Lack of association of the HMGA1 IVS5-13insC variant with type 2 diabetes in an ethnically diverse hypertensive case control cohort

Directory of Open Access Journals (Sweden)

Karnes Jason H

2013-01-01

Full Text Available Abstract Background Recently, the high-mobility group A1 gene (HMGA1 variant IVS5-13insC has been associated with type 2 diabetes, but reported associations are inconsistent and data are lacking in Hispanic and African American populations. We sought to investigate the HMGA1-diabetes association and to characterize IVS5-13insC allele frequencies and linkage disequilibrium (LD in 3,070 Caucasian, Hispanic, and African American patients from the INternational VErapamil SR-Trandolapril STudy (INVEST. Methods INVEST was a randomized, multicenter trial comparing two antihypertensive treatment strategies in an ethnically diverse cohort of hypertensive, coronary artery disease patients. Controls, who were diabetes-free throughout the study, and type 2 diabetes cases, either prevalent or incident, were genotyped for IVS5-13insC using Taqman®, confirmed with Pyrosequencing and Sanger sequencing. For LD analysis, genotyping for eight additional HMGA1 single nucleotide polymorphisms (SNPs was performed using the Illumina® HumanCVD BeadChip. We used logistic regression to test association of the HMGA1 IVS5-13insC and diabetes, adjusted for age, gender, body mass index, and percentage European, African, and Native American ancestry. Results We observed IVS5-13insC minor allele frequencies consistent with previous literature in Caucasians and African Americans (0.03 in cases and 0.04 in controls for both race/ethnic groups, and higher frequencies in Hispanics (0.07 in cases and 0.07 in controls. The IVS5-13insC was not associated with type 2 diabetes overall (odds ratio 0.98 [0.76-1.26], p=0.88 or in any race/ethnic group. Pairwise LD (r2 of IVS5-13insC and rs9394200, a SNP previously used as a tag SNP for IVS5-13insC, was low (r2=0.47 in Caucasians, r2=0.25 in Hispanics, and r2=0.06 in African Americans. Furthermore, in silico analysis suggested a lack of functional consequences for the IVS5-13insC variant. Conclusions Our results suggest that IVS5-13ins

Incidência de ocratoxina A em café torrado e moído e em café solúvel consumido na cidade de Belo Horizonte, MG

Directory of Open Access Journals (Sweden)

PRADO Guilherme

2000-01-01

Full Text Available A ocorrência de ocratoxina A foi verificada em amostras de café solúvel e café torrado e moído, comercializados em Belo Horizonte/MG, no período de outubro/1998 a maio/1999. O método usado para a determinação de ocratoxina A foi a cromatografia líquida de alta eficiência (CLAE em combinação com cromatografia de imunoafinidade. Os valores de recuperação e coeficiente de variação de ocratoxina A foram superiores a 73% e inferiores 15%, respectivamente. As amostras de café solúvel e café torrado e moído, continham níveis de ocratoxina A entre 0,31 e 1,78ng/g e 0,99 e 5,87ng/g, respectivamente. Os resultados revelaram que o café não apresenta níveis de contaminação significativos.

¿El beber café es salud?

Directory of Open Access Journals (Sweden)

María Del Rosario Alvarez-Ramirez

2005-12-01

Full Text Available El café es una bebida universal responsable de levantar a muchos cada mañana. El uso continuo de bebidas con cafeína también produce efectos a largo plazo. Los cuales aumentan su riesgo a 120% si bebe diariamente 6 o más tazas de café. La cafeína también puede causar úlceras en el estómago, producir alergias, insomnios, irritabilidad, palpitaciones, fiebre y otros síntomas como: aumentar los niveles de noradrenalina (neurotransmisor que produce un estado de alerta. Por las mismas razones que el café aumenta el estado de alerta y estimula el rendimiento mental, una taza de café es una forma ideal de comenzar el día.

Fabrication and spectral properties of Nd, La: CaF2 transparent ceramics

Science.gov (United States)

Xie, Xiaoyu; Mei, Bingchu; Song, Jinghong; Li, Weiwei; Su, Liangbi

2018-02-01

1 at.% Nd: CaF2 nanoparticles doped with different concentrations of La3+ ions (from 0 to 5 at.%) were synthesized by co-precipitation method. Phase identification, morphology of the nanoparticles were investigated by XRD and SEM measurements. The Nd, La: CaF2 ceramics were fabricated by hot-pressed method in the vacuum environment. The transmittance of all the ceramics reached 88% at the wavelength of 1400 nm. The luminescence intensities and decay lifetimes enhanced significantly with the increasing of La3+ concentration. The Nd, La: CaF2 ceramics have broad and flat emission band at 1050 nm with the largest FWHM of 28.16 nm. In addition, the spectrum results indicated that the fluorescence lifetime of Nd, La: CaF2 ceramics was longer than that of the Nd, Y: CaF2 ceramics with the same doping concentration.

What matters to infrequent customers: a pragmatic approach to understanding perceived value and intention to revisit trendy coffee caf?

OpenAIRE

Ting, Hiram; Thurasamy, Ramayah

2016-01-01

Notwithstanding the rise of trendy coffee caf?, little is done to investigate revisit intention towards the caf? in the context of developing markets. In particular, there is a lack of study which provides theoretical and practical explanation to the perceptions and behaviours of infrequent customers. Hence, the study aims to look into the subject matter by using the theory of reasoned action and social exchange theory as the underpinning basis. The framework proposed by Pine and Gilmore (Str...

The CMS CERN Analysis Facility (CAF)

Energy Technology Data Exchange (ETDEWEB)

Buchmueller, O [Imperial College (United Kingdom); Bonacorsi, D [Universita and INFN, Bologna (Italy); Fanzago, F [Universita and INFN, Padova (Italy); Gowdy, S; Malgeri, L; Panzer-Steindel, B; Schwickerath, U; Spiga, D; Toebbicke, Rainer [Conseil Europeen Recherche Nucl. (CERN) Switzerland (Switzerland); Kreuzer, P [Rheinisch-Westfaelische Tech. Hoch. (RWTH) (Germany); Mankel, R [Deutsches Elektronen-Synchrotron (DESY) (Germany); Metson, S [University of Bristol (United Kingdom); Sanches, J Afonso; Teodoro, D, E-mail: Peter.Kreuzer@cern.c [Universidade do Estado do Rio De Janeiro (UERJ) (Brazil)

2010-04-01

The CMS CERN Analysis Facility (CAF) was primarily designed to host a large variety of latency-critical workflows. These break down into alignment and calibration, detector commissioning and diagnosis, and high-interest physics analysis requiring fast-turnaround. In addition to the low latency requirement on the batch farm, another mandatory condition is the efficient access to the RAW detector data stored at the CERN Tier-0 facility. The CMS CAF also foresees resources for interactive login by a large number of CMS collaborators located at CERN, as an entry point for their day-by-day analysis. These resources will run on a separate partition in order to protect the high-priority use-cases described above. While the CMS CAF represents only a modest fraction of the overall CMS resources on the WLCG GRID, an appropriately sized user-support service needs to be provided. We will describe the building, commissioning and operation of the CMS CAF during the year 2008. The facility was heavily and routinely used by almost 250 users during multiple commissioning and data challenge periods. It reached a CPU capacity of 1.4MSI2K and a disk capacity at the Peta byte scale. In particular, we will focus on the performances in terms of networking, disk access and job efficiency and extrapolate prospects for the upcoming LHC first year data taking. We will also present the experience gained and the limitations observed in operating such a large facility, in which well controlled workflows are combined with more chaotic type analysis by a large number of physicists.

The CMS CERN Analysis Facility (CAF)

International Nuclear Information System (INIS)

Buchmueller, O; Bonacorsi, D; Fanzago, F; Gowdy, S; Malgeri, L; Panzer-Steindel, B; Schwickerath, U; Spiga, D; Toebbicke, Rainer; Kreuzer, P; Mankel, R; Metson, S; Sanches, J Afonso; Teodoro, D

2010-01-01

The CMS CERN Analysis Facility (CAF) was primarily designed to host a large variety of latency-critical workflows. These break down into alignment and calibration, detector commissioning and diagnosis, and high-interest physics analysis requiring fast-turnaround. In addition to the low latency requirement on the batch farm, another mandatory condition is the efficient access to the RAW detector data stored at the CERN Tier-0 facility. The CMS CAF also foresees resources for interactive login by a large number of CMS collaborators located at CERN, as an entry point for their day-by-day analysis. These resources will run on a separate partition in order to protect the high-priority use-cases described above. While the CMS CAF represents only a modest fraction of the overall CMS resources on the WLCG GRID, an appropriately sized user-support service needs to be provided. We will describe the building, commissioning and operation of the CMS CAF during the year 2008. The facility was heavily and routinely used by almost 250 users during multiple commissioning and data challenge periods. It reached a CPU capacity of 1.4MSI2K and a disk capacity at the Peta byte scale. In particular, we will focus on the performances in terms of networking, disk access and job efficiency and extrapolate prospects for the upcoming LHC first year data taking. We will also present the experience gained and the limitations observed in operating such a large facility, in which well controlled workflows are combined with more chaotic type analysis by a large number of physicists.

Efecto de cinco Dosis de Heterorhabditis indica Poinat cepa P2M sobre la broca del café (Hypothenemus hampei Ferrari).

OpenAIRE

Yander Fernández Cancio; Marcos Tulio García González; Manuel Rodríguez González

2015-01-01

Con el objetivo de evaluar el efecto de Heterorhaditis indica cepa P2M en el manejo de la broca del café (Hypotenemushampei Ferrari) se realizó la investigación en condiciones controladas en el Laboratorio Provincial de Sanidad Vegetal de Sancti Spíritus con cinco dosis del patógeno: 20, 45, 75, 100 y 200 individuos juveniles infestiles/adulto (iji/adulto). Se diseñaron dos experimentos: variante 1 con aplicaciones directa sobre los adultos del insecto en placas Petri con siete repeticiones y...

CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets.

Directory of Open Access Journals (Sweden)

Cyril Jean-Marie Martel

Full Text Available Trivalent inactivated vaccines (TIV against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01 was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.

Designing CAF-adjuvanted dry powder vaccines: Spray drying preserves the adjuvant activity of CAF01

DEFF Research Database (Denmark)

Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis

2013-01-01

spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol...... parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray...... drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome...

Delta Cafés (Portugal: Sustainable Business Development

Directory of Open Access Journals (Sweden)

Olgierd Swiatkiewicz

2017-12-01

Full Text Available In the case study of Delta Cafés we discuss the sustainable development of the Portuguese company and brand over the 55 years of their existence. Delta Cafés has already been analyzed in terms of marketing activity, social responsibility, management control systems, etc. In this paper, we refer to these studies, and we reach the sources, i.e. the information provided by the Delta Cafés itself. Due to the nature of the coffee market and the use of case study methodology, we start the presentation of this case from a broader context, describing the coffee market in the world and characterizing the coffee market in Portugal as well. Then we present the history of the development of the company and the brand Delta Cafés. The paper ends with concluding remarks in which we discuss the issues of social and environmental responsibility in the light of the development of Delta Cafés business and brand strategies. 

Control of trichome branching by Chromatin Assembly Factor-1

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Hennig Lars

2008-05-01

Full Text Available Abstract Background Chromatin dynamics and stability are both required to control normal development of multicellular organisms. Chromatin assembly factor CAF-1 is a histone chaperone that facilitates chromatin formation and the maintenance of specific chromatin states. In plants and animals CAF-1 is essential for normal development, but it is poorly understood which developmental pathways require CAF-1 function. Results Mutations in all three CAF-1 subunits affect Arabidopsis trichome morphology and lack of CAF-1 function results in formation of trichomes with supernumerary branches. This phenotype can be partially alleviated by external sucrose. In contrast, other aspects of the CAF-1 mutant phenotype, such as defective meristem function and organ formation, are aggravated by external sucrose. Double mutant analyses revealed epistatic interactions between CAF-1 mutants and stichel, but non-epistatic interactions between CAF-1 mutants and glabra3 and kaktus. In addition, mutations in CAF-1 could partly suppress the strong overbranching and polyploidization phenotype of kaktus mutants. Conclusion CAF-1 is required for cell differentiation and regulates trichome development together with STICHEL in an endoreduplication-independent pathway. This function of CAF-1 can be partially substituted by application of exogenous sucrose. Finally, CAF-1 is also needed for the high degree of endoreduplication in kaktus mutants and thus for the realization of kaktus' extreme overbranching phenotype.

Business Location and Success: The Case of Internet Café Business in Indonesia

OpenAIRE

Nurul Indarti

2004-01-01

This research aims to examine the relationship between business location decision and business success. The case is Internet café business in Indonesia. This research is addressed to answer these main questions: (1) what factors do underlie location decision for an Internet café business?; and (2) does location decision determine success of Internet café business? A field research is conducted to answer these questions. Factor analysis applied to 17 location factors reveals five underlying...

Shock Compression Response of Calcium Fluoride (CaF2)

Science.gov (United States)

Root, Seth

2017-06-01

The fluorite crystal structure is a textbook lattice that is observed for many systems, such as CaF2, Mg2 Si, and CeO2. Specifically, CaF2 is a useful material for studying the fluorite system because it is readily available as a single crystal. Under static compression, CaF2 is known to have at least three solid phases: fluorite, cotunnite, and a Ni2 In phase. Along the Hugoniot CaF2 undergoes a fluorite to cotunnite phase transition, however, at higher shock pressures it is unknown whether CaF2 undergoes another solid phase transition or melts directly from the cotunnite phase. In this work, we conducted planar shock compression experiments on CaF2 using Sandia's Z-machine and a two-stage light gun up to 900 GPa. In addition, we use density functional theory (DFT) based quantum molecular dynamics (QMD) simulations to provide insight into the CaF2 state along the Hugoniot. In collaboration with: Michael Desjarlais, Ray Lemke, Patricia Kalita, Scott Alexander, Sandia National Laboratories. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL850.

An Update on Neurofibromatosis Type 1: Not Just Café-au-Lait Spots and Freckling. Part II. Other Skin Manifestations Characteristic of NF1. NF1 and Cancer.

Science.gov (United States)

Hernández-Martín, A; Duat-Rodríguez, A

2016-01-01

Neurofibromatosis type 1 (NF1) is the most common neurocutaneous syndrome and probably the one best known to dermatologists. Although the genetic locus of NF1 was identified on chromosome 17 in 1987, diagnosis of the disease is still based primarily on clinical observations. The 7 diagnostic criteria of the National Institutes of Health, which were established in 1988, include 3 skin manifestations (café-au-lait spots, freckling on flexural areas, and cutaneous neurofibromas). The age at which these diagnostic lesions appear is variable: onset can be late in some patients while others never develop certain symptoms. Definitive diagnosis may therefore be delayed by years. Although the appearance of the characteristic café-au-lait spots and freckling in the early years of childhood are very suggestive of the disease, these signs are not pathognomonic and, in isolation, do not constitute sufficient evidence to establish a definitive diagnosis. Thus, other diagnoses should be considered in patients whose only symptoms are café-au-lait spots and freckling. By contrast, the presence of multiple cutaneous neurofibromas or at least 1 plexiform neurofibroma is a very specific indication of NF1. Identification of the different types of neurofibroma allows us to confirm the diagnosis and initiate appropriate management. Copyright © 2016 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Electronic properties of CaF sub 2 nanodimensional islands on Si(0 0 1) An MDS and UPS study

CERN Document Server

Pasquali, L; Sokolov, N; Selvaggi, G; D'Addato, S; Nannarone, S

2002-01-01

The joint use of metastable deexcitation spectroscopy and angle resolved ultraviolet photoemission gives a valuable contribution to the comprehension of the physical-chemical reactions occurring during the formation of an interface between different materials. This approach has been applied to study the evolution of the surface valence band of CaF sub 2 deposited on Si(0 0 1) at different temperatures. Under suitable growth conditions, CaF sub 2 nanostructures of different shape and size can be obtained. Information regarding the chemical reactions taking place within the first deposited layer and the dependence of the electronic properties on film thickness was derived.

Extracción de aceite de café

Directory of Open Access Journals (Sweden)

Elkin Mauricio López Fontal

2007-01-01

Full Text Available En el presente trabajo se realiza la extracción de aceite de café mediante el método de extrusión. En dicho proceso se obtienen dos productos: el aceite de café y la torta. Para tal propósito se utilizó café tostado, el cual se caracteriza por poseer una elevada cantidad de compuestos odoríferos; es importante saber que un criterio significativo en la valoración de la calidad del café, es su aroma. Al extraer el aceite, una parte significativa del contenido aromático del café tostado, que varía según el método de extracción usado, sale con él. Es asI como se obtiene un aceite filo con una alta carga volátil, el cual presenta características organolépticas favorables. Al segundo producto que se obtiene, se le realizó análisis físico-químico en aras de mostrar sus bondades y propiedades particulares, y de acuerdo a los resultados obtenidos, es un producto que presenta un amplio potencial de utilización.

Respuesta de plántulas de café a la fertilización foliar y la aplicación de pulpa de café compostada.

Directory of Open Access Journals (Sweden)

Posada Tobón Claudia

2003-06-01

Full Text Available El objetivo de este trabajo fue evaluar la respuesta de plántulas de café a la aplicación de fertilizantes foliares y compost de pulpa de café como parte del sustrato de crecimiento. Las plántulas de café (Coffea arabica L c.v. Colombia se transplantaron a bolsas plásticas que contenían suelo (Typic Dystrudept o una mezcla suelo con pulpa (suelo+pulpa en proporción 3:1. Treinta días después del trasplante las plántulas de café recibieron uno de cinco fertilizantes foliares (16-16-2-EM, 18-10-4-EM, 10-4-7-0.5, 12-60-0 y 7.5-0.5-3.5. Las aplicaciones se repitieron cada treinta días durante los siguientes cinco meses. Para ambos sustratos (suelo y suelo+pulpa se incluyeron testigos sin fertilización foliar. Los tratamientos se organizaron en un diseño experimental completamente al azar con cuatro repeticiones por tratamiento. Mensualmente se evaluó el número de hojas y la altura de las plantas. Ciento ochenta días después del trasplante se cosecharon las plántulas y se determinó la masa seca aérea y radical. Los resultados indican que solamente hubo respuesta significativa (P  0.01 de las plántulas de café a la fertilización foliar cuando el sustrato fue suelo+pulpa. El fertilizante foliar 12-60-0 incrementó significativamente el crecimiento de las plantas por encima de los otros fertilizantes. Los resultados son discutidos en términos de los cambios en la fertilidad del suelo debido a la aplicación de la pulpa de café y al balance nutricional que pueden proveer los fertilizantes foliares.

Estimation of ultraviolet radiation dose using CaF2:Tb phosphor

International Nuclear Information System (INIS)

Fukuda, Y.; Ohtaki, H.; Owaki, S.

1996-01-01

To observe and estimate the dose of ultraviolet (UV) radiation in sunlight, the available thermoluminescence (TL) materials were studied. Several kinds of lanthanide elements were doped in pure CaF 2 powdered crystal and the properties of the Tl for UV were observed. The TL intensity from CaF 2 :Tb was the highest among the samples doped with various lanthanide elements, and form the TL emission spectra (380-540 nm) the TL is estimated to be due to inner transition of Tb 3+ . The peak wavelength of the TL excitation light was located approximately at 235 nm and light of a longer wavelength than 320 nm was unable to excite the TL. The ultraviolet response of CaF 2 :Tb depended on its sintering temperature. Even without γ ray pre-irradiation the CaF 2 :Tb sample with 1 h exposure to sunlight has enough sensitivity to estimate the change of UV. Seasonal change of UV intensity in sunlight was measured with this TLD during four months in 1993. The results agreed with that of other institutes in Japan. (author)

Ultraviolet radiation dosimetry using CaF2 TL phosphors- state of the art

International Nuclear Information System (INIS)

Nagpal, J.S.

2001-01-01

Photoluminescence (PL), optical absorption (OA) and thermoluminescence (TL) of undoped and Dy, Tb- and Eu activated CaF 2 TL phosphors has been re-investigated after heat treatment (600-1100 degC) in air. The study confirmed the earlier observed increase in intrinsic UV response of CaF 2 : Dy 3+ after 900 degC heat treatment. Enhancement in UV response was also observed in undoped CaF 2 thus indicating the base matrix related phenomenon. However, the enhancement observed in UV sensitivity and the optimum treatment temperature for high UV sensitivity is different for different activators. It is activator specific and needs further probing. UV response of undoped CaF 2 monotonically increases as the treatment temperature (in air) is increased from 600 degC to 1100 degC. Similar increase is observed in case of CaF 2 : Tb 3+ also. However, CaF 2 : Dy 3+ and CaF 2 :Eu 2+ follow a different pattern. Heat treatment in air increases UV response of CaF 2 : Dy 3+ up to 900 degC, and a decrease is observed at higher temperatures. UV response of CaF 2 : Eu 2+ is maximum for 600 degC treatment in air and decreases thereafter. TL response of CaF 2 : Tb and CaF 2 : Eu 2+ phosphors to UV is high, can be employed over the range 10 -2 - 2 mJ.cm -2 and is rate independent for 250±10 nm UV. (author)

Preparation of chromatographically pure specimens, crystallization, and X-ray diffraction study of the periplasmatic chaperone protein Caf1M from Y. Pestis

International Nuclear Information System (INIS)

Mikhailov, A.M.; Vainshtein, B.K.; Chernovskaya, T.V.; Vasil'ev, A.M.; Rudenko, E.G.; Abramov, V.M.; Zav'yalov, V.P.; Kornev, A.N.; Kornilov, V.V.; Karlyshev, A.V.; MacIntyre, Sh.

1999-01-01

The for growing conditions perfect single crystals of the protein Caf1M have been established. The unit-cell parameters of the crystals are (a=112.6 A, b=78.1 A, c=65.3 A, sp. gr. P2 1 2 1 2 1 ), molecular weight is 28 kDa), which is a representative of molecular periplasmatic chaperones, were found. This investigation is the first necessary stage of determination the three-dimensional structure of this biomacromolecule at atomic resolution. Taking into account that the primary amino acid sequences of the protein Caf1M and of the structurally studied protein PapD and also their secondary structures are homologous, the phase problem can be solved by the molecular replacement method

Designing CAF-adjuvanted dry powder vaccines: spray drying preserves the adjuvant activity of CAF01.

Science.gov (United States)

Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis; Larsen, Niels Bent; Hinrichs, Wouter Leonardus Joseph; Andersen, Peter; Rantanen, Jukka; Nielsen, Hanne Mørck; Yang, Mingshi; Foged, Camilla

2013-05-10

Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) via spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol. Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassy matrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations. Copyright © 2013 Elsevier B.V. All rights reserved.

Scintillation and optical stimulated luminescence of Ce-doped CaF2

International Nuclear Information System (INIS)

Yanagida, Takayuki; Fujimoto, Yutaka; Watanabe, Kenichi; Fukuda, Kentaro; Kawaguchi, Noriaki; Miyamoto, Yuka; Nanto, Hidehito

2014-01-01

Scintillation and optical stimulated luminescence of Ce 0.1–20% doped CaF 2 crystals prepared by Tokuyama Corp. were investigated. In X-ray induced scintillation spectra, luminescence due to Ce 3+ 5d–4f transition appeared around 320 nm with typically 40 ns decay time. By 241 Am 5.5 MeV α-ray irradiation, 0.1% doped one showed the highest scintillation light yield and the light yield monotonically decreased with Ce concentrations. Optically stimulated luminescence after X-ray irradiation was observed around 320 nm under 550 or 830 nm stimulation in all samples. As a result, intensities of optically stimulated luminescence were proportional to Ce concentrations. Consequently, scintillation and optically stimulated luminescence resulted to have a complementary relation in Ce-doped CaF 2 system. - Highlights: • Optical, scintillation, and OSL properties of Ce 0.1–20% doped CaF 2 were studied. • Scintillation light yield exhibited inverse proportionality to Ce concentrations. • OSL intensities showed proportionality to Ce concentrations. • Complementary relation of scintillation and OSL was experimentally confirmed

Synthesis, characterization of CaF2 doped silicate glass-ceramics.

Science.gov (United States)

Riaz, Madeeha; Zia, Rehana; Mirza, Ambreen; Hussain, Tousif; Bashir, Farooq; Anjum, Safia

2017-06-01

This paper reports the fabrication and characterization of silicate glass-ceramics doped with (0-12mol%) CaF 2 . TGA-DSC analysis was carried out to determine the crystallization temperature and stability of glass measured by two glass parameters; Hruby parameter K H =(T x -T g )/(T L -T x ) and Weinberg parameter K W =(T c -T g )/T L . It was found that with CaF 2 doping improved sinterability at low temperature and provided stability to the glass. The XRD pattern exhibits a single phase of combeite and doping of CaF 2 cause increase in crystallite size. Microstructure of samples was also improved with CaF 2 addition, pores were significantly reduced. After 15days immersion in simulated body fluid all samples developed apatite layer onto its surface. Hence, the addition of CaF 2 provided bioactive glass-ceramic material having a low processing temperature. Copyright © 2017 Elsevier B.V. All rights reserved.

Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic

DEFF Research Database (Denmark)

Ahlborn, Lise B; Dandanell, Mette; Steffensen, Ane Y

2015-01-01

by functional analysis at the protein level. Results from a validated mini-gene splicing assay indicated that nine BRCA1 variants resulted in splicing aberrations leading to truncated transcripts and thus can be considered pathogenic (c.4987A>T/p.Met1663Leu, c.4988T>A/p.Met1663Lys, c.5072C>T/p.Thr1691Ile, c......Pathogenic germline mutations in the BRCA1 gene predispose carriers to early onset breast and ovarian cancer. Clinical genetic screening of BRCA1 often reveals variants with uncertain clinical significance, complicating patient and family management. Therefore, functional examinations are urgently...... needed to classify whether these uncertain variants are pathogenic or benign. In this study, we investigated 14 BRCA1 variants by in silico splicing analysis and mini-gene splicing assay. All 14 alterations were missense variants located within the BRCT domain of BRCA1 and had previously been examined...

La caféine : esquisse d'une histoire phytochimique

OpenAIRE

Jaussaud, Philippe

2016-01-01

article électronique déposé sur le blog Interfaces/Livres anciens de l'Université de Lyonhttp://bibulyon.hypotheses.org/6616; Présente dans les trois boissons chaudes habituellement associées à nos petits-déjeuners - café, thé et chocolat -, la caféine est une méthylxanthine. Elle existe dans des plantes taxinomiquement très variées, comme : le Caféier (Coffea arabica, Coffea canefora, etc.), le Maté (Ilex paraguariensis), le Guarana (Paullinia cupana), le Théier (Camellia sinensis), le Kolat...

Transporte de Café Cereza por Cable Aéreo de Gravedad

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Parra Rodríguez Henry

1989-12-01

Full Text Available Con el fin de determinar los parámetros que gobiernan el transporte de café cereza por cable aéreo de gravedad, se construyó en el Centro Nacional de Investigaciones del Café “CENICAFE”, un banco de pruebas con longitud de 38.5m y de altura variable, para simular diferentes condiciones topográficas. En el trabajo se determinaron las mejores combinaciones de flecha-pendiente que no requieran de ningún dispositivo de frenado de una carga de 60kg, en el punto de descarga. Para pendientes mayores del 15% se debe implementar un sistema de amortiguación o control de la velocidad de las cargas. Flechas mayores al 6% no son recomendables para el sistema de transporte de café cereza por cable aéreo de gravedad, debido a la presencia indeseable de una onda en el cable que distorsiona el descenso de las cargas. Teniendo en cuenta los valores de flecha-pendiente anotados anteriormente, el diámetro mínimo del cable de acero recomendado para transpotadores de gravedad, debe de ser “para longitudes de 300m, por cada 120m adicionales de longitud se debe aumentar el diámetro en 1/8 de pulgada. La capacidad de transporte de café cereza en el banco de pruebas, enviando cargas de 60kg, fue mayor a 5000 kg de café cereza por hora para las diferentes combinaciones de flecha-pendiente experimentadas.

Structural Phase Transition and Compressibility of CaF2 Nanocrystals under High Pressure

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Jingshu Wang

2018-05-01

Full Text Available The structural phase transition and compressibility of CaF2 nanocrystals with size of 23 nm under high pressure were investigated by synchrotron X-ray diffraction measurement. A pressure-induced fluorite to α-PbCl2-type phase transition starts at 9.5 GPa and completes at 20.2 GPa. The phase-transition pressure is lower than that of 8 nm CaF2 nanocrystals and closer to bulk CaF2. Upon decompression, the fluorite and α-PbCl2-type structure co-exist at the ambient pressure. The bulk modulus B0 of the 23 nm CaF2 nanocrystals for the fluorite and α-PbCl2-type phase are 103(2 and 78(2 GPa, which are both larger than those of the bulk CaF2. The CaF2 nanocrystals exhibit obviously higher incompressibility compare to bulk CaF2. Further analysis demonstrates that the defect effect in our CaF2 nanocrystals plays a dominant role in the structural stability.

Teen Science Cafés: A Vehicle for Scientists Seeking Broader Impacts

Science.gov (United States)

Hall, M.; Mayhew, M. A.

2015-12-01

Teen Science Cafés are a global phenomenon where scientists and teenagers engage in lively conversations about current, relevant, and intriguing science. In the past two years, Teen Café programs have been initiated in 41 sites in 18 U.S. states via the Teen Science Cafe Network, teensciencecafe.org. Other such programs are growing in the UK, eastern Africa, South Africa, and Singapore. The events are a free, informal, and low risk way for scientists to share their science with a receptive audience much focused on future careers. The success of a Café depends on the core principle that rich conversation occurs; a Café program is not a lecture series. Engaging teen participants brings out different perspectives and new dimensions to the topic; this has typically given scientists new ways of thinking about their own research! Presenting the event as a conversation and inviting the teens to bring in questions and points of view is key to fostering a dynamic Café. Scientists report that the training provided for these engagements has changed the way they talk about their science to peers, managers, and funding agencies. Teen Cafés have been shown to significantly change teens' view of the importance of science in their lives, positively influence teens' understanding of science in the news, and increase their ability and confidence to use facts to support scientific points of view. The Café events also positively influenced teens' interest in science and science careers, and revealed to them the true nature of scientific research and the interesting lives that scientists lead. Cafés are an excellent vehicle for scientists to have broader impact on the current generation of students, our future adult citizens. The Teen Science Café Network is an open community of practice committed to helping others implement Teen Cafés.

Divergent biophysical properties, gating mechanisms, and possible functions of the two skeletal muscle Ca(V)1.1 calcium channel splice variants.

Science.gov (United States)

Tuluc, Petronel; Flucher, Bernhard E

2011-12-01

Voltage-gated calcium channels are multi-subunit protein complexes that specifically allow calcium ions to enter the cell in response to membrane depolarization. But, for many years it seemed that the skeletal muscle calcium channel Ca(V)1.1 is the exception. The classical splice variant Ca(V)1.1a activates slowly, has a very small current amplitude and poor voltage sensitivity. In fact adult muscle fibers work perfectly well even in the absence of calcium influx. Recently a new splice variant of the skeletal muscle calcium channel Ca(V)1.1e has been characterized. The lack of the 19 amino acid exon 29 in this splice variant results in a rapidly activating calcium channel with high current amplitude and good voltage sensitivity. Ca(V)1.1e is the dominant channel in embryonic muscle, where the expression of this high calcium-conducting Ca(V)1.1 isoform readily explains developmental processes depending on L-type calcium currents. Moreover, the availability of these two structurally similar but functionally distinct channel variants facilitates the analysis of the molecular mechanisms underlying the unique current properties of the classical Ca(V)1.1a channel.

Volátiles De Maíz {lea mays, cebada (Hordeum vulgare y café (Coffea arábica tostados. influencia de la adición de estos cereales en el aroma del café

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Margoth Suárez

2010-07-01

Full Text Available Los volátiles de café a dos grados de torrefacción, como también los del maíz y los de cebada tostados, fueron extraídos por "Headspace" dinámico. La composición de los volátiles fue determinada por Cromatografía de Gases de Alta Resolución acoplada a Espectrometría de Masas (CGAREM. Los constituyentes mayoritarios del café torrefactado a 230 "C durante 8 minutos fueron el furfural 2-metil-3-dihidrofuranona y 2,3- pentadiona mientras que a230"Cy 10 minutos fueron el 2-furanmetanol, 3-metilpirazina, la 1,6-dimetilpirazina y acetato de 2-furanmetanol. Los constituyentes de mayor concentración en el maíz fueron el furfural y el 5-metilfurfuraI y en la cebada el 2-metilbutanal, el 3-metilbutanal y el furano. El análisis sensorial del café y mezclas de café con maiz y cebada permitió detectar adulteración a partir de 20% de cereal en un café torrefactado durante 8 min., pero cuando la torrefacción se realizó por 10 min. fue muy difícil percibir el aroma a cereal, principalmente cuando éste es cebada. Los resultados fueron utilizados como indicadores de la adulteración del café con cereales y como un criterio de evaluación para garantizar la pureza del café Colombiano.

COMBINED RAMAN AND SEM STUDY ON CAF2 FORMED ON/IN ENAMEL BY APF TREATMENTS

NARCIS (Netherlands)

TSUDA, H; JONGEBLOED, WL; STOKROOS, [No Value; ARENDS, J

1993-01-01

Raman spectra containing the distinct band at 322 cm(-1) due to CaF2 or CaF2-like material formed in/on fluoridated bovine enamel were recorded using a micro-Raman spectrograph. Due to increasing levels of background fluorescence with increasing thickness of enamel, the Raman measurements were

Nanotechnology in Dutch science cafés: Public risk perceptions contextualised.

Science.gov (United States)

Dijkstra, Anne M; Critchley, Christine R

2016-01-01

Understanding public perceptions of and attitudes to nanotechnology is important in order to understand and facilitate processes of dialogue and public participation. This research quantitatively analysed risk perceptions and attitudes of Dutch science café participants (n = 233) and compared these with members of the Dutch public (n = 378) who had not attended a café but were interested in science and technology as well. A qualitative analysis of the meetings contextualised and enriched the quantitative findings. Both groups shared similar key attitudes and were positive about nanotechnology while the Dutch café participants were even more positive about nanotechnology than the group of non-participants. The perception that nanotechnology would lead to risk applications was only predictive of attitudes for the non-participants. The qualitative analysis showed that café participants and speakers considered discussion of the risks, benefits and related issues important. Further research could investigate how science cafés can play a role in the science-society debate. © The Author(s) 2014.

Selection and characterization of T-cell variants lacking molecules involved in T-cell activation (T3 T-cell receptor, T44, and T11): analysis of the functional relationship among different pathways of activation

International Nuclear Information System (INIS)

Moretta, A.; Poggi, A.; Olive, D.; Bottino, C.; Fortis, C.; Pantaleo, G.; Moretta, L.

1987-01-01

A clone of the interleukin 2-producing Jurkat leukemia cell line termed JA3 (surface phenotype, T3 + , Ti + , T44 + , T11 + , T40 + ) has been used to induce and select cell variants lacking surface molecules involved in T-cell activation. Following 200 rad of γ-radiation (1 rad = 0.01 Gy), cells were treated with monoclonal antibodies (mAbs) directed to T3, Ti, T44, or T11 antigen and complement. After growth of the residual cells in culture, negative cells were cloned under limiting conditions. Depending on the specificity of the mAb used for the immunoselection, three groups of variants were obtained. (i) The use of mAbs directed to T3 or Ti resulted in cell variants that expressed the T3 - Ti - T44 + Leu1 + T11 + T40 + 4F2 + HLA class I + surface phenotype. (ii) Immunoselection with anti-T44 mAb resulted in 2 variants that shared the T3 - Ti - T44 - Leu1 - T11 - T40 - 4F2 - HLA class I + phenotype. (iii) Cell treatment with anti-T11 mAb resulted in 15 variants characterized by the lack of T11 antigen expression and of all the other T-cell-specific surface antigens. Therefore, it appears that the different sets of JA3 cell variants, like T cells at discrete stages of intrathymic differentiation, may follow a coordinated expression of surface differentiation antigens. Analysis of the functional responsiveness of the three distinct groups of JA3 cell variants to different stimuli showed that all produced interleukin 2 in response to A23187 calcium ionophore plus phorbol 12-myristate 13-acetate

Complex phenotype of dyskeratosis congenita and mood dysregulation with novel homozygous RTEL1 and TPH1 variants.

Science.gov (United States)

Ungar, Rachel A; Giri, Neelam; Pao, Maryland; Khincha, Payal P; Zhou, Weiyin; Alter, Blanche P; Savage, Sharon A

2018-06-01

Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome caused by germline mutations in telomere biology genes. Patients have extremely short telomeres for their age and a complex phenotype including oral leukoplakia, abnormal skin pigmentation, and dysplastic nails in addition to bone marrow failure, pulmonary fibrosis, stenosis of the esophagus, lacrimal ducts and urethra, developmental anomalies, and high risk of cancer. We evaluated a patient with features of DC, mood dysregulation, diabetes, and lack of pubertal development. Family history was not available but genome-wide genotyping was consistent with consanguinity. Whole exome sequencing identified 82 variants of interest in 80 genes based on the following criteria: homozygous, <0.1% minor allele frequency in public and in-house databases, nonsynonymous, and predicted deleterious by multiple in silico prediction programs. Six genes were identified likely contributory to the clinical presentation. The cause of DC is likely due to homozygous splice site variants in regulator of telomere elongation helicase 1, a known DC and telomere biology gene. A homozygous, missense variant in tryptophan hydroxylase 1 may be clinically important as this gene encodes the rate limiting step in serotonin biosynthesis, a biologic pathway connected with mood disorders. Four additional genes (SCN4A, LRP4, GDAP1L1, and SPTBN5) had rare, missense homozygous variants that we speculate may contribute to portions of the clinical phenotype. This case illustrates the value of conducting detailed clinical and genomic evaluations on rare patients in order to identify new areas of research into the functional consequences of rare variants and their contribution to human disease. © 2018 Wiley Periodicals, Inc.

Identification of a novel splice variant of human PD-L1 mRNA encoding an isoform-lacking Igv-like domain.

Science.gov (United States)

He, Xian-hui; Xu, Li-hui; Liu, Yi

2005-04-01

To investigate the expression and regulation of PD-1 ligand 1 (PD-L1) in peripheral blood mononuclear cells (PBMC). The cDNA encoding human PD-L1 precursor was cloned from the total RNA extracted from the resting and phorbol dibutyrate plus ionomycin- or phytohemagglutinin-activated PBMC, by reverse transcription polymerase chain reaction (RT-PCR), and independent clones were sequenced and analyzed. The expression and subcellular localization were examined in transiently transfected cells. The PD-L1 gene expression in different PBMC was also analyzed by RT-PCR. A novel human PD-L1 splice variant was identified from the activated PBMC. It was generated by splicing out exon? encoding an immunoglobulin variable domain (Igv)-like domain but retaining all other exons without a frame-shift. Consequently, the putative translated protein contained all other domains including the transmembrane region except for the Igv-like domain. Furthermore, the conventional isoform was expressed on the plasma surface whereas the novel isoform showed a pattern of intracellular membrane distribution in transiently transfected K562 cells. In addition, the expression pattern of the PD-L1 splice variant was variable in different individuals and in different cellular status. PD-L1 expression may be regulated at the posttranscriptional level through alternative splicing, and modulation of the PD-L1 isoform expression may influence the outcome of specific immune responses in the peripheral tissues.

Synthesis and characterization of Er3+ doped CaF2 nanoparticles

International Nuclear Information System (INIS)

Zhi Guanglin; Song Jinghong; Mei Bingchu; Zhou Weibing

2011-01-01

Highlights: → Er 3+ :CaF 2 nanoparticles were synthesized by co-precipitation method with particle size of 8-36 nm. → Increasing dopant concentration increases lattice constants and decreases grain size. → Annealing treatment has a remarkable effect on luminescence properties. → Luminescence intensity decrease with the increasing of the dopant concentration. - Abstract: Er 3+ doped CaF 2 nanoparticles were synthesized by a chemical co-precipitation method. Effect of the dopant concentrations on the structure and optical properties of the CaF 2 nanoparticles was investigated. The X-ray powder diffraction and transmission electron microscopy analysis was used to characterize the structure and morphology of the nanoparticles. The nanoparticles with different dopant concentration exhibited a sphere-like morphology with diameters of about 8-36 nm. The incorporation of Er 3+ ions into CaF 2 resulted in the decrease in grain size and deterioration of crystallinity, but enlarged the lattice constants of CaF 2 . Additional annealing treatment at 400 deg. C to the prepared CaF 2 removed the NO 3 - and OH - groups adsorbed on the particles' surfaces, and improved the optical properties of the nanoparticles. The fluorescence intensity, with a maximum at approximately 0.4 mol%, decreased with the increase in doping concentration because of concentration quenching.

Experiencing contemporary cafés and changes in the characteristic of third places

Science.gov (United States)

Nurliani Lukito, Yulia; Puspita Xenia, Anneli

2018-03-01

The fast development of modern cafés in the city is related to the creation of urban public space. The idea of a café as a public space is not new but how a café creates a convenience public space for people with different backgrounds is still an interesting phenomenon. Modern cafés like Starbucks and Crematology – famously known as a sign of globalization and consumerism – have spread to both campus and working areas. Oldenburg distinguishes “third places” as the public places on neutral ground where people can gather, interact and enjoy the surroundings (Oldenburg, 1991). In contrast to first places (home) and second places (work), third places serve as places for social interaction and often considered anchors of community life. This paper discusses how modern cafés in UI campus and working areas actually show modifications for the characteristic of Oldenburg’s third places. The study tries to connect how modern cafés appear to be a remarkably social space where some of the barriers to social interaction declines and in the end will promote social attachment. The argument in this paper is that modern cafés offer a comforting and neutral, yet generic enough to lend itself to whatever meaning people want to use it. The method conducted is through direct observations and qualitative analyses of the Starbucks café located at Universitas Indonesia Depok campus and the Crematology café near Sudirman, Jakarta, as the case studies.

What matters to infrequent customers: a pragmatic approach to understanding perceived value and intention to revisit trendy coffee café.

Science.gov (United States)

Ting, Hiram; Thurasamy, Ramayah

2016-01-01

Notwithstanding the rise of trendy coffee café, little is done to investigate revisit intention towards the café in the context of developing markets. In particular, there is a lack of study which provides theoretical and practical explanation to the perceptions and behaviours of infrequent customers. Hence, the study aims to look into the subject matter by using the theory of reasoned action and social exchange theory as the underpinning basis. The framework proposed by Pine and Gilmore (Strat Leadersh 28:18-23, 2000), which asserts the importance of product quality, service quality and experience quality in a progressive manner, is used to decompose perceived value in the model so as to determine their effects on intention to revisit the café. Given the importance to gain practical insights into revisit intention of infrequent customers, pragmatism stance is assumed. Explanatory sequential mixed-method design is thus adopted whereby qualitative approach is used to confirm and complement quantitative findings. Self-administered questionnaire-based survey is first administered before personal interview is carried out at various cafés. Partial least squares structural equation modelling and content analysis are appropriated successively. In the quantitative findings, although product quality, service quality and experience quality are found to have positive effect on perceived value and revisit intention towards trendy coffee café, experience quality is found to have the greater effect than the others among the infrequent customers. The qualitative findings not only confirm their importance, but most importantly explain the favourable impressions they have at trendy coffee café based on their last in-store experience. While product and service quality might not necessary stimulate them to revisit trendy coffee café, experience quality driven by purposes of visit would likely affect their intention to revisit. As retaining customers is of utmost importance to

Polycrystalline dosimetric discs of natural CaF2

International Nuclear Information System (INIS)

Okuno, E.; Ferreira, M.M.; Cruz, M.T.; Watanabe, S.

1977-01-01

A new method to prepare TL dosimeters in solid discs form, by the application of cold press in a mixture of KCL and fluorite in powder form, is investigated. By this method, it is possible to obtain thousands of dosimeters without difficulty much more uniform than that obtained from monocrystal ingots. The results show that the new dosimeters present the same properties as the fluorite in powder form, with the advantage that it is easier to handle in routine work. The ratio of 2 to 1 for KCL mass to CaF 2 mass presents good Tl sensitivity to ionizing radiation and sufficient mechanical resistivity. The minimum detectable exposure is approximately 10 mR. 83% from 442 CaF 2 solid discs gave TL response within 10% of mean value. Energy dependence is also presented [pt

Suppression in the electrical hysteresis by using CaF2 dielectric layer for p-GaN MIS capacitors

Science.gov (United States)

Sang, Liwen; Ren, Bing; Liao, Meiyong; Koide, Yasuo; Sumiya, Masatomo

2018-04-01

The capacitance-voltage (C-V) hysteresis in the bidirectional measurements of the p-GaN metal-insulator-semiconductor (MIS) capacitor is suppressed by using a CaF2 dielectric layer and a post annealing treatment. The density of trapped charge states at the CaF2/p-GaN interface is dramatically reduced from 1.3 × 1013 cm2 to 1.1 × 1011/cm2 compared to that of the Al2O3/p-GaN interface with a large C-V hysteresis. It is observed that the disordered oxidized interfacial layer can be avoided by using the CaF2 dielectric. The downward band bending of p-GaN is decreased from 1.51 to 0.85 eV as a result of the low-density oxides-related trap states. Our work indicates that the CaF2 can be used as a promising dielectric layer for the p-GaN MIS structures.

NMNAT1 variants cause cone and cone-rod dystrophy.

Science.gov (United States)

Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

2018-03-01

Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

Ingeniería y café en Colombia

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C.E. Oliveros-Tascón

2011-06-01

Full Text Available Los aportes de ingeniería son claves para la sostenibilidad económica, ambiental y social de la caficultura, que en Colombia desarrollan cerca de 600.000 familias. La ingeniería ha contribuido con tecnologías que han permitido hacer más eficientes y sostenibles las labores agrícolas y el procesamiento del café a través de trabajos de investigación rigurosos. Se han generado tecnologías para recolección del café, para el beneficio ecológico del café por vía húmeda con reducción en el consumo de agua y control de la contaminación de más del 90%; así mismo, se han entregado tecnologías apropiadas para el secado solar y mecánico de café./ Engineering contributions are crucial for the economic, environmental and social sustainability of coffee growing in Colombia, undertaken by approximately 600.000 families. Through rigorous research, engineering has allowed the development of technologies that render agricultural labors and processes more efficient and sustainable. Technologies have been developed for manual harvesting, wet processing of coffee with a reduction of over 98% of water consumption and over 90% of water contamination, and appropriate efficient solar and mechanical coffee dryers.

Fading of LiF and CaF2:Dy

International Nuclear Information System (INIS)

Ben-Shachar, B.; German, U.; Weiser, G.

1983-03-01

The fading of LiF and CaF 2 :Dy was investigated and the results were compared to the literature. The effect of thermal annealing was studied in order to reduce the fading in both phosphors and to minimize the effects of the environment on CaF 2 :Dy. Minimizing the fading and knowing its time dependence make possible the exact personal and environmental dosimetry. (Author)

Podoplanin-positive cancer-associated fibroblast recruitment within cancer stroma is associated with a higher number of single nucleotide variants in cancer cells in lung adenocarcinoma.

Science.gov (United States)

Nakasone, Shoko; Mimaki, Sachiyo; Ichikawa, Tomohiro; Aokage, Keiju; Miyoshi, Tomohiro; Sugano, Masato; Kojima, Motohiro; Fujii, Satoshi; Kuwata, Takeshi; Ochiai, Atsushi; Tsuboi, Masahiro; Goto, Koichi; Tsuchihara, Katsuya; Ishii, Genichiro

2018-05-01

Podoplanin-positive cancer-associated fibroblasts (CAFs) play an essential role in tumor progression. However, it is still unclear whether specific genomic alterations of cancer cells are required to recruit podoplanin-positive CAFs. The aim of this study was to investigate the relationship between the mutation status of lung adenocarcinoma cells and the presence of podoplanin-positive CAFs. Ninety-seven lung adenocarcinomas for which whole exome sequencing data were available were enrolled. First, we analyzed the clinicopathological features of the cases, and then, evaluated the relationship between genetic features of cancer cells (major driver mutations and the number of single nucleotide variants, SNVs) and the presence of podoplanin-positive CAFs. The presence of podoplanin-positive CAFs was associated with smoking history, solid predominant subtype, and lymph node metastasis. We could not find any significant correlations between major genetic mutations (EGFR, KRAS, TP53, MET, ERBB2, BRAF, and PIC3CA) in cancer cells and the presence of podoplanin-positive CAFs. However, cases with podoplanin-positive CAFs had a significantly higher number of SNVs in cancer cells than the podoplanin-negative CAFs cases (median 84 vs 37, respectively; p = 0.001). This was also detected in a non-smoker subgroup (p = 0.037). Multivariate analyses revealed that the number of SNVs in cancer cells was the only statistically significant independent predictor for the presence of podoplanin-positive CAFs (p = 0.044). In lung adenocarcinoma, the presence of podoplanin-positive CAFs was associated with higher numbers of SNVs in cancer cells, suggesting a relationship between accumulations of SNVs in cancer cells and the generation of a tumor-promoting microenvironment.

A Pilot Memory Café for People with Learning Disabilities and Memory Difficulties

Science.gov (United States)

Kiddle, Hannah; Drew, Neil; Crabbe, Paul; Wigmore, Jonathan

2016-01-01

Memory cafés have been found to normalise experiences of dementia and provide access to an accepting social network. People with learning disabilities are at increased risk of developing dementia, but the possible benefits of attending a memory café are not known. This study evaluates a 12-week pilot memory café for people with learning…

Fabrication and characterisation of nanostructures on CaF2

International Nuclear Information System (INIS)

Batzill, M.M.

1999-04-01

Novel nanostructure fabrication techniques are described in this dissertation. Furthermore, an unusual two dimensional phase segregation on CaF 2 surfaces after glancing incidence ion beam irradiation is reported. Atomic force microscope (AFM)-tip assisted self-organisation of clusters on anisotropic surfaces is illustrated. This new technique for the fabrication of periodic structures has been demonstrated using silver clusters grown on vicinal CaF 2 (111) surfaces. The scanning action of the tip aligns silver clusters along crystal step edges on the vicinal surface. Nanowire arrays of silver with a uniform periodicity of 20-50 nm and wire widths of 5-7 nm have been achieved over the entire area scanned by the AFM. Calcium remaining on CaF 2 surfaces after electron irradiation induced depletion of the surface of fluorine is found to re-organise itself into island structures. These islands show a shape transition, upon reaching a critical size of ∼ 20 nm in diameter, from a compact to an elongated island shape. Crystal step edge erosion of fluorine allows the formation of long ranging nanowires. These wires have a uniform width of ∼ 15 nm. The observed island shape transition and the width of the wires has been explained by the presence of strain in the islands. This is the first experimental observation confirming a theoretical prediction of the reduction of island width with increasing length for strained islands. A novel technique of ion beam assisted fabrication of periodic nanowire arrays over macroscopic areas is reported. Potential sputtering of CaF 2 surfaces leads to a calcium enriched surface that organised itself in stress domains due to the lattice misfit between calcium and CaF 2 . These stress domains can be oriented by directed ion beam irradiation under glancing angles in parallel stripes with a periodicity of 8-12 nm. A phase segregation on the CaF 2 (111) surface has been observed upon glancing incidence ion beam irradiation under certain

Lack of Association of CD55 Receptor Genetic Variants and Severe Malaria in Ghanaian Children

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Kathrin Schuldt

2017-03-01

Full Text Available In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by Plasmodium falciparum, the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human CD55 gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes. A total of 26 genetic variants were detected in coding and regulatory regions of CD55. Five variants were previously unknown. None of the single variants, rare variants, or haplotypes showed evidence for association with SM or P. falciparum density. Here, we present the first comprehensive analysis of variation in the CD55 gene in the context of SM and show that genetic variants present in a Ghanaian study group appear not to influence susceptibility to the disease.

The Consequences of Internet Café Use on Turkish College Students' Social Capital

Science.gov (United States)

Koç, Mustafa; Ferneding, Karen Ann

2007-01-01

This paper draws on a part of the doctoral research study that investigates the potential impacts of Internet café use on Turkish college students' social capital. In this study, Internet café usage was portrayed by the amount of time spent and the frequency of online activities engaged at the cafés. Social capital, on the other hand, was…

Embalagens alternativas para café solúvel

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ALVES Rosa M. Vercelino

2000-01-01

Full Text Available O objetivo deste trabalho foi estimar a vida útil de café solúvel em novas opções de potes plásticos através de modelo matemático, que relaciona o aumento de umidade do produto, com a barreira à umidade da embalagem. Os potes plásticos foram caracterizados quanto às dimensões, à capacidade volumétrica, à taxa de permeabilidade ao vapor d'água (TPVA e ao torque de abertura. Caracterizou-se os dois tipos de café solúvel (aglomerado e em pó quanto à umidade inicial e crítica e à isoterma de sorção de umidade. Os potes plásticos de poliéster (PET mostraram-se cerca de dez vezes mais permeáveis que os de polipropileno (PP. Observou-se aglomeração nos produtos com 7,0% b.s. de umidade a 30ºC, mas a umidade crítica foi considerada como sendo de 5,0% b.s., que é o teor fixado pela legislação. Os resultados indicaram que, nos potes de PP, os períodos de vida útil dos cafés solúveis aglomerado e em pó foram superiores a 1,8 anos e 2,5 anos, respectivamente, a 30ºC/80%UR. Entretanto, o uso de potes de poliéster (PET não se mostrou viável devido aos baixos períodos de vida útil estimados a 30ºC/80%UR (inferiores a 4 meses.

Science cafés. Cross-cultural adaptation and educational applications

Directory of Open Access Journals (Sweden)

M. Norton

2009-10-01

Full Text Available Tokyo Institute of Technology (TokyoTech has been developing a number of methodologies to teach graduate students the theory and practice of science communication since 2005. One of the tools used is the science café, where students are taught about the background based primarily on theoretical models developed in the UK. They then apply that knowledge and adapt it the Japanese cultural context and plan, execute and review outcomes as part of their course. In this paper we review 4 years of experience in using science cafés in this educational context; we review the background to the students’ decision-making and consensus-building process towards deciding on the style and subject to be used, and the value this has in illuminating the cultural influences on the science café design and implementation. We also review the value of the science café as an educational tool and conclude that it has contributed to a number of teaching goals related to both knowledge and the personal skills required to function effectively in an international environment.

Adsorción de Cr VI sobre residuos de café

OpenAIRE

Pablo Cubides Guerrero; José Herney Ramírez Franco

2014-01-01

En el presente trabajo se estudió el proceso de adsorción de cromo VI en 3 diferentes adsorbentes; carbón activado comercial, carbón activado preparado a partir de residuos de café y los residuos de café. De estos se eligió el residuo de café (cuncho), como la mejor alternativa entre las analizadas, para este propósito se trabajó como modelo de estudio, soluciones acuosas de dicromato de potasio en concentraciones de 5μg/ml (expresada como cromo VI) y diferentes dosificaciones de residuo de c...

Planeamiento estratégico para la industria peruana del café

OpenAIRE

Castrillón Sandoval, José Carlos; Morán Romero, Tania; Prado Vilca, Esteban Fernando; Zevallos Revollar, Martha Ivette

2017-01-01

xiii, 173 h. : il. ; 30 cm. En el presente documento se ha elaborado el Planeamiento Estratégico de la Industria Peruana de Café, para lo cual se realizó un análisis de los principales factores tanto internos como externos que influyen en esta industria. Este análisis permitió diseñar las estrategias orientadas a posicionar al Perú dentro de los principales países exportadores de café a nivel mundial. El café es un cultivo de alta importancia económica para el Perú por ser uno ...

The heterogeneity of maid cafés: Exploring object-oriented fandom in Japan

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Luke Sharp

2014-06-01

Full Text Available Maid cafés may be positioned as objects of (often oversimplified fan communities in Japan; their heterogeneous qualities may be explored by presenting chronotopes with which they may be reconsidered. The problematics of viewing maid cafés in a homogeneous or reductive way (via iyashi-kei, "relaxation purposes," and moe-kei, "entertainment purposes" are considered, and the results of empirical research conducted at establishments across Honshū in Japan are presented. The vast differences in the services and interactivities provided in maid café settings are at odds with the homogenized fashion in which these venues have been treated in the popular press, in local promotional publications, and often in the academic literature. By presenting chronotopes and case studies with which maid cafés may be reconsidered, what it means to discuss maid cafés as a holistic phenomenon is challenged, and a heuristic for examining how spaces are constructed inside such establishments is provided.

Size Controlled CaF2 Nanocubes and Their Dosimetric Properties Using Photoluminescence Technique

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Najlaa D. Alharbi

2015-01-01

Full Text Available A new synthetic chemical coprecipitation route for the preparation of well-crystallized size controlled nano- and microcrystalline cubes of CaF2 is reported. Crystalline cubes in the range of 2 μm–20 nm could be synthesized and their sizes were controlled by varying the solvent : cosolvent ratio. The as-synthesized CaF2 nanocubes were characterized by different techniques. Photoluminescence (PL emission spectrum of CaF2 nanocrystalline powder showed strong emission band at 415 nm. Moreover, the effect of Eu as a dopant on the emission spectrum of CaF2 was investigated. This dopant was found to get incorporated in its Eu2+ and Eu3+ forms. The as-produced nanocubes were exposed to UV irradiation and the corresponding PL emission was studied. Excellent results are obtained, where CaF2:Eu nanocubes were found to be highly sensitive and might be suitable for esteeming the doses of UV irradiation using the PL technique.

Alzheimer Café : Prima Praktijken

NARCIS (Netherlands)

Frans Nauta; Marica Crombach

2010-01-01

In Nederland lijden zo’n 230.000 mensen aan een vorm van dementie. Door de vergrijzing en veroudering van de bevolking zal dit aantal de komende decennia alleen maar toenemen. Psychogerontoloog Bère Miesen heeft voor deze doelgroep het Alzheimer Café opgericht: een maandelijkse bijeenkomst in de

Crisis del Café y el Desarrollo Regional

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Aguilar Zambrano Luis Ignacio

2003-08-01

Full Text Available

Aguilar, Luis Ignacio. "Crisis del Café y el Desarrollo Regional", cuadernos de Economía, V. XXII, n. 38, Bogotá, 2003, páginas 239-272.

Este articulo describe y analiza la situación de precios internacionales del café y su impacto en el sector cafetero colombiano. Se plantea que con la forma tradicional de producción, el café ha dejado de ser rentable y se propone y una nueva forma de entender el papel del sector cafetero en el desarrollo económico. El trabajo señala la importancia de la reorganización del sector cafetero en colombia y centra su atencia en la estructura de la propiedad y en la dotacion de factores para que los productores sean mas competitivos en el mercado internacional. Para un caso particular en un departamento colombiano, se describen en el trabajo las orientaciones de instituciones públicas y privadas hacia sectores diferentes al cafetero, cuyo objetivo es la mejora de las condiciones de vida de la poblacion afectada.

Electrical and structural properties of CaF sub 2 films

CERN Document Server

Kim, D Y; Yi, J S

1999-01-01

Fluoride films have many practical applications such as gate insulators for thin-film transistors(TFTs), anti-reflection coatings, and optical waveguides. We have investigated fluoride films as gate insulators for TFT applications. Most of gate oxide films of TFTs, like SiO sub 2 , Ta sub 2 O sub 5 , Al sub 2 O sub 3 , and SiO sub x , exhibited problems with the trap charge density, lattice mismatch, and interface states, As a way of circumventing these problems in conventional gate insulators, we investigated CaF sub 2 which has a low interface trap charge density and lattice constant similar to that of the Si surface. We were able to achieve almost epitaxial CaF sub 2 film growth in the (200) plane on a (100) p-type Si substrate. Investigations of the structural properties of CaF sub 2 films for various substrate temperatures resulted in the best lattice mismatch of 0.7 % and an average surface roughness of 8.4 A. The C-V results for the Metal-Insulator-Semiconductor (MIS) structure of the CaF sub 2 films s...

Measurements of CaF2 concentration in fluorite ore using thermoluminescence techniques

International Nuclear Information System (INIS)

Lembo, L.; Maestri, G.; Pimpinella, M.; Benzi, V.; Muntoni, C.

1990-01-01

Fluorite powder is produced by means of a flotation process on crude ore extracted by the mines. A full automation of the flotation plant would reduce the operating cost and improve the quality and recovery of fluorite production. However, taking into account that the efficiency of a flotation cycle is directly dependent on the CaF 2 content in the concentrate and tail products, this automation requires a quasi-real-time quantitative analysis of CaF 2 concentration in the floated pulp. The feasibility was studied of using a thermoluminescence technique as an on-line analysis method to measure the CaF 2 concentration during the flotation cycle. A first set of experimental conditions to determine CaF 2 content in acid-grade fluorspar has been already developed and the preliminary results so far obtained are presented. (author)

Myopathy With SQSTM1 and TIA1 Variants: Clinical and Pathological Features

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Zhiyv Niu

2018-03-01

Full Text Available ObjectiveThe aim of this study is to identify the molecular defect of three unrelated individuals with late-onset predominant distal myopathy; to describe the spectrum of phenotype resulting from the contributing role of two variants in genes located on two different chromosomes; and to highlight the underappreciated complex forms of genetic myopathies.Patients and methodsClinical and laboratory data of three unrelated probands with predominantly distal weakness manifesting in the sixth-seventh decade of life, and available affected and unaffected family members were reviewed. Next-generation sequencing panel, whole exome sequencing, and targeted analyses of family members were performed to elucidate the genetic etiology of the myopathy.ResultsGenetic analyses detected two contributing variants located on different chromosomes in three unrelated probands: a heterozygous pathogenic mutation in SQSTM1 (c.1175C>T, p.Pro392Leu and a heterozygous variant in TIA1 (c.1070A>G, p.Asn357Ser. The affected fraternal twin of one proband also carries both variants, while the unaffected family members harbor one or none. Two unrelated probands (family 1, II.3, and family 3, II.1 have a distal myopathy with rimmed vacuoles that manifested with index extensor weakness; the other proband (family 2, I.1 has myofibrillar myopathy manifesting with hypercapnic respiratory insufficiency and distal weakness.ConclusionThe findings indicate that all the affected individuals have a myopathy associated with both variants in SQSTM1 and TIA1, respectively, suggesting that the two variants determine the phenotype and likely functionally interact. We speculate that the TIA1 variant is a modifier of the SQSTM1 mutation. We identify the combination of SQSTM1 and TIA1 variants as a novel genetic defect associated with myofibrillar myopathy and suggest to consider sequencing both genes in the molecular investigation of myopathy with rimmed vacuoles and myofibrillar myopathy

Myopathy With SQSTM1 and TIA1 Variants: Clinical and Pathological Features.

Science.gov (United States)

Niu, Zhiyv; Pontifex, Carly Sabine; Berini, Sarah; Hamilton, Leslie E; Naddaf, Elie; Wieben, Eric; Aleff, Ross A; Martens, Kristina; Gruber, Angela; Engel, Andrew G; Pfeffer, Gerald; Milone, Margherita

2018-01-01

The aim of this study is to identify the molecular defect of three unrelated individuals with late-onset predominant distal myopathy; to describe the spectrum of phenotype resulting from the contributing role of two variants in genes located on two different chromosomes; and to highlight the underappreciated complex forms of genetic myopathies. Clinical and laboratory data of three unrelated probands with predominantly distal weakness manifesting in the sixth-seventh decade of life, and available affected and unaffected family members were reviewed. Next-generation sequencing panel, whole exome sequencing, and targeted analyses of family members were performed to elucidate the genetic etiology of the myopathy. Genetic analyses detected two contributing variants located on different chromosomes in three unrelated probands: a heterozygous pathogenic mutation in SQSTM1 (c.1175C>T, p.Pro392Leu) and a heterozygous variant in TIA1 (c.1070A>G, p.Asn357Ser). The affected fraternal twin of one proband also carries both variants, while the unaffected family members harbor one or none. Two unrelated probands (family 1, II.3, and family 3, II.1) have a distal myopathy with rimmed vacuoles that manifested with index extensor weakness; the other proband (family 2, I.1) has myofibrillar myopathy manifesting with hypercapnic respiratory insufficiency and distal weakness. The findings indicate that all the affected individuals have a myopathy associated with both variants in SQSTM1 and TIA1 , respectively, suggesting that the two variants determine the phenotype and likely functionally interact. We speculate that the TIA1 variant is a modifier of the SQSTM1 mutation. We identify the combination of SQSTM1 and TIA1 variants as a novel genetic defect associated with myofibrillar myopathy and suggest to consider sequencing both genes in the molecular investigation of myopathy with rimmed vacuoles and myofibrillar myopathy although additional studies are needed to investigate the

Business model for Indian retail sector: The Café Coffee Day case

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Ashis Mishra

2013-09-01

Full Text Available Given the distinctiveness of the Indian retail sector, and the lack of reliable data on the sector, developing an appropriate business model for the Indian retail sector is a challenge. In this exploratory study of the Café Coffee Day (CCD chain of cafes, we use corporate presentations of the organisation and interview its Chairman, Mr. V.G. Siddhartha, to develop a business model along the parameters of customer value proposition, profit formula, key processes, and key resources to develop a retail model for Coffee Day Company. We generalise the model to the Indian retail sector to improve its sustainability and scalability.

Optical annealing of CaF2:Mn for cooled optically stimulated luminescence

International Nuclear Information System (INIS)

Miller, S.D.; Stahl, K.A.; Endres, G.W.R.; McDonald, J.C.

1989-01-01

Optical annealing of the cooled optically stimulated luminescence in CaF 2 :Mn at room temperature has been demonstrated. The laser of choice for optical annealing of CaF 2 : Mn is a 326 nm helium-cadmium ultraviolet laser. A complete cycle of readout and annealing of the CaF 2 :Mn cooled optically stimulated dosemeters can now be accomplished without heating the dosemeters above room temperature. This annealing work represents the next step toward creating a proton-recoil-based fast neutron dosimetry system based on the cooled optically stimulated luminescence technique. (author)

Interfacial chemical bonding state and band alignment of CaF2/hydrogen-terminated diamond heterojunction

International Nuclear Information System (INIS)

Liu, J. W.; Liao, M. Y.; Cheng, S. H.; Imura, M.; Koide, Y.

2013-01-01

CaF 2 films are deposited on hydrogen-terminated diamond (H-diamond) by a radio-frequency sputter-deposition technique at room temperature. Interfacial chemical bonding state and band alignment of CaF 2 /H-diamond heterojunction are investigated by X-ray photoelectron spectroscopy. It is confirmed that there are only C-Ca bonds at the CaF 2 /H-diamond heterointerface. Valence and conductance band offsets of the CaF 2 /H-diamond heterojunciton are determined to be 3.7 ± 0.2 and 0.3 ± 0.2 eV, respectively. It shows a type I straddling band configuration. The large valence band offset suggests advantage of the CaF 2 /H-diamond heterojunciton for the development of high power and high frequency field effect transistors.

Evaluación de un Secador Intermitente de Flujos Concurrentes (IFC para Café

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Ospina Machado Julio E.

1991-09-01

Full Text Available En Colombia, el secado de café pergamino, beneficiado por vía húmeda se realiza en dos sistemas: al sol y mecánico. El secado mecánico más utilizado es el estático, el cual presenta algunas desventajas, entre ellas, la desuniformidad en el contenido de humedad final del grano. Con el fin de disponer de una tecnología alterna de secado, el Centro Nacional de Investigaciones del Café (CENICAFE, desarrolló un proyecto de investigación sobre secado dinámico, para lo cual diseñó y evaluó un secador intermitente de flujos concurrentes (FC. En este trabajo se presentan los resultados de la evaluación de un secador tipo IFC de capacidad de 500 kg de café pergamino seco (c.p.s. y el sistema de transporte utilizado durante el secado. Las diferencias del contenido de humedad final de la masa de grano fue menor al 1% base seca (b.s. Las mejores condiciones de operación del secador fueron: temperatura del aire de secado, 80°C; flujo de grano, 0,04 m3/ min.m2 (volumen de grano; flujo de aire, 210 m3 / min.ton de café pergamino seco y tiempo de secado, 28 horas; incluyendo dos horas de aireación al final del proceso. Como resultado del análisis de calidad del café pergamino seco se encontró un promedio de 0,6% de grano pelado y una cantidad de pasillas en la almendra inferior al 5%. Después de cuatro meses de almacenamiento del café, en condiciones ambientales diferentes, la prueba de taza dio un café bueno (aroma. y sabor normal. El consumo de combustible (ACP M en promedio fue de 0,5 galones por hora y un rendimiento térmico de 5.600 KJ/ kg de agua evaporada. El transportador de cangilones de descarga por gravedad demostró ser una buena alternativa para mover el grano en este sistema de secado.

Adsorción de Cr VI sobre residuos de café

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Pablo Cubides Guerrero

2014-12-01

Full Text Available En el presente trabajo se estudió el proceso de adsorción de cromo VI en 3 diferentes adsorbentes; carbón activado comercial, carbón activado preparado a partir de residuos de café y los residuos de café. De estos se eligió el residuo de café (cuncho, como la mejor alternativa entre las analizadas, para este propósito se trabajó como modelo de estudio, soluciones acuosas de dicromato de potasio en concentraciones de 5μg/ml (expresada como cromo VI y diferentes dosificaciones de residuo de café; la concentración de cromo VI se analizó por espectrofotometría a 540 nm y la de cromo total se realizó por absorción atómica, para este proceso se analizaron las isotermas de adsorción y se determinó que el proceso se adapta al modelo de Freundlich, la cinética de la adsorción es de segundo orden y se llegaron a obtener adsorciones superiores al 95% de cromo VI.

The characteristics of CaF2:Tm crystals (TLD-300) irradiated by electromagnetic radiation

International Nuclear Information System (INIS)

Ben-Shachar, B.; Yona, S.; Laichter, Y.; German, U.; Weiser, G.

1985-09-01

The main characteristics of the CaF 2 :Tm crystals (TLD-300), as a dosimeter, were measured: the glow curve, sensitivity, linearity, fading and energy dependence for photons, and compared to those of LiF (TLD-100) and CaF 2 :Dy (TLD-200). It was found that CaF 2 :Tm can be used for environmental dosimetry by reading the crystals after four days. (Author)

Discovery Café Now Offers Online Ordering for Catering | Poster

Science.gov (United States)

If you need to have a breakfast or lunch event/meeting catered, look no further than the Discovery Café in Building 549. You can now place catering orders online for groups of five or more. The café will provide catering services for events or meetings held onsite, as well as those held at the Advanced Technology Research Facility. Orders are delivered to the site of the event

Solid solubility of MgO in the calcium silicates of portland clinker. The effect of CaF2

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Puertas, F.

1992-03-01

Full Text Available The solid solubility of MgO in the calcium silicates of portland clinker has been determined by XRD and XDS. The influence that the presence of CaF2 has on said solubility has also been verified. The solid solution limit of MgO in C3S at 1275 ºC lies at about 1.0% wt, where the triclinic form II stabilizes. The presence of CaF2 does not alter the maximum value of the MgO solubilized in that silicate, although there does take place the stabilization of the triclinic polymorph II at lower MgO contents (between 0.3 - 0.6% wt. The maximum amount of solubilized MgO in βC2 at 1.050 ºC lies around 0.5% wt. This value does not change by the presence of CaF2.Se ha determinado por DRX y EDX la solubilidad sólida del MgO en los silicatos cálcicos del clínker portland. Se ha comprobado, así mismo la influencia que sobre dicha solubilidad tiene la presencia de CaF2. El límite de disolución sólida del MgO en el C3S a 1.275º C se sitúa alrededor del 1,0% en peso, estabilizándose la forma triclínica II. La presencia de CaF2 no altera el valor máximo de MgO solubilizado en este silicato, aunque si se produce la estabilización del polimorfo triclínico II a contenidos menores de MgO (entre 0,3 – 0,6% en peso. La cantidad máxima de MgO solubilizado en e/ βC2S a 1.050 ºC se sitúa en torno al 0,5% en peso. Este valor no se ve modificado por la presencia de CaF2.

4He adsorption and third-sound propagation on rough CaF2 surfaces

International Nuclear Information System (INIS)

Herrmann, J.C.; Hallock, R.B.

2003-01-01

We have investigated the propagation of third sound on well characterized rough CaF 2 surfaces as a function of 4 He film thickness. In addition we have measured the adsorption of 4 He to the CaF 2 surfaces using quartz crystal microbalances. We report values for the superfluid depletion thickness D for the three surfaces examined here. A model for the reduction of the third-sound speed due to the increased helium adsorption on rough CaF 2 is explored

Desenvolvimento de formulações de biscoitos tipo cookie contendo café Development of cookie formulations containing coffee

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Melissa de Abreu Andrade Rodrigues

2007-03-01

Full Text Available Este trabalho teve como objetivo desenvolver formulações de biscoitos tipo cookie contendo café. Desenvolveram-se três formulações com inserção de café como: bebida tipo expresso, café solúvel e café torrado e moído, utilizando como base uma formulação americana adaptada aos ingredientes brasileiros e à inserção de café. A composição centésimal média (base seca foi: 7% umidade, 70% carboidratos, 8% proteínas, 21% gorduras e 1% minerais, com valor calórico médio de 499 kcal.100 g -1. A composição centesimal e o valor calórico observados foram similares a valores reportados para biscoitos cookie comercialmente disponíveis. A forma de inserção de café afetou as características sensoriais dos produtos, avaliados por metodologia descritiva de perfil de sabor e de textura. A Formulação 1 (bebida tipo expresso apresentou valores inferiores para a intensidade dos atributos referentes à presença de rachaduras, fragmentação, presença de pontos escuros, aroma de café e queimado. A Formulação 2 (café solúvel apresentou notas superiores de intensidade dos atributos de cor marrom, brilho, sabor amargo e de queimado, sabor residual de açúcar mascavo e crocância da borda e inferiores para concavidade. A Formulação 3 (café torrado e moído apresentou valores superiores para a presença de pontos escuros. As três formulações apresentaram notas satisfatórias e equivalentes de aceitação por crianças.The aim of the present study is to develop cookie formulations containing coffee. Three formulations were developed, each with a distinct way of adding coffee: espresso beverage, instant coffee and roasted coffee powder. The average proximate composition (dry basis of the formulations was 7% moisture, 70% carbohydrates, 8% protein, 21% fat and 1% minerals, resulting in an average caloric value of 499 kcal per 100 g product. Both the proximate composition and average caloric value were similar to values reported

The Café Wall Illusion: Local and Global Perception from Multiple Scales to Multiscale

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Nasim Nematzadeh

2017-01-01

Full Text Available Geometrical illusions are a subclass of optical illusions in which the geometrical characteristics of patterns in particular orientations and angles are distorted and misperceived as a result of low-to-high-level retinal/cortical processing. Modelling the detection of tilt in these illusions, and its strength, is a challenging task and leads to the development of techniques that explain important features of human perception. We present here a predictive and quantitative approach for modelling foveal and peripheral vision for the induced tilt in the Café Wall illusion, in which parallel mortar lines between shifted rows of black and white tiles appear to converge and diverge. Difference of Gaussians is used to define a bioderived filtering model for the responses of retinal simple cells to the stimulus, while an analytical processing pipeline is developed to quantify the angle of tilt in the model and develop confidence intervals around them. Several sampling sizes and aspect ratios are explored to model variant foveal views, and a variety of pattern configurations are tested to model variant Gestalt views. The analysis of our model across this range of test configurations presents a precisely quantified comparison contrasting local tilt detection in the foveal sample sets with pattern-wide Gestalt tilt.

Secado de café en lecho fluidizado

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Elkin Mauricio López Fontal

2006-01-01

Full Text Available Todo el café se cosecha en grano cereza, el cual se beneficia en forma tradicional o aplicando el método Becolsub o de beneficio ecológico. Una vez lavado el café pergamino obtenido, se seca en forma natural o mecánicamente. Los secadores mecánicos más utilizados son de tipo estático, en los cuales generalmente se presentan problemas de desuniformidad en el contenido de humedad final del grano, la cual debe oscilar entre 10 y 12% b.h. En el presente trabalo de investigación se empleó el sistema de secado mediante fluidización, el cual convierte un lecho de partIculas sólidas en una masa suspendida y expandida que posee muchas de las propiedades de un lIquido. Se diseno y construyó un prototipo de 5.000 g de capacidad, en el cual se secó café balo tres condiciones de temperatura del aire de secado: 42, 46 y 49°C. El tiempo de secado varió de 6 a 8 horas. Se obtuvo una buena uniformidad en el contenido de humedad final del grano, con diferencias menores a 0.86%. Además al grano se le hizo prueba de taza, obteniéndose que el producto presenta caracterIsticas organolépticas de buena calidad.

Stress and psychopathology and its impact on quality of life in chronic anal fissure (CAF) patients.

Science.gov (United States)

Arısoy, Özden; Şengül, Neriman; Çakir, Affan

2017-06-01

Chronic anal fissure (CAF) onset, exacerbation, and impact on quality of life are influenced by a host of psychological, physiological, and social factors. We aimed to investigate the difference in psychopathology and stress between normal and CAF groups. Thirty CAF patients and 20 age-sex matched healthy controls were evaluated for Axis I psychopathology, depression, anxiety, and stress with Hamilton and Hospital Depression-Anxiety Scales, Perceived Stress Scale, and SF-36. With a mean age of 39.47, 83.3% of CAF patients were female. Anxiety-depression and stress scores were all significantly higher and functionality was lower in the CAF group compared to controls (p psychopathology while 50% had a previous psychopathology. Pain (96.7% had pain (VAS = 6.55)) and bleeding (83.3% had bleeding (VAS = 4.14)) severity showed a negative impact on bodily pain and role limitations emotional subscales of SF36. There is a high comorbidity of psychopathology in the CAF patients and depression and anxiety severities show a negative impact on the quality of life. Stress acts as both a triggering and an exacerbating factor in CAF.

Caféiculture : il faut veiller au grain | CRDI - Centre de recherches ...

International Development Research Centre (IDRC) Digital Library (Canada)

31 janv. 2011 ... Selon l'Organisation internationale du café (OIC), l'organisme ... On a proposé, notamment, une définition claire et reconnue à l'échelle internationale de la pérennité, un dispositif de ... Caféiculteurs : le droit à un revenu juste.

Execution Model of Three Parallel Languages: OpenMP, UPC and CAF

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Ami Marowka

2005-01-01

Full Text Available The aim of this paper is to present a qualitative evaluation of three state-of-the-art parallel languages: OpenMP, Unified Parallel C (UPC and Co-Array Fortran (CAF. OpenMP and UPC are explicit parallel programming languages based on the ANSI standard. CAF is an implicit programming language. On the one hand, OpenMP designs for shared-memory architectures and extends the base-language by using compiler directives that annotate the original source-code. On the other hand, UPC and CAF designs for distribute-shared memory architectures and extends the base-language by new parallel constructs. We deconstruct each language into its basic components, show examples, make a detailed analysis, compare them, and finally draw some conclusions.

Dégradation de la caféine par Aspergillus sp. et Penicillium sp. : étude physiologique et biochimique

OpenAIRE

Denis, Sylvain

1996-01-01

Ce travail a été axé sur la compréhension des mécanismes physiologiques et biochimiques de la dégradation de la caféine (ou 1,3,7-triméthylxanthine) par deux champignons filamenteux cultivés en milieu liquide synthétique à base de caféine et de saccharose. Les deux souches retenues pour cette étude appartiennent aux genres #Aspergillus$ et #Penicillium$. Deux méthodes chromatographiques (CLHP et CCM) ont été optimisées pour la détermination qualitative et quantitative de la caféine et de tout...

Multi-photon microscopy with a low-cost and highly efficient Cr:LiCAF laser

Science.gov (United States)

Sakadić, Sava; Demirbas, Umit; Mempel, Thorsten R.; Moore, Anna; Ruvinskaya, Svetlana; Boas, David A.; Sennaroglu, Alphan; Kartner, Franz X.; Fujimoto, James G.

2009-01-01

Multi-photon microscopy (MPM) is a powerful tool for biomedical imaging, enabling molecular contrast and integrated structural and functional imaging on the cellular and subcellular level. However, the cost and complexity of femtosecond laser sources that are required in MPM are significant hurdles to widespread adoption of this important imaging modality. In this work, we describe femtosecond diode pumped Cr:LiCAF laser technology as a low cost alternative to femtosecond Ti:Sapphire lasers for MPM. Using single mode pump diodes which cost only $150 each, a diode pumped Cr:LiCAF laser generates ~70-fs duration, 1.8-nJ pulses at ~800 nm wavelengths, with a repetition rate of 100 MHz and average output power of 180 mW. Representative examples of MPM imaging in neuroscience, immunology, endocrinology and cancer research using Cr:LiCAF laser technology are presented. These studies demonstrate the potential of this laser source for use in a broad range of MPM applications. PMID:19065223

Lack of Frank Agrammatism in the Nonfluent Agrammatic Variant of Primary Progressive Aphasia

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Naida L. Graham

2016-09-01

Full Text Available Background/Aims: Frank agrammatism, defined as the omission and/or substitution of grammatical morphemes with associated grammatical errors, is variably reported in patients with nonfluent variant primary progressive aphasia (nfPPA. This study addressed whether frank agrammatism is typical in agrammatic nfPPA patients when this feature is not required for diagnosis. Method: We assessed grammatical production in 9 patients who satisfied current diagnostic criteria. Although the focus was agrammatism, motor speech skills were also evaluated to determine whether dysfluency arose primarily from apraxia of speech (AOS, instead of, or in addition to, agrammatism. Volumetric MRI analyses provided impartial imaging-supported diagnosis. Results: The majority of cases exhibited neither frank agrammatism nor AOS. Conclusion: There are nfPPA patients with imaging-supported diagnosis and preserved motor speech skills who do not exhibit frank agrammatism, and this may persist beyond the earliest stages of the illness. Because absence of frank agrammatism is a subsidiary diagnostic feature in the logopenic variant of PPA, this result has implications for differentiation of the nonfluent and logopenic variants, and indicates that PPA patients with nonfluent speech in the absence of frank agrammatism or AOS do not necessarily have the logopenic variant.

Sauver le café | CRDI - Centre de recherches pour le ...

International Development Research Centre (IDRC) Digital Library (Canada)

D'un tiroir de la collection entomologique de Cenicafé, où sont conservés 38 000 spécimens, Álvaro Gaitán extrait le coupable, un minuscule insecte brunâtre qui a fait perdre à lui seul un demi-milliard de dollars par an à l'industrie du café dans les dernières années. Le scolyte du caféier (la broca, en espagnol) se nourrit ...

TIAM1 variants improve clinical outcome in neuroblastoma.

Science.gov (United States)

Sanmartín, Elena; Yáñez, Yania; Fornés-Ferrer, Victoria; Zugaza, José L; Cañete, Adela; Castel, Victoria; Font de Mora, Jaime

2017-07-11

Identification of tumor driver mutations is crucial for improving clinical outcome using a personalized approach to the treatment of cancer. Neuroblastoma is a tumor of the peripheral sympathetic nervous system for which only a few driver alterations have been described including MYCN amplification and ALK mutations. We assessed 106 primary neuroblastoma tumors by next generation sequencing using a customized amplicon-based gene panel. Our results reveal that genetic variants in TIAM1 gene associate with better clinical outcome, suggesting a role for these TIAM1 variants in preventing progression of this disease. The detected variants are located within the different domains of TIAM1 that signal to the upstream regulator RAS and downstream effector molecules MYC and RAC, which are all implicated in neuroblastoma etiology and progression. Clinical outcome was improved in tumors where a TIAM1 variant was present concomitantly with either ALK mutation or MYCN amplification. Given the function of these signaling molecules in cell survival, proliferation, differentiation and neurite outgrowth, our data suggest that the TIAM1-mediated network is essential to neuroblastoma and thus, inhibiting TIAM1 reflects a rational strategy for improving therapy efficacy in neuroblastoma.

Vote for the GridCafé!

CERN Multimedia

2004-01-01

CERN's GridCafé website (http://www.gridcafe.org) has been nominated for the 8th Annual Webby Awards, together with four other finalists in the Technical Achievement category. The Webby Awards have been hailed as the "online Oscars" by Time Magazine, and are the leading international honours for websites, so this nomination represents a significant achievement. The winner in this category last year was Google. The GridCafé website, which was launched at Telecom '03 and forms part of the Microcosm exhibit on computing, introduces Grid technology to the general public, and provides information on all major Grid projects around the world, focusing in particular on the pioneering Grid developments being carried out by CERN and its many international partners for the Large Hadron Collider project. Being nominated for a Webby Award represents a great opportunity to draw positive media attention to Grid technology, to CERN and to science in general. Last year's nominees were covered...

Teen Science Cafés: A Model for Addressing Broader Impacts, Diversity, and Recruitment

Science.gov (United States)

Hall, M.; Mayhew, M. A.

2017-12-01

Teen Science Café programs (TeenScienceCafe.org) are a free and fun way for teens to explore science and technology affecting their lives. Through lively presentations, conversation, and activities to explore a topic deeply, Café programs open doors for teens to learn from experts about exciting and rewarding STEM career pathways. The programs are local and led by teens with the help of an adult mentor. The Teen Science Café Network (teensciencecafe.org) provides mentoring and resources, including small grants, to help organizations get started with and then maintain successful "teen café" programs. Through membership in the Network, more than 80 Teen Science Cafés have sprung up across the country, from rural towns to major cities. They serve a critical need for teens - meeting and engaging with STEM professionals, learning about their career paths, and seeing their passion for the work they do. Teen Science Café programs can offer geoscience departments a substantive, yet low cost, way to meet the challenges many of them face: finding ways to increase enrollment, helping faculty satisfy the broader impacts requirements of funding agencies, connecting with the surrounding communities, and providing opportunities for faculty and graduate students to learn how to communicate their science effectively to the public audience. The typical experience of scientists who have presented in teen cafés throughout the Network is that the communication skills learned spill over into their courses, proposals, and presentations to administrators and program officers. A department might partner with one or more organizations in their surrounding communities—libraries, for example—and engage its faculty and its graduate students—and even its undergraduates—in providing geoscience programming across multiple disciplines to local teens. Besides the internal benefits to the department's personnel and the value of establishing connections with community organizations

Exome-Wide Association Study Identifies New Low-Frequency and Rare UGT1A1 Coding Variants and UGT1A6 Coding Variants Influencing Serum Bilirubin in Elderly Subjects

Science.gov (United States)

Oussalah, Abderrahim; Bosco, Paolo; Anello, Guido; Spada, Rosario; Guéant-Rodriguez, Rosa-Maria; Chery, Céline; Rouyer, Pierre; Josse, Thomas; Romano, Antonino; Elia, Maurizzio; Bronowicki, Jean-Pierre; Guéant, Jean-Louis

2015-01-01

Abstract Genome-wide association studies (GWASs) have identified loci contributing to total serum bilirubin level. However, no exome-wide approaches have been performed to address this question. Using exome-wide approach, we assessed the influence of protein-coding variants on unconjugated, conjugated, and total serum bilirubin levels in a well-characterized cohort of 773 ambulatory elderly subjects from Italy. Coding variants were replicated in 227 elderly subjects from the same area. We identified 4 missense rare (minor allele frequency, MAF bilirubin level (P = 2.34 × 10−34, P = 7.02 × 10−34, and P = 8.27 × 10−34), as well as unconjugated, and conjugated bilirubin levels. We also identified UGT1A6 variants in association with total (rs6759892, p.Ser7Ala, P = 1.98 × 10−26; rs2070959, p.Thr181Ala, P = 2.87 × 10−27; and rs1105879, p.Arg184Ser, P = 3.27 × 10−29), unconjugated, and conjugated bilirubin levels. All UGT1A1 intronic variants (rs887829, rs6742078, and rs4148325) and UGT1A6 coding variants (rs6759892, rs2070959, and rs1105879) were significantly associated with gallstone-related cholecystectomy risk. The UGT1A6 variant rs2070959 (p.Thr181Ala) was associated with the highest risk of gallstone–related cholecystectomy (OR, 4.58; 95% CI, 1.58–13.28; P = 3.21 × 10−3). Using an exome-wide approach we identified coding variants on UGT1A1 and UGT1A6 genes in association with serum bilirubin level and hyperbilirubinemia risk in elderly subjects. UGT1A1 intronic single-nucleotide polymorphisms (SNPs) (rs6742078, rs887829, rs4148324) serve as proxy markers for the low-frequency and rare UGT1A1 variants, thereby providing mechanistic explanation to the relationship between UGT1A1 intronic SNPs and the UGT1A1 enzyme activity. UGT1A1 and UGT1A6 variants might be potentially associated with gallstone-related cholecystectomy risk. PMID:26039129

Caregiver Café: Providing Education and Support to Family Caregivers of Patients With Cancer
.

Science.gov (United States)

Finley, Joanne P

2018-02-01

The many burdens faced by caregivers of patients with cancer are well documented. Caregivers are asked to perform procedures, make assessments, coordinate care, and communicate with healthcare providers at an increasingly complex level. A caregiver quality improvement project, in the form of a Caregiver Café, was instituted at a National Cancer Institute-designated comprehensive cancer center.
. The objectives of the café are to (a) provide respite and a place for caregivers to relax and be nurtured, (b) provide a place for caregivers to meet and support each other, (c) provide answers to caregiver questions, and (d) recommend appropriate caregiver resources.
. The weekly Caregiver Café is led by an advanced practice nurse, and the format varies depending on the needs of the caregivers who attend.
. Caregivers have verbalized the importance of the café in helping them cope with their loved ones' cancers and treatments, and many attend on a regular basis. The Caregiver Café provides support and information and a place to get away from it all.

Estudios comparativos para la determinación de Ocratoxina A en granos de café verde

Directory of Open Access Journals (Sweden)

Carlos Vallejos

2006-02-01

Full Text Available LA OCRATOXINA A (OTA ES UNA DE LAS MICOTOXINAS MÁS NEFROTÓXICA y nefrocancerígena producida por varias especies de Aspergillus y Penicillium. OTA se encuentra frecuentemente en productos de origen vegetal como cereales, cerveza, vino, granos de café, cacahuetes y frutas secas. Desde que se ha descrito su presencia en el café verde, las compañías de café han prestado mucha atención a la calidad micotóxica del café verde para garantizar la seguridad alimentaria. En este estudio se comparan tres métodos para la determinación de OTA: Cromatografía de capa fina-TLC, Cromatografía líquida de alta resolución-HPLC y Vicam Ochratest en muestras de café, y se ha validado el Vicam Ochratest para el análisis de OTA en el café con columnas de inmunoafinidad. Por su bajo costo y la similitud de los resultados comparados con el método HPLC, el uso del método Vicam Ochratest se presenta como muy útil para los pequeños productores de café de Nicaragua, pues les permitirá mejorar su competitividad en el mercado internacional.

Observation of ultraslow stress release in silicon nitride films on CaF2

International Nuclear Information System (INIS)

Guo, Tianyi; Deen, M. Jamal; Xu, Changqing; Fang, Qiyin; Selvaganapathy, P. Ravi; Zhang, Haiying

2015-01-01

Silicon nitride thin films are deposited by plasma-enhanced chemical vapor deposition on (100) and (111) CaF 2 crystalline substrates. Delaminated wavy buckles formed during the release of internal compressive stress in the films and the stress releasing processes are observed macroscopically and microscopically. The stress release patterns start from the substrate edges and propagate to the center along defined directions aligned with the crystallographic orientations of the substrate. The stress releasing velocity of SiN x film on (111) CaF 2 is larger than that of SiN x film with the same thickness on (100) CaF 2 . The velocities of SiN x film on both (100) and (111) CaF 2 increase with the film thickness. The stress releasing process is initiated when the films are exposed to atmosphere, but it is not a chemical change from x-ray photoelectron spectroscopy

Mechanoluminescence by impulsive deformation of γ-irradiated Er-doped CaF2 crystals

International Nuclear Information System (INIS)

Brahme, Nameeta; Shukla, Manju; Bisen, D.P.; Kurrey, U.; Choubey, Anil; Kher, R.S.; Singh, Manisha

2011-01-01

An impulsive technique has been used for mechanoluminescence (ML) measurements in γ-irradiated Er doped CaF 2 crystals. When the ML is excited impulsively by the impact of moving piston on to γ-irradiated CaF 2 :Er crystals, two peaks are observed in ML intensity with time and it is seen that the peak intensities of first and second peaks (I m1 and I m2 ) increase with increasing impact velocity. However the time corresponding to first and second peaks (t m1 and t m2 ) shifts towards shorter time values with increasing impact velocity. It is also seen that the total ML intensity I Total initially increases with the impact velocity and then it attains a saturation value for higher values of the impact velocity. We have presented a theoretical explanation for the observed results. - Research highlights: → Impulsive technique has been used for mechanoluminescence (ML) studies in γ-irradiated Er doped CaF 2 crystals. → ML intensity exhibited two peaks with time (I m1 and I m2 ), where the intensity of both the peaks increased with increasing impact velocity. → The time of occurrence of the peaks (t m1 and t m2 ) reduced with increasing the impact velocity. → Total ML intensity (I Total ) first increases and then attains a saturation value with an increment in the impact velocity. → A theoretical explanation is presented to the observed results.

LOX-1 and Its Splice Variants: A New Challenge for Atherosclerosis and Cancer-Targeted Therapies

Science.gov (United States)

Rizzacasa, Barbara; Morini, Elena; Pucci, Sabina; Murdocca, Michela; Novelli, Giuseppe; Amati, Francesca

2017-01-01

Alternative splicing (AS) is a process in which precursor messenger RNA (pre-mRNA) splicing sites are differentially selected to diversify the protein isoform population. Changes in AS patterns have an essential role in normal development, differentiation and response to physiological stimuli. It is documented that AS can generate both “risk” and “protective” splice variants that can contribute to the pathogenesis of several diseases including atherosclerosis. The main endothelial receptor for oxidized low-density lipoprotein (ox-LDLs) is LOX-1 receptor protein encoded by the OLR1 gene. When OLR1 undergoes AS events, it generates three variants: OLR1, OLR1D4 and LOXIN. The latter lacks exon 5 and two-thirds of the functional domain. Literature data demonstrate a protective role of LOXIN in pathologies correlated with LOX-1 overexpression such as atherosclerosis and tumors. In this review, we summarize recent developments in understanding of OLR1 AS while also highlighting data warranting further investigation of this process as a novel therapeutic target. PMID:28146073

Luminescence Properties of CaF2 Nanostructure Activated by Different Elements

Directory of Open Access Journals (Sweden)

Numan Salah

2015-01-01

Full Text Available Nanostructures of calcium fluoride (CaF2 doped with Eu, Tb, Dy, Cu, and Ag were synthesized by the coprecipitation method and studied for their thermoluminescence (TL and photoluminescence (PL properties. The PL emission spectrum of pure CaF2 nanostructure has a broad band in the 370–550 nm range. Similar spectra were observed in case of doped samples, beside extra bands related to these impurities. The maximum PL intensity was observed in Eu doped sample. The TL results of Eu, Cu, Ag, and Tb doped samples show weak glow peaks below 125°C, whereas Dy doped one is found to be highly sensitive with a prominent peak at 165°C. This sample was further exposed to a wide range of gamma rays exposures from 137Cs source. The response curve is linear in the 100 Gy-10 kGy range. It is also observed that the particle size of CaF2 nanostructure was significantly reduced by increasing Dy concentration. These results showed that Dy is a proper activator in the host of CaF2 nanostructure, providing a highly sensitive dosimeter in a wide range of exposures and also plays a role as a controlling agent for particle size growth.

Interface reaction and wetting in the CaF2/Me systems

International Nuclear Information System (INIS)

Barzilai, S.; Aizenshtein, M.; Lomberg, M.; Froumin, N.; Frage, N.

2008-01-01

Wetting experiments using the sessile drop method were performed in the CaF 2 -Me systems (Me = Cu, Ge, Al, In and Ga). Liquid Cu, Ge, In and Ga, do not wet the CaF 2 substrate and contact angles are significantly higher than 90 deg. No condensed products were found at the metal/ceramic interface. In the CaF 2 /Al system, evidence of an interface interaction was detected and the contact angle is about 92 deg. It was established that the spreading behavior and the values of the apparent contact angle depend on the rate of evaporation of the molten metals, the rate of sublimation of the substrate and on the value of the work of adhesion at the interface. The experimental observations are well accounted for by a thermodynamic analysis of the ternary Ca-Me-F systems

2.4 μm diode-pumped Dy2+:CaF2 laser

Science.gov (United States)

Švejkar, Richard; Papashvili, Alexander G.; Šulc, Jan; Němec, Michal; Jelínková, Helena; Doroshenko, Maxim E.; Batygov, Sergei H.; Osiko, Vyacheslav V.

2018-01-01

In this work, a cryogenic cooled, longitudinal diode-pumped Dy2+ :CaF2 laser was investigated for the first time. The temperature dependence of the spectroscopy and the laser properties of Dy2+ :CaF2 are presented. The tested Dy2+ :CaF2 crystal was a longitudinal pump in a near-IR region (926 nm) by laser diode radiation. The maximal mean output power and slope efficiency at 78 K during the pulse regime of the laser were 57.5 mW and 7%, respectively. Furthermore, the CW regime was successfully tested and a maximum output power of 0.37 W was obtained for the absorbed pumping power 5.7 W. The emission laser wavelength was 2367 nm.

O café na evolução de São Paulo

Directory of Open Access Journals (Sweden)

Florestan Fernandes

1959-12-01

Full Text Available Ninguém ignora que o café foi o principal fator do desenvolvimento econômico e da prosperidade de São Paulo. Graças ao café, a vida econômica de São Paulo saiu do marasmo em que se mantinha durante o fim do século XVIII e a primeira metade do século XIX e integrou-se, ràpidamente, no sistema econômico tropical, com profundas transformações no cenário natural e humano da região. O fenômeno ocorreu com tamanha rapidez, que mesmo os observadores mais argutos acaba-ram representando o café como um "fator" de povoamento, de enriquecimento e de progresso.

Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia.

Science.gov (United States)

Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A; Cogan, Joy; Blackwell, Timothy S; Phillips, John A; Bush, William S; Meiler, Jens; Capra, John A

2018-01-23

Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease. To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function. Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating

Genome wide analysis of drug-induced torsades de pointes: lack of common variants with large effect sizes.

Directory of Open Access Journals (Sweden)

Elijah R Behr

Full Text Available Marked prolongation of the QT interval on the electrocardiogram associated with the polymorphic ventricular tachycardia Torsades de Pointes is a serious adverse event during treatment with antiarrhythmic drugs and other culprit medications, and is a common cause for drug relabeling and withdrawal. Although clinical risk factors have been identified, the syndrome remains unpredictable in an individual patient. Here we used genome-wide association analysis to search for common predisposing genetic variants. Cases of drug-induced Torsades de Pointes (diTdP, treatment tolerant controls, and general population controls were ascertained across multiple sites using common definitions, and genotyped on the Illumina 610k or 1M-Duo BeadChips. Principal Components Analysis was used to select 216 Northwestern European diTdP cases and 771 ancestry-matched controls, including treatment-tolerant and general population subjects. With these sample sizes, there is 80% power to detect a variant at genome-wide significance with minor allele frequency of 10% and conferring an odds ratio of ≥2.7. Tests of association were carried out for each single nucleotide polymorphism (SNP by logistic regression adjusting for gender and population structure. No SNP reached genome wide-significance; the variant with the lowest P value was rs2276314, a non-synonymous coding variant in C18orf21 (p  =  3×10(-7, odds ratio = 2, 95% confidence intervals: 1.5-2.6. The haplotype formed by rs2276314 and a second SNP, rs767531, was significantly more frequent in controls than cases (p  =  3×10(-9. Expanding the number of controls and a gene-based analysis did not yield significant associations. This study argues that common genomic variants do not contribute importantly to risk for drug-induced Torsades de Pointes across multiple drugs.

Analysing dutch Science cafés to better understand the science-society relationship

NARCIS (Netherlands)

Dijkstra, Anne M.

2017-01-01

Science cafés offer a place for information and discussion for all who are interested in science and its broader implications for society. In this paper, science cafés are explored as a means of informal science dialogue in order to gain more understanding of the science-society relationship.

Heterozygous RTEL1 variants in bone marrow failure and myeloid neoplasms.

Science.gov (United States)

Marsh, Judith C W; Gutierrez-Rodrigues, Fernanda; Cooper, James; Jiang, Jie; Gandhi, Shreyans; Kajigaya, Sachiko; Feng, Xingmin; Ibanez, Maria Del Pilar F; Donaires, Flávia S; Lopes da Silva, João P; Li, Zejuan; Das, Soma; Ibanez, Maria; Smith, Alexander E; Lea, Nicholas; Best, Steven; Ireland, Robin; Kulasekararaj, Austin G; McLornan, Donal P; Pagliuca, Anthony; Callebaut, Isabelle; Young, Neal S; Calado, Rodrigo T; Townsley, Danielle M; Mufti, Ghulam J

2018-01-09

Biallelic germline mutations in RTEL1 (regulator of telomere elongation helicase 1) result in pathologic telomere erosion and cause dyskeratosis congenita. However, the role of RTEL1 mutations in other bone marrow failure (BMF) syndromes and myeloid neoplasms, and the contribution of monoallelic RTEL1 mutations to disease development are not well defined. We screened 516 patients for germline mutations in telomere-associated genes by next-generation sequencing in 2 independent cohorts; one constituting unselected patients with idiopathic BMF, unexplained cytopenia, or myeloid neoplasms (n = 457) and a second cohort comprising selected patients on the basis of the suspicion of constitutional/familial BMF (n = 59). Twenty-three RTEL1 variants were identified in 27 unrelated patients from both cohorts: 7 variants were likely pathogenic, 13 were of uncertain significance, and 3 were likely benign. Likely pathogenic RTEL1 variants were identified in 9 unrelated patients (7 heterozygous and 2 biallelic). Most patients were suspected to have constitutional BMF, which included aplastic anemia (AA), unexplained cytopenia, hypoplastic myelodysplastic syndrome, and macrocytosis with hypocellular bone marrow. In the other 18 patients, RTEL1 variants were likely benign or of uncertain significance. Telomeres were short in 21 patients (78%), and 3' telomeric overhangs were significantly eroded in 4. In summary, heterozygous RTEL1 variants were associated with marrow failure, and telomere length measurement alone may not identify patients with telomere dysfunction carrying RTEL1 variants. Pathogenicity assessment of heterozygous RTEL1 variants relied on a combination of clinical, computational, and functional data required to avoid misinterpretation of common variants.

Afterglow properties of CaF2:Tm nanoparticles and its potential application in photodynamic therapy

International Nuclear Information System (INIS)

Zahedifar, M.; Sadeghi, E.; Shanei, M.M.; Sazgarnia, A.; Mehrabi, M.

2016-01-01

CaF 2 :Tm nanoparticles (NPs) were synthesized by the hydrothermal method. Intense afterglow emission with long life time was found for the produced NPs, so its applicability in photodynamic therapy was investigated. Since the wavelength of the afterglow emission of the NPs fairly matches with the absorption band of the PpIX sensitizer, especially in the red region, the Cystein mediator was used to bond NPs with the PpIX sensitizer. The CaF 2 :Tm NPs conjugated with PpIX was exposed to X-ray and by using the Antracene as detector, the production of the singlet oxygen was verified. Therefore, the produced NPs are recommended as a source of energy that improves photodynamic therapy beyond its current limitations. - Highlights: • Intense afterglow emission found for the synthesized CaF 2 :Tm nanoparticles. • CaF 2 :Tm emission band fairly matched with PpIX sensitizer's absorption band. • CaF 2 :Tm conjugated with the sensitized is a good candidate for photodynamic therapy. • The application of nanoparticles in producing singlet oxygen was verified.

Functional significance of SPINK1 promoter variants in chronic pancreatitis.

Science.gov (United States)

Derikx, Monique H M; Geisz, Andrea; Kereszturi, Éva; Sahin-Tóth, Miklós

2015-05-01

Chronic pancreatitis is a progressive inflammatory disorder of the pancreas, which often develops as a result of genetic predisposition. Some of the most frequently identified risk factors affect the serine protease inhibitor Kazal type 1 (SPINK1) gene, which encodes a trypsin inhibitor responsible for protecting the pancreas from premature trypsinogen activation. Recent genetic and functional studies indicated that promoter variants in the SPINK1 gene might contribute to disease risk in carriers. Here, we investigated the functional effects of 17 SPINK1 promoter variants using luciferase reporter gene expression assay in four different cell lines, including three pancreatic acinar cell lines (rat AR42J with or without dexamethasone-induced differentiation and mouse 266-6) and human embryonic kidney 293T cells. We found that most variants caused relatively small changes in promoter activity. Surprisingly, however, we observed significant variations in the effects of the promoter variants in the different cell lines. Only four variants exhibited consistently reduced promoter activity in all acinar cell lines, confirming previous reports that variants c.-108G>T, c.-142T>C, and c.-147A>G are risk factors for chronic pancreatitis and identifying c.-52G>T as a novel risk variant. In contrast, variant c.-215G>A, which is linked with the disease-associated splice-site mutation c.194 + 2T>C, caused increased promoter activity, which may mitigate the overall effect of the pathogenic haplotype. Our study lends further support to the notion that sequence evaluation of the SPINK1 promoter region in patients with chronic pancreatitis is justified as part of the etiological investigation. Copyright © 2015 the American Physiological Society.

Impactos do crescimento do consumo de cafés especiais na competitividade inter-regional da atividade cafeeira

Directory of Open Access Journals (Sweden)

Mônica de Moura Pires

2003-01-01

Full Text Available Este trabalho tem como objetivo avaliar os impactos da expansão do consumo de cafés especiais no crescimento da competitividade inter-regional da atividade cafeeira e na distribuição funcional da renda. Os fluxos de bens e serviços contidos na Matriz de Contabilidade Social - MCS constituíram a base de dados para a construção do modelo aplicado de equilíbrio geral - MCEG. Um aumento de 1% no consumo mundial de café foi distribuído de forma diferenciada por região produtora: 30% para o Oeste Baiano, 25% para o Cerrado Mineiro, 25% para o Sul de Minas e 20% para a Zona da Mata Mineira. Os resultados indicam que a expansão da demanda internacional revela efeito positivo sobre as regiões produtoras com maior potencial de crescimento para a oferta de cafés especiais. O choque na demanda de café não foi acompanhado por choques de demanda em outros setores, o que provocou elevação nos preços dos fatores e, conseqüentemente, diminuição nos níveis do emprego dos fatores produtivos. A reestruturação espacial da atividade produtiva, para atender à demanda de nichos de mercados, apresenta-se, assim, potencialmente promissora para o produtor como forma de manutenção da competitividade do café brasileiro no mercado internacional.

Fungos associados a grãos de café (Coffea arabica L. beneficiados no sudoeste da Bahia

Directory of Open Access Journals (Sweden)

Gabriel Fernandes Pinto Ferreira

2011-09-01

Full Text Available Diversos fatores podem interferir na qualidade do café, especialmente aqueles relacionados às etapas pós-colheita de processamento e secagem. Algumas espécies de fungos podem se associar a grãos de café durante a pós-colheita, podendo ocasionar alterações indesejáveis. O objetivo deste estudo foi avaliar a influência dos processamentos via seca (natural, seco em terreiro de terra, e via úmida (despolpado, seco em terreiro de cimento, tradicionalmente empregados na região sudoeste da Bahia, na incidência de fungos em grãos de café beneficiados produzidos na safra 2007/2008. O experimento consistiu de 4 tratamentos: a café natural de Barra do Choça; b café natural de Encruzilhada; c café despolpado de Barra do Choça e d café despolpado de Encruzilhada; e 5 repetições. Foram coletadas 20 amostras de grãos de café oriundas de diferentes propriedades cafeeiras nestes municípios. Os resultados obtidos foram avaliados pelo teste de médias t de Bonferroni a 5% de probabilidade. Houve diferença estatística significativa entre os tratamentos analisados para a infestação fúngica. Os gêneros detectados foram: Aspergillus, Penicillium e Fusarium, sendo que o gênero Aspergillus foi o de maior incidência, no qual foram identificadas oito espécies: Aspergillus ochraceus, A. niger, A. flavus, A. foetidus, A. tubingensis, A. auricomus, A. sojae e A. oryzae. Foi detectada a maior incidência de fungos em grãos de café oriundos de processamento natural do que de processamento despolpado.

CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets

DEFF Research Database (Denmark)

Martel, Cyril Jean-Marie; Agger, Else Marie; Poulsen, Julie Juul

2011-01-01

response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different...

Crystallization kinetics and spectroscopic investigations on Tb3+ and Yb3+ codoped glass ceramics containing CaF2 nanocrystals

International Nuclear Information System (INIS)

Huang Lihui; Qin Guanshi; Arai, Yusuke; Jose, Rajan; Suzuki, Takenobu; Ohishi, Yasutake; Yamashita, Tatsuya; Akimoto, Yusuke

2007-01-01

Transparent Tb 3+ and Yb 3+ codoped oxyfluoride glass ceramics containing CaF 2 nanocrystals were prepared by melt quenching and subsequent heat treatment. Crystallization kinetics of CaF 2 nanocrystals was investigated by differential scanning calorimetric method. The average apparent activation energy E a of the crystallization was ∼498 kJ/mol. Moreover, the value of the Avrami exponent n was 1.01. These results suggest that the crystallization mechanism of CaF 2 is a diffusion controlled growth process of needles and plates of finite long dimensions. X-ray diffraction patterns and transmission electron microscopy image confirmed the CaF 2 nanocrystals in the glass ceramic. Ultraviolet (UV) and visible emission spectra of the as-made glass and the glass ceramic with an excitation of a 974 nm laser diode were recorded at room temperature. An intense UV emission at 381 nm was observed in the glass ceramic. The origin of the enhancement of the emission at 381 nm was investigated using spectroscopic technique and Judd-Ofelt analysis. The enhancement of the emission at 381 nm could be attributed to the change of the ligand field of Tb 3+ ions due to the incorporation of some Tb 3+ and Yb 3+ ions into CaF 2 nanocrystals in the glass ceramic

Crise convulsive chez les abuseurs de Tramadol et caféine: à ...

African Journals Online (AJOL)

Nous rapportons Huit cas de crises convulsives diagnostiquées comme maladie épileptique après ingestion de Tramadol et d'autres substances psychotropes dont la Caféine dans une région ou maladie épileptique et addiction au café sont fréquentes. L'objectif de ce travail était d'informer les praticiens sur le risque de ...

Thermal evolution of low-temperature manganese centers in X-irradiated CaF2:Mn

International Nuclear Information System (INIS)

Jahan, M.S.; Cooke, D.W.

1984-01-01

Thermal evolution of the radiation-induced defects in CaF 2 :Mn (0.1% by weight) are investigated by ESR techniques. The Mn + resonance is found to decay at 200 K with an activation energy of 0.44 eV and frequency factor 2.8 x 10 8 s -1 which agree with previous luminescence and optical absorption measurements. This activation energy and decay temperature also agree with that of the previously described H center. It is concluded that the luminescence in CaF 2 :Mn results from thermal release of holes at H centers with ultimate recombination at Mn + ions producing excited state Mn 2+ (*). Relaxation yields the observed 500 nm emission characteristic of Mn 2+ . A second defect which decays at 150 K is observed but not identified. (author)

eCD4-Ig variants that more potently neutralize HIV-1.

Science.gov (United States)

Fetzer, Ina; Gardner, Matthew R; Davis-Gardner, Meredith E; Prasad, Neha R; Alfant, Barnett; Weber, Jesse A; Farzan, Michael

2018-03-28

The HIV-1 entry inhibitor eCD4-Ig is a fusion of CD4-Ig and a coreceptor-mimetic peptide. eCD4-Ig is markedly more potent than CD4-Ig, with neutralization efficiencies approaching those of HIV-1 broadly neutralizing antibodies (bNAbs). However, unlike bNAbs, eCD4-Ig neutralizes all HIV-1, HIV-2 and SIV isolates that it has been tested against, suggesting that it may be useful in clinical settings where antibody escape is a concern. Here we characterize three new eCD4-Ig variants, each with different architectures and each utilizing D1.22, a stabilized form of CD4 domain 1. These variants were 10- to 20-fold more potent than our original eCD4-Ig variant, with a construct bearing four D1.22 domains (eD1.22-HL-Ig) exhibiting the greatest potency. However, this variant mediated less efficient antibody-dependent cell-mediated cytotoxicity (ADCC) activity than eCD4-Ig itself or several other eCD4-Ig variants, including the smallest variant (eD1.22-Ig). A variant with the same architecture as original eCD4-Ig (eD1.22-D2-Ig) showed modestly higher thermal stability and best prevented promotion of infection of CCR5-positive, CD4-negative cells. All three variants, and eCD4-Ig itself, mediated more efficient shedding of the HIV-1 envelope glycoprotein gp120 than did CD4-Ig. Finally, we show that only three D1.22 mutations contributed to the potency of eD1.22-D2-Ig, and that introduction of these changes into eCD4-Ig resulted in a variant 9-fold more potent than eCD4-Ig and 2-fold more potent than eD1.22-D2-Ig. These studies will assist in developing eCD4-Ig variants with properties optimized for prophylaxis, therapy, and cure applications. IMPORTANCE HIV-1 bNAbs have properties different from antiretroviral compounds. Specifically, antibodies can enlist immune effector cells to eliminate infected cells, whereas antiretroviral compounds simply interfere with various steps in the viral lifecycle. Unfortunately, HIV-1 is adept at evading antibody recognition, limiting the

Functional Properties of a Newly Identified C-terminal Splice Variant of Cav1.3 L-type Ca2+ Channels*

Science.gov (United States)

Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E.; Sinnegger-Brauns, Martina J.; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

2011-01-01

An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Cav1.3 L-type Ca2+ channels (Cav1.3L) is a major determinant of their voltage- and Ca2+-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Cav1.342A channels that activate at a more negative voltage range and exhibit more pronounced Ca2+-dependent inactivation. Here we describe the discovery of a novel short splice variant (Cav1.343S) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Cav1.342A, still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Cav1.343S also activated at more negative voltages like Cav1.342A but Ca2+-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Cav1.3L. The presence of the proximal C terminus in Cav1.343S channels preserved their modulation by distal C terminus-containing Cav1.3- and Cav1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca2+ influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Cav1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca2+ channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca2+ accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca2+-induced neurodegenerative processes. PMID:21998310

Engineered Cpf1 variants with altered PAM specificities.

Science.gov (United States)

Gao, Linyi; Cox, David B T; Yan, Winston X; Manteiga, John C; Schneider, Martin W; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-08-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS indicated that these variants retain high DNA-targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified PAM-interacting mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately threefold in human coding sequences to one cleavage site per ∼11 bp.

Changes in classification of genetic variants in BRCA1 and BRCA2.

Science.gov (United States)

Kast, Karin; Wimberger, Pauline; Arnold, Norbert

2018-02-01

Classification of variants of unknown significance (VUS) in the breast cancer genes BRCA1 and BRCA2 changes with accumulating evidence for clinical relevance. In most cases down-staging towards neutral variants without clinical significance is possible. We searched the database of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) for changes in classification of genetic variants as an update to our earlier publication on genetic variants in the Centre of Dresden. Changes between 2015 and 2017 were recorded. In the group of variants of unclassified significance (VUS, Class 3, uncertain), only changes of classification towards neutral genetic variants were noted. In BRCA1, 25% of the Class 3 variants (n = 2/8) changed to Class 2 (likely benign) and Class 1 (benign). In BRCA2, in 50% of the Class 3 variants (n = 16/32), a change to Class 2 (n = 10/16) or Class 1 (n = 6/16) was observed. No change in classification was noted in Class 4 (likely pathogenic) and Class 5 (pathogenic) genetic variants in both genes. No up-staging from Class 1, Class 2 or Class 3 to more clinical significance was observed. All variants with a change in classification in our cohort were down-staged towards no clinical significance by a panel of experts of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC). Prevention in families with Class 3 variants should be based on pedigree based risks and should not be guided by the presence of a VUS.

Unique spectrum of SPAST variants in Estonian HSP patients: presence of benign missense changes but lack of exonic rearrangements

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Gross-Paju Katrin

2010-03-01

Full Text Available Abstract Background Hereditary spastic paraplegia (HSP is a clinically and genetically heterogeneous disorder that can be an autosomal-dominant, autosomal-recessive, or X-linked disease. The most common autosomal-dominant form of the disease derives from mutations in the SPAST gene. Methods The aim of this study was to analyze 49 patients diagnosed with HSP from the Estonian population for sequence variants of the SPAST gene and to describe the associated phenotypes. Healthy control individuals (n = 100 with no family history of HSP were also analyzed. All patient samples were screened using denaturing high performance liquid chromatography (DHPLC and multiplex ligation-dependent probe amplification (MLPA assay. Samples with abnormal DHPLC and MLPA profiles were sequenced, with the same regions sequenced in control samples. Results Sequence variants of SPAST were identified in 19/49 HSP patients (38.8%, twelve among them had pathogenic mutations. Within the latter group there was one sporadic case. Eight patients had pure, and four - complex HSP. The twelve variants were identified: seven pathogenic (c.1174-1G>C, c.1185delA, c.1276C>T, c.1352_1356delGAGAA, c.1378C>A, c.1518_1519insTC, c.1841_1842insA and five non-pathogenic (c.131C>T, c.484G>A, c.685A>G, c.1245+202delG, c.1245+215G>C. Only 2 of these mutations had previously been described (c.131C>T, c.1245+202delG. Three mutations, c.1174-1G>C, c.1276 C>T, c.1378C>A, showed intrafamilial segregation. Conclusion This study identified new variants of the SPAST gene which included benign missense variants and short insertions/deletions. No large rearrangements were found. Based on these data, 7 new pathogenic variants of HSP are associated with clinical phenotypes.

A Novel Human Ghrelin Variant (In1-Ghrelin) and Ghrelin-O-Acyltransferase Are Overexpressed in Breast Cancer: Potential Pathophysiological Relevance

Science.gov (United States)

Gahete, Manuel D.; Córdoba-Chacón, José; Hergueta-Redondo, Marta; Martínez-Fuentes, Antonio J.; Kineman, Rhonda D.; Moreno-Bueno, Gema

2011-01-01

The human ghrelin gene, which encodes the ghrelin and obestatin peptides, contains 5 exons (Ex), with Ex1-Ex4 encoding a 117 amino-acid (aa) preproprotein that is known to be processed to yield a 28-aa (ghrelin) and/or a 23-aa (obestatin) mature peptides, which possess biological activities in multiple tissues. However, the ghrelin gene also encodes additional peptides through alternative splicing or post-translational modifications. Indeed, we previously identified a spliced mRNA ghrelin variant in mouse (In2-ghrelin-variant), which is regulated in a tissue-dependent manner by metabolic status and may thus be of biological relevance. Here, we have characterized a new human ghrelin variant that contains Ex0-1, intron (In) 1, and Ex2 and lacks Ex3-4. This human In1-ghrelin variant would encode a new prepropeptide that conserves the first 12aa of native-ghrelin (including the Ser3-potential octanoylation site) but has a different C-terminal tail. Expression of In1-variant was detected in 22 human tissues and its levels were positively correlated with those of ghrelin-O-acyltransferase (GOAT; p = 0.0001) but not with native-ghrelin expression, suggesting that In1-ghrelin could be a primary substrate for GOAT in human tissues. Interestingly, levels of In1-ghrelin variant expression in breast cancer samples were 8-times higher than those of normal mammary tissue, and showed a strong correlation in breast tumors with GOAT (p = 0.0001), ghrelin receptor-type 1b (GHSR1b; p = 0.049) and cyclin-D3 (a cell-cycle inducer/proliferation marker; p = 0.009), but not with native-ghrelin or GHSR1a expression. Interestingly, In1-ghrelin variant overexpression increased basal proliferation of MDA-MB-231 breast cancer cells. Taken together, our results provide evidence that In1-ghrelin is a novel element of the ghrelin family with a potential pathophysiological role in breast cancer. PMID:21829727

Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin.

Science.gov (United States)

Omland, Silje Haukali; Wettergren, Erika Elgstrand; Mollerup, Sarah; Asplund, Maria; Mourier, Tobias; Hansen, Anders Johannes; Gniadecki, Robert

2017-10-07

Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) in the microenvironment are essential for tumour growth in a variety of neoplasms but their role in BCC is poorly understood. Material included facial BCC and control skin from the peritumoural area and from the buttocks. With next-generation sequencing (NGS) we compared mRNA expression between BCC and peritumoural skin. qRT-PCR, immunohistochemical and immunofluorescent staining were performed to validate the NGS results and to investigate CAF-related cyto-and chemokines. NGS revealed upregulation of 65 genes in BCC coding for extracellular matrix components pointing at CAF-related matrix remodeling. qRT-PCR showed increased mRNA expression of CAF markers FAP-α, PDGFR-β and prolyl-4-hydroxylase in BCC. Peritumoural skin (but not buttock skin) also exhibited high expression of PDGFR-β and prolyl-4-hydroxylase but not FAP-α. We found a similar pattern for the CAF-associated chemokines CCL17, CCL18, CCL22, CCL25, CXCL12 and IL6 with high expression in BCC and peritumoural skin but absence in buttock skin. Immunofluorescence revealed correlation between FAP-α and PDGFR-β and CXCL12 and CCL17. Matrix remodeling is the most prominent molecular feature of BCC. CAFs are present within BCC stroma and associated with increased expression of chemokines involved in tumour progression and immunosuppression (CXCL12, CCL17). Fibroblasts from chronically sun-exposed skin near tumours show gene expression patterns resembling that of CAFs, indicating that stromal fibroblasts in cancer-free surgical BCC margins exhibit a tumour promoting phenotype.

A combination of nootropic ingredients (CAF+) is not better than caffeine in improving cognitive functions

NARCIS (Netherlands)

Caldenhove, Stephanie; Sambeth, Anke; Sharma, S.; G., Woo; Blokland, A.

2017-01-01

Many nootropic compounds claim to have positive effects on cognitive performance. In this study, we tested the effects of the nootropic compound CAF+ on cognitive functioning. CAF+ contains a combination of ingredients that has separately shown to boost cognitive performance, including caffeine,

Dark matter search with CaF sub 2 scintillators in Osaka

CERN Document Server

Ogawa, I; Hazama, R; Ajimura, S; Matsuoka, K; Suzuki, N; Nitta, T; Miyawaki, H; Shiomi, S; Tanaka, Y; Ejiri, H; Kudomi, N; Kume, K; Ohsumi, H; Fushimi, K

2000-01-01

A detector system which consists of CaF sub 2 scintillators surrounded by active and passive shields, is developed to search for spin coupled dark matter. The whole system is in operation at the underground laboratory located in Nara (Oto Cosmo Observatory) which has effectively 1.2 km water equivalent shield. In this article our current status of the investigation is described.

Cuantificación de minerales K, Ca, Mg y P en pulpa y pergamino de café (Coffea arabica L. var. Typica

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Johanna Mendoza Abarca

2010-01-01

Full Text Available Se trabajó con muestras de café Coffea arabica L., variedad Typica de tres lugares en Ecuador: Palanda, Vilcabamba y El Pangui, seleccionados por su disponibilidad y condiciones geográficas. Se analizó potasio, calcio y magnesio por espectrofotometría de absorción atómica; y fósforo por espectrofotometría visible, utilizando en todos los casos la digestión ácida para la preparación de las muestras. Con el objetivo de mantener la trazabilidad de los residuos se realizó el beneficio húmedo del café. Los resultados obtenidos para la pulpa de café expresados en base seca fueron: K 3,1 ± 0,43 %; Ca 0,46 ± 0,06 %; Mg 0,14 ± 0,01 % y P 0,13 ± 0,01 %. Para pergamino de café: K 0,16 ± 0,02 %; Ca 0,14 ± 0,05 %; Mg 0,06 ± 0,01 % y P 0,02 ± 0,01 %. En adición, se determinaron los minerales en el grano de café. Con estos resultados podemos mencionar que la pulpa de café es una buena fuente de potasio (especialmente, magnesio y fósforo. El pergamino pudiera ser considerado como fuente de fósforo.

Cuantificación de minerales K, Ca, Mg y P en pulpa y pergamino de café (Coffea arabica L. var. Typica

Directory of Open Access Journals (Sweden)

Jorge Geovanny Figueroa Hurtado

2010-12-01

Full Text Available Se trabajó con muestras de café Coffea arabica L., variedad Typica de tres lugares en Ecuador: Palanda, Vilcabamba y El Pangui, seleccionados por su disponibilidad y condiciones geográficas. Se analizó potasio, calcio y magnesio por espectrofotometría de absorción atómica; y fósforo por espectrofotometría visible, utilizando en todos los casos la digestión ácida para la preparación de las muestras. Con el objetivo de mantener la trazabilidad de los residuos se realizó el beneficio húmedo del café. Los resultados obtenidos para la pulpa de café expresados en base seca fueron: K 3,1 ± 0,43 %; Ca 0,46 ± 0,06 %; Mg 0,14 ± 0,01 % y P 0,13 ± 0,01 %. Para pergamino de café: K 0,16 ± 0,02 %; Ca 0,14 ± 0,05 %; Mg 0,06 ± 0,01 % y P 0,02 ± 0,01 %. En adición, se determinaron los minerales en el grano de café. Con estos resultados podemos mencionar que la pulpa de café es una buena fuente de potasio (especialmente, magnesio y fósforo. El pergamino pudiera ser considerado como fuente de fósforo.

La "broca del café" no existe en haití.

OpenAIRE

T. Mendes, Luis O.

2013-01-01

La "Broca del café" nunca ha existido en el citado país. Como se verá, si nosotros nos sorprendimos con la noticia del señor Chardón que anunciaba la existencia de la plaga en Haití, más sorprendido quedó el entomólogo oficial de aquel país, por la falsedad del hecho. Los cafetales de Haití no están por lo tanto amenazados por la "Broca del café" y mucho menos las plantaciones de Colombia. Esta rectificación la registramos con gran placer, para que las instituciones oficiales y los cult...

Biochemical characterization of the GM2 gangliosidosis B1 variant

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Tutor J.C.

2004-01-01

Full Text Available The deficiency of the A isoenzyme of ß-hexosaminidase (Hex produced by different mutations of the gene that codes for the alpha subunit (Tay-Sachs disease has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic alpha subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-ß-D-glucosaminide, may offer a valid alternative. The presence of an alpha subunit in the alphaß heterodimer Hex A means that its activation energy (41.8 kJ/mol is significantly lower than that of the ßß homodimer Hex B (75.1 kJ/mol; however, as mutation inactivates the alpha subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme.

NEW MODEL OF QUALITY ASSESSMENT IN PUBLIC ADMINISTRATION - UPGRADING THE COMMON ASSESSMENT FRAMEWORK (CAF

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Mirna Macur

2017-01-01

Full Text Available In our study, we developed new model of quality assessment in public administration. The Common Assessment Framework (CAF is frequently used in continental Europe for this purpose. Its use has many benefits, however we believe its assessment logic is not adequate for public administration. Upgraded version of CAF is conceptually different: instead of analytical and linear CAF we get the instrument that measures organisation as a network of complex processes. Original and upgraded assessment approaches are presented in the paper and compared in the case of self-assessment of selected public administration organisation. The two approaches produced different, sometimes contradictory results. The upgraded model proved to be logically more consistent and it produced higher interpretation capacity.

THE THERMODYNAMIC PROPERTIES OF MELTS OF DOUBLE SYSTEM MgO – Al2O3, MgO – SiO2, MgO – CaF2, Al2O3 – SiO2, Al2O3 – CaF2, SiO2 – CaF2

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В. Судавцова

2012-04-01

Full Text Available Methodology of prognostication of thermodynamics properties of melts is presented from the coordinatesof liquidus of diagram of the state in area of equilibria a hard component is solution, on which energies ofmixing of Gibbs are expected in the double border systems of MgO – Al2O3, MgO – SiO2, MgO – CaF2,Al2O3 – SiO2, Al2O3 - CaF2, SiO2 - CaF2. For the areas of equilibrium there is quasibinary connection(MgAl2O4, Mg2SiO4, Al6Si2O13 – a grout at calculations was used equalization of Hauffe-Wagner. Theobtained data comport with literary

Functional genetic variants in the vesicular monoamine transporter 1 (VMAT1) modulate emotion processing

Science.gov (United States)

Lohoff, Falk W.; Hodge, Rachel; Narasimhan, Sneha; Nall, Aleksandra; Ferraro, Thomas N.; Mickey, Brian J.; Heitzeg, Mary M.; Langenecker, Scott A.; Zubieta, Jon-Kar; Bogdan, Ryan; Nikolova, Yuliya S.; Drabant, Emily; Hariri, Ahmad R.; Bevilacqua, Laura; Goldman, David; Doyle, Glenn A.

2012-01-01

SUMMARY Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits, and risk for psychopathology. PMID:23337945

Rare variants in RTEL1 are associated with familial interstitial pneumonia.

Science.gov (United States)

Cogan, Joy D; Kropski, Jonathan A; Zhao, Min; Mitchell, Daphne B; Rives, Lynette; Markin, Cheryl; Garnett, Errine T; Montgomery, Keri H; Mason, Wendi R; McKean, David F; Powers, Julia; Murphy, Elissa; Olson, Lana M; Choi, Leena; Cheng, Dong-Sheng; Blue, Elizabeth Marchani; Young, Lisa R; Lancaster, Lisa H; Steele, Mark P; Brown, Kevin K; Schwarz, Marvin I; Fingerlin, Tasha E; Schwartz, David A; Lawson, William E; Loyd, James E; Zhao, Zhongming; Phillips, John A; Blackwell, Timothy S

2015-03-15

Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (RTEL1 function. Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis.

Planeamiento estratégico del café en el Perú

OpenAIRE

Ayala Gómez, Erika Jesús; Bernabé Ponte, Elí; Montoya Amemiya, Magally; Pinedo Gamarra, Joel Ángel

2016-01-01

El sector cafetalero peruano registró en los últimos años decrecimiento en la producción de granos de café a causa de la crisis generada por el virus de la roya el 2013, lo cual afectó la mayor parte de las plantaciones de cafeto y demostró que muchos de los productores no estaban debidamente capacitados para afrontarla. Sin embargo, el café del Perú ha sido reconocido como uno de los productos tradicionales más importantes que el Perú exporta, ello se ve reflejado en el aumento de su demanda...

Estudio de la biosorción de cromo con hoja de café

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Luis Carlos Florez García

2009-05-01

Full Text Available El objeto de este trabajo es proveer una alternativa para la remoción de metales pesados como el cromo de las aguas residua- les (efluentes de la industria del cuero y de electrorrecubrimientos de piezas metálicas (galvanoplastia, utilizando como bioma- sa hojas de café. A condiciones de operación de pH de la disolución de 4, grado de agitación 0 rpm, tamaño de partícula de la biomasa de 0,149 mm de diámetro y relación masa de biomasa / volumen de disolución de 0,85 gr/ml, se obtuvieron eficien- cias en la remoción de cromo, con la hoja de café variedad castillo, coffee arabica del 82% para disoluciones sintéticas de1.000 mg/L.

Influencia del CaF2 sobre la capacidad de reacción de crudos de cemento

OpenAIRE

Palomo, Ángel; Blanco, M. Teresa

1982-01-01

En este trabajo se estudia el efecto de una pequeña cantidad de CaF2 sobre la capacidad de reacción de crudos de cemento, para lo cual se comparan los comportamientos térmicos en función del tiempo de clinkerización de un crudo comercial con y sin adición de CaF2. Se da una estimación de los tiempos necesarios para completar las reacciones a diferentes temperaturas. El efecto mineralizador del espato-fluor pasa por un máximo a temperaturas de clinkerización del orden de 1.200ºC y tiempos d...

Lynch syndrome associated with two MLH1 promoter variants and allelic imbalance of MLH1 expression.

Science.gov (United States)

Hesson, Luke B; Packham, Deborah; Kwok, Chau-To; Nunez, Andrea C; Ng, Benedict; Schmidt, Christa; Fields, Michael; Wong, Jason W H; Sloane, Mathew A; Ward, Robyn L

2015-06-01

Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) within the MLH1 5'untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expression and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A>G and c.-7C>T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5'UTR in the pathogenesis of Lynch syndrome. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

Functional significance of rare neuroligin 1 variants found in autism.

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Moe Nakanishi

2017-08-01

Full Text Available Genetic mutations contribute to the etiology of autism spectrum disorder (ASD, a common, heterogeneous neurodevelopmental disorder characterized by impairments in social interaction, communication, and repetitive and restricted patterns of behavior. Since neuroligin3 (NLGN3, a cell adhesion molecule at the neuronal synapse, was first identified as a risk gene for ASD, several additional variants in NLGN3 and NLGN4 were found in ASD patients. Moreover, synaptopathies are now known to cause several neuropsychiatric disorders including ASD. In humans, NLGNs consist of five family members, and neuroligin1 (NLGN1 is a major component forming a complex on excitatory glutamatergic synapses. However, the significance of NLGN1 in neuropsychiatric disorders remains unknown. Here, we systematically examine five missense variants of NLGN1 that were detected in ASD patients, and show molecular and cellular alterations caused by these variants. We show that a novel NLGN1 Pro89Leu (P89L missense variant found in two ASD siblings leads to changes in cellular localization, protein degradation, and to the impairment of spine formation. Furthermore, we generated the knock-in P89L mice, and we show that the P89L heterozygote mice display abnormal social behavior, a core feature of ASD. These results, for the first time, implicate rare variants in NLGN1 as functionally significant and support that the NLGN synaptic pathway is of importance in the etiology of neuropsychiatric disorders.

Two new splice variants in porcine PPARGC1A

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Peelman Luc J

2008-12-01

Full Text Available Abstract Background Peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A is a coactivator with a vital and central role in fat and energy metabolism. It is considered to be a candidate gene for meat quality in pigs and is involved in the development of obesity and diabetes in humans. How its many functions are regulated, is however still largely unclear. Therefore a transcription profile of PPARGC1A in 32 tissues and 4 embryonic developmental stages in the pig was constructed by screening its cDNA for possible splice variants with exon-spanning primers. Findings This led to the discovery of 2 new splice variants in the pig, which were subsequently also detected in human tissues. In these variants, exon 8 was either completely or partly (the last 66 bp were conserved spliced out, potentially coding for a much shorter protein of respectively 337 and 359 amino acids (aa, of which the first 291 aa would be the same compared to the complete protein (796 aa. Conclusion Considering the functional domains of the PPARGC1A protein, it is very likely these splice variants considerably affect the function of the protein and alternative splicing could be one of the mechanisms by which the diverse functions of PPARGC1A are regulated.

Carcinoma associated fibroblasts (CAFs) promote breast cancer motility by suppressing mammalian Diaphanous-related formin-2 (mDia2).

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Dvorak, Kaitlyn M; Pettee, Krista M; Rubinic-Minotti, Kaitlin; Su, Robin; Nestor-Kalinoski, Andrea; Eisenmann, Kathryn M

2018-01-01

The tumor microenvironment (TME) promotes tumor cell invasion and metastasis. An important step in the shift to a pro-cancerous microenvironment is the transformation of normal stromal fibroblasts to carcinoma-associated fibroblasts (CAFs). CAFs are present in a majority of solid tumors and can directly promote tumor cell motility via cytokine, chemokine and growth factor secretion into the TME. The exact effects that the TME has upon cytoskeletal regulation in motile tumor cells remain enigmatic. The conserved formin family of cytoskeleton regulating proteins plays an essential role in the assembly and/or bundling of unbranched actin filaments. Mammalian Diaphanous-related formin 2 (mDia2/DIAPH3/Drf3/Dia) assembles a dynamic F-actin cytoskeleton that underlies tumor cell migration and invasion. We therefore sought to understand whether CAF-derived chemokines impact breast tumor cell motility through modification of the formin-assembled F-actin cytoskeleton. In MDA-MB-231 cells, conditioned media (CM) from WS19T CAFs, a human breast tumor-adjacent CAF line, significantly and robustly increased wound closure and invasion relative to normal human mammary fibroblast (HMF)-CM. WS19T-CM also promoted proteasome-mediated mDia2 degradation in MDA-MB-231 cells relative to control HMF-CM and WS21T CAF-CM, a breast CAF cell line that failed to promote robust MDA-MB-231 migration. Cytokine array analysis of CM identified up-regulated secreted factors in WS19T relative to control WS21T CM. We identified CXCL12 as a CM factor influencing loss of mDia2 protein while increasing MDA-MB-231 cell migration. Our data suggest a mechanism whereby CAFs promote tumor cell migration and invasion through CXCL12 secretion to regulate the mDia2-directed cytoskeleton in breast tumor cells.

The effect of computer usage in internet café on cigarette smoking and alcohol use among chinese adolescents and youth: a longitudinal study.

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Wu, Liyun; Delva, Jorge

2012-02-01

We used longitudinal data to investigate the relationship between computer use in internet cafés and smoking/drinking behavior among Chinese adolescents and young adults. Data are from two waves of the China Health and Nutrition Survey (2004 and 2006). Fixed effects models were used to examine if changes in internet café use were associated with changes in cigarette smoking and drinking of alcohol. Male café users spent on average 17.3 hours in front of the computer/week. This was associated with an increase in the probability of being a current smoker by 13.3% and with smoking 1.7 more cigarettes. Female café users spent on average 11 hours on the computer/week. This was associated with an increase in the probability of drinking wine and/or liquor by 14.74% and was not associated with smoking. Internet cafés are an important venue by which adolescent and young adults in China are exposed to smoking and drinking. Multi-component interventions are needed ranging from policies regulating cigarette and alcohol availability in these venues to anti-tobacco campaigns aimed at the general population but also at individuals who frequent these establishments.

CO2 laser irradiation enhances CaF2 formation and inhibits lesion progression on demineralized dental enamel-in vitro study.

Science.gov (United States)

Zancopé, Bruna R; Rodrigues, Lívia P; Parisotto, Thais M; Steiner-Oliveira, Carolina; Rodrigues, Lidiany K A; Nobre-dos-Santos, Marinês

2016-04-01

This study evaluated if Carbon dioxide (CO2) (λ 10.6 μm) laser irradiation combined with acidulated phosphate fluoride gel application (APF gel) enhances "CaF2" uptake by demineralized enamel specimens (DES) and inhibits enamel lesion progression. Thus, two studies were conducted and DES were subjected to APF gel combined or not with CO2 laser irradiation (11.3 or 20.0 J/cm(2), 0.4 or 0.7 W) performed before, during, or after APF gel application. In study 1, 165 DES were allocated to 11 groups. Fluoride as "CaF2 like material" formed on enamel was determined in 100 DES (n = 10/group), and the surface morphologies of 50 specimens were evaluated by scanning electron microscopy (SEM) before and after "CaF2" extraction. In study 2, 165 DES (11 groups, n = 15), subjected to the same treatments as in study 1, were further subjected to a pH-cycling model to simulate a high cariogenic challenge. The progression of demineralization in DES was evaluated by cross-sectional microhardness and polarized light microscopy analyses. Laser at 11.3 J/cm(2) applied during APF gel application increased "CaF2" uptake on enamel surface. Laser irradiation and APF gel alone arrested the lesion progression compared with the control (p enamel surface and a synergistic effect was found. However, regarding the inhibition of caries lesion progression, no synergistic effect could be demonstrated. In conclusion, the results have shown that irradiation with specific laser parameters significantly enhanced CaF2 uptake by demineralized enamel and inhibited lesion progression.

Wetting induced by near-surface Ti-enrichment in the CaF2/In-Ti and CaF2/Cu-Ti systems

International Nuclear Information System (INIS)

Froumin, N.; Barzilai, S.; Aizenshtein, M.; Lomberg, M.; Frage, N.

2008-01-01

This paper is concerned with the wetting of CaF 2 by liquid Cu and In and with the effect of Ti additions to the melt. According to thermodynamic analysis and to the experimental observations, the significantly decreased contact angle following the addition of Ti to the molten metals is not due to the formation of interfacial fluoride phases, in contrast to previously reported results. Ab initio density functional calculations indicate that preferential Ti adsorption takes place at the near CaF 2 surface. It is suggested that the presence of a Ti-enriched liquid, adjacent to the substrate, gives rise, by means of heterogeneous nucleation, to the formation of a thin intermetallic compound layer that stands behind the experimentally observed enhanced wetting. The suggested wetting mechanism is supported by the notable correlation that has been observed between the temperature dependence of the contact angle and the temperature domains, associated with the presence of intermetallic compounds in both Me-Ti (Me = Cu, In) binary systems

Functional properties of a newly identified C-terminal splice variant of Cav1.3 L-type Ca2+ channels.

Science.gov (United States)

Bock, Gabriella; Gebhart, Mathias; Scharinger, Anja; Jangsangthong, Wanchana; Busquet, Perrine; Poggiani, Chiara; Sartori, Simone; Mangoni, Matteo E; Sinnegger-Brauns, Martina J; Herzig, Stefan; Striessnig, Jörg; Koschak, Alexandra

2011-12-09

An intramolecular interaction between a distal (DCRD) and a proximal regulatory domain (PCRD) within the C terminus of long Ca(v)1.3 L-type Ca(2+) channels (Ca(v)1.3(L)) is a major determinant of their voltage- and Ca(2+)-dependent gating kinetics. Removal of these regulatory domains by alternative splicing generates Ca(v)1.3(42A) channels that activate at a more negative voltage range and exhibit more pronounced Ca(2+)-dependent inactivation. Here we describe the discovery of a novel short splice variant (Ca(v)1.3(43S)) that is expressed at high levels in the brain but not in the heart. It lacks the DCRD but, in contrast to Ca(v)1.3(42A), still contains PCRD. When expressed together with α2δ1 and β3 subunits in tsA-201 cells, Ca(v)1.3(43S) also activated at more negative voltages like Ca(v)1.3(42A) but Ca(2+)-dependent inactivation was less pronounced. Single channel recordings revealed much higher channel open probabilities for both short splice variants as compared with Ca(v)1.3(L). The presence of the proximal C terminus in Ca(v)1.3(43S) channels preserved their modulation by distal C terminus-containing Ca(v)1.3- and Ca(v)1.2-derived C-terminal peptides. Removal of the C-terminal modulation by alternative splicing also induced a faster decay of Ca(2+) influx during electrical activities mimicking trains of neuronal action potentials. Our findings extend the spectrum of functionally diverse Ca(v)1.3 L-type channels produced by tissue-specific alternative splicing. This diversity may help to fine tune Ca(2+) channel signaling and, in the case of short variants lacking a functional C-terminal modulation, prevent excessive Ca(2+) accumulation during burst firing in neurons. This may be especially important in neurons that are affected by Ca(2+)-induced neurodegenerative processes.

Hb Melusine and Hb Athens-Georgia: potentially underreported in the Belgian population? Four cases demonstrating the lack of detection using common CE-HPLC methods either for glycated hemoglobin (HbA1C) analysis or Hb variant screening.

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Peeters, Bart; Brandt, Inger; Desmet, Koenraad; Harteveld, Cornelis L; Kieffer, Davy

2016-12-01

Suspected hemoglobin (Hb) variants, detected during HbA 1C measurements should be further investigated, determining the extent of the interference with each method. This is the first report of Hb Melusine and Hb Athens-Georgia in Caucasian Belgian patients. Intervention & Technique: Since common CE-HPLC methods for HbA 1C analysis or Hb variant screening are apparently unable to detect these Hb variants, their presence might be underestimated. HbA 1C analysis using CZE, however, alerted for their presence. Moreover, in case of Hb Melusine, even Hb variant screening using CZE was unsuccessful in its detection. Fortunately, carriage of Hb Melusine or Hb Athens-Georgia variants has no clinical implications and, as shown in this report, no apparent difference in HbA 1C should be expected.

Exportadores y consignatarios del café costarricense a finales del siglo XIX.

OpenAIRE

Peters Solórzano, Gertrud

2004-01-01

ResumenEste artículo analiza las transformaciones que sufrieron los exportadores y consignatarios en la cadena de comercialización del café de Costa Rica a finales del siglo XIX. Además se hace énfasis en cuáles estrategias de competitividad utilizó el sector cafetalero para mantenerse y extender su participación en el mercado internacional y la vulnerabilidad de las empresas comerciales ante la crisis de precios mundiales del café al caer el siglo XIX.AbstractThis article intends to study th...

Café as third place and the creation of a unique space of interaction in UI Campus

Science.gov (United States)

Nurliani Lukito, Yulia; Puspita Xenia, Anneli

2017-12-01

The emergence of modern cafés is an interesting phenomenon in the city and it is related to globalization and the creation of urban public space. This paper explores the idea of café as third place and social interaction occurs in the café with Starbucks café as the focus of discussion. We argue that modern café like Starbucks offers a comforting and neutral ground for social interaction but some other characteristic of social interaction come up as the result of modern technology. Oldenburg distinguishes third places as public places on neutral ground where people can gather and interact (Oldenburg, 1991). In contrast to first places (home) and second places (work), third places serve as places for creative and social interaction and often considered anchors of community life. The characteristic of cafés as third space relates to the social interaction occurs at the neighborhood that in terms may enhances quality of life and provide social bounding. With the development of information technology, some characteristics of third places are changed although third places still become an important medium for social interaction as well as in increasing the ability of the city to be more adaptable to changes. Conversation is still the main activity at third place but many people use their electronic devices alongside face-to-face conversations. As a method, this study uses direct observations and qualitative analyses of UI Starbucks in as case studies.

Influence of irradiation and Caf EDTA on the metabolism of nucleus acid of the different radiosensitive crops

International Nuclear Information System (INIS)

Song Daojun

1997-01-01

Irradiation and damage repair inhibitor (Caf and EDTA) post-treatment had a substantial effect on DNA and RNA content and DNA self-repairing synthesis. The experiment results showed the content of DNA and RNA increased with increase doses in the seedling hypocotyl of soybean and rape, Caf and EDTA post-treatment made them further higher than that of H 2 O-treatment. Meanwhile, the content of DNA and RNA in hypocotyl of soybean seedling was more than that of rape. Radioactive 3 H-TdR incorporation experiment showed γ-ray irradiated seeds induced unshunted DNA synthesis in the primary cultivated seeds of two crops, which was inhibited by Caf, EDTA and C + E post-treatment in the order of C + E>Caf>EDTA. Experiment also revealed irradiation and repair repressor post-treatment affected normal shunted DNA synthesis, postponed the cycle of cell division

A review of variant hemoglobins interfering with hemoglobin A1c measurement.

Science.gov (United States)

Little, Randie R; Roberts, William L

2009-05-01

Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences. 2009 Diabetes Technology Society.

Cosecha manual de café con asistencia neumática.

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Palencia López Francisco Obdulio

2002-06-01

Full Text Available En Cenicafé se evaluó un nuevo método para la cosecha manual de café en el cual se utiliza un procedimiento simplificado para desprender las cerezas y un dispositivo neumático para transportarlas desde la base del árbol hasta el almacenamiento temporal. El método simplificado propuesto por Vélez et. al para desprender las cerezas utilizado consta de únicamente cuatro actividades (Transportar vacío buscando, Sostener, Arrancar y Dejar carga en lugar de las seis identificadas por Vélez et al en la cosecha manual tradicional. El dispositivo neumático, semiestacionario, desarrollado consta de: seis tolvas receptoras (sombrillas invertidas, que se colocan en la base de igual número de árboles para recibir el café desprendido por los recolectores; mangueras flexibles para transportar el café hasta la tolva de almacenamiento temporal; y un ventilador centrífugo accionado por un motor a gasolina. Los resultados obtenidos indican que con el nuevo método de recolección se mejoran los indicadores eficiencia y pérdidas de frutos al suelo. La calidad de la recolección con los dispositivos evaluados fue igual. El rendimiento operativo con el nuevo método fue inferior al observado con el método tradicional.

Eczematous Dermatitis Occurring on a Café-au-Lait Spot Long after Laser Radiation.

Science.gov (United States)

Mihara, Motoyuki

2013-05-01

A 40-year-old woman presented with an itchy erythematosquamous change of a café-au-lait spot in her face. The onset of this change occurred just after her relocation. The café-au-lait spot had been irradiated by laser approximately 20 years ago. Clinically, there was a coin-sized erythema with a slight scale on the pigmented lesion in the left lateral orbital region. Histopathologically, the lesion demonstrated both spongiotic dermatitis and interface dermatitis together with lymphohistiocytic cell infiltration, in addition to moderate acanthosis and elongation of rete ridges with slight basal hyperpigmentation. From these clinical and histopathological findings, the lesion was diagnosed as eczematous dermatitis occurring on the café-au-lait spot after laser radiation. Another interesting histopathological finding was that some parts of a lobule of the sebaceous gland were occupied exclusively by degenerative atrophic sebocytes. From the viewpoint of pathogenesis, the eczematous dermatitis of this patient could have been an accompanying feature of a neurogenic inflammation occurring on the café-au-lait spot after laser radiation, and the atrophic change of a part of the sebaceous lobule might have been induced by a morphogenetic alteration of certain germinative cells of the sebaceous lobule due to laser radiation.

Sensory evaluation of black instant coffee beverage with some volatile compounds present in aromatic oil from roasted coffee Análise sensorial de bebida preparada com café instantâneo com alguns compostos voláteis presentes no óleo aromático de café torrado

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Alessandra Lopes de Oliveira

2009-03-01

influence with respect to flavour.O óleo do café torrado Brasileiro obtido através de extração com CO2 supercrítico mostrou consideráveis propriedades aromáticas, constituído principalmente por cinco compostos aromáticos: 2-metilpirazina; 2-furfuril álcool, 2,5-dimetilpirazina; γ -butirolactona e 2-furfuril acetato. Análises sensoriais foram usadas para verificar a influência da mistura destas importantes classes de compostos aromáticos de café (pirazinas, furanos e lactonas e do óleo aromático de café torrado no aroma e sabor de bebidas preparadas com café solúvel instantâneo liofilizado e seco por spray dryer. Na análise da aceitação do aroma, a amostra preparada com café liofilizado sem a mistura de compostos voláteis (amostra 4 não diferiu da amostra de café liofilizados com adição de óleo (amostra 5 nem tão pouco da amostra de café liofilizado com adição da mistura dos cinco voláteis (amostra 3, coincidentemente oriundas do mesmo processo de secagem. Entretanto a amostra 3 não diferiu das amostras preparadas com café seco por spray dryer sem (amostra 1 e com (amostra 2 a mistura de voláteis. Indicando que a adição desta mistura, com relação a este atributo não interfere na aceitação desta bebida. Na avaliação do sabor, as amostras preparadas com café solúvel liofilizado enriquecida com óleo aromático (5 e as amostras com (3 e sem (4 a mistura dos cinco voláteis não diferiram significativamente, entretanto a amostra (4 não diferiu das amostras (1 e (2. Para este atributo, a adição do óleo aromático de café torrado ou da mistura de voláteis nas amostras de café liofilizado fez com que tivessem uma melhor aceitação que aquelas secas por spray dryer (1 e (2. Desta forma, o enriquecimento das bebidas com o óleo aromático de café torrado, ou mesmo com a mistura dos cinco componentes não influenciou a aceitação do consumidor com relação ao aroma, mas exerce influência com relação ao sabor.

Stability and function of interdomain linker variants of glucoamylase 1 from Aspergillus niger.

Science.gov (United States)

Sauer, J; Christensen, T; Frandsen, T P; Mirgorodskaya, E; McGuire, K A; Driguez, H; Roepstorff, P; Sigurskjold, B W; Svensson, B

2001-08-07

Several variants of glucoamylase 1 (GA1) from Aspergillus niger were created in which the highly O-glycosylated peptide (aa 468--508) connecting the (alpha/alpha)(6)-barrel catalytic domain and the starch binding domain was substituted at the gene level by equivalent segments of glucoamylases from Hormoconis resinae, Humicola grisea, and Rhizopus oryzae encoding 5, 19, and 36 amino acid residues. Variants were constructed in which the H. resinae linker was elongated by proline-rich sequences as this linker itself apparently was too short to allow formation of the corresponding protein variant. Size and isoelectric point of GA1 variants reflected differences in linker length, posttranslational modification, and net charge. While calculated polypeptide chain molecular masses for wild-type GA1, a nonnatural proline-rich linker variant, H. grisea, and R. oryzae linker variants were 65,784, 63,777, 63,912, and 65,614 Da, respectively, MALDI-TOF-MS gave values of 82,042, 73,800, 73,413, and 90,793 Da, respectively, where the latter value could partly be explained by an N-glycosylation site introduced near the linker C-terminus. The k(cat) and K(m) for hydrolysis of maltooligodextrins and soluble starch, and the rate of hydrolysis of barley starch granules were essentially the same for the variants as for wild-type GA1. beta-Cyclodextrin, acarbose, and two heterobidentate inhibitors were found by isothermal titration calorimetry to bind to the catalytic and starch binding domains of the linker variants, indicating that the function of the active site and the starch binding site was maintained. The stability of GA1 linker variants toward GdnHCl and heat, however, was reduced compared to wild-type.

The Effect of Computer Usage in Internet Café on Cigarette Smoking and Alcohol Use among Chinese Adolescents and Youth: A Longitudinal Study

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Jorge Delva

2012-02-01

Full Text Available We used longitudinal data to investigate the relationship between computer use in internet cafés and smoking/drinking behavior among Chinese adolescents and young adults. Data are from two waves of the China Health and Nutrition Survey (2004 and 2006. Fixed effects models were used to examine if changes in internet café use were associated with changes in cigarette smoking and drinking of alcohol. Male café users spent on average 17.3 hours in front of the computer/week. This was associated with an increase in the probability of being a current smoker by 13.3% and with smoking 1.7 more cigarettes. Female café users spent on average 11 hours on the computer/week. This was associated with an increase in the probability of drinking wine and/or liquor by 14.74% and was not associated with smoking. Internet cafés are an important venue by which adolescent and young adults in China are exposed to smoking and drinking. Multi-component interventions are needed ranging from policies regulating cigarette and alcohol availability in these venues to anti-tobacco campaigns aimed at the general population but also at individuals who frequent these establishments.

U1 small nuclear RNA variants differentially form ribonucleoprotein particles in vitro.

Science.gov (United States)

Somarelli, Jason A; Mesa, Annia; Rodriguez, Carol E; Sharma, Shalini; Herrera, Rene J

2014-04-25

The U1 small nuclear (sn)RNA participates in splicing of pre-mRNAs by recognizing and binding to 5' splice sites at exon/intron boundaries. U1 snRNAs associate with 5' splice sites in the form of ribonucleoprotein particles (snRNPs) that are comprised of the U1 snRNA and 10 core components, including U1A, U1-70K, U1C and the 'Smith antigen', or Sm, heptamer. The U1 snRNA is highly conserved across a wide range of taxa; however, a number of reports have identified the presence of expressed U1-like snRNAs in multiple species, including humans. While numerous U1-like molecules have been shown to be expressed, it is unclear whether these variant snRNAs have the capacity to form snRNPs and participate in splicing. The purpose of the present study was to further characterize biochemically the ability of previously identified human U1-like variants to form snRNPs and bind to U1 snRNP proteins. A bioinformatics analysis provided support for the existence of multiple expressed variants. In vitro gel shift assays, competition assays, and immunoprecipitations (IPs) revealed that the variants formed high molecular weight assemblies to varying degrees and associated with core U1 snRNP proteins to a lesser extent than the canonical U1 snRNA. Together, these data suggest that the human U1 snRNA variants analyzed here are unable to efficiently bind U1 snRNP proteins. The current work provides additional biochemical insights into the ability of the variants to assemble into snRNPs. Copyright © 2014 Elsevier B.V. All rights reserved.

Hb variants in Korea: effect on HbA1c using five routine methods.

Science.gov (United States)

Yun, Yeo-Min; Ji, Misuk; Ko, Dae-Hyun; Chun, Sail; Kwon, Gye Cheol; Lee, Kyunghoon; Song, Sang Hoon; Seong, Moon Woo; Park, Sung Sup; Song, Junghan

2017-07-26

Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were "acceptable", within the criteria of ±7% compared to IFCC RMP target values. However, percentage of "unacceptable" results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

Consumo de café y colesterol sérico

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Montero Rodríguez, M. G.

1999-04-01

Full Text Available Different topics related to the kind and variety of coffee with commercial value, specially of the chemical composition of the green and toasted grain and particularly of the composition of the lipid fraction, are firstly revised. Secondly, the possible relationship between coffee consumption and some risk factors of cardiovascular diseases are also analysed, searching for the effect of different kinds of coffee, ways of preparation and the presence of the cafestol and kahweol diterpens on the level of serum lipids and lipoproteins on consumers. Among other conclusions, the loss of the hypercholesterolemic effect when the boiled preparations are filtered is noted.

Se revisan en primer lugar aspectos sobre los tipos y variedades de café de importancia comercial, con especial mención de la composición química del grano verde y del tostado; y particularmente de la fracción lipídica. En segundo lugar se analiza la posible relación del consumo de café y algunos factores de riesgo de enfermedades cardiovasculares, con especial interés en el estudio del efecto de los diferentes tipos de café, sus formas de preparación y la presencia de los diterpenos cafestol y kahweol sobre la concentración de los lípidos y lipoproteínas séricas de los consumidores. Entre otros aspectos se señala la pérdida del efecto hipercolesterolemiante de las preparaciones hervidas cuando son filtradas.

Incidência de microorganismos em sementes de café robusta durante o armazenamento

OpenAIRE

BRACCINI,ALESSANDRO DE LUCCA E; SCAPIM,CARLOS ALBERTO; BRACCINI,MARIA DO CARMO LANA; ANDRADE,CARLOS ALBERTO DE BASTOS; VIDIGAL FILHO,PEDRO SOARES

1999-01-01

Foi realizado um trabalho com o objetivo de isolar e identificar os microrganismos presentes em sementes de café robusta (Coffea canephora Pierre ex Froehner) no decorrer do armazenamento. Para tanto, sementes de café do cultivar Conillon, acondicionadas em diferentes embalagens (saco de polietileno transparente, saco de papel kraft e saco de algodão) e com graus de umidade iniciais distintos (25 e 35%) foram submetidas a cinco períodos de armazenamento (0, 3, 6, 9 e 12 meses), em condições c...

Efficient continuous-wave, broadly tunable and passive Q-switching lasers based on a Tm3+:CaF2 crystal

Science.gov (United States)

Liu, Jingjing; Zhang, Cheng; Zu, Yuqian; Fan, Xiuwei; Liu, Jie; Guo, Xinsheng; Qian, Xiaobo; Su, Liangbi

2018-04-01

Laser operations in the continuous-wave as well as in the pulsed regime of a 4 at.% Tm3+:CaF2 crystal are reported. For the continuous-wave operation, a maximum average output power of 1.15 W was achieved, and the corresponding slope efficiency was more than 64%. A continuous tuning range of about 160 nm from 1877-2036 nm was achieved using a birefringent filter. Using Argentum nanorods as a saturable absorber, the significant pulsed operation of a passively Q-switched Tm3+:CaF2 laser was observed at 1935.4 nm for the first time, to the best of our knowledge. A maximum output power of 385 mW with 41.4 µJ pulse energy was obtained under an absorbed pump power of 2.04 W. The present results indicate that the Tm3+:CaF2 lasers could be promising laser sources to operate in the eye-safe spectral region.

Controle massal da broca-do-café com armadilhas de garrafa Pet vermelha em cafeeiro

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Flávio Lemes Fernandes

2014-08-01

Full Text Available O objetivo deste trabalho foi avaliar a eficácia de armadilha de garrafa Pet vermelha contendo compostos voláteis alcoólicos atrativos, no controle massal da broca-do-café (Hypothenemus hampei. As avaliações foram realizadas em quatro lavouras de café, durante dois anos. Foram distribuídas 900 armadilhas de garrafa Pet, pintadas de vermelho, em três das quatro lavouras; uma lavoura sem armadilhas foi usada como controle. O broqueamento dos frutos (% foi determinado nessas lavouras. Houve redução do broqueamento de frutos nas lavouras com armadilhas, da safra 2007/2008 para a safra 2008/2009. As maiores densidades da broca-do-café nas armadilhas foram observadas nos estádios de floração e de frutos chumbinho. A armadilha de garrafa Pet vermelha é eficaz no controle massal da população da broca-do-café, por reduzir a percentagem de frutos broqueados em 57%; entretanto, essa redução não é suficiente para manter as densidades da broca abaixo do nível de controle.

Influence of HFE variants and cellular iron on monocyte chemoattractant protein-1

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Simmons Zachary

2009-02-01

Full Text Available Abstract Background Polymorphisms in the MHC class 1-like gene known as HFE have been proposed as genetic modifiers of neurodegenerative diseases that include neuroinflammation as part of the disease process. Variants of HFE are relatively common in the general population and are most commonly associated with iron overload, but can promote subclinical cellular iron loading even in the absence of clinically identified disease. The effects of the variants as well as the resulting cellular iron dyshomeostasis potentially impact a number of disease-associated pathways. We tested the hypothesis that the two most common HFE variants, H63D and C282Y, would affect cellular secretion of cytokines and trophic factors. Methods We screened a panel of cytokines and trophic factors using a multiplexed immunoassay in human neuroblastoma SH-SY5Y cells expressing different variants of HFE. The influence of cellular iron secretion on the potent chemokine monocyte chemoattractant protein-1 (MCP-1 was assessed using ferric ammonium citrate and the iron chelator, desferroxamine. Additionally, an antioxidant, Trolox, and an anti-inflammatory, minocycline, were tested for their effects on MCP-1 secretion in the presence of HFE variants. Results Expression of the HFE variants altered the labile iron pool in SH-SY5Y cells. Of the panel of cytokines and trophic factors analyzed, only the release of MCP-1 was affected by the HFE variants. We further examined the relationship between iron and MCP-1 and found MCP-1 secretion tightly associated with intracellular iron status. A potential direct effect of HFE is considered because, despite having similar levels of intracellular iron, the association between HFE genotype and MCP-1 expression was different for the H63D and C282Y HFE variants. Moreover, HFE genotype was a factor in the effect of minocycline, a multifaceted antibiotic used in treating a number of neurologic conditions associated with inflammation, on MCP-1

Enrichment of deleterious variants of mitochondrial DNA polymerase gene (POLG1) in bipolar disorder.

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Kasahara, Takaoki; Ishiwata, Mizuho; Kakiuchi, Chihiro; Fuke, Satoshi; Iwata, Nakao; Ozaki, Norio; Kunugi, Hiroshi; Minabe, Yoshio; Nakamura, Kazuhiko; Iwata, Yasuhide; Fujii, Kumiko; Kanba, Shigenobu; Ujike, Hiroshi; Kusumi, Ichiro; Kataoka, Muneko; Matoba, Nana; Takata, Atsushi; Iwamoto, Kazuya; Yoshikawa, Takeo; Kato, Tadafumi

2017-08-01

Rare missense variants, which likely account for a substantial portion of the genetic 'dark matter' for a common complex disease, are challenging because the impacts of variants on disease development are difficult to substantiate. This study aimed to examine the impacts of amino acid substitution variants in the POLG1 found in bipolar disorder, as an example and proof of concept, in three different modalities of assessment: in silico predictions, in vitro biochemical assays, and clinical evaluation. We then tested whether deleterious variants in POLG1 contributed to the genetics of bipolar disorder. We searched for variants in the POLG1 gene in 796 Japanese patients with bipolar disorder and 767 controls and comprehensively investigated all 23 identified variants in the three modalities of assessment. POLG1 encodes mitochondrial DNA polymerase and is one of the causative genes for a Mendelian-inheritance mitochondrial disease, which is occasionally accompanied by mood disorders. The healthy control data from the Tohoku Medical Megabank Organization were also employed. Although the frequency of carriers of deleterious variants varied from one method to another, every assessment achieved the same conclusion that deleterious POLG1 variants were significantly enriched in the variants identified in patients with bipolar disorder compared to those in controls. Together with mitochondrial dysfunction in bipolar disorder, the present results suggested deleterious POLG1 variants as a credible risk for the multifactorial disease. © 2016 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Institutionalized unpredictability and café routines: The case of young people in Bosnia and Herzegovina

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Čelebičić Vanja

2017-01-01

Full Text Available When life is very unpredictable or uncertain, a routine set of practices may become a very significant element in a person’s daily life, as it may allow a sense of protection from the unknown (Ehn & Löfgren 2010 and encourage feelings of belonging (Rapport & Dawson 1998. In this article I explore how people relate to the immediate future when their presents are filled with unpredictability. More specifically, I explore the everyday practices around café routines of some young people living in Bihać, a town in northwestern Bosnia- Herzegovina (BiH. Popular discourses often link between young people's tendencies to spend time in cafés with apathy and letargy, or alternativley with bad economic conditions. However, these views, whether empathetic or critical, are neither adeqate nor very empowering. Instead, I suggest that we must view café routines within the context of what I call ‘institutionalized unpredictability’. This allows us to distance ourselves from thinking about young people’s practices through dominant paradigms of engagement and disengagement and opens up the possibility to view café routines as ‘radically unpolitical' acts (Farthing 2010. I argue that café routines are both young people’s response to ‘institutionalized unpredictability’, as well as their way to criticize and reproduce it. I further show how institutionalized unpredictability was shaping and shaped by both state and nonstate related practices, relationships, processes and aspirations, suggesting that this is precisely what made it so powerfully pervasive and debilitating.

Enfriamiento de café pergamino seco a granel utilizando aireación mecánica controlada

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Julio E. Ospina M.

1992-05-01

Full Text Available Con el fin de garantizar que el café almacenado a granel conserve su calidad durante el tiempo necesario de almacenamiento, se estudió el enfriamiento del café pergamino seco en silos experimentales de dimensiones: 0.5m x 0.5m y 2.8 m de altura, utilizando aire enfriado mecánicamente. Los rangos estudiados fueron: temperatura de 10 a 220C humedad relativa de 66 a 98%y contenido de humedad del grano de 8 a 13.57% b.h. Durante la etapa de almacenamiento se evaluó la variación de la calidad del café según los criterios de coloración de la almendra, población de microorganismos y prueba de taza; paralelamente se dejaron muestras almacenadas en sacosa las condiciones de Chinchiná, como muestra testigo buscando determinar la bondad del almacenamiento a granel, también se dejó un silo sin aireación para determinar el efecto de la aireación controlada en la calidad del café.

Immunologic basis of resistance to rl male 1 induced by immunoselected thy-1.2 negative variants

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Buxbaum, J.N.; Basch, R.S.

1980-01-01

Variant cell lines that have lost the Thy-1 antigen have a reduced capacity to induce tumors in syngeneic recipients when compared to Thy-1 positive clones. The negative variants are cloned, cultured cells obtained from the Thy-1.2(theta) positive BALB/c lymphoma RL male 1 in a single-step immunoselection procedure. The reduction appears to be related to an alteration in the host response to the tumor, since both the variant and parental cells induce tumors equally well in irradiated mice. Males are much more susceptible to the inoculated tumor cells, suggesting that the relevant response is restricted to females. A majority of female animals that survive challenge with the variant do not allow growth of the parental tumor when they are injected with a quantity of cells that is uniformly fatal in untreated recipients. Most of the surviving females have an antibody in their sera that is cytotoxic for the variant, its parent, and normal thymocytes. None of the few surviving males had significant titers of the antibody. Cell-mediated immunity directed toward the positive and negative tumor cells was demonstrable in half the surviving animals of both sexes

Lack of Association between SLC30A8 Variants and Type 2 Diabetes in Mexican American Families

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Hemant Kulkarni

2016-01-01

Full Text Available SLC30A8 encodes zinc transporter 8 which is involved in packaging and release of insulin. Evidence for the association of SLC30A8 variants with type 2 diabetes (T2D is inconclusive. We interrogated single nucleotide polymorphisms (SNPs around SLC30A8 for association with T2D in high-risk, pedigreed individuals from extended Mexican American families. This study of 118 SNPs within 50 kb of the SLC30A8 locus tested the association with eight T2D-related traits at four levels: (i each SNP using measured genotype approach (MGA; (ii interaction of SNPs with age and sex; (iii combinations of SNPs using Bayesian Quantitative Trait Nucleotide (BQTN analyses; and (iv entire gene locus using the gene burden test. Only one SNP (rs7817754 was significantly associated with incident T2D but a summary statistic based on all T2D-related traits identified 11 novel SNPs. Three SNPs and one SNP were weakly but interactively associated with age and sex, respectively. BQTN analyses could not demonstrate any informative combination of SNPs over MGA. Lastly, gene burden test results showed that at best the SLC30A8 locus could account for only 1-2% of the variability in T2D-related traits. Our results indicate a lack of association of the SLC30A8 SNPs with T2D in Mexican American families.

Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.

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Zhou, Yebin; Wu, Jianming; Kucik, Dennis F; White, Nathan B; Redden, David T; Szalai, Alexander J; Bullard, Daniel C; Edberg, Jeffrey C

2013-11-01

Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1. Neutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Mac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE

Carcinoma-risk variant of EBNA1 deregulates Epstein-Barr Virus episomal latency.

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Dheekollu, Jayaraju; Malecka, Kimberly; Wiedmer, Andreas; Delecluse, Henri-Jacques; Chiang, Alan K S; Altieri, Dario C; Messick, Troy E; Lieberman, Paul M

2017-01-31

Epstein-Barr Virus (EBV) latent infection is a causative co-factor for endemic Nasopharyngeal Carcinoma (NPC). NPC-associated variants have been identified in EBV-encoded nuclear antigen EBNA1. Here, we solve the X-ray crystal structure of an NPC-derived EBNA1 DNA binding domain (DBD) and show that variant amino acids are found on the surface away from the DNA binding interface. We show that NPC-derived EBNA1 is compromised for DNA replication and episome maintenance functions. Recombinant virus containing the NPC EBNA1 DBD are impaired in their ability to immortalize primary B-lymphocytes and suppress lytic transcription during early stages of B-cell infection. We identify Survivin as a host protein deficiently bound by the NPC variant of EBNA1 and show that Survivin depletion compromises EBV episome maintenance in multiple cell types. We propose that endemic variants of EBNA1 play a significant role in EBV-driven carcinogenesis by altering key regulatory interactions that destabilize latent infection.

BACH1 Ser919Pro variant and breast cancer risk

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Eerola Hannaleena

2006-01-01

Full Text Available Abstract Background BACH1 (BRCA1-associated C-terminal helicase 1; also known as BRCA1-interacting protein 1, BRIP1 is a helicase protein that interacts in vivo with BRCA1, the protein product of one of the major genes for hereditary predisposition to breast cancer. Previously, two BACH1 germ line missense mutations have been identified in early-onset breast cancer patients with and without family history of breast and ovarian cancer. In this study, we aimed to evaluate whether there are BACH1 genetic variants that contribute to breast cancer risk in Finland. Methods The BACH1 gene was screened for germ line alterations among probands from 43 Finnish BRCA1/2 negative breast cancer families. Recently, one of the observed common variants, Ser-allele of the Ser919Pro polymorphism, was suggested to associate with an increased breast cancer risk, and was here evaluated in an independent, large series of 888 unselected breast cancer patients and in 736 healthy controls. Results Six BACH1 germ line alterations were observed in the mutation analysis, but none of these were found to associate with the cancer phenotype. The Val193Ile variant that was seen in only one family was further screened in an independent series of 346 familial breast cancer cases and 183 healthy controls, but no additional carriers were observed. Individuals with the BACH1 Ser919-allele were not found to have an increased breast cancer risk when the Pro/Ser heterozygotes (OR 0.90; 95% CI 0.70–1.16; p = 0.427 or Ser/Ser homozygotes (OR 1.02; 95% CI 0.76–1.35; p = 0.91 were compared to Pro/Pro homozygotes, and there was no association of the variant with any breast tumor characteristics, age at cancer diagnosis, family history of cancer, or survival. Conclusion Our results suggest that the BACH1 Ser919 is not a breast cancer predisposition allele in the Finnish study population. Together with previous studies, our results also indicate that although some rare germ line variants

BACH1 Ser919Pro variant and breast cancer risk

International Nuclear Information System (INIS)

Vahteristo, Pia; Yliannala, Kristiina; Tamminen, Anitta; Eerola, Hannaleena; Blomqvist, Carl; Nevanlinna, Heli

2006-01-01

BACH1 (BRCA1-associated C-terminal helicase 1; also known as BRCA1-interacting protein 1, BRIP1) is a helicase protein that interacts in vivo with BRCA1, the protein product of one of the major genes for hereditary predisposition to breast cancer. Previously, two BACH1 germ line missense mutations have been identified in early-onset breast cancer patients with and without family history of breast and ovarian cancer. In this study, we aimed to evaluate whether there are BACH1 genetic variants that contribute to breast cancer risk in Finland. The BACH1 gene was screened for germ line alterations among probands from 43 Finnish BRCA1/2 negative breast cancer families. Recently, one of the observed common variants, Ser-allele of the Ser919Pro polymorphism, was suggested to associate with an increased breast cancer risk, and was here evaluated in an independent, large series of 888 unselected breast cancer patients and in 736 healthy controls. Six BACH1 germ line alterations were observed in the mutation analysis, but none of these were found to associate with the cancer phenotype. The Val193Ile variant that was seen in only one family was further screened in an independent series of 346 familial breast cancer cases and 183 healthy controls, but no additional carriers were observed. Individuals with the BACH1 Ser919-allele were not found to have an increased breast cancer risk when the Pro/Ser heterozygotes (OR 0.90; 95% CI 0.70–1.16; p = 0.427) or Ser/Ser homozygotes (OR 1.02; 95% CI 0.76–1.35; p = 0.91) were compared to Pro/Pro homozygotes, and there was no association of the variant with any breast tumor characteristics, age at cancer diagnosis, family history of cancer, or survival. Our results suggest that the BACH1 Ser919 is not a breast cancer predisposition allele in the Finnish study population. Together with previous studies, our results also indicate that although some rare germ line variants in BACH1 may contribute to breast cancer development, the

Effects of common hemoglobin variants on HbA1c measurements in China: results for α- and β-globin variants measured by six methods.

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Xu, Anping; Chen, Weidong; Xia, Yong; Zhou, Yu; Ji, Ling

2018-04-07

HbA1c is a widely used biomarker for diabetes mellitus management. Here, we evaluated the accuracy of six methods for determining HbA1c values in Chinese patients with common α- and β-globin chains variants in China. Blood samples from normal subjects and individuals exhibiting hemoglobin variants were analyzed for HbA1c, using Sebia Capillarys 2 Flex Piercing (C2FP), Bio-Rad Variant II Turbo 2.0, Tosoh HLC-723 G8 (ver. 5.24), Arkray ADAMS A1c HA-8180V fast mode, Cobas c501 and Trinity Ultra2 systems. DNA sequencing revealed five common β-globin chain variants and three common α-globin chain variants. The most common variant was Hb E, followed by Hb New York, Hb J-Bangkok, Hb G-Coushatta, Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2 and Hb G-Taipei. Variant II Turbo 2.0, Ultra2 and Cobas c501 showed good agreement with C2FP for most samples with variants. HLC-723 G8 yielded no HbA1c values for Hb J-Bangkok, Hb Q-Thailand and Hb G-Honolulu. Samples with Hb E, Hb G-Coushatta, Hb G-Taipei and Hb Ube-2 produced significant negative biases for HLC-723 G8. HA-8180V showed statistically significant differences for Hb E, Hb G-Coushatta, Hb G-Taipei, Hb Q-Thailand and Hb G-Honolulu. HA-8180V yielded no HbA1c values for Hb J-Bangkok. All methods showed good agreement for samples with Hb New York. Some common hemoglobin variants can interfere with HbA1c determination by the most popular methods in China.

Gated SPECT evaluation of myocardial perfusion defects and left ventricular function in chronic atrial fibrillation (CAF) patients - a prevalence study between a General Hospital (GH) and a referral Cardiology Hospital (CH)

International Nuclear Information System (INIS)

Rocha, G.; Guimaraes, M.; Marroni, B.; Zagoury, E.; Sprinz, C.; Andrea, S.; Louzada, A.; Ludwig, R.; Graef, C.

2002-01-01

Aims: to evaluate myocardial perfusion defects (MPD) prevalence and left ventricular function in CAF patients from a distinct referral basis (a GH and CH populations). Materials and Methods: a retrospective cross-sectional survey including 171 CAF (43 from GH and 128 from CH) and 5415 control patients (2222 from GH and 3193 from CH) submitted to rest/stress myocardial perfusion gated SPECT with Tc99m-MIBI. The following items were collected from CAF patients: the percentage of patients with MPD, the type (fixed, reversible or mixed) and number of segments with MPD and left ventricular ejection fraction (LVEF). The control patients percentage of MPD, their type and number were also collected. Results: CAF from GH and CH were not significantly different in the number of patients with MPD, mean number of segments affected, and LVEF. In GH patients, the CAF group had more segments with MPD (2,4x1,6 p<0,01) and lower LVEF (37%x52% p<0,01) than control group. CAF patients from CH also showed lower LVEF (40%x58% p<0,01) and more fixed MPD (40%x18% p<0,01) than their control group population. Conclusion: our data showed similar prevalence of MPD and reduced LVEF values between CAF patients from a GH and referral CH. The CAF group from CH seemed to have more fixed MPD perhaps reflecting more severe coronary artery disease population or referral bias. The data appears to support the evaluation of myocardial ischemia as a part of CAF possible etiologies. Caution is advised in LVEF evaluation of CAF patients due to increased variability of R-R interval

Incidência de microorganismos em sementes de café robusta durante o armazenamento

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BRACCINI ALESSANDRO DE LUCCA E

1999-01-01

Full Text Available Foi realizado um trabalho com o objetivo de isolar e identificar os microrganismos presentes em sementes de café robusta (Coffea canephora Pierre ex Froehner no decorrer do armazenamento. Para tanto, sementes de café do cultivar Conillon, acondicionadas em diferentes embalagens (saco de polietileno transparente, saco de papel kraft e saco de algodão e com graus de umidade iniciais distintos (25 e 35% foram submetidas a cinco períodos de armazenamento (0, 3, 6, 9 e 12 meses, em condições controladas. Após cada um desses períodos, as sementes foram avaliadas, em laboratório, quanto à sanidade (método do papel-filtro, germinação e grau de umidade. Foram isolados e identificados cinco gêneros dife-rentes de fungos infestando as sementes de café robusta, a saber: Fusarium semitectum, Colletotrichum spp., Alternaria spp., Aspergillus spp. e Penicillium spp. Observou-se predominância de Fusarium semitectum e de Alternaria spp., no início do armazenamento das sementes, com incidência variando de 63-73% e 7-11% respectivamente. No decorrer do armazenamento, houve grande elevação na incidência dos fungos de armazenamento dos gêneros Aspergillus spp. e Penicillium spp. nas sementes acondicionadas em diferentes embalagens. A incidência dos microrganismos mostrou grande variação, em função do tipo de embalagem utilizado durante o armazenamento. O aumento na incidência dos microrganismos esteve associado com a redução na germinação das sementes de café. O fungo Fusarium semitectum manteve-se em níveis elevados até por 12 meses nas sementes acondicionadas em embalagens de papel kraft e algodão. A embalagem de polietileno, associada ao grau de umidade inicial mais elevado, foi mais favorável na conservação das sementes de café robusta.

Genomic constitution of an H-2:Tla variant leukemia.

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Shen, F W; Chaganti, R S; Doucette, L A; Litman, G W; Steinmetz, M; Hood, L; Boyse, E A

1984-10-01

A TL+ leukemia of a (B6 X A)F1 hybrid mouse (H-2b/H-2a) was previously subjected to immunoselection against H-2a by passage in (B6 X A.SW)F1 mice (H-2b/H-2s). A variant leukemia line was obtained that serologically lacked not only the H-2a phenotype but also the TL phenotype determined by the linked cis Tlaa allele of strain A. The H-2b phenotype and the TL phenotype of the Tlab allele of the B6 strain, which is expressed only by leukemia cells, were retained by the variant. Southern blotting with an H-2 cDNA probe that identifies restriction fragment polymorphisms distinguishing alleles of the H-2 and Tla regions of the B6 and A strains indicates that both the H-2a and Tlaa alleles are missing from the genome of this H-2a:Tlaa negative variant. Since the variant has two apparently unaltered chromosomes 17, where the H-2:Tla complex is situated, and since the intensity of bands in Southern blotting is suggestive of H-2b homozygosity, it is considered that loss of the H-2a:Tlaa haplotype by the variant was accompanied by duplication of the H-2b:Tlab haplotype. The implied change from heterozygosity to homozygosity that the variant has undergone with respect to H-2:Tla was not paralleled by a similar change at the three other loci tested, since the variant retained heterozygosity for Pep-3 (chromosome 1), Gpi-1 (chromosome 7), and Es-1 (chromosome 8).

New limits on 2β processes in 40Ca and 46Ca by using low radioactive CaF2(Eu) crystal scintillators

International Nuclear Information System (INIS)

Belli, P.; Bernabei, R.; Dai, C.J.

2001-01-01

The development of highly radiopure CaF 2 (Eu) crystal scintillators has been performed aiming at a substantial sensitivity enhancement of the 2β decay investigation and of the search for dark matter particles with spin-dependent (SD) interaction. The results of CaF 2 (Eu) background measurements and simulation are presented. New and highly improved T 1/2 limits on the 2β decay of 46 Ca and the double electron capture of 40 Ca are obtained

Characterization of the Ala62Pro polymorphic variant of human cytochrome P450 1A1 using recombinant protein expression

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Lee, Seung Heon; Kang, Sukmo [College of Veterinary Medicine, BK21plus Program for Creative Veterinary Science Research, and Research Institute for Veterinary Science, Seoul National University, Seoul (Korea, Republic of); Dong, Mi Sook [School of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Park, Jung-Duck [College of Medicine, Chung-Ang University, Seoul (Korea, Republic of); Park, Jinseo; Rhee, Sangkee [College of Agriculture of Life Science, Seoul National University, Seoul (Korea, Republic of); Ryu, Doug-Young, E-mail: dyryu@snu.ac.kr [College of Veterinary Medicine, BK21plus Program for Creative Veterinary Science Research, and Research Institute for Veterinary Science, Seoul National University, Seoul (Korea, Republic of)

2015-06-15

Cytochrome P450 (CYP) 1A1 is a heme-containing enzyme involved in detoxification of hydrophobic pollutants. Its Ala62Pro variant has been identified previously. Ala62 is located in α-helix A of CYP1A1. Residues such as Pro and Gly are α-helix breakers. In this study, the Ala62Pro variant was characterized using heterologous expression. E. coli expressing the Ala62Pro variant, and the purified variant protein, had lower CYP (i.e. holoenzyme) contents than their wild-type (WT) equivalents. The CYP variant from E. coli and mammalian cells exhibited lower 7-ethoxyresorufin O-dealkylation (EROD) and benzo[a]pyrene hydroxylation activities than the WT. Enhanced supplementation of a heme precursor during E. coli culture did not increase CYP content in E. coli expressing the variant, but did for the WT. As for Ala62Pro, E. coli expressing an Ala62Gly variant had a lower CYP content than the WT counterpart, but substitution of Ala62 with α-helix-compatible residues such as Ser and Val partially recovered the level of CYP produced. Microsomes from mammalian cells expressing Ala62Pro and Ala62Gly variants exhibited lower EROD activities than those expressing the WT or Ala62Val variant. A region harboring α-helix A has interactions with another region containing heme-interacting residues. Site-directed mutagenesis analyses suggest the importance of interactions between the two regions on holoenzyme expression. Together, these findings suggest that the Ala62Pro substitution leads to changes in protein characteristics and function of CYP1A1 via structural disturbance of the region where the residue is located. - Highlights: • Ala62 is located in α-helix A of the carcinogen-metabolizing enzyme CYP1A1. • Pro acts as an α-helix breaker. • A variant protein of CYP1A1, Ala62Pro, had lower heme content than the wild-type. • The variant of CYP1A1 had lower enzyme activities than the wild-type.

Femtosecond Cr:LiSAF and Cr:LiCAF lasers pumped by tapered diode lasers.

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Demirbas, Umit; Schmalz, Michael; Sumpf, Bernd; Erbert, Götz; Petrich, Gale S; Kolodziejski, Leslie A; Fujimoto, James G; Kärtner, Franz X; Leitenstorfer, Alfred

2011-10-10

We report compact, low-cost and efficient Cr:Colquiriite lasers that are pumped by high brightness tapered laser diodes. The tapered laser diodes provided 1 to 1.2 W of output power around 675 nm, at an electrical-to-optical conversion efficiency of about 30%. Using a single tapered diode laser as the pump source, we have demonstrated output powers of 500 mW and 410 mW together with slope efficiencies of 47% and 41% from continuous wave (cw) Cr:LiSAF and Cr:LiCAF lasers, respectively. In cw mode-locked operation, sub-100-fs pulse trains with average power between 200 mW and 250 mW were obtained at repetition rates around 100 MHz. Upon pumping the Cr:Colquiriite lasers with two tapered laser diodes (one from each side of the crystal), we have observed scaling of cw powers to 850 mW in Cr:LiSAF and to 650 mW in Cr:LiCAF. From the double side pumped Cr:LiCAF laser, we have also obtained ~220 fs long pulses with 5.4 nJ of pulse energy at 77 MHz repetition rate. These are the highest energy levels reported from Cr:Colquiriite so far at these repetition rates. Our findings indicate that tapered diodes in the red spectral region are likely to become the standard pump source for Cr:Colquiriite lasers in the near future. Moreover, the simplified pumping scheme might facilitate efficient commercialization of Cr:Colquiriite systems, bearing the potential to significantly boost applications of cw and femtosecond lasers in this spectral region (750-1000 nm).

Characterization of a cancer cell line that expresses a splicing variant form of 53BP1: Separation of checkpoint and repair functions in 53BP1

International Nuclear Information System (INIS)

Iwabuchi, Kuniyoshi; Matsui, Tadashi; Hashimoto, Mitsumasa; Matsumoto, Yoshihisa; Kurihara, Takayuki; Date, Takayasu

2008-01-01

53BP1 plays important roles in checkpoint signaling and repair for DNA double-strand breaks. We found that a colon cancer cell line, SW48, expressed a splicing variant form of 53BP1, which lacks the residues corresponding to exons 10 and 11. Activation of ATM and phosphorylation of ATM and ATR targets occurred in SW48 cells in response to X-irradiation, and these X-ray-induced responses were not enhanced by expression of full-length 53BP1 in SW48 cells, indicating that this splicing variant fully activates the major checkpoint signaling in SW48 cells. In contrast, the expression of full-length 53BP1 in SW48 cells promoted the repair of X-ray-induced DNA damage, evidenced by faster disappearance of X-ray-induced γ-H2AX foci, a marker for DNA damage, and less residual chromosomal aberrations after X-irradiation. We conclude that the two major roles of 53BP1, the checkpoint signaling and repair for DNA damage, can be functionally separated

Defect-induced wetting on BaF 2(111) and CaF 2(111) at ambient conditions

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Cardellach, M.; Verdaguer, A.; Fraxedas, J.

2011-12-01

The interaction of water with freshly cleaved (111) surfaces of isostructural BaF2 and CaF2 single crystals at ambient conditions (room temperature and under controlled humidity) has been studied using scanning force microscopy in different operation modes and optical microscopy. Such surfaces exhibit contrasting behaviors for both materials: while on BaF2(111) two-dimensional water layers are formed after accumulation at step edges, CaF2(111) does not promote the formation of such layers. We attribute such opposed behavior to lattice match (mismatch) between hexagonal water ice and the hexagonal (111) surfaces of BaF2(CaF2). Optical microscope images reveal that this behavior also determines the way the surfaces become wetted at a macroscopic level.

Calcium flouride (CaF2) from oyster shell as a raw material for thermoluminescence dosimeter

International Nuclear Information System (INIS)

Coloma, Lyra C.; Fanuga, Lyn N.; Ocreto, Cherries Ann; Rodriguez, Richita

2006-03-01

This study aims to develop a thermoluminescence dosimeter raw material made of calcium fluoride from locally available seashells that is suitable for personal radiation monitoring. Oyster shells were collected and grounded as powder samples and analyzed for calcium fluoride (CaF 2 ) content using XRF and XRD testing. Samples include pure CaF 2 , pure oyster shell, and oyster shells treated with acid. Based from the XRF results, natural oyster shell (w/ and w/o HNO 3 ) had high percentage of calcium about 49.64% and 47.45%, next to the pure calcium fluoride of 51.08%. X-ray diffractrogram shows that oyster sample had the nearest desired structure of CaF 2 compared with two seashells relative to the pure CaF 2 as standard materials. Results show that all of the natural oyster samples displayed TL emission glow curves at the temperature range 200-300 o C. It was also found that pure oyster sample has better TL response as compared to the treated ones. The researchers concluded that the calcium fluoride from oyster shells (without acid and heated) is a potentially good low-cost TLD raw material and may be used as an alternative for the much more expensive LiF dosimeters. (Authors)

Fast neutron responses of CaF2:Tm Teflon TLD discs of different thicknesses

International Nuclear Information System (INIS)

Pradhan, A.S.; Hoffmann, W.

1986-01-01

The fact that in CaF 2 :Tm (TLD-300) the ratio of the heights of thermoluminescence (TL) glow peaks at 240 0 C and 150 0 C is greater for irradiations by high LET radiations than by gamma rays has been found useful for the simultaneous and separate measurement of fast neutron and gamma ray absorbed doses. A recent study has indicated that the mixed field dosimetric characteristics of CaF 2 :Tm could be significantly improved by using thin TLDs. In the present study, CaF 2 :Tm Teflon TLD discs of thickness as low as 0.05 mm were evaluated. The thin discs could be read out by using normal planchette heating if a 400 0 C heat treatment is given to the discs prior to irradiation and TL readout. Influence of encapsulation of thin dosemeters was studied and their utility in situations such as interface dosimetry is discussed. (author)

Genetic variants of FOXP1 and FOXF1 are associated with the ...

Indian Academy of Sciences (India)

JIE ZHANG

2018-03-01

Mar 1, 2018 ... This study aimed to investigate whether the genetic variants of CRTC1, BARX1, FOXP1 and ... The student's t-test was used to compare FOXP1 expression in the tumour and the adjacent normal tissues. .... Quantitative PCR was carried out ..... Expression (GTEx) pilot analysis: multitissue gene regulation.

DND/CAF energy horizons from historical data to the potential exploitation of emerging technologies

Energy Technology Data Exchange (ETDEWEB)

Labbe, P., E-mail: Paul.Labbe@drdc-rddc.gc.ca [Defence Research and Development Canada (DRDC), Ottawa, ON (Canada)

2015-07-01

This paper reviews the energy portfolio of Department of National Defence (DND) and of the Canadian Armed Forces (CAF) from different perspectives based on recent data analyses of the energy used over several years. Then it shows a projection of the potential impacts on current and future DND/CAF capabilities of selected emerging technologies (nuclear and non-nuclear). When possible, it estimates the potential life-cycle cost savings from the hypothetical adoption of such technologies that minimize operational cost and waste management burden. (author)

DND/CAF energy horizons from historical data to the potential exploitation of emerging technologies

Energy Technology Data Exchange (ETDEWEB)

Labbe, P. [Defence Research and Development Canada (DRDC), Ottawa, Ontario (Canada)

2016-03-15

This paper reviews the energy portfolio of Department of National Defence (DND) and of the Canadian Armed Forces (CAF) from different perspectives based on recent data analyses of the energy used over several years. Then it shows a projection of the potential impacts on current and future DND/CAF capabilities of selected emerging technologies (nuclear and non-nuclear). When possible, it estimates the potential life-cycle cost savings from the hypothetical adoption of such technologies that minimize operational cost and waste management burden. (author)

Impacto aromático dos componentes voláteis do café soluvél : uma abordagem analítica e sensorial

OpenAIRE

Denisley Gentil Bassoli

2006-01-01

A aplicação de métodos instrumentais e analíticos cada vez mais sofisticados tem aprimorado a avaliação objetiva do aroma, característica determinante da qualidade de alimentos e de sua aceitabilidade, tendo sido detectados mais de oitocentos componentes voláteis no café torrado, mas com escassa informação disponível para café solúvel. Atualmente, a produção mundial de café solúvel é de aproximadamente quinhentas mil toneladas, sendo o Brasil um importante produtor. O café solúvel é obtido a ...

Factores que influyen en la dispersión espacio-temporal de broca del café #Hypothenemus hampei# (Coleoptera: Curculionidae)

OpenAIRE

Roman Ruiz, Ariana Karina

2017-01-01

La broca del café, Hypothenemus hampei (Ferrari), es la plaga más importante del café, Coffea spp., en el mundo. Este insecto ha sido motivo de numerosos estudios, sin embargo, muchos aspectos de su dispersión se desconocen o requieren ser determinados. La presente investigación tuvo el objetivo de estudiar los factores que influyen en la dispersión espacio-temporal de la broca del café. Dado que la dispersión es un proceso complejo, para ser estudiada se desarrollaron técnicas para la obtenc...

Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.

Science.gov (United States)

de Boer, Ynto S; van Gerven, Nicole M F; Zwiers, Antonie; Verwer, Bart J; van Hoek, Bart; van Erpecum, Karel J; Beuers, Ulrich; van Buuren, Henk R; Drenth, Joost P H; den Ouden, Jannie W; Verdonk, Robert C; Koek, Ger H; Brouwer, Johannes T; Guichelaar, Maureen M J; Vrolijk, Jan M; Kraal, Georg; Mulder, Chris J J; van Nieuwkerk, Carin M J; Fischer, Janett; Berg, Thomas; Stickel, Felix; Sarrazin, Christoph; Schramm, Christoph; Lohse, Ansgar W; Weiler-Normann, Christina; Lerch, Markus M; Nauck, Matthias; Völzke, Henry; Homuth, Georg; Bloemena, Elisabeth; Verspaget, Hein W; Kumar, Vinod; Zhernakova, Alexandra; Wijmenga, Cisca; Franke, Lude; Bouma, Gerd

2014-08-01

Autoimmune hepatitis (AIH) is an uncommon autoimmune liver disease of unknown etiology. We used a genome-wide approach to identify genetic variants that predispose individuals to AIH. We performed a genome-wide association study of 649 adults in The Netherlands with AIH type 1 and 13,436 controls. Initial associations were further analyzed in an independent replication panel comprising 451 patients with AIH type 1 in Germany and 4103 controls. We also performed an association analysis in the discovery cohort using imputed genotypes of the major histocompatibility complex region. We associated AIH with a variant in the major histocompatibility complex region at rs2187668 (P = 1.5 × 10(-78)). Analysis of this variant in the discovery cohort identified HLA-DRB1*0301 (P = 5.3 × 10(-49)) as a primary susceptibility genotype and HLA-DRB1*0401 (P = 2.8 × 10(-18)) as a secondary susceptibility genotype. We also associated AIH with variants of SH2B3 (rs3184504, 12q24; P = 7.7 × 10(-8)) and CARD10 (rs6000782, 22q13.1; P = 3.0 × 10(-6)). In addition, strong inflation of association signal was found with single-nucleotide polymorphisms associated with other immune-mediated diseases, including primary sclerosing cholangitis and primary biliary cirrhosis, but not with single-nucleotide polymorphisms associated with other genetic traits. In a genome-wide association study, we associated AIH type 1 with variants in the major histocompatibility complex region, and identified variants of SH2B3and CARD10 as likely risk factors. These findings support a complex genetic basis for AIH pathogenesis and indicate that part of the genetic susceptibility overlaps with that for other immune-mediated liver diseases. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

Evaluation of granulated BGO, GSO:Ce, YAG:Ce, CaF2:Eu and ZnS:Ag for alpha/beta pulse shape discrimination in a flow-cell radiation detector

International Nuclear Information System (INIS)

DeVol, T.A.; Chotoo, S.B.; Fjeld, R.A.

1999-01-01

Granulated BGO, GSO:Ce, YAG:Ce, and CaF 2 :Eu; CaF 2 :Eu coated with a fluorescent polymer, and combinations of coated and uncoated CaF 2 :Eu with ZnS:Ag were evaluated for their ability to discriminate between alpha and beta particles in a flow-cell radiation detector. The evaluations were based on the analysis of pulse shape spectra. Various granulated scintillators were packed into flow cell detectors that were coils of 3.0 mm ODx1.5 mm ID fluorinated ethylene propylene Teflon[reg] tubing positioned between dual photomultiplier tubes for analysis. The best pulse shape discrimination was obtained for a combination of equal masses of uncoated CaF 2 :Eu (63-90 μm) and ZnS:Ag (10 μm), which had a 9% spillover. Additional research is needed to reduce the spillover

Constituintes voláteis de cafés "gourmet" e mole do cerrado do triângulo mineiro em função da torra

Directory of Open Access Journals (Sweden)

Nascimento Evandro Afonso do

2003-01-01

Full Text Available Neste trabalho foi estudada a variação da composição dos voláteis de dois cafés "gourmet" e de um café mole em função do grau de torrefação. Os cafés provenientes de Araguari, cerrado do Triângulo Mineiro, foram submetidos à torra americana (grãos marrons claros, média (grãos marrons e forte (grãos pretos e, em seguida, moídos e submetidos a uma destilação por arraste de vapor em contra-corrente com diclorometano. A análise de cromatografia gasosa acoplada à espectrometria de massas (CG-EM dos constituintes voláteis mostrou que piridina, pirazina e derivados, furfural e derivados são os principais constituintes voláteis dos cafés analisados. Mostrou ainda que não é possível diferenciar os três tipos de café pelos compostos dominantes (concentração acima de 1% no aroma. Foi observado também que a torra afeta sensivelmente os resultados, sendo que a torra americana, usada normalmente na prova da xícara para classificação sensorial de cafés, produz alguns voláteis de forte impacto no aroma que não aparecem na torra média nem na forte, além de apresentar concentrações dos componentes mais comuns muito diferentes daquelas observadas nas outras duas torras.

Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants.

Science.gov (United States)

Johnston, Jennifer J; van der Smagt, Jasper J; Rosenfeld, Jill A; Pagnamenta, Alistair T; Alswaid, Abdulrahman; Baker, Eva H; Blair, Edward; Borck, Guntram; Brinkmann, Julia; Craigen, William; Dung, Vu Chi; Emrick, Lisa; Everman, David B; van Gassen, Koen L; Gulsuner, Suleyman; Harr, Margaret H; Jain, Mahim; Kuechler, Alma; Leppig, Kathleen A; McDonald-McGinn, Donna M; Can, Ngoc Thi Bich; Peleg, Amir; Roeder, Elizabeth R; Rogers, R Curtis; Sagi-Dain, Lena; Sapp, Julie C; Schäffer, Alejandro A; Schanze, Denny; Stewart, Helen; Taylor, Jenny C; Verbeek, Nienke E; Walkiewicz, Magdalena A; Zackai, Elaine H; Zweier, Christiane; Zenker, Martin; Lee, Brendan; Biesecker, Leslie G

2018-02-22

PurposeTo characterize the molecular genetics of autosomal recessive Noonan syndrome.MethodsFamilies underwent phenotyping for features of Noonan syndrome in children and their parents. Two multiplex families underwent linkage analysis. Exome, genome, or multigene panel sequencing was used to identify variants. The molecular consequences of observed splice variants were evaluated by reverse-transcription polymerase chain reaction.ResultsTwelve families with a total of 23 affected children with features of Noonan syndrome were evaluated. The phenotypic range included mildly affected patients, but it was lethal in some, with cardiac disease and leukemia. All of the parents were unaffected. Linkage analysis using a recessive model supported a candidate region in chromosome 22q11, which includes LZTR1, previously shown to harbor mutations in patients with Noonan syndrome inherited in a dominant pattern. Sequencing analyses of 21 live-born patients and a stillbirth identified biallelic pathogenic variants in LZTR1, including putative loss-of-function, missense, and canonical and noncanonical splicing variants in the affected children, with heterozygous, clinically unaffected parents and heterozygous or normal genotypes in unaffected siblings.ConclusionThese clinical and genetic data confirm the existence of a form of Noonan syndrome that is inherited in an autosomal recessive pattern and identify biallelic mutations in LZTR1.Genet Med advance online publication, 22 February 2018; doi:10.1038/gim.2017.249.

Liposome-based cationic adjuvant CAF01 enhances the protection conferred by a commercial inactivated influenza vaccine in ferrets

DEFF Research Database (Denmark)

Martel, Cyril Jean-Marie; Agger, Else Marie; Jensen, Trine Hammer

Objectives: To assess the effect of CAF01 adjuvant associated to a commercial trivalent inactivated influenza vaccine in the ferret model. Methods:  Ferrets were vaccinated with a range of doses of Sanofi-Pasteur's Vaxigrip with or without the CAF01 adjuvant, and challenged with either one of two H...

Novel P-TEN-induced putative kinase 1 (PINK1) variant in Indian Parkinson's disease patient.

Science.gov (United States)

Halder, Tamali; Raj, Janak; Sharma, Vivek; Das, Parimal

2015-09-25

Loss-of-function mutation in PINK1 is known for causing autosomal recessive early onset Parkinsonism accounting approximately 6.5% of PD cases. Recently, PINK1 has also been shown to cause Parkinson's disease (PD) in eastern India. Present study is aimed to see its contribution in north-Indian PD patients. A total of 106 PD patients and 60 ethnically matched healthy controls were included in the study. All the patients were screened for mutation in PINK1 by direct DNA sequence analysis of the PCR amplicons covering all exons and exon-intron boundaries. Identified novel variant was reconfirmed by DNA sequencing of 10 randomly selected TA clones containing the variant amplicon. In vitro functional assay of the mutant protein was performed by transfecting COS-7 cell line with wild type and mutant (created by site-directed-mutagenesis) cDNA construct of PINK1 fused to N' terminal GFP followed by western blot analysis. Two potentially pathogenic, one being novel (p.Q267X) and 6 other apparently non-pathogenic variants were identified. Western blot analysis reveals production of truncated PINK1 fusion protein of ∼55kDa in p.Q267X mutant instead of 82/93kDa of wild type PINK1 fusion protein (molecular weight of GFP is ∼27kDa). Our study concludes that PINK1 variants are prevalent for causing Parkinson's disease (PD) in India, as revealed by the occurrence of 1.8% (2/106) in PD patients from north Indian population. The novel homozygous variant of PINK1 (c.799C>T) reported here is the plausible cause for disease manifestation in this patient. Future study, however, would be helpful to understand the functional mechanism how this premature PINK1 protein (p.Q267X) responds to cellular stress leading to the PD pathophysiology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Geografía, café y prosperidad en los andes occidentales de Colombia

Directory of Open Access Journals (Sweden)

Juan Barón

2011-07-01

Full Text Available Compuesta por los departamentos de Antioquia, Caldas, Quindío, Risaralda y Valle del Cauca, los Andes Occidentales ha sido por mucho años una de las regiones más prósperas de Colombia. Esta prosperidad se ha traducido en condiciones de vida e infraestructura superiores a las del resto del país. El éxito y bienestar que presentan hoy en día los Andes Occidentales están estrechamente ligados a la concentración de la producción de café, que se dio allí durante gran parte del siglo XX. El arraigo del café en la región no sólo se dio debido a que la geografía ofrecía las condiciones ideales para el cultivo, sino también a las instituciones cafeteras creadas para organizar la industria del café. A pesar de esta prosperidad, el constante descenso del precio internacional del café después del rompimiento del pacto de cuotas de producción en 1989, sumado al estancamiento de la industria manufacturera en algunos departamentos de la región, han afectado las economías departamentales menos diversificadas. Es así como la región de los Andes Occidentales Colombianos presenta las tasas de desempleo más altas del país, tasas que se han visto afectadas aún más con la crisis financiera internacional a través del menor flujo de remesas que los trabajadores oriundos de la región, y residentes en el exterior envían a sus familias.

CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants

Directory of Open Access Journals (Sweden)

Roseli da Silva

2013-01-01

Full Text Available OBJECTIVES: We investigated four components of the Wnt signaling pathway in medulloblastomas. Medulloblastoma is the most common type of malignant pediatric brain tumor, and the Wnt signaling pathway has been shown to be activated in this type of tumor. METHODS: Sixty-one medulloblastoma cases were analyzed for β-catenin gene (CTNNB1 mutations, β-catenin protein expression via immunostaining and Wnt signaling pathway-related gene expression. All data were correlated with histological subtypes and patient clinical information. RESULTS: CTNNB1 sequencing analysis revealed that 11 out of 61 medulloblastomas harbored missense mutations in residues 32, 33, 34 and 37, which are located in exon 3. These mutations alter the glycogen synthase kinase-3β phosphorylation sites, which participate in β-catenin degradation. No significant differences were observed between mutation status and histological medulloblastoma type, patient age and overall or progression-free survival times. Nuclear β-catenin accumulation, which was observed in 27.9% of the cases, was not associated with the histological type, CTNNB1 mutation status or tumor cell dissemination. The relative expression levels of genes that code for proteins involved in the Wnt signaling pathway (CTNNB1, APC, AXIN1 and WNT1 were also analyzed, but no significant correlations were found. In addition, large-cell variant medulloblastomas presented lower relative CTNNB1 expression as compared to the other tumor variants. CONCLUSIONS: A small subset of medulloblastomas carry CTNNB1 mutations with consequent nuclear accumulation of β-catenin. The Wnt signaling pathway plays a role in classic, desmoplastic and extensive nodularity medulloblastoma variants but not in large-cell medulloblastomas.

A guide for functional analysis of BRCA1 variants of uncertain significance

DEFF Research Database (Denmark)

Millot, Gaël A; Carvalho, Marcelo A; Caputo, Sandrine M

2012-01-01

of these variants, the effect on protein function is unknown making it difficult to infer the consequences on risks of breast and ovarian cancers. Thus, many individuals undergoing genetic testing for BRCA1 mutations receive test results reporting a variant of uncertain clinical significance (VUS), leading...... to issues in risk assessment, counseling, and preventive care. Here, we describe functional assays for BRCA1 to directly or indirectly assess the impact of a variant on protein conformation or function and how these results can be used to complement genetic data to classify a VUS as to its clinical...

Induction of CD8+ T-cell responses against subunit antigens by the novel cationic liposomal CAF09 adjuvant

DEFF Research Database (Denmark)

Korsholm, Karen Smith; Hansen, Jon; Karlsen, Kasper

2014-01-01

previously described CTL-inducing adjuvants, CAF05 (DDA/trehalose dibehenate (TDB)/Poly(I:C)), Aluminium/monophosphoryl lipid-A (MPL) and Montanide/CpG/IL-2. The optimal effect was obtained when the CAF09-adjuvanted vaccine was administered by the i.p. route, whereas s.c. administration primed limited CD8+ T...

KIR And HLA Haplotype Analysis in a Family Lacking The KIR 2DL1-2DP1 Genes

Directory of Open Access Journals (Sweden)

Vojvodić Svetlana

2015-06-01

Full Text Available The killer cell immunoglobulin-like receptor (KIR gene cluster exhibits extensive allelic and haplotypic diversity that is observed as presence/absence of genes, resulting in expansion and contraction of KIR haplotypes and by allelic variation of individual KIR genes. We report a case of KIR pseudogene 2DP1 and 2DL1 gene absence in members of one family with the children suffering from acute myelogenous leukemia (AML. Killer cell immunoglo-bulin-like receptor low resolution genotyping was performed by the polymerase chain reaction (PCR-sequencespecific primers (SSP/sequence-specific oligonucleotide (SSO method and haplotype assignment was done by gene content analysis. Both parents and the maternal grandfather, shared the same Cen-B2 KIR haplotype, containing KIR 3DL3, -2DS2, -2DL2 and -3DP1 genes. The second haplotype in the KIR genotype of the mother and grandfather was Tel-A1 with KIR 2DL4 (normal and deleted variant, -3DL1, -22 bp deletion variant of the 2DS4 gene and -3DL2, while the second haplotype in the KIR genotype of the father was Tel-B1 with 2DL4 (normal variant, -3DS1, -2DL5, -2DS5, -2DS1 and 3DL2 genes. Haplotype analysis in all three offsprings revealed that the children inherited the Cen-B2 haplotype with the same gene content but two of the children inherited a deleted variant of the 2DL4 gene, while the third child inherited a normal one. The second haplotype of all three offspring contained KIR 2DL4, -2DL5, -2DS1, -2DS4 (del 22bp variant, -2DS5, -3DL1 and -3DL2 genes, which was the basis of the assumption that there is a hybrid haplotype and that the present 3DL1 gene is a variant of the 3DS1 gene. Due to consanguinity among the ancestors, the results of KIR segregation analysis showed the existence of a very rare KIR genotype in the offspring. The family who is the subject of this case is even more interesting because the father was 10/10 human leukocyte antigen (HLA-matched to his daughter, all members of the family have

Variants in the interleukin-1 alpha and beta genes, and the risk for periodontal disease in dogs.

Science.gov (United States)

Albuquerque, C; Morinha, F; Magalhães, J; Requicha, J; Dias, I; Guedes-Pinto, H; Bastos, E; Viegas, C

2015-12-01

Elevated levels of interleukin-1 (IL-1) have been shown to amplify the inflammatory response against periodontopathogenic bacteria.In humans,polymorphisms in the IL1A and IL1B genes are the most well-studied genetic polymorphisms associated with periodontal disease (PD). In contrast to human, there is a lack of knowledge on the genetic basis of canine PD. A case-control study was conducted in which a molecular analysis of dog IL1A and IL1B genes was performed. Of the eight genetic variants identified, seven in IL1A gene and one in IL1B gene, IL1A/1_g.388A>C and IL1A /1_g.521T>A showed statistically significant differences between groups (adjusted OR (95% CI): 0.15 (0.03-0.76),P=0.022; 5.76 (1.03-32.1),P=0.046, respectively). It suggests that in the studied population the IL1A/1_g.388C allele is associated with a decreased PD risk, whereas the IL1A/1_g.521A allele can confer an increased risk. Additionally, the IL1A/2_g.515G>T variation resulted in a change of amino acid, i.e. glycine to valine. In silico analysis suggests that this change can alter protein structure and function, predicting it to be deleterious or damaging. This work suggests that IL1 genetic variants may be important in PD susceptibility in canines.

Evaluación de un cosechador de café por vibración circular al tallo.

Directory of Open Access Journals (Sweden)

Ramírez V Carlos Mario

2003-06-01

Full Text Available Un prototipo para aplicar vibración circular al tallo del cafeto, desarrollado en el Centro Nacional de Investigaciones de Café CENICAFÉ, fue evaluado en campo para estudiar su factibilidad técnica en la cosecha mecanizada de café. La evaluación consistió en determinar el efecto de la frecuencia, excentricidad y punto de aplicación de la vibración circular en la selectividad y el rendimiento del desprendimiento de frutos de café. El análisis estadístico indicó que el mejor tratamiento para vibrar el tallo (chupón y tocón de la zoca del café corresponde a una frecuencia de excitación de 2000 c.p.m, con una excentricidad de 2,5 cm aplicada en el chupón, lográndose desprender hasta el 45% de los frutos maduros presentes en el árbol con un porcentaje de frutos verdes desprendidos de 27%. Se encontró como en otros trabajos previos que el desprendimiento de los frutos depende del incremento de la amplitud (mayor excentricidad y de la frecuencia de vibración. La selectividad de este desprendimiento depende también del porcentaje inicial de frutos maduros presentes en los árboles.

Random Plant Viral Variants Attain Temporal Advantages During Systemic Infections and in Turn Resist other Variants of the Same Virus.

Science.gov (United States)

Zhang, Xiao-Feng; Guo, Jiangbo; Zhang, Xiuchun; Meulia, Tea; Paul, Pierce; Madden, Laurence V; Li, Dawei; Qu, Feng

2015-10-20

Infection of plants with viruses containing multiple variants frequently leads to dominance by a few random variants in the systemically infected leaves (SLs), for which a plausible explanation is lacking. We show here that SL dominance by a given viral variant is adequately explained by its fortuitous lead in systemic spread, coupled with its resistance to superinfection by other variants. We analyzed the fate of a multi-variant turnip crinkle virus (TCV) population in Arabidopsis and N. benthamiana plants. Both wild-type and RNA silencing-defective plants displayed a similar pattern of random dominance by a few variant genotypes, thus discounting a prominent role for RNA silencing. When introduced to plants sequentially as two subpopulations, a twelve-hour head-start was sufficient for the first set to dominate. Finally, SLs of TCV-infected plants became highly resistant to secondary invasions of another TCV variant. We propose that random distribution of variant foci on inoculated leaves allows different variants to lead systemic movement in different plants. The leading variants then colonize large areas of SLs, and resist the superinfection of lagging variants in the same areas. In conclusion, superinfection resistance is the primary driver of random enrichment of viral variants in systemically infected plants.

Androgen receptor and its splice variant, AR-V7, differentially regulate FOXA1 sensitive genes in LNCaP prostate cancer cells.

Science.gov (United States)

Krause, William C; Shafi, Ayesha A; Nakka, Manjula; Weigel, Nancy L

2014-09-01

Prostate cancer (PCa) is an androgen-dependent disease, and tumors that are resistant to androgen ablation therapy often remain androgen receptor (AR) dependent. Among the contributors to castration-resistant PCa are AR splice variants that lack the ligand-binding domain (LBD). Instead, they have small amounts of unique sequence derived from cryptic exons or from out of frame translation. The AR-V7 (or AR3) variant is constitutively active and is expressed under conditions consistent with CRPC. AR-V7 is reported to regulate a transcriptional program that is similar but not identical to that of AR. However, it is unknown whether these differences are due to the unique sequence in AR-V7, or simply to loss of the LBD. To examine transcriptional regulation by AR-V7, we have used lentiviruses encoding AR-V7 (amino acids 1-627 of AR with the 16 amino acids unique to the variant) to prepare a derivative of the androgen-dependent LNCaP cells with inducible expression of AR-V7. An additional cell line was generated with regulated expression of AR-NTD (amino acids 1-660 of AR); this mutant lacks the LBD but does not have the AR-V7 specific sequence. We find that AR and AR-V7 have distinct activities on target genes that are co-regulated by FOXA1. Transcripts regulated by AR-V7 were similarly regulated by AR-NTD, indicating that loss of the LBD is sufficient for the observed differences. Differential regulation of target genes correlates with preferential recruitment of AR or AR-V7 to specific cis-regulatory DNA sequences providing an explanation for some of the observed differences in target gene regulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diode-pumped femtosecond mode-locked Nd, Y-codoped CaF2 laser

International Nuclear Information System (INIS)

Zhu, Jiangfeng; Zhang, Lijuan; Gao, Ziye; Wang, Junli; Wang, Zhaohua; Wei, Zhiyi; Su, Liangbi; Zheng, Lihe; Wang, Jingya; Xu, Jun

2015-01-01

A passively mode-locked femtosecond laser based on an Nd, Y-codoped CaF 2 disordered crystal was demonstrated. The Y 3+ -codoping in Nd : CaF 2 markedly suppressed the quenching effect and improved the fluorescence quantum efficiency and emission spectra. With a fiber-coupled laser diode as the pump source, the continuous wave tuning range covering from 1042 to 1076 nm was realized, while the mode-locked operation generated 264 fs pulses with an average output power of 180 mW at a repetition rate of 85 MHz. The experimental results show that the Nd, Y-codoped CaF 2 disordered crystal has potential in a new generation diode-pumped high repetition rate chirped pulse amplifier. (letter)

A variant in CDKAL1 influences insulin response and risk of type 2 diabetes

DEFF Research Database (Denmark)

Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Reynisdottir, Inga

2007-01-01

We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified...... risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0...... was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion....

Modelagem matemática e determinação das propriedades termodinâmicas do café (Coffea arabica L. durante o processo de secagem

Directory of Open Access Journals (Sweden)

Paulo Cesar Corrêa

2010-10-01

Full Text Available A secagem de produtos agrícolas é largamente utilizada no mundo para o controle e a manutenção da qualidade dos produtos agrícolas. O objetivo do presente trabalho foi modelar o processo de secagem e obter os parâmetros termodinâmicos de frutos de café (Coffea Arabica L., cultivar Catuaí Amarelo, para três diferentes condições de temperatura e umidade relativa (35 ºC e 32,1%; 45 ºC e 15,7%; e 55 ºC e 10,2%. Foram utilizados frutos de café colhidos manualmente com teor inicial de água de 1,25 (b.s. e submetidos à secagem até atingirem o teor médio de 0,13 (b.s. Seis modelos matemáticos usualmente utilizados para a representação do processo de secagem de produtos agrícolas foram ajustados aos dados experimentais. A segunda lei de Fick foi utilizada para obter os coeficientes de difusão dos frutos de café por meio da cinética da secagem. A energia de ativação para a secagem dos frutos de café, bem como a entropia, entalpia e energia livre de Gibbs, foram obtidas. O modelo de Midili modificado foi o que melhor representou o fenômeno de secagem de frutos de café. Os valores do coeficiente de difusão obtidos foram 2,99 x 10-11, 2,39 x 10-11 e 5,98 x 10-11 m² s-1 para as temperaturas de 35, 45 e 55 ºC, respectivamente. A entalpia diminuiu com o aumento da temperatura do ar de secagem, bem como a entropia. A energia livre de Gibbs aumentou com o aumento da temperatura.

Usability Assessment of E-Café Operational Management Simulation Game

Science.gov (United States)

Chang, Chiung-sui; Huang, Ya-Ping

2013-01-01

To ensure the quality of digital simulation game, we utilized the usability evaluation heuristic in the design and development processes of e-café operational management game-based learning material for students. The application of usability evaluations during this study is described. Additionally, participant selection, data collection and…

A novel KCNQ1 nonsense variant in the isoform-specific first exon causes both jervell and Lange-Nielsen syndrome 1 and long QT syndrome 1: a case report.

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Nishimura, Motoi; Ueda, Marehiko; Ebata, Ryota; Utsuno, Emi; Ishii, Takuma; Matsushita, Kazuyuki; Ohara, Osamu; Shimojo, Naoki; Kobayashi, Yoshio; Nomura, Fumio

2017-06-08

According to previous KCNQ1 (potassium channel, voltage gated, KQT-like subfamily, member 1) gene screening studies, missense variants, but not nonsense or frame-shift variants, cause the majority of long QT syndrome (LQTS; Romano-Ward syndrome [RWS]) 1 cases. Several missense variants are reported to cause RWS by a dominant-negative mechanism, and some KCNQ1 variants can cause both Jervell and Lange-Nielsen Syndrome (JLNS; in an autosomal recessive manner) and LQTS1 (in an autosomal dominant manner), while other KCNQ1 variants cause only JLNS. The human KCNQ1 gene is known to have two transcript isoforms (kidney isoform and pancreas isoform), and both isoforms can form a functional cardiac potassium channel. Here, we report a novel nonsense KCNQ1 variant causing not only JLNS, but also significant QTc prolongation identical to RWS in an autosomal dominant manner. Our case study supports that haploinsufficiency in the KCNQ1 gene is causative of significant QTc prolongation identical to RWS. Interestingly, the nonsense variant (NM_000218.2:c.115G > T [p.Glu39X]) locates in exon 1a of KCNQ1, which is a kidney-isoform specific exon. The variant is located closer to the N-terminus than previously identified nonsense or frame-shift variants. To the best of our knowledge, this is the first report showing that a nonsense variant in exon 1a of KCNQ1, which is the kidney-isoform specific exon, causes JLNS. Our findings may be informative to the genetic pathogenesis of RWS and JLNS caused by KCNQ1 variants.

Rare A2ML1 variants confer susceptibility to otitis media

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Santos-Cortez, Regie Lyn P.; Chiong, Charlotte M.; Reyes-Quintos, Ma. Rina T.; Tantoco, Ma. Leah C.; Wang, Xin; Acharya, Anushree; Abbe, Izoduwa; Giese, Arnaud P.; Smith, Joshua D.; Allen, E. Kaitlynn; Li, Biao; Cutiongco-de la Paz, Eva Maria; Garcia, Marieflor Cristy; Llanes, Erasmo Gonzalo D.V.; Labra, Patrick John; Gloria-Cruz, Teresa Luisa I.; Chan, Abner L.; Wang, Gao T.; Daly, Kathleen A.; Shendure, Jay; Bamshad, Michael J.; Nickerson, Deborah A.; Patel, Janak A.; Riazuddin, Saima; Sale, Michele M.; Chonmaitree, Tasnee; Ahmed, Zubair M.; Abes, Generoso T.; Leal, Suzanne M.

2015-01-01

A duplication variant within middle-ear-specific gene A2ML1 co-segregates with otitis media in an indigenous Filipino pedigree (LOD score=7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by three otitis-prone European- and Hispanic-American children, but is absent in non-otitis-prone children and >62,000 next-generation sequences. Seven additional A2ML1 variants were identified in six otitis-prone children. Collectively our studies support a role for A2ML1 in the pathophysiology of otitis media. PMID:26121085

El café de Colombia Un modelo de diferenciación de producto, posicionamiento de marca y valor agregado

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Miguel Samir Kiuhan

2006-07-01

Full Text Available Nuevas alternativas de comercialización de Café de Colombia. Después de la crisis generada por la terminación del pacto cafetero mundial, Café de Colombia ha apelado a su institucionalidad, su tradición de calidad, su imagen y marca

Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome

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Quartier, Angélique; Poquet, Hélène; Gilbert-Dussardier, Brigitte; Rossi, Massimiliano; Casteleyn, Anne-Sophie; Portes, Vincent des; Feger, Claire; Nourisson, Elsa; Kuentz, Paul; Redin, Claire; Thevenon, Julien; Mosca-Boidron, Anne-Laure; Callier, Patrick; Muller, Jean; Lesca, Gaetan; Huet, Frédéric; Geoffroy, Véronique; El Chehadeh, Salima; Jung, Matthieu; Trojak, Benoit; Le Gras, Stéphanie; Lehalle, Daphné; Jost, Bernard; Maury, Stéphanie; Masurel, Alice; Edery, Patrick; Thauvin-Robinet, Christel; Gérard, Bénédicte; Mandel, Jean-Louis; Faivre, Laurence; Piton, Amélie

2017-01-01

Fragile-X syndrome (FXS) is a frequent genetic form of intellectual disability (ID). The main recurrent mutagenic mechanism causing FXS is the expansion of a CGG repeat sequence in the 5′-UTR of the FMR1 gene, therefore, routinely tested in ID patients. We report here three FMR1 intragenic pathogenic variants not affecting this sequence, identified using high-throughput sequencing (HTS): a previously reported hemizygous deletion encompassing the last exon of FMR1, too small to be detected by array-CGH and inducing decreased expression of a truncated form of FMRP protein, in three brothers with ID (family 1) and two splice variants in boys with sporadic ID: a de novo variant c.990+1G>A (family 2) and a maternally inherited c.420-8A>G variant (family 3). After clinical reevaluation, the five patients presented features consistent with FXS (mean Hagerman's scores=15). We conducted a systematic review of all rare non-synonymous variants previously reported in FMR1 in ID patients and showed that six of them are convincing pathogenic variants. This study suggests that intragenic FMR1 variants, although much less frequent than CGG expansions, are a significant mutational mechanism leading to FXS and demonstrates the interest of HTS approaches to detect them in ID patients with a negative standard work-up. PMID:28176767

Exposición laboral a hongos en una planta de procesamiento de café

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Rosa María Alonso Espadalé

2008-06-01

Full Text Available El café verde, en función del tratamiento que recibe después de la cosecha, puede llegar a las plantas de procesamiento contaminado por hongos, pudiendo producir efectos sobre la salud de los trabajadores que manipulan café, principalmente en forma de reacciones alérgicas y enfermedades respiratorias. Objetivos: El objetivo de este estudio es determinar la concentración ambiental de hongos a los que están expuestos los trabajadores en las diferentes operaciones que se realizan en una planta de procesamiento de café. Material y métodos: Las muestras ambientales se obtuvieron por el método de impactación en placa con el equipo M Air T de Millipore. Se determinó la concentración de hongos totales y se identificaron los géneros fúngicos mayoritarios. Resultados: Se ha obtenido una concentración fúngica ambiental superior a 12000 ufc/m³ durante las operaciones de descarga del café. Los géneros mayoritarios identificados han sido Aspergillus (A. flavus, A. niger y A. ochraceus, Fusarium, Moniliella, Mucor, Rhizopus, Scopulariopsis y Syncephalastrum racemosum. Conclusión: Los trabajadores de las plantas de procesamiento de café pueden estar expuestos a elevadas concentraciones ambientales de hongos durante las operaciones de descarga del café. Además, debido a la presencia de especies fúngicas toxigénicas, no se puede descartar una potencial exposición a las micotoxinas producidas por estos hongos.The green coffee, depending on the treatment that receives after the crop can reach the processing plants contaminated by fungi. This exposure may produce some effects on the workers health, causing allergic reactions and respiratory diseases. Objectives: The aim of this study was to determinate the fungi concentrations which are exposed to the workers in the different operations that are done in a coffee processing plant. Materials and methods: The environmental samples were obtained by plate impactation with the M Air T Millipore

DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder.

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Bjarte Håvik

Full Text Available Doublecortin and calmodulin like kinase 1 (DCLK1 is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders that have neuro-cognitive dysfunctions: schizophrenia (SCZ, bipolar affective disorder (BP and attention deficit/hyperactivity disorder (ADHD. We mined six genome wide association studies (GWASs that were available publically or through collaboration; three for BP, two for SCZ and one for ADHD. We also genotyped the DCLK1 region in additional samples of cases with SCZ, BP or ADHD and controls that had not been whole-genome typed. In total, 9895 subjects were analysed, including 5308 normal controls and 4,587 patients (1,125 with SCZ, 2,496 with BP and 966 with ADHD. Several DCLK1 variants were associated with disease phenotypes in the different samples. The main effect was observed for rs7989807 in intron 3, which was strongly associated with SCZ alone and even more so when cases with SCZ and ADHD were combined (P-value = 4 × 10(-5 and 4 × 10(-6, respectively. Associations were also observed with additional markers in intron 3 (combination of SCZ, ADHD and BP, intron 19 (SCZ+BP and the 3'UTR (SCZ+BP. Our results suggest that genetic variants in DCLK1 are associated with SCZ and, to a lesser extent, with ADHD and BP. Interestingly the association is strongest when SCZ and ADHD are considered together, suggesting common genetic susceptibility. Given that DCLK1 variants were previously found to be associated with cognitive traits, these results are consistent with the role of DCLK1 in neurodevelopment and synaptic plasticity.

The CXC chemokine cCAF stimulates precocious deposition of ECM molecules by wound fibroblasts, accelerating development of granulation tissue

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Li Qi-Jing

2002-06-01

Full Text Available Abstract Background During wound repair, fibroblasts orchestrate replacement of the provisional matrix formed during clotting with tenascin, cellular fibronectin and collagen III. These, in turn, are critical for migration of endothelial cells, keratinocytes and additional fibroblasts into the wound site. Fibroblasts are also important in the deposition of collagen I during scar formation. The CXC chemokine chicken Chemotactic and Angiogenic Factor (cCAF, is highly expressed by fibroblasts after wounding and during development of the granulation tissue, especially in areas where extracellular matrix (ECM is abundant. We hypothesized that cCAF stimulates fibroblasts to produce these matrix molecules. Results Here we show that this chemokine can stimulate precocious deposition of tenascin, fibronectin and collagen I, but not collagen III. Studies in culture and in vivo show that tenascin stimulation can also be achieved by the N-terminal 15 aas of the protein and occurs at the level of gene expression. In contrast, stimulation of fibronectin and collagen I both require the entire molecule and do not involve changes in gene expression. Fibronectin accumulation appears to be linked to tenascin production, and collagen I to decreased MMP-1 levels. In addition, cCAF is chemotactic for fibroblasts and accelerates their migration. Conclusions These previously unknown functions for chemokines suggest that cCAF, the chicken orthologue of human IL-8, enhances healing by rapidly chemoattracting fibroblasts into the wound site and stimulating them to produce ECM molecules, leading to precocious development of granulation tissue. This acceleration of the repair process may have important application to healing of impaired wounds.

[Homozygous ectonucleotide pyrophosphatase/phosphodiesterase 1 variants in a girl with hypophosphatemic rickets and literature review].

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Liu, Z Q; Chen, X B; Song, F Y; Gao, K; Qiu, M F; Qian, Y; Du, M

2017-11-02

Objective: To investigate the clinical features and genetic characteristics of patients with ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) gene variants. Method: The clinical data of a patient with ENPP1 homozygous variants from Capital Institute of Pediatrics was collected, the related literature was searched from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, National Center from Biotechnology Information and PubMed by using search term "ENPP1" , "hypophosphatemic rickets" . The literature retrieval was confined from 1980 to February 2017. The clinical manifestations, bone metabolism examinations, X-RAY and genotypes were reviewed. Result: Our patient was an 11 years old girl, with 7 years history of lower limb malformation. She showed significant valgus deformity of the knee (genu valgum). Metabolic examination revealed reduced level of plasma phosphate (0.86 mmol/L), a normal level of plasma calcium (2.30 mmol/L) and an elevated alkaline phosphatase level of 688 IU/L. The calcium-phosphorus product was 25.9. A homozygous nonsense variants of ENPP1 gene, c.783C>G (p.Tyr261X) in exon 7 was identified in the patient. Both parents were heterozygous carriers. Literature review identified 3 Chinese patients from one publication and 17 cases from twenty one publications around the world. None of the patients was found PHEX variants which is the most common variants among hypophosphatemic rickets patients. The disease onset age was 11 months to 10 years. Eight patients had short stature, five patients had the history of generalized arterial calcification of infancy. Four suffered from deafness, three showed localized calcifications of arteries, three patients manifested pseudoxanthoma elasticum and two suffered from ossification of posterior longitudinal ligament. Nine missense variants, six splicing variants and 4 nonsense variants were reported among these twenty patients. c.783C>G was found in two Chinese patients

Partial unilateral lentiginosis is mosaic neurofibromatosis type 1 or not?

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Yaşar, Şirin; Ersanli, Ayşegül; Göktay, Fatih; Aytekin, Sema; Cebeci, Dua; Güneş, Pembegül

2017-01-01

Partial unilateral lentiginosis (PUL) is a rare pigmentation disorder characterized by numerous lentigines with sharp margins in the midline in one or more dermatomes. Its segmental pattern suggests that this presentation accompanied by café-au-lait spots, Lisch nodule or neurofibromas has a close relationship with mosaic neurofibromatosis type 1 or segmental neurofibromatosis (NF) in particular. In a group of 16 patients with PUL, who presented at the dermatology outpatient clinic between 1998 and 2015, an examination was made of consanguineous marriage in the family history, the presence of a similar lesion or NF in first-degree relatives, neurofibroma in the physical examination, the involvement pattern, axillary/inguinal freckling and the presence and number of café-au-lait spots. The ophthalmological examination investigated Lisch nodule and optic glioma. The skeletal system was examined for NF involvement. Of 16 patients, 13 (81.2%) were female and three (18.8%) were male with a mean age of 31.19 years (range, 15-48). There was no family history of PUL in any case. Consanguineous marriage was absent in 15 patients (93.8%). While there were accompanying café-au-lait spots in three patients (18.8%). Lisch nodule was an accompanying finding in three patients (18.8%). Axillary freckling was detected in four (25%) patients. Neurofibroma was found in only one patient. Although café-au-lait spots, axillary freckling, neurofibroma and Lisch nodule were present in a small number of the patients, the presence of the findings may be considered to be specific to NF suggests that PUL is a variant of mosaic NF-1. Genetic studies will help to further elucidate this subject. © 2016 Japanese Dermatological Association.

Two novel haemoglobin variants that affect haemoglobin A1c measurement by ion-exchange chromatography

NARCIS (Netherlands)

Bots, Michael; Stroobants, An K.; Delzenne, Barend; Soeters, Maarten R.; de Vries, Johan E.; Weykamp, Cas W.; Norg, Roelf J. C.; Veldthuis, Martijn; van Zwieten, Rob

2015-01-01

Haemoglobin (Hb) variants are well-known factors interfering with accurate HbA1c testing. This report describes two novel Hb variants leading to inappropriate quantification of HbA1c by ion-exchange chromatography. Glycated forms of novel Hb variants were recognised in the blood of two patients with

Progresso genético da produtividade de café beneficiado com a seleção de clones de cafeeiro 'Conilon'

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André Rostand Ramalho

2016-09-01

Full Text Available RESUMO A espécie Coffea canephora Pierre ex Froehner possui ampla distribuição geográfica, com ocorrência em regiões tropicais de diversos continentes. Aproximadamente 30% da produção brasileira de café é proveniente do cultivo dessa espécie, sendo que o Estado de Rondónia se destaca como seu segundo maior produtor. Este trabalho teve como objetivo estimar os parâmetros genéticos com a seleção de clones de C. canephora, da variedade botânica 'Conilon', visando caracterizar a variabilidade genética e estimar o progresso genético da produtividade de café beneficiado. A análise de variância da produção de café beneficiado evidenciou que a fonte de variação "clones" foi significativa nas safras avaliadas, de acordo com o teste F a 1% de significância. A predominância do componente genético na expressão dessa característica, associado a uma boa precisão experimental, indica a possibilidade de obtenção de ganhos com a seleção de plantas. O progresso genético da produção de café beneficiado com o plantio dos clones selecionados foi de 57,85%, que equivale a um aumento na média em quatro anos de 44,75 sacas ha-1, para 70,64 sacas ha-1. Além do incremento na produtividade de grãos, os clones de ciclo intermediário selecionados favorecem a concentração da colheita e a redução dos custos operacionais.

New genetic variants of LATS1 detected in urinary bladder and colon cancer.

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Saadeldin, Mona K; Shawer, Heba; Mostafa, Ahmed; Kassem, Neemat M; Amleh, Asma; Siam, Rania

2014-01-01

LATS1, the large tumor suppressor 1 gene, encodes for a serine/threonine kinase protein and is implicated in cell cycle progression. LATS1 is down-regulated in various human cancers, such as breast cancer, and astrocytoma. Point mutations in LATS1 were reported in human sarcomas. Additionally, loss of heterozygosity of LATS1 chromosomal region predisposes to breast, ovarian, and cervical tumors. In the current study, we investigated LATS1 genetic variations including single nucleotide polymorphisms (SNPs), in 28 Egyptian patients with either urinary bladder or colon cancers. The LATS1 gene was amplified and sequenced and the expression of LATS1 at the RNA level was assessed in 12 urinary bladder cancer samples. We report, the identification of a total of 29 variants including previously identified SNPs within LATS1 coding and non-coding sequences. A total of 18 variants were novel. Majority of the novel variants, 13, were mapped to intronic sequences and un-translated regions of the gene. Four of the five novel variants located in the coding region of the gene, represented missense mutations within the serine/threonine kinase catalytic domain. Interestingly, LATS1 RNA steady state levels was lost in urinary bladder cancerous tissue harboring four specific SNPs (16045 + 41736 + 34614 + 56177) positioned in the 5'UTR, intron 6, and two silent mutations within exon 4 and exon 8, respectively. This study identifies novel single-base-sequence alterations in the LATS1 gene. These newly identified variants could potentially be used as novel diagnostic or prognostic tools in cancer.

Evaluation of granulated BGO, GSO:Ce, YAG:Ce, CaF sub 2 :Eu and ZnS:Ag for alpha/beta pulse shape discrimination in a flow-cell radiation detector

CERN Document Server

Devol, T A; Fjeld, R A

1999-01-01

Granulated BGO, GSO:Ce, YAG:Ce, and CaF sub 2 :Eu; CaF sub 2 :Eu coated with a fluorescent polymer, and combinations of coated and uncoated CaF sub 2 :Eu with ZnS:Ag were evaluated for their ability to discriminate between alpha and beta particles in a flow-cell radiation detector. The evaluations were based on the analysis of pulse shape spectra. Various granulated scintillators were packed into flow cell detectors that were coils of 3.0 mm ODx1.5 mm ID fluorinated ethylene propylene Teflon[reg] tubing positioned between dual photomultiplier tubes for analysis. The best pulse shape discrimination was obtained for a combination of equal masses of uncoated CaF sub 2 :Eu (63-90 mu m) and ZnS:Ag (10 mu m), which had a 9% spillover. Additional research is needed to reduce the spillover.

Cambios en la demanda mundial de alimentos y la exportación de café orgánico (2005-2012)

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Escalante Candiotti, Nadiezhda Yenny

2014-01-01

Determina en qué medida se relacionan los cambios en la demanda mundial de alimentos orgánicos con las exportaciones de café orgánico, para cuyo proceso se analiza la evolución de las exportaciones del café orgánico y su participación en las agroexportaciones y en las exportaciones totales del país; asimismo, se determina cómo inciden las tendencias en la estructura poblacional de los principales países desarrollados a favor de las personas de la tercera edad sobre la demanda del café orgánic...

Carboidratos na bebida do café preparado sob diferentes processos Coffee carbohydrates in different preparations of the beverage

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Marina Câmara Mattos Martins

2005-06-01

Full Text Available O café é uma das bebidas mais consumidas no mundo e seus polissacarídeos têm sido investigados devido a sua grande importância comercial. Os principais polissacarídeos de café são os galactomananos e arabinogalactanos, considerados como fibras alimentares não digeridas no sistema digestivo humano. O presente trabalho teve por objetivo quantificar e determinar a composição de monossacarídeos e de polissacarídeos na bebida do café. As preparações foram realizadas em coador de papel tradicional, em cafeteira elétrica e em máquina expresso, utilizando café Arábica (Coffea arabica. Determinações quantitativas e qualitativas dos açúcares foram realizadas, respectivamente, por análises colorimétricas e cromatografia de troca aniônica (HPAEC. O rendimento de sólidos solúveis foi maior em café expresso, sendo os valores cerca de 3,6 vezes superiores àqueles de café de cafeteira elétrica com filtro de papel. Preparações de café expresso foram as que resultaram em maiores teores de açúcares totais não redutores por volume de bebida. Entretanto, os valores de açúcares totais foram significativamente maiores na preparação em cafeteira elétrica, quando expressos pelo total de sólidos solúveis extraídos, indicando que o tempo de extração é provavelmente mais eficiente do que a temperatura. A composição em monossacarídeos foi similar em todas as amostras e independente do modo de preparação do café. Todos apresentaram arabinose (14-15%, galactose (29-30%, glucose (6% e manose 48-49%. Não se sabe se os polissacarídeos de café exercem as mesmas funções que a goma guar como fibra, mas, se isto ocorrer, esta é possivelmente uma das mais importantes fibras alimentares que ingerimos, levando em consideração a popularidade do café.Coffee is highly consumed worldwide and therefore one of the best studied beverages regarding chemical composition. Most of the soluble solids in coffee are carbohydrates

The gene expression profiles of canine mammary cancer cells grown with carcinoma-associated fibroblasts (CAFs as a co-culture in vitro

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Król Magdalena

2012-03-01

Full Text Available Abstract Background It is supposed that fibroblasts present in tumour microenvironment increase cancer invasiveness and its ability to metastasize but the mechanisms have not been clearly defined yet. Thus, the current study was designed to assess changes in gene expression in five various cancer cell lines grown as a co-culture with the carcinoma-associated fibroblasts (CAFs in vitro. Results A carcinoma-associated fibroblast cell line was isolated from a canine mammary cancer. Then, a co-culture of cancer cells with the CAFs was established and maintained for 72 hrs. Having sorted the cells, a global gene expression in cancer cells using DNA microarrays was examined. The analysis revealed an up-regulation of 100 genes and a down-regulation of 106 genes in the cancer cells grown as a co-culture with the CAFs in comparison to control conditions. The PANTHER binomial statistics tool was applied to determine statistically over-manifested pathways (p Conclusion The results of the current study showed that the co-culturing of cancer cells and the CAFs caused significant changes to the cancer gene expression. The presence of the CAFs in a microenvironment of cancer cells promotes adhesion, angiogenesis and EMT.

Genetic variants in CHI3L1 influencing YKL-40 levels

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Kjaergaard, Alisa D; Johansen, Julia S; Nordestgaard, Børge G

2013-01-01

Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population.......Despite its important role in many serious diseases, the genetic background for plasma YKL-40 has still not been systematically catalogued. Therefore, we aimed at identifying genetic variants in CHI3L1 influencing plasma YKL-40 levels in the general population....

Proyección de cifras de producción de café colombiano utilizando cadenas de Markov

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Yenny Londoño Salazar

2013-01-01

Full Text Available El café es considerado el producto agrícola más importante en Colombia, además de ser un gran símbolo en su carta de presentación; sin embargo, el peso relativo de la caficultura aportado al PIB ha disminuido notablemente en los últimos años, reflejado en un descenso en la producción de sacos de café, situación que afecta directamente la cantidad exportada, dando lugar a una pérdida significativa de participación en el mercado mundial de este producto. En este artículo se presenta un estudio sobre el modelamiento matemático del número de sacos de 60 kg de café exportados, aplicando cadenas de Markov discretas en el estado y continuas en el tiempo, utilizando los datos históricos de producción de café para los meses comprendidos entre enero de 2010 y octubre de 2012. Los resultados obtenidos mediante esta técnica matemática muestran que las metas propuestas por el Comité de Cafeteros no se cumplirán si no hay una intervención eficiente en este mercado.

Altered endoribonuclease activity of apurinic/apyrimidinic endonuclease 1 variants identified in the human population.

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Wan Cheol Kim

Full Text Available Apurinic/apyrimidinic endonuclease 1 (APE1 is the major mammalian enzyme in the DNA base excision repair pathway and cleaves the DNA phosphodiester backbone immediately 5' to abasic sites. APE1 also has 3'-5' DNA exonuclease and 3' DNA phosphodiesterase activities, and regulates transcription factor DNA binding through its redox regulatory function. The human APE1 has recently been shown to endonucleolytically cleave single-stranded regions of RNA. Towards understanding the biological significance of the endoribonuclease activity of APE1, we examined eight different amino acid substitution variants of APE1 previously identified in the human population. Our study shows that six APE1 variants, D148E, Q51H, I64V, G241R, R237A, and G306A, exhibit a 76-85% reduction in endoribonuclease activity against a specific coding region of the c-myc RNA, yet fully retain the ability to cleave apurinic/apyrimidinic DNA. We found that two APE1 variants, L104R and E126D, exhibit a unique RNase inhibitor-resistant endoribonuclease activity, where the proteins cleave c-myc RNA 3' of specific single-stranded guanosine residues. Expression of L104R and E126D APE1 variants in bacterial Origami cells leads to a 60-80% reduction in colony formation and a 1.5-fold increase in cell doubling time, whereas the other variants, which exhibit diminished endoribonuclease activity, had no effect. These data indicate that two human APE1 variants exhibit a unique endoribonuclease activity, which correlates with their ability to induce cytotoxicity or slow down growth in bacterial cells and supports the notion of their biological functionality.

Estratégia de Diferenciação no Mercado Brasileiro de CaféDifferentiation Strategy in the Brazilian Coffee MarketEstrategia de Diferenciación en el Mercado Brasileño del Café

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SILVA, Christian Luiz da

2006-05-01

Full Text Available RESUMOEste artigo tem como objetivo verificar se as estratégias de diferenciação das empresas de torrefação e moagem por meio de novas tecnologias de produto têm sido percebidas pelos consumidores brasileiros. Para isso, foi correlacionado o perfil da demanda com a evolução de consumo (preço e quantidade dos diferentes tipos de café, adquiridos a partir de dados mensais de 2002 a 2004, classificados em grupos de produtos: café Gourmet, Tradicional moído e moído a Vácuo puro. Os principais resultados mostraram uma mudança comportamental, ainda que singela, no período analisado. Os cafés Gourmet e a Vácuo ganharam mercado em relação ao produto tradicional, uma vez que apresenta maior valor agregado. Considerando a pequena modificação da restrição orçamentária no período em análise na região estudada, concluiu-se que a mudança estratégica permitiu ampliar a participação do café na cesta de produto dos consumidores a partir do valor adicionado, conquistado pela diferenciação nas características, principalmente, sensorial do produto.ABSTRACTThis article aims to verify whether Brazilian consumers have perceived the differentiation strategies of roasting and grinding companies. For that purpose, the profile of the demand for different types of coffee was correlated with their consumption history (price and quantity. 2002 and 2004 monthly data series from Sao Paulo metropolitan region were classified into the following groups of coffee products: Gourmet, Ground Traditional and Vacuum Ground. The main results showed a behavioral change, albeit small, in the period studied. Compared against the Traditional type, the Gourmet and Vacuum types have gained market share, once they present a higher added value. Considering that there was an almost imperceptible change in the budgetary restriction of the consumers in the period and region analyzed, it is concluded that the strategic change, i.e., added value through

DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder

DEFF Research Database (Denmark)

Håvik, Bjarte; Degenhardt, Franziska A; Johansson, Stefan

2012-01-01

that have neuro-cognitive dysfunctions: schizophrenia (SCZ), bipolar affective disorder (BP) and attention deficit/hyperactivity disorder (ADHD). We mined six genome wide association studies (GWASs) that were available publically or through collaboration; three for BP, two for SCZ and one for ADHD. We also......Doublecortin and calmodulin like kinase 1 (DCLK1) is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders...

Radiation dosimetry by optically stimulated phosphorescence of CaF2:Mn

International Nuclear Information System (INIS)

Bernhardt, R.

1974-01-01

In addition to the light emission which occurs in TL, trapped electrons in CaF 2 :Mn can also be released by stimulation with visible and UV light. The measurement of stimulated light emission is disturbed by illumination. But there is an optically-stimulated phosphorescence, which permits to separate measurement of stimulated light emission and illumination. A theory is given. During illumination a part of the released electrons are captured by flat traps, which are emptied at room temperature. A dose dependent signal can be measured at a defined time after the stimulating pulse of visible light. Dosimeters (CaF 2 :Mn teflon disks) were illuminated by the light of a tungsten lamp. The dose response curve was found to be linear from 1 to 10 5 rads. The response curve obtained for optical stimulation was similar to the TL-response curve. Fading of the optically-stimulated signal was higher than TL-fading. Repeated readings of a single sample are possible. The number of readings is dependent on illumination conditions. Accuracy of sample to sample was about 3.5% (standard deviation). There are two background signals. (1) Post-irradiation phosphorescence occurs. Flat traps are also filled after 60 Co gamma excitation. The measurement of the signal is possible after decay of post-irradiation phosphorescence. (2) There is an optically-excited phosphorescence, which also occurs if all trapped electrons are released. The lower limit of dose measurements is given by deviations of optically-excited emission and the dark-current of the photomultiplier tube. (author)

Genetic variant of AMD1 is associated with obesity in urban Indian children.

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Rubina Tabassum

Full Text Available Hyperhomocysteinemia is regarded as a risk factor for cardiovascular diseases, diabetes and obesity. Manifestation of these chronic metabolic disorders starts in early life marked by increase in body mass index (BMI. We hypothesized that perturbations in homocysteine metabolism in early life could be a link between childhood obesity and adult metabolic disorders. Thus here we investigated association of common variants from homocysteine metabolism pathway genes with obesity in 3,168 urban Indian children.We genotyped 90 common variants from 18 genes in 1,325 children comprising of 862 normal-weight (NW and 463 over-weight/obese (OW/OB children in stage 1. The top signal obtained was replicated in an independent sample set of 1843 children (1,399 NW and 444 OW/OB in stage 2. Stage 1 association analysis revealed association between seven variants and childhood obesity at P<0.05, but association of only rs2796749 in AMD1 [OR = 1.41, P = 1.5×10(-4] remained significant after multiple testing correction. Association of rs2796749 with childhood obesity was validated in stage 2 [OR = 1.28, P = 4.2×10(-3] and meta-analysis [OR = 1.35, P = 1.9×10(-6]. AMD1 variant rs2796749 was also associated with quantitative measures of adiposity and plasma leptin levels that was also replicated and corroborated in combined analysis.Our study provides first evidence for the association of AMD1 variant with obesity and plasma leptin levels in children. Further studies to confirm this association, its functional significance and mechanism of action need to be undertaken.

[Minor phenotypic variants in patients with acute lymphoblastic leukemia from west Mexico].

Science.gov (United States)

Estrada-Padilla, S A; Corona-Rivera, J R; Sánchez-Zubieta, F; Bobadilla-Morales, L; Corona-Rivera, A

2015-02-01

Acute lymphoblastic leukemia (ALL) has been associated with an excess of minor phenotypic variants (MPV), including common variants and minor anomalies, indicative of an altered phenogenesis. The objective of the study was to determine the association between MPV and ALL. In a hospital based case-control study, we studied 120 children with ALL (including standard and high risk) and 120 healthy children as a control group, matched for age and sex, seen in the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico). In both groups, 28 anthropometric measurements were made, as well as a systematic search for 405 MPV, through a physical examination. Adjusted odds ratio was estimated (aOR) with its intervening variables by logistic regression. The confidence interval was 95% (95%CI). Anthropometric signs associated with ALL were: long upper segment (aOR= 2.19, 95%CI: 1.01-4.76), broad jaw (aOR= 2.62, 95%CI: 1.29-5.30), narrow ears (aOR= 6.22, 95%CI: 2.60-14.85), and increase in internipple distance (aOR= 2.53, 95%CI: 1.07-5.98). The hypoplasia mesofacial, broad forehead, small nose, short columella, narrow ears, telethelia, Sydney crease (SC), Greek type feet and café-au-lait spots (CALS), had a 3 to 17 times higher frequency in children with ALL. By number, an association was found from ≥4 MPV (aOR= 2.14, 95%CI: 1.25-3.66, P=.004). From ≥4 MPV, an association was found with ALL, suggesting prenatal factors in phenogenesis and leukemogenesis. CALS and SC were confirmed as MPV in children with ALL. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Functional and clinical relevance of novel and known PCSK1 variants for childhood obesity and glucose metabolism

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Dennis Löffler

2017-03-01

Full Text Available Objective: Variants in Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1 may be causative for obesity as suggested by monogenic cases and association studies. Here we assessed the functional relevance in experimental studies and the clinical relevance through detailed metabolic phenotyping of newly identified and known PCSK1 variants in children. Results: In 52 obese children selected for elevated proinsulin levels and/or impaired glucose tolerance, we found eight known variants and two novel heterozygous variants (c.1095 + 1G > A and p.S24C by sequencing the PCSK1 gene. Patients with the new variants presented with extreme obesity, impaired glucose tolerance, and PCOS. Functionally, c.1095 + 1G > A caused skipping of exon8 translation and a complete loss of enzymatic activity. The protein was retained within the endoplasmic reticulum (ER causing ER stress. The p.S24C variant had no functional effect on protein size, cell trafficking, or enzymatic activity. The known variants rs6230, rs35753085, and rs725522 in the 5′ end did not affect PCSK1 promoter activity.In clinical association studies in 1673 lean and obese children, we confirmed associations of rs6232 and rs6234 with BMI-SDS and of rs725522 with glucose stimulated insulin secretion and Matsuda index. We did not find the new variants in any other subjects. Conclusions: We identified and functionally characterized two rare novel PCSK1 variants of which c.1095 + 1G > A caused complete loss of protein function. In addition to confirming rs6232 and rs6234 in PCSK1 as polygenic risk variants for childhood obesity, we describe an association of rs725522 with insulin metabolism. Our results support the contribution of PCSK1 variants to obesity predisposition in children. Keywords: PCSK1, PC1/3, Obesity, Children, Prohormone convertase 1/3

Targeted deep resequencing identifies coding variants in the PEAR1 gene that play a role in platelet aggregation.

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Yoonhee Kim

Full Text Available Platelet aggregation is heritable, and genome-wide association studies have detected strong associations with a common intronic variant of the platelet endothelial aggregation receptor1 (PEAR1 gene both in African American and European American individuals. In this study, we used a sequencing approach to identify additional exonic variants in PEAR1 that may also determine variability in platelet aggregation in the GeneSTAR Study. A 0.3 Mb targeted region on chromosome 1q23.1 including the entire PEAR1 gene was Sanger sequenced in 104 subjects (45% male, 49% African American, age = 52±13 selected on the basis of hyper- and hypo- aggregation across three different agonists (collagen, epinephrine, and adenosine diphosphate. Single-variant and multi-variant burden tests for association were performed. Of the 235 variants identified through sequencing, 61 were novel, and three of these were missense variants. More rare variants (MAF<5% were noted in African Americans compared to European Americans (108 vs. 45. The common intronic GWAS-identified variant (rs12041331 demonstrated the most significant association signal in African Americans (p = 4.020×10(-4; no association was seen for additional exonic variants in this group. In contrast, multi-variant burden tests indicated that exonic variants play a more significant role in European Americans (p = 0.0099 for the collective coding variants compared to p = 0.0565 for intronic variant rs12041331. Imputation of the individual exonic variants in the rest of the GeneSTAR European American cohort (N = 1,965 supports the results noted in the sequenced discovery sample: p = 3.56×10(-4, 2.27×10(-7, 5.20×10(-5 for coding synonymous variant rs56260937 and collagen, epinephrine and adenosine diphosphate induced platelet aggregation, respectively. Sequencing approaches confirm that a common intronic variant has the strongest association with platelet aggregation in African Americans

Portfolio Café oli abiks eneseväljendamisel ja raha teenimisel / Piret Potisepp

Index Scriptorium Estoniae

Potisepp, Piret

2011-01-01

VI Disainifestivali Disainiöö ja Euroopa Innovatsioonifestivali IF... programmi kuulus sel aastal esimest korda Eesti Kunstiakadeemia poolt läbi viidud disainimagistrantide ja noorte disainerite Portfolio Café

Construction of Nef-positive doxycycline-dependent HIV-1 variants using bicistronic expression elements

Energy Technology Data Exchange (ETDEWEB)

Velden, Yme U. van der; Kleibeuker, Wendy; Harwig, Alex; Klaver, Bep; Siteur-van Rijnstra, Esther; Frankin, Esmay; Berkhout, Ben; Das, Atze T., E-mail: a.t.das@amc.uva.nl

2016-01-15

Conditionally replicating HIV-1 variants that can be switched on and off at will are attractive tools for HIV research. We previously developed a genetically modified HIV-1 variant that replicates exclusively when doxycycline (dox) is administered. The nef gene in this HIV-rtTA variant was replaced with the gene encoding the dox-dependent rtTA transcriptional activator. Because loss of Nef expression compromises virus replication in primary cells and precludes studies on Nef function, we tested different approaches to restore Nef production in HIV-rtTA. Strategies that involved translation via an EMCV or synthetic internal ribosome entry site (IRES) failed because these elements were incompatible with efficient virus replication. Fusion protein approaches with the FMDV 2A peptide and human ubiquitin were successful and resulted in genetically-stable Nef-expressing HIV-rtTA strains that replicate more efficiently in primary T-cells and human immune system (HIS) mice than Nef-deficient variants, thus confirming the positive effect of Nef on in vivo virus replication. - Highlights: • Different approaches to encode additional proteins in the HIV-1 genome were tested. • IRES translation elements are incompatible with efficient HIV-1 replication. • Ubiquitin and 2A fusion protein approaches allow efficient HIV-1 replication. • Doxycycline-controlled HIV-1 variants that encode all viral proteins were developed. • Nef stimulates HIV-rtTA replication in primary cells and human immune system mice.

Thermal neutrons thermoluminescence dosimetry using CaF2 + KBr e CaSO4: Dy + Br

International Nuclear Information System (INIS)

Leite, A.M.P.

1979-01-01

Cold-pressed samples of CaF 2 + KBr and CaSO 4 :Dy + KBr have been used in the thermal neutron detection by the thermoluminescence technique. The amount of 100 mg of the TL phosphor added to 80 mg of KBr showed to be the optimum mixture regarding sensitivity as well as the handling of the dosimeters. The detection is based on the self-irradiation of the phosphor by the Br isotopes activated by exposure to a neutron-gama field. The prompt dose and consequentely the gama contribution are erased by post-irradiation thermal annealing. A linear dependence has been found between the TL self-induced signal and the thermal neutron flux in the range 10 6 n.cm -2 .seg -1 -10 -12 n.cm -2 .seg -1 . The minimum detectable fluence has benn determined as 10 9 n.cm -2 and 10 6 n.cm -2 using pellets of CaF 2 + KBr and CaSO 4 :Dy + KBr, respectively. The main results suggest the use of CaSO 4 :Dy + KBr pellets and TL as a complementary technique for thermal neutron detection. (author) [pt

Cerebral visual impairment and intellectual disability caused by PGAP1 variants.

Science.gov (United States)

Bosch, Daniëlle G M; Boonstra, F Nienke; Kinoshita, Taroh; Jhangiani, Shalini; de Ligt, Joep; Cremers, Frans P M; Lupski, James R; Murakami, Yoshiko; de Vries, Bert B A

2015-12-01

Homozygous variants in PGAP1 (post-GPI attachment to proteins 1) have recently been identified in two families with developmental delay, seizures and/or spasticity. PGAP1 is a member of the glycosylphosphatidylinositol anchor biosynthesis and remodeling pathway and defects in this pathway are a subclass of congenital disorders of glycosylation. Here we performed whole-exome sequencing in an individual with cerebral visual impairment (CVI), intellectual disability (ID), and factor XII deficiency and revealed compound heterozygous variants in PGAP1, c.274_276del (p.(Pro92del)) and c.921_925del (p.(Lys308Asnfs*25)). Subsequently, PGAP1-deficient Chinese hamster ovary (CHO)-cell lines were transfected with either mutant or wild-type constructs and their sensitivity to phosphatidylinositol-specific phospholipase C (PI-PLC) treatment was measured. The mutant constructs could not rescue the PGAP1-deficient CHO cell lines resistance to PI-PLC treatment. In addition, lymphoblastoid cell lines (LCLs) of the affected individual showed no sensitivity to PI-PLC treatment, whereas the LCLs of the heterozygous carrier parents were partially resistant. In conclusion, we report novel PGAP1 variants in a boy with CVI and ID and a proven functional loss of PGAP1 and show, to our knowledge, for the first time this genetic association with CVI.

Novel compound heterozygous NMNAT1 variants associated with Leber congenital amaurosis

DEFF Research Database (Denmark)

Siemiatkowska, Anna M; van den Born, L Ingeborgh; van Genderen, Maria M

2014-01-01

, were screened in 532 additional patients with retinal dystrophies. This cohort encompassed 108 persons with isolated or autosomal recessive cone-rod dystrophy (CRD), 271 with isolated or autosomal recessive retinitis pigmentosa (RP), and 49 with autosomal dominant RP, as well as 104 persons with LCA...... and associated phenotypes in different types of inherited retinal dystrophies. METHODS: DNA samples of 161 patients with LCA without genetic diagnosis were analyzed for variants in NMNAT1 using Sanger sequencing. Variants in exon 5 of NMNAT1, which harbors the majority of the previously identified mutations...

Adsorption effect in non-reaction wetting: In-Ti on CaF2

International Nuclear Information System (INIS)

Glickman, E.; Fuks, D.; Frage, N.; Barzilai, S.; Froumin, N.

2012-01-01

The experiments show that the alloying liquid In with only (0.1-0.5) at% Ti dramatically reduces the equilibrium contact angle Θ ∞ formed by In on the surface of CaF 2 . The aim of this paper is to clarify whether this practically important and conceptually challenging effect can be explained solely by Ti adsorption at the F-terminated solid-liquid interface without resorting to any other Ti-induced effect. The combination of ab initio calculations and regular solution approximation was proposed for finding the binding energy, ΔE Ti of Ti adatom with the interface ''CaF 2 /liquid solutions In-Ti.'' With thus obtained ΔE Ti =1.16 eV, we calculated from the Shishkovsky isotherm the reduction in the solid-liquid interface energy, Δγ SL induced by Ti adsorption from liquid In with various Ti concentration, C. It was found that Δγ SL (C) dependence demonstrated close inverse correspondence with Θ ∞ (C) and that the theory fitted very well all available experimental data on the concentration and temperature dependence of Δγ SL . It was concluded that the Ti adsorption effect is large enough to account for the observed wetting improvement. The proposed multiscale modeling approach to the role of adsorption in wetting can be applied also to other nonreactive systems ''liquid metal-ceramics'' where the substrate determines the surface density of the adsorption sites for the active element. (orig.)

Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

Energy Technology Data Exchange (ETDEWEB)

Vogelsang, Matjaz; Comino, Aleksandra; Zupanec, Neja [Department for Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana (Slovenia); Hudler, Petra [Medical Center for Molecular Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana (Slovenia); Komel, Radovan [Department for Biosynthesis and Biotransformation, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana (Slovenia); Medical Center for Molecular Biology, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, SI-1000 Ljubljana (Slovenia)

2009-10-28

Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

Directory of Open Access Journals (Sweden)

Hudler Petra

2009-10-01

Full Text Available Abstract Background Loss of DNA mismatch repair (MMR in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC. Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Methods Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. Results The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Conclusion Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene.

Assessing pathogenicity of MLH1 variants by co-expression of human MLH1 and PMS2 genes in yeast

International Nuclear Information System (INIS)

Vogelsang, Matjaz; Comino, Aleksandra; Zupanec, Neja; Hudler, Petra; Komel, Radovan

2009-01-01

Loss of DNA mismatch repair (MMR) in humans, mainly due to mutations in the hMLH1 gene, is linked to hereditary nonpolyposis colorectal cancer (HNPCC). Because not all MLH1 alterations result in loss of MMR function, accurate characterization of variants and their classification in terms of their effect on MMR function is essential for reliable genetic testing and effective treatment. To date, in vivo assays for functional characterization of MLH1 mutations performed in various model systems have used episomal expression of the modified MMR genes. We describe here a novel approach to determine accurately the functional significance of hMLH1 mutations in vivo, based on co-expression of human MLH1 and PMS2 in yeast cells. Yeast MLH1 and PMS1 genes, whose protein products form the MutLα complex, were replaced by human orthologs directly on yeast chromosomes by homologous recombination, and the resulting MMR activity was tested. The yeast strain co-expressing hMLH1 and hPMS2 exhibited the same mutation rate as the wild-type. Eight cancer-related MLH1 variants were introduced, using the same approach, into the prepared yeast model, and their effect on MMR function was determined. Five variants (A92P, S93G, I219V, K618R and K618T) were classified as non-pathogenic, whereas variants T117M, Y646C and R659Q were characterized as pathogenic. Results of our in vivo yeast-based approach correlate well with clinical data in five out of seven hMLH1 variants and the described model was thus shown to be useful for functional characterization of MLH1 variants in cancer patients found throughout the entire coding region of the gene

SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease.

Science.gov (United States)

Nicolas, G; Charbonnier, C; Wallon, D; Quenez, O; Bellenguez, C; Grenier-Boley, B; Rousseau, S; Richard, A-C; Rovelet-Lecrux, A; Le Guennec, K; Bacq, D; Garnier, J-G; Olaso, R; Boland, A; Meyer, V; Deleuze, J-F; Amouyel, P; Munter, H M; Bourque, G; Lathrop, M; Frebourg, T; Redon, R; Letenneur, L; Dartigues, J-F; Génin, E; Lambert, J-C; Hannequin, D; Campion, D

2016-06-01

The SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimer's disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of disruptive and predicted damaging missense SORL1 variants in cases (odds radio (OR)=5.03, 95% confidence interval (CI)=(2.02-14.99), P=7.49.10(-5)). This enrichment was even stronger when restricting the analysis to the 205 cases with a positive family history (OR=8.86, 95% CI=(3.35-27.31), P=3.82.10(-7)). We conclude that predicted damaging rare SORL1 variants are a strong risk factor for EOAD and that the association signal is mainly driven by cases with positive family history.

Jaffe-Campanacci syndrome, revisited: detailed clinical and molecular analyses determine whether patients have neurofibromatosis type 1, coincidental manifestations, or a distinct disorder

NARCIS (Netherlands)

Stewart, Douglas R.; Brems, Hilde; Gomes, Alicia G.; Ruppert, Sarah L.; Callens, Tom; Williams, Jennifer; Claes, Kathleen; Bober, Michael B.; Hachen, Rachel; Kaban, Leonard B.; Li, Hua; Lin, Angela; McDonald, Marie; Melancon, Serge; Ortenberg, June; Radtke, Heather B.; Samson, Ignace; Saul, Robert A.; Shen, Joseph; Siqveland, Elizabeth; Toler, Tomi L.; van Maarle, Merel; Wallace, Margaret; Williams, Misti; Legius, Eric; Messiaen, Ludwine

2014-01-01

"Jaffe-Campanacci syndrome" describes the complex of multiple nonossifying fibromas of the long bones, mandibular giant cell lesions, and café-au-lait macules in individuals without neurofibromas. We sought to determine whether Jaffe-Campanacci syndrome is a distinct genetic entity or a variant of

The Variant p.(Arg183Trp) in SPTLC2 Causes Late-Onset Hereditary Sensory Neuropathy.

Science.gov (United States)

Suriyanarayanan, Saranya; Auranen, Mari; Toppila, Jussi; Paetau, Anders; Shcherbii, Maria; Palin, Eino; Wei, Yu; Lohioja, Tarja; Schlotter-Weigel, Beate; Schön, Ulrike; Abicht, Angela; Rautenstrauss, Bernd; Tyynismaa, Henna; Walter, Maggie C; Hornemann, Thorsten; Ylikallio, Emil

2016-03-01

Hereditary sensory and autonomic neuropathy 1 (HSAN1) is an autosomal dominant disorder that can be caused by variants in SPTLC1 or SPTLC2, encoding subunits of serine palmitoyl-CoA transferase. Disease variants alter the enzyme's substrate specificity and lead to accumulation of neurotoxic 1-deoxysphingolipids. We describe two families with autosomal dominant HSAN1C caused by a new variant in SPTLC2, c.547C>T, p.(Arg183Trp). The variant changed a conserved amino acid and was not found in public variant databases. All patients had a relatively mild progressive distal sensory impairment, with onset after age 50. Small fibers were affected early, leading to abnormalities on quantitative sensory testing. Sural biopsy revealed a severe chronic axonal neuropathy with subtotal loss of myelinated axons, relatively preserved number of non-myelinated fibers and no signs for regeneration. Skin biopsy with PGP9.5 labeling showed lack of intraepidermal nerve endings early in the disease. Motor manifestations developed later in the disease course, but there was no evidence of autonomic involvement. Patients had elevated serum 1-deoxysphingolipids, and the variant protein produced elevated amounts of 1-deoxysphingolipids in vitro, which proved the pathogenicity of the variant. Our results expand the genetic spectrum of HSAN1C and provide further detail about the clinical characteristics. Sequencing of SPTLC2 should be considered in all patients presenting with mild late-onset sensory-predominant small or large fiber neuropathy.

Effects of a one year physical activity program on serum C Terminal Agrin Fragment (CAF) concentrations among mobility limited older adults

Science.gov (United States)

OBJECTIVES: C terminal Agrin Fragment (CAF) has been proposed as a potential circulating biomarker for predicting changes in physical function among older adults. To determine the effect of a one year PA intervention on changes in CAF concentrations and to evaluate baseline and longitudinal associat...

Variants in calcium voltage-gated channel subunit Alpha1 C-gene (CACNA1C are associated with sleep latency in infants.

Directory of Open Access Journals (Sweden)

Katri Kantojärvi

Full Text Available Genetic variants in CACNA1C (calcium voltage-gated channel subunit alpha1 C are associated with bipolar disorder and schizophrenia where sleep disturbances are common. In an experimental model, Cacna1c has been found to modulate the electrophysiological architecture of sleep. There are strong genetic influences for consolidation of sleep in infancy, but only a few studies have thus far researched the genetic factors underlying the process. We hypothesized that genetic variants in CACNA1C affect the regulation of sleep in early development. Seven variants that were earlier associated (genome-wide significantly with psychiatric disorders at CACNA1C were selected for analyses. The study sample consists of 1086 infants (520 girls and 566 boys from the Finnish CHILD-SLEEP birth cohort (genotyped by Illumina Infinium PsychArray BeadChip. Sleep length, latency, and nightly awakenings were reported by the parents of the infants with a home-delivered questionnaire at 8 months of age. The genetic influence of CACNA1C variants on sleep in infants was examined by using PLINK software. Three of the examined CACNA1C variants, rs4765913, rs4765914, and rs2239063, were associated with sleep latency (permuted P<0.05. There was no significant association between studied variants and night awakenings or sleep duration. CACNA1C variants for psychiatric disorders were found to be associated with long sleep latency among 8-month-old infants. It remains to be clarified whether the findings refer to defective regulation of sleep, or to distractibility of sleep under external influences.

Ab initio modeling of Al adsorption on CaF2 surfaces

International Nuclear Information System (INIS)

Barzilai, S.; Argaman, N.; Froumin, N.; Fuks, D.; Frage, N.

2008-01-01

Ab initio simulations of the adsorption of Al atoms on CaF 2 (0 0 1) and (1 1 1) surfaces have been performed for supercells with 7 different atomic configurations, using density functional theory. For (1 1 1) surfaces, a repulsive interaction was observed for most configurations, while a weak attraction was obtained when the Al atom was placed above F atoms. For the Ca-terminated (0 0 1) surface, the adsorption energy was about 5 times larger, whereas for the F-terminated (0 0 1) surface it was about 20 times greater. The comparative analysis indicates that the (0 0 1) surfaces are reactive and have a strong Al adatom bonding (chemisorption), especially for the F-terminated substrate. On the contrary, the (1 1 1) plane may be considered as non-reactive (physisorption), having a weak bonding of the Al adatom above the F site

Uncovering the Rare Variants of DLC1 Isoform 1 and Their Functional Effects in a Chinese Sporadic Congenital Heart Disease Cohort

Science.gov (United States)

Wang, Zhen; Tan, Huilian; Kong, Xianghua; Shu, Yang; Zhang, Yuchao; Huang, Yun; Zhu, Yufei; Xu, Heng; Wang, Zhiqiang; Wang, Ping; Ning, Guang; Kong, Xiangyin; Hu, Guohong; Hu, Landian

2014-01-01

Congenital heart disease (CHD) is the most common birth defect affecting the structure and function of fetal hearts. Despite decades of extensive studies, the genetic mechanism of sporadic CHD remains obscure. Deleted in liver cancer 1 (DLC1) gene, encoding a GTPase-activating protein, is highly expressed in heart and essential for heart development according to the knowledge of Dlc1-deficient mice. To determine whether DLC1 is a susceptibility gene for sporadic CHD, we sequenced the coding region of DLC1 isoform 1 in 151 sporadic CHD patients and identified 13 non-synonymous rare variants (including 6 private variants) in the case cohort. Importantly, these rare variants (8/13) were enriched in the N-terminal region of the DLC1 isoform 1 protein. Seven of eight amino acids at the N-terminal variant positions were conserved among the primates. Among the 9 rare variants that were predicted as “damaging”, five were located at the N-terminal region. Ensuing in vitro functional assays showed that three private variants (Met360Lys, Glu418Lys and Asp554Val) impaired the ability of DLC1 to inhibit cell migration or altered the subcellular location of the protein compared to wild-type DLC1 isoform 1. These data suggest that DLC1 might act as a CHD-associated gene in addition to its role as a tumor suppressor in cancer. PMID:24587289

El Parque Nacional del Café

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Ernesto Barrera Duque

2013-03-01

Full Text Available Claudia Guevara, gerente de mercadeo, enfrenta la meta de 520.000 visitas para el año 2006, y por este motivo debe presentar un plan comercial para lograr este objetivo. Se presenta información relevante sobre la historia del Parque Nacional del Café (PNC, el producto, mercado, precios, canales y acciones de comercialización, comunicación comercial que permitirá discutir qué estrategias y tácticas emprender para la temporada de diciembre y para el siguiente año de operaciones. Entre los objetivos a lograr está potenciar la diferenciación, aumentar la base de visitantes y atraer turistas extranjeros.

Detection of GSTM1, GSTT1 and the Ile105Val GSTP1 gene variants

DEFF Research Database (Denmark)

Buchard, Anders; Sanchez, Juan J.; Dalhoff, Kim

2008-01-01

We have developed a PCR multiplex method that in a fast, inexpensive and reliable manner can detect if a person has two, one or no GSTM1 and GSTT1 genes and which at the same time can detect the allelic status of the GSTP1 Ile105Val genetic variant. A total of 200 Danes, 100 Somalis and 100...

Satisfied, but Will They Spread a Word? The Role of Customer Satisfaction at Jamu Café

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Usep Suhud

2018-03-01

Full Text Available This research aimed to investigate consumers’ intention to repurchase jamu at Jamu Café. Service quality, customer satisfaction, and Word-of-Mouth (WOM were selected as the predictor variables. In total, 200 participants who purchased jamu at the café were selected conveniently. Data were analyzed using exploratory and confirmatory factor analyses as well as Structural Equation Model (SEM. As a result, service quality influences customer satisfaction significantly. As customers are satisfied, they do word-of-mouth and repurchase. On the other hand, WOM has an insignificant impact on repurchase intention.

PGC1? ?1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals

OpenAIRE

Henagan, Tara M.; Stewart, Laura K.; Forney, Laura A.; Sparks, Lauren M.; Johannsen, Neil; Church, Timothy S.

2014-01-01

PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically re...

Ochratoxin A in brazilian instant coffee Ocratoxina A em café solúvel brasileiro

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Adriana P. de Almeida

2007-06-01

Full Text Available The aim of this study was to determine the ochratoxin A (OTA contamination of instant coffee samples collected in the market of the city of São Paulo, Brazil from August to December, 2004. The EN 14133/2003 method, originally developed to quantify OTA in wine, grape juice and beer samples, was evaluated and approved for analyzing OTA in instant coffee samples. OTA was isolated in an immunoaffinity column and quantified by HPLC with fluorescence detection. The established detection and quantification limits were 0.16 and 0.52 ng/g, respectively. The recoveries from spiked samples were 92.6 ± 1.7, 83.7 ± 0.8, and 91.0 ± 1.2 % at levels of 3.0, 5.0, and 8.0 ng/g, respectively. Of a total of 82 samples analised, 81 (98.8% contained OTA at levels ranging from 0.17 to 6.29 ng/g. The high frequency of OTA occurrence in the instant coffee samples demonstrates the importance of an effective control of this product by governmental authorities and industries. The rapid methodology for OTA analysis in instant coffee used in this study was defined and validated, permitting it´s use for quality control of this product.O objetivo do presente estudo foi determinar a contaminação por OTA em amostras de café solúvel comercializadas na cidade de São Paulo, Brasil no período de agosto a dezembro de 2004. O método EN 14133/2003, originalmente desenvolvido para quantificar OTA em amostras de vinho, suco de uva e cerveja, foi avaliado e aprovado para análise de OTA em amostras de café solúvel. OTA foi isolada em coluna de imunoafinidade e quantificada por CLAE com detecção em fluorescência. Os limites de detecção e quantificação do método foram 0,16 e 0,52 ng/g, respectivamente. Os percentuais médios de recuperação foram de 92,6% (3 ng/g, 83,7% (5 ng/g e 91,0% (8 ng/g, com coeficientes de variação de 1,7 (3 ng/g, 0,8 (5 ng/g e 1,2 (8 ng/g. A análise das 82 amostras de café solúvel revelou a presença de ocratoxina A em 81 amostras (98

Electronic Coffee Grains Separator Separador Electrónico de Granos de Café

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Juan Rodrigo Sanz-Uribe

2011-12-01

Full Text Available Accurate coffee sorting is a response to pressures for product quality and to a growing market for specialty coffees. One of the major challenges in this regard is to prepare the raw coffee fruits for sorting in one-by-one electronic machines. In this paper, we present a mechanical device developed to separate clusters and impurities from the main process. The mechanical device consists of two inclined belt conveyors with upward motion, working in series. This arrangement conveys upwards any elements with more than three contact points on the belt's flat surface, while quasi-spherical elements (fruits roll down on the belts. The experimental set up was designed to allow each belt's inclination and speed to vary, in order to run a 3 x 3 factorial treatment design (Three inclinations: 10º, 14º and 18º and three speeds: 0.17, 0.20 and 0.24 m s-1. The belt transport surface material was PVC. The best performance was obtained at the speed of 0.20 m s-1 and between 10º and 14º of inclination. After these findings, three treatments were conducted at a working speed of 0.20 m s-1 and three inclinations between 10º and 14º, finding the best performance at 11º. In these conditions the mean efficacy of separation was 98.8%, varying within a range between 97.5% and 100%. The resulting system from this research work is suitable to run as pretreatment of one-by-one electronic sorters of coffee and coffee-like products.La clasificación precisa del café surge como respuesta a las exigencias de calidad del producto en los crecientes mercados de cafés especiales. Uno de los retos más importantes al respecto, es la preparación de los frutos del café en bruto para que sean clasificados uno por uno por las máquinas electrónicas. En este trabajo se presenta un dispositivo mecánico desarrollado para separar glomérulos y las impurezas del proceso principal. El dispositivo mecánico consiste en dos cintas transportadoras inclinadas con movimiento

Complex refractive index measurements for BaF 2 and CaF 2 via single-angle infrared reflectance spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Kelly-Gorham, Molly Rose K.; DeVetter, Brent M.; Brauer, Carolyn S.; Cannon, Bret D.; Burton, Sarah D.; Bliss, Mary; Johnson, Timothy J.; Myers, Tanya L.

2017-10-01

We have re-investigated the optical constants n and k for the homologous series of inorganic salts barium fluoride (BaF2) and calcium fluoride (CaF2) using a single-angle near-normal incidence reflectance device in combination with a calibrated Fourier transform infrared (FTIR) spectrometer. Our results are in good qualitative agreement with most previous works. However, certain features of the previously published data near the reststrahlen band exhibit distinct differences in spectral characteristics. Notably, our measurements of BaF2 do not include a spectral feature in the ~250 cm-1 reststrahlen band that was previously published. Additionally, CaF2 exhibits a distinct wavelength shift relative to the model derived from previously published data. We confirmed our results with recently published works that use significantly more modern instrumentation and data reduction techniques

Health promotion practices of restaurants and cafés in Australia: changes from 1997 to 2000 using an annual telemarketing intervention.

Science.gov (United States)

Licata, Milly; Gillham, Karen; Campbell, Elizabeth

2002-09-01

This study looked at whether rates of health promotion practices among restaurants and cafés in the Hunter Region of New South Wales (NSW), Australia, increased between 1997 and 2000. During the project period all restaurants and cafés in the region were offered an annual direct marketing telephone interview (1997, 1998 and 1999), during which resources were offered to assist in the adoption of health promotion practices. Owners or managers of restaurants and cafés completed phone interviews that assessed 18 health promotion practices relating to: environmental tobacco smoke (two practices); responsible service of alcohol (five practices); healthy food choices (one practice); food safety (four practices); occupational health and safety (three practices); and the prevention of infectious diseases (three practices). Changes in practices were examined by comparing data from cross-sectional samples in 1997 (before any offers of resources) and 2000 (after up to three annual telemarketing calls), and among a cohort interviewed in both 1997 and 2000. Ninety-one per cent of restaurants and cafés (321) participated in the 1997 survey and 239 (81%) participated in the 2000 survey. A cohort of 122 restaurants and cafés participated in both surveys. Significant increases were present for 14 of the 18 health promotion initiatives in the cross-sectional sample and for 10 of the 18 health promotion initiatives in the cohort. For both cross-sectional and cohort samples, a change in at least one practice in each area was evident, with the exception of nutrition. The proportion of restaurants and cafés in the project region that undertake health promotion initiatives is increasing. A telephone-based intervention may contribute to such an increase. The suggestion that the prevalence of health promotion initiatives in restaurants and cafés can be increased highlights the potential for health promotion to be more actively involved in this setting.

The Café Femenino Peru story : evaluating the potential of a for-profit gender equitable value chain

OpenAIRE

Shah, Kanira; Bjørndal, Trond

2016-01-01

The focus of this paper is on evaluating how Café Femenino Peru, an organically grown coffee produced by women, is successful in promoting gender equity, while being a for-profit business. Using the ‘pro-poor perspective’ of Porter’s value chain analysis as its primary methodology, this research identifies links and dynamics in the value chain of Café Femenino Peru but with a gender lens perspective. Results reveal that the combined increases in income and the increased access to assista...

Influences of Er3+ content on structure and upconversion emission of oxyfluoride glass ceramics containing CaF2 nanocrystals

International Nuclear Information System (INIS)

Chen Daqin; Wang Yuansheng; Yu Yunlong; Ma En; Bao Feng; Hu Zhongjian; Cheng Yao

2006-01-01

Transparent 45SiO 2 -25Al 2 O 3 -5CaO-10NaF-15CaF 2 glass ceramics doped with different content of erbium ion (Er 3+ ) were prepared. X-ray diffraction (XRD) and transmission electron microscope (TEM) analyses evidenced the spherical CaF 2 nanocrystals homogeneously embedded among the glassy matrix. With increasing of Er 3+ content, the size of CaF 2 nanocrystals decreased while the number density increased. The crystallization kinetics studies revealed that CaF 2 crystallization was a diffusion-controlled growth process from small dimensions with decreasing nucleation rate. Er 3+ could act as nucleating agent to lower down crystallization temperature, while some of them may stay at the crystal surfaces to retard the growth of crystal. Intense red and weak green upconversion emissions were recorded for glass ceramics and their intensities increased with the increasing of Er 3+ content under 980 nm excitation. However, the concentration quenching effect appeared when Er 3+ doping reached 2 mol%. These results could be attributed to the change of ligand field of Er 3+ ions due to the incorporation of Er 3+ ions into precipitated fluoride nanocrystals

The BARD1 Cys557Ser variant and breast cancer risk in Iceland.

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Simon N Stacey

2006-07-01

Full Text Available Most, if not all, of the cellular functions of the BRCA1 protein are mediated through heterodimeric complexes composed of BRCA1 and a related protein, BARD1. Some breast-cancer-associated BRCA1 missense mutations disrupt the function of the BRCA1/BARD1 complex. It is therefore pertinent to determine whether variants of BARD1 confer susceptibility to breast cancer. Recently, a missense BARD1 variant, Cys557Ser, was reported to be at increased frequencies in breast cancer families. We investigated the role of the BARD1 Cys557Ser variant in a population-based cohort of 1,090 Icelandic patients with invasive breast cancer and 703 controls. We then used a computerized genealogy of the Icelandic population to study the relationships between the Cys557Ser variant and familial clustering of breast cancer.The Cys557Ser allele was present at a frequency of 0.028 in patients with invasive breast cancer and 0.016 in controls (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.11-3.01, p = 0.014. The alleleic frequency was 0.037 in a high-predisposition group of cases defined by having a family history of breast cancer, early onset of breast cancer, or multiple primary breast cancers (OR = 2.41, 95% CI 1.22-4.75, p = 0.015. Carriers of the common Icelandic BRCA2 999del5 mutation were found to have their risk of breast cancer further increased if they also carried the BARD1 variant: the frequency of the BARD1 variant allele was 0.047 (OR = 3.11, 95% CI 1.16-8.40, p = 0.046 in 999del5 carriers with breast cancer. This suggests that the lifetime probability of a BARD1 Cys557Ser/BRCA2 999del5 double carrier developing breast cancer could approach certainty. Cys557Ser carriers, with or without the BRCA2 mutation, had an increased risk of subsequent primary breast tumors after the first breast cancer diagnosis compared to non-carriers. Lobular and medullary breast carcinomas were overrepresented amongst Cys557Ser carriers. We found that an excess of ancestors

Participatory methods for research prioritization in primary care: an analysis of the World Café approach in Ireland and the USA.

Science.gov (United States)

MacFarlane, Anne; Galvin, Rose; O'Sullivan, Madeleine; McInerney, Chris; Meagher, Eoghan; Burke, Daniel; LeMaster, Joseph W

2017-06-01

There are increasing imperatives for patients and members of the public to engage as partners in identifying health research priorities. The use of participatory methods to engage stakeholders in health care in research prioritization is not commonly reported. This article analyses the use of World Cafés as a participatory method for research prioritization with marginalized communities in Ireland and the USA. The principles of purposeful and snowball sampling were followed in both settings and a diverse range of community and health care stakeholders participated (n = 63 Ireland and n = 55 USA). The principles for a classic World Café were employed but there were novel features in each setting as well. Stewart et al.'s (Patients' and clinicians' research priorities. Health Expect 2011; 14: 439-48, conceptual framework for patient engagement was adapted and used to comparatively analyse the strengths and weaknesses of the World Cafés, focusing on agenda setting, engagement with research processes, interactional features and outputs. Design principles for World Cafés were found to align with high-quality patient engagement for research prioritization in both settings. They served to facilitate meaningful collaboration among stakeholder groups in research prioritization (research agenda setting) and explored research priorities (engagement with research). The café ambience, emphasis on hospitality and self-facilitation created an environment for dialogues within and across participating groups (interactional features). There was a commitment to follow-up actions with reference to possible subsequent research (outputs). The World Café is a valuable, participatory, flexible method that can be used with community and health care stakeholders for research prioritization with marginalized communities. © The Author 2016. Published by Oxford University Press.

The energy response of CaF2:Dy

International Nuclear Information System (INIS)

Ben-Shachar, B.; German, U.; Weiser, G.

1982-11-01

The energy response of CaF 2 :Dy was measured for 40-1250 keV photons and a very strong dependence was found below 200 keV. In order to fit the crystal to the requirements of the American Standards for Environmental Dosimetry, a number of filters which improve the energy dependence, were checked. It was found that the best filter is one which is made of 3 layers: tantalum, lead and aluminium, 0.018, 0.014 and 0.26 cm thick, respectively. (Author)

Neurodevelopmental Disorders Caused by De Novo Variants in KCNB1 Genotypes and Phenotypes

DEFF Research Database (Denmark)

de Kovel, Carolien G F; Syrbe, Steffen; Brilstra, Eva H

2017-01-01

Importance: Knowing the range of symptoms seen in patients with a missense or loss-of-function variant in KCNB1 and how these symptoms correlate with the type of variant will help clinicians with diagnosis and prognosis when treating new patients. Objectives: To investigate the clinical spectrum ...

De novo and inherited private variants in MAP1B in periventricular nodular heterotopia.

Science.gov (United States)

Heinzen, Erin L; O'Neill, Adam C; Zhu, Xiaolin; Allen, Andrew S; Bahlo, Melanie; Chelly, Jamel; Dobyns, William B; Freytag, Saskia; Guerrini, Renzo; Leventer, Richard J; Poduri, Annapurna; Robertson, Stephen P; Walsh, Christopher A; Zhang, Mengqi

2018-05-08

Periventricular nodular heterotopia (PVNH) is a malformation of cortical development commonly associated with epilepsy. We exome sequenced 202 individuals with sporadic PVNH to identify novel genetic risk loci. We first performed a trio-based analysis and identified 219 de novo variants. Although no novel genes were implicated in this initial analysis, PVNH cases were found overall to have a significant excess of nonsynonymous de novo variants in intolerant genes (p = 3.27x10-7), suggesting a role for rare new alleles in genes yet to be associated with the condition. Using a gene-level collapsing analysis comparing cases and controls, we identified a genome-wide significant signal driven by four ultra-rare loss-of-function heterozygous variants in MAP1B, including one de novo variant. In at least one instance, the MAP1B variant was inherited from a parent with previously undiagnosed PVNH. The PVNH was frontally predominant and associated with perisylvian polymicrogyria. These results implicate MAP1B in PVNH. More broadly, our findings suggest that detrimental mutations likely arising in immediately preceding generations with incomplete penetrance may also be responsible for some apparently sporadic diseases.

PGC1α −1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals

Directory of Open Access Journals (Sweden)

Tara M. Henagan

2014-01-01

Full Text Available PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α. CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal muscle PGC1α  −1 nucleosome (−1N position is associated with splice variant NTPGC1α but not FLPGC1α expression. Division of participants based on the −1N position revealed that those individuals with a −1N phased further upstream from the transcriptional start site (UP expressed lower levels of NTPGC1α than those with the −1N more proximal to TSS (DN. UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the −1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and −1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifier NCT00458133.

Sensory characterization of commercial soluble coffees by Flash ProfileCaracterização sensorial de cafés solúveis comerciais por Perfil Flash

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Marta de Toledo Benassi

Full Text Available In today’s competitive market, there is a lack of simple methods for sensory characterization of products. The Flash Profile is a combination of the Free Choice Profiling terms selection with a ranking method, based on the simultaneous presentation of all samples to be evaluated, providing a quick description and discrimination of a set of products. Thus, this study aimed to apply the Flash profile method on the characterization of commercial soluble coffees. Four soluble coffees selected by presenting diversity in the production process and composition were evaluated by 32 assessors in a single session. The coffee brews were prepared with 28 g of soluble coffee per 1000 mL of purified water, and added of 9.5 % sucrose. Initially, the whole set of samples were presented simultaneously for the glossary development. In individual discussion, each assessor was assisted on the elaboration of individual score sheet with the definition of each attribute. Subsequently, the four coffee beverages were presented simultaneously to the assessor, who ordered the samples in ascending order for the intensity of each attribute on its score sheet. The results were analyzed by Generalized Procrustes Analysis. The most relevant attributes in the description and discrimination of sweetened coffee brews were brown color, aroma and flavor of coffee, bitter taste, sweet taste and the presence of oil on the brew surface. The Flash Profile method was efficient on the description and discrimination of a complex food matrix as soluble coffee, presenting consensus among the assessors, and a fast assessment.Dentro do competitivo mercado atual, há demanda por métodos mais simples na descrição de produtos. O Perfil Flash (Flash Profile é uma combinação do levantamento de atributos do Perfil Livre com um método de ordenação, baseado na apresentação simultânea de todas as amostras a serem avaliadas, proporcionando uma descrição e discriminação rápida de um

High prevalence of the c.74A>C SPINK1 variant in miniature and standard Schnauzers.

Science.gov (United States)

Furrow, E; Armstrong, P J; Patterson, E E

2012-01-01

Variants in the serine protease inhibitor Kazal type 1 (SPINK1) gene have been associated with pancreatitis in Miniature Schnauzers. Replication of the association in an independent population is necessary to determine if genetic screening for SPINK1 variants should be considered in clinical practice. An association between the SPINK1 exonic variant c.74A > C and pancreatitis exists in Miniature Schnauzers. In addition, the variant is absent or rare in Standard Schnauzers, a related breed that is not reported to have an increased risk for pancreatitis. Case-control study. Seventeen Miniature Schnauzers with pancreatitis (cases), 60 mature Miniature Schnauzers with no substantial history of gastrointestinal signs in their lifetime (controls), and 31 Standard Schnauzers of unknown pancreatitis status. A PCR-RFLP assay was used to genotype dogs for the c.74A > C SPINK1 variant. Allele and genotype frequencies were reported for Schnauzers and compared between case and control Miniature Schnauzers. The c.74A > C variant was the major allele in both Schnauzer breeds with a frequency of 0.77 in Miniatures and 0.55 in Standards. The allele and genotype frequencies were similar between Miniature Schnauzers with and without a history of pancreatitis and did not impart an increased risk for pancreatitis. Genotyping a larger population of the Miniature Schnauzer breed than a previous study, along with a Standard Schnauzer cohort, demonstrated that the SPINK1 c.74A > C variant is a common polymorphism in the Schnauzer lineage. Furthermore, we were unable to confirm a relationship between the variant and clinically detectable pancreatitis in Miniature Schnauzers. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Co-expression of human cytochrome P4501A1 (CYP1A1) variants and human NADPH-cytochrome P450 reductase in the baculovirus/insect cell system.

Science.gov (United States)

Schwarz, D; Kisselev, P; Honeck, H; Cascorbi, I; Schunck, W H; Roots, I

2001-06-01

1. Three human cytochrome P4501A1 (CYP1A1) variants, wild-type (CYP1A1.1), CYP1A1.2 (1462V) and CYP1A1.4 (T461N), were co-expressed with human NADPH-P450 reductase (OR) in Spodoptera frugiperda (Sf9) insect cells by baculovirus co-infection to elaborate a suitable system for studying the role of CYPA1 polymorphism in the metabolism of exogenous and endogenous substrates. 2. A wide range of conditions was examined to optimize co-expression with regard to such parameters as relative multiplicity of infection (MOI), time of harvest, haem precursor supplementation and post-translational stabilization. tinder optimized conditions, almost identical expression levels and molar OR/CYP1A1 ratios (20:1) were attained for all CYP1A1 variants. 3. Microsomes isolated from co-infected cells demonstrated ethoxyresorufin deethlylase activities (nmol/min(-1) nmol(-1) CYP1A1) of 16.0 (CYP1A1.1), 20.5 (CYP1A1.2) and 22.5 (CYP1A1.4). Pentoxyresorufin was dealkylated approximately 10-20 times slower with all enzyme variants. 4. All three CYP1A1 variants were active in metabolizing the precarcinogen benzo[a]pyrene (B[a]P), with wild-type enzyme showing the highest activity, followed by CYP1A1.4 (60%) and CYP1A1.2 (40%). Each variant produced all major metabolites including B[a]P-7,8-dihydrodiol, the precursor of the ultimate carcinogenic species. 5. These studies demonstrate that the baculovirus-mediated co-expression-by-co-infection approach all CYP1A1 variants yields functionally active enzyme systems with similar molar OR/CYP1A1 ratios, thus providing suitable preconditions to examine the metabolism of and environmental chemicals by the different CY1A1 variants.

Mapping of Epitopes Occurring in Bovine α(s1)-Casein Variants by Peptide Microarray Immunoassay.

Science.gov (United States)

Lisson, Maria; Erhardt, Georg

2016-01-01

Immunoglobulin E epitope mapping of milk proteins reveals important information about their immunologic properties. Genetic variants of αS1-casein, one of the major allergens in bovine milk, are until now not considered when discussing the allergenic potential. Here we describe the complete procedure to assess the allergenicity of αS1-casein variants B and C, which are frequent in most breeds, starting from milk with identification and purification of casein variants by isoelectric focusing (IEF) and anion-exchange chromatography, followed by in vitro gastrointestinal digestion of the casein variants, identification of the resulting peptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), in silico analysis of the variant-specific peptides as allergenic epitopes, and determination of their IgE-binding properties by microarray immunoassay with cow's milk allergic human sera.

Engineered Cpf1 variants with altered PAM specificities increase genome targeting range

Science.gov (United States)

Gao, Linyi; Cox, David B.T.; Yan, Winston X.; Manteiga, John C.; Schneider, Martin W.; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-01-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells1–7. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS7 assay indicated that these variants retain high DNA targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately three-fold in human coding sequences to one cleavage site per ~11 bp. PMID:28581492

Evaluación de la conversión a café orgánico usando la metodología de opciones reales

OpenAIRE

Delgado Juárez Gabriel; Pérez Akaki Pablo

2013-01-01

A partir de la desregulación del mercado de café en 1989, las crisis de precios dan muestra de la incertidumbre y el riesgo alrededor de los ingresos de los productores de café, en especial para los pequeños productores mexicanos quienes han tomado acciones como convertir sus cultivos tradicionales hacia el sistema de producción orgánico, el cual -además de la importancia ecológica- les permite mayores ingresos que en el café convencional. En este trabajo se presenta como una opción real comp...

Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome.

Science.gov (United States)

Yamamoto, Guilherme Lopes; Aguena, Meire; Gos, Monika; Hung, Christina; Pilch, Jacek; Fahiminiya, Somayyeh; Abramowicz, Anna; Cristian, Ingrid; Buscarilli, Michelle; Naslavsky, Michel Satya; Malaquias, Alexsandra C; Zatz, Mayana; Bodamer, Olaf; Majewski, Jacek; Jorge, Alexander A L; Pereira, Alexandre C; Kim, Chong Ae; Passos-Bueno, Maria Rita; Bertola, Débora Romeo

2015-06-01

Noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. Heterozygous, pathogenic variants in 11 known genes account for approximately 80% of cases. The identification of novel genes associated with Noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. A cohort of 50 Brazilian probands negative for pathogenic variants in the known genes associated with Noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. Families from the USA and Poland with mutations in the newly identified genes were included subsequently. We identified rare, segregating or de novo missense variants in SOS2 and LZTR1 in 4% and 8%, respectively, of the 50 Brazilian probands. SOS2 and LZTR1 variants were also found to segregate in one American and one Polish family. Notably, SOS2 variants were identified in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. Mutations in these genes are responsible for approximately 3% of all patients with Noonan syndrome. While SOS2 is a natural candidate, because of its homology with SOS1, the functional role of LZTR1 in the RAS/MAPK pathway is not known, and it could not have been identified without the large pedigrees. Additional functional studies are needed to elucidate the role of LZTR1 in RAS/MAPK signalling and in the pathogenesis of Noonan syndrome. 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.

Psoriasis Patients Are Enriched for Genetic Variants That Protect against HIV-1 Disease

Science.gov (United States)

Chen, Haoyan; Hayashi, Genki; Lai, Olivia Y.; Dilthey, Alexander; Kuebler, Peter J.; Wong, Tami V.; Martin, Maureen P.; Fernandez Vina, Marcelo A.; McVean, Gil; Wabl, Matthias; Leslie, Kieron S.; Maurer, Toby; Martin, Jeffrey N.; Deeks, Steven G.; Carrington, Mary; Bowcock, Anne M.; Nixon, Douglas F.; Liao, Wilson

2012-01-01

An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis. PMID:22577363

Caracterización socioeconómica y ambiental de la producción de café orgánico en el Perú

OpenAIRE

TUDELA MAMANI, JUAN WALTER; UNIVERSIDAD NACIONAL DEL ALTIPLANO

2015-01-01

El presente estudio identifica los elementos que hacen que un productor de café en el Perú, produzca de forma orgánica. Así a través de modelos logit y probit se identifican los determinantes sociales, económicos y ambientales. Se utiliza información del IV Censo Nacional Agropecuario – 2012. Los productores con mayor experiencia en el cultivo del café, los hombres, los más educados, los que participan en asociaciones, comités o cooperativas, los que tienen mayor superficie sembrada de café, ...

Emoções, sensações e afeições do consumidor brasileiro pelo café

OpenAIRE

Emilia Alice Fonseca Ricardi

2016-01-01

Resumo: O café é um dos produtos de consumo mais relevante para o Brasil, o maior produtor mundial, e onde está presente em 95% dos lares. Hoje é considerado um mercado em transformação, com consumidores que estão ampliando a experimentação e valorizando produtos de melhor qualidade. Este cenário destaca a importância de entender as preferências do consumidor e avaliar a qualidade de cafés brasileiros. O presente estudo teve, primeiramente, o objetivo de desenvolver um glossário de termos de ...

Plan de mercadeo Café Castillo de Wandra

OpenAIRE

Jaramillo Peña, Omar Darío

2015-01-01

Café Castillo de Wandra es el resultado que se obtuvo al buscar una buena forma para mejorar los ingresos en la finca Santana del municipio de Támesis (Antioquia), a partir de agregarle valor al grano producido en ella -- Para poder cumplir los objetivos de ventas e ingresos, es necesario elaborar un plan de mercadeo ejecutable a un año que contenga todas las variables del mix de mercadeo y que permita que el producto tenga un posicionamiento estratégico dentro de su mercado objetivo -- El pl...

Caféiculture : il faut veiller au grain | IDRC - International ...

International Development Research Centre (IDRC) Digital Library (Canada)

31 janv. 2011 ... Dans les années 1960, les tentatives visant à éliminer le cercle vicieux de la pauvreté dans lequel les caféiculteurs se trouvaient piégés ont donné naissance au mouvement en faveur du commerce équitable. Aujourd'hui, quelque 800 000 producteurs de plus de 45 pays travaillent en fonction des normes ...

Broadening of the T-cell repertoire to HIV-1 Gag p24 by vaccination of HLA-A2/DR transgenic mice with overlapping peptides in the CAF05 adjuvant

DEFF Research Database (Denmark)

Korsholm, Karen S; Karlsson, Ingrid; Tang, Sheila T

2013-01-01

Induction of broad T-cell immune responses is regarded as critical for vaccines against the human immunodeficiency virus type 1 (HIV-1) which exhibit high diversity and, therefore, focus has been on inducing cytotoxic CD8 T-cell responses against the more conserved parts of the virus, such as the....../DR-transgenic mouse model. Thus, combining overlapping Gag p24 peptides with CAF05 appears to be a promising and simple strategy for inducing broader T-cell responses to multiple conserved epitopes which will be relevant for both prophylactic and therapeutic HIV-1 vaccines....

Germline-specific H1 variants: the "sexy" linker histones.

Science.gov (United States)

Pérez-Montero, Salvador; Carbonell, Albert; Azorín, Fernando

2016-03-01

The eukaryotic genome is packed into chromatin, a nucleoprotein complex mainly formed by the interaction of DNA with the abundant basic histone proteins. The fundamental structural and functional subunit of chromatin is the nucleosome core particle, which is composed by 146 bp of DNA wrapped around an octameric protein complex formed by two copies of each core histone H2A, H2B, H3, and H4. In addition, although not an intrinsic component of the nucleosome core particle, linker histone H1 directly interacts with it in a monomeric form. Histone H1 binds nucleosomes near the exit/entry sites of linker DNA, determines nucleosome repeat length and stabilizes higher-order organization of nucleosomes into the ∼30 nm chromatin fiber. In comparison to core histones, histone H1 is less well conserved through evolution. Furthermore, histone H1 composition in metazoans is generally complex with most species containing multiple variants that play redundant as well as specific functions. In this regard, a characteristic feature is the presence of specific H1 variants that replace somatic H1s in the germline and during early embryogenesis. In this review, we summarize our current knowledge about their structural and functional properties.

Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

Science.gov (United States)

Freedman, B I; Julian, B A; Pastan, S O; Israni, A K; Schladt, D; Gautreaux, M D; Hauptfeld, V; Bray, R A; Gebel, H M; Kirk, A D; Gaston, R S; Rogers, J; Farney, A C; Orlando, G; Stratta, R J; Mohan, S; Ma, L; Langefeld, C D; Hicks, P J; Palmer, N D; Adams, P L; Palanisamy, A; Reeves-Daniel, A M; Divers, J

2015-06-01

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Highly aqueous soluble CaF2:Ce/Tb nanocrystals: effect of surface functionalization on structural, optical band gap, and photoluminescence properties.

Science.gov (United States)

Ansari, Anees A; Parchur, Abdul K; Kumar, Brijesh; Rai, S B

2016-12-01

The design of nanostructured materials with highly stable water-dispersion and luminescence efficiency is an important concern in nanotechnology and nanomedicine. In this paper, we described the synthesis and distinct surface modification on the morphological structure and optical (optical absorption, band gap energy, excitation, emission, decay time, etc.) properties of highly crystalline water-dispersible CaF 2 :Ce/Tb nanocrystals (core-nanocrystals). The epitaxial growth of inert CaF 2 and silica shell, respectively, on their surface forming as CaF 2 :Ce/Tb@CaF 2 (core/shell) and CaF 2 :Ce/Tb@CaF 2 @SiO 2 (core/shell/SiO 2 ) nanoarchitecture. X-ray diffraction and transmission electron microscope image shows that the nanocrystals were in irregular spherical phase, highly crystalline (~20 nm) with narrow size distribution. The core/shell nanocrystals confirm that the surface coating is responsible in the change of symmetrical nanostructure, which was determined from the band gap energy and luminescent properties. It was found that an inert inorganic shell formation effectively enhances the luminescence efficiency and silica shell makes the nanocrystals highly water-dispersible. In addition, Ce 3+ /Tb 3+ -co-doped CaF 2 nanocrystals show efficient energy transfer from Ce 3+ to Tb 3+ ion and strong green luminescence of Tb 3+ ion at 541 nm( 5 D 4 → 7 F 5 ). Luminescence decay curves of core and core/shell nanocrystals were fitted using mono and biexponential equations, and R 2 regression coefficient criteria were used to discriminate the goodness of the fitted model. The lifetime values for the core/shell nanocrystals are higher than core-nanocrystals. Considering the high stable water-dispersion and intensive luminescence emission in the visible region, these luminescent core/shell nanocrystals could be potential candidates for luminescent bio-imaging, optical bio-probe, displays, staining, and multianalyte optical sensing. A newly designed CaF 2 :Ce

Common nonsynonymous variants in PCSK1 confer risk of obesity

DEFF Research Database (Denmark)

Benzinou, Michael; Creemers, John W M; Choquet, Helene

2008-01-01

Mutations in PCSK1 cause monogenic obesity. To assess the contribution of PCSK1 to polygenic obesity risk, we genotyped tag SNPs in a total of 13,659 individuals of European ancestry from eight independent case-control or family-based cohorts. The nonsynonymous variants rs6232, encoding N221D...

Phenotypes and genotypes in individuals with SMC1A variants

DEFF Research Database (Denmark)

Huisman, Sylvia; Mulder, Paul A; Redeker, Egbert

2017-01-01

, stereotypic movements, and (in some) regression. Their missense, nonsense, and frameshift mutations are evenly spread over the gene. We conclude that SMC1A variants can result in a phenotype resembling CdLS and a phenotype resembling Rett syndrome. Resemblances between the SMC1A group and the NIPBL group...

HbA1c levels in individuals heterozygous for hemoglobin variants.

Science.gov (United States)

Tavares, Ricardo Silva; Souza, Fábio Oliveira de; Francescantonio, Isabel Cristina Carvalho Medeiros; Soares, Weslley Carvalho; Mesquita, Mauro Meira

2017-04-01

To evaluate the levels of glycated hemoglobin (HbA1c) in patients heterozygous for hemoglobin variants and compare the results of this test with those of a control group. This was an experimental study based on the comparison of HbA1c tests in two different populations, with a test group represented by individuals heterozygous for hemoglobin variants (AS and AC) and a control group consisting of people with electrophoretic profile AA. The two populations were required to meet the following inclusion criteria: Normal levels of fasting glucose, hemoglobin, urea and triglycerides, bilirubin > 20 mg/dL and non-use of acetylsalicylic acid. 50 heterozygous subjects and 50 controls were evaluated between August 2013 and May 2014. The comparison of HbA1c levels between heterozygous individuals and control subjects was performed based on standard deviation, mean and G-Test. The study assessed a test group and a control group, both with 39 adults and 11 children. The mean among heterozygous adults for HbA1c was 5.0%, while the control group showed a rate of 5.74%. Heterozygous children presented mean HbA1c at 5.11%, while the controls were at 5.78%. G-Test yielded p=0.93 for children and p=0.89 for adults. Our study evaluated HbA1c using ion exchange chromatography resins, and the patients heterozygous for hemoglobin variants showed no significant difference from the control group.

[Approach to diagnosis and management of myeloproliferative neoplasm variants].

Science.gov (United States)

Mitsumori, Toru; Kirito, Keita

2015-08-01

Myeloproliferative neoplasm (MPN) variants are defined as relatively uncommon myeloid neoplasms which do not meet the criteria for either classical MPN or myelodysplastic syndrome. Due to the lack of specific markers, it has been challenging to accurately diagnose these malignant diseases. Recent studies have revealed new genetic abnormalities in MPN variants. These research advances are anticipated to open new approaches to not only achieving accurate diagnosis but also novel therapeutic options for these diseases.

Assessment of polymorphic variants in the melanocortin-1 receptor gene with cutaneous pigmentation using an evolutionary approach.

Science.gov (United States)

Kanetsky, Peter A; Ge, Fan; Najarian, Derek; Swoyer, Jennifer; Panossian, Saarene; Schuchter, Lynn; Holmes, Robin; Guerry, DuPont; Rebbeck, Timothy R

2004-05-01

The melanocortin-1 receptor gene (MC1R) encodes a membrane-bound receptor protein that is central to melanin synthesis. The coding region of MC1R is highly polymorphic and associations of variants with pigmentation phenotypes and risk for cutaneous neoplasms have been reported. We sought to determine the distribution and frequency of MC1R variants and their relationship to pigmentation characteristics in 179 Caucasian controls from the United States. One hundred thirty-five (75.4%) subjects carried one or more variants, and we determined that carriage of the previously designated "red hair color" (RHC) alleles, R151C, R160W, and D294H was strongly associated with fair pigmentation phenotypes including light hair and eye color, tendency to burn, decreased tendency to tan, and freckling. We used SIFT software to define MC1R protein positions that were predicted intolerant to amino acid substitutions; detected variants that corresponded to intolerant substitutions were D84E, R142H, R151C, I155T, R160W, and D294H. Carriage of one or more of these putative functionally important variants or the frameshift variant ins86A was significantly associated with fair pigmentation phenotypes. Analyses limited to carriage of ins86A and the three non-RHC alleles identified by SIFT were attenuated and no longer reached statistical significance. This is the first study to describe MC1R variants among control subjects from the U.S. Our results indicate that the frequency of variants is similar to that previously observed among non-U.S. Caucasians. Risk variants defined by either the published literature or by evolutionary criteria are strongly and significantly associated with all fair pigmentation phenotypes that were measured.

Diseño y Construcción de un Transportador Mecánico de Café Cereza por Cable Aéreo

Directory of Open Access Journals (Sweden)

Patiño Valencia Fernando

1994-09-01

Full Text Available Debido a que la zona cafetera colombiana es de difícil topografía, el transporte del café desde las plantaciones hasta el beneficiadero se hace complicado y requiere de la utilización de animales de carga, fuerza humana y/o vehículos para trasladar por medios mecánicos el café cereza recién cosechado, se diseñó y construyó un transportador en el Centro Nacional de Investigaciones de café “CENICAFE” ubicado en el municipio de Chinchiná (Caldas, empleando un cable aéreo, proyectado para que enviara el café cereza a granel desde el sitio de cargue (parte baja del terreno hasta el sitio de descargue (parte alta localizada en el beneficiadero experimental . El medio de tracción es un cable tractor "abierto" unido por un extremo al lomo de fuerza motriz y por el otro a la carga. Se aprovechó la pendiente del terreno para enviar, por gravedad, la vagoneta al lugar de cargue. El control de velocidad de descenso se hizo a través del freno del malacate El transportador se diseñó para superar pendientes del 30 % con una carga total de 300 kg (24 @, de los cuales 175 kg (14 @ corresponden al peso del café cereza y los 125 kg (10 @ restantes al peso de la vagoneta. La longitud de recorrido del transportador es de 180 m y la velocidad de traslación de la vagoneta cargada es de 1.3 m.s2 El ciclo completo de cargue y descargue del material es de unos 400 s; por lo tanto, la capacidad del transportador es de 1.6 * 10 kg.h^-1 Las características topográficas del terreno y el espacio disponible, hicieron necesario orientar el cable aéreo portante en tres sentidos, con pendientes y tramos diferentes. Se identificó el cable aéreo como el elemento principal del estudio, razón por la cual se determinaron las tensiones y desplazamientos en el mismo utilizando para ello un programa desarrollado durante el trabajo (programa "CABLE. BAS " . Con base en los resultados obtenidos, fueron dimensionados los elementos principales

Inhibitory activity and conformational transition of alpha 1-proteinase inhibitor variants

NARCIS (Netherlands)

Schulze, A.J.; Huber, R.; Degryse, E.; Speck, D.; Bischoff, Rainer

1991-01-01

Several variants of alpha 1-proteinase inhibitor (alpha 1-PI) were investigated by spectroscopic methods and characterized according to their inhibitory activity. Replacement of Thr345 (P14) with Arg in alpha 1-PI containing an Arg residue in position 358 (yielding [Thr345----Arg,

Three types of preS1 start codon deletion variants in the natural course of chronic hepatitis B infection.

Science.gov (United States)

Choe, Won Hyeok; Kim, Hong; Lee, So-Young; Choi, Yu-Min; Kwon, So Young; Moon, Hee Won; Hur, Mina; Kim, Bum-Joon

2017-12-12

Naturally occurring hepatitis B virus variants carrying a deletion in the preS1 start codon region may evolve during long-lasting virus-host interactions in chronic hepatitis B (CHB). The aim of this study was to determine the immune phase-specific prevalent patterns of preS1 start codon deletion variants and related factors during the natural course of CHB. A total of 399 CHB patients were enrolled. Genotypic analysis of three different preS1 start codon deletion variants (classified by deletion size: 15-base pair [bp], 18-bp, and 21-bp deletion variants) was performed. PreS1 start codon deletion variants were detected in 155 of 399 patients (38.8%). The predominant variant was a 15-bp deletion in the immune-tolerance phase (18/50, 36%) and an 18-bp deletion in the immune-clearance phase (69/183, 37.7%). A 21-bp deletion was the predominant variant in the low replicative phase (3/25, 12.0%) and reactivated hepatitis Be antigen (HBeAg)-negative phase (22/141, 15.6%). The 15-bp and 18-bp deletion variants were more frequently found in HBeAg-positive patients (P start codon deletion variants changes according to the immune phases of CHB infection, and each variant type is associated with different clinical parameters. PreS1 start codon deletion variants might interact with the host immune response differently according to their variant types. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Pan-cancer analysis reveals technical artifacts in TCGA germline variant calls.

Science.gov (United States)

Buckley, Alexandra R; Standish, Kristopher A; Bhutani, Kunal; Ideker, Trey; Lasken, Roger S; Carter, Hannah; Harismendy, Olivier; Schork, Nicholas J

2017-06-12

Cancer research to date has largely focused on somatically acquired genetic aberrations. In contrast, the degree to which germline, or inherited, variation contributes to tumorigenesis remains unclear, possibly due to a lack of accessible germline variant data. Here we called germline variants on 9618 cases from The Cancer Genome Atlas (TCGA) database representing 31 cancer types. We identified batch effects affecting loss of function (LOF) variant calls that can be traced back to differences in the way the sequence data were generated both within and across cancer types. Overall, LOF indel calls were more sensitive to technical artifacts than LOF Single Nucleotide Variant (SNV) calls. In particular, whole genome amplification of DNA prior to sequencing led to an artificially increased burden of LOF indel calls, which confounded association analyses relating germline variants to tumor type despite stringent indel filtering strategies. The samples affected by these technical artifacts include all acute myeloid leukemia and practically all ovarian cancer samples. We demonstrate how technical artifacts induced by whole genome amplification of DNA can lead to false positive germline-tumor type associations and suggest TCGA whole genome amplified samples be used with caution. This study draws attention to the need to be sensitive to problems associated with a lack of uniformity in data generation in TCGA data.

Efectos del mercado desregulado sobre los campesinos productores de café de Los Altos de Chiapas: el caso de UCIPA

Directory of Open Access Journals (Sweden)

Eliezer Fernando Pérez Pérez

2018-01-01

Full Text Available Se analizan las consecuencias del mercado desregulado sobre la producción y la comercialización del café de los campesinos agrupados en la Unión de Comunidades Indígenas de Producción Agrícola Santa Catarina Pantelhó (UCIPA, en la región Altos de Chiapas, quienes desde 2000, contra la lógica de las organizaciones de café orgánico, incursionaron en el mercado del café convencional. Se reflexiona sobre el presente y las perspectivas en una economía basada en la racionalidad neoliberal, sin regulación del Estado. Destacan las estrategias de los productores para sortear las dificultades de las relaciones de mercado y los efectos del cambio climático.

Molecular Evolution of the VP1 Gene in Human Norovirus GII.4 Variants in 1974–2015

Directory of Open Access Journals (Sweden)

Takumi Motoya

2017-12-01

Full Text Available Human norovirus (HuNoV is a leading cause of viral gastroenteritis worldwide, of which GII.4 is the most predominant genotype. Unlike other genotypes, GII.4 has created various variants that escaped from previously acquired immunity of the host and caused repeated epidemics. However, the molecular evolutionary differences among all GII.4 variants, including recently discovered strains, have not been elucidated. Thus, we conducted a series of bioinformatic analyses using numerous, globally collected, full-length GII.4 major capsid (VP1 gene sequences (466 strains to compare the evolutionary patterns among GII.4 variants. The time-scaled phylogenetic tree constructed using the Bayesian Markov chain Monte Carlo (MCMC method showed that the common ancestor of the GII.4 VP1 gene diverged from GII.20 in 1840. The GII.4 genotype emerged in 1932, and then formed seven clusters including 14 known variants after 1980. The evolutionary rate of GII.4 strains was estimated to be 7.68 × 10−3 substitutions/site/year. The evolutionary rates probably differed among variants as well as domains [protruding 1 (P1, shell, and P2 domains]. The Osaka 2007 variant strains probably contained more nucleotide substitutions than any other variant. Few conformational epitopes were located in the shell and P1 domains, although most were contained in the P2 domain, which, as previously established, is associated with attachment to host factors and antigenicity. We found that positive selection sites for the whole GII.4 genotype existed in the shell and P1 domains, while Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants were under positive selection in the P2 domain. Amino acid substitutions overlapped with putative epitopes or were located around the epitopes in the P2 domain. The effective population sizes of the present strains increased stepwise for Den Haag 2006b, New Orleans 2009, and Sydney 2012 variants. These results suggest that HuNoV GII.4 rapidly

Rare genetic variants in the endocannabinoid system genes CNR1 and DAGLA are associated with neurological phenotypes in humans.

Directory of Open Access Journals (Sweden)

Douglas R Smith

Full Text Available Rare genetic variants in the core endocannabinoid system genes CNR1, CNR2, DAGLA, MGLL and FAAH were identified in molecular testing data from 6,032 patients with a broad spectrum of neurological disorders. The variants were evaluated for association with phenotypes similar to those observed in the orthologous gene knockouts in mice. Heterozygous rare coding variants in CNR1, which encodes the type 1 cannabinoid receptor (CB1, were found to be significantly associated with pain sensitivity (especially migraine, sleep and memory disorders-alone or in combination with anxiety-compared to a set of controls without such CNR1 variants. Similarly, heterozygous rare variants in DAGLA, which encodes diacylglycerol lipase alpha, were found to be significantly associated with seizures and neurodevelopmental disorders, including autism and abnormalities of brain morphology, compared to controls. Rare variants in MGLL, FAAH and CNR2 were not associated with any neurological phenotypes in the patients tested. Diacylglycerol lipase alpha synthesizes the endocannabinoid 2-AG in the brain, which interacts with CB1 receptors. The phenotypes associated with rare CNR1 variants are reminiscent of those implicated in the theory of clinical endocannabinoid deficiency syndrome. The severe phenotypes associated with rare DAGLA variants underscore the critical role of rapid 2-AG synthesis and the endocannabinoid system in regulating neurological function and development. Mapping of the variants to the 3D structure of the type 1 cannabinoid receptor, or primary structure of diacylglycerol lipase alpha, reveals clustering of variants in certain structural regions and is consistent with impacts to function.

Inter-individual Variability in CAF: A Case Study of Two Individuals and Two Pairs’ Written Productions

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Mahboobeh Saadat

2017-06-01

Full Text Available The present study tracked the development of general measures of complexity, accuracy and fluency (CAF, and specific measures of accuracy and complexity in the writings of two EFL learners writing individually, and those of two pairs of EFL learners writing in pairs within the framework of dynamic systems theory. The individuals and the pairs were similarly asked to do 7 tasks during a semester. The learners’ developmental pathways as well as the differences between individuals and pairs in terms of general and specific measures of CAF across the 7 tasks were depicted through graphs. Results indicated that the performance of learners in each of the measures was non-linear during the semester. Moreover, concerning general measures of CAF, learners writing individually outperformed in terms of fluency and complexity features. However, no clear distinction emerged in terms of general accuracy measures of their writings. Furthermore, development of general and specific accuracy measures in the writings was consistent. However, although it was found that the learners writing individually outperformed in terms of general measure of complexity, this developmental pattern was not evident in their performance in terms of specific complexity measures.

Deceased-Donor Apolipoprotein L1 Renal-Risk Variants Have Minimal Effects on Liver Transplant Outcomes.

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Casey R Dorr

Full Text Available Apolipoprotein L1 gene (APOL1 G1 and G2 renal-risk variants, common in populations with recent African ancestry, are strongly associated with non-diabetic nephropathy, end-stage kidney disease, and shorter allograft survival in deceased-donor kidneys (autosomal recessive inheritance. Circulating APOL1 protein is synthesized primarily in the liver and hydrodynamic gene delivery of APOL1 G1 and G2 risk variants has caused hepatic necrosis in a murine model.To evaluate the impact of these variants in liver transplantation, this multicenter study investigated the association of APOL1 G1 and G2 alleles in deceased African American liver donors with allograft survival. Transplant recipients were followed for liver allograft survival using data from the Scientific Registry of Transplant Recipients.Of the 639 liver donors evaluated, 247 had no APOL1 risk allele, 300 had 1 risk allele, and 92 had 2 risk alleles. Graft failure assessed at 15 days, 6 months, 1 year and total was not significantly associated with donor APOL1 genotype (p-values = 0.25, 0.19, 0.67 and 0.89, respectively.In contrast to kidney transplantation, deceased-donor APOL1 G1 and G2 risk variants do not significantly impact outcomes in liver transplantation.

Consommation de caféine pendant la grossesse : retentissements maternels, foetaux, néonatals et infantiles

OpenAIRE

ALTIERI, Marie

2015-01-01

Introduction : La caféine, essentiellement présente dans le café, le thé, les boissons énergisantes, le cola, le cacao et certains médicaments, est la substance psychoactive la plus consommée pendant la grossesse. Elle traverse la barrière placentaire et présente une élimination ralentie chez la femme enceinte, le foetus et le nourrisson. Les études animales ont mis en évidence sa tératogénicité et sa toxicité pour la gestation et la santé des progénitures. Qu’en est-il du déroulement de la g...

The prevalence of PAI-1 4G/5G gene variant in Serbian population

Directory of Open Access Journals (Sweden)

Đorđević Valentina

2013-01-01

Full Text Available Introduction: Plasminogen activator inhibitor 1 (PAI-1 has a major role in inhibition of firinolysis and normal haemostasis. The presence of the PAI-1 4G/4G genotype leads to increased expression of PAI-1. High blood level of PAI-1 is associated with many diseases such as thrombosis, cerebral insult, myocardial infarction, pregnancy loss, preeclampsia, insulin resistance, type 2 diabetes, breast cancer and asthma. In this study, the prevalence of PAI-1 4G/5G gene variant was determined in healthy subjects from Serbian population. Methods: The study was carried out in a group of 210 healthy subjects (105 women and 105 men. The presence of PAI-1 4G/5G gene variant was detected by PCR-RFLP analysis. Results: The prevalence of PAI-1 4G/4G genotype was 34.76% and it was increased compared to PAI-1 5G/5G genotype (19.05%. The most frequent was PAI-1 4G/5G genotype (46.19%. Allelic frequency for 4G allele was higher (0.58 compared to 5G allele (0.42. Conclusions: The prevalence of PAI-1 4G/5G gene variant in Serbian population is similar to the neighboring populations. Results of this study represent the first data for Serbian population. This study could be useful for further research where the role of PAI-1 4G/5G gene variant will be assessed in the pathogenesis of many diseases.

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes

DEFF Research Database (Denmark)

Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav

2016-01-01

OBJECTIVE: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are...

Laser grade CaF2 with controllable properties: growing conditions and structural imperfection

International Nuclear Information System (INIS)

Mouchovski, J T; Temelkov, K A; Vuchkov, N K; Sabotinov, N V

2007-01-01

Optical properties of CaF 2 , grown by a controlled Bridgman-Stockbarger technique, are studied by CuBr and SrBr 2 vapour lasers. Absorption losses are determined as a function of the grown crystal volume, the crystallization front (CF), and the real crystallization rate. It is found that the absorption losses are relatively independent of the transmitted wavelengths in a wide spectral range from the deep ultraviolet (DUV) to the middle infrared (MIR) spectral region and their minimum corresponds to CF positions within the upper half of the adiabatic furnace zone, where the CR reaches a constant value slightly higher than the speed of crucible movement. The crystal quality conforms to laser grade CaF 2 for the DUV, visible and MIR spectral regions and may be controlled efficiently by introducing an appropriate systematic correction in the furnace temperature field, which shifts the CF position

Evaluation of a 5-tier scheme proposed for classification of sequence variants using bioinformatic and splicing assay data

DEFF Research Database (Denmark)

Walker, Logan C; Whiley, Phillip J; Houdayer, Claude

2013-01-01

BRCA1 and 176 BRCA2 unique variants, from 77 publications. At least six independent reviewers from research and/or clinical settings comprehensively examined splicing assay methods and data reported for 22 variant assays of 21 variants in four publications, and classified the variants using the 5-tier......Splicing assays are commonly undertaken in the clinical setting to assess the clinical relevance of sequence variants in disease predisposition genes. A 5-tier classification system incorporating both bioinformatic and splicing assay information was previously proposed as a method to provide...... of results, and the lack of quantitative data for the aberrant transcripts. We propose suggestions for minimum reporting guidelines for splicing assays, and improvements to the 5-tier splicing classification system to allow future evaluation of its performance as a clinical tool....

Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1.

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Philipp Harter

Full Text Available Identification of families at risk for ovarian cancer offers the opportunity to consider prophylactic surgery thus reducing ovarian cancer mortality. So far, identification of potentially affected families in Germany was solely performed via family history and numbers of affected family members with breast or ovarian cancer. However, neither the prevalence of deleterious variants in BRCA1/2 in ovarian cancer in Germany nor the reliability of family history as trigger for genetic counselling has ever been evaluated.Prospective counseling and germline testing of consecutive patients with primary diagnosis or with platinum-sensitive relapse of an invasive epithelial ovarian cancer. Testing included 25 candidate and established risk genes. Among these 25 genes, 16 genes (ATM, BRCA1, BRCA2, CDH1, CHEK2, MLH1, MSH2, MSH6, NBN, PMS2, PTEN, PALB2, RAD51C, RAD51D, STK11, TP53 were defined as established cancer risk genes. A positive family history was defined as at least one relative with breast cancer or ovarian cancer or breast cancer in personal history.In total, we analyzed 523 patients: 281 patients with primary diagnosis of ovarian cancer and 242 patients with relapsed disease. Median age at primary diagnosis was 58 years (range 16-93 and 406 patients (77.6% had a high-grade serous ovarian cancer. In total, 27.9% of the patients showed at least one deleterious variant in all 25 investigated genes and 26.4% in the defined 16 risk genes. Deleterious variants were most prevalent in the BRCA1 (15.5%, BRCA2 (5.5%, RAD51C (2.5% and PALB2 (1.1% genes. The prevalence of deleterious variants did not differ significantly between patients at primary diagnosis and relapse. The prevalence of deleterious variants in BRCA1/2 (and in all 16 risk genes in patients <60 years was 30.2% (33.2% versus 10.6% (18.9% in patients ≥60 years. Family history was positive in 43% of all patients. Patients with a positive family history had a prevalence of deleterious variants

Screening for coding variants in FTO and SH2B1 genes in Chinese patients with obesity.

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Zhaojing Zheng

Full Text Available To investigate potential functional variants in FTO and SH2B1 genes among Chinese children with obesity.Sanger sequencing of PCR products of all FTO and SH2B1 exons and their flanking regions were performed in 338 Chinese Han children with obesity and 221 age- and sex-matched lean controls.A total of seven and five rare non-synonymous variants were identified in FTO and SH2B1, respectively. The overall frequencies of FTO and SH2B1 rare non-synonymous variants were similar in obese and lean children (2.37% and 0.90% vs. 1.81% and 1.36%, P>0.05. However, four out of the seven variants in FTO were novel and all were unique to obese children (p>0.05. None of the novel variants was consistently being predicted to be deleterious. Four out of five variants in SH2B1 were novel and one was unique to obese children (p>0.05. One variant (L293R that was consistently being predicted as deleterious in SH2B1 gene was unique to lean control. While rare missense mutations were more frequently detected in girls from obesity as well as lean control than boys, the difference was not statistically significant. In addition, it's shown that the prevalence of rare missense mutations of FTO as well as SH2B1 was similar across different ethnic groups.The rare missense mutations of FTO and SH2B1 did not confer risks of obesity in Chinese Han children in our cohort.

Expression defect size among unclassified MLH1 variants determines pathogenicity in Lynch syndrome diagnosis

DEFF Research Database (Denmark)

Hinrichsen, Inga; Brieger, Angela; Trojan, Jörg

2013-01-01

Lynch syndrome is caused by a germline mutation in a mismatch repair gene, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants with unclear clinical significance. The functionality of these variants can be tested in the laboratory, but the results...

Geographical distribution of complement receptor type 1 variants and their associated disease risk.

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Thaisa Lucas Sandri

Full Text Available Pathogens exert selective pressure which may lead to substantial changes in host immune responses. The human complement receptor type 1 (CR1 is an innate immune recognition glycoprotein that regulates the activation of the complement pathway and removes opsonized immune complexes. CR1 genetic variants in exon 29 have been associated with expression levels, C1q or C3b binding and increased susceptibility to several infectious diseases. Five distinct CR1 nucleotide substitutions determine the Knops blood group phenotypes, namely Kna/b, McCa/b, Sl1/Sl2, Sl4/Sl5 and KCAM+/-.CR1 variants were genotyped by direct sequencing in a cohort of 441 healthy individuals from Brazil, Vietnam, India, Republic of Congo and Ghana.The distribution of the CR1 alleles, genotypes and haplotypes differed significantly among geographical settings (p≤0.001. CR1 variants rs17047660A/G (McCa/b and rs17047661A/G (Sl1/Sl2 were exclusively observed to be polymorphic in African populations compared to the groups from Asia and South-America, strongly suggesting that these two SNPs may be subjected to selection. This is further substantiated by a high linkage disequilibrium between the two variants in the Congolese and Ghanaian populations. A total of nine CR1 haplotypes were observed. The CR1*AGAATA haplotype was found more frequently among the Brazilian and Vietnamese study groups; the CR1*AGAATG haplotype was frequent in the Indian and Vietnamese populations, while the CR1*AGAGTG haplotype was frequent among Congolese and Ghanaian individuals.The African populations included in this study might have a selective advantage conferred to immune genes involved in pathogen recognition and signaling, possibly contributing to disease susceptibility or resistance.

Análise sensorial de diferentes marcas comerciais de café (Coffea arabica L.) orgânico

OpenAIRE

Silva,Aline Fonseca da; Minim,Valéria Paula Rodrigues; Ribeiro,Milene Moreira

2005-01-01

Produtos orgânicos são polêmicos quanto a sua qualidade sensorial. Neste estudo foi realizado um teste de aceitação em relação a um conjunto de atributos: cor, aroma, sabor e impressão global, no qual sessenta e seis consumidores avaliaram quatro amostras de café orgânico e uma amostra de café convencional de quatro diferentes marcas comerciais. Para a realização desse teste utilizou-se uma escala hedônica de nove pontos e os resultados obtidos foram avaliados por meio de Mapa de Preferência ...

Cationic liposomes formulated with synthetic mycobacterial cordfactor (CAF01: a versatile adjuvant for vaccines with different immunological requirements.

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Else Marie Agger

Full Text Available BACKGROUND: It is now emerging that for vaccines against a range of diseases including influenza, malaria and HIV, the induction of a humoral response is insufficient and a substantial complementary cell-mediated immune response is necessary for adequate protection. Furthermore, for some diseases such as tuberculosis, a cellular response seems to be the sole effector mechanism required for protection. The development of new adjuvants capable of inducing highly complex immune responses with strong antigen-specific T-cell responses in addition to antibodies is therefore urgently needed. METHODS AND FINDINGS: Herein, we describe a cationic adjuvant formulation (CAF01 consisting of DDA as a delivery vehicle and synthetic mycobacterial cordfactor as immunomodulator. CAF01 primes strong and complex immune responses and using ovalbumin as a model vaccine antigen in mice, antigen specific cell-mediated- and humoral responses were obtained at a level clearly above a range of currently used adjuvants (Aluminium, monophosphoryl lipid A, CFA/IFA, Montanide. This response occurs through Toll-like receptor 2, 3, 4 and 7-independent pathways whereas the response is partly reduced in MyD88-deficient mice. In three animal models of diseases with markedly different immunological requirement; Mycobacterium tuberculosis (cell-mediated, Chlamydia trachomatis (cell-mediated/humoral and malaria (humoral immunization with CAF01-based vaccines elicited significant protective immunity against challenge. CONCLUSION: CAF01 is potentially a suitable adjuvant for a wide range of diseases including targets requiring both CMI and humoral immune responses for protection.

Increased frequency of FBN1 truncating and splicing variants in Marfan syndrome patients with aortic events.

Science.gov (United States)

Baudhuin, Linnea M; Kotzer, Katrina E; Lagerstedt, Susan A

2015-03-01

Marfan syndrome is a systemic disorder that typically involves FBN1 mutations and cardiovascular manifestations. We investigated FBN1 genotype-phenotype correlations with aortic events (aortic dissection and prophylactic aortic surgery) in patients with Marfan syndrome. Genotype and phenotype information from probands (n = 179) with an FBN1 pathogenic or likely pathogenic variant were assessed. A higher frequency of truncating or splicing FBN1 variants was observed in Ghent criteria-positive patients with an aortic event (n = 34) as compared with all other probands (n = 145) without a reported aortic event (79 vs. 39%; P Marfan syndrome patients with FBN1 truncating and splicing variants.Genet Med 17 3, 177-187.

Furaldehyde substrate specificity and kinetics of Saccharomyces cerevisiae alcohol dehydrogenase 1 variants.

Science.gov (United States)

Laadan, Boaz; Wallace-Salinas, Valeria; Carlsson, Åsa Janfalk; Almeida, João Rm; Rådström, Peter; Gorwa-Grauslund, Marie F

2014-08-09

A previously discovered mutant of Saccharomyces cerevisiae alcohol dehydrogenase 1 (Adh1p) was shown to enable a unique NADH-dependent reduction of 5-hydroxymethylfurfural (HMF), a well-known inhibitor of yeast fermentation. In the present study, site-directed mutagenesis of both native and mutated ADH1 genes was performed in order to identify the key amino acids involved in this substrate shift, resulting in Adh1p-variants with different substrate specificities. In vitro activities of the Adh1p-variants using two furaldehydes, HMF and furfural, revealed that HMF reduction ability could be acquired after a single amino acid substitution (Y295C). The highest activity, however, was reached with the double mutation S110P Y295C. Kinetic characterization with both aldehydes and the in vivo primary substrate acetaldehyde also enabled to correlate the alterations in substrate affinity with the different amino acid substitutions. We demonstrated the key role of Y295C mutation in HMF reduction by Adh1p. We generated and kinetically characterized a group of protein variants using two furaldehyde compounds of industrial relevance. Also, we showed that there is a threshold after which higher in vitro HMF reduction activities do not correlate any more with faster in vivo rates of HMF conversion, indicating other cell limitations in the conversion of HMF.

Cultivo de la trucha café anádroma: una nueva alternativa para la diversificación de la salmonicultura nacional

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Nelson Colihueque

2015-03-01

Full Text Available Con el propósito de aportar información para contribuir al desarrollo del cultivo de la trucha café anádroma (Salmo trutta trutta en Chile, también llamada seatrout, en este trabajo se revisan los siguientes aspectos: i características genéticas y origen evolutivo de la trucha café naturalizada existente en el país, ii rendimiento reproductivo bajo condiciones de cautiverio, and iii eficiencia del proceso de esmoltificación, tasa de crecimiento y maduración sexual en agua dulce y agua de mar de la trucha café anádroma. Estos últimos parámetros son particularmente relevantes para una apropiada evaluación de su desempeño bajo condiciones de cultivo intensivo. El análisis de estos aspectos indica que las poblaciones naturalizadas de trucha café en Chile presentan un alto grado de variación genética, junto con un probable origen único (línea filogenética Atlántica, norte de Europa; éstas también presentan un rendimiento reproductivo óptimo, que excede aquel observado en otros salmónidos. Además, el proceso de esmoltificación de la trucha café anádroma es equivalente al observado en salmónidos totalmente anádromos, como el salmón del Atlántico y el salmón coho. Asimismo, con excepción de la maduración precoz, que es más alta que en el salmón del Atlántico, sobre todo en los machos, esta variedad también muestra una favorable tasa de crecimiento y sobrevivencia en agua de mar. Todos estos antecedentes indican que el cultivo de la trucha café anádroma es una alternativa interesante, con potencial para ser incorporada en la salmonicultura nacional.

A de novo variant in the ASPRV1 gene in a dog with ichthyosis.

Science.gov (United States)

Bauer, Anina; Waluk, Dominik P; Galichet, Arnaud; Timm, Katrin; Jagannathan, Vidhya; Sayar, Beyza S; Wiener, Dominique J; Dietschi, Elisabeth; Müller, Eliane J; Roosje, Petra; Welle, Monika M; Leeb, Tosso

2017-03-01

Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key player in the formation of the stratum corneum, the uppermost layer of the epidermis and therefore crucial for barrier function. During terminal differentiation of keratinocytes, the precursor profilaggrin is cleaved by several proteases into filaggrin monomers and eventually processed into free amino acids contributing to the hydration of the cornified layer. We studied a German Shepherd dog with a novel form of ichthyosis. Comparing the genome sequence of the affected dog with 288 genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding "aspartic peptidase, retroviral-like 1", which is also known as skin aspartic protease (SASPase). The variant was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro). ASPRV1 encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. By immunofluorescence staining we showed that the filaggrin expression pattern was altered in the affected dog. Thus, our findings provide strong evidence that the identified de novo variant is causative for the ichthyosis in the affected dog and that ASPRV1 plays an essential role in skin barrier formation. ASPRV1 is thus a novel candidate gene for unexplained human forms of ichthyoses.

A de novo variant in the ASPRV1 gene in a dog with ichthyosis.

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Anina Bauer

2017-03-01

Full Text Available Ichthyoses are a heterogeneous group of inherited cornification disorders characterized by generalized dry skin, scaling and/or hyperkeratosis. Ichthyosis vulgaris is the most common form of ichthyosis in humans and caused by genetic variants in the FLG gene encoding filaggrin. Filaggrin is a key player in the formation of the stratum corneum, the uppermost layer of the epidermis and therefore crucial for barrier function. During terminal differentiation of keratinocytes, the precursor profilaggrin is cleaved by several proteases into filaggrin monomers and eventually processed into free amino acids contributing to the hydration of the cornified layer. We studied a German Shepherd dog with a novel form of ichthyosis. Comparing the genome sequence of the affected dog with 288 genomes from genetically diverse non-affected dogs we identified a private heterozygous variant in the ASPRV1 gene encoding "aspartic peptidase, retroviral-like 1", which is also known as skin aspartic protease (SASPase. The variant was absent in both parents and therefore due to a de novo mutation event. It was a missense variant, c.1052T>C, affecting a conserved residue close to an autoprocessing cleavage site, p.(Leu351Pro. ASPRV1 encodes a retroviral-like protease involved in profilaggrin-to-filaggrin processing. By immunofluorescence staining we showed that the filaggrin expression pattern was altered in the affected dog. Thus, our findings provide strong evidence that the identified de novo variant is causative for the ichthyosis in the affected dog and that ASPRV1 plays an essential role in skin barrier formation. ASPRV1 is thus a novel candidate gene for unexplained human forms of ichthyoses.

PC-1 amino acid variant (K121Q) has no impact on progression of diabetic nephropathy in type 1 diabetic patients

DEFF Research Database (Denmark)

Jacobsen, Peter; Grarup, Niels; Tarnow, Lise

2002-01-01

Recently, an amino acid variant (K121Q) in the glycoprotein PC-1 (Q allele) has been associated with faster progression of diabetic nephropathy, as estimated by calculated creatinine clearance. We tested the impact of the PC-1 (K121Q) variant on loss of glomerular filtration rate (GFR) measured...

MSX1 gene variant - its presence in tooth absence - a case control genetic study.

Science.gov (United States)

Reddy, Naveen Admala; Adusumilli, Gopinath; Devanna, Raghu; Pichai, Saravanan; Rohra, Mayur Gobindram; Arjunan, Sharmila

2013-10-01

Non Syndromic tooth agenesis is a congenital anomaly with significant medical, psychological and social ramifications. There is sufficient evidence to hypothesize that locus for this condition can be identified by candidate genes. The aim of this study was to test whether MSX1 671 T>C gene variant was involved in etiology of Non Syndromic tooth agenesis in Raichur Patients. Blood samples were collected with informed consent from 50 subjects having Non Syndromic tooth agenesis and 50 controls. Genomic DNA was extracted from the blood samples, Polymerase Chain Reaction was performed (PCR) and Restriction Fragment Length Polymorphism (RFLP) was performed for digestion products that were evaluated. The RESULTS showed positive correlation between MSX1671 T>C gene variant and Non Syndromic tooth agenesis in Raichur Patients. MSX1 671 T>C gene variant may be a good screening marker for Non Syndromic tooth agenesis in Raichur Patients . How to cite this article:Reddy NA, Adusumilli G, Devanna R, Pichai S, Rohra MG, Arjunan S. Msx1 Gene Variant - Its Presence in Tooth Absence - A Case Control Genetic Study. J Int Oral Health 2013; 5(5):20-6.

Functional characterizations of rare UBA1 variants in X-linked Spinal Muscular Atrophy [version 1; referees: 2 approved

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Chris D. Balak

2017-09-01

Full Text Available Background: X-linked spinal muscular atrophy (XL-SMA results from mutations in the Ubiquitin-Like Modifier Activating Enzyme 1 (UBA1. Previously, four novel closely clustered mutations have been shown to cause this fatal infantile disorder affecting only males. These mutations, three missense and one synonymous, all lie within Exon15 of the UBA1 gene, which contains the active adenylation domain (AAD. Methods: In this study, our group characterized the three known missense variants in vitro. Using a novel Uba1 assay and other methods, we investigated Uba1 adenylation, thioester, and transthioesterification reactions in vitro to determine possible biochemical effects of the missense variants. Results: Our data revealed that only one of the three XL-SMA missense variants impairs the Ubiquitin-adenylating ability of Uba1. Additionally, these missense variants retained Ubiquitin thioester bond formation and transthioesterification rates equal to that found in the wild type. Conclusions: Our results demonstrate a surprising shift from the likelihood of these XL-SMA mutations playing a damaging role in Uba1’s enzymatic activity with Ubiquitin, to other roles such as altering UBA1 mRNA splicing via the disruption of splicing factor binding sites, similar to a mechanism in traditional SMA, or disrupting binding to other important in vivo binding partners.  These findings help to narrow the search for the areas of possible dysfunction in the Ubiquitin-proteasome pathway that ultimately result in XL-SMA. Moreover, this investigation provides additional critical understanding of the mutations’ biochemical mechanisms, vital for the development of future effective diagnostic assays and therapeutics.

Método Posible para la Comprobación de la Cáscara de Cacao en el Café Molido.

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Jaramillo Madariaga G.

1940-06-01

Full Text Available Un café sobre todo si se halla finamente molido, puede contener hasta un 30% de cáscara de cacao, sin que su aspecto físico haga aparente la adulteración. La prueba cualitativa de dicha adulteración sólo puede obtenerse mediante el microscopio, lo cual requiere bastante experiencia. La adición al café de 20% de cáscara de cacao, causa en los componentes anotados, variaciones tan pequeñas que, por lo general, se hallan dentro de los límites aceptados para cafés de distintas procedencias. El punto de partida de nuestra investigación ha sido la separación de la cáscara por gravedad. Entre las diversas soluciones ensayadas con tal fin, hallamos la de hiposulfito de sodio más conveniente, por la gran solubilidad de esta sal y por ser el hiposulfito un producto barato, fácil de obtener en cualquier parte.

Spatially selective Er/Yb-doped CaF2 crystal formation by CO2 laser exposure

International Nuclear Information System (INIS)

Kim, Dong-Seon; Lee, Jin-Ho; Lim, Ki-Soo

2014-01-01

Highlights: • Oxyfluoride glass–ceramics containing CaF 2 nanocrystals doped with Er 3+ and Yb 3+ ions were formed on the glass surface by CO 2 laser and a heat gun exposure. • Most of Er and Yb ions were distributed inside CaF 2 nanocrystals and fluorine loss was observed in the EDS element maps. • IR-to-VIS upconversion emission efficiency of laser annealed glass ceramics was much increased and compared with that of the furnace-annealed glass ceramics. • Distributed volume of the glass ceramics were estimated by a confocal fluorescence microscope imaging. - Abstract: We report the glass–ceramic precipitation on the oxyfluoride glass surface by spatially selective annealing with a CO 2 laser and a heat gun exposure. X-ray diffraction analysis showed the formation of major CaF 2 and miner Ca 2 SiO 4 nanoparticles. We observed ∼100 nm nanoparticle aggregation by tunneling electron microscopy and element distribution in glass and crystal phases. Spatial distribution of glass ceramics near the glass surface was probed by confocal fluorescence microscope by using much enhanced emission from the Er ions in the laser-treated area. Strong emissions at 365 nm excitation and visible up-conversion emissions at 980 nm excitation also indicated well incorporation of Er and Yb ions into a crystalline environment

Spatially selective Er/Yb-doped CaF2 crystal formation by CO2 laser exposure

International Nuclear Information System (INIS)

Kim, Dong-Seon; Lee, Jin-Ho; Lim, Ki-Soo

2015-01-01

Highlights: • Oxyfluoride glass–ceramics containing CaF 2 nanocrystals doped with Er 3+ and Yb 3+ ions were formed on the glass surface by CO 2 laser and a heat gun exposure. • Most of Er and Yb ions were distributed inside CaF 2 nanocrystals and fluorine loss was observed in the EDS element maps. • IR-to-VIS upconversion emission efficiency of laser annealed glass ceramics was much increased and compared with that of the furnace-annealed glass ceramics. • Distributed volume of the glass ceramics were estimated by a confocal fluorescence microscope imaging. - Abstract: We report the glass–ceramic precipitation on the oxyfluoride glass surface by spatially selective annealing with a CO 2 laser and a heat gun exposure. X-ray diffraction analysis showed the formation of major CaF 2 and miner Ca 2 SiO 4 nanoparticles. We observed ∼100 nm nanoparticle aggregation by tunneling electron microscopy and element distribution in glass and crystal phases. Spatial distribution of glass ceramics near the glass surface was probed by confocal fluorescence microscope by using much enhanced emission from the Er ions in the laser-treated area. Strong emissions at 365 nm excitation and visible up-conversion emissions at 980 nm excitation also indicated well incorporation of Er and Yb ions into a crystalline environment

Enriching Discovery Layers: A Product Comparison of Content Enrichment Services Syndetic Solutions and Content Café 2

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Allison DaSilva

2014-10-01

Full Text Available A comparative analysis of content enrichment services, Syndetic Solutions and Content Café 2, was undertaken to explore which service would provide public library users with a superior online search and discovery experience through the enriched data elements offered, specifically looking at the cover image data element and exploring what factors impact the display of said element. A data-set of 250 items in five different formats, including books, CDs, DVDs, e-books, and video games, was searched in four North American public libraries’ discovery layers to compare the integration, extent, and quality of the cover image data element supplied by Syndetic Solutions and Content Café 2. Based on an analysis of the URLs, ISBNs, and UPCs for each of the 250 items, it was determined that the integration, and therefore the display, of the cover image data element was impacted by: (1 whether or not an ISBN or UPC was listed in the MARC bibliographic record; (2 which ISBN or UPC was listed, as items could potentially have more than one; (3 the inclusion of both ISBNs and UPCs in the record and the settings of the discovery tool; (4 the order in which the ISBNs or UPCs were listed in the record; and (5 whether or not Syndetic Solutions or Content Café 2 had the image data in its database at the time of the search. The quality of the cover image displayed was found to be impacted by the size requested by the library and the size of the image provided by the publisher. These findings may also have implications for the integration of other enriched data elements.

Compostos bioativos e atividade antioxidante do café (Coffea arabica L. Coffee (Coffea arabica L. bioactive compounds and antioxidant activity

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Sheila Andrade Abrahão

2010-04-01

Full Text Available Conduziu-se este trabalho, com a proposta de avaliar o potencial antioxidante de dois padrões da bebida do café (rio e mole, verdes e torrados, utilizando modelos in vitro. Foram determinados o teor de fenólicos totais, ácido clorogênico (ácido 5-cafeoilquínico e cafeína das bebidas. A avaliação in vitro do potencial antioxidante foi investigada pelos métodos de captação do radical DPPH e pelo poder redutor de metais. Os dois padrões de bebida do café analisados não apresentaram diferenças quanto aos parâmetros cor, ácido clorogênico e cafeína. Observou-se que houve redução nos valores de ácido clorogênico à medida que os grãos foram torrados. O café verde bebida rio apresentou maior teor de fenólicos totais que o café bebida mole. Nos grãos torrados não foi observada diferença. A bebida do café independente da qualidade sensorial apresentou alto poder redutor e importante atividade sequestrante de radicais livres. A atividade sequestrante de radicais livres foi significativamente superior nas amostras obtidas a partir dos grãos torrados, quando comparados aos extratos dos grãos verdes. A torração, porém, reduziu o poder redutor das bebidas do café. Os dados obtidos permitem sugerir que, independente da classificação sensorial da bebida, o café apresenta expressiva capacidade sequestrante de radicais livres e poder redutor de metais.The present work intended to evaluate the antioxidant potential of two coffee sorts (soft and river, green and roasted, in vitro. Phenolic compounds content, chlorogenic acid (5-cafeoyolquinic and caffeine of the beverages were evaluated. In vitro evaluation of the antioxidant potential was investigated by DPPH radical scavenging assay and by reducing the power of metals. Both sorts of coffee did not present statistical differences for color, chlorogenic acid and caffeine. After roasting, 5-cafeoyolquinic acid levels decreased. River coffee beverage presented greater content

Protein structure and phenotypic analysis of pathogenic and population missense variants in STXBP1

OpenAIRE

Suri, Mohnish; Evers, Jochem M. G.; Laskowski, Roman A.; O'Brien, Sinead; Baker, Kate; Clayton‐Smith, Jill; Dabir, Tabib; Josifova, Dragana; Joss, Shelagh; Kerr, Bronwyn; Kraus, Alison; McEntagart, Meriel; Morton, Jenny; Smith, Audrey; Splitt, Miranda

2017-01-01

Abstract Background Syntaxin‐binding protein 1, encoded by STXBP1, is highly expressed in the brain and involved in fusing synaptic vesicles with the plasma membrane. Studies have shown that pathogenic loss‐of‐function variants in this gene result in various types of epilepsies, mostly beginning early in life. We were interested to model pathogenic missense variants on the protein structure to investigate the mechanism of pathogenicity and genotype–phenotype correlations. Methods We report 11...

Paenibacillus polymyxa PKB1 produces variants of polymyxin B-type antibiotics.

Science.gov (United States)

Shaheen, Mohamed; Li, Jingru; Ross, Avena C; Vederas, John C; Jensen, Susan E

2011-12-23

Polymyxins are cationic lipopeptide antibiotics active against many species of Gram-negative bacteria. We sequenced the gene cluster for polymyxin biosynthesis from Paenibacillus polymyxa PKB1. The 40.8 kb gene cluster comprises three nonribosomal peptide synthetase-encoding genes and two ABC transporter-like genes. Disruption of a peptide synthetase gene abolished all antibiotic production, whereas deletion of one or both transporter genes only reduced antibiotic production. Computational analysis of the peptide synthetase modules suggested that the enzyme system produces variant forms of polymyxin B (1 and 2), with D-2,4-diaminobutyrate instead of L-2,4-diaminobutyrate in amino acid position 3. Two antibacterial metabolites were resolved by HPLC and identified by high-resolution mass spectrometry and MS/MS sequencing as the expected variants 3 and 4 of polymyxin B(1) (1) and B(2) (2). Stereochemical analysis confirmed the presence of both D-2,4-diaminobutyrate and L-2,4-diaminobutyrate residues. Copyright © 2011 Elsevier Ltd. All rights reserved.

McCune Albright syndrome - association of fibrous dysplasia, café-au-lait skin spots and hyperthyroidism - case report.

Science.gov (United States)

Raus, Iulian; Coroiu, Roxana Elena

2016-01-01

McCune-Albright syndrome is a rare sporadic disease characterized by bone fibrous dysplasia, café-au-lait skin spots and a variable association of hyperfunctional endocrine disorders. Fibrous dysplasia (FD), which can involve the craniofacial, axial, and appendicular skeleton, may range from an isolated, asymptomatic monostotic lesion to a severe disabling polyostotic disease involving the entire skeleton. A twenty-five-year old male patient presented to our clinic with recently developed heart palpitations. He had also been feeling pain in the right femur since he was younger, without any trauma history, leading to difficulties of ambulation and limping occasionally. His physical examination revealed café-au-lait spots with irregular borders and right testicular agenesis. Laboratory findings identified hyperthyroidism with hyperparathyroidism. Radiographs of the pelvis revealed multiple lytic lesions of the right femur and magnetic resonance imaging (MRI) characterized these lesions as specific to fibrous dysplasia of the bone, without any insufficiency fracture at this level. The association of café-au-lait skin spots with bone fibrous dysplasia, and hyperthyroidism in this patient suggested the diagnosis of McCune - Albright syndrome.

Evaluating how variants of floristic quality assessment indicate wetland condition.

Science.gov (United States)

Kutcher, Thomas E; Forrester, Graham E

2018-03-28

Biological indicators are useful tools for the assessment of ecosystem condition. Multi-metric and multi-taxa indicators may respond to a broader range of disturbances than simpler indicators, but their complexity can make them difficult to interpret, which is critical to indicator utility for ecosystem management. Floristic Quality Assessment (FQA) is an example of a biological assessment approach that has been widely tested for indicating freshwater wetland condition, but less attention has been given to clarifying the factors controlling its response. FQA quantifies the aggregate of vascular plant species tolerance to habitat degradation (conservatism), and model variants have incorporated species richness, abundance, and indigenity (native or non-native). To assess bias, we tested FQA variants in open-canopy freshwater wetlands against three independent reference measures, using practical vegetation sampling methods. FQA variants incorporating species richness did not correlate with our reference measures and were influenced by wetland size and hydrogeomorphic class. In contrast, FQA variants lacking measures of species richness responded linearly to reference measures quantifying individual and aggregate stresses, suggesting a broad response to cumulative degradation. FQA variants incorporating non-native species, and a variant additionally incorporating relative species abundance, improved performance over using only native species. We relate our empirical findings to ecological theory to clarify the functional properties and implications of the FQA variants. Our analysis indicates that (1) aggregate conservatism reliably declines with increased disturbance; (2) species richness has varying relationships with disturbance and increases with site area, confounding FQA response; and (3) non-native species signal human disturbance. We propose that incorporating species abundance can improve FQA site-level relevance with little extra sampling effort. Using our

Evaluación de la conversión a café orgánico usando la metodología de opciones reales

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Gabriel Delgado Juárez

2013-01-01

Full Text Available A partir de la desregulación del mercado de café en 1989, las crisis de precios dan muestra de la incertidumbre y el riesgo alrededor de los ingresos de los productores de café, en especial para los pequeños productores mexicanos quienes han tomado acciones como convertir sus cultivos tradicionales hacia el sistema de producción orgánico, el cual -además de la importancia ecológica- les permite mayores ingresos que en el café convencional. En este trabajo se presenta como una opción real compuesta la transición en la conversión de un sistema a otro incluida la factibilidad de abandonar esa decisión estratégica.

Comparison of Ion Personal Genome Machine Platforms for the Detection of Variants in BRCA1 and BRCA2.

Science.gov (United States)

Hwang, Sang Mee; Lee, Ki Chan; Lee, Min Seob; Park, Kyoung Un

2018-01-01

Transition to next generation sequencing (NGS) for BRCA1 / BRCA2 analysis in clinical laboratories is ongoing but different platforms and/or data analysis pipelines give different results resulting in difficulties in implementation. We have evaluated the Ion Personal Genome Machine (PGM) Platforms (Ion PGM, Ion PGM Dx, Thermo Fisher Scientific) for the analysis of BRCA1 /2. The results of Ion PGM with OTG-snpcaller, a pipeline based on Torrent mapping alignment program and Genome Analysis Toolkit, from 75 clinical samples and 14 reference DNA samples were compared with Sanger sequencing for BRCA1 / BRCA2 . Ten clinical samples and 14 reference DNA samples were additionally sequenced by Ion PGM Dx with Torrent Suite. Fifty types of variants including 18 pathogenic or variants of unknown significance were identified from 75 clinical samples and known variants of the reference samples were confirmed by Sanger sequencing and/or NGS. One false-negative results were present for Ion PGM/OTG-snpcaller for an indel variant misidentified as a single nucleotide variant. However, eight discordant results were present for Ion PGM Dx/Torrent Suite with both false-positive and -negative results. A 40-bp deletion, a 4-bp deletion and a 1-bp deletion variant was not called and a false-positive deletion was identified. Four other variants were misidentified as another variant. Ion PGM/OTG-snpcaller showed acceptable performance with good concordance with Sanger sequencing. However, Ion PGM Dx/Torrent Suite showed many discrepant results not suitable for use in a clinical laboratory, requiring further optimization of the data analysis for calling variants.

HABP2 G534E Variant in Papillary Thyroid Carcinoma.

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Jerneja Tomsic

Full Text Available The main nonmedullary form of thyroid cancer is papillary thyroid carcinoma (PTC that accounts for 80-90% of all thyroid malignancies. Only 3-10% of PTC patients have a positive family history of PTC yet the familiality is one of the highest of all cancers as measured by case control studies. A handful of genes have been implicated accounting for a small fraction of this genetic predisposition. It was therefore of considerable interest that a mutation in the HABP2 gene was recently implicated in familial PTC. The present work was undertaken to examine the extent of HABP2 variant involvement in PTC. The HABP2 G534E variant (rs7080536 was genotyped in blood DNA from 179 PTC families (one affected individual per family, 1160 sporadic PTC cases and 1395 controls. RNA expression of HABP2 was tested by qPCR in RNA extracted from tumor and normal thyroid tissue from individuals that are homozygous wild-type or heterozygous for the variant. The variant was found to be present in 6.1% familial cases, 8.0% sporadic cases (2 individuals were homozygous for the variant and 8.7% controls. The variant did not segregate with PTC in one large and 6 smaller families in which it occurred. In keeping with data from the literature and databases the expression of HABP2 was highest in the liver, much lower in 3 other tested tissues (breast, kidney, brain but not found in thyroid. Given these results showing lack of any involvement we suggest that the putative role of variant HABP2 in PTC should be carefully scrutinized.

A Crohn's disease variant in Atg16l1 enhances its degradation by caspase 3

Science.gov (United States)

Murthy, Aditya; Li, Yun; Peng, Ivan; Reichelt, Mike; Katakam, Anand Kumar; Noubade, Rajkumar; Roose-Girma, Merone; Devoss, Jason; Diehl, Lauri; Graham, Robert R.; van Lookeren Campagne, Menno

2014-02-01

Crohn's disease is a debilitating inflammatory bowel disease (IBD) that can involve the entire digestive tract. A single-nucleotide polymorphism (SNP) encoding a missense variant in the autophagy gene ATG16L1 (rs2241880, Thr300Ala) is strongly associated with the incidence of Crohn's disease. Numerous studies have demonstrated the effect of ATG16L1 deletion or deficiency; however, the molecular consequences of the Thr300Ala (T300A) variant remains unknown. Here we show that amino acids 296-299 constitute a caspase cleavage motif in ATG16L1 and that the T300A variant (T316A in mice) significantly increases ATG16L1 sensitization to caspase-3-mediated processing. We observed that death-receptor activation or starvation-induced metabolic stress in human and murine macrophages increased degradation of the T300A or T316A variants of ATG16L1, respectively, resulting in diminished autophagy. Knock-in mice harbouring the T316A variant showed defective clearance of the ileal pathogen Yersinia enterocolitica and an elevated inflammatory cytokine response. In turn, deletion of the caspase-3-encoding gene, Casp3, or elimination of the caspase cleavage site by site-directed mutagenesis rescued starvation-induced autophagy and pathogen clearance, respectively. These findings demonstrate that caspase 3 activation in the presence of a common risk allele leads to accelerated degradation of ATG16L1, placing cellular stress, apoptotic stimuli and impaired autophagy in a unified pathway that predisposes to Crohn's disease.

The BRCA1 variant p.Ser36Tyr abrogates BRCA1 protein function and potentially confers a moderate risk of breast cancer.

Science.gov (United States)

Christou, Charita M; Hadjisavvas, Andreas; Kyratzi, Maria; Flouri, Christina; Neophytou, Ioanna; Anastasiadou, Violetta; Loizidou, Maria A; Kyriacou, Kyriacos

2014-01-01

The identification of variants of unknown clinical significance (VUS) in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02) in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.

The BRCA1 variant p.Ser36Tyr abrogates BRCA1 protein function and potentially confers a moderate risk of breast cancer.

Directory of Open Access Journals (Sweden)

Charita M Christou

Full Text Available The identification of variants of unknown clinical significance (VUS in the BRCA1 gene complicates genetic counselling and causes additional anxiety to carriers. In silico approaches currently used for VUS pathogenicity assessment are predictive and often produce conflicting data. Furthermore, functional assays are either domain or function specific, thus they do not examine the entire spectrum of BRCA1 functions and interpretation of individual assay results can be misleading. PolyPhen algorithm predicted that the BRCA1 p.Ser36Tyr VUS identified in the Cypriot population was damaging, whereas Align-GVGD predicted that it was possibly of no significance. In addition the BRCA1 p.Ser36Tyr variant was found to be associated with increased risk (OR = 3.47, 95% CI 1.13-10.67, P = 0.02 in a single case-control series of 1174 cases and 1109 controls. We describe a cellular system for examining the function of exogenous full-length BRCA1 and for classifying VUS. We achieved strong protein expression of full-length BRCA1 in transiently transfected HEK293T cells. The p.Ser36Tyr VUS exhibited low protein expression similar to the known pathogenic variant p.Cys61Gly. Co-precipitation analysis further demonstrated that it has a reduced ability to interact with BARD1. Further, co-precipitation analysis of nuclear and cytosolic extracts as well as immunofluorescence studies showed that a high proportion of the p.Ser36Tyr variant is withheld in the cytoplasm contrary to wild type protein. In addition the ability of p.Ser36Tyr to co-localize with conjugated ubiquitin foci in the nuclei of S-phase synchronized cells following genotoxic stress with hydroxyurea is impaired at more pronounced levels than that of the p.Cys61Gly pathogenic variant. The p.Ser36Tyr variant demonstrates abrogated function, and based on epidemiological, genetic, and clinical data we conclude that the p.Ser36Tyr variant is probably associated with a moderate breast cancer risk.

TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes.

Science.gov (United States)

Redondo, Maria J; Geyer, Susan; Steck, Andrea K; Sosenko, Jay; Anderson, Mark; Antinozzi, Peter; Michels, Aaron; Wentworth, John; Xu, Ping; Pugliese, Alberto

2018-02-01

The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 ( TCF7L2 ) single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis. We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data ( n = 810; median age 13.6 years; range 3.3-58.6). We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders. The rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], P = 0.024). Interaction analysis demonstrated that this association was only significant in participants ≥12 years old ( n = 504; OR 2.12 [1.29, 3.47], P = 0.003) but not younger ones ( n = 306, P = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) ( P = 0.008) and lower mean glucose AUC ( P = 0.0127). The results were similar for the rs7901695 SNP. In this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes-linked TCF7L2 variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms. © 2017 by the American Diabetes Association.

Intracavity Cr3+:LiCAF + PPSLT optical parametric oscillator with self-injection-locked pump wave

International Nuclear Information System (INIS)

Maestre, H; Torregrosa, A J; Capmany, J

2013-01-01

In this letter we present an intracavity pumped continuous wave (CW) doubly resonant optical parametric oscillator (OPO) based on Cr 3+ :LiCaAlF 6 (Cr:LiCAF) as the material generating the OPO pump wave and periodically poled stoichiometric lithium tantalate (PPSLT) as the nonlinear material. The OPO pump wave is spectrally narrowed and tuned by means of an external cavity, thus allowing self-injection locking of the OPO pump wavelength. When operated near degeneracy, the constructed OPO enables a fast tuning of the parametrically generated wavelengths in response to small perturbations of the phase-matching condition. The Cr:LiCAF emission band is especially well suited to provide dual-wavelength oscillation in the optical communications 1550 nm band as a result of the parametric oscillation in PPSLT. (letter)

Os fluxos, as relações e os agentes envolvidos na produção e comercialização do café produzido atualmente no Brasil

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Amanda Duarte Mergulhão

2017-09-01

Full Text Available A cultura secular da produção de café tem papel de destaque nas exportações brasileiras. As negociações dos preços nos mercados internacionais influenciam na escolha dos tipos de café a serem plantados, na possibilidade de ampliar ou não a industrialização do café verde para venda no mercado doméstico, na contratação de mão-de-obra para trabalhar nas plantações e na quantidade de estoques do grão. Atualmente, o consumo do café está em crescimento, mas a indústria decide a quantidade a ser produzida de acordo com os preços estimados e a quantidade do produto já disponível. Dentre as empresas torrefadoras se destacam grandes grupos econômicos, enquanto cooperativas, pequenos e médios produtores tem participação marcante na produção do café em grão nacional. Estudar estas e demais características presentes nas relações entre os agentes que participam do circuito espacial de produção do café são objetivos deste trabalho que é enriquecido com dados provenientes de diversas fontes oficiais.

Characterization of Transient Receptor Potential Vanilloid-1 (TRPV1) Variant Activation by Coal Fly Ash Particles and Associations with Altered Transient Receptor Potential Ankyrin-1 (TRPA1) Expression and Asthma.

Science.gov (United States)

Deering-Rice, Cassandra E; Stockmann, Chris; Romero, Erin G; Lu, Zhenyu; Shapiro, Darien; Stone, Bryan L; Fassl, Bernhard; Nkoy, Flory; Uchida, Derek A; Ward, Robert M; Veranth, John M; Reilly, Christopher A

2016-11-25

Transient receptor potential (TRP) channels are activated by environmental particulate materials. We hypothesized that polymorphic variants of transient receptor potential vanilloid-1 (TRPV1) would be uniquely responsive to insoluble coal fly ash compared with the prototypical soluble agonist capsaicin. Furthermore, these changes would manifest as differences in lung cell responses to these agonists and perhaps correlate with changes in asthma symptom control. The TRPV1-I315M and -T469I variants were more responsive to capsaicin and coal fly ash. The I585V variant was less responsive to coal fly ash particles due to reduced translation of protein and an apparent role for Ile-585 in activation by particles. In HEK-293 cells, I585V had an inhibitory effect on wild-type TRPV1 expression, activation, and internalization/agonist-induced desensitization. In normal human bronchial epithelial cells, IL-8 secretion in response to coal fly ash treatment was reduced for cells heterozygous for TRPV1-I585V. Finally, both the I315M and I585V variants were associated with worse asthma symptom control with the effects of I315M manifesting in mild asthma and those of the I585V variant manifesting in severe, steroid-insensitive individuals. This effect may be due in part to increased transient receptor potential ankyrin-1 (TRPA1) expression by lung epithelial cells expressing the TRPV1-I585V variant. These findings suggest that specific molecular interactions control TRPV1 activation by particles, differential activation, and desensitization of TRPV1 by particles and/or other agonists, and cellular changes in the expression of TRPA1 as a result of I585V expression could contribute to variations in asthma symptom control. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

A novel missense KIT mutation causing piebaldism in one Chinese family associated with café-au-lait macules and intertriginous freckling

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Jia WX

2015-04-01

Full Text Available Wei-Xue Jia,1,2 Xue-Min Xiao,1,2 Jian-Bing Wu,1,2 Yi-Ping Ma,1,2 Yi-Ping Ge,1,2 Qi Li,1,2 Qiu-Xia Mao,1,2 Cheng-Rang Li1,2 1Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China; 2Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, Jiangsu, China Abstract: Piebaldism is a rare autosomal dominant genodermatosis, manifesting as congenital and stable depigmentation of the skin and white forelock. It has been found to be associated with mutations in the KIT or SLUG genes. We report a Chinese piebaldism family including a 28-year-old woman and her 3-year-old son with characteristics of white patches and forelock associated with numerous brown macules and patches. Genomic DNA samples of the proband and her son were extracted from their peripheral blood. One hundred unrelated healthy individuals were used as controls. All coding regions of KIT, SLUG, and NF1 genes were amplified by polymerase chain reaction using exon flanking intronic primers and Sanger sequencings were performed. DNA sequencing revealed heterozygous missense c.2431T>G mutation in exon 17 of the KIT gene in the proband and the affected son. No potentially pathogenic variant was identified in SLUG or NF1 genes. The nucleotide substitution was not found in 100 unrelated control individuals. This study reveals a novel KIT mutation in piebaldism, and it further supports that café-au-lait macules and intertriginous freckling of piebaldism are parts of pigmented anomaly in piebaldism, which does not necessarily represent coexistence of neurofibromatosis type 1 (NF1. Keywords: novel mutation, KIT gene, neurofibromatosis type 1 

Fine mapping of genetic variants in BIN1, CLU, CR1 and PICALM for association with cerebrospinal fluid biomarkers for Alzheimer's disease

NARCIS (Netherlands)

Kauwe, John S. K.; Cruchaga, Carlos; Karch, Celeste M.; Sadler, Brooke; Lee, Mo; Mayo, Kevin; Latu, Wayne; Su'a, Manti; Fagan, Anne M.; Holtzman, David M.; Morris, John C.; Goate, Alison M.; Saradha, A.; Abdi, Hervé; Abeliovich, Asa; Abellan van Kan, Gabor; Abner, Erin; Acharya, Deepa; Adams, Nicholas; Adler, Daniel; Agrusti, Antonella; Agyemang, Alex; Ahdidan, Jamila; Ahn, Jae Eun; Aisen, Paul; Aksu, Yaman; Al-Akhras, Mousa; Alarcon, Marcelo; Alberca, Roman; Alexander, Gene; Alexander, Daniel; Almeida, Fabio; Amlien, Inge; Anand, Shyam; Andrew, Marilee; Angersbach, Steve; Anjum, Ayesha; Aoyama, Eiji; Arfanakis, Konstantinos; Armor, Tom; Arnold, Steven; Asatryan, Albert; Ashe-McNalley, Cody; Ashiga, Hirokazu; Assareh, Arezoo; Le Page, Aurelie; Avants, Brian; Avinash, Gopal; Awasthi, Sukrati; Ayan-Oshodi, Mosun; Babic, Tomislav; Baek, Young; Bagci, Ulas; Bai, Shuyang; Baird, Geoffrey; Baker, John; Banks, Sarah; Bard, Jonathan; Barnes, Josephine; Barret, Olivier; Bartlett, Jonathan; Bartzokis, George; Barua, Neil; Bauer, Corinna; Becker, James; Becker, J. Alex; Beckett, Laurel; Bednar, Martin; Beg, Mirza Faisal; Bek, Stephan; Belmokhtar, Nabil; Bernard, Charlotte; Bertram, Lars; Bhaskar, Uday; Biffi, Alessandro; Bigler, Erin; Bilgic, Basar; Bishop, Courtney; Bittner, Daniel; Black, Ronald; Blennow, Kaj; Bogorodzki, Piotr; Bokde, Arun; Bonner-Jackson, Aaron; Boppana, Madhu; Bourgeat, Pierrick; Bowes, Mike; Bowman, Gene; Braskie, Meredith; Braunewell, Karl; Breitner, Joihn; Brewer, James; Brickman, Adam; Britschgi, Markus; Broadbent, Steve; Brogren, Jacob; Brooks, David; Browndyke, Jeffrey; Brunton, Simon; Buchert, Ralph; Buchsbaum, Monte; Buckley, Chris; Buerger, Katharina; Burger, Cyrill; Burnham, Samantha; Burns, Jeffrey; Burton, David; Butman, John; Cabeza, Rafael; Cairns, Nigel; Callhoff, Johanna; Calvini, Piero; Cantillon, Marc; Capella, Heraldo; Cardona-Sanclemente, Luis Eduardo; Carle, Adam; Carmasin, Jeremy; Carranza-Ath, Fredy; Casabianca, Jodi; Casanova, Ramon; Cash, David; Cedarbaum, Jesse; Cella, Massimo; Celsis, Pierre; Chaney, Megan; Chanu, Pascal; Chao, Linda; Charil, Arnaud; Chemali, Zeina; Chen, Kewei; Chen, Minhua; Chen, Rong; Chen, Baojiang; Chen, Jake; Chen, Gennan; Chen, Wei; Cheng, Wei-Chen; Chertkow, Howard; Cheung, Charlton; Cheung, Vinci; Chiang, Gloria; Chiba, Koji; Chin, Simon; Chisholm, Jane; Cho, Youngsang; Choe, John; Choubey, Suresh; Christensen, Anette Luther; Clark, Chris; Clark, David; Clarkson, Matt; Clayton, David; Clunie, David; Coimbra, Alexandre; Compton, David; Coppola, Giovanni; Cover, Keith S.; Crane, Paul; Crans, Gerald; Croop, Robert; Crowther, Daniel; Crum, William; Cui, Yue; Curry, Charles; Curtis, Steven; Cutter, Gary; Daiello, Lori; Dake, Michael; Dale, Anders; Daliri, Mohammad Reza; Damato, Vito Domenico; Darby, Eveleen; Darkner, Sune; Davatzikos, Christos; Dave, Jay; David, Renaud; Davidson, Julie; de Bruijne, Marleen; de Meyer, Geert; de Nunzio, Giorgio; Decarli, Charles; Dechairo, Bryan; DeDuck, Kristina; Dehghan, Hossein; Dejkam, Arsalan; Delfino, Manuel; Dellavedova, Luca; Delpassand, Ebrahim; Delrieu, Julien; Deniz, Oscar; Denney, Douglas; DeOrchis, Vincent; Dépy Carron, Delphine; deToledo-Morrell, Leyla; Devanand, Davangere; Devanarayan, Viswanath; Diaz-Arrastia, Ramon; Dickerson, Bradford; Ding, Xiaobo; Dinov, Ivo; Dobson, Howard; Dodge, Hiroko; Donohue, Michael; Dore, Vincent; Dorflinger, Ernest; Dowling, Maritza; Duan, Xujun; Dubal, Dena; Duchesne, Simon; Duff, Kevin; Dukart, Jürgen; Durazzo, Timothy; Dykstra, Kevin; Earl, Nancy; Edula, Goutham; Ekin, Ahmet; Elcoroaristizabal, Xabier; Emahazion, Tesfai; Engelman, Corinne; Epstein, Noam; Erten-Lyons, Deniz; Eskildsen, Simon; Falcone, Guido; Fan, Yong; Fan, Lingzhong; Farb, Norman; Farnum, Michael; Farrer, Lindsay; Farzan, Ali; Faux, Noel; Feldman, Howard; Feldman, Susan; Fennema-Notestine, Christine; Fernandes, Michel; Fernandez, Elsa; Ferrarini, Luca; Ferreira, Manuel Joao; Ferrer, Eugene; Figurski, Michal; Filipovych, Roman; Fillit, Howard; Finch, Stephen; Finlay, Daniel; Fiot, Jean-Baptiste; Flenniken, Derek; Fletcher, P. Thomas; Fletcher, Evan; Flynn Longmire, Crystal; Focke, Niels; Forman, Mark; Forsythe, Alan; Fox, Steven; Fox-Bosetti, Sabrina; Francis, Alexander L.; Franco-Villalobos, Conrado; Franko, Edit; Freeman, Stefanie; Friedrich, Christoph M.; Friesenhahn, Michel; Frings, Lars; Frisoni, Giovanni; Fritzsche, Klaus; Fujimoto, Yoko; Fujiwara, Ken; Fullerton, Terence; Furney, Simon; Gallins, Paul; Gamst, Anthony; Gan, Ke; Garcia, Maria Teresa; Garg, Gaurav; Gaser, Christian; Gastineau, Edward; Gauthier, Serge; Gavett, Brandon; Gavidia, Giovana; Gazdzinski, Stefan; Ge, Qi; Gemme, Gianluca; Geraci, Joseph; German, Dwight; Ghassabi, Zeinab; Gieschke, Ronald; Gil, Juan E.; Gill, Ryan; Gitelman, Darren; Gleason, Carey; Godbey, Michael; Goghari, Vina; Gold, Michael; Goldberg, Terry; Gomeni, Roberto; Gong, Shangwenyan; Gonzales, Celedon; Goodro, Robert; Gordon, Brian; Gorriz, Juan Manuel; Grachev, Igor; Grandey, Emily; Grasela, Thaddeus; Gratt, Jeremy; Gray, Katherine; Greenberg, Barry; Gregg, Keith; Gregory, Erik; Greicius, Michael; Greve, Douglas; Grill, Joshua; Gross, Alden; Gross, Alan; Guignot, Isabelle; Guo, Qimiao; Guo, Hongbin; Guo, Lianghao; Guo, Jeffrey; Habeck, Christian; Hai, Yizhen; Haight, Thaddeus; Hammarstrom, Per; Hampel, Harald; Han, Jian; Han, Tony; Hanif, Muhammad; Hanna, Yousef; Hardy, Peter; Harvey, Danielle; Hasan, Md Kamrul; Hayashi, Toshihiro; Hazart, Aurelien; He, Huiguang; He, Yong; Head, Denise; Heckemann, Rolf; Heidebrink, Judith; Henderson, David; Henrard, Sébastien; Herholz, Karl; Hernandez, Monica; Herskovits, A. Zara; Hess, Christopher; Hildenbrand, Maike; Hobart, Jeremy; Hoffman, John; Holder, Daniel; Honigberg, Lee; Hoppin, Jack; Horsfield, Mark; Hou, Yangyang; Hsu, Ailing; Hsu, Wei-Wen; Hu, Zhiwei; Hu, Xiaolan; Hu, Zhenghui; Hu, William; Huang, Chien-Chih; Huang, Chingwen; Huang, Shuai; Huang, Yifan; Huang, Juebin; Huang, Chun-Jung; Huang, Shu-Pang; Huang, Fude; Hubbard, Rebecca; Huentelman, Matthew; Hui, Shen; Huppertz, Hans-Jürgen; Hurko, Orest; Hurt, Stephen; Huyck, Susan; Hwang, Scott; Hyun, JungMoon; Ifeachor, Emmanuel; Iglesias, Martina; Ikari, Yasuhiko; Ikonomidou, Vasiliki; Immermann, Fred; Inoue, Lurdes; Insel, Philip; Irizarry, Michael; Irungu, Benson mwangi; Ishibashi, Taro; Ishii, Kenji; Ismail, Sara; Ismail, Shahina; Ito, Kaori; Iturria-Medina, Yasser; Iwatsubo, Takeshi; Iyer, Madhumitha; Jacobson, Mark; Jafari, Aria; Jafari-Khouzani, Kourosh; Jaffe, Carl; Jagust, William; Jara, Hernan; Jasperse, Bas; Jedynak, Bruno; Jefferson, Angela; Jennings, J. Richard; Jessen, Walter; Jia, Fucang; Jiang, Tianzi; Jing, Huang; Johnson, David K.; Jones, Richard; Juengling, Freimut; Juh, Rahyeong; Julin, Per; Uday Bhaskar, K.; Kadish, Bill; Kahle-Wrobleski, Kristin; Kallam, Hanimi Reddy; Kamboh, M. Ilyas; Kaneko, Tomoki; Kaneta, Tomohiro; Karageorgiou, Elissaios; Karantzoulis, Stella; Karlawish, Jason; Katz, Elyse; Kaushik, Sandeep S.; Kauwe, John; Kawakami, Hirofumi; Kazimipoor, Borhan; Kelleher, Thomas; Kennedy, Richard; Kerr, Douglas; Kerrouche, Nacer; Khalil, Iya; Khalil, Andre; Killeen, Neil; Killiany, Ron; Kim, Ana; Kim, Yeonhee; Kim, Heeyoung; Kim, Jong Hun; Kim, Hyoungkyu; Kim, Seongkyun; Kim, Hyewon; Kimberg, Daniel; Kimura, Tokunori; King, Richard; Kirby, Justin; Kirsch, Wolff; Klimas, Michael; Kline, Richard; Kling, Mitchel; Klopfenstein, Erin; Kobayashi, Dione; Koikkalainen, Juha; Kokomoor, Anders; Kolasny, Anthony; Koppel, Jeremy; Korolev, Igor; Kotran, Nickolas; Kouassi, Alex; Kowalczyk, Adam; Kozma, Lynn; Kratzer, Martina; Kuceyeski, Amy; Kuhn, Félix Pierre; Kulkarni, Mauktik; Kumar, Sreedhar; Kuo, Hsun Ting; Kuo, Julie; Kurosawa, Ken; Kwon, Oh Hun; Laforet, Genevieve; Lai, Song; Lakatos, Anita; Lam, On Ki; Lampron, Antoine; Landau, Susan; Landen, Jaren; Lane, Richard; Langbaum, Jessica; Langford, Dianne; Lanius, Vivian; Lavault, Romain; Laxamana, Joel; Le, Trung; Leahy, Richard; Lee, Noah; Lee, Dongsoo; Lee, Vita; Lee, Joseph H.; Lee, Jong-Min; Lefkimmiatis, Stamatis; Lemaitre, Herve; Lenz, Robert; Lester, Gayle; Levey, Allan; Li, Wenjun; Li, Shanshan; Li, Xiaodong; Li, Gang; Li, Ming; Li, Chin-Shang; Li, Lexin; Li, Jinhe; Li, Quanzheng; Li, Yi; Li, Rui; Li, Shi-jiang; Liang, Peipeng; Liang, Lichen; Liang, Kuchang; Liao, Yuan-Lin; Lin, Ling-chih; Lin, Mingkuan; Lin, Ai-Ling; Lin, Lan; Liu, Tianming; Liu, Meijie; Liu, Tao; Liu, Li; Liu, Xiuwen; Liu, Sophia; Liu, Dazhong; Liu, Songling; Liu, Yuan; Liu, Pu; Lo, Raymond; Lobanov, Victor; Loewenstein, David; Logovinsky, Veronika; Long, Xiaojing; Long, Ziyi; Looi, Jeffrey; Lu, Po-Haong; Lukic, Ana; Lull, Juan J.; Luo, Xiongjian; Lynch, John; Ma, Lei; Mackin, Scott; Magda, Sebastian; Maglio, Silvio; Mak, Henry Ka-Fung; Malave, Vicente; Maldjian, Joseph; Mandal, Pravat; Mangin, Jean-Francois; Manjon, Jose; Manohar, Deepak; Mansouri, Chemseddine; Mantri, Ninad; Manzour, Amir; Marambaud, Philippe; Marchewka, Artur; Marek, Kenneth; Markind, Samuel; Marshall, Gad; Martinez Torteya, Antonio; Mather, Mara; Mathis, Chester; Matoug, Sofia; Matsuo, Yoshiyuki; Matthews, Dawn; McArdle, John; McEvoy, Linda; McGeown, William; McIntyre, John; McQuail, Joseph; Meadowcroft, Mark; Meda, Shashwath; Mehta, Nirav; Mendonca, Brian; Menendez, Manuel; Meredith, Jere; Merrill, David; Mesulam, Marek-Marsel; Metti, Andrea; Meyer, Carsten; Mez, Jesse; Mickael, Guedj; Miftahof, Roustem; Mikhno, Arthur; Miller, David; Millikin, Colleen; Min, Ye; Mirza, Mubeena; Mitsis, Effie; Mohan, Ananth; Montana, Giovanni; Moore, Dana; Moradi Birgani, Parmida; Moratal, David; Morimoto, Bruce; Mortamet, Bénédicte; Moscato, Pablo; Motyl, Rafal; Mueller, Kathyrne; Mueller, Susanne; Mueller, Notger; Mukherjee, Shubhabrata; Mulder, Emma; Murayama, Shigeo; Murphy, Michael; Murray, Brian; Musiek, Erik; Myers, Amanda; Najafi, Shahla; Nazarparvar, Babak; Nazeri, Arash; Nettiksimmons, Jasmine; Neu, Scott; Neves, Simone; Ng, Yen-Bee; Nguyen, Nghi; Nguyen Xuan, Tuong; Nicodemus, Kristin; Niecko, Timothy; Nielsen, Casper; Notomi, Keiji; Nuneez Benjumea, Francisco; O'Bryant, Sid; O'Neil, Alison; Obisesan, Thomas; Oh, Dong Hoon; Oh, Joonmi; Okonkwo, Ozioma; Olde Rikkert, Marcel; Olmos, Salvador; Ortner, Marion; Ostrowitzki, Susanne; Oswald, Annahita; Ott, Brian; Ourselin, Sebastien; Ouyang, Gaoxiang; Paiva, Renata; Pan, Zhifang; Pande, Yogesh; Pardo, Jose; Pardoe, Heath; Park, Hyunjin; Park, Moon Ho; Park, Sang hyun; Park, Kee Hyung; Park, Sujin; Parsey, Ramin; Parveen, Riswana; Paskavitz, James; Patel, Yogen; Patil, Manasi; Pawlak, Mikolaj; Payoux, Pierre; Pearson, Jim; Peavy, Guerry; Pell, Gaby; Peng, Yahong; Pennec, Xavier; Pepin, Jean louis; Perea, Rodrigo; Perneczky, Robert; Petitti, Diana; Petrella, Jeffrey; Peyrat, Jean-Marc; Pezoa, Jorge; Pham, Chi-Tuan; Phillips, Nicole; Pierson, Ronald; Piovezan, Mauro; Podhorski, Adam; Pollari, Mika; Pontecorvo, Michael; Poppenk, Jordan; Posner, Holly; Potkin, Steven; Potter, Elizabeth; Poulin, Stephane; Prasad, Gautam; Prenger, Kurt; Prince, Jerry; Priya, Anandh; Puchakayala, Shashidhar Reddy; Qiu, Anqi; Qiu, Ruolun; Qiu, Wendy; Qualls, Constance Dean; Rabie, Huwaida; Rajeesh, Rajeesh; Rallabandi, V. P. Subramanyam; Ramage, Amy; Randolph, Christopher; Rao, Anil; Rao, Divya; Raubertas, Richard; Ray, Debashis; Razak, Hana; Redolfi, Alberto; Reed, Bruce; Reid, Andrew; Reilhac, Anthonin; Reinsberger, Claus; Restrepo, Lucas; Retico, Alessandra; Rezaeitabar, Yousef; Richards, John; Richter, Mirco; Riddle, William; Ries, Michele; Rincón, Mariano; Rischall, Matt; Robieson, Weining; Rocha-Rego, Vanessa; Rogalski, Emily; Rogers, Elizabeth; Rojas, Ignacio; Rojas Balderrama, Javier; Romero, Klaus; Rorden, Chris; Rosand, Jonathan; Rosen, Allyson; Rosen, Ori; Rosenberg, Paul; Ross, David; Ross, Joel; Roubini, Eli; Rousseau, François; Rowe, Christopher; Rubin, Daniel; Rubright, Jonathan; Ruiz, Agustin; Rusinek, Henry; Ryan, Laurie; Saad, Ahmed; Sabbagh, Marway; Sabuncu, Mert; Sachs, Michael; Sacuiu, Simona; Sadeghi, Ali; Said, Yasmine; Saint-Aubert, Laure; Sakata, Muneyuki; Salat, David; Salmon, David; Salomi, Sharmila; Salter, Hugh; Samwald, Matthias; Sanchez, Luciano; Sanders, Elizabeth; Sanjo, Nobuo; Sarnel, Haldun; Sato, Shinji; Sato, Hajime; Saumier, Daniel; Savio, Alexandre; Sawada, Ikuhisa; Saykin, Andrew; Schaffer, J. David; Scharre, Douglas; Schegerin, Marc; Schlosser, Gretchen; Schmand, Ben; Schmansky, Nick; Schmidt, Mark; Schneider, Lon; Schramm, Hauke; Schuerch, Markus; Schwartz, Craig; Schwartz, Eben; Schwarz, Adam; Seethamraju, Ravi; Seixas, Flavio; Selnes, Per; Senjem, Matthew; Senlin, Wang; Seo, Sang Won; Sethuraman, Gopalan; Sevigny, Jeffrey; Sfikas, Giorgos; Sghedoni, Roberto; Shah, Said Khalid; Shahbaba, Babak; Shams, Soheil; Shattuck, David; Shaw, Leslie; Sheela, Jaba; Shen, Weijia; Shen, Qian; Shera, David; Sherman, John; Sherva, Richard; Shi, Feng; Shukla, Vinay; Shuler, Catherine; Shulman, Joshua; Siegel, Rene; Siemers, Eric; Silveira, Margarida; Silver, Michael; Silverman, Daniel; Sim, Ida; Simmons, Andy; Simoes, Rita; Simon, Melvin; Simpson, Ivor; Singh, Simer Preet; Singh, Nikhil; Siuciak, Judy; Sjögren, Niclas; Skup, Martha; Small, Gary; Smith, Michael; Smith, Charles; Smith, Benjamin; Smyth, Timothy; Snow, Sarah; Soares, Holly; Soldea, Octavian; Solomon, Alan; Solomon, Paul; Som, Subhojit; Song, Changhong; Song, Mingli; Sorensen, Greg; Soudah, Eduardo; Spampinato, Maria Vittoria; Spenger, Christian; Sperling, Reisa; Spiegel, René; Spies, Lothar; Squarcia, Sandro; Squire, Larry; Staff, Roger; Stern, Yaakov; Straw, Jack; Strittmatter, Stephen; Stühler, Elisabeth; Styren, Scot; Subramanian, Vijayalakshmi; Sugishita, Morihiro; Sukkar, Rafid; Sun, Ying; Sun, Yu; Sun, Jia; Sundell, Karen; Suri, Muhammad; Suzuki, Akiyuki; Svetnik, Vladimir; Swan, Melanie; Takahasi, Tetsuhiko; Takeuchi, Tomoko; Tanaka, Shoji; Tancredi, Daniel; Tang, Songyuan; Tao, Dacheng; Tao, Wenwen; Tariot, Pierre; Taylor-Reinwald, Lisa; Teng, Edmond; Terlizzi, Rita; Thiele, Frank; Thomas, Ronald; Thomas, Benjamin; Thompson, Paul; Thompson, Wesley; Thornton-Wells, Tricia; Thurfjell, Lennart; Titeux, Laurence; Tokuda, Takahiko; Toledo, Juan B.; Tolli, Tuomas; Toma, Ahmed; Tomita, Naoki; Toro, Roberto; Tosun, Duygu; Tousian, Mona; Toussaint, Paule; Toyoshiba, Hiroyoshi; Tractenberg, Rochelle E.; Trittschuh, Emily; Trojanowski, John; Truran, Diana; Tsechpenakis, Gavriil; Tucker-Drob, Elliot; Tufail, Ahsan; Tung, Joyce; Ueda, Yoji; Ullrich, Lauren; Umadevi Venkataraju, Kannan; Umar, Nisser; Uzunbas, Gokhan; van de Nes, Joseph; van der Brug, Marcel; van Horn, John; van Leemput, Koen; van Train, Kenneth; van Zeeland, Ashley; Vasanawala, Minal; Vemuri, Prashanthi; Verwaerde, Philippe; Videbaek, Charlotte; Vidoni, Eric; Vigneron, Vincent; Villanueva-Meyer, Javier; Visser, Pieter Jelle; Vitolo, Ottavio; Vounou, Maria; Wade, Sara; Walhovd, Kristine B.; Wan, Hong; Wang, Lubin; Wang, Xu; Wang, Ze; Wang, Angela; Wang, Tiger; Wang, Yongmei Michelle; Wang, Yaping; Wang, Wei; Wang, Huali; Wang, Yue; Wang, Li-San; Wang, Huanli; Wang, Alex; Wang, Yalin; Wang, Lei; Ward, Michael; Warfield, Simon; Waring, Stephen; Watanabe, Toshiyuki; Webb, David; Wei, Lili; Weiner, Michael; Wen, Shu-Hui; Wenjing, Li; Wenzel, Fabian; Westlye, Lars T.; Whitcher, Brandon; Whitlow, Christopher; Whitwell, Jennifer; Wilhelmsen, Kirk; Williams, David; Wilmot, Beth; Wingo, Thomas; Winkler, Andreas; Wiste, Heather; Wolfson, Tanya; Wolke, Ira; Wolz, Robin; Woo, Jongwook; Woo, Ellen; Woods, Lynn; Worth, Andrew; Worth, Eric; Wouters, Hans; Wu, Teresa; Wu, Ellen; Wu, Yi-Gen; Wu, Liang; Wu, Xiaoling; Wyman, Bradley; Wyss-Coray, Tony; Xiao, Liu; Xiao, Guanghua; Xie, Sharon; Xu, Jun; Xu, Ye; Xu, Yi-Zheng; Xu, Guofan; Yamane, Tomohiko; Yamashita, Fumio; Yan, Yunyi; Yan, Pingkun; Yang, Jinzhong; Yang, Qing X.; Yang, Zijiang; Yang, Guang; Yang, Wenlu; Yang, Eric; Yang, Zhitong; Ye, Jieping; Ye, Jong; Ye, Liang; Ye, Byoung Seok; Yee, Laura; Yesavage, Jerome; Ying, Song; Yoo, Bongin; Young, Jonathan; Yu, Dongchuan; Yu, Shiwei; Yuan, Kai; Yuan, Guihong; Yushkevich, Paul; Zaborszky, Laszlo; Zagorodnov, Vitali; Zagorski, Michael; Zawadzki, Rezi; Zeitzer, Jamie; Zhang, Huixiong; Zhang, Tianhao; Zhang, Ping; Zhang, Xin; Zhang, Bin; Zhang, Jing; Zhang, Linda; Zhang, Lijun; Zhang, Kurt; Zhao, Jim; Zhao, Peng; Zhao, Qinying; Zhen, Xiantong; Zheng, Yuanjie; Zhijun, Yao; Zhou, Sheng; Zhou, Bin; Zhu, Wanlin; Zhu, Hongtu; Zhu, Wen; Zito, Giancarlo; Zou, Heng

2011-01-01

Recent genome-wide association studies of Alzheimer's disease (AD) have identified variants in BIN1, CLU, CR1 and PICALM that show replicable association with risk for disease. We have thoroughly sampled common variation in these genes, genotyping 355 variants in over 600 individuals for whom

Waster water treatment with Cavitation Air Flotation (CAF) system; Tratamiento de las aguas residuales utilizando el sistema de flotacion por aire inducido (CAF)

Energy Technology Data Exchange (ETDEWEB)

Escofet Lugstenmann, I.

1998-12-01

In wastewater treatment from industries, the flotation process as physical-chemical treatment or primary treatment, based on the difference of densities of the solid-liquid suspension, is an important step for the elimination of the contaminant material, both as suspended solids and oils and greases. The Cavitation Air Flotation (CAF) system is an unique, innovative and very easy method which introduces air into the flotation system. It was created to come over the problems and limitations of more conventional techniques of Dissolved Air Flotation (DAF). (Author) 9 refs.

A novel homozygous variant in SERPINH1 associated with a severe, lethal presentation of osteogenesis imperfecta with hydranencephaly.

Science.gov (United States)

Marshall, Charlotte; Lopez, Jaime; Crookes, Laura; Pollitt, Rebecca C; Balasubramanian, Meena

2016-12-20

Osteogenesis imperfecta (OI) is a genetic disorder characterised by low bone mineral density resulting in fractures. 85-90% of patients with OI carry a variant in the type 1 collagen genes, COL1A1 and COL1A2, which follows an autosomal dominant pattern of inheritance. However, within the last two decades, there have been growing number of variants identified in genes that follow an autosomal recessive pattern of inheritance. Our proband is a child born in Mexico with multiple fractures of ribs, minimal calvarial mineralisation, platyspondyly, marked compression and deformed long bones. He also presented with significant hydranencephaly, requiring ventilatory support from birth, and died at 8days of age. A homozygous c.338_357delins22 variant in exon 2 of SERPINH1 was identified. This gene encodes heat shock protein 47, a collagen-specific chaperone which binds to the procollagen triple helix and is responsible for collagen stabilisation in the endoplasmic reticulum. There is minimal literature on the mechanism of action for variants in SERPINH1 resulting in osteogenesis imperfecta. Here we discuss this rare, previously unreported variant, and expand on the phenotypic presentation of this novel variant resulting in a severe, lethal phenotype of OI in association with hydranencephaly. Copyright © 2016 Elsevier B.V. All rights reserved.

An Evaluation of Factors Associated With Pathogenic PRSS1, SPINK1, CTFR, and/or CTRC Genetic Variants in Patients With Idiopathic Pancreatitis.

Science.gov (United States)

Jalaly, Niloofar Y; Moran, Robert A; Fargahi, Farshid; Khashab, Mouen A; Kamal, Ayesha; Lennon, Anne Marie; Walsh, Christi; Makary, Martin A; Whitcomb, David C; Yadav, Dhiraj; Cebotaru, Liudmila; Singh, Vikesh K

2017-08-01

We evaluated factors associated with pathogenic genetic variants in patients with idiopathic pancreatitis. Genetic testing (PRSS1, CFTR, SPINK1, and CTRC) was performed in all eligible patients with idiopathic pancreatitis between 2010 to 2015. Patients were classified into the following groups based on a review of medical records: (1) acute recurrent idiopathic pancreatitis (ARIP) with or without underlying chronic pancreatitis; (2) idiopathic chronic pancreatitis (ICP) without a history of ARP; (3) an unexplained first episode of acute pancreatitis (AP)pancreatitis. Logistic regression analysis was used to determine the factors associated with pathogenic genetic variants. Among 197 ARIP and/or ICP patients evaluated from 2010 to 2015, 134 underwent genetic testing. A total of 88 pathogenic genetic variants were found in 64 (47.8%) patients. Pathogenic genetic variants were identified in 58, 63, and 27% of patients with ARIP, an unexplained first episode of AP <35 years of age, and ICP without ARP, respectively. ARIP (OR: 18.12; 95% CI: 2.16-151.87; P=0.008) and an unexplained first episode of AP<35 years of age (OR: 2.46; 95% CI: 1.18-5.15; P=0.017), but not ICP, were independently associated with pathogenic genetic variants in the adjusted analysis. Pathogenic genetic variants are most likely to be identified in patients with ARIP and an unexplained first episode of AP<35 years of age. Genetic testing in these patient populations may delineate an etiology and prevent unnecessary diagnostic testing and procedures.

Genomic and Phenotypic Analyses Reveal the Emergence of an Atypical Salmonella enterica Serovar Senftenberg Variant in China

KAUST Repository

Abd El Ghany, Moataz

2016-05-25

Human infections with Salmonella enterica subspecies enterica serovar Senftenberg are often associated with exposure to poultry flocks, farm environments, or contaminated food. The recent emergence of multidrug-resistant isolates has raised public health concerns. In this study, comparative genomics and phenotypic analysis were used to characterize 14 Salmonella Senftenberg clinical isolates recovered from multiple outbreaks in Shenzhen and Shanghai, China, between 2002 and 2011. Single-nucleotide polymorphism analyses identified two phylogenetically distinct clades of S. Senftenberg, designated SC1 and SC2, harboring variations in Salmonella pathogenicity island 1 (SPI-1) and SPI-2 and exhibiting distinct biochemical and phenotypic signatures. Although the two variants shared the same serotype, the SC2 isolates of sequence type 14 (ST14) harbored intact SPI-1 and -2 and hence were characterized by possessing efficient invasion capabilities. In contrast, the SC1 isolates had structural deletion patterns in both SPI-1 and -2 that correlated with an impaired capacity to invade cultured human cells and also the year of their isolation. These atypical SC1 isolates also lacked the capacity to produce hydrogen sulfide. These findings highlight the emergence of atypical Salmonella Senftenberg variants in China and provide genetic validation that variants lacking SPI-1 and regions of SPI-2, which leads to impaired invasion capacity, can still cause clinical disease. These data have identified an emerging public health concern and highlight the need to strengthen surveillance to detect the prevalence and transmission of nontyphoidal Salmonella species.

Evaluation of Presumably Disease Causing SCN1A Variants in a Cohort of Common Epilepsy Syndromes.

Science.gov (United States)

Lal, Dennis; Reinthaler, Eva M; Dejanovic, Borislav; May, Patrick; Thiele, Holger; Lehesjoki, Anna-Elina; Schwarz, Günter; Riesch, Erik; Ikram, M Arfan; van Duijn, Cornelia M; Uitterlinden, Andre G; Hofman, Albert; Steinböck, Hannelore; Gruber-Sedlmayr, Ursula; Neophytou, Birgit; Zara, Federico; Hahn, Andreas; Gormley, Padhraig; Becker, Felicitas; Weber, Yvonne G; Cilio, Maria Roberta; Kunz, Wolfram S; Krause, Roland; Zimprich, Fritz; Lemke, Johannes R; Nürnberg, Peter; Sander, Thomas; Lerche, Holger; Neubauer, Bernd A

2016-01-01

The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. We identified 8 known missense mutations, previously reported as pathogenic, in a total of 17 unrelated epilepsy patients (17/448; 3.80%). Our re-evaluation indicates that 7 out of these 8 variants (p.R27T; p.R28C; p.R542Q; p.R604H; p.T1250M; p.E1308D; p.R1928G; NP_001159435.1) are not pathogenic. Only the p.T1174S mutation may be considered as a genetic risk factor for epilepsy of small effect size based on the enrichment in patients (P = 6.60 x 10-4; OR = 0.32, fishers exact test), previous functional studies but incomplete penetrance. Thus, incorporation of previous studies in genetic counseling of SCN1A sequencing results is challenging and may produce incorrect conclusions.

Biodiversidade de fungos filamentosos em grãos de café cultivados em sistema orgânico e convencional

OpenAIRE

Couto, Fabiana Aparecida; Monteiro, Mônica Cristina Pereira; Silva, Daiani Maria da; Cirillo, Marcelo Ângelo; Batista, Luis Roberto

2012-01-01

Os frutos de café produzidos de forma orgânica ou convencional estão sujeitos à contaminação de diversas espécies de fungos que podem estar relacionados à má qualidade da bebida e à produção de micotoxinas. Realizou-se este estudo para identificar a biodiversidade de fungos filamentosos isolados nos grãos de café produzidos em fazendas orgânicas e convencionais de uma mesma localidade. Das 15 amostras analisadas, foram identificados 212 isolados, pertencentes a 11 diferentes gêner...

CDKL5 variants

Science.gov (United States)

Kalscheuer, Vera M.; Hennig, Friederike; Leonard, Helen; Downs, Jenny; Clarke, Angus; Benke, Tim A.; Armstrong, Judith; Pineda, Mercedes; Bailey, Mark E.S.; Cobb, Stuart R.

2017-01-01

Objective: To provide new insights into the interpretation of genetic variants in a rare neurologic disorder, CDKL5 deficiency, in the contexts of population sequencing data and an updated characterization of the CDKL5 gene. Methods: We analyzed all known potentially pathogenic CDKL5 variants by combining data from large-scale population sequencing studies with CDKL5 variants from new and all available clinical cohorts and combined this with computational methods to predict pathogenicity. Results: The study has identified several variants that can be reclassified as benign or likely benign. With the addition of novel CDKL5 variants, we confirm that pathogenic missense variants cluster in the catalytic domain of CDKL5 and reclassify a purported missense variant as having a splicing consequence. We provide further evidence that missense variants in the final 3 exons are likely to be benign and not important to disease pathology. We also describe benign splicing and nonsense variants within these exons, suggesting that isoform hCDKL5_5 is likely to have little or no neurologic significance. We also use the available data to make a preliminary estimate of minimum incidence of CDKL5 deficiency. Conclusions: These findings have implications for genetic diagnosis, providing evidence for the reclassification of specific variants previously thought to result in CDKL5 deficiency. Together, these analyses support the view that the predominant brain isoform in humans (hCDKL5_1) is crucial for normal neurodevelopment and that the catalytic domain is the primary functional domain. PMID:29264392

A selective splicing variant of hepcidin mRNA in hepatocellular carcinoma cell lines

International Nuclear Information System (INIS)

Toki, Yasumichi; Sasaki, Katsunori; Tanaka, Hiroki; Yamamoto, Masayo; Hatayama, Mayumi; Ito, Satoshi; Ikuta, Katsuya; Shindo, Motohiro; Hasebe, Takumu; Nakajima, Shunsuke; Sawada, Koji; Fujiya, Mikihiro; Torimoto, Yoshihiro; Ohtake, Takaaki; Kohgo, Yutaka

2016-01-01

Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. By RT-PCR/agarose gel electrophoresis of hepcidin mRNA in a hepatocellular carcinoma cell line HLF, a smaller mRNA band was shown in addition to the wild-type hepcidin mRNA. From sequencing analysis, this additional band was a selective splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene, producing the transcript that encodes truncated peptide lacking 20 amino acids at the middle of preprohepcidin. In the present study, we used the digital PCR, because such a small amount of variant mRNA was difficult to quantitate by the conventional RT-PCR amplification. Among seven hepatoma-derived cell lines, six cell lines have significant copy numbers of this variant mRNA, but not in one cell line. In the transient transfection analysis of variant-type hepcidin cDNA, truncated preprohepcidin has a different character comparing with native preprohepcidin: its product is insensitive to digestion, and secreted into the medium as a whole preprohepcidin form without maturation. Loss or reduction of function of HAMP gene by aberrantly splicing may be a suitable phenomenon to obtain the proliferating advantage of hepatoma cells. - Highlights: • An aberrant splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene. • Absolute quantification of hepcidin mRNA by digital PCR amplification. • Hepatoma-derived cell lines have significant copies of variant-type hepcidin mRNA. • Truncated preprohepcidin is secreted from cells without posttranslational cleavage.

A selective splicing variant of hepcidin mRNA in hepatocellular carcinoma cell lines

Energy Technology Data Exchange (ETDEWEB)

Toki, Yasumichi [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido 078-8510 (Japan); Sasaki, Katsunori, E-mail: k-sasaki@asahikawa-med.ac.jp [Department of Gastrointestinal Immunology and Regenerative Medicine, Asahikawa Medical University, Hokkaido 078-8510 (Japan); Tanaka, Hiroki [Department of Legal Medicine, Asahikawa Medical University, Hokkaido 078-8510 (Japan); Yamamoto, Masayo; Hatayama, Mayumi; Ito, Satoshi; Ikuta, Katsuya; Shindo, Motohiro; Hasebe, Takumu; Nakajima, Shunsuke; Sawada, Koji; Fujiya, Mikihiro [Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, Hokkaido 078-8510 (Japan); Torimoto, Yoshihiro [Oncology Center, Asahikawa Medical University Hospital, Hokkaido 078-8510 (Japan); Ohtake, Takaaki; Kohgo, Yutaka [Department of Gastroenterology, International University of Health and Welfare Hospital, Tochigi 329-2763 (Japan)

2016-08-05

Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. By RT-PCR/agarose gel electrophoresis of hepcidin mRNA in a hepatocellular carcinoma cell line HLF, a smaller mRNA band was shown in addition to the wild-type hepcidin mRNA. From sequencing analysis, this additional band was a selective splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene, producing the transcript that encodes truncated peptide lacking 20 amino acids at the middle of preprohepcidin. In the present study, we used the digital PCR, because such a small amount of variant mRNA was difficult to quantitate by the conventional RT-PCR amplification. Among seven hepatoma-derived cell lines, six cell lines have significant copy numbers of this variant mRNA, but not in one cell line. In the transient transfection analysis of variant-type hepcidin cDNA, truncated preprohepcidin has a different character comparing with native preprohepcidin: its product is insensitive to digestion, and secreted into the medium as a whole preprohepcidin form without maturation. Loss or reduction of function of HAMP gene by aberrantly splicing may be a suitable phenomenon to obtain the proliferating advantage of hepatoma cells. - Highlights: • An aberrant splicing variant of hepcidin mRNA lacking exon 2 of HAMP gene. • Absolute quantification of hepcidin mRNA by digital PCR amplification. • Hepatoma-derived cell lines have significant copies of variant-type hepcidin mRNA. • Truncated preprohepcidin is secreted from cells without posttranslational cleavage.

A CACNA1C variant associated with reduced voltage-dependent inactivation, increased CaV1.2 channel window current, and arrhythmogenesis.

Directory of Open Access Journals (Sweden)

Jessica A Hennessey

Full Text Available Mutations in CACNA1C that increase current through the CaV1.2 L-type Ca2+ channel underlie rare forms of long QT syndrome (LQTS, and Timothy syndrome (TS. We identified a variant in CACNA1C in a male child of Filipino descent with arrhythmias and extracardiac features by candidate gene sequencing and performed functional expression studies to electrophysiologically characterize the effects of the variant on CaV1.2 channels. As a baby, the subject developed seizures and displayed developmental delays at 30 months of age. At age 5 years, he displayed a QTc of 520 ms and experienced recurrent VT. Physical exam at 17 years of age was notable for microcephaly, short stature, lower extremity weakness and atrophy with hyperreflexia, spastic diplegia, multiple dental caries and episodes of rhabdomyolysis. Candidate gene sequencing identified a G>C transversion at position 5731 of CACNA1C (rs374528680 predicting a glycine>arginine substitution at residue 1911 (p.G1911R of CaV1.2. The allele frequency of this variant is 0.01 in Malays, but absent in 984 Caucasian alleles and in the 1000 genomes project. In electrophysiological analyses, the variant decreased voltage-dependent inactivation, thus causing a gain of function of CaV1.2. We also observed a negative shift of V1/2 of activation and positive shift of V1/2 of channel inactivation, resulting in an increase of the window current. Together, these suggest a gain-of-function effect on CaV1.2 and suggest increased susceptibility for arrhythmias in certain clinical settings. The p.G1911R variant was also identified in a case of sudden unexplained infant death (SUID, for which an increasing number of clinical observations have demonstrated can be associated with arrhythmogenic mutations in cardiac ion channels. In summary, the combined effects of the CACNA1C variant to diminish voltage-dependent inactivation of CaV1.2 and increase window current expand our appreciation of mechanisms by which a gain of

Functional paraoxonase 1 variants modify the risk of Parkinson's disease due to organophosphate exposure.

Science.gov (United States)

Lee, Pei-Chen; Rhodes, Shannon L; Sinsheimer, Janet S; Bronstein, Jeff; Ritz, Beate

2013-06-01

We previously demonstrated that carriers of the "slower metabolizer" MM genotype of paraoxonase (PON1) who were also exposed to ambient organophosphate (OP) pesticides at their residences were at increased risk of developing Parkinson's disease (PD). Here, with a larger sample size, we extend our previous investigation to consider additional sources of ambient exposure and examined two additional functional PON1 variants. From 2001 to 2011, we enrolled incident cases of idiopathic PD and population controls living in central California. We genotyped three well-known functional PON1 SNPs: two exonic polymorphisms (PON1L55M and PON1Q192R) and the promoter region variant (PON1C-108T). Ambient exposures to diazinon, chlorpyrifos, and parathion at residential and workplace addresses were assessed using a validated geographic information system-based model incorporating records of agricultural pesticide applications in California. The odds ratio (OR) for Caucasians exposed to OPs at either residential or workplace addresses varied by PON1 genotype; for exposed carriers of the "faster" metabolizer genotypes, ML or LL, we estimated lower odds ratios (range, 1.20-1.39) than for exposed carriers of the "slower" metabolizer genotype MM (range, 1.78-2.45) relative to unexposed carriers of the faster genotypes. We observed similarly increased ORs for exposure across PON1Q192R genotypes, but no differences across PON1C-108T genotypes. The largest ORs were estimated for exposed carriers of both PON1192QQ and PON155MM (OR range, 2.84-3.57). Several functional PON1 variants may act together to modify PD risk for ambient OP exposures. While either PON1L55M or PON1Q192R may be sufficient to identify increased susceptibility, carriers of both slow metabolizer variants seem most susceptible to OP exposures. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rare Variants in Genes Encoding MuRF1 and MuRF2 Are Modifiers of Hypertrophic Cardiomyopathy

Directory of Open Access Journals (Sweden)

Ming Su

2014-05-01

Full Text Available Modifier genes contribute to the diverse clinical manifestations of hypertrophic cardiomyopathy (HCM, but are still largely unknown. Muscle ring finger (MuRF proteins are a class of muscle-specific ubiquitin E3-ligases that appear to modulate cardiac mass and function by regulating the ubiquitin-proteasome system. In this study we screened all the three members of the MuRF family, MuRF1, MuRF2 and MuRF3, in 594 unrelated HCM patients and 307 healthy controls by targeted resequencing. Identified rare variants were confirmed by capillary Sanger sequencing. The prevalence of rare variants in both MuRF1 and MuRF2 in HCM patients was higher than that in control subjects (MuRF1 13/594 (2.2% vs. 1/307 (0.3%, p = 0.04; MuRF2 22/594 (3.7% vs. 2/307 (0.7%; p = 0.007. Patients with rare variants in MuRF1 or MuRF2 were younger (p = 0.04 and had greater maximum left ventricular wall thickness (p = 0.006 than those without such variants. Mutations in genes encoding sarcomere proteins were present in 19 (55.9% of the 34 HCM patients with rare variants in MuRF1 and MuRF2. These data strongly supported that rare variants in MuRF1 and MuRF2 are associated with higher penetrance and more severe clinical manifestations of HCM. The findings suggest that dysregulation of the ubiquitin-proteasome system contributes to the pathogenesis of HCM.

Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin

DEFF Research Database (Denmark)

Omland, Silje Haukali; Wettergren, Erika Elgstrand; Mollerup, Sarah

2017-01-01

of chemokines involved in tumour progression and immunosuppression (CXCL12, CCL17). Fibroblasts from chronically sun-exposed skin near tumours show gene expression patterns resembling that of CAFs, indicating that stromal fibroblasts in cancer-free surgical BCC margins exhibit a tumour promoting phenotype.......BACKGROUND: Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) in the microenvironment are essential for tumour growth in a variety...... of neoplasms but their role in BCC is poorly understood. METHODS: Material included facial BCC and control skin from the peritumoural area and from the buttocks. With next-generation sequencing (NGS) we compared mRNA expression between BCC and peritumoural skin. qRT-PCR, immunohistochemical...

Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin

DEFF Research Database (Denmark)

Omland, Silje Haukali; Wettergren, Erika Elgstrand; Mourier, Tobias

2017-01-01

of chemokines involved in tumour progression and immunosuppression (CXCL12, CCL17). Fibroblasts from chronically sun-exposed skin near tumours show gene expression patterns resembling that of CAFs, indicating that stromal fibroblasts in cancer-free surgical BCC margins exhibit a tumour promoting phenotype.......Background: Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) in the microenvironment are essential for tumour growth in a variety...... of neoplasms but their role in BCC is poorly understood. Methods: Material included facial BCC and control skin from the peritumoural area and from the buttocks. With next-generation sequencing (NGS) we compared mRNA expression between BCC and peritumoural skin. qRT-PCR, immunohistochemical...

Functional assays for analysis of variants of uncertain significance in BRCA2

DEFF Research Database (Denmark)

Guidugli, Lucia; Carreira, Aura; Caputo, Sandrine M

2014-01-01

Missense variants in the BRCA2 gene are routinely detected during clinical screening for pathogenic mutations in patients with a family history of breast and ovarian cancer. These subtle changes frequently remain of unknown clinical significance because of the lack of genetic information that may...... of uncertain significance analyzed, and describe a validation set of (genetically) proven pathogenic and neutral missense variants to serve as a golden standard for the validation of each assay. Guidelines are proposed to enable implementation of laboratory-based methods to assess the impact of the variant...

Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

Directory of Open Access Journals (Sweden)

Julia Diegelmann

Full Text Available OBJECTIVES: DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs regarding inflammatory bowel disease (IBD susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. METHODS: Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. RESULTS: IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7, OR 1.42; 95% CI 1.24-1.63. All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18. The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. CONCLUSION: We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important

Intestinal DMBT1 expression is modulated by Crohn's disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2.

Science.gov (United States)

Diegelmann, Julia; Czamara, Darina; Le Bras, Emmanuelle; Zimmermann, Eva; Olszak, Torsten; Bedynek, Andrea; Göke, Burkhard; Franke, Andre; Glas, Jürgen; Brand, Stephan

2013-01-01

DMBT is an antibacterial pattern recognition and scavenger receptor. In this study, we analyzed the role of DMBT1 single nucleotide polymorphisms (SNPs) regarding inflammatory bowel disease (IBD) susceptibility and examined their functional impact on transcription factor binding and downstream gene expression. Seven SNPs in the DMBT1 gene region were analyzed in 2073 individuals including 818 Crohn's disease (CD) patients and 972 healthy controls in two independent case-control panels. Comprehensive epistasis analyses for the known CD susceptibility genes NOD2, IL23R and IL27 were performed. The influence of IL23R variants on DMBT1 expression was analyzed. Functional analysis included siRNA transfection, quantitative PCR, western blot, electrophoretic mobility shift and luciferase assays. IL-22 induces DMBT1 protein expression in intestinal epithelial cells dependent on STAT3, ATF-2 and CREB1. IL-22 expression-modulating, CD risk-associated IL23R variants influence DMBT1 expression in CD patients and DMBT1 levels are increased in the inflamed intestinal mucosa of CD patients. Several DMBT1 SNPs were associated with CD susceptibility. SNP rs2981804 was most strongly associated with CD in the combined panel (p = 3.0 × 10(-7), OR 1.42; 95% CI 1.24-1.63). All haplotype groups tested showed highly significant associations with CD (including omnibus P-values as low as 6.1 × 10(-18)). The most strongly CD risk-associated, non-coding DMBT1 SNP rs2981804 modifies the DNA binding sites for the transcription factors CREB1 and ATF-2 and the respective genomic region comprising rs2981804 is able to act as a transcriptional regulator in vitro. Intestinal DMBT1 expression is decreased in CD patients carrying the rs2981804 CD risk allele. We identified novel associations of DMBT1 variants with CD susceptibility and discovered a novel functional role of rs2981804 in regulating DMBT1 expression. Our data suggest an important role of DMBT1 in CD pathogenesis.

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170

NARCIS (Netherlands)

A.M. Dunning (Alison); K. Michailidou (Kyriaki); K.B. Kuchenbaecker (Karoline); D. Thompson (Deborah); J.D. French (Juliet); J. Beesley (Jonathan); S. Healey (Sue); S. Kar (Siddhartha); K.A. Pooley (Karen); E. Lopez-Knowles (Elena); E. Dicks (Ed); D. Barrowdale (Daniel); N.A. Sinnott-Armstrong (Nicholas A); R.C. Sallari (Richard C); K.M. Hillman (Kristine); S. Kaufmann (Susanne); H. Sivakumaran (Haran); M.M. Marjaneh (Mahdi Moradi); J.S. Lee (Jason); M. Hills (Margaret); M. Jarosz (Monika); S. Drury (Suzie); S. Canisius (Sander); M. KBolla (Manjeet); J. Dennis (Joe); Q. Wang (Qin); J. LHopper (John); M.C. Southey (Mellissa C.); A. Broeks (Annegien); M.K. Schmidt (Marjanka); A. Lophatananon (Artitaya); K.R. Muir (K.); M.W. Beckmann (Matthias); P.A. Fasching (Peter); I. dos Santos Silva (Isabel); J. Peto (Julian); E.J. Sawyer (Elinor); I. Tomlinson (Ian); B. Burwinkel (Barbara); F. Marme (Federick); P. Guénel (Pascal); T. Truong (Thérèse); S.E. Bojesen (Stig); H. Flyger (Henrik); A. Gonzlez-Neira (Anna); J.I.A. Perez (Jose I.A.); H. Anton-Culver (Hoda); L. Eunjung (Lee); V. Arndt (Volker); H. Brenner (Hermann); A. Meindl (Alfons); R.K. Schmutzler (Rita); H. Brauch (Hiltrud); U. Hamann (Ute); K. Aittomki (Kristiina); C. Blomqvist (Carl); H. Ito (Hidemi); K. Matsuo (Keitaro); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); V-M. Kosma (Veli-Matti); A. Mannermaa (Arto); C.-C. Tseng (Chiu-Chen); A.H. Wu (Anna); D. Lambrechts (Diether); H. Wildiers (Hans); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Peterlongo (Paolo); P. Radice (Paolo); J. EOlson (Janet); G. GGiles (Graham); R.L. Milne (Roger L); C.A. Haiman (Christopher A.); B.E. Henderson (Brian); M.S. Goldberg (Mark); S.H. Teo (Soo Hwang); C.H. Yip (Cheng Har); S. Nord (Silje); A.-L. Borresen-Dale (Anne-Lise); V. Kristensen (Vessela); J. Long (Jirong); W. Zheng (Wei); K. Pylks (Katri); R. Winqvist (Robert); I.L. Andrulis (Irene); J.A. Knight (Julia A.); P. Devilee (Peter); C.M. Seynaeve (Caroline); J.D. Figueroa (Jonine); M.E. Sherman (Mark); K. Czene (Kamila); H. Darabi (Hatef); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); K. Humphreys (Keith); Y.-T. Gao (Yu-Tang); X.-O. Shu (Xiao-Ou); A. Cox (Angela); S.S. Cross (Simon); W.J. Blot (William); Q. Cai (Qiuyin); M. Ghoussaini (Maya); B. Perkins (Barbara); M. Shah (Mitul); J.-Y. Choi (Ji-Yeob); D. Kang (Daehee); S.C. Lee (Soo Chin); J.M. Hartman (Joost); M. Kabisch (Maria); D. Torres (Diana); A. Jakubowska (Anna); J. Lubinski (Jan); P. Brennan (Paul); S. Sangrajrang (Suleeporn); C.B. Ambrosone (Christine); A.E. Toland (Amanda); C-Y. Shen (Chen-Yang); P.-E. Wu (Pei-Ei); N. Orr (Nick); A.J. Swerdlow (Anthony ); L. McGuffog (Lesley); S. Healey (Sue); A. Lee (Andrew); M.K. Kapuscinski (Miroslav K.); E.M. John (Esther); M.B. Terry (Mary Beth); M.B. Daly (Mary B.); D. Goldgar (David); S.S. Buys (Saundra); R. Janavicius (Ramunas); L. Tihomirova (Laima); N. Tung (Nadine); C.M. Dorfling (Cecilia); E.J. van Rensburg (Elizabeth); S.L. Neuhausen (Susan); B. Ejlertsen (Bent); T.V. OHansen (Thomas V); A. Osorio (Ana); J. Benítez (Javier); R. Rando (Rachel); J.N. Weitzel (Jeffrey); B. Bonnani (Bernardo); B. Peissel (Bernard); S. Manoukian (Siranoush); L. Papi (Laura); L. Ottini (Laura); I. Konstantopoulou (I.); P. Apostolou (Paraskevi); J. Garber (Judy); M.U. Rashid (Muhammad Usman); D. Frost (Debra); L. Izatt (Louise); S.D. Ellis (Steve); A.K. Godwin (Andrew K.); N. Arnold (Norbert); D. Niederacher (Dieter); K. Rhiem (Kerstin); N. Bogdanova-Markov (Nadja); C. Sagne (Charlotte); D. Stoppa-Lyonnet (Dominique); F. Damiola (Francesca); O. Sinilnikova (Olga); S. Mazoyer (Sylvie); C. Isaacs (Claudine); K.B. MClaes (Kathleen B); K. De Leeneer (Kim); M. de La Hoya (Miguel); T. Caldes (Trinidad); H. Nevanlinna (Heli); S. Khan (Sofia); A.R. Mensenkamp (Arjen); M.J. Hooning (Maartje); M.A. Rookus (Matti); A. Kwong (Ava); E. Olah (Edith); O. Díez (Orland); J. Brunet (Joan); M.A. Pujana (Miguel); J. Gronwald (Jacek); T. Huzarski (Tomasz); R.B. Barkardottir (Rosa); R. Laframboise (Rachel); P. Soucy (Penny); M. Montagna (Marco); S. Agata (Simona); P.J. Teixeira; S. Kyung Park (Sue); N.M. Lindor (Noralane); F.J. Couch (Fergus J); M. Tischkowitz (Marc); L. Foretova (Lenka); J. Vijai (Joseph); K. Offit (Kenneth); C.F. Singer (Christian); C. Rappaport (Christine); C. MPhelan (Catherine); M.H. Greene (Mark H.); P.L. Mai (Phuong); G. Rennert (Gad); E.N. Imyanitov (Evgeny); P.J. Hulick (Peter); K.-A. Phillips (Kelly-Anne); M. Piedmonte (Marion); A.-M. Mulligan (Anna-Marie); G. Glendon (Gord); A. Bojesen (Anders); M. Thomassen (Mads); M.A. Caligo (Maria); S.-Y. Yoon (Sook-Yee); E. Friedman (Eitan); Y. Laitman (Yael); Å. Borg (Åke); A. von Wachenfeldt (Anna); H. Ehrencrona (Hans); J. Rantala (Johanna); O.I. Olopade (Olufunmilayo I.); P.A. Ganz (Patricia A.); R. Nussbaum (Robert); S.A. Gayther (Simon); K. LNathanson (Katherine); S.M. Domchek (Susan); B.K. Arun (Banu); G. Mitchell (Gillian); B.Y. Karlan (Beth Y.); K.J. Lester (Kathryn); G. Maskarinec (Gertraud); C. Woolcott (Christy); C.G. Scott (Christopher G.); J. Stone (Jennifer); C. Apicella (Carmel); R. Tamimi (Rulla); R.N. Luben (Robert); K.-T. Khaw (Kay-Tee); S. Helland (Slaug); V. Haakensen (Vilde); M. Dowsett (Mitch); P.D.P. Pharoah (Paul); J. Simard (Jacques); P. Hall (Per); M. Garca-Closas (Montserrat); C. Vachon (Celine); G. Chenevix-Trench (Georgia); A.C. Antoniou (Antonis C.); D.F. Easton (Douglas F.); S.L. Edwards (Stacey)

2016-01-01

textabstractWe analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen

Pharmacogenetic characterization of naturally occurring germline NT5C1A variants to chemotherapeutic nucleoside analogs

Science.gov (United States)

Saliba, Jason; Zabriskie, Ryan; Ghosh, Rajarshi; Powell, Bradford C; Hicks, Stephanie; Kimmel, Marek; Meng, Qingchang; Ritter, Deborah I; Wheeler, David A; Gibbs, Richard A; Tsai, Francis T F; Plon, Sharon E

2016-01-01

Background Mutations or alteration in expression of the 5’ nucleotidase gene family can confer altered responses to treatment with nucleoside analogs. While investigating leukemia susceptibility genes, we discovered a very rare p.L254P NT5C1A missense variant in the substrate recognition motif. Given the paucity of cellular drug response data from NT5C1A germline variation, we characterized p.L254P and eight rare variants of NT5C1A from genomic databases. Methods Through lentiviral infection, we created HEK293 cell lines that stably overexpress wildtype NT5C1A, p.L254P, or eight NT5C1A variants reported in the NHLBI Exome Variant server (one truncating and seven missense). IC50 values were determined by cytotoxicity assays after exposure to chemotherapeutic nucleoside analogs (Cladribine, Gemcitabine, 5-Fluorouracil). In addition, we used structure-based homology modeling to generate a 3D model for the C-terminal region of NT5C1A. Results The p.R180X (truncating), p.A214T, and p.L254P missense changes were the only variants that significantly impaired protein function across all nucleotide analogs tested (>5-fold difference versus WT; p<.05). Several of the remaining variants individually displayed differential effects (both more and less resistant) across the analogs tested. The homology model provided a structural framework to understand the impact of NT5C1A mutants on catalysis and drug processing. The model predicted active site residues within NT5C1A motif III and we experimentally confirmed that p.K314 (not p.K320) is required for NT5C1A activity. Conclusion We characterized germline variation and predicted protein structures of NT5C1A. Individual missense changes showed substantial variation in response to the different nucleoside analogs tested, which may impact patients’ responses to treatment. PMID:26906009

Discussions in a Socrates Café: Implications for Critical Thinking in Teacher Education

Science.gov (United States)

Piro, Jody; Anderson, Gina

2015-01-01

The purpose of this study was to benchmark the types of Socratic questioning that were occurring in a Socrates Café, an online discussion forum, in a graduate-level diversity course in teacher education. The Universal Intellectual Standards were used to analyze Socratic questioning. Results suggested that the nine Universal Intellectual Standards…

The NRG1 exon 11 missense variant is not associated with autism in the Central Valley of Costa Rica

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Fallas Marietha

2007-05-01

Full Text Available Abstract Background We are conducting a genetic study of autism in the isolated population of the Central Valley of Costa Rica (CVCR. A novel Neuregulin 1 (NRG1 missense variant (exon 11 G>T was recently associated with psychosis and schizophrenia (SCZ in the same population isolate. Methods We genotyped the NRG1 exon 11 missense variant in 146 cases with autism, or autism spectrum disorder, with CVCR ancestry, and both parents when available (N = 267 parents from 143 independent families. Additional microsatellites were genotyped to examine haplotypes bearing the exon 11 variant. Results The NRG1 exon 11 G>T variant was found in 4/146 cases including one de novo occurrence. The frequency of the variant in case chromosomes was 0.014 and 0.045 in the parental non-transmitted chromosomes. At least 6 haplotypes extending 0.229 Mb were associated with the T allele. Three independent individuals, with no personal or family history of psychiatric disorder, shared at least a 1 megabase haplotype 5' to the T allele. Conclusion The NRG1 exon 11 missense variant is not associated with autism in the CVCR.

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

Science.gov (United States)

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

Cancer-Associated Fibroblasts Regulate Tumor-Initiating Cell Plasticity in Hepatocellular Carcinoma through c-Met/FRA1/HEY1 Signaling

Directory of Open Access Journals (Sweden)

Eunice Yuen Ting Lau

2016-05-01

Full Text Available Like normal stem cells, tumor-initiating cells (T-ICs are regulated extrinsically within the tumor microenvironment. Because HCC develops primarily in the context of cirrhosis, in which there is an enrichment of activated fibroblasts, we hypothesized that cancer-associated fibroblasts (CAFs would regulate liver T-ICs. We found that the presence of α-SMA(+ CAFs correlates with poor clinical outcome. CAF-derived HGF regulates liver T-ICs via activation of FRA1 in an Erk1,2-dependent manner. Further functional analysis identifies HEY1 as a direct downstream effector of FRA1. Using the STAM NASH-HCC mouse model, we find that HGF-induced FRA1 activation is associated with the fibrosis-dependent development of HCC. Thus, targeting the CAF-derived, HGF-mediated c-Met/FRA1/HEY1 cascade may be a therapeutic strategy for the treatment of HCC.

APOBEC3G Variants and Protection against HIV-1 Infection in Burkina Faso.

Science.gov (United States)

Compaore, Tegwinde Rebeca; Soubeiga, Serge Theophile; Ouattara, Abdoul Karim; Obiri-Yeboah, Dorcas; Tchelougou, Damehan; Maiga, Mamoudou; Assih, Maleki; Bisseye, Cyrille; Bakouan, Didier; Compaore, Issaka Pierre; Dembele, Augustine; Martinson, Jeremy; Simpore, Jacques

2016-01-01

Studies on host factors, particularly the APOBEC3G gene, have previously found an association with AIDS progression in some populations and against some HIV-1 strains but not others. Our study had two main objectives: firstly, to screen a population from Burkina Faso for three variants of APOBEC3G previously described, and secondly to analyze the effect of these three variants and their haplotypes on HIV-1 infection with Circulating Recombinant Forms (CRFs) present in Burkina Faso. This case control study involved 708 seropositive and seronegative individuals. Genotyping was done by the TaqMan allelic discrimination method. Minor allele frequencies of rs6001417 (p<0.05), rs8177832 (P<0.05), and rs35228531 (P<0.001) were higher in seronegative subjects. The rs6001417 and rs8177832 SNPs were associated with HIV-1 infection in an additive model (P<0.01). Furthermore the SNP rs35228531 was also associated with HIV-1 infection in a dominant model (P<0.001). Odds ratio analysis of genotypes and alleles of the different APOBEC3G variants showed that there is a strong association between the minor genetic variants, genotype of the three SNPs, and HIV-1 status. Haplotype analysis demonstrated that rs6001417, rs8177832, and rs35228531 are in linkage disequilibrium. The haplotype GGT from the rs6001417, rs8177832 and rs35228531 respectively has a protective effect OR = 0.54 [0.43-0.68] with P<0.001. There was also associations between the haplotypes GGC OR = 1.6 [1.1;-2.3] P<0.05, and CGC OR = 5.21 [2.4-11.3] P<0.001, which increase the risk of infection by HIV-1 from almost two (2) to five (5) fold. This study demonstrates an association of rs6001417, rs8177832, and rs35228531 of APOBEC3G with HIV-1 infection in a population from Burkina Faso.

APOBEC3G Variants and Protection against HIV-1 Infection in Burkina Faso.

Directory of Open Access Journals (Sweden)

Tegwinde Rebeca Compaore

Full Text Available Studies on host factors, particularly the APOBEC3G gene, have previously found an association with AIDS progression in some populations and against some HIV-1 strains but not others. Our study had two main objectives: firstly, to screen a population from Burkina Faso for three variants of APOBEC3G previously described, and secondly to analyze the effect of these three variants and their haplotypes on HIV-1 infection with Circulating Recombinant Forms (CRFs present in Burkina Faso. This case control study involved 708 seropositive and seronegative individuals. Genotyping was done by the TaqMan allelic discrimination method. Minor allele frequencies of rs6001417 (p<0.05, rs8177832 (P<0.05, and rs35228531 (P<0.001 were higher in seronegative subjects. The rs6001417 and rs8177832 SNPs were associated with HIV-1 infection in an additive model (P<0.01. Furthermore the SNP rs35228531 was also associated with HIV-1 infection in a dominant model (P<0.001. Odds ratio analysis of genotypes and alleles of the different APOBEC3G variants showed that there is a strong association between the minor genetic variants, genotype of the three SNPs, and HIV-1 status. Haplotype analysis demonstrated that rs6001417, rs8177832, and rs35228531 are in linkage disequilibrium. The haplotype GGT from the rs6001417, rs8177832 and rs35228531 respectively has a protective effect OR = 0.54 [0.43-0.68] with P<0.001. There was also associations between the haplotypes GGC OR = 1.6 [1.1;-2.3] P<0.05, and CGC OR = 5.21 [2.4-11.3] P<0.001, which increase the risk of infection by HIV-1 from almost two (2 to five (5 fold. This study demonstrates an association of rs6001417, rs8177832, and rs35228531 of APOBEC3G with HIV-1 infection in a population from Burkina Faso.

Nicaragua y la exportación de café. Un análisis de regresión

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Ana Lissette Amaya L.

2014-11-01

Full Text Available El artículo explica la relación existente entre los volumenes exportados de café oro, el área cultivada expresadas en manzanas, y los precios promedios obtenidos por los productores por quintal de café oro exportando, para el caso de Nicaragua. Utilizando un modelo de regresión lineal múltiple. La fuente de información utilizada fueron las estadísticas del Banco Central de Nicaragua. El software estadístico fue el InfoStat.Se concluye que la relación existente entre las variables seleccionadas, es significativa, con un coeficiente de determinación del 68%, y con los distintos indicadores de significacia dentro de los rangos establecidos.

Functional modulation of the glutamate transporter variant GLT1b by the PDZ domain protein PICK1

DEFF Research Database (Denmark)

Søgaard, Rikke; Borre, Lars; Braunstein, Thomas H

2013-01-01

The dominant glutamate transporter isoform in the mammalian brain, GLT1, exists as at least three splice variants, GLT1a, GLT1b, and GLT1c. GLT1b interacts with the scaffold protein PICK1 (protein interacting with kinase C1), which is implicated in glutamatergic neurotransmission via its regulato...

Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families.

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Gormley, Padhraig; Kurki, Mitja I; Hiekkala, Marjo Eveliina; Veerapen, Kumar; Häppölä, Paavo; Mitchell, Adele A; Lal, Dennis; Palta, Priit; Surakka, Ida; Kaunisto, Mari Anneli; Hämäläinen, Eija; Vepsäläinen, Salli; Havanka, Hannele; Harno, Hanna; Ilmavirta, Matti; Nissilä, Markku; Säkö, Erkki; Sumelahti, Marja-Liisa; Liukkonen, Jarmo; Sillanpää, Matti; Metsähonkala, Liisa; Koskinen, Seppo; Lehtimäki, Terho; Raitakari, Olli; Männikkö, Minna; Ran, Caroline; Belin, Andrea Carmine; Jousilahti, Pekka; Anttila, Verneri; Salomaa, Veikko; Artto, Ville; Färkkilä, Markus; Runz, Heiko; Daly, Mark J; Neale, Benjamin M; Ripatti, Samuli; Kallela, Mikko; Wessman, Maija; Palotie, Aarno

2018-05-16

Complex traits, including migraine, often aggregate in families, but the underlying genetic architecture behind this is not well understood. The aggregation could be explained by rare, penetrant variants that segregate according to Mendelian inheritance or by the sufficient polygenic accumulation of common variants, each with an individually small effect, or a combination of the two hypotheses. In 8,319 individuals across 1,589 migraine families, we calculated migraine polygenic risk scores (PRS) and found a significantly higher common variant burden in familial cases (n = 5,317, OR = 1.76, 95% CI = 1.71-1.81, p = 1.7 × 10 -109 ) compared to population cases from the FINRISK cohort (n = 1,101, OR = 1.32, 95% CI = 1.25-1.38, p = 7.2 × 10 -17 ). The PRS explained 1.6% of the phenotypic variance in the population cases and 3.5% in the familial cases (including 2.9% for migraine without aura, 5.5% for migraine with typical aura, and 8.2% for hemiplegic migraine). The results demonstrate a significant contribution of common polygenic variation to the familial aggregation of migraine. Copyright © 2018 Elsevier Inc. All rights reserved.

Accumulation of MxB/Mx2-resistant HIV-1 Capsid Variants During Expansion of the HIV-1 Epidemic in Human Populations.

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Wei, Wei; Guo, Haoran; Ma, Min; Markham, Richard; Yu, Xiao-Fang

2016-06-01

Recent studies have identified human myxovirus resistance protein 2 (MxB or Mx2) as an interferon induced inhibitor of HIV-1 replication. However, whether HIV-1 can overcome MxB restriction without compromise of viral fitness has been undefined. Here, we have discovered that naturally occurring capsid (CA) variants can render HIV-1 resistant to the activity of MxB without losing viral infectivity or the ability to escape from interferon induction. Moreover, these MxB resistant HIV-1 variants do not lose MxB recognition. Surprisingly, MxB resistant CA variants are most commonly found in the Clade C HIV-1 that is the most rapidly expanding Clade throughout the world. Accumulation of MxB resistant mutations is also observed during HIV-1 spreading in human populations. These findings support a potential role for MxB as a selective force during HIV-1 transmission and evolution. Copyright © 2016. Published by Elsevier B.V.

Aplicação do agente biológico Cladosporium cladosporioides (Fresen) de Vries “Cladosporin” como bioprotetor da qualidade do café (Coffea arabica L.)

OpenAIRE

Angélico, Caroline Lima

2013-01-01

O produto à base do agente bioprotetor da qualidade do café Cladosporium cladosporioides (Fresen) de Vries é uma alternativa promissora para a aplicação nos frutos de café ainda na lavoura, por se tratar de um produto biológico contendo um micro-organismo com características GRAS (General Regarded as Safe) e com reconhecida ação deletéria sobre fungos prejudiciais à qualidade do produto final. A aplicação do produto nos frutos poderia promover a manutenção ou a melhoria da qualidade de cafés ...

Serum cholinesterase polymorphism (CHE1 and CHE2 loci) among several Indian groups from Amazon region of Brazil, and segregation of the C5 variant in families.

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Guerreiro, J F; Santos, S E; Aguiar, G F

1989-04-01

Eight Indian tribes from the Amazon region of Brazil (Araweté, Arara, Yamamadi, Kararaô, Karitiana, Waiampi, Surui and Cinta Larga) were studied for the distribution of the atypical and C5 variants of serum cholinesterase. None of them presented the CHE1*A allele, but the C5 variant was found in the Araweté (20.4%), Kararaô (15.6%), Karitiana (50.5%), Surui (12.3%) and Cinta Larga (19.6%) tribes. The frequency of the C5+ phenotype in the Karitiana is the highest reported thus far in human populations. Segregation studies considering the C5 variant were made among the Karitiana, and also among the Urubu-Kaapor and Munduruku tribes previously studied by Guerreiro et al [1987a, 1987b]. Most of the data were in agreement with the genetic hypothesis, but they also revealed a significant lack of the C5+ phenotype in offspring from C5+ X C5+ matings, as well as the occurrence of two C5+ children from C5- X C5- unions, in the Urubu-Kaapor tribe.

Swift heavy ion irradiation of CaF2 - from grooves to hillocks in a single ion track

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Gruber, Elisabeth; Salou, Pierre; Bergen, Lorenz; El Kharrazi, Mourad; Lattouf, Elie; Grygiel, Clara; Wang, Yuyu; Benyagoub, Abdenacer; Levavasseur, Delphine; Rangama, Jimmy; Lebius, Henning; Ban-d'Etat, Brigitte; Schleberger, Marika; Aumayr, Friedrich

2016-10-01

A novel form of ion-tracks, namely nanogrooves and hillocks, are observed on CaF2 after irradiation with xenon and lead ions of about 100 MeV kinetic energy. The irradiation is performed under grazing incidence (0.3°-3°) which forces the track to a region in close vicinity to the surface. Atomic force microscopy imaging of the impact sites with high spatial resolution reveals that the surface track consists in fact of three distinct parts: each swift heavy ion impacting on the CaF2 surface first opens a several 100 nm long groove bordered by a series of nanohillocks on both sides. The end of the groove is marked by a huge single hillock and the further penetration of the swift projectile into deeper layers of the target is accompanied by a single protrusion of several 100 nm in length slowly fading until the track vanishes. By comparing experimental data for various impact angles with results of a simulation, based on a three-dimensional version of the two-temperature-model (TTM), we are able to link the crater and hillock formation to sublimation and melting processes of CaF2 due to the local energy deposition by swift heavy ions.

Listeners' processing of a given reduced word pronunciation variant directly reflects their exposure to this variant: Evidence from native listeners and learners of French.

Science.gov (United States)

Brand, Sophie; Ernestus, Mirjam

2018-05-01

In casual conversations, words often lack segments. This study investigates whether listeners rely on their experience with reduced word pronunciation variants during the processing of single segment reduction. We tested three groups of listeners in a lexical decision experiment with French words produced either with or without word-medial schwa (e.g., /ʀvy/ and /ʀvy/ for revue). Participants also rated the relative frequencies of the two pronunciation variants of the words. If the recognition accuracy and reaction times (RTs) for a given listener group correlate best with the frequencies of occurrence holding for that given listener group, recognition is influenced by listeners' exposure to these variants. Native listeners' relative frequency ratings correlated well with their accuracy scores and RTs. Dutch advanced learners' accuracy scores and RTs were best predicted by their own ratings. In contrast, the accuracy and RTs from Dutch beginner learners of French could not be predicted by any relative frequency rating; the rating task was probably too difficult for them. The participant groups showed behaviour reflecting their difference in experience with the pronunciation variants. Our results strongly suggest that listeners store the frequencies of occurrence of pronunciation variants, and consequently the variants themselves.

Impact of ABCB1 variants on neutrophil depression: a prospective study

DEFF Research Database (Denmark)

Bergmann, Troels Korshøj; Andersen, Charlotte Brasch; Gréen, Henrik

2010-01-01

toxicity was registered. Patients carrying one or two variant alleles of ABCB1 C3435T had progressively more pronounced neutrophil decrease at nadir (P-value 0.03). The same association was found for ABCB1 C1236T and G2677T/A with P-values of 0.06 and 0.02. No statistically significant correlations were...

Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking.

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Rachel F Tyndale

Full Text Available CHRNA5-A3-B4 variants, rs16969968, rs588765 and rs578776, are consistently associated with tobacco consumption among smokers, but the association with smoking cessation is less consistent. Among the studies that reported significant associations with cessation, the effects were observed in smokers treated with placebo treatment in some studies and conversely in those receiving active pharmacological therapy (bupropion and nicotine replacement therapies in others. Thus, it remains unclear whether CHRNA5-A3-B4 is a useful marker for optimizing smoking cessation. Using data from 654 Caucasian smokers treated with placebo, nicotine patch or varenicline, we investigated whether CHRNA5-A3-B4 variants were associated with smoking cessation outcomes, and whether there were significant genotype-by-treatment or haplotype-by-treatment interactions. We observed no significant associations between CHRNA5-A3-B4 variants and smoking cessation, despite replicating previous associations with baseline tobacco consumption. At end of treatment the effect size on smoking cessation in the placebo, patch and varenicline groups for rs16969968 [GG vs. GA+AA] was OR = 0.66 (P = 0.23, OR = 1.01 (P = 0.99, and OR = 1.30 (P = 0.36 respectively, of rs588765 [CC vs. CT+TT] was OR = 0.96 (P = 0.90, OR = 0.84 (P = 0.58, and OR = 0.74 (P = 0.29 respectively, and for rs578776 [GG vs. GA+AA] on smoking cessation was OR = 1.02 (P = 0.95, OR = 0.75 (P = 0.35, and OR = 1.20 (P = 0.51 respectively. Furthermore, we observed no associations with cessation using the CHRNA5-A3-B4 haplotype (constructed using rs16969968 and rs588765, nor did we observe any significant genotype-by-treatment interactions, with or without adjusting for the rate of nicotine metabolism (all P>0.05. We also observed no significant genetic associations with 6 month or 12 month smoking abstinence. In conclusion, we found no association between CHRNA5-A3-B4 variants and smoking cessation rates in this clinical

Pancreatic Fibroblasts Stimulate the Motility of Pancreatic Cancer Cells through IGF1/IGF1R Signaling under Hypoxia.

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Toshiki Hirakawa

Full Text Available Pancreatic ductal adenocarcinoma (PDAC is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs, the expression of insulin-like growth factor-1 (IGF1 and IGF1 receptor (IGF1R was evaluated by RT-PCR, FACScan, western blot, or ELISA. Correlation between IGF1R and the hypoxia marker carbonic anhydrase 9 (CA9 was examined by immunohistochemical staining of 120 pancreatic specimens. The effects of CAFs, IGF1, and IGF1R inhibitors on the motility of cancer cells were examined by wound-healing assay or invasion assay under normoxia (20% O2 and hypoxia (1% O2. IGF1R expression was significantly higher in RWP-1, MiaPaCa-2, and OCUP-AT cells than in Panc-1 cells. Hypoxia increased the expression level of IGF1R in RWP-1, MiaPaCa-2, and OCUP-AT cells. CA9 expression was correlated with IGF1R expression in pancreatic specimens. CAFs produced IGF1 under hypoxia, but PDAC cells did not. A conditioned medium from CAFs, which expressed αSMA, stimulated the migration and invasion ability of MiaPaCa-2, RWP-1, and OCUP-AT cells. The motility of all PDAC cells was greater under hypoxia than under normoxia. The motility-stimulating ability of CAFs was decreased by IGF1R inhibitors. These findings might suggest that pancreas CAFs stimulate the invasion activity of PDAC cells through paracrine IGF1/IGF1R signaling, especially under hypoxia. Therefore the targeting of IGF1R signaling might represent a promising therapeutic approach in IGF1R-dependent PDAC.

Desarrollo de método cromatográfico para la determinación de plaguicidas organoclorados en muestras de café

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Gema Medina

2009-08-01

Full Text Available A pesar de que existe el compromiso de cumplir con el Convenio de Estocolmo, en Nicaragua se siguen utilizando plaguicidas organoclorados en la producción de café y otros rubros de exportación. En esta investigación se ha hecho un inventario delos plaguicidas más utilizados en la producción de café en Nicaragua, y a partir de la evaluación del inventario, se ha considerado oportuno poner a punto un procedimiento cromatográfico para la determinación de plaguicidas organoclorados en muestras de café.La determinación se ha llevado a cabo mediante cromatografía de gases con columna capilar y un detector de captura de electrones específico para el análisis de estos plaguicidas. Previo a la determinación cromatográfica se ha optimizado un método de extracción y purificación a fin de eliminar componentes de la matriz que pudieraninterferir en la cuantificación de los plaguicidas.Con esta investigación se pretende apoyar al sector cafetalero en el análisis de estos plaguicidas, lo que constituye un parámetro de control de calidad que exigen actualmente los importadores de café y está contemplado en las legislaciones de los países.

Evolution of simeprevir-resistant variants over time by ultra-deep sequencing in HCV genotype 1b.

Science.gov (United States)

Akuta, Norio; Suzuki, Fumitaka; Sezaki, Hitomi; Suzuki, Yoshiyuki; Hosaka, Tetsuya; Kobayashi, Masahiro; Kobayashi, Mariko; Saitoh, Satoshi; Ikeda, Kenji; Kumada, Hiromitsu

2014-08-01

Using ultra-deep sequencing technology, the present study was designed to investigate the evolution of simeprevir-resistant variants (amino acid substitutions of aa80, aa155, aa156, and aa168 positions in HCV NS3 region) over time. In Toranomon Hospital, 18 Japanese patients infected with HCV genotype 1b, received triple therapy of simeprevir/PEG-IFN/ribavirin (DRAGON or CONCERT study). Sustained virological response rate was 67%, and that was significantly higher in patients with IL28B rs8099917 TT than in those with non-TT. Six patients, who did not achieve sustained virological response, were tested for resistant variants by ultra-deep sequencing, at the baseline, at the time of re-elevation of viral loads, and at 96 weeks after the completion of treatment. Twelve of 18 resistant variants, detected at re-elevation of viral load, were de novo resistant variants. Ten of 12 de novo resistant variants become undetectable over time, and that five of seven resistant variants, detected at baseline, persisted over time. In one patient, variants of Q80R at baseline (0.3%) increased at 96-week after the cessation of treatment (10.2%), and de novo resistant variants of D168E (0.3%) also increased at 96-week after the cessation of treatment (9.7%). In conclusion, the present study indicates that the emergence of simeprevir-resistant variants after the start of treatment could not be predicted at baseline, and the majority of de novo resistant variants become undetectable over time. Further large-scale prospective studies should be performed to investigate the clinical utility in detecting simeprevir-resistant variants. © 2014 Wiley Periodicals, Inc.

Café convencional versus café orgânico: perspectivas de sustentabilidade socioeconômica dos agricultores familiares do Espírito Santo