bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central role and mechanisms of β‐cell dysfunction and death in friedreich ataxia–associated diabetes
Authors: Cnop Miriam , Igoillo‐Esteve Mariana , Rai Myriam , Begu Audrey , Serroukh Yasmina , Depondt Chantal , Musuaya Anyishai E. , Marhfour Ihsane , Ladrière Laurence , Moles Lopez Xavier , Lefkaditis Dionysios , Moore Fabrice , Brion Jean‐Pierre , Cooper J. Mark , Schapira Anthony H. V. , Clark Anne , Koeppen Arnulf H. , Marchetti Piero , Pandolfo Massimo , Eizirik Décio L. , Féry Françoise 
Published: July 2012

AbstractObjective:Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused in almost all cases by homozygosity for a GAA trinucleotide repeat expansion in the frataxin gene. Frataxin is a mitochondrial protein involved in iron homeostasis. FRDA patients have a high prevalence of diabetes, the pathogenesis of which is not known. We aimed to evaluate the relative contribution of insulin resistance and β‐cell failure and the pathogenic mechanisms involved in FRDA diabetes.Methods:Forty‐one FRDA patients, 26 heterozygous carriers of a GAA expansion, and 53 controls underwent oral and intravenous glucose tolerance tests. β‐Cell proportion was quantified in postmortem pancreas sections from 9 unrelated FRDA patients. Using an in vitro disease model, we studied how frataxin deficiency affects β‐cell function and survival.Results:FRDA patients had increased abdominal fat and were insulin resistant. This was not compensated for by increased insulin secretion, resulting in a markedly reduced disposition index, indicative of pancreatic β‐cell failure. Loss of glucose tolerance was driven by β‐cell dysfunction, which correlated with abdominal fatness. In postmortem pancreas sections, pancreatic islets of FRDA patients had a lower β‐cell content. RNA interference–mediated frataxin knockdown impaired glucose‐stimulated insulin secretion and induced apoptosis in rat β cells and human islets. Frataxin deficiency sensitized β cells to oleate‐induced and endoplasmic reticulum stress‐induced apoptosis, which could be prevented by the incretins glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide.Interpretation:Pancreatic β‐cell dysfunction is central to diabetes development in FRDA as a result of mitochondrial dysfunction and higher sensitivity to metabolic and endoplasmic reticulum stress‐induced β‐cell death. ANN NEUROL 2012;72:971–982
Protective effects of enalapril, an angiotensin‐converting enzyme inhibitor, on multiple organ damage following scald injury in rats
Authors: Zhang Bing‐Qian , Wang Guang , Zhang Jia‐Ping , Hu Jiong‐Yu , Xiao Rong , Lei Ze‐Yuan , Ruan Jing , Dang Yong‐Ming , Zhang Dong‐Xia , Bian Xiu‐Wu , Huang Yue‐Sheng 
Published: July 2012

AbstractThe aim of this study is to investigate the effects of enalapril, an angiotensin‐converting enzyme inhibitor, on multiple organ damage after scald injury. Healthy adult rats (half male and half female; 8–12 weeks old) were randomly assigned to the following treatments: sham operation, scald injury, and intraperitoneal enalapril (1, 2, and 4 mg/kg body weight) treatment after scalding. At 1, 12, and 24 H postscald, left ventricular and aortic hemodynamics were measured using a multichannel physiological recorder. Functional and pathological changes of the heart, liver, and kidney were examined by biochemical and histological methods. Compared with sham controls, untreated scalded animals showed decreased hemodynamic parameters and increased myocardial angiotensin II, serum creatine kinase heart isoenzyme, and serum cardiac troponin I and histopathological inflammation in the myocardium 12 H postscald. These hemodynamic, functional, and pathological changes were attenuated by 1 mg/kg enalapril. Enalapril reversed scald‐induced elevations in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and blood creatinine 12 H postscald, and ameliorated focal necrosis in the liver and erythrocyte cast formation in renal tubules. However, higher doses of enalapril yielded less or no improvement in organ dysfunction. Enalapril at 1 mg/kg attenuates scald‐induced multiple organ damage in rats.
In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen
Authors: Tsume Yasuhiro , Langguth Peter , Garcia‐Arieta Alfredo , Amidon Gordon L. 
Published: July 2012

ABSTRACTThe FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate‐release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l ‐1/pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l ‐1/pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.
Mutations in Lyar and p53 are synergistically lethal in female mice
Authors: Wang Guan , Fulkerson Christopher M. , Malek Reem , Ghassemifar Sara , Snyder Paul W. , Mendrysa Susan M. 
Published: July 2012

AbstractBACKGROUNDLy‐1 antibody reactive clone (LYAR) is a nucleolar zinc finger protein that has been implicated in cell growth, self‐renewal of embryonic stem cells, and medulloblastoma. To test whether LYAR is critical for cell growth and development, we generated Lyar mutant mice.METHODSMice carrying the mutant Lyargt allele were generated from embryonic stem cells that contained a gene‐trap insertion in the Lyar gene. Phenotypic analyses were performed on Lyar mutant mice and mouse embryonic fibroblasts. Lyargt/gt mice were crossed to mice lacking the p53 tumor suppressor protein and Lyar/p53 compound mutants scored for external abnormalities.RESULTSLyargt/gt homozygotes are viable, fertile, and indistinguishable from wild type littermates. However, the growth of Lyar+/gt and Lyargt/gt mouse embryonic fibroblasts (MEFs) was impaired, coincident with an increase in the steady‐state level of p53 and a key p53 effector of growth arrest, p21, suggesting that a cellular stress response is triggered in the absence of a wild type level of LYAR. Remarkably, the majority of Lyar+/gt and Lyargt/gt female mice lacking p53 mice failed to survive. The neural tube defect (NTD) exencephaly was observed in ≈26% and ≈61% of female Lyar+/gt;p53−/− and Lyargt/gt;p53−/− embryos, respectively.CONCLUSIONSLyar/p53 mutant mice represent a new digenic model of NTDs. Furthermore, these studies identify Lyar as a novel candidate gene for a role in human NTDs. These results provide new data to support the idea that loss of a p53‐mediated developmental checkpoint may increase the risk of NTDs owing to some germline mutations. © Birth Defects Research (Part A) 94:729–737, 2012. Published 2012 Wiley Periodicals, Inc.
Microarray analysis of Xenopus endoderm expressing Ptf1a
Authors: Bilogan Cassandra K. , Horb Marko E. 
Published: July 2012

AbstractPancreas‐specific transcription factor 1a (Ptf1a), a bHLH transcription factor, has two temporally distinct functions during pancreas development; initially it is required for early specification of the entire pancreas, while later it is required for proper differentiation and maintenance of only acinar cells. The importance of Ptf1a function was revealed by the fact that loss of Ptf1a leads to pancreas agenesis in humans. While Ptf1a is one of the most important pancreatic transcription factors, little is known about the differences between the regulatory networks it controls during initial specification of the pancreas as opposed to acinar cell development, and to date no comprehensive analysis of its downstream targets has been published. In this article, we use Xenopus embryos to identify putative downstream targets of Ptf1a. We isolated anterior endoderm tissue overexpressing Ptf1a at two early stages, NF32 and NF36, and compared their gene expression profiles using microarrays. Our results revealed that Ptf1a regulates genes with a wide variety of functions, providing insight into the complexity of the regulatory network required for pancreas specification. genesis 50:853–870, 2012. © 2012 Wiley Periodicals, Inc.
TIE2-expressing monocytes as a diagnostic marker for hepatocellular carcinoma correlates with angiogenesis
Authors: Matsubara Tokuhiro , Kanto Tatsuya , Kuroda Shoko , Yoshio Sachiyo , Higashitani Koyo , Kakita Naruyasu , Miyazaki Masanori , Sakakibara Mitsuru , Hiramatsu Naoki , Kasahara Akinori , Tomimaru Yoshito , Tomokuni Akira , Nagano Hiroaki , Hayashi Norio , Takehara Tetsuo 
Published: July 2012

Abstract

Angiogenesis is a critical step in the development and progression of hepatocellular carcinoma (HCC). Myeloid lineage cells, such as macrophages and monocytes, have been reported to regulate angiogenesis in mouse tumor models. TIE2, a receptor of angiopoietins, conveys pro-angiogenic signals and identifies a monocyte/macrophage subset with pro-angiogenic activity. Here, we analyzed the occurrence and kinetics of TIE2-expressing monocytes/macrophages (TEMs) in HCC patients. This study enrolled 168 HCV-infected patients including 89 with HCC. We examined the frequency of TEMs, as defined as CD14+CD16+TIE2+ cells, in the peripheral blood and liver. The localization of TEMs in the liver was determined by immunofluorescence staining. Micro-vessel density in the liver was measured by counting CD34+ vascular structures. We found that the frequency of circulating TEMs was significantly higher in HCC than non-HCC patients, while being higher in the liver than in the blood. In patients who underwent local radio-ablation or resection of HCC, the frequency of TEMs dynamically changed in the blood in parallel with HCC recurrence. Most TEMs were identified in the perivascular areas of tumor tissue. A significant positive correlation was observed between micro-vessel density in HCC and frequency of TEMs in the blood or tumors, suggesting that TEMs are involved in HCC angiogenesis. Receiver operating characteristic analyses revealed the superiority of TEM frequency to AFP, PIVKA-II and ANG-2 serum levels as diagnostic marker for HCC. Conclusion: TEMs increase in patients with HCC and their frequency changes with the therapeutic response or recurrence. We thus suggest that TEM frequency can be used as a diagnostic marker for HCC, potentially reflecting angiogenesis in the liver.
Incidence, risk factors and management of pleural effusions during dasatinib treatment in unselected elderly patients with chronic myelogenous leukaemia
Authors: Latagliata Roberto , Breccia Massimo , Fava Carmen , Stagno Fabio , Tiribelli Mario , Luciano Luigiana , Gozzini Antonella , Gugliotta Gabriele , Annunziata Mario , Cavazzini Francesco , Ferrero Dario , Musto Pellegrino , Capodanno Isabella , Iurlo Alessandra , Visani Giuseppe , Crugnola Monica , Calistri Elisabetta , Castagnetti Fausto , Vigneri Paolo , Alimena Giuliana 
Published: July 2012

AbstractTo assess the most important features and clinical impact of pleural effusions, which are a common toxicity during dasatinib treatment and often impair its high efficacy, 172 unselected consecutive patients with chronic myelogenous leukaemia in chronic phase treated in 27 Italian centres, with dasatinib when aged >60 years for resistance/intolerance to imatinib, were examined. During treatment, 52/172 patients (30.2%) presented pleural effusion, which was grades 1–2 in 38 patients and grades 3–4 in 14 patients (8.1% of the entire cohort of patients), according to the WHO scale; in 14/52 patients (26.9%), there was a concomitant pericardial effusion. Pleural effusion was recurrent in 25/52 patients (48.0%). Median time from dasatinib to first pleural effusion was 11.0 months (interquartile range 3.6–18.6). Eleven patients (6.4%) required permanent dasatinib discontinuation. Only presence of concomitant pulmonary disease ( p = 0.035) and initial daily dose of dasatinib (140 mg vs 100 mg, p = 0.014) were significantly associated with pleural effusions. There were no differences among patients with or without pleural effusions as concerns response rates and overall survival. Pleural effusions were common in our unselected ‘real‐life’ population of elderly patients but were clinically manageable and did not seem to affect treatment results. Copyright © 2012 John Wiley & Sons, Ltd.
Construction and hemocompatibility study of highly bioactive heparin‐functionalized surface
Authors: Yang Zhi‐Lu , Zhou Shuo , Lu Lei , Wang Xin , Wang Jin , Huang Nan 
Published: July 2012

AbstractA simple method is developed to construct anticoagulant surfaces via passive adsorption of heparin onto the protonated plasma‐polymerized allylamine (PPAam) films from phosphate‐buffered saline (PBS). These protonated PPAam surfaces are found to have high affinity to heparin. Importantly, the heparin‐functionalized PPAam (Hep–PPAam) surfaces show good retention of heparin after long‐term immersion in PBS. The Hep–PPAam surface prolongs the activated partial thromboplastin time for about 20 s as compared to 316L stainless steel even though the adsorption amount of heparin is only about 300 ng/cm2. This indicates that the heparin bound to the protonated PPAam surfaces in this way maintains a high bioactivity. Blood platelet adhesion and activation on this surface is remarkably reduced and adsorption and activation of fibrinogen is inhibited. Thus, Hep–PPAam surface modification leads to a significant improve of the hemocompatibility. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3124–3133, 2012.
Histocompatibility and in vivo signal throughput for PEDOT, PEDOP, P3MT, and polycarbazole electrodes
Authors: Forcelli Patrick A. , Sweeney Cameron T. , Kammerich Anthony D. , Lee Brian C.‐W. , Rubinson Laura H. , Kayinamura Yohani P. , Gale Karen , Rubinson Judith F. 
Published: July 2012

AbstractStimulation and recording of the in vivo electrical activity of neurons are critical functions in contemporary biomedical research and in treatment of patients with neurological disorders. The electrodes presently in use tend to exhibit short effective lifespans due to degradation of signal transmission resulting from the tissue response at the electrode–brain interface, with signal throughput suffering most at the low frequencies relevant for biosignals. To overcome these limitations, new electrode designs to minimize tissue responses, including conducting polymers (CPs) have been explored. Here, we report the short‐term histocompatibility and signal throughput results comparing platinum and CP‐modified platinum electrodes in a Sprague–Dawley rat model. Two of the polymers tested elicited significantly decreased astrocyte responses relative to platinum. These polymers also showed improved signal throughput at low frequencies and comparable signal‐to‐noise ratios during targeted intracranial electroencephalograms. These results suggest that CP electrodes may present viable alternatives to the metal electrodes that are currently in use. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A:3455–3462, 2012.
Reversine promotes porcine muscle derived stem cells (PMDSCs) differentiation into female germ‐like cells
Authors: Lv Xiao , Zhu Haijing , Bai Yaofu , Chu Zhili , Hu Yue , Cao Hui , Liu Chao , He Xin , Peng Sha , Gao Zhimin , Yang Chunrong , Hua Jinlian 
Published: July 2012

AbstractA small molecular chemical‐Reversine has been shown to promote cell reprogramming and induce dedifferentiation of multiple terminally differentiated mesodermal origin cells, and then differentiate into other cell types within mesodermal lineages as well as neuroectodermal. However, the possibilities of these cells to give rise to germ cell lineages have not been examined. The objective of the current study was to detect the effect of Reversine on PMDSCs differentiation into germ cells. PMDSCs from fetal porcine skeletal muscle and their potential of differentiation into germ cells in vitro were investigated. The phenotype, proliferation potential, characteristic markers of the first adhesion cells (pp1), and the purified 2 times cells (pp3) were analyzed by growth curve, FACS, and RT‐PCR, respectively. Then, the purified cells were induced with 10% or 20% bovine follicular fluid (FF), the results showed that some of the induced pp3 cells were similar as porcine oocyte, and expressed germ cell and oocyte markers analyzed by semi‐quantitative RT‐PCR and immunofluorescent staining. Reversine clearly increased the potentiality of PMDSCs differentiation into large round germ‐like cells in FF induction medium analyzed by morpholgogy, QRT‐PCR and immunofluoresce. The BrdU labeled PMDSCs might differentiate into female germ‐like cells in recipient's kidney capsule, which were positive for germ cell and meiotic markers (Dazl, Vasa, Figla, Stra8, Scp3) and oocyte markers (Zp2, Zp3). These findings provided an efficient model to study the mechanism of cell proliferation and germ cell differentiation in livestock promoted by Reversine. J. Cell. Biochem. 113: 3629–3642, 2012. © 2012 Wiley Periodicals, Inc.
A Novel Pattern of Placental Leucine Transfer During Mid to Late Gestation in a Highly Placentotrophic Viviparous Lizard
Authors: Itonaga Keisuke , Wapstra Erik , Jones Susan M. 
Published: July 2012

ABSTRACTPlacentotrophy is the nourishment of embryos by resources provided via the placenta during gestation. The magnitude and timing of placental nutrient support during pregnancy are important for embryonic growth, especially in highly placentotrophic animals such as mammals. However, no study has yet investigated how placental organic nutrient support may change during pregnancy in highly placentotrophic viviparous reptiles. Amino acids are essential nutrients for embryonic growth and leucine is a common amino acid. The magnitude and timing of placental leucine transfer may affect embryonic growth and mass and, therefore, offspring phenotype. In this study, female Pseudemoia entrecasteauxii, a highly placentotrophic viviparous skink, were collected throughout gestation. We injected 3H‐leucine into these gravid females and assessed the transfer of 3H‐leucine into maternal compartments (i.e., the blood and the liver), and into embryonic compartments (i.e., the embryo, the yolk, and the amniotic fluid). At either 60 or 120 min post‐injection, the radioactivity in each sample was extracted and then counted, and the transfer ratio was calculated. Our results provide direct evidence that circulating maternal leucine passes through the placenta into the embryos in this species. The relative rate of placental leucine transfer did not alter during mid to late gestation. This suggests the steady somatic growth of the embryos during mid‐late pregnancy is dependent upon the placental transfer of nutrients rather than yolk stores. This pattern of placental nutrient support may determine offspring body size at birth and, therefore, offspring fitness in P. entrecasteauxii. J. Exp. Zool. (Mol. Dev. Evol.) 318:308–315, 2012. © 2012 Wiley Periodicals, Inc.
The evolution, development and skeletal identity of the crocodylian pelvis: Revisiting a forgotten scientific debate
Authors: Claessens Leon P.A.M. , Vickaryous Matthew K. 
Published: July 2012

AbstractUnlike most tetrapods, in extant crocodylians the acetabulum is formed by only two of the three skeletal elements that constitute the pelvis, the ilium, and ischium. This peculiar arrangement is further confused by various observations that suggest the crocodylian pelvis initially develops from four skeletal elements: the ilium, ischium, pubis, and a novel element, the prepubis. According to one popular historical hypothesis, in crocodylians (and many extinct archosaurs), the pubis fuses with the ischium during skeletogenesis, leaving the prepubis as a distinct element, albeit one which is excluded from the acetabulum. Whereas the notion of a distinct prepubic element was once a topic of considerable interest, it has never been properly resolved. Here, we combine data gleaned from a developmental series of Alligator mississippiensis embryos, with a revised interpretation of fossil evidence from numerous outgroups to Crocodylia. We demonstrate that the modern crocodylian pelvis is composed of only three elements: the ilium, ischium, and pubis. The reported fourth pelvic element is an unossified portion of the ischium. Interpretations of pelvic skeletal homology have featured prominently in sauropsid systematics, and the unambiguous identification of the crocodylian pubis provides an important contribution to address larger scale evolutionary questions associated with locomotion and respiration. J. Morphol. , 2012. © 2012 Wiley Periodicals, Inc.
Determination of amylopectin structure and physicochemical properties in rice endosperm starch of mutant lines derived from Malaysian rice cultivar MR219
Authors: Mar Nyo Nyo , Umemoto Takayuki , Ismail Maznah , Abdullah Siti Nor Akma , Maziah Mahmood 
Published: July 2012

AbstractBACKGROUND: Characterization of starch properties and functionality can apply breeding program selection for desirable traits such as eating, cooking and processing qualities to meet consumer preference. Low amylose content is generally preferred in Malaysia because of cohesive, tender and glossy cooked rice. Rice high in short‐chain amylopectin has a lower transition temperature of starch gelatinization. In the continuing search for improved starch quality in rice cultivars a study was carried out with new mutant lines MR219‐4 and MR219‐9, derived from MR219.RESULTS: MR219 and its mutant lines contain L‐type amylopectin, being high in amylopectin of intermediate chain length with degree of polymerization 12‐21. The apparent amylose content (AAC) in MR219‐4 had lower AAC value (19.2%) compared to other lines. A strongly negative correlation was found between chain‐length fraction of amylopectin and transition temperatures—onset temperature peak temperature, and conclusion temperature (0.992, 0.958, 0.950; P < 0.01)—with fraction b1 (fb1), respectively.CONCLUSION: The Malaysian lines studied contain L‐type amylopectin and offer a better understanding of grain quality improvement in terms of starch properties and functionality. This information will be directly applicable to select for desirable traits in future breeding programs. Copyright © 2012 Society of Chemical Industry