bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thapsigargin down‐regulates protein levels of GRP78/BiP in INS‐1E cells
Authors: Rosengren Victoria , Johansson Henrik , Lehtiö Janne , Fransson Liselotte , Sjöholm Åke , Ortsäter Henrik 
Published: December 2011

AbstractPancreatic β‐cells have a well‐developed endoplasmic reticulum (ER) and express large amounts of chaperones and protein disulfide isomerases (PDI) to meet the high demand for synthesis of proteins. We have observed an unexpected decrease in chaperone protein level in the β‐cell model INS‐1E after exposure to the ER stress inducing agent thapsigargin. As these cells are a commonly used model for primary β‐cells and has been shown to be vulnerable to ER stress, we hypothesize these cells are incapable of mounting a chaperone defense upon activation of ER stress. To investigate the chaperone expression during an ER stress response, induced by thapsigargin in INS‐1E cells, we used quantitative mass spectrometry based proteomics. The results displayed a decrease of GRP78/BiP, PDIA3 and PDIA6. Decrease of GRP78/BiP was verified by Western blot and occurred in parallel with enhanced levels of p‐eIF2α and CHOP. In contrast to INS‐1E cells, GRP78/BiP was not decreased in MIN6 cell or rat and mouse islets after thapsigargin exposure. Investigation of the decreased protein levels of GRP78/BiP indicates that this is not a consequence of reduced mRNA expression. Rather the reduction results from the combined effect of reduced protein synthesis and enhanced proteosomal degradation and possibly also degradation via autophagy. Induction of ER stress with thapsigargin leads to lower protein levels of GRP78/BiP, PDIA3 and PDIA6 in INS‐1E cells which may contribute to the susceptibility of ER stress in this β‐cell model. J. Cell. Biochem. 113: 1635–1644, 2012. © 2011 Wiley Periodicals, Inc.
Umami taste receptor functions as an amino acid sensor via Gαs subunit in N1E‐115 neuroblastoma cells
Authors: Muroi Yoshikage , Ishii Toshiaki 
Published: December 2011

AbstractThe sensing of the nutritional level of the body fluid is pivotal for maintaining homeostasis in animals. However, it is not yet understood how the cells detect nutritional levels. In the present study, we examined the function of umami taste receptor, which has a dimeric protein structure composed of Tas1r1 and Tas1r3, as amino acid sensor in the cells. We found that deprivation of amino acids induced neurite outgrowth in N1E‐115 cells. The neurite outgrowth was inhibited by almost all of the amino acids tested. To investigate the involvement of the umami taste receptor, siRNA against each of Tas1r1 or Tas1r3 was administered, resulting in suppression of the inhibitory effects of amino acids on neurite outgrowth. In addition, inosine 5′‐monophosphate, which potentiates the response to amino acids in the taste cells, enhanced the inhibitory effect of glutamine on neurite outgrowth. These results suggest that Tas1r1 + 3 functions as an amino acid sensor in N1E‐115 cells. Because glutamine increased intracellular cAMP concentration, we investigated the involvement of the Gαs subunit of the heterotrimeric G protein in signal transduction. The treatments to inhibit the Gαs subunit significantly suppressed the increase of intracellular cAMP concentration induced by glutamine and the inhibitory effect of amino acids on neurite outgrowth. In addition, the reagents for increasing intracellular cAMP concentration inhibited neurite outgrowth induced by deprivation of amino acids. We concluded that Tas1r1 + 3 functions as an amino acid sensor and activates the intracellular signaling pathway through the Gαs subunit in N1E‐115 cells. J. Cell. Biochem. 113: 1654–1662, 2012. © 2011 Wiley Periodicals, Inc.
The hydroxylation activity of Jmjd6 is required for its homo‐oligomerization
Authors: Han Gang , Li Jiajia , Wang Yiqin , Li Xia , Mao Hailei , Liu Yifan , Chen Charlie Degui 
Published: December 2011

AbstractJumonji C‐terminal (JmjC) domain‐containing proteins are protein hydroxylases and histone demethylases that control gene expression. Jumonji domain‐containing protein 6 (Jmjd6) is indispensable for embryonic development and has both histone arginine demethylase and lysyl‐hydroxylase activities. The protein undergoes post‐translational homo‐oligomerization, but the underlying mechanism remains unknown. In this study, we examined the enzymatic activity of Jmjd6 and uncovered the mechanism underlying its homo‐oligomerization. An in vitro enzymatic assay monitored by matrix‐assisted laser desorption‐ionization time‐of‐flight (MALDI‐TOF) mass spectrometry indicates that Jmjd6 is unable to remove the methyl group from histone arginine residues but can hydroxylate the histone H4 tail at lysine residues in a 2‐oxoglutarate (2‐OG)‐ and Fe (II)‐dependent manner. A mutational analysis reveals that the homo‐oligomerization of Jmjd6 requires its enzymatic activity and the N‐ and C‐termini. Using an in vitro enzymatic assay, we further demonstrate that Jmjd6 can hydroxylate its N‐terminus but not its C‐terminus. In summary, we did not detect arginine demethylase activity for Jmjd6, but we did confirm that it could catalyze the lysyl‐hydroxylation of histone peptides. In addition, we demonstrated that the homo‐oligomerization of Jmjd6 requires its own enzymatic activity and the N‐ and C‐termini. We propose that Jmjd6 forms intermolecular covalent bonds between its N‐ and C‐termini via autohydroxylation. J. Cell. Biochem. 113: 1663–1670, 2012. © 2011 Wiley Periodicals, Inc.
Novel synthesis of some new pyrimido[1,6‐a]pyrimidine and pyrazolo[1,5‐a]pyrimidine derivatives
Authors: Hussein Ahmed M. 
Published: December 2011

AbstractAn easy and efficient route for synthesis of some pyrimido[1,6‐a]pyrimidine and pyrazolo[1,5‐a]pyrimidine derivatives was described through the reaction of sodium salts of formyl ketones with 6‐aminothiouracil and 5‐aminopyrazole derivatives, respectively. The characterization of the reaction products was confirmed by using elemental analysis and spectral data. J. Heterocyclic Chem., (2012).
Experimental evidence that pristanic acid disrupts mitochondrial homeostasis in brain of young rats
Authors: Busanello Estela Natacha Brandt , Amaral Alexandre Umpierrez , Tonin Anelise Miotti , Grings Mateus , Moura Alana Pimentel , Eichler Paula , Vargas Carmen Regla , Wajner Moacir 
Published: December 2011

AbstractPatients affected by peroxisomal disorders commonly present neurologic dysfunction and brain abnormalities, whose neuropathology is poorly understood. Given that high sustained concentrations of pristanic acid (Prist) are found in the brain of these patients, it is conceivable that this complex branched‐chain fatty acid is neurotoxic. Therefore, the present work investigated the in vitro effects of Prist at similar concentrations found in plasma of affected patients with some peroxisomal disorders on important parameters of energy homeostasis, including respiratory parameters determined by oxygen consumption, membrane potential (ΔΨm), NAD(P)H content, and swelling in mitochondrial preparations obtained from brain of young rats using glutamate plus malate or succinate as respiratory substrates. Prist markedly increased state 4 respiration and decreased state 3 respiration, the respiratory control ratio (RCR), and the ADP/O ratio with both substrates. The mitochondrial ΔΨm and the matrix NAD(P)H content were also decreased by Prist, which was also able to provoke mitochondrial swelling. Furthermore, Prist‐induced mitochondrial swelling was dependent on oxidative damage to the permeability transition pore (PTP), because cyclosporine A and the thiol‐reducing agent N‐acetylcysteine totally prevented mitochondrial swelling. These data suggest that Prist impairs mitochondrial homeostasis, acting as an uncoupler of oxidative phosphorylation and as a metabolic inhibitor, besides causing mitochondrial swelling probably mediated by the permeability transition pore. It is proposed that these pathomechanisms may potentially be involved in the neurological abnormalities characteristic of the peroxisomal diseases in which Prist accumulates. © 2011 Wiley Periodicals, Inc.
Epigenetic regulation of self‐renewal and fate determination in neural stem cells
Authors: Mohamed Ariff Iqbal , Mitra Arinjay , Basu Anirban 
Published: December 2011

AbstractDifferentiation and self‐renewal are two primary properties that characterize stem cells. Differentiation of neural stem/precursor cells (NSPCs) gives rise to multiple neural lineages, including neurons, astrocytes, and oligodendrocytes. Self‐renewal, by definition, signifies the progressive growth of cells, while preserving an undifferentiated state. A large number of interdependent factors, including transcription factors, epigenetic control, and micro‐RNA regulators, modulate these opposing processes without disrupting the regular neural network. The epigenetic modification of developmental genes, including alterations in DNA methylation, histone modifications, polycomb gene group and noncoding RNA expression, which are passed on through successive cell divisions, has proved to be one of the major mechanisms determining the fate of neural stem cells. Here, we review the diverse epigenetic pathways that decide whether NSPCs undergo proliferation or differentiation into different neuronal cell lineages. © 2011 Wiley Periodicals, Inc.
Voltage‐dependent ionic channels in differentiating neural precursor cells collected from adult mouse brains six hours post‐mortem
Authors: Bellardita Carmelo , Bolzoni Francesco , Sorosina Melissa , Marfia Giovanni , Carelli Stephana , Gorio Alfredo , Formenti Alessandro 
Published: December 2011

AbstractA novel type of adult neural precursor cells (NPCs) has been isolated from the subventricular zone of the mouse 6 hr after animal death (T6‐NPCs). This condition is supposed to select hypoxia‐resistant cells of scientific and clinical interest. Ionic channels are ultimately the expression of the functional maturation of neurons, so the aim of this research was to characterize the pattern of the main voltage‐dependent ionic channels in T6‐NPCs differentiating to a neuronal phenotype, comparing it with NPCs isolated soon after death (T0‐NPCs). T6‐ and T0‐NPCs grow in medium containing epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). Differentiation was performed in small wells without the addition of growth factors, in the presence of adhesion molecules, fetal bovine serum, and leukemia inhibitory factor. Ionic currents, recorded by means of whole‐cell patch‐clamp, namely, ICa2+ HVA, both L‐ and non‐L‐type, IK+ delayed rectifying, IK+ inward rectifier, transient IK+A, and TTX‐sensitive INa+ have been found, although Na+ currents were found in only a small percentage of cells and after the fifth week of differentiation. No significant differences in current types, density, orcell capacitance were observed between T6‐NPCs and T0‐NPCs. The sequence in which the markers appear in new neural cells is not necessarily a fixed program, but the discrepancies in morphological, biochemical, and electrophysiological maturation of mouse NPCs to neurons, possibly different in vivo, suggest that the various steps of the differentiation are independently regulated. Therefore, in addition to morphological and biochemical data, functional tests should be considered for characterizing the maturation of neurons. © 2011 Wiley Periodicals, Inc.
Neoadjuvant chemotherapy with FOLFOX: Improved outcomes in Chinese patients with locally advanced gastric cancer
Authors: Li Zi‐Yu , Koh Cherry E. , Bu Zhao‐De , Wu Ai‐Wen , Zhang Lian‐Hai , Wu Xiao‐Jiang , Wu Qi , Zong Xiang‐Long , Ren Hui , Tang Lei , Zhang Xiao‐Peng , Li Ji‐You , Hu Ying , Shen Lin , Ji Jia‐Fu 
Published: December 2011

AbstractBackgroundAlthough the role of peri‐operative chemotherapy is established in the treatment of locally advanced gastric cancer, the optimal regime remains to be determined. FOLFOX has been used in palliative setting with good response rates but its role in a neoadjuvant setting is not well established.MethodsThis is a prospective non‐randomized study comparing peri‐operative FOLFOX versus adjuvant FOLFOX in patients with resectable locally advanced gastric cancer. Response to chemotherapy was assessed according to WHO criteria and pathological changes. Kaplan–Meier log rank test was used to calculate and compare survival differences.ResultsThere were 73 patients (neoadjuvant = 36). Complete and partial response was observed in 2 (6%) and 21 (64%) patients, respectively. Four‐year overall survival (OS) in the neoadjuvant arm was 78% versus 51% in the adjuvant arm (P = 0.031). Subgroup analysis found R0 resection (86% vs. 55%, P = 0.011) and patients with proximal cancers (87% vs. 14%, P < 0.001) to have improved OS. The most common side effect was grade 1–2 leukopenia. There were no grade 3 neuropathies, grade 4 cytopaenias, or treatment related deaths.ConclusionPeri‐operative treatment with FOLFOX shows promise in patients with resectable locally advanced gastric cancer. It warrants further evaluation and should be considered an alternative to peri‐operative ECF. J. Surg. Oncol. 2012; 105:793–799. © 2011 Wiley Periodicals, Inc.
The decision criterion of histological mixed type in “T1/T2” gastric carcinoma—comparison between TNM classification and Japanese classification of gastric cancer
Authors: Shimizu Hiroki , Ichikawa Daisuke , Komatsu Shuhei , Okamoto Kazuma , Shiozaki Atsushi , Fujiwara Hitoshi , Murayama Yasutoshi , Kuriu Yoshiaki , Ikoma Hisashi , Nakanishi Masayoshi , Ochiai Toshiya , Kokuba Yukihito , Kishimoto Mitsuo , Yanagisawa Akio , Otsuji Eigo 
Published: December 2011

AbstractBackgroundThis study was designed to evaluate the clinical significance of undifferentiated component in differentiated T1/T2 gastric adenocarcinoma.MethodsTwo hundred thirty‐one patients who underwent curative gastrectomy were diagnosed pathologically as differentiated type T1/T2 gastric cancer according to Japanese Classification of Gastric Carcinoma (JCGC). The patients were divided into subgroups, pure differentiated type (pure D group, 181 patients) and differentiated‐predominant mixed type (D > U group, 51 patients). The clinicopathological features of D > U group were compared with those of pure D group, and also those of undifferentiated‐predominant type (U > D group).ResultsPatients in D > U group were more likely to have larger and deeper tumors with lymphatic invasion and metastases than pure D group. However, there was no significant difference in clinicopathological factors between D > U and U > D groups, except for depth of tumor invasion. The postoperative 5‐year survival rate of D > U group was significantly poorer than that of pure D group (88% and 98%, P = 0.011). Multivariate analysis revealed the presence of undifferentiated component was an independent prognostic factor.ConclusionsThe presence of undifferentiated component in differentiated T1/T2 gastric cancer is associated with tumor progression. Therefore, the decision criterion of histological mixed type in TNM classification is better suited than JCGC in T1/T2 gastric cancer. J. Surg. Oncol. 2012; 105:800–804. © 2012 Wiley Periodicals, Inc.
Factors that Affect the Levels of Tourists' Satisfaction and Loyalty towards Food Festivals: a Case Study of Macau
Authors: Wan Yim King Penny , Chan Sow Hup Joanne 
Published: December 2011

ABSTRACTThe present study investigates the factors that affect tourists' satisfaction towards food festivals and explores whether tourists intend to revisit and/or recommend food festivals to others. Based on personal interviews with 40 study subjects, eight factors that affect their satisfaction levels were identified: location and accessibility, food, venue facility, environment/ambiance, service, entertainment, timing and festival size. The majority of tourists were satisfied with the Macau Food Festival and intended to revisit and recommend it to others. The presented findings have practical implications for food festival organizers to further attract food tourists. Copyright © 2011 John Wiley & Sons, Ltd.
Zinc Ion Uniquely Induced Triple Shape Memory Effect of Dipole–Dipole Reinforced Ultra‐High Strength Hydrogels
Authors: Han Yanjiao , Bai Tao , Liu Yuan , Zhai Xinyun , Liu Wenguang 
Published: December 2011

AbstractIn this study, we demonstrate that dipole–dipole interaction can be employed to not only tremendously enhance the mechanical properties of hydrogel, but also impart the gel to an amazing ability to memorize two temporary shapes. Cross‐linked hydrogels synthesized by copolymerization of acrylonitrile, a dipole–dipole containing monomer and hydrophilic comonomer are shown to exhibit triple shape memory (SM) triggered by the dynamic association and dissociation of dipole–dipole pairing between cynao groups uniquely responding to zinc ion species and concentration. This approach contributes to design and fabrication of novel SM hydrogels in a distinct way from conventional SM materials.
In utero and postnatal exposure to isoflavones results in a reduced responsivity of the mammary gland towards estradiol
Authors: Molzberger Almut F. , Vollmer Günter , Hertrampf Torsten , Möller Frank Josef , Kulling Sabine , Diel Patrick 
Published: December 2011

AbstractScope Exposure scenarios during different stages of development of an organism are discussed to trigger adverse and beneficial effects of isoflavones (ISO). The aim of this study was to investigate how in utero and postnatal ISO exposure modulates the estrogen sensitivity of the mammary gland and to identify the underlying molecular mechanisms.Methods and results Therefore, rats were exposed to either ISO‐free (IDD), ISO‐rich (IRD) or genistein‐rich diet (GRD), up to young adulthood. Proliferative activity (PCNA expression) in the mammary gland at different ages and the estrogen sensitivity of the mammary gland to estradiol (E2) or genistein (GEN) in adult ovariectomized animals was determined and compared with different treatments. Treatment with E2 resulted in a significant lower proliferative and estrogenic response of the mammary gland in IRD and GRD compared with IDD. This correlates to a change in the gene expression pattern and a decrease in the ratio of estrogen receptor alpha (ERα) beta (ERβConclusions Our results provide evidence that in utero and postnatal exposure to a diet rich in ISO but also to GEN reduces the sensitivity of the mammary gland toward estrogens and support the hypothesis that in utero and postnatal ISO exposure reduces the risk to develop breast cancer.
Patient Satisfaction with Postoperative Follow‐up by a Hand Therapist
Authors: Elnikety Sherif , El‐Husseiny Moataz , Kamal Tamer , Talawadekar Gautam D. , Richards Hayley , Smith Andrew M. 
Published: December 2011

AbstractPurposeThere has been a move to reduce and, indeed, stop postoperative appointments for uncomplicated surgical procedures within the National Health Service. The purpose of this study was to measure patient satisfaction with postoperative follow‐up conducted by a hand therapist, with no routine postoperative follow‐up by the surgeon.MethodsA total of 124 patients were recruited over two years. Fifty patients post‐simple trapeziectomy and 74 patients post‐single‐digit Dupuytren's fasciectomy were prospectively surveyed for their opinion on their postoperative care and whether or not they would have liked to be reviewed by the surgeon in a routine postoperative follow‐up appointment. All patients included in this study had their operations performed by one surgeon in one hospital. All patients were reviewed by a hand therapist within two weeks of surgery.ResultsA total of 116 patients completed the study, of whom 106 patients (91%) were satisfied with their postoperative management and 99 patients (85%) did not want to be reviewed by the surgeon in a postoperative outpatient follow‐up appointment.DiscussionThis study reflects the successful application of postoperative follow‐up by a hand therapist. Copyright © 2011 John Wiley & Sons, Ltd.
Racial differences in female urethral morphology and levator hiatal dimensions: An ultrasound study
Authors: Derpapas Alexandros , Ahmed Shahla , Vijaya Gopalan , Digesu Giuseppe Alessandro , Regan Lesley , Fernando Ruwan , Khullar Vik 
Published: December 2011

AbstractAimTo compare the urethral sphincter morphology and levator hiatal dimensions between white and black premenopausal nulliparous asymptomatic women using 3D/4D translabial ultrasonography.MethodsNulliparous black and white women were recruited in a tertiary gynecological center. All women were completely asymptomatic for pelvic floor dysfunction. Women were assessed with 3D/4D translabial ultrasound scan of the pelvic floor, at rest. Measurements of the total urethral sphincter volume (TSV), rhabdosphincter volume, (RSV) and levator hiatal dimensions (LH) were taken at rest, after voiding.ResultsTwenty‐three white and 14 black women (37 in total) were investigated. Subjects did not differ by age or body mass index (BMI). Black women were found to have significantly larger rhabdosphincters (RS) than their white counterparts (8.88 cm3 ± 1.65 vs. 5.97 cm3 ± 1.82, respectively, P = 0.000). With respect to levator hiatal dimensions at rest, black women had a significantly wider transverse diameter (LHt) than white women (mean difference of LHt = 0.43 cm, 95% CI 0.08–0.78, P < 0.05).ConclusionsAsymptomatic black nulliparous women have significantly larger rhabdosphincters than their white counterparts. Racial differences in the female urethral morphology could provide an insight on the pathophysiology of stress urinary incontinence. Neurourol. Urodynam. 31:502–507, 2012. © 2011 Wiley Periodicals, Inc.
Initial testing of the multitargeted kinase inhibitor pazopanib by the pediatric preclinical testing program
Authors: Keir Stephen T. , Morton Christopher L. , Wu Jianrong , Kurmasheva Raushan T. , Houghton Peter J. , Smith Malcolm A. 
Published: December 2011

AbstractPazopanib is an oral angiogenesis inhibitor targeting vascular growth factor receptor‐1, ‐2, and ‐3, platelet derived growth factor receptor‐α, platelet derived growth factor receptor‐β, and KIT that has demonstrated activity against a variety of adult cancer xenografts. Pazopanib was tested against a panel of pediatric rhabdomyosarcoma and Ewing sarcoma xenografts at a dose of 108 mg/kg/day or 100 mg/kg twice daily, administered orally for 28 days. While no objective responses were observed, pazopanib induced statistically significant differences in event‐free survival compared to controls in approximately one‐half of the sarcoma xenograft models tested. Though well tolerated, pazopanib showed limited activity against the sarcoma models evaluated, with the best tumor responses being growth delay. Pediatr Blood Cancer 2012;59:586–588. © 2011 Wiley Periodicals, Inc.