November 2008 Volume 14 Number 11, pp 1129 - 1290
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The Charles Carrington Prize in Molecular Mechanisms of Disease
The Department of Pathology at Stanford University School of Medicine,
with the support from the Wolfe and Gita Churg Foundation, annually
awards this $15,000 prize to an investigator in the field of experimental
pathology.
For more information, please click here:
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CA6E0Eh
or email cllanes@stanford.edu.
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EDITORIAL
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Research and recovery p1129
The global economy is in trouble. Investment in biomedical research should be a key ingredient in any recovery plan.
doi:10.1038/nm1108-1129
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAra0EB
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NEWS
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US researchers await key science appointments by next president p1131
Amber Dance
doi:10.1038/nm1108-1131
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArb0EC
China takes first steps toward healthcare and drug reforms p1132
Virginia Hughes
doi:10.1038/nm1108-1132a
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArc0ED
Nobel decision stirs viral dismay p1132
Coco Ballantyne
doi:10.1038/nm1108-1132b
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArd0EE
India plans for interdisciplinary neuroscience research center p1133
TV Padma
doi:10.1038/nm1108-1133a
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAre0EF
Publication is positively skewed p1133
Genevive Bjorn
doi:10.1038/nm1108-1133b
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArf0EG
Australia grants license for therapeutic cloning p1134
Simon Grose
doi:10.1038/nm1108-1134a
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArg0EH
Safer stem cells p1134
Genevive Bjorn
doi:10.1038/nm1108-1134b
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArh0EI
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NEWS FEATURE
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The chronic debate over Lyme disease pp1135 - 1139
A small group of doctors[mdash]and a large number of patients[mdash]say Lyme disease can sometimes manifest as a chronic illness, one that evades conventional medical tests and treatments. The physicians who support this theory flout standard medical guidelines and treat patients with long-term antibiotic therapies that mainstream researchers say are unproven and potentially dangerous. Coco Ballantyne reports on how the controversy over Lyme disease has become increasing polarized.
doi:10.1038/nm1108-1135
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAri0EJ
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NEWS
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News in brief pp1140 - 1141
doi:10.1038/nm1108-1140
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArj0EK
Straight talk with...Ray Moynihan pp1142 - 1143
The relationship between pharmaceutical companies and medical professionals has become too close for comfort, say many experts. They fear that the situation can breed conflicts of interest that lead to the creation of new, poorly defined concepts of illnesses[mdash]so called 'disease mongering'. The problem is a growing one, according to Ray Moynihan, honorary lecturer on topics such as 'medicine and the media' at the School of Medicine and Public Health at the University of Newcastle in Callaghan, Australia and co-author of the book Selling Sickness: How the World's Biggest Pharmaceutical Companies Are Turning Us All into Patients. Genevive Bjorn talked with Moynihan, who helped organize the first world conference on disease mongering, about how this phenomenon affects health priorities.
doi:10.1038/nm1108-1142
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArk0EL
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BOOK REVIEW
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Putting alternative medicine to the test p1145
Brian Dolan reviews Snake Oil Science: The Truth About Complementary and Alternative MedicineR. Barker Bausell
doi:10.1038/nm1108-1145
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArl0EM
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NEWS AND VIEWS
----------------------
Healing hemangiomas pp1147 - 1148
Defective signaling of vascular endothelial growth factor seems to underlie the development of hemangiomas, disfiguring tumors arising early in life (pages 1236-1246).
Lena Claesson-Welsh
doi:10.1038/nm1108-1147
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArm0EN
Epstein-Barr virus sustains tumor killers pp1148 - 1150
The immune system's response to a latent and ubiquitous virus is harnessed to kill tumors in a small study of humans. The approach overcomes a major barrier to effective tumor immunotherapy[mdash]generating a sustained immune response (pages 1264-1270).
Richard J O'Reilly
doi:10.1038/nm1108-1148
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArn0EO
HLA class I: friend and foe of multiple sclerosis pp1150 - 1151
Findings in a mouse model of multiple sclerosis highlight the contribution of CD8+ T cells, previously largely ignored in this disease. The work also helps answer why certain variants of the human leukocyte antigen (HLA) complex are protective, while others increase risk for disease (pages 1227-1235).
Roland Martin
doi:10.1038/nm1108-1150
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAro0EP
RIG-ing an antitumor response pp1152 - 1153
A small interfering RNA has been engineered to silence an oncogene and activate the immune response simultaneously. The approach shrinks tumors in mice (pages 1256-1263).
Fabio Petrocca and Judy Lieberman
doi:10.1038/nm1108-1152
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArp0EQ
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COMMUNITY CORNER
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Community corner p1154
doi:10.1038/nm1108-1154
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArq0ER
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BETWEEN BEDSIDE AND BENCH
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Graft-versus-host disease: suppression by statins pp1155 - 1156
Two big challenges of transplantation biology are controlling the reaction of the graft to the host after hematopoietic stem cell transplantation and preventing rejection of donor organs by the host. Raewyn Broady and Megan K. Levings discuss the first challenge, examining studies suggesting that statins might be helpful to control graft-versus-host disease. Kathryn Wood tackles the second challenge in the context of the 'Edmonton protocol', a procedure that can restore the ability to control blood glucose in people with type 1 diabetes[mdash]but only in the short term.
Raewyn Broady and Megan K Levings
doi:10.1038/nm1108-1155
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArr0ES
Outlook for longer-lasting islets pp1156 - 1157
Kathryn Wood
doi:10.1038/nm1108-1156
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArs0ET
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RESEARCH HIGHLIGHTS
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Research Highlights pp1158 - 1159
doi:10.1038/nm1108-1158
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArt0EU
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FOCUS ON REPRODUCTIVE BIOLOGY
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INTRODUCTION
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Reproductive biology p1166
In what direction is the field of reproductive biology moving? Do funding priorities match hot research areas? In this special focus, we try to find out.
doi:10.1038/nm1108-1166
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAru0EV
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NEWS
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As obesity epidemic grows, research shows fitness benefits fetal development p1167
Genevive Bjorn
doi:10.1038/nm1108-1167
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArv0EW
Interventions might offer a pregnant pause in addiction p1168
Erika Check Hayden
doi:10.1038/nm1108-1168
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArw0EX
Better tests boost IVF success p1169
Coco Ballantyne
doi:10.1038/nm1108-1169a
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArx0EY
Delivery decision is nothing to sneeze at p1169
doi:10.1038/nm1108-1169b
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAry0EZ
Male biological clock possibly linked to autism, other disorders p1170
Charlotte Schubert
doi:10.1038/nm1108-1170a
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CArz0Ea
New techniques preserve fertility hope for women p1170
doi:10.1038/nm1108-1170b
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAr10EN
As IVF becomes more common, some concerns remain p1171
Prashant Nair
doi:10.1038/nm1108-1171a
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAr20EO
p1171
Apoorva Mandavilli
doi:10.1038/nm1108-1171b
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAr30EP
Common reproductive disorders may have immunological basis p1172
Alisa Opar
doi:10.1038/nm1108-1172
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAr40EQ
My mother's keeper p1173
Coco Ballantyne
doi:10.1038/nm1108-1173
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAr50ER
Geneticists crack the code of infertility p1174
Virginia Hughes
doi:10.1038/nm1108-1174
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAr60ES
DATA PAGE
By the numbers... p1175
doi:10.1038/nm1108-1175
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAr70ET
NEWS FEATURE
Tinkering in the womb: the future of fetal surgery pp1176 - 1177
Cassandra Willyard
doi:10.1038/nm1108-1176
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAr80EU
----------------------
ANALYSIS
----------------------
The top papers on reproduction research 2004-2008 pp1178 - 1179
Which papers have provided the most interesting advances in reproduction research over the past three or four years? Which new discoveries have been the most important to or are likely to have the highest impact on the field?
doi:10.1038/nm1108-1178
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsA0Ee
Highly cited papers on reproductive biology (2005-2007) pp1180 - 1181
doi:10.1038/nm1108-1180
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsB0Ef
----------------------
NEWS AND VIEWS
----------------------
Advances in fertility preservation for female cancer survivors pp1182 - 1184
A method using tissue engineering principles for the culture of immature ovarian follicles followed by fertilization of oocytes in vitro has been presented by Xu et al.. This methodology is a great step forward toward new technology for fertility preservation in female cancer patients.
Mats Brannstrom and Milan Milenkovic
doi:10.1038/nm1108-1182
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsC0Eg
The upside of natural killers pp1184 - 1185
Natural killer (NK) cells, originally so named because they have the capacity to kill other cells without activation, can be licensed and educated to regulate tissue homeostasis. This notion has recently been shown in reproduction[mdash]in both normal physiology by Hanna et al. and severe pathophysiology (preeclampsia) by Hiby et al..
Khalil Karimi, Sandra M Blois and Petra C Arck
doi:10.1038/nm1108-1184
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsD0Eh
Is it my grandparents' fault? pp1186 - 1187
Results from two independent groups of researchers have revolutionized our thinking about the potential long-term consequences of exposure to common foreign chemicals, or xenobiotics. The studies indicate that exposure to such chemicals during key windows of gestation can affect not only the children exposed in utero, but also their children and perhaps even their grandchildren.
Bernard Robaire
doi:10.1038/nm1108-1186
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsE0Ei
Angiogenesis factors and preeclampsia pp1187 - 1188
Two recent studies[mdash]one in humans by Levine et al. in 2004 and one in mice by Venkatesha et al. in 2006[mdash]have shown an important role for placental-derived soluble antiangiogenic factors as mediators of the pathologies associated with preeclampsia. These findings may have profound implications for the diagnosis, treatment and prevention of this devastating condition.
Ralf Dechend and Friedrich C Luft
doi:10.1038/nm1108-1187
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsF0Ej
From stem cells to germ cells and back again pp1188 - 1190
Producing germ cells in vitro would open important new avenues for regenerative medicine, and obtaining alternative sources of pluripotent stem cells is desirable. In this regard, Geijsen et al. have shown that it is possible to differentiate stem cells into cells similar to male gametes, whereas Guan et al. reported the ability to turn undifferentiated germ cells into pluripotent stem cells.
Marco Conti and Linda Giudice
doi:10.1038/nm1108-1188
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsG0Ek
Making eggs: is it now or later? pp1190 - 1191
Although it has been thought that female mammals develop all the eggs they will ever have by the time they are born, new research suggesting otherwise has now sparked a debate.
Teresa K Woodruff
doi:10.1038/nm1108-1190
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsH0El
Two faces of PTEN pp1192 - 1193
A small number of women (approximately 1%) suffer from premature ovarian failure in which their ovarian follicle reserve is exhausted before age 40. Recent studies in mice show that the absence of a tumor suppressor gene, PTEN, in oocytes prematurely induces global follicular activation, depleting the follicle reserve in a manner similar to premature ovarian failure.
Takiko Daikoku and Sudhansu K Dey
doi:10.1038/nm1108-1192
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsI0Em
Research Highlights p1194
doi:10.1038/nm1108-1194
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsJ0En
Timeline: the role of kisspeptins in reproductive biology p1196
Although the focus of this issue is on contributions published over the past three to four years, the discovery of the kisspeptins was hailed as an important breakthrough by our advisors so frequently that we had to include it. Manuel Tena-Sempere guides us on a tour of the key findings that have shaped this blossoming field.
Manuel Tena-Sempere
doi:10.1038/nm1108-1196
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsK0Eo
----------------------
REVIEW
----------------------
The biology of infertility: research advances and clinical challenges pp1197 - 1213
Martin M Matzuk and Dolores J Lamb
doi:10.1038/nm.f.1895
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsL0Ep
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsM0Eq
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COMMENTARIES
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Funding for the reproductive sciences in the US pp1214 - 1217
Jerome F Strauss, III and Louis V De Paolo
doi:10.1038/nm1108-1214
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsN0Er
Funding for research in reproduction in the European Union pp1218 - 1220
Gerard Chaouat
doi:10.1038/nm1108-1218
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsO0Es
European funding for reproduction research - A multinational perspective p1222
Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.
Carlos Simon
doi:10.1038/nm1108-1222a
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsP0Et
European funding for reproduction research - A multinational perspective p1222
Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.
Thomas M D'Hooghe
doi:10.1038/nm1108-1222b
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsQ0Eu
European funding for reproduction research - A multinational perspective p1223
Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.
Daniel Rukavina
doi:10.1038/nm1108-1223a
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsR0Ev
European funding for reproduction research - A multinational perspective p1223
Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.
Antonis Makrigiannakis
doi:10.1038/nm1108-1223b
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsS0Ew
European funding for reproduction research - A multinational perspective p1224
Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.
Hilary Critchley and Philippa Saunders
doi:10.1038/nm1108-1224a
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsT0Ex
European funding for reproduction research - A multinational perspective p1224
Funds from the European Union are not the only source available to the continent's reproductive research community. Each country independently sponsors the work of these scientists, but, as illustrated by snapshots in the following pages, there are huge differences in the commitment of the various European nations to tackle the challenges of reproductive biomedicine.
Thomas Strowitzki
doi:10.1038/nm1108-1224b
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsU0Ey
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ARTICLES
----------------------
Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis pp1227 - 1235
Although major histocompatibility complex (MHC) class II alleles and CD4+ T cells have been implicated in multiple sclerosis, Friese et al. provide here the first direct evidence incriminating MHC class I genes and CD8+ T cells in the pathogenesis of this autoimmune disorder.
Manuel A Friese et al.
doi:10.1038/nm.1881
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsV0Ez
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsW0E1
Suppressed NFAT-dependent VEGFR1 expression and constitutive VEGFR2 signaling in infantile hemangioma pp1236 - 1246
Bjorn Olsen and his coworkers shed light on the molecular mechanisms underpinning the proangiogenic properties of endothelial cells in hemangiomas, tracing these properties to decreased activity of a signaling pathway involving NFAT transcription factor regulation of VEGFR1 receptor expression. They also identify germline mutations in genes encoding elements of this signaling pathway in a subset of individuals with hemangioma and suggest that interventions in this pathway could have therapeutic effects.
Masatoshi Jinnin et al.
doi:10.1038/nm.1877
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsX0E2
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsY0E3
Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium pp1247 - 1255
Niemann-Pick type C1 is a lysosomal storage disease caused by mutations in the NPC1 gene. The authors show that NPC1 regulates calcium levels in the lysosome, and calcium dysregulation could be the proximal event in inducing the accumulation of lipids that characterizes the disease.
Emyr Lloyd-Evans et al.
doi:10.1038/nm.1876
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsZ0E4
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsa0EC
5'-triphosphate-siRNA: turning gene silencing and Rig-I activation against melanoma pp1256 - 1263
siRNA is used to silence expression of a specific gene and, if modified by a triphosphate at the 5' end, will also activate the helicase Rig-I, leading to interferon production. Poeck et al. now combine both of these activities in a single siRNA to kill melanoma cells by crippling a crucial tumor cell survival pathway and triggering an interferon-dependent antitumor immune response.
Hendrik Poeck et al.
doi:10.1038/nm.1887
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsb0ED
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsc0EE
Virus-specific T cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma pp1264 - 1270
The promise of engineered T cells for treating cancer has been mitigated by their poor persistence when transferred to patients. Pule et al. now show that dual-specific T cells that recognize an Epstein-Barr virus (EBV) antigen and a tumor antigen survive longer in individuals with neuroblastoma. Engineering virus-specific T cells to recognize tumor antigens may improve the efficacy of this immunotherapy in latently infected cancer patients.
Martin A Pule et al.
doi:10.1038/nm.1882
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsd0EF
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAse0EG
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LETTER
----------------------
The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities pp1271 - 1277
Two microRNAs, miR-15a and miR-16, localize to a chromosome region that is frequently deleted in cancer. Bonci et al. now show that these microRNAs have tumor suppressive effects in prostate cancer cells and regulate the expression of crucial oncogenic targets.
Desiree Bonci et al.
doi:10.1038/nm.1880
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsf0EH
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsg0EI
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TECHNICAL REPORTS
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Engineering microRNA responsiveness to decrease virus pathogenicity pp1278 - 1283
Elizabeth J Kelly, Elizabeth M Hadac, Suzanne Greiner and Stephen J Russell
doi:10.1038/nm.1776
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsh0EJ
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsi0EK
HIT: a versatile proteomics platform for multianalyte phenotyping of cytokines, intracellular proteins and surface molecules pp1284 - 1289
Michael G Kattah et al.
doi:10.1038/nm.1755
Abstract: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsj0EL
Article: http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsk0EM
----------------------
ERRATUM
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Erratum: Straight talk with...Charles Grassley p1290
Meredith Wadman
doi:10.1038/nm1108-1290
http://ealerts.nature.com/cgi-bin24/DM/y/eof60Xztnp0HjT0CAsl0EN
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