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olmesartan
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Wang Y
Zhang S
Nakao K
Zhang Y
Kanie O
Lee SJ
Wang C
Asanuma T
Zhao L
Cheng CY

Is the suicide rate related to increased rates of mining and industrial production in Australia?

Fujita Y , Inoue K , Nata M , Miyazawa T , Inoue T

West Indian Med J.2009 Jan ; 58(1):77-8.

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PMID: 19569265 [PubMed - indexed for MEDLINE]

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The type Ia supernova SNLS-03D3bb from a super-Chandrasekhar-mass white dwarf star.

Howell D Andrew , Sullivan Mark , Nugent Peter E , Ellis Richard S , Conley Alexander J , Le Borgne Damien , Carlberg Raymond G , Guy Julien , Balam David , Basa Stephane , Fouchez Dominique , Hook Isobel M , Hsiao Eric Y , Neill James D , Pain Reynald , Perrett Kathryn M , Pritchet Christopher J
Nature.2006 Sep 21 ; 443(7109):308-11.
PMID: 16988705[]

先週： 3位

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The accelerating expansion of the Universe, and the need for dark energy, were inferred from observations of type Ia supernovae. There is a consensus that type Ia supernovae are thermonuclear explosions that destroy carbon-oxygen white dwarf stars that have accreted matter from a companion star, although the nature of this companion remains uncertain. These supernovae are thought to be reliable distance indicators because they have a standard amount of fuel and a uniform trigger: they are predicted to explode when the mass of the white dwarf nears the Chandrasekhar mass of 1.4 solar masses (M(o)). Here we show that the high-redshift supernova SNLS-03D3bb has an exceptionally high luminosity and low kinetic energy that both imply a super-Chandrasekhar-mass progenitor. Super-Chandrasekhar-mass supernovae should occur preferentially in a young stellar population, so this may provide an explanation for the observed trend that overluminous type Ia supernovae occur only in 'young' environments. As this supernova does not obey the relations that allow type Ia supernovae to be calibrated as standard candles, and as no counterparts have been found at low redshift, future cosmology studies will have to consider possible contamination from such events.

2',5,7-Trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone purified from Cudrania tricuspidata induces apoptotic cell death of human leukemia U937 cells.

Rho Yoon-Hwa , Yoon Soo-Hyun , Kim Eun-Kyung , Kang Ji-Young , Lee Byong-Won , Park Ki-Hun , Bae Young-Seuk
Nat Prod Res.2007 Jun ; 21(7):616-24.
PMID: 17613819[]

先週： 2位

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Cellular DNA topoisomerase I is an important target in cancer chemotherapy. A chloroform extract of the root barks of Cudrania tricuspidata showed an inhibitory effect on mammalian DNA topoisomerase I. The topoisomerase I inhibitory compound was purified and identified as 2',5,7-trihydroxy-4',5'-(2,2-dimethylchromeno)-8-(3-hydroxy-3-methylbutyl) flavanone. The compound, temporarily designated as PKH-3, was shown to inhibit the activity of topoisomerase I with IC50 about 1.0 mM. Concentration of 10 microM PKH-3 caused 50% growth inhibition of human cancer cell U937. PKH-3-induced cell death was characterized with the cleavage of poly(ADP-ribose) polymerase (PARP) and pro-caspase 3. Furthermore, PKH-3 induced the fragmentation of DNA into multiples of 180 b.p. (an apoptotic DNA ladder), indicating that the inhibitor triggered apoptosis. This induction of apoptosis by PKH-3 was also confirmed using flow cytometry analysis. Taken together, these results suggest that PKH-3 may function by inhibiting oncogenic disease, at least in part, through the inhibition of topoisomerase I activity.

Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements.

Lepper Christoph , Conway Simon J , Fan Chen-Ming
Nature.2009 Jul 30 ; 460(7255):627-31.
PMID: 19554048[]

先週： 1位

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Myogenic potential, survival and expansion of mammalian muscle progenitors depend on the myogenic determinants Pax3 and Pax7 embryonically, and Pax7 alone perinatally. Several in vitro studies support the critical role of Pax7 in these functions of adult muscle stem cells (satellite cells), but a formal demonstration has been lacking in vivo. Here we show, through the application of inducible Cre/loxP lineage tracing and conditional gene inactivation to the tibialis anterior muscle regeneration paradigm, that, unexpectedly, when Pax7 is inactivated in adult mice, mutant satellite cells are not compromised in muscle regeneration, they can proliferate and reoccupy the sublaminal satellite niche, and they are able to support further regenerative processes. Dual adult inactivation of Pax3 and Pax7 also results in normal muscle regeneration. Multiple time points of gene inactivation reveal that Pax7 is only required up to the juvenile period when progenitor cells make the transition into quiescence. Furthermore, we demonstrate a cell-intrinsic difference between neonatal progenitor and adult satellite cells in their Pax7-dependency. Our finding of an age-dependent change in the genetic requirement for muscle stem cells cautions against inferring adult stem-cell biology from embryonic studies, and has direct implications for the use of stem cells from hosts of different ages in transplantation-based therapy.

Effects of olmesartan, an angiotensin II receptor blocker, and amlodipine, a calcium channel blocker, on Cardio-Ankle Vascular Index (CAVI) in type 2 diabetic patients with hypertension.

Miyashita Yoh , Saiki Atsuhito , Endo Kei , Ban Noriko , Yamaguchi Takashi , Kawana Hidetoshi , Nagayama Daiji , Ohira Masahiro , Oyama Tomokazu , Shirai Kohji
J Atheroscler Thromb.2009 Oct ; 16(5):621-6.
PMID: 19907103[]

先週： 5位

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AIM: Recently, a novel device for measuring the cardio-ankle vascular index (CAVI) as an arterial stiffness parameter has been developed. In this study, we evaluated the effect of angiotensin II receptor blocker (ARB) and calcium channel (Ca) blocker on CAVI in type 2 diabetic patients with hypertension.METHODS: Seventy type 2 diabetes mellitus patients with hypertension were enrolled and randomly divided into two groups. One group was administered olmesartan medoxomil 10 mg/day for 12 months (ARB group), and the other group was administered amlodipine besilate 5 mg/day for 12 months (Ca blocker group).RESULTS: In the ARB group, a significant decrease in CAVI was observed after 12 months; however, no significant change in CAVI was observed in the Ca blocker group although changes in blood pressure were almost the same. By simple regression analyses, CAVI changes correlated positively with 8-OHdG changes.CONCLUSIONS: Olmesartan, an ARB, improved arterial stiffness more than amlodipine, and this effect might be due to not only the blood pressure-lowering effect but also to reducing the potential of oxidative stress recognized in olmesartan.

A novel GSK-3beta inhibitor reduces Alzheimer's pathology and rescues neuronal loss in vivo.

Serenó L , Coma M , Rodríguez M , Sánchez-Ferrer P , Sánchez M B , Gich I , Agulló J M , Pérez M , Avila J , Guardia-Laguarta C , Clarimón J , Lleó A , Gómez-Isla T
Neurobiol Dis.2009 Sep ; 35(3):359-67.
PMID: 19523516[]

先週： 6位

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Amyloid deposits, neurofibrillary tangles, and neuronal cell death in selectively vulnerable brain regions are the chief hallmarks in Alzheimer's (AD) brains. Glycogen synthase kinase-3 (GSK-3) is one of the key kinases required for AD-type abnormal hyperphosphorylation of tau, which is believed to be a critical event in neurofibrillary tangle formation. GSK-3 has also been recently implicated in amyloid precursor protein (APP) processing/Abeta production, apoptotic cell death, and learning and memory. Thus, GSK-3 inhibition represents a very attractive drug target in AD and other neurodegenerative disorders. To investigate whether GSK-3 inhibition can reduce amyloid and tau pathologies, neuronal cell death and memory deficits in vivo, double transgenic mice coexpressing human mutant APP and tau were treated with a novel non-ATP competitive GSK-3beta inhibitor, NP12. Treatment with this thiadiazolidinone compound resulted in lower levels of tau phosphorylation, decreased amyloid deposition and plaque-associated astrocytic proliferation, protection of neurons in the entorhinal cortex and CA1 hippocampal subfield against cell death, and prevention of memory deficits in this transgenic mouse model. These results show that this novel GSK-3 inhibitor has a dual impact on amyloid and tau alterations and, perhaps even more important, on neuronal survival in vivo further suggesting that GSK-3 is a relevant therapeutic target in AD.

RORgamma-expressing Th17 cells induce murine chronic intestinal inflammation via redundant effects of IL-17A and IL-17F.

Leppkes Moritz , Becker Christoph , Ivanov Ivaylo I , Hirth Sebastian , Wirtz Stefan , Neufert Clemens , Pouly Sandrine , Murphy Andrew J , Valenzuela David M , Yancopoulos George D , Becher Burkhard , Littman Dan R , Neurath Markus F
Gastroenterology.2009 Jan ; 136(1):257-67.
PMID: 18992745[]

先週： 4位

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BACKGROUND AND AIMS: IL-17-producing CD4(+) T-helper cells (Th17) contribute to chronic autoimmune inflammation in the brain, and levels of Th17-derived cytokines increase in patients with colitis, suggesting a role in pathogenesis. We analyzed the roles of Th17 cells and the transcription factor retinoic acid receptor-related organ receptor (ROR)gamma, which regulates Th17 differentiation, in chronic intestinal inflammation. METHODS: Using an adoptive transfer model of colitis, we compared the colitogenic potential of wild-type, interleukin-17A (IL-17A)-, IL-17F-, IL-22-, and RORgamma-deficient CD4(+)CD25(-) T cells in RAG1-null mice. RESULTS: Adoptive transfer of IL-17A-, IL-17F-, or IL-22-deficient T lymphocytes into RAG1-null mice caused severe colitis that was indistinguishable from that caused by wild-type cells. In contrast, transfer of RORgamma-null T cells failed to increase mucosal IL-17 cytokine levels and did not induce colitis. Treatment with IL-17A was able to restore colitis after transfer of RORgamma-null T cells, indicating a crucial role for Th17 cells in pathogenesis. Treatment of RAG1 mice that received IL-17F-null (but not wild-type) T cells with a neutralizing anti-IL-17A antibody significantly suppressed disease, indicating redundant biological effects of IL-17A and IL-17F. CONCLUSIONS: We have identified a crucial role of RORgamma-expressing Th17 cells in chronic intestinal inflammation. RORgamma controls IL-17A and IL-17F production, and these cytokines have a redundant but highly pathogenic role in gut inflammation. Reagents that target RORgamma or a combination of anti-IL-17A and anti-IL-17F might be developed as therapeutics for chronic colitis.

IL-17A versus IL-17F induced intracellular signal transduction pathways and modulation by IL-17RA and IL-17RC RNA interference in AGS gastric adenocarcinoma cells.

Zhou Yuan , Toh Myew-Ling , Zrioual Saloua , Miossec Pierre
Cytokine.2007 Jun ; 38(3):157-64.
PMID: 17644350[]

先週： 7位

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Inflammatory processes are implicated in gastric cancer development. In contrast, the role of inflammation and proinflammatory cytokines in established cancer remains to be clarified. We investigated the contribution of IL-17A versus IL-17F-mediated intracellular signalling pathways in human gastric adenocarcinoma AGS cells. IL-8 secretion was evaluated by ELISA, mitogen-activated protein kinase (MAPK)(4) by Western blotting, and activator protein 1(AP-1) and nuclear factor kappa B (NFkappaB) by TransAM transcription factor assay or qRT-PCR. IL-17RA and IL-17RC inhibition were achieved by small interfering RNA (siRNA). IL-17A significantly induced activation of all three MAPK (ERK, p38 and JNK) and downstream transcription factors AP-1 and p65 NFkappaB. IL-17F was less potent but induced a significant activation of p65 NFkappaB. Consistently, IL-17A was more potent to induce IL-8 secretion than IL-17F. Inhibition of either IL-17RA or IL-17RC expression via siRNA led to near complete abrogation of IL-17A-mediated c-Jun and p65 activation. These data suggest that in gastric cancer, absence of either IL-17RA or IL-17RC can inhibit IL-17 responsiveness. Conversely, downstream of IL-17R binding, IL-17A and IL-17F induce key signal transduction pathways implicated in inflammation and carcinogenesis. IL-17A, and possibly IL-17F, may contribute to amplification and persistence of inflammatory processes implicated in inflammation-associated cancer.

Effect of valsartan or olmesartan addition to amlodipine on ankle edema in hypertensive patients.

Fogari Roberto , Malamani Gian , Corradi Luca , Mugellini Amedeo , Preti Paola , Zoppi Annalisa , Derosa Giuseppe
Adv Ther.2010 Feb 19 ; ():.
PMID: 20174905[]

先週： 8位

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INTRODUCTION: The objective of this study was to compare the effect on ankle edema of adding valsartan (V) or olmesartan (O) to amlodipine (A) in the treatment of hypertension. METHODS: After a 4-week placebo period, 74 adult outpatients with essential hypertension (diastolic blood pressure [DBP] >90 and <110 mmHg, and systolic blood pressure [SBP] >140 mmHg) were treated with A 10 mg once daily for 4 weeks. Thereafter, nonresponder patients (DBP >90 mmHg and/or SBP >140 mmHg; n=51) were randomized to receive additional V 160 mg once daily or O 20 mg once daily for 8 weeks in two crossover periods, each separated by a 4-week placebo period. Clinic blood pressure (BP), heart rate, and ankle/foot volume (AFV) were evaluated and blood samples were drawn to evaluate plasma norepinephrine (NE) levels. RESULTS: Both V/A and O/A induced a greater SBP/DBP reduction than A monotherapy (-26.4/-20.8 mmHg and -24.4/-19.1 mmHg, respectively; all P<0.001 vs. baseline and P<0.01 vs. A). A monotherapy increased AFV by 24%, P<0.001 vs. baseline, while the addition of either V or A reduced such increases. However, with V/A the AFV increase (+9.7%, P<0.05 vs. baseline, P<0.01 vs. A) was lower than with O/A (+16.7%, P<0.01 vs. baseline, P<0.05 vs. A); the difference between the two combinations was significant. Plasma NE levels were significantly increased by A (+44.6%) and values did not change with the addition of V (+35.2%) or O (+33.7%). Plasma active renin (PAR) was unchanged by A but increased by V/A (+214.4%, P<0.05 vs. baseline) and further by O/A (+325.6%, P<0.01 vs. baseline; difference between the 2 combinations: P<0.05). An inverse correlation was found between the AFV decrease and PAR increase (r=-0.31, P<0.05). CONCLUSION: Adding V or O to A reduced ankle edema, but this effect was more pronounced with V. The greater degree of renin-angiotensin system activation observed with Ocould be related to such a difference.

Trypanocidal diarylheptanoids from Aframomum letestuianum.

Kamnaing Pierre , Tsopmo Apollinaire , Tanifum Eric A , Tchuendem Marguerite H K , Tane Pierre , Ayafor Johnson F , Sterner Olov , Rattendi Donna , Iwu Maurice M , Schuster Brian , Bacchi Cyrus
J Nat Prod.2003 Mar ; 66(3):364-7.
PMID: 12662093[]

先週： 9位

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Three new diarylheptanoids, (4Z,6E)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)hepta-4,6-dien-3-one, letestuianin A (1), (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-4,6-dien-3-one, letestuianin B (2), and 1,7-bis(4-hydroxyphenyl)heptan-3,5-dione, letestuianin C (3), as well as the known (4Z,6E)-5-hydroxy-1,7-bis(4-hydroxyphenyl)hepta-4,6-dien-3-one (5) were isolated from Aframomum letestuianum. The known flavonoids 3-acetoxy-5,7,4'-trihydroxyflavanone, 3-acetoxy-7-methoxy-5,4'-dihydroxyflavanone, 7-methoxy-3,5,4'-trihydroxyflavone, and 3,3',4',5,7-pentahydroxyflavan were also obtained from this plant. Their structures were determined using a combination of 1D and 2D NMR techniques. The four diarylheptanoids were tested for growth inhibitory activity in vitro versus bloodstream forms of African trypanosomes. IC(50) values in the range of 1-3 microg/mL were found for compounds 3 and 5.

A randomized, double-blind, four-arm parallel-group study of the efficacy and safety of azelnidipine and olmesartan medoxomil combination therapy compared with each monotherapy in Japanese patients with essential hypertension: the REZALT study.

Hypertens Res.2009 Oct 9 ; ():.
PMID: 19816505[]

先週： 18位

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A 12-week randomized, double-blind, four-arm parallel-group, comparative study was conducted in patients with essential hypertension to evaluate the antihypertensive effect and safety of combination therapy with olmesartan medoxomil (OLM, an angiotensin-receptor blocker) 20 mg plus azelnidipine (AZL, a long-acting dihydropyridine calcium channel blocker) 16 mg, (O/A (20/16)), or OLM 10 mg/AZL 8 mg (O/A (10/8)) compared with those of monotherapy with OLM 20 mg (OLM (20)) or AZL 16 mg (AZL (16)). The change from baseline to week 12 in seated blood pressure (SeBP) was -23.6/-14.2 mm Hg (systolic/diastolic BP) in the O/A (20/16) group, and -20.3/-13.0 mm Hg in the O/A (10/8) group, which was a significantly greater reduction in SeBP than in the monotherapy groups (-15.7/-9.9 mm Hg in OLM (20); -15.0/-9.4 mm Hg in AZL (16)). The change from baseline in 24-h ambulatory BP was also significantly greater in the O/A (20/16) and O/A (10/8) combination groups (-22.1/-13.5 and -18.2/-10.6 mm Hg, respectively) than in the OLM (20) and AZL (16) monotherapy groups (-12.1/-6.9 and -12.0/-6.9 mm Hg). The proportion of patients achieving the SeBP goal (<130/85 mm Hg for normal BP or <140/90 mm Hg for high-normal BP) was significantly higher in the O/A (20/16) combination group than in the monotherapy groups. The incidence of adverse events was similar in the O/A combination groups and the monotherapy groups. These results showed that combination therapy with O/A was well tolerated and exerted a stronger antihypertensive effect compared with monotherapy with OLM or AZL in patients with essential hypertension.Hypertension Research advance online publication, 9 October 2009; doi:10.1038/hr.2009.163.

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A randomized, double-blind, four-arm parallel-group study of the efficacy and safety of azelnidipine and olmesartan medoxomil combination therapy compared with each monotherapy in Japanese patients with essential hypertension: the REZALT study.

Hypertens Res.2009 Oct 9 ; ():.
PMID: 19816505[]

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Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension.

Hypertens Res.2009 Nov 20 ; ():.
PMID: 19927151[]

先週： 2位

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In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB.A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n=25): continuous candesartan treatment at a stable dose; and olmesartan group (n=25): candesartan (8 mg day(-1)) was changed to olmesartan given at a dose of 20 mg day(-1). There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135+/-36 vs. 123+/-29 g m(-2); P<0.01).These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.Hypertension Research advance online publication, 20 November 2009; doi:10.1038/hr.2009.192.

The differentiation of rat adipose-derived stem cells into OEC-like cells on collagen scaffolds by co-culturing with OECs.

Wang Bin , Han Jin , Gao Yuan , Xiao Zhifeng , Chen Bing , Wang Xia , Zhao Wenxue , Dai Jianwu
Neurosci Lett.2007 Jun 29 ; 421(3):191-6.
PMID: 17574753[]

先週： 3位

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Olfactory ensheathing cells (OECs) transplantation is a promising or potential therapy for spinal cord injury (SCI). However, their clinical use is limited because of the availability. Adipose-derived stem cells (ADSCs) have been identified as an alternative source of adult stem cells in recent years. ADSCs could be differentiated into various mesenchymal tissues cells such as chondrocytes, adipocytes, osteoblasts, and myocytes and also could be differentiated into neural lineages. In this study, we examined the feasibility of using ADSCs as a source of stem cells for the differentiation of OECs by co-culture approach. When co-cultured with OECs, the ADSCs on three-dimensional collagen scaffolds were differentiated into OEC-like cells, with similar morphology and antigenic phenotypes (p75NTR+/Nestin+/GFAP-) of OECs. Co-cultured ADSCs were positive for several important functional markers of mature OECs such as neurotrophic factor GDNF, BDNF and myelin protein PLP and the conditioned medium of OEC-like cells could significantly promote DRG neuron growth and axon sprouting without NGF supporting in contrast to that of the ADSCs. Our results showed that ADSCs had the potential to differentiate into OEC-like cells on the three-dimensional collagen scaffolds in vitro.

Blood pressure goal achievement with olmesartan medoxomil-based treatment: additional analysis of the OLMEBEST study.

Barrios Vivencio , Escobar Carlos , Calderon Alberto , Böhm Michael
Vasc Health Risk Manag.2009 ; 5():723-9.
PMID: 19756164[]

先週： 4位

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AIMS: Guidelines recommend blood pressure (BP) in hypertensive patients should be <140 systolic BP (SBP) and <90 diastolic BP (DBP) mmHg. This analysis assessed goal rate achievement in hypertensive patients receiving olmesartan-based treatment in the OLMEBEST study. METHODS: Patients with essential hypertension (DBP > or = 90 mmHg and <110 mmHg) received open-label olmesartan medoxomil 20 mg/day (n = 2306). After 8 weeks, patients with DBP > or = 90 mmHg (n = 627) were randomized to 4 weeks' double-blind treatment with olmesartan 40 mg/day monotherapy or olmesartan 20 mg/day plus hydrochlorothiazide (HCTZ) 12.5 mg/day. For this analysis, the numbers and proportions of patients who achieved SBP < 140 mmHg and/or DBP < 90 mmHg at the end of the 4 weeks were calculated. RESULTS: In patients who achieved DBP normalization (<90 mmHg) at week 8 (n = 1546) and continued open-label olmesartan 20 mg/day, 66.7% achieved SBP/DBP < 140/90 mmHg at Week 12. In patients who did not achieve DBP normalization at Week 8, 26.8% of those randomized to olmesartan 40 mg/day and 42.5% of those randomized to olmesartan 20 mg/day plus HCTZ 12.5 mg/day achieved a SBP/DBP < 140/90 mmHg at Week 12. CONCLUSION: Olmesartan 40 mg/day and olmesartan 20 mg/day plus HCTZ 12.5 mg/day allow substantial proportions of patients to achieve BP goals.

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior.

Mol Psychiatry.2009 Oct 27 ; ():.
PMID: 19859069[]

先週： 5位

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Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential candidates for treatment of neurodegenerative disorders, because of their ability to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural lineages as well as by expressing neurotrophic factors that enhance the survival and differentiation of neural progenitor cells. Depression has been associated with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the aim of this study was to analyze the therapeutic potential of MSCs in the Flinders sensitive line (FSL), a rat animal model for depression. Rats received an intracerebroventricular injection of culture-expanded and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow-derived MSCs (10(5) cells). MSC-transplanted FSL rats showed significant improvement in their behavioral performance, as measured by the forced swim test and the dominant-submissive relationship (DSR) paradigm. After transplantation, MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated with MSC engraftment and behavioral performance. We therefore postulate that MSCs may serve as a novel modality for treating depressive disorders.Molecular Psychiatry advance online publication, 27 October 2009; doi:10.1038/mp.2009.110.

Adult satellite cells and embryonic muscle progenitors have distinct genetic requirements.

Lepper Christoph , Conway Simon J , Fan Chen-Ming
Nature.2009 Jul 30 ; 460(7255):627-31.
PMID: 19554048[]

先週： 6位

57view,6users

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Angiotensin II receptor blocker and statins lower elevated levels of osteopontin in essential hypertension-Results from the EUTOPIA trial.

Atherosclerosis.2009 Sep 12 ; ():.
PMID: 19801149[]

先週： 7位

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BACKGROUND: Osteopontin is a pleiotropic cytokine that has been implicated as a key factor in the development of atherosclerosis, a major complication of hypertension. We have earlier shown that olmesartan reduces mediators of vascular inflammation in patients with hypertension and cardiovascular disease. We aimed at studying the effect of olmesartan and/or pravastatin on osteopontin plasma levels, and the association between vascular inflammation markers and osteopontin in hypertensive patients. METHODS: We assessed a panel of vascular inflammation markers and osteopontin during 12 weeks of therapy with 20mg olmesartan (n=94) or placebo (n=96) in a prospective, double-blind, multi-center study in patients with essential hypertension (re-evaluation of the EUTOPIA trial blood samples). Pravastatin (20mg) was added to the double-blind therapy at week 6 in both arms. The association of demographic variables and inflammation markers with osteopontin has been analyzed as well. RESULTS: Baseline osteopontin plasma concentrations in the study population were elevated compared to healthy controls (32.85+/-19.04ng/mL vs. 23.82+/-3.69ng/mL, p=0.027). Mono-therapy with olmesartan and co-therapy with pravastatin reduced levels of circulating osteopontin (p<0.001). The addition of pravastatin to the placebo treatment-arm resulted in a reduction of osteopontin levels as well (p<0.01). osteopontin plasma levels correlated with VCAM-1 (r=0.27; p=0.0002), ICAM-1 (r=0.18; p=0.015), IL-6 (r=0.35; p<0.0001) and hsCRP (r=0.22; p=0.0022). CONCLUSION: We show, for the first time, that olmesartan significantly decreases osteopontin concentrations. Co-therapy with pravastatin also reduces osteopontin levels. Elevated osteopontin levels in hypertensive patients correlate with adhesion molecules and inflammation markers.

Localization of jointless-2 gene in the centromeric region of tomato chromosome 12 based on high resolution genetic and physical mapping.

Budiman M A , Chang S-B , Lee S , Yang T J , Zhang H-B , de Jong H , Wing R A
Theor Appl Genet.2004 Jan ; 108(2):190-6.
PMID: 14504748[]

先週： 8位

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Abscission is a universal process whereby plants shed their organs, such as flowers, fruit and leaves. In tomato, the non-allelic mutations jointless and jointless-2 have been discovered as recessive mutations that completely suppress the formation of pedicel abscission zones. A high resolution genetic map of jointless-2 was constructed using 1,122 jointless F2 plants. Restriction fragment length polymorphism (RFLP) marker RPD140 completely co-segregated with the jointless-2 locus and mapped in a 2.4 cM interval between RFLP markers CD22 and TG618. To chromosome walk to jointless-2, all three markers were used to screen a bacterial artificial chromosome (BAC) library and contigs were developed. Intensive efforts to expand and merge the BAC contigs were unsuccessful because of the highly repetitive sequence content on the distal ends of each contig. To determine the physical distance between and the orientation of the three contigs, we used high resolution pachytene fluorescence in situ hybridization (FISH) mapping. The RPD140 contig was positioned in the centromeric region of chromosome 12 between two large pericentric heterochromatin blocks, about 50 Mb from the TG618 contig on the short arm and 10 Mb from the CD22 contig on the long arm, respectively. Based on high resolution genetic and physical mapping, we conclude that the jointless-2 gene is located within or near the chromosome 12 centromere where 1 cM is approximately 25 Mb in length.

In-depth sequence analysis of the tomato chromosome 12 centromeric region: identification of a large CAA block and characterization of pericentromere retrotranposons.

Yang Tae-Jin , Lee Seunghee , Chang Song-Bin , Yu Yeisoo , de Jong Hans , Wing Rod A
Chromosoma.2005 Jul ; 114(2):103-17.
PMID: 15965704[]

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We sequenced a continuous 326-kb DNA stretch of a microscopically defined centromeric region of tomato chromosome 12. A total of 84% of the sequence (270 kb) was composed of a nested complex of repeat sequences including 27 retrotransposons, two transposable elements, three MITEs, two terminal repeat retrotransposons in miniature (TRIMs), ten unclassified repeats and three chloroplast DNA insertions. The retrotransposons were grouped into three families of Ty3-Gypsy type long terminal repeat (LTR) retrotransposons (PCRT1-PCRT3) and one LINE-like retrotransposon (PCRT4). High-resolution fluorescence in situ hybridization analyses on pachytene complements revealed that PCRT1a occurs on the pericentromere heterochromatin blocks. PCRT1 was the prevalent retrotransposon family occupying more than 60% of the 326-kb sequence with 19 members grouped into eight subfamilies (PCRT1a-PCRT1h) based on LTR sequence. The PCRT1a subfamily is a rapidly amplified element occupying tens of megabases. The other PCRT1 subfamilies (PCRT1b-PCRT1h) were highly degenerated and interrupted by insertions of other elements. The PCRT1 family shows identity with a previously identified tomato-specific repeat TGR2 and a CENP-B like sequence. A second previously described genomic repeat, TGR3, was identified as a part of the LTR sequence of an Athila-like PCRT2 element of which four copies were found in the 326-kb stretch. A large block of trinucleotide microsatellite (CAA)n occupies the centromere and large portions of the flanking pericentromere heterochromatin blocks of chromosome 12 and most of the other chromosomes. Five putative genes in the remaining 14% of the centromere region were identified, of which one is similar to a transcription regulator (ToCPL1) and a candidate jointless-2 gene.

Sodium-translocating NADH:Quinone oxidoreductase as a redox-driven ion pump.

Verkhovsky Michael I , Bogachev Alexander V
Biochim Biophys Acta.2010 Jan 4 ; ():.
PMID: 20056102[]

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The Na(+)-translocating NADH:ubiquinone oxidoreductase (Na(+)-NQR) is a component of the respiratory chain of various bacteria. This enzyme is an analogous but not homologous counterpart of mitochondrial Complex I. Na(+)-NQR drives the same chemistry and also uses released energy to translocate ions across the membrane, but it pumps Na(+) instead of H(+). Most likely the mechanism of sodium pumping is quite different from that of proton pumping (for example, it could not accommodate the Grotthuss mechanism of ion movement); this is why the enzyme structure, subunits and prosthetic groups are completely special. This review summarizes modern knowledge on the structural and catalytic properties of bacterial Na(+)-translocating NADH:quinone oxidoreductases. The sequence of electron transfer through the enzyme cofactors and thermodynamic properties of those cofactors are discussed. The resolution of the intermediates of the catalytic cycle and localization of sodium-dependent steps are combined in a possible molecular mechanism of sodium transfer by the enzyme.

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The Journal of biological chemistry

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Proceedings of the National Academy of Sciences of the United States of America

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Journal of immunology (Baltimore, Md. : 1950)

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Biochemistry

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Blood

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Cancer research

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Giornale di psichiatria e di neuropatologia

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Journal of virology

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Biochemical and biophysical research communications

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Science (New York, N.Y.)

先週： 10位

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The Journal of biological chemistry

先週： 1位

4,703view , 113users

Proceedings of the National Academy of Sciences of the United States of America

先週： 2位

2,532view , 81users

Journal of immunology (Baltimore, Md. : 1950)

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PloS one

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Journal of agricultural and food chemistry

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Hypertension research : official journal of the Japanese Society of Hypertension

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Biochemical and biophysical research communications

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European journal of immunology

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Science (New York, N.Y.)

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Giornale di psichiatria e di neuropatologia

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T300A polymorphism of ATG16L1 and susceptibility to inflammatory bowel diseases: A meta-analysis.

Cheng Jia-Fei , Ning Yue-Ji , Zhang Wei , Lu Zong-Hai , Lin Lin
World J Gastroenterol.2010 Mar 14 ; 16(10):1258-66.
PMID: 20222171[]

2010/03/11

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AIM: To evaluate the association of the autophagy-related 16-like 1 (ATG16L1) T300A polymorphism (rs2241880) with predisposition to inflammatory bowel diseases (IBD) by means of meta-analysis. METHODS: Publications addressing the relationship between rs2241880/T300A polymorphism of ATG16L1 and Crohn's disease (CD) and ulcerative colitis (UC) were selected from the MEDLINE and EMBASE databases. To make direct comparisons between the data collected in these studies, the individual authors were contacted when necessary to generate a standardized set of data from these studies. From these data, odds ratio (OR) with 95% confidence interval (CI) were calculated. RESULTS: Twenty-five studies of CD were analyzed, 14 of which involved cases of UC. The variant G allele of ATG16L1 was positively associated with CD (OR = 1.32, 95% CI: 1.26-1.39, P < 0.00001) and UC (OR = 1.06, 95% CI: 1.01-1.10, P = 0.02). For child-onset IBD, a higher G allele frequency was found for cases of CD (OR = 1.35, 95% CI: 1.16-1.57, P = 0.0001) than for cases of UC (OR = 0.98, 95% CI: 0.81-1.19, P = 0.84) relative to controls. CONCLUSION: The ATG16L1 T300A polymorphism contributes to susceptibility to CD and UC in adults, but different in children, which implicates a role for autophagy in the pathogenesis of IBD.

Levels of phosphodiesterase 4A and 4B are altered by chronic treatment with psychotropic medications in rat frontal cortex.

Fatemi S Hossein , Folsom Timothy D , Reutiman Teri J , Braun Natalie N , Lavergne Luke G
Synapse.2010 Mar 10 ; 64(7):550-555.
PMID: 20222156[]

2010/03/11

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Our laboratory has recently demonstrated altered expression of phosphodiesterase (PDE) 4A and 4B in subjects with autism, bipolar disorder, and schizophrenia, suggesting disrupted cAMP signaling in these diagnostic groups. In the current study, we measured expression of PDEs in rat frontal cortex (FC) following chronic treatment with clozapine, fluoxetine, haloperidol, lithium, olanzapine, valproic acid (VPA), or sterile saline for 21 days. Western blotting experiments showed decreased expression of PDE4A subtypes in FC following treatment with clozapine, haloperidol, lithium, and VPA. PDE4B subtypes were similarly reduced in FC following treatment with clozapine, fluoxetine, and lithium. We also measured levels of nine PDE subtypes via qRT-PCR in FC and found significant upregulation of PDE1A and PDE8B following treatment with olanzapine, while treatment with lithium reduced expression of mRNA for PDE8B. Our results demonstrate altered expression of PDE4A and PDE4B in response to a variety of psychotropic medications suggesting potentially new therapeutic avenues for treatment of neuropsychiatric diseases. Synapse 64:550-555, 2010. (c) 2010 Wiley-Liss, Inc.

Urinary biomarkers involved in type 2 diabetes: a review.

Matheson Agnès , Willcox Mark D P , Flanagan Judith , Walsh Bradley J
Diabetes Metab Res Rev.2010 Mar 10 ; ():.
PMID: 20222150[]

2010/03/11

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Diabetes mellitus is one of the most challenging health concerns of the 21st century. With at least 30% of the diabetic population remaining undiagnosed, effective and early diagnosis is of critical concern. Development of a diagnostic test, more convenient and reliable than those currently used, would therefore be highly beneficial. Urine as a diagnostic medium allows for non-invasive detection of biomarkers, including some associated with type 2 diabetes and its complications. This review provides a synopsis of those urinary biomarkers that potentially may provide a basis for the development of improved diagnostic tests. Three main pathways for the sourcing of potential makers are identified: kidney damage, oxidative stress and low-grade inflammation including atherosclerosis/vascular damage. This review briefly presents each pathway and some of the most relevant urinary biomarkers that may be used to monitor the development or progression of diabetes and its complications. In particular, biomarkers of renal dysfunction such as transferrin, type IV collagen and N-acetyl-beta-D-glucosaminidase might prove to be more sensitive than urinary albumin, the current gold standard, in the detection of incipient nephropathy and risk assessment of cardiovascular disease. Inflammatory markers including orosomucoid, tumour necrosis factor-alpha, transforming growth factor-beta, vascular endothelial growth factor and monocyte chemoattractant protein-1, as well as oxidative stress markers such as 8-hydroxy-2'deoxyguanosine may also be useful biomarkers for diagnosis or monitoring of diabetic complications, particularly kidney disease. However, the sensitivity of these markers compared with albumin requires further investigation. Copyright (c) 2010 John Wiley & Sons, Ltd.

Role of ERK map kinase and CRM1 in IL-1beta-stimulated release of HMGB1 from cortical astrocytes.

Hayakawa Kazuhide , Arai Ken , Lo Eng H
Glia.2010 Mar 10 ; ():.
PMID: 20222144[]

2010/03/11

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Reactive astrocytes are traditionally thought to impede brain plasticity after stroke. However, we previously showed that reactive astrocytes may also contribute to stroke recovery, partly via the release of a nuclear protein called high-mobility group box 1 (HMGB1). Here, we investigate the mechanisms that allow stimulated astrocytes to release HMGB1. Exposure of rat primary astrocytes to IL-1beta for 24 h elicited a dose-dependent HMGB1 response. Immunostaining and western blots of cell lysates showed increased intracellular levels of HMGB1. Western blots confirmed that IL-1beta induced a release of HMGB1 into astrocyte conditioned media. MAP kinase signaling was involved. Levels of phospho-ERK were increased by IL-1beta, and the MEK/ERK inhibitor U0126 decreased HMGB1 upregulation in the stimulated astrocytes. Since HMGB1 is a nuclear protein, the role of the nuclear protein exporter, chromosome region maintenance 1 (CRM1), was assessed as a candidate mechanism for linking MAP kinase signaling to HMGB1 release. IL-1beta increased CRM1 expression in concert with a translocation of HMGB1 from nucleus into cytoplasm. Blockade of IL-1beta-stimulated HMGB1 release with the ERK inhibitor U0126 was accompanied by a downregulation of CRM1. Our findings reveal that IL-1beta stimulates the release of HMGB1 from activated astrocytes via ERK MAP kinase and CRM1 signaling. These data suggest a novel pathway by which inflammatory cytokines may enhance the ability of reactive astrocytes to release prorecovery mediators after stroke. (c) 2010 Wiley-Liss, Inc.

Expression of the antimicrobial peptide alpha-defensin/cryptdins in intestinal crypts decreases at the initial phase of intestinal inflammation in a model of inflammatory bowel disease, IL-10-deficient mice.

Inaba Yuhei , Ashida Toshifumi , Ito Takahiro , Ishikawa Chisato , Tanabe Hiroki , Maemoto Atsuo , Watari Jiro , Ayabe Tokiyoshi , Mizukami Yusuke , Fujiya Mikihiro , Kohgo Yutaka
Inflamm Bowel Dis.2010 Mar 10 ; ():.
PMID: 20222124[]

2010/03/11

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BACKGROUND:: The etiology of inflammatory bowel disease (IBD) is associated with an altered microflora due to a failure of the immune system. This study investigated the expression of the intestinal antimicrobial peptide alpha-defensin, which plays a pivotal role in the regulation of the intestinal microflora in a representative model of IBD, interleukin (IL)-10-deficient mice. METHODS:: The expression of alpha-defensin/cryptdins in IL-10-deficient mice was assessed by real-time polymerase chain reaction (PCR) and acid/urea polyacrylamide gel (AU-PAGE). The alteration of alpha-defensin/cryptdins expression was compared with the inflammatory grade of mice intestine at various weeks from birth. RESULTS:: The weight, length, and inflammation grade of the mouse intestines were assessed at 5, 7, 9, 11, 13, and 15 weeks from birth. While the weight of the large intestine was heavier at 15 weeks after birth in the IL-10-deficient mice than in the control mice, histological inflammation began from 7 weeks after birth. Real-time PCR and AU-PAGE identified a significant decrease in the expression of alpha-defensin/cryptdins at 7 weeks after birth in the IL-10 knockout mice, thus illustrating the involvement of alpha-defensin/cryptdins in the etiology of the intestinal inflammation in IBD. This study also identified the expression of alpha-defensin/cryptdins to be inversely proportional to age until 11 weeks, suggesting a relationship between the formation of the intestinal microflora and a reduction in the expression of alpha-defensin/cryptdins. CONCLUSIONS:: The altered expression of antimicrobial peptide alpha-defensin may cause the onset of intestinal inflammation due to a failure to regulate intestinal microflora. (Inflamm Bowel Dis 2010).

Adiponectin stimulates prostaglandin E(2) production in rheumatoid synovial fibroblasts.

Kusunoki Natsuko , Kitahara Kanako , Kojima Fumiaki , Tanaka Nahoko , Kaneko Kaichi , Endo Hirahito , Suguro Toru , Kawai Shinichi
Arthritis Rheum.2010 Mar 10 ; ():.
PMID: 20222108[]

2010/03/11

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OBJECTIVE:: Since adipokines may possibly influence the inflammatory and/or immune responses, we examined whether adiponectin affected the production of prostaglandin (PG) E(2) by rheumatoid synovial fibroblasts (RSF). METHODS:: Synovial tissues were obtained from patients with rheumatoid arthritis (RA) at the time of joint replacement surgery. Fibroblast-like cells from the third or fourth passage were used as RSF. Expression of adiponectin receptor mRNA and protein was detected. PGE(2) (converted from arachidonic acid) was measured by enzyme-linked immunosorbent assay (ELISA). Expression of mRNA and protein for cyclooxygenase (COX)-2 and membrane-associated PGE synthase-1 (mPGES-1), key enzymes involved in PGE(2) synthesis, was detected in RSF. The effects of RNAi targeting the adiponectin receptor genes and the receptor signal inhibitors were examined. The influence of adiponectin on nuclear factor (NF)-kappaB activation in RSF was measured with an ELISA kit. RESULTS:: Adiponectin receptors were detected in RSF. Adiponectin increased both COX-2 and mPGES-1 mRNA and protein expression by RSF in a time- and a concentration-dependent manner. PGE(2) production by RSF was also increased by the addition of adiponectin, and this increase was inhibited by RNAi for the adiponectin receptor gene, or co-incubation with the receptor signal inhibitors. Enhancement of NF-kappaB activation by adiponectin as well as by interleukin-1beta was observed in RSF. CONCLUSION:: Adiponectin induced COX-2 and mPGES-1 expression, resulting in the enhancement of PGE(2) production by RSF. Thus, adiponectin may play a role in the pathogenesis of synovitis in RA patients.

An Unexpected Michael-Aldol-Smiles Rearrangement Sequence for the Synthesis of Versatile Optically Active Bicyclic Structures by Using Asymmetric Organocatalysis.

Holub Nicole , Jiang Hao , Paixão Marcio W , Tiberi Caterina , Jørgensen Karl A
Chemistry.2010 Mar 10 ; ():.
PMID: 20222091[]

2010/03/11

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A facile and simple organocatalytic procedure to generate optically active 6-alkyl- and 6-aryl-substituted bicyclo[2.2.2]oct-5-en-2-ones is presented. The reaction is catalysed by a 9-amino-9-deoxyepiquinine trifluoroacetic acid salt, which activates alpha,beta-unsaturated cyclic ketones for the 1,4-addition of beta-keto benzothiazoyl sulfones in a stereoselective fashion. Subsequent intramolecular aldol reaction and Smiles rearrangement gives rise to important optically active bicycles, which are a common motif in natural products, ligands in asymmetric catalysis and substrates for Cope rearrangements, photochemical reactions, radical cyclisations and metathesis. Different bicyclic structures were obtained by utilisation of various cyclic enones or by performing ring-expanding reactions. Furthermore, two possible mechanistic pathways are outlined and discussed.

Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa.

Gao Shan , Nielsen Boye Schnack , Krogdahl Annelise , Sørensen Jens Ahm , Tagesen Jan , Dabelsteen Sally , Dabelsteen Erik , Andreasen Peter A
Genes Chromosomes Cancer.2010 Mar 10 ; ():.
PMID: 20222049[]

2010/03/11

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A high level of plasminogen activator inhibitor-1 (PAI-1 or SERPINE1) in tumor extracts is a marker of a poor prognosis in human cancers, including oral carcinomas. However, the mechanisms responsible for the upregulation of PAI-1 in cancers remain unclear. Investigating specific PAI-1 expressing cells in oral carcinomas by immunohistochemistry, we found that PAI-1 was expressed in 18 of the 20 patients, mainly by cancer cells. Two showed PAI-1 positive stromal cells surrounding the tumor areas and five showed PAI-1 positive cells in tumor-adjacent normal epithelium. By real-time RT-PCR analysis, 17 of 20 patients with oral carcinoma were found to have between 2.5- and 50-fold increased tumor PAI-1 mRNA level, as compared with the matched tumor-adjacent normal tissues. The PAI-1 mRNA level in connective tissues from 15 healthy volunteers was similar to the level in tumor-adjacent normal tissues, but the level in epithelium was 5- to 10-fold lower. Analyzing DNA methylation of 25 CpG sites within 960 bp around the transcription initiation site of the SERPINE1 gene by bisulfite sequencing, we did the surprising observation that both tumors and tumor-adjacent normal tissue had a significant level of methylation, whereas there was very little methylation in tissue from healthy volunteers, suggesting that tumor-adjacent normal tissue already contains transformation-associated epigenetic changes. However, there was no general inverse correlation between PAI-1 mRNA levels and SERPINE1 gene methylation in all tissues, showing that CpG methylation is not the main determinant of the PAI-1 expression level in oral tissue. (c) 2010 Wiley-Liss, Inc.

Pharmacodynamic evaluation of temsirolimus in patients with newly diagnosed advanced-stage head and neck squamous cell carcinoma.

Ekshyyan Oleksandr , Mills Glenn M , Lian Timothy , Amirghahari Nazanin , Rong Xiaohua , Lowery-Nordberg Mary , Abreo Fleurette , Veillon Diana M , Caldito Gloria , Speicher Lisa , Glass Jonathan , Nathan Cherie-Ann O
Head Neck.2010 Mar 10 ; ():.
PMID: 20222045[]

2010/03/11

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BACKGROUND:: Activation of the mammalian target of rapamycin (mTOR) pathway in surgical margins of head and neck squamous cell carcinoma (HNSCC) is a predictor of recurrence and patients with minimal residual disease may benefit from adjuvant therapy with temsirolimus, an mTOR inhibitor. METHODS:: The effects of 3 weekly doses of 25 mg of temsirolimus on Akt/mTOR pathway biomarkers were evaluated in tumor and peripheral blood mononuclear cells (PBMCs) of patients with HNSCC. Adverse events were assessed. RESULTS:: Temsirolimus significantly decreased pS6 and p4E-BP1 in tumors, and pS6 and pAkt in PBMCs (p < .05). There was no significant upregulation of pAkt(Ser(473)) in tumor tissue. Side effects were minimal and reversible. CONCLUSION:: Significant inhibition of the mTOR pathway was noted in both tumors and PBMCs of HNSCC with minimal side effects. The mTOR inhibitors can potentially be used as adjuvant therapy for patients with minimal residual disease and PBMCs are potential surrogate markers in this setting. (c) 2010 Wiley Periodicals, Inc. Head Neck, 2010.

Involvement of ER-calreticulin-Ca(2+) signaling in the regulation of porcine oocyte meiotic maturation and maternal gene expression.

Zhang Ding-Xiao , Li Xiao-Ping , Sun Shao-Chen , Shen Xing-Hui , Cui Xiang-Shun , Kim Nam-Hyung
Mol Reprod Dev.2010 Mar 10 ; ():.
PMID: 20222029[]

2010/03/11

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Calcium is one of the most ubiquitous signaling molecules, and controls a wide variety of cellular processes. It is mainly stored in the endoplasmic reticulum (ER), bound to lumenal proteins. Calreticulin is the major Ca(2+)-binding chaperone in oocytes, and is integral to numerous cellular functions. To better understand the role of the ER- calreticulin-Ca(2+) pathway in oocyte maturation and early embryogenesis, we characterized the porcine calreticulin gene and investigated its expression profile during oocyte maturation and early embryonic development. Calreticulin was widely expressed in pig tissues and its transcripts were downregulated during maturation, especially at 44 hr, and were undetectable at the blastocyst stage. We also investigated the effect of increased cytosolic Ca(2+) induced by the Ca(2+)-ATPase inhibitor, cyclopiazonic acid (CPA), on pig oocyte maturation and maternal gene expression. CPA at 10 microM did not inhibit germinal vesicle breakdown, but did result in the arrest of 38.6% oocytes at or before the MI stage. In addition, expression of the maternal genes C-mos, BMP15, GDF9, and Cyclin B1 was significantly increased in CPA-treated MII oocytes compared with control groups. These data were supported by the results of poly(A)-test PCR, which revealed that the cyclin B1 short isoform (CB-S), GDF9, and C-mos underwent more intensive polyadenylation modification in CPA-treated oocytes than control oocytes, suggesting that polyadenylation may influence Ca(2+)-modulated changes in gene expression. Furthermore, CPA treatment decreased the percentage of four-cell parthenotes that developed into blastocysts, suggesting the need for functional SR/ER Ca(2+)-ATPase pumps or Ca(2+) signals during early embryo development after zygotic genome activation. Together, these data indicate that ER-calreticulin-associated Ca(2+) homeostasis plays a role in oocyte and embryo development, and that alterations in maternal gene expression may contribute to the underlying molecular mechanism, at least partially, via polyadenylation. Mol. Reprod. Dev. 2010. (c) 2010 Wiley-Liss, Inc.

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