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Find video protocols related to scientific articles indexed in Pubmed.
ERK1/2 is involved in luteal cell autophagy regulation during corpus luteum regression via an mTOR-independent pathway.
Mol. Hum. Reprod.
PUBLISHED: 08-08-2014
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Autophagy is known to be regulated by the phosphoinositide-3 kinase (PI3K)-protein kinase B (AKT) and/or mitogen-activated protein kinase 1/2 (MEK1/2)-extracellular signal-regulated kinase 1/2 (ERK1/2) pathways, leading to activation of mammalian target of rapamycin (mTOR), a major negative regulator of autophagy. However, some reports have also suggested that autophagic regulation by the PI3K-AKT and/or MEK1/2-ERK1/2 pathways may not be mediated by mTOR activity, and there is no direct evidence of the involvement of these pathways in luteal cell autophagy regulation. To elucidate the luteal cell-specific regulatory mechanisms of autophagy induction during corpus luteum (CL) regression, we evaluated whether luteal cell autophagy is regulated by the PI3K-AKT pathway and/or MEK1/2-ERK1/2 pathway and if this regulation is mediated by mTOR. We found that autophagy induction increased despite mTOR activation in luteal cells cultured with prostaglandin F2? (PGF2?), an important mediator of CL regression, suggesting that PGF2?-induced autophagy is independent of mTOR regulation. We also found that PGF2?-induced autophagy was not mediated by AKT activity, because AKT inhibition using a PI3K inhibitor (wortmannin) did not change autophagy induction or mTOR activity. In contrast, ERK1/2 activity increased in PGF2?-treated luteal cells, as did the levels of autophagy induction despite increased mTOR activity. Furthermore, PGF2?-mediated up-regulation of luteal cell autophagy was reversed by addition of ERK1/2 inhibitors, despite a decrease in mTOR activity. These in vitro results suggest that luteal cell autophagy is induced by increased ERK1/2 activity during CL regression, and is independent of mTOR activity. This finding was further supported by in vivo experiments in a pseudo-pregnant rat model, which showed that induction of luteal cell autophagy increased during luteal stage progression and that this was accompanied by increased ERK1/2 and mTOR activity. Taken together, our findings indicate that activation of ERK1/2 is a key event in the induction of luteal cell autophagy during CL regression which is not associated with mTOR regulation.
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Effects of long-term postoperative oral contraceptive use for the prevention of endometrioma recurrence on bone mineral density in young women.
Gynecol. Endocrinol.
PUBLISHED: 06-13-2014
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Concerns for negative effects of oral contraceptives (OCs) on bone mineral density (BMD) in long-term users have been raised, since OCs suppress the hypothalamic-pituitary-ovarian axis. However, there have been still limited data regarding the effects of long-term OC use on BMD in young women in the twenties. We investigated the effects of long-term OC use for the prevention of endometrioma recurrence on BMD in young women. Ninety-two women aged 20-30 years who underwent conservative surgery for endometrioma and used postoperative OC for at least 12 months to prevent the recurrence were included for this cross-sectional study, and BMDs after OC use were analyzed. The mean age at starting OC and duration of OC use was 25.6?±?2.9 years and 40.7?±?28.5 months, respectively. No correlation was found between BMDs and age at starting OC at all sites. In addition, BMDs were also not correlated with the duration of OC use, and were comparable according to the dose of OC (20 versus 30??g). In conclusion, long-term use of OCs has no adverse effect on BMD in post-adolescent young women.
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Differential induction of autophagy by mTOR is associated with abnormal apoptosis in ovarian endometriotic cysts.
Mol. Hum. Reprod.
PUBLISHED: 12-06-2013
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Mammalian target of rapamycin (mTOR) is known to be a major negative regulator of autophagy. Recent studies have shown that mTOR activity is abnormally increased in endometriotic lesions. In endometriosis, abnormal mTOR activity may contribute to the alteration of endometrial cell autophagy, which may affect apoptosis because endometrial cell autophagy is directly involved in the regulation of apoptosis. To test this hypothesis, we investigated whether endometrial cell autophagy is altered by aberrant mTOR activity and is associated with apoptosis in ovarian endometriotic cysts. Our results show that endometrial cell autophagy induction was increased by mTOR inhibition as the menstrual cycle progresses in the normal endometrium, and that it is correlated with apoptosis. However, in endometriotic tissues from ovarian endometriotic cysts, autophagy, mTOR activity and apoptosis were constant throughout the menstrual cycle, suggesting that a constant level of autophagy is maintained by disinhibition of mTOR activity during the menstrual cycle in endometriotic tissues and is related to decreased apoptosis. Indeed, compared with normal endometrium, increased mTOR activity during the secretory phase in endometriotic tissues inhibited autophagy and apoptosis induction. In addition, to determine the direct effect of autophagy induction mediated by mTOR on endometriotic cell apoptosis, endometriotic cells were treated with rapamacin (mTOR inhibitor) with and without 3-methyladenine (3-MA, autophagy inhibitor). Although rapamycin treatment induced autophagy and led to apoptosis promotion, the pro-apoptotic effect of rapamycin was reversed by the addition of 3-MA, suggesting that mTOR inhibition promotes endometriotic cell apoptosis via autophagy induction. In conclusion, our results suggest that aberrant mTOR activity in ovarian endometriotic cysts leads to alteration of endometrial cell autophagy, which is associated with abnormal apoptosis.
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AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia.
Reproduction
PUBLISHED: 10-18-2013
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In this study, we examined whether granulosa cell autophagy during follicular development and atresia was regulated by the class I phosphoinositide-3 kinase/protein kinase B (AKT) pathway, which is known to control the activity of mammalian target of rapamycin (mTOR), a major negative regulator of autophagy. Ovaries and granulosa cells were obtained using an established gonadotropin-primed immature rat model that induces follicular development and atresia. Autophagy was evaluated by measuring the expression level of microtubule-associated protein light chain 3-II (LC3-II) using western blots and immunohistochemistry. The activity of AKT and mTOR was also examined by observing the phosphorylation of AKT and ribosomal protein S6 kinase (S6K) respectively. After gonadotropin injection, LC3-II expression was suppressed and phosphorylation of AKT and S6K increased in rat granulosa cells. By contrast, gonadotropin withdrawal by metabolic clearance promoted LC3-II expression and decreased phosphorylation of AKT and S6K. In addition, in-vitro FSH treatment of rat granulosa cells also indicated inhibition of LC3-II expression accompanied by a marked increase in phosphorylation of AKT and S6K. Inhibition of AKT phosphorylation using AKT inhibitor VIII suppressed FSH-mediated phosphorylation of S6K, followed by an increase in LC3-II expression. Furthermore, co-treatment with FSH and AKT inhibitor increased the levels of apoptosis and cell death of granulosa cells compared with the single treatment with FSH. Taken together, our findings indicated that AKT-mediated activation of mTOR suppresses granulosa cell autophagy during follicular development and is involved in the regulation of apoptotic cell death.
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Factors associated with the laterality of recurrent endometriomas after conservative surgery.
Gynecol. Endocrinol.
PUBLISHED: 09-04-2013
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We evaluated the laterality of primary endometrioma and characteristics of patients according to the laterality of recurrent endometrioma in 140 women with recurrent endometrioma after conservative surgery. Histologically confirmed recurrent endometriomas were found on the left side in 49 patients (35.0%), the right in 44 (31.4%) and bilaterally in 47 (33.6%). The sites of primary endometrioma were not associated with those of recurrent endometrioma, and the recurrence rate in the treated ovary (59.8%) was similar to that of the intact ovary (69.0%) at the primary surgery. Proportions of stage IV endometriosis and posterior cul-de-sac obliteration were higher in patients with bilateral recurrence than in those with unilateral recurrence (p?
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Effects of adding alendronate to ongoing hormone therapy on bone mineral density in postmenopausal Korean women: a randomized, double-blind, placebo-controlled clinical trial.
Menopause
PUBLISHED: 02-14-2013
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This study was conducted to evaluate the effects of adding the bisphosphonate alendronate (ALEN) to ongoing hormone therapy (HT) on bone mineral density (BMD) in postmenopausal Korean women.
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Effects of black cohosh on the plasminogen activator system in vascular smooth muscle cells.
Maturitas
PUBLISHED: 01-25-2013
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The rhizome of the Cimicifuga racemosa plant (commonly known as black cohosh) has been used for menopausal complaints. Studies regarding the cardiovascular effects of black cohosh are lacking. We investigated the effect of black cohosh on the plasminogen activator system in cultured vascular smooth muscle cells (VSMCs).
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Clinical characteristics of adolescent endometrioma.
J Pediatr Adolesc Gynecol
PUBLISHED: 01-20-2013
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To evaluate the clinical characteristics of endometrioma in adolescent women compared to women of other age groups.
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Estrogen requirements in girls with Turner syndrome; how low is enough for initiating puberty and uterine development?
Gynecol. Endocrinol.
PUBLISHED: 07-27-2011
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We conducted this study to find the adequate initial estrogen dose for adolescent girls with Turner Syndrome (TS). We reviewed the medical records of 19 girls with TS and premature ovarian failure (POF), aged 13 to 17 years, who were referred to our adolescent gynecology clinic for ERT. Nine patients were treated with 0.5 mg estradiol valerate (EV) and 10 patients were treated with 1 mg EV as an initial estrogen dose for 1 year. Breast development, changes in uterine size and bone mineral density were measured before and after 1 year of ERT. All patients showed breast budding after 1 year of ERT regardless of estrogen dosage. Uterine development in patients treated with 1 mg EV advanced farther in 1 year of treatment than in patients given 0.5 mg EV. In patients treated with 1 mg EV, uterine length increased by 39.8% and AP fundal diameter by 46%, increments greater than in patients receiving 0.5 mg EV. After 1 year of ERT, bone mineral densities (BMD) increased significantly in both groups, although BMD did not differ significantly between the groups. In conclusion, ERT with 1mg of EV, as a starting dose induced better uterine development than 0.5 mg in prepubertal girls with TS.
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Prevalence of hyperprolactinemia in adolescents and young women with menstruation-related problems.
Am. J. Obstet. Gynecol.
PUBLISHED: 07-08-2011
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The aim of this study was to evaluate the prevalence of hyperprolactinemia in adolescents and young women with menstrual problems.
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The role of autophagy in corpus luteum regression in the rat.
Biol. Reprod.
PUBLISHED: 05-18-2011
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Autophagy is associated with luteal cells death during regression of the corpus luteum (CL) in some species. However, the involvement of autophagy or the association between autophagy and apoptosis in CL regression are largely unknown. Therefore, we investigated the role of autophagy in CL regression and its association with apoptosis. Ovaries were obtained from pseudopregnant rats at Days 2 (early), 7 (mid-), and 14 and 20 (late-luteal stage) of the pseudopregnancy; autophagy-associated protein (microtuble-associated protein light chain 3 [LC3]) was immunolocalized and its expression level was measured. Luteal cell apoptosis was evaluated by measuring cleaved caspase 3 expression. LC3 expression increased slightly from early to mid-luteal stage, with maximal levels detected at the late-luteal stage in steroidogenic luteal cells. The expression level of the membrane form of LC3 (LC3-II) also increased during luteal stage progression, and reached a maximum at the end point of late-luteal stage (Day 20). This pattern coincided with cleaved caspase 3 expression. Furthermore, LC3-II expression increased, as did levels of cleaved caspase 3 in luteal cells cultured with prostaglandin F(2alpha) known to induce CL regression. These findings suggest that luteal cell autophagy is directly involved in CL regression, and is correlated with increased apoptosis. In addition, autophagic processes were inhibited using 3-methyladenine or bafilomycin A1 to evaluate the role of autophagy in apoptosis induction. Inhibition of autophagosome degradation by fusion with lysosomes (bafilomycin A1) increased apoptosis and cell death. Furthermore, inhibition of autophagosome formation (3-methyladenine) decreased apoptosis and cell death, suggesting that the accumulation of autophagosomes induces luteal cell apoptosis. In conclusion, these results indicate that autophagy is involved in rat luteal cell death through apoptosis, and is most prominent during CL regression.
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Clinical characteristics of ovarian teratoma: age-focused retrospective analysis of 580 cases.
Am. J. Obstet. Gynecol.
PUBLISHED: 02-07-2011
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The objective of the study was to evaluate the clinical characteristics of ovarian teratoma by age.
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Asian study of effects of premenstrual symptoms on activities of daily life.
Menopause Int
PUBLISHED: 12-16-2010
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The aim of this paper is to assess the effects of premenstrual symptoms on quality of life as measured by the impact symptoms have on womens activities of daily life (ADL).
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A population-based survey of Asian womens experience of premenstrual symptoms.
Menopause Int
PUBLISHED: 12-16-2010
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This paper aims to explore womens experiences of premenstrual symptoms in three Asian countries and the factors affecting the prevalence of these symptoms.
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Effects of laparoscopic surgery on serum anti-Müllerian hormone levels in reproductive-aged women with endometrioma.
Gynecol. Endocrinol.
PUBLISHED: 12-15-2010
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A few studies have investigated the effects of laparoscopic cystectomy for endometrioma on ovarian reserve using serum anti-Müllerian hormone (AMH) levels and have shown inconsistent results. This prospective study was performed to estimate early changes in serum AMH after laparoscopic surgery for endometrioma. In 27 women aged 21-46 years who underwent laparoscopic unilateral cystectomy (n = 13) or oophorectomy (n = 14) for endometrioma, we measured pre- and postoperative serum AMH levels at baseline and 1 week, 1 month, and 3 months after surgery. Serial changes in serum AMH levels were analyzed according to the operation type using analysis of variance. Mean levels of serum AMH decreased significantly immediately after surgery and remained for up to 3 months in both operation types (P = 0.002 for cystectomy group and P <0.001 for oophorectomy group). In addition, the serum AMH levels showed similar patterns of change after cystectomy or oophorectomy. In conclusion, laparoscopic ovarian cystectomy for endometrioma appears to decrease serum AMH levels immediately after surgery.
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Post-operative cyclic oral contraceptive use after gonadotrophin-releasing hormone agonist treatment effectively prevents endometrioma recurrence.
Hum. Reprod.
PUBLISHED: 10-11-2010
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Currently, no standard post-operative medical therapy has been shown to be superior in reducing the recurrence of endometrioma. This retrospective study was performed to evaluate the efficacy of post-operative cyclic oral contraceptive (OC) use after GnRH agonist (GnRHa) treatment for the prevention of endometrioma recurrence.
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The efficacy and tolerability of short-term low-dose estrogen-only add-back therapy during post-operative GnRH agonist treatment for endometriosis.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 07-16-2010
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To evaluate the efficacy and tolerability of a low-dose estrogen-only regimen as a short-term add-back therapy during post-operative GnRH agonist (GnRHa) treatment of patients with endometriosis.
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Determination of an applicable FRAX model in Korean women.
J. Korean Med. Sci.
PUBLISHED: 03-17-2010
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We investigated which of the three FRAX fracture risk assessment tool models is most applicable to Korean women. For 306 postmenopausal women (mean age, 77 yr) with a hip fracture, fracture probabilities were calculated using FRAX models from Japan, Turkey and China. Data on bone mineral density (BMD) at the femoral neck were available for 103 patients. Significant differences existed among the models, independent of the inclusion of BMD in the calculation of fracture probabilities. The probabilities of both major osteoporotic fractures and hip fractures were significantly higher in the Japanese model than in the Turkish or Chinese models. In all of the models, the probabilities of a major osteoporotic fracture, but not of a hip fracture, decreased significantly if calculated without BMD values. By applying the Japanese model, the ten-year probabilities for major osteoporotic and hip fractures increased significantly with age. Our results suggest that the Japanese FRAX model might be the most appropriate for Korean women.
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Clinical characteristics of adnexal masses in Korean children and adolescents: retrospective analysis of 409 cases.
J Minim Invasive Gynecol
PUBLISHED: 03-16-2010
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To analyze the clinical characteristics of young Korean female children and adolescents who underwent surgery because of adnexal masses during the last 14 years.
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Reproductive health characteristics of urban South Korean women.
Gynecol. Obstet. Invest.
PUBLISHED: 02-20-2010
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To characterize the reproductive health of urban South Korean women of reproductive age.
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Induction of apoptotic cell death via accumulation of autophagosomes in rat granulosa cells.
Fertil. Steril.
PUBLISHED: 02-17-2010
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This study evaluated the effect of autophagosome accumulation on apoptotic cell death in granulosa cells from developing follicles. Our results indicate that the accumulation of autophagosomes induces apoptotic cell death of granulosa cells through decreased bcl-2 expression and subsequent caspase activation.
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Change in the ovarian environment after hysterectomy as assessed by ovarian arterial blood flow indices and serum anti-Müllerian hormone levels.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 02-15-2010
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The aim of this prospective study was to evaluate the changes in the ovarian environment after hysterectomy based on ovarian arterial blood flow indices and serum anti-Müllerian hormone (AMH) levels.
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The impact of premenstrual symptoms on activities of daily life in Korean women.
J Psychosom Obstet Gynaecol
PUBLISHED: 02-12-2010
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To evaluate the impact of premenstrual symptoms on activities of daily life (ADL) of Korean women, and their knowledge and treatment seeking regarding premenstrual syndromes (PMSs).
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Postoperative long-term maintenance therapy with oral contraceptives after gonadotropin-releasing hormone analog treatment in women with ovarian endometrioma.
J Minim Invasive Gynecol
PUBLISHED: 03-27-2009
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The goal of this preliminary study was to assess the effect of cyclic monophasic oral contraceptives (OCs) as a postoperative long-term maintenance therapy (median 33.2 months) to suppress recurrence of endometrioma after conservative ovarian surgery followed by gonadotropin-releasing hormone (GnRH) analog treatment.
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Altered vascular endothelial growth factor expression during GnRH antagonist protocol in women of reproductive age with normal baseline hormone profiles.
Fertil. Steril.
PUBLISHED: 03-20-2009
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To explain the unexpected low response to GnRH antagonist protocol in reproductive women with normal baseline hormone profiles.
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GnRH agonist therapy to protect ovarian function in young Korean breast cancer patients.
J. Korean Med. Sci.
PUBLISHED: 02-25-2009
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The increased survival of patients with breast cancer has given rise to other problems associated with the complications of chemotherapy. One major complication is premature ovarian failure, an especially harmful outcome for women of reproductive age. This study was performed to evaluate the efficacy of GnRH agonist (GnRHa) treatment on protecting ovarian function in young breast cancer patients (30.59+/-5.1 yr) receiving chemotherapy after surgery. Twenty-two women were enrolled and given subcutaneous injections of leuprolide acetate (3.75 mg) every 4 weeks during chemotherapy. Follow-up laboratory tests (luteinizing hormone [LH], follicle stimulating hormone [FSH], and estradiol) were performed 1, 3, and 6 months after chemotherapy. Menstruation patterns and clinical symptoms were followed up for a mean duration of 35.6+/-1.7 months. FSH and LH levels were normal in all patients 6 months after completing chemotherapy (8.0+/-5.3, 4.4+/-2.7 mIU/mL, respectively). During follow-up, none of the patients complained of menopausal symptoms and 81.8% experienced recovery of menstruation. This report is the first trial of GnRHa as a treatment modality to protect ovarian function during adjuvant chemotherapy in young Korean breast cancer patients.
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Guidelines for the use and interpretation of assays for monitoring autophagy.
Daniel J Klionsky, Fábio C Abdalla, Hagai Abeliovich, Robert T Abraham, Abraham Acevedo-Arozena, Khosrow Adeli, Lotta Agholme, Maria Agnello, Patrizia Agostinis, Julio A Aguirre-Ghiso, Hyung Jun Ahn, Ouardia Ait-Mohamed, Slimane Ait-Si-Ali, Takahiko Akematsu, Shizuo Akira, Hesham M Al-Younes, Munir A Al-Zeer, Matthew L Albert, Roger L Albin, Javier Alegre-Abarrategui, Maria Francesca Aleo, Mehrdad Alirezaei, Alexandru Almasan, Maylin Almonte-Becerril, Atsuo Amano, Ravi Amaravadi, Shoba Amarnath, Amal O Amer, Nathalie Andrieu-Abadie, Vellareddy Anantharam, David K Ann, Shailendra Anoopkumar-Dukie, Hiroshi Aoki, Nadezda Apostolova, Giuseppe Arancia, John P Aris, Katsuhiko Asanuma, Nana Y O Asare, Hisashi Ashida, Valerie Askanas, David S Askew, Patrick Auberger, Misuzu Baba, Steven K Backues, Eric H Baehrecke, Ben A Bahr, Xue-Yuan Bai, Yannick Bailly, Robert Baiocchi, Giulia Baldini, Walter Balduini, Andrea Ballabio, Bruce A Bamber, Edward T W Bampton, Gábor Bánhegyi, Clinton R Bartholomew, Diane C Bassham, Robert C Bast, Henri Batoko, Boon-Huat Bay, Isabelle Beau, Daniel M Béchet, Thomas J Begley, Christian Behl, Christian Behrends, Soumeya Bekri, Bryan Bellaire, Linda J Bendall, Luca Benetti, Laura Berliocchi, Henri Bernardi, Francesca Bernassola, Sébastien Besteiro, Ingrid Bhatia-Kiššová, Xiaoning Bi, Martine Biard-Piechaczyk, Janice S Blum, Lawrence H Boise, Paolo Bonaldo, David L Boone, Beat C Bornhauser, Karina R Bortoluci, Ioannis Bossis, Fréderic Bost, Jean-Pierre Bourquin, Patricia Boya, Michaël Boyer-Guittaut, Peter V Bozhkov, Nathan R Brady, Claudio Brancolini, Andreas Brech, Jay E Brenman, Ana Brennand, Emery H Bresnick, Patrick Brest, Dave Bridges, Molly L Bristol, Paul S Brookes, Eric J Brown, John H Brumell, Nicola Brunetti-Pierri, Ulf T Brunk, Dennis E Bulman, Scott J Bultman, Geert Bultynck, Lena F Burbulla, Wilfried Bursch, Jonathan P Butchar, Wanda Buzgariu, Sérgio P Bydlowski, Ken Cadwell, Monika Cahova, Dongsheng Cai, Jiyang Cai, Qian Cai, Bruno Calabretta, Javier Calvo-Garrido, Nadine Camougrand, Michelangelo Campanella, Jenny Campos-Salinas, Eleonora Candi, Lizhi Cao, Allan B Caplan, Simon R Carding, Sandra M Cardoso, Jennifer S Carew, Cathleen R Carlin, Virginie Carmignac, Leticia A M Carneiro, Serena Carra, Rosario A Caruso, Giorgio Casari, Caty Casas, Roberta Castino, Eduardo Cebollero, Francesco Cecconi, Jean Celli, Hassan Chaachouay, Han-Jung Chae, Chee-Yin Chai, David C Chan, Edmond Y Chan, Raymond Chuen-Chung Chang, Chi-Ming Che, Ching-Chow Chen, Guang-Chao Chen, Guo-Qiang Chen, Min Chen, Quan Chen, Steve S-L Chen, WenLi Chen, Xi Chen, Xiangmei Chen, Xiequn Chen, Ye-Guang Chen, Yingyu Chen, Yongqiang Chen, Yu-Jen Chen, Zhixiang Chen, Alan Cheng, Christopher H K Cheng, Yan Cheng, Heesun Cheong, Jae-Ho Cheong, Sara Cherry, Russ Chess-Williams, Zelda H Cheung, Eric Chevet, Hui-Ling Chiang, Roberto Chiarelli, Tomoki Chiba, Lih-Shen Chin, Shih-Hwa Chiou, Francis V Chisari, Chi Hin Cho, Dong-Hyung Cho, Augustine M K Choi, DooSeok Choi, Kyeong Sook Choi, Mary E Choi, Salem Chouaib, Divaker Choubey, Vinay Choubey, Charleen T Chu, Tsung-Hsien Chuang, Sheau-Huei Chueh, Taehoon Chun, Yong-Joon Chwae, Mee-Len Chye, Roberto Ciarcia, Maria R Ciriolo, Michael J Clague, Robert S B Clark, Peter G H Clarke, Robert Clarke, Patrice Codogno, Hilary A Coller, María I Colombo, Sergio Comincini, Maria Condello, Fabrizio Condorelli, Mark R Cookson, Graham H Coombs, Isabelle Coppens, Ramón Corbalán, Pascale Cossart, Paola Costelli, Safia Costes, Ana Coto-Montes, Eduardo Couve, Fraser P Coxon, James M Cregg, José L Crespo, Marianne J Cronjé, Ana Maria Cuervo, Joseph J Cullen, Mark J Czaja, Marcello D'Amelio, Arlette Darfeuille-Michaud, Lester M Davids, Faith E Davies, Massimo De Felici, John F de Groot, Cornelis A M de Haan, Luisa De Martino, Angelo De Milito, Vincenzo De Tata, Jayanta Debnath, Alexei Degterev, Benjamin Dehay, Lea M D Delbridge, Francesca Demarchi, Yi Zhen Deng, Jörn Dengjel, Paul Dent, Donna Denton, Vojo Deretic, Shyamal D Desai, Rodney J Devenish, Mario Di Gioacchino, Gilbert Di Paolo, Chiara Di Pietro, Guillermo Díaz-Araya, Inés Díaz-Laviada, Maria T Diaz-Meco, Javier Diaz-Nido, Ivan Dikic, Savithramma P Dinesh-Kumar, Wen-Xing Ding, Clark W Distelhorst, Abhinav Diwan, Mojgan Djavaheri-Mergny, Svetlana Dokudovskaya, Zheng Dong, Frank C Dorsey, Victor Dosenko, James J Dowling, Stephen Doxsey, Marlène Dreux, Mark E Drew, Qiuhong Duan, Michel A Duchosal, Karen Duff, Isabelle Dugail, Madeleine Durbeej, Michael Duszenko, Charles L Edelstein, Aimee L Edinger, Gustavo Egea, Ludwig Eichinger, N Tony Eissa, Suhendan Ekmekcioglu, Wafik S El-Deiry, Zvulun Elazar, Mohamed Elgendy, Lisa M Ellerby, Kai Er Eng, Anna-Mart Engelbrecht, Simone Engelender, Jekaterina Erenpreisa, Ricardo Escalante, Audrey Esclatine, Eeva-Liisa Eskelinen, Lucile Espert, Virginia Espina, Huizhou Fan, Jia Fan, Qi-Wen Fan, Zhen Fan, Shengyun Fang, Yongqi Fang, Manolis Fanto, Alessandro Fanzani, Thomas Farkas, Jean-Claude Farré, Mathias Faure, Marcus Fechheimer, Carl G Feng, Jian Feng, Qili Feng, Youji Feng, László Fésüs, Ralph Feuer, Maria E Figueiredo-Pereira, Gian Maria Fimia, Diane C Fingar, Steven Finkbeiner, Toren Finkel, Kim D Finley, Filomena Fiorito, Edward A Fisher, Paul B Fisher, Marc Flajolet, Maria L Florez-McClure, Salvatore Florio, Edward A Fon, Francesco Fornai, Franco Fortunato, Rati Fotedar, Daniel H Fowler, Howard S Fox, Rodrigo Franco, Lisa B Frankel, Marc Fransen, José M Fuentes, Juan Fueyo, Jun Fujii, Kozo Fujisaki, Eriko Fujita, Mitsunori Fukuda, Ruth H Furukawa, Matthias Gaestel, Philippe Gailly, Malgorzata Gajewska, Brigitte Galliot, Vincent Galy, Subramaniam Ganesh, Barry Ganetzky, Ian G Ganley, Fen-Biao Gao, George F Gao, Jinming Gao, Lorena Garcia, Guillermo Garcia-Manero, Mikel Garcia-Marcos, Marjan Garmyn, Andrei L Gartel, Evelina Gatti, Mathias Gautel, Thomas R Gawriluk, Matthew E Gegg, Jiefei Geng, Marc Germain, Jason E Gestwicki, David A Gewirtz, Saeid Ghavami, Pradipta Ghosh, Anna M Giammarioli, Alexandra N Giatromanolaki, Spencer B Gibson, Robert W Gilkerson, Michael L Ginger, Henry N Ginsberg, Jakub Golab, Michael S Goligorsky, Pierre Golstein, Candelaria Gomez-Manzano, Ebru Goncu, Céline Gongora, Claudio D Gonzalez, Ramon Gonzalez, Cristina González-Estévez, Rosa Ana González-Polo, Elena Gonzalez-Rey, Nikolai V Gorbunov, Sharon Gorski, Sandro Goruppi, Roberta A Gottlieb, Devrim Gozuacik, Giovanna Elvira Granato, Gary D Grant, Kim N Green, Aleš Gregorc, Frédéric Gros, Charles Grose, Thomas W Grunt, Philippe Gual, Jun-Lin Guan, Kun-Liang Guan, Sylvie M Guichard, Anna S Gukovskaya, Ilya Gukovsky, Jan Gunst, Asa B Gustafsson, Andrew J Halayko, Amber N Hale, Sandra K Halonen, Maho Hamasaki, Feng Han, Ting Han, Michael K Hancock, Malene Hansen, Hisashi Harada, Masaru Harada, Stefan E Hardt, J Wade Harper, Adrian L Harris, James Harris, Steven D Harris, Makoto Hashimoto, Jeffrey A Haspel, Shin-Ichiro Hayashi, Lori A Hazelhurst, Congcong He, You-Wen He, Marie-Josee Hebert, Kim A Heidenreich, Miep H Helfrich, Gudmundur V Helgason, Elizabeth P Henske, Brian Herman, Paul K Herman, Claudio Hetz, Sabine Hilfiker, Joseph A Hill, Lynne J Hocking, Paul Hofman, Thomas G Hofmann, Jörg Höhfeld, Tessa L Holyoake, Ming-Huang Hong, David A Hood, Gökhan S Hotamisligil, Ewout J Houwerzijl, Maria Høyer-Hansen, Bingren Hu, Chien-An A Hu, Hong-Ming Hu, Ya Hua, Canhua Huang, Ju Huang, Shengbing Huang, Wei-Pang Huang, Tobias B Huber, Won-Ki Huh, Tai-Ho Hung, Ted R Hupp, Gang Min Hur, James B Hurley, Sabah N A Hussain, Patrick J Hussey, Jung Jin Hwang, Seungmin Hwang, Atsuhiro Ichihara, Shirin Ilkhanizadeh, Ken Inoki, Takeshi Into, Valentina Iovane, Juan L Iovanna, Nancy Y Ip, Yoshitaka Isaka, Hiroyuki Ishida, Ciro Isidoro, Ken-Ichi Isobe, Akiko Iwasaki, Marta Izquierdo, Yotaro Izumi, Panu M Jaakkola, Marja Jäättelä, George R Jackson, William T Jackson, Bassam Janji, Marina Jendrach, Ju-Hong Jeon, Eui-Bae Jeung, Hong Jiang, Hongchi Jiang, Jean X Jiang, Ming Jiang, Qing Jiang, Xuejun Jiang, Alberto Jiménez, Meiyan Jin, Shengkan Jin, Cheol O Joe, Terje Johansen, Daniel E Johnson, Gail V W Johnson, Nicola L Jones, Bertrand Joseph, Suresh K Joseph, Annie M Joubert, Gábor Juhász, Lucienne Juillerat-Jeanneret, Chang Hwa Jung, Yong-Keun Jung, Kai Kaarniranta, Allen Kaasik, Tomohiro Kabuta, Motoni Kadowaki, Katarina Kågedal, Yoshiaki Kamada, Vitaliy O Kaminskyy, Harm H Kampinga, Hiromitsu Kanamori, Chanhee Kang, Khong Bee Kang, Kwang Il Kang, Rui Kang, Yoon-A Kang, Tomotake Kanki, Thirumala-Devi Kanneganti, Haruo Kanno, Anumantha G Kanthasamy, Arthi Kanthasamy, Vassiliki Karantza, Gur P Kaushal, Susmita Kaushik, Yoshinori Kawazoe, Po-Yuan Ke, John H Kehrl, Ameeta Kelekar, Claus Kerkhoff, David H Kessel, Hany Khalil, Jan A K W Kiel, Amy A Kiger, Akio Kihara, Deok Ryong Kim, Do-Hyung Kim, Dong-Hou Kim, Eun-Kyoung Kim, Hyung-Ryong Kim, Jae-Sung Kim, Jeong Hun Kim, Jin Cheon Kim, John K Kim, Peter K Kim, Seong Who Kim, Yong-Sun Kim, Yonghyun Kim, Adi Kimchi, Alec C Kimmelman, Jason S King, Timothy J Kinsella, Vladimir Kirkin, Lorrie A Kirshenbaum, Katsuhiko Kitamoto, Kaio Kitazato, Ludger Klein, Walter T Klimecki, Jochen Klucken, Erwin Knecht, Ben C B Ko, Jan C Koch, Hiroshi Koga, Jae-Young Koh, Young Ho Koh, Masato Koike, Masaaki Komatsu, Eiki Kominami, Hee Jeong Kong, Wei-jia Kong, Viktor I Korolchuk, Yaichiro Kotake, Michael I Koukourakis, Juan B Kouri Flores, Attila L Kovács, Claudine Kraft, Dimitri Krainc, Helmut Krämer, Carole Kretz-Remy, Anna M Krichevsky, Guido Kroemer, Rejko Krüger, Oleg Krut, Nicholas T Ktistakis, Chia-Yi Kuan, Róza Kucharczyk, Ashok Kumar, Raj Kumar, Sharad Kumar, Mondira Kundu, Hsing-Jien Kung, Tino Kurz, Ho Jeong Kwon, Albert R La Spada, Frank Lafont, Trond Lamark, Jacques Landry, Jon D Lane, Pierre Lapaquette, Jocelyn F Laporte, Lajos László, Sergio Lavandero, Josée N Lavoie, Robert Layfield, Pedro A Lazo, Weidong Le, Laurent Le Cam, Daniel J Ledbetter, Alvin J X Lee, Byung-Wan Lee, Gyun Min Lee, Jongdae Lee, Ju-Hyun Lee, Michael Lee, Myung-Shik Lee, Sug Hyung Lee, Christiaan Leeuwenburgh, Patrick Legembre, Renaud Legouis, Michael Lehmann, Huan-Yao Lei, Qun-Ying Lei, David A Leib, José Leiro, John J Lemasters, Antoinette Lemoine, Maciej S Lesniak, Dina Lev, Victor V Levenson, Beth Levine, Efrat Levy, Faqiang Li, Jun-lin Li, Lian Li, Sheng Li, Weijie Li, Xue-Jun Li, Yan-Bo Li, Yi-Ping Li, Chengyu Liang, Qiangrong Liang, Yung-Feng Liao, Pawel P Liberski, Andrew Lieberman, Hyunjung J Lim, Kah-Leong Lim, Kyu Lim, Chiou-Feng Lin, Fu-Cheng Lin, Jian Lin, Jiandie D Lin, Kui Lin, Wan-Wan Lin, Weei-Chin Lin, Yi-Ling Lin, Rafael Linden, Paul Lingor, Jennifer Lippincott-Schwartz, Michael P Lisanti, Paloma B Liton, Bo Liu, Chun-Feng Liu, Kaiyu Liu, Leyuan Liu, Qiong A Liu, Wei Liu, Young-Chau Liu, Yule Liu, Richard A Lockshin, Chun-Nam Lok, Sagar Lonial, Benjamin Loos, Gabriel Lopez-Berestein, Carlos Lopez-Otin, Laura Lossi, Michael T Lotze, Péter Low, Binfeng Lu, Bingwei Lu, Bo Lu, Zhen Lu, Fredéric Luciano, Nicholas W Lukacs, Anders H Lund, Melinda A Lynch-Day, Yong Ma, Fernando Macian, Jeff P MacKeigan, Kay F Macleod, Frank Madeo, Luigi Maiuri, Maria Chiara Maiuri, Davide Malagoli, May Christine V Malicdan, Walter Malorni, Na Man, Eva-Maria Mandelkow, Stéphen Manon, Irena Manov, Kai Mao, Xiang Mao, Zixu Mao, Philippe Marambaud, Daniela Marazziti, Yves L Marcel, Katie Marchbank, Piero Marchetti, Stefan J Marciniak, Mateus Marcondes, Mohsen Mardi, Gabriella Marfè, Guillermo Mariño, Maria Markaki, Mark R Marten, Seamus J Martin, Camille Martinand-Mari, Wim Martinet, Marta Martinez-Vicente, Matilde Masini, Paola Matarrese, Saburo Matsuo, Raffaele Matteoni, Andreas Mayer, Nathalie M Mazure, David J McConkey, Melanie J McConnell, Catherine McDermott, Christine McDonald, Gerald M McInerney, Sharon L McKenna, BethAnn McLaughlin, Pamela J McLean, Christopher R McMaster, G Angus McQuibban, Alfred J Meijer, Miriam H Meisler, Alicia Meléndez, Thomas J Melia, Gerry Melino, Maria A Mena, Javier A Menendez, Rubem F S Menna-Barreto, Manoj B Menon, Fiona M Menzies, Carol A Mercer, Adalberto Merighi, Diane E Merry, Stefania Meschini, Christian G Meyer, Thomas F Meyer, Chao-Yu Miao, Jun-Ying Miao, Paul A M Michels, Carine Michiels, Dalibor Mijaljica, Ana Milojkovic, Saverio Minucci, Clelia Miracco, Cindy K Miranti, Ioannis Mitroulis, Keisuke Miyazawa, Noboru Mizushima, Baharia Mograbi, Simin Mohseni, Xavier Molero, Bertrand Mollereau, Faustino Mollinedo, Takashi Momoi, Iryna Monastyrska, Martha M Monick, Mervyn J Monteiro, Michael N Moore, Rodrigo Mora, Kevin Moreau, Paula I Moreira, Yuji Moriyasu, Jorge Moscat, Serge Mostowy, Jeremy C Mottram, Tomasz Motyl, Charbel E-H Moussa, Sylke Müller, Sylviane Muller, Karl Münger, Christian Münz, Leon O Murphy, Maureen E Murphy, Antonio Musarò, Indira Mysorekar, Eiichiro Nagata, Kazuhiro Nagata, Aimable Nahimana, Usha Nair, Toshiyuki Nakagawa, Kiichi Nakahira, Hiroyasu Nakano, Hitoshi Nakatogawa, Meera Nanjundan, Naweed I Naqvi, Derek P Narendra, Masashi Narita, Miguel Navarro, Steffan T Nawrocki, Taras Y Nazarko, Andriy Nemchenko, Mihai G Netea, Thomas P Neufeld, Paul A Ney, Ioannis P Nezis, Huu Phuc Nguyen, Daotai Nie, Ichizo Nishino, Corey Nislow, Ralph A Nixon, Takeshi Noda, Angelika A Noegel, Anna Nogalska, Satoru Noguchi, Lucia Notterpek, Ivana Novak, Tomoyoshi Nozaki, Nobuyuki Nukina, Thorsten Nürnberger, Beat Nyfeler, Keisuke Obara, Terry D Oberley, Salvatore Oddo, Michinaga Ogawa, Toya Ohashi, Koji Okamoto, Nancy L Oleinick, F Javier Oliver, Laura J Olsen, Stefan Olsson, Onya Opota, Timothy F Osborne, Gary K Ostrander, Kinya Otsu, Jing-hsiung James Ou, Mireille Ouimet, Michael Overholtzer, Bulent Ozpolat, Paolo Paganetti, Ugo Pagnini, Nicolas Pallet, Glen E Palmer, Camilla Palumbo, Tianhong Pan, Theocharis Panaretakis, Udai Bhan Pandey, Zuzana Papackova, Issidora Papassideri, Irmgard Paris, Junsoo Park, Ohkmae K Park, Jan B Parys, Katherine R Parzych, Susann Patschan, Cam Patterson, Sophie Pattingre, John M Pawelek, Jianxin Peng, David H Perlmutter, Ida Perrotta, George Perry, Shazib Pervaiz, Matthias Peter, Godefridus J Peters, Morten Petersen, Goran Petrovski, James M Phang, Mauro Piacentini, Philippe Pierre, Valérie Pierrefite-Carle, Gérard Pierron, Ronit Pinkas-Kramarski, Antonio Piras, Natik Piri, Leonidas C Platanias, Stefanie Pöggeler, Marc Poirot, Angelo Poletti, Christian Poüs, Mercedes Pozuelo-Rubio, Mette Prætorius-Ibba, Anil Prasad, Mark Prescott, Muriel Priault, Nathalie Produit-Zengaffinen, Ann Progulske-Fox, Tassula Proikas-Cezanne, Serge Przedborski, Karin Przyklenk, Rosa Puertollano, Julien Puyal, Shu-Bing Qian, Liang Qin, Zheng-Hong Qin, Susan E Quaggin, Nina Raben, Hannah Rabinowich, Simon W Rabkin, Irfan Rahman, Abdelhaq Rami, Georg Ramm, Glenn Randall, Felix Randow, V Ashutosh Rao, Jeffrey C Rathmell, Brinda Ravikumar, Swapan K Ray, Bruce H Reed, John C Reed, Fulvio Reggiori, Anne Regnier-Vigouroux, Andreas S Reichert, John J Reiners, Russel J Reiter, Jun Ren, Jose L Revuelta, Christopher J Rhodes, Konstantinos Ritis, Elizete Rizzo, Jeffrey Robbins, Michel Roberge, Hernan Roca, Maria C Roccheri, Stéphane Rocchi, H Peter Rodemann, Santiago Rodríguez de Córdoba, Bärbel Rohrer, Igor B Roninson, Kirill Rosen, Magdalena M Rost-Roszkowska, Mustapha Rouis, Kasper M A Rouschop, Francesca Rovetta, Brian P Rubin, David C Rubinsztein, Klaus Ruckdeschel, Edmund B Rucker, Assaf Rudich, Emil Rudolf, Nelson Ruiz-Opazo, Rossella Russo, Tor Erik Rusten, Kevin M Ryan, Stefan W Ryter, David M Sabatini, Junichi Sadoshima, Tapas Saha, Tatsuya Saitoh, Hiroshi Sakagami, Yasuyoshi Sakai, Ghasem Hoseini Salekdeh, Paolo Salomoni, Paul M Salvaterra, Guy Salvesen, Rosa Salvioli, Anthony M J Sanchez, José A Sánchez-Alcázar, Ricardo Sánchez-Prieto, Marco Sandri, Uma Sankar, Poonam Sansanwal, Laura Santambrogio, Shweta Saran, Sovan Sarkar, Minnie Sarwal, Chihiro Sasakawa, Ausra Sasnauskiene, Miklós Sass, Ken Sato, Miyuki Sato, Anthony H V Schapira, Michael Scharl, Hermann M Schätzl, Wiep Scheper, Stefano Schiaffino, Claudio Schneider, Marion E Schneider, Regine Schneider-Stock, Patricia V Schoenlein, Daniel F Schorderet, Christoph Schüller, Gary K Schwartz, Luca Scorrano, Linda Sealy, Per O Seglen, Juan Segura-Aguilar, Iban Seiliez, Oleksandr Seleverstov, Christian Sell, Jong Bok Seo, Duska Separovic, Vijayasaradhi Setaluri, Takao Setoguchi, Carmine Settembre, John J Shacka, Mala Shanmugam, Irving M Shapiro, Eitan Shaulian, Reuben J Shaw, James H Shelhamer, Han-Ming Shen, Wei-Chiang Shen, Zu-Hang Sheng, Yang Shi, Kenichi Shibuya, Yoshihiro Shidoji, Jeng-Jer Shieh, Chwen-Ming Shih, Yohta Shimada, Shigeomi Shimizu, Takahiro Shintani, Orian S Shirihai, Gordon C Shore, Andriy A Sibirny, Stan B Sidhu, Beata Sikorska, Elaine C M Silva-Zacarin, Alison Simmons, Anna Katharina Simon, Hans-Uwe Simon, Cristiano Simone, Anne Simonsen, David A Sinclair, Rajat Singh, Debasish Sinha, Frank A Sinicrope, Agnieszka Sirko, Parco M Siu, Efthimios Sivridis, Vojtech Skop, Vladimir P Skulachev, Ruth S Slack, Soraya S Smaili, Duncan R Smith, María S Soengas, Thierry Soldati, Xueqin Song, Anil K Sood, Tuck Wah Soong, Federica Sotgia, Stephen A Spector, Claudia D Spies, Wolfdieter Springer, Srinivasa M Srinivasula, Leonidas Stefanis, Joan S Steffan, Ruediger Stendel, Harald Stenmark, Anastasis Stephanou, Stephan T Stern, Cinthya Sternberg, Björn Stork, Peter Stralfors, Carlos S Subauste, Xinbing Sui, David Sulzer, Jiaren Sun, Shi-Yong Sun, Zhi-Jun Sun, Joseph J Y Sung, Kuninori Suzuki, Toshihiko Suzuki, Michele S Swanson, Charles Swanton, Sean T Sweeney, Lai-King Sy, Gyorgy Szabadkai, Ira Tabas, Heinrich Taegtmeyer, Marco Tafani, Krisztina Takács-Vellai, Yoshitaka Takano, Kaoru Takegawa, Genzou Takemura, Fumihiko Takeshita, Nicholas J Talbot, Kevin S W Tan, Keiji Tanaka, Kozo Tanaka, Daolin Tang, Dingzhong Tang, Isei Tanida, Bakhos A Tannous, Nektarios Tavernarakis, Graham S Taylor, Gregory A Taylor, J Paul Taylor, Lance S Terada, Alexei Terman, Gianluca Tettamanti, Karin Thevissen, Craig B Thompson, Andrew Thorburn, Michael Thumm, Fengfeng Tian, Yuan Tian, Glauco Tocchini-Valentini, Aviva M Tolkovsky, Yasuhiko Tomino, Lars Tönges, Sharon A Tooze, Cathy Tournier, John Tower, Roberto Towns, Vladimir Trajkovic, Leonardo H Travassos, Ting-Fen Tsai, Mario P Tschan, Takeshi Tsubata, Allan Tsung, Boris Turk, Lorianne S Turner, Suresh C Tyagi, Yasuo Uchiyama, Takashi Ueno, Midori Umekawa, Rika Umemiya-Shirafuji, Vivek K Unni, Maria I Vaccaro, Enza Maria Valente, Greet Van den Berghe, Ida J van der Klei, Wouter van Doorn, Linda F van Dyk, Marjolein van Egmond, Leo A van Grunsven, Peter Vandenabeele, Wim P Vandenberghe, Ilse Vanhorebeek, Eva C Vaquero, Guillermo Velasco, Tibor Vellai, Jose Miguel Vicencio, Richard D Vierstra, Miquel Vila, Cécile Vindis, Giampietro Viola, Maria Teresa Viscomi, Olga V Voitsekhovskaja, Clarissa von Haefen, Marcela Votruba, Keiji Wada, Richard Wade-Martins, Cheryl L Walker, Craig M Walsh, Jochen Walter, Xiang-Bo Wan, Aimin Wang, Chenguang Wang, Dawei Wang, Fan Wang, Fen Wang, Guanghui Wang, Haichao Wang, Hong-Gang Wang, Horng-Dar Wang, Jin Wang, Ke Wang, Mei Wang, Richard C Wang, Xinglong Wang, Xuejun Wang, Ying-Jan Wang, Yipeng Wang, Zhen Wang, Zhigang Charles Wang, Zhinong Wang, Derick G Wansink, Diane M Ward, Hirotaka Watada, Sarah L Waters, Paul Webster, Lixin Wei, Conrad C Weihl, William A Weiss, Scott M Welford, Long-Ping Wen, Caroline A Whitehouse, J Lindsay Whitton, Alexander J Whitworth, Tom Wileman, John W Wiley, Simon Wilkinson, Dieter Willbold, Roger L Williams, Peter R Williamson, Bradly G Wouters, Chenghan Wu, Dao-Cheng Wu, William K K Wu, Andreas Wyttenbach, Ramnik J Xavier, Zhijun Xi, Pu Xia, Gengfu Xiao, Zhiping Xie, Zhonglin Xie, Da-zhi Xu, Jianzhen Xu, Liang Xu, Xiaolei Xu, Ai Yamamoto, Akitsugu Yamamoto, Shunhei Yamashina, Michiaki Yamashita, Xianghua Yan, Mitsuhiro Yanagida, Dun-Sheng Yang, Elizabeth Yang, Jin-Ming Yang, Shi Yu Yang, Wannian Yang, Wei Yuan Yang, Zhifen Yang, Meng-Chao Yao, Tso-Pang Yao, Behzad Yeganeh, Wei-Lien Yen, Jia-Jing Yin, Xiao-Ming Yin, Ook-Joon Yoo, Gyesoon Yoon, Seung-Yong Yoon, Tomohiro Yorimitsu, Yuko Yoshikawa, Tamotsu Yoshimori, Kohki Yoshimoto, Ho Jin You, Richard J Youle, Anas Younes, Li Yu, Long Yu, Seong-Woon Yu, Wai Haung Yu, Zhi-Min Yuan, Zhenyu Yue, Cheol-Heui Yun, Michisuke Yuzaki, Olga Zabirnyk, Elaine Silva-Zacarin, David Zacks, Eldad Zacksenhaus, Nadia Zaffaroni, Zahra Zakeri, Herbert J Zeh, Scott O Zeitlin, Hong Zhang, Hui-Ling Zhang, Jianhua Zhang, Jing-Pu Zhang, Lin Zhang, Long Zhang, Ming-Yong Zhang, Xu Dong Zhang, Mantong Zhao, Yi-Fang Zhao, Ying Zhao, Zhizhuang J Zhao, Xiaoxiang Zheng, Boris Zhivotovsky, Qing Zhong, Cong-Zhao Zhou, Changlian Zhu, Wei-Guo Zhu, Xiao-feng Zhu, Xiongwei Zhu, Yuangang Zhu, Teresa Zoladek, Wei-Xing Zong, Antonio Zorzano, Jürgen Zschocke, Brian Zuckerbraun.
Autophagy
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In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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Impact of lysophosphatidylcholine on the plasminogen activator system in cultured vascular smooth muscle cells.
J. Korean Med. Sci.
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The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-?B, blocked this lysoPC effect. Indeed, lysoPC induced the NF-?B-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-?B and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.
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Factors associated with sexual debut during adolescence in the Republic of Korea.
Sex Transm Infect
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To investigate the factors associated with sexual debut among Korean adolescents.
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Association between cognitive impairment and bone mineral density in postmenopausal women.
Menopause
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This study estimated an association between cognitive impairment and bone mineral density (BMD), a surrogate marker for cumulative estrogen exposure.
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