[Morphea or juvenile localised scleroderma: Case report].

Science.gov (United States)

Strickler, Alexis; Gallo, Silvanna; Jaramillo, Pedro; de Toro, Gonzalo

2016-01-01

Morphea or juvenile localised scleroderma (JLS) is an autoimmune, inflammatory, chronic, slowly progressive connective tissue disease of unknown cause that preferably affects skin and underlying tissues. To report a case of Juvenil Localised scleroderma in an 8-year old girl, contributing to an early diagnosis and treatment. The case is presented of an 8 year-old girl who presented with indurated hypopigmented plaques, of linear distribution in the right upper extremity of two years onset, together with papery texture hyperpigmented indurated plaques with whitish areas of thinned skin in right lower extremity, and leg and ankle swelling. The clinical features and diagnostic tests, including histology were compatible with linear and pansclerotic JLS. She started with immunosuppressive therapy, physiotherapy, and occupational therapy. We report a case of linear and pansclerotic ELJ type, in which there was a 2 year delay in diagnosis, however the response to treatment was positive as expected. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Experiences with a new breast localisation needle

International Nuclear Information System (INIS)

Hergan, K.; Amann, T.; Doringer, W.; Hollenstein, P.

1990-01-01

In view of the increasing number of biopsies of non-palpable lesions of the female breast we found an ideal localisation system in the Hawkins breast localisation needle. Localisation was successful without technical problems in 31 out of 34 patients. The special advantages of the needle are its stability in position and excellent manoeverability due to the construction of the needle. The very simple handling of the needle is an advantage not only for the radiologist but also for the surgeon. (orig.) [de

Localisation of Abundant and Organ-Specific Genes Expressed in Rosa hybrida Leaves and Flower Buds by Direct In Situ RT-PCR

Directory of Open Access Journals (Sweden)

Agata Jedrzejuk

2012-01-01

Full Text Available In situ PCR is a technique that allows specific nucleic acid sequences to be detected in individual cells and tissues. In situ PCR and IS-RT-PCR are elegant techniques that can increase both sensitivity and throughput, but they are, at best, only semiquantitative; therefore, it is desirable first to ascertain the expression pattern by conventional means to establish the suitable conditions for each probe. In plants, in situ RT-PCR is widely used in the expression localisation of specific genes, including MADS-box and other function-specific genes or housekeeping genes in floral buds and other organs. This method is especially useful in small organs or during early developmental stages when the separation of particular parts is impossible. In this paper, we compared three different labelling and immunodetection methods by using in situ RT-PCR in Rosa hybrida flower buds and leaves. As target genes, we used the abundant β-actin and RhFUL gene, which is expressed only in the leaves and petals/sepals of flower buds. We used digoxygenin-11-dUTP, biotin-11-dUTP, and fluorescein-12-dUTP-labelled nucleotides and antidig-AP/ streptavidin-fluorescein-labelled antibodies. All of the used methods gave strong, specific signal and all of them may be used in localization of gene expression on tissue level in rose organs.

Strain localisation in granular media

OpenAIRE

Desrues , Jacques

1984-01-01

This study is devoted to strain localisation in Granular materials. Both experimental and theoretical results have been obtained.The first part of the thesis is a review of the methods and theories about rupture in sols mechanics and more generally, in solid mechanics. The classical framework of Shear Band analysis is presented, and the main results available for different classes of materials are discussed.The second part describes an experimental study of strain localisation in sand specime...

Feasibility of magnetic marker localisation for non-palpable breast cancer.

Science.gov (United States)

Schermers, B; van der Hage, J A; Loo, C E; Vrancken Peeters, M T F D; Winter-Warnars, H A O; van Duijnhoven, F; Ten Haken, B; Muller, S H; Ruers, T J M

2017-06-01

Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high administrative burden (radioactive localisation). We present MAgnetic MArker LOCalisation (MaMaLoc), a novel technology that aims to overcome these disadvantages using a magnetic marker and a magnetic detection probe. This feasibility study reports on the first experience with this new technology for breast cancer localisation. Fifteen patients with unifocal, non-palpable breast cancer were recruited. They received concurrent placement of the magnetic marker in addition to a radioactive iodine seed, which is standard of care in our clinic. In a subset of five patients, migration of the magnetic marker was studied. During surgery, a magnetic probe and gammaprobe were alternately used to localise the markers and guide surgery. The primary outcome parameter was successful transcutaneous identification of the magnetic marker. Additionally, data on radiologist and surgeon satisfaction were collected. Magnetic marker placement was successful in all cases. Radiologists could easily adapt to the technology in the clinical workflow. Migration of the magnetic marker was negligible. The primary endpoint of the study was met with an identification rate of 100%. Both radiologists and surgeons reflected that the technology was intuitive to use and that it was comparable to radioactive iodine seed localisation. Magnetic marker localisation for non-palpable breast cancer is feasible and safe, and may be a viable non-radioactive alternative to current localisation technologies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multimodal Localisation: Analysis, Algorithms and Experimental Evaluation

NARCIS (Netherlands)

Kavitha Muthukrishnan, K.

2009-01-01

The term localisation is derived from the word locale, which traditionally means a small area or vicinity. In ancient days, localisation meant navigation -- an art of finding the way from one place to another. Tremendous advancement in the science of navigation dates back to the sixteenth century,

Feasibility of magnetic marker localisation for non-palpable breast cancer

NARCIS (Netherlands)

Schermers, B.; van der Hage, Jos A.; Loo, C.E.; Vrancken Peeters, M.T.F.D.; Winter-Warnars, H. A.O.; Duijnhoven, F.H.; ten Haken, B.; Muller, S.H.; Ruers, T. J.M.

2017-01-01

Objectives Accurate tumour localisation is essential for breast-conserving surgery of non-palpable tumours. Current localisation technologies are associated with disadvantages such as logistical challenges and migration issues (wire guided localisation) or legislative complexities and high

Prediction of three-dimensional residual stresses at localised indentations in pipes

International Nuclear Information System (INIS)

Hyde, T.H.; Luo, R.; Becker, A.A.

2012-01-01

Residual stresses are investigated using Finite Element (FE) analyses at localised indentations in pipes with and without internal pressures due to reverse plasticity caused by springback of the surrounding material after removal of the indenter. The indentation loading is applied via rigid 3D short indenters. The effects of the residual indentation depth, internal pressure, indenter size and different material properties on the residual stresses for different pipes have been investigated by carrying out parametric sensitivity studies. In order to predict the residual stresses, empirical formulations have been developed, which show a good correlation with the FE for residual stresses for pipes with diameter to thickness ratios of 35–72. - Highlights: ► A comprehensive elastic–plastic FE analysis of residual stresses caused by localised pipe indentations is presented. ► The effects of residual indentation depth, internal pressure, indenter size and material properties have been studied. ► Empirical formulations have been developed, which show a good correlation with the FE for residual stresses for pipes with diameter to thickness ratios of 35–72.

Hydroxysteroid dehydrogenase HSD1L is localised to the pituitary–gonadal axis of primates

Directory of Open Access Journals (Sweden)

A Daniel Bird

2017-09-01

Full Text Available Steroid hormones play clinically important and specific regulatory roles in the development, growth, metabolism, reproduction and brain function in human. The type 1 and 2 11-beta hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 2 have key roles in the pre-receptor modification of glucocorticoids allowing aldosterone regulation of blood pressure, control of systemic fluid and electrolyte homeostasis and modulation of integrated metabolism and brain function. Although the activity and function of 11β-HSDs is thought to be understood, there exists an open reading frame for a distinct 11βHSD-like gene; HSD11B1L, which is present in human, non-human primate, sheep, pig and many other higher organisms, whereas an orthologue is absent in the genomes of mouse, rat and rabbit. We have now characterised this novel HSD11B1L gene as encoded by 9 exons and analysis of EST library transcripts indicated the use of two alternate ATG start sites in exons 2 and 3, and alternate splicing in exon 9. Relatively strong HSD11B1L gene expression was detected in human, non-human primate and sheep tissue samples from the brain, ovary and testis. Analysis in non-human primates and sheep by immunohistochemistry localised HSD11B1L protein to the cytoplasm of ovarian granulosa cells, testis Leydig cells, and gonadatroph cells in the anterior pituitary. Intracellular localisation analysis in transfected human HEK293 cells showed HSD1L protein within the endoplasmic reticulum and sequence analysis suggests that similar to 11βHSD1 it is membrane bound. The endogenous substrate of this third HSD enzyme remains elusive with localisation and expression data suggesting a reproductive hormone as a likely substrate.

Implementing localisation programmes in South Africa

CSIR Research Space (South Africa)

Strachan, Garth

2017-10-01

Full Text Available challenges – from job creation and poverty reduction to participating in the technological revolution and global value chains, from promoting efficient and clean energy to mitigating climate change and greening the economy – without using some kind... sector value chains where the public sector supports supplier development – e.g. automotives, retail, clothing and textiles etc. Support for technology localisation and diffusion – The Technology Localisation and Implementation Unit [TLIU...

Generalised two target localisation using passive monopulse radar

KAUST Repository

Jardak, Seifallah; Ahmed, Sajid; Alouini, Mohamed-Slim

2017-01-01

The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localisation and tracking purposes. Many works focused on accurately localising one or two targets lying within a narrow beam centred around

Impact source localisation in aerospace composite structures

Science.gov (United States)

De Simone, Mario Emanuele; Ciampa, Francesco; Boccardi, Salvatore; Meo, Michele

2017-12-01

The most commonly encountered type of damage in aircraft composite structures is caused by low-velocity impacts due to foreign objects such as hail stones, tool drops and bird strikes. Often these events can cause severe internal material damage that is difficult to detect and may lead to a significant reduction of the structure’s strength and fatigue life. For this reason there is an urgent need to develop structural health monitoring systems able to localise low-velocity impacts in both metallic and composite components as they occur. This article proposes a novel monitoring system for impact localisation in aluminium and composite structures, which is able to determine the impact location in real-time without a-priori knowledge of the mechanical properties of the material. This method relies on an optimal configuration of receiving sensors, which allows linearization of well-known nonlinear systems of equations for the estimation of the impact location. The proposed algorithm is based on the time of arrival identification of the elastic waves generated by the impact source using the Akaike Information Criterion. The proposed approach was demonstrated successfully on both isotropic and orthotropic materials by using a network of closely spaced surface-bonded piezoelectric transducers. The results obtained show the validity of the proposed algorithm, since the impact sources were detected with a high level of accuracy. The proposed impact detection system overcomes current limitations of other methods and can be retrofitted easily on existing aerospace structures allowing timely detection of an impact event.

Neuronal NOS localises to human airway cilia.

Science.gov (United States)

Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

2015-01-30

Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

Localisation of RNAs into the germ plasm of vitellogenic Xenopus oocytes.

Directory of Open Access Journals (Sweden)

Sarbjit Nijjar

Full Text Available We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2, we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the "late", Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others.

Indoor Localisation Based on GSM Signals: Multistorey Building Study

Directory of Open Access Journals (Sweden)

Rafał Górak

2016-01-01

Full Text Available Among the accurate indoor localisation systems that are using WiFi, Bluetooth, or infrared technologies, the ones that are based on the GSM rely on a stable external infrastructure that can be used even in an emergency. This paper presents an accurate GSM indoor localisation system that achieves a median error of 4.39 metres in horizontal coordinates and up to 64 percent accuracy in floor prediction (for 84 percent of cases the floor prediction is mistaken by not more than a single floor. The test and reference measurements were made inside a six-floor academic building, with an irregular shape, whose dimensions are around 50 metres by 70 metres. The localisation algorithm uses GSM signal readings from the 7 strongest cells available in the GSM standard (or fewer, if fewer than 7 are available. We estimate the location by a three-step method. Firstly, we propose a point localisation solution (i.e., localisation based on only one measurement. Then, by applying the central tendency filters and the Multilayer Perceptron, we build a localisation system that uses a sequence of estimations of current and past locations. We also discuss major accuracy factors such as the number of observed signals or the types of spaces in the building.

Control of ADAM17 activity by regulation of its cellular localisation

Science.gov (United States)

Lorenzen, Inken; Lokau, Juliane; Korpys, Yvonne; Oldefest, Mirja; Flynn, Charlotte M.; Künzel, Ulrike; Garbers, Christoph; Freeman, Matthew; Grötzinger, Joachim; Düsterhöft, Stefan

2016-01-01

An important, irreversible step in many signalling pathways is the shedding of membrane-anchored proteins. A Disintegrin And Metalloproteinase (ADAM) 17 is one of the major sheddases involved in a variety of physiological and pathophysiological processes including regeneration, differentiation, and cancer progression. This central role in signalling implies that ADAM17 activity has to be tightly regulated, including at the level of localisation. Most mature ADAM17 is localised intracellularly, with only a small amount at the cell surface. We found that ADAM17 is constitutively internalised by clathrin-coated pits and that physiological stimulators such as GPCR ligands induce ADAM17-mediated shedding, but do not alter the cell-surface abundance of the protease. In contrast, the PKC-activating phorbol ester PMA, often used as a strong inducer of ADAM17, causes not only proteolysis by ADAM17 but also a rapid increase of the mature protease at the cell surface. This is followed by internalisation and subsequent degradation of the protease. Eventually, this leads to a substantial downregulation of mature ADAM17. Our results therefore imply that physiological activation of ADAM17 does not rely on its relocalisation, but that PMA-induced PKC activity drastically dysregulates the localisation of ADAM17. PMID:27731361

Generalised two target localisation using passive monopulse radar

KAUST Repository

Jardak, Seifallah

2017-04-07

The simultaneous lobing technique, also known as monopulse technique, has been widely used for fast target localisation and tracking purposes. Many works focused on accurately localising one or two targets lying within a narrow beam centred around the monopulse antenna boresight. In this study, a new approach is proposed, which uses the outputs of four antennas to rapidly localise two point targets present in the hemisphere. If both targets have the same elevation angle, the proposed scheme cannot detect them. To detect such targets, a second set of antennas is required. In this study, to detect two targets at generalised locations, the antenna array is divided into multiple overlapping sets each of four antennas. Two algorithms are proposed to combine the outputs from multiple sets and improve the detection performance. Simulation results show that the algorithm is able to localise both targets with <;2° mean square error in azimuth and elevation.

Localisation for industrial development

CSIR Research Space (South Africa)

Bhugwandin, Ashley

2017-10-01

Full Text Available This presentation focuses on localisation for industrial development, and is presented by Ashley Bhugwandin at The 6th CSIR Conference: Ideas that work for industrial development, 5-6 October 2017, CSIR International Convention Centre, Pretoria...

Enantioselective cellular localisation of europium(iii) coordination complexes.

Science.gov (United States)

Frawley, Andrew T; Linford, Holly V; Starck, Matthieu; Pal, Robert; Parker, David

2018-01-28

The selective mitochondrial localisation of the Λ enantiomer of three different emissive europium(iii) complexes in NIH 3T3 and MCF7 cells contrasts with the behaviour of the Δ enantiomer, for which a predominant lysosomal localisation was observed by confocal microscopy. In each case, cell uptake occurs via macropinocytosis.

Localisation of relaxin peptides in the brain: comparative mapping of relaxin-R2 and the novel relaxin-R3 gene expression

International Nuclear Information System (INIS)

Burazin, T.C.D.; Macris, M.; Gundlach, A.L.; Tregear, G.W.

2002-01-01

Full text: Relaxin is a peptide hormone with known actions in the female reproductive tract that has also been identified in brain. Until recently, only one relaxin gene has been described in the rat and mouse. However, we have recently identified a new member of the relaxin gene family, relaxin gene-3, expressed in human, mouse and rat. Using [ 35 S]-labelled oligonucleotide probes and in situ hybridisation histochemistry, the current studies describe the distribution of mRNA encoding rat relaxin gene-1 (R1) and rat relaxin gene-3 (R3) in the adult rat brain. R1 mRNA was detected in several regions including the anterior olfactory nucleus, tenia tecta, orbital, frontal and piriform cortices, and in lower abundance in the hippocampus. In contrast, highly abundant expression of R3 mRNA was more restricted being present in the pars ventromedialis subdivision of the dorsal tegmental nucleus (vmDTg), with some low level expression in the hippocampus. Autoradiographic visualisation of [ 33 P]-labelled human relaxin binding sites revealed the presence of putative relaxin receptors in the DTg centralis and vmDTg, as well as in several forebrain areas previously identified. Studies are currently underway to investigate the activity-dependent regulation and developmental expression of relaxin transcripts, including the possible co-localisation of R3 mRNA with neurotransmitters such as GABA and 5- HT, and other peptides. These studies are consistent with an important role for these novel relaxin peptides in the rat central nervous system. Copyright (2002) Australian Neuroscience Society

Treatment of localised resectable neuroblastoma. Results of the LNESG1 study by the SIOP Europe Neuroblastoma Group

NARCIS (Netherlands)

de Bernardi, B.; Mosseri, V.; Rubie, H.; Castel, V.; Foot, A.; Ladenstein, R.; Laureys, G.; Beck-Popovic, M.; de Lacerda, A. F.; Pearson, A. D. J.; de Kraker, J.; Ambros, P. F.; de Rycke, Y.; Conte, M.; Bruzzi, P.; Michon, J.

2008-01-01

Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal

To localise or to be localised with Wifi in the Hubei museum?

NARCIS (Netherlands)

Verbree, E.; Zlatanova, S.; Van Winden, K.; Van der Laan, E.B.; Makri, A.; Taizhou, L.; Haojun, A.

2013-01-01

Indoor localisation is in demand for a variety of applications within the built environment. An overall solution based on a single technology has not yet been determined. The aim of this paper is to gain insight on Signal Strength monitoring by a special kind of WiFi Monitors in comparison to the

Anderson localisation and optical-event horizons in rogue-soliton generation.

Science.gov (United States)

Saleh, Mohammed F; Conti, Claudio; Biancalana, Fabio

2017-03-06

We unveil the relation between the linear Anderson localisation process and nonlinear modulation instability. Anderson localised modes are formed in certain temporal intervals due to the random background noise. Such localised modes seed the formation of solitary waves that will appear during the modulation instability process at those preferred intervals. Afterwards, optical-event horizon effects between dispersive waves and solitons produce an artificial collective acceleration that favours the collision of solitons, which could eventually lead to a rogue-soliton generation.

Germ plasm localisation of the HELICc of Vasa in Drosophila: analysis of domain sufficiency and amino acids critical for localisation

Science.gov (United States)

Wang, Szu-Chieh; Hsu, Hao-Jen; Lin, Gee-Way; Wang, Ting-Fang; Chang, Chun-Che; Lin, Ming-Der

2015-09-01

Formation of the germ plasm drives germline specification in Drosophila and some other insects such as aphids. Identification of the DEAD-box protein Vasa (Vas) as a conserved germline marker in flies and aphids suggests that they share common components for assembling the germ plasm. However, to which extent the assembly order is conserved and the correlation between functions and sequences of Vas remain unclear. Ectopic expression of the pea aphid Vas (ApVas1) in Drosophila did not drive its localisation to the germ plasm, but ApVas1 with a replaced C-terminal domain (HELICc) of Drosophila Vas (DmVas) became germ-plasm restricted. We found that HELICc itself, through the interaction with Oskar (Osk), was sufficient for germ-plasm localisation. Similarly, HELICc of the grasshopper Vas could be recruited to the germ plasm in Drosophila. Nonetheless, germ-plasm localisation was not seen in the Drosophila oocytes expressing HELICcs of Vas orthologues from aphids, crickets, and mice. We further identified that glutamine (Gln) 527 within HELICc of DmVas was critical for localisation, and its corresponding residue could also be detected in grasshopper Vas yet missing in the other three species. This suggests that Gln527 is a direct target of Osk or critical to the maintenance of HELICc conformation.

Localised boundary air layer and clothing evaporative resistances for individual body segments.

Science.gov (United States)

Wang, Faming; del Ferraro, Simona; Lin, Li-Yen; Sotto Mayor, Tiago; Molinaro, Vincenzo; Ribeiro, Miguel; Gao, Chuansi; Kuklane, Kalev; Holmér, Ingvar

2012-01-01

Evaporative resistance is an important parameter to characterise clothing thermal comfort. However, previous work has focused mainly on either total static or dynamic evaporative resistance. There is a lack of investigation of localised clothing evaporative resistance. The objective of this study was to study localised evaporative resistance using sweating thermal manikins. The individual and interaction effects of air and body movements on localised resultant evaporative resistance were examined in a strict protocol. The boundary air layer's localised evaporative resistance was investigated on nude sweating manikins at three different air velocity levels (0.18, 0.48 and 0.78 m/s) and three different walking speeds (0, 0.96 and 1.17 m/s). Similarly, localised clothing evaporative resistance was measured on sweating manikins at three different air velocities (0.13, 0.48 and 0.70 m/s) and three walking speeds (0, 0.96 and 1.17 m/s). Results showed that the wind speed has distinct effects on local body segments. In contrast, walking speed brought much more effect on the limbs, such as thigh and forearm, than on body torso, such as back and waist. In addition, the combined effect of body and air movement on localised evaporative resistance demonstrated that the walking effect has more influence on the extremities than on the torso. Therefore, localised evaporative resistance values should be provided when reporting test results in order to clearly describe clothing local moisture transfer characteristics. Localised boundary air layer and clothing evaporative resistances are essential data for clothing design and assessment of thermal comfort. A comprehensive understanding of the effects of air and body movement on localised evaporative resistance is also necessary by both textile and apparel researchers and industry.

Localisation of beam offset jitter sources at ATF2

CERN Document Server

Pfingstner, J; Patecki, M; Schulte, D; Tomás, R

2014-01-01

For the commissioning and operation of modern particle accelerators, automated error detection and diagnostics methods are becoming increasingly important. In this paper, we present two such methods, which are capable of localising sources of beam offset jitter with a combination of correlation studies and so called degree of freedom plots. The methods were applied to the ATF2 beam line at KEK, where one of the major goals is the reduction of the beam offset jitter. Results of this localisation are shown in this paper. A big advantage of the presented method is its high robustness especially to varying optics parameters. Therefore, we believe that the developed beam offset jitter localisation methods can be easily applied to other accelerators.

Localisation system in wireless sensor networks using ns-2

CSIR Research Space (South Africa)

Abu-Mahfouz, Adnan M

2012-04-01

Full Text Available -1 /************************************************************************** ********** * * File: readme.asn * * Author: Adnan Abu-Mahfouz * * Date: March 2012 * * Description: Localisation system in wireless sensor networks using ns-2... *************************************************************************** *********/ /************************************************************************** *************************************************************************** *****/ 1. Introduction: ns-2 contains several flexible features that encourage researchers to use ns-2 to investigate the characteristics of wireless sensor networks (WSNs). However, to implement and evaluate localisation algorithms, the current ns- 2...

Rare localisations of osteochondrosis juvenilis

Energy Technology Data Exchange (ETDEWEB)

Schumacher, R; Schuster, W; Mueller, U

1981-04-01

A survey of rare localisations of osteochondrosis juvenilis is given and illustrated by cases of Morbus Friedrich, Morbus Panner, Vertebra plana Calve, Morbus Blount, Morbus Iselin, Morbus Hegemann and Morbus Thiemann. This is followed by discussion of etiology and differential diagnosis.

Differences in finger localisation performance of patients with finger agnosia

NARCIS (Netherlands)

Anema, H.A.; Kessels, R.P.C.; de Haan, E.H.F.; Kappelle, L.J.; Leijten, F.S.; van Zandvoort, M.J.E.; Dijkerman, H.C.

2008-01-01

Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports

Differences in finger localisation performance of patients with finger agnosia.

NARCIS (Netherlands)

Anema, H.A.; Kessels, R.P.C.; Haan, E.H.F. de; Kappelle, L.J.; Leijten, F.S.S.; Zandvoort, M.J. Van; Dijkerman, H.C.

2008-01-01

Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports

Kyste hydatique à localisation costo vertébrale

Science.gov (United States)

Marouf, Rachid

2014-01-01

L'hydatidose est une affection parasitaire due à la contamination de l'homme par la forme larvaire de ténia échinococcus granulosus, la forme costo vertébrale est une localisation très rare qui représente 0,18 à 1,21% de l'ensemble des localisations hydatiques. Nous rapportons le cas d'une femme de 32 ans qui présente un kyste hydatique multi vésiculaire à localisation costovertébrale, traité par chirurgie radicale associée à un traitement médical anti parasitaire pour une durée de 6 mois, avec bonne évolution. L'atteinte costo-vertébrale par la maladie hydatique est rare et l’évolution est insidieuse. Malgré un traitement chirurgical radical, la fréquence des récidives rend le pronostic sombre. PMID:25922632

Differences in finger localisation performance of patients with finger agnosia

NARCIS (Netherlands)

Anema, H.A.; Kessels, R.P.C.; Haan, E.H.F. de; Kappelle, L.J.; Leijten, F.S.S.; Zandvoort, M.J.E. van; Dijkerman, H.C.

2008-01-01

Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on ones own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports describe

Neuroglobin in the rat brain (II): co-localisation with neurotransmitters

DEFF Research Database (Denmark)

Hundahl, Christian Ansgar; Kelsen, Jesper; Dewilde, Sylvia

2008-01-01

In an accompanying article, we found that neuroglobin (Ngb) was expressed in a few well-defined nuclei in the rat brain. Here, we show by use of immunohistochemistry and in situ hybridisation (ISH) that Ngb co-localise with several specific neurotransmitters. Ngb co-localise consistently with tyr...

Is the Pauli exclusion principle the origin of electron localisation?

Science.gov (United States)

Rincón, Luis; Torres, F. Javier; Almeida, Rafael

2018-03-01

In this work, we inquire into the origins of the electron localisation as obtained from the information content of the same-spin pair density, γσ, σ(r2∣r1). To this end, we consider systems of non-interacting and interacting identical Fermions contained in two simple 1D potential models: (1) an infinite potential well and (2) the Kronig-Penney periodic potential. The interparticle interaction is considered through the Hartree-Fock approximation as well as the configuration interaction expansion. Morover, the electron localisation is described through the Kullback-Leibler divergence between γσ, σ(r2∣r1) and its associated marginal probability. The results show that, as long as the adopted method properly includes the Pauli principle, the electronic localisation depends only modestly on the interparticle interaction. In view of the latter, one may conclude that the Pauli principle is the main responsible for the electron localisation.

Electron localisation in static and time-dependent one-dimensional model systems

Science.gov (United States)

Durrant, T. R.; Hodgson, M. J. P.; Ramsden, J. D.; Godby, R. W.

2018-02-01

The most direct signature of electron localisation is the tendency of an electron in a many-body system to exclude other same-spin electrons from its vicinity. By applying this concept directly to the exact many-body wavefunction, we find that localisation can vary considerably between different ground-state systems, and can also be strongly disrupted, as a function of time, when a system is driven by an applied electric field. We use this measure to assess the well-known electron localisation function (ELF), both in its approximate single-particle form (often applied within density-functional theory) and its full many-particle form. The full ELF always gives an excellent description of localisation, but the approximate ELF fails in time-dependent situations, even when the exact Kohn-Sham orbitals are employed.

Localisation of gluconeogenesis and tricarboxylic acid (TCA)-cycle enzymes and first functional analysis of the TCA cycle in Toxoplasma gondii.

Science.gov (United States)

Fleige, Tobias; Pfaff, Nils; Gross, Uwe; Bohne, Wolfgang

2008-08-01

The apicomplexan parasite Toxoplasma gondii displays some unusual localisations of carbohydrate converting enzymes, which is due to the presence of a vestigial, non-photosynthetic plastid, referred to as the apicoplast. It was recently demonstrated that the single pyruvate dehydrogenase complex (PDH) in T. gondii is exclusively localised inside the apicoplast but absent in the mitochondrion. This raises the question about expression, localisation and function of enzymes for the tricarboxylic acid (TCA)-cycle, which normally depends on PDH generated acetyl-CoA. Based on the expression and localisation of epitope-tagged fusion proteins, we show that all analysed TCA cycle enzymes are localised in the mitochondrion, including both isoforms of malate dehydrogenase. The absence of a cytosolic malate dehydrogenase suggests that a typical malate-aspartate shuttle for transfer of reduction equivalents is missing in T. gondii. We also localised various enzymes which catalyse the irreversible steps in gluconeogenesis to a cellular compartment and examined mRNA expression levels for gluconeogenesis and TCA cycle genes between tachyzoites and in vitro bradyzoites. In order to get functional information on the TCA cycle for the parasite energy metabolism, we created a conditional knock-out mutant for the succinyl-CoA synthetase. Disruption of the sixth step in the TCA cycle should leave the biosynthetic parts of the cycle intact, but prevent FADH2 production. The succinyl-CoA synthetase depletion mutant displayed a 30% reduction in growth rate, which could be restored by supplementation with 2 microM succinate in the tissue culture medium. The mitochondrial membrane potential in these parasites was found to be unaltered. The lack of a more severe phenotype suggests that a functional TCA cycle is not essential for T. gondii replication and for maintenance of the mitochondrial membrane potential.

A high-density SNP genetic linkage map for the silver-lipped pearl oyster, Pinctada maxima: a valuable resource for gene localisation and marker-assisted selection.

Science.gov (United States)

Jones, David B; Jerry, Dean R; Khatkar, Mehar S; Raadsma, Herman W; Zenger, Kyall R

2013-11-20

The silver-lipped pearl oyster, Pinctada maxima, is an important tropical aquaculture species extensively farmed for the highly sought "South Sea" pearls. Traditional breeding programs have been initiated for this species in order to select for improved pearl quality, but many economic traits under selection are complex, polygenic and confounded with environmental factors, limiting the accuracy of selection. The incorporation of a marker-assisted selection (MAS) breeding approach would greatly benefit pearl breeding programs by allowing the direct selection of genes responsible for pearl quality. However, before MAS can be incorporated, substantial genomic resources such as genetic linkage maps need to be generated. The construction of a high-density genetic linkage map for P. maxima is not only essential for unravelling the genomic architecture of complex pearl quality traits, but also provides indispensable information on the genome structure of pearl oysters. A total of 1,189 informative genome-wide single nucleotide polymorphisms (SNPs) were incorporated into linkage map construction. The final linkage map consisted of 887 SNPs in 14 linkage groups, spans a total genetic distance of 831.7 centimorgans (cM), and covers an estimated 96% of the P. maxima genome. Assessment of sex-specific recombination across all linkage groups revealed limited overall heterochiasmy between the sexes (i.e. 1.15:1 F/M map length ratio). However, there were pronounced localised differences throughout the linkage groups, whereby male recombination was suppressed near the centromeres compared to female recombination, but inflated towards telomeric regions. Mean values of LD for adjacent SNP pairs suggest that a higher density of markers will be required for powerful genome-wide association studies. Finally, numerous nacre biomineralization genes were localised providing novel positional information for these genes. This high-density SNP genetic map is the first comprehensive linkage

Deconfinement, chiral transition and localisation in a QCD-like model

Energy Technology Data Exchange (ETDEWEB)

Giordano, Matteo; Katz, Sándor D. [Institute for Theoretical Physics, Eötvös University,Pázmány P. sétány 1/A, H-1117 Budapest (Hungary); MTA-ELTE “Lendület” Lattice Gauge Theory Research Group,Pázmány P. sétány 1/A, H-1117 Budapest (Hungary); Kovács, Tamás G. [Institute for Nuclear Research of the Hungarian Academy of Sciences,Bem tér 18/c, H-4026 Debrecen (Hungary); Pittler, Ferenc [HISKP(Theory), University of Bonn,Nussallee 14-16, D-53115 Bonn (Germany)

2017-02-10

We study the problems of deconfinement, chiral symmetry restoration and localisation of the low Dirac eigenmodes in a toy model of QCD, namely unimproved staggered fermions on lattices of temporal extension N{sub T}=4. This model displays a genuine deconfining and chirally-restoring first-order phase transition at some critical value of the gauge coupling. Our results indicate that the onset of localisation of the lowest Dirac eigenmodes takes place at the same critical coupling where the system undergoes the first-order phase transition. This provides further evidence of the close relation between deconfinement, chiral symmetry restoration and localisation of the low modes of the Dirac operator on the lattice.

Evaluating ALWadHA for providing secure localisation for wireless sensor networks

CSIR Research Space (South Africa)

Abu-Mahfouz, Adnan M

2013-09-01

Full Text Available secure localisation algorithms that are able to work in a hostile environment. An attacker could compromise, or masquerade as, a beacon node and send incorrect location information. Localisation in a hostile environment is a critical problem in wireless...

Immunogold staining procedure for the localisation of regulatory peptides.

Science.gov (United States)

Varndell, I M; Tapia, F J; Probert, L; Buchan, A M; Gu, J; De Mey, J; Bloom, S R; Polak, J M

1982-01-01

The use of protein A- and IgG-conjugated colloidal gold staining methods for the immuno-localisation of peptide hormones and neurotransmitters at light- and electron microscope level are described and discussed. Bright-field and dark-ground illumination modes have been used to visualise the gold-labelled antigenic sites at the light microscope level. Immunogold staining procedures at the ultrastructural level using region-specific antisera have been adopted to localise specific molecular forms of peptides including gastrin (G17 and G34), glucagon and pro-glucagon, insulin and pro-insulin, in normal tissue and in tumours of the gastroenteropancreatic system. Similar methods have been used to demonstrate the heterogeneity of p-type nerves in the enteric nervous system. Vasoactive intestinal polypeptide (VIP) has been localised to granular sites (mean +/- S.D. granule diameter = 98 +/- 19 nm) in nerve terminals of the enteric plexuses and in tumour cells of diarrhoeogenic VIP-producing neoplasias (mean +/- S.D. granule diameter = 126 +/- 37 nm) using immunogold procedures applied to ultraviolet-cured ultrathin sections. Co-localisation of amines and peptides in carotid body type I cells and in chromaffin cells of normal adrenal medulla and phaeochromocytomas has also been demonstrated. Advantages of the immunogold procedures over alternative immunocytochemical techniques are discussed.

Immunohistochemical localisation of d-β-aspartic acid in pingueculae

OpenAIRE

Kaji, Y; Oshika, T; Okamoto, F; Fujii, N

2009-01-01

Background: D-β-Aspartic acid residues, which are biologically uncommon, have been reported to accumulate in various proteins of the living body with age. In the present study, D-β-aspartic acid-containing proteins were found to be localised in pingueculae, which represent one of the most prominent age-related ocular changes.Methods: Surgical specimens of conjunctivae with or without pingueculae were obtained from eight patients. Immunohistochemical localisation of D-β-aspartic acid-containin...

Radioguided localisation of impalpable breast lesions using 99m-Technetium macroaggregated albumin: Lessons learnt during introduction of a new technique to guide preoperative localisation

Energy Technology Data Exchange (ETDEWEB)

Landman, Joanne [Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia (Australia); Kulawansa, Sagarika [Department of Diagnostic and Interventional Radiology, Royal Perth Hospital, Perth, Western Australia (Australia); McCarthy, Michael; Troedson, Russell [Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia (Australia); Phillips, Michael [Western Australian Institute for Medical Research, University of Western Australia, Perth, Western Australia (Australia); Tinning, Jill [The Multidisciplinary Breast Service, Royal Perth Hospital, Perth, Western Australia (Australia); Taylor, Donna, E-mail: Donna.Taylor@health.wa.gov.au [Department of Diagnostic and Interventional Radiology, Royal Perth Hospital, Perth, Western Australia (Australia); School of Surgery, University of Western Australia, Perth, Western Australia (Australia); Department of Nuclear Medicine, Royal Perth Hospital, Perth, Western Australia (Australia)

2015-03-15

Preoperative wire-guided localisation (WGL) of impalpable breast lesions is widely used but can be technically difficult. Risks include wire migration, inaccurate placement, and inadequate surgical margins. Research shows that radioguided occult lesion localisation (ROLL) is quicker, easier, and can improve surgical and cosmetic outcomes. An audited introduction of ROLL was conducted to validate the technique as a feasible alternative to WGL. Fifty patients with single impalpable lesions and biopsy proven malignancy or indeterminate histology underwent WGL followed by intralesional radiopharmaceutical injection of 99m-Technetium macroaggregated albumin. Postprocedural mammography was performed to demonstrate wire position, and scintigraphy to evaluate radiopharmaceutical migration. Lymphoscintigraphy and intraoperative sentinel node biopsy were performed if indicated, followed by lesion localisation and excision using a gamma probe. Specimen imaging was performed, with immediate reexcision for visibly inadequate margins. Accurate localisation was achieved in 86% of patients with ROLL compared to 72% with WGL. All lesions were successfully removed, with clear margins in 71.8% of malignant lesions. Reexcision and intraoperative sentinel node localisation rates were equivalent to preaudit figures for WGL. ROLL was easy to perform and problems were infrequent. Inaccurate radiopharmaceutical placement necessitating WGL occurred in four patients. Minor radiopharmaceutical migration was common, but precluded using ROLL in only two cases. ROLL is effective, simple, inexpensive, and easily learnt; however, preoperative confirmation of correct radiopharmaceutical placement using mammography and the gamma probe is important to help ensure successful lesion removal. Insertion of a backup hookwire is recommended during the initial introduction of ROLL.

Loss of Sfpq Causes Long-Gene Transcriptopathy in the Brain

Directory of Open Access Journals (Sweden)

Akihide Takeuchi

2018-05-01

Full Text Available Summary: Genes specifically expressed in neurons contain members with extended long introns. Longer genes present a problem with respect to fulfilment of gene length transcription, and evidence suggests that dysregulation of long genes is a mechanism underlying neurodegenerative and psychiatric disorders. Here, we report the discovery that RNA-binding protein Sfpq is a critical factor for maintaining transcriptional elongation of long genes. We demonstrate that Sfpq co-transcriptionally binds to long introns and is required for sustaining long-gene transcription by RNA polymerase II through mediating the interaction of cyclin-dependent kinase 9 with the elongation complex. Phenotypically, Sfpq disruption caused neuronal apoptosis in developing mouse brains. Expression analysis of Sfpq-regulated genes revealed specific downregulation of developmentally essential neuronal genes longer than 100 kb in Sfpq-disrupted brains; those genes are enriched in associations with neurodegenerative and psychiatric diseases. The identified molecular machinery yields directions for targeted investigations of the association between long-gene transcriptopathy and neuronal diseases. : It has been a long-standing question how mammalian neuronal cells achieve full gene length transcription of extra-long genes. Takeuchi et al. show that RNA-binding protein Sfpq sustains long-gene transcription through Pol II-CTD activation. Loss of Sfpq caused long-gene transcriptopathy, which could be the cause of neurodegenerative and psychiatric disorders. Keywords: RNA-binding protein, transcriptional regulation, RNA polymerase II, cyclin-dependent kinase 9, RBP/transcript-dependent elongation, long-gene transcriptotherapy, neuronal development, neurological and psychiatric diseases, long-gene diseases, long genopathies

Amelogenesis imperfecta and localised aggressive periodontitis: A rare clinical entity

Directory of Open Access Journals (Sweden)

Gayatri Gundannavar

2013-01-01

Full Text Available This case report presents two female patients whose chief complaint was discoloration of teeth. On careful clinical examination it was found that the patients had features of amelogenesis imperfecta and localised aggressive periodontitis. This article will give an insight of clinical and radiographic features of amelogenesis imperfecta with localised aggressive periodontitis, which is a rare clinical entity.

Localised corrosion in AA 2099-T83 aluminium-lithium alloy: The role of grain orientation

International Nuclear Information System (INIS)

Ma, Y.; Zhou, X.; Liao, Y.; Yi, Y.; Wu, H.; Wang, Z.; Huang, W.

2016-01-01

Highlights: • Schmid factor of the grain/subgrain can indicate its corrosion susceptibility. • The localised corrosion prefers the grain with relatively large Schmid factor. • The localised corrosion is related to selective dissolution of T_1 phase. - Abstract: The mechanism for localised corrosion in AA 2099-T83 alloy during immersion in 3.5% NaCl solution is investigated. It is found that localised corrosion tends to occur in the grain with relatively large Schmid factor. The localised corrosion is related to selective dissolution of T_1 (Al_2CuLi) phase that preferentially precipitates at grain/subgrain boundaries and dislocations within grain interiors. A model is proposed to explain the development of the localised corrosion in the alloy by taking into account heterogeneous plastic deformation during cold working and preferential precipitation of T_1 phase at crystallographic defects within deformed grains.

The Role of Localisation in Advertising Translation

Institute of Scientific and Technical Information of China (English)

ZHANG Ying

2016-01-01

Today, a growing number of international corporations have been seeking to boost their sales on the global scale. To achieve this, adverting, one of the most common way to stimulate consumption, is widely used in which translation is involved because of diverse languages. Thus, how to translate a source advertising in a target culture has a decisive influence on a compa-ny’s marketing. The aim of the target advertising is to sell products to the locals. In this sense, localisation plays a significant role in the translation of advertising. This essay will discuss the importance of localisation in the translation of advertising and analyse cases of English-Chinese advertising translation based on the purpose of advertising and advertising translation.

Neuromorphic Audio-Visual Sensor Fusion on a Sound-Localising Robot

Directory of Open Access Journals (Sweden)

Vincent Yue-Sek Chan

2012-02-01

Full Text Available This paper presents the first robotic system featuring audio-visual sensor fusion with neuromorphic sensors. We combine a pair of silicon cochleae and a silicon retina on a robotic platform to allow the robot to learn sound localisation through self-motion and visual feedback, using an adaptive ITD-based sound localisation algorithm. After training, the robot can localise sound sources (white or pink noise in a reverberant environment with an RMS error of 4 to 5 degrees in azimuth. In the second part of the paper, we investigate the source binding problem. An experiment is conducted to test the effectiveness of matching an audio event with a corresponding visual event based on their onset time. The results show that this technique can be quite effective, despite its simplicity.

A new range-free localisation in wireless sensor networks using support vector machine

Science.gov (United States)

Wang, Zengfeng; Zhang, Hao; Lu, Tingting; Sun, Yujuan; Liu, Xing

2018-02-01

Location information of sensor nodes is of vital importance for most applications in wireless sensor networks (WSNs). This paper proposes a new range-free localisation algorithm using support vector machine (SVM) and polar coordinate system (PCS), LSVM-PCS. In LSVM-PCS, two sets of classes are first constructed based on sensor nodes' polar coordinates. Using the boundaries of the defined classes, the operation region of WSN field is partitioned into a finite number of polar grids. Each sensor node can be localised into one of the polar grids by executing two localisation algorithms that are developed on the basis of SVM classification. The centre of the resident polar grid is then estimated as the location of the sensor node. In addition, a two-hop mass-spring optimisation (THMSO) is also proposed to further improve the localisation accuracy of LSVM-PCS. In THMSO, both neighbourhood information and non-neighbourhood information are used to refine the sensor node location. The results obtained verify that the proposed algorithm provides a significant improvement over existing localisation methods.

Problems associated with localised skin exposures

International Nuclear Information System (INIS)

Wells, J.

1986-01-01

The possible sources of localised skin exposure include small commercial sources (for radiotherapy, for example), radiopharmaceuticals, collimated microbeams, and both fission and activation products from nuclear reactors, neutron generators and associated facilities. Each of these sources has its own particular characteristics and associated problems. Recommendations and regulations relating to limits on skin dose for such exposures have been constrained by inadequate radiobiological data and the limitations inherent in personal dosimetric techniques. A growing body of data is now available for beta-emitters which allows a preliminary reassessment of some aspects of the currently recommended dose limits for localised skin exposures. How the skin dose is measured is particularly important for such exposures, as doses often have to be averaged over a specific area. The area chosen for dose measurement and the depth at which the measurement is made are crucial to understanding the possible biological consequences and for formulating appropriate protection criteria. (author)

Localised Microwave Bursts During ELMs on MAST

Directory of Open Access Journals (Sweden)

Freethy Simon

2015-01-01

Full Text Available Bursts of microwave emission are observed during ELM events on the Mega Ampère Spherical Tokamak. In agreement with observations on other machines, these bursts are up to 3 orders of magnitude more intense than the thermal background, but are electron cyclotron in nature. The peak in microwave emission is ~20μ before the peak in midplane Dα emission. Using the Synthetic Aperture Microwave Imaging radiometer, we are able to demonstrate that these bursts are often highly spatially localised and preferentially occur at the tokamak midplane. It is hypothesised that the localisation is a result of Doppler resonance broadening for electron Bernstein waves and the high perpendicular electron energies could be the result of pitch angle scattering in high collisionality regions of the plasma.

Strain localisation in mechanically layered rocks beneath detachment zones: insights from numerical modelling

Directory of Open Access Journals (Sweden)

L. Le Pourhiet

2013-04-01

Full Text Available We have designed a series of fully dynamic numerical simulations aimed at assessing how the orientation of mechanical layering in rocks controls the orientation of shear bands and the depth of penetration of strain in the footwall of detachment zones. Two parametric studies are presented. In the first one, the influence of stratification orientation on the occurrence and mode of strain localisation is tested by varying initial dip of inherited layering in the footwall with regard to the orientation of simple shear applied at the rigid boundary simulating a rigid hanging wall, all scaling and rheological parameter kept constant. It appears that when Mohr–Coulomb plasticity is being used, shear bands are found to localise only when the layering is being stretched. This corresponds to early deformational stages for inital layering dipping in the same direction as the shear is applied, and to later stages for intial layering dipping towards the opposite direction of shear. In all the cases, localisation of the strain after only γ=1 requires plastic yielding to be activated in the strong layer. The second parametric study shows that results are length-scale independent and that orientation of shear bands is not sensitive to the viscosity contrast or the strain rate. However, decreasing or increasing strain rate is shown to reduce the capacity of the shear zone to localise strain. In the later case, the strain pattern resembles a mylonitic band but the rheology is shown to be effectively linear. Based on the results, a conceptual model for strain localisation under detachment faults is presented. In the early stages, strain localisation occurs at slow rates by viscous shear instabilities but as the layered media is exhumed, the temperature drops and the strong layers start yielding plastically, forming shear bands and localising strain at the top of the shear zone. Once strain localisation has occured, the deformation in the shear band becomes

The nature of carrier localisation in polar and nonpolar InGaN/GaN quantum wells

Energy Technology Data Exchange (ETDEWEB)

Dawson, P., E-mail: philip.dawson@manchester.ac.uk [School of Physics and Astronomy, Photon Science Institute, University of Manchester, Manchester M13 9PL (United Kingdom); Schulz, S. [Photonics Theory Group, Tyndall National Institute, Dyke Parade, Cork (Ireland); Oliver, R. A.; Kappers, M. J.; Humphreys, C. J. [Department of Material Science and Metallurgy, 27 Charles Babbage Road, University of Cambridge, Cambridge CB3 0FS (United Kingdom)

2016-05-14

In this paper, we compare and contrast the experimental data and the theoretical predictions of the low temperature optical properties of polar and nonpolar InGaN/GaN quantum well structures. In both types of structure, the optical properties at low temperatures are governed by the effects of carrier localisation. In polar structures, the effect of the in-built electric field leads to electrons being mainly localised at well width fluctuations, whereas holes are localised at regions within the quantum wells, where the random In distribution leads to local minima in potential energy. This leads to a system of independently localised electrons and holes. In nonpolar quantum wells, the nature of the hole localisation is essentially the same as the polar case but the electrons are now coulombically bound to the holes forming localised excitons. These localisation mechanisms are compatible with the large photoluminescence linewidths of the polar and nonpolar quantum wells as well as the different time scales and form of the radiative recombination decay curves.

Colonoscopy and computerised tomography scan are not sufficient to localise right sided colonic lesions accurately.

LENUS (Irish Health Repository)

Solon, Jacqueline Gemma

2009-11-23

: Aim: accurate pre-operative localisation of colonic lesions is critical especially in laparoscopic colectomy where tactile localisation is absent particularly in screen-detected tumours. The study aimed to evaluate the accuracy of colonoscopy and double-contrast computerised tomography (CT) to localise lesions treated by right hemicolectomy. Method: a retrospective chart review was performed of patients treated by right hemicolectomy under the colorectal service between July 2003 and October 2006. Pre-operative tumour location determined by CT scan and colonoscopy were compared with the intra-operative and histopathologic findings. Results: of 101 patients, 73 (73%) were for adenoma or cancer, with a final diagnosis of adenocarcinoma in 59 (59%). Pre-operative localisation was inaccurate in 29% of lesions using both CT and colonoscopy. In the transverse colon colonoscopy alone was only 37.5% accurate, increasing to 62.5% when information from the CT scan was added. Conclusion: pre-operative localisation of right-sided colon cancers using colonoscopy and CT scanning is unreliable in at least 29% of cases. Inaccurate localisation of transverse colon tumours risks inadequate lymphadenectomy with an adverse cancer outcome. Pre-operative abdominal CT scan improves accuracy but endoscopic tattoo localisation should be employed routinely especially in patients undergoing laparoscopic resection.

Isolation, sequencing and expression of RED, a novel human gene encoding an acidic-basic dipeptide repeat.

Science.gov (United States)

Assier, E; Bouzinba-Segard, H; Stolzenberg, M C; Stephens, R; Bardos, J; Freemont, P; Charron, D; Trowsdale, J; Rich, T

1999-04-16

A novel human gene RED, and the murine homologue, MuRED, were cloned. These genes were named after the extensive stretch of alternating arginine (R) and glutamic acid (E) or aspartic acid (D) residues that they contain. We term this the 'RED' repeat. The genes of both species were expressed in a wide range of tissues and we have mapped the human gene to chromosome 5q22-24. MuRED and RED shared 98% sequence identity at the amino acid level. The open reading frame of both genes encodes a 557 amino acid protein. RED fused to a fluorescent tag was expressed in nuclei of transfected cells and localised to nuclear dots. Co-localisation studies showed that these nuclear dots did not contain either PML or Coilin, which are commonly found in the POD or coiled body nuclear compartments. Deletion of the amino terminal 265 amino acids resulted in a failure to sort efficiently to the nucleus, though nuclear dots were formed. Deletion of a further 50 amino acids from the amino terminus generates a protein that can sort to the nucleus but is unable to generate nuclear dots. Neither construct localised to the nucleolus. The characteristics of RED and its nuclear localisation implicate it as a regulatory protein, possibly involved in transcription.

An ultrastructural and irradiation study of diffuse and localised kinetochore

International Nuclear Information System (INIS)

Bokhari, F.S.

1979-05-01

An electron microscope study of plant types Luzula nivea and Cyperus eragrostis with diffuse kinetochores and Crepis neglecta with localised kinetochore showed that Luzula has a rather different kinetochore organisation from Cyperus, with features approaching the localised type of Crepis. These studies included an examination of the ultrastructure of the kinetochore at metaphase at low magnification in control and irradiated material of Luzula; the chromosomal ultrastructure at high magnification at interphase and all stages of mitosis in Luzula, Cyperus and Crepis; and the ultrastructure of the nucleolus in Luzula, Cyperus and Crepis. Light microscopic studies were also performed showing the effects of irradiation on first mitotic division in Cyperus, Luzula and Crepis, mitotic aberrations in Cyperus and Crepis and meiosis in Cyperus. Finally, the survival with the diffuse as opposed to the localised kinetochore in M 1 and M 2 generations following seed irradiation was studied. (U.K.)

A Localised Corrosion Cell for Industrial Applications

DEFF Research Database (Denmark)

Andersen, A.; Hilbert, Lisbeth Rischel; Jansen, P.

2003-01-01

The LOCORR-CELL™ developed by FORCE TECHNOLOGY is an electrochemical cell for industrial applications estimating localised corrosion. The cell is constructed in a carbon steel casing for direct mounting into the system. It is based on an oxygen concentration element reflecting the interaction...... between the environment formed under a deposit or in a crevice. The essential feature of the method is that it reflects the influence of oxygen content, conductivity and temperature as well as the influence of corrosion inhibitors, MIC and other effects that have an effect on localised corrosion under...... deposits and in crevices. The measuring principle in the cell is based on measurements of the galvanic current flow between the steel anode covered by a porous glass frit and the surrounding steel casing. The current is measured by a zero-resistance circuit-instrument and the activity can be presented...

Differences in finger localisation performance of patients with finger agnosia.

Science.gov (United States)

Anema, Helen A; Kessels, Roy P C; de Haan, Edward H F; Kappelle, L Jaap; Leijten, Frans S; van Zandvoort, Martine J E; Dijkerman, H Chris

2008-09-17

Several neuropsychological studies have suggested parallel processing of somatosensory input when localising a tactile stimulus on one's own by pointing towards it (body schema) and when localising this touched location by pointing to it on a map of a hand (body image). Usually these reports describe patients with impaired detection, but intact sensorimotor localisation. This study examined three patients with a lesion of the angular gyrus with intact somatosensory processing, but with selectively disturbed finger identification (finger agnosia). These patients performed normally when pointing towards the touched finger on their own hand but failed to indicate this finger on a drawing of a hand or to name it. Similar defects in the perception of other body parts were not observed. The findings provide converging evidence for the dissociation between body image and body schema and, more importantly, reveal for the first time that this distinction is also present in higher-order cognitive processes selectively for the fingers.

Monitoring corrosion rates and localised corrosion in low conductivity water

DEFF Research Database (Denmark)

Hilbert, Lisbeth Rischel

2006-01-01

Monitoring of low corrosion rates and localised corrosion in a media with low conductivity is a challenge. In municipal district heating, quality control may be improved by implementing on-line corrosion monitoring if a suitable technique can be identified to measure both uniform and localised...... corrosion. Electrochemical techniques (LPR, EIS, crevice corrosion current) as well as direct measurement techniques (high-sensitive electrical resistance, weight loss) have been applied in operating plants. Changes in the corrosion processes are best monitored in non-aggressive, low conductivity media...

Fault kinematics and localised inversion within the Troms-Finnmark Fault Complex, SW Barents Sea

Science.gov (United States)

Zervas, I.; Omosanya, K. O.; Lippard, S. J.; Johansen, S. E.

2018-04-01

The areas bounding the Troms-Finnmark Fault Complex are affected by complex tectonic evolution. In this work, the history of fault growth, reactivation, and inversion of major faults in the Troms-Finnmark Fault Complex and the Ringvassøy Loppa Fault Complex is interpreted from three-dimensional seismic data, structural maps and fault displacement plots. Our results reveal eight normal faults bounding rotated fault blocks in the Troms-Finnmark Fault Complex. Both the throw-depth and displacement-distance plots show that the faults exhibit complex configurations of lateral and vertical segmentation with varied profiles. Some of the faults were reactivated by dip-linkages during the Late Jurassic and exhibit polycyclic fault growth, including radial, syn-sedimentary, and hybrid propagation. Localised positive inversion is the main mechanism of fault reactivation occurring at the Troms-Finnmark Fault Complex. The observed structural styles include folds associated with extensional faults, folded growth wedges and inverted depocentres. Localised inversion was intermittent with rifting during the Middle Jurassic-Early Cretaceous at the boundaries of the Troms-Finnmark Fault Complex to the Finnmark Platform. Additionally, tectonic inversion was more intense at the boundaries of the two fault complexes, affecting Middle Triassic to Early Cretaceous strata. Our study shows that localised folding is either a product of compressional forces or of lateral movements in the Troms-Finnmark Fault Complex. Regional stresses due to the uplift in the Loppa High and halokinesis in the Tromsø Basin are likely additional causes of inversion in the Troms-Finnmark Fault Complex.

Search and localisation of CERN buildings

CERN Multimedia

TS/FM - Patrimony and Site Information Section

2005-01-01

A new, updated version of the web application allowing search and localisation of CERN buildings has been available since 20 May 2005. You can now find a specific building, road, car-park and other information regarding the CERN sites. For comments or enquiries please contact SIG.Support@cern.ch TS/FM - Patrimony and Site Information Section (ISP)

Diagnostic approach to localised organising pneumonia--A case report.

Science.gov (United States)

Djurić, Mirna; Považan, Djordje; Djurić, Dejan; Eri, Živka; Trudić, Anika

2015-08-01

Localised organising pneumonia, radiologically presented with oval or round shadows mimicing lung cancer or metastases, is a major issue in differential diagnosis. A female patient was hospitalized to clarified the etiology of multiple nodular lung lesions. The chest X-ray and the chest computed tomography (CT) revealed bilateral patchy and nodular shadows, and round lung lesions, respectively. Neither sputum analyses, nor histology of bronchoscopy samples clarified the etiology of these lung lesions. As secondary deposits in the lungs were suspected, video-assisted thoracoscopy and anterolateral right minithoracotomy with atypical upper and lower lobe resection were performed. The frozen-section analysis suggested the benign nature of the lesion, and the definite histopathological finding of localised organising pneumonia was established. Due to bilateral lung lesions, corticosteroids were applied. Seven weeks later, the chest CT finding revealed a total regression of the lesions. A surgical resection was necessary to diagnose the localised organising pneumonia which mimiced secondary malignant lesions, thus establishing the definite etiology of lung lesions. Bronchoscopic cryobiopsy, recently introduced in order to obtain peripheral lung biopsy samples, has provided new possibilities in the diagnosis and treatment of neoplastic and non-neoplastic lung diseases.

Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa

Science.gov (United States)

Daiger, Stephen P.; Bowne, Sara J.; Sullivan, Lori S.

2015-01-01

Retinitis pigmentosa (RP) has a prevalence of approximately one in 4000; 25%–30% of these cases are autosomal dominant retinitis pigmentosa (adRP). Like other forms of inherited retinal disease, adRP is exceptionally heterogeneous. Mutations in more than 25 genes are known to cause adRP, more than 1000 mutations have been reported in these genes, clinical findings are highly variable, and there is considerable overlap with other types of inherited disease. Currently, it is possible to detect disease-causing mutations in 50%–75% of adRP families in select populations. Genetic diagnosis of adRP has advantages over other forms of RP because segregation of disease in families is a useful tool for identifying and confirming potentially pathogenic variants, but there are disadvantages too. In addition to identifying the cause of disease in the remaining 25% of adRP families, a central challenge is reconciling clinical diagnosis, family history, and molecular findings in patients and families. PMID:25304133

Primary localised cutaneous amyloidosis - a systematic review

DEFF Research Database (Denmark)

Kaltoft, Britta; Schmidt, Grethe; Lauritzen, Anne Falensteen

2013-01-01

Amyloidosis is defined as extracellular deposits of heterogenic, misfolded proteins, amyloid fibrils, in various tissues. The aim of our study was to review the literature and to evaluate the risk of developing systemic amyloidosis (SA) and the risk of local recurrence of primary localised...

Diagnosis and localisation of insulinoma: the value of modern magnetic resonance imaging in conjunction with calcium stimulation catheterisation.

Science.gov (United States)

Druce, Maralyn R; Muthuppalaniappan, Vasantha M; O'Leary, Benjamin; Chew, Shern L; Drake, William M; Monson, John P; Akker, Scott A; Besser, Michael; Sahdev, Anju; Rockall, Andrea; Vyas, Soumil; Bhattacharya, Satya; Matson, Matthew; Berney, Daniel; Reznek, R H; Grossman, Ashley B

2010-05-01

Preoperative localisation of insulinoma improves cure rate and reduces complications, but may be challenging. To review diagnostic features and localisation accuracy for insulinomas. Cross-sectional, retrospective analysis. A single tertiary referral centre. Patients with insulinoma in the years 1990-2009, including sporadic tumours and those in patients with multiple endocrine neoplasia syndromes. Patients were identified from a database, and case notes and investigation results were reviewed. Tumour localisation by computed tomography (CT), magnetic resonance imaging (MRI), octreotide scanning, endoscopic ultrasound (EUS) and calcium stimulation was evaluated. Insulinoma localisation was compared to histologically confirmed location following surgical excision. Thirty-seven instances of biochemically and/or histologically proven insulinoma were identified in 36 patients, of which seven were managed medically. Of the 30 treated surgically, 25 had CT (83.3%) and 28 had MRI (90.3%), with successful localisation in 16 (64%) by CT and 21 (75%) by MRI respectively. Considered together, such imaging correctly localised 80% of lesions. Radiolabelled octreotide scanning was positive in 10 out of 20 cases (50%); EUS correctly identified 17 lesions in 26 patients (65.4%). Twenty-seven patients had calcium stimulation testing, of which 6 (22%) did not localise, 17 (63%) were correctly localised, and 4 (15%) gave discordant or confusing results. Preoperative localisation of insulinomas remains challenging. A pragmatic combination of CT and especially MRI predicts tumour localisation with high accuracy. Radionuclide imaging and EUS were less helpful but may be valuable in selected cases. Calcium stimulation currently remains useful in providing an additional functional perspective.

Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and import

International Nuclear Information System (INIS)

Kaellstroem, Helena; Lindqvist, Arne; Pospisil, Vitek; Lundgren, Andreas; Karlsson Rosenthal, Christina

2005-01-01

The Cdc25 phosphatases play crucial roles in cell cycle progression by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases. Cdc25A is an important regulator of the G1/S transition but functions also in the mitotic phase of the human cell cycle. In this paper, we investigate the sub-cellular localisation of exogenously expressed Cdc25A. We show that YFP-Cdc25A is localised both in the nucleus and the cytoplasm of HeLa cells and untransformed fibroblasts. Cell fusion assays and fluorescence loss in photobleaching (FLIP) assays reveal that the localisation is dynamic and the protein shuttles between the nucleus and the cytoplasm. We demonstrate that nuclear export of Cdc25A is partly mediated by an N-terminal nuclear export sequence (NES), in a manner not sensitive to the Exportin 1-inhibitor leptomycin B. A nuclear localisation signal (NLS) is also characterised, mutation of which leads to cytoplasmic localisation of Cdc25A. Our results imply that the Cdc25A phosphatase may interact with substrates and regulators both in the nucleus and the cytoplasm

Congenital Hypothyroidism Caused by a PAX8 Gene Mutation Manifested as Sodium/Iodide Symporter Gene Defect

Directory of Open Access Journals (Sweden)

Wakako Jo

2010-01-01

Full Text Available Loss-of-function mutations of the PAX8 gene are considered to mainly cause congenital hypothyroidism (CH due to thyroid hypoplasia. However, some patients with PAX8 mutation have demonstrated a normal-sized thyroid gland. Here we report a CH patient caused by a PAX8 mutation, which manifested as iodide transport defect (ITD. Hypothyroidism was detected by neonatal screening and L-thyroxine replacement was started immediately. Although 123I scintigraphy at 5 years of age showed that the thyroid gland was in the normal position and of small size, his iodide trapping was low. The ratio of the saliva/plasma radioactive iodide was low. He did not have goiter; however laboratory findings suggested that he had partial ITD. Gene analyses showed that the sodium/iodide symporter (NIS gene was normal; instead, a mutation in the PAX8 gene causing R31H substitution was identified. The present report demonstrates that individuals with defective PAX8 can have partial ITD, and thus genetic analysis is useful for differential diagnosis.

Comparing mobile robot localisation algorithms using Kalmtool

DEFF Research Database (Denmark)

Mogensen, Lars Valdemar; Hansen, Søren; Ravn, Ole

2009-01-01

In this paper we present an estimation platform with simulation capabilities to evaluate methods for localisation of a mobile robot using a feature map. The platform is based on the Kalmtool 4 toolbox which is a set of MATLAB tools for state estimation of nonlinear systems. The toolbox contains...

Accuracy of target localisation and alignment in stereotactic radiosurgery at Royal Prince Alfred Hospital

International Nuclear Information System (INIS)

Downes, S.

1996-01-01

Full text: Over the last 30 years, stereotactic radiosurgery has become an effective clinical tool in the treatment of intra-cranial lesions. The use of high doses to a specific target volume in a single fraction and the proximity of critical organs requires very accurate geometric localisation of the various cranial structures (using CT, MRI and angiography imaging) and accurate alignment of the target volume prior to treatment. The purpose of this paper was to determine the accuracy of localising cranial structures using computed tomography and angiographic imaging modalities and to determine the accuracy of aligning the treatment isocentre to the specified coordinates. The sum of these two errors will give the total deviation of the treated target from the actual target. Measurements were made using an anthropomorphic (ART) phantom of an adult male and a cerrobend target. The ART phantom was immobilised using the Brown-Roberts-Wells (BRW) ring. The cerrobend target was inserted into the skull at 10 different positions. Each of these 10 positions were scanned using CT and angiographic imaging and localised using the stereotactic planning software. For each test position, the ART phantom was placed on the treatment couch and aligned to the treatment coordinates determined using localisation (CT and angiography). A-P and lateral port films were then made of the target. The distance between the centre of the cerrobend target (intended target) and the centre of radiation (actual target) was the total error in localisation and alignment of the target. For computed tomography, the measurements showed the average error in localisation and alignment of the target was ±0.7mm. In terms of coordinate axis, the average error was: A-P axis = ±0.5mm, Lateral(left-right) Axis = ±0.3mm, Vertical(inferior superior) Axis ±0.4mm. From these measurements it was shown that using the stereotactic radiosurgery planning system and hardware, cranial lesions could be localised and

Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing.

Directory of Open Access Journals (Sweden)

Olivier J Becherel

2013-04-01

Full Text Available Senataxin, mutated in the human genetic disorder ataxia with oculomotor apraxia type 2 (AOA2, plays an important role in maintaining genome integrity by coordination of transcription, DNA replication, and the DNA damage response. We demonstrate that senataxin is essential for spermatogenesis and that it functions at two stages in meiosis during crossing-over in homologous recombination and in meiotic sex chromosome inactivation (MSCI. Disruption of the Setx gene caused persistence of DNA double-strand breaks, a defect in disassembly of Rad51 filaments, accumulation of DNA:RNA hybrids (R-loops, and ultimately a failure of crossing-over. Senataxin localised to the XY body in a Brca1-dependent manner, and in its absence there was incomplete localisation of DNA damage response proteins to the XY chromosomes and ATR was retained on the axial elements of these chromosomes, failing to diffuse out into chromatin. Furthermore persistence of RNA polymerase II activity, altered ubH2A distribution, and abnormal XY-linked gene expression in Setx⁻/⁻ revealed an essential role for senataxin in MSCI. These data support key roles for senataxin in coordinating meiotic crossing-over with transcription and in gene silencing to protect the integrity of the genome.

Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion

NARCIS (Netherlands)

Jonkman, MF; Scheffer, H; Stulp, R; Pas, HH; Nijenhuis, Albertine; Heeres, K; Owaribe, K; Pulkkinen, L; Uitto, J

1997-01-01

Mitotic gene conversion acting as reverse mutation has not been previously demonstrated in human. We report here that the revertant mosaicism of a compound heterozygous proband with an autosomal recessive genodermatosis, generalized atrophic benign epidermolysis bullosa, is caused by mitotic gene

Differential gene expression patterns between smokers and non-smokers : cause or consequence?

NARCIS (Netherlands)

Vink, Jacqueline M; Jansen, Rick; Brooks, Andy; Willemsen, Gonneke; van Grootheest, Gerard; de Geus, Eco; Smit, Jan H; Penninx, Brenda W; Boomsma, Dorret I

The molecular mechanisms causing smoking-induced health decline are largely unknown. To elucidate the molecular pathways involved in cause and consequences of smoking behavior, we conducted a genome-wide gene expression study in peripheral blood samples targeting 18 238 genes. Data of 743 smokers,

Differential gene expression patterns between smokers and non-smokers: Cause or consequence?

NARCIS (Netherlands)

Vink, J.M.; Jansen, R.; Brooks, A.I.; Willemsen, G.; Grootheest, G. van; Geus, E.J.C. de; Smit, J.H.; Penninx, B.W.J.H.; Boomsma, D.I.

2017-01-01

The molecular mechanisms causing smoking-induced health decline are largely unknown. To elucidate the molecular pathways involved in cause and consequences of smoking behavior, we conducted a genome-wide gene expression study in peripheral blood samples targeting 18 238 genes. Data of 743 smokers,

Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy

Science.gov (United States)

Maspero, Matteo; van den Berg, Cornelis A. T.; Zijlstra, Frank; Sikkes, Gonda G.; de Boer, Hans C. J.; Meijer, Gert J.; Kerkmeijer, Linda G. W.; Viergever, Max A.; Lagendijk, Jan J. W.; Seevinck, Peter R.

2017-10-01

An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning. Currently, MR-based FM localisation is clinically performed manually. This is sub-optimal, as manual interaction increases the workload. Attempts to perform automatic FM detection often rely on being able to detect signal voids induced by the FMs in magnitude images. However, signal voids may not always be sufficiently specific, hampering accurate and robust automatic FM localisation. Here, we present an approach that aims at automatic MR-based FM localisation. This method is based on template matching using a library of simulated complex-valued templates, and exploiting the behaviour of the complex MR signal in the vicinity of the FM. Clinical evaluation was performed on seventeen prostate cancer patients undergoing external beam radiotherapy treatment. Automatic MR-based FM localisation was compared to manual MR-based and semi-automatic CT-based localisation (the current gold standard) in terms of detection rate and the spatial accuracy and precision of localisation. The proposed method correctly detected all three FMs in 15/17 patients. The spatial accuracy (mean) and precision (STD) were 0.9 mm and 0.5 mm respectively, which is below the voxel size of 1.1 × 1.1 × 1.2 mm3 and comparable to MR-based manual localisation. FM localisation failed (3/51 FMs) in the presence of bleeding or calcifications in the direct vicinity of the FM. The method was found to be spatially accurate and precise, which is essential for clinical use. To overcome any missed detection, we envision the use of the proposed method along with verification by an observer. This will result in a

Evaluation of an automatic MR-based gold fiducial marker localisation method for MR-only prostate radiotherapy.

Science.gov (United States)

Maspero, Matteo; van den Berg, Cornelis A T; Zijlstra, Frank; Sikkes, Gonda G; de Boer, Hans C J; Meijer, Gert J; Kerkmeijer, Linda G W; Viergever, Max A; Lagendijk, Jan J W; Seevinck, Peter R

2017-10-03

An MR-only radiotherapy planning (RTP) workflow would reduce the cost, radiation exposure and uncertainties introduced by CT-MRI registrations. In the case of prostate treatment, one of the remaining challenges currently holding back the implementation of an RTP workflow is the MR-based localisation of intraprostatic gold fiducial markers (FMs), which is crucial for accurate patient positioning. Currently, MR-based FM localisation is clinically performed manually. This is sub-optimal, as manual interaction increases the workload. Attempts to perform automatic FM detection often rely on being able to detect signal voids induced by the FMs in magnitude images. However, signal voids may not always be sufficiently specific, hampering accurate and robust automatic FM localisation. Here, we present an approach that aims at automatic MR-based FM localisation. This method is based on template matching using a library of simulated complex-valued templates, and exploiting the behaviour of the complex MR signal in the vicinity of the FM. Clinical evaluation was performed on seventeen prostate cancer patients undergoing external beam radiotherapy treatment. Automatic MR-based FM localisation was compared to manual MR-based and semi-automatic CT-based localisation (the current gold standard) in terms of detection rate and the spatial accuracy and precision of localisation. The proposed method correctly detected all three FMs in 15/17 patients. The spatial accuracy (mean) and precision (STD) were 0.9 mm and 0.5 mm respectively, which is below the voxel size of [Formula: see text] mm 3 and comparable to MR-based manual localisation. FM localisation failed (3/51 FMs) in the presence of bleeding or calcifications in the direct vicinity of the FM. The method was found to be spatially accurate and precise, which is essential for clinical use. To overcome any missed detection, we envision the use of the proposed method along with verification by an observer. This will result in a

Localised task-dependent motor-unit recruitment in the masseter.

Science.gov (United States)

Schindler, H J; Hellmann, D; Giannakopoulos, N N; Eiglsperger, U; van Dijk, J P; Lapatki, B G

2014-07-01

Localised motor-unit (MU) recruitment in the masseter was analysed in this study. We investigated whether differential activation behaviour, which has already been reported for distant masseter regions, can also be detected in small muscle subvolumes at the level of single MUs. Two bipolar fine-wire electrodes and an intra-oral 3D bite-force transmitter were used to record intra-muscular electromyograms (EMG) resulting from controlled bite-forces of 10 healthy human subjects (mean age 24.1 ± 1.2 years). Two-hundred and seventeen decomposed MUs were organised into localised MU task groups with different (P < 0.001) force-direction-specific behaviour. Proportions of MUs involved in one, two, three or four examined tasks were 46%, 31%, 18% and 5%, respectively. This study provides evidence of the ability of the neuromuscular system to modify the mechanical output of small masseter subvolumes by differential control of adjacent MUs belonging to distinct task groups. Localised differential activation behaviour of the masseter may be the crucial factor enabling highly flexible and efficient adjustment of the muscle activity in response to complex local biomechanical needs, for example, continually varying bite-forces during the demanding masticatory process. © 2014 John Wiley & Sons Ltd.

An Autonomous Wearable System for Predicting and Detecting Localised Muscle Fatigue

Science.gov (United States)

Al-Mulla, Mohamed R.; Sepulveda, Francisco; Colley, Martin

2011-01-01

Muscle fatigue is an established area of research and various types of muscle fatigue have been clinically investigated in order to fully understand the condition. This paper demonstrates a non-invasive technique used to automate the fatigue detection and prediction process. The system utilises the clinical aspects such as kinematics and surface electromyography (sEMG) of an athlete during isometric contractions. Various signal analysis methods are used illustrating their applicability in real-time settings. This demonstrated system can be used in sports scenarios to promote muscle growth/performance or prevent injury. To date, research on localised muscle fatigue focuses on the clinical side and lacks the implementation for detecting/predicting localised muscle fatigue using an autonomous system. Results show that automating the process of localised muscle fatigue detection/prediction is promising. The autonomous fatigue system was tested on five individuals showing 90.37% accuracy on average of correct classification and an error of 4.35% in predicting the time to when fatigue will onset. PMID:22319367

An Autonomous Wearable System for Predicting and Detecting Localised Muscle Fatigue

Directory of Open Access Journals (Sweden)

Martin Colley

2011-01-01

Full Text Available Muscle fatigue is an established area of research and various types of muscle fatigue have been clinically investigated in order to fully understand the condition. This paper demonstrates a non-invasive technique used to automate the fatigue detection and prediction process. The system utilises the clinical aspects such as kinematics and surface electromyography (sEMG of an athlete during isometric contractions. Various signal analysis methods are used illustrating their applicability in real-time settings. This demonstrated system can be used in sports scenarios to promote muscle growth/performance or prevent injury. To date, research on localised muscle fatigue focuses on the clinical side and lacks the implementation for detecting/predicting localised muscle fatigue using an autonomous system. Results show that automating the process of localised muscle fatigue detection/prediction is promising. The autonomous fatigue system was tested on five individuals showing 90.37% accuracy on average of correct classification and an error of 4.35% in predicting the time to when fatigue will onset.

Towards a Multimodal Methodology for the Analysis of Translated/Localised Games

Directory of Open Access Journals (Sweden)

Bárbara Resende Coelho

2016-12-01

Full Text Available Multimedia materials require research methodologies that are able to comprehend all of their assets. Videogames are the epitome of multimedia, joining image, sound, video, animation, graphics and text with the interactivity factor. A methodology to conduct research into translation and localisation of videogames should be able to analyse all of its assets and features. This paper sets out to develop a research methodology for games and their translations/localisations that goes beyond the collection and analysis of “screenshots” and includes as many of their assets as possible. Using the fully localised version of the game Watchdogs, this papers shows how tools and technologies allow for transcending the mere analysis of linguistic contents within multimedia materials. Using software ELAN Language Archive to analyse Portuguese-language dubbed and English-language subtitled excerpts from the videogame, it was possible to identify patterns in both linguistic and audio-visual elements, as well as to correlate them.

Approach to sensor node calibration for efficient localisation in wireless sensor networks in realistic scenarios

CSIR Research Space (South Africa)

Mwila, MK

2014-06-01

Full Text Available Localisation or position determination is one of the most important applications for the wireless sensor networks. Numerous current techniques for localisation of sensor nodes use the Received Signal Strength Indicator (RSSI) from sensor nodes...

Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody

Energy Technology Data Exchange (ETDEWEB)

Markham, N; Ritson, A; James, O; Curtin, N; Bassendine, M; Sikora, K

1986-01-01

A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30,000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with /sup 131/I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. The authors conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease. 16 refs.; 4 figs.; 1 table.

Pulmonary fibrosis caused by histiocytosis X

International Nuclear Information System (INIS)

Reinbold, W.D.; Seemann, W.R.; Ruehle, K.H.

1984-01-01

This paper reports on a 23-year-old man suffering from pulmonary fibrosis caused by localised histiocytosis X. Although chest film examination shows diffuse pulmonary involvement the patient is asymptomatic. No other organ systems are involved. The different forms and prognosis of histiocytosis X are discussed. (orig.)

Channelrhodopsin-2 localised to the axon initial segment.

Directory of Open Access Journals (Sweden)

Matthew S Grubb

2010-10-01

Full Text Available The light-gated cation channel Channelrhodopsin-2 (ChR2 is a powerful and versatile tool for controlling neuronal activity. Currently available versions of ChR2 either distribute uniformly throughout the plasma membrane or are localised specifically to somatodendritic or synaptic domains. Localising ChR2 instead to the axon initial segment (AIS could prove an extremely useful addition to the optogenetic repertoire, targeting the channel directly to the site of action potential initiation, and limiting depolarisation and associated calcium entry elsewhere in the neuron. Here, we describe a ChR2 construct that we localised specifically to the AIS by adding the ankyrinG-binding loop of voltage-gated sodium channels (Na(vII-III to its intracellular terminus. Expression of ChR2-YFP-Na(vII-III did not significantly affect the passive or active electrical properties of cultured rat hippocampal neurons. However, the tiny ChR2 currents and small membrane depolarisations resulting from AIS targeting meant that optogenetic control of action potential firing with ChR2-YFP-Na(vII-III was unsuccessful in baseline conditions. We did succeed in stimulating action potentials with light in some ChR2-YFP-Na(vII-III-expressing neurons, but only when blocking KCNQ voltage-gated potassium channels. We discuss possible alternative approaches to obtaining precise control of neuronal spiking with AIS-targeted optogenetic constructs and propose potential uses for our ChR2-YFP-Na(vII-III probe where subthreshold modulation of action potential initiation is desirable.

KMeyeDB: a graphical database of mutations in genes that cause eye diseases.

Science.gov (United States)

Kawamura, Takashi; Ohtsubo, Masafumi; Mitsuyama, Susumu; Ohno-Nakamura, Saho; Shimizu, Nobuyoshi; Minoshima, Shinsei

2010-06-01

KMeyeDB (http://mutview.dmb.med.keio.ac.jp/) is a database of human gene mutations that cause eye diseases. We have substantially enriched the amount of data in the database, which now contains information about the mutations of 167 human genes causing eye-related diseases including retinitis pigmentosa, cone-rod dystrophy, night blindness, Oguchi disease, Stargardt disease, macular degeneration, Leber congenital amaurosis, corneal dystrophy, cataract, glaucoma, retinoblastoma, Bardet-Biedl syndrome, and Usher syndrome. KMeyeDB is operated using the database software MutationView, which deals with various characters of mutations, gene structure, protein functional domains, and polymerase chain reaction (PCR) primers, as well as clinical data for each case. Users can access the database using an ordinary Internet browser with smooth user-interface, without user registration. The results are displayed on the graphical windows together with statistical calculations. All mutations and associated data have been collected from published articles. Careful data analysis with KMeyeDB revealed many interesting features regarding the mutations in 167 genes that cause 326 different types of eye diseases. Some genes are involved in multiple types of eye diseases, whereas several eye diseases are caused by different mutations in one gene.

Human SLAM, indoor localisation of devices and users

NARCIS (Netherlands)

Bulten, W.; Rossum, A.C. van; Haselager, W.F.G.; Guerrero, J.E.

2016-01-01

The indoor localisation problem is more complex than just finding whereabouts of users. Finding positions of users relative to the devices of a smart space is even more important. Unfortunately, configuring such systems manually is a tedious process, requires expert knowledge, and is sensitive to

Localised burst reconstruction from space-time PODs in a turbulent channel

Science.gov (United States)

Garcia-Gutierrez, Adrian; Jimenez, Javier

2017-11-01

The traditional proper orthogonal decomposition of the turbulent velocity fluctuations in a channel is extended to time under the assumption that the attractor is statistically stationary and can be treated as periodic for long-enough times. The objective is to extract space- and time-localised eddies that optimally represent the kinetic energy (and two-event correlation) of the flow. Using time-resolved data of a small-box simulation at Reτ = 1880 , minimal for y / h 0.25 , PODs are computed from the two-point spectral-density tensor Φ(kx ,kz , y ,y' , ω) . They are Fourier components in x, z and time, and depend on y and on the temporal frequency ω, or, equivalently, on the convection velocity c = ω /kx . Although the latter depends on y, a spatially and temporally localised `burst' can be synthesised by adding a range of PODs with specific phases. The results are localised bursts that are amplified and tilted, in a time-periodic version of Orr-like behaviour. Funded by the ERC COTURB project.

Fukunaga-Koontz feature transformation for statistical structural damage detection and hierarchical neuro-fuzzy damage localisation

Science.gov (United States)

Hoell, Simon; Omenzetter, Piotr

2017-07-01

Considering jointly damage sensitive features (DSFs) of signals recorded by multiple sensors, applying advanced transformations to these DSFs and assessing systematically their contribution to damage detectability and localisation can significantly enhance the performance of structural health monitoring systems. This philosophy is explored here for partial autocorrelation coefficients (PACCs) of acceleration responses. They are interrogated with the help of the linear discriminant analysis based on the Fukunaga-Koontz transformation using datasets of the healthy and selected reference damage states. Then, a simple but efficient fast forward selection procedure is applied to rank the DSF components with respect to statistical distance measures specialised for either damage detection or localisation. For the damage detection task, the optimal feature subsets are identified based on the statistical hypothesis testing. For damage localisation, a hierarchical neuro-fuzzy tool is developed that uses the DSF ranking to establish its own optimal architecture. The proposed approaches are evaluated experimentally on data from non-destructively simulated damage in a laboratory scale wind turbine blade. The results support our claim of being able to enhance damage detectability and localisation performance by transforming and optimally selecting DSFs. It is demonstrated that the optimally selected PACCs from multiple sensors or their Fukunaga-Koontz transformed versions can not only improve the detectability of damage via statistical hypothesis testing but also increase the accuracy of damage localisation when used as inputs into a hierarchical neuro-fuzzy network. Furthermore, the computational effort of employing these advanced soft computing models for damage localisation can be significantly reduced by using transformed DSFs.

Resonant photoluminescence studies of carrier localisation in c-plane InGaN/GaN quantum well structures

Science.gov (United States)

Blenkhorn, W. E.; Schulz, S.; Tanner, D. S. P.; Oliver, R. A.; Kappers, M. J.; Humphreys, C. J.; Dawson, P.

2018-05-01

In this paper we report on changes in the form of the low temperature (12 K) photoluminescence spectra of an InGaN/GaN quantum well structure as a function of excitation photon energy. As the photon energy is progressively reduced we observe at a critical energy a change in the form of the spectra from one which is determined by the occupation of the complete distribution of hole localisation centres to one which is determined by the resonant excitation of specific localisation sites. This change is governed by an effective mobility edge whereby the photo-excited holes remain localised at their initial energy and are prevented from scattering to other localisation sites. This assignment is confirmed by the results of atomistic tight binding calculations which show that the wave function overlap of the lowest lying localised holes with other hole states is low compared with the overlap of higher lying hole states with other higher lying hole states.

Mesenteric vein thrombosis after percitaneous transhepatic portal vein catheterisation for the localisation of an insulinoma

International Nuclear Information System (INIS)

Luska, G.; Langer, H.E.; Le Blanc, S.; Medizinische Hochschule Hannover

1984-01-01

The authors report on a fatal mesenteric vein thrombosis following an uncomplicated percutaneous transhepatic portal vein catheterisation for the localisation of an insulinoma. Several hours after the procedure the patient developed an acute abdomen. An emergency laparotomy revealed a haemorrhagic infarct of the ileum. The resected specimen showed an acute phlebitis with fresh thrombus. The cause of the phlebothrombosis was thought to be intimal damage from high osmolar contrast medium. There was no evidence of damage due to the catheder, either on the phlebogram or pathologically. (orig.) [de

Localised proton magnetic resonance spectroscopy of the brain after perinatal hypoxia: a preliminary report

International Nuclear Information System (INIS)

Chateil, J.F.; Quesson, B.; Thiaudiere, E.; Delalande, C.; Canioni, P.; Brun, M.; Diard, F.; Sarlangue, J.; Billeaud, C.

1999-01-01

Objectives. Perinatal hypoxic ischaemic injury is a significant cause of neurodevelopmental impairment. The aim of this study was to evaluate localised proton magnetic resonance spectroscopy ( 1 H-MRS) after birth asphyxia. Materials and methods. Thirty newborn infants suspected of having perinatal asphyxia (Apgar score 1 H-MRS was recorded in a single voxel, localised in white matter, using a STEAM sequence. Results. Image quality was good in 25 of 30 babies. 1 H-MRS was performed in 19 of 30 subjects, with adequate quality in 16. Choline, creatine/phosphocreatine and N-acetylaspartate peaks and peak-area ratios were analysed. Lactate was detected in four infants. The N-acetylaspartate/choline ratio was lower in infants with an impaired neurological outcome, but the difference was not statistically significant. Conclusions. This study suggests that 1 H-MRS may be useful for assessing cerebral metabolism in the neonate. A raised lactate level and decreased N-acetylaspartate/choline ratio may be predictive of a poor outcome. However, in our experience this method is limited by the difficulty in performing the examination during the first hours after birth in critically ill babies, the problems related to use of a monovoxel sequence, the dispersion of the ratios and the lack of determination of the absolute concentration of the metabolites. (orig.)

The Subcellular Localisation of the Human Papillomavirus (HPV 16 E7 Protein in Cervical Cancer Cells and Its Perturbation by RNA Aptamers

Directory of Open Access Journals (Sweden)

Özlem Cesur

2015-06-01

Full Text Available Human papillomavirus (HPV is the most common viral infection of the reproductive tract, affecting both men and women. High-risk oncogenic types are responsible for almost 90% of anogenital and oropharyngeal cancers including cervical cancer. Some of the HPV “early” genes, particularly E6 and E7, are known to act as oncogenes that promote tumour growth and malignant transformation. Most notably, HPV-16 E7 interacts with the tumour suppressor protein pRb, promoting its degradation, leading to cell cycle dysregulation in infected cells. We have previously shown that an RNA aptamer (termed A2 selectively binds to HPV16 E7 and is able to induce apoptosis in HPV16-transformed cervical carcinoma cell lines (SiHa through reduction of E7 levels. In this study, we investigated the effects of the A2 aptamer on E7 localisation in order to define its effects on E7 activity. We demonstrate for the first time that E7 localised to the plasma membrane. In addition, we show that A2 enhanced E7 localisation in the ER and that the A2-mediated reduction of E7 was not associated with proteasomal degradation. These data suggest that A2 perturbs normal E7 trafficking through promoting E7 ER retention.

Neurotrophin gene therapy for sustained neural preservation after deafness.

Science.gov (United States)

Atkinson, Patrick J; Wise, Andrew K; Flynn, Brianna O; Nayagam, Bryony A; Hume, Clifford R; O'Leary, Stephen J; Shepherd, Robert K; Richardson, Rachael T

2012-01-01

The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the residual spiral ganglion neurons. These neurons, however, undergo progressive degeneration after hearing loss, marked initially by peripheral fibre retraction and ultimately culminating in cell death. This research aims to use gene therapy techniques to both hold and reverse this degeneration by providing a sustained and localised source of neurotrophins to the deafened cochlea. Adenoviral vectors containing green fluorescent protein, with or without neurotrophin-3 and brain derived neurotrophic factor, were injected into the lower basal turn of scala media of guinea pigs ototoxically deafened one week prior to intervention. This single injection resulted in localised and sustained gene expression, principally in the supporting cells within the organ of Corti. Guinea pigs treated with adenoviral neurotrophin-gene therapy had greater neuronal survival compared to contralateral non-treated cochleae when examined at 7 and 11 weeks post injection. Moreover; there was evidence of directed peripheral fibre regrowth towards cells expressing neurotrophin genes after both treatment periods. These data suggest that neurotrophin-gene therapy can provide sustained protection of spiral ganglion neurons and peripheral fibres after hearing loss.

'Localised creativity: a life span perspective'

OpenAIRE

Worth, Piers J.

2000-01-01

This thesis is based around a biographic study of the lives of 40 individuals (24 men and 16 women) with a reputation for creative work in a localised context (such as an organisation). The study examines life span development patterns from birth to middle age (45 - 60 years of age) with data gained by biographic interview and thematic analysis. Participants selected for this study are creative in that they have a reputation for producing new, novel and useful or appropriate contributions in ...

CT-assisted localisation of intracranial processes

Energy Technology Data Exchange (ETDEWEB)

Luft, C.; Trenkler, J.; Hammer, B.; Valencak, E.

1986-01-01

With the software developed for the SOMATOM DRH computerized tomograph it is possible to mix a ROI into the digital radiogram (topogram) for projection of a lesion, such as a tumor, onto the topogram plane; the software also allows an image reconstruction taking the topogram as a reference image (topogram-initiated reconstruction). Combining these two relatively simple methods, and adding distance measurements in two planes, the neurosurgeon has at his disposal an objective CT-assisted means of precisely localising intracranial processes before surgery.

Localised sarcoptic mange in dogs: a retrospective study of 10 cases.

Science.gov (United States)

Pin, D; Bensignor, E; Carlotti, D-N; Cadiergues, M C

2006-10-01

The authors report 10 cases of localised sarcoptic mange in dogs. In each case, lesions were localised to one precise area of the skin. Pruritus was present in nine cases and absent in one. Affected areas were the feet (one case), the face and/or the pinnae (six cases), the abdominal skin (one case), the flank (one case) and the lumbar area (one case). The types of lesions were erythema, papules, lichenification, scales, crusts and alopecia. Parasites were found in all cases except one, in which anti-immunoglobulin G Sarcoptes serology was positive. The acaricidal treatments given were lindane, ivermectin or selamectin and were all successful.

Development of a prototype of the tele-localisation system in radiotherapy using personal digital assistant via wireless communication.

Science.gov (United States)

Wu, Vincent Wing-Cheung; Tang, Fuk-hay; Cheung, Wai-kwan; Chan, Kit-chi

2013-02-01

In localisation of radiotherapy treatment field, the oncologist is present at the simulator to approve treatment details produced by the therapist. Problems may arise if the oncologist is not available and the patient requires urgent treatment. The development of a tele-localisation system is a potential solution, where the oncologist uses a personal digital assistant (PDA) to localise the treatment field on the image sent from the simulator through wireless communication and returns the information to the therapist after his or her approval. Our team developed the first tele-localisation prototype, which consisted of a server workstation (simulator) for the administration of digital imaging and communication in medicine localisation images including viewing and communication with the PDA via a Wi-Fi network; a PDA (oncologist's site) installed with the custom-built programme that synchronises with the server workstation and performs treatment field editing. Trial tests on accuracy and speed of the prototype system were conducted on 30 subjects with the treatment regions covering the neck, skull, chest and pelvis. The average time required in performing the localisation using the PDA was less than 1.5 min, with the blocked field longer than the open field. The transmission speed of the four treatment regions was similar. The average physical distortion of the images was within 4.4% and the accuracy of field size indication was within 5.3%. Compared with the manual method, the tele-localisation system presented with an average deviation of 5.5%. The prototype system fulfilled the planned objectives of tele-localisation procedure with reasonable speed and accuracy. © 2012 The Authors. Journal of Medical Imaging and Radiation Oncology © 2012 The Royal Australian and New Zealand College of Radiologists.

Interdependency of formation and localisation of the Min complex controls symmetric plastid division.

Science.gov (United States)

Maple, Jodi; Møller, Simon G

2007-10-01

Plastid division represents a fundamental biological process essential for plant development; however, the molecular basis of symmetric plastid division is unclear. AtMinE1 plays a pivotal role in selection of the plastid division site in concert with AtMinD1. AtMinE1 localises to discrete foci in chloroplasts and interacts with AtMinD1, which shows a similar localisation pattern. Here, we investigate the importance of Min protein complex formation during the chloroplast division process. Dissection of the assembly of the Min protein complex and determination of the interdependency of complex assembly and localisation in planta allow us to present a model of the molecular basis of selection of the division site in plastids. Moreover, functional analysis of AtMinE1 in bacteria demonstrates the level of functional conservation and divergence of the plastidic MinE proteins.

Techniques avancées du traitement d'antennes pour la localisation de sources : application à la localisation de mobile: cas du système UMTS.

OpenAIRE

Grosicki , Emmanuele

2003-01-01

La thèse a porté sur la localisation de mobile pour les systèmes UMTS-FDD. Il s'agit d'un sujet qui intéresse de plus en plus les opérateurs, notamment dans le cas de système UMTS-FDD où il existe très peu de réseaux réels. Les différentes approches permettant de localiser un émetteur ont ainsi été envisagées, et plus particulièrement, celles basées sur les mesures de puissances, les temps d'arrivée (TOA) en liaison descendante ou encore celles basées sur les angles d'arrivée (AOA) et sur tou...

Capsule-odometer: a concept to improve accurate lesion localisation.

Science.gov (United States)

Karargyris, Alexandros; Koulaouzidis, Anastasios

2013-09-21

In order to improve lesion localisation in small-bowel capsule endoscopy, a modified capsule design has been proposed incorporating localisation and - in theory - stabilization capabilities. The proposed design consists of a capsule fitted with protruding wheels attached to a spring-mechanism. This would act as a miniature odometer, leading to more accurate lesion localization information in relation to the onset of the investigation (spring expansion e.g., pyloric opening). Furthermore, this capsule could allow stabilization of the recorded video as any erratic, non-forward movement through the gut is minimised. Three-dimensional (3-D) printing technology was used to build a capsule prototype. Thereafter, miniature wheels were also 3-D printed and mounted on a spring which was attached to conventional capsule endoscopes for the purpose of this proof-of-concept experiment. In vitro and ex vivo experiments with porcine small-bowel are presented herein. Further experiments have been scheduled.

Time Localisation of Surface Defects on Optical Discs

DEFF Research Database (Denmark)

Odgaard, Peter Fogh; Wickerhauser, M.V.

Many have experienced problems with their Compact Disc player when a disc with a scratch or a finger print is tried played. One way to improve the playability of discs with such a defect, is to locate the defect in time and then handle it in a special way. As a consequence this time localisation...

Scanning Kelvin Probe applied to localised corrosion | Haque ...

African Journals Online (AJOL)

This paper focuses on specific applications of the SKP system. The instrument is calibrated, using different thickness of a model polymer Poly Vinyl Butyral (PVB) on mild steel and on galvanised steel. Artificial defects are used to show how the instrument is capable of detecting a localised corrosion cell and its ability to ...

Mutations in the pericentrin (PCNT) gene cause primordial dwarfism

NARCIS (Netherlands)

Rauch, Anita; Thiel, Christian T.; Schindler, Detlev; Wick, Ursula; Crow, Yanick J.; Ekici, Arif B.; van Essen, Anthonie J.; Goecke, Timm O.; Al-Gazali, Lihadh; Chrzanowska, Krystyna H.; Zweier, Christiane; Brunner, Han G.; Becker, Kristin; Curry, Cynthia J.; Dallapiccola, Bruno; Devriendt, Koenraad; Doerfler, Arnd; Kinning, Esther; Megarbane, Andre; Meinecke, Peter; Semple, Robert K.; Spranger, Stephanie; Toutain, Annick; Trembath, Richard C.; Voss, Egbert; Wilson, Louise; Hennekam, Raoul; de Zegher, Francis; Doerr, Helmuth-Guenther; Reis, Andre

2008-01-01

Fundamental processes influencing human growth can be revealed by studying extreme short stature. Using genetic linkage analysis, we find that biallelic loss- of- function mutations in the centrosomal pericentrin ( PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial

ANALYSIS OF SLG GENE – THE MOLECULAR MARKER IN HYBRID BREEDING OF OIL SEED RAPE

Directory of Open Access Journals (Sweden)

L DOLANSKÁ

2004-07-01

Full Text Available Oil seed rape (Brassica napus L. cultivars, donors of quality (SC and self-incompatible (SI lines have been analysed using identification of S-locus. In several Brassica napus cultivars one S-locus SLG gene was detected as dominant and the second S-locus as recessive. Amplification class II SLG gene screened recessive gene in all analysed samples (SC and SI. The DNA fragment of recessive gene corresponded to SLG gene W found in cv. Westar. S-haplotypes were analysed by PCR-RFLP. Different Brassica napus cultivars had an identical electrophoretic profile conforming with nonfunctional A10 allele in B. campestris. In B. napus A10 allele is localised in genome A. The functional recessive SLG gene is probably localised in genome C. Model of their segregation was suggested. SC and SI plants segregated in F2 generation at the ratio of approximately 3:1. This indicates a recessive monogenic disposition of SI in the experimental population.

Differential gene expression patterns between smokers and non‐smokers: cause or consequence?

Science.gov (United States)

Jansen, Rick; Brooks, Andy; Willemsen, Gonneke; van Grootheest, Gerard; de Geus, Eco; Smit, Jan H.; Penninx, Brenda W.; Boomsma, Dorret I.

2015-01-01

Abstract The molecular mechanisms causing smoking‐induced health decline are largely unknown. To elucidate the molecular pathways involved in cause and consequences of smoking behavior, we conducted a genome‐wide gene expression study in peripheral blood samples targeting 18 238 genes. Data of 743 smokers, 1686 never smokers and 890 ex‐smokers were available from two population‐based cohorts from the Netherlands. In addition, data of 56 monozygotic twin pairs discordant for ever smoking were used. One hundred thirty‐two genes were differentially expressed between current smokers and never smokers (P smokers into account, expression of these 132 genes was classified into reversible (94 genes), slowly reversible (31 genes), irreversible (6 genes) or inconclusive (1 gene). Expression of 6 of the 132 genes (three reversible and three slowly reversible) was confirmed to be reactive to smoking as they were differentially expressed in monozygotic pairs discordant for smoking. Cis‐expression quantitative trait loci for GPR56 and RARRES3 (downregulated in smokers) were associated with increased number of cigarettes smoked per day in a large genome‐wide association meta‐analysis, suggesting a causative effect of GPR56 and RARRES3 expression on smoking behavior. In conclusion, differential gene expression patterns in smokers are extensive and cluster in several underlying disease pathways. Gene expression differences seem mainly direct consequences of smoking, and largely reversible after smoking cessation. However, we also identified DNA variants that may influence smoking behavior via the mediating gene expression. PMID:26594007

CT-assisted localisation of intracranial processes

International Nuclear Information System (INIS)

Luft, C.; Trenkler, J.; Hammer, B.; Valencak, E.

1986-01-01

With the software developed for the SOMATOM DRH computerized tomograph it is possible to mix a ROI into the digital radiogram (topogram) for projection of a lesion, such as a tumor, onto the topogram plane; the software also allows an image reconstruction taking the topogram as a reference image (topogram-initiated reconstruction). Combining these two relatively simple methods, and adding distance measurements in two planes, the neurosurgeon has at his disposal an objective CT-assisted means of precisely localising intracranial processes before surgery. (orig.) [de

Mutations in the pericentrin (PCNT) gene cause primordial dwarfism

NARCIS (Netherlands)

Rauch, Anita; Thiel, Christian T.; Schindler, Detlev; Wick, Ursula; Crow, Yanick J.; Ekici, Arif B.; van Essen, Anthonie J.; Goecke, Timm O.; Al-Gazali, Lihadh; Chrzanowska, Krystyna H.; Zweier, Christiane; Brunner, Han G.; Becker, Kristin; Curry, Cynthia J.; Dallapiccola, Bruno; Devriendt, Koenraad; Dörfler, Arnd; Kinning, Esther; Megarbane, André; Meinecke, Peter; Semple, Robert K.; Spranger, Stephanie; Toutain, Annick; Trembath, Richard C.; Voss, Egbert; Wilson, Louise; Hennekam, Raoul; de Zegher, Francis; Dörr, Helmuth-Günther; Reis, André

2008-01-01

Fundamental processes influencing human growth can be revealed by studying extreme short stature. Using genetic linkage analysis, we find that biallelic loss-of-function mutations in the centrosomal pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism

Aesthetic Proximity: the Role of Stylistic Programme Elements in Format Localisation

Directory of Open Access Journals (Sweden)

Jolien van Keulen

2016-08-01

Full Text Available Implications of the transnationalisation of television are often studied by focusing on the localisation of the content of formatted programmes. Although television is essentially an audio-visual medium, little attention has been paid to the aesthetic aspects of television texts in relation to transnationalisation and formatting. Transnationalisation of production practices, such as through formatting, implies a transnational aesthetic. At the same time, aspects of style are specific to place, culture or audience. In this article, the localisation of stylistic programme elements is explored using a comparison of two reality format adaptations. It is argued that style plays an important role in the expression of the local in a transnational industry.

Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

Directory of Open Access Journals (Sweden)

Reverter Antonio

2008-09-01

Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

Somatostatin receptor scintigraphy and intraoperative gamma probe detection in the localisation and treatment of pancreatic insulinoma

International Nuclear Information System (INIS)

Loh, Nelson K.; Macdonald, William B.; Dunne, Marina L.; Rao, Sudhakar

2009-01-01

Full text: Aims: We report a case of insulinoma that was successfully enucleated under radio-guidance after an initial unsuccessful laparotomy. This case highlights the utility of Somatostatin Receptor Scintigraphy (SRS) and gamma probe in the localisation and treatment of neuroendocrine tumours. Methods: The patient presented with recurrent hypoglycaemia. An abdominal CT scan identified a lesion in the uncinate process of the pancreas, however, laparotomy with use of intraoperative ultrasound failed to localise the lesion. SRS with SPECTICT was then requested by the surgical team with a view to radio-guided surgery. Results: SRS demonstrated an octreotide-avid tumour in the posterior uncinate process of the pancreas, and confirmed suitability for radio-guided surgery. At re-exploration, the surgeon was again unable to palpate the lesion or localise it with intraoperative ultrasound, however, the lesion was successfully detected and removed with the use of a gamma probe. A postoperative SRS confirmed complete excision and histopathology was diagnostic of insulinoma. Conclusion: This case highlights the utility of SRS in the intraoperative localisation and surgical excision of neuroendocrine tumours. The lesion was unable to be localised clinically or with intraoperative ultrasound but was successfully detected with scintigraphic techniques. The surgical team acknowledge that the use of a gamma probe enabled enucleation of the insulinoma, which obviated the need for an invasive Whipple's procedure.

La Carte de Localisation Probable des Avalanches (CPLA

Directory of Open Access Journals (Sweden)

Gilles BORREL

1994-12-01

Full Text Available La Carte de Localisation Probable des Avalanches (CPLA indique l’enveloppe des limites extrêmes connues atteintes par les avalanches, ainsi que les travaux de protection associés. Il s’agit d’un document informatif et non d’une carte de risque. Depuis 1990, les données thématiques sont numérisées.

Orthogonal views improves localisation in bone scans of wrist

International Nuclear Information System (INIS)

Roth, A.L.

1997-01-01

Full text: Of all nuclear medicine studies, bone scans are the most fundamental. However, straightforward these may seem, there are always mechanisms that can be implemented which assist in a more precise diagnosis, particularly in areas with an intricate bone structure. An 18-year-old right-handed student presented to her doctor with a one month history of pain over the right distal radio-ulna joint area. Clinically, she had prominence of the right ulna, which suggested that there may have been a previous injury to the wrist. Also, pronation/supination were painful where there was swelling of the extensor carpi ulnaris tendon, as well as some discomfort with clicking in ulna deviation/rotation. The X-rays demonstrated some premature radial epiphysial closure. A bone scan was requested to attempt to localise the main inflammatory focus. The dynamic study was performed in the planar projection with an immediate blood pool for 300k being taken. These demonstrated a vascular blush medially. A medial blood pool image was acquired and it localised the abnormal vascularity as being dorsal. A separate focal area of less intense blood pooling was also noted in the line of the distal ulna. Delayed images showed increased uptake localised to the ulna styloid. Anatomically, the superficial vascular blush correlated with tenosynovitis. Hence, the orthogonal initial and delayed images were definitive in the diagnoses of tenosynovitis of the extensor carpi ulnaris tendon. This clearly complements the information provided by the palmar view. However, it is important to remember that an increased radiation dose to the technologist is incurred as a result of the extra orthogonal view, hence attention to technique is imperative

Orthogonal views improves localisation in bone scans of wrist

Energy Technology Data Exchange (ETDEWEB)

Roth, A.L.

1997-09-01

Full text: Of all nuclear medicine studies, bone scans are the most fundamental. However, straightforward these may seem, there are always mechanisms that can be implemented which assist in a more precise diagnosis, particularly in areas with an intricate bone structure. An 18-year-old right-handed student presented to her doctor with a one month history of pain over the right distal radio-ulna joint area. Clinically, she had prominence of the right ulna, which suggested that there may have been a previous injury to the wrist. Also, pronation/supination were painful where there was swelling of the extensor carpi ulnaris tendon, as well as some discomfort with clicking in ulna deviation/rotation. The X-rays demonstrated some premature radial epiphysial closure. A bone scan was requested to attempt to localise the main inflammatory focus. The dynamic study was performed in the planar projection with an immediate blood pool for 300k being taken. These demonstrated a vascular blush medially. A medial blood pool image was acquired and it localised the abnormal vascularity as being dorsal. A separate focal area of less intense blood pooling was also noted in the line of the distal ulna. Delayed images showed increased uptake localised to the ulna styloid. Anatomically, the superficial vascular blush correlated with tenosynovitis. Hence, the orthogonal initial and delayed images were definitive in the diagnoses of tenosynovitis of the extensor carpi ulnaris tendon. This clearly complements the information provided by the palmar view. However, it is important to remember that an increased radiation dose to the technologist is incurred as a result of the extra orthogonal view, hence attention to technique is imperative.

Prevalence of coagulase gene polymorphism in Staphylococcus aureus isolates causing bovine mastitis

DEFF Research Database (Denmark)

Aarestrup, Frank Møller; Dangler, C. A.; Sordillo, L. M.

1995-01-01

This study was conducted to investigate polymorphism of the coagulase gene of Staphylococcus aureus causing bovine mastitis. One hundred eighty-seven strains of S. aureus were isolated from bovine mastitic milk samples obtained from 187 different Danish dairy farms. The isolates were characterised......% of the isolates. The ease of analysing coagulase gene polymorphisms among a large number of strains, and the multiple distinct polymorphic patterns generated, supports the use of this technique in epidemiological investigations of bovine mastitis. The predominating variants may have predelection for causing...

Intracellular localisation of proteins to specific cellular areas by nanocapsule mediated delivery.

Science.gov (United States)

Wang, Huabin; Chen, Ligang; Sun, Xianchao; Fu, Ailing

2017-09-01

Nanocapsules are promising carriers with great potential for intracellular protein transport. Although many studies have intended to improve cell uptake efficacy, there is an increasing interest in understanding of subcellular distribution of cargoes inside cells, which is essential for purposeful delivery of biomolecules into specific sites within cells. Herein, we interrogate the intracellular localisation of exogenous proteins, including fluorescein isothiocyanate (FITC)-labelled bovine serum albumin (BSA) and green fluorescent protein (GFP), mediated by specially designed nanocapsules. The results show that the designed nanocapsules can deliver the two types of fluorescent proteins into different cellular destinations (cytosol, nucleus or the whole cell), depending on the composition of nanocapsules. Meanwhile, several impact factors that influence the distribution of proteins in cells have also been investigated, and the results suggest that the localisation of capsule-mediated proteins in cells is strongly affected by the surface properties of nanocapsules, the types of stabilisers and proteins, and environmental temperatures. The rational control of intracellular localised delivery of exogenous proteins as we demonstrated in this study might open new avenues to obtain desired magnitude of drug effects for modulating cell activity.

Clinical study of DMD gene point mutation causing Becker muscular dystrophy

Directory of Open Access Journals (Sweden)

Ji-qing CAO

2015-07-01

Full Text Available Background  DMD gene point mutation, mainly nonsense mutation, always cause the most severe Duchenne muscular dystrophy (DMD. However, we also observed some cases of Becker muscular dystrophy (BMD carrying DMD point mutation. This paper aims to explore the mechanism of DMD point mutation causing BMD, in order to enhance the understanding of mutation types of BMD.  Methods  Sequence analysis was performed in 11 cases of BMD confirmed by typical clinical manifestations and muscle biopsy. The exon of DMD gene was detected non-deletion or duplication by multiplex ligation-dependent probe amplification (MLPA.  Results  Eleven patients carried 10 mutation types without mutational hotspot. Six patients carried nonsense mutations [c.5002G>T, p.(Glu1668X; c.1615C > T, p.(Arg539X; c.7105G > T, p.(Glu2369X; c.5287C > T, p.(Arg1763X; c.9284T > G, p.(Leu3095X]. One patient carried missense mutation [c.5234G > A, p.(Arg1745His]. Two patients carried frameshift mutations (c.10231dupT, c.10491delC. Two patients carried splicing site mutations (c.4518 + 3A > T, c.649 + 2T > C.  Conclusions  DMD gene point mutation may result in BMD with mild clinical symptoms. When clinical manifestations suggest the possibility of BMD and MLPA reveals non?deletion or duplication mutation of DMD gene, BMD should be considered. Study on the mechanism of DMD point mutation causing BMD is very important for gene therapy of DMD. DOI: 10.3969/j.issn.1672-6731.2015.06.005

PROTEIN TARGETING TO STARCH is required for localising GRANULE-BOUND STARCH SYNTHASE to starch granules and for normal amylose synthesis in Arabidopsis.

Directory of Open Access Journals (Sweden)

David Seung

2015-02-01

Full Text Available The domestication of starch crops underpinned the development of human civilisation, yet we still do not fully understand how plants make starch. Starch is composed of glucose polymers that are branched (amylopectin or linear (amylose. The amount of amylose strongly influences the physico-chemical behaviour of starchy foods during cooking and of starch mixtures in non-food manufacturing processes. The GRANULE-BOUND STARCH SYNTHASE (GBSS is the glucosyltransferase specifically responsible for elongating amylose polymers and was the only protein known to be required for its biosynthesis. Here, we demonstrate that PROTEIN TARGETING TO STARCH (PTST is also specifically required for amylose synthesis in Arabidopsis. PTST is a plastidial protein possessing an N-terminal coiled coil domain and a C-terminal carbohydrate binding module (CBM. We discovered that Arabidopsis ptst mutants synthesise amylose-free starch and are phenotypically similar to mutants lacking GBSS. Analysis of granule-bound proteins showed a dramatic reduction of GBSS protein in ptst mutant starch granules. Pull-down assays with recombinant proteins in vitro, as well as immunoprecipitation assays in planta, revealed that GBSS physically interacts with PTST via a coiled coil. Furthermore, we show that the CBM domain of PTST, which mediates its interaction with starch granules, is also required for correct GBSS localisation. Fluorescently tagged Arabidopsis GBSS, expressed either in tobacco or Arabidopsis leaves, required the presence of Arabidopsis PTST to localise to starch granules. Mutation of the CBM of PTST caused GBSS to remain in the plastid stroma. PTST fulfils a previously unknown function in targeting GBSS to starch. This sheds new light on the importance of targeting biosynthetic enzymes to sub-cellular sites where their action is required. Importantly, PTST represents a promising new gene target for the biotechnological modification of starch composition, as it is

Neuroserpin polymers cause oxidative stress in a neuronal model of the dementia FENIB.

Science.gov (United States)

Guadagno, Noemi A; Moriconi, Claudia; Licursi, Valerio; D'Acunto, Emanuela; Nisi, Paola S; Carucci, Nicoletta; De Jaco, Antonella; Cacci, Emanuele; Negri, Rodolfo; Lupo, Giuseppe; Miranda, Elena

2017-07-01

The serpinopathies are human pathologies caused by mutations that promote polymerisation and intracellular deposition of proteins of the serpin superfamily, leading to a poorly understood cell toxicity. The dementia FENIB is caused by polymerisation of the neuronal serpin neuroserpin (NS) within the endoplasmic reticulum (ER) of neurons. With the aim of understanding the toxicity due to intracellular accumulation of neuroserpin polymers, we have generated transgenic neural progenitor cell (NPC) cultures from mouse foetal cerebral cortex, stably expressing the control protein GFP (green fluorescent protein), or human wild type, G392E or delta NS. We have characterised these cell lines in the proliferative state and after differentiation to neurons. Our results show that G392E NS formed polymers that were mostly retained within the ER, while wild type NS was correctly secreted as a monomeric protein into the culture medium. Delta NS was absent at steady state due to its rapid degradation, but it was easily detected upon proteasomal block. Looking at their intracellular distribution, wild type NS was found in partial co-localisation with ER and Golgi markers, while G392E NS was localised within the ER only. Furthermore, polymers of NS were detected by ELISA and immunofluorescence in neurons expressing the mutant but not the wild type protein. We used control GFP and G392E NPCs differentiated to neurons to investigate which cellular pathways were modulated by intracellular polymers by performing RNA sequencing. We identified 747 genes with a significant upregulation (623) or downregulation (124) in G392E NS-expressing cells, and we focused our attention on several genes involved in the defence against oxidative stress that were up-regulated in cells expressing G392E NS (Aldh1b1, Apoe, Gpx1, Gstm1, Prdx6, Scara3, Sod2). Inhibition of intracellular anti-oxidants by specific pharmacological reagents uncovered the damaging effects of NS polymers. Our results support a role

Cutting Edge Localisation in an Edge Profile Milling Head

NARCIS (Netherlands)

Fernandez Robles, Laura; Azzopardi, George; Alegre, Enrique; Petkov, Nicolai

2015-01-01

Wear evaluation of cutting tools is a key issue for prolonging their lifetime and ensuring high quality of products. In this paper, we present a method for the effective localisation of cutting edges of inserts in digital images of an edge profile milling head. We introduce a new image data set of

Null stream analysis of Pulsar Timing Array data: localisation of resolvable gravitational wave sources

Science.gov (United States)

Goldstein, Janna; Veitch, John; Sesana, Alberto; Vecchio, Alberto

2018-04-01

Super-massive black hole binaries are expected to produce a gravitational wave (GW) signal in the nano-Hertz frequency band which may be detected by pulsar timing arrays (PTAs) in the coming years. The signal is composed of both stochastic and individually resolvable components. Here we develop a generic Bayesian method for the analysis of resolvable sources based on the construction of `null-streams' which cancel the part of the signal held in common for each pulsar (the Earth-term). For an array of N pulsars there are N - 2 independent null-streams that cancel the GW signal from a particular sky location. This method is applied to the localisation of quasi-circular binaries undergoing adiabatic inspiral. We carry out a systematic investigation of the scaling of the localisation accuracy with signal strength and number of pulsars in the PTA. Additionally, we find that source sky localisation with the International PTA data release one is vastly superior than what is achieved by its constituent regional PTAs.

The Anderson model for electron localisation

International Nuclear Information System (INIS)

Pruisken, A.M.M.; Schaefer, L.

1982-01-01

The Anderson model for localisation problems is treated with field theory employing the replica trick. We show that no valid perturbation theory results out of the usual (S2)2 formalism due to mishandling of symmetries. The problem is reformulated in terms of matrix fields. It is shown that the Anderson model asymptotically exhibits an exact local gauge symmetry. Elimination of massive longitudinal components leads to a non-compact sigma model, obtained earlier for the description of electronic disorder. We thus establish that the Anderson model is in the same universality class as Wegner's gauge invariant real matrix model. (orig.)

Gene repair of an Usher syndrome causing mutation by zinc-finger nuclease mediated homologous recombination.

Science.gov (United States)

Overlack, Nora; Goldmann, Tobias; Wolfrum, Uwe; Nagel-Wolfrum, Kerstin

2012-06-26

Human Usher syndrome (USH) is the most frequent cause of inherited deaf-blindness. It is clinically and genetically heterogeneous, assigned to three clinical types of which the most severe type is USH1. No effective treatment for the ophthalmic component of USH exists. Gene augmentation is an attractive strategy for hereditary retinal diseases. However, several USH genes, like USH1C, are expressed in various isoforms, hampering gene augmentation. As an alternative treatment strategy, we applied the zinc-finger nuclease (ZFN) technology for targeted gene repair of an USH1C, causing mutation by homologous recombination. We designed ZFNs customized for the p.R31X nonsense mutation in Ush1c. We evaluated ZFNs for DNA cleavage capability and analyzed ZFNs biocompatibilities by XTT assays. We demonstrated ZFNs mediated gene repair on genomic level by digestion assays and DNA sequencing, and on protein level by indirect immunofluorescence and Western blot analyses. The specifically designed ZFNs did not show cytotoxic effects in a p.R31X cell line. We demonstrated that ZFN induced cleavage of their target sequence. We showed that simultaneous application of ZFN and rescue DNA induced gene repair of the disease-causing mutation on the genomic level, resulting in recovery of protein expression. In our present study, we analyzed for the first time ZFN-activated gene repair of an USH gene. The data highlight the ability of ZFNs to induce targeted homologous recombination and mediate gene repair in USH. We provide further evidence that the ZFN technology holds great potential to recover disease-causing mutations in inherited retinal disorders.

Novel maximum likelihood approach for passive detection and localisation of multiple emitters

Science.gov (United States)

Hernandez, Marcel

2017-12-01

In this paper, a novel target acquisition and localisation algorithm (TALA) is introduced that offers a capability for detecting and localising multiple targets using the intermittent "signals-of-opportunity" (e.g. acoustic impulses or radio frequency transmissions) they generate. The TALA is a batch estimator that addresses the complex multi-sensor/multi-target data association problem in order to estimate the locations of an unknown number of targets. The TALA is unique in that it does not require measurements to be of a specific type, and can be implemented for systems composed of either homogeneous or heterogeneous sensors. The performance of the TALA is demonstrated in simulated scenarios with a network of 20 sensors and up to 10 targets. The sensors generate angle-of-arrival (AOA), time-of-arrival (TOA), or hybrid AOA/TOA measurements. It is shown that the TALA is able to successfully detect 83-99% of the targets, with a negligible number of false targets declared. Furthermore, the localisation errors of the TALA are typically within 10% of the errors generated by a "genie" algorithm that is given the correct measurement-to-target associations. The TALA also performs well in comparison with an optimistic Cramér-Rao lower bound, with typical differences in performance of 10-20%, and differences in performance of 40-50% in the most difficult scenarios considered. The computational expense of the TALA is also controllable, which allows the TALA to maintain computational feasibility even in the most challenging scenarios considered. This allows the approach to be implemented in time-critical scenarios, such as in the localisation of artillery firing events. It is concluded that the TALA provides a powerful situational awareness aid for passive surveillance operations.

Application of the Localisation Platform Crowdin in Translator Education

Science.gov (United States)

Kudla, Dominik

2017-01-01

This article is an attempt to briefly describe the potential of the online localisation platform Crowdin for the education of the future translators at universities and in private courses or workshops. This description is provided on the basis of the information gathered through the user experience of the author and uses the example of the Khan…

Flows and Stratification of an Enclosure Containing Both Localised and Vertically Distributed Sources of Buoyancy

Science.gov (United States)

Partridge, Jamie; Linden, Paul

2013-11-01

We examine the flows and stratification established in a naturally ventilated enclosure containing both a localised and vertically distributed source of buoyancy. The enclosure is ventilated through upper and lower openings which connect the space to an external ambient. Small scale laboratory experiments were carried out with water as the working medium and buoyancy being driven directly by temperature differences. A point source plume gave localised heating while the distributed source was driven by a controllable heater mat located in the side wall of the enclosure. The transient temperatures, as well as steady state temperature profiles, were recorded and are reported here. The temperature profiles inside the enclosure were found to be dependent on the effective opening area A*, a combination of the upper and lower openings, and the ratio of buoyancy fluxes from the distributed and localised source Ψ =Bw/Bp . Industrial CASE award with ARUP.

Automaticity and localisation of concurrents predicts colour area activity in grapheme-colour synaesthesia.

Science.gov (United States)

Gould van Praag, Cassandra D; Garfinkel, Sarah; Ward, Jamie; Bor, Daniel; Seth, Anil K

2016-07-29

In grapheme-colour synaesthesia (GCS), the presentation of letters or numbers induces an additional 'concurrent' experience of colour. Early functional MRI (fMRI) investigations of GCS reported activation in colour-selective area V4 during the concurrent experience. However, others have failed to replicate this key finding. We reasoned that individual differences in synaesthetic phenomenology might explain this inconsistency in the literature. To test this hypothesis, we examined fMRI BOLD responses in a group of grapheme-colour synaesthetes (n=20) and matched controls (n=20) while characterising the individual phenomenology of the synaesthetes along dimensions of 'automaticity' and 'localisation'. We used an independent functional localiser to identify colour-selective areas in both groups. Activations in these areas were then assessed during achromatic synaesthesia-inducing, and non-inducing conditions; we also explored whole brain activations, where we sought to replicate the existing literature regarding synaesthesia effects. Controls showed no significant activations in the contrast of inducing > non-inducing synaesthetic stimuli, in colour-selective ROIs or at the whole brain level. In the synaesthete group, we correlated activation within colour-selective ROIs with individual differences in phenomenology using the Coloured Letters and Numbers (CLaN) questionnaire which measures, amongst other attributes, the subjective automaticity/attention in synaesthetic concurrents, and their spatial localisation. Supporting our hypothesis, we found significant correlations between individual measures of synaesthetic phenomenology and BOLD responses in colour-selective areas, when contrasting inducing against non-inducing stimuli. Specifically, left-hemisphere colour area responses were stronger for synaesthetes scoring high on phenomenological localisation and automaticity/attention, while right-hemisphere colour area responses showed a relationship with localisation

Machine learning approach for single molecule localisation microscopy.

Science.gov (United States)

Colabrese, Silvia; Castello, Marco; Vicidomini, Giuseppe; Del Bue, Alessio

2018-04-01

Single molecule localisation (SML) microscopy is a fundamental tool for biological discoveries; it provides sub-diffraction spatial resolution images by detecting and localizing "all" the fluorescent molecules labeling the structure of interest. For this reason, the effective resolution of SML microscopy strictly depends on the algorithm used to detect and localize the single molecules from the series of microscopy frames. To adapt to the different imaging conditions that can occur in a SML experiment, all current localisation algorithms request, from the microscopy users, the choice of different parameters. This choice is not always easy and their wrong selection can lead to poor performance. Here we overcome this weakness with the use of machine learning. We propose a parameter-free pipeline for SML learning based on support vector machine (SVM). This strategy requires a short supervised training that consists in selecting by the user few fluorescent molecules (∼ 10-20) from the frames under analysis. The algorithm has been extensively tested on both synthetic and real acquisitions. Results are qualitatively and quantitatively consistent with the state of the art in SML microscopy and demonstrate that the introduction of machine learning can lead to a new class of algorithms competitive and conceived from the user point of view.

Noonan syndrome-causing genes: Molecular update and an assessment of the mutation rate

Directory of Open Access Journals (Sweden)

Ihssane El Bouchikhi

2016-12-01

Full Text Available Noonan syndrome is a common autosomal dominant disorder characterized by short stature, congenital heart disease and facial dysmorphia with an incidence of 1/1000 to 2500 live births. Up to now, several genes have been proven to be involved in the disturbance of the transduction signal through the RAS-MAP Kinase pathway and the manifestation of Noonan syndrome. The first gene described was PTPN11, followed by SOS1, RAF1, KRAS, BRAF, NRAS, MAP2K1, and RIT1, and recently SOS2, LZTR1, and A2ML1, among others. Progressively, the physiopathology and molecular etiology of most signs of Noonan syndrome have been demonstrated, and inheritance patterns as well as genetic counseling have been established. In this review, we summarize the data concerning clinical features frequently observed in Noonan syndrome, and then, we describe the molecular etiology as well as the physiopathology of most Noonan syndrome-causing genes. In the second part of this review, we assess the mutational rate of Noonan syndrome-causing genes reported up to now in most screening studies. This review should give clinicians as well as geneticists a full view of the molecular aspects of Noonan syndrome and the authentic prevalence of the mutational events of its causing-genes. It will also facilitate laying the groundwork for future molecular diagnosis research, and the development of novel treatment strategies.

From extended integrity monitoring to the safety evaluation of satellite-based localisation system

International Nuclear Information System (INIS)

Legrand, Cyril; Beugin, Julie; Marais, Juliette; Conrard, Blaise; El-Koursi, El-Miloudi; Berbineau, Marion

2016-01-01

Global Navigation Satellite Systems (GNSS) such as GPS, already used in aeronautics for safety-related applications, can play a major role in railway safety by allowing a train to locate itself safely. However, in order to implement this positioning solution in any embedded system, its performances must be evaluated according to railway standards. The evaluation of GNSS performances is not based on the same attributes class than RAMS evaluation. Face to these diffculties, we propose to express the integrity attribute, performance of satellite-based localisation. This attribute comes from aeronautical standards and for a hybridised GNSS with inertial system. To achieve this objective, the integrity attribute must be extended to this kind of system and algorithms initially devoted to GNSS integrity monitoring only must be adapted. Thereafter, the formalisation of this integrity attribute permits us to analyse the safety quantitatively through the probabilities of integrity risk and wrong-side failure. In this paper, after an introductory discussion about the use of localisation systems in railway safety context together with integrity issues, a particular integrity monitoring is proposed and described. The detection events of this algorithm permit us to conclude about safety level of satellite-based localisation system.

Localised states in organic semiconductors and their detection

Science.gov (United States)

Imperia, Paolo

2002-06-01

New polymers and low molecular compounds, suitable for organic light emitting devices and organic electronic applications, have been synthesised in this years in order to obtain electron transport characteristics compatible with requirements for applications in real plastic devices. However, despite of the technological importance and of the relevant progress in devices manufacture, fundamental physical properties of such class of materials are still not enough studied. In particular extensive presence of distributions of localised states inside the band gap has a deep impact on their electronic properties. Such presence of shallow traps as well as the influence of the sample preparation conditions on deep and shallow localised states have not been, until now, systematically explored. The thermal techniques are powerful tools in order to study localised levels in inorganic and organic materials. Thermally stimulated luminescence (TSL), thermally stimulated currents (TSC) and thermally stimulated depolarisation currents (TSDC) allow to deeply look to shallow and deep trap levels as well as they permit to study, in synergy with dielectric spectroscopy (DES), polarisation and depolarisation effects. We studied, by means of numerical simulations, the first and the second order kinetic equations characterised by negligible and strong re-trapping respectively. We included in the equations Gaussian, exponential and quasi-continuous distributions of localised states. The shapes of the theoretical peaks have been investigated by means of systematic variation of the two main parameters of the equations, i. e. the energy trap depth E and the frequency factor a and of the parameters regulating the distributions, in particular for a Gaussian distribution the distribution width s and the integration limits. The theoretical findings have been applied to experimental glow curves. Thin films of polymers and low molecular compounds. Polyphenylquinoxalines, trisphenylquinoxalines and

Several adaptor proteins promote intracellular localisation of the transporter MRP4/ABCC4 in platelets and haematopoietic cells.

Science.gov (United States)

Schaletzki, Yvonne; Kromrey, Marie-Luise; Bröderdorf, Susanne; Hammer, Elke; Grube, Markus; Hagen, Paul; Sucic, Sonja; Freissmuth, Michael; Völker, Uwe; Greinacher, Andreas; Rauch, Bernhard H; Kroemer, Heyo K; Jedlitschky, Gabriele

2017-01-05

The multidrug resistance protein 4 (MRP4/ABCC4) has been identified as an important transporter for signalling molecules including cyclic nucleotides and several lipid mediators in platelets and may thus represent a novel target to interfere with platelet function. Besides its localisation in the plasma membrane, MRP4 has been also detected in the membrane of dense granules in resting platelets. In polarised cells it is localised at the basolateral or apical plasma membrane. To date, the mechanism of MRP4 trafficking has not been elucidated; protein interactions may regulate both the localisation and function of this transporter. We approached this issue by searching for interacting proteins by in vitro binding assays, followed by immunoblotting and mass spectrometry, and by visualising their co-localisation in platelets and haematopoietic cells. We identified the PDZ domain containing scaffold proteins ezrin-binding protein 50 (EBP50/NHERF1), postsynaptic density protein 95 (PSD95), and sorting nexin 27 (SNX27), but also the adaptor protein complex 3 subunit β3A (AP3B1) and the heat shock protein HSP90 as putative interaction partners of MRP4. The knock-down of SNX27, PSD95, and AP3B1 by siRNA in megakaryoblastic leukaemia cells led to a redistribution of MRP4 from intracellular structures to the plasma membrane. Inhibition of HSP90 led to a diminished expression and retention of MRP4 in the endoplasmic reticulum. These results indicate that MRP4 localisation and function are regulated by multiple protein interactions. Changes in the adaptor proteins can hence lead to altered localisation and function of the transporter.

Critical Factors in Transnational Oil Companies Localisation Decisions - Clusters and Portfolio Optimisation

International Nuclear Information System (INIS)

Kind, Hans Jarle; Osmundsen, Petter; Tverteraas, Ragnar

2001-10-01

Enhanced understanding of the factors determining trans national companies' localisation decisions is important for regulators and other stake holders concerned about maintaining current activity levels in a petroleum producing country. This article discusses localisation decisions in the context of theories of industrial clusters and real portfolio optimisation theory (materiality), which we argue are two fruitful lines of explanation for trans national companies' behaviour. The industrial cluster literature is concerned about the level of positive externalities associated with geographic clustering of related production activities. The concept of materiality, implying that investment projects in an oil province must be of a certain minimum size in order to be interesting for oil companies, is evaluated empirically and compared to predictions of mainstream economic theory. (author)

Critical Factors in Transnational Oil Companies Localisation Decisions - Clusters and Portfolio Optimisation

Energy Technology Data Exchange (ETDEWEB)

Kind, Hans Jarle; Osmundsen, Petter; Tverteraas, Ragnar

2001-10-01

Enhanced understanding of the factors determining transnational companies' localisation decisions is important for regulators and other stakeholders concerned about maintaining current activity levels in a petroleum producing country. This article discusses localisation decisions in the context of theories of industrial clusters and real portfolio optimisation theory (materiality), which we argue are two fruitful lines of explanation for transnational companies' behaviour. The industrial cluster literature is concerned about the level of positive externalities associated with geographic clustering of related production activities. The concept of materiality, implying that investment projects in an oil province must be of a certain minimum size in order to be interesting for oil companies, is evaluated empirically and compared to predictions of mainstream economic theory. (author)

Localisation in a Growth Model with Interaction

Science.gov (United States)

Costa, M.; Menshikov, M.; Shcherbakov, V.; Vachkovskaia, M.

2018-05-01

This paper concerns the long term behaviour of a growth model describing a random sequential allocation of particles on a finite cycle graph. The model can be regarded as a reinforced urn model with graph-based interaction. It is motivated by cooperative sequential adsorption, where adsorption rates at a site depend on the configuration of existing particles in the neighbourhood of that site. Our main result is that, with probability one, the growth process will eventually localise either at a single site, or at a pair of neighbouring sites.

A Novel Mutation in ERCC8 Gene Causing Cockayne Syndrome

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Maryam Taghdiri

2017-08-01

Full Text Available Cockayne syndrome (CS is a rare autosomal recessive multisystem disorder characterized by impaired neurological and sensory functions, cachectic dwarfism, microcephaly, and photosensitivity. This syndrome shows a variable age of onset and rate of progression, and its phenotypic spectrum include a wide range of severity. Due to the progressive nature of this disorder, diagnosis can be more important when additional signs and symptoms appear gradually and become steadily worse over time. Therefore, mutation analysis of genes involved in CS pathogenesis can be helpful to confirm the suspected clinical diagnosis. Here, we report a novel mutation in ERCC8 gene in a 16-year-old boy who suffers from poor weight gain, short stature, microcephaly, intellectual disability, and photosensitivity. The patient was born to consanguineous family with no previous documented disease in his parents. To identify disease-causing mutation in the patient, whole exome sequencing utilizing next-generation sequencing on an Illumina HiSeq 2000 platform was performed. Results revealed a novel homozygote mutation in ERCC8 gene (NM_000082: exon 11, c.1122G>C in our patient. Another gene (ERCC6, which is also involved in CS did not have any disease-causing mutations in the proband. The new identified mutation was then confirmed by Sanger sequencing in the proband, his parents, and extended family members, confirming co-segregation with the disease. In addition, different bioinformatics programs which included MutationTaster, I-Mutant v2.0, NNSplice, Combined Annotation Dependent Depletion, The PhastCons, Genomic Evolutationary Rate Profiling conservation score, and T-Coffee Multiple Sequence Alignment predicted the pathogenicity of the mutation. Our study identified a rare novel mutation in ERCC8 gene and help to provide accurate genetic counseling and prenatal diagnosis to minimize new affected individuals in this family.

A Novel Mutation in ERCC8 Gene Causing Cockayne Syndrome.

Science.gov (United States)

Taghdiri, Maryam; Dastsooz, Hassan; Fardaei, Majid; Mohammadi, Sanaz; Farazi Fard, Mohammad Ali; Faghihi, Mohammad Ali

2017-01-01

Cockayne syndrome (CS) is a rare autosomal recessive multisystem disorder characterized by impaired neurological and sensory functions, cachectic dwarfism, microcephaly, and photosensitivity. This syndrome shows a variable age of onset and rate of progression, and its phenotypic spectrum include a wide range of severity. Due to the progressive nature of this disorder, diagnosis can be more important when additional signs and symptoms appear gradually and become steadily worse over time. Therefore, mutation analysis of genes involved in CS pathogenesis can be helpful to confirm the suspected clinical diagnosis. Here, we report a novel mutation in ERCC8 gene in a 16-year-old boy who suffers from poor weight gain, short stature, microcephaly, intellectual disability, and photosensitivity. The patient was born to consanguineous family with no previous documented disease in his parents. To identify disease-causing mutation in the patient, whole exome sequencing utilizing next-generation sequencing on an Illumina HiSeq 2000 platform was performed. Results revealed a novel homozygote mutation in ERCC8 gene (NM_000082: exon 11, c.1122G>C) in our patient. Another gene ( ERCC6 ), which is also involved in CS did not have any disease-causing mutations in the proband. The new identified mutation was then confirmed by Sanger sequencing in the proband, his parents, and extended family members, confirming co-segregation with the disease. In addition, different bioinformatics programs which included MutationTaster, I-Mutant v2.0, NNSplice, Combined Annotation Dependent Depletion, The PhastCons, Genomic Evolutationary Rate Profiling conservation score, and T-Coffee Multiple Sequence Alignment predicted the pathogenicity of the mutation. Our study identified a rare novel mutation in ERCC8 gene and help to provide accurate genetic counseling and prenatal diagnosis to minimize new affected individuals in this family.

Effects of Energy Deposition Characteristics on Localised Forced Ignition of Homogeneous Mixtures

Directory of Open Access Journals (Sweden)

Dipal Patel

2015-06-01

Full Text Available The effects of the characteristic width of the energy deposition profile and the duration of energy deposition by the ignitor on localised forced ignition of stoichiometric and fuel-lean homogeneous mixtures have been analysed using simplified chemistry three-dimensional compressible Direct Numerical Simulation (DNS for different values of root-mean-square turbulent velocity fluctuation. The localised forced ignition is modelled using a source term in the energy transport equation, which deposits energy in a Gaussian manner from the centre of the ignitor over a stipulated period of time. It has been shown that the width of ignition energy deposition and the duration over which ignition energy is deposited have significant influences on the success of ignition and subsequent flame propagation. An increase in the width of ignition energy deposition (duration of energy deposition for a given amount of ignition energy has been found to have a detrimental effect on the ignition event, which may ultimately lead to misfire. Moreover, an increase in u′ gives rise to augmented heat transfer rate from the hot gas kernel, which in turn leads to a reduction in the extent of overall burning for both stoichiometric and fuel-lean homogeneous mixtures but the detrimental effects of high values of u′ on localised ignition are particularly prevalent for fuel-lean mixtures.

Leakage localisation method in a water distribution system based on sensitivity matrix: methodology and real test

OpenAIRE

Pascual Pañach, Josep

2010-01-01

Leaks are present in all water distribution systems. In this paper a method for leakage detection and localisation is presented. It uses pressure measurements and simulation models. Leakage localisation methodology is based on pressure sensitivity matrix. Sensitivity is normalised and binarised using a common threshold for all nodes, so a signatures matrix is obtained. A pressure sensor optimal distribution methodology is developed too, but it is not used in the real test. To validate this...

Detection and localisation of the abalone probiotic Vibrio midae SY9 and its extracellular protease, VmproA, within the digestive tract of the South African abalone, Haliotis midae.

Directory of Open Access Journals (Sweden)

Robert J Huddy

Full Text Available Probiotics have been widely reported to increase the growth rate of commercially important fish and shellfish by enhancing the digestion of ingested feed through the production of extracellular enzymes such as proteases and alginases. In order to investigate this further, the objective of this study was to localise the bacterial probiont Vibrio midae SY9 and one of the extracellular proteases it produces in the digestive tract of the South African abalone Haliotis midae. This was accomplished by inserting a promotorless gfp gene into the chromosome of the bacterium which was incorporated in an artificial, fishmeal-based abalone feed. In situ histological comparison of abalone fed either a basal diet or the basal diet supplemented with V. midae SY9::Tn10.52 using a cocktail of DNA probes to the gfp gene localised the probiont to the crop/stomach and intestinal regions of the H. midae digestive tract. Generally, the ingested probiotic bacterium occurred in association with feed and particulate matter within the crop/stomach and intestinal regions, as well as adhered to the wall of the crop/stomach. Histological immunohistochemical examination using polyclonal anti-VmproA antibodies localised an extracellular protease produced by V. midae SY9 to the H. midae crop/stomach and intestine where it appeared to be associated with feed and/or other particulate matter in the abalone gut. Thus the data suggests that V. midae SY9 colonises and/or adheres to the mucous lining of the abalone gut. Furthermore, the close association observed between the bacterium, its extracellular protease and ingested feed particles supports the theory that V. midae SY9 elevates in situ digestive enzyme levels and thus enhances feed digestion in farmed abalone.

Detection and localisation of the abalone probiotic Vibrio midae SY9 and its extracellular protease, VmproA, within the digestive tract of the South African abalone, Haliotis midae.

Science.gov (United States)

Huddy, Robert J; Coyne, Vernon E

2014-01-01

Probiotics have been widely reported to increase the growth rate of commercially important fish and shellfish by enhancing the digestion of ingested feed through the production of extracellular enzymes such as proteases and alginases. In order to investigate this further, the objective of this study was to localise the bacterial probiont Vibrio midae SY9 and one of the extracellular proteases it produces in the digestive tract of the South African abalone Haliotis midae. This was accomplished by inserting a promotorless gfp gene into the chromosome of the bacterium which was incorporated in an artificial, fishmeal-based abalone feed. In situ histological comparison of abalone fed either a basal diet or the basal diet supplemented with V. midae SY9::Tn10.52 using a cocktail of DNA probes to the gfp gene localised the probiont to the crop/stomach and intestinal regions of the H. midae digestive tract. Generally, the ingested probiotic bacterium occurred in association with feed and particulate matter within the crop/stomach and intestinal regions, as well as adhered to the wall of the crop/stomach. Histological immunohistochemical examination using polyclonal anti-VmproA antibodies localised an extracellular protease produced by V. midae SY9 to the H. midae crop/stomach and intestine where it appeared to be associated with feed and/or other particulate matter in the abalone gut. Thus the data suggests that V. midae SY9 colonises and/or adheres to the mucous lining of the abalone gut. Furthermore, the close association observed between the bacterium, its extracellular protease and ingested feed particles supports the theory that V. midae SY9 elevates in situ digestive enzyme levels and thus enhances feed digestion in farmed abalone.

An approach for evaluating the general and localised corrosion of carbon steel containers for nuclear waste disposal

International Nuclear Information System (INIS)

Marsh, G.P.; Taylor, K.J.; Sharland, S.M.; Tasker, P.W.

1987-06-01

The paper considers the long term corrosion of carbon steel containers for heat generating nuclear waste in a granitic repository. Under such conditions carbon steel may exhibit general, localised or passive corrosion behaviour depending on the exact composition and redox potential of the groundwater contacting the containers; localised corrosion being of most concern because it has the fastest propagation rate. It is well established, however, that such localised corrosion is only possible when the environment is sufficiently oxidising to maintain a positive potential gradient between the cathodic surface and the corrosion sites, which requires that species which oxidising potentials greater than water need to be present. This fact provides a basis for estimating the periods during which containers may be subject to localised and subsequently to general corrosion, and hence for making an overall assessment of the metal allowance required for a specified container life. A model for the diffusion transport of oxygen has been developed, and a sensitivity analysis has shown that the period of possible attack is strongly dependent on the passive film leakage current, the radiation dose rate and the oxygen diffusion coefficient. (orig.)

Momentum and scalar transport in a localised synthetic turbulence in a channel flow with a short contraction

Energy Technology Data Exchange (ETDEWEB)

Lefeuvre, N; Djenidi, L [University of Newcastle, NSW Australia (Australia); Tardu, S, E-mail: nathan.lefeuvre@uon.edu.au [Laboratoire des Ecoulements Geophysiques et Industriels (LEGI), Grenoble (France)

2011-12-22

A numerical simulation is undertaken to investigate the transport of momentum and a passive scalar in a localised turbulence in a channel with a contraction. The simulation is carried out using a hybrid method which combines the lattice Boltzmann method (LBM, for the velocity field) and the energy equation (for the temperature field). The localised turbulence is generated through pulsed jets issued in the Poiseuille flow developing in the channel at a Reynolds number of about 1000. The aim of the study is twofold : i) determine effect of the contraction on the localised turbulence, and ii) study how the passive scalar behaves in such contracted localised turbulence. The contraction increase the averaged vorticity in the channel flow, which is accompanied by an increase in the averaged kinetic energy. The contraction also tends to reduce the Reynolds stresses. These results are similar those obtained in turbulent pipe flow with an axisymmetric contraction and in a turbulent boundary layer subjected to a favourable pressure gradient. However, it is found that the heat transport in the normal to the wall direction is more dramatically affected (reduced) than that in the direction of the flow.

Cause of focal uptake in the cervical vertebral column in routine bone scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Buell, U.; Winkler, U.

1983-09-01

Focal uptake was seen in the cervical vertebral column of 61 patients in the course of routine bone scintigraphy. These focal increases were subjected to close analysis. In 60 of these patients (98.4%) degenerative lesions became manifest as the cause of the scintigraphic finding already by the bone scintigraphy pattern (paravertebral localisation in the posterior and dorsal localisation in the lateral. Two typical examples of metastatic changes are presented to facilitate differentiation. The bone scintigraphic pattern in arthrosis of the intervertebral joint is so typical that X-ray control examinations to confirm the diagnosis can be omitted in many cases.

Retinoschisislike alterations in the mouse eye caused by gene targeting of the Norrie disease gene.

Science.gov (United States)

Ruether, K; van de Pol, D; Jaissle, G; Berger, W; Tornow, R P; Zrenner, E

1997-03-01

To investigate the retinal function and morphology of mice carrying a replacement mutation in exon 2 of the Norrie disease gene. Recently, Norrie disease mutant mice have been generated using gene targeting technology. The mutation removes the 56 N-terminal amino acids of the Norrie gene product. Ganzfeld electroretinograms (ERGs) were obtained in five animals hemizygous or homozygous for the mutant gene and in three female animals heterozygous for the mutant gene. As controls, three males carrying the wild-type gene were examined. Electroretinogram testing included rod a- and b-wave V-log I functions, oscillatory potentials, and cone responses. The fundus morphology has been visualized by scanning laser ophthalmoscopy. Rod and cone ERG responses and fundus morphology were not significantly different among female heterozygotes and wild-type mice. In contrast, the hemizygous mice displayed a severe loss of ERG b-wave, leading to a negatively shaped scotopic ERG and a marked reduction of oscillatory potentials. The a-wave was normal at low intensities, and only with brighter flashes was there a moderate amplitude loss. Cone amplitudes were barely recordable in the gene-targeted males. Ophthalmoscopy revealed snowflakelike vitreal changes, retinoschisis, and pigment epithelium irregularities in hemizygotes and homozygotes, but no changes in female heterozygotes. The negatively shaped scotopic ERG in male mice with a Norrie disease gene mutation probably was caused by retinoschisis. Pigment epithelial changes and degenerations of the outer retina are relatively mild. These findings may be a clue to the embryonal retinoschisislike pathogenesis of Norrie disease in humans or it may indicate a different expression of the Norrie disease gene defect in mice compared to that in humans.

Usefulness and limits of ultrasound guided hook-wire positioning for localisation of soft tissue lesions prior to surgery

International Nuclear Information System (INIS)

Trenaghi, Alberto; Dal Bosco, Chiara; Talenti, Enrico; Rubaltelli, Enrico; Borsato, Simonetta; Rossi, Carlo Riccardo; Lumachi, Franco

2005-01-01

Purpose. The aim of our study was to assess the usefulness of positioning metal wires under ultrasound guidance for localising soft tissue lesions in the preoperative phase. Materials and methods. We studied superficial soft-tissue lesions in 12 patients, using hooked mammographic wires of different lengths. One patient had a multifocal growth of disease which required a double localisation procedure. Correct positioning of the wire was confirmed by ultrasonography. All patients underwent surgery within five hours of hook-wire positioning. Results. Correct wire position was confirmed at surgery in 12 out of 13 procedures. In one case the hook-wire reached the margin of the lesion. In all cases, the preoperative localisation procedure facilitated identification and resection of the masses. Conclusions. In our experience, the main indications for hook-wire positioning before surgery are: marking of small lesions, localisation of lesions in anatomic areas structurally subverted by previous surgery and consequently difficult to detect, guidance for surgical sectioning in order to safeguard the noble structures dose to the lesions [it

Human perception of indoor environment generated by chilled ceiling combined with mixing ventilation or localised chilled beam under cooling mode

DEFF Research Database (Denmark)

Bolashikov, Zhecho Dimitrov; Nygaard, Linette; Uth, Simon C.

2014-01-01

Experiments with 24 subjects were performed to study and compare the human perception of the indoor environment under summer conditions generated by a chilled ceiling combined with overhead mixing ventilation and localised chilled beam. The experiments were performed in an experimental chamber (4....../s and 16 0C. The localised chilled beam was installed over the workstation placed by the simulated window. During the experiment the subjects were delegated control over the primary flow rate supplied by the localised chilled beam. The whole exposure lasted 2 hours with 30 min of acclimatisation before...

Contralateral routing of signals disrupts monaural level and spectral cues to sound localisation on the horizontal plane.

Science.gov (United States)

Pedley, Adam J; Kitterick, Pádraig T

2017-09-01

Contra-lateral routing of signals (CROS) devices re-route sound between the deaf and hearing ears of unilaterally-deaf individuals. This rerouting would be expected to disrupt access to monaural level cues that can support monaural localisation in the horizontal plane. However, such a detrimental effect has not been confirmed by clinical studies of CROS use. The present study aimed to exercise strict experimental control over the availability of monaural cues to localisation in the horizontal plane and the fitting of the CROS device to assess whether signal routing can impair the ability to locate sources of sound and, if so, whether CROS selectively disrupts monaural level or spectral cues to horizontal location, or both. Unilateral deafness and CROS device use were simulated in twelve normal hearing participants. Monaural recordings of broadband white noise presented from three spatial locations (-60°, 0°, and +60°) were made in the ear canal of a model listener using a probe microphone with and without a CROS device. The recordings were presented to participants via an insert earphone placed in their right ear. The recordings were processed to disrupt either monaural level or spectral cues to horizontal sound location by roving presentation level or the energy across adjacent frequency bands, respectively. Localisation ability was assessed using a three-alternative forced-choice spatial discrimination task. Participants localised above chance levels in all conditions. Spatial discrimination accuracy was poorer when participants only had access to monaural spectral cues compared to when monaural level cues were available. CROS use impaired localisation significantly regardless of whether level or spectral cues were available. For both cues, signal re-routing had a detrimental effect on the ability to localise sounds originating from the side of the deaf ear (-60°). CROS use also impaired the ability to use level cues to localise sounds originating from

Subcellular localisation of BAG-1 and its regulation of vitamin D receptor-mediated transactivation and involucrin expression in oral keratinocytes: Implications for oral carcinogenesis

International Nuclear Information System (INIS)

Lee, San San; Crabb, Simon J.; Janghra, Nari; Carlberg, Carsten; Williams, Ann C.; Cutress, Ramsey I.; Packham, Graham; Hague, Angela

2007-01-01

In oral cancers, cytoplasmic BAG-1 overexpression is a marker of poor prognosis. BAG-1 regulates cellular growth, differentiation and survival through interactions with diverse proteins, including the vitamin D receptor (VDR), a key regulator of keratinocyte growth and differentiation. BAG-1 is expressed ubiquitously in human cells as three major isoforms of 50 kDa (BAG-1L), 46 kDa (BAG-1M) and 36 kDa (BAG-1S) from a single mRNA. In oral keratinocytes BAG-1L, but not BAG-1M and BAG-1S, enhanced VDR transactivation in response to 1α,25-dihydroxyvitamin D 3. BAG-1L was nucleoplasmic and nucleolar, whereas BAG-1S and BAG-1M were cytoplasmic and nucleoplasmic in localisation. Having identified the nucleolar localisation sequence in BAG-1L, we showed that mutation of this sequence did not prevent BAG-1L from potentiating VDR activity. BAG-1L also potentiated transactivation of known vitamin-D-responsive gene promoters, osteocalcin and 24-hydroxylase, and enhanced VDR-dependent transcription and protein expression of the keratinocyte differentiation marker, involucrin. These results demonstrate endogenous gene regulation by BAG-1L by potentiating nuclear hormone receptor function and suggest a role for BAG-1L in 24-hydroxylase regulation of vitamin D metabolism and the cellular response of oral keratinocytes to 1α,25-dihydroxyvitamin D 3 . By contrast to the cytoplasmic BAG-1 isoforms, BAG-1L may act to suppress tumorigenesis

Periostitis and localised myositis in polyarteritis nodosa

International Nuclear Information System (INIS)

Macdonald, W.B.G.; Blake, M.P.

2003-01-01

Full text: A 20-year-old man with previously diagnosed polyarteritis nodosa was referred for a bone scan to investigate longstanding knee and lower leg pain. The patient's symptoms worsened with any reduction of steroid dose and his physician was concerned about avascular necrosis of the hips. Plain x-rays of the lower limbs were normal. The blood pool images showed bilaterally increased activity in the anterior muscle compartments of the lower legs, suggestive of localised myositis. Three-hour delayed images showed widespread, increased subperiosteal activity with no evidence of avascular necrosis. Subsequent MRI scanning showed patchy muscle enhancement in both lower legs, also typical of myositis. A muscle biopsy was performed which demonstrated features of both myositis and vasculitis. The patient remains dependent on high-dose steroids for symptom relief. Localised myositis has previously been reported in polyarteritis nodosa and is a recognised, albeit rare, complication of the disorder, the basis of which is not well understood. Diagnostic muscle biopsy should be directed at involved muscle groups, which are best detected with MRI. Lower limb periostitis is well described in polyarteritis nodosa and may result in gross deformity. Several cases have previously been reported in the literature based on radiographic abnormalities, which were not present in our patient. Bone scanning demonstrated the sub-periosteal activity well in our subject and is suggested as a useful investigation in patients with polyarteritis nodosa who complain of lower limb pain. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

Suppressing proton decay in theories with localised fermions

International Nuclear Information System (INIS)

Acharya, B.S.; Valandro, R.

2005-12-01

We calculate the contribution to the proton decay amplitude from Kaluza-Klein lepto-quarks in theories with extra dimensions, localised fermions and gauge fields which propagate in the bulk. Such models naturally occur within the context of M theory. In SU(5) models we show that carefully including all such modes gives a distinctive pattern of decays through various channels including a strong suppression of decays into neutrinos or right handed positrons. By contrast there is no such suppression for SO(10). (author)

Quantum localisation on the circle

Science.gov (United States)

Fresneda, Rodrigo; Gazeau, Jean Pierre; Noguera, Diego

2018-05-01

Covariant integral quantisation using coherent states for semi-direct product groups is implemented for the motion of a particle on the circle. In this case, the phase space is the cylinder, which is viewed as a left coset of the Euclidean group E(2). Coherent states issued from fiducial vectors are labeled by points in the cylinder and depend also on extra parameters. We carry out the corresponding quantisations of the basic classical observables, particularly the angular momentum and the 2π-periodic discontinuous angle function. We compute their corresponding lower symbols. The quantum localisation on the circle is examined through the properties of the angle operator yielded by our procedure, its spectrum and lower symbol, its commutator with the quantum angular momentum, and the resulting Heisenberg inequality. Comparison with other approaches to the long-standing question of the quantum angle is discussed.

Østebø, Terje. — Localising Salafism

OpenAIRE

Vezzadini, Elena

2012-01-01

Localising Salafism est une étude approfondie sur l’origine et le développement du salafisme dans le Bale, une province au sud-est de l’Éthiopie, habitée majoritairement par les Oromo qui y constituent environ 90 % de la population. il s’agit aussi d’une région à grande majorité musulmane (92 %), qui fait partie des neuf divisions administratives de l’Éthiopie, connue comme Oromiyaa. L’auteur travaille donc sur une région très peu étudiée, et sur un sujet, l’islam en Éthiopie, encore marginal...

An innovative localisation algorithm for railway vehicles

Science.gov (United States)

Allotta, B.; D'Adamio, P.; Malvezzi, M.; Pugi, L.; Ridolfi, A.; Rindi, A.; Vettori, G.

2014-11-01

In modern railway automatic train protection and automatic train control systems, odometry is a safety relevant on-board subsystem which estimates the instantaneous speed and the travelled distance of the train; a high reliability of the odometry estimate is fundamental, since an error on the train position may lead to a potentially dangerous overestimation of the distance available for braking. To improve the odometry estimate accuracy, data fusion of different inputs coming from a redundant sensor layout may be used. The aim of this work has been developing an innovative localisation algorithm for railway vehicles able to enhance the performances, in terms of speed and position estimation accuracy, of the classical odometry algorithms, such as the Italian Sistema Controllo Marcia Treno (SCMT). The proposed strategy consists of a sensor fusion between the information coming from a tachometer and an Inertial Measurements Unit (IMU). The sensor outputs have been simulated through a 3D multibody model of a railway vehicle. The work has provided the development of a custom IMU, designed by ECM S.p.a, in order to meet their industrial and business requirements. The industrial requirements have to be compliant with the European Train Control System (ETCS) standards: the European Rail Traffic Management System (ERTMS), a project developed by the European Union to improve the interoperability among different countries, in particular as regards the train control and command systems, fixes some standard values for the odometric (ODO) performance, in terms of speed and travelled distance estimation. The reliability of the ODO estimation has to be taken into account basing on the allowed speed profiles. The results of the currently used ODO algorithms can be improved, especially in case of degraded adhesion conditions; it has been verified in the simulation environment that the results of the proposed localisation algorithm are always compliant with the ERTMS requirements

Organisation as a key factor in Localised Agri-Food Systems (LAFS

Directory of Open Access Journals (Sweden)

Corrado Giacomini

2015-05-01

Full Text Available Most studies of Localised Agri-Food Systems (LAFS focus on the localised concentration of members and firms, and pay less attention to organisational factors, particularly those of an exogenous nature. This paper focuses on the role of organisation in a LAFS, assessing the efficacy of EU organisational measures aimed at strengthening the concentration of supply from the recent CAP reform 2014-2020. The paper has three sections. Part One describes the evolution of the concept of LAFS. Part Two examines the leading role played by institutions in organising relationships between firms in a LAFS. The example provided is that of the measures affecting the organisation of supply introduced by the recent CAP reform, 2014-2020. It makes particular reference to the Distretto del pomodoro da industria – Nord Italia (‘Industrial Tomato District – Northern Italy’. Part Three describes how organisational factors can lead to the creation of a LAFS, while the criterion of proximity is necessary but not sufficient.

Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells

International Nuclear Information System (INIS)

Kalayda, Ganna V; Wagner, Christina H; Buß, Irina; Reedijk, Jan; Jaehde, Ulrich

2008-01-01

Copper homeostasis proteins ATP7A and ATP7B are assumed to be involved in the intracellular transport of cisplatin. The aim of the present study was to assess the relevance of sub cellular localisation of these transporters for acquired cisplatin resistance in vitro. For this purpose, localisation of ATP7A and ATP7B in A2780 human ovarian carcinoma cells and their cisplatin-resistant variant, A2780cis, was investigated. Sub cellular localisation of ATP7A and ATP7B in sensitive and resistant cells was investigated using confocal fluorescence microscopy after immunohistochemical staining. Co-localisation experiments with a cisplatin analogue modified with a carboxyfluorescein-diacetate residue were performed. Cytotoxicity of the fluorescent cisplatin analogue in A2780 and A2780cis cells was determined using an MTT-based assay. The significance of differences was analysed using Student's t test or Mann-Whitney test as appropriate, p values of < 0.05 were considered significant. In the sensitive cells, both transporters are mainly localised in the trans-Golgi network, whereas they are sequestrated in more peripherally located vesicles in the resistant cells. Altered localisation of ATP7A and ATP7B in A2780cis cells is likely to be a consequence of major abnormalities in intracellular protein trafficking related to a reduced lysosomal compartment in this cell line. Changes in sub cellular localisation of ATP7A and ATP7B may facilitate sequestration of cisplatin in the vesicular structures of A2780cis cells, which may prevent drug binding to genomic DNA and thereby contribute to cisplatin resistance. Our results indicate that alterations in sub cellular localisation of transport proteins may contribute to cisplatin resistance in vitro. Investigation of intracellular protein localisation in primary tumour cell cultures and tumour tissues may help to develop markers of clinically relevant cisplatin resistance. Detection of resistant tumours in patients may in turn

Altered localisation of the copper efflux transporters ATP7A and ATP7B associated with cisplatin resistance in human ovarian carcinoma cells

Directory of Open Access Journals (Sweden)

Reedijk Jan

2008-06-01

Full Text Available Abstract Background Copper homeostasis proteins ATP7A and ATP7B are assumed to be involved in the intracellular transport of cisplatin. The aim of the present study was to assess the relevance of sub cellular localisation of these transporters for acquired cisplatin resistance in vitro. For this purpose, localisation of ATP7A and ATP7B in A2780 human ovarian carcinoma cells and their cisplatin-resistant variant, A2780cis, was investigated. Methods Sub cellular localisation of ATP7A and ATP7B in sensitive and resistant cells was investigated using confocal fluorescence microscopy after immunohistochemical staining. Co-localisation experiments with a cisplatin analogue modified with a carboxyfluorescein-diacetate residue were performed. Cytotoxicity of the fluorescent cisplatin analogue in A2780 and A2780cis cells was determined using an MTT-based assay. The significance of differences was analysed using Student's t test or Mann-Whitney test as appropriate, p values of Results In the sensitive cells, both transporters are mainly localised in the trans-Golgi network, whereas they are sequestrated in more peripherally located vesicles in the resistant cells. Altered localisation of ATP7A and ATP7B in A2780cis cells is likely to be a consequence of major abnormalities in intracellular protein trafficking related to a reduced lysosomal compartment in this cell line. Changes in sub cellular localisation of ATP7A and ATP7B may facilitate sequestration of cisplatin in the vesicular structures of A2780cis cells, which may prevent drug binding to genomic DNA and thereby contribute to cisplatin resistance. Conclusion Our results indicate that alterations in sub cellular localisation of transport proteins may contribute to cisplatin resistance in vitro. Investigation of intracellular protein localisation in primary tumour cell cultures and tumour tissues may help to develop markers of clinically relevant cisplatin resistance. Detection of resistant tumours

Deletion of P2 promoter of GJB1 gene a cause of Charcot-Marie-Tooth disease.

Science.gov (United States)

Kulshrestha, R; Burton-Jones, S; Antoniadi, T; Rogers, M; Jaunmuktane, Z; Brandner, S; Kiely, N; Manuel, R; Willis, T

2017-08-01

X-linked Charcot-Marie-Tooth disease (CMT) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene. This gene has nerve specific P2 promoter that work synergistically with SOX10 and EGR2 genes to initiate transcription. Mutation in this region is known to cause Schwann cell dysfunction. A single large family of X linked peripheral neuropathy was identified in our practice. Next generation sequencing for targeted panel assay identified an upstream exon-splicing deletion identified extending from nucleotide c.-5413 to approximately - c.-49. This matches the sequence of 32 nucleotides at positions c.*218-*249 in the 3'UTR downstream of the GJB1 gene. The deleted fragment included the entire P2 promoter region. The deletion segregated with the disease. To our knowledge a deletion of the P2 promoter alone as a cause of CMT has not been reported previously. Copyright © 2017 Elsevier B.V. All rights reserved.

An Efficient Approach for Node Localisation and Tracking in Wireless Sensor Networks

CSIR Research Space (South Africa)

Mwila, Martin

2014-08-01

Full Text Available -1 An Efficient Approach for Node Localisation and Tracking in Wireless Sensor Networks Martin K. Mwila Submitted in partial fulfilment of the requirements for the degree Magister Technologiae: Electrical Engineering in the Department of Electrical Engineering...

Hydrocephalus caused by conditional ablation of the Pten or beta-catenin gene

Directory of Open Access Journals (Sweden)

Ohtoshi Akihira

2008-10-01

Full Text Available Abstract To investigate the roles of Pten and β-Catenin in the midbrain, either the Pten gene or the β-catenin gene was conditionally ablated, using Dmbx1 (diencephalon/mesencephalon-expressed brain homeobox gene 1-Cre mice. Homozygous disruption of the Pten or β-catenin gene in Dmbx1-expressing cells caused severe hydrocephalus and mortality during the postnatal period. Conditional deletion of Pten resulted in enlargement of midbrain structures. β-catenin conditional mutant mice showed malformation of the superior and inferior colliculi and stenosis of the midbrain aqueduct. These results demonstrate that both Pten and β-Catenin are essential for proper midbrain development, and provide the direct evidence that mutations of both Pten and β-catenin lead to hydrocephalus.

An efficient approach to node localisation and tracking in wireless sensor networks

CSIR Research Space (South Africa)

Mwila, MK

2014-12-01

Full Text Available and efficient localisation method that makes use of an improved RSSI distance estimation model by including the antenna radiation pattern as well as nodes orientations is presented. Mathematical models for distance estimation, cost function and gradient of cost...

Mozart's African jacket: Die Zauberflöte and its localisation in The ...

African Journals Online (AJOL)

, the change in time, space, context and symbolism in a localised or indigenised South African version of Mozart's Die Zauberflöte, K. 620. It addresses the lacunae between desiderata expressed in the White Paper on Arts, Culture and ...

Cytotoxicity, DNA binding and localisation of novel bis-naphthalimidopropyl polyamine derivatives.

Science.gov (United States)

Pavlov, V; Kong Thoo Lin, P; Rodilla, V

2001-07-31

Bis-naphthalimidopropyl spermidine (BNIPSpd), spermine (BNIPSpm) and oxa-spermine (BNIPOSpm) showed high in vitro cytotoxicity against human breast cancer MCF-7 cells with IC(50) values of 1.38, 2.91 and 8.45 microM, respectively. These compounds were found to effectively displace the intercalating agent ethidium bromide bound to the calf thymus DNA using fluorimetric methods (C(50) 0.08-0.12 microM) and their apparent equilibrium binding constants (K(app)) were calculated to be in the range of 10.5-18 x 10(7) M(-1). Furthermore, strong stabilisation of calf thymus DNA duplex in the presence of bis-naphthalimidopropyl polyamine derivatives (BNIPSpd, BNIPSpm and BNIPOSpm) was observed by UV spectrophotometric analysis (T(m)=93.3-97 degrees C compared with 75 degrees C for calf thymus DNA without drug). Because of their inherent fluorescence, these compounds were localised preferentially inside the nucleus as evidenced by their direct observation under the fluorescence microscope. The results obtained suggest that the cytotoxic activity of the bis-naphthalimidopropyl polyamines may be in part, caused by their effects on DNA.

Comparison of the time taken for localised breast surgery pre- and post-introduction of intra-operative digital specimen mammography.

Science.gov (United States)

Carraro do Nascimento, Vinicius; Bourke, Anita G

2018-02-01

More than half of the patients with an impalpable malignant breast lesion have a mammographically detected and imaged-guided localisation, which can be technically challenging for the breast surgeon. Specimen imaging is used to confirm successful excision of the localised index lesion and has improved the operating list efficiency resulting in a higher number of excisions per surgical list. The aim of this study was to evaluate whether introducing IDSM (intra-operative digital specimen mammography) saved operation time for localised breast surgery. A single-centre retrospective review was undertaken to compare the operation time (from incision to wound closure) taken for excision of 114 consecutive image-guided localised impalpable breast lesions, performed using departmental specimen radiography (DSR), 6 months prior to the introduction of IDSM (Hologic, Trident ® ) in March 2013, with the theatre time taken for excision of 121 consecutive image-guided localised impalpable breast lesions in the 6 months following introduction of IDSM. There was no significant difference in mean surgical time, which were 47.8 (±27.3) minutes in the CSR group and 48.8 (±25.7) minutes in the IDSM group. We were expecting to confirm a reduction in theatre time with the introduction of IDSM. Surprisingly, no difference in operating times was demonstrated. Factors that influenced the impact of IDSM included the proximity of the imaging department to the operating theatre. © 2017 The Royal Australian and New Zealand College of Radiologists.

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

Science.gov (United States)

Braun, Daniela A; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A; Schanze, Denny; Ashraf, Shazia; Ullmann, Jeremy F P; Hoogstraten, Charlotte A; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I Chiara; Sanchez-Ferras, Oraly; Hu, Jennifer F; Boschat, Anne-Claire; Sanquer, Sylvia; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E; Pabst, Werner L; Warejko, Jillian K; Daga, Ankana; Basta, Tamara; Matejas, Verena; Scharmann, Karin; Kienast, Sandra D; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T; Gaffney, Patrick M; Gipson, Patrick E; Hsu, Chyong-Hsin; Kari, Jameela A; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-Ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okashah; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Ozaltin, Fatih; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth R; Rump, Patrick; Schnur, Rhonda E; Shiihara, Takashi; Sinha, Manish D; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A; Tsai, Wen-Hui; Tsai, Jeng-Daw; Topaloglu, Rezan; Vester, Udo; Viskochil, David H; Vatanavicharn, Nithiwat; Waxler, Jessica L; Wierenga, Klaas J; Wolf, Matthias T F; Wong, Sik-Nin; Leidel, Sebastian A; Truglio, Gessica; Dedon, Peter C; Poduri, Annapurna; Mane, Shrikant; Lifton, Richard P; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Callewaert, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

2017-10-01

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.

A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR

Energy Technology Data Exchange (ETDEWEB)

Inoue, K.; Sugiyama, N.; Kawanishi, C. [Yokohama City Univ., Yokohama (Japan)] [and others

1996-07-01

Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10% - 25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be an important genetic abnormality in PMD and affect myelin formation. 38 ref., 5 figs., 2 tabs.

A novel nonsense mutation in the WFS1 gene causes the Wolfram syndrome.

Science.gov (United States)

Noorian, Shahab; Savad, Shahram; Mohammadi, Davood Shah

2016-05-01

Wolfram syndrome is a rare autosomal recessive neurodegenerative disorder, which is mostly caused by mutations in the WFS1 gene. The WFS1 gene product, which is called wolframin, is thought to regulate the function of endoplasmic reticulum. The endoplasmic reticulum has a critical role in protein folding and material transportation within the cell or to the surface of the cell. Identification of new mutations in WFS1 gene will unravel the molecular pathology of WS. The aim of this case report study is to describe a novel mutation in exon 4 of the WFS1 gene (c.330C>A) in a 9-year-old boy with WS.

On the cause of focal uptake in the cervical vertebral column in routine bone scintigraphy

International Nuclear Information System (INIS)

Buell, U.; Winkler, U.

1983-01-01

Focal uptake was seen in the cervical vertebral column of 61 patients in the course of routine bone scintigraphy. These focal increases were subjected to close analysis. In 60 of these patients (98.4%) degenerative lesions became manifest as the cause of the scintigraphic finding already by the bone scintigraphy pattern (paravertebral localisation in the posterior and dorsal localisation in the lateral. Two typical examples of metastatic changes are presented to facilitate differentiation. The bone scintigraphic pattern in arthrosis of the intervertebral joint is so typical that X-ray control examinations to confirm the diagnosis can be omitted in many cases. (orig.) [de

Reduction in expression of the benign AR transcriptome is a hallmark of localised prostate cancer progression.

Science.gov (United States)

Stuchbery, Ryan; Macintyre, Geoff; Cmero, Marek; Harewood, Laurence M; Peters, Justin S; Costello, Anthony J; Hovens, Christopher M; Corcoran, Niall M

2016-05-24

Despite the importance of androgen receptor (AR) signalling to prostate cancer development, little is known about how this signalling pathway changes with increasing grade and stage of the disease. To explore changes in the normal AR transcriptome in localised prostate cancer, and its relation to adverse pathological features and disease recurrence. Publically accessible human prostate cancer expression arrays as well as RNA sequencing data from the prostate TCGA. Tumour associated PSA and PSAD were calculated for a large cohort of men (n=1108) undergoing prostatectomy. We performed a meta-analysis of the expression of an androgen-regulated gene set across datasets using Oncomine. Differential expression of selected genes in the prostate TCGA database was probed using the edgeR Bioconductor package. Changes in tumour PSA density with stage and grade were assessed by Student's t-test, and its association with biochemical recurrence explored by Kaplan-Meier curves and Cox regression. Meta-analysis revealed a systematic decline in the expression of a previously identified benign prostate androgen-regulated gene set with increasing tumour grade, reaching significance in nine of 25 genes tested despite increasing AR expression. These results were confirmed in a large independent dataset from the TCGA. At the protein level, when serum PSA was corrected for tumour volume, significantly lower levels were observed with increasing tumour grade and stage, and predicted disease recurrence. Lower PSA secretion-per-tumour-volume is associated with increasing grade and stage of prostate cancer, has prognostic relevance, and reflects a systematic perturbation of androgen signalling.

Fine mapping of Best`s macular dystrophy localises the gene in close proximity to, but distinct from, the D115480/ROM1

Energy Technology Data Exchange (ETDEWEB)

Graff, C.; Ahlbom, B.E.; Anneren, G. [University Hospital, Uppsala (Sweden)] [and others

1994-09-01

Best`s macular dystrophy (BMD) is an autosomal dominant disease characterized by accumulation of lipofuscin beneath the pigment epithelium of the macula, leading to early-onset impairment of central vision. The gene has previously been mapped to 11q13. Based on DNA from 191 people from a large 12-generation family, the gene now has been mapped to a 1.5 cM interval between the markers Fc{epsilon}RI and D11S480/ROM1. By disequilibrium analysis the gene was estimated to be 0.321 cM centromeric to the marker D11S480. Since this on average corresponds to 300 kb, the gene may be at a distance contained in YAC molecules. To physically characterize this region, YAC clones positive for markers flanking BMD have been identified. Sequence analysis of the candidate gene ROM1 did not reveal any mutation. However, one recombination between intragenic ROM1 polymorphisms and BMD was detected, which make it highly unlikely that mutations in ROM1 are causing BMD.

A novel mutation of the fibrillin gene causing Ectopia lentis

Energy Technology Data Exchange (ETDEWEB)

Loennqvist, L.; Kainulainen, K.; Puhakka, L.; Peltonen, L. (National Public Health Institute, Helsinki (Finland)); Child, A. (St. George' s Hospital Medical School, London (United Kingdom)); Peltonen, L. (Duncan Guthrie Institute, Glasgow, Scotland (United Kingdom))

1994-02-01

Ectopia lentis (EL), a dominantly inherited connective tissue disorder, has been genetically linked to the fibrillin gene on chromosome 15 (FBN1) in earlier studies. Here, the authors report the first EL mutation in the FBN1 gene confirming that EL is caused by mutations of this gene. So far, several mutations in the FBN1 gene have been reported in patients with Marfan syndrome (MFS). EL and MFS are clinically related but distinct conditions with typical manifestations in the ocular and skeletal systems, the fundamental difference between them being the absence of cardiovascular involvement in EL. They report a point mutation, cosegregating with the disease in the described family, that displays EL over four generations. The mutation changes a conserved glutamic acid residue in an EGF-like motif, which is the major structural component of the fibrillin and is repeated throughout the polypeptide. In vitro mutagenetic studies have demonstrated the necessity of an analogous glutamic acid residue for calcium binding in an EGF-like repeat of human factor IX. This provides a possible explanation for the role of this mutation in the disease pathogenesis. 32 refs., 2 figs., 1 tab.

Investigation into Generation of Micro Features by Localised Electrochemical Deposition

Science.gov (United States)

Debnath, Subhrajit; Laskar, Hanimur Rahaman; Bhattacharyya, B.

2017-11-01

With the fast advancement of technology, localised electrochemical deposition (LECD) is becoming very advantageous in generating high aspect ratio micro features to meet the steep demand in modern precision industries of the present world. Except many other advantages, this technology is highly uncomplicated and economical for fabricating metal micro-parts with in micron ranges. In the present study, copper micro-columns have been fabricated utilizing LECD process. Different process parameters such as voltage, frequency, duty ratio and electrolyte concentration, which affect the deposition performance have been identified and their effects on deposition performances such as deposition rate, height and diameter of the micro-columns have been experimentally investigated. Taguchi's methodology has been used to study the effects as well as to obtain the optimum values of process parameters so that localised deposition with best performance can be achieved. Moreover, the generated micro-columns were carefully observed under optical and scanning electron microscope from where the surface quality of the deposited micro-columns has been studied qualitatively. Also, an array of copper micro-columns has been fabricated on stainless steel (SS-304) substrate for further exploration of LECD process capability.

Localised and Learnt Applications of Machine Learning for Robotic Incremental Sheet Forming

DEFF Research Database (Denmark)

Nicholas, Paul; Zwierzycki, Mateusz; Ramsgaard Thomsen, Mette

2017-01-01

Sheet Forming (ISF) and exemplified in the fabrication of a bridge structure. The methods we describe compensate for springback and improve forming tolerance by using localised in-process distance sensing to adapt tool-paths, and by using pre-process supervised machine learning to predict stringback...

Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a likely cause of PMS2 gene inactivation.

Science.gov (United States)

Auclair, Jessie; Leroux, Dominique; Desseigne, Françoise; Lasset, Christine; Saurin, Jean Christophe; Joly, Marie Odile; Pinson, Stéphane; Xu, Xiao Li; Montmain, Gilles; Ruano, Eric; Navarro, Claudine; Puisieux, Alain; Wang, Qing

2007-11-01

Since the first report by our group in 1999, more than 20 unrelated biallelic mutations in DNA mismatch repair genes (MMR) have been identified. In the present report, we describe two novel cases: one carrying compound heterozygous mutations in the MSH6 gene; and the other, compound heterozygous mutations in the PMS2 gene. Interestingly, the inactivation of one PMS2 allele was likely caused by gene conversion. Although gene conversion has been suggested to be a mutation mechanism underlying PMS2 inactivation, this is the first report of its involvement in a pathogenic mutation. The clinical features of biallelic mutation carriers were similar to other previously described patients, with the presence of café-au-lait spots (CALS), early onset of brain tumors, and colorectal neoplasia. Our data provide further evidence of the existence, although rare, of a distinct recessively inherited syndrome on the basis of MMR constitutional inactivation. The identification of this syndrome should be useful for genetic counseling, especially in families with atypical hereditary nonpolyposis colon cancer (HNPCC) associated with childhood cancers, and for the clinical surveillance of these mutation carriers. 2007 Wiley-Liss, Inc.

Globalisation and Localisation in Music Education in Hong Kong and Taiwan

Science.gov (United States)

Ho, Wai-Chung

2013-01-01

The purpose of the study is to analyse and discuss the influences of globalisation and localisation on music education in Hong Kong and Taiwan. It argues that the reform of music education concerns changes to the contents of the curriculum that envisage the cultural and political developments that arise from processes of globalisation and…

Localisation of lung cancer by a radiolabelled monoclonal antibody against the c-myc oncogene product

Energy Technology Data Exchange (ETDEWEB)

Chan, S Y.T.; Evan, G I; Ritson, A; Watson, J; Wraight, P; Sikora, K

1986-11-01

A set of mouse monoclonal antibodies against the c-myc oncogene product, a 62,000 dalton nuclear binding protein involved in cell cycle control, has been constructed by immunisation with synthetic peptide fragments. One such antibody, CT14, was radiolabelled with /sup 131/I and administered to 20 patients with different malignant diseases. Good tumour localisation was observed in 12 out of 14 patients with primary bronchial carcinoma but not in patients with pulmonary metastases from primary tumours elsewhere. Successfully localised tumours were all 3 cm or more in diameter. Monoclonal antibodies against oncogene products may provide novel selective tools for the diagnosis and therapy of cancer.

Aseptic necrosis at multiple localisations in a lupus patient with lymphoma.

Science.gov (United States)

Bazso, A; Bazso, T; Szodoray, P; Poor, G; Kiss, E

2014-04-01

Avascular or aseptic necrosis is a well-defined entity leading to the degradation of cellular elements of the bone. The pathogenesis of osteonecrosis (ON) is still unknown. There are two main types of ON: traumatic or non-traumatic. Several clinical entities could associate with ON, systemic diseases, environmental factors, pregnancy, systemic autoimmune or rheumatic diseases, thrombophilia, corticosteroid therapy, cytotoxic dugs, infections, metabolic and hematologic diseases, etc. Corticosteroids (CS) are still the most frequently used therapeutic options in the early phase and during flares of these diseases. Inflammatory cytokines and antibodies have been described to participate in the pathogenesis of ON. The infiltrative disorders of the bone marrow could also contribute to the development of ON. Hereby, we describe a female patient with NHL followed by SLE in whom ON has developed at least in two localisations. Lupus flare, long-term CS therapy, lymphoma relapse or the presence of antiphospholipid antibodies were excluded. Although the bi-localised ON could be contributed to immunologic factors or trauma, the exact aetiology in this case could not be elucidated.

Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis.

Science.gov (United States)

Cooperberg, Matthew R; Ramakrishna, Naren R; Duff, Steven B; Hughes, Kathleen E; Sadownik, Sara; Smith, Joseph A; Tewari, Ashutosh K

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Multiple treatment alternatives exist for localised prostate cancer, with few high-quality studies directly comparing their comparative effectiveness and costs. The present study is the most comprehensive cost-effectiveness analysis to date for localised prostate cancer, conducted with a lifetime horizon and accounting for survival, health-related quality-of-life, and cost impact of secondary treatments and other downstream events, as well as primary treatment choices. The analysis found minor differences, generally slightly favouring surgical methods, in quality-adjusted life years across treatment options. However, radiation therapy (RT) was consistently more expensive than surgery, and some alternatives, e.g. intensity-modulated RT for low-risk disease, were dominated - that is, both more expensive and less effective than competing alternatives. To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model. A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis. Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to

The utility of 99mTc-sestamibi scintigraphy in the localisation of parathyroid adenomas in primary hyperparathyroidism.

LENUS (Irish Health Repository)

Glynn, N

2012-02-01

BACKGROUND: There are conflicting data in the literature about the sensitivity of sestamibi scintigraphy in parathyroid tumour localisation in primary hyperparathyroidism (PHPT). AIM: We aimed to evaluate the overall sensitivity of this modality in parathyroid tumour localisation and to determine clinical and biochemical factors which influence sensitivity of this method. METHODS: We performed a retrospective review of 57 patients with a biochemical diagnosis of PHPT who had sestamibi scintigraphy performed. RESULTS: The sensitivity of sestamibi scanning was 56% in whole group and 63% in those without nodular thyroid disease. Among the patients with confirmed single gland disease (biochemical cure after surgical removal of a single adenoma), sensitivity was 71%. A positive scan was associated with younger age, greater adenoma weight and higher pre-operative serum calcium. Concordance between the sestamibi and neck ultrasonography was 92% accurate in pre-operative tumour localisation. CONCLUSION: Sestamibi scintigraphy was more likely to be positive in younger patients without nodular thyroid disease who have larger parathyroid adenomas with more severe hyperparathyroidism.

Immunohistochemical localisation and developmental aspects of epidermal growth factor in the rat

DEFF Research Database (Denmark)

Raaberg, L; Nexø, E; Damsgaard Mikkelsen, J

1988-01-01

The tissue localisation and time of first appearance of Epidermal Growth Factor (EGF) in the developing rat were investigated by means of immunohistochemistry, radioimmunoassay and radioreceptor assay. In this study we were able to show, that EGF appears prenatally in the lung and the kidney from...

Influence of the radio-tracer used in diagnostic nuclear medicine upon the dose at the nucleus of cellular localisation

International Nuclear Information System (INIS)

Gardin, I.; Faraggi, M.; Stievenart, J.L; Le Guludec, D.; Bok, B.

1997-01-01

In the classical dosimetry one supposes a uniform distribution of the radio-pharmaceuticals at the source organ level as well as a homogeneous distribution of the absorbed dose. This hypotheses are not always verified in biology, and the influence of the tracer localisation on the dose delivered at the cellular nucleus has been studied. The average dose delivered by the electron emission of different radio-isotopes used in diagnosis has been calculated by taking into account the radioactivity localized upon the target cell (Dself), and upon the neighbouring cells (Dcross). Nuclear, cytoplasmic and membranous localizations of the tracer were simulated for different cellular sizes. In the particular case of 99m Tc and cells of nuclear radius about 4 μm and cellular radios about 8 μ, Dcross is independent of the intra-cellular localisation of the tracer. On the contrary, for a nuclear localisation Dself is 52 and 157 times more important than for the cytoplasmic and membranous localisation, respectively. The dose at the cellular nucleus due to electron emission of 99m Tc is under-estimated by a factor 2.6 by classical dosimetry when the radioactivity is nuclear. On the contrary, the classical model over-estimates by a factor 1.2 the dose at nucleus for cytoplasmic and membranous localizations. This study shows that the dose delivered at cellular nucleus by the electron emissions of 99m Tc depends on the localisation of the tracer. The modelling proposed allows a better evaluation of the radiobiological hazards related to the administration of radiopharmaceuticals in diagnostic nuclear medicine

Pharmacologic modulation of protein kinase C isozymes: the role of RACKs and subcellular localisation.

Science.gov (United States)

Csukai, M; Mochly-Rosen, D

1999-04-01

Protein kinase C (PKC) isozymes are highly homologous kinases and several different isozymes can be present in a cell. Each isozyme is likely to mediate unique functions, but pharmacological tools to explore their isozyme-specific roles have not been available until recently. In this review, we describe the development and application of isozyme-selective inhibitors of PKC. The identification of these inhibitors stems from the observation that PKC isozymes are each localised to unique subcellular locations following activation. Inhibitors of this isozyme-unique localisation have been shown to act as selective inhibitors of the functions of individual isozymes. The identification of isozyme-specific inhibitors should allow the exploration of individual PKC isozyme function in a wide range of cell systems. Copyright 1999 The Italian Pharmacological Society.

Paxillin localisation in osteocytes-Is it determined by the direction of loading?

International Nuclear Information System (INIS)

Vatsa, A.; Semeins, C.M.; Smit, T.H.; Klein-Nulend, J.

2008-01-01

External mechanical loading of cells aligns cytoskeletal stress fibres in the direction of principle strains and localises paxillin to the mechanosensing region. If the osteocyte cell body can indeed directly sense matrix strains, then cytoskeletal alignment and distribution of paxillin in osteocytes in situ will bear alignment to the different mechanical loading patterns in fibulae and calvariae. We used confocal microscopy to visualise the immunofluorescence-labelled actin cytoskeleton in viable osteocytes and paxillin distribution in fixated osteocytes in situ. In fibular osteocyte cell bodies, actin cytoskeleton and nuclei were elongated and aligned parallel to the principal (longitudinal) mechanical loading direction. Paxillin was localised to the 'poles' of elongated osteocyte cell bodies. In calvarial osteocyte cell bodies, actin cytoskeleton and nuclei were relatively more round. Paxillin was distributed evenly in the osteocyte cell bodies. Thus in osteocyte cell bodies in situ, the external mechanical loading pattern likely determines the orientation of the actin cytoskeleton, and focal adhesions mediate direct mechanosensation of matrix strains.

Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

Energy Technology Data Exchange (ETDEWEB)

Thys, Ryan G., E-mail: rthys@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Lehman, Christine E., E-mail: clehman@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Pierce, Levi C.T., E-mail: Levipierce@gmail.com [Human Longevity, Inc., San Diego, California 92121 (United States); Wang, Yuh-Hwa, E-mail: yw4b@virginia.edu [Department of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908-0733 (United States)

2015-09-15

Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

International Nuclear Information System (INIS)

Thys, Ryan G.; Lehman, Christine E.; Pierce, Levi C.T.; Wang, Yuh-Hwa

2015-01-01

Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

X-Linked Dyskeratosis Congenita Is Predominantly Caused by Missense Mutations in the DKC1 Gene

OpenAIRE

Knight, S.W.; Heiss, N.S.; Vulliamy, T.J.; Greschner, S.; Stavrides, G.; Pai, G.S.; Lestringant, G.; Varma, N.; Mason, P.J.; Dokal, I.; Poustka, A.

1999-01-01

Dyskeratosis congenita is a rare inherited bone marrow-failure syndrome characterized by abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. More than 80% of patients develop bone-marrow failure, and this is the major cause of premature death. The X-linked form of the disease (MIM 305000) has been shown to be caused by mutations in the DKC1 gene. The gene encodes a 514-amino-acid protein, dyskerin, that is homologous to Saccharomyces cerevisiae Cbf5p and rat Nap57 proteins. B...

Localisation of SCN10A gene product Na(v)1.8 and novel pain-related ion channels in human heart.

Science.gov (United States)

Facer, Paul; Punjabi, Prakash P; Abrari, Andleeb; Kaba, Riyaz A; Severs, Nicholas J; Chambers, John; Kooner, Jaspal S; Anand, Praveen

2011-01-01

We have shown that the gene SCN10A encoding the sodium channel Na(v)1.8 is a susceptibility factor for heart block and serious ventricular arrhythmia. Since Na(v)1.8 is known to be present in nerve fibres that mediate pain, it may be related to both cardiac pain and dysrhythmia. The localisation of Na(v)1.8 and other key nociceptive ion channels, including Na(v)1.7, Na(v)1.9, capsaicin receptor TRPV1, and purinergic receptor P2X(3), have not been reported in human heart. The aim of this study was to determine the distribution of Na(v)1.8, related sodium and other sensory channels in human cardiac tissue, and correlate their density with sympathetic nerves, regenerating nerves (GAP-43), and vascularity. Human heart atrial appendage tissues (n = 13) were collected during surgery for valve disease. Tissues were investigated by immunohistology using specific antibodies to Na(v)1.8 and other markers. Na(v)1.8 immunoreactivity was detected in nerve fibres and fascicles in the myocardium, often closely associated with small capillaries. Na(v)1.8 nerve fibres per mm(2) correlated significantly with vascular markers. Na(v)1.8-immunoreactivity was present also in cardiomyocytes with a similar distribution pattern to that seen with connexins, the specialised gap junction proteins of myocardial intercalated discs. Na(v)1.5-immunoreactivity was detected in cardiomyocytes but not in nerve fibres. Na(v)1.7, Na(v)1.9, TRPV1, P2X(3)/P2X(2), and GAP43 positive nerve fibres were relatively sparse, whereas sympathetic innervation and connexin43 were abundant. We conclude that sodium channel Na(v)1.8 is present in sensory nerves and cardiomyocytes of human heart. Na(v)1.8 and other pain channels provide new targets for the understanding and treatment of cardiac pain and dysrhythmia.

The importance of strain localisation in shear zones

Science.gov (United States)

Bons, Paul D.; Finch, Melanie; Gomez-Rivas, Enrique; Griera, Albert; Llorens, Maria-Gema; Steinbach, Florian; Weikusat, Ilka

2016-04-01

The occurrence of various types of shear bands (C, C', C'') in shear zones indicate that heterogeneity of strain is common in strongly deformed rocks. However, the importance of strain localisation is difficult to ascertain if suitable strain markers are lacking, which is usually the case. Numerical modelling with the finite-element method has so far not given much insight in the development of shear bands. We suggest that this is not only because the modelled strains are often not high enough, but also because this technique (that usually assumes isotropic material properties within elements) does not properly incorporate mineral deformation behaviour. We simulated high-strain, simple-shear deformation in single- and polyphase materials with a full-field theory (FFT) model coupled to the Elle modelling platform (www.elle.ws; Lebensohn 2001; Bons et al. 2008). The FFT-approach simulates visco-plastic deformation by dislocation glide, taking into account the different available slip systems and their critical resolved shear stresses in relations to the applied stresses. Griera et al. (2011; 2013) have shown that this approach is particularly well suited for strongly anisotropic minerals, such as mica and ice Ih (Llorens 2015). We modelled single- and polyphase composites of minerals with different anisotropies and strengths, roughly equivalent to minerals such as ice Ih, mica, quartz and feldspar. Single-phase polycrystalline aggregates show distinct heterogeneity of strain rate, especially in case of ice Ih, which is mechanically close to mica (see also Griera et al. 2015). Finite strain distributions are heterogeneous as well, but the patterns may differ from that of the strain rate distribution. Dynamic recrystallisation, however, usually masks any strain and strain rate localisation (Llorens 2015). In case of polyphase aggregates, equivalent to e.g. a granite, we observe extensive localisation in both syn- and antithetic shear bands. The antithetic shear bands

Multi-particle Anderson Localisation: Induction on the Number of Particles

International Nuclear Information System (INIS)

Chulaevsky, Victor; Suhov, Yuri

2009-01-01

This paper is a follow-up of our recent papers Chulaevsky and Suhov (Commun Math Phys 283:479-489, 2008) and Chulaevsky and Suhov (Commun Math Phys in press, 2009) covering the two-particle Anderson model. Here we establish the phenomenon of Anderson localisation for a quantum N-particle system on a lattice with short-range interaction and in presence of an IID external potential with sufficiently regular marginal cumulative distribution function (CDF). Our main method is an adaptation of the multi-scale analysis (MSA; cf. Froehlich and Spencer, Commun Math Phys 88:151-184, 1983; Froehlich et al., Commun Math Phys 101:21-46, 1985; von Dreifus and Klein, Commun Math Phys 124:285-299, 1989) to multi-particle systems, in combination with an induction on the number of particles, as was proposed in our earlier manuscript (Chulaevsky and Suhov 2007). Recently, Aizenman and Warzel (2008) proved spectral and dynamical localisation for N-particle lattice systems with a short-range interaction, using an extension of the Fractional-Moment Method (FMM) developed earlier for single-particle models in Aizenman and Molchanov (Commun Math Phys 157:245-278, 1993) and Aizenman et al. (Commun Math Phys 224:219-253, 2001) (see also references therein) which is also combined with an induction on the number of particles

Quantitative Evaluation of Stereo Visual Odometry for Autonomous Vessel Localisation in Inland Waterway Sensing Applications

Directory of Open Access Journals (Sweden)

Thomas Kriechbaumer

2015-12-01

Full Text Available Autonomous survey vessels can increase the efficiency and availability of wide-area river environment surveying as a tool for environment protection and conservation. A key challenge is the accurate localisation of the vessel, where bank-side vegetation or urban settlement preclude the conventional use of line-of-sight global navigation satellite systems (GNSS. In this paper, we evaluate unaided visual odometry, via an on-board stereo camera rig attached to the survey vessel, as a novel, low-cost localisation strategy. Feature-based and appearance-based visual odometry algorithms are implemented on a six degrees of freedom platform operating under guided motion, but stochastic variation in yaw, pitch and roll. Evaluation is based on a 663 m-long trajectory (>15,000 image frames and statistical error analysis against ground truth position from a target tracking tachymeter integrating electronic distance and angular measurements. The position error of the feature-based technique (mean of ±0.067 m is three times smaller than that of the appearance-based algorithm. From multi-variable statistical regression, we are able to attribute this error to the depth of tracked features from the camera in the scene and variations in platform yaw. Our findings inform effective strategies to enhance stereo visual localisation for the specific application of river monitoring.

TOR complex 2 localises to the cytokinetic actomyosin ring and controls the fidelity of cytokinesis.

Science.gov (United States)

Baker, Karen; Kirkham, Sara; Halova, Lenka; Atkin, Jane; Franz-Wachtel, Mirita; Cobley, David; Krug, Karsten; Maček, Boris; Mulvihill, Daniel P; Petersen, Janni

2016-07-01

The timing of cell division is controlled by the coupled regulation of growth and division. The target of rapamycin (TOR) signalling network synchronises these processes with the environmental setting. Here, we describe a novel interaction of the fission yeast TOR complex 2 (TORC2) with the cytokinetic actomyosin ring (CAR), and a novel role for TORC2 in regulating the timing and fidelity of cytokinesis. Disruption of TORC2 or its localisation results in defects in CAR morphology and constriction. We provide evidence that the myosin II protein Myp2 and the myosin V protein Myo51 play roles in recruiting TORC2 to the CAR. We show that Myp2 and TORC2 are co-dependent upon each other for their normal localisation to the cytokinetic machinery. We go on to show that TORC2-dependent phosphorylation of actin-capping protein 1 (Acp1, a known regulator of cytokinesis) controls CAR stability, modulates Acp1-Acp2 (the equivalent of the mammalian CAPZA-CAPZB) heterodimer formation and is essential for survival upon stress. Thus, TORC2 localisation to the CAR, and TORC2-dependent Acp1 phosphorylation contributes to timely control and the fidelity of cytokinesis and cell division. © 2016. Published by The Company of Biologists Ltd.

Localised proton magnetic resonance spectroscopy of the brain after perinatal hypoxia: a preliminary report

Energy Technology Data Exchange (ETDEWEB)

Chateil, J.F. [Service de Radiologie A, Hopital Pellegrin, Bordeaux (France)]|[Unite de Radiopediatrie, Hopital Pellegrin, Bordeaux (France); Quesson, B.; Thiaudiere, E.; Delalande, C.; Canioni, P. [Resonance Magnetique des Systemes Biologiques, CNRS, Bordeaux (France); Brun, M.; Diard, F. [Service de Radiologie A, Hopital Pellegrin, Bordeaux (France); Sarlangue, J.; Billeaud, C. [Service de Neonatalogie, Hopital Pellegrin, Bordeaux (France)

1999-03-01

Objectives. Perinatal hypoxic ischaemic injury is a significant cause of neurodevelopmental impairment. The aim of this study was to evaluate localised proton magnetic resonance spectroscopy ({sup 1}H-MRS) after birth asphyxia. Materials and methods. Thirty newborn infants suspected of having perinatal asphyxia (Apgar score < 3) were studied. The mean gestational age was 37 weeks, mean age at the MR examination was 18 days and mean weight was 2.9 kg. A 1.5-T unit was used for imaging and spectroscopy. None of the babies had mechanically assisted ventilation. No sedation was used. Axial T1-weighted and T2-weighted images were obtained. {sup 1}H-MRS was recorded in a single voxel, localised in white matter, using a STEAM sequence. Results. Image quality was good in 25 of 30 babies. {sup 1}H-MRS was performed in 19 of 30 subjects, with adequate quality in 16. Choline, creatine/phosphocreatine and N-acetylaspartate peaks and peak-area ratios were analysed. Lactate was detected in four infants. The N-acetylaspartate/choline ratio was lower in infants with an impaired neurological outcome, but the difference was not statistically significant. Conclusions. This study suggests that {sup 1}H-MRS may be useful for assessing cerebral metabolism in the neonate. A raised lactate level and decreased N-acetylaspartate/choline ratio may be predictive of a poor outcome. However, in our experience this method is limited by the difficulty in performing the examination during the first hours after birth in critically ill babies, the problems related to use of a monovoxel sequence, the dispersion of the ratios and the lack of determination of the absolute concentration of the metabolites. (orig.) With 3 figs., 2 tabs., 20 refs.

Network analysis of differential expression for the identification of disease-causing genes.

Directory of Open Access Journals (Sweden)

Daniela Nitsch

Full Text Available Genetic studies (in particular linkage and association studies identify chromosomal regions involved in a disease or phenotype of interest, but those regions often contain many candidate genes, only a few of which can be followed-up for biological validation. Recently, computational methods to identify (prioritize the most promising candidates within a region have been proposed, but they are usually not applicable to cases where little is known about the phenotype (no or few confirmed disease genes, fragmentary understanding of the biological cascades involved. We seek to overcome this limitation by replacing knowledge about the biological process by experimental data on differential gene expression between affected and healthy individuals. Considering the problem from the perspective of a gene/protein network, we assess a candidate gene by considering the level of differential expression in its neighborhood under the assumption that strong candidates will tend to be surrounded by differentially expressed neighbors. We define a notion of soft neighborhood where each gene is given a contributing weight, which decreases with the distance from the candidate gene on the protein network. To account for multiple paths between genes, we define the distance using the Laplacian exponential diffusion kernel. We score candidates by aggregating the differential expression of neighbors weighted as a function of distance. Through a randomization procedure, we rank candidates by p-values. We illustrate our approach on four monogenic diseases and successfully prioritize the known disease causing genes.

CpG island methylator phenotype (CIMP) in cancer: causes and implications.

Science.gov (United States)

Teodoridis, Jens M; Hardie, Catriona; Brown, Robert

2008-09-18

Strong evidence exists for a subgroup of tumours, from a variety of tissue types, exhibiting concordant tumour specific DNA methylation: the "CpG island methylator phenotype" (CIMP). Occurrence of CIMP is associated with a range of genetic and environmental factors, although the molecular causes are not well-understood. Both increased expression and aberrant targeting of DNA methyltransferases (DNMTs) could contribute to the occurrence of CIMP. One under-explored area is the possibility that DNA damage may induce or select for CIMP during carcinogenesis or treatment of tumours with chemotherapy. DNA damaging agents can induce DNA damage at guanine rich regions throughout the genome, including CpG islands. This DNA damage can result in stalled DNA synthesis, which will lead to localised increased DNMT1 concentration and therefore potentially increased DNA methylation at these sites. Chemotherapy can select for cells which have increased tolerance to DNA damage due to increased lesion bypass, in some cases by mechanisms which involve inactivation of genes by CpG island methylation. CIMP has been associated with worse patient prognosis, probably due to increased epigenetic plasticity. Therefore, further clinical testing of the diagnostic and prognostic value of the current CIMP markers, as well as increasing our understanding of the molecular causes underlying CIMP are required.

Réseau africain consacré à la localisation | CRDI - Centre de ...

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

Ce projet s'attaquera à la question de la localisation et des langues locales dans le domaine des technologies de l'information et de la communication (TIC), au moyen de neuf sous-projets dont voici une brève description. Création de paramètres de lieu - l'équipe créera des paramètres de lieu africains pour 100 grandes ...

Photon counting imaging and centroiding with an electron-bombarded CCD using single molecule localisation software

International Nuclear Information System (INIS)

Hirvonen, Liisa M.; Barber, Matthew J.; Suhling, Klaus

2016-01-01

Photon event centroiding in photon counting imaging and single-molecule localisation in super-resolution fluorescence microscopy share many traits. Although photon event centroiding has traditionally been performed with simple single-iteration algorithms, we recently reported that iterative fitting algorithms originally developed for single-molecule localisation fluorescence microscopy work very well when applied to centroiding photon events imaged with an MCP-intensified CMOS camera. Here, we have applied these algorithms for centroiding of photon events from an electron-bombarded CCD (EBCCD). We find that centroiding algorithms based on iterative fitting of the photon events yield excellent results and allow fitting of overlapping photon events, a feature not reported before and an important aspect to facilitate an increased count rate and shorter acquisition times.

A rare case of localised pigmented villonodular synovitis in the knee of a 24-year-old female soccer player

DEFF Research Database (Denmark)

Falster, Casper; Stockmann Poulsen, Simon; Joergensen, Uffe

2017-01-01

Localised pigmented villonodular synovitis (PVNS) of the knee is a rare diagnosis, with clinical signs and symptoms mimicking meniscal damage or other common knee injuries. We report the case of a 24-year-old female soccer player, seeking treatment after 7 months of persisting knee pain...... analyses confirmed the diagnosis of localised PVNS. The patient was subsequently free of symptoms with no signs of recurrence on MRI and had resumed soccer practice at the 1-year follow-up appointment....

Quantitation and localisation of (in vitro) transglutaminase-catalysed glutamine hydroxylation using mass spectrometry

NARCIS (Netherlands)

Piersma, S.R.; Pijpekamp, A. van de; Wijngaards, G.; Gruppen, H.; Boumans, H.

2002-01-01

A mass spectrometric approach was chosen to quantify and localise in vitro enzymatically modified glutamine (Gln) residues in a glutamine-rich protein. This protein (named dB1), a cloned domain of the high molecular weight wheat glutenin subunit Dx5, was modified by microbial transglutaminase

Reaction-Diffusion Automata Phenomenology, Localisations, Computation

CERN Document Server

Adamatzky, Andrew

2013-01-01

Reaction-diffusion and excitable media are amongst most intriguing substrates. Despite apparent simplicity of the physical processes involved the media exhibit a wide range of amazing patterns: from target and spiral waves to travelling localisations and stationary breathing patterns. These media are at the heart of most natural processes, including morphogenesis of living beings, geological formations, nervous and muscular activity, and socio-economic developments.   This book explores a minimalist paradigm of studying reaction-diffusion and excitable media using locally-connected networks of finite-state machines: cellular automata and automata on proximity graphs. Cellular automata are marvellous objects per se because they show us how to generate and manage complexity using very simple rules of dynamical transitions. When combined with the reaction-diffusion paradigm the cellular automata become an essential user-friendly tool for modelling natural systems and designing future and emergent computing arch...

Une localisation exceptionnelle de la tuberculose vertébrale Mal de Pott sous-occipital

Science.gov (United States)

Yahyaoui, Sana; Majdoub, Senda; Zaghouani, Houneida; Fradj, Hosni Ben; Bakir, Dejla; Bouajina, Elyes; Kraiem, Chakib

2013-01-01

Le mal de Pott est la forme la plus commune de la tuberculose osseuse touchant essentiellement le rachis dorso-lombaire. La localisation sous-occipitale reste exceptionnelle. Le diagnostic de cette entité est le plus souvent tardif ce qui expose à des complications graves. Les radiographies standard ne sont parlantes qu’à un stade tardif de la maladie, d'où l'intérêt de l'imagerie moderne notamment la tomodensitométrie (TDM) et l'imagerie par résonance magnétique (IRM) qui permettent un diagnostic précoce. Nous rapportons un nouveau cas de tuberculose sous-occipitale. Le diagnostic était posé sur l'imagerie en coupe et confirmé histologiquement à la biopsie transorale. Sont rappelés les aspects en imagerie de cette localisation particulière du mal de Pott. PMID:23819005

Association between PSA kinetics and cancer-specific mortality in patients with localised prostate cancer

DEFF Research Database (Denmark)

Thomsen, Frederik Birkebæk; Brasso, Klaus; Berg, Kasper Drimer

2016-01-01

BACKGROUND: The prognostic value of prostate-specific antigen (PSA) kinetics in untreated prostate cancer (PCa) patients is debatable. We investigated the association between PSA doubling time (PSAdt), PSA velocity (PSAvel) and PSAvel risk count (PSAvRC) and PCa mortality in a cohort of patients...... with localised PCa managed on watchful waiting. PATIENTS AND METHODS: Patients with clinically localised PCa managed observationally, who were randomised to and remained on placebo for minimum 18 months in the SPCG-6 study, were included. All patients survived at least 2 years and had a minimum of three PSA...... determinations available. The prognostic value of PSA kinetics was analysed and patients were stratified according to their PSA at consent: ≤10, 10.1-25, and >25 ng/ml. Cumulative incidences of PCa-specific mortality were estimated with the Aalen-Johansen method. RESULTS: Two hundred and sixty-three patients...

A Review of Non-Invasive Techniques to Detect and Predict Localised Muscle Fatigue

Directory of Open Access Journals (Sweden)

Mohamed R. Al-Mulla

2011-03-01

Full Text Available Muscle fatigue is an established area of research and various types of muscle fatigue have been investigated in order to fully understand the condition. This paper gives an overview of the various non-invasive techniques available for use in automated fatigue detection, such as mechanomyography, electromyography, near-infrared spectroscopy and ultrasound for both isometric and non-isometric contractions. Various signal analysis methods are compared by illustrating their applicability in real-time settings. This paper will be of interest to researchers who wish to select the most appropriate methodology for research on muscle fatigue detection or prediction, or for the development of devices that can be used in, e.g., sports scenarios to improve performance or prevent injury. To date, research on localised muscle fatigue focuses mainly on the clinical side. There is very little research carried out on the implementation of detecting/predicting fatigue using an autonomous system, although recent research on automating the process of localised muscle fatigue detection/prediction shows promising results.

A Review of Non-Invasive Techniques to Detect and Predict Localised Muscle Fatigue

Science.gov (United States)

Al-Mulla, Mohamed R.; Sepulveda, Francisco; Colley, Martin

2011-01-01

Muscle fatigue is an established area of research and various types of muscle fatigue have been investigated in order to fully understand the condition. This paper gives an overview of the various non-invasive techniques available for use in automated fatigue detection, such as mechanomyography, electromyography, near-infrared spectroscopy and ultrasound for both isometric and non-isometric contractions. Various signal analysis methods are compared by illustrating their applicability in real-time settings. This paper will be of interest to researchers who wish to select the most appropriate methodology for research on muscle fatigue detection or prediction, or for the development of devices that can be used in, e.g., sports scenarios to improve performance or prevent injury. To date, research on localised muscle fatigue focuses mainly on the clinical side. There is very little research carried out on the implementation of detecting/predicting fatigue using an autonomous system, although recent research on automating the process of localised muscle fatigue detection/prediction shows promising results. PMID:22163810

Localisation of the gene for achondroplasia to the telomeric region of chromosome 4p

Energy Technology Data Exchange (ETDEWEB)

Stoilov, I.; Velinov, M.; Kilpatrick, M.W. [and others

1994-09-01

Achondroplasia (ACH), the most common type of genetic dwarfism, is characterized by a variety of skeletal anomalies including disproportionate short stature and rhizomelic shortening of the extremities. The disorder is inherited as an autosomal dominant trait, with a prevalence of 1-15 per 100,000 live births. The etiology of ACH remains unknown, although evidence points to a defect in the maturation of the chondrocytes in the growth plate of the cartilage. To determine the location of the gene responsible for ACH, a panel of 14 families with a total of 43 meioses was genotyped for 40 polymorphic markers for loci randomly distributed throughout the genome. The first significant positive Lod score was obtained for the locus D4S127 (Zmax=3.65 at {theta}=0.03). A series of 20 markers for chromosome 4p16.3 loci were then used to determine the most likely position of the ACH gene. Two additional loci, D4S412 and IDUA, showed strong linkage to the disease (Zmax=3.34 at {theta}=0.03 and Zmax=3.35 at {theta}=0.0, respectively). Multipoint analysis and direct counting of recombinants places the ACH gene in a 2.5 cM region between the marker D4S43 and the chromosome 4p telomere. No evidence was found for genetic heterogeneity. The ACH region contains a number of genes, including that for the fibroblast growth factor receptor FGFR3, which are being evaluated as candidates for the ACH gene. This identification of tightly linked polymorphic markers, as well as being the first step in the characterization of the ACH gene, offers the possibility of DNA based prenatal diagnosis of this disorder.

Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.

Science.gov (United States)

Maugeri, A; Klevering, B J; Rohrschneider, K; Blankenagel, A; Brunner, H G; Deutman, A F; Hoyng, C B; Cremers, F P

2000-10-01

The photoreceptor cell-specific ATP-binding cassette transporter gene (ABCA4; previously denoted "ABCR") is mutated, in most patients, with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients from Germany and The Netherlands with isolated CRD. Single-strand conformation-polymorphism analysis and sequencing revealed 19 ABCA4 mutations in 13 (65%) of 20 patients. In six patients, mutations were identified in both ABCA4 alleles; in seven patients, mutations were detected in one allele. One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. These findings suggest that mutations in the ABCA4 gene are the major cause of AR CRD. A primary role of the ABCA4 gene in STGD1/FFM and AR CRD, together with the gene's involvement in an as-yet-unknown proportion of cases with AR RP, strengthens the idea that mutations in the ABCA4 gene could be the most frequent cause of inherited retinal dystrophy in humans.

Germline heterozygous variants in genes associated with familial hemophagocytic lymphohistiocytosis as a cause of increased bleeding

DEFF Research Database (Denmark)

Fager Ferrari, Marcus; Leinoe, Eva; Rossing, Maria

2018-01-01

Familial hemophagocytic lymphohistiocytosis (FHL) is caused by biallelic variants in genes regulating granule secretion in cytotoxic lymphocytes. In FHL3-5, the affected genes UNC13D, STX11 and STXBP2 have further been shown to regulate the secretion of platelet granules, giving rise to compromised...

Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects

DEFF Research Database (Denmark)

Koene, S; Rodenburg, R J; van der Knaap, M S

2012-01-01

cases and 126 from literature) with mutations in nuclear genes encoding structural complex I proteins or those involved in its assembly. Complex I deficiency caused by a nuclear gene defect is usually a non-dysmorphic syndrome, characterized by severe multi-system organ involvement and a poor prognosis...

Quality of Life Outcomes after Primary Treatment for Clinically Localised Prostate Cancer: A Systematic Review.

Science.gov (United States)

Lardas, Michael; Liew, Matthew; van den Bergh, Roderick C; De Santis, Maria; Bellmunt, Joaquim; Van den Broeck, Thomas; Cornford, Philip; Cumberbatch, Marcus G; Fossati, Nicola; Gross, Tobias; Henry, Ann M; Bolla, Michel; Briers, Erik; Joniau, Steven; Lam, Thomas B; Mason, Malcolm D; Mottet, Nicolas; van der Poel, Henk G; Rouvière, Olivier; Schoots, Ivo G; Wiegel, Thomas; Willemse, Peter-Paul M; Yuan, Cathy Yuhong; Bourke, Liam

2017-12-01

Current evidence-based management for clinically localised prostate cancer includes active surveillance, surgery, external beam radiotherapy (EBRT) and brachytherapy. The impact of these treatment modalities on quality of life (QoL) is uncertain. To systematically review comparative studies investigating disease-specific QoL outcomes as assessed by validated cancer-specific patient-reported outcome measures with at least 1 yr of follow-up after primary treatment for clinically localised prostate cancer. MEDLINE, EMBASE, AMED, PsycINFO, and Cochrane Library were searched to identify relevant studies. Studies were critically appraised for the risk of bias. A narrative synthesis was undertaken. Of 11486 articles identified, 18 studies were eligible for inclusion, including three randomised controlled trials (RCTs; follow-up range: 60-72 mo) and 15 nonrandomised comparative studies (follow-up range: 12-180 mo) recruiting a total of 13604 patients. Two RCTs recruited small cohorts and only one was judged to have a low risk of bias. The quality of evidence from observational studies was low to moderate. For a follow-up of up to 6 yr, active surveillance was found to have the lowest impact on cancer-specific QoL, surgery had a negative impact on urinary and sexual function when compared with active surveillance and EBRT, and EBRT had a negative impact on bowel function when compared with active surveillance and surgery. Data from one small RCT reported that brachytherapy has a negative impact on urinary function 1 yr post-treatment, but no significant urinary toxicity was reported at 5 yr. This is the first systematic review comparing the impact of different primary treatments on cancer-specific QoL for men with clinically localised prostate cancer, using validated cancer-specific patient-reported outcome measures only. There is robust evidence that choice of primary treatment for localised prostate cancer has distinct impacts on patients' QoL. This should be discussed in

Localisation and quantification of alkali-labile sites in human spermatozoa by DNA breakage detection-fluorescence in situ hybridisation.

Science.gov (United States)

Cortés-Gutiérrez, E I; Dávila-Rodríguez, M I; Cerda-Flores, R M; Fernández, J L; López-Fernández, C; Aragón Tovar, A R; Gosálvez, J

2015-03-01

The localisation and quantification of constitutive alkali-labile sites (ALSs) were investigated using a protocol of DNA breakage detection plus fluorescence in situ hybridisation (DBD-FISH) and alkaline single-cell gel electrophoresis (SCGE or comet assay), in spermatozoa of infertile and fertile men. Semen samples from 10 normozoospermic patients undergoing infertility treatment and 10 fertile men were included in this study. ALSs were localised and quantified by DBD-FISH. The region most sensitive to alkali treatment in human spermatozoa was located in the basal region of the head. ALSs were more frequent in spermatozoa of infertile men than in those of fertile men. These results were confirmed by SCGE comet assays. In conclusion, the most intense localisation of hybridisation signals in human spermatozoa, representing the highest density of constitutive ALSs, was not randomly distributed and was predominantly located in the base of the head. Moreover, infertile men presented with an increase in ALS frequency. Further studies are necessary to determine the association between ALS, sperm chromatin organisation and infertility. © 2014 Blackwell Verlag GmbH.

A machine-hearing system exploiting head movements for binaural sound localisation in reverberant conditions

DEFF Research Database (Denmark)

May, Tobias; Ma, Ning; Wierstorf, Hagen

2015-01-01

This paper is concerned with machine localisation of multiple active speech sources in reverberant environments using two (binaural) microphones. Such conditions typically present a problem for ‘classical’ binaural models. Inspired by the human ability to utilise head movements, the current study...

Schizophrenia: A Pathogenetic Autoimmune Disease Caused by Viruses and Pathogens and Dependent on Genes

Directory of Open Access Journals (Sweden)

C. J. Carter

2011-01-01

Full Text Available Many genes have been implicated in schizophrenia as have viral prenatal or adult infections and toxoplasmosis or Lyme disease. Several autoantigens also target key pathology-related proteins. These factors are interrelated. Susceptibility genes encode for proteins homologous to those of the pathogens while the autoantigens are homologous to pathogens' proteins, suggesting that the risk-promoting effects of genes and risk factors are conditional upon each other, and dependent upon protein matching between pathogen and susceptibility gene products. Pathogens' proteins may act as dummy ligands, decoy receptors, or via interactome interference. Many such proteins are immunogenic suggesting that antibody mediated knockdown of multiple schizophrenia gene products could contribute to the disease, explaining the immune activation in the brain and lymphocytes in schizophrenia, and the preponderance of immune-related gene variants in the schizophrenia genome. Schizophrenia may thus be a “pathogenetic” autoimmune disorder, caused by pathogens, genes, and the immune system acting together, and perhaps preventable by pathogen elimination, or curable by the removal of culpable antibodies and antigens.

A single gene causes an interspecific difference in pigmentation in Drosophila.

Science.gov (United States)

Ahmed-Braimah, Yasir H; Sweigart, Andrea L

2015-05-01

The genetic basis of species differences remains understudied. Studies in insects have contributed significantly to our understanding of morphological evolution. Pigmentation traits in particular have received a great deal of attention and several genes in the insect pigmentation pathway have been implicated in inter- and intraspecific differences. Nonetheless, much remains unknown about many of the genes in this pathway and their potential role in understudied taxa. Here we genetically analyze the puparium color difference between members of the virilis group of Drosophila. The puparium of Drosophila virilis is black, while those of D. americana, D. novamexicana, and D. lummei are brown. We used a series of backcross hybrid populations between D. americana and D. virilis to map the genomic interval responsible for the difference between this species pair. First, we show that the pupal case color difference is caused by a single Mendelizing factor, which we ultimately map to an ∼11-kb region on chromosome 5. The mapped interval includes only the first exon and regulatory region(s) of the dopamine N-acetyltransferase gene (Dat). This gene encodes an enzyme that is known to play a part in the insect pigmentation pathway. Second, we show that this gene is highly expressed at the onset of pupation in light brown taxa (D. americana and D. novamexicana) relative to D. virilis, but not in the dark brown D. lummei. Finally, we examine the role of Dat in adult pigmentation between D. americana (heavily melanized) and D. novamexicana (lightly melanized) and find no discernible effect of this gene in adults. Our results demonstrate that a single gene is entirely or almost entirely responsible for a morphological difference between species. Copyright © 2015 by the Genetics Society of America.

TET-mediated oxidation of methylcytosine causes TDG or NEIL glycosylase dependent gene reactivation.

Science.gov (United States)

Müller, Udo; Bauer, Christina; Siegl, Michael; Rottach, Andrea; Leonhardt, Heinrich

2014-07-01

The discovery of hydroxymethyl-, formyl- and carboxylcytosine, generated through oxidation of methylcytosine by TET dioxygenases, raised the question how these modifications contribute to epigenetic regulation. As they are subjected to complex regulation in vivo, we dissected links to gene expression with in vitro modified reporter constructs. We used an Oct4 promoter-driven reporter gene and demonstrated that in vitro methylation causes gene silencing while subsequent oxidation with purified catalytic domain of TET1 leads to gene reactivation. To identify proteins involved in this pathway we screened for TET interacting factors and identified TDG, PARP1, XRCC1 and LIG3 that are involved in base-excision repair. Knockout and rescue experiments demonstrated that gene reactivation depended on the glycosylase TDG, but not MBD4, while NEIL1, 2 and 3 could partially rescue the loss of TDG. These results clearly show that oxidation of methylcytosine by TET dioxygenases and subsequent removal by TDG or NEIL glycosylases and the BER pathway results in reactivation of epigenetically silenced genes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Zinc fingers 1, 2, 5 and 6 of transcriptional regulator, PRDM4, are required for its nuclear localisation

Energy Technology Data Exchange (ETDEWEB)

Tunbak, Hale, E-mail: h.tunbak@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Georgiou, Christiana, E-mail: christiana.georgiou.10@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Guan, Cui, E-mail: c.guan@qmul.ac.uk [School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS (United Kingdom); Richardson, William David, E-mail: w.richardson@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom); Chittka, Alexandra, E-mail: a.chittka@ucl.ac.uk [The Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT (United Kingdom)

2016-05-27

PRDM4 is a member of the PRDM family of transcriptional regulators which control various aspects of cellular differentiation and proliferation. PRDM proteins exert their biological functions both in the cytosol and the nucleus of cells. All PRDM proteins are characterised by the presence of two distinct structural motifs, the PR/SET domain and the zinc finger (ZF) motifs. We previously observed that deletion of all six zinc fingers found in PRDM4 leads to its accumulation in the cytosol, whereas overexpressed full length PRDM4 is found predominantly in the nucleus. Here, we investigated the requirements for single zinc fingers in the nuclear localisation of PRDM4. We demonstrate that ZF's 1, 2, 5 and 6 contribute to the accumulation of PRDM4 in the nucleus. Their effect is additive as deleting either ZF1-2 or ZF 5–6 redistributes PRDM4 protein from being almost exclusively nuclear to cytosolic and nuclear. We investigated the potential mechanism of nuclear shuttling of PRDM4 via the importin α/β-mediated pathway and find that PRDM4 nuclear targeting is independent of α/β-mediated nuclear import. -- Highlights: •Zinc fingers 1, 2, 5, and 6 are necessary for efficient nuclear localisation of PRDM4. •Zinc fingers 3 and 4 are dispensable for nuclear localisation of PRDM4. •Zinc knuckle is dispensable for nuclear localisation of PRDM4. •PRDM4 nuclear transport is independent of importin α/β-mediated pathway of nuclear import.

Autosomal recessive retinitis pigmentosa caused by mutations in the MAK gene.

Science.gov (United States)

Stone, Edwin M; Luo, Xunda; Héon, Elise; Lam, Byron L; Weleber, Richard G; Halder, Jennifer A; Affatigato, Louisa M; Goldberg, Jacqueline B; Sumaroka, Alexander; Schwartz, Sharon B; Cideciyan, Artur V; Jacobson, Samuel G

2011-12-28

To determine the disease expression in autosomal recessive (ar) retinitis pigmentosa (RP) caused by mutations in the MAK (male germ cell-associated kinase) gene. Patients with RP and MAK gene mutations (n = 24; age, 32-77 years at first visit) were studied by ocular examination, perimetry, and optical coherence tomography (OCT). All but one MAK patient were homozygous for an identical truncating mutation in exon 9 and had Ashkenazi Jewish heritage. The carrier frequency of this mutation among 1207 unrelated Ashkenazi control subjects was 1 in 55, making it the most common cause of heritable retinal disease in this population and MAK-associated RP the sixth most common Mendelian disease overall in this group. Visual acuities could be normal into the eighth decade of life. Kinetic fields showed early loss in the superior-temporal quadrant. With more advanced disease, superior and midperipheral function was lost, but the nasal field remained. Only a central island was present at late stages. Pigmentary retinopathy was less prominent in the superior nasal quadrant. Rod-mediated vision was abnormal but detectable in the residual field; all patients had rod>cone dysfunction. Photoreceptor layer thickness was normal centrally but decreased with eccentricity. At the stages studied, there was no evidence of photoreceptor ciliary elongation. The patterns of disease expression in the MAK form of arRP showed some resemblance to patterns described in autosomal dominant RP, especially the form caused by RP1 mutations. The similarity in phenotypes is of interest, considering that there is experimental evidence of interaction between Mak and RP1 in the photoreceptor cilium.

Correlative and integrated light and electron microscopy of in-resin GFP fluorescence, used to localise diacylglycerol in mammalian cells

Energy Technology Data Exchange (ETDEWEB)

Peddie, Christopher J.; Blight, Ken; Wilson, Emma [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Melia, Charlotte [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Department of Molecular Cell Biology, Leiden University Medical Centre, 2300 RC Leiden (Netherlands); Marrison, Jo [Department of Biology, The University of York, Heslington, York (United Kingdom); Carzaniga, Raffaella [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Domart, Marie-Charlotte [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); O' Toole, Peter [Department of Biology, The University of York, Heslington, York (United Kingdom); Larijani, Banafshe [Cell Biophysics Laboratory, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom); Cell Biophysics Laboratory, Unidad de Biofísica (CSIC-UPV/EHU),Sarriena s/n, 48940 Leioa (Spain); IKERBASQUE, Basque Foundation for Science, Bilbao (Spain); Collinson, Lucy M. [Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY (United Kingdom)

2014-08-01

Fluorescence microscopy of GFP-tagged proteins is a fundamental tool in cell biology, but without seeing the structure of the surrounding cellular space, functional information can be lost. Here we present a protocol that preserves GFP and mCherry fluorescence in mammalian cells embedded in resin with electron contrast to reveal cellular ultrastructure. Ultrathin in-resin fluorescence (IRF) sections were imaged simultaneously for fluorescence and electron signals in an integrated light and scanning electron microscope. We show, for the first time, that GFP is stable and active in resin sections in vacuo. We applied our protocol to study the subcellular localisation of diacylglycerol (DAG), a modulator of membrane morphology and membrane dynamics in nuclear envelope assembly. We show that DAG is localised to the nuclear envelope, nucleoplasmic reticulum and curved tips of the Golgi apparatus. With these developments, we demonstrate that integrated imaging is maturing into a powerful tool for accurate molecular localisation to structure. - Highlights: • GFP and mCherry fluorescence are preserved in heavy-metal stained mammalian cells embedded in resin • Fluorophores are stable and intensity is sufficient for detection in ultrathin sections • Overlay of separate LM and EM images from the same ultrathin section improves CLEM protein localisation precision • GFP is stable and active in the vacuum of an integrated light and scanning EM • Integrated light and electron microscopy shows new subcellular locations of the lipid diacylglycerol.

[From gene to disease; genetic causes of hearing loss and visual impairment sometimes accompanied by vestibular problems (Usher syndrome)].

Science.gov (United States)

Pennings, R J E; Kremer, H; Deutman, A F; Kimberling, W J; Cremers, C W R J

2002-12-07

Usher syndrome is an autosomal recessively inherited disease, characterised by sensorineural hearing loss, tapetoretinal degeneration and in some cases vestibular problems. Based on the clinical heterogeneity, the disease can be classified into three clinical types (I, II and III), which have their own genetic subtypes (Usher 1A-Usher IG, Usher 2A-Usher 2C and Usher 3). The majority of the Usher type I cases are caused by mutations in the MYO7A gene (Usher 1B) while mutations in the USH2A gene (Usher 2A) are the cause of most cases of type II. Usher syndrome type III, caused by mutations in the USH3 gene, is frequently seen only in Finland.

XLID-Causing Mutations and Associated Genes Challenged in Light of Data From Large-Scale Human Exome Sequencing

OpenAIRE

Piton, Amélie; Redin, Claire; Mandel, Jean-Louis

2013-01-01

Because of the unbalanced sex ratio (1.3–1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive...

Contiguous gene deletion of chromosome 2p16.3-p21 as a cause of Lynch syndrome.

Science.gov (United States)

Salo-Mullen, Erin E; Lynn, Patricio B; Wang, Lu; Walsh, Michael; Gopalan, Anuradha; Shia, Jinru; Tran, Christina; Man, Fung Ying; McBride, Sean; Schattner, Mark; Zhang, Liying; Weiser, Martin R; Stadler, Zsofia K

2018-01-01

Lynch syndrome is an autosomal dominant condition caused by pathogenic mutations in the DNA mismatch repair (MMR) genes. Although commonly associated with clinical features such as intellectual disability and congenital anomalies, contiguous gene deletions may also result in cancer predisposition syndromes. We report on a 52-year-old male with Lynch syndrome caused by deletion of chromosome 2p16.3-p21. The patient had intellectual disability and presented with a prostatic adenocarcinoma with an incidentally identified synchronous sigmoid adenocarcinoma that exhibited deficient MMR with an absence of MSH2 and MSH6 protein expression. Family history was unrevealing. Physical exam revealed short stature, brachycephaly with a narrow forehead and short philtrum, brachydactyly of the hands, palmar transverse crease, broad and small feet with hyperpigmentation of the soles. The patient underwent total colectomy with ileorectal anastomosis for a pT3N1 sigmoid adenocarcinoma. Germline genetic testing of the MSH2, MSH6, and EPCAM genes revealed full gene deletions. SNP-array based DNA copy number analysis identified a deletion of 4.8 Mb at 2p16.3-p21. In addition to the three Lynch syndrome associated genes, the deleted chromosomal section encompassed genes including NRXN1, CRIPT, CALM2, FBXO11, LHCGR, MCFD2, TTC7A, EPAS1, PRKCE, and 15 others. Contiguous gene deletions have been described in other inherited cancer predisposition syndromes, such as Familial Adenomatous Polyposis. Our report and review of the literature suggests that contiguous gene deletion within the 2p16-p21 chromosomal region is a rare cause of Lynch syndrome, but presents with distinct phenotypic features, highlighting the need for recognition and awareness of this syndromic entity.

Evc is a positive mediator of Ihh-regulated bone growth that localises at the base of chondrocyte cilia.

Science.gov (United States)

Ruiz-Perez, Victor L; Blair, Helen J; Rodriguez-Andres, M Elena; Blanco, Maria Jose; Wilson, Amy; Liu, Yu-Ning; Miles, Colin; Peters, Heiko; Goodship, Judith A

2007-08-01

EVC is a novel protein mutated in the human chondroectodermal dysplasia Ellis-van Creveld syndrome (EvC; OMIM: 225500). We have inactivated Evc in the mouse and show that Evc(-/-) mice develop an EvC-like syndrome, including short ribs, short limbs and dental abnormalities. lacZ driven by the Evc promoter revealed that Evc is expressed in the developing bones and the orofacial region. Antibodies developed against Evc locate the protein at the base of the primary cilium. The growth plate of Evc(-/-) mice shows delayed bone collar formation and advanced maturation of chondrocytes. Indian hedgehog (Ihh) is expressed normally in the growth plates of Evc(-/-) mice, but expression of the Ihh downstream genes Ptch1 and Gli1 was markedly decreased. Recent studies have shown that Smo localises to primary cilia and that Gli3 processing is defective in intraflagellar transport mutants. In vitro studies using Evc(-/-) cells demonstrate that the defect lies downstream of Smo. Chondrocyte cilia are present in Evc(-/-) mice and Gli3 processing appears normal by western blot analysis. We conclude that Evc is an intracellular component of the hedgehog signal transduction pathway that is required for normal transcriptional activation of Ihh target genes.

Intraoperative Localisation of Impalpable Breast Lesions Utilising the ROLLIS Technique Following Peritumoral 99mTc-colloid Sentinel Node Lymphoscintigraphy.

Science.gov (United States)

Hung, Te-Jui; Burrage, John; Bourke, Anita; Taylor, Donna

2017-08-24

Ultrasound or stereotactic guided hook-wire localisation has been the standard-of-care for the pre-surgical localisation of impalpable breast lesions, which account for approximately a third of all breast cancer. Radioguided occult lesion localisation using I-125 seeds (ROLLIS) is a relatively new technique for guiding surgical excision of impalpable breast lesions, and is a promising alternative to the traditional hook-wire method. When combined with Tc-99m labelled colloid for sentinel node mapping in clinically indicated cases, there has been uncertainty regarding whether the downscatter of Tc-99m into the I-125 energy spectrum could adversely affect the intra-operative detection of the I-125 seed, especially pertaining to a peritumoral injection. To evaluate the percentage contribution of downscattered activity from Tc-99m into the I-125 energy spectrum in simulated intra-operative resections of an I-125 seed following different sentinel node injection techniques. Two scenarios were simulated using breast phantoms with lean chicken breast. The first scenario, with a 2cm distance between the Tc-99m injection site and the I-125 seed, simulated a periareolar ipsiquadrant injection with the subdermal or intradermal technique. The second scenario simulated a peritumoral injection technique with the Tc-99m bolus and an I-125 seed at the same site. Count rates were acquired with a hand-held gamma probe, and the percentage contribution of downscattered Tc-99m gamma photons to the I-125 energy window was calculated. In scenarios one and two, downscattered Tc-99m activity contributed 0.5% and 33% respectively to the detected count rate in the I-125 energy window. In both scenarios, the I-125 seed was successfully localised and removed using the gamma probe. There is no significant contribution of downscattered activity associated with a peritumoral injection of Tc-99m to adversely affect the accurate intra-operative localisation of an I- 125 seed. Copyright© Bentham

Characterization of the Kin17 gene, a new component of the cellular response to ultra-violet radiations in mammals

International Nuclear Information System (INIS)

Kannouche, Patricia-Laila

1998-01-01

The objective of this research thesis is to characterize the expression of a mammal gene, called Kin-17, which codes for a protein which has a structural homology with the RecA protein of E. coli. This protein plays a crucial role in the cellular response to irradiations and in mutagenesis. In order to better understand the Kin 17 protein function, the author determined the Kin 17 gene expression profile in tissues and cells in culture. It appears that this expression is ubiquitous and weak. The Kin 17 protein quantity and localisation are also studied. The author suggests that this protein belongs to an intra-nuclear network of proteins required during cell growth, and might influence biological processes related to the cellular cycle. The co-localisation of the protein with the T-antigen is studied by immunofluorescence. The expression profile of different Kin-17 genes in cells after UV irradiation has been studied. The obtained results and observations suggest that the Kin 17 protein intervenes in a biological process which allows a cell to counterbalance toxic effects of UV radiations [fr

No muscle involvement in myoclonus-dystonia caused by epsilon-sarcoglycan gene mutations1

DEFF Research Database (Denmark)

Hjermind, L.E.; Vissing, J.; Asmus, F.

2008-01-01

Mutations in the epsilon-sarcoglycan gene (SGCE) can cause autosomal dominant inherited myoclonus-dystonia (M-D). Defects in other sarcoglycans; alpha-, beta-, gamma-, and delta can cause autosomal recessive inherited limb girdle muscular dystrophies. epsilon- and alpha-sarcoglycans are very...... strength and mass showed no difference between M-D patients and controls. Our findings indicate that patients with M-D have no signs or symptoms of muscle disease. This suggests a different role of the sarcoglycan complex epsilonbetagammadelta versus alphabetagammadelta complex in humans, as earlier...

Reliability of horizontal and vertical tube shift techniques in the localisation of supernumerary teeth.

Science.gov (United States)

Mallineni, S K; Anthonappa, R P; King, N M

2016-12-01

To assess the reliability of the vertical tube shift technique (VTST) and horizontal tube shift technique (HTST) for the localisation of unerupted supernumerary teeth (ST) in the anterior region of the maxilla. A convenience sample of 83 patients who attended a major teaching hospital because of unerupted ST was selected. Only non-syndromic patients with ST and who had complete clinical and radiographic and surgical records were included in the study. Ten examiners independently rated the paired set of radiographs for each technique. Chi-square test, paired t test and kappa statistics were employed to assess the intra- and inter-examiner reliability. Paired sets of 1660 radiographs (830 pairs for each technique) were available for the analysis. The overall sensitivity for VTST and HTST was 80.6 and 72.1% respectively, with slight inter-examiner and good intra-examiner reliability. Statistically significant differences were evident between the two localisation techniques (p HTST in the anterior region of the maxilla.

An efficient distributed localisation algorithm for wireless sensor networks: based on smart reference-selection method

CSIR Research Space (South Africa)

Abu-Mahfouz, Adnan M

2013-05-01

Full Text Available Determining the location of nodes is a key part of wireless sensor networks (WSNs). Many WSN applications require knowledge of nodes’ locations to perform their functions successfully. Several localisation algorithms rely on using all or most...

Mps1 kinase-dependent Sgo2 centromere localisation mediates cohesin protection in mouse oocyte meiosis I.

Science.gov (United States)

El Yakoubi, Warif; Buffin, Eulalie; Cladière, Damien; Gryaznova, Yulia; Berenguer, Inés; Touati, Sandra A; Gómez, Rocío; Suja, José A; van Deursen, Jan M; Wassmann, Katja

2017-09-25

A key feature of meiosis is the step-wise removal of cohesin, the protein complex holding sister chromatids together, first from arms in meiosis I and then from the centromere region in meiosis II. Centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage, in order to maintain sister chromatids together until their separation in meiosis II. Failures in step-wise cohesin removal result in aneuploid gametes, preventing the generation of healthy embryos. Here, we report that kinase activities of Bub1 and Mps1 are required for Sgo2 localisation to the centromere region. Mps1 inhibitor-treated oocytes are defective in centromeric cohesin protection, whereas oocytes devoid of Bub1 kinase activity, which cannot phosphorylate H2A at T121, are not perturbed in cohesin protection as long as Mps1 is functional. Mps1 and Bub1 kinase activities localise Sgo2 in meiosis I preferentially to the centromere and pericentromere respectively, indicating that Sgo2 at the centromere is required for protection.In meiosis I centromeric cohesin is protected by Sgo2 from Separase-mediated cleavage ensuring that sister chromatids are kept together until their separation in meiosis II. Here the authors demonstrate that Bub1 and Mps1 kinase activities are required for Sgo2 localisation to the centromere region.

Hydrodynamic gene delivery in human skin using a hollow microneedle device.

Science.gov (United States)

Dul, M; Stefanidou, M; Porta, P; Serve, J; O'Mahony, C; Malissen, B; Henri, S; Levin, Y; Kochba, E; Wong, F S; Dayan, C; Coulman, S A; Birchall, J C

2017-11-10

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Dark matter and localised fermions from spherical orbifolds?

Energy Technology Data Exchange (ETDEWEB)

Cacciapaglia, Giacomo; Deandrea, Aldo [Université de Lyon,Lyon (France); Université Lyon 1, CNRS/IN2P3, UMR5822 IPNL,F-69622 Villeurbanne Cedex (France); Deutschmann, Nicolas [Université de Lyon,Lyon (France); Université Lyon 1, CNRS/IN2P3, UMR5822 IPNL,F-69622 Villeurbanne Cedex (France); Centre for Cosmology, Particle Physics and Phenomenology (CP3),Université catholique de Louvain,Chemin du Cyclotron 2, B-1348 Louvain-la-Neuve (Belgium)

2016-04-14

We study a class of six-dimensional models based on positive curvature surfaces (spherical 2-orbifolds) as extra-spaces. Using the Newman-Penrose formalism, we discuss the particle spectrum in this class of models. The fermion spectrum problem, which has been addressed with flux compactifications in the past, can be avoided using localised fermions. In this framework, we find that there are four types of geometry compatible with the existence of a stable dark matter candidate and we study the simplest case in detail. Using the complementarity between collider resonance searches and relic density constraints, we show that this class of models is under tension, unless the model lies in a funnel region characterised by a resonant Higgs s-channel in the dark matter annihilation.

Gene amplification as a cause of inherited thyroxine-binding globulin excess in two Japanese families

Energy Technology Data Exchange (ETDEWEB)

Mori, Yuichi; Miura, Yoshitaka; Saito, Hidehiko [Toyota Memorial Hospital (Japan)] [and others

1995-12-01

T{sub 4}-binding globulin (TBG) is the major thyroid hormone transport protein in man. Inherited abnormalities in the level of serum TBG have been classified as partial deficiency, complete deficiency, and excess. Sequencing analysis of the TBG gene, located on Xq21-22, has uncovered the molecular defects causing partial and complete deficiency. However, the mechanism leading to inherited TBG excess remains unknown. In this study, two Japanese families, F-A and F-T, with inherited TBG excess were analyzed. Serum TBG levels in hemizygous males were 58 and 44 {mu}g/mL, 3- and 2-fold the normal value, respectively. The molecule had normal properties in terms of heat stability and isoelectric focussing pattern. The sequence of the coding region and the promoter activity of the TBG gene were also indistinguishable between hemizygotes and normal subjects. The gene dosage of TBG relative to that of {beta}-globin, which is located on chromosome 11, and Duchenne muscular dystropy, which is located on Xp, was evaluated by coamplification of these target genes using polymerase chain reaction and subsequent quantitation by HPLC. The TBG/{beta}-globin ratios of the affected male and female of F-A were 3.13 and 4.13 times, respectively, that in the normal males. The TBG/Duchenne muscular dystrophy ratios were 2.92 and 2.09 times the normal value, respectively. These results are compatible with three copies of TBG gene on the affected X-chromosome. Similarly, a 2-fold increase in gene dosage was demonstrated in the affected hemizygote of F-T. A 3-fold tandem amplification of the TBG gene was shown by in situ hybridization of prometaphase and interphase chromosomes from the affected male with a biotinylated genomic TBG probe, confirming the gene dosage results. Gene amplification of TBG is the cause of inherited TBG excess in these two families. 35 refs., 3 figs., 2 tabs.

Fear of new or recurrent melanoma after treatment for localised melanoma.

Science.gov (United States)

Bell, Katy J L; Mehta, Yachna; Turner, Robin M; Morton, Rachael L; Dieng, Mbathio; Saw, Robyn; Guitera, Pascale; McCaffery, Kirsten; Low, Donald; Low, Cynthia; Jenkins, Marisa; Irwig, Les; Webster, Angela C

2017-11-01

To estimate the amount of fear of new or recurrent melanoma among people treated for localised melanoma in an Australian specialist centre. We randomly selected 400 potential participants from all those treated for localised melanoma at the Melanoma Institute Australia during 2014 (n = 902). They were asked to complete an adapted version of the Fear of Cancer Recurrence Inventory (FCRI). We calculated summary statistics for demographics, clinical variables and total FCRI and subscale scores. Two hundred fifteen people (54%) completed the FCRI questionnaire. The overall mean severity subscale score was 15.0 (95% CI 14.0-16.1). A high proportion of participants had scores above a proposed threshold to screen for clinical fear of cancer recurrence (77% and 63% of participants with and without new or recurrent melanoma had severity subscale scores ≥13). Most participants also had scores above a threshold found to have high specificity for clinical fear of cancer recurrence (65% and 48% of participants with and without new or recurrent melanoma had severity subscale scores ≥16). The severity subscale appeared to discriminate well between groups with differing levels of risk of new or recurrent melanoma. There is a substantial amount of fear of new or recurrent melanoma among this population, despite most having a very good prognosis. Copyright © 2017 John Wiley & Sons, Ltd.

How active ingredient localisation in plant tissues determines the targeted pest spectrum of different chemistries

DEFF Research Database (Denmark)

Buchholz, Anke; Trapp, Stefan

2016-01-01

information sets revealed that the intracellular localisation of active ingredients determines the performance of test compounds against different target pests because of different feeding behaviours: mites feed on mesophyll, and aphids and whiteflies mostly in the vascular system. Polar compounds have a slow...

[Using exon combined target region capture sequencing chip to detect the disease-causing genes of retinitis pigmentosa].

Science.gov (United States)

Rong, Weining; Chen, Xuejuan; Li, Huiping; Liu, Yani; Sheng, Xunlun

2014-06-01

To detect the disease-causing genes of 10 retinitis pigmentosa pedigrees by using exon combined target region capture sequencing chip. Pedigree investigation study. From October 2010 to December 2013, 10 RP pedigrees were recruited for this study in Ningxia Eye Hospital. All the patients and family members received complete ophthalmic examinations. DNA was abstracted from patients, family members and controls. Using exon combined target region capture sequencing chip to screen the candidate disease-causing mutations. Polymerase chain reaction (PCR) and direct sequencing were used to confirm the disease-causing mutations. Seventy patients and 23 normal family members were recruited from 10 pedigrees. Among 10 RP pedigrees, 1 was autosomal dominant pedigrees and 9 were autosomal recessive pedigrees. 7 mutations related to 5 genes of 5 pedigrees were detected. A frameshift mutation on BBS7 gene was detected in No.2 pedigree, the patients of this pedigree combined with central obesity, polydactyly and mental handicap. No.2 pedigree was diagnosed as Bardet-Biedl syndrome finally. A missense mutation was detected in No.7 and No.10 pedigrees respectively. Because the patients suffered deafness meanwhile, the final diagnosis was Usher syndrome. A missense mutation on C3 gene related to age-related macular degeneration was also detected in No. 7 pedigrees. A nonsense mutation and a missense mutation on CRB1 gene were detected in No. 1 pedigree and a splicesite mutation on PROM1 gene was detected in No. 5 pedigree. Retinitis pigmentosa is a kind of genetic eye disease with diversity clinical phenotypes. Rapid and effective genetic diagnosis technology combined with clinical characteristics analysis is helpful to improve the level of clinical diagnosis of RP.

Localisation of the neuropeptide PACAP and its receptors in the rat parathyroid and thyroid glands

DEFF Research Database (Denmark)

Fahrenkrug, Jan; Hannibal, Jens

2011-01-01

PACAP (pituitary adenylate cyclase activating polypeptide) is widely distributed neuropeptide acting via three subtypes of receptors, PAC(1), VPAC(1) and VPAC(2). Here we examined the localisation and nature of PACAP-immunoreactive nerves in the rat thyroid and parathyroid glands and defined the ...

'Glocal' disorder: causes, conduct and consequences of the 2008 Greek unrest

OpenAIRE

Xenakis, Sappho; Cheliotis, L.K.

2016-01-01

This article examines the unrest that emanated in Athens and rolled out across Greek cities in December 2008 as a case through which to advance understanding of how local, national and international arenas may together shape localised episodes of disorder. We begin by addressing the proximate and structural causes of the unrest, before turning to explore the multifarious character of protest actions, including novel and derivative forms of contestation deployed by protestors, and public debat...

Allogeneic transplantation for multiple myeloma: late relapse may occur as localised lytic lesion/plasmacytoma despite ongoing molecular remission.

Science.gov (United States)

Byrne, J L; Fairbairn, J; Davy, B; Carter, I G; Bessell, E M; Russell, N H

2003-02-01

Allogeneic SCT for myeloma may be curative for young patients, but its role remains controversial because of a reported high TRM in some series. Since 1991, we have performed 25 allografts for myeloma using fully matched sibling donors. Of the 18 evaluable patients, 13 achieved CR at a median time of 2.5 months post-transplant. The five patients who were not in CR when assessed at 3 months received a short course of alpha-interferon and four subsequently achieved CR with this approach at a median of 82 days. One patient who failed to respond to IFN went on to achieve CR after four doses of DLI therapy, thus giving an overall CR rate of 72%. Seven patients have relapsed at a median of 4.7 years post-transplant (range 1.38-7.7 years) including two patients who had received IFN therapy. In five of these cases, relapse has been as a localised area of bone disease or isolated plasmacytoma with no evidence of marrow involvement by trephine biopsy or molecular analysis. All patients with localised relapse were treated with local radiotherapy +/-DLI and four are currently disease free despite two patients having had further treatment for a second localised lesion. Six patients died of TRM (24%) and the OS at 8 years is currently 69% with an EFS of 26%. These results suggest that allogeneic SCT for myeloma can be carried out with an acceptable TRM and a high CR rate. However, late relapses as localised disease may be a frequent finding and may represent foci of myeloma not eradicated by the conditioning. The use of pretransplant MRI scanning and top-up radiotherapy to involved areas may be useful in preventing this type of relapse.

Splicing defect in FKBP10 gene causes autosomal recessive osteogenesis imperfecta disease: a case report.

Science.gov (United States)

Maghami, Fatemeh; Tabei, Seyed Mohammad Bagher; Moravej, Hossein; Dastsooz, Hassan; Modarresi, Farzaneh; Silawi, Mohammad; Faghihi, Mohammad Ali

2018-05-25

Osteogenesis imperfecta (OI) is a group of connective tissue disorder caused by mutations of genes involved in the production of collagen and its supporting proteins. Although the majority of reported OI variants are in COL1A1 and COL1A2 genes, recent reports have shown problems in other non-collagenous genes involved in the post translational modifications, folding and transport, transcription and proliferation of osteoblasts, bone mineralization, and cell signaling. Up to now, 17 types of OI have been reported in which types I to IV are the most frequent cases with autosomal dominant pattern of inheritance. Here we report an 8- year- old boy with OI who has had multiple fractures since birth and now he is wheelchair-dependent. To identify genetic cause of OI in our patient, whole exome sequencing (WES) was carried out and it revealed a novel deleterious homozygote splice acceptor site mutation (c.1257-2A > G, IVS7-2A > G) in FKBP10 gene in the patient. Then, the identified mutation was confirmed using Sanger sequencing in the proband as homozygous and in his parents as heterozygous, indicating its autosomal recessive pattern of inheritance. In addition, we performed RT-PCR on RNA transcripts originated from skin fibroblast of the proband to analyze the functional effect of the mutation on splicing pattern of FKBP10 gene and it showed skipping of the exon 8 of this gene. Moreover, Real-Time PCR was carried out to quantify the expression level of FKBP10 in the proband and his family members in which it revealed nearly the full decrease in the level of FKBP10 expression in the proband and around 75% decrease in its level in the carriers of the mutation, strongly suggesting the pathogenicity of the mutation. Our study identified, for the first time, a private pathogenic splice site mutation in FKBP10 gene and further prove the involvement of this gene in the rare cases of autosomal recessive OI type XI with distinguished clinical manifestations.

A discussion on the merits and limitations of using drive-by monitoring to detect localised damage in a bridge

Science.gov (United States)

Hester, David; González, Arturo

2017-06-01

Given the large number of bridges that currently have no instrumentation, there are obvious advantages in monitoring the condition of a bridge by analysing the response of a vehicle crossing it. As a result, the last two decades have seen a rise in the research attempting to solve the problem of identifying damage in a bridge from vehicle measurements. This paper examines the theoretical feasibility and practical limitations of a drive-by system in identifying damage associated to localised stiffness losses. First, the nature of the damage feature that is sought within the vehicle response needs to be characterized. For this purpose, the total vehicle response is considered to be made of 'static' and 'dynamic' components, and where the bridge has experienced a localised loss in stiffness, an additional 'damage' component. Understanding the nature of this 'damage' component is crucial to have an informed discussion on how damage can be identified and localised. Leveraging this new understanding, the authors propose a wavelet-based drive-by algorithm. By comparing the effect of the 'damage' component to other key effects defining the measurements such as 'vehicle speed', the 'road profile' and 'noise' on a wavelet contour plot, it is possible to establish if there is a frequency range where drive-by can be successful. The algorithm uses then specific frequency bands to improve the sensitivity to damage with respect to limitations imposed by Vehicle-Bridge vibrations. Recommendations on the selection of the mother wavelet and frequency band are provided. Finally, the paper discusses the impact of noise and road profile on the ability of the approach to identify damage and how periodic measurements can be effective at monitoring localised stiffness changes.

Comparison of 68Ga-DOTANOC PET/CT and contrast-enhanced CT in localisation of tumours in ectopic ACTH syndrome

Science.gov (United States)

Jadhav, Swati S; Lila, Anurag R; Kasaliwal, Rajeev; Khare, Shruti; Yerawar, Chaitanya G; Hira, Priya; Phadke, Uday; Shah, Hina; Lele, Vikram R; Malhotra, Gaurav; Bandgar, Tushar; Shah, Nalini S

2016-01-01

Background Localising ectopic adrenocorticotrophic hormone (ACTH) syndrome (EAS) tumour source is challenging. Somatostatin receptor-based PET imaging has shown promising results, but the data is limited to case reports and small case series. We reviewed here the performance of 68Ga-DOTANOC positron emission tomography (PET)/computed tomography (CT) and contrast-enhanced CT (CECT) in our cohort of 12 consecutive EAS patients. Materials and methods Retrospective data analysis of 12 consecutive patients of EAS presenting to a single tertiary care centre in a period between January 2013 and December 2014 was done. CECT and 68Ga-DOTANOC PET/CT were reported (blinded) by an experienced radiologist and a nuclear medicine physician, respectively. The performance of CECT and 68Ga-DOTANOC PET/CT was compared. Results Tumours could be localised in 11 out of 12 patients at initial presentation (overt cases), whereas in one patient, tumour remained occult. Thirteen lesions were identified in 11 patients as EAS source (true positives). CECT localised 12 out of these 13 lesions (sensitivity 92.3%) and identified five false-positive lesions (positive predictive value (PPV) 70.5%). Compared with false-positive lesions, true-positive lesions had greater mean contrast enhancement at 60s (33.2 vs 5.6 Hounsfield units (HU)). 68Ga-DOTANOC PET/CT was able to identify 9 out of 13 lesions (sensitivity 69.2%) and reported no false-positive lesions (PPV 100%). Conclusion CECT remains the first-line investigation in localisation of EAS. The contrast enhancement pattern on CECT can further aid in characterisation of the lesions. 68Ga-DOTANOC PET/CT can be added to CECT, to enhance positive prediction of the suggestive lesions. PMID:27006371

Flow in a circular expansion pipe flow: effect of a vortex perturbation on localised turbulence

Energy Technology Data Exchange (ETDEWEB)

Selvam, Kamal; Peixinho, Jorge [Laboratoire Ondes Milieux Complexes, CNRS and Université du Havre, F-76600 Le Havre (France); Willis, Ashley P, E-mail: jorge.peixinho@univ-lehavre.fr [School of Mathematics and Statistics, University of Sheffield, Sheffield S3 7RH (United Kingdom)

2016-12-15

We report the results of three-dimensional direct numerical simulations for incompressible viscous fluid in a circular pipe flow with a sudden expansion. At the inlet, a parabolic velocity profile is applied together with a finite amplitude perturbation in the form of a vortex with its axis parallel to the axis of the pipe. At sufficiently high Reynolds numbers the recirculation region breaks into a turbulent patch that changes position axially, depending on the strength of the perturbation. This vortex perturbation is believed to produce a less abrupt transition than in previous studies, which applied a tilt perturbation, as the localised turbulence is observed via the formation of a wavy structure at a low order azimuthal mode, which resembles an optimally amplified perturbation. For large vortex amplitude, the localised turbulence remains at a constant axial position. It is further investigated using proper orthogonal decomposition, which indicates that the centre region close to the expansion is highly energetic. (paper)

Active surveillance strategy for patients with localised prostate cancer

DEFF Research Database (Denmark)

Thomsen, Frederik Birkebæk

2014-01-01

BACKGROUND: Active surveillance - an initial observational strategy - offers a tailored management of patients with localised prostate cancer. The aim of the strategy is to appoint patients with potentially lethal prostate cancer to curatively intended treatment, while patients with slowly evolving...... measurements, repeated biopsies, and regular digital rectal examinations. The programme recommended change of management from active surveillance to curatively intended treatment based on PSA doubling time, deteriorating histopathology in repeated prostatic biopsies, and increased clinical tumour category...... with defined final histopathological findings at radical prostatectomy that was perceived as unacceptable for a continued observational strategy. CONCLUSION: The thesis has demonstrated that active surveillance is feasible and reduces the number of patients undergoing curative intended treatment. However...

Familial Dilated Cardiomyopathy Caused by a Novel Frameshift in the BAG3 Gene.

Directory of Open Access Journals (Sweden)

Rocio Toro

Full Text Available Dilated cardiomyopathy, a major cause of chronic heart failure and cardiac transplantation, is characterized by left ventricular or biventricular heart dilatation. In nearly 50% of cases the pathology is inherited, and more than 60 genes have been reported as disease-causing. However, in 30% of familial cases the mutation remains unidentified even after comprehensive genetic analysis. This study clinically and genetically assessed a large Spanish family affected by dilated cardiomyopathy to search for novel variations.Our study included a total of 100 family members. Clinical assessment was performed in alive, and genetic analysis was also performed in alive and 1 deceased relative. Genetic screening included resequencing of 55 genes associated with sudden cardiac death, and Sanger sequencing of main disease-associated genes. Genetic analysis identified a frame-shift variation in BAG3 (p.H243Tfr*64 in 32 patients. Genotype-phenotype correlation identified substantial heterogeneity in disease expression. Of 32 genetic carriers (one deceased, 21 relatives were clinically affected, and 10 were asymptomatic. Seventeen of the symptomatic genetic carriers exhibited proto-diastolic septal knock by echocardiographic assessment.We report p.H243Tfr*64_BAG3 as a novel pathogenic variation responsible for familial dilated cardiomyopathy. This variation correlates with a more severe phenotype of the disease, mainly in younger individuals. Genetic analysis in families, even asymptomatic individuals, enables early identification of individuals at risk and allows implementation of preventive measures.

Tumour Suppressor Adenomatous Polyposis Coli (APC) localisation is regulated by both Kinesin-1 and Kinesin-2

NARCIS (Netherlands)

Ruane, Peter T; Gumy, Laura F; Bola, Becky; Anderson, Beverley; Wozniak, Marcin J; Hoogenraad, Casper C; Allan, Victoria J

2016-01-01

Microtubules and their associated proteins (MAPs) underpin the polarity of specialised cells. Adenomatous polyposis coli (APC) is one such MAP with a multifunctional agenda that requires precise intracellular localisations. Although APC has been found to associate with kinesin-2 subfamily members,

Gene expression profiling: cell cycle deregulation and aneuploidy do not cause breast cancer formation in WAP-SVT/t transgenic animals.

Science.gov (United States)

Klein, Andreas; Guhl, Eva; Zollinger, Raphael; Tzeng, Yin-Jeh; Wessel, Ralf; Hummel, Michael; Graessmann, Monika; Graessmann, Adolf

2005-05-01

Microarray studies revealed that as a first hit the SV40 T/t antigen causes deregulation of 462 genes in mammary gland cells (ME cells) of WAP-SVT/t transgenic animals. The majority of deregulated genes are cell proliferation specific and Rb-E2F dependent, causing ME cell proliferation and gland hyperplasia but not breast cancer formation. In the breast tumor cells a further 207 genes are differentially expressed, most of them belonging to the cell communication category. In tissue culture breast tumor cells frequently switch off WAP-SVT/t transgene expression and regain the morphology and growth characteristics of normal ME cells, although the tumor-revertant cells are aneuploid and only 114 genes regain the expression level of normal ME cells. The profile of retransformants shows that only 38 deregulated genes are tumor-specific, and that none of them is considered to be a typical breast cancer gene.

Methamphetamine causes differential alterations in gene expression and patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens.

Directory of Open Access Journals (Sweden)

Tracey A Martin

Full Text Available Methamphetamine (METH addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC. Our study investigated the effects of a non-toxic METH injection (20 mg/kg on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT, ATF2, and of the histone deacetylases (HDACs, HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf. In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck. Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac and lysine 18 (H3K18ac in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and

Improvement of localised corrosion resistance of AISI 2205 Duplex Stainless Steel joints made by gas metal arc welding under electromagnetic interaction of low intensity

Energy Technology Data Exchange (ETDEWEB)

García-Rentería, M.A., E-mail: crazyfim@gmail.com [Instituto de Investigación en Metalurgia y Materiales, Universidad Michoacana de San Nicolás de Hidalgo, A.P. 888, CP 58000, Morelia, Michoacán (Mexico); López-Morelos, V.H., E-mail: vhlopez@umich.mx [Instituto de Investigación en Metalurgia y Materiales, Universidad Michoacana de San Nicolás de Hidalgo, A.P. 888, CP 58000, Morelia, Michoacán (Mexico); García-Hernández, R., E-mail: rgarcia@umich.mx [Instituto de Investigación en Metalurgia y Materiales, Universidad Michoacana de San Nicolás de Hidalgo, A.P. 888, CP 58000, Morelia, Michoacán (Mexico); Dzib-Pérez, L., E-mail: luirdzib@uacam.mx [Centre for Corrosion Research, Autonomous University of Campeche, Av. Agustín Melgar s/n, Col. Buenavista, CP 24039, Campeche, Cam (Mexico); García-Ochoa, E.M., E-mail: emgarcia@uacam.mx [Centre for Corrosion Research, Autonomous University of Campeche, Av. Agustín Melgar s/n, Col. Buenavista, CP 24039, Campeche, Cam (Mexico); González-Sánchez, J., E-mail: jagonzal@uacam.mx [Centre for Corrosion Research, Autonomous University of Campeche, Av. Agustín Melgar s/n, Col. Buenavista, CP 24039, Campeche, Cam (Mexico)

2014-12-01

Highlights: • Electromagnetic interaction in welding improved localised corrosion resistance. • Electromagnetic interaction in welding enhanced γ/δ phase balance of DuplexSS. • Welding under Electromagnetic interaction repress formation and growth of detrimental phases. • Welds made with gas protection (2% O{sub 2} + 98% Ar) have better microstructural evolution during welding. - Abstract: The resistance to localised corrosion of AISI 2205 duplex stainless steel plates joined by Gas Metal Arc Welding (GMAW) under the effect of electromagnetic interaction of low intensity (EMILI) was evaluated with sensitive electrochemical methods. Welds were made using two shielding gas mixtures: 98% Ar + 2% O{sub 2} (M1) and 97% Ar + 3% N{sub 2} (M2). Plates were welded under EMILI using the M1 gas with constant welding parameters. The modified microstructural evolution in the high temperature heat affected zone and at the fusion zone induced by application of EMILI during welding is associated with the increase of resistance to localised corrosion of the welded joints. Joints made by GMAW using the shielding gas M2 without the application of magnetic field presented high resistance to general corrosion but high susceptibility to undergo localised attack.

Radio-guided occult lesion localisation using iodine-125 seeds ('ROLLIS') for removal of impalpable breast lesions: first Australian experience

International Nuclear Information System (INIS)

Taylor, Donna B.; Bourke, Anita G.; Westcott, Eliza

2015-01-01

Approximately one-third of breast cancers are impalpable and require pre-operative image-guided localisation. Hook-wire localisation (HWL) is commonly used but has several disadvantages. Use of a low-activity radioactive iodine-125 seed is a promising alternative technique used in the USA and the Netherlands. This pilot study describes the first use of this in Australia. In this prospective pilot study, 21 participants with biopsy-proven breast cancer underwent radio guided occult lesion localisation using iodine-125 seed(s) (ROLLIS) with insertion of a hook-wire for back up. Sentinel node biopsy was performed where indicated. Ease of hook-wire and seed insertion, duration of the procedure, dependence on the seed versus hook-wire during surgery, lesion location within the specimen, histopathology including size of radial margins, the ease of seed retrieval in pathology, and safe return of seeds for disposal were documented. Radiation dosimetry of staff was performed. All seeds were placed within 3.5 mm of the lesion. All lesions and seeds were removed. One participant needed re-excision for involved margins. Radiologists and surgeons both preferred ROLLIS. Surgeons were able to depend on the seed for localisation in all but one case. Sentinel node biopsy was successfully performed when required. Pathologists found seed retrieval quick and easy, with no detrimental effect on tissue processing. No radiation doses measurably above background were received by staff. ROLLIS is an easily learnt, safe and effective alternative technique to standard HWL.

Two patients with localised hyperhidrosis of the hand based on functional and structural abnormalities of sweat glands

DEFF Research Database (Denmark)

Kristiansen, Bjørn H; Lindahl, Kim H; Pallesen, Kristine A U

2018-01-01

A 14-year-old girl and a 30-year-old woman presented with localised hyperhidrosis on the dorsal hand and wrist, respectively, provoked by different stimuli such as physical activity and minor trauma to the skin. The skin was seemingly normal in both patients where an iodine-starch test revealed...... a well-demarcated area of hyperhidrosis. Following histopathological examination, the diagnosis was unilateral localised hyperhidrosis in both cases; one with normal histology and one with a nevus sudoriferous. Both patients were successfully treated with botulinum toxin type A. The 30-year-old woman...... additionally used low-dose propantheline bromide periodically and experienced long-term remission on this therapy. Hyperhidrosis may embarrass and interfere with patients' school and careers, and it is therefore important to tailor an effective individual treatment....

Study of the possibility of localising a channel instability in Forsmark-1

International Nuclear Information System (INIS)

Karlsson, J.K-H.; Pazsit, I.

1998-01-01

A special type of instability occurred in the Swedish BWR Forsmark 1 in 1996. In contrast to the better known global or regional instabilities, the decay ratio appeared to be very high in one half of the core and quite low in the other half. A more detailed analysis showed that the most likely reason for the observed behaviour is a local perturbation of thermohydraulic character induced by the incorrect positioning of a fuel assembly. In such a case it is of importance to determine the position of the unseated assembly already during operation so that it can be easily found during reloading. The subject of this paper is to report on development and application of a method by which the position of such a local perturbation can be determined. The method can be separated into two parts that support and complement each other. First a visualisation technique was elaborated which displays the space-time behaviour of the neutron flux oscillations in the core. This visualisation expedites a very good qualitative comprehension of the situation and can be useful for the operators. It also gives a basis for the application of the localisation algorithm. Second, a quantitative localisation method, based on reactor physical models of the perturbation and of the transfer function between the perturbation and the flux oscillations, was elaborated. This latter takes noise spectra from selected detectors as input and yields the perturbation position as output. The strength of the method lies in its potentially high spatial resolution, which is smaller than the typical distance between two adjacent LPRM detectors. The method was tested on simulated data, and then applied to the Forsmark measurements. The location of the disturbance, found by the algorithm, is in accordance with independent judgements for the case, and close to a position where an unseated assembly was found during refuelling. The purpose of this study was to develop and test the localisation method. To apply the

The impact of bladder preparation protocols on post treatment toxicity in radiotherapy for localised prostate cancer patients

Directory of Open Access Journals (Sweden)

Yat Man Tsang

2017-09-01

Conclusion: The empty bladder preparation approach has non-inferior acute and intermediate post RT GI and GU toxicities in patients treated for localised prostate cancer with advanced radiotherapy techniques compared to the full bladder preparation.

Neonatal Marfan syndrome caused by an exon 25 mutation of the fibrillin-1 gene.

Science.gov (United States)

Elçioglu, N H; Akalin, F; Elçioglu, M; Comeglio, P; Child, A H

2004-01-01

Neonatal Marfan syndrome caused by an exon 25 mutation of the Fibrillin-1 gene: We describe a male infant with severe arachnodactyly, hypermobility of the fingers, flexion contractures of elbows, wrists, hips, and knees, microretrognathia, crumpled ears, rockerbottom feet, loose redundant skin, and lens dislocations. Cardiac valve insufficiency and aortic dilatation resulted in cardiac failure, decompensated with digitalisation and death occurred at the age of 4 months. This case represents the severe end of the clinical spectrum of Marfan syndrome, namely neonatal Marfan syndrome. Molecular diagnostic analyses confirmed a de novo exon 25 mutation in the FBN1 gene.

Exploiting deep neural networks and head movements for binaural localisation of multiple speakers in reverberant conditions

DEFF Research Database (Denmark)

Ma, Ning; Brown, Guy J.; May, Tobias

2015-01-01

This paper presents a novel machine-hearing system that exploits deep neural networks (DNNs) and head movements for binaural localisation of multiple speakers in reverberant conditions. DNNs are used to map binaural features, consisting of the complete crosscorrelation function (CCF) and interaural...

Genes and Gut Bacteria Involved in Luminal Butyrate Reduction Caused by Diet and Loperamide.

Science.gov (United States)

Hwang, Nakwon; Eom, Taekil; Gupta, Sachin K; Jeong, Seong-Yeop; Jeong, Do-Youn; Kim, Yong Sung; Lee, Ji-Hoon; Sadowsky, Michael J; Unno, Tatsuya

2017-11-28

Unbalanced dietary habits and gut dysmotility are causative factors in metabolic and functional gut disorders, including obesity, diabetes, and constipation. Reduction in luminal butyrate synthesis is known to be associated with gut dysbioses, and studies have suggested that restoring butyrate formation in the colon may improve gut health. In contrast, shifts in different types of gut microbiota may inhibit luminal butyrate synthesis, requiring different treatments to restore colonic bacterial butyrate synthesis. We investigated the influence of high-fat diets (HFD) and low-fiber diets (LFD), and loperamide (LPM) administration, on key bacteria and genes involved in reduction of butyrate synthesis in mice. MiSeq-based microbiota analysis and HiSeq-based differential gene analysis indicated that different types of bacteria and genes were involved in butyrate metabolism in each treatment. Dietary modulation depleted butyrate kinase and phosphate butyryl transferase by decreasing members of the Bacteroidales and Parabacteroides . The HFD also depleted genes involved in succinate synthesis by decreasing Lactobacillus . The LFD and LPM treatments depleted genes involved in crotonoyl-CoA synthesis by decreasing Roseburia and Oscilllibacter . Taken together, our results suggest that different types of bacteria and genes were involved in gut dysbiosis, and that selected treatments may be needed depending on the cause of gut dysfunction.

Hydrodynamic gene delivery in human skin using a hollow microneedle device

OpenAIRE

Dul, M.; Stefanidou, M.; Porta, P.; Serve, J.; O'Mahony, Conor; Malissen, B.; Henri, S.; Levin, Y.; Kochba, E.; Wong, F. S.; Dayan, C.; Coulman, S. A.; Birchall, J. C.

2017-01-01

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potenti...

Development of an explanatory model of sexual intimacy following treatment for localised prostate cancer: A systematic review and meta-synthesis of qualitative evidence.

Science.gov (United States)

Tucker, Samantha R; Speer, Susan A; Peters, Sarah

2016-08-01

Prostate cancer is a leading cause of cancer in men, affecting one in eight. An ageing population coupled with increased testing indicates that the incidence of early-stage prostate cancer is rising rapidly. Treatments are effective, but all can result in chronic sexual side effects and impact on the psychological, emotional and relational components of sexual functioning. Whilst the physical consequences of treatment are well documented, we lack a comprehensive picture of the effects of localised prostate cancer treatment on men's experience of sexual intimacy and how this may affect survivorship and recovery. This study synthesises the qualitative literature related to men's experience of sexual intimacy in the context of localised prostate cancer. A systematic search strategy identified 12 studies, which were assessed using a modified version of the Critical Appraisal Skills Programme. Using Noblit and Hare's (1988) approach, a meta-synthesis was conducted. Findings are organised within four inter-related themes that form the basis of a new conceptual explanatory model: (i) Loss and grief: Destroyed intimacy; (ii) Going through the motions: Artificial intimacy; (iii) Fear of failure: Avoiding intimacy and (iv) Breaking barriers: Constructing an alternative intimacy. The LMAC (Loss, Motions, Avoidance and Construction) model provides a new way of conceptualising sexual recovery following prostate cancer treatment and opportunities for health care professionals to support men and their partners. Copyright © 2016 Elsevier Ltd. All rights reserved.

3D Image Fusion to Localise Intercostal Arteries During TEVAR

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G. Koutouzi

Full Text Available Purpose: Preservation of intercostal arteries during thoracic aortic procedures reduces the risk of post-operative paraparesis. The origins of the intercostal arteries are visible on pre-operative computed tomography angiography (CTA, but rarely on intra-operative angiography. The purpose of this report is to suggest an image fusion technique for intra-operative localisation of the intercostal arteries during thoracic endovascular repair (TEVAR. Technique: The ostia of the intercostal arteries are identified and manually marked with rings on the pre-operative CTA. The optimal distal landing site in the descending aorta is determined and marked, allowing enough length for an adequate seal and attachment without covering more intercostal arteries than necessary. After 3D/3D fusion of the pre-operative CTA with an intra-operative cone-beam CT (CBCT, the markings are overlaid on the live fluoroscopy screen for guidance. The accuracy of the overlay is confirmed with digital subtraction angiography (DSA and the overlay is adjusted when needed. Stent graft deployment is guided by the markings. The initial experience of this technique in seven patients is presented. Results: 3D image fusion was feasible in all cases. Follow-up CTA after 1 month revealed that all intercostal arteries planned for preservation, were patent. None of the patients developed signs of spinal cord ischaemia. Conclusion: 3D image fusion can be used to localise the intercostal arteries during TEVAR. This may preserve some intercostal arteries and reduce the risk of post-operative spinal cord ischaemia. Keywords: TEVAR, Intercostal artery, Spinal cord ischaemia, 3D image fusion, Image guidance, Cone-beam CT

Screening for mutations in the androgen receptor gene (AR) causing infertility in Syrian men using real-time PCR

International Nuclear Information System (INIS)

Madania, A.; Ghouri, I.; Abou-Alshamat, Gh.; Issa, M.; Al-Halabi, M.

2012-01-01

14 known point mutations in the androgen receptor gene (AR) causing male infertility were screened by real time PCR and by DNA sequencing, in order to identify point mutations in the AR gene causing infertility in azoospermic men. We screened 110 Syrian patients suffering from non-obstructive azoospermia with no chromosomal aberrations or AZF micro deletions. We discovered a new AR mutation, del 57Leu, described for the first time as a possible cause of male infertility. Furthermore, we found two patients with the Ala474Val mutation and one patient bearing the Pro390Ser mutation. Our results indicate that these mutations are significant markers for idiopathic male infertility in the Syrian society and in Mediterranean populations in general. (author)

Characterisation of the NUCKS gene on human chromosome 1q32.1 and the presence of a homologous gene in different species

International Nuclear Information System (INIS)

Grundt, Kirsten; Haga, Ingvild Vagslid; Aleporou-Marinou, Vasiliki; Drosos, Yiannis; Wanvik, Birgit; Ostvold, Anne Carine

2004-01-01

The NUCKS gene is located on human chromosome 1q32.1 and consists of seven exons and six introns. The gene lacks a TATA box but contains two Inr elements, two GC boxes, and one consensus-binding site for E2F-1. NUCKS is expressed in all human adult and foetal tissues investigated, and has all the features of being a housekeeping gene. Both data searches and Western immunoblotting experiments show that a homologous protein is present in fish, amphibians, and birds but not in insects and yeast, suggesting that NUCKS is a vertebrate specific gene. In all the species investigated, the protein contains several consensus phosphorylation sites for cyclin-dependent kinases and CK-2, and we have shown that the fish protein (like mammalian NUCKS) indeed is a substrate for CDK1 and CK-2 in vitro. The NUCKS protein is also conserved with respect to a DNA-binding domain previously characterised in mammals, and two putative bipartite nuclear localisation signals

Expression and Immunohistochemical Localisation of the G beta gamma activated and Calcineurin-inhibited Adenylyl Cyclase Isoforms in Rat Articular Chondrocytes

International Nuclear Information System (INIS)

Memon, I.; Khan, K.M.; Siddiqui, S.; Perveen, S.; Ishaq, M.

2016-01-01

Objective: To determine the expression and localisation of the Gβγ-activated adenylyl cyclase (AC) isoforms 2, 4, and 7 and calcineurin-inhibited AC isoform 9 in rat articular chondrocytes. Study Design: Experimental study. Place and Duration of Study: Jumma Research Laboratory and Histology Laboratory, The Aga Khan University, Karachi, from 2009 to 2011. Methodology: Fresh slices of articular cartilage were taken from various synovial joints of rats of different age groups. The expression of AC isoforms was determined by RT-PCR and immunohistochemistry was performed to localise these isoforms in articular chondrocytes. Tissue sections were processed for immunostaining with respective antibodies. The color was developed by diaminobenzidine. Results: All the studied AC isoforms were found to be differentially expressed in different zones of the rat articular cartilage. Generally, expression of all AC isoforms studied increased with age. The expression of the AC isoforms through PCR was almost consistent with the localisation of these isoforms by immunohistochemistry. Conclusion: These data add to the information about signalling cascades possibly involved in articular chondrocytes. Variable expression of AC isoforms 2, 4, 7, and 9 suggest a role for the signalling cascades regulated by the AC isoforms in articular chondrocytes. (author)

Quantitative elemental localisation in leaves and stems of nickel hyperaccumulating shrub Hybanthusfloribundus subsp. floribundus using micro-PIXE spectroscopy

International Nuclear Information System (INIS)

Kachenko, Anthony G; Singh, Balwant; Bhatia, Naveen P; Siegele, Rainer

2008-01-01

Hybanthusfloribundus (Lindl.) F.Muell. subsp. floribundus is a native Australian nickel (Ni) hyperaccumulating shrub and a promising species for rehabilitation and phytoremediation of Ni tailings. Spatial localisation and quantification of Ni in leaf and stem tissues of H.floribundus subsp. floribundus was studied using micro-proton-induced X-ray emission (micro-PIXE) spectroscopy. Young plants, grown in a potting mix under controlled glasshouse conditions were exposed to Ni concentrations of 0 and 26 mM kg -1 for 20 weeks. Leaf and stem samples were hand-sectioned and freeze-dried prior to micro-PIXE analysis. Elemental distribution maps of leaves revealed Ni concentration of 7800 mg kg -1 dry weight (DW) in whole leaf sections, which was identical to the bulk tissue analysis. Elemental maps showed that Ni was preferentially localised in the adaxial epidermis (10,000 mg kg -1 DW) and reached a maximum of up to 10,000 mg kg -1 DW in the leaf margin. Freeze-dried stem sections from the same plants contained lower Ni than leaf tissues (1800 mg kg -1 versus 7800 mg kg -1 DW, respectively), however did not resolve a clear pattern of compartmentalisation across different anatomical regions. Our results suggest localisation in epidermal cells is an important physiological mechanism involved in Ni accumulation and tolerance in leaves of H.floribundus subsp. floribundus

First contiguous gene deletion causing biotinidase deficiency: The enzyme deficiency in three Sri Lankan children

Directory of Open Access Journals (Sweden)

Danika Nadeen Senanayake

2015-03-01

Full Text Available We report three symptomatic children with profound biotinidase deficiency from Sri Lanka. All three children presented with typical clinical features of the disorder. The first is homozygous for a missense mutation in the BTD gene (c.98_104 del7insTCC; p.Cys33PhefsX36 that is commonly seen in the western countries, the second is homozygous for a novel missense mutation (p.Ala439Asp, and the third is the first reported instance of a contiguous gene deletion causing the enzyme deficiency. In addition, this latter finding exemplifies the importance of considering a deletion within the BTD gene for reconciling enzymatic activity with genotype, which can occur in asymptomatic children who are identified by newborn screening.

Improvement of localised corrosion resistance of AISI 2205 Duplex Stainless Steel joints made by gas metal arc welding under electromagnetic interaction of low intensity

Science.gov (United States)

García-Rentería, M. A.; López-Morelos, V. H.; García-Hernández, R.; Dzib-Pérez, L.; García-Ochoa, E. M.; González-Sánchez, J.

2014-12-01

The resistance to localised corrosion of AISI 2205 duplex stainless steel plates joined by Gas Metal Arc Welding (GMAW) under the effect of electromagnetic interaction of low intensity (EMILI) was evaluated with sensitive electrochemical methods. Welds were made using two shielding gas mixtures: 98% Ar + 2% O2 (M1) and 97% Ar + 3% N2 (M2). Plates were welded under EMILI using the M1 gas with constant welding parameters. The modified microstructural evolution in the high temperature heat affected zone and at the fusion zone induced by application of EMILI during welding is associated with the increase of resistance to localised corrosion of the welded joints. Joints made by GMAW using the shielding gas M2 without the application of magnetic field presented high resistance to general corrosion but high susceptibility to undergo localised attack.

Plant immune and growth receptors share common signalling components but localise to distinct plasma membrane nanodomains.

Science.gov (United States)

Bücherl, Christoph A; Jarsch, Iris K; Schudoma, Christian; Segonzac, Cécile; Mbengue, Malick; Robatzek, Silke; MacLean, Daniel; Ott, Thomas; Zipfel, Cyril

2017-03-06

Cell surface receptors govern a multitude of signalling pathways in multicellular organisms. In plants, prominent examples are the receptor kinases FLS2 and BRI1, which activate immunity and steroid-mediated growth, respectively. Intriguingly, despite inducing distinct signalling outputs, both receptors employ common downstream signalling components, which exist in plasma membrane (PM)-localised protein complexes. An important question is thus how these receptor complexes maintain signalling specificity. Live-cell imaging revealed that FLS2 and BRI1 form PM nanoclusters. Using single-particle tracking we could discriminate both cluster populations and we observed spatiotemporal separation between immune and growth signalling platforms. This finding was confirmed by visualising FLS2 and BRI1 within distinct PM nanodomains marked by specific remorin proteins and differential co-localisation with the cytoskeleton. Our results thus suggest that signalling specificity between these pathways may be explained by the spatial separation of FLS2 and BRI1 with their associated signalling components within dedicated PM nanodomains.

An insect-inspired bionic sensor for tactile localisation and material classification with state-dependent modulation

Directory of Open Access Journals (Sweden)

Luca ePatanè

2012-08-01

Full Text Available Insects carry a pair of antennae on their head: multimodal sensory organs that serve a wide range of sensory-guided behaviours. During locomotion, antennae are involved in near-range orientation, for example in detecting, localising, probing and negotiating obstacles.Here we present a bionic, active tactile sensing system inspired by insect antennae. It comprises an actuated elastic rod equipped with a terminal acceleration sensor. The measurement principle is based on the analysis of damped harmonic oscillations registered upon contact with an object. The dominant frequency of the oscillation is extracted to determine the distance of the contact point along the probe, and basal angular encoders allow tactile localisation in a polar coordinate system. Finally, the damping behaviour of the registered signal is exploited to determine the most likely material.The tactile sensor is tested in four approaches with increasing neural plausibility: First, we show that peak extraction from the Fourier spectrum is sufficient for tactile localisation with position errors below 1%. Also, the damping property of the extracted frequency is used for material classification. Second, we show that the Fourier spectrum can be analysed by an Artificial Neural Network which can be trained to decode contact distance and to classify contact materials. Thirdly, we show how efficiency can be improved by band-pass filtering the Fourier spectrum by application of non-negative matrix factorisation. This reduces the input dimension by 95% while reducing classification performance by 8% only. Finally, we replace the FFT by an array of spiking neurons with gradually differing resonance properties, such that their spike rate is a function of the input frequency. We show that this network can be applied to detect tactile contact events of a wheeled robot, and how detrimental effects of robot velocity on antennal dynamics can be suppressed by state-dependent modulation of the

A Case of Definitive Therapy for Localised Prostate Cancer: Report of a Urological Nightmare

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Andreas Sommerhuber

2012-01-01

Full Text Available Radical prostatectomy, external beam radiotherapy and permanent brachytherapy are the most common treatment options for nonmetastatic localised adenocarcinoma of the prostate (PCa. Accurate pretherapeutic clinical staging is difficult, the number of positive cores after biopsy does not imperatively represent the extension of the cancer. Furthermore postoperative upgrading in Gleason score is frequently observed. Even in a localised setting a certain amount of patients with organ-confined PCa will develop biochemical progression. In case of a rise in PSA level after radiation the majority of patients will receive androgen deprivation therapy what must be considered as palliative. If local or systemic progressive disease is associated with evolving neuroendocrine differentiation hormonal manipulation is increasingly ineffective; radiotherapy and systemic chemotherapy with a platinum agent and etoposide are recommended. In case of local progression complications such as pelvic pain, gross haematuria, infravesical obstruction and rectal invasion with obstruction and consecutive ileus can possibly occur. In this situation palliative radical surgery is a therapy option especially in the absence of distant metastases. A case with local and later systemic progression after permanent brachytherapy is presented here.

Multisensory stimuli improve relative localisation judgments compared to unisensory auditory or visual stimuli

OpenAIRE

Bizley, Jennifer; Wood, Katherine; Freeman, Laura

2018-01-01

Observers performed a relative localisation task in which they reported whether the second of two sequentially presented signals occurred to the left or right of the first. Stimuli were detectability-matched auditory, visual, or auditory-visual signals and the goal was to compare changes in performance with eccentricity across modalities. Visual performance was superior to auditory at the midline, but inferior in the periphery, while auditory-visual performance exceeded both at all locations....

Effect of season on peripheral resistance to localised cold stress

Science.gov (United States)

Tanaka, M.; Harimura, Y.; Tochihara, Y.; Yamazaki, S.; Ohnaka, T.; Matsui, J.; Yoshida, K.

1984-03-01

This study was carried out to determine the effect that seasonal changes have on the effect of localised cold stress on peripheral temperatures using the foot immersion method with a cold water bath. The subjects were six males and four females. The data were obtained in April, July, October and January. Skin temperature of the right index finger, the forehead, the arm, the cheek, the second toe and the instep were measured before, during and after the immersion of the feet in water at 15°C for 10 mins, as well as oxygen consumption before immersion of the feet. The average finger temperature was highest during foot immersion in the summer, next highest in the winter, then spring, and the lowest during foot immersion in the autumn. The finger temperatures during the pre-immersion period in the autumn tended to be lower than in other seasons. The finger temperatures during the pre-immersion period affected the temperature change of the finger during the immersion period. The rate of increase of the toe temperature and the foot temperature during post-immersion in the summer and the spring were greater than those in the autumn and winter. Oxygen consumption during the pre-immersion period in the autumn was significantly lower than in the other seasons (pCooling the feet caused no significant changes in the temperatures the cheek, forehead or forearm. The cheek temperature in the summer and autumn was cooler than corresponding temperatures taken in the winter and spring.

Sarcomeric gene mutations in sudden infant death syndrome (SIDS).

Science.gov (United States)

Brion, Maria; Allegue, Catarina; Santori, Montserrat; Gil, Rocio; Blanco-Verea, Alejandro; Haas, Cordula; Bartsch, Christine; Poster, Simone; Madea, Burkhard; Campuzano, Oscar; Brugada, Ramon; Carracedo, Angel

2012-06-10

In developed countries, sudden infant death syndrome (SIDS) represents the most prevalent cause of death in children between 1 month and 1 year of age. SIDS is a diagnosis of exclusion, a negative autopsy which requires the absence of structural organ disease. Although investigators have confirmed that a significant percentage of SIDS cases are actually channelopathies, no data have been made available as to whether other sudden cardiac death-associated diseases, such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of SIDS. The presence of a genetic mutation in the sarcomeric protein usually affects the force of contraction of the myocyte, whose weakness is compensated with progressive hypertrophy and disarray. However, it is unclear whether in the most incipient forms, that is, first years of life, the lack of these phenotypes still confers a risk of arrhythmogenesis. The main goal of the present study is to wonder whether genetic defects in the sarcomeric proteins, previously associated with HCM, could be responsible for SIDS. We have analysed 286 SIDS cases for the most common genes implicated in HCM in adults. A total of 680 mutations localised in 16 genes were analysed by semi-automated matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF-MS) using the Sequenom MassARRAY(®) System. Ten subjects with completely normal hearts showed mutated alleles at nine of the genetic variants analysed, and one additional novel mutation was detected by conventional sequencing. Therefore, a genetic mutation associated with HCM may cause sudden cardiac death in the absence of an identifiable phenotype. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Ureteric angioplasty balloon placement to increase localised dosage of BCG for renal pelvis TCC.

LENUS (Irish Health Repository)

Forde, J C

2012-03-01

Endoscopic percutaneous resection of a renal pelvis transitional cell carcinoma (TCC) is a viable treatment option in those who would be rendered dialysis dependent following a nephroureterectomy. We report endoscopic percutaneous resection of an upper tract TCC recurrence in a single functioning kidney followed by antegrade renal pelvis BCG instillation with novel placement of inflated angioplasty balloon in the ureter to help localise its effect.

Robust localisation of automated guided vehicles for computer-integrated manufacturing environments

Directory of Open Access Journals (Sweden)

Dixon, R. C.

2013-05-01

Full Text Available As industry moves toward an era of complete automation and mass customisation, automated guided vehicles (AGVs are used as material handling systems. However, the current techniques that provide navigation, control, and manoeuvrability of automated guided vehicles threaten to create bottlenecks and inefficiencies in manufacturing environments that strive towards the optimisation of part production. This paper proposes a decentralised localisation technique for an automated guided vehicle without any non-holonomic constraints. Incorporation of these vehicles into the material handling system of a computer-integrated manufacturing environment would increase the characteristics of robustness, efficiency, flexibility, and advanced manoeuvrability.

Localisation d'une source sonore par un réseau de microphones

OpenAIRE

Thaljaoui , Adel; Brulin , Damien; Val , Thierry; Nasri , Nejah

2014-01-01

National audience; L'assistance à domicile d'une personne âgée, notamment la connaissance de sa position géographique en tout instant, est devenue actuellement l'une des problématiques les plus urgentes. L'exploitation de l'information audio captée par un réseau de capteurs munis de microphones constitue un axe de recherche prometteur qui pourrait contribuer à une meilleure localisation dans le cadre des maisons intelligentes. Nous introduisons, dans cet article, nos premiers travaux sur la l...

Hypomorphic mutation in mouse Nppc gene causes retarded bone growth due to impaired endochondral ossification

International Nuclear Information System (INIS)

Tsuji, Takehito; Kondo, Eri; Yasoda, Akihiro; Inamoto, Masataka; Kiyosu, Chiyo; Nakao, Kazuwa; Kunieda, Tetsuo

2008-01-01

Long bone abnormality (lbab/lbab) is a spontaneous mutant mouse characterized by dwarfism with shorter long bones. A missense mutation was reported in the Nppc gene, which encodes C-type natriuretic peptide (CNP), but it has not been confirmed whether this mutation is responsible for the dwarf phenotype. To verify that the mutation causes the dwarfism of lbab/lbab mice, we first investigated the effect of CNP in lbab/lbab mice. By transgenic rescue with chondrocyte-specific expression of CNP, the dwarf phenotype in lbab/lbab mice was completely compensated. Next, we revealed that CNP derived from the lbab allele retained only slight activity to induce cGMP production through its receptor. Histological analysis showed that both proliferative and hypertrophic zones of chondrocytes in the growth plate of lbab/lbab mice were markedly reduced. Our results demonstrate that lbab/lbab mice have a hypomorphic mutation in the Nppc gene that is responsible for dwarfism caused by impaired endochondral ossification

Alu-mediated large deletion of the CDSN gene as a cause of peeling skin disease.

Science.gov (United States)

Wada, T; Matsuda, Y; Muraoka, M; Toma, T; Takehara, K; Fujimoto, M; Yachie, A

2014-10-01

Peeling skin disease (PSD) is an autosomal recessive skin disorder caused by mutations in CDSN and is characterized by superficial peeling of the upper epidermis. Corneodesmosin (CDSN) is a major component of corneodesmosomes that plays an important role in maintaining epidermis integrity. Herein, we report a patient with PSD caused by a novel homozygous large deletion in the 6p21.3 region encompassing the CDSN gene, which abrogates CDSN expression. Several genes including C6orf15, PSORS1C1, PSORS1C2, CCHCR1, and TCF19 were also deleted, however, the patient showed only clinical features typical of PSD. The deletion size was 59.1 kb. Analysis of the sequence surrounding the breakpoint showed that both telomeric and centromeric breakpoints existed within Alu-S sequences that were oriented in opposite directions. These results suggest an Alu-mediated recombination event as the mechanism underlying the deletion in our patient. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

Energy Technology Data Exchange (ETDEWEB)

Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

2005-10-01

Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

Audit of preoperative localisation of tumor with tattoo for patients undergoing laparoscopic colorectal surgery.

Science.gov (United States)

Saleh, A; Ihedioha, U; Babu, B; Evans, J; Kang, P

2016-08-01

Preoperative localisation of tumour is an essential requirement in laparoscopic colorectal surgery. Since the introduction of laparoscopic colorectal resections in NGH in February 2010, the difficulties of tumour localisation at the time of surgery without tattoo have been highlighted. Furthermore, endoscopic documentation of site of tattoo with respect to the tumour can be inconsistent and at times misleading or difficult to interpret. Tattooing guidelines should be simple to follow and consistent for all lesions irrespective of the location of the tumour. The recommendations were to place at least three spots of tattoo one mucosal fold distal to the lesion and clearly document site of tattoo with respect to tumour in the endoscopy report. We identified 100 patients undergoing elective laparoscopic colorectal cancer resections over a two-year period. Data were collected regarding presence of tattoo preoperatively as documented in the colonoscopy report and subsequently the visibility of the tattoo at time of laparoscopy and its accuracy in relation to the tumour. Abdominoperineal resections and emergency colorectal operations were excluded. Only 59% of the patients had a visible and accurate tattoo. In 17% of the patients, the tattoo was not visible at all, although it was documented in the endoscopy report that it had been administered. In 4% of patients, it was visible but inaccurately placed. In 20% of the patients, there were no tattoos at all, necessitating on table endoscopy and intraoperative specimen analysis to confirm that the tumour/lesion was within the resection specimen. Preoperative tumour localisation is extremely important to correctly identify the site of tumour or lesion at laparoscopy. A standardised departmental protocol should be implemented by all endoscopists to place three spots of tattoo one mucosal fold distal to any significant lesions found. Failure to tattoo lesions/cancers preoperatively can lead to intraoperative delays and

Evaluation of specimen preparation techniques for micro-PIXE localisation of elements in hyperaccumulating plants

International Nuclear Information System (INIS)

Kachenko, Anthony G.; Siegele, Rainer; Bhatia, Naveen P.; Singh, Balwant; Ionescu, Mihail

2008-01-01

Hybanthus floribundus subsp. floribundus, a rare Australian Ni-hyperaccumulating shrub and Pityrogramma calomelanos var. austroamericana, an Australian naturalized As-hyperaccumulating fern are promising species for use in phytoremediation of contaminated sites. Micro-proton-induced X-ray emission (μ-PIXE) spectroscopy was used to map the elemental distribution of the accumulated metal(loid)s, Ca and K in leaf or pinnule tissues of the two plant species. Samples were prepared by two contrasting specimen preparation techniques: freeze-substitution in tetrahydrofuran (THF) and freeze-drying. The specimens were analysed to compare the suitability of each technique in preserving (i) the spatial elemental distribution and (ii) the tissue structure of the specimens. Further, the μ-PIXE results were compared with concentration of elements in the bulk tissue obtained by ICP-AES analysis. In H. floribundus subsp. floribundus, μ-PIXE analysis revealed Ni, Ca and K concentrations in freeze-dried leaf tissues were at par with bulk tissue concentrations. Elemental distribution maps illustrated that Ni was preferentially localised in the adaxial epidermal tissues (1% DW) and least concentration was found in spongy mesophyll tissues (0.53% DW). Conversely, elemental distribution maps of THF freeze-substituted tissues indicated significantly lower Ni, Ca and K concentrations than freeze-dried specimens and bulk tissue concentrations. Moreover, Ni concentrations were uniform across the whole specimen and no localisation was observed. In P. calomelanos var. austroamericana freeze-dried pinnule tissues, μ-PIXE revealed statistically similar As, Ca and K concentrations as compared to bulk tissue concentrations. Elemental distribution maps showed that As localisation was relatively uniform across the whole specimen. Once again, THF freeze-substituted tissues revealed a significant loss of As compared to freeze-dried specimens and the concentrations obtained by bulk tissue analysis

Gene Therapy for the Retinal Degeneration of Usher Syndrome Caused by Mutations in MYO7A.

Science.gov (United States)

Lopes, Vanda S; Williams, David S

2015-01-20

Usher syndrome is a deaf-blindness disorder. One of the subtypes, Usher 1B, is caused by loss of function of the gene encoding the unconventional myosin, MYO7A. A variety of different viral-based delivery approaches have been tested for retinal gene therapy to prevent the blindness of Usher 1B, and a clinical trial based on one of these approaches has begun. This review evaluates the different approaches. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Waardenburg syndrome type II in a Chinese patient caused by a novel nonsense mutation in the SOX10 gene.

Science.gov (United States)

Ma, Jing; Zhang, Tie-Song; Lin, Ken; Sun, Hao; Jiang, Hong-Chao; Yang, Yan-Li; Low, Fan; Gao, Ying-Qin; Ruan, Biao

2016-06-01

Waardenburg syndrome is a congenital genetic disorder. It is the most common type of syndromic hearing impairment with highly genetic heterogeneity and proved to be related by 6 genes as follows: PAX3, MITF, SNAI2, EDN3, EDNRB and SOX10. This article aims to identify the genetic causes of a Chinese WS child patient. A Chinese WS child was collected for clinical data collection by questionnaire survey. DNA samples of proband and his parents were extracted from peripheral blood samples. Six candidate genes were sequenced by the Trusight One sequencing panel on the illumina NextSeq 500 platform. A novel nonsense heterozygous mutation was found in the coding region of exon 2 in the SOX10 gene of proband. The novel nonsense heterozygous mutation could cause the replacement of the 55th lysine codon by stop codon (484T > C, C142R) and further more possibly cause terminating the protein translation in advance. However, both proband's parents had no mutation of genes above mentioned. The gene mutation of SOX10 [NM_006941.3 c.163A > T] is a novel nonsense mutation. No record of this mutation has been found in dbSNP, HGMD, 1000 Genomes Project, ClinVar and ESP6500 databases. It meets the condition of PS2 of strong evidence in 2015 ACMG Standards and Guidelines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Expression analysis of the Theileria parva subtelomere-encoded variable secreted protein gene family.

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Jacqueline Schmuckli-Maurer

Full Text Available The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm.We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals.Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic

Poinsettia protoplasts - a simple, robust and efficient system for transient gene expression studies

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Pitzschke Andrea

2012-05-01

Full Text Available Abstract Background Transient gene expression systems are indispensable tools in molecular biology. Yet, their routine application is limited to few plant species often requiring substantial equipment and facilities. High chloroplast and chlorophyll content may further impede downstream applications of transformed cells from green plant tissue. Results Here, we describe a fast and simple technique for the high-yield isolation and efficient transformation (>70% of mesophyll-derived protoplasts from red leaves of the perennial plant Poinsettia (Euphorbia pulccherrima. In this method no particular growth facilities or expensive equipments are needed. Poinsettia protoplasts display an astonishing robustness and can be employed in a variety of commonly-used downstream applications, such as subcellular localisation (multi-colour fluorescence or promoter activity studies. Due to low abundance of chloroplasts or chromoplasts, problems encountered in other mesophyll-derived protoplast systems (particularly autofluorescence are alleviated. Furthermore, the transgene expression is detectable within 90 minutes of transformation and lasts for several days. Conclusions The simplicity of the isolation and transformation procedure renders Poinsettia protoplasts an attractive system for transient gene expression experiments, including multi-colour fluorescence, subcellular localisation and promoter activity studies. In addition, they offer hitherto unknown possibilities for anthocyan research and industrial applications.

Localisation of metastatic carcinoma by a radiolabelled monoclonal antibody

Energy Technology Data Exchange (ETDEWEB)

Smedley, H M; Ritson, A; Wraight, P; Sikora, K [Addenbrooke' s Hospital, Cambridge (UK); Hinchingbrooke Hospital, Huntingdon (UK)); Finan, P [St. James Hospital, Leeds (UK); Lennox, E S; Takei, F [Medical Research Council, Cambridge (UK)

1983-02-01

Rat monoclonal antibodies were prepared by immunising rats with human colorectal carcinoma cell membranes and fusing splenic lymphocytes with a rat myeloma. Hybridoma supernatants were screened by binding assays on membranes prepared from colorectal carcinoma tissue. One hybridoma supernatant, containing a monoclonal antibody with high binding activity on malignant compared to normal colon sections, was grown in large quantities in serum-free medium. After ammonium sulphate precipitation the antibody was purified by ion-exchange chromatography and labelled with /sup 131/I. Radiolabelled antibody was administered i.v. to 27 patients with colonic and other tumours. Scintigrams were obtained at 48 h. Computerised subtraction of the blood pool image revealed localised areas of uptake corresponding with areas of known disease in 13/16 patients with colorectal carcinoma and 3/4 patients with breast cancer.

Differences in acidity of apples are probably mainly caused by a malic acid transporter gene on LG16

NARCIS (Netherlands)

Khan, S.A.; Beekwilder, J.; Schaart, J.G.; Mumm, R.; Soriano, J.M.; Jacobsen, E.; Schouten, H.J.

2013-01-01

Acidity has profound effects on the taste of apples (Malus × domestica). Malic acid is the predominant organic acid in apples. Differences in malic acid content are caused by differences in accumulation of malic acid in the vacuole. This accumulation may be caused by a gene that is responsible for

Localising QTLs for leaf rust resistance and agronomic traits in barley (¤Hordeum vulgare¤ L.)

DEFF Research Database (Denmark)

Kicherer, S.; Backes, G.; Walther, U.

2000-01-01

to leaf rust by means of artificial infection, heading date, plant height and Kernel weight were assessed. For leaf rust resistance, 4 QTLs were localised, that explained 96.1% of the genetic variation. One QTL on chromosome 4H confirmed a position found in another genetic background and one mapped...

Primary user localisation and uplink resource allocation in orthogonal frequency division multiple access cognitive radio systems

KAUST Repository

Nam, Haewoon

2015-05-21

In cognitive radio networks, secondary users (SUs) can share spectrum with primary users (PUs) under the condition that no interference is caused to the PUs. To evaluate the interference imposed to the PUs, the cognitive systems discussed in the literature usually assume that the channel state information (CSI) of the link from a secondary transmitter to a primary receiver (interference link) is known at the secondary transmitter. However, this assumption may often be impractical in cognitive radio systems, since the PUs need to be oblivious to the presence of the SUs. The authors first discuss PU localisation and then introduce an uplink resource allocation algorithm for orthogonal frequency division multiple access-based cognitive radio systems, where relative location information between primary and SUs is used instead of CSI of the interference link to estimate the interference. Numerical and simulation results show that it is indeed effective to use location information as a part of resource allocation and thus a near-optimal capacity is achieved. © The Institution of Engineering and Technology 2015.

Localising welfare-to-work? Territorial flexibility and the New Deal for Young People

OpenAIRE

Corinne Nativel; Peter Sunley; Ron Martin

2002-01-01

The move towards workfare and active labour-market policies is often alleged to be closely associated with the decentralisation and localisation of welfare delivery and agencies. In the United Kingdom, the New Deal for the young unemployed was designed to introduce local flexibility and discretion in delivery to mainstream labour-market policy. We use case studies of five local areas to examine the extent to which the programme has actually been decentralised and benefited from 'local flexibi...

Ribosomal protein gene knockdown causes developmental defects in zebrafish.

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Tamayo Uechi

Full Text Available The ribosomal proteins (RPs form the majority of cellular proteins and are mandatory for cellular growth. RP genes have been linked, either directly or indirectly, to various diseases in humans. Mutations in RP genes are also associated with tissue-specific phenotypes, suggesting a possible role in organ development during early embryogenesis. However, it is not yet known how mutations in a particular RP gene result in specific cellular changes, or how RP genes might contribute to human diseases. The development of animal models with defects in RP genes will be essential for studying these questions. In this study, we knocked down 21 RP genes in zebrafish by using morpholino antisense oligos to inhibit their translation. Of these 21, knockdown of 19 RPs resulted in the development of morphants with obvious deformities. Although mutations in RP genes, like other housekeeping genes, would be expected to result in nonspecific developmental defects with widespread phenotypes, we found that knockdown of some RP genes resulted in phenotypes specific to each gene, with varying degrees of abnormality in the brain, body trunk, eyes, and ears at about 25 hours post fertilization. We focused further on the organogenesis of the brain. Each knocked-down gene that affected the morphogenesis of the brain produced a different pattern of abnormality. Among the 7 RP genes whose knockdown produced severe brain phenotypes, 3 human orthologs are located within chromosomal regions that have been linked to brain-associated diseases, suggesting a possible involvement of RP genes in brain or neurological diseases. The RP gene knockdown system developed in this study could be a powerful tool for studying the roles of ribosomes in human diseases.

A novel mutation in the SH3BP2 gene causes cherubism: case report

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Yu Shi-Feng

2006-12-01

Full Text Available Abstract Background Cherubism is a rare hereditary multi-cystic disease of the jaws, characterized by its typical appearance in early childhood, and stabilization and remission after puberty. It is genetically transmitted in an autosomal dominant fashion and the gene coding for SH3-binding protein 2 (SH3BP2 may be involved. Case presentation We investigated a family consisting of 21 members with 3 female affected individuals with cherubism from Northern China. Of these 21 family members, 17 were recruited for the genetic analysis. We conducted the direct sequence analysis of the SH3BP2 gene among these 17 family members. A disease-causing mutation was identified in exon 9 of the gene. It was an A1517G base change, which leads to a D419G amino acid substitution. Conclusion To our knowledge, the A1517G mutation has not been reported previously in cherubism. This finding is novel.

Multiple organ gigantism caused by mutation in VmPPD gene in blackgram (Vigna mungo).

Science.gov (United States)

Naito, Ken; Takahashi, Yu; Chaitieng, Bubpa; Hirano, Kumi; Kaga, Akito; Takagi, Kyoko; Ogiso-Tanaka, Eri; Thavarasook, Charaspon; Ishimoto, Masao; Tomooka, Norihiko

2017-03-01

Seed size is one of the most important traits in leguminous crops. We obtained a recessive mutant of blackgram that had greatly enlarged leaves, stems and seeds. The mutant produced 100% bigger leaves, 50% more biomass and 70% larger seeds though it produced 40% less number of seeds. We designated the mutant as multiple-organ-gigantism ( mog ) and found the mog phenotype was due to increase in cell numbers but not in cell size. We also found the mog mutant showed a rippled leaf ( rl ) phenotype, which was probably caused by a pleiotropic effect of the mutation. We performed a map-based cloning and successfully identified an 8 bp deletion in the coding sequence of VmPPD gene, an orthologue of Arabidopsis PEAPOD ( PPD ) that regulates arrest of cell divisions in meristematic cells . We found no other mutations in the neighboring genes between the mutant and the wild type. We also knocked down GmPPD genes and reproduced both the mog and rl phenotypes in soybean. Controlling PPD genes to produce the mog phenotype is highly valuable for breeding since larger seed size could directly increase the commercial values of grain legumes.

Induced pluripotent stem cells derived from a patient with autosomal dominant familial neurohypophyseal diabetes insipidus caused by a variant in the AVP gene

DEFF Research Database (Denmark)

Toustrup, Lise Bols; Zhou, Yan; Kvistgaard, Helene

2017-01-01

Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by variants in the arginine vasopressin (AVP) gene. Here we report the generation of induced pluripotent stem cells (iPSCs) from a 42-year-old man carrying an adFNDI causing variant in exon 1 of the AVP gene using...

Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome.

Science.gov (United States)

Santen, Gijs W E; Aten, Emmelien; Sun, Yu; Almomani, Rowida; Gilissen, Christian; Nielsen, Maartje; Kant, Sarina G; Snoeck, Irina N; Peeters, Els A J; Hilhorst-Hofstee, Yvonne; Wessels, Marja W; den Hollander, Nicolette S; Ruivenkamp, Claudia A L; van Ommen, Gert-Jan B; Breuning, Martijn H; den Dunnen, Johan T; van Haeringen, Arie; Kriek, Marjolein

2012-03-18

We identified de novo truncating mutations in ARID1B in three individuals with Coffin-Siris syndrome (CSS) by exome sequencing. Array-based copy-number variation (CNV) analysis in 2,000 individuals with intellectual disability revealed deletions encompassing ARID1B in 3 subjects with phenotypes partially overlapping that of CSS. Taken together with published data, these results indicate that haploinsufficiency of the ARID1B gene, which encodes an epigenetic modifier of chromatin structure, is an important cause of CSS and is potentially a common cause of intellectual disability and speech impairment.

An assessment of the importance ofexposure routes to the uptake and internal localisation of fluorescent nanoparticles in zebrafish (Danio rerio), using light sheet microscopy

DEFF Research Database (Denmark)

Skjolding, Lars Michael; Ašmonaitė, G; Jølck, Rasmus Irming

2017-01-01

A major challenge in nanoecotoxicology is finding suitable methods to determine the uptake and localisation of nanoparticles on a whole-organism level. Some uptake methods have been associated with artefacts induced by sample preparation, including staining for electron microscopy. This study used...... light sheet microscopy (LSM) to define the uptake and localisation of fluorescently labelled nanoparticles in living organisms with minimal sample preparation. Zebrafish (Danio rerio) were exposed to fluorescent gold nanoparticles (Au NPs) and fluorescent polystyrene NPs via aqueous or dietary exposure...

Modernization of the accident localisation system and relevant dose exposure on unit four of KNPP

International Nuclear Information System (INIS)

Valtchev, G.; Neshkova, M.; Nikilov, A.

2005-01-01

In 2001 a modernization of the accident localisation system (ALS) on Unit 4 was accomplished. The outage duration was longer then usually and special dose budget was elaborated. All ALS work was performed by external organisation. An ALARA implementation was recognised priority. The really accumulated collective doses were analysed and conclusions drawn. A short film on CD was prepared. (authors)

Resistance genes in barley (Hordeum vulgare L.) and their identification with molecular markers.

Science.gov (United States)

Chełkowski, Jerzy; Tyrka, Mirosław; Sobkiewicz, Andrzej

2003-01-01

Current information on barley resistance genes available from scientific papers and on-line databases is summarised. The recent literature contains information on 107 major resistance genes (R genes) against fungal pathogens (excluding powdery mildew), pathogenic viruses and aphids identified in Hordeum vulgare accessions. The highest number of resistance genes was identified against Puccinia hordei, Rhynchosporium secalis, and the viruses BaYMV and BaMMV, with 17, 14 and 13 genes respectively. There is still a lot of confusion regarding symbols for R genes against powdery mildew. Among the 23 loci described to date, two regions Mla and Mlo comprise approximately 31 and 25 alleles. Over 50 R genes have already been localised and over 30 mapped on 7 barley chromosomes. Four barley R genes have been cloned recently: Mlo, Rpg1, Mla1 and Mla6, and their structures (sequences) are available. The paper presents a catalogue of barley resistance gene symbols, their chromosomalocation and the list of available DNA markers useful in characterising cultivars and breeding accessions.

Localised in vivo 1H spectroscopy of human bone and soft tissue tumours

International Nuclear Information System (INIS)

Bongers, H.; Schick, F.; Skalej, M.; Hess, C.F.; Jung, W.I.

1992-01-01

Localised 1 H in vivo magnetic resonance spectroscopy was applied to fibrous and bone tumours before and during cytostatic treatment and radiotherapy. The results of 24 studies in 18 patients with malignant tumours of the leg or pelvis are presented including cases of sarcoma, malignant fibrous histiocytoma, multiple myeloma, malignant lymphoma and metastasis. A double spin echo localisation method with water suppression was implemented on a 1.5 Tesla whole body unit. Voxel size was (13 mm) 3 or (20 mm) 3 . The most common resonances besides lipids (16/18) were those of choline (10/18) and creatine (5/18). Creatine was always decreased in comparison to choline and often absent from tumour spectra. Additional resonances with phase distorsions from J-coupling (chemical shift region 1.8-2.5 and 2.2-4.0 ppm) were recorded. In the presence of lipids, lactate remained undetectable because special editing techniques were not available. Significant spectral differences between different tumour types were not evident. In about 30% of the investigations the spectra contained only water and lipid signals. Follow-up studies in three patients during radio- and chemotherapy showed a decrease in metabolites (choline, creatine, unassigned signals between 1.0 and 2.5 ppm) after weeks and months. The decrease in choline was most pronounced paralleled by an increase in lipid/choline ratios. (orig.)

c.376G>A mutation in WFS1 gene causes Wolfram syndrome without deafness.

Science.gov (United States)

Safarpour Lima, Behnam; Ghaedi, Hamid; Daftarian, Narsis; Ahmadieh, Hamid; Jamshidi, Javad; Khorrami, Mehdi; Noroozi, Rezvan; Sohrabifar, Nasim; Assarzadegan, Farhad; Hesami, Omid; Taghavi, Shaghayegh; Ahmadifard, Azadeh; Atakhorrami, Minoo; Rahimi-Aliabadi, Simin; Shahmohammadibeni, Neda; Alehabib, Elham; Andarva, Monavvar; Darvish, Hossein; Emamalizadeh, Babak

2016-02-01

Wolfram syndrome is one of the rare autosomal recessive, progressive, neurodegenerative disorders, characterized by diabetes mellitus and optic atrophy. Several other features are observed in patients including deafness, ataxia, and peripheral neuropathy. A gene called WFS1 is identified on chromosome 4p, responsible for Wolfram syndrome. We investigated a family consisted of parents and 8 children, which 5 of them have been diagnosed for Wolfram syndrome. WFS1 gene in all family members was sequenced for causative mutations. A mutation (c.376G>A, p.A126T) was found in all affected members in homozygous state and in both parents in heterozygous state. The bioinformatics analysis showed the deleterious effects of this nucleotide change on the structure and function of the protein product. As all of the patients in the family showed the homozygote mutation, and parents were both heterozygote, this mutation is probably the cause of the disease. We identified this mutation in homozygous state for the first time as Wolfram syndrome causation. We also showed that this mutation probably doesn't cause deafness in affected individuals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A single point-mutation within the melanophilin gene causes the lavender plumage colour dilution phenotype in the chicken

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Tixier-Boichard Michèle

2008-01-01

Full Text Available Abstract Background The lavender phenotype in the chicken causes the dilution of both black (eumelanin and red/brown (phaeomelanin pigments. Defects in three genes involved in intracellular melanosomal transport, previously described in mammals, give rise to similar diluted pigmentation phenotypes as those seen in lavender chickens. Results We have used a candidate-gene approach based on an expectation of homology with mammals to isolate a gene involved in pigmentation in chicken. Comparative sequence analysis of candidate genes in the chicken identified a strong association between a mutation in the MLPH gene and the diluted pigmentation phenotype. This mutation results in the amino acid change R35W, at a site also associated with similar phenotypes in mice, humans and cats. Conclusion This is the first time that an avian species with a mutation in the MLPH gene has been reported.

Effects of fuel Lewis number on localised forced ignition of turbulent homogeneous mixtures: A numerical investigation

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Dipal Patel

2016-09-01

Full Text Available The influences of fuel Lewis number LeF (ranging from 0.8 to 1.2 on localised forced ignition and early stages of combustion of stoichiometric and fuel-lean homogeneous mixtures have been analysed using simple chemistry three-dimensional compressible direct numerical simulations for different values of root-mean-square velocity fluctuation and the energy deposition characteristics (i.e. characteristic width and the duration of energy deposition by the ignitor. The localised forced ignition is modelled using a source term in the energy transport equation, which deposits energy in a Gaussian manner from the centre of the ignitor over a stipulated period of time. The fuel Lewis number LeF has been found to have significant influences on the extent of burning of stoichiometric and fuel-lean homogeneous mixtures. It has been shown that the width of ignition energy deposition and the duration over which the ignition energy is deposited have significant influences on the success of ignition and subsequent flame propagation. An increase in the width of ignition energy deposition and the duration of energy deposition for a given amount of ignition energy have been found to have detrimental effects on the ignition event, which may ultimately lead to misfire. For a given value of u' (LeF, the rate of heat transfer from the hot gas kernel increases with increasing LeF (u', which in turn leads to a reduction in the extent of overall burning for both stoichiometric and fuel-lean homogeneous mixtures but the detrimental effects of high values of u' on localised forced ignition are particularly prevalent for fuel-lean mixtures. Detailed physical explanations have been provided for the observed LeF,u' and energy deposition characteristics effects.

Identification of Two Disease-causing Genes TJP2 and GJB2 in a Chinese Family with Unconditional Autosomal Dominant Nonsyndromic Hereditary Hearing Impairment

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Hong-Yang Wang

2015-01-01

Full Text Available Background: There are more than 300 genetic loci that have been found to be related to hereditary hearing impairment (HHI, including 92 causative genes for nonsyndromic hearing loss, among which 34 genes are related to autosomal dominant nonsyndromic HHI (ADNSHHI. Traditional linkage analysis and candidate gene sequencing are not effective at detecting the ADNSHHI, especially for the unconditional families that may have more than one pathogenic cause. This study identified two disease-causing genes TJP2 and GJB2 in a Chinese family with unconditional ADNSHHI. Methods: To decipher the genetic code of a Chinese family (family 686 with ADNSHHI, different gene screening techniques have been performed, including linkage analysis, candidate genes screening, high-throughput sequencing and Sanger sequencing. These techniques were done on samples obtained from this family over a period of 10 years. Results: We identified a pathogenic missense mutation, c. 2081G>A (p.G694E, in TJP2, a gene that plays a crucial role in apoptosis and age-related hearing loss (ARHL. The mutation was co-segregated in this pedigree in all, but not in the two patients who presented with different phenotypes from the other affected family members. In one of the two patients, we confirmed that the compound heterozygosity for p.Y136FNx01 and p.G45E in the GJB2 gene may account for the phenotype shown in this patient. Conclusions: We identified the co-occurrence of two genetic causes in family 686. The possible disease-causing missense mutation of TJP2 in family 686 presents an opportunity for further investigation into ARHL. It is necessary to combine various genes screening methods, especially for some unconventional cases.

The Reduction of Vertical Interchannel Crosstalk: The Analysis of Localisation Thresholds for Natural Sound Sources

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Rory Wallis

2017-03-01

Full Text Available In subjective listening tests, natural sound sources were presented to subjects as vertically-oriented phantom images from two layers of loudspeakers, ‘height’ and ‘main’. Subjects were required to reduce the amplitude of the height layer until the position of the resultant sound source matched that of the same source presented from the main layer only (the localisation threshold. Delays of 0, 1 and 10 ms were applied to the height layer with respect to the main, with vertical stereophonic and quadraphonic conditions being tested. The results of the study showed that the localisation thresholds obtained were not significantly affected by sound source or presentation method. Instead, the only variable whose effect was significant was interchannel time difference (ICTD. For ICTD of 0 ms, the median threshold was −9.5 dB, which was significantly lower than the −7 dB found for both 1 and 10 ms. The results of the study have implications both for the recording of sound sources for three-dimensional (3D audio reproduction formats and also for the rendering of 3D images.

Hydrogen-induced strain localisation in oxygen-free copper in the initial stage of plastic deformation

Science.gov (United States)

Yagodzinskyy, Yuriy; Malitckii, Evgenii; Tuomisto, Filip; Hänninen, Hannu

2018-03-01

Single crystals of oxygen-free copper oriented to easy glide of dislocations were tensile tested in order to study the hydrogen effects on the strain localisation in the form of slip bands appearing on the polished specimen surface under tensile straining. It was found that hydrogen increases the plastic flow stress in Stage I of deformation. The dislocation slip localisation in the form of slip bands was observed and analysed using an online optical monitoring system and atomic force microscopy. The fine structure of the slip bands observed with AFM shows that they consist of a number of dislocation slip offsets which spacing in the presence of hydrogen is markedly reduced as compared to that in the hydrogen-free specimens. The tensile tests and AFM observations were accompanied with positron annihilation lifetime measurements showing that straining of pure copper in the presence of hydrogen results in free volume generation in the form of vacancy complexes. Hydrogen-enhanced free-volume generation is discussed in terms of hydrogen interactions with edge dislocation dipoles forming in double cross-slip of screw dislocations in the initial stage of plastic deformation of pure copper.

Globally reasoning about localised security policies in distributed systems

DEFF Research Database (Denmark)

Hernandez, Alejandro Mario

In this report, we aim at establishing proper ways for model checking the global security of distributed systems, which are designed consisting of set of localised security policies that enforce specific issues about the security expected. The systems are formally specified following a syntax......, defined in detail in this report, and their behaviour is clearly established by the Semantics, also defined in detail in this report. The systems include the formal attachment of security policies into their locations, whose intended interactions are trapped by the policies, aiming at taking access...... control decisions of the system, and the Semantics also takes care of this. Using the Semantics, a Labelled Transition System (LTS) can be induced for every particular system, and over this LTS some model checking tasks could be done. We identify how this LTS is indeed obtained, and propose an alternative...

Ogura-CMS in Chinese cabbage (Brassica rapa ssp. pekinensis) causes delayed expression of many nuclear genes.

Science.gov (United States)

Dong, Xiangshu; Kim, Wan Kyu; Lim, Yong-Pyo; Kim, Yeon-Ki; Hur, Yoonkang

2013-02-01

We investigated the mechanism regulating cytoplasmic male sterility (CMS) in Brassica rapa ssp. pekinensis using floral bud transcriptome analyses of Ogura-CMS Chinese cabbage and its maintainer line in B. rapa 300-K oligomeric probe (Br300K) microarrays. Ogura-CMS Chinese cabbage produced few and infertile pollen grains on indehiscent anthers. Compared to the maintainer line, CMS plants had shorter filaments and plant growth, and delayed flowering and pollen development. In microarray analysis, 4646 genes showed different expression, depending on floral bud size, between Ogura-CMS and its maintainer line. We found 108 and 62 genes specifically expressed in Ogura-CMS and its maintainer line, respectively. Ogura-CMS line-specific genes included stress-related, redox-related, and B. rapa novel genes. In the maintainer line, genes related to pollen coat and germination were specifically expressed in floral buds longer than 3mm, suggesting insufficient expression of these genes in Ogura-CMS is directly related to dysfunctional pollen. In addition, many nuclear genes associated with auxin response, ATP synthesis, pollen development and stress response had delayed expression in Ogura-CMS plants compared to the maintainer line, which is consistent with the delay in growth and development of Ogura-CMS plants. Delayed expression may reduce pollen grain production and/or cause sterility, implying that mitochondrial, retrograde signaling delays nuclear gene expression. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Controlled light localisation and nonlinear-optical interactions of short laser pulses in holey fibres

International Nuclear Information System (INIS)

Fedotov, Andrei B; Zheltikov, Aleksei M; Golovan', Leonid A; Kashkarov, Pavel K; Tarasevitch, A P; Podshivalov, Alexey A; Alfimov, Mikhail V; Ivanov, Anatoliy A; Beloglazov, V I; Haus, J W; Linde, D von der

2001-01-01

The influence of the structure of holey-fibre cladding on the effective waveguide mode area and the spectral broadening of femtosecond pulses of titanium-sapphire and forsterite lasers is experimentally studied. These experiments demonstrate that the increase in the air-filling fraction of the holey-fibre cladding may substantially enhance the spectral broadening of laser pulses due to the increase in the degree of light localisation in the fibre core. (femtosecond technologies)

Rapid characterization of disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene by overexpression in COS cells

DEFF Research Database (Denmark)

Jensen, T G; Andresen, B S; Jensen, H K

1996-01-01

To characterize disease-causing mutations in the low density lipoprotein receptor (LDL-R) gene, COS cells are transfected with the mutant gene in an EBV-based expression vector and characterized by flow cytometry. Using antibodies against the LDL-receptor the amount of receptor protein on the cel...

Normalization of Overexpressed α-Synuclein Causing Parkinson's Disease By a Moderate Gene Silencing With RNA Interference

Directory of Open Access Journals (Sweden)

Masaki Takahashi

2015-01-01

Full Text Available The α-synuclein (SNCA gene is a responsible gene for Parkinson's disease (PD; and not only nucleotide variations but also overexpression of SNCA appears to be involved in the pathogenesis of PD. A specific inhibition against mutant SNCA genes carrying nucleotide variations may be feasible by a specific silencing such as an allele-specific RNA interference (RNAi; however, there is no method for restoring the SNCA overexpression to a normal level. Here, we show that an atypical RNAi using small interfering RNAs (siRNAs that confer a moderate level of gene silencing is capable of controlling overexpressed SNCA genes to return to a normal level; named “expression-control RNAi” (ExCont-RNAi. ExCont-RNAi exhibited little or no significant off-target effects in its treated PD patient's fibroblasts that carry SNCA triplication. To further assess the therapeutic effect of ExCont-RNAi, PD-model flies that carried the human SNCA gene underwent an ExCont-RNAi treatment. The treated PD-flies demonstrated a significant improvement in their motor function. Our current findings suggested that ExCont-RNAi might be capable of becoming a novel therapeutic procedure for PD with the SNCA overexpression, and that siRNAs conferring a moderate level of gene silencing to target genes, which have been abandoned as useless siRNAs so far, might be available for controlling abnormally expressed disease-causing genes without producing adverse effects.

Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome.

Science.gov (United States)

Lynch, Danielle C; Revil, Timothée; Schwartzentruber, Jeremy; Bhoj, Elizabeth J; Innes, A Micheil; Lamont, Ryan E; Lemire, Edmond G; Chodirker, Bernard N; Taylor, Juliet P; Zackai, Elaine H; McLeod, D Ross; Kirk, Edwin P; Hoover-Fong, Julie; Fleming, Leah; Savarirayan, Ravi; Majewski, Jacek; Jerome-Majewska, Loydie A; Parboosingh, Jillian S; Bernier, Francois P

2014-07-22

Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro-costo-mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development.

Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro–costo–mandibular syndrome

Science.gov (United States)

Lynch, Danielle C.; Revil, Timothée; Schwartzentruber, Jeremy; Bhoj, Elizabeth J.; Innes, A. Micheil; Lamont, Ryan E.; Lemire, Edmond G.; Chodirker, Bernard N.; Taylor, Juliet P.; Zackai, Elaine H.; McLeod, D. Ross; Kirk, Edwin P.; Hoover-Fong, Julie; Fleming, Leah; Savarirayan, Ravi; Boycott, Kym; MacKenzie, Alex; Brudno, Michael; Bulman, Dennis; Dyment, David; Majewski, Jacek; Jerome-Majewska, Loydie A.; Parboosingh, Jillian S.; Bernier, Francois P.

2014-01-01

Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro–costo–mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development. PMID:25047197

Prediction and comparison of down-link electric field and uplink localised SAR values for realistic indoor wireless planning

International Nuclear Information System (INIS)

Plets, David; Joseph, Wout; Aerts, Sam; Vanhecke, Kris; Vermeeren, Guenter; Martens, Luc

2014-01-01

In this paper, for the first time a heuristic network calculator for both whole-body exposure due to indoor base station antennas or access points (down-link exposure) and localised exposure due to the mobile device (uplink exposure) in indoor wireless networks is presented. As an application, three phone call scenarios are investigated (Universal Mobile Telecommunications System (UMTS) macro-cell, UMTS femto-cell and WiFi voice-over-IP) and compared with respect to the electric-field strength and localised specific absorption rate (SAR) distribution. Prediction models are created and successfully validated with an accuracy of 3 dB. The benefits of the UMTS power control mechanisms are demonstrated. However, dependent on the macro-cell connection quality and on the user's average phone call connection time, also the macro-cell solution might be preferential from an exposure point of view for the considered scenario. (authors)

Alu element insertion in PKLR gene as a novel cause of pyruvate kinase deficiency in Middle Eastern patients.

Science.gov (United States)

Lesmana, Harry; Dyer, Lisa; Li, Xia; Denton, James; Griffiths, Jenna; Chonat, Satheesh; Seu, Katie G; Heeney, Matthew M; Zhang, Kejian; Hopkin, Robert J; Kalfa, Theodosia A

2018-03-01

Pyruvate kinase deficiency (PKD) is the most frequent red blood cell enzyme abnormality of the glycolytic pathway and the most common cause of hereditary nonspherocytic hemolytic anemia. Over 250 PKLR-gene mutations have been described, including missense/nonsense, splicing and regulatory mutations, small insertions, small and gross deletions, causing PKD and hemolytic anemia of variable severity. Alu retrotransposons are the most abundant mobile DNA sequences in the human genome, contributing to almost 11% of its mass. Alu insertions have been associated with a number of human diseases either by disrupting a coding region or a splice signal. Here, we report on two unrelated Middle Eastern patients, both born from consanguineous parents, with transfusion-dependent hemolytic anemia, where sequence analysis revealed a homozygous insertion of AluYb9 within exon 6 of the PKLR gene, causing precipitous decrease of PKLR RNA levels. This Alu element insertion consists a previously unrecognized mechanism underlying pathogenesis of PKD. © 2017 Wiley Periodicals, Inc.

Phenotypic spectrum of autosomal recessive cone-rod dystrophies caused by mutations in the ABCA4 (ABCR) gene.

Science.gov (United States)

Klevering, B Jeroen; Blankenagel, Anita; Maugeri, Alessandra; Cremers, Frans P M; Hoyng, Carel B; Rohrschneider, Klaus

2002-06-01

To describe the phenotype of 12 patients with autosomal recessive or isolated cone-rod types of progressive retinal degeneration (CRD) caused by mutations in the ABCA4 gene. The charts of patients who had originally received a diagnosis of isolated or autosomal recessive CRD were reviewed after molecular analysis revealed mutations in the ABCA4 gene. In two of the patients both the photopic and scotopic electroretinogram were nonrecordable. In the remainder, the photopic cone b-wave amplitudes appeared to be more seriously affected than the scotopic rod b-wave amplitudes. Although the clinical presentation was heterogeneous, all patients experienced visual loss early in life, impaired color vision, and a central scotoma. Fundoscopy revealed evidence of early-onset maculopathy, sometimes accompanied by involvement of the retinal periphery in the later stages of the disease. Mutations in the ABCA4 gene are the pathologic cause of the CRD-like dystrophy in these patients, and the resultant clinical pictures are complex and heterogeneous. Given this wide clinical spectrum of CRD-like phenotypes associated with ABCA4 mutations, detailed clinical subclassifications are difficult and may not be very useful.

Gliadin peptide P31-43 localises to endocytic vesicles and interferes with their maturation.

Directory of Open Access Journals (Sweden)

Maria Vittoria Barone

Full Text Available BACKGROUND: Celiac Disease (CD is both a frequent disease (1:100 and an interesting model of a disease induced by food. It consists in an immunogenic reaction to wheat gluten and glutenins that has been found to arise in a specific genetic background; however, this reaction is still only partially understood. Activation of innate immunity by gliadin peptides is an important component of the early events of the disease. In particular the so-called "toxic" A-gliadin peptide P31-43 induces several pleiotropic effects including Epidermal Growth Factor Receptor (EGFR-dependent actin remodelling and proliferation in cultured cell lines and in enterocytes from CD patients. These effects are mediated by delayed EGFR degradation and prolonged EGFR activation in endocytic vesicles. In the present study we investigated the effects of gliadin peptides on the trafficking and maturation of endocytic vesicles. METHODS/PRINCIPAL FINDINGS: Both P31-43 and the control P57-68 peptide labelled with fluorochromes were found to enter CaCo-2 cells and interact with the endocytic compartment in pulse and chase, time-lapse, experiments. P31-43 was localised to vesicles carrying early endocytic markers at time points when P57-68-carrying vesicles mature into late endosomes. In time-lapse experiments the trafficking of P31-43-labelled vesicles was delayed, regardless of the cargo they were carrying. Furthermore in celiac enterocytes, from cultured duodenal biopsies, P31-43 trafficking is delayed in early endocytic vesicles. A sequence similarity search revealed that P31-43 is strikingly similar to Hrs, a key molecule regulating endocytic maturation. A-gliadin peptide P31-43 interfered with Hrs correct localisation to early endosomes as revealed by western blot and immunofluorescence microscopy. CONCLUSIONS: P31-43 and P57-68 enter cells by endocytosis. Only P31-43 localises at the endocytic membranes and delays vesicle trafficking by interfering with Hrs

Optimal localisation of next generation Biofuel production in Sweden

Energy Technology Data Exchange (ETDEWEB)

Wetterlund, Elisabeth [Linkoeping Univ., Linkoeping (Sweden); Pettersson, Karin [Chalmers Univ. of Technology, Goeteborg (Sweden); Mossberg, Johanna [SP Technical Research Inst. of Sweden, Boraas (Sweden)] [and others

2013-09-01

With a high availability of lignocellulosic biomass and various types of cellulosic by-products, as well as a large number of industries, Sweden is a country of great interest for future large scale production of sustainable, next generation biofuels. This is most likely also a necessity as Sweden has the ambition to be independent of fossil fuels in the transport sector by the year 2030 and completely fossil free by 2050. In order to reach competitive biofuel production costs, plants with large production capacities are likely to be required. Feedstock intake capacities in the range of about 1-2 million tonnes per year, corresponding to a biomass feed of 300-600 MW, can be expected, which may lead to major logistical challenges. To enable expansion of biofuel production in such large plants, as well as provide for associated distribution requirements, it is clear that substantial infrastructure planning will be needed. The geographical location of the production plant facilities is therefore of crucial importance and must be strategic to minimise the transports of raw material as well as of final product. Competition for the available feedstock, from for example forest industries and CHP plants (combined heat and power) further complicates the localisation problem. Since the potential for an increased biomass utilisation is limited, high overall resource efficiency is of great importance. Integration of biofuel production processes in existing industries or in district heating systems may be beneficial from several aspects, such as opportunities for efficient heat integration, feedstock and equipment integration, as well as access to existing experience and know-how. This report describes the development of Be Where Sweden, a geographically explicit optimisation model for localisation of next generation biofuel production plants in Sweden. The main objective of developing such a model is to be able to assess production plant locations that are robust to varying

Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

Science.gov (United States)

Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

2017-03-07

Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the

Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

Energy Technology Data Exchange (ETDEWEB)

Kissel, Maria; Peschke, Peter; Strunz, Anke M.; Kuehnlein, Rainer; Debus, Juergen [Department of Radiation Oncology, E0505, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Subr, Vladimir; Ulbrich, Karel [Institute of Macromolecular Chemistry, Prague (Czech Republic); Friedrich, Eckhard [Division of Biology, University of Koblenz-Landau, Landau (Germany)

2002-08-01

Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules. (orig.)

Detection and cellular localisation of the synthetic soluble macromolecular drug carrier pHPMA

International Nuclear Information System (INIS)

Kissel, Maria; Peschke, Peter; Strunz, Anke M.; Kuehnlein, Rainer; Debus, Juergen; Subr, Vladimir; Ulbrich, Karel; Friedrich, Eckhard

2002-01-01

Synthetic macromolecules such as copolymers of N-(2-hydroxypropyl)methacrylamide (pHPMA) are potential carriers for the delivery of drugs owing to their ability to passively accumulate in solid tumours [enhanced permeation and retention (EPR) effect]. To gain further knowledge about the biodistribution and the cellular localisation, poly(HPMA) was prepared for labelling by introducing biotin molecules. Biotinylated pHPMA (5 mol%) was intravenously injected into tumour-bearing rats and the accumulation of biotin-pHPMA was visualised using a streptavidin-alkaline phosphatase technique at day 7 post injection. In spite of the high solubility of pHPMA copolymers and the lack of attachment to cell structures, the biotinylated polymer could be easily detected in tissues fixed in 10% paraformaldehyde-phosphate buffer at 4 C for 48 h. While biotin-pHPMA could be detected intracytoplasmically in liver and spleen, a predominantly interstitial localisation was observed within the anaplastic prostate carcinoma (Dunning R3327-AT1). How biotin as a label influences the biodistribution of poly(HPMA) was assessed by scintigraphy, autoradiography and histology comparing homopolymer poly(HPMA) with biotin-pHPMA. The organ distribution patterns of the two polymers correlated well, except with respect to kidney. It is assumed that the accumulation of biotin-pHPMA in the distal tubuli is due to a biotin transporter in the brush border membrane. The technique presented is useful for a more comprehensive understanding of the biodistribution of soluble macromolecules. (orig.)

Magneto-hydro-dynamic simulation of Edge-Localised-Modes in tokamaks

International Nuclear Information System (INIS)

Pamela, S.

2010-01-01

In order to produce energy from fusion reactions in a tokamak, the plasma must reach temperatures higher than that of our sun. The operation regime called H-mode enables one to acquire a plasma confinement close to fusion conditions. Due to the formation of a transport barrier at the plasma edge, turbulent transport is reduced, and the total plasma pressure increases, resulting in a strong pressure gradient at the edge. If this pressure gradient, localised at the plasma-vacuum boundary, becomes too steep, a magneto-hydro-dynamic instability is triggered and part of the plasma pressure is lost. This instability, hence called Edge-Localised-Mode, provokes large heat fluxes on some of the plasma-facing components of the machine, which could set operational limits for a tokamak the size of ITER. In order to understand this instability, and to determine the non-linear mechanisms behind the ELMs, the JOREK code is used. The work presented in this thesis is based on MHD simulations of ballooning modes (responsible for ELMs) with the JOREK code. At first, simulations are done for standard plasmas, inspired of experimental machines. In particular, the plasma rotation at equilibrium, in the region of the edge pressure gradient, is studied in order to obtain an analysis of the effects that such a rotation can have on the linear stability of ELMs and on their non-linear evolution. Then, as a second step, simulations are applied to plasmas of the experimental tokamaks JET and MAST (England). This permits the direct comparison of simulation results with experimental observations, with the main goal of improving our global understanding of ELMs. Adding to this physics aspect, the confrontation of the JOREK code with diagnostics of JET and MAST brings to a validation of simulations, which should prove that the simulations which were obtained do correspond to ELM instabilities. This first step towards the validation of the code is crucial concerning the simulation of ELMs in ITER

Passive RFID Localisation Framework in Smart Homes Healthcare Settings.

Science.gov (United States)

Alsinglawi, Belal; Liu, Tony; Nguyen, Quang Vinh; Gunawardana, Upul; Maeder, Anthony; Simoff, Simeon

2016-01-01

In recent years, Smart Homes have become a solution to benefit impaired individuals and elderly in their daily life settings. In healthcare applications, pervasive technologies have enabled the practicality of personal monitoring using Indoor positioning technologies. Radio-Frequency Identification (RFID) is a promising technology, which is useful for non-invasive tracking of activities of daily living. Many implementations have focused on using battery-enabled tags like in RFID active tags, which require frequent maintenance and they are costly. Other systems can use wearable sensors requiring individuals to wear tags which may be inappropriate for elders. Successful implementations of a tracking system are dependent on multiple considerations beyond the physical performance of the solution, such as affordability and human acceptance. This paper presents a localisation framework using passive RFID sensors. It aims to provide a low cost solution for subject location in Smart Homes healthcare.

Mutations in the ABCA4 (ABCR) Gene Are the Major Cause of Autosomal Recessive Cone-Rod Dystrophy

OpenAIRE

Maugeri, Alessandra; Klevering, B. Jeroen; Rohrschneider, Klaus; Blankenagel, Anita; Brunner, Han G.; Deutman, August F.; Hoyng, Carel B.; Cremers, Frans P. M.

2000-01-01

The photoreceptor cell–specific ATP-binding cassette transporter gene (ABCA4; previously denoted “ABCR”) is mutated in most patients with autosomal recessive (AR) Stargardt disease (STGD1) or fundus flavimaculatus (FFM). In addition, a few cases with AR retinitis pigmentosa (RP) and AR cone-rod dystrophy (CRD) have been found to have ABCA4 mutations. To evaluate the importance of the ABCA4 gene as a cause of AR CRD, we selected 5 patients with AR CRD and 15 patients with isolated CRD, all fro...

Gitelman or Bartter type 3 syndrome? A case of distal convoluted tubulopathy caused by CLCNKB gene mutation.

Science.gov (United States)

Cruz, António José; Castro, Alexandra

2013-01-22

A 32-year-old woman with no significant medical history was sent to our consultation due to hypokalaemia (syndrome (GS) came negative. CLCNKB gene mutation analysis present in both GS and Bartter (BS) type 3 syndromes was positive. The patient is now being treated with potassium and magnesium oral supplements, ramipril and spironolactone with stable near-normal potassium and magnesium levels. This article presents the case of a patient with hypokalaemia caused by CLCNKB gene mutation hard to categorise as GS or BS type 3.

Identification of three novel OA1 gene mutations identified in three families misdiagnosed with congenital nystagmus and carrier status determination by real-time quantitative PCR assay

Directory of Open Access Journals (Sweden)

Hamel Christian

2003-01-01

Full Text Available Abstract Background X-linked ocular albinism type 1 (OA1 is caused by mutations in OA1 gene, which encodes a membrane glycoprotein localised to melanosomes. OA1 mainly affects pigment production in the eye, resulting in optic changes associated with albinism including hypopigmentation of the retina, nystagmus, strabismus, foveal hypoplasia, abnormal crossing of the optic fibers and reduced visual acuity. Affected Caucasian males usually appear to have normal skin and hair pigment. Results We identified three previously undescribed mutations consisting of two intragenic deletions (one encompassing exon 6, the other encompassing exons 7–8, and a point mutation (310delG in exon 2. We report the development of a new method for diagnosis of heterozygous deletions in OA1 gene based on measurement of gene copy number using real-time quantitative PCR from genomic DNA. Conclusion The identification of OA1 mutations in families earlier reported as families with hereditary nystagmus indicate that ocular albinism type 1 is probably underdiagnosed. Our method of real-time quantitative PCR of OA1 exons with DMD exon as external standard performed on the LightCycler™ allows quick and accurate carrier-status assessment for at-risk females.

FLNC Gene Splice Mutations Cause Dilated Cardiomyopathy

Directory of Open Access Journals (Sweden)

Rene L. Begay, BS

2016-08-01

Full Text Available A genetic etiology has been identified in 30% to 40% of dilated cardiomyopathy (DCM patients, yet only 50% of these cases are associated with a known causative gene variant. Thus, in order to understand the pathophysiology of DCM, it is necessary to identify and characterize additional genes. In this study, whole exome sequencing in combination with segregation analysis was used to identify mutations in a novel gene, filamin C (FLNC, resulting in a cardiac-restricted DCM pathology. Here we provide functional data via zebrafish studies and protein analysis to support a model implicating FLNC haploinsufficiency as a mechanism of DCM.

Sub-cellular localisation studies may spuriously detect the Yes-associated protein, YAP, in nucleoli leading to potentially invalid conclusions of its function.

Science.gov (United States)

Finch, Megan L; Passman, Adam M; Strauss, Robyn P; Yeoh, George C; Callus, Bernard A

2015-01-01

The Yes-associated protein (YAP) is a potent transcriptional co-activator that functions as a nuclear effector of the Hippo signaling pathway. YAP is oncogenic and its activity is linked to its cellular abundance and nuclear localisation. Activation of the Hippo pathway restricts YAP nuclear entry via its phosphorylation by Lats kinases and consequent cytoplasmic retention bound to 14-3-3 proteins. We examined YAP expression in liver progenitor cells (LPCs) and surprisingly found that transformed LPCs did not show an increase in YAP abundance compared to the non-transformed LPCs from which they were derived. We then sought to ascertain whether nuclear YAP was more abundant in transformed LPCs. We used an antibody that we confirmed was specific for YAP by immunoblotting to determine YAP's sub-cellular localisation by immunofluorescence. This antibody showed diffuse staining for YAP within the cytosol and nuclei, but, noticeably, it showed intense staining of the nucleoli of LPCs. This staining was non-specific, as shRNA treatment of cells abolished YAP expression to undetectable levels by Western blot yet the nucleolar staining remained. Similar spurious YAP nucleolar staining was also seen in mouse embryonic fibroblasts and mouse liver tissue, indicating that this antibody is unsuitable for immunological applications to determine YAP sub-cellular localisation in mouse cells or tissues. Interestingly nucleolar staining was not evident in D645 cells suggesting the antibody may be suitable for use in human cells. Given the large body of published work on YAP in recent years, many of which utilise this antibody, this study raises concerns regarding its use for determining sub-cellular localisation. From a broader perspective, it serves as a timely reminder of the need to perform appropriate controls to ensure the validity of published data.

Localisation and identification of radioactive particles in solid samples by means of a nuclear track technique

International Nuclear Information System (INIS)

Boehnke, Antje; Treutler, Hanns-Christian; Freyer, Klaus; Schubert, Michael; Holger Weiss

2005-01-01

This study is aimed to develop a generally applicable methodology of investigation that can be used for the localisation of single alpha-active particles in solid samples, such as industrial dust or natural soils, sediments and rocks by autoradiography using solid-state nuclear track detectors. The developed technique allows the detection of local enrichments of alpha-emitters in any solid material. The results of such an investigation are of interest from technical, biological and environmental points of view. The idea behind the methodology is to locate the position of alpha-active spots in a sample by attaching the track detector to the sample in a defined manner, thoroughly described in the paper. The located alpha-active particles are subsequently analysed by an electron microscope and an electron microprobe. An example of the application of this methodology is also given. An ultra-fine -grained ore-processing residue, which causes serious environmental pollution in the respective mining district and thus limits possible land use and affects quality of life in the area, was examined using the described technique. The investigation revealed considerable amounts of alpha-active particles in this material

Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients

NARCIS (Netherlands)

Hawinkels, L.J.A.C.; Verspaget, H.W.; Duijn, W. van; Zon, J.M. van der; Zuidwijk, K.; Kubben, F.J.G.M.; Verheijen, J.H.; Hommes, D.W.; Lamers, C.B.H.W.; Sier, C.F.M.

2007-01-01

Transforming growth factor-β1 (TGF-β1), a tumour suppressing as well as tumour-promoting cytokine, is stored as an extracellular matrix-bound latent complex. We examined TGF-β1 activation and localisation of TGF-β1 activity in gastric cancer. Gastric tumours showed increased stromal and epithelial

Gene transposition causing natural variation for growth in Arabidopsis thaliana.

Science.gov (United States)

Vlad, Daniela; Rappaport, Fabrice; Simon, Matthieu; Loudet, Olivier

2010-05-13

A major challenge in biology is to identify molecular polymorphisms responsible for variation in complex traits of evolutionary and agricultural interest. Using the advantages of Arabidopsis thaliana as a model species, we sought to identify new genes and genetic mechanisms underlying natural variation for shoot growth using quantitative genetic strategies. More quantitative trait loci (QTL) still need be resolved to draw a general picture as to how and where in the pathways adaptation is shaping natural variation and the type of molecular variation involved. Phenotypic variation for shoot growth in the Bur-0 x Col-0 recombinant inbred line set was decomposed into several QTLs. Nearly-isogenic lines generated from the residual heterozygosity segregating among lines revealed an even more complex picture, with major variation controlled by opposite linked loci and masked by the segregation bias due to the defective phenotype of SG3 (Shoot Growth-3), as well as epistasis with SG3i (SG3-interactor). Using principally a fine-mapping strategy, we have identified the underlying gene causing phenotypic variation at SG3: At4g30720 codes for a new chloroplast-located protein essential to ensure a correct electron flow through the photosynthetic chain and, hence, photosynthesis efficiency and normal growth. The SG3/SG3i interaction is the result of a structural polymorphism originating from the duplication of the gene followed by divergent paralogue's loss between parental accessions. Species-wide, our results illustrate the very dynamic rate of duplication/transposition, even over short periods of time, resulting in several divergent--but still functional-combinations of alleles fixed in different backgrounds. In predominantly selfing species like Arabidopsis, this variation remains hidden in wild populations but is potentially revealed when divergent individuals outcross. This work highlights the need for improved tools and algorithms to resolve structural variation

Human case of bacteremia caused by Streptococcus canis sequence type 9 harboring the scm gene.

Science.gov (United States)

Taniyama, Daisuke; Abe, Yoshihiko; Sakai, Tetsuya; Kikuchi, Takahide; Takahashi, Takashi

2017-01-01

Streptococcus canis (Sc) is a zoonotic pathogen that is transferred mainly from companion animals to humans. One of the major virulence factors in Sc is the M-like protein encoded by the scm gene, which is involved in anti-phagocytic activities, as well as the recruitment of plasminogen to the bacterial surface in cooperation with enolase, and the consequent enhancement of bacterial transmigration and survival. This is the first reported human case of uncomplicated bacteremia following a dog bite, caused by Streptococcus canis harboring the scm gene. The similarity of the 16S rRNA from the infecting species to that of the Sc type strain, as well as the amplification of the species-specific cfg gene, encoding a co-hemolysin, was used to confirm the species identity. Furthermore, the isolate was confirmed as sequence type 9. The partial scm gene sequence harbored by the isolate was closely related to those of other two Sc strains. While this isolate did not possess the erm (A), erm (B), or mef (A), macrolide/lincosamide resistance genes, it was not susceptible to azithromycin: its susceptibility was intermediate. Even though human Sc bacteremia is rare, clinicians should be aware of this microorganism, as well as Pasteurella sp., Prevotella sp., and Capnocytophaga sp., when examining and treating patients with fever who maintain close contact with companion animals.

Localised Agri-food Systems in Italy: strategies for competitiveness and role of institutional factors

OpenAIRE

Mantino, Francesco

2014-01-01

This paper focuses on the notion of localised agricultural and agro-food system as unit of analysis (LAFS). LAFSs appear to be as quite resilient and dynamic systems. As we will see, the analysis of exports in the last years can provide enough evidence of their strong resilience and capability to respond to economic crisis. This dynamics does not seem understandable by only using either classical variables (size of farm holdings, intensity of capital investment, human capital, rate of technol...

Evaluation of a three-dimensional ultrasound localisation system incorporating probe pressure correction for use in partial breast irradiation.

Science.gov (United States)

Harris, E J; Symonds-Taylor, R; Treece, G M; Gee, A H; Prager, R W; Brabants, P; Evans, P M

2009-10-01

This work evaluates a three-dimensional (3D) freehand ultrasound-based localisation system with new probe pressure correction for use in partial breast irradiation. Accuracy and precision of absolute position measurement was measured as a function of imaging depth (ID), object depth, scanning direction and time using a water phantom containing crossed wires. To quantify the improvement in accuracy due to pressure correction, 3D scans of a breast phantom containing ball bearings were obtained with and without pressure. Ball bearing displacements were then measured with and without pressure correction. Using a single scan direction (for all imaging depths), the mean error was <1.3 mm, with the exception of the wires at 68.5 mm imaged with an ID of 85 mm, which gave a mean error of -2.3 mm. Precision was greater than 1 mm for any single scan direction. For multiple scan directions, precision was within 1.7 mm. Probe pressure corrections of between 0 mm and 2.2 mm have been observed for pressure displacements of 1.1 mm to 4.2 mm. Overall, anteroposterior position measurement accuracy increased from 2.2 mm to 1.6 mm and to 1.4 mm for the two opposing scanning directions. Precision is comparable to that reported for other commercially available ultrasound localisation systems, provided that 3D image acquisition is performed in the same scan direction. The existing temporal calibration is imperfect and a "per installation" calibration would further improve the accuracy and precision. Probe pressure correction was shown to improve the accuracy and will be useful for the localisation of the excision cavity in partial breast radiotherapy.

Localisation of a channel instability in a BWR via neutron noise methods

International Nuclear Information System (INIS)

Karlsson, J.K.H.; Pazsit, I.

1998-01-01

A special type of instability occurred in the Swedish BWR Forsmark 1 in 1996. In contrast to the better known global or regional (out-of-phase) instabilities, the decay ratio appeared to be very high in one half of the core and quite low in the other half. A more detailed analysis showed that the most likely reason for the observed behaviour is a local perturbation of thermohydraulic character, e.g. a density wave oscillation (DWO), induced by the incorrect positioning of a fuel assembly (an 'unseated' assembly). In such a case it is of large importance to determine the position of the unseated assembly already during operation such that it can be easily found during reloading. The subject of this paper is to report on development and application of methods by which the position of such a local perturbation can be determined. Two different methods that support and complement each other were used. First a visualisation technique was elaborated which expedites a very good qualitative comprehension of the situation and which can be useful for the operators. It also gives an important basis for the application of the localisation algorithm. Second, a quantitative (algorithmic) localisation method, suited for this type of perturbation, was elaborated. This latter takes noise spectra from selected detectors as input and yields the perturbation position as output. The method was tested on simulated data, and then applied to the Forsmark measurements. The location of the disturbance, found by the algorithm, is in accordance with independent judgements for the case, and close to a position where an unseated assembly was found during refuelling. (author)

Study of genes induced by ionizing radiations at Arabidopsis thaliana: identification and molecular characterization of the ATGR1 gene, a new gene encoding a protein involved in plant cell division

International Nuclear Information System (INIS)

Deveaux, Yves

1999-01-01

DNA damage, that can be experimentally introduced by ionizing radiation (IR), induces complex signal transduction pathways leading to cell recovery or, alternatively to programmed cell death if damages are too severe. To identify the inducible components of the response to genotoxic stress in plants, we have screened by Differential Display for mRNAs that rapidly and strongly accumulate after IR treatment in A. thaliana cells. We have characterized ATGR1, a new single copy Arabidopsis gene encoding a PEST-box protein of unknown function. In unstressed plant organs the ATGR1 mRNA is hardly detectable, whereas the protein is present in extracts prepared from roots, shoot meristems and inflorescences, that all contain large amounts of actively dividing cells. This pattern is confirmed by immuno localisation on tissue sections that shows constitutive ATGR1 protein expression covering the root elongation zone, the shoot meristem, leaf primordial and the ovules of developing flowers. Histochemical analysis of transgenic plants expressing the GUS reporter gene under the control of the ATGR1 promoter, demonstrate that the developmental and tissue-specific profile of ATGR1 protein expression is conferred by the gene promoter. The massive, transient and dose-dependent accumulation of ATGR1 transcripts after IR treatment observed in all plant organs does not lead to significant changes in ATGR1 protein pattern. Stable ATGR1 protein overexpression, as exemplified by transgenic A. thaliana plants that contain a 35S promoter-ATGR1 gene fusion, does not induce notable changes of the overall ATGR1 protein level, but leads to male and female sterility. The cause of sterility is a lack of correct chromosome assembly and distribution at the stage metaphase II of meiosis. Taken together our results show that i) ATGR1 gene expression is associated to cell division during plant development ii) the ATGR1 protein level is regulated at the transcriptional and post-transcriptional level iii

State and localisation of the nuclear wastes in France. Index established by the ANDRA observatory

International Nuclear Information System (INIS)

1999-01-01

This index is the seventh edition of the the national index on nuclear wastes state and localisation. Its purpose is to index the sites where people could find radioactive wastes in France (great industry as EDF or Cogema but also little producers, national defense sites and research laboratories) and the sealed sources distributors. Law texts concerning the radioactive wastes and general information on nuclear elements or radioactivity are also provided. (A.L.B.)

Campylobacter jejuni, an uncommon cause of splenic abscess diagnosed by 16S rRNA gene sequencing

Directory of Open Access Journals (Sweden)

Piseth Seng

2014-12-01

Full Text Available Splenic abscess is a rare disease that primarily occurs in patients with splenic trauma, endocarditis, sickle cell anemia, or other diseases that compromise the immune system. This report describes a culture-negative splenic abscess in an immunocompetent patient caused by Campylobacter jejuni, as determined by 16S rRNA gene sequencing.

Wolbachia lipoproteins: abundance, localisation and serology of Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6 from Brugia malayi and Aedes albopictus.

Science.gov (United States)

Voronin, Denis; Guimarães, Ana F; Molyneux, Gemma R; Johnston, Kelly L; Ford, Louise; Taylor, Mark J

2014-10-06

Lipoproteins are the major agonists of Wolbachia-dependent inflammatory pathogenesis in filariasis and a validated target for drug discovery. Here we characterise the abundance, localisation and serology of the Wolbachia lipoproteins: Wolbachia peptidoglycan associated lipoprotein and the Type IV Secretion System component, VirB6. We used proteomics to confirm lipoprotein presence and relative abundance; fractionation, immunoblotting and confocal and electron immuno-microscopy for localisation and ELISA for serological analysis. Proteomic analysis of Brugia malayi adult female protein extracts confirmed the presence of two lipoproteins, previously predicted through bioinformatics: Wolbachia peptidoglycan associated lipoprotein (wBmPAL) and the Type IV Secretion System component, VirB6 (wBmVirB6). wBmPAL was among the most abundant Wolbachia proteins present in an extract of adult female worms with wBmVirB6 only detected at a much lower abundance. This differential abundance was reflected in the immunogold-labelling, which showed wBmPAL localised at numerous sites within the bacterial membranes, whereas wBmVirB6 was present as a single cluster on each bacterial cell and also located within the bacterial membranes. Immunoblotting of fractionated extracts confirmed the localisation of wBmPAL to membranes and its absence from cytosolic fractions of C6/36 mosquito cells infected with wAlbB. In whole worm mounts, antibody labelling of both lipoproteins were associated with Wolbachia. Serological analysis showed that both proteins were immunogenic and raised antibody responses in the majority of individuals infected with Wuchereria bancrofti. Two Wolbachia lipoproteins, wBmPAL and wBmVirB6, are present in extracts of Brugia malayi with wBmPAL among the most abundant of Wolbachia proteins. Both lipoproteins localised to bacterial membranes with wBmVirB6 present as a single cluster suggesting a single Type IV Secretory System on each Wolbachia cell.

Basolateral localisation of KCNQ1 potassium channels in MDCK cells: molecular identification of an N-terminal targeting motif

DEFF Research Database (Denmark)

Jespersen, Thomas; Rasmussen, Hanne B; Grunnet, Morten

2004-01-01

of the tyrosine residue at position 51 resulted in a non-polarized steady-state distribution of the channel. The importance of tyrosine 51 in basolateral localisation was emphasized by the fact that a short peptide comprising this tyrosine was able to redirect the p75 neurotrophin receptor, an otherwise apically...

Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain

Directory of Open Access Journals (Sweden)

Puri Raj K

2008-06-01

Full Text Available Abstract Background Neurovirulent Venezuelan equine encephalitis virus (VEEV causes lethal encephalitis in equines and is transmitted to humans by mosquitoes. VEEV is highly infectious when transmitted by aerosol and has been developed as a bio-warfare agent, making it an important pathogen to study from a military and civilian standpoint. Molecular mechanisms of VEE pathogenesis are poorly understood. To study these, the gene expression profile of VEEV infected mouse brains was investigated. Changes in gene expression were correlated with histological changes in the brain. In addition, a molecular framework of changes in gene expression associated with progression of the disease was studied. Results Our results demonstrate that genes related to important immune pathways such as antigen presentation, inflammation, apoptosis and response to virus (Cxcl10, CxCl11, Ccl5, Ifr7, Ifi27 Oas1b, Fcerg1,Mif, Clusterin and MHC class II were upregulated as a result of virus infection. The number of over-expressed genes (>1.5-fold level increased as the disease progressed (from 197, 296, 400, to 1086 at 24, 48, 72 and 96 hours post infection, respectively. Conclusion Identification of differentially expressed genes in brain will help in the understanding of VEEV-induced pathogenesis and selection of biomarkers for diagnosis and targeted therapy of VEEV-induced neurodegeneration.

Simplified segmented human models for whole body and localised SAR evaluation of 20 MHz to 6 GHz electromagnetic field exposures

International Nuclear Information System (INIS)

Wu, T.; Shao, Q.; Yang, L.

2013-01-01

The digital human model is a key element in evaluating the electromagnetic field (EMF) exposure. This paper proposes the application of simplified segmented human models for EMF exposure compliance evaluation with the whole body and the localised limits. The method is based on the fact that most of the EMF power absorption is concentrated in several major tissues. Two kinds of human models were simply (the proposed method) and precisely segmented from two sets of whole body magnetic resonance imaging (MRI) scanned images. The whole body average-specific absorption rate (WBA-SAR) and the peak localised SAR averaging over 10 g tissues for the two kinds of models are calculated for various exposure configurations. The results confirmed the efficiency and the validity of the proposed method. The application as evaluating the MRI radiofrequency EMF exposure is also discussed in the paper. (authors)

Phenotypic spectrum of autosomal recessive cone-rod dystrophies caused by mutations in the ABCA4 (ABCR) gene.

NARCIS (Netherlands)

Klevering, B.J.; Blankenagel, A.; Maugeri, A.; Cremers, F.P.M.; Hoyng, C.B.; Rohrschneider, K.

2002-01-01

PURPOSE: To describe the phenotype of 12 patients with autosomal recessive or isolated cone-rod types of progressive retinal degeneration (CRD) caused by mutations in the ABCA4 gene. METHODS: The charts of patients who had originally received a diagnosis of isolated or autosomal recessive CRD were

Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes.

Science.gov (United States)

Torsvik, Janniche; Johansson, Stefan; Johansen, Anders; Ek, Jakob; Minton, Jayne; Raeder, Helge; Ellard, Sian; Hattersley, Andrew; Pedersen, Oluf; Hansen, Torben; Molven, Anders; Njølstad, Pål R

2010-01-01

We have previously shown that heterozygous single-base deletions in the carboxyl-ester lipase (CEL) gene cause exocrine and endocrine pancreatic dysfunction in two multigenerational families. These deletions were found in the first and fourth repeats of a variable number of tandem repeats (VNTR), which has proven challenging to sequence due to high GC-content and considerable length variation. We have therefore developed a screening method consisting of a multiplex PCR followed by fragment analysis. The method detected putative disease-causing insertions and deletions in the proximal repeats of the VNTR, and determined the VNTR-length of each allele. When blindly testing 56 members of the two families with known single-base deletions in the CEL VNTR, the method correctly assessed the mutation carriers. Screening of 241 probands from suspected maturity-onset diabetes of the young (MODY) families negative for mutations in known MODY genes (95 individuals from Denmark and 146 individuals from UK) revealed no deletions in the proximal repeats of the CEL VNTR. However, we found one Danish patient with a short, novel CEL allele containing only three VNTR repeats (normal range 7-23 in healthy controls). This allele co-segregated with diabetes or impaired glucose tolerance in the patient's family as six of seven mutation carriers were affected. We also identified individuals who had three copies of a complete CEL VNTR. In conclusion, the CEL gene is highly polymorphic, but mutations in CEL are likely to be a rare cause of monogenic diabetes.

Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

Science.gov (United States)

van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

2015-12-01

A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. Georg Thieme Verlag KG Stuttgart · New York.

XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing.

Science.gov (United States)

Piton, Amélie; Redin, Claire; Mandel, Jean-Louis

2013-08-08

Because of the unbalanced sex ratio (1.3-1.4 to 1) observed in intellectual disability (ID) and the identification of large ID-affected families showing X-linked segregation, much attention has been focused on the genetics of X-linked ID (XLID). Mutations causing monogenic XLID have now been reported in over 100 genes, most of which are commonly included in XLID diagnostic gene panels. Nonetheless, the boundary between true mutations and rare non-disease-causing variants often remains elusive. The sequencing of a large number of control X chromosomes, required for avoiding false-positive results, was not systematically possible in the past. Such information is now available thanks to large-scale sequencing projects such as the National Heart, Lung, and Blood (NHLBI) Exome Sequencing Project, which provides variation information on 10,563 X chromosomes from the general population. We used this NHLBI cohort to systematically reassess the implication of 106 genes proposed to be involved in monogenic forms of XLID. We particularly question the implication in XLID of ten of them (AGTR2, MAGT1, ZNF674, SRPX2, ATP6AP2, ARHGEF6, NXF5, ZCCHC12, ZNF41, and ZNF81), in which truncating variants or previously published mutations are observed at a relatively high frequency within this cohort. We also highlight 15 other genes (CCDC22, CLIC2, CNKSR2, FRMPD4, HCFC1, IGBP1, KIAA2022, KLF8, MAOA, NAA10, NLGN3, RPL10, SHROOM4, ZDHHC15, and ZNF261) for which replication studies are warranted. We propose that similar reassessment of reported mutations (and genes) with the use of data from large-scale human exome sequencing would be relevant for a wide range of other genetic diseases. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Induced pluripotent stem cells derived from a patient with autosomal dominant familial neurohypophyseal diabetes insipidus caused by a variant in the AVP gene

Directory of Open Access Journals (Sweden)

Lise Bols Toustrup

2017-03-01

Full Text Available Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI is caused by variants in the arginine vasopressin (AVP gene. Here we report the generation of induced pluripotent stem cells (iPSCs from a 42-year-old man carrying an adFNDI causing variant in exon 1 of the AVP gene using lentivirus-mediated nuclear reprogramming. The iPSCs carried the expected variant in the AVP gene. Furthermore, the iPSCs expressed pluripotency markers; displayed in vitro differentiation potential to the three germ layers and had a normal karyotype consistent with the original fibroblasts. This iPSC line is useful in future studies focusing on the pathogenesis of adFNDI.

Three-dimensional sound localisation with a lizard peripheral auditory model

DEFF Research Database (Denmark)

Kjær Schmidt, Michael; Shaikh, Danish

the networks learned a transfer function that translated the three-dimensional non-linear mapping into estimated azimuth and elevation values for the acoustic target. The neural network with two hidden layers as expected performed better than that with only one hidden layer. Our approach assumes that for any...... location of an acoustic target in three dimensions. Our approach utilises a model of the peripheral auditory system of lizards [Christensen-Dalsgaard and Manley 2005] coupled with a multi-layer perceptron neural network. The peripheral auditory model’s response to sound input encodes sound direction...... information in a single plane which by itself is insufficient to localise the acoustic target in three dimensions. A multi-layer perceptron neural network is used to combine two independent responses of the model, corresponding to two rotational movements, into an estimate of the sound direction in terms...

MASA syndrome is caused by mutations in the neural cell adhesion gene, L1CAM

Energy Technology Data Exchange (ETDEWEB)

Schwartz, C.E.; Wang, Y.; Schroer, R.J.; Stevenson, R.E. [Greenwood Genetic Center, SC (United States)

1994-09-01

The MASA syndrome is a recessive X-linked disorder characterized by Mental retardation, Adducted thumbs, Shuffling gait and Aphasia. Recently we found that MASA in one family was likely caused by a point mutation in exon 6 of the L1CAM gene. This gene has also been shown to be involved in X-linked hydrocephalus (HSAS). We have screened 60 patients with either sporadic HSAS or MASA as well as two additional families with MASA. For the screening, we initially utilized 3 cDNA probes for the L1CAM gene. In one of the MASA families, K8310, two affected males were found to have an altered BglII band. The band was present in their carrier mother but not in their normal brothers. This band was detected by the entire cDNA probe as well as the cDNA probe for 3{prime} end of the gene. Analysis of the L1CAM sequence indicated the altered BglII site is distal to the exon 28 but proximal to the punative poly A signal site. It is hypothesized that this point mutation alters the stability of the L1CAM mRNA. This is being tested using cell lines established from the two affected males.

Deletion of ETS-1, a gene in the Jacobsen syndrome critical region, causes ventricular septal defects and abnormal ventricular morphology in mice

Science.gov (United States)

Ye, Maoqing; Coldren, Chris; Liang, Xingqun; Mattina, Teresa; Goldmuntz, Elizabeth; Benson, D. Woodrow; Ivy, Dunbar; Perryman, M.B.; Garrett-Sinha, Lee Ann; Grossfeld, Paul

2010-01-01

Congenital heart defects comprise the most common form of major birth defects, affecting 0.7% of all newborn infants. Jacobsen syndrome (11q-) is a rare chromosomal disorder caused by deletions in distal 11q. We have previously determined that a wide spectrum of the most common congenital heart defects occur in 11q-, including an unprecedented high frequency of hypoplastic left heart syndrome (HLHS). We identified an ∼7 Mb ‘cardiac critical region’ in distal 11q that contains a putative causative gene(s) for congenital heart disease. In this study, we utilized chromosomal microarray mapping to characterize three patients with 11q- and congenital heart defects that carry interstitial deletions overlapping the 7 Mb cardiac critical region. We propose that this 1.2 Mb region of overlap harbors a gene(s) that causes at least a subset of the congenital heart defects that occur in 11q-. We demonstrate that one gene in this region, ETS-1 (a member of the ETS family of transcription factors), is expressed in the endocardium and neural crest during early mouse heart development. Gene-targeted deletion of ETS-1 in mice in a C57/B6 background causes, with high penetrance, large membranous ventricular septal defects and a bifid cardiac apex, and less frequently a non-apex-forming left ventricle (one of the hallmarks of HLHS). Our results implicate an important role for the ETS-1 transcription factor in mammalian heart development and should provide important insights into some of the most common forms of congenital heart disease. PMID:19942620

Bacillus anthracis TIR Domain-Containing Protein Localises to Cellular Microtubule Structures and Induces Autophagy.

Science.gov (United States)

Carlsson, Emil; Thwaite, Joanne E; Jenner, Dominic C; Spear, Abigail M; Flick-Smith, Helen; Atkins, Helen S; Byrne, Bernadette; Ding, Jeak Ling

2016-01-01

Toll-like receptors (TLRs) recognise invading pathogens and mediate downstream immune signalling via Toll/IL-1 receptor (TIR) domains. TIR domain proteins (Tdps) have been identified in multiple pathogenic bacteria and have recently been implicated as negative regulators of host innate immune activation. A Tdp has been identified in Bacillus anthracis, the causative agent of anthrax. Here we present the first study of this protein, designated BaTdp. Recombinantly expressed and purified BaTdp TIR domain interacted with several human TIR domains, including that of the key TLR adaptor MyD88, although BaTdp expression in cultured HEK293 cells had no effect on TLR4- or TLR2- mediated immune activation. During expression in mammalian cells, BaTdp localised to microtubular networks and caused an increase in lipidated cytosolic microtubule-associated protein 1A/1B-light chain 3 (LC3), indicative of autophagosome formation. In vivo intra-nasal infection experiments in mice showed that a BaTdp knockout strain colonised host tissue faster with higher bacterial load within 4 days post-infection compared to the wild type B. anthracis. Taken together, these findings indicate that BaTdp does not play an immune suppressive role, but rather, its absence increases virulence. BaTdp present in wild type B. anthracis plausibly interact with the infected host cell, which undergoes autophagy in self-defence.

Towards understanding edge localised mode mitigation by resonant magnetic perturbations in MAST

Energy Technology Data Exchange (ETDEWEB)

Chapman, I. T.; Kirk, A.; Ham, C. J.; Harrison, J. R.; Liu, Y. Q.; Saarelma, S.; Scannell, R.; Thornton, A. J.; Team, MAST [EURATOM/CCFE Fusion Association, Culham Science Centre, Abingdon, Oxfordshire OX14 3DB (United Kingdom); Becoulet, M.; Orain, F. [Association Euratom/CEA, CEA Cadarache, IRFM, F-13108, St. Paul-lez-Durance (France); Cooper, W. A. [CRPP, Association EURATOM/Confédération Suisse, EPFL, 1015 Lausanne (Switzerland); Pamela, S. [IIFS-PIIM. Aix Marseille Université—CNRS, 13397 Marseille Cedex 20 (France)

2013-05-15

Type-I Edge Localised Modes (ELMs) have been mitigated in MAST through the application of n=3,4, and 6 resonant magnetic perturbations. For each toroidal mode number of the non-axisymmetric applied fields, the frequency of the ELMs has been increased significantly, and the peak heat flux on the divertor plates reduced commensurately. This increase in ELM frequency occurs despite a significant drop in the edge pressure gradient, which would be expected to stabilise the peeling-ballooning modes thought to be responsible for type-I ELMs. Various mechanisms which could cause a destabilisation of the peeling-ballooning modes are presented, including pedestal widening, plasma rotation braking, three dimensional corrugation of the plasma boundary, and the existence of radially extended lobe structures near to the X-point. This leads to a model aimed at resolving the apparent dichotomy of ELM control, which is to say ELM suppression occurring due to the pedestal pressure reduction below the peeling-ballooning stability boundary, whilst the reduction in pressure can also lead to ELM mitigation, which is ostensibly a destabilisation of peeling-ballooning modes. In the case of ELM mitigation, the pedestal broadening, 3d corrugation, or lobes near the X-point degrade ballooning stability so much that the pedestal recovers rapidly to cross the new stability boundary at lower pressure more frequently, whilst in the case of suppression, the plasma parameters are such that the particle transport reduces the edge pressure below the stability boundary, which is only mildly affected by negligible rotation braking, small edge corrugation or short, broad lobe structures.

Somatic USP8 Gene Mutations Are a Common Cause of Pediatric Cushing Disease.

Science.gov (United States)

Faucz, Fabio R; Tirosh, Amit; Tatsi, Christina; Berthon, Annabel; Hernández-Ramírez, Laura C; Settas, Nikolaos; Angelousi, Anna; Correa, Ricardo; Papadakis, Georgios Z; Chittiboina, Prashant; Quezado, Martha; Pankratz, Nathan; Lane, John; Dimopoulos, Aggeliki; Mills, James L; Lodish, Maya; Stratakis, Constantine A

2017-08-01

Somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have been recently identified as the most common genetic alteration in patients with Cushing disease (CD). However, the frequency of these mutations in the pediatric population has not been extensively assessed. We investigated the status of the USP8 gene at the somatic level in a cohort of pediatric patients with corticotroph adenomas. The USP8 gene was fully sequenced in both germline and tumor DNA samples from 42 pediatric patients with CD. Clinical, biochemical, and imaging data were compared between patients with and without somatic USP8 mutations. Five different USP8 mutations (three missense, one frameshift, and one in-frame deletion) were identified in 13 patients (31%), all of them located in exon 14 at the previously described mutational hotspot, affecting the 14-3-3 binding motif of the protein. Patients with somatic mutations were older at disease presentation [mean 5.1 ± 2.1 standard deviation (SD) vs 13.1 ± 3.6 years, P = 0.03]. Levels of urinary free cortisol, midnight serum cortisol, and adrenocorticotropic hormone, as well as tumor size and frequency of invasion of the cavernous sinus, were not significantly different between the two groups. However, patients harboring somatic USP8 mutations had a higher likelihood of recurrence compared with patients without mutations (46.2% vs 10.3%, P = 0.009). Somatic USP8 gene mutations are a common cause of pediatric CD. Patients harboring a somatic mutation had a higher likelihood of tumor recurrence, highlighting the potential importance of this molecular defect for the disease prognosis and the development of targeted therapeutic options. Copyright © 2017 Endocrine Society

An innovative strategy to clone positive modifier genes of defects caused by mtDNA mutations: MRPS18C as suppressor gene of m.3946G>A mutation in MT-ND1 gene.

Science.gov (United States)

Rodríguez-García, María Elena; Cotrina-Vinagre, Francisco Javier; Carnicero-Rodríguez, Patricia; Martínez-Azorín, Francisco

2017-07-01

We have developed a new functional complementation approach to clone modifier genes which overexpression is able to suppress the biochemical defects caused by mtDNA mutations (suppressor genes). This strategy consists in transferring human genes into respiratory chain-deficient fibroblasts, followed by a metabolic selection in a highly selective medium. We used a normalized expression cDNA library in an episomal vector (pREP4) to transfect the fibroblasts, and a medium with glutamine and devoid of any carbohydrate source to select metabolically. Growing the patient's fibroblasts in this selective medium, the deficient cells rapidly disappear unless they are rescued by the cDNA of a suppressor gene. The use of an episomal vector allows us to carry out several rounds of transfection/selection (cyclical phenotypic rescue) to enrich the rescue with true clones of suppressor genes. Using fibroblasts from a patient with epileptic encephalopathy with the m.3946G>A (p.E214K) mutation in the MT-ND1 gene, several candidate genes were identified and one of them was characterized functionally. Thus, overexpression of MRPS18C gene (that encode for bS18m protein) suppressed the molecular defects produced by this mtDNA mutation, recovering the complex I activity and reducing the ROS produced by this complex to normal levels. We suggest that modulation of bS18m expression may be an effective therapeutic strategy for the patients with this mutation.

North Carolina macular dystrophy (MCDR1) caused by a novel tandem duplication of the PRDM13 gene.

Science.gov (United States)

Bowne, Sara J; Sullivan, Lori S; Wheaton, Dianna K; Locke, Kirsten G; Jones, Kaylie D; Koboldt, Daniel C; Fulton, Robert S; Wilson, Richard K; Blanton, Susan H; Birch, David G; Daiger, Stephen P

2016-01-01

To identify the underlying cause of disease in a large family with North Carolina macular dystrophy (NCMD). A large four-generation family (RFS355) with an autosomal dominant form of NCMD was ascertained. Family members underwent comprehensive visual function evaluations. Blood or saliva from six affected family members and three unaffected spouses was collected and DNA tested for linkage to the MCDR1 locus on chromosome 6q12. Three affected family members and two unaffected spouses underwent whole exome sequencing (WES) and subsequently, custom capture of the linkage region followed by next-generation sequencing (NGS). Standard PCR and dideoxy sequencing were used to further characterize the mutation. Of the 12 eyes examined in six affected individuals, all but two had Gass grade 3 macular degeneration features. Large central excavation of the retinal and choroid layers, referred to as a macular caldera, was seen in an age-independent manner in the grade 3 eyes. The calderas are unique to affected individuals with MCDR1. Genome-wide linkage mapping and haplotype analysis of markers from the chromosome 6q region were consistent with linkage to the MCDR1 locus. Whole exome sequencing and custom-capture NGS failed to reveal any rare coding variants segregating with the phenotype. Analysis of the custom-capture NGS sequencing data for copy number variants uncovered a tandem duplication of approximately 60 kb on chromosome 6q. This region contains two genes, CCNC and PRDM13 . The duplication creates a partial copy of CCNC and a complete copy of PRDM13 . The duplication was found in all affected members of the family and is not present in any unaffected members. The duplication was not seen in 200 ethnically matched normal chromosomes. The cause of disease in the original family with MCDR1 and several others has been recently reported to be dysregulation of the PRDM13 gene, caused by either single base substitutions in a DNase 1 hypersensitive site upstream of the CCNC

Challenges to Globalisation, Localisation and Sinophilia in Music Education: A Comparative Study of Hong Kong, Shanghai and Taipei

Science.gov (United States)

Ho, Wai-Chung; Law, Wing-Wah

2006-01-01

In the past, the music curricula of Hong Kong (HK), Mainland China and Taiwan have focused on Western music, but with the advent of music technology and the new tripartite paradigm of globalisation, localisation and Sinophilia this has begun to change. Hong Kong, Shanghai and Taipei share a common historical culture and their populations are…

Can MRI Localise the Cause of Chronic Low Backache in Lumbar Spondylosis and Help Guide Specific Management?

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Joish Upendra Kumar

2017-10-01

Full Text Available Introduction: MRI is a primary imaging modality in assessing chronic low backache. Many of the findings identified on MRI may not be symptomatic. Nerve root compressions, compression of cauda equina, posterior annular tear, facetal arthropathy are more likely to be symptomatic. Management of each of these pathologies vary. It is essential to identify the pathologies that can cause pain and symptoms in lumbar spondylosis. Aim: To identify the specific finding/pathology on MRI that corresponds to the clinical presentation of the patient with lumbar spondylosis. Materials and Methods: The study was done between May and December 2016 and included 100 patients who were referred for MRI of lumbosacral spine with history of debilitating backache for more than 2 weeks. After ruling out other causes, clinical evaluation of patients was done to localize leve; and type of pain. T1, T2 weighted and STIR imaging of lumbo-sacral spine was done. The images were studied to localize the pathology which most likely caused the pattern of pain the patient experienced. Results: The study included 55 ladies and 45 men. 42 people had radiculopathy. In 86% of cases, MRI helped in localizing the exact pathology responsible for the pattern of pain the patients experienced. Nerve compressions were seen in 86% of patients with radiculopathy. Among the people without radiculopathy, the cause for pain could be localized in 86%. The most common cause of pain identified was horizontal posterior annular fissure (40%. Conclusion: In a significant number of patients with chronic low backache, we can identify the specific pathology that corroborates with the clinical symptomatology of the patient. This aids in guiding specific management to provide symptomatic relief.

Telomeric repeat-containing RNA/G-quadruplex-forming sequences cause genome-wide alteration of gene expression in human cancer cells in vivo.

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Hirashima, Kyotaro; Seimiya, Hiroyuki

2015-02-27

Telomere erosion causes cell mortality, suggesting that longer telomeres enable more cell divisions. In telomerase-positive human cancer cells, however, telomeres are often kept shorter than those of surrounding normal tissues. Recently, we showed that cancer cell telomere elongation represses innate immune genes and promotes their differentiation in vivo. This implies that short telomeres contribute to cancer malignancy, but it is unclear how such genetic repression is caused by elongated telomeres. Here, we report that telomeric repeat-containing RNA (TERRA) induces a genome-wide alteration of gene expression in telomere-elongated cancer cells. Using three different cell lines, we found that telomere elongation up-regulates TERRA signal and down-regulates innate immune genes such as STAT1, ISG15 and OAS3 in vivo. Ectopic TERRA oligonucleotides repressed these genes even in cells with short telomeres under three-dimensional culture conditions. This appeared to occur from the action of G-quadruplexes (G4) in TERRA, because control oligonucleotides had no effect and a nontelomeric G4-forming oligonucleotide phenocopied the TERRA oligonucleotide. Telomere elongation and G4-forming oligonucleotides showed similar gene expression signatures. Most of the commonly suppressed genes were involved in the innate immune system and were up-regulated in various cancers. We propose that TERRA G4 counteracts cancer malignancy by suppressing innate immune genes. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome.

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Damien F Hudson

2016-12-01

Full Text Available Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene is the BLM helicase that is a member of a protein complex along with topoisomerase III alpha, RMI1 and 2, which maintains replication fork stability and dissolves double Holliday junctions to prevent genome instability. Here we report the identification of a second gene, RMI2, that is deleted in affected siblings with Bloom-like features. Cells from homozygous individuals exhibit elevated rates of sister chromatid exchange, anaphase DNA bridges and micronuclei. Similar genome and chromosome instability phenotypes are observed in independently derived RMI2 knockout cells. In both patient and knockout cell lines reduced localisation of BLM to ultra fine DNA bridges and FANCD2 at foci linking bridges are observed. Overall, loss of RMI2 produces a partially active BLM complex with mild features of Bloom syndrome.

How AI localisation in plant tissues determines the targeted pest spectrum of different chemistries

DEFF Research Database (Denmark)

Buchholz, Anke; Trapp, Stefan

penetration as first crucial step can be modified by formulation whereas the active ingredient (AI) distribution within cells is usually solely determined by physicochemical properties. This passive AI distribution was calculated with the Fick-Nernst-Planck equation implemented in a cell model....... The predictions were compared to the measured biological effects against three different arthropods. Test compounds differed in log P (-0.1 to 4.3) and pKa (4.1 to 10.7). Efficacies in different bioassays are discussed with the postulated cellular AI localisation and the individual feeding behaviour...

Fibre Tip Sensors for Localised Temperature Sensing Based on Rare Earth-Doped Glass Coatings

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Erik P. Schartner

2014-11-01

Full Text Available We report the development of a point temperature sensor, based on monitoring upconversion emission from erbium:ytterbium-doped tellurite coatings on the tips of optical fibres. The dip coating technique allows multiple sensors to be fabricated simultaneously, while confining the temperature-sensitive region to a localised region on the end-face of the fibre. The strong response of the rare earth ions to changing temperature allows a resolution of 0.1–0.3 °C to be recorded over the biologically relevant range of temperatures from 23–39 °C.

Subdiffraction field localisation in the scattering of femtosecond laser radiation by a dielectric microsphere

Energy Technology Data Exchange (ETDEWEB)

Geints, Yu E; Zemlyanov, A A; Panina, E K [V.E. Zuev Institute of Atmospheric Optics, Siberian Branch, Russian Academy of Sciences, Tomsk (Russian Federation)

2014-01-31

The time dynamics of the optical field was theoretically considered in the near-field diffraction zone in the scattering of a femtosecond laser pulse by a transparent spherical microparticle. The spatial region of field focusing by the particle (the 'photonic jet' zone) was investigated; the evolution of the jet shape and the peak intensity in this region were analysed. For the first time it was determined that an extremely tight optical field localisation to a subdiffraction size is possible at a certain (resonance) temporal stage of photonic jet development. (radiation scattering)

Sentinel node localisation using pre-operative lymphoscintigraphy and intraoperative gamma probe in early oral cavity cancer

International Nuclear Information System (INIS)

Ikram, M.; Akhtar, S.; Junaid, M.; Dhari, T.; Zaman, M.U.; Hussain, R.

2013-01-01

Objectives: To assess the diagnostic value of sentinel lymph node localisation using pre-operative lymphoscintigraphy and intra-operative gamma probe radio localisation in Pakistani patients suffering from early stage squamous cell carcinoma of the oral cavity. Methods: The prospective case series was conducted between September 2007 and April 2010 at the Aga Khan University Hospital, Karachi. It comprised patients with T1 and T2 oral cavity cancer with clinically and radiologically negative neck. Pre-operative lymphoscintigraphy was performed one day before surgery and intra-operative gamma probe was used to detect sentinel node. Final histo-pathological evaluation was taken as the gold standard. Results: The study comprised 42 patients: 32(76%) males and 10(24%) females. The primary tumour site was buccal mucosa in 25 (60%) patients, and tongue in 17 (40%). Sentinel lymph node was detected in 38 (90%) patients. On final histopathological identification, 7 (17%) patients had cancer in the neck nodes. In all patients with metastasis, sentinel lymph node technique correctly identified the involved neck level. None of the patients revealed metastasis in non-sentinel lymph nodes. Conclusion:Evidence suggested the use of sentinel node biopsy in patients with head and neck squamous cell carcinoma. (author)

A new mutation of the fukutin gene causing late-onset limb girdle muscular dystrophy

DEFF Research Database (Denmark)

Riisager, Maria; Duno, M; Hansen, Flemming Juul

2013-01-01

to aberrations of FKTN is rare, with only eight reported cases of limb girdle phenotype (LGMD2M). We describe the mildest affected patient outside Japan with genetically confirmed LGMD2M and onset of symptoms at age 14. She was brought to medical attention at age 12, not because of muscle weakness, but due...... to episodes of tachycardia caused by Wolff-Parkinson-White syndrome. On examination, she had rigid spine syndrome, a typical limb girdle dystrophy pattern of muscle weakness, cardiomyopathy, and serum CK levels >2000 IU/L (normal G; p.Y306C mutation in the FKTN gene was found. The case confirms FKTN mutations...... as a cause of LGMD2M without mental retardation and expands the phenotypic spectrum for LGMD2M to include cardiomyopathy and rigid spine syndrome in the mildest affected non-Japanese patient reported so far....

Generation and analysis of knock-in mice carrying pseudohypoaldosteronism type II-causing mutations in the cullin 3 gene.

Science.gov (United States)

Araki, Yuya; Rai, Tatemitsu; Sohara, Eisei; Mori, Takayasu; Inoue, Yuichi; Isobe, Kiyoshi; Kikuchi, Eriko; Ohta, Akihito; Sasaki, Sei; Uchida, Shinichi

2015-10-21

Pseudohypoaldosteronism type II (PHAII) is a hereditary hypertensive disease caused by mutations in four different genes: with-no-lysine kinases (WNK) 1 and 4, Kelch-like family member 3 (KLHL3), and cullin 3 (Cul3). Cul3 and KLHL3 form an E3 ligase complex that ubiquitinates and reduces the expression level of WNK4. PHAII-causing mutations in WNK4 and KLHL3 impair WNK4 ubiquitination. However, the molecular pathogenesis of PHAII caused by Cul3 mutations is unclear. In cultured cells and human leukocytes, PHAII-causing Cul3 mutations result in the skipping of exon 9, producing mutant Cul3 protein lacking 57 amino acids. However, whether this phenomenon occurs in the kidneys and is responsible for the pathogenesis of PHAII in vivo is unknown. We generated knock-in mice carrying a mutation in the C-terminus of intron 8 of Cul3, c.1207-1G>A, which corresponds to a PHAII-causing mutation in the human Cul3 gene. Heterozygous Cul3(G(-1)A/+) knock-in mice did not exhibit PHAII phenotypes, and the skipping of exon 9 was not evident in their kidneys. However, the level of Cul3 mRNA expression in the kidneys of heterozygous knock-in mice was approximately half that of wild-type mice. Furthermore, homozygous knock-in mice were nonviable. It suggested that the mutant allele behaved like a knockout allele and did not produce Cul3 mRNA lacking exon 9. A reduction in Cul3 expression alone was not sufficient to develop PHAII in the knock-in mice. Our findings highlighted the pathogenic role of mutant Cul3 protein and provided insight to explain why PHAII-causing mutations in Cul3 cause kidney-predominant PHAII phenotypes. © 2015. Published by The Company of Biologists Ltd.

Evaluation of different types of sensors and their positioning for on-line PD detection and localisation in distribution cables

NARCIS (Netherlands)

Wielen, van der P.C.J.M.; Veen, J.; Wouters, P.A.A.F.

2003-01-01

Different types of sensors can be used for on-line detection and localisation of PDs in medium voltage cables. These sensors can be placed on different locations in the substa-tions where the cable under test is terminated. Both aspects have a significant influence on the measured signals. In this

Verticillium dahliae-Arabidopsis Interaction Causes Changes in Gene Expression Profiles and Jasmonate Levels on Different Time Scales

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Sandra S. Scholz

2018-02-01

Full Text Available Verticillium dahliae is a soil-borne vascular pathogen that causes severe wilt symptoms in a wide range of plants. Co-culture of the fungus with Arabidopsis roots for 24 h induces many changes in the gene expression profiles of both partners, even before defense-related phytohormone levels are induced in the plant. Both partners reprogram sugar and amino acid metabolism, activate genes for signal perception and transduction, and induce defense- and stress-responsive genes. Furthermore, analysis of Arabidopsis expression profiles suggests a redirection from growth to defense. After 3 weeks, severe disease symptoms can be detected for wild-type plants while mutants impaired in jasmonate synthesis and perception perform much better. Thus, plant jasmonates have an important influence on the interaction, which is already visible at the mRNA level before hormone changes occur. The plant and fungal genes that rapidly respond to the presence of the partner might be crucial for early recognition steps and the future development of the interaction. Thus they are potential targets for the control of V. dahliae-induced wilt diseases.

Spontaneous Pancreatitis Caused by Tissue-Specific Gene Ablation of Hhex in MiceSummary

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Mark J. Ferreira

2015-09-01

Full Text Available Background & Aims: Perturbations in pancreatic ductal bicarbonate secretion cause chronic pancreatitis. The physiologic mechanism of ductal secretion is known, but its transcriptional control is not. We determine the role of the transcription factor hematopoietically expressed homeobox protein (Hhex in ductal secretion and pancreatitis. Methods: We derived mice with pancreas-specific, Cre-mediated Hhex gene ablation to determine the requirement of Hhex in the pancreatic duct in early life and in adult stages. Histologic and immunostaining analyses were used to detect the presence of pathology. Pancreatic primary ductal cells were isolated to discover differentially expressed transcripts upon acute Hhex ablation on a cell autonomous level. Results: Hhex protein was detected throughout the embryonic and adult ductal trees. Ablation of Hhex in pancreatic progenitors resulted in postnatal ductal ectasia associated with acinar-to-ductal metaplasia, a progressive phenotype that ultimately resulted in chronic pancreatitis. Hhex ablation in adult mice, however, did not cause any detectable pathology. Ductal ectasia in young mice did not result from perturbation of expression of Hnf6, Hnf1β, or the primary cilia genes. RNA-seq analysis of Hhex-ablated pancreatic primary ductal cells showed mRNA levels of the G-protein coupled receptor natriuretic peptide receptor 3 (Npr3, implicated in paracrine signaling, up-regulated by 4.70-fold. Conclusions: Although Hhex is dispensable for ductal cell function in the adult, ablation of Hhex in pancreatic progenitors results in pancreatitis. Our data highlight the critical role of Hhex in maintaining ductal homeostasis in early life and support ductal hypersecretion as a novel etiology of pediatric chronic pancreatitis. Keywords: Npr3, Pancreatic Ducts, Primary Cilia

Development of a new fluorescent reporter:operator system: location of AraC regulated genes in Escherichia coli K-12.

Science.gov (United States)

Sellars, Laura E; Bryant, Jack A; Sánchez-Romero, María-Antonia; Sánchez-Morán, Eugenio; Busby, Stephen J W; Lee, David J

2017-08-03

In bacteria, many transcription activator and repressor proteins regulate multiple transcription units that are often distally distributed on the bacterial genome. To investigate the subcellular location of DNA bound proteins in the folded bacterial nucleoid, fluorescent reporters have been developed which can be targeted to specific DNA operator sites. Such Fluorescent Reporter-Operator System (FROS) probes consist of a fluorescent protein fused to a DNA binding protein, which binds to an array of DNA operator sites located within the genome. Here we have developed a new FROS probe using the Escherichia coli MalI transcription factor, fused to mCherry fluorescent protein. We have used this in combination with a LacI repressor::GFP protein based FROS probe to assess the cellular location of commonly regulated transcription units that are distal on the Escherichia coli genome. We developed a new DNA binding fluorescent reporter, consisting of the Escherichia coli MalI protein fused to the mCherry fluorescent protein. This was used in combination with a Lac repressor:green fluorescent protein fusion to examine the spatial positioning and possible co-localisation of target genes, regulated by the Escherichia coli AraC protein. We report that induction of gene expression with arabinose does not result in co-localisation of AraC-regulated transcription units. However, measurable repositioning was observed when gene expression was induced at the AraC-regulated promoter controlling expression of the araFGH genes, located close to the DNA replication terminus on the chromosome. Moreover, in dividing cells, arabinose-induced expression at the araFGH locus enhanced chromosome segregation after replication. Regions of the chromosome regulated by AraC do not colocalise, but transcription events can induce movement of chromosome loci in bacteria and our observations suggest a role for gene expression in chromosome segregation.

Gene Therapy

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Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene

International Nuclear Information System (INIS)

Lichter-Konecki, U.; Konecki, D.S.; DiLella, A.G.; Brayton, K.; Marvit, J.; Hahn, T.M.; Trefz, E.K.; Woo, S.L.C.

1988-01-01

A novel restriction fragment length polymorphism in the phenylalanine hydroxylase (PAH) locus generated by the restriction endonuclease MspI was observed in a German phenylketonuria (PKU) patient. Molecular cloning and DNA sequence analyses revealed that the MspI polymorphism was created by a T to C transition in exon 9 of the human PAH gene, which also resulted in the conversion of a leucine codon to proline codon. The effect of the amino acid substitution was investigated by creating a corresponding mutation in a full-length human PAD cDNA by site-directed mutagenesis followed by expression analysis in cultured mammalian cells. Results demonstrate that the mutation in the gene causes the synthesis of an unstable protein in the cell corresponding to a CRM - phenotype. Together with the other mutations recently reported in the PAH gene,the data support previous biochemical and clinical observations that PKU is a heterogeneous disorder at the gene level

Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene

Energy Technology Data Exchange (ETDEWEB)

Lichter-Konecki, U.; Konecki, D.S.; DiLella, A.G.; Brayton, K.; Marvit, J.; Hahn, T.M.; Trefz, E.K.; Woo, S.L.C.

1988-04-19

A novel restriction fragment length polymorphism in the phenylalanine hydroxylase (PAH) locus generated by the restriction endonuclease MspI was observed in a German phenylketonuria (PKU) patient. Molecular cloning and DNA sequence analyses revealed that the MspI polymorphism was created by a T to C transition in exon 9 of the human PAH gene, which also resulted in the conversion of a leucine codon to proline codon. The effect of the amino acid substitution was investigated by creating a corresponding mutation in a full-length human PAD cDNA by site-directed mutagenesis followed by expression analysis in cultured mammalian cells. Results demonstrate that the mutation in the gene causes the synthesis of an unstable protein in the cell corresponding to a CRM/sup -/ phenotype. Together with the other mutations recently reported in the PAH gene,the data support previous biochemical and clinical observations that PKU is a heterogeneous disorder at the gene level.

Le kyste hydatique du cordon spermatique: une localisation exceptionnelle

Science.gov (United States)

Hamdane, Mohamed Moncef; Bougrine, Fethi; Msakni, Issam; Dhaoui-Ghozzi, Amen; Bouziani, Ammar

2011-01-01

L’ hydatidose est une anthropo-zoonose due au développement chez l'homme de la forme larvaire du taenia Echinococcus granulosis. La plupart des kystes hydatiques se localisent dans le foie et les poumons. Le kyste hydatique du cordon spermatique est extrêmement rare avec seulement 4 cas rapportés dans la littérature. Les auteurs rapportent dans cet article un nouveau cas d'hydatidose du cordon spermatique. Il s'agissait d'un homme de 40 ans qui consultait pour des douleurs scrotales évoluant depuis huit mois. L'examen clinique a mis en évidence une tuméfaction mobile, inguino-scrotale, droite. L’échographie testiculaire a objectivé une hernie inguinale droite associée à deux kystes épididymaires bilatéraux. Le patient a été opéré pour cure de son hernie avec découverte en per-opératoire d'un kyste du cordon spermatique qui a été réséqué. L'examen anatomopathologique a conclu à une hydatidose du cordon spermatique. PMID:22384304

Conditional ablation of the choroideremia gene causes age-related changes in mouse retinal pigment epithelium.

Science.gov (United States)

Wavre-Shapton, Silène T; Tolmachova, Tanya; Lopes da Silva, Mafalda; da Silva, Mafalda Lopes; Futter, Clare E; Seabra, Miguel C

2013-01-01

The retinal pigment epithelium (RPE) is a pigmented monolayer of cells lying between the photoreceptors and a layer of fenestrated capillaries, the choriocapillaris. Choroideremia (CHM) is an X-linked progressive degeneration of these three layers caused by the loss of function of Rab Escort protein-1 (REP1). REP1 is involved in the prenylation of Rab proteins, key regulators of membrane trafficking. To study the pathological consequences of chronic disruption of membrane traffic in the RPE we used a cell type-specific knock-out mouse model of the disease, where the Chm/Rep1 gene is deleted only in pigmented cells (Chm(Flox), Tyr-Cre+). Transmission electron microscopy (TEM) was used to quantitate the melanosome distribution in the RPE and immunofluorescent staining of rhodopsin was used to quantitate phagocytosed rod outer segments in retinal sections. The ultrastructure of the RPE and Bruch's membrane at different ages was characterised by TEM to analyse age-related changes occurring as a result of defects in membrane traffic pathways. Chm/Rep1 gene knockout in RPE cells resulted in reduced numbers of melanosomes in the apical processes and delayed phagosome degradation. In addition, the RPE accumulated pathological changes at 5-6 months of age similar to those observed in 2-year old controls. These included the intracellular accumulation of lipofuscin-containing deposits, disorganised basal infoldings and the extracellular accumulation of basal laminar and basal linear deposits. The phenotype of the Chm(Flox), Tyr-Cre+ mice suggests that loss of the Chm/Rep1 gene causes premature accumulation of features of aging in the RPE. Furthermore, the striking similarities between the present observations and some of the phenotypes reported in age-related macular degeneration (AMD) suggest that membrane traffic defects may contribute to the pathogenesis of AMD.

Conditional ablation of the choroideremia gene causes age-related changes in mouse retinal pigment epithelium.

Directory of Open Access Journals (Sweden)

Silène T Wavre-Shapton

Full Text Available The retinal pigment epithelium (RPE is a pigmented monolayer of cells lying between the photoreceptors and a layer of fenestrated capillaries, the choriocapillaris. Choroideremia (CHM is an X-linked progressive degeneration of these three layers caused by the loss of function of Rab Escort protein-1 (REP1. REP1 is involved in the prenylation of Rab proteins, key regulators of membrane trafficking. To study the pathological consequences of chronic disruption of membrane traffic in the RPE we used a cell type-specific knock-out mouse model of the disease, where the Chm/Rep1 gene is deleted only in pigmented cells (Chm(Flox, Tyr-Cre+. Transmission electron microscopy (TEM was used to quantitate the melanosome distribution in the RPE and immunofluorescent staining of rhodopsin was used to quantitate phagocytosed rod outer segments in retinal sections. The ultrastructure of the RPE and Bruch's membrane at different ages was characterised by TEM to analyse age-related changes occurring as a result of defects in membrane traffic pathways. Chm/Rep1 gene knockout in RPE cells resulted in reduced numbers of melanosomes in the apical processes and delayed phagosome degradation. In addition, the RPE accumulated pathological changes at 5-6 months of age similar to those observed in 2-year old controls. These included the intracellular accumulation of lipofuscin-containing deposits, disorganised basal infoldings and the extracellular accumulation of basal laminar and basal linear deposits. The phenotype of the Chm(Flox, Tyr-Cre+ mice suggests that loss of the Chm/Rep1 gene causes premature accumulation of features of aging in the RPE. Furthermore, the striking similarities between the present observations and some of the phenotypes reported in age-related macular degeneration (AMD suggest that membrane traffic defects may contribute to the pathogenesis of AMD.

VIP Gene Deletion in Mice Causes Cardiomyopathy Associated with Upregulation of Heart Failure Genes

Energy Technology Data Exchange (ETDEWEB)

Szema, Anthony M.; Hamidi, Sayyed A.; Smith, S. David; Benveniste, Helene; Katare, Rajesh Gopalrao

2013-05-20

Vasoactive Intestinal Peptide (VIP), a pulmonary vasodilator and inhibitor of vascular smooth muscle proliferation, is absent in pulmonary arteries of patients with idiopathic pulmonary arterial hypertension (PAH). We previously determined that targeted deletion of the VIP gene in mice leads to PAH with pulmonary vascular remodeling and right ventricular (RV) dilatation. Whether the left ventricle is also affected by VIP gene deletion is unknown. In the current study, we examined if VIP knockout mice (VIP-/-) develop both right (RV) and left ventricular (LV) cardiomyopathy, manifested by LV dilatation and systolic dysfunction, as well as overexpression of genes conducive to heart failure.

Heart failure and sudden cardiac death in heritable thoracic aortic disease caused by pathogenic variants in the SMAD3 gene.

Science.gov (United States)

Backer, Julie De; Braverman, Alan C

2018-05-01

Predominant cardiovascular manifestations in the spectrum of Heritable Thoracic Aortic Disease include by default aortic root aneurysms- and dissections, which may be associated with aortic valve disease. Mitral- and tricuspid valve prolapse are other commonly recognized features. Myocardial disease, characterized by heart failure and/or malignant arrhythmias has been reported in humans and in animal models harboring pathogenic variants in the Fibrillin1 gene. Description of clinical history of three cases from one family in Ghent (Belgium) and one family in St. Louis (US). We report on three cases from two families presenting end-stage heart failure (in two) and lethal arrhythmias associated with moderate left ventricular dilatation (in one). All three cases harbor a pathogenic variant in the SMAD3 gene, known to cause aneurysm osteoarthritis syndrome, Loeys-Dietz syndrome type 3 or isolated Heritable Thoracic Aortic Disease. These unusual presentations warrant awareness for myocardial disease in patients harboring pathogenic variants in genes causing Heritable Thoracic Aortic Disease and indicate the need for prospective studies in larger cohorts. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes

NARCIS (Netherlands)

van de Pol, L.A.; Wolf, N.I.; van Weissenbruch, M.M.; Stam, C.J.; Weiss, M.M.; Waisfisz, Q.; Kevelam, S.H.; Bugiani, M.; van de Kamp, J.M.; Knaap, M.

2015-01-01

A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an

Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a mutation in the arginine-vasopressin II gene in four generations of a Korean family

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Myo-Jing Kim

2014-12-01

Full Text Available Autosomal dominant neurohypophyseal diabetes insipidus is a rare form of central diabetes insipidus that is caused by mutations in the vasopressin-neurophysin II (AVP-NPII gene. It is characterized by persistent polydipsia and polyuria induced by deficient or absent secretion of arginine vasopressin (AVP. Here we report a case of familial neurohypophyseal diabetes insipidus in four generations of a Korean family, caused by heterozygous missense mutation in exon 2 of the AVP-NPII gene (c.286G>T. This is the first report of such a case in Korea.

Gonadal mosaicism in ARID1B gene causes intellectual disability and dysmorphic features in three siblings.

Science.gov (United States)

Ben-Salem, Salma; Sobreira, Nara; Akawi, Nadia A; Al-Shamsi, Aisha M; John, Anne; Pramathan, Thachillath; Valle, David; Ali, Bassam R; Al-Gazali, Lihadh

2016-01-01

The gene encoding the AT-rich interaction domain-containing protein 1B (ARID1B) has recently been shown to be one of the most frequently mutated genes in patients with intellectual disability (ID). The phenotypic spectrums associated with variants in this gene vary widely ranging for mild to severe non-specific ID to Coffin-Siris syndrome. In this study, we evaluated three children from a consanguineous Emirati family affected with ID and dysmorphic features. Genomic DNA from all affected siblings was analyzed using CGH array and whole-exome sequencing (WES). Based on a recessive mode of inheritance, homozygous or compound heterozygous variants shared among all three affected children could not be identified. However, further analysis revealed a heterozygous variant (c.4318C>T; p.Q1440*) in the three affected children in an autosomal dominant ID causing gene, ARID1B. This variant was absent in peripheral blood samples obtained from both parents and unaffected siblings. Therefore, we propose that the most likely explanation for this situation is that one of the parents is a gonadal mosaic for the variant. To the best of our knowledge, this is the first report of a gonadal mosaicism inheritance of an ARID1B variant leading to familial ID recurrence. © 2015 Wiley Periodicals, Inc.

Les facteurs de localisation d’un nouveau type d’établissements tertiaires : les datacentres

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Henry Bakis

2015-02-01

Full Text Available Les centres de traitement de données ou datacentres (data centers sont de nouveaux types d’établissements tertiaires rendus nécessaires par suite du développement d’Internet (sites web, cloud. Ils assurent notamment l’hébergement de serveurs (housing d’entreprises ou de particuliers en location ou colocation d’espaces. Cet article tente de présenter ce type d’établissements tertiaires et de mettre l’accent sur leurs enjeux en termes de localisation et d’environnement. Il met notamment l’accent sur leur consommation énergétique.

Immunoelectron microscopic localisation of keratin and luminal epithelial antigens in normal and neoplastic urothelium.

Science.gov (United States)

Wilson, P D; Nathrath, W B; Trejdosiewicz, L K

1982-01-01

Immunoelectron microscope cytochemistry was carried out on 2% paraformaldehyde fixed, 50 mu sections of normal urothelium and bladder carcinoma cells in culture using antisera raised in rabbits to human 40-63 000 MW epidermal "broad spectrum" keratin and calf urothelial "luminal epithelial antigen" (aLEA) Both the unconjugated and indirect immunoperoxidase-DAB techniques were used before routine embedding. The localisation of both keratin and luminal epithelial antigen (LEA) was similar in normal and neoplastic cells and reaction product was associated not only with tonofilaments but also lining membrane vesicles and on fine filaments in the cytoplasmic ground substance.

Characterisation of a novel proteolytic enzyme localised to goblet cells in rat and man

DEFF Research Database (Denmark)

Poulsen, Steen Seier

1984-01-01

A proteolytic enzyme, ingobsin , purified from rat duodenal extracts is shown to be localised to intestinal goblet cells of both man and rat. Enzyme positive cells decrease in number from duodenum to colon. The enzyme is a 33 000 Mr protein with an isoelectric point of 5.1. The pH optimum...... for enzymatic activity is 7.4-8.0. Based on substrate specificity for arg-x, lys-x and to a lesser degree tyr-x, on the effect of diisopropylphosphorofluoride , Trasylol and phenylmethylsulfonylfluoride and on proteolytic activity towards intact proteins, ingobsin is classified as a serine proteinase...

Clinical experience with a new stereotactic localisation method for fractionated radiotherapy of extracranial lesions

International Nuclear Information System (INIS)

Engenhart-Cabillic, R.; Pastyr, O.; Wenz, F.; Debus, J.; Schlegel, W.; Bahner, M.L.; Wannenmacher, M.

1996-01-01

Purpose/Objective: Effectiveness of radiotherapy in terms of local control has been shown to be linked with treatment accuracy. Conformal radiation therapy outside the brain maybe limited by relative inaccuracy of positioning and repositioning uncertainty during treatment planning, simulation and radiotherapy. It has been shown that stereotactic localisation methods provide an excellent localisation accuracy for intracranial lesions. The aim of this study was to develop a stereotactic system for the whole body and to test the feasibility in a clinical study. Materials and Method: The system includes a reversible stereotactic patient fixation, localization and positioning system which can be used during CT-imaging for simulation and for treatment. The target volume and adjacent critical structures were outlined for treatment three dimensional planning and the coordinates of the target point were calculated. The overall accuracy of target localization including soft and hardware inaccuracy was measured by a phantom. Three patients with spinal and paraspinal tumors were treated by conventionally fractionated high precision megavoltage radiotherapy with this system. The treatment time was 6 weeks in each patients. The stereotactic coordinates of anatomical landmarks as well as implanted fiducals were measured by CT-imaging, X-ray localization and electronic portal imaging at 20 different paraspinal localisations. Stereotactic CT-imaging was performed for treatment planning and once a week during treatment. Results: Standard deviation of stereotactic coordinats in the phantom was 0.5 mm in the lateral direction (x), 1.0 mm in the cranio-caudal orientation (z) and 1.2 mm in the dorso-ventral orientation. About 60 minutes are required to immobilise the patient properly for the first set-up and the subsequent daily set-up time during therapy was 10 min. In patients a total of 18 CT examination and 56 portal images have been analysed. The mean variation of the stereotactic

Inactivation of the Tumor Suppressor Genes Causing the Hereditary Syndromes Predisposing to Head and Neck Cancer via Promoter Hypermethylation in Sporadic Head and Neck Cancers

OpenAIRE

Smith, Ian M.; Mithani, Suhail K.; Mydlarz, Wojciech K.; Chang, Steven S.; Califano, Joseph A.

2010-01-01

Fanconi anemia (FA) and dyskeratosis congenita (DC) are rare inherited syndromes that cause head and neck squamous cell cancer (HNSCC). Prior studies of inherited forms of cancer have been extremely important in elucidating tumor suppressor genes inactivated in sporadic tumors. Here, we studied whether sporadic tumors have epigenetic silencing of the genes causing the inherited forms of HNSCC. Using bisulfite sequencing, we investigated the incidence of promoter hypermethylation of the 17 Fan...

Current strategies for monitoring men with localised prostate cancer lack a strong evidence base: observational longitudinal study.

Science.gov (United States)

Metcalfe, C; Tilling, K; Davis, M; Lane, J A; Martin, R M; Kynaston, H; Powell, P; Neal, D E; Hamdy, F; Donovan, J L

2009-08-04

The UK National Institute for Health and Clinical Excellence (NICE) guidance recommends conservative management of men with 'low-risk' localised prostate cancer, monitoring the disease using prostate-specific antigen (PSA) kinetics and re-biopsy. However, there is little evidence of the changes in PSA level that should alert to the need for clinical re-assessment. This study compares the alerts resulting from PSA kinetics and a novel longitudinal reference range approach, which incorporates age-related changes, during the monitoring of 408 men with localised prostate cancer. Men were monitored by regular PSA tests over a mean of 2.9 years, recording when a man's PSA doubling time fell below 2 years, PSA velocity exceeded 2 ng ml(-1) per year, or when his upper 10% reference range was exceeded. Prostate-specific antigen doubling time and PSA velocity alerted a high proportion of men initially but became unresponsive to changes with successive tests. Calculating doubling time using recent PSA measurements reduced the decline in response. The reference range method maintained responsiveness to changes in PSA level throughout the monitoring. The increasing unresponsiveness of PSA kinetics is a consequence of the underlying regression model. Novel methods are needed for evaluation in cohorts currently being managed by monitoring. Meanwhile, the NICE guidance should be cautious.

Application of a Null-Beamformer to Source Localisation in MEG Data of Deep Brain Stimulation

DEFF Research Database (Denmark)

Mohseni, Hamid R.; Kringelbach, Morten L.; Smith, Penny Probert

2010-01-01

In this paper, we present an analysis of magnetoencephalography (MEG) signals from a patient with whole-body chronic pain in order to investigate changes in neural activity induced by DBS. The patient is one of the few cases treated using DBS of the anterior cingulate cortex (ACC). Using MEG...... the accuracy of our source localisation by correlating the predicted DBS electrode positions with their actual positions, previously identified using anatomical imaging. We also demonstrated increased activity in pain-related regions including the pre-supplementary motor area, brainstem periaqueductal gray...

A novel recessive mutation in the gene ELOVL4 causes a neuro-ichthyotic disorder with variable expressivity

Science.gov (United States)

2014-01-01

Background A rare neuro-ichthyotic disorder characterized by ichthyosis, spastic quadriplegia and intellectual disability and caused by recessive mutations in ELOVL4, encoding elongase-4 protein has recently been described. The objective of the study was to search for sequence variants in the gene ELOVL4 in three affected individuals of a consanguineous Pakistani family exhibiting features of neuro-ichthyotic disorder. Methods Linkage in the family was searched by genotyping microsatellite markers linked to the gene ELOVL4, mapped at chromosome 6p14.1. Exons and splice junction sites of the gene ELOVL4 were polymerase chain reaction amplified and sequenced in an automated DNA sequencer. Results DNA sequence analysis revealed a novel homozygous nonsense mutation (c.78C > G; p.Tyr26*). Conclusions Our report further confirms the recently described ELOVL4-related neuro-ichthyosis and shows that the neurological phenotype can be absent in some individuals. PMID:24571530

An siRNA-based functional genomics screen for the identification of regulators of ciliogenesis and ciliopathy genes

Science.gov (United States)

Racher, Hilary; Phelps, Ian G.; Toedt, Grischa; Kennedy, Julie; Wunderlich, Kirsten A.; Sorusch, Nasrin; Abdelhamed, Zakia A.; Natarajan, Subaashini; Herridge, Warren; van Reeuwijk, Jeroen; Horn, Nicola; Boldt, Karsten; Parry, David A.; Letteboer, Stef J.F.; Roosing, Susanne; Adams, Matthew; Bell, Sandra M.; Bond, Jacquelyn; Higgins, Julie; Morrison, Ewan E.; Tomlinson, Darren C.; Slaats, Gisela G.; van Dam, Teunis J. P.; Huang, Lijia; Kessler, Kristin; Giessl, Andreas; Logan, Clare V.; Boyle, Evan A.; Shendure, Jay; Anazi, Shamsa; Aldahmesh, Mohammed; Al Hazzaa, Selwa; Hegele, Robert A.; Ober, Carole; Frosk, Patrick; Mhanni, Aizeddin A.; Chodirker, Bernard N.; Chudley, Albert E.; Lamont, Ryan; Bernier, Francois P.; Beaulieu, Chandree L.; Gordon, Paul; Pon, Richard T.; Donahue, Clem; Barkovich, A. James; Wolf, Louis; Toomes, Carmel; Thiel, Christian T.; Boycott, Kym M.; McKibbin, Martin; Inglehearn, Chris F.; Stewart, Fiona; Omran, Heymut; Huynen, Martijn A.; Sergouniotis, Panagiotis I.; Alkuraya, Fowzan S.; Parboosingh, Jillian S.; Innes, A Micheil; Willoughby, Colin E.; Giles, Rachel H.; Webster, Andrew R.; Ueffing, Marius; Blacque, Oliver; Gleeson, Joseph G.; Wolfrum, Uwe; Beales, Philip L.; Gibson, Toby

2015-01-01

Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and three pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localise to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1/CEP90 and C21orf2/LRRC76 as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2-variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease. PMID:26167768

A novel mutation in PGAP2 gene causes developmental delay, intellectual disability, epilepsy and microcephaly in consanguineous Saudi family.

Science.gov (United States)

Naseer, Muhammad Imran; Rasool, Mahmood; Jan, Mohammed M; Chaudhary, Adeel G; Pushparaj, Peter Natesan; Abuzenadah, Adel M; Al-Qahtani, Mohammad H

2016-12-15

PGAP2 (Post-GPI Attachment to Proteins 2) gene is involved in lipid remodeling steps of Glycosylphosphatidylinositol (GPI)-anchor maturation. At the surface of the cell this gene is required for proper expression of GPI-anchored proteins. Hyperphosphatasia with mental retardation syndrome-3 is an autosomal recessive disorder usually characterized by severe mental retardation. Mutations in the PGAP2 gene cause hyperphosphatasia mental retardation syndrome-3. We have identified a large consanguineous family from Saudi origin segregating developmental delay, intellectual disability, epilepsy and microcephaly. Whole exome sequencing with 100× coverage was performed on two affected siblings of the family. Data analysis in the patient revealed a novel missense mutation c.191C>T in PGAP2 gene resulting in Alanine to Valine substitution (Ala64Val). The mutation was reconfirmed and validated by subsequent Sanger sequencing method. The mutation was ruled out in 100 unrelated healthy controls. We suggest that this pathogenic mutation disrupts the proper function of the gene proteins resulting in the disease state. Copyright © 2016 Elsevier B.V. All rights reserved.

Post-epizootic chronic dolphin morbillivirus infection in Mediterranean striped dolphins Stenella coeruleoalba.

Science.gov (United States)

Soto, Sara; Alba, Ana; Ganges, Llilianne; Vidal, Enric; Raga, Juan Antonio; Alegre, Ferrán; González, Beatriz; Medina, Pascual; Zorrilla, Irene; Martínez, Jorge; Marco, Alberto; Pérez, Mónica; Pérez, Blanca; Pérez de Vargas Mesas, Ana; Martínez Valverde, Rosa; Domingo, Mariano

2011-10-06

Dolphin morbillivirus (DMV) has caused 2 epizootics with high mortality rates on the Spanish Mediterranean coast, in 1990 and 2006-07, mainly affecting striped dolphins Stenella coeruleoalba. Following the first epizootic unusual DMV infections affecting only the central nervous system of striped dolphins were found, with histological features similar to subacute sclerosing panencephalitis and old dog encephalitis, the chronic latent localised infections caused by defective forms of measles virus and canine distemper virus, respectively. Between 2008 and 2010, monitoring by microscopic and immunohistochemical (IHC) studies of 118 striped dolphins stranded along Catalonia, the Valencia Region and Andalusia showed similar localised DMV nervous system infections in 25.0, 28.6 and 27.4% of cases, respectively, with no significant differences among regions or sex. The body length of DMV-infected dolphins was statistically greater than that of non-infected dolphins (196.5 vs. 160.5 cm; p dolphins with positive IHC-DMV had positive PCR results. All 6 cases were positive with the 78 bp RT-PCR. These findings contraindicate the use of the 429 bp RT-PCR protocol based on the P gene to detect this specific form of DMV. DMV localised nervous infection constitutes the most relevant single cause of stranding and death in Mediterranean striped dolphins in the years following a DMV epizootic, and it might even overwhelm the effects of the epizootic itself, at least in 2007.

Point mutation in the MITF gene causing Waardenburg syndrome type II in a three-generation Indian family.

Science.gov (United States)

Lalwani, A K; Attaie, A; Randolph, F T; Deshmukh, D; Wang, C; Mhatre, A; Wilcox, E

1998-12-04

Waardenburg syndrome (WS) is an autosomal-dominant neural crest cell disorder phenotypically characterized by hearing impairment and disturbance of pigmentation. A presence of dystopia canthorum is indicative of WS type 1, caused by loss of function mutation in the PAX3 gene. In contrast, type 2 WS (WS2) is characterized by normally placed medial canthi and is genetically heterogeneous; mutations in MITF (microphthalmia associated transcription factor) associated with WS2 have been identified in some but not all affected families. Here, we report on a three-generation Indian family with a point mutation in the MITF gene causing WS2. This mutation, initially reported in a Northern European family, creates a stop codon in exon 7 and is predicted to result in a truncated protein lacking the HLH-Zip or Zip structure necessary for normal interaction with its target DNA motif. Comparison of the phenotype between the two families demonstrates a significant difference in pigmentary disturbance of the eye. This family, with the first documented case of two unrelated WS2 families harboring identical mutations, provides additional evidence for the importance of genetic background on the clinical phenotype.

Development of in vitro transposon assisted signal sequence trapping and its use in screening Bacillus halodurans C125 and Sulfolobus solfataricus P2 gene libraries

DEFF Research Database (Denmark)

Becker, F.; Schnorr, K.; Wilting, R.

2004-01-01

To identify genes encoding extracytosolic proteins, a minitransposon, TnSig, containing a signal-less beta-lactamase ('bla) as reporter gene, was constructed and used for in vitro transposition of genomic libraries made in Escherichia coli. The 'bla gene was cloned into a bacteriophage MU...... minitransposon enabling translational fusions between 'bla and target genes. Fusion of TnSig in the correct reading frame to a protein carrying transmembrane domains or signal peptides resulted in ampicillin resistance of the corresponding clone. Prokaryotic gene libraries from the alkaliphilic bacterium...... Bacillus halodurans C125 and the hyperthermophilic archaeon Sulfolobus solfataricus P2 were tagged with TnSig. The genomic sequences, which are publicly available (EMBL BA000004 and EMBL AE006641), were used for rapid open reading frame (ORF) identification and prediction of protein localisation...

A novel frameshift deletion in the albumin gene causes analbuminemia in a young Turkish woman.

Science.gov (United States)

Dagnino, Monica; Caridi, Gianluca; Aydin, Zeki; Ozturk, Savas; Karaali, Zeynep; Kazancioglu, Rumeyza; Cefle, Kivanc; Gursu, Meltem; Campagnoli, Monica; Galliano, Monica; Minchiotti, Lorenzo

2010-11-11

Analbuminemia is a rare autosomal recessive disorder manifested by the absence, or severe reduction, of circulating serum albumin. The analbuminemic trait was diagnosed in a young Turkish woman on the basis of her clinical symptoms (bilateral lower limb edema) and biochemical findings (minimal albumin amount and variable increases in other protein fractions). Total DNA from the analbuminemic proband and her parents was PCR-amplified using oligonucleotide primers designed to amplify the 14 exons of the albumin gene (ALB) and the flanking intron regions. The products were screened for mutations by single-strand conformation polymorphism (SSCP) and heteroduplex analyses (HA). HA allowed the identification of the mutation site in exon 12. Direct DNA sequencing of this abnormal fragment revealed that the analbuminemic trait was caused by a homozygous CA deletion at nucleotide positions c. 1614-1615 in the codons for Cys538 and Thr539. The subsequent frameshift should give rise to a putative truncated albumin variant in which the sequence Cys(538)-Thr-Leu-Ser has been changed to Cys(538)-Thr-Phe-Stop. The parents were heterozygous for the same mutation. Gel-based mutation detection and DNA sequencing substantiate the clinical diagnosis of congenital analbuminemia in our patient and show that the condition is caused by a novel mutation within the ALB gene. These results contribute to shed light on the molecular basis of this rare condition. 2010 Elsevier B.V. All rights reserved.

Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene.

Science.gov (United States)

Karimzadeh, Parvaneh; Naderi, Samaneh; Modarresi, Farzaneh; Dastsooz, Hassan; Nemati, Hamid; Farokhashtiani, Tayebeh; Shamsian, Bibi Shahin; Inaloo, Soroor; Faghihi, Mohammad Ali

2017-07-17

Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3-4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types. Here, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from "Lurs" ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presentations were ataxia, gate disturbances and dystonia leading to wheelchair-dependent disability, regression of intellectual abilities, and general developmental regression. They all were born in consanguineous families with no previous documented similar disease in their parents. A homozygote missense mutation in GLB1 gene (c. 601 G > A, p.R201C) was found in all patients. Using Sanger sequencing this identified mutation was confirmed in the proband, their parents, grandparents, and extended family members, confirming

Digital gene expression analysis of corky split vein caused by boron deficiency in 'Newhall' Navel Orange (Citrus sinensis Osbeck for selecting differentially expressed genes related to vascular hypertrophy.

Directory of Open Access Journals (Sweden)

Cheng-Quan Yang

Full Text Available Corky split vein caused by boron (B deficiency in 'Newhall' Navel Orange was studied in the present research. The boron-deficient citrus exhibited a symptom of corky split vein in mature leaves. Morphologic and anatomical surveys at four representative phases of corky split veins showed that the symptom was the result of vascular hypertrophy. Digital gene expression (DGE analysis was performed based on the Illumina HiSeq™ 2000 platform, which was applied to analyze the gene expression profilings of corky split veins at four morphologic phases. Over 5.3 million clean reads per library were successfully mapped to the reference database and more than 22897 mapped genes per library were simultaneously obtained. Analysis of the differentially expressed genes (DEGs revealed that the expressions of genes associated with cytokinin signal transduction, cell division, vascular development, lignin biosynthesis and photosynthesis in corky split veins were all affected. The expressions of WOL and ARR12 involved in the cytokinin signal transduction pathway were up-regulated at 1(st phase of corky split vein development. Furthermore, the expressions of some cell cycle genes, CYCs and CDKB, and vascular development genes, WOX4 and VND7, were up-regulated at the following 2(nd and 3(rd phases. These findings indicated that the cytokinin signal transduction pathway may play a role in initiating symptom observed in our study.

[Association between S100B gene polymorphisms and hand, foot and mouth disease caused by enterovirus 71 infection].

Science.gov (United States)

Li, Jing; Shan, Ruo-Bing; Liu, Rui-Hai; Xu, Ying-Jun; Qu, Ni-Yan; Pan, Gui-Mei; Zhang, Na; Yang, Na; Chen, Zhen-Zhen; Zhang, Wen-Xiang; Li, Zi-Pu

2017-08-01

To investigate the association between rs9722 polymorphisms in the S100B gene and hand, foot and mouth disease (HFMD) caused by enterovirus 71. A total of 124 HFMD children with enterovirus 71 infection were enrolled as subjects, and 56 healthy children were enrolled as control group. The rs9722 polymorphisms in the S100B gene were detected for both groups, and the serum level of S100B protein was measured for 74 HFMD children. The rs9722 locus of the S100B gene had three genotypes, CC, CT, and TT, and the genotype frequencies were in accordance with Hardy-Weinberg equilibrium. Compared with the control group, the HFMD group had significant increases in the frequencies of TT genotype and T allele (Penterovirus 71 infection had significantly higher frequencies of TT genotype and T allele than those with moderate or mild HFMD (Penterovirus 71 infection.

Correlating gene expression with deformities caused by aryl hydrocarbon receptor agonists in zebrafish (Danio rerio)

Energy Technology Data Exchange (ETDEWEB)

Bugiak, B.; Weber, L. [Saskatchewan Univ., Saskatoon, SK (Canada)

2009-07-01

Exposure to aryl hydrocarbon receptor (AhR) agonists in fish causes lethal disturbances in fish development, but the effects of acute AhR agonist exposure on the cardiovascular system and deformities remain unclear. This study addressed this issue by performing a series of experiments on zebrafish (Danio rerio). The authors hypothesized that genes needed for cardiovascular regulation (PTGS) would exhibit a stronger link to deformities than detoxification enzymes (CYPs). Zebrafish eggs were exposed aqueously until 4 days post-fertilization (dpf) to the AhR agonists benzo(a)pyrene (BaP) or 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD) alone and in combination with the putative AhR antagonists resveratrol or alpha-naphthoflavone (ANF). Gene expression was measured using real-time, reverse transcriptase PCR in zebrafish at 5 and 10 dpf. Although the mortalities did not differ considerably among groups at 10 dpf, the deformities increased significantly after BaP-ANF at 5 dpf and after BaP at 10 dpf, but not after TCDD treatment. CYP and PTGS isozymes exhibited small, but statistically significant changes at 5 dpf. By 10 dpf, the expression returned to control values. In general, CYP1A and PTGS-1 expression at 5 dpf were positively correlated with deformities, while all other genes were negatively correlated with deformities. It was concluded that changes in CYP1A, CYP1C2, and PTGS-1 gene expression at 5 dpf are associated with developmental deformities, but additional work is needed to determine which has the most important mechanistic link.

A partial gene deletion of SLC45A2 causes oculocutaneous albinism in Doberman pinscher dogs.

Directory of Open Access Journals (Sweden)

Paige A Winkler

Full Text Available The first white Doberman pinscher (WDP dog was registered by the American Kennel Club in 1976. The novelty of the white coat color resulted in extensive line breeding of this dog and her offspring. The WDP phenotype closely resembles human oculocutaneous albinism (OCA and clinicians noticed a seemingly high prevalence of pigmented masses on these dogs. This study had three specific aims: (1 produce a detailed description of the ocular phenotype of WDPs, (2 objectively determine if an increased prevalence of ocular and cutaneous melanocytic tumors was present in WDPs, and (3 determine if a genetic mutation in any of the genes known to cause human OCA is causal for the WDP phenotype. WDPs have a consistent ocular phenotype of photophobia, hypopigmented adnexal structures, blue irides with a tan periphery and hypopigmented retinal pigment epithelium and choroid. WDPs have a higher prevalence of cutaneous melanocytic neoplasms compared with control standard color Doberman pinschers (SDPs; cutaneous tumors were noted in 12/20 WDP (5 years of age: 8/8 and 1/20 SDPs (p<0.00001. Using exclusion analysis, four OCA causative genes were investigated for their association with WDP phenotype; TYR, OCA2, TYRP1 and SLC45A2. SLC45A2 was found to be linked to the phenotype and gene sequencing revealed a 4,081 base pair deletion resulting in loss of the terminus of exon seven of SLC45A2 (chr4∶77,062,968-77,067,051. This mutation is highly likely to be the cause of the WDP phenotype and is supported by a lack of detectable SLC45A2 transcript levels by reverse transcriptase PCR. The WDP provides a valuable model for studying OCA4 visual disturbances and melanocytic neoplasms in a large animal model.

Gas in the rectum tends to reduce during radical external beam radiotherapy for localised prostate cancer

International Nuclear Information System (INIS)

Nakamura, Naoki; Mizuno, Norifumo; Endo, Haruna; Ogita, Mami; Kawamori, Jiro; Sekigucho, Kenji; Hatanaka, Shogo; Takahashi, Osamu; Tamaki, Seiichi; Shikama, Naoto

2014-01-01

This study aims to clarify the time-course of gas accumulation in the rectum during treatment as guidance for the management of rectal volumes. We reviewed 2042 sets (35.2 sets per patient) of anteroposterior and right–left mega voltage (MV) images obtained for daily set-up from 58 patients who underwent radical external beam radiotherapy for localised prostate cancer. The patients were instructed to take magnesium oxide tablets during radiotherapy. They were also encouraged to avoid foods that might cause intestinal gas during radiotherapy. Gas accumulation in the rectum was graded into three classes by the same radiation oncologist. If no gas was seen in the rectum, it was classified as grade 0. A small amount of gas was classified as grade 1, whereas a marked amount of gas that required removal was classified as grade 2. Of the 2042 sets of MV images, grades 1 and 2 gas accumulation were seen in 332 (16%) and 156 (8%), respectively. By the trend test, gas accumulation significantly decreased towards the end of treatment (P=0.02 for grade 1 or 2 and P=0.02 for grade 2). On multivariate analysis, we did not identify any significant independent predictors for either baseline gas accumulation or gas reduction. Gas accumulation tended to decrease until the end of treatment. This tendency should be reconfirmed by other institutions.

Neurophysiological localisation of ulnar neuropathy at the elbow: validation of diagnostic criteria developed by a taskforce of the Danish Society of Clinical Neurophysiology

DEFF Research Database (Denmark)

Pugdahl, Kirsten; Beniczky, Sándor; Wanscher, Benedikte

2017-01-01

OBJECTIVE: This study validates consensus criteria for localisation of ulnar neuropathy at elbow (UNE) developed by a taskforce of the Danish Society of Clinical Neurophysiology and compares them to the existing criteria from the American Association of Neuromuscular and Electrodiagnostic Medicine...

Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family.

Science.gov (United States)

Zobor, Ditta; Balousha, Ghassan; Baumann, Britta; Wissinger, Bernd

2014-01-01

Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes. The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister. We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease onset with moderate to rapid progression

Higher phylogeny of frugivorous flies (Diptera, Tephritidae, Dacini): localised partition conflicts and a novel generic classification.

Science.gov (United States)

Virgilio, Massimiliano; Jordaens, Kurt; Verwimp, Christophe; White, Ian M; De Meyer, Marc

2015-04-01

The phylogenetic relationships within and among subtribes of the fruit fly tribe Dacini (Ceratitidina, Dacina, Gastrozonina) were investigated by sequencing four mitochondrial and one nuclear gene fragment. Bayesian, maximum likelihood and maximum parsimony analyses were implemented on two datasets. The first, aiming at obtaining the strongest phylogenetic signal (yet, having lower taxon coverage), consisted of 98 vouchers and 2338 concatenated base pairs (bp). The second, aiming at obtaining the largest taxonomic coverage (yet, providing lower resolution), included 159 vouchers and 1200 concatenated bp. Phylogenetic relationships inferred by different tree reconstruction methods were largely congruent and showed a general agreement between concatenated tree topologies. Yet, local conflicts in phylogenetic signals evidenced a number of critical sectors in the phylogeny of Dacini fruit flies. All three Dacini subtribes were recovered as monophyletic. Yet, within the subtribe Ceratitidina only Perilampsis and Capparimyia formed well-resolved monophyletic groups while Ceratitis and Trirhithrum did not. Carpophthoromyia was paraphyletic because it included Trirhithrum demeyeri and Ceratitis connexa. Complex phylogenetic relationships and localised conflict in phylogenetic signals were observed within subtribe Dacina with (a) Dacus, (b) Bactrocera (Zeugodacus) and (c) all other Bactrocera species forming separate clades. The subgenus Bactrocera (Zeugodacus) is therefore raised to generic rank (Zeugodacus Hendel stat. nov.). Additionally, Bactrocera subgenera grouped under the Zeugodacus group should be considered under new generic combinations. Although there are indications that Zeugodacus and Dacus are sister groups, the exact relationship between Zeugodacus stat. nov., Dacus and Bactrocera still needs to be properly resolved. Copyright © 2015 Elsevier Inc. All rights reserved.

Hyperthyroidism caused by a germline activating mutation of the thyrotropin receptor gene: difficulties in diagnosis and therapy.

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Bertalan, Rita; Sallai, Agnes; Sólyom, János; Lotz, Gábor; Szabó, István; Kovács, Balázs; Szabó, Eva; Patócs, Attila; Rácz, Károly

2010-03-01

Germline activating mutations of the thyrotropin receptor (TSHR) gene have been considered as the only known cause of sporadic nonautoimmune hyperthyroidism in the pediatric population. Here we describe the long-term follow-up and evaluation of a patient with sporadic nonautoimmune primary hyperthyroidism who was found to have a de novo germline activating mutation of the TSHR gene. The patient was an infant who presented at the age of 10 months in an unconscious state with exsiccation, wet skin, fever, and tachycardia. Nonautoimmune primary hyperthyroidism was diagnosed, and brain magnetic resonance imaging and computed tomography showed also Arnold-Chiari malformation type I. Continuous propylthiouracil treatment resulted in a prolonged clinical cure lasting for 10 years. At the age of 11 years and 5 months the patient underwent subtotal thyroidectomy because of symptoms of trachea compression caused by a progressive multinodular goiter. However, 2 months after surgery, hormonal evaluation indicated recurrent hyperthyroidism and the patient was treated with propylthiouracil during the next 4 years. At the age of 15 years the patient again developed symptoms of trachea compression. Radioiodine treatment resulted in a regression of the recurrent goiter and a permanent cure of hyperthyroidism without relapse during the last 3 years of his follow-up. Sequencing of exon 10 of the TSHR gene showed a de novo heterozygous germline I630L mutation, which has been previously described as activating mutation at somatic level in toxic thyroid nodules. The I630L mutation of the TSHR gene occurs not only at somatic level in toxic thyroid nodules, but also its presence in germline is associated with nonautoimmune primary hyperthyroidism. Our case report demonstrates that in this disorder a continuous growth of the thyroid occurs without any evidence of elevated TSH due to antithyroid drug overdosing. This may justify previous recommendations for early treatment of affected

Functional analysis and localisation of a delta-class glutathione S-transferase from Sarcoptes scabiei.

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Pettersson, Eva U; Ljunggren, Erland L; Morrison, David A; Mattsson, Jens G

2005-01-01

The mite Sarcoptes scabiei causes sarcoptic mange, or scabies, a disease that affects both animals and humans worldwide. Our interest in S. scabiei led us to further characterise a glutathione S-transferase. This multifunctional enzyme is a target for vaccine and drug development in several parasitic diseases. The S. scabiei glutathione S-transferase open reading frame reported here is 684 nucleotides long and yields a protein with a predicted molecular mass of 26 kDa. Through phylogenetic analysis the enzyme was classified as a delta-class glutathione S-transferase, and our paper is the first to report that delta-class glutathione S-transferases occur in organisms other than insects. The recombinant S. scabiei glutathione S-transferase was expressed in Escherichia coli via three different constructs and purified for biochemical analysis. The S. scabiei glutathione S-transferase was active towards the substrate 1-chloro-2,4-dinitrobenzene, though the positioning of fusion partners influenced the kinetic activity of the enzyme. Polyclonal antibodies raised against S. scabiei glutathione S-transferase specifically localised the enzyme to the integument of the epidermis and cavities surrounding internal organs in adult parasites. However, some minor staining of parasite intestines was observed. No staining was seen in host tissues, nor could we detect any antibody response against S. scabiei glutathione S-transferase in sera from naturally S. scabiei infected dogs or pigs. Additionally, the polyclonal sera raised against recombinant S. scabiei glutathione S-transferase readily detected a protein from mites, corresponding to the predicted size of native glutathione S-transferase.

Effect of coulomb interaction on Anderson localization; Effet de l'interaction coulombienne sur la localisation d'Anderson dans des systemes de basses dimensions

Energy Technology Data Exchange (ETDEWEB)

Waintal, X

1999-09-10

We study the quantum mechanics of interacting particles in a disordered system, and in particular, what happens to Anderson localisation when interaction is taken into account. In the first part,one looks at the excited states of two particles in one dimension. For this model, it has been shown (Shepelyansky 1994) that a local repulsive interaction can partially destroy Anderson localisation. Here, we show that this model has similarities with the three-dimensional Anderson model at the metal-insulator transition. In particular, the maximum of rigidity obtained in the spectral statistics correspond to some intermediary statistics that cannot be described by random matrix theory neither by a Poisson statistics. The wave functions show a multifractal behaviour and the spreading of the center of mass of a wave packet is logarithmic in time. The second part deals with the ground state of a finite density of spinless fermions in two dimensions. After the scaling theory of localisation, it was commonly accepted that there was no metal in two dimensions. This idea has been challenged by the observation of a metal-insulator transition in low density electron gas (Kravchenko et al. 1994). We propose a scenario in which a metallic phase occurs between the Anderson insulator and the pinned Wigner crystal. This intermediate phase is characterized by an alignment of the local currents flowing in the system. (author)

Linear study and bundle adjustment data fusion; Application to vision localization; Recherche lineaire et fusion de donnees par ajustement de faisceaux; Application a la localisation par vision

Energy Technology Data Exchange (ETDEWEB)

Michot, J.

2010-12-09

The works presented in this manuscript are in the field of computer vision, and tackle the problem of real-time vision based localization and 3D reconstruction. In this context, the trajectory of a camera and the 3D structure of the filmed scene are initially estimated by linear algorithms and then optimized by a nonlinear algorithm, bundle adjustment. The thesis first presents a new technique of line search, dedicated to the nonlinear minimization algorithms used in Structure-from-Motion. The proposed technique is not iterative and can be quickly installed in traditional bundle adjustment frameworks. This technique, called Global Algebraic Line Search (G-ALS), and its two-dimensional variant (Two way-ALS), accelerate the convergence of the bundle adjustment algorithm. The approximation of the re-projection error by an algebraic distance enables the analytical calculation of an effective displacement amplitude (or two amplitudes for the Two way-ALS variant) by solving a degree 3 (G-ALS) or 5 (Two way-ALS) polynomial. Our experiments, conducted on simulated and real data, show that this amplitude, which is optimal for the algebraic distance, is also efficient for the Euclidean distance and reduces the convergence time of minimizations. One difficulty of real-time tracking algorithms (monocular SLAM) is that the estimated trajectory is often affected by drifts: on the absolute orientation, position and scale. Since these algorithms are incremental, errors and approximations are accumulated throughout the trajectory and cause global drifts. In addition, a tracking vision system can always be dazzled or used under conditions which prevented temporarily to calculate the location of the system. To solve these problems, we propose to use an additional sensor measuring the displacement of the camera. The type of sensor used will vary depending on the targeted application (an odometer for a vehicle, a lightweight inertial navigation system for a person). We propose to

[Gene doping: gene transfer and possible molecular detection].

Science.gov (United States)

Argüelles, Carlos Francisco; Hernández-Zamora, Edgar

2007-01-01

The use of illegal substances in sports to enhance athletic performance during competition has caused international sports organizations such as the COI and WADA to take anti doping measures. A new doping method know as gene doping is defined as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". However, gene doping in sports is not easily identified and can cause serious consequences. Molecular biology techniques are needed in order to distinguish the difference between a "normal" and an "altered" genome. Further, we need to develop new analytic methods and biological molecular techniques in anti-doping laboratories, and design programs that avoid the non therapeutic use of genes.

Heterozygous Germline Mutations in the CBL Tumor-Suppressor Gene Cause a Noonan Syndrome-like Phenotype

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Martinelli, Simone; De Luca, Alessandro; Stellacci, Emilia; Rossi, Cesare; Checquolo, Saula; Lepri, Francesca; Caputo, Viviana; Silvano, Marianna; Buscherini, Francesco; Consoli, Federica; Ferrara, Grazia; Digilio, Maria C.; Cavaliere, Maria L.; van Hagen, Johanna M.; Zampino, Giuseppe; van der Burgt, Ineke; Ferrero, Giovanni B.; Mazzanti, Laura; Screpanti, Isabella; Yntema, Helger G.; Nillesen, Willy M.; Savarirayan, Ravi; Zenker, Martin; Dallapiccola, Bruno; Gelb, Bruce D.; Tartaglia, Marco

2010-01-01

RAS signaling plays a key role in controlling appropriate cell responses to extracellular stimuli and participates in early and late developmental processes. Although enhanced flow through this pathway has been established as a major contributor to oncogenesis, recent discoveries have revealed that aberrant RAS activation causes a group of clinically related developmental disorders characterized by facial dysmorphism, a wide spectrum of cardiac disease, reduced growth, variable cognitive deficits, ectodermal and musculoskeletal anomalies, and increased risk for certain malignancies. Here, we report that heterozygous germline mutations in CBL, a tumor-suppressor gene that is mutated in myeloid malignancies and encodes a multivalent adaptor protein with E3 ubiquitin ligase activity, can underlie a phenotype with clinical features fitting or partially overlapping Noonan syndrome (NS), the most common condition of this disease family. Independent CBL mutations were identified in two sporadic cases and two families from among 365 unrelated subjects who had NS or suggestive features and were negative for mutations in previously identified disease genes. Phenotypic heterogeneity and variable expressivity were documented. Mutations were missense changes altering evolutionarily conserved residues located in the RING finger domain or the linker connecting this domain to the N-terminal tyrosine kinase binding domain, a known mutational hot spot in myeloid malignancies. Mutations were shown to affect CBL-mediated receptor ubiquitylation and dysregulate signal flow through RAS. These findings document that germline mutations in CBL alter development to cause a clinically variable condition that resembles NS and that possibly predisposes to malignancies. PMID:20619386

A core outcome set for localised prostate cancer effectiveness trials: protocol for a systematic review of the literature and stakeholder involvement through interviews and a Delphi survey.

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MacLennan, Steven; Bekema, Hendrika J; Williamson, Paula R; Campbell, Marion K; Stewart, Fiona; MacLennan, Sara J; N'Dow, James M O; Lam, Thomas B L

2015-03-04

Prostate cancer is a growing health problem worldwide. The management of localised prostate cancer is controversial. It is unclear which of several surgical, radiotherapeutic, ablative, and surveillance treatments is the most effective. All have cost, process and recovery, and morbidity implications which add to treatment decision-making complexity for patients and healthcare professionals. Evidence from randomised controlled trials (RCTs) is not optimal because of uncertainty as to what constitutes important outcomes. Another issue hampering evidence synthesis is heterogeneity of outcome definition, measurement, and reporting. This project aims to determine which outcomes are the most important to patients and healthcare professionals, and use these findings to recommend a standardised core outcome set for comparative effectiveness trials of treatments for localised prostate cancer, to optimise decision-making. The range of potentially important outcomes and measures will be identified through systematic reviews of the literature and semi-structured interviews with patients. A consultation exercise involving representatives from two key stakeholder groups (patients and healthcare professionals) will ratify the list of outcomes to be entered into a three round Delphi study. The Delphi process will refine and prioritise the list of identified outcomes. A methodological substudy (nested RCT design) will also be undertaken. Participants will be randomised after round one of the Delphi study to one of three feedback groups, based on different feedback strategies, in order to explore the potential impact of feedback strategies on participant responses. This may assist the design of a future core outcome set and Delphi studies. Following the Delphi study, a final consensus meeting attended by representatives from both stakeholder groups will determine the final recommended core outcome set. This study will inform clinical practice and future trials of interventions of

Localisation of the brain in fetal MRI using bundled SIFT features.

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Keraudren, Kevin; Kyriakopoulou, Vanessa; Rutherford, Mary; Hajnal, Joseph V; Rueckert, Daniel

2013-01-01

Fetal MRI is a rapidly emerging diagnostic imaging tool. Its main focus is currently on brain imaging, but there is a huge potential for whole body studies. We propose a method for accurate and robust localisation of the fetal brain in MRI when the image data is acquired as a stack of 2D slices misaligned due to fetal motion. We first detect possible brain locations in 2D images with a Bag-of-Words model using SIFT features aggregated within Maximally Stable Extremal Regions (called bundled SIFT), followed by a robust fitting of an axis-aligned 3D box to the selected regions. We rely on prior knowledge of the fetal brain development to define size and shape constraints. In a cross-validation experiment, we obtained a median error distance of 5.7mm from the ground truth and no missed detection on a database of 59 fetuses. This 2D approach thus allows a robust detection even in the presence of substantial fetal motion.

Optimisation of platelet concentrates therapy: Composition, localisation, and duration of action

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Yuk-Lin Yung

2017-01-01

Full Text Available Platelet concentrates (PC generally refers to a group of products that are prepared from autologous blood intended to enhance healing activities. PC therapy is now very popular in treating musculoskeletal injuries; however, inconsistent clinical results urge the need to understand the working mechanism of PC. It is generally believed that the platelet-derived bioactive factors are the active constituents, and their bioavailability in the vicinity of the lesion sites determines the treatment efficacies. Therefore, the composition, localisation, and duration of the action of PC would be key determinants. In this review, we discuss how different preparations and delivery methods of PC would affect the treatment outcomes with respect to clinical evidence about PC therapy for osteoarthritis, tendinopathies, rotator cuff tears, anterior cruciate ligament injuries, and bone fractures. This review can be used as a quick guide for the use of PC therapy and provide insights for the further optimisation of the therapy in the near future.

A physical map of the heterozygous grapevine 'Cabernet Sauvignon' allows mapping candidate genes for disease resistance

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Scalabrin Simone

2008-06-01

Full Text Available Abstract Background Whole-genome physical maps facilitate genome sequencing, sequence assembly, mapping of candidate genes, and the design of targeted genetic markers. An automated protocol was used to construct a Vitis vinifera 'Cabernet Sauvignon' physical map. The quality of the result was addressed with regard to the effect of high heterozygosity on the accuracy of contig assembly. Its usefulness for the genome-wide mapping of genes for disease resistance, which is an important trait for grapevine, was then assessed. Results The physical map included 29,727 BAC clones assembled into 1,770 contigs, spanning 715,684 kbp, and corresponding to 1.5-fold the genome size. Map inflation was due to high heterozygosity, which caused either the separation of allelic BACs in two different contigs, or local mis-assembly in contigs containing BACs from the two haplotypes. Genetic markers anchored 395 contigs or 255,476 kbp to chromosomes. The fully automated assembly and anchorage procedures were validated by BAC-by-BAC blast of the end sequences against the grape genome sequence, unveiling 7.3% of chimerical contigs. The distribution across the physical map of candidate genes for non-host and host resistance, and for defence signalling pathways was then studied. NBS-LRR and RLK genes for host resistance were found in 424 contigs, 133 of them (32% were assigned to chromosomes, on which they are mostly organised in clusters. Non-host and defence signalling genes were found in 99 contigs dispersed without a discernable pattern across the genome. Conclusion Despite some limitations that interfere with the correct assembly of heterozygous clones into contigs, the 'Cabernet Sauvignon' physical map is a useful and reliable intermediary step between a genetic map and the genome sequence. This tool was successfully exploited for a quick mapping of complex families of genes, and it strengthened previous clues of co-localisation of major NBS-LRR clusters and

The Drosophila cell adhesion molecule Neuroglian regulates Lissencephaly-1 localisation in circulating immunosurveillance cells

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Williams Michael J

2009-03-01

Full Text Available Abstract Background When the parasitoid wasp Leptopilina boulardi lays its eggs in Drosophila larvae phagocytic cells called plasmatocytes and specialized cells known as lamellocytes encapsulate the egg. This requires these circulating immunosurveillance cells (haemocytes to change from a non-adhesive to an adhesive state enabling them to bind to the invader. Interestingly, attachment of leukocytes, platelets, and insect haemocytes requires the same adhesion complexes as epithelial and neuronal cells. Results Here evidence is presented showing that the Drosophila L1-type cell adhesion molecule Neuroglian (Nrg is required for haemocytes to encapsulate L. boulardi wasp eggs. The amino acid sequence FIGQY containing a conserved phosphorylated tyrosine is found in the intracellular domain of all L1-type cell adhesion molecules. This conserved tyrosine is phosphorylated at the cell periphery of plasmatocytes and lamellocytes prior to parasitisation, but dephosphorylated after immune activation. Intriguingly, another pool of Nrg located near the nucleus of plasmatocytes remains phosphorylated after parasitisation. In mammalian neuronal cells phosphorylated neurofascin, another L1-type cell adhesion molecule interacts with a nucleokinesis complex containing the microtubule binding protein lissencephaly-1 (Lis1 1. Interestingly in plasmatocytes from Nrg mutants the nucleokinesis regulating protein Lissencephaly-1 (Lis1 fails to localise properly around the nucleus and is instead found diffuse throughout the cytoplasm and at unidentified perinuclear structures. After attaching to the wasp egg control plasmatocytes extend filopodia laterally from their cell periphery; as well as extending lateral filopodia plasmatocytes from Nrg mutants also extend many filopodia from their apical surface. Conclusion The Drosophila cellular adhesion molecule Neuroglian is expressed in haemocytes and its activity is required for the encapsulation of L. boularli eggs. At

Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.

Science.gov (United States)

Grønskov, Karen; Dooley, Christopher M; Østergaard, Elsebet; Kelsh, Robert N; Hansen, Lars; Levesque, Mitchell P; Vilhelmsen, Kaj; Møllgård, Kjeld; Stemple, Derek L; Rosenberg, Thomas

2013-03-07

Autosomal-recessive albinism is a hypopigmentation disorder with a broad phenotypic range. A substantial fraction of individuals with albinism remain genetically unresolved, and it has been hypothesized that more genes are to be identified. By using homozygosity mapping of an inbred Faroese family, we identified a 3.5 Mb homozygous region (10q22.2-q22.3) on chromosome 10. The region contains five protein-coding genes, and sequencing of one of these, C10orf11, revealed a nonsense mutation that segregated with the disease and showed a recessive inheritance pattern. Investigation of additional albinism-affected individuals from the Faroe Islands revealed that five out of eight unrelated affected persons had the nonsense mutation in C10orf11. Screening of a cohort of autosomal-recessive-albinism-affected individuals residing in Denmark showed a homozygous 1 bp duplication in C10orf11 in an individual originating from Lithuania. Immunohistochemistry showed localization of C10orf11 in melanoblasts and melanocytes in human fetal tissue, but no localization was seen in retinal pigment epithelial cells. Knockdown of the zebrafish (Danio rerio) homolog with the use of morpholinos resulted in substantially decreased pigmentation and a reduction of the apparent number of pigmented melanocytes. The morphant phenotype was rescued by wild-type C10orf11, but not by mutant C10orf11. In conclusion, we have identified a melanocyte-differentiation gene, C10orf11, which when mutated causes autosomal-recessive albinism in humans. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Investigation of the mechanisms by which UV irradiation activates the tyrosinase gene

International Nuclear Information System (INIS)

Bao, Y.

2000-04-01

Tyrosinase, tyrosinase related protein-1 (TRP-1) and tyrosinase related protein-2 (TRP-2) are the enzymes involved in melanin pigment synthesis. They are expressed specifically in melanocytic cells. UV irradiation is the major physiological stimulant of melanogenesis. Tyrosinase is the rate-limiting enzyme in melanin synthesis and its activity is regulated by UV irradiation in melanocytes. The molecular mechanism underlying the activation of tyrosinase by UV is still not clear. In this thesis, the effects of UV irradiation on tyrosinase, TRP-1 and TRP-2 gene expression in mouse B16 melanoma cells were studied as well as the effects of UV irradiation on the activity of the tyrosinase promoter in mouse, and human melanoma cells. UV irradiation caused an increase in tyrosinase mRNA level, without change in either TRP-1 or TRP-2 mRNA levels, as determined by Northern blot analysis. In order to determine whether UV- induced increase of tyrosinase mRNA expression involved modulation of tyrosinase promoter activity, transient transfection approaches involving a series of constructs containing either chloramphenicol acetyl transferase (CAT) or luciferase reporter genes linked to different lengths of the tyrosinase gene- promoter were used. UV irradiation specifically induced CAT gene expression from both the mouse and the human tyrosinase promoters, suggesting that UV irradiation induced the transcription of the tyrosinase gene. These observations indicated that the promoter region between -250 and -150 bp of the human tyrosinase promoter may contain important cis-regulatory elements involved in the UV response. To localise the cis-regulatory elements responsible for the UV response of the tyrosinase promoter, the 100-bp between -250 bp and -150 bp of the tyrosinase promoter was inserted upstream of a CAT reporter. It was shown that transcription from the 100-bp promoter fragment was activated by UV irradiation. Mutations of a potential cAMP response element (CRE) motif

TDP-43 Loss-of-Function Causes Neuronal Loss Due to Defective Steroid Receptor-Mediated Gene Program Switching in Drosophila

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Lies Vanden Broeck

2013-01-01

Full Text Available TDP-43 proteinopathy is strongly implicated in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative disorders. Whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function is unknown. We increased and decreased expression of TDP-43 (dTDP-43 in Drosophila. Although upregulation of dTDP-43 induced neuronal ubiquitin and dTDP-43-positive inclusions, both up- and downregulated dTDP-43 resulted in selective apoptosis of bursicon neurons and highly similar transcriptome alterations at the pupal-adult transition. Gene network analysis and genetic validation showed that both up- and downregulated dTDP-43 directly and dramatically increased the expression of the neuronal microtubule-associated protein Map205, resulting in cytoplasmic accumulations of the ecdysteroid receptor (EcR and a failure to switch EcR-dependent gene programs from a pupal to adult pattern. We propose that dTDP-43 neurotoxicity is caused by a loss of its normal function.

A novel point mutation within the EDA gene causes an exon dropping in mature RNA in Holstein Friesian cattle breed affected by X-linked anhidrotic ectodermal dysplasia

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Pariset Lorraine

2011-07-01

Full Text Available Abstract Background X-linked anhidrotic ectodermal dysplasia is a disorder characterized by abnormal development of tissues and organs of ectodermal origin caused by mutations in the EDA gene. The bovine EDA gene encodes the ectodysplasin A, a membrane protein expressed in keratinocytes, hair follicles and sweat glands, which is involved in the interactions between cell and cell and/or cell and matrix. Four mutations causing ectodermal dysplasia in cattle have been described so far. Results We identified a new single nucleotide polymorphism (SNP at the 9th base of exon 8 in the EDA gene in two calves of Holstein Friesian cattle breed affected by ectodermal dysplasia. This SNP is located in the exonic splicing enhancer (ESEs recognized by SRp40 protein. As a consequence, the spliceosome machinery is no longer able to recognize the sequence as exonic and causes exon skipping. The mutation determines the deletion of the entire exon (131 bp in the RNA processing, causing a severe alteration of the protein structure and thus the disease. Conclusion We identified a mutation, never described before, that changes the regulation of alternative splicing in the EDA gene and causes ectodermal dysplasia in cattle. The analysis of the SNP allows the identification of carriers that can transmit the disease to the offspring. This mutation can thus be exploited for a rational and efficient selection of unequivocally healthy cows for breeding.

Partial Gene Deletions of PMP22 Causing Hereditary Neuropathy with Liability to Pressure Palsies

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Sun-Mi Cho

2014-01-01

Full Text Available Hereditary neuropathy with liability to pressure palsies (HNPP is an autosomal neuropathy that is commonly caused by a reciprocal 1.5 Mb deletion on chromosome 17p11.2, at the site of the peripheral myelin protein 22 (PMP22 gene. Other patients with similar phenotypes have been shown to harbor point mutations or small deletions, although there is some clinical variation across these patients. In this report, we describe a case of HNPP with copy number changes in exon or promoter regions of PMP22. Multiplex ligation-dependent probe analysis revealed an exon 1b deletion in the patient, who had been diagnosed with HNPP in the first decade of life using molecular analysis.

Mutations in OTOF, CLDN14 & SLC26A4 genes as major causes of hearing impairment in Dhadkai village, Jammu & Kashmir, India

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Nishtha Pandey

2017-01-01

Interpretation & conclusions: This study suggested considerable genetic heterogeneity in the causation of hearing loss in Dhadkai. Recessive mutations were observed in at least three genes causing hearing loss: OTOF (p.R708X, SLC26A4 (p.Y556X and CLDN14 (p.V85D. Mutation p.R708X appeared to be the major cause of hearing impairment in Dhadkai.

Toxin Gene Analysis of a Variant Strain of Clostridium difficile That Causes Human Clinical Disease

Science.gov (United States)

Sambol, Susan P.; Merrigan, Michelle M.; Lyerly, David; Gerding, Dale N.; Johnson, Stuart

2000-01-01

A toxin variant strain of Clostridium difficile was isolated from two patients with C. difficile-associated disease (CDAD), one of whom died from extensive pseudomembranous colitis. This strain, identified by restriction endonuclease analysis (REA) as type CF2, was not detected by an immunoassay for C. difficile toxin A. Culture supernatants of CF2 failed to elicit significant enterotoxic activity in the rabbit ileal loop assay but did produce atypical cytopathic effects in cell culture assay. Southern hybridization, PCR amplification, and DNA sequence analyses were performed on the toxin A (tcdA) and toxin B (tcdB) genes of type CF2 isolate 5340. Type CF2 5340 tcdA exhibited a 1,821-bp truncation, due to three deletions in the 3′ end of the gene, and a point mutation in the 5′ end of the gene, resulting in a premature stop codon at tcdA position 139. Type CF2 5340 tcdB exhibited multiple nucleotide base substitutions in the 5′ end of the gene compared to tcdB of the standard toxigenic strain VPI 10463. Type CF2 5340 toxin gene nucleotide sequences and deduced amino acid sequences showed a strong resemblance to those of the previously described variant C. difficile strain 1470, a strain reported to have reduced pathogenicity and no association with clinical illness in humans. REA of strain 1470 identified this strain as a distinct type (CF1) within the same REA group as the closely related type CF2. A review of our clinical-isolate collection identified five additional patients infected with type CF2, three of whom had documented CDAD. PCR amplification of the 3′ end of tcdA demonstrated identical 1.8-kb deletions in all seven type CF2 isolates. REA type CF2 is a toxin variant strain of C. difficile that retains the ability to cause disease in humans but is not detected in clinical immunoassays for toxin A. PMID:10992443

Game Localisation as Software-Mediated Cultural Experience: Shedding Light on the Changing Role of Translation in Intercultural Communication in the Digital Age

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O'Hagan, Minako

2015-01-01

In this rapidly technologising age translation practice has been undergoing formidable changes with the implication that there is a need to expand the disciplinary scope of translation studies. Taking the case of game localisation this article problematises the role of translation as intercultural communication by focusing on cultural elements of…

Multiple Genes Cause Postmating Prezygotic Reproductive Isolation in the Drosophila virilis Group.

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Ahmed-Braimah, Yasir H

2016-12-07

Understanding the genetic basis of speciation is a central problem in evolutionary biology. Studies of reproductive isolation have provided several insights into the genetic causes of speciation, especially in taxa that lend themselves to detailed genetic scrutiny. Reproductive barriers have usually been divided into those that occur before zygote formation (prezygotic) and after (postzygotic), with the latter receiving a great deal of attention over several decades. Reproductive barriers that occur after mating but before zygote formation [postmating prezygotic (PMPZ)] are especially understudied at the genetic level. Here, I present a phenotypic and genetic analysis of a PMPZ reproductive barrier between two species of the Drosophila virilis group: D. americana and D. virilis This species pair shows strong PMPZ isolation, especially when D. americana males mate with D. virilis females: ∼99% of eggs laid after these heterospecific copulations are not fertilized. Previous work has shown that the paternal loci contributing to this incompatibility reside on two chromosomes, one of which (chromosome 5) likely carries multiple factors. The other (chromosome 2) is fixed for a paracentric inversion that encompasses nearly half the chromosome. Here, I present two results. First, I show that PMPZ in this species cross is largely due to defective sperm storage in heterospecific copulations. Second, using advanced intercross and backcross mapping approaches, I identify genomic regions that carry genes capable of rescuing heterospecific fertilization. I conclude that paternal incompatibility between D. americana males and D. virilis females is underlain by four or more genes on chromosomes 2 and 5. Copyright © 2016 Ahmed-Braimah.

Mineral Replacement Reactions as a Precursor to Strain Localisation: an (HR-)EBSD approach

Science.gov (United States)

Gardner, J.; Wheeler, J.; Wallis, D.; Hansen, L. N.; Mariani, E.

2017-12-01

Much remains to be learned about the links between metamorphism and deformation. Our work investigates the behaviour of fluid-mediated mineral replacement reaction products when exposed to subsequent shear stresses. We focus on albite from a metagabbro that has experienced metamorphism and subsequent deformation at greenschist facies, resulting in a reduction in grain size and associated strain localisation. EBSD maps show that prior to grain size reduction, product grains are highly distorted, yet they formed, and subsequently deformed, at temperatures at which extensive dislocation creep is unlikely. The Weighted Burgers Vector can be used to quantitatively describe the types of Burgers vectors present in geometrically necessary dislocation (GND) populations derived from 2-D EBSD map data. Application of this technique to the distorted product grains reveals the prominence of, among others, dislocations with apparent [010] Burgers vectors. This supports (with some caveats) the idea that dislocation creep is not responsible for the observed lattice distortion, as there are no known slip systems in plagioclase with a [010] Burgers vector. Distortion in a replacement microstructure has also been attributed to the presence of nanoscale product grains, which share very similar, but not identical, orientations due to topotactic nucleation from adjacent sites on the same substrate. As a precipitate, the product grains should be expected to be largely free of elastic strain. However, high angular resolution EBSD results demonstrate that product grains contain both elastic strains (> 10-3) and residual stresses (several hundred MPa), as well as GND densities on the order of 1014-1015 m-2. Thus we suggest the observed distortion (elastic strain plus rotations) in the lattice is produced during the mineral replacement reaction by a lattice mismatch and volume change between parent and product. Stored strain energy then provides a driving force for recovery and

FCJ-171 Expectations denied: Fan and industry conflict around the localisation of the Japanese video game Yakuza 3

Directory of Open Access Journals (Sweden)

Craig Norris

2014-12-01

Full Text Available Online fan cultures provides researchers with a space to observe and analyse the development and establishment of fan participation with media properties. The visibility of, and zealous postings by, fans on online forums offers a valuable opportunity to explore what happens when fans feel their expectations are being denied or limited by creator or industry actions. This article examines the fallout around the localisation of the Japanese video game Yakuza 3 into the West in 2010.

UMD-USHbases: a comprehensive set of databases to record and analyse pathogenic mutations and unclassified variants in seven Usher syndrome causing genes.

Science.gov (United States)

Baux, David; Faugère, Valérie; Larrieu, Lise; Le Guédard-Méreuze, Sandie; Hamroun, Dalil; Béroud, Christophe; Malcolm, Sue; Claustres, Mireille; Roux, Anne-Françoise

2008-08-01

Using the Universal Mutation Database (UMD) software, we have constructed "UMD-USHbases", a set of relational databases of nucleotide variations for seven genes involved in Usher syndrome (MYO7A, CDH23, PCDH15, USH1C, USH1G, USH3A and USH2A). Mutations in the Usher syndrome type I causing genes are also recorded in non-syndromic hearing loss cases and mutations in USH2A in non-syndromic retinitis pigmentosa. Usher syndrome provides a particular challenge for molecular diagnostics because of the clinical and molecular heterogeneity. As many mutations are missense changes, and all the genes also contain apparently non-pathogenic polymorphisms, well-curated databases are crucial for accurate interpretation of pathogenicity. Tools are provided to assess the pathogenicity of mutations, including conservation of amino acids and analysis of splice-sites. Reference amino acid alignments are provided. Apparently non-pathogenic variants in patients with Usher syndrome, at both the nucleotide and amino acid level, are included. The UMD-USHbases currently contain more than 2,830 entries including disease causing mutations, unclassified variants or non-pathogenic polymorphisms identified in over 938 patients. In addition to data collected from 89 publications, 15 novel mutations identified in our laboratory are recorded in MYO7A (6), CDH23 (8), or PCDH15 (1) genes. Information is given on the relative involvement of the seven genes, the number and distribution of variants in each gene. UMD-USHbases give access to a software package that provides specific routines and optimized multicriteria research and sorting tools. These databases should assist clinicians and geneticists seeking information about mutations responsible for Usher syndrome.

The instability of internal gravity waves to localised disturbances

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J. Vanneste

1995-02-01

Full Text Available The instability of an internal gravity wave due to nonlinear wave-wave interaction is studied theoretically and numerically. Three different aspects of this phenomenon are examined. 1. The influence of dissipation on both the resonant and the nonresonant interactions is analysed using a normal mode expansion of the basic equations. In particular, the modifications induced in the interaction domain are calculated and as a result some modes are shown to be destabilised by dissipation. 2. The evolution of an initial unstable disturbance of finite vertical extent is described as the growth of two secondary wave packets travelling at the same group velocity. A quasi-linear correction to the basic primary wave is calculated, corresponding to a localised amplitude decrease due to the disturbance growth. 3. Numerical experiments are carried out to study the effect of a basic shear on wave instability. It appears that the growing secondary waves can have a frequency larger than that of the primary wave, provided that the shear is sufficient. The instability of waves with large amplitude and long period, such as tides or planetary waves, could therefore be invoked as a possible mechanism for the generation of gravity waves with shorter period in the middle atmosphere.

Two α1-Globin Gene Point Mutations Causing Severe Hb H Disease.

Science.gov (United States)

Jiang, Hua; Huang, Lv-Yin; Zhen, Li; Jiang, Fan; Li, Dong-Zhi

Hb H disease is generally a moderate form of α-thalassemia (α-thal) that rarely requires regular blood transfusions. In this study, two Chinese families with members carrying transfusion-dependent Hb H disease were investigated for rare mutations on the α-globin genes (HBA1, HBA2). In one family, Hb Zürich-Albisrieden [α59(E8)Gly→Arg; HBA1: c.178G>C] in combination with the Southeast Asian (- - SEA ) deletion was the defect responsible for the severe phenotype. In another family, a novel hemoglobin (Hb) variant named Hb Sichuan (HBA1: c.393_394insT), causes α-thal and a severe phenotype when associated with the - - SEA deletion. As these two HBA1 mutations can present as continuous blood transfusion-dependent α-thal, it is important to take this point into account for detecting the carriers, especially in couples in which one partner is already a known α 0 -thal carrier.

Genetic interactions between planar cell polarity genes cause diverse neural tube defects in mice

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Jennifer N. Murdoch

2014-10-01

Full Text Available Neural tube defects (NTDs are among the commonest and most severe forms of developmental defect, characterized by disruption of the early embryonic events of central nervous system formation. NTDs have long been known to exhibit a strong genetic dependence, yet the identity of the genetic determinants remains largely undiscovered. Initiation of neural tube closure is disrupted in mice homozygous for mutations in planar cell polarity (PCP pathway genes, providing a strong link between NTDs and PCP signaling. Recently, missense gene variants have been identified in PCP genes in humans with NTDs, although the range of phenotypes is greater than in the mouse mutants. In addition, the sequence variants detected in affected humans are heterozygous, and can often be detected in unaffected individuals. It has been suggested that interactions between multiple heterozygous gene mutations cause the NTDs in humans. To determine the phenotypes produced in double heterozygotes, we bred mice with all three pairwise combinations of Vangl2Lp, ScribCrc and Celsr1Crsh mutations, the most intensively studied PCP mutants. The majority of double-mutant embryos had open NTDs, with the range of phenotypes including anencephaly and spina bifida, therefore reflecting the defects observed in humans. Strikingly, even on a uniform genetic background, variability in the penetrance and severity of the mutant phenotypes was observed between the different double-heterozygote combinations. Phenotypically, Celsr1Crsh;Vangl2Lp;ScribCrc triply heterozygous mutants were no more severe than doubly heterozygous or singly homozygous mutants. We propose that some of the variation between double-mutant phenotypes could be attributed to the nature of the protein disruption in each allele: whereas ScribCrc is a null mutant and produces no Scrib protein, Celsr1Crsh and Vangl2Lp homozygotes both express mutant proteins, consistent with dominant effects. The variable outcomes of these genetic

Overexpression of mouse TTF-2 gene causes cleft palate

Science.gov (United States)

Meng, Tian; Shi, Jia-Yu; Wu, Min; Wang, Yan; Li, Ling; Liu, Yan; Zheng, Qian; Huang, Lei; Shi, Bing

2012-01-01

In humans, mutations of the gene encoding for thyroid transcription factor-2 (TTF-2 or FOXE1) result in Bamforth syndrome. Bamforth syndrome is characterized by agenesis, cleft palate, spiky hair and choanal atresia. TTF-2 null mice (TTF-2−/−) also exhibit cleft palate, suggesting its involvement in the palatogenesis. However, the molecular pathology and genetic regulation by TTF2 remain largely unknown. In the present study, the recombinant expression vector pBROAD3-TTF-2 containing the promoter of the mouse ROSA26 gene was created to form the structural gene of mouse TTF-2 and was microinjected into the male pronuclei of fertilized ova. Sequence analysis confirmed that the TTF-2 transgenic mouse model was established successfully. The transgenic mice displayed a phenotype of cleft palate. In addition, we found that TTF-2 was highly expressed in the medial edge epithelium (MEE) from the embryonic day 12.5 (E12.5) to E14.5 in TTF-2 transgenic mice. These observations suggest that overexpression of TTF-2 during palatogenesis may contribute to formation of cleft palate. PMID:22304410

Somatic mutations in mismatch repair genes in sporadic gastric carcinomas are not a cause but a consequence of the mutator phenotype

NARCIS (Netherlands)

Pinto, Mafalda; Wub, Ying; Mensink, Rob G. J.; Cirnes, Luis; Seruca, Raquel; Hofstra, Robert M. W.

2008-01-01

In hereditary nonpolyposis colorectal cancer (HNPCC), patients' mismatch repair (MMR) gene mutations cause MMR deficiency, leading to microsatellite instability (MSI-H). MSI-H is also found in a substantial fraction of sporadic gastric carcinomas (SGC), mainly due to MLH1 promoter hypermethylation,

An assessment of the importance ofexposure routes to the uptake and internal localisation of fluorescent nanoparticles in zebrafish (Danio rerio), using light sheet microscopy

DEFF Research Database (Denmark)

Skjolding, Lars Michael; Ašmonaitė, G; Jølck, Rasmus Irming

2017-01-01

A major challenge in nanoecotoxicology is finding suitable methods to determine the uptake and localisation of nanoparticles on a whole-organism level. Some uptake methods have been associated with artefacts induced by sample preparation, including staining for electron microscopy. This study use...

EPILEPSY CAUSED BY PCDH19 GENE MUTATION: A REVIEW OF LITERATURE AND THE AUTHORS’ OBSERVATIONS

Directory of Open Access Journals (Sweden)

K. Yu. Mukhin

2016-01-01

Full Text Available Mutation in the PCDH19 gene was first described by L.M. Dibbens et al. in 2008. Mutations in this gene are associated with epilepsy and mental retardation limited to females. The clinical manifestations that are observed in some patients with PCDH19 mutation and Dravet syndrome that is caused by mutation in the SCN1A gene include the onset of febrile and afebrile seizures in infancy, serial seizures during fever, and regression in development after the onset of seizures. Due to the fact that the two diseases have common clinical signs, it is best to test for PCDH19 mutation in patients with the clinical picture of Dravet syndrome and a negative test for SCN1A. In general, the number of scientific papers devoted to analysis and recommendations for the choice of therapy in patients with rare genetic pathology is small now. We analyzed the specific features of clinical signs and therapy in our two observed female patients aged 4 and 11 years with verified PCDH19 mutation. Both patients were noted to have severe epilepsy with febrile convulsions with the development of status epilepticus and to be unresponsive to antiepileptic therapy. The use of different antiepileptic drugs (valproate, oxcarbazepine, phenobarbital, topiramate, levetiracetam at different combinations failed to control the course of epilepsy in the 4-year-old patient whereas the 11-year-old patient who took a combination of valproic acid and benzodiazepines achieved a positive effect.

Localisation of deformations of the midfacial complex in subjects with class III malocclusions employing thin-plate spline analysis.

Science.gov (United States)

Singh, G D; McNamara, J A; Lozanoff, S

1997-11-01

This study determines deformations of the midface that contribute to a class III appearance, employing thinplate spline analysis. A total of 135 lateral cephalographs of prepubertal children of European-American descent with either class III malocclusions or a class I molar occlusion were compared. The cephalographs were traced and checked, and 7 homologous landmarks of the midface were identified and digitised. The data sets were scaled to an equivalent size and subjected to Procrustes analysis. These statistical tests indicated significant differences (P spline analysis indicated that both affine and nonaffine transformations contribute towards the total spline for the averaged midfacial configuration. For nonaffine transformations, partial warp 3 had the highest magnitude, indicating the large scale deformations of the midfacial configuration. These deformations affected the palatal landmarks, and were associated with compression of the midfacial complex in the anteroposterior plane predominantly. Partial warp 4 produced some vertical compression of the posterior aspect of the midfacial complex whereas partial warps 1 and 2 indicated localised shape changes of the maxillary alveolus region. large spatial-scale deformations therefore affect the midfacial complex in an anteroposterior axis, in combination with vertical compression and localised distortions. These deformations may represent a developmental diminution of the palatal complex anteroposteriorly that, allied with vertical shortening of midfacial height posteriorly, results in class III malocclusions with a retrusive midfacial profile.

Two novel mutations in the sixth transmembrane segment of the thyrotropin receptor gene causing hyperfunctioning thyroid nodules.

Science.gov (United States)

Gozu, Hulya; Avsar, Melike; Bircan, Rifat; Claus, Maren; Sahin, Serap; Sezgin, Ozlem; Deyneli, Oguzhan; Paschke, Ralf; Cirakoglu, Beyazit; Akalin, Sema

2005-04-01

Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning adenomas or toxic multinodular goiters. In the last decade, a large number of activating mutations have been identified in the thyrotropin receptor (TSHR) gene in autonomously functioning thyroid nodules. Most have been situated close to, or within the sixth transmembrane segment and third intracellular loop of the TSHR where the receptor interacts with the Gs protein. In this study we describe two novel mutations in the sixth transmembrane segment of the TSHR causing hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two patients with toxic multinodular goiter. After amplifying the related regions, TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. We identified two novel TSHR mutations in two hyperfunctioning thyroid nodules: Phe631Val in the first patient and Iso630Met in the second patient. Both mutant receptors display an increase in constitutive stimulation of basal cyclic adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This confirms that these mutant receptors cause hyperfunctioning thyroid nodules.

Inflammatory peeling skin syndrome caused by homozygous genomic deletion in the PSORS1 region encompassing the CDSN gene.

Science.gov (United States)

Ishida-Yamamoto, Akemi; Furio, Laetitia; Igawa, Satomi; Honma, Masaru; Tron, Elodie; Malan, Valerie; Murakami, Masamoto; Hovnanian, Alain

2014-01-01

Peeling skin syndrome (PSS) type B is a rare recessive genodermatosis characterized by lifelong widespread, reddish peeling of the skin with pruritus. The disease is caused by small-scale mutations in the Corneodesmosin gene (CDSN) leading to premature termination codons. We report for the first time a Japanese case resulting from complete deletion of CDSN. Corneodesmosin was undetectable in the epidermis, and CDSN was unamplifiable by PCR. QMPSF analysis demonstrated deletion of CDSN exons inherited from each parent. Deletion mapping using microsatellite haplotyping, CGH array and PCR analysis established that the genomic deletion spanned 49-72 kb between HCG22 and TCF19, removing CDSN as well as five other genes within the psoriasis susceptibility region 1 (PSORS1) on 6p21.33. This observation widens the spectrum of molecular defects underlying PSS type B and shows that loss of these five genes from the PSORS1 region does not result in an additional cutaneous phenotype. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS) Gene

NARCIS (Netherlands)

Nakajima, Yoko; Meijer, Judith; Zhang, Chunhua; Wang, Xu; Kondo, Tomomi; Ito, Tetsuya; Dobritzsch, Doreen; van Kuilenburg, André B. P.

2016-01-01

Dihydropyrimidinase (DHP) deficiency is an autosomal recessive disease caused by mutations in the DPYS gene. Patients present with highly elevated levels of dihydrouracil and dihydrothymine in their urine, blood and cerebrospinal fluid. The analysis of the effect of mutations in DPYS on pre-mRNA

On the non-existence of totally localised intersections of D3/D5 branes in type IIB SUGRA

Energy Technology Data Exchange (ETDEWEB)

Patino, Leonardo [Department of Mathematical Sciences, University of Durham, Durham, DH1 3LE (United Kingdom); Smith, Douglas [Department of Mathematical Sciences, University of Durham, Durham, DH1 3LE (United Kingdom)

2005-04-01

In the present paper we study the most general configuration of intersecting D3/D5 branes in type IIB supergravity satisfying Poincare invariance in the directions common to the branes and SO(3) symmetry in the totally perpendicular directions. The form of these configurations is greatly restricted by the Killing spinor equations and the equations of motion, which among other things, force the Ramond-Ramond scalar to be zero and do not permit the existence of totally localised intersections of this kind.

On the non-existence of totally localised intersections of D3/D5 branes in type IIB SUGRA

International Nuclear Information System (INIS)

Patino, Leonardo; Smith, Douglas

2005-01-01

In the present paper we study the most general configuration of intersecting D3/D5 branes in type IIB supergravity satisfying Poincare invariance in the directions common to the branes and SO(3) symmetry in the totally perpendicular directions. The form of these configurations is greatly restricted by the Killing spinor equations and the equations of motion, which among other things, force the Ramond-Ramond scalar to be zero and do not permit the existence of totally localised intersections of this kind

A novel mutation in the EDAR gene causes severe autosomal recessive hypohidrotic ectodermal dysplasia.

Science.gov (United States)

Henningsen, Emil; Svendsen, Mathias Tiedemann; Lildballe, Dorte Launholt; Jensen, Peter Kjestrup Axel

2014-08-01

We report on a 2-year-old girl presenting with a severe form of hypohidrotic ectodermal dysplasia (HED). The patient presented with hypotrichosis, anodontia, hypohidrosis, frontal bossing, prominent lips and ears, dry, pale skin, and dermatitis. The patient had chronic rhinitis with malodorous nasal discharge. The girl was the second born child of first-cousin immigrants from Northern Iraq. A novel homozygous mutation (c.84delC) in the EDAR gene was identified. This mutation most likely causes a frameshift in the protein product (p.S29fs*74). This results in abolition of all ectodysplasin-mediated NF-kB signalling. This complete loss-of-function mutation likely accounts for the severe clinical abnormalities in ectodermal structures in the described patient. © 2014 Wiley Periodicals, Inc.

The localisation of treponemes and characterisation of the inflammatory infiltrate in skin biopsies from patients with primary or secondary syphilis, or early infectious yaws

NARCIS (Netherlands)

Engelkens, H. J.; ten Kate, F. J.; Judanarso, J.; Vuzevski, V. D.; van Lier, J. B.; Godschalk, J. C.; van der Sluis, J. J.; Stolz, E.

1993-01-01

To study the localisation of treponemes and to analyse the inflammatory infiltrate in biopsy specimens from patients with primary or secondary syphilis, or early infectious yaws. Skin biopsies originating from human lesions of primary (29x) or secondary (15x) syphilis (Rotterdam), or early yaws

Cloning, nucleotide sequence and transcriptional analysis of the uvrA gene from Neisseria gonorrhoeae

International Nuclear Information System (INIS)

Black, C.G.; Fyfe, J.A.M.; Davies, J.K.

1997-01-01

A recombinant plasmid capable of restoring UV resistance to an Escherichia coli uvrA mutant was isolated from a genomic library of Neisseria gonorrhoeae. Sequence analysis revealed an open reading frame whose deduced amino acid sequence displayed significant similarity to those of the UvrA proteins of other bacterial species. A second open reading frame (ORF259) was identified upstream from, and in the opposite orientation to the gonococcal uvrA gene. Transcriptional fusions between portions of the gonococcal uvrA upstream region and a reporter gene were used to localise promoter activity in both E. coli and N. gonorrhoeae. The transcriptional starting points of uvrA and ORF259 were mapped in E. coli by primer extension analysis, and corresponding σ 70 promoters were identified. The arrangement of the uvrA-ORF259 intergenic region is similar to that of the gonococcal recA-aroD intergenic region. Both contain inverted copies of the 10 bp neisserial DNA uptake sequence situated between divergently transcribed genes. However, there is no evidence that either the uptake sequence or the proximity of the promoters influences expression of these genes. (author)

Generation of an isogenic, gene-corrected iPSC line from a symptomatic 59-year-old female patient with frontotemporal dementia caused by an R406W mutation in the microtubule associated protein tau (MAPT) gene

DEFF Research Database (Denmark)

Nimsanor, Natakarn; Poulsen, Ulla; Rasmussen, Mikkel A.

2016-01-01

pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation......Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced...... of genetically corrected iPSCs from a 59-year-old female FTD-17 patient carrying an R406W mutation in the MAPT-gene....

Generation of an isogenic, gene-corrected iPSC line from a symptomatic 57-year-old female patient with frontotemporal dementia caused by a P301L mutation in the microtubule associated protein tau (MAPT) gene

DEFF Research Database (Denmark)

Nimsanor, Natakarn; Kitiyanant, Narisorn; Poulsen, Ulla

2016-01-01

pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control. Here, we report the generation......Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau)-gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced...... of genetically corrected iPSCs from a 57-year-old female FTD-17 patient carrying an P301L mutation in the MAPT-gene....

Two novel mutations in the PPIB gene cause a rare pedigree of osteogenesis imperfecta type IX.

Science.gov (United States)

Jiang, Yu; Pan, Jingxin; Guo, Dongwei; Zhang, Wei; Xie, Jie; Fang, Zishui; Guo, Chunmiao; Fang, Qun; Jiang, Weiying; Guo, Yibin

2017-06-01

Osteogenesis imperfecta (OI) is a rare genetic skeletal disorder characterized by increased bone fragility and vulnerability to fractures. PPIB is identified as a candidate gene for OI-IX, here we detect two pathogenic mutations in PPIB and analyze the genotype-phenotype correlation in a Chinese family with OI. Next-generation sequencing (NGS) was used to screen the whole exome of the parents of proband. Screening of variation frequency, evolutionary conservation comparisons, pathogenicity evaluation, and protein structure prediction were conducted to assess the pathogenicity of the novel mutations. Sanger sequencing was used to confirm the candidate variants. RTQ-PCR was used to analyze the PPIB gene expression. All mutant genes screened out by NGS were excluded except PPIB. Two novel heterozygous PPIB mutations (father, c.25A>G; mother, c.509G>A) were identified in relation to osteogenesis imperfecta type IX. Both mutations were predicted to be pathogenic by bioinformatics analysis and RTQ-PCR analysis revealed downregulated PPIB expression in the two carriers. We report a rare pedigree with an autosomal recessive osteogenesis imperfecta type IX (OI-IX) caused by two novel PPIB mutations identified for the first time in China. The current study expands our knowledge of PPIB mutations and their associated phenotypes, and provides new information on the genetic defects associated with this disease for clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Translational read-through as an alternative approach for ocular gene therapy of retinal dystrophies caused by in-frame nonsense mutations.

Science.gov (United States)

Nagel-Wolfrum, Kerstin; Möller, Fabian; Penner, Inessa; Wolfrum, Uwe

2014-09-01

The eye has become an excellent target for gene therapy, and gene augmentation therapy of inherited retinal disorders has made major progress in recent years. Nevertheless, a recent study indicated that gene augmentation intervention might not stop the progression of retinal degeneration in patients. In addition, for many genes, viral-mediated gene augmentation is currently not feasible due to gene size and limited packaging capacity of viral vectors as well as expression of various heterogeneous isoforms of the target gene. Thus, alternative gene-based strategies to stop or delay the retinal degeneration are necessary. This review focuses on an alternative pharmacologic treatment strategy based on the usage of translational read-through inducing drugs (TRIDs) such as PTC124, aminoglycoside antibiotics, and designer aminoglycosides for overreading in-frame nonsense mutations. This strategy has emerged as an option for up to 30-50% of all cases of recessive hereditary retinal dystrophies. In-frame nonsense mutations are single-nucleotide alterations within the gene coding sequence resulting in a premature stop codon. Consequently, translation of such mutated genes leads to the synthesis of truncated proteins, which are unable to fulfill their physiologic functions. In this context, application of TRIDs facilitates the recoding of the premature termination codon into a sense codon, thus restoring syntheses of full-length proteins. So far, clinical trials for non-ocular diseases have been initiated for diverse TRIDs. Although the clinical outcome is not analyzed in detail, an excellent safety profile, namely for PTC124, was clearly demonstrated. Moreover, recent data demonstrated sustained read-through efficacies of nonsense mutations causing retinal degeneration, as manifested in the human Usher syndrome. In addition, a strong retinal biocompatibility for PTC124 and designer aminoglycosides has been demonstrated. In conclusion, recent progress emphasizes the

Pressure-induced localisation of the hydrogen-bond network in KOH-VI

Energy Technology Data Exchange (ETDEWEB)

Hermann, Andreas, E-mail: a.hermann@ed.ac.uk; Nelmes, Richard J.; Loveday, John S. [Centre for Science at Extreme Conditions and SUPA, School of Physics and Astronomy, The University of Edinburgh, Edinburgh EH9 3JZ (United Kingdom); Guthrie, Malcolm [Centre for Science at Extreme Conditions and SUPA, School of Physics and Astronomy, The University of Edinburgh, Edinburgh EH9 3JZ (United Kingdom); European Spallation Source AB, P.O. Box 176, SE-22100 Lund (Sweden)

2015-12-28

Using a combination of ab initio crystal structure prediction and neutron diffraction techniques, we have solved the full structure of KOH-VI at 7 GPa. Rather than being orthorhombic and proton-ordered as had previously be proposed, we find that this high-pressure phase of potassium hydroxide is tetragonal (space group I4/mmm) and proton disordered. It has an unusual hydrogen bond topology, where the hydroxyl groups form isolated hydrogen-bonded square planar (OH){sub 4} units. This structure is stable above 6.5 GPa and, despite being macroscopically proton-disordered, local ice rules enforce microscopic order of the hydrogen bonds. We suggest the use of this novel type of structure to study concerted proton tunneling in the solid state, while the topology of the hydrogen bond network could conceivably be exploited in data storage applications based solely on the manipulations of hydrogen bonds. The unusual localisation of the hydrogen bond network under applied pressure is found to be favored by a more compact packing of the constituents in a distorted cesium chloride structure.

Location service for wireless network using improved RSS-based cellular localisation

Science.gov (United States)

Fayaz, Sara; Sarrafian, Sara

2014-06-01

Value-added services, especially in mobile environments, have recently become the key component of making more profit and attracting more subscribers. One of the most commonly used such service is location-based advertiser services. The main issue which should be considered in providing such services is determining the position of the mobile terminals precisely. In this paper, one pattern recognition localisation method based on the signal strength appropriated for implementing a location-based service is presented. The main aim is to introduce some practical solutions to decrease error and computational load and also eliminate the necessity of updating the database. Practical results illustrate high accuracy of this technique and its suitability to apply in such services. The mean error declines to 9.7 m and mean error corresponding to CDF = 67% and CDF = 95% are less than 11 m and 23 m, respectively. We also present a location-based advertising service, in which the customer's interests and local time are considered, in order to enhance the efficiency and individualism of this service.

Ancient expansion of the hox cluster in lepidoptera generated four homeobox genes implicated in extra-embryonic tissue formation.

Directory of Open Access Journals (Sweden)

Laura Ferguson

2014-10-01

Full Text Available Gene duplications within the conserved Hox cluster are rare in animal evolution, but in Lepidoptera an array of divergent Hox-related genes (Shx genes has been reported between pb and zen. Here, we use genome sequencing of five lepidopteran species (Polygonia c-album, Pararge aegeria, Callimorpha dominula, Cameraria ohridella, Hepialus sylvina plus a caddisfly outgroup (Glyphotaelius pellucidus to trace the evolution of the lepidopteran Shx genes. We demonstrate that Shx genes originated by tandem duplication of zen early in the evolution of large clade Ditrysia; Shx are not found in a caddisfly and a member of the basally diverging Hepialidae (swift moths. Four distinct Shx genes were generated early in ditrysian evolution, and were stably retained in all descendent Lepidoptera except the silkmoth which has additional duplications. Despite extensive sequence divergence, molecular modelling indicates that all four Shx genes have the potential to encode stable homeodomains. The four Shx genes have distinct spatiotemporal expression patterns in early development of the Speckled Wood butterfly (Pararge aegeria, with ShxC demarcating the future sites of extraembryonic tissue formation via strikingly localised maternal RNA in the oocyte. All four genes are also expressed in presumptive serosal cells, prior to the onset of zen expression. Lepidopteran Shx genes represent an unusual example of Hox cluster expansion and integration of novel genes into ancient developmental regulatory networks.

De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies

DEFF Research Database (Denmark)

2014-01-01

in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p...... = 8.2 × 10(-4)), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have...... analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1...

In normal human fibroblasts variation in DSB repair capacity cannot be ascribed to radiation-induced changes in the localisation, expression or activity of major NHEJ proteins

DEFF Research Database (Denmark)

Kasten-Pisula, Ulla; Vronskaja, Svetlana; Overgaard, Jens

2008-01-01

in the activity of the DNA-PK complex induced upon irradiation. CONCLUSIONS: For normal human fibroblasts, the level or activity of NHEJ proteins measured prior to or after irradiation cannot be used to predict the DSB repair capacity or cellular radiosensitivity. Udgivelsesdato: 2008-Mar......BACKGROUND AND PURPOSE: The aim of the present study was to test whether for normal human fibroblasts the variation in double-strand break (DSB) repair capacity results from radiation-induced differences in localisation, expression or activity of major non-homologous end-joining (NHEJ) proteins....... MATERIALS AND METHODS: Experiments were performed with 11 normal human fibroblast strains AF01-11. NHEJ proteins were determined by Western blot and DNA-PK activity by pulldown-assay. RESULTS: The four NHEJ proteins tested (Ku70, Ku80, XRCC4 and DNA-PKcs) were found to be localised almost exclusively...

Mutations in the LHX2 gene are not a frequent cause of micro/anophthalmia.

Science.gov (United States)

Desmaison, Annaïck; Vigouroux, Adeline; Rieubland, Claudine; Peres, Christine; Calvas, Patrick; Chassaing, Nicolas

2010-12-18

Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (orthodenticle homeobox 2 [OTX2], retina and anterior neural fold homeobox [RAX], SRY-box 2 [SOX2], CEH10 homeodomain-containing homolog [CHX10], and growth differentiation factor 6 [GDF6]) have been implicated mainly in isolated micro/anophthalmia but causative mutations of these genes explain less than a quarter of these developmental defects. The essential role of the LIM homeobox 2 (LHX2) transcription factor in early eye development has recently been documented. We postulated that mutations in this gene could lead to micro/anophthalmia, and thus performed molecular screening of its sequence in patients having micro/anophthalmia. Seventy patients having non-syndromic forms of colobomatous microphthalmia (n=25), isolated microphthalmia (n=18), or anophthalmia (n=17), and syndromic forms of micro/anophthalmia (n=10) were included in this study after negative molecular screening for OTX2, RAX, SOX2, and CHX10 mutations. Mutation screening of LHX2 was performed by direct sequencing of the coding sequences and intron/exon boundaries. Two heterozygous variants of unknown significance (c.128C>G [p.Pro43Arg]; c.776C>A [p.Pro259Gln]) were identified in LHX2 among the 70 patients. These variations were not identified in a panel of 100 control patients of mixed origins. The variation c.776C>A (p.Pro259Gln) was considered as non pathogenic by in silico analysis, while the variation c.128C>G (p.Pro43Arg) considered as deleterious by in silico analysis and was inherited from the asymptomatic father. Mutations in LHX2 do not represent a frequent cause of micro/anophthalmia.

Enantioselective cellular localisation of europium(iii) coordination complexes† †Electronic supplementary information (ESI) available: Complex synthesis and characterisation, selected cell images showing correspondence with commercial lysosomal or mitochondrial stains and spectral imaging profiles. See DOI: 10.1039/c7sc04422d

Science.gov (United States)

Frawley, Andrew T.; Linford, Holly V.; Starck, Matthieu; Pal, Robert

2017-01-01

The selective mitochondrial localisation of the Λ enantiomer of three different emissive europium(iii) complexes in NIH 3T3 and MCF7 cells contrasts with the behaviour of the Δ enantiomer, for which a predominant lysosomal localisation was observed by confocal microscopy. In each case, cell uptake occurs via macropinocytosis. PMID:29675151

Severe manifestation of Bartter syndrome Type IV caused by a novel insertion mutation in the BSND gene.

Science.gov (United States)

de Pablos, Augusto Luque; García-Nieto, Victor; López-Menchero, Jesús C; Ramos-Trujillo, Elena; González-Acosta, Hilaria; Claverie-Martín, Félix

2014-05-01

Bartter syndrome Type IV is a rare subtype of the Bartter syndromes that leads to both severe renal salt wasting and sensorineural deafness. This autosomal recessive disease is caused by mutations in the gene encoding barttin, BSND, an essential subunit of the ClC-K chloride channels expressed in renal and inner ear epithelia. Patients differ in the severity of renal symptoms, which appears to depend on the modification of channel function by the mutant barttin. To date, only a few BSND mutations have been reported, most of which are missense or nonsense mutations. In this study, we report the identification of the first insertion mutation, p.W102Vfs*7, in the BSND gene of a newborn girl with acute clinical symptoms including early-onset chronic renal failure. The results support previous data indicating that mutations that are predicted to abolish barttin expression are associated with a severe phenotype and early onset renal failure.

Autosomal recessive posterior column ataxia with retinitis pigmentosa caused by novel mutations in the FLVCR1 gene.

Science.gov (United States)

Shaibani, Aziz; Wong, Lee-Jun; Wei Zhang, Victor; Lewis, Richard Alan; Shinawi, Marwan

2015-01-01

Posterior column ataxia with retinitis pigmentosa (PCARP) is an autosomal recessive disorder characterized by severe sensory ataxia, muscle weakness and atrophy, and progressive pigmentary retinopathy. Recently, mutations in the FLVCR1 gene were described in four families with this condition. We investigated the molecular basis and studied the phenotype of PCARP in a new family. The proband is a 33-year-old woman presented with sensory polyneuropathy and retinitis pigmentosa (RP). The constellation of clinical findings with normal metabolic and genetic evaluation, including mitochondrial DNA (mtDNA) analysis and normal levels of phytanic acid and vitamin E, prompted us to seek other causes of our patient's condition. Sequencing of FLVCR1 in the proband and targeted mutation testing in her two affected siblings revealed two novel variants, c.1547G > A (p.R516Q) and c.1593+5_+8delGTAA predicted, respectively, to be highly conserved throughout evolution and affecting the normal splicing, therefore, deleterious. This study supports the pathogenic role of FLVCR1 in PCARP and expands the molecular and clinical spectra of PCARP. We show for the first time that nontransmembrane domain (TMD) mutations in the FLVCR1 can cause PCARP, suggesting different mechanisms for pathogenicity. Our clinical data reveal that impaired sensation can be part of the phenotypic spectrum of PCARP. This study along with previously reported cases suggests that targeted sequencing of the FLVCR1 gene should be considered in patients with severe sensory ataxia, RP, and peripheral sensory neuropathy.

Congenital analbuminemia caused by a novel aberrant splicing in the albumin gene.

Science.gov (United States)

Caridi, Gianluca; Dagnino, Monica; Erdeve, Omer; Di Duca, Marco; Yildiz, Duran; Alan, Serdar; Atasay, Begum; Arsan, Saadet; Campagnoli, Monica; Galliano, Monica; Minchiotti, Lorenzo

2014-01-01

Congenital analbuminemia is a rare autosomal recessive disorder manifested by the presence of a very low amount of circulating serum albumin. It is an allelic heterogeneous defect, caused by variety of mutations within the albumin gene in homozygous or compound heterozygous state. Herein we report the clinical and molecular characterization of a new case of congenital analbuminemia diagnosed in a female newborn of consanguineous (first degree cousins) parents from Ankara, Turkey, who presented with a low albumin concentration (A transition at position c.1652+1, the first base of intron 12, which inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of this intron. The splicing defect results in the complete skipping of the preceding exon (exon 12) and in a frame-shift within exon 13 with a premature stop codon after the translation of three mutant amino acid residues. Our results confirm the clinical diagnosis of congenital analbuminemia in the proband and the inheritance of the trait and contribute to shed light on the molecular genetics of analbuminemia.

Damage localisation and fracture propagation in granite: 4D synchrotron x-ray microtomographic observations from an in-situ triaxial deformation experiment at SOLEIL

Science.gov (United States)

Cartwright-Taylor, Alexis; Fusseis, Florian; Butler, Ian; Flynn, Michael; King, Andrew

2017-04-01

To date, most studies of damage localisation and failure have utilised indirect techniques to visualise the pathway to failure. The advent of synchrotron tomography and x-ray transparent experimental cells provides for the first time the opportunity to image localisation and fracture propagation in-situ, in real time with spatial resolutions of a few microns. We present 4D x-ray microtomographic data collected during a triaxial deformation experiment carried out at the imaging beamline PSICHE at the French Synchrotron SOLEIL. The data document damage localisation and fracture propagation in a microgranite. The sample was deformed at 15 MPa confining pressure and 3x10-5 s-1 strain rate, in a novel, miniature, x-ray transparent, triaxial deformation apparatus, designed and built at the University of Edinburgh. We used a 2.97 mm diameter x 9.46 mm long cylindrical sample of Ailsa Craig microgranite, heat treated to 600 ˚ C to introduce flaws in the form of pervasive crack damage. As the sample was loaded to failure, 21 microtomographic volumes were acquired in intervals of 5-20 MPa (decreasing as failure approached), including one scan at peak differential stress of 200 MPa (1.4 kN end load) and three post-failure scans. The scan at peak stress contained the incipient fault, and the sample failed immediately when loading continued afterwards. During scanning, a constant stress level was maintained. Individual datasets were collected in ˜10 minutes using a white beam with an energy maximum at 66 keV in a spiral configuration. Reconstructions yielded image stacks with a dimension of 1700x1700x4102 voxels with a voxel size of 2.7 μm. We analysed damage localisation and fracture propagation in the time series data. Fractures were segmented from the image data using a Multiscale Hessian fracture filter [1] and analysed for their orientations, dimensions and spatial distributions and changes in these properties during loading. Local changes in volumetric and shear

A case report of novel mutation in PRF1 gene, which causes familial autosomal recessive hemophagocytic lymphohistiocytosis.

Science.gov (United States)

Bordbar, Mohammad Reza; Modarresi, Farzaneh; Farazi Fard, Mohammad Ali; Dastsooz, Hassan; Shakib Azad, Nader; Faghihi, Mohammad Ali

2017-05-03

Hemophagocytic Lymphohistiocytosis (HLH) is a life-threatening immunodeficiency and multi-organ disease that affects people of all ages and ethnic groups. Common symptoms and signs of this disease are high fever, hepatosplenomegaly, and cytopenias. Familial form of HLH disease, which is an autosomal recessive hematological disorder is due to disease-causing mutations in several genes essential for NK and T-cell granule-mediated cytotoxic function. For an effective cytotoxic response from cytotoxic T lymphocyte or NK cell encountering an infected cell or tumor cell, different processes are required, including trafficking, docking, priming, membrane fusion, and entry of cytotoxic granules into the target cell leading to apoptosis. Therefore, genes involved in these steps play important roles in the pathogenesis of HLH disease which include PRF1, UNC13D (MUNC13-4), STX11, and STXBP2 (MUNC18-2). Here, we report a novel missense mutation in an 8-year-old boy suffered from hepatosplenomegaly, hepatitis, epilepsy and pancytopenia. The patient was born to a first-cousin parents with no previous documented disease in his parents. To identify mutated gene in the proband, Whole Exome Sequencing (WES) utilizing next generation sequencing was used on an Illumina HiSeq 2000 platform on DNA sample from the patient. Results showed a novel deleterious homozygous missense mutation in PRF1 gene (NM_001083116: exon3: c. 1120 T > G, p.W374G) in the patient and then using Sanger sequencing it was confirmed in the proband and his parents. Since his parents were heterozygous for the identified mutation, autosomal recessive pattern of inheritance was confirmed in the family. Our study identified a rare new pathogenic missense mutation in PRF1 gene in patient with HLH disease and it is the first report of mutation in PRF1 in Iranian patients with this disease.

Recurring dominant-negative mutations in the AVP-NPII gene cause neurohypophyseal diabetes insipidus

Energy Technology Data Exchange (ETDEWEB)

Repaske, D.R. [Children`s Hospital Medical Center, Cincinnati, OH (United States); Phillips, J.A.; Krishnamani, M.R.S. [Vanderbilt Univ. School of Medicine, Nashville, TN (United States)] [and others

1994-09-01

Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a familial form of arginine vasopressin (or antidiuretic hormone) deficiency that is usually manifest in early childhood with polyuria, polydipsia and an antidiuretic response to exogenous vasopressin or its analogs. The phenotype is postulated to arise from gliosis and depletion of the magnocellular neurons that produce vasopressin in the supraoptic and paraventricular nuclei of the hypothalamus. ADNDI is caused by heterozygosity for a variety of mutations in the AVP-NPII gene which encodes vasopressin, its carrier protein (NPII) and a glycoprotein (copeptin) of unknown function. These mutations include: (1) Ala 19{r_arrow}Thr (G279A) in AVP`s signal peptide, (2) Gly 17{r_arrow}Val (G1740T), (3) Pro 24{r_arrow}Leu (C1761T), (4) Gly 57{r_arrow}Ser (G1859A) and (5) del Glu 47({delta}AGG 1824-26), all of which occur in NPII. In characterizing the AVP-NPII mutations in five non-related ADNDI kindreds, we have detected two kindreds having mutation 1 (G279A), two having mutation 3 (C1761T) and one having mutation 4 (G1859A) without any other allelic changes being detected. Two of these recurring mutations (G279A and G1859A) are transitions that occur at CpG dinucleotides while the third (C1761T) does not. Interestingly, families with the same mutations differed in their ethnicity or in their affected AVP-NPII allele`s associated haplotype of closely linked DNA polymorphisms. Our data indicated that at least three of five known AVP-NPII mutations causing ADNDI tend to recur but the mechanisms by which these dominant-negative mutations cause variable or progressive expression of the ADNDI phenotype remain unclear.

A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans

DEFF Research Database (Denmark)

Brophy, Patrick D.; Rasmussen, Maria; Parida, Mrutyunjaya

2017-01-01

investigations have identified several gene variants that cause RA, including EYA1, LHX1, and WT1 However, whereas compound null mutations of genes encoding α and γ retinoic acid receptors (RARs) cause RA in mice, to date there have been no reports of variants in RAR genes causing RA in humans. In this study, we...... in humans....

LOW MOLECULAR MASS POLYPEPTIDE AND TRANSPORTER ANTIGEN PEPTIDE GENES POLYMORPHISM AS THE RISK FACTORS OF CERVICAL CANCER WHICH CAUSED BY HUMAN PAPILLOMAVIRUS TYPE-16 INFECTION IN BALI

Directory of Open Access Journals (Sweden)

I N. B. Mahendra

2015-12-01

Full Text Available Background: Until recently, cervical cancer is one of the major problem in women’s health issue related to its high incidence and mortality rate. The etiology of cervical cancer is the high risk oncogenic group of Human Papillomavirus (HPV, especially HPV-16 and 18 and its phylogenies. Meanwhile in Bali, more than 50% of infection are caused by HPV-16 infection. The main objective of this study was to investigate the role of LMP-2, LMP-7, TAP-1 and TAP-2 gene polymorphism as the risk factor in the cervical cancer carcinogenesis that is caused by HPV-16 infection. Method: A nested non-paired case-control study was conducted at Obstetric and Gynecologic Department Sanglah General Hospital, Bali-Indonesia from March 1 until August 31, 2013. Laboratory testing was carried out at Laboratory of Histopathology Leiden University Medical Centre, Netherlands,. Results: A total of 40 samples were collected, consist of 20epithelial cervical cancer patients with positive HPV-16 infection as the case group and 20 non-cervical cancer patients with positive HPV-16 infection as the control group. Women infected by HPV-16 with LMP-7 gene polymorphism had a higher risk (OR=7.36, CI 95%=1.38-40.55, p=0.013 to be diagnosed with cervical cancer. Balinese women who were infected by HPV-16 with TAP-2 gene polymorphism had a higher risk (OR= 9.33, CI 95%=2.18-39.96, p=0.001 to be diagnosed with cervical cancer. Meanwhile, Balinese women who were infected by HPV-16 with LMP-7 and TAP-2 genes polymorphism had a higher risk (OR=12.67, CI 95%=1.40-114.42, p=0.020 to be diagnosed with cervical cancer. As the result, it was shown that both of this gene polymorphism was working synergistically. Conclusion: TAP-2 and LMP-7 genes polymorphism play a role in the carcinogenesis mechanism of cervical cancer that is caused by HPV-16 infection in Bali. Meanwhile, LMP-2 and TAP-1 genes polymorphism were not found to play a role in the immunology pathway of cervical cancer that is

Novel Hypomorphic Alleles of the Mouse Tyrosinase Gene Induced by CRISPR-Cas9 Nucleases Cause Non-Albino Pigmentation Phenotypes.

Science.gov (United States)

Challa, Anil K; Boitet, Evan R; Turner, Ashley N; Johnson, Larry W; Kennedy, Daniel; Downs, Ethan R; Hymel, Katherine M; Gross, Alecia K; Kesterson, Robert A

2016-01-01

Tyrosinase is a key enzyme in melanin biosynthesis. Mutations in the gene encoding tyrosinase (Tyr) cause oculocutaneous albinism (OCA1) in humans. Alleles of the Tyr gene have been useful in studying pigment biology and coat color formation. Over 100 different Tyr alleles have been reported in mice, of which ≈24% are spontaneous mutations, ≈60% are radiation-induced, and the remaining alleles were obtained by chemical mutagenesis and gene targeting. Therefore, most mutations were random and could not be predicted a priori. Using the CRISPR-Cas9 system, we targeted two distinct regions of exon 1 to induce pigmentation changes and used an in vivo visual phenotype along with heteroduplex mobility assays (HMA) as readouts of CRISPR-Cas9 activity. Most of the mutant alleles result in complete loss of tyrosinase activity leading to an albino phenotype. In this study, we describe two novel in-frame deletion alleles of Tyr, dhoosara (Sanskrit for gray) and chandana (Sanskrit for sandalwood). These alleles are hypomorphic and show lighter pigmentation phenotypes of the body and eyes. This study demonstrates the utility of CRISPR-Cas9 system in generating domain-specific in-frame deletions and helps gain further insights into structure-function of Tyr gene.

Novel Hypomorphic Alleles of the Mouse Tyrosinase Gene Induced by CRISPR-Cas9 Nucleases Cause Non-Albino Pigmentation Phenotypes.

Directory of Open Access Journals (Sweden)

Anil K Challa

Full Text Available Tyrosinase is a key enzyme in melanin biosynthesis. Mutations in the gene encoding tyrosinase (Tyr cause oculocutaneous albinism (OCA1 in humans. Alleles of the Tyr gene have been useful in studying pigment biology and coat color formation. Over 100 different Tyr alleles have been reported in mice, of which ≈24% are spontaneous mutations, ≈60% are radiation-induced, and the remaining alleles were obtained by chemical mutagenesis and gene targeting. Therefore, most mutations were random and could not be predicted a priori. Using the CRISPR-Cas9 system, we targeted two distinct regions of exon 1 to induce pigmentation changes and used an in vivo visual phenotype along with heteroduplex mobility assays (HMA as readouts of CRISPR-Cas9 activity. Most of the mutant alleles result in complete loss of tyrosinase activity leading to an albino phenotype. In this study, we describe two novel in-frame deletion alleles of Tyr, dhoosara (Sanskrit for gray and chandana (Sanskrit for sandalwood. These alleles are hypomorphic and show lighter pigmentation phenotypes of the body and eyes. This study demonstrates the utility of CRISPR-Cas9 system in generating domain-specific in-frame deletions and helps gain further insights into structure-function of Tyr gene.

Mutations in the evolutionarily highly conserved KEOPS complex genes cause nephrotic syndrome with microcephaly

Science.gov (United States)

Braun, Daniela A.; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A.; Schanze, Denny; Ashraf, Shazia; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I. Chiara; Sanchez-Ferras, Oraly; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E.; Pabst, Werner L.; Warejko, Jillian; Daga, Ankana; LeBerre, Tamara Basta; Matejas, Verena; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T.; Gipson, Patrick E.; Hsu, Chyong-Hsin; Kari, Jameela A.; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okasha; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth; Rump, Patrick; Schnur, Rhonda E.; Shiihara, Takashi; Sinha, Manish; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A.; Tsai, Wen-Hui; Tsai, Jeng-Daw; Vester, Udo; Viskochil, David H.; Vatanavicharn, Nithiwat; Waxler, Jessica L.; Wolf, Matthias T.F.; Wong, Sik-Nin; Poduri, Annapurna; Truglio, Gessica; Mane, Shrikant; Lifton, Richard P.; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Calleweart, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

2018-01-01

Galloway-Mowat syndrome (GAMOS) is a severe autosomal-recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies. To date, mutations of WDR73 are the only known monogenic cause of GAMOS and in most affected individuals the molecular diagnosis remains elusive. We here identify recessive mutations of OSGEP, TP53RK, TPRKB, or LAGE3, encoding the 4 subunits of the KEOPS complex in 33 individuals of 30 families with GAMOS. CRISPR/Cas9 knockout in zebrafish and mice recapitulates the human phenotype of microcephaly and results in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibits cell proliferation, which human mutations fail to rescue, and knockdown of either gene activates DNA damage response signaling and induces apoptosis. OSGEP and TP53RK molecularly interact and co-localize with the actin-regulating ARP2/3 complex. Furthermore, knockdown of OSGEP and TP53RK induces defects of the actin cytoskeleton and reduces migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identify 4 novel monogenic causes of GAMOS, describe the first link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. PMID:28805828

Another explanation for the cause of heterosis phenomenon

Indian Academy of Sciences (India)

of depression and the increase in individual genetic diversity is the cause of heterosis. ... Keywords. nonsense gene; vital gene; gene products; individual genetic diversity; number ..... These values of a variety created by hybrid method as well.

Lyme disease caused by Borrelia burgdorferi with two homeologous 16S rRNA genes: a case report

Directory of Open Access Journals (Sweden)

Lee SH

2016-04-01

Full Text Available Sin Hang Lee,1,21Pathology Department, Milford Hospital, Milford, CT, USA; 2Milford Molecular Diagnostics, Milford, CT, USA Abstract: Lyme disease (LD, the most common tick-borne disease in North America, is believed to be caused exclusively by Borrelia burgdorferi sensu stricto and is usually diagnosed by clinical evaluation and serologic assays. As reported previously in a peer-reviewed article, a 13-year-old boy living in the Northeast of the USA was initially diagnosed with LD based on evaluation of his clinical presentations and on serologic test results. The patient was treated with a course of oral doxycycline for 28 days, and the symptoms resolved. A year later, the boy developed a series of unusual symptoms and did not attend school for 1 year. A LD specialist reviewed the case and found the serologic test band patterns nondiagnostic of LD. The boy was admitted to a psychiatric hospital. After discharge from the psychiatric hospital, a polymerase chain reaction test performed in a winter month when the boy was 16 years old showed a low density of B. burgdorferi sensu lato in the blood of the patient, confirmed by partial 16S rRNA (ribosomal RNA gene sequencing. Subsequent DNA sequencing analysis presented in this report demonstrated that the spirochete isolate was a novel strain of B. burgdorferi with two homeologous 16S rRNA genes, which has never been reported in the world literature. This case report shows that direct DNA sequencing is a valuable tool for reliable molecular diagnosis of Lyme and related borrelioses, as well as for studies of the diversity of the causative agents of LD because LD patients infected by a rare or novel borrelial variant may produce an antibody pattern that can be different from the pattern characteristic of an infection caused by a typical B. burgdorferi sensu stricto strain. Keywords: Lyme disease, Borrelia burgdorferi, homeologous 16S rRNA genes, DNA sequencing

Polymorphisms in metabolism and repair genes affects DNA damage caused by open-cast coal mining exposure.

Science.gov (United States)

Espitia-Pérez, Lyda; Sosa, Milton Quintana; Salcedo-Arteaga, Shirley; León-Mejía, Grethel; Hoyos-Giraldo, Luz Stella; Brango, Hugo; Kvitko, Katia; da Silva, Juliana; Henriques, João A P

2016-09-15

Increasing evidence suggest that occupational exposure to open-cast coal mining residues like dust particles, heavy metals and Polycyclic Aromatic Hydrocarbons (PAHs) may cause a wide range of DNA damage and genomic instability that could be associated to initial steps in cancer development and other work-related diseases. The aim of our study was to evaluate if key polymorphisms in metabolism genes CYP1A1Msp1, GSTM1Null, GSTT1Null and DNA repair genes XRCC1Arg194Trp and hOGG1Ser326Cys could modify individual susceptibility to adverse coal exposure effects, considering the DNA damage (Comet assay) and micronucleus formation in lymphocytes (CBMN) and buccal mucosa cells (BMNCyt) as endpoints for genotoxicity. The study population is comprised of 200 healthy male subjects, 100 open-cast coal-mining workers from "El Cerrejón" (world's largest open-cast coal mine located in Guajira - Colombia) and 100 non-exposed referents from general population. The data revealed a significant increase of CBMN frequency in peripheral lymphocytes of occupationally exposed workers carrying the wild-type variant of GSTT1 (+) gene. Exposed subjects carrying GSTT1null polymorphism showed a lower micronucleus frequency compared with their positive counterparts (FR: 0.83; P=0.04), while BMNCyt, frequency and Comet assay parameters in lymphocytes: Damage Index (DI) and percentage of DNA in the tail (Tail % DNA) were significantly higher in exposed workers with the GSTM1Null polymorphism. Other exfoliated buccal mucosa abnormalities related to cell death (Karyorrhexis and Karyolysis) were increased in GSTT/M1Null carriers. Nuclear buds were significantly higher in workers carrying the CYP1A1Msp1 (m1/m2, m2/m2) allele. Moreover, BMNCyt frequency and Comet assay parameters were significantly lower in exposed carriers of XRCC1Arg194Trp (Arg/Trp, Trp/Trp) and hOGG1Ser326Cys (Ser/Cys, Cys/Cys), thereby providing new data to the increasing evidence about the protective role of these polymorphisms

Cellular localisation of the anti-cancer drug camptothecin in Camptotheca acuminata Decne (Nyssaceae

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G Pasqua

2009-06-01

Full Text Available In Camptotheca acuminata, we studied the cellular sites of accumulation of the alkaloid camptothecin (CPT, in both plants grown in the field and those grown in a greenhouse, subjecting the latter to stress (i.e., draught, nutritional deficit, and pruning. Fresh sections of the leaf, stem, and root were analysed for the presence of CPT by examining the autofluorescence that the CPT molecule emits when exposed to UV radiation. In the plants grown in the field, CPT was observed only rarely. In the greenhouse plants, CPT had accumulated in crystalline form in the vacuole of specialised cells (i.e., segregator idioblasts, which were not morphologically distinguishable from the cells of the surrounding tissues. In the organs examined, the segregator idioblasts were localised in parenchymatic and epidermal tissues. CPT crystals were also detected in the glandular trichomes on both the stem and leaf.

Chronic granulomatous disease caused by mutations other than the common GT deletion in NCF1, the gene encoding the p47phox component of the phagocyte NADPH oxidase

NARCIS (Netherlands)

Roos, Dirk; de Boer, Martin; Köker, M. Yavuz; Dekker, Jan; Singh-Gupta, Vinita; Ahlin, Anders; Palmblad, Jan; Sanal, Ozden; Kurenko-Deptuch, Magdalena; Jolles, Stephen; Wolach, Baruch

2006-01-01

Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by defects in any of four genes encoding components of the leukocyte nicotinamide dinucleotide phosphate, reduced (NADPH) oxidase. One of these is the autosomal neutrophil cytosolic factor 1 (NCF1) gene encoding the p47phox

Ultrastructural morphology and localisation of cisplatin-induced platinum-DNA adducts in a cisplatin-sensitive and -resistant human small cell lung cancer cell line using electron microscopy

NARCIS (Netherlands)

Meijer, C; van Luyn, MJA; Nienhuis, EF; Blom, N; Mulder, NH; de Vries, EGE

2001-01-01

Ultrastructural morphology (transmission electron microscopy) and localisation of cisplatin-induced platinum (Pt)-DNA adducts (immunoelectron microscopy) were analysed in the human small cell lung cancer cell line GLC(4) and its 40-fold in vitro acquired cisplatin-resistant subline GLC(4)-CDDP,

Altered Rhythm of Adrenal Clock Genes, StAR and Serum Corticosterone in VIP Receptor 2-Deficient Mice

DEFF Research Database (Denmark)

Fahrenkrug, Jan; Georg, Birgitte; Hannibal, Jens

2012-01-01

oscillator based on a group of clock genes and their protein products. Mice lacking the VPAC2 receptor display disrupted circadian rhythm of physiology and behaviour, and therefore, we using real-time RT-PCR quantified (1) the mRNAs for the clock genes Per1 and Bmal1 in the adrenal gland and SCN, (2......RNA expression and serum corticosterone concentration. Double immunohistochemistry showed that the PER1 protein and StAR were co-localised in the same steroidogenic cells. Circulating corticosterone plays a role in the circadian timing system and the misaligned corticosterone rhythm in the VPAC2 receptor......The circadian time-keeping system consists of clocks in the suprachiasmatic nucleus (SCN) and in peripheral organs including an adrenal clock linked to the rhythmic corticosteroid production by regulating steroidogenic acute regulatory protein (StAR). Clock cells contain an autonomous molecular...

Gene therapy: An overview

Directory of Open Access Journals (Sweden)

Sudip Indu

2013-01-01

Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

Radiographer-led breast boost localisation – A service evaluation study

International Nuclear Information System (INIS)

Smith, S.; Comins, C.

2015-01-01

A radiation boost to the tumour bed as part of breast conserving therapy reduces the rate of local recurrence. Radiographer-led planning for tangential field radiotherapy has been the practice at our centre since 2007. The transition from conventional simulation to computed tomography (CT) and virtual simulation enhanced the radiographer's role in the breast planning process. Electron boost mark ups continued to be marked up freehand by doctors using available imaging to determine tumour bed. The paper reports on a service evaluation undertaken to establish a change in practice for electron breast boosts to be simulated using the virtual simulator by suitably trained radiographers. The retrospective simulation of ten patients confirmed the consistency of radiographer tumour bed localisation, followed by the prospective simulation of ten patients' boost fields. The introduction of a radiographer-led planning breast boost service has given greater autonomy and job satisfaction to individuals as well as resulting in a cost effective use of available resources. - Highlights: • A service evaluation study was undertaken to train a radiographer to perform breast boost planning. • Retrospective breast boost planning established proposed technique was workable. • Prospective planning by radiographer proved their competence. • Introduction of new technique provided job satisfaction and service improvement

The Competition Between a Localised and Distributed Source of Buoyancy

Science.gov (United States)

Partridge, Jamie; Linden, Paul

2012-11-01

We propose a new mathematical model to study the competition between localised and distributed sources of buoyancy within a naturally ventilated filling box. The main controlling parameters in this configuration are the buoyancy fluxes of the distributed and local source, specifically their ratio Ψ. The steady state dynamics of the flow are heavily dependent on this parameter. For large Ψ, where the distributed source dominates, we find the space becomes well mixed as expected if driven by an distributed source alone. Conversely, for small Ψ we find the space reaches a stable two layer stratification. This is analogous to the classical case of a purely local source but here the lower layer is buoyant compared to the ambient, due to the constant flux of buoyancy emanating from the distributed source. The ventilation flow rate, buoyancy of the layers and also the location of the interface height, which separates the two layer stratification, are obtainable from the model. To validate the theoretical model, small scale laboratory experiments were carried out. Water was used as the working medium with buoyancy being driven directly by temperature differences. Theoretical results were compared with experimental data and overall good agreement was found. A CASE award project with Arup.

Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene.

Science.gov (United States)

Gonçalves, Ana; Oliveira, Jorge; Coelho, Teresa; Taipa, Ricardo; Melo-Pires, Manuel; Sousa, Mário; Santos, Rosário

2017-10-03

A broad mutational spectrum in the dystrophin ( DMD ) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD , adding to the diversity of mutational events that give rise to D/BMD.

Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene

Science.gov (United States)

Gonçalves, Ana; Coelho, Teresa; Melo-Pires, Manuel; Sousa, Mário

2017-01-01

A broad mutational spectrum in the dystrophin (DMD) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD, adding to the diversity of mutational events that give rise to D/BMD. PMID:28972564

MADIBA: A web server toolkit for biological interpretation of Plasmodium and plant gene clusters

Directory of Open Access Journals (Sweden)

Louw Abraham I

2008-02-01

Full Text Available Abstract Background Microarray technology makes it possible to identify changes in gene expression of an organism, under various conditions. Data mining is thus essential for deducing significant biological information such as the identification of new biological mechanisms or putative drug targets. While many algorithms and software have been developed for analysing gene expression, the extraction of relevant information from experimental data is still a substantial challenge, requiring significant time and skill. Description MADIBA (MicroArray Data Interface for Biological Annotation facilitates the assignment of biological meaning to gene expression clusters by automating the post-processing stage. A relational database has been designed to store the data from gene to pathway for Plasmodium, rice and Arabidopsis. Tools within the web interface allow rapid analyses for the identification of the Gene Ontology terms relevant to each cluster; visualising the metabolic pathways where the genes are implicated, their genomic localisations, putative common transcriptional regulatory elements in the upstream sequences, and an analysis specific to the organism being studied. Conclusion MADIBA is an integrated, online tool that will assist researchers in interpreting their results and understand the meaning of the co-expression of a cluster of genes. Functionality of MADIBA was validated by analysing a number of gene clusters from several published experiments – expression profiling of the Plasmodium life cycle, and salt stress treatments of Arabidopsis and rice. In most of the cases, the same conclusions found by the authors were quickly and easily obtained after analysing the gene clusters with MADIBA.

Natural selection in a population of Drosophila melanogaster explained by changes in gene expression caused by sequence variation in core promoter regions.

Science.gov (United States)

Sato, Mitsuhiko P; Makino, Takashi; Kawata, Masakado

2016-02-09

Understanding the evolutionary forces that influence variation in gene regulatory regions in natural populations is an important challenge for evolutionary biology because natural selection for such variations could promote adaptive phenotypic evolution. Recently, whole-genome sequence analyses have identified regulatory regions subject to natural selection. However, these studies could not identify the relationship between sequence variation in the detected regions and change in gene expression levels. We analyzed sequence variations in core promoter regions, which are critical regions for gene regulation in higher eukaryotes, in a natural population of Drosophila melanogaster, and identified core promoter sequence variations associated with differences in gene expression levels subjected to natural selection. Among the core promoter regions whose sequence variation could change transcription factor binding sites and explain differences in expression levels, three core promoter regions were detected as candidates associated with purifying selection or selective sweep and seven as candidates associated with balancing selection, excluding the possibility of linkage between these regions and core promoter regions. CHKov1, which confers resistance to the sigma virus and related insecticides, was identified as core promoter regions that has been subject to selective sweep, although it could not be denied that selection for variation in core promoter regions was due to linked single nucleotide polymorphisms in the regulatory region outside core promoter regions. Nucleotide changes in core promoter regions of CHKov1 caused the loss of two basal transcription factor binding sites and acquisition of one transcription factor binding site, resulting in decreased gene expression levels. Of nine core promoter regions regions associated with balancing selection, brat, and CG9044 are associated with neuromuscular junction development, and Nmda1 are associated with learning

Antimicrobial Susceptibility of Bordetella bronchiseptica Isolates from Swine and Companion Animals and Detection of Resistance Genes.

Directory of Open Access Journals (Sweden)

Sandra Prüller

Full Text Available Bordetella bronchiseptica causes infections of the respiratory tract in swine and other mammals and is a precursor for secondary infections with Pasteurella multocida. Treatment of B. bronchiseptica infections is conducted primarily with antimicrobial agents. Therefore it is essential to get an overview of the susceptibility status of these bacteria. The aim of this study was to comparatively analyse broth microdilution susceptibility testing according to CLSI recommendations with an incubation time of 16 to 20 hours and a longer incubation time of 24 hours, as recently proposed to obtain more homogenous MICs. Susceptibility testing against a panel of 22 antimicrobial agents and two fixed combinations was performed with 107 porcine isolates from different farms and regions in Germany and 43 isolates obtained from companion animals in Germany and other European countries. Isolates with increased MICs were investigated by PCR assays for the presence of resistance genes. For ampicillin, all 107 porcine isolates were classified as resistant, whereas only a single isolate was resistant to florfenicol. All isolates obtained from companion animals showed elevated MICs for β-lactam antibiotics and demonstrated an overall low susceptibility to cephalosporines. Extension of the incubation time resulted in 1-2 dilution steps higher MIC50 values of porcine isolates for seven antimicrobial agents tested, while isolates from companion animals exhibited twofold higher MIC50/90 values only for tetracycline and cefotaxime. For three antimicrobial agents, lower MIC50 and MIC90 values were detected for both, porcine and companion animal isolates. Among the 150 isolates tested, the resistance genes blaBOR-1 (n = 147, blaOXA-2, (n = 4, strA and strB (n = 17, sul1 (n = 10, sul2 (n = 73, dfrA7 (n = 3 and tet(A (n = 8 were detected and a plasmid localisation was identified for several of the resistance genes.

Imaging cellular structures in super-resolution with SIM, STED and Localisation Microscopy: A practical comparison.