julilili42/papers huggingface dataset:
Environmental and Genetic Determinants of Fatty Liver in Humans
2010-01-01

Non-alcoholic fatty liver represents one of the most prevalent conditions affecting about one third of the general population in the Western world, and its prevalence is continuously increasing parallel to the epidemics of obesity. Non-alcoholic fatty liver is a strong predictor of non-alcoholic steatohepatitis, but also of cirrhosis, end-stage liver disease and hepatocellular carcinoma. In recent years, non-alcoholic fatty liver (in addition to overall and visceral obesity) has emerged as a risk factor for insulin resistance, hypertension, dyslipidemia, cardiovascular events and type 2 diabetes. This review summarizes the information currently available about the mechanisms involved in liver fat accumulation (e.g. hepatic lipid supply, de novo lipogenesis, lipid oxidation and the packaging and secretion of triglycerides in the form of very-low-density lipoproteins). New aspects concerning mechanisms potentially leading to a ‘dissociation’ of fatty liver and insulin resistance are also discussed. Understanding the pathogenesis of fatty liver and its complications, including the identification of new factors secreted from the liver under excess fat accumulation that are involved in the regulation of metabolism (‘hepatokines’), is crucial in order to develop and implement efficient prevention and treatment strategies.
A Generic Framework for Real-Time Multi-Channel Neuronal Signal Analysis, Telemetry Control, and Sub-Millisecond Latency Feedback Generation
2010-01-01

Distinct modules of the neural circuitry interact with each other and (through the motor-sensory loop) with the environment, forming a complex dynamic system. Neuro-prosthetic devices seeking to modulate or restore CNS function need to interact with the information flow at the level of neural modules electrically, bi-directionally and in real-time. A set of freely available generic tools is presented that allow computationally demanding multi-channel short-latency bi-directional interactions to be realized in in vivo and in vitro preparations using standard PC data acquisition and processing hardware and software (Mathworks Matlab and Simulink). A commercially available 60-channel extracellular multi-electrode recording and stimulation set-up connected to an ex vivo developing cortical neuronal culture is used as a model system to validate the method. We demonstrate how complex high-bandwidth (>10 MBit/s) neural recording data can be analyzed in real-time while simultaneously generating specific complex electrical stimulation feedback with deterministically timed responses at sub-millisecond resolution.
Dental and Craniofacial Anomalies Associated with Axenfeld-Rieger Syndrome with PITX2 Mutation
2010-01-01

Axenfeld-Rieger syndrome (ARS) (OMIM Nr.: 180500) is a rare autosomal dominant disorder (1 : 200000) with genetic and morphologic variability. Glaucoma is associated in 50% of the patients. Craniofacial and dental anomalies are frequently reported with ARS. The present study was designed as a multidisciplinary analysis of orthodontic, ophthalmologic, and genotypical features. A three-generation pedigree was ascertained through a family with ARS. Clinically, radiographic and genetic analyses were performed. Despite an identical genotype in all patients, the phenotype varies in expressivity of craniofacial and dental morphology. Screening for PITX2 and FOXC1 mutations by direct DNA-sequencing revealed a P64L missense mutation in PITX2 in all family members, supporting earlier reports that PITX2 is an essential factor in morphogenesis of teeth and craniofacial skeleton. Despite the fact that the family members had identical mutations, morphologic differences were evident. The concomitant occurrence of rare dental and craniofacial anomalies may be early diagnostic indications of ARS. Early detection of ARS and elevated intraocular pressure (IOP) helps to prevent visual field loss.
Validation of a New Method for Automated Determination of Bone Age in Japanese Children
2010-01-01

BoneXpert, an automated method for analysis of hand radiographs of children, has recently been developed and validated in European children. It determines Tanner-Whitehouse (TW) and Greulich Pyle (GP) bone ages (BA). The purpose of this work is to validate BoneXpert BA in Japanese children and determine the following two properties of the method: (1) The &lt;i&gt;accuracy&lt;/i&gt; of the BA, i.e. the standard deviation from an experienced Japanese TW BA rater. (2) The &lt;i&gt;precision &lt;/i&gt;of the BA, i.e. BoneXpert’s ability to yield the same BA value on a repeated radiograph. The data consist of two studies: 185 radiographs of 22 normal children followed longitudinally from approximately 7 years to full maturity, and 284 radiographs of 22 patients with growth hormone deficiency treated with growth hormone and gonadotropin-releasing hormone analogue followed from an age of 4–11 years to almost full maturity. All radiographs were rated manually according to the TW-Japan system. BoneXpert processed all images, and the accuracy (SD) of TW-Japan BA was 0.72 years (95% CI 0.68–0.76). The precision error (SD) on a single determination of GP BA was 0.17 years (95% CI 0.15–0.19). It is concluded that BoneXpert performs as well in Japanese children as it does in Caucasian children. This study accomplishes a calibration of BoneXpert to the TW-Japan standard, which performs well for the entire BA range from 4 years up to full maturity.
Downregulation of Mouse Intestinal Na+-coupled Glucose Transporter SGLT1 by Gum Arabic (Acacia Senegal)
2010-01-01

Intestinal Na(+)-coupled glucose transporter SGLT1 determines the rate of glucose transport, which in turn influences glucose-induced insulin release and development of obesity. The present study explored effects of Gum Arabic (GA), a dietary polysaccharide from dried exudates of Acacia Senegal, on intestinal glucose transport and body weight in wild-type C57Bl/6 mice. Treatment with GA (100 g/l) in drinking water for four weeks did not affect intestinal SGLT1 transcript levels but decreased SGLT1 protein abundance in jejunal brush border membrane vesicles. Glucose-induced jejunal short-circuit currents revealed that GA treatment decreased electrogenic glucose transport. Drinking a 20% glucose solution for four weeks significantly increased body weight and fasting plasma glucose concentrations, effects significantly blunted by simultaneous treatment with GA. GA further significantly blunted the increase in body weight, fasting plasma glucose and fasting insulin concentrations during high fat diet. In conclusion, the present observations disclose a completely novel effect of gum arabic, i.e. its ability to decrease intestinal SGLT1 expression and activity and thus to counteract glucose-induced obesity.
Rare-earth metal bis(tetramethylaluminate) complexes supported by a sterically crowded triazenido ligand
2010-01-01

Complexes [NNN]Ln(AlMe(4))(2) (Ln = Y, La, Nd, Lu) bearing the sterically demanding aryl-substituted triazenido ligand [(Tph)(2)N(3)] (Tph = [2-(2,4,6-iPr(3)C(6)H(2))C(6)H(4)]) can be obtained from homoleptic complexes Ln(AlMe(4))(3) in moderate yields, both via protonolysis with [(Tph)(2)N(3)]H and a salt metathesis reaction pathway utilizing [(Tph)(2)N(3)]K. In the solid state the Y and Lu derivatives are isostructural, with both tetramethylaluminate groups coordinated in an eta(2) fashion, while one of the [AlMe(4)] ligands of the Nd derivative features a distorted eta(2) coordination mode. Due to the high affinity of the triazenido ligand toward the more Lewis-acidic and harder aluminium cation compared to the softer rare-earth metal centres, ligand redistribution is observed in solution and formation of byproduct [(Tph)(2)N(3)]AlMe(2) is prominent. While the monoanionic triazenido ligand coordinates the rare-earth metal centres in an asymmetrical syn/anti fashion, it adopts an almost symmetric syn/syn configuration in the aluminium complex. Attempts were also made to produce putative dimethyl complexes {[(Tph)(2)N(3)]LnMe(2)} (Ln = Y, Lu) via cleavage of the aluminate moieties with diethyl ether. Furthermore, the intrinsic redistribution reactions are proposed to affect the performance of complexes [(Tph)(2)N(3)]Ln(AlMe(4))(2) in isoprene polymerization.
Circadian Expression of Clock- and Tumor Suppressor Genes in Human Oral Mucosa
2010-01-01

Our study revealed a proper circadian regulation profile of several clock- and tumor suppressor genes at defined points in time in the participants studied. These findings could provide important information regarding genes displaying the same expression profile in the gastrointestinal tract amounting to a physiological expression profile of healthy humans. In the future asynchronous regulations of those genes might be an additional assistant method to detect derivations distinguishing normal from malignant tissue or assessing risk factors for cancer.
A method for patterned in situ biofunctionalization in injection-molded microfluidic devices
2010-01-01

We developed a method to modify the surface in injection molded polymer microdevices prior to bonding and to pattern biomolecules in the completed microsystem in situ by a sequence of simple perfusion steps directly before utilization of the device. This method is compatible with production technology such as injection molding and bonding processes currently employed in the fabrication of polymer microsystems. It solves the problem of the inherent incompatibility of biomolecules with microfabrication technology as it allows for the biofunctionalization step to be performed after completion of the microsystem. Injection molded cyclic olefin copolymer (COC) microfluidic chips were modified by irradiating the surface with UV-light at lambda = 185 nm. This results in the formation of stable acidic groups which were further modified by binding of the extracellular matrix protein collagen type I. Non-irradiated surfaces were modified by binding of Pluronic® F-127 to become non-adhesive. Density of acid groups decreases to 50% within 45 days and to 25% within 19 weeks after irradiation. However, even then the remaining density of functional groups was shown to be sufficient to bind proteins and promote cell adhesion. Selective adhesion of primary hepatocytes on surfaces patterned by UV-irradiation and a biofunctional coating with collagen type I were demonstrated in injection molded microsystems.
Sporadic Blau Syndrome With Onset of Widespread Granulomatous Dermatitis in the Newborn Period
2010-01-01

Blau syndrome is a dominantly inherited, chronic autoinflammatory disorder characterized by the clinical triad of granulomatous dermatitis, symmetric arthritis, and recurrent uveitis with onset below 4 years of age. It is caused by activating mutations in the nucleotide-binding oligomerization domain 2 (NOD2) gene, previously referred to as CARD15 gene. Noncaseating granulomas in affected tissues are the pathologic hallmark of the condition. We report the lifelong severe disease course in a 14-year-old Caucasian boy with sporadic Blau syndrome. Unusually, granulomatous dermatitis started in the first week of life. Whereas skin involvement faded away spontaneously in subsequent years, polyarthritis and anterior uveitis appeared in the second and third year of life respectively. Mutational analysis of the NOD2 gene revealed a missense mutation (R334W) previously detected in other Blau syndrome pedigrees. With this report, we would like to stress the rare possibility of Blau syndrome in generalized papular rashes of infancy and the importance of histopathologic study for clarification. The finding of early-onset widespread granulomatous dermatitis should prompt eye and joint examination in regular intervals and entail mutational analysis of the NOD2 gene.
60kDa Lysophospholipase, a New Sgk1 Molecular Partner Involved in the Regulation of ENaC
2010-01-01

The serum- and glucocorticoid-regulated kinase (Sgk1) is essential for hormonal regulation of ENaC-mediated sodium transport and is involved in the transduction of growth-factor-dependent cell survival and proliferation. The identification of molecular partners for Sgk1 is crucial for the understanding of its mechanisms of action. We performed a yeast two-hybrid screening based on a human kidney cDNA library to identify molecular partners of Sgk1. As a result the screening revealed a specific interaction between Sgk1 and a 60 kDa Lysophospholipase (LysoLP). LysoLP is a poorly characterized enzyme that, based on sequence analysis, might possess lysophospholipase and asparaginase activities. We demonstrate that LysoLP has indeed a lysophospholipase activity and affects metabolic functions related to cell proliferation and regulation of membrane channels. Moreover we demonstrate in the Xenopus oocyte expression system that LysoLP downregulates basal and Sgk1-dependent ENaC activity. In conclusion LysoLP may represent a new player in the regulation of ENaC and Sgk1-dependent signaling.
Platelet aggregation monitoring with a newly developed quartz crystal microbalance system as an alternative to optical platelet aggregometry
2010-01-01

The objective of this study was to establish a new test system for the monitoring of platelet aggregation during extracorporeal circulation (ECC) procedures. Even though extensive progress has been made in improving the haemocompatibility of extracorporeal circulation devices, activation of blood coagulation, blood platelets and inflammatory responses are still undesired outcomes of cardiopulmonary bypass. This study deals with an approach towards a platelet aggregation measuring system using a newly developed quartz crystal microbalance (QCM) system. Since QCM is a rarely used technique in the field of blood analytics, the challenge was to transfer the well established methods of aggregometry to the new test system. In a QCM system, either bare gold or fibrinogen-coated sensors were incubated with ADP or arachidonic acid (AA) stimulated platelet rich plasma. For negative controls the GPIIb/IIIa inhibitory antibody abciximab (Reopro®) was used as an inhibitor of platelet aggregation. During incubation, the frequency shifts of the sensors were recorded. The results gained from the QCM system were compared to results gained by optical platelet aggregometry (born aggregometry). For additional visualization of platelet adhesion to the sensor surfaces, fluorescent microscopy and scanning electron microscopy were used. The QCM sensor was able to detect platelet aggregation in both uncoated and fibrinogen coated sensors. The measuring curves of aggregation measurements and controls were clearly distinguishable from each other in terms of frequency shifts and kinetics. For aggregation measurements and inhibited controls the therapeutic diagnosis of platelet function is identical between aggregometer and QCM data. In future, QCM based measuring devices may become an alternative to established point of care methods for rapid bedside testing of platelet aggregation.
Membrane receptor signaling and control of DNA repair after exposure to ionizing radiation
2010-01-01

Summary Accumulated evidence indicates that activation of erbB family of receptors, when mutated or over-expressed, mediates chemoand radiotherapy resistance. In this context signaling pathways down-stream of epidermal growth factor receptor (EGFR), when abnormally activated, invoke cell survival mechanisms, which leads to resistance against radiation. In several reports it has been demonstrated that molecular targeting of EGFR signaling enhances the cytotoxic effects of radiotherapy. The radiosensitizing effects of EGFR antagonists correlate with a suppression of the ability of tumor cells to repair radiation-induced DNA double strand breaks (DNA-DSBs) through non-homologous endjoining repair pathway (NHEJ). The purpose of this review is to highlight the function of EGFR and erbB2 receptors on signaling pathways, i. e. PI3K/Akt activated by ionizing radiation (IR) and involved in repair of DNA-DSB which can explain the radiosensitizing effects of related antagonists. Advances in understanding the mechanism of erbB-signaling in regulating DNA-DSB repair will promote translational approaches to test new strategies for clinically applicable molecular targeting.
SGK1-dependent Intestinal Tumor Growth in APC-deficient Mice
2010-01-01

Adenomatous polyposis coli (APC) is inactivated in familial adenomatous polyposis and sporadic colorectal cancer. Mice carrying defective APC (apc(Min/+)) spontaneously develop gastrointestinal tumors. APC binds GSK3beta, which phosphorylates beta-catenin thus fostering its degradation. beta-catenin upregulates the serum- and glucocorticoid-inducible kinase Sgk1, which inhibits GSK3beta. The present study explored the role of SGK1 in tumor growth of apc(Min/+)mice. apc(Min/+)mice were crossed with SGK1-knockout mice (sgk1(-/-)) and their wild type littermates (sgk1(+/+)) generating apc(Min/+)/sgk1(-/-)mice and apc(Min/+)/sgk1(+/+)mice. beta-catenin abundance was determined by Western blotting and confocal microscopy. As a result apc(Min/+)/sgk1(+/+)mice developed significantly more intestinal tumors than apc(Min/+)/sgk1(-/-)mice. Following chemical cancerogenesis, colonic beta-catenin protein abundance was significantly higher in sgk1(+/+)mice than in sgk1(-/-)mice. beta-catenin expression was significantly increased in HEK293 cells treated with dexamethasone for upregulation of Sgk1. In conclusion, SGK1 expression favors the development of intestinal tumors in APC-deficient mice, an effect at least partially due to enhanced beta-catenin protein abundance.
A Clustering Optimization Strategy for Molecular Taxonomy Applied to Planktonic Foraminifera SSU rDNA
2010-01-01

Identifying species is challenging in the case of organisms for which primarily molecular data are available. Even if morphological features are available, molecular taxonomy is often necessary to revise taxonomic concepts and to analyze environmental DNA sequences. However, clustering approaches to delineate molecular operational taxonomic units often rely on arbitrary parameter choices. Also, distance calculation is difficult for highly alignment-ambiguous sequences. Here, we applied a recently described clustering optimization method to highly divergent planktonic foraminifera SSU rDNA sequences. We determined the distance function and the clustering setting that result in the highest agreement with morphological reference data. Alignment-free distance calculation, when adapted to the use with partly non-homologous sequences caused by distinct primer pairs, outperformed multiple sequence alignment. Clustering optimization offers new perspectives for the barcoding of species diversity and for environmental sequencing. It bridges the gap between traditional and modern taxonomic disciplines by specifically addressing the issue of how to optimally account for both genetic divergence and given species concepts.
Clinical Recommendations of DEGRO and AGO on Preferred Standard Palliative Radiotherapy of Bone and Cerebral Metastases, Metastatic Spinal Cord Compression, and Leptomeningeal Carcinomatosis in Breast Cancer
2010-01-01

RT is an effective tool in palliation treatment of bone metastasis (BM), cerebral metastasis (CM) and metastatic spinal cord compression (MSCC), or leptomeningeal carcinomatosis (LC) and plays a central role in an interdisciplinary approach. Preferred technique, targeting, and different dose schedules are described in detail in the DEGRO guidelines, which are also integrated in the updated 2010 AGO recommendations.
Early Surgical Treatment in Unilateral Coronoid Hyperplasia and Facial Asymmetry
2010-01-01

Unilateral coronoid hyperplasia is a rare condition in the pediatric age. It may be an unrecognized cause of restricted mouth opening in children.The limited jaw movement is due to the enlargement of the coronoid process of the mandible that impinges on the zygomatic arch during mouth opening. This pathologic condition is still unknown and often misdiagnosed.Although in the past the term osteochondroma has been used to describe most of the unilateral and a few of the bilateral cases, there is no histologic evidence that the process has a neoplastic origin.Microscopic examination of the removed coronoid process has revealed hyperplastic compact bone covered with a thin layer of normal cartilage.There are multiple causes of mandibular hypomobility, each of them associated with different anatomic structures and etiologies, and a large number of cases, mostly bilateral, are idiopathic in nature.Several theories of pathogenesis have been proposed: temporomandibular joint dysfunctions, mandibular hypomobility, temporalis hyperactivity, hormonal stimulus, persistent cartilage growth center, genetic inheritance, and family factors.Unilateral coronoid hyperplasia is usually due to a trauma or a pathologic condition and is associated with facial asymmetry, being more frequently seen in women with histologic chondromatous or neoplastic changes. A thorough clinical history should include information about the onset and progression of pain and other subjective symptoms.In this study, we present a case of unilateral hyperplasia of the coronoid process in a 3 year-old female who, to the best of our knowledge, is the youngest patient so far reported with such anomaly.Our findings support the recommendation that early surgical treatment and aggressive postoperative physical therapy should be taken into account to allow for recovery of morphology and growth function in children.
TNF Induces Choroid Plexus Epithelial Cell Barrier Alterations by Apoptotic and Nonapoptotic Mechanisms
2010-01-01

The choroid plexus epithelium constitutes the structural basis of the blood-cerebrospinal fluid barrier. Since the cytokine TNF is markedly increased during inflammatory diseases in the blood and the central nervous system, we investigated by which mechanisms TNF induces barrier alteration in porcine choroid plexus epithelial cells. We found a dose-dependent decrease of transepithelial electrical resistance, increase of paracellular inulin-flux, and induction of histone-associated DNA fragmentation and caspase-3 activation after TNF stimulation. This response was strongly aggravated by the addition of cycloheximide and could partially be inhibited by the NF-B inhibitor CAPE, but most effectively by the pan-caspase-inhibitor zVAD-fmk and not by the JNK inhibitor SP600125. Partial loss of cell viability could also be attenuated by CAPE. Immunostaining showed cell condensation and nuclear binding of high-mobility group box 1 protein as a sign of apoptosis after TNF stimulation. Taken together our findings indicate that TNF compromises PCPEC barrier function by caspase and NF-B dependent mechanisms.
Controversy: Ocular Sarcoidosis
2010-01-01

The recent publication of diagnostic criteria for ocular sarcoidosis has renewed interest in this enigmatic and often controversial disease. The aim of the present review was to report on the results of a survey of leading ophthalmologists in which we asked them to address some of the most important issues related to the diagnosis and treatment of ocular sarcoidosis. The survey revealed that there is significant uptake and use of the diagnostic criteria for ocular sarcoidosis, although there still remained considerable differences in opinion with regard to whether or not this was an isolated condition affecting only the eye and how this should be diagnosed and appropriately managed.
Donor-assisted tetramethylaluminate/gallate exchange in organolanthanide complexes: pushing the limits of Pearson's HSAB concept
2010-01-01

La(GaMe(4))(3) and (C(5)Me(5))La(GaMe(4))(2) are obtained by reacting La(AlMe(4))(3) and (C(5)Me(5))La(AlMe(4))(2), respectively, with GaMe(3).OEt(2). Diethyl ether as a donor reverses the commonly observed Ln-GaR(4)--> Ln-AlR(4) transformation by producing the more stable AlMe(3).OEt(2), thus making homoleptic and half-sandwich tetramethylgallate complexes of the largest rare-earth metal accessible.