bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unusual orbital lymphoma undetectable by magnetic resonance imaging: a case report
Authors: Tatsugawa Maria , Noma Hidetaka , Mimura Tatsuya , Funatsu Hideharu 
Published: November 2009

Abstract

Introduction
We report the case of a patient with orbital malignant lymphoma that was not detected by imaging studies when she presented with impaired vision, which lead to her eventual loss of sight.

Case presentation
A 71-year-old Japanese woman complained of deteriorating vision in her left eye. On examination, papilledema was detected, but magnetic resonance imaging only showed slight thickening and enhancement of the left optic nerve. A diagnosis of idiopathic optic neuritis was made and corticosteroid pulse therapy was administered. During the next four months, the patient received a total of four courses of corticosteroid pulse therapy, but she still suffered from bilateral loss of vision. A second magnetic resonance imaging procedure revealed tumors in both orbits and a biopsy showed diffuse large B-cell malignant lymphoma.

Conclusion
The possibility of malignant lymphoma should be considered in patients with recurrent optic neuropathy despite administration of corticosteroid pulse therapy, even when there are no abnormalities on cerebrospinal fluid examination or magnetic resonance imaging.
Laboratory-scale method for enzymatic saccharification of lignocellulosic biomass at high-solids loadings
Authors: Roche Christine M , Dibble Clare J , Stickel Jonathan J 
Published: November 2009

Abstract

Background
Screening new lignocellulosic biomass pretreatments and advanced enzyme systems at process relevant conditions is a key factor in the development of economically viable lignocellulosic ethanol. Shake flasks, the reaction vessel commonly used for screening enzymatic saccharifications of cellulosic biomass, do not provide adequate mixing at high-solids concentrations when shaking is not supplemented with hand mixing.

Results
We identified roller bottle reactors (RBRs) as laboratory-scale reaction vessels that can provide adequate mixing for enzymatic saccharifications at high-solids biomass loadings without any additional hand mixing. Using the RBRs, we developed a method for screening both pretreated biomass and enzyme systems at process-relevant conditions. RBRs were shown to be scalable between 125 mL and 2 L. Results from enzymatic saccharifications of five biomass pretreatments of different severities and two enzyme preparations suggest that this system will work well for a variety of biomass substrates and enzyme systems. A study of intermittent mixing regimes suggests that mass transfer limitations of enzymatic saccharifications at high-solids loadings are significant but can be mitigated with a relatively low amount of mixing input.

Conclusion
Effective initial mixing to promote good enzyme distribution and continued, but not necessarily continuous, mixing is necessary in order to facilitate high biomass conversion rates. The simplicity and robustness of the bench-scale RBR system, combined with its ability to accommodate numerous reaction vessels, will be useful in screening new biomass pretreatments and advanced enzyme systems at high-solids loadings.
microRNAs and genetic diseases
Authors: Meola Nicola , Gennarino Vincenzo Alessandro , Banfi Sandro 
Published: November 2009

Abstract
microRNAs (miRNAs) are a class of small RNAs (19-25 nucleotides in length) processed from double-stranded hairpin precursors. They negatively regulate gene expression in animals, by binding, with imperfect base pairing, to target sites in messenger RNAs (usually in 3' untranslated regions) thereby either reducing translational efficiency or determining transcript degradation. Considering that each miRNA can regulate, on average, the expression of approximately several hundred target genes, the miRNA apparatus can participate in the control of the gene expression of a large quota of mammalian transcriptomes and proteomes. As a consequence, miRNAs are expected to regulate various developmental and physiological processes, such as the development and function of many tissue and organs. Due to the strong impact of miRNAs on the biological processes, it is expected that mutations affecting miRNA function have a pathogenic role in human genetic diseases, similar to protein-coding genes. In this review, we provide an overview of the evidence available to date which support the pathogenic role of miRNAs in human genetic diseases. We will first describe the main types of mutation mechanisms affecting miRNA function that can result in human genetic disorders, namely: (1) mutations affecting miRNA sequences; (2) mutations in the recognition sites for miRNAs harboured in target mRNAs; and (3) mutations in genes that participate in the general processes of miRNA processing and function. Finally, we will also describe the results of recent studies, mostly based on animal models, indicating the phenotypic consequences of miRNA alterations on the function of several tissues and organs. These studies suggest that the spectrum of genetic diseases possibly caused by mutations in miRNAs is wide and is only starting to be unravelled.
Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1β-induced NF-κB-mediated inflammation and apoptosis
Authors: Csaki Constanze , Mobasheri Ali , Shakibaei Mehdi 
Published: November 2009

Abstract
Introduction
Currently available treatments for osteoarthritis (OA) are restricted to nonsteroidal anti-inflammatory drugs, which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the NF-κB signalling pathway.

Methods
We have recently demonstrated that in chondrocytes resveratrol modulates the NF-κB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-κB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on IL-1β-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy.

Results
Treatment with curcumin and resveratrol suppressed NF-κB-regulated gene products involved in inflammation (cyclooxygenase-2, matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor), inhibited apoptosis (Bcl-2, Bcl-xL, and TNF-α receptor-associated factor 1) and prevented activation of caspase-3. IL-1β-induced NF-κB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Iκκ and proteasome activation, inhibition of IκBα phosphorylation and degradation, and inhibition of nuclear translocation of NF-κB. The modulatory effects of curcumin and resveratrol on IL-1β-induced expression of cartilage specific matrix and proinflammatory enzymes were mediated in part by the cartilage-specific transcription factor Sox-9.

Conclusions
We propose that combining these natural compounds may be a useful strategy in OA therapy as compared with separate treatment with each individual compound.
Effect of small interference RNA (siRNA) for ADAMTS5on intervertebral disc degeneration in the rabbit anular needle-puncture model
Authors: Seki Shoji , Asanuma-Abe Yumiko , Masuda Koichi , Kawaguchi Yoshiharu , Asanuma Kunihiro , Muehleman Carol , Iwai Akiko , Kimura Tomoatsu 
Published: November 2009

Abstract
Introduction
The etiology of degenerative disc disease is unknown. Several investigators have reported the presence of proteolytic enzymes, such as the matrix metalloproteinase (MMP) and ADAMTS (a disintegrin and metalloprotease with thrombospondin-like repeats) families, in degenerated human discs. Glasson and colleagues recently reported that a significant reduction occurs in the severity of cartilage destruction in ADAMTS5 knockout mice compared with wild-type mice. The purpose of this study was to evaluate the suppressive effects of injections of ADAMTS5 small interference RNA (siRNA) oligonucleotide on intervertebral disc degeneration in the rabbit anular needle-puncture model.

Methods
Rabbit nucleus pulposus (NP) cells were transfected with siRNA oligonucleotides specific for ADAMTS5 or the control. The suppression of the ADAMTS5 gene by siRNA transfection was assessed by using real-time polymerase chain reaction (PCR), both in monolayer and alginate bead cultures with or without interleukin-1β (IL-1β) stimulation. The effect of siRNA was determined in vivo by using the rabbit anular needle-puncture model (control group: n = 8; ADAMTS5 group: n = 8). One week after the initial anular puncture, the animals received an injection of the control or anti-ADAMTS5 oligonucleotide (100 μg each at the L2/3 and L4/5 level; 16 discs/group). Disc height, magnetic resonance imaging (MRI) (Thompson classification and signal intensity), and safranin-O staining (histologic grade) were assessed.

Results
IL-1β treatment significantly increased the ADAMTS5 mRNA level in NP cells (P < 0.01). ADAMTS5 gene suppression was 70% compared with the control oligonucleotide in both monolayer and alginate bead culture with or without stimulation with IL-1β. The injection of anti-ADAMTS5 oligonucleotide in vivo resulted in improved MRI scores with increased signal intensity and improved histologic grade scores with statistical significance (P < 0.05). No significant change in disc height was observed.

Conclusions
A single injection of ADAMTS5 siRNA induced the suppression of degradation in NP tissues, as shown by significantly improved MRI and histologic grades. The mechanism of response to siRNA may be worthy of exploration for possible therapeutic purposes.
Multidisciplinary care for tracheostomy patients: a systematic review
Authors: Garrubba Marie , Turner Tari , Grieveson Clare 
Published: November 2009

Abstract
Introduction
Appropriate care for patients with tracheostomies in hospital settings is an important issue. Each year more than 7000 patients receive tracheostomies in Australia and New Zealand alone. Many of these tracheostomy patients commence their care in the intensive care unit (ICU) and once stabilised are then transferred to a general ward. Insufficient skills and experience of staff caring for tracheostomy patients may lead to sub-optimal care and increased morbidity. The purpose of this review was to identify whether multidisciplinary tracheostomy outreach teams enable the reduction in time to decannulation and length of stay in acute and sub-acute settings, improve quality of care or decrease adverse events for patients with a tracheostomy.

Methods
We included all relevant trials published in English. We searched Medline, CINAHL, All EBM and EMBASE in June 2009. Studies were selected and appraised by two reviewers in consultation with colleagues, using inclusion, exclusion and appraisal criteria established a priori.

Results
Three studies were identified which met the study selection criteria. All were cohort studies with historical controls. All studies included adult patients with tracheostomies. One study was conducted in the UK and the other two in Australia. Risk of bias was moderate to high in all studies. All papers concluded that the introduction of multidisciplinary care reduces the average time to decannulation for tracheostomy patients discharged from the ICU. Two papers also reported that multidisciplinary care reduced the overall length of stay in hospital as well as the length of stay following ICU discharge.

Conclusions
In the papers we appraised, patients with a tracheostomy tube in situ discharged from an ICU to a general ward who received care from a dedicated multidisciplinary team as compared with standard care showed reductions in time to decannulation, length of stay and adverse events. Impacts on quality of care were not reported.
These results should be interpreted with caution due to the methodological weaknesses in the historical control studies.
Effects of TWEAK (TNF Superfamily Member 12) on Differentiation, Metabolism, and Secretory Function of Human Primary Preadipocytes and Adipocytes
Authors: Tiller Gabriele , Fischer-Posovszky Pamela , Laumen Helmut , Finck Andreas , Skurk Thomas , Keuper Michaela , Brinkmann Ulrich , Wabitsch Martin , Link Dieter , Hauner Hans 
Published: November 2009

Abstract
Expansion of adipose tissue mass by hypertrophy and hyperplasia is the hallmark of obesity. An automated cDNA screen was established to identify secreted human proteins with an inhibitory effect on adipocyte differentiation and, thereby, a potential inhibitory effect on adipose tissue growth. A member of the TNF superfamily, TNF-like weak inducer of apoptosis (TWEAK; TNF superfamily 12) was identified by means of high-throughput screening with the lipophilic dye Nile Red as an inhibitor of murine adipocyte differentiation and, subsequently, also of human adipocyte differentiation. TWEAK inhibited lipid deposition in a dose-dependent manner without causing cytotoxic effects. This inhibitory action was mimicked by an agonistic antibody of the TWEAK receptor. The TWEAK receptor (fibroblast growth factor inducible 14; CD266) was expressed on human primary preadipocytes and mature adipocytes. Knockdown of TWEAK receptor by short-hairpin RNA abolished the inhibitory effect of TWEAK on cell differentiation, demonstrating that the effects of TWEAK are mediated by its specific receptor. Inhibition of differentiation was the result of interference at an early step of transcriptional activation as assessed by decreased peroxisome proliferator-activated receptor-γ, CCAAT enhancer-binding protein α (C/EBPα), and CCAAT enhancer-binding protein β (C/EBPβ) mRNA expression. In contrast to TNFα, basal and insulin-stimulated glucose uptake and lipolysis of terminally differentiated mature adipocytes and secretion of proinflammatory cytokines were not altered in the presence of TWEAK, and nuclear factor κ B activity was only weakly induced. We conclude from our findings that TWEAK and the corresponding agonistic antibody have the potential to prevent adipose tissue growth without adversely influencing central metabolic pathways or proinflammatory cytokine secretion in adipose tissue.
Wingless (Wnt)-3A Induces Trophoblast Migration and Matrix Metalloproteinase-2 Secretion through Canonical Wnt Signaling and Protein Kinase B/AKT Activation
Authors: Sonderegger Stefan , Haslinger Peter , Sabri Alia , Leisser Christina , Otten Jan V. , Fiala Christian , Knöfler Martin 
Published: November 2009

AbstractInvasion of human trophoblasts is promoted through activation of wingless (Wnt) signaling, suggesting a role of the pathway in placental development and morphogenesis. However, details on the process such as involvement of canonical and/or noncanonical Wnt signaling cascades as well as their target genes are largely unknown. Hence, signal transduction via canonical Wnt signaling or phosphatidylinositide 3-kinase (PI3K)/AKT and their cross talk as well as trophoblast-specific protease expression were investigated in trophoblastic SGHPL-5 cells and primary extravillous trophoblasts purified from first-trimester placentas. Western blot analyses revealed that the recombinant Wnt ligand Wnt-3A increased phosphorylation of AKT and the downstream kinase glycogen synthase kinase (GSK)-3β as well as accumulation of activated, nuclear β-catenin. In accordance, luciferase expression of a canonical Wnt/TCF reporter and cell migration in first-trimester villous explant cultures and of SGHPL-5 cells were stimulated. Chemical inhibition of PI3K abolished Wnt-dependent phosphorylation of AKT and GSK-3β and trophoblast motility but did not affect appearance of activated β-catenin or Wnt/TCF reporter activity. In contrast, inhibition of the canonical pathway through soluble Dickkopf-1 did not influence AKT and GSK-3β phosphorylation but reduced Wnt reporter activity, accumulation of active β-catenin, and cell migration. Both inhibitors decreased Wnt-3A-induced secretion of pro- and active matrix metalloproteinase-2 from SGHPL-5 cells and pure EVT. The data suggest that Wnt-3A may activate canonical Wnt signaling and PI3K/AKT through distinct receptors. The two signaling cascades act independently in trophoblasts; however, both pathways promote Wnt-dependent migration and the release of matrix metalloproteinase-2, which has been identified as novel Wnt target in invasive trophoblasts.
Peroxisome Proliferator-Activated Receptor-α Control of Lipid and Glucose Metabolism in Human White Adipocytes
Authors: Ribet Carole , Montastier Emilie , Valle Carine , Bezaire Véronic , Mazzucotelli Anne , Mairal Aline , Viguerie Nathalie , Langin Dominique 
Published: November 2009

Abstract
This work aimed at characterizing the role of peroxisome proliferator-activated receptors (PPAR)α in human white adipocyte metabolism and at comparing PPARα and PPARγ actions in these cells. Primary cultures of human fat cells were treated with the PPARα agonist GW7647 or the PPARγ agonist rosiglitazone. Changes in gene expression were determined using DNA microrrays and quantitative RT-PCR. Western blot and metabolic studies were performed to identify the biological effects elicited by PPAR agonist treatments. GW7647 induced an up-regulation of β-oxidation gene expression and increased palmitate oxidation. Unexpectedly, glycolysis was strongly reduced at transcriptional and functional levels by GW7647 leading to a decrease in pyruvate and lactate production. Glucose oxidation was decreased. Triglyceride esterification and de novo lipogenesis were inhibited by the PPARα agonist. GW7647-induced alterations were abolished by a treatment with a PPARα antagonist. Small interfering RNA-mediated extinction of PPARα gene expression in hMADS adipocytes attenuated GW7647 induction of palmitate oxidation. Rosiglitazone had no major impact on glycolysis and β-oxidation. Altogether these results show that PPARα can selectively up-regulate β-oxidation and decrease glucose utilization in human white adipocytes.
Deletion of the Novel Oocyte-Enriched Gene, Gpr149, Leads to Increased Fertility in Mice
Authors: Edson Mark A. , Lin Yi-Nan , Matzuk Martin M. 
Published: November 2009

Abstract
Through in silico subtraction and microarray analysis, we identified mouse Gpr149, a novel, oocyte-enriched transcript that encodes a predicted orphan G-protein-coupled receptor (GPR). Phylogenetic analysis of GPR149 from fish to mammals suggests that it is widely conserved in vertebrates. By multitissue RT-PCR analysis, we found that Gpr149 is highly expressed in the ovary and also in the brain and the digestive tract at low levels. Gpr149 levels are low in newborn ovaries but increase throughout folliculogenesis. In the ovary, we found that granulosa cells did not express Gpr149, whereas germinal vesicle and meiosis II stage oocytes showed high levels of Gpr149 expression. After fertilization, Gpr149 expression declined, becoming undetectable by the two-cell stage. To study the function of GPR149 in oocyte growth and maturation, we generated Gpr149 null mice. Surprisingly, Gpr149 null mice are viable and have normal folliculogenesis, but demonstrate increased fertility, enhanced ovulation, increased oocyte Gdf9 mRNA levels, and increased levels of FSH receptor and cyclin D2 mRNA levels in granulosa cells. Thus, Gpr149 null mice are one of the few models with enhanced fertility, and GPR149 could be a target for small molecules to enhance fertility in the assisted reproductive technology clinic.
Central Insulin Signaling Is Attenuated by Long-Term Insulin Exposure via Insulin Receptor Substrate-1 Serine Phosphorylation, Proteasomal Degradation, and Lysosomal Insulin Receptor Degradation
Authors: Mayer Christopher M. , Belsham Denise D. 
Published: November 2009

AbstractCentral insulin signaling is critical for the prevention of insulin resistance. Hyperinsulinemia contributes to insulin resistance, but it is not yet clear whether neurons are subject to cellular insulin resistance. We used an immortalized, hypothalamic, clonal cell line, mHypoE-46, which exemplifies neuronal function and expresses the components of the insulin signaling pathway, to determine how hyperinsulinemia modifies neuronal function. Western blot analysis indicated that prolonged insulin treatment of mHypoE-46 cells attenuated insulin signaling through phospho-Akt. To understand the mechanisms involved, time-course analysis was performed. Insulin exposure for 4 and 8 h phosphorylated Akt and p70-S6 kinase (S6K1), whereas 8 and 24 h treatment decreased insulin receptor (IR) and IR substrate 1 (IRS-1) protein levels. Insulin phosphorylation of S6K1 correlated with IRS-1 ser1101 phosphorylation and the mTOR-S6K1 pathway inhibitor rapamycin prevented IRS-1 serine phosphorylation. The proteasomal inhibitor epoxomicin and the lysosomal pathway inhibitor 3-methyladenine prevented the degradation of IRS-1 and IR by insulin, respectively, and pretreatment with rapamycin, epoxomicin, or 3-methyladenine prevented attenuation of insulin signaling by long-term insulin exposure. Thus, a sustained elevation of insulin levels diminishes neuronal insulin signaling through mTOR-S6K1-mediated IRS-1 serine phosphorylation, proteasomal degradation of IRS-1 and lysosomal degradation of the IR.
Up-Regulation of Toll-Like Receptor 4/Nuclear Factor-κB Signaling Is Associated with Enhanced Adipogenesis and Insulin Resistance in Fetal Skeletal Muscle of Obese Sheep at Late Gestation
Authors: Yan Xu , Zhu Mei J. , Xu Wei , Tong Jun F. , Ford Stephen P. , Nathanielsz Peter W. , Du Min 
Published: November 2009

Abstract
Maternal obesity is increasing at an alarming rate. We previously showed that maternal obesity induces an inflammatory response and enhances adipogenesis in fetal skeletal muscle at midgestation. The objective of this study was to evaluate effects of maternal obesity on adipogenesis, inflammatory signaling, and insulin pathways at late gestation when ovine fetal skeletal muscle matures. Nonpregnant ewes were assigned to a control diet (Con, fed 100% of National Research Council nutrient recommendations, n = 6) or obesogenic diet (OB, fed 150% of National Research Council recommendations, n = 6) from 60 d before to 135 d after conception (term 148 d) when the fetal semitendenosus skeletal muscle was sampled. Expression of the adipogenic marker, peroxisome proliferator-activated receptor-γ, was increased in OB compared with Con fetal semitendenosus muscle, indicating up-regulation of adipogenesis. More intramuscular adipocytes were observed in OB muscle. Phosphorylation of inhibitor-κB kinase-α/β and nuclear factor-κB RelA/p65 were both increased in OB fetal muscle, indicating activation of nuclear factor-κB pathway. Phosphorylation of c-Jun N-terminal kinase and c-Jun (at Ser 63 and Ser 73) was also elevated. Toll-like receptor 4 expression was higher in OB than Con fetal muscle. Moreover, despite higher insulin concentrations in OB vs. Con fetal plasma (2.89 ± 0.53 vs. 1.06 ± 0.52 ng/ml; P &lt; 0.05), phosphorylation of protein kinase B at Ser 473 was reduced, indicating insulin resistance. In conclusion, our data show maternal obesity-induced inflammatory signaling in late gestation fetal muscle, which correlates with increased im adipogenesis and insulin resistance, which may predispose offspring to later-life obesity and diabetes.