEWEB)

Kamada, Katsuhiko; De Angelis, Jacqueline; Roeder, Robert G.; Burley, Stephen K. (Rockefeller)

2012-12-13

The x-ray structure of a C-terminal fragment of the RAP74 subunit of human transcription factor (TF) IIF has been determined at 1.02-{angstrom} resolution. The {alpha}/{beta} structure is strikingly similar to the globular domain of linker histone H5 and the DNA-binding domain of hepatocyte nuclear factor 3{gamma} (HNF-3{gamma}), making it a winged-helix protein. The surface electrostatic properties of this compact domain differ significantly from those of bona fide winged-helix transcription factors (HNF-3{gamma} and RFX1) and from the winged-helix domains found within the RAP30 subunit of TFIIF and the {beta} subunit of TFIIE. RAP74 has been shown to interact with the TFIIF-associated C-terminal domain phosphatase FCP1, and a putative phosphatase binding site has been identified within the RAP74 winged-helix domain.

Pearl Harbor bombing attack: a contamination legacy revealed in the sedimentary record

International Nuclear Information System (INIS)

Ashwood, T.L.; Olsen, C.R.

1988-01-01

Sediment cores collected from Middle Loch and West Loch of Pearl Harbor were dated using fallout 137 Cs and excess 210 Pb and analysed for several major elements and trace metals. Results indicate that sediment deposited immediately following the 7 December, 1941, bombing attack on Pearl Harbor contained elevated levels of several trace metals. (author)

Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

Directory of Open Access Journals (Sweden)

de Beaufort Carine

2010-09-01

Full Text Available Abstract Background To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative for pancreatic autoantibodies [islet cell autoantibodies(ICA, glutamic acid decarboxylase antibodies (GADA and insulinoma-associated antigen-2 antibodies (IA-2A]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes. Materials and methods In 261 newly diagnosed children with type 1 diabetes, we measured residual β-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis. The genes KCNJ11, ABCC8, HNF1A, HNF4A and INS were sequenced in subjects AAB negative at diagnosis. We expressed recombinant K-ATP channels in Xenopus oocytes to analyse the functional effects of an ABCC8 mutation. Results Twenty-four patients (9.1% tested AAB negative after one month. Patients, who were AAB-negative throughout the 12-month period, had higher residual β-cell function (P = 0.002, lower blood glucose (P = 0.004, received less insulin (P = 0.05 and had lower HbA1c (P = 0.02 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution of arginine at residue 1530 of SUR1 (ABCC8 by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the K-ATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide. Conclusion GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation in ABCC8, suggesting that screening of ABCC8 should be considered in patients with AAB negative type 1 diabetes.

Environmental space management in the harbor of Amsterdam, Netherlands; Milieuruimtemanagement haven Amsterdam

Energy Technology Data Exchange (ETDEWEB)

Klok, L.; Hulskotte, J. [TNO Built Environment and Geosciences, Den Haag (Netherlands); Van Breemen, T. [Haven Amsterdam, Amsterdam (Netherlands)

2012-02-15

A new calculation tool will quickly offer the Harbor of Amsterdam insight in the effect of activities in the harbor on the air quality and hence the available environmental space. [Dutch] Een nieuw rekeninstrument geeft Haven Amsterdam snel inzicht in het effect van alle activiteiten in de haven op de luchtkwaliteit en daarmee in de beschikbare milieuruimte.

Pearl Harbor bombing attack: a contamination legacy revealed in the sedimentary record

Energy Technology Data Exchange (ETDEWEB)

Ashwood, T.L.; Olsen, C.R.

1988-02-01

Sediment cores collected from Middle Loch and West Loch of Pearl Harbor were dated using fallout /sup 137/Cs and excess /sup 210/Pb and analysed for several major elements and trace metals. Results indicate that sediment deposited immediately following the 7 December, 1941, bombing attack on Pearl Harbor contained elevated levels of several trace metals.

Army Engineers at Pearl Harbor

Science.gov (United States)

2011-01-01

siblings, he was the grandson of David Belden Lyman—a Christian missionary from New England who settled in the Hilo , Hawaii area—and the descendent of...of Hawaii appeared over Oahu. Some headed for Ameri- can warships at Pearl Harbor and the planes on the ground at nearby Hickam Field; oth- ers...hit Schofield Barracks, Wheeler Field, and Bellows Field. USACE in Hawaii con- sisted of Soldier-engineers in the Army’s Hawaiian Depart- ment and

Evaluation of older bay mud sediment from Richmond Harbor, California

Energy Technology Data Exchange (ETDEWEB)

Pinza, M.R.; Mayhew, H.L.; Word, J.Q.

1996-09-01

The older, bay mud (OBM) unit predates modem man and could act as a barrier to the downward transport of contaminants from the younger bay mud (YBM) because of its hard-packed consistency. However, its chemical and biological nature have not been well characterized. Battelle/Marine Sciences Laboratory (MSL) conducted three independent studies of OBM sediment in January 1993, January 1994, and October 1994. These studies evaluated potential chemical contamination and biological effects of OBM that could occur as a result of dredging and disposal activities. These evaluations were performed by conducting chemical analysis, solid-phase toxicity tests, suspended- particulate-phase (SPP) toxicity tests, and bioaccumulation tests on the OBM sediment. If the sediment chemistry and toxicity results showed no or minimal contamination and toxicological responses, then either the OBM could be left exposed in Richmond Harbor after dredging the YBM without leaving a source of contamination, or if the project depths necessitate, the OBM would be acceptable for disposal at an appropriate disposal site.

Multivariate analysis of heavy metal contaminations in seawater and sediments from a heavily industrialized harbor in Southern Taiwan

International Nuclear Information System (INIS)

Lin, Yung-Chang; Chang-Chien, Guo-Ping; Chiang, Pen-Chi; Chen, Wei-Hsiang; Lin, Yuan-Chung

2013-01-01

Highlights: • Kaohsiung Harbor is the largest international commercial port in Taiwan. • The metal distributions in the seawater and sediments were investigated. • Many metals exhibited higher levels of enrichment inside the harbor. • Multivariate statistical analysis was used to characterize the metal pollutions. • Two complex arrays of contamination behaviors exist inside and outside the harbor. -- Abstract: Heavy metal pollution, including chromium, zinc, arsenic, cadmium, mercury, copper, lead, and aluminum, in the largest industrial harbor in southern Taiwan was investigated. Increasing metal contamination was observed by monitoring heavy metal concentrations in seawater and sediments and estimating the enrichment factors, particularly those inside the harbor. Compared to other metal-polluted harbors worldwide, the presence of chromium in the sediments was relatively high. Excluding the background contribution, the harbor area was polluted by outflows from river mouths, wastewater discharging pipes, and point sources near industrial activities within the harbor. It is shown by principal component and cluster analyses that metal contamination was affected by a wide range of different and complex contamination mechanisms inside and outside the harbor, suggesting managing the pollution using straightforward strategies, i.e., solutions that only consider a single source or single pathway of metal emissions, is problematic

Towards a new point of view on the phenotype of patients with a 17q12 microdeletion syndrome.

Science.gov (United States)

Laffargue, Fanny; Bourthoumieu, Sylvie; Llanas, Brigitte; Baudouin, Véronique; Lahoche, Annie; Morin, Denis; Bessenay, Lucie; De Parscau, Loïc; Cloarec, Sylvie; Delrue, Marie-Ange; Taupiac, Emmanuelle; Dizier, Emilie; Laroche, Cécile; Bahans, Claire; Yardin, Catherine; Lacombe, Didier; Guigonis, Vincent

2015-03-01

17q12 microdeletion syndrome involves 15 genes, including HNF1B, and is considered to confer a high risk of neuropsychiatric disorders. Patients with HNF1B gene deletion diagnosed secondary to renal disorders are only very rarely reported to have neuropsychiatric disorders. Interestingly, however, when tested, patients with HNF1B gene deletion are found to have 17q12 deletion. This brings into question the extent to which 17q12 deletion is genuinely associated with severe neuropsychological disorders and in which patients. In this study, we sought to confirm 17q12 microdeletion in kidney patients initially diagnosed with HNF1B gene deletion and evaluate neuropsychological disorders in these patients compared with those with HNF1B point mutation. Thirty-nine children with HNF1B disorders (26 with deletions) diagnosed secondary to renal abnormalities were included in this prospective study and tested for 17q12 microdeletion and neuropsychological disorders. The same 17q12 microdeletion found in patients with neuropsychological disorders was identified in all of our patients with HNF1B deletion. Neurological examinations found no severe impairments except for one patient with autism. No significant differences were found between patients with deletions and those with point mutations as concerns learning abilities and schooling. Nevertheless, patients with deletions tended to have lower developmental quotients and more difficulties at school. Complete deletion of the HNF1B gene and 17q12 microdeletion syndrome are actually the same genetic disorder. The neuropsychological phenotype of patients appears less severe when 17q12 deletion is diagnosed secondary to kidney rather than neuropsychological abnormalities. These data may influence antenatal counselling. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The hearing threshold of a harbor porpoise (Phocoena phocoena) for impulsive sounds (L)

NARCIS (Netherlands)

Kastelein, R.A.; Gransier, R.; Hoek, L.; Jong, C.A.F. de

2012-01-01

The distance at which harbor porpoises can hear underwater detonation sounds is unknown, but depends, among other factors, on the hearing threshold of the species for impulsive sounds. Therefore, the underwater hearing threshold of a young harbor porpoise for an impulsive sound, designed to mimic a

75 FR 17692 - Foreign-Trade Zone 75 -- Phoenix, Arizona, Application for Reorganization under Alternative Site...

Science.gov (United States)

2010-04-07

...'' in the context of the Board's standard 2,000-acre activation limit for a general-purpose zone project... terminal at the Phoenix Sky Harbor International Airport, Phoenix; Site 2 (18 acres) CC&F South Valley..., 4747 West Buckeye Road, Phoenix; Site 4 (18 acres) - Santa Fe Business Park, 47th Avenue and Campbell...

Geographic Response Plan (GRP) Sensitive Site Points (Editable), Guam, 2016, US EPA Region 9

Data.gov (United States)

U.S. Environmental Protection Agency — This is an editable point feature data set with points over Apra Harbor in Guam. These points represent sensitive sites such as access points for public use and...

Movements and foraging effort of Steller's Eiders and Harlequin Ducks wintering near Dutch Harbor, Alaska

Science.gov (United States)

Reed, J.A.; Flint, Paul L.

2007-01-01

We studied the movements and foraging effort of radio-marked Steller's Eiders (Polysticta stelleri) and Harlequin Ducks (Histrionicus histrionicus) to evaluate habitat quality in an area impacted by industrial activity near Dutch Harbor, Alaska. Foraging effort was relatively low, with Steller's Eiders foraging only 2.7 ± 0.6 (SE) hours per day and Harlequin Ducks 4.1 ± 0.5 hours per day. Low-foraging effort during periods of high-energetic demand generally suggests high food availability, and high food availability frequently corresponds with reductions in home range size. However, the winter ranges of Harlequin Ducks did not appear to be smaller than usual, with the mean range size in our study (5.5 ± 1.1 km2) similar to that reported by previous investigators. The mean size of the winter ranges of Steller's Eiders was similar (5.1 ± 1.3 km2), but no comparable estimates are available. Eutrophication of the waters near Dutch Harbor caused by seafood processing and municipal sewage effluent may have increased populations of the invertebrate prey of these sea ducks and contributed to their low-foraging effort. The threat of predation by Bald Eagles (Haliaeetus leucocephalus) that winter near Dutch Harbor may cause Steller's Eiders and Harlequin Ducks to move further offshore when not foraging, contributing to an increase in range sizes. Thus, the movement patterns and foraging behavior of these ducks likely represent a balance between the cost and benefits of wintering in a human-influenced environment.

Environment-Dependent Distribution of the Sediment nifH-Harboring Microbiota in the Northern South China Sea

Science.gov (United States)

Yang, Jinying; Li, Jing; Luan, Xiwu; Zhang, Yunbo; Gu, Guizhou; Xue, Rongrong; Zong, Mingyue; Klotz, Martin G.

2013-01-01

The South China Sea (SCS), the largest marginal sea in the Western Pacific Ocean, is a huge oligotrophic water body with very limited influx of nitrogenous nutrients. This suggests that sediment microbial N2 fixation plays an important role in the production of bioavailable nitrogen. To test the molecular underpinning of this hypothesis, the diversity, abundance, biogeographical distribution, and community structure of the sediment diazotrophic microbiota were investigated at 12 sampling sites, including estuarine, coastal, offshore, deep-sea, and methane hydrate reservoirs or their prospective areas by targeting nifH and some other functional biomarker genes. Diverse and novel nifH sequences were obtained, significantly extending the evolutionary complexity of extant nifH genes. Statistical analyses indicate that sediment in situ temperature is the most significant environmental factor influencing the abundance, community structure, and spatial distribution of the sediment nifH-harboring microbial assemblages in the northern SCS (nSCS). The significantly positive correlation of the sediment pore water NH4+ concentration with the nifH gene abundance suggests that the nSCS sediment nifH-harboring microbiota is active in N2 fixation and NH4+ production. Several other environmental factors, including sediment pore water PO43− concentration, sediment organic carbon, nitrogen and phosphorus levels, etc., are also important in influencing the community structure, spatial distribution, or abundance of the nifH-harboring microbial assemblages. We also confirmed that the nifH genes encoded by archaeal diazotrophs in the ANME-2c subgroup occur exclusively in the deep-sea methane seep areas, providing for the possibility to develop ANME-2c nifH genes as a diagnostic tool for deep-sea methane hydrate reservoir discovery. PMID:23064334

75 FR 4693 - Drawbridge Operation Regulation; Inner Harbor Navigational Canal, New Orleans, LA

Science.gov (United States)

2010-01-29

... Operation Regulation; Inner Harbor Navigational Canal, New Orleans, LA AGENCY: Coast Guard, DHS. ACTION... C. Simon) Bascule Bridge across the Inner Harbor Navigational Canal, mile 4.6, at New Orleans, LA... Ochsner Ironman 70.3 New Orleans event. This deviation allows the bridge to remain closed during the event...

Bluff evolution along coastal drumlins: Boston Harbor Islands, Massachusetts

Science.gov (United States)

Himmelstoss, E.A.; FitzGerald, D.M.; Rosen, P.S.; Allen, J.R.

2006-01-01

A series of partially drowned drumlins forms the backbone of the inner islands within Boston Harbor. The shoreline of these rounded glacial deposits is composed of actively retreating bluffs formed by continual wave attack. Comparisons of bluffs reveal variability in their height and lateral extent, as well as in the dominant mechanism causing their retreat. Two processes are responsible for bluff erosion and yield distinct bluff morphologies: (1) wave attack undercuts the bluff and causes episodic slumping, yielding planar bluff slopes, and (2) subaerial processes such as rainfall create irregular slopes characterized by rills and gullies. We propose a model of drumlin bluff evolution that is based on processes of erosion and physical characteristics such as bluff height, slope morphology, and the orientation of the bluff with respect to the long axis of the drumlin and its topographic crest. The four phases of drumlin bluff evolution consist of (1) initial formation of bluff, with retreat dominated by wave notching and slumping processes; (2) rill and gully development as bluff heights exceed 10 m and slumped sediment at bluff base inhibits wave attack; (3) return of wave notching and slumping as bluff heights decrease; and (4) final development of boulder retreat lag as last remnants of drumlin are eroded by wave action. These phases capture the important physical processes of drumlin evolution in Boston Harbor and could apply to other eroding coastal drumlin deposits.