bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes‐ and angiotensin II‐induced cardiac endoplasmic reticulum stress and cell death: metallothionein protection
Authors: Xu Jiancheng , Wang Guanjun , Wang Yuehui , Liu Qiuju , Xu Wei , Tan Yi , Cai Lu 
Published: July 2009

AbstractWe have shown cardiac protection by metallothionein (MT) in the development of diabetic cardiomyopathy (DCM) via suppression of cardiac cell death in cardiac‐specific MT‐overexpressing transgenic (MT‐TG) mice. The present study was undertaken to define whether diabetes can induce cardiac endoplasmic reticulum (ER) stress and whether MT can prevent cardiac cell death via attenuating ER stress. Diabetes was induced by streptozotocin in both MT‐TG and wild‐type (WT) mice. Two weeks, and 2 and 5 months after diabetes onset, cardiac ER stress was detected by expression of ER chaperones, and apoptosis was detected by CCAAT/enhancer‐binding protein (C/EBP) homologous protein (CHOP) and cleaved caspase‐3 and caspase‐12. Cardiac apoptosis in the WT diabetic mice, but not in MT‐TG diabetic mice, was significantly increased 2 weeks after diabetes onset. In parallel with apoptotic effect, significant up‐regulation of the ER chaperones, including glucose‐regulated protein (GRP)78 and GRP94, cleaved ATF6 and phosporylated eIF2α, in the hearts of WT, but not MT‐TG diabetic mice. Infusion of angiotensin II (Ang II) also significantly induced ER stress and apoptosis in the hearts of WT, but not in MT‐TG mice. Direct administration of chemical ER stress activator tunicamycin significantly increased cardiac cell death only in WT mice. Pre‐treatment with antioxidants completely prevented Ang II‐induced ER stress and apoptosis in the cultured cardiac cells. These results suggest that ER stress exists in the diabetic heart, which may cause the cardiac cell death. MT prevents both diabetes‐ and Ang II‐induced cardiac ER stress and associated cell death most likely via its antioxidant action, which may be responsible for MT's prevention of DCM.
Image‐guided tissue engineering
Authors: Ballyns Jeffrey J. , Bonassar Lawrence J. 
Published: July 2009

Abstract
Introduction
Imaging techniques
Fabrication techniques
Conclusions
Replication of anatomic shape is a significant challenge in developing implants for regenerative medicine. This has lead to significant interest in using medical imaging techniques such as magnetic resonance imaging and computed tomography to design tissue engineered constructs. Implementation of medical imaging and computer aided design in combination with technologies for rapid prototyping of living implants enables the generation of highly reproducible constructs with spatial resolution up to 25 μm. In this paper, we review the medical imaging modalities available and a paradigm for choosing a particular imaging technique. We also present fabrication techniques and methodologies for producing cellular engineered constructs. Finally, we comment on future challenges involved with image guided tissue engineering and efforts to generate engineered constructs ready for implantation.
Cyclin A2 confers cisplatin resistance to endometrial carcinoma cells via up‐regulation of an Akt‐binding protein, periplakin
Authors: Suzuki Akihisa , Horiuchi Akiko , Ashida Takashi , Miyamoto Tsutomu , Kashima Hiroyasu , Nikaido Toshio , Konishi Ikuo , Shiozawa Tanri 
Published: July 2009

AbstractAlthough overexpression of cyclin A2 is reportedly an indicator of a poor prognosis of various malignancies including endometrial carcinoma, its molecular mechanism remains undetermined. To address this issue, we examined the effect of cyclin A2 on the development of resistance to chemotherapeutic drugs. The expression of cyclin A2 protein was increased in advanced‐stage and chemotherapy‐refractory stage endometrial carcinomas compared with that in early‐stage tumours. The expression levels of cyclin A2 in endometrial carcinoma cell lines correlated positively with the IC50 for cisplatin. Endometrial carcinoma HHUA cells that overexpressed cyclin A2 showed increased resistance to cisplatin in vitro and in vivo, via the activation of a survival pathway, the inositol‐3 phosphate kinase (PI3K) cascade. The use of a cDNA microarray identified an Akt‐binding protein, periplakin, as a novel target of cyclin A2. The cyclin A2‐induced up‐regulation of periplakin was mediated via direct binding of Sp1 to the promoter that was activated by cyclin A2 along with chromatin remodelling involving CBP/p300, and the siRNA‐mediated silencing of periplakin suppressed the PI3K pathway. These results indicate cyclin A2 to be involved in the acquisition of aggressive behaviour of tumour cells through the activation of PI3K by cyclin A2‐induced periplakin, and to be a promising therapeutic target.
A novel recombinant immunotoxin with the smallest ribosome‐inactivating protein Luffin P1: T‐cell cytotoxicity and prolongation of allograft survival
Authors: Wang Rupeng , Gan Chenjun , Gao Wenda , He Weifeng , Wang Xiaojuan , Peng Yanmeng , Zhuo Junyi , Tan Jianglin , Peng Xu , Wu Jun , Luo Gaoxing 
Published: July 2009

AbstractIn the creation of stable tolerance to MHC‐incompatible allografts, reducing the large mass of donor‐reactive cells via apoptosis is often required. Apoptosis induction by immunotoxins targeting surface molecules specifically presented on donor‐reactive cytopathic T effector (Teff) cells is a promising strategy. Traditionally, the toxin moieties are bacterial exotoxins or plant‐derived ribosome‐inactivating proteins (RIPs) with large molecular size and strong immunogenicity, hence causing the problems of tissue penetration, host immune reaction and quick clearance. We have identified a novel class of small molecule RIPs (<10 kD) from the seeds of the plant Luffa cylindrica. The smallest member of this family, Luffin P1, has a molecular weight of 5226.8 Da, yet possessing a highly potent inhibitory activity on cell‐free protein synthesis with IC50 of 0.88 nM. We now report a recombinant hIL‐2‐Luffin P1 immunotoxin, which strongly inhibited T‐cell proliferation in mixed lymphocyte reaction and ConA response with IC50 of 1.8–10 nM. In vivo, hIL‐2‐Luffin P1 significantly prolonged the survival of major MHC‐mismatched skin and kidney allografts in animal models. Thus, we demonstrate for the first time the efficacy of the smallest immunotoxin that could be further combined with other pharmacological and immunological reagents for synergistic control of pathogenic lymphocytes in immune‐mediated diseases.
Lysyl oxidase interacts with AGE signalling to modulate collagen synthesis in polycystic ovarian tissue
Authors: Papachroni Katerina K. , Piperi Christina , Levidou Georgia , Korkolopoulou Penelope , Pawelczyk Leszek , Diamanti‐Kandarakis Evanthia , Papavassiliou Athanasios G. 
Published: July 2009

AbstractConnective tissue components – collagen types I, III and IV – surrounding the ovarian follicles undergo drastic changes during ovulation. Abnormal collagen synthesis and increased volume and density of ovarian stroma characterize the polycystic ovary syndrome (PCOS). During the ovulatory process, collagen synthesis is regulated by prolyl hydroxylase and lysyl oxidase (LOX) activity in ovarian follicles. LOX catalyzes collagen and elastin cross‐linking and plays essential role in coordinating the control of ovarian extracellular matrix (ECM) during follicular development. We have recently shown accumulation of advanced glycation end products (AGEs), molecules that stimulate ECM production and abnormal collagen cross‐linking, in ovarian tissue. However, the possible link between LOX and AGEs‐induced signalling in collagen production and stroma formation in ovarian tissue from PCOS remains elusive. The present study investigates the hypothesis of AGE signalling pathway interaction with LOX gene activity in polycystic ovarian (PCO) tissue. We show an increased distribution and co‐localization of LOX, collagen type IV and AGE molecules in the PCO tissue compared to control, as well as augmented expression of AGE signalling mediators/effectors, phospho(p)‐ERK, phospho(p)‐c‐Jun and nuclear factor κB (NF‐κB) in pathological tissue. Moreover, we demonstrate binding of AGE‐induced transcription factors, NF‐κB and activator protein‐1 (AP‐1) on LOX promoter, indicating a possible involvement of AGEs in LOX gene regulation, which may account for the documented increase in LOX mRNA and protein levels compared to control. These findings suggest that deposition of excess collagen in PCO tissue that induces cystogenesis may, in part, be due to AGE‐mediated stimulation of LOX activity.
RNA‐binding proteins implicated in the hypoxic response
Authors: Masuda Kiyoshi , Abdelmohsen Kotb , Gorospe Myriam 
Published: July 2009

Abstract

Introduction
Post‐transcriptional gene regulation by hypoxia
HuR
PTB
Other RBPs implicated in the response to hypoxia
Perspective

In cells responding to low oxygen levels, gene expression patterns are strongly influenced by post‐transcriptional processes. RNA‐binding proteins (RBPs) are pivotal regulators of gene expression in response to numerous stresses, including hypoxia. Here, we review the RBPs that modulate mRNA turnover and translation in response to hypoxic challenge. The RBPs HuR (human antigen R) and PTB (polypyrimidine tract‐binding protein) associate with mRNAs encoding hypoxia‐response proteins such as HIF‐1α and VEGF mRNAs, enhance their expression after hypoxia and play a major role in establishing hypoxic gene expression patterns. Additional RBPs such as iron‐response element‐binding proteins (IRPs), cytoplasmic polyadenylation‐element‐binding proteins (CPEBs) and several heterogeneous nuclear ribonucleoproteins (hnRNPs) also bind to hypoxia‐regulated transcripts and modulate the levels of the encoded proteins. We discuss the efficient regulation of hypoxic gene expression by RBPs and the mounting interest in targeting hypoxia‐regulatory RBPs in diseases with aberrant hypoxic responses.
Influence of heat stress to matrix on bone formation
Authors: Yoshida Keiko , Uoshima Katsumi , Oda Kimimitsu , Maeda Takeyasu 
Published: July 2009

AbstractObjectives: It is important to know the etiology of implant failure. It has been reported that heat stress during drilling was one of the causes for failure and the threshold was 47°C. However, clinically, we encounter cases in which overheating does not seem to affect osseointegration eventually. The purpose of this study was to assess histologically the spatio‐temporal effect of heat stress on bone formation after overheating the bone matrix.Material and methods: Rat calvarial bone was heated to 37°C, 43°C, 45°C and 48°C for 15 min by a temperature stimulator. Paraffin sections were prepared 1, 3 and 5 weeks after heating and investigated histologically under light microscopy. Hematoxylin and eosin staining, alkaline phosphatase (ALP), osteopontin (OPN), heat shock protein 27 (Hsp27) and heat shock protein 70 (Hsp70) immunohistochemistry and tartrate‐resistant acid phosphatase (TRAP) enzyme histochemistry were carried out. The area of dead osteocytes was calculated and statistically analyzed. Apoptotic osteocytes were detected by the terminal deoxynucleotidyltransferase‐mediated dUTP nick end‐labeling (TUNEL) method.Results: Along with the temperature increase, the area of dead osteocytes increased and regeneration of the periosteal membrane was delayed. Hsps‐ and TUNEL‐positive cells were only seen in the 48°C group. Spatio‐temporal changes of TRAP‐ and ALP‐positive cell numbers were observed, while OPN expression was mostly absent. Even after 48°C stimulation, bone formation on the calvarial surface was observed after 5 weeks.Conclusions: Although there was a temperature‐dependent delay in bone formation after heat stress, the 48°C heat stress did not obstruct bone formation eventually. This delay was probably caused by slow periosteal membrane regeneration.
Surface‐modified zirconia implants: tissue response in rabbits
Authors: Rocchietta Isabella , Fontana Filippo , Addis Alessandro , Schupbach Peter , Simion Massimo 
Published: July 2009

AbstractAim: To evaluate the bone tissue response to zirconia implants with three different surface modifications in comparison with the oxidized titanium surface with the goal to optimize osseointegration in terms of strength and speed.Materials and methods: A total of 18 rabbits with 143 implants were used. One hundred and twenty‐three were threaded zirconia ceramic implants with three different surface topographies and 20 modified titanium oxide implants were controls. Each rabbit received eight implants and sacrificed after 3 weeks. The removal torque test (RTQ) and histology were performed.Results: Sixteen out of 18 rabbits completed the study with a total of 110 implants. No statistical significance was observed between the chemical modification implants compared with the topographically modified zirconia implant in terms of interfacial shear strength proven by the RTQ applied. No statistical significance was also observed in the bone‐to‐implant contact between the zirconia implants and the control oxidized implants.Conclusions: The findings suggest that additional specific chemical modifications of the topographically modified zirconia implants do not seem to enhance the bone‐to‐implant contact and appear not to increase the interfacial shear strength.
Cyclosporine A enhances apoptosis in gingival keratinocytes of rats and in OECM1 cells via the mitochondrial pathway
Authors: Tu H.‐P. , Chen Y.‐T. , Chiu H.‐C. , Chin Y.‐T. , Huang S.‐M. , Cheng L.‐C. , Fu E. , Chiang C.‐Y. 
Published: July 2009

Background and Objective:  We reported previously that cyclosporine A induces a high level of expression of p21 in rat gingival keratinocytes and in OECM1 cells. In this study, the apoptosis of gingival keratinocytes after treatment with cyclosporine A was evaluated using the same models.Material and Methods:  Forty Sprague–Dawley rats with right edentulous ridges were assigned into cyclosporine A (30 mg/kg) and control groups. Four weeks later, gingivae were screened for expression of apoptotic genes using microarray analyses and DNA fragmentation. The expression of bcl2‐associated X protein (Bax), apoptosis‐inducing factor (AIF) and Caspase 3 mRNAs, and the expression of Bax, AIF, Caspase 9 and Fas proteins, were analyzed using the reverse transcription–polymerase chain reaction and immunohistochemistry, respectively. Apoptosis in OECM1 cells (keratinocytes of a gingival carcinoma cell line), after treatment with cyclosporine A, was evaluated by 4′,6‐diamidino‐2‐phenylindole (DAPI) staining and flow cytometry, whereas the expression of Bax, AIF, Caspase 3 and 8, Bcl‐2 and Fas proteins were examined using western blotting.Results:  According to microarray analyses, the expression of certain apoptotic genes was altered in the gingiva of rats who received cyclosporine A, and increased number of DNA fragments were detected. Expression of mRNA or protein for Bax, AIF and Caspase 3 and 9 in the gingivae of rats increased after treatment with cyclosporine A. An increased number of apoptotic bodies and of OECM1 cells in the sub‐G1 phase was observed after treatment with cyclosporine A. Increased expression of AIF, Bax and Caspase 3 protein, but not of bcl‐2, Caspase 8 or Fas protein, was observed in cells after treatment with cyclosporine A.Conclusion:  Based on the above findings, we suggest that cyclosporine A might enhance the apoptosis of gingival keratinocytes, mainly via the mitochondrial pathway.
Thiopental pharmacokinetics in newborn infants: a case report of overdose
Authors: Norman Elisabeth , Malmqvist Ulf , Westrin Per , Fellman Vineta 
Published: July 2009

AbstractThiopental may be used for sedation before intubation in newborn infants. A boy, born at 33 weeks of gestation (gw); birth weight 2435 g, was prescribed thiopental 3 mg/kg before intubation. He developed temporary hypotension and oxygen desaturation, and remained unconscious for longer than expected with a suppressed electroencephalography for 48 h. Serum thiopental concentration was 82, 59, 42 and 32 μmol/L after 20 min and 6, 24 and 68 h respectively. Serum concentrations from five newborn infants at the same time points after intubation with the same thiopental dose were used as reference values, and indicated a 10‐fold overdose in the index case. The cause of the overdose could not be identified. The infant recovered; cerebral magnetic resonance imaging at the age of 42 gw and psychomotor development at 2 years were normal. These results show that thiopental concentrations are variable in neonates and there is a high risk of dosage error as no specific paediatric formulation is available.Conclusion:  Well‐designed procedures and continuous education are required to prevent errors and adverse events during drug delivery to newborn infants. To develop a safe method of administration for thiopental, an extended pharmacokinetic and pharmacodynamic study in neonates is warranted.
Quality of performance of everyday activities in children with spina bifida: a population‐based study
Authors: Peny‐Dahlstrand M , Åhlander A‐C , Krumlinde‐Sundholm L , Gosman‐Hedström G 
Published: July 2009

AbstractAim:  The aim of this study was to evaluate the quality of the performance of everyday activities in children with spina bifida.Methods:  Fifty children with spina bifida (of 65 children in a geographic cohort), aged 6 to14 years, were evaluated with Assessment of Motor and Process Skills.Results:  Compared with age‐normative values, 60% of the children with spina bifida were found to have motor ability measures below 2 SD and 48% process ability measures below 2 SD. Most of the children with spina bifida had difficulties performing well‐known everyday activities in an effortless, efficient and independent way, relating to both motor and process skills. The motor skills hardest to accomplish involved motor planning and the process skills hardest to accomplish were adaptation of performance and initiations of new steps, thus actually getting the task done.Conclusion:  To reach autonomy in life, children with spina bifida may need particular guidance to learn not only how to do things but also how to get things done.
Correlation and Quantitative Trait Loci Analyses of Total Chlorophyll Content and Photosynthetic Rate of Rice (Oryza sativa) under Water Stress and Well‐watered Conditions
Authors: Hu Song‐Ping , Zhou Ying , Zhang Lin , Zhu Xiu‐Dong , Li Lin , Luo Li‐Jun , Liu Guo‐Lan , Zhou Qing‐Ming 
Published: July 2009

Abstract In order to explore the relevant molecular genetic mechanisms of photosynthetic rate (PR) and chlorophyll content (CC) in rice (Oryza sativa L.), we conducted a series of related experiments using a population of recombinant inbred lines (Zhenshan97B × IRAT109). We found a significant correlation between CC and PR (R= 0.19**) in well‐watered conditions, but no significant correlation during water stress (r= 0.08). We detected 13 main quantitative trait loci (QTLs) located on chromosomes 1, 2, 3, 4, 5, 6, and 10, which were associated with CC, including six QTLs located on chromosomes 1, 2, 3, 4, and 5 during water stress, and seven QTLs located on chromosomes 2, 3, 4, 6, and 10 in well‐watered conditions. These QTLs explained 47.39% of phenotypic variation during water stress and 56.19% in well‐watered conditions. We detected four main QTLs associated with PR; three of them (qPR2, qPR10, qPR11) were located on chromosomes 2, 10, and 11 during water stress, and one (qPR10) was located on chromosome 10 in well‐watered conditions. These QTLs explained 34.37% and 18.41% of the phenotypic variation in water stress and well‐watered conditions, respectively. In total, CC was largely controlled by main QTLs, and PR was mainly controlled by epistatic QTL pairs.
Premature Tapetum Degeneration: a Major Cause of Abortive Pollen Development in Photoperiod Sensitive Genic Male Sterility in Rice
Authors: Shi Yinlian , Zhao Sha , Yao Jialing 
Published: July 2009

Abstract Photoperiod‐sensitive genic male‐sterile (PSGMS) rice (Oryza sativa L.), a natural mutant found in the rice cultivar Nongken 58, is very useful for the development of hybrid rice cultivars. Despite its widespread use in breeding programs, the initial stage of the abortive development of PSGMS rice and the possible cytological mechanisms of pollen abortion have not been determined. In the present study, a systematic cytological comparison of the anther development of PSGMS rice with its normal fertile counterpart is conducted. The results show that pollen abortion in PSGMS rice first occurs before the pollen mother cell (PMC) stage, and continues during the entire process of pollen development until pollen degradation. The abortive process was closely associated with the abnormal behavior of the tapetum. Although tapetum degeneration in PSGMS rice initiates already at the PMC stage, it proceeds slowly and does not complete until the breakdown of the pollen. Such cytological observations were supported by the results of the TUNEL (TdT‐mediated dUTP Nick End Labeling) assay, which detects DNA fragmentation resulting from programmed cell death (PCD), indicating that the premature tapetum degeneration is in the process of PCD.
Rapid and easy semi‐quantitative evaluation method for diacylglycerol and inositol‐1,4,5‐trisphosphate generation in orexin receptor signalling
Authors: Ekholm M. E. , Johansson L. , Kukkonen J. P. 
Published: July 2009

AbstractAim:  Fluorescent protein‐based indicators have enabled measurement of intracellular signals previously nearly inaccessible for studies. However, indicators showing intracellular translocation upon response suffer from serious limitations, especially the very time‐consuming data collection. We therefore set out in this study to evaluate whether fixing and counting cells showing translocation could mend this issue.Methods:  Altogether three different genetically encoded indicators for diacylglycerol and inositol‐1,4,5‐trisphosphate were transiently expressed in Chinese hamster ovary cells stably expressing human OX1 orexin receptors. Upon stimulation with orexin‐A, the cells were fixed with six different protocols.Results:  Different protocols showed clear differences in their ability to preserve the indicator’s localization (i.e. translocation after stimulus) and its fluorescence, and the best results for each indicator were obtained with a different protocol. The concentration–response data obtained with cell counting are mostly comparable to the real‐time translocation and biochemical data.Conclusion:  The counting method, as used here, works at single time point and looses the single‐cell‐quantitative aspect. However, it also has some useful properties. First, it easily allows processing of a 100‐ to 1000‐fold higher cell numbers than real‐time imaging producing statistically consistent population‐quantitative data much faster. Secondly, it does not require expensive real‐time imaging equipment. Fluorescence in fixed cells can also be quantitated, though this analysis would be more time‐consuming than cell counting. Thirdly, in addition to the quantitative data collection, the method could be applied for identifying responsive cells. This might be very useful in identification of e.g. orexin‐responding neurones in a large population of non‐responsive cells in primary cultures.