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Article ; Online: Rab3a, a small GTP-binding protein, is required for the stabilization of the murine leukaemia virus Gag protein.

Izumida, Mai / Kakoki, Katsura / Hayashi, Hideki / Matsuyama, Toshifumi / Kubo, Yoshinao

2021 Volume 13, Issue 1, Page(s) 162–182

Abstract: We recently identified a CD63-interacting protein to understand the role of CD63 in virion production of the human immunodeficiency virus type 1, and we have found that Rab3a forms a complex with CD63. In this study, we analysed the effect of Rab3a on ... ...

Abstract	We recently identified a CD63-interacting protein to understand the role of CD63 in virion production of the human immunodeficiency virus type 1, and we have found that Rab3a forms a complex with CD63. In this study, we analysed the effect of Rab3a on virion production of the murine leukaemia virus (MLV), which is another member of the retrovirus family. We found that Rab3a silencing induced lysosomal degradation of the MLV Gag protein, and recovery of the Rab3a expression restored the level of the Gag protein through a complex formation of MLV Gag and Rab3a, indicating that Rab3a is required for MLV Gag protein expression. In contrast, CD63 silencing decreased the infectivity of released virions but had no effect on virion production, indicating that CD63 facilitates the infectivity of released MLV particles. Although Rab3a induced CD63 degradation in uninfected cells, the complex of MLV Gag and Rab3a suppressed the Rab3a-mediated CD63 degradation in MLV-infected cells. Finally, we found that the MLV Gag protein interacts with Rab3a to stabilize its own protein and CD63 that facilitates the infectivity of released MLV particles. Considering the involvement of Rab3a in lysosome trafficking to the plasma membrane, it may also induce cell surface transport of the MLV Gag protein.
MeSH term(s)	Mice ; Animals ; Humans ; Gene Products, gag/metabolism ; Leukemia Virus, Murine/metabolism ; Virion/metabolism ; Cell Membrane/metabolism ; GTP-Binding Proteins/metabolism
Chemical Substances	Gene Products, gag ; GTP-Binding Proteins (EC 3.6.1.-)
Language	English
Publishing date	2021-06-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2682247-7
ISSN	2154-1256 ; 2154-1248
ISSN (online)	2154-1256
ISSN	2154-1248
DOI	10.1080/21541248.2021.1939631
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Article: Renal dysfunction due to hydronephrosis by SAPHO syndrome: a case report.

Kakoki, Katsura / Miyata, Yasuyoshi / Enokizono, Mikako / Uetani, Masataka / Sakai, Hideki

Clinical case reports

2015 Volume 3, Issue 8, Page(s) 686–689

Abstract: Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO) syndrome shows varied pathological symptoms. This is the first report of hydronephrosis due to the mechanical compression of bilateral ureters as a result of SAPHO syndrome. From our experience, ...

Abstract	Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO) syndrome shows varied pathological symptoms. This is the first report of hydronephrosis due to the mechanical compression of bilateral ureters as a result of SAPHO syndrome. From our experience, MRI is the most useful imaging examination to check the upper urinary tract in SAPHO syndrome.
Language	English
Publishing date	2015-06-20
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.286
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Article: Rab3a-Bound CD63 Is Degraded and Rab3a-Free CD63 Is Incorporated into HIV-1 Particles.

Kubo, Yoshinao / Masumoto, Hiroshi / Izumida, Mai / Kakoki, Katsura / Hayashi, Hideki / Matsuyama, Toshifumi

Frontiers in microbiology

2017 Volume 8, Page(s) 1653

Abstract: CD63, a member of the tetraspanin family, is involved in virion production by human immunodeficiency virus type 1 (HIV-1), but its mechanism is unknown. In this study, we showed that a small GTP-binding protein, Rab3a, interacts with CD63. When Rab3a was ...

Abstract	CD63, a member of the tetraspanin family, is involved in virion production by human immunodeficiency virus type 1 (HIV-1), but its mechanism is unknown. In this study, we showed that a small GTP-binding protein, Rab3a, interacts with CD63. When Rab3a was exogenously expressed, the amounts of CD63 decreased in cells. The Rab3a-mediated reduction of CD63 was suppressed by lysosomal and proteasomal inhibitors. The amount of CD63 was increased by reducing the endogenous Rab3a level using a specific shRNA. These results indicate that Rab3a binds to CD63 to induce the degradation of CD63. Rab3a is thought to be involved in exocytosis, but we found that another function of Rab3a affects the fate of CD63 in lysosomes. CD63 interacted with Rab3a and was incorporated into HIV-1 particles. However, Rab3a was not detected in HIV-1 virions, thereby indicating that Rab3a-free CD63, but not Rab3a-bound CD63, is incorporated into HIV-1 particles. Overexpression or silencing of Rab3a moderately reduced HIV-1 virion formation. Overexpression of Rab3a decreased CD63 levels, but did not affect the incorporation of CD63 into HIV-1 particles. This study showed that Rab3a binds to CD63 to induce the degradation of CD63, and only Rab3a-free CD63 is incorporated into HIV-1 particles.
Language	English
Publishing date	2017-08-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2017.01653
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Article ; Online: The efficacy of mirabegron additional therapy for lower urinary tract symptoms after treatment with α1-adrenergic receptor blocker monotherapy: prospective analysis of elderly men.

Matsuo, Tomohiro / Miyata, Yasuyoshi / Kakoki, Katsura / Yuzuriha, Miki / Asai, Akihiro / Ohba, Kojiro / Sakai, Hideki

BMC urology

2016 Volume 16, Issue 1, Page(s) 45

Abstract: Background: Mirabegron is a β3-adrenoreceptor agonist developed for treatment of overactive bladder (OAB). α1-Adrenergic receptor blockers are effective for lower urinary tract symptoms (LUTS) in male patients. However, the efficacy of mirabegron ... ...

Abstract	Background: Mirabegron is a β3-adrenoreceptor agonist developed for treatment of overactive bladder (OAB). α1-Adrenergic receptor blockers are effective for lower urinary tract symptoms (LUTS) in male patients. However, the efficacy of mirabegron additional treatment in elderly male patients with persistent male LUTS, especially in OAB after monotherapy with α1-adrenergic blockers, is not fully understood. Methods: This study was conducted in male LUTS patients who were ≥ 65 years of age and had persistent OAB symptoms, regardless of whether they took an α1-adrenergic receptor blocker orally. Before and 12 weeks after mirabegron additional therapy (50 mg once daily), we evaluated the efficacy of this treatment using the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score (IPSS), and changes in the maximum flow rate (Qmax) and post-void residual urine volume (PVR). We evaluated patients overall and divided into two groups by age: young-old (from 65 to 74 years old) and old-old (from 75 to 84 years old). Results: Fifty men were enrolled in this study. Mirabegron additional therapy improved the total OABSS, total IPSS, and IPSS-quality of life (QOL) score. The voided volume (VV) and Qmax improved after treatment in patients overall. However, there was no significant change in PVR. The total OABSS, total IPSS, and IPSS-QOL score significantly improved in both of the young-old and old-old groups. However, a significant increasing of VV was detected in the young-old group. There were no significant differences in the Qmax or PVR in either group. Conclusions: Mirabegron additional therapy was effective for male patients whose persistent LUTS and particularly OAB was not controlled with α1-adrenergic receptor blocker monotherapy, and mirabegron did not have negative effects on voiding function. Additionally, mirabegron additional therapy was considered effective regardless of patient age. Trial registration: Trial registration number (TRN) trial registration number (TRN) and date of registration: ISRCTN16759097 in July 8, 2016.
MeSH term(s)	Acetanilides/therapeutic use ; Adrenergic alpha-1 Receptor Antagonists/therapeutic use ; Adrenergic beta-3 Receptor Agonists/therapeutic use ; Aged ; Aged, 80 and over ; Drug Therapy, Combination ; Humans ; Lower Urinary Tract Symptoms/drug therapy ; Male ; Prospective Studies ; Thiazoles/therapeutic use ; Treatment Outcome ; Urinary Bladder, Overactive
Chemical Substances	Acetanilides ; Adrenergic alpha-1 Receptor Antagonists ; Adrenergic beta-3 Receptor Agonists ; Thiazoles ; mirabegron (MVR3JL3B2V)
Language	English
Publishing date	2016-07-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2059857-9
ISSN	1471-2490 ; 1471-2490
ISSN (online)	1471-2490
ISSN	1471-2490
DOI	10.1186/s12894-016-0165-3
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Article ; Online: Long-term Treatment With Sequential Molecular Targeted Therapy for Xp11.2 Translocation Renal Cell Carcinoma: A Case Report and Review of the Literature.

Kakoki, Katsura / Miyata, Yasuyoshi / Mochizuki, Yasushi / Iwata, Takahisa / Obatake, Masayuki / Abe, Kuniko / Nagayasu, Takeshi / Sakai, Hideki

Clinical genitourinary cancer

2016 Volume 15, Issue 3, Page(s) e503–e506

MeSH term(s)	Adult ; Age of Onset ; Antineoplastic Agents/therapeutic use ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Carcinoma, Renal Cell/drug therapy ; Carcinoma, Renal Cell/genetics ; Catheter Ablation ; Child ; Combined Modality Therapy/methods ; Everolimus/therapeutic use ; Fatal Outcome ; Humans ; Imidazoles/therapeutic use ; Indazoles/therapeutic use ; Indoles/therapeutic use ; Kidney Neoplasms/drug therapy ; Kidney Neoplasms/genetics ; Male ; Molecular Targeted Therapy/methods ; Niacinamide/analogs & derivatives ; Niacinamide/therapeutic use ; Oncogene Fusion ; Phenylurea Compounds/therapeutic use ; Pyrroles/therapeutic use ; Translocation, Genetic ; Young Adult
Chemical Substances	Antineoplastic Agents ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Imidazoles ; Indazoles ; Indoles ; Phenylurea Compounds ; Pyrroles ; TFE3 protein, human ; Niacinamide (25X51I8RD4) ; Everolimus (9HW64Q8G6G) ; sorafenib (9ZOQ3TZI87) ; axitinib (C9LVQ0YUXG) ; sunitinib (V99T50803M)
Language	English
Publishing date	2016-12-29
Publishing country	United States
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2225121-2
ISSN	1938-0682 ; 1558-7673
ISSN (online)	1938-0682
ISSN	1558-7673
DOI	10.1016/j.clgc.2016.12.026
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Article ; Online: Androgen-independent proliferation of LNCaP prostate cancer cells infected by xenotropic murine leukemia virus-related virus.

Kakoki, Katsura / Kamiyama, Haruka / Izumida, Mai / Yashima, Yuka / Hayashi, Hideki / Yamamoto, Naoki / Matsuyama, Toshifumi / Igawa, Tsukasa / Sakai, Hideki / Kubo, Yoshinao

Biochemical and biophysical research communications

2014 Volume 447, Issue 1, Page(s) 216–222

Abstract: Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus that was originally isolated from human prostate cancer. It is now believed that XMRV is not the etiologic agent of prostate cancer. An analysis of murine leukemia virus ( ... ...

Abstract	Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus that was originally isolated from human prostate cancer. It is now believed that XMRV is not the etiologic agent of prostate cancer. An analysis of murine leukemia virus (MLV) infection in various human cell lines revealed that prostate cancer cell lines are preferentially infected by XMRV, and this suggested that XMRV infection may confer some sort of growth advantage to prostate cancer cell lines. To examine this hypothesis, androgen-dependent LNCaP cells were infected with XMRV and tested for changes in certain cell growth properties. We found that XMRV-infected LNCaP cells can proliferate in the absence of the androgen dihydrotestosterone. Moreover, androgen receptor expression is significantly reduced in XMRV-infected LNCaP cells. Such alterations were not observed in uninfected and amphotropic MLV-infected LNCaP cells. This finding explains why prostate cancer cell lines are preferentially infected with XMRV.
MeSH term(s)	Androgen Receptor Antagonists/pharmacology ; Androgens/pharmacology ; Anilides/pharmacology ; Animals ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dihydrotestosterone/pharmacology ; Humans ; Male ; Mice ; Nitriles/pharmacology ; Prostatic Neoplasms/virology ; Rats ; Receptors, Androgen/biosynthesis ; Receptors, Androgen/drug effects ; Tosyl Compounds/pharmacology ; Xenotropic murine leukemia virus-related virus/physiology
Chemical Substances	Androgen Receptor Antagonists ; Androgens ; Anilides ; Nitriles ; Receptors, Androgen ; Tosyl Compounds ; Dihydrotestosterone (08J2K08A3Y) ; bicalutamide (A0Z3NAU9DP)
Language	English
Publishing date	2014-04-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2014.03.154
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Article: Androgen-independent proliferation of LNCaP prostate cancer cells infected by xenotropic murine leukemia virus-related virus

Kakoki, Katsura / Kamiyama, Haruka / Izumida, Mai / Yashima, Yuka / Hayashi, Hideki / Yamamoto, Naoki / Matsuyama, Toshifumi / Igawa, Tsukasa / Sakai, Hideki / Kubo, Yoshinao

Biochemical and biophysical research communications. 2014 Apr. 25, v. 447

2014

Abstract	Xenotropic murine leukemia virus-related virus (XMRV) is a novel gammaretrovirus that was originally isolated from human prostate cancer. It is now believed that XMRV is not the etiologic agent of prostate cancer. An analysis of murine leukemia virus (MLV) infection in various human cell lines revealed that prostate cancer cell lines are preferentially infected by XMRV, and this suggested that XMRV infection may confer some sort of growth advantage to prostate cancer cell lines. To examine this hypothesis, androgen-dependent LNCaP cells were infected with XMRV and tested for changes in certain cell growth properties. We found that XMRV-infected LNCaP cells can proliferate in the absence of the androgen dihydrotestosterone. Moreover, androgen receptor expression is significantly reduced in XMRV-infected LNCaP cells. Such alterations were not observed in uninfected and amphotropic MLV-infected LNCaP cells. This finding explains why prostate cancer cell lines are preferentially infected with XMRV.
Keywords	Murine leukemia virus ; androgen receptors ; cell growth ; etiology ; human cell lines ; humans ; leukemia ; mice ; neoplasm cells ; prostatic neoplasms ; viruses
Language	English
Dates of publication	2014-0425
Size	p. 216-222.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2014.03.154
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Article: Susceptibility of muridae cell lines to ecotropic murine leukemia virus and the cationic amino acid transporter 1 viral receptor sequences: implications for evolution of the viral receptor

Kakoki, Katsura / Shinohara, Akio / Izumida, Mai / Koizumi, Yosuke / Honda, Eri / Kato, Goro / Igawa, Tsukasa / Sakai, Hideki / Hayashi, Hideki / Matsuyama, Toshifumi / Morita, Tetsuo / Koshimoto, Chihiro / Kubo, Yoshinao

Virus genes. 2014 June, v. 48, no. 3

2014

Abstract: Ecotropic murine leukemia viruses (Eco-MLVs) infect mouse and rat, but not other mammalian cells, and gain access for infection through binding the cationic amino acid transporter 1 (CAT1). Glycosylation of the rat and hamster CAT1s inhibits Eco-MLV ... ...

Abstract	Ecotropic murine leukemia viruses (Eco-MLVs) infect mouse and rat, but not other mammalian cells, and gain access for infection through binding the cationic amino acid transporter 1 (CAT1). Glycosylation of the rat and hamster CAT1s inhibits Eco-MLV infection, and treatment of rat and hamster cells with a glycosylation inhibitor, tunicamycin, enhances Eco-MLV infection. Although the mouse CAT1 is also glycosylated, it does not inhibit Eco-MLV infection. Comparison of amino acid sequences between the rat and mouse CAT1s shows amino acid insertions in the rat protein near the Eco-MLV-binding motif. In addition to the insertion present in the rat CAT1, the hamster CAT1 has additional amino acid insertions. In contrast, tunicamycin treatment of mink and human cells does not elevate the infection, because their CAT1s do not have the Eco-MLV-binding motif. To define the evolutionary pathway of the Eco-MLV receptor, we analyzed CAT1 sequences and susceptibility to Eco-MLV infection of other several murinae animals, including the southern vole (Microtus rossiaemeridionalis), large Japanese field mouse (Apodemus speciosus), and Eurasian harvest mouse (Micromys minutus). Eco-MLV infection was enhanced by tunicamycin in these cells, and their CAT1 sequences have the insertions like the hamster CAT1. Phylogenetic analysis of mammalian CAT1s suggested that the ancestral CAT1 does not have the Eco-MLV-binding motif, like the human CAT1, and the mouse CAT1 is thought to be generated by the amino acid deletions in the third extracellular loop of CAT1.
Keywords	Apodemus speciosus ; Microtus ; Murine leukemia virus ; amino acid sequences ; amino acid transporters ; glycosylation ; hamsters ; humans ; leukemia ; mice ; mink ; phylogeny ; rats ; tunicamycin ; viruses
Language	English
Dates of publication	2014-06
Size	p. 448-456.
Publishing place	Springer-Verlag
Document type	Article
ZDB-ID	639496-6
ISSN	1572-994X ; 0920-8569
ISSN (online)	1572-994X
ISSN	0920-8569
DOI	10.1007/s11262-014-1036-1
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Article ; Online: Pheochromocytoma multisystem crisis treated with emergency surgery: a case report and literature review.

Kakoki, Katsura / Miyata, Yasuyoshi / Shida, Youhei / Hakariya, Tomoaki / Takehara, Kosuke / Izumida, Seiya / Sekino, Motohiro / Kinoshita, Naoe / Igawa, Tsukasa / Fukuoka, Junya / Sakai, Hideki

BMC research notes

2015 Volume 8, Page(s) 758

Abstract: Background: Pheochromocytoma is a neuroendocrine tumor that predominantly presents with hypertension, palpitations, and tachycardia due to excessive catecholamine excretion. Although pheochromocytoma multisystem crisis (PMC) is relatively rare, ... ...

Abstract	Background: Pheochromocytoma is a neuroendocrine tumor that predominantly presents with hypertension, palpitations, and tachycardia due to excessive catecholamine excretion. Although pheochromocytoma multisystem crisis (PMC) is relatively rare, urologists and clinicians should focus on early diagnosis as delay in initiating the appropriate treatment can lead to mortality Case presentation: A 70-year-old man developed ileus after a few days of medication for hypertension. Computed tomography incidentally revealed a left adrenal mass. This finding together with his clinical course was compatible with pheochromocytoma. An α-blocker was administered immediately, and his blood pressure was well controlled. However, his general condition and laboratory data deteriorated rapidly, and the patient was diagnosed with PMC with lethal status. Thus, emergency adrenalectomy was performed without confirmation of catecholamine levels. From the resected specimen, his tumor was judged as pheochromocytoma. On immunohistochemical analysis, the proliferation index evaluated by Ki-67 staining was 9.7 %. This case report was approved by the Human Ethics Review Committee of the Nagasaki University Hospital. Conclusion: The present case of PMC was successfully treated with emergency surgery. The benign pheochromocytoma also presented with high cell proliferation potential, which may be a cause of the extreme aggressiveness of PMC.
MeSH term(s)	Adrenal Gland Neoplasms/complications ; Adrenal Gland Neoplasms/diagnosis ; Adrenal Gland Neoplasms/surgery ; Aged ; Humans ; Male ; Pheochromocytoma/complications ; Pheochromocytoma/diagnosis ; Pheochromocytoma/surgery
Language	English
Publishing date	2015-12-09
Publishing country	England
Document type	Case Reports ; Journal Article ; Review
ZDB-ID	2413336-X
ISSN	1756-0500 ; 1756-0500
ISSN (online)	1756-0500
ISSN	1756-0500
DOI	10.1186/s13104-015-1738-z
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Article ; Online: Infection of XC cells by MLVs and Ebola virus is endosome-dependent but acidification-independent.

Kamiyama, Haruka / Kakoki, Katsura / Yoshii, Hiroaki / Iwao, Masatomo / Igawa, Tsukasa / Sakai, Hideki / Hayashi, Hideki / Matsuyama, Toshifumi / Yamamoto, Naoki / Kubo, Yoshinao

PloS one

2011 Volume 6, Issue 10, Page(s) e26180

Abstract: Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine ...

Abstract	Inhibitors of endosome acidification or cathepsin proteases attenuated infections mediated by envelope proteins of xenotropic murine leukemia virus-related virus (XMRV) and Ebola virus, as well as ecotropic, amphotropic, polytropic, and xenotropic murine leukemia viruses (MLVs), indicating that infections by these viruses occur through acidic endosomes and require cathepsin proteases in the susceptible cells such as TE671 cells. However, as previously shown, the endosome acidification inhibitors did not inhibit these viral infections in XC cells. It is generally accepted that the ecotropic MLV infection in XC cells occurs at the plasma membrane. Because cathepsin proteases are activated by low pH in acidic endosomes, the acidification inhibitors may inhibit the viral infections by suppressing cathepsin protease activation. The acidification inhibitors attenuated the activities of cathepsin proteases B and L in TE671 cells, but not in XC cells. Processing of cathepsin protease L was suppressed by the acidification inhibitor in NIH3T3 cells, but again not in XC cells. These results indicate that cathepsin proteases are activated without endosome acidification in XC cells. Treatment with an endocytosis inhibitor or knockdown of dynamin 2 expression by siRNAs suppressed MLV infections in all examined cells including XC cells. Furthermore, endosomal cathepsin proteases were required for these viral infections in XC cells as other susceptible cells. These results suggest that infections of XC cells by the MLVs and Ebola virus occur through endosomes and pH-independent cathepsin activation induces pH-independent infection in XC cells.
MeSH term(s)	Acids/metabolism ; Animals ; Cathepsin B/metabolism ; Concanavalin A/pharmacology ; Culture Media, Conditioned/pharmacology ; Dynamins/metabolism ; Ebolavirus/drug effects ; Ebolavirus/physiology ; Endocytosis/drug effects ; Endosomes/drug effects ; Endosomes/metabolism ; Endosomes/virology ; Enzyme Activation/drug effects ; Gene Products, env/metabolism ; Genetic Vectors/genetics ; Hemorrhagic Fever, Ebola/pathology ; Hemorrhagic Fever, Ebola/virology ; Humans ; Hydrazones/pharmacology ; Hydrogen-Ion Concentration/drug effects ; Leukemia, Experimental/pathology ; Leukemia, Experimental/virology ; Mice ; Models, Biological ; Moloney murine leukemia virus/drug effects ; Moloney murine leukemia virus/physiology ; NIH 3T3 Cells ; Organ Specificity/drug effects ; RNA, Small Interfering/metabolism ; Rats
Chemical Substances	Acids ; Culture Media, Conditioned ; Gene Products, env ; Hydrazones ; N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide ; RNA, Small Interfering ; Concanavalin A (11028-71-0) ; Cathepsin B (EC 3.4.22.1) ; Dynamins (EC 3.6.5.5)
Language	English
Publishing date	2011-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0026180
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