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Exon Skipping of Cathepsin B

Kathrin Müntener, Roman Zwicky, Gabor Csucs, Jack Rohrer, Antonio Baici
2004 Journal of Biological Chemistry  
The alternatively spliced messenger RNA of the human cysteine peptidase cathepsin B missing exons 2 and 3 encodes a truncated form of the enzyme lacking the signal peptide and part of the inhibitory propeptide. This deletion results in a new N-terminal leader sequence characteristic of proteins predestined for transport into mitochondria. We determined enzyme targeting to intracellular organelles by transfecting HeLa cells with constructs containing segments of variable length of the N terminus
more » ... h of the N terminus of truncated cathepsin B fused to green fluorescent protein. Co-localization of the constructs with mitochondria and the endoplasmic reticulum was probed with specific markers. None of the chimeric products were found in the endoplasmic reticulum, showing that truncated cathepsin B is misrouted from its regular biosynthetic pathway and forced to enter the mitochondria instead of lysosomes as its final destination. The first 20 amino acids of the new N terminus were necessary and sufficient for mitochondrial targeting, but only cells expressing the complete truncated cathepsin B sequence died by nuclear fragmentation. This new and unexpected behavior draws attention to an additional extralysosomal role for a cysteine peptidase with several recognized important pathophysiological functions. Mitochondrial targeting of cathepsin B may have significant consequences on cell life in pathological or physiological situations characterized by excessive transcription of the cathepsin B message lacking exons 2 and 3, as observed for instance in osteoarthritic cartilage.
doi:10.1074/jbc.m405333200 pmid:15262981 fatcat:uz6hoqaik5dlhbumm4g46zwbgm

Regulation of human cathepsin B by alternative mRNA splicing: homeostasis, fatal errors and cell death

Antonio Baici, Kathrin Müntener, Anna Willimann, Roman Zwicky
2006 Biological chemistry  
One of the control mechanisms of cathepsin B biosynthesis and trafficking operates through alternative splicing of pre-mRNA. An mRNA lacking exon 2 is more efficiently translated than that containing all exons, and may be responsible for elevated biosynthesis and enzyme routing to the extracellular space, with critical consequences for connective tissue integrity in pathologies such as cancer and arthritis. mRNA missing exons 2 and 3 encodes a truncated procathepsin B form that is targeted to
more » ... at is targeted to mitochondria. This enzyme variant is catalytically inactive because it cannot properly fold. However, it provokes a cascade of events, which result first in morphological changes in intracellular organelles and the nucleus, finally leading to cell death.
doi:10.1515/bc.2006.125 pmid:16895470 fatcat:cpecfembyjglnb3gqiqria3lca

Cathepsin B expression and down-regulation by gene silencing and antisense DNA in human chondrocytes

Roman ZWICKY, Kathrin MÜNTENER, Mary B. GOLDRING, Antonio BAICI
2002 Biochemical Journal  
Cathepsin B, a marker of the dedifferentiated chondrocyte phenotype, contributes to cartilage destruction in osteoarthritis and pathological proteolysis in rheumatoid arthritis and cancer. In search of possible means for neutralizing the action of this enzyme, we compared its expression, biosynthesis and distribution in articular chondrocytes and two lines of immortalized human chondrocytes. Native articular chondrocytes in primary culture and the polyclonal T\C-28a2 chondrocyte cell line were
more » ... yte cell line were similar with respect to the number of endosomes and lysosomes, the distribution of three alternatively spliced cathepsin B mRNA forms, and the cathepsin B activity. In contrast, the clonal C-28\I2 cell line contained four times higher levels of intracellular cathepsin B activity, slightly higher numbers of endosomes and lysosomes, and uniform distribution of all three cathepsin B transcripts and thus resembled subcultured chondrocytes at an early stage of dedifferentiation. Transfection of T\C-28a2 chondrocytes with double-stranded cathepsin B mRNA resulted
doi:10.1042/bj20020210 pmid:12086583 pmcid:PMC1222861 fatcat:frgfpkrixzgmbcfcbcrsq2epi4

Towards an Observatory for Network Transparency Research

Stephan Neuhaus, Roman Müntener, Korian Edeline, Benoit Donnet, Elio Gubser
2016 Proceedings of the 2016 workshop on Applied Networking Research Workshop - ANRW 16  
The Internet is full of middleboxes that change packets and flows. In fact, there is probably no IP or TCP header that is not affected by at least one middlebox. Obviously, middleboxes impede path transparency, i.e., the idea that an exchange of messages results in more or less the same packets, no matter what path the packets takes. But no one seems to have a truly global view of what middleboxes do to packets on what Internet paths, which would however be an essential knowledge for new
more » ... edge for new transport protocols to be successfully deployed. We address these concerns in the MAMI project by building an observatory of path transparency measurements. The project hosts an extensive set of path transparency measurements -we believe it to be the first dataset to deal specifically with middlebox involvement. In this paper, we describe that Observatory and a number of questions that we want to address with the data in that Observatory. Eventually, the project will provide public access to that Observatory so that researchers and the interested public can ask their own questions about path transparency issues and middlebox involvement.
doi:10.1145/2959424.2959425 fatcat:etay2vqulfa5jbinfw2pk7dmw4

A path layer for the Internet: Enabling network operations on encrypted protocols

Mirja Kuhlewind, Tobias Buhler, Brian Trammell, Stephan Neuhaus, Roman Muntener, Gorry Fairhurst
2017 2017 13th International Conference on Network and Service Management (CNSM)  
The deployment of encrypted transport protocols imposes new challenges for network operations. Key in-network functions such as those implemented by firewalls and passive measurement devices currently rely on information exposed by the transport layer. Encryption, in addition to improving privacy, helps to address ossification of network protocols caused by middleboxes that assume certain information to be present in the clear. However, "encrypting it all" risks diminishing the utility of these
more » ... he utility of these middleboxes for the traffic management tasks for which they were designed. A middlebox cannot use what it cannot see. We propose an architectural solution to this issue, by introducing a new "path layer" for transport-independent, in-band signaling between Internet endpoints and network elements on the paths between them, and using this layer to reinforce the boundary between the hop-by-hop network layer and the end-toend transport layer. We define a path layer header on top of UDP to provide a common wire image for new, encrypted transports. This path layer header provides information to a transportindependent on-path state machine that replaces stateful handling currently based on exposed header flags and fields in TCP; it enables explicit measurability of transport layer performance; and offers extensibility by sender-to-path and path-to-receiver communications for diagnostics and management. This provides not only a replacement for signals that are not available with encrypted traffic, but also allows integrity-protected, enhanced signaling under endpoint control. We present an implementation of this wire image integrated with the QUIC protocol, as well as a basic stateful middlebox built on Vector Packet Processing (VPP) provided by FD.io.
doi:10.23919/cnsm.2017.8255973 dblp:conf/cnsm/KuhlewindBTNMF17 fatcat:7swsb2mhvvbntklp5cn3uxwbx4

A Path Layer for the Internet: Enabling Network Operations on Encrypted Protocols

Mirja Kühlewind, Tobias Bühler, Brian Trammell, Roman Müntener, Stephan Neuhaus, Gorry Fairhurst
2017
The deployment of encrypted transport protocols imposes new challenges for network management. Key in-network functions such as those implemented by firewalls and passive measurement devices currently rely on information exposed by the transport layer. Encryption, in addition to improving privacy, helps to address ossification of network protocols caused by middleboxes that assume certain information to be present in the clear. However, "encrypting it all" risks diminishing the utility of these
more » ... he utility of these middleboxes for the network management tasks for which they were designed. A middlebox cannot use what it cannot see. We propose an architectural solution to this issue, by introducing a new "path layer" for transport-independent, in-band signaling between Internet endpoints and network elements on the paths between them, and using this layer to reinforce the boundary between the hop-by-hop network layer and the end-toend transport layer. We define a path layer header on top of UDP to provide a common wire image for new, encrypted transports. This path layer header provides information to a transportindependent on-path state machine that replaces stateful handling currently based on exposed header flags and fields in TCP; it enables explicit measurability of transport layer performance; and offers extensibility by sender-to-path and path-to-receiver communications for diagnostics and management. This provides not only a replacement for signals that are not available with encrypted traffic, but also allows integrity-protected, enhanced signaling under endpoint control. We present an implementation of this wire image integrated with the QUIC protocol, as well as a basic stateful middlebox built on Vector Packet Processing (VPP) provided by FD.io.
doi:10.3929/ethz-b-000218005 fatcat:el6z4ib43vdfhjqrirw6nco4lq

Page 303 of National Union Catalog Vol. 28, Issue [page]

1942 National Union Catalog  
Numismatics, Medieval. 2 Numismatics matics—Holy Roman empirc Netherlands. 3. Numis- 14-16653 Library of Congress AS244.1122 €J2976.C49 vol. 26 9 cnn noes Cig 8 Chijs, Pieter Otto van der, 1802-1867.  ...  De munten der Frankische- en Duitsch-Nederlandsche vorsten, door P. 0. van der Chijs ... uitg. door Teylers tweede genootschap. Haarlem, De erven F.  ... 

Munt, wissel en bank bij de oude Grieken

Raymond Bogaert
1970 Handelingen - Koninklijke Zuid-Nederlandse Maatschappij voor Taal- en Letterkunde en Geschiedenis  
Methods to Determination of the Weight Standards of Roman Coins, Num .  ...  Chron. (1942) 86-91-Hemmy heeft een methode bepaald om de voor de wisselaar geen geheimen hebben 28 Some Notes on Ancien/ Dies and Coining Methods (London 1954) ; -, Minting Greek and Roman Coins, Archaeoiogy  ... 
doi:10.21825/kzm.v21i0.20804 fatcat:t4a2dil7rjfszcpfw6li3po4pa

Page 85 of American Architect and Architecture Vol. 2, Issue 105 [page]

1877 American Architect and Architecture  
Munten for ) ! 4 @lazed Bash g End view of Munten for Uog!  ...  Chimney Tops and Garden Vases, DRAIN AND SEWER PIPE, FIRE-BRICK, LAND TILE, ENGLISH ROMAN, AND PORTLAND CEMENT. WALDO BROTHERS, No. % WATER STREET, BosToN.  ... 

Studenten strooien hete centen voor het volk. Stedelijke identiteit en de geschiedenis van een omstreden herinnering in Leiden (1841-2016)

Bart Van der Steen, Peter Burger
2018 Tijdschrift voor Sociale en Economische Geschiedenis  
Het verhaal ontwikkelde zich tot een retorische toop die regelmatig werd aangehaald in nieuwsberichten, maar ook in persoonlijke verslagen, verhalen en romans.  ...  Van de overige 149 bronnen gaan er 50 over strooien met gloeiende munten in Leiden (1841-2016); 5 over strooien met onverhitte munten in Leiden (1860-1940); 38 over gloeiende munten elders in Nederland  ... 
doi:10.18352/tseg.1015 fatcat:hdmnlvy57jaldouc4xnvd5ybda

Antieke munten als historische informatiedragers

Koenraad Verboven
1970 Handelingen - Koninklijke Zuid-Nederlandse Maatschappij voor Taal- en Letterkunde en Geschiedenis  
., Roman Republican Coin Hoards, London, 1969 (Royal Numismacic Society.  ...  ., Roman Republican Coinage. 2 vols, Cambridge, 1974 ; cf. ook BACKEND0RF Dirk, Römische Münzschatze des zweiten und ersten Jahrhunderts v. Chr. vom italienischen Festland  ... 
doi:10.21825/kzm.v60i0.17406 fatcat:olq4zeve2zbfxob6ddybhmssva

Page 37 of American Architect and Architecture Vol. 1, Issue 53 [page]

1876 American Architect and Architecture  
American, Roman, and Portland Cement, LIME, SAND, &c. WALDO BROTHERS, No. 94 Water Street, Bostow. NGRAVINGS FROM LANDSEER.  ...  End view of Munten for Giazed Sash. End view of Munten for Unglazed Sash ~ — 2 The use of these Sashes rama perfect security without the usual gratings that have a prison-like appearance.  ... 

Page 188 of American Architect and Architecture Vol. 6, Issue 209 [page]

1879 American Architect and Architecture  
J Pad view of y i Munten for i Glazed Sash | __i End view of Munten for Unglazed Sash The use of these Sashes gives perfect security without the usual gratings that have a prison-like appearance.  ...  THE STRONGEST, THE BEST, THE GENUINE ROMAN CEMENT. - +» SWANSCOMBE, ENGLAND. PINE STREET. KEENE’S CEMENT WORKS . . NEW YORE OFFICE: 10 . . . . . . . . . . . . .  ... 

Page 499 of National Union Catalog Vol. 10, Issue [page]

1963 National Union Catalog  
(Sertes : a a sian. i 70 gon yen oie te, Muntens, Peenes. yang Jon chit-yoan li shia 70 yon yeu chu so ches an ) 7U romeeein shh ene lun ae chi shth shu lun kao.  ...  Facsimile reproduction of ms. copy i Fp Mt fa 1 Title, Title romanized: Han-kuang li ti wen kao. C 64-321 Japanese Library 5558 Harvard Univ.  ... 

Nouvelles du corps médical

2012 Bulletin des Médecins Suisses  
Birmannsgasse 14, 4055 Basel GE Nathalie Fiore, Médecin praticien 20, rue des Deux-Ponts, 1205 Genève SG Hansjakob Aegerter, Facharzt für Allgemeine Innere Medizin, Wiesenstrasse 1, 9650 Nesslau Carmen Müntener  ...  Allgemeine Innere Medizin, 4460 Gelterkinden Praxiseröffnung / Nouveaux cabinets médicaux / Nuovi studi medici BE Catherine Leuch-Hofmann, Fachärztin für Gynäkologie und Geburtshilfe, Riedweg 3, 3012 Bern BL Roman  ... 
doi:10.4414/bms.2012.90030 fatcat:wk5n34m3x5emll6t73gjx32gtm
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