Title: Elsevier Solutions for the Digital Library
1Elsevier Solutions for the Digital Library
- Geoffrey Adams
- Director, IT Solutions
- Global Sales Organization
Part I Distributing Academic Information Japan,
May 2003
2Overview
- Historical Context
- Electronic Publishing at Elsevier Science
- Implications of the Move From Paper to Electronic
- Overhauling Elsevier Science
3Anno 1637
Print publication by the brothers Elsevier,
Leyden, The Netherlands, 364 years ago Still
available in the Leyden University Library
4Anno 1979
Electronic publication, also Leyden, The
Netherlands, 22 years ago Not available in the
Leyden University Library or anywhere
else (Luckily I made a printout !)
5- Digital information lasts forever
6- Digital information lasts forever
- or 5 years, whichever comes first
- Jeff Rothenberg, Rand Corporation, USA
7The Scientific Publishing Cycle
Author
Reader
Editorial Board
Library
Publisher
8Traditional publishing
- One input
- One product
- paper print
9Accepted manuscript
Xenopus kidney hyaluronidase-1 (XKH1), a novel
type of membrane-bound hyaluronidase solely
degrades hyaluronan at neutral pH Â Stephan
Reitinger, Johannes Müllegger, Günter
Lepperdinger  Institute of Molecular Biology,
Austrian Academy of Sciences, Billrothstr. 11,
A-5020 Salzburg, Austria  Edited by Pierre
Jolles  Corresponding author.
NIH/NICHD/LMG/SVD, Bethesda, MD 20892, USA. Fax
(1)-301-496 0243. E-mail address
lepperdg_at_mail.nih.gov (G. Lepperdinger). Â Abstrac
t In search for Xenopus laevis hyaluronidase
genes, a cDNA encoding a putative PH-20-like
enzyme was isolated. In the adult frog, this mRNA
was only found to be expressed in the kidney and
therefore named XKH1. When expressed by means of
cRNA injection into frog oocytes, XKH1 solely
exhibited at physiologic ionic strength
hyaluronidase activity at neutral pH and in
weakly acidic solutions. The enzyme was inactive
below pH 5.4. In addition to hyaluronic acid
hydrolysis, chondroitin sulfate also was degraded
at low yield as assessed by fluorophoreassisted
carbohydrate electrophoresis analysis of the
degradation products. The enzyme is sorted to the
outer surface of the cell membrane of XKH1
expressing oocytes. From there, it could not be
removed by phospholipase C nor was secreted
hyaluronidase activity detectable. We conclude
that XKH1 represents a membrane-bound
hyaluronan-degrading enzyme exclusively expressed
in cells of the adult frog kidney where it either
may be involved in the reorganization of the
extracellular architecture or in supporting
physiological demands for proper renal functions.
 Key words Hyaluronan Hyaluronidase PH-20
Kidney  1. Introduction Hyaluronan (hyaluronic
acid, HA), a linear polysaccharide, is a
component of the extracellular matrix of higher
animals with sugar moieties all connected by
ß-linkages. Sugar polymers with ß -glycosidic
bonds are rare in vertebrate tissues and require
specialized enzymes for turnover 1. HA
catabolism depends primarily on hyaluronidases,
endoglycolytic enzymes with, in most cases, an
exclusive specificity for the ß -1,4 glycosidic
bond between glucuronic acid and N-acetyl
glucosamine 2. The first eukaryotic
hyaluronidase analyzed at the molecular level was
the one from bee venom. This enzyme shares
significant homology with a sperm head protein
termed PH-20 3. The human genome is known to
contain at least seven hyaluronidase genes. Six
of those are arranged in two clusters, one on
chromosome 3p21 and another on chromosome
7q31. Â This arrangement suggests that two tandem
gene duplication events from an original ancient
sequence were followed by a more recent
duplication and translocation, thus yielding the
final chromosomal localizations 4. In the
course of our studies on hyaluronidase genes in
the African clawed frog, Xenopus laevis, we
isolated a cDNA sequence with striking
similarities to the PH-20-type enzymes. Recently,
the embryonic hyaluronidase expression pattern of
a Xenopus cDNA sequence, XEH1, has been reported
5. In spite of different biochemical
properties, it is very likely that the sequence
presented here is the twin homolog to XEH1 within
the pseudotetraploid arrangement of this frogs
genome 6. In analogy and the fact, that this
gene is only expressed in the adult kidney we
named it Xenopus kidney hyaluronidase-1
(XKH1). Â 2. Materials and methods 2.1. Isolation
and Northern analysis of XKH1 human Hyal2
(GenBank accession AJ000099). Polymerase chain
reaction (PCR) amplication of cDNA fragments
encoding the open reading frame of XKH1 were
performed using the following primer pair up
GAC TTA TGC GCT GCA CAA TGG CAA AAC down TTA
AGA GTA TGA TCT ACT TGT TAT TTA TGT TC.
cDNA inserts were sequenced on both strands with
the aid of an automated LICOR system (MWG,
Germany). The GenBank accession number AF394961
was assigned to XKH1. Total RNA was extracted
from tissues of adult X. laevis and Northern blot
analysis was performed as described earlier
7. 2.2. Frog surgery, oocyte preparation A
small lobe of the ovary was surgically removed
from an adult X. laevis female. The incision in
the body was then sutured and the animal was left
to recover in shallow water. The isolated ovary
was rinsed in OR2 buer (82.5 mM NaCl, 2.5 mM
KCl, 1 mM CaCl2, 1 mM MgCl2, 1 mM Na2HPO4, 5 mM
HEPES, pH 7.2) and individual oocytes were
manually defolliculated using ne watchmaker's
forceps. Oocytes were cultured in OR2 containing
100 U/ml penicillin and 100 Wg/ml streptomycin at
16³C. Â
10Article in Print
11The traditional publishing process
Manuscript
Print stylesheet
Article in print presentation
12Electronic Publishing at Elsevier Science
- Online hosts
- secondary databases EMBASE (since 1974)
- available via Dialog, DIMDI, etc.
- CD-Rom
- ADONIS (since 1987)
- BBAs CDROM archive (experiment in 1989)
- Internet
- CITED (1989-1991)
- TULIP (1992-1995), succeeded by EES (since 1995)
- Electronic journals at Elseviers website (since
1993) - ScienceDirect (since 1997)
- Acquisition of Electronic Press (BioMedNet /
ChemWeb since 1997) - Acquisition of Harcourt (integration of IDEAL
into ScienceDirect since 2002)
13TULIP - A Landmark Technology Project
- The University LIcensing Project
- 1991-1995, 9 USA universities
- delivery via the internet of scanned pages and
structured headers from 43 material science
journals - desk top access for the researcher
- Conclusions
- managing digital collections is harder than
printed collections - relationship between librarians and publishers is
changing and becoming closer
14Elsevier Electronic Subscriptions
- Commercial product since 1996
- Built on our TULIP Experience
- Developed to full 1100 titles
- Provided Researchers with
- 24x7 access to content
- No worries about material having been taken out
from library - Access from place of work
- Conclusions
- Critical Mass in a Discipline Is Crucial
- Elsevier Electronic Subscriptions, later renamed
to ScienceDirect OnSite (SDOS) the local digital
library
15The Milestones - Miami Project
- A watershed project - experimenting on the Web
- 1994-1996
- Started with a small group focused on design
functionality, but a large number of developers - Required building a generic platform for
e-solutions triggered by acquisition of
Lexis-Nexis - Scalable - to host unlimited content
- Robust - reliable system
- Flexible, modular - support all kinds of content
with a wide range of functionality - Back office - support finance, billing and
content, etc. - Commercial product - ScienceDirect - from 1999
- The remote digital library via the Web
16Implications of the Move From Paper to Electronic
17Electronic publishing
- One input
- Many products
- Paper
- Web
- Email
- Database
18Content Structure Styling Presentation
Manuscript
Structure (DTD)
SGML file according to article structure
Print stylesheet
Web stylesheet
Article in print presentation
Article in Web presentation
19Accepted manuscript
Xenopus kidney hyaluronidase-1 (XKH1), a novel
type of membrane-bound hyaluronidase solely
degrades hyaluronan at neutral pH Â Stephan
Reitinger, Johannes Müllegger, Günter
Lepperdinger  Institute of Molecular Biology,
Austrian Academy of Sciences, Billrothstr. 11,
A-5020 Salzburg, Austria  Edited by Pierre
Jolles  Corresponding author.
NIH/NICHD/LMG/SVD, Bethesda, MD 20892, USA. Fax
(1)-301-496 0243. E-mail address
lepperdg_at_mail.nih.gov (G. Lepperdinger). Â Abstrac
t In search for Xenopus laevis hyaluronidase
genes, a cDNA encoding a putative PH-20-like
enzyme was isolated. In the adult frog, this mRNA
was only found to be expressed in the kidney and
therefore named XKH1. When expressed by means of
cRNA injection into frog oocytes, XKH1 solely
exhibited at physiologic ionic strength
hyaluronidase activity at neutral pH and in
weakly acidic solutions. The enzyme was inactive
below pH 5.4. In addition to hyaluronic acid
hydrolysis, chondroitin sulfate also was degraded
at low yield as assessed by fluorophoreassisted
carbohydrate electrophoresis analysis of the
degradation products. The enzyme is sorted to the
outer surface of the cell membrane of XKH1
expressing oocytes. From there, it could not be
removed by phospholipase C nor was secreted
hyaluronidase activity detectable. We conclude
that XKH1 represents a membrane-bound
hyaluronan-degrading enzyme exclusively expressed
in cells of the adult frog kidney where it either
may be involved in the reorganization of the
extracellular architecture or in supporting
physiological demands for proper renal functions.
 Key words Hyaluronan Hyaluronidase PH-20
Kidney  1. Introduction Hyaluronan (hyaluronic
acid, HA), a linear polysaccharide, is a
component of the extracellular matrix of higher
animals with sugar moieties all connected by
ß-linkages. Sugar polymers with ß -glycosidic
bonds are rare in vertebrate tissues and require
specialized enzymes for turnover 1. HA
catabolism depends primarily on hyaluronidases,
endoglycolytic enzymes with, in most cases, an
exclusive specificity for the ß -1,4 glycosidic
bond between glucuronic acid and N-acetyl
glucosamine 2. The first eukaryotic
hyaluronidase analyzed at the molecular level was
the one from bee venom. This enzyme shares
significant homology with a sperm head protein
termed PH-20 3. The human genome is known to
contain at least seven hyaluronidase genes. Six
of those are arranged in two clusters, one on
chromosome 3p21 and another on chromosome
7q31. Â This arrangement suggests that two tandem
gene duplication events from an original ancient
sequence were followed by a more recent
duplication and translocation, thus yielding the
final chromosomal localizations 4. In the
course of our studies on hyaluronidase genes in
the African clawed frog, Xenopus laevis, we
isolated a cDNA sequence with striking
similarities to the PH-20-type enzymes. Recently,
the embryonic hyaluronidase expression pattern of
a Xenopus cDNA sequence, XEH1, has been reported
5. In spite of different biochemical
properties, it is very likely that the sequence
presented here is the twin homolog to XEH1 within
the pseudotetraploid arrangement of this frogs
genome 6. In analogy and the fact, that this
gene is only expressed in the adult kidney we
named it Xenopus kidney hyaluronidase-1
(XKH1). Â 2. Materials and methods 2.1. Isolation
and Northern analysis of XKH1 human Hyal2
(GenBank accession AJ000099). Polymerase chain
reaction (PCR) amplication of cDNA fragments
encoding the open reading frame of XKH1 were
performed using the following primer pair up
GAC TTA TGC GCT GCA CAA TGG CAA AAC down TTA
AGA GTA TGA TCT ACT TGT TAT TTA TGT TC.
cDNA inserts were sequenced on both strands with
the aid of an automated LICOR system (MWG,
Germany). The GenBank accession number AF394961
was assigned to XKH1. Total RNA was extracted
from tissues of adult X. laevis and Northern blot
analysis was performed as described earlier
7. 2.2. Frog surgery, oocyte preparation A
small lobe of the ovary was surgically removed
from an adult X. laevis female. The incision in
the body was then sutured and the animal was left
to recover in shallow water. The isolated ovary
was rinsed in OR2 buer (82.5 mM NaCl, 2.5 mM
KCl, 1 mM CaCl2, 1 mM MgCl2, 1 mM Na2HPO4, 5 mM
HEPES, pH 7.2) and individual oocytes were
manually defolliculated using ne watchmaker's
forceps. Oocytes were cultured in OR2 containing
100 U/ml penicillin and 100 Wg/ml streptomycin at
16³C. Â
20Structured version (SGML/XML)
ltART VERSION"4.2.0" JTL"EPSL"
PII"S0014579301028137" ARTTY"FLA"
LANGUAGE"EN"gt ltFMgtltATLgtltIgtXenopuslt/Igt kidney
hyaluronidase ndash 1 (XKH1), a novel type of
membranendashbound hyaluronidase solely
degrades hyaluronan at neutral pHlt/ATLgt
ltAUGgtltAUgtltFNMgtStephanlt/FNMgtltSNMgtReitingerlt/SNMgtltOR
F ID"a/gtlt/AUgt ltAUgtltFNMgtJohanneslt/FNM
gtltSNMgtMuumllleggerlt/SNMgtltORF ID"a/gtlt/AUgt ltCOR
gtltAUgtltFNMgtGuumlnterlt/FNMgtltSNMgtLepperdingerlt/SNMgt
ltORF IDa/gtlt/AUgtlt/CORgt ltAFFgtltOID
ID"a"gtInstitute of Molecular Biology, Austrian
Academy of Sciences, Billrothstr.
11ltCTYgtAndash5020 , Salzburglt/CTYgtltCNYgtAustrialt/
CNYgtlt/AFFgt lt/AUGgt ltRE DAY9" MO"7"
YR"2001"/gt ltRV DAY"2" MO"8" YR"2001"/gt
ltACC DAY"10" MO"8" YR"2001"/gt ltABS
LANGUAGE"EN"gtltPgtIn search for ltIgtXenopus
laevislt/Igt hyaluronidase genes, a cDNA encoding
a putative PHndash20ndashlike enzyme was
isolated. In the adult frog, this mRNA was only
found to be expressed in the kidney and therefore
named XKH1. When expressed by means of cRNA
injection into frog oocytes, XKH1 solely
exhibited at physiologic ionic strength
hyaluronidase activity at neutral pH and in
weakly acidic solutions. The enzyme was inactive
below pH 5.4. In addition to hyaluronic acid
hydrolysis, chondroitin sulfate also was
degraded at low yield as assessed by
fluorophorendashassisted carbohydrate
electrophoresis analysis of the degradation
products. The enzyme is sorted to the outer
surface of the cell membrane of XKH1 expressing
oocytes. From there, it could not be removed by
phospholipase C nor was secreted hyaluronidase
activity detectable. We conclude that XKH1
represents a membrane ndashbound
hyaluronanndashdegrading enzyme exclusively
expressed in cells of the adult frog kidney where
it either may be involved in the reorganization
of the extracellular architecture or in
supporting physiological demands for proper
renal functions.lt/Pgt lt/ABSgt
ltKWDGgtltKWDgtHyaluronanlt/KWDgtltKWDgtHyaluronidaselt/KWD
gt ltKWDgtPHndash20lt/KWDgtltKWDgtKidneylt/KWDgt
lt/KWDGgt lt/FMgt
21Article in print presentation (PDF)
In-depth reading, note-taking Portable Serendip
ity Print quality / resolution Versatility
in sizes
22Article in Web presentation (ScienceDirect)
Searching, browsing, scanning, surfing,
glancing, verifying Speed Restrictive
screendimensions
23Article in Web presentation (ScienceDirect
OnSite Taiwan)
24Article in Web presentation (ScienceDirect
OnSite CSIRO )
25Content Structure Styling Presentation
Manuscript
Structure (DTD)
SGML file according to article structure
Print stylesheet
Web stylesheet
Article in print presentation
Article in Web presentation
26Overhauling Elsevier Science
27Electronic Production Flow
28What Customers Are Asking For...
- FTP of Datasets via the Internet
- XML coming soon!
- Multi-Media Content
- Other Possible Types of Content
- Book Serials
- Major Reference Works
- Databases
- More Breadth and Depth of Content
- Possible Embedded Searching Aids
29More choice in content
Comprehensiveness
10,000 titles
Navigational layer
New
3rd party
3rd party
Full-Text ES journals 1,700 (including IDEAL)
New (MRW, Books, patents)
40,000,000 abstracts
Navigational layer
Depth
Backfiles
CrossRef
30Back-Files in Perspective
Rembrandt Tower Amsterdam 135 meters 40 floors
8 million articles
70 million pages 35 million doublesided
sheets
3.8 kilometers
30 x RembrandtTowers
31Thank you