julilili42/papers huggingface dataset:
Genetic Ablation of cGMP-Dependent Protein Kinase Type I Causes Liver Inflammation and Fasting Hyperglycemia
2011-04-05

OBJECTIVE The nitric oxide/cGMP/cGMP-dependent protein kinase type I (cGKI) signaling pathway regulates cell functions that play a pivotal role in the pathogenesis of type 2 diabetes. However, the impact of a dysfunction of this pathway for glucose metabolism in vivo is unknown. RESEARCH DESIGN AND METHODS The expression of cGKI in tissues relevant to insulin action was analyzed by immunohistochemistry. The metabolic consequences of a genetic deletion of cGKI were studied in mice that express cGKI selectively in smooth muscle but not in other cell types (cGKI-SM mice). RESULTS In wild-type mice, cGKI protein was detected in hepatic stellate cells, but not in hepatocytes, skeletal muscle, fat cells, or pancreatic β-cells. Compared with control animals, cGKI-SM mice had higher energy expenditure in the light phase associated with lower body weight and fat mass and increased insulin sensitivity. Mutant mice also showed higher fasting glucose levels, whereas insulin levels and intraperitoneal glucose tolerance test results were similar to those in control animals. Interleukin (IL)-6 signaling was strongly activated in the liver of cGKI-SM mice as demonstrated by increased levels of IL-6, phospho-signal transducer and activator of transcription 3 (Tyr 705), suppressor of cytokine signaling-3, and serum amyloid A2. Insulin-stimulated tyrosine phosphorylation of the insulin receptor in the liver was impaired in cGKI-SM mice. The fraction of Mac-2–positive macrophages in the liver was significantly higher in cGKI-SM mice than in control mice. In contrast with cGKI-SM mice, conditional knockout mice lacking cGKI only in the nervous system were normal with respect to body weight, energy expenditure, fasting glucose, IL-6, and insulin action in the liver. CONCLUSIONS Genetic deletion of cGKI in non-neuronal cells results in a complex metabolic phenotype, including liver inflammation and fasting hyperglycemia. Loss of cGKI in hepatic stellate cells may affect liver metabolism via a paracrine mechanism that involves enhanced macrophage infiltration and IL-6 signaling.
Effects of extraction treatment on maxillary and mandibular sagittal development in growing patients
2011-04-05

This retrospective investigation was designed to assess the effects of extraction treatment on the sagittal dimensions of the maxillary and mandibular skeletal structures of growing patients. The records of 40 patients (17 girls, 23 boys; median age 10 years 11 months) whose orthodontic treatment involved extraction of four premolars were evaluated and compared with a control group of 100 patients (54 girls, 46 boys; median age 10 years 7 months) treated non-extraction. Two lateral cephalograms were obtained of each patient, the first before the extractions, T1, and the second at a later point, T2 (mean difference 59 months). Linear parameters, including S-N, the maxillary/mandibular alveolar process, and maxillary/mandibular base, were measured. The same parameters were determined in the control group at corresponding time points (mean difference 63 months). For analysis, the sagittal dimensions of the alveolar processes and jaw bases were compared with each other. The relationships were also established to a reference line known to be unaffected by extraction treatment (S-N). This procedure was performed for the whole sample and for three subgroups formed according to the Wits appraisal. Statistical analysis was carried out using a Student's t-test. Comparisons of the total sample showed differences between the groups, which were statistically significant for the maxillary alveolar process, the mandibular alveolar process, and the mandibular base. They varied however in the different subgroups. Whenever extraction treatment is considered, it should be borne in mind that the effects on the sagittal dimension of different bony structures may vary.
Transcorneal Electrical Stimulation for Patients with Retinitis Pigmentosa: A Prospective, Randomized, Sham-Controlled Exploratory Study
2011-04-06

TES was found to be safe in RP patients. Positive trends were discovered, but due to the small sample size of this exploratory study, statistical significance was reached only for VF area and scotopic b-wave amplitude. Further studies with larger sample sizes and longer duration are needed to confirm the findings and to define optimal stimulation parameters. (ClinicalTrials.gov number, NCT00804102.).
IL‐22 and TNF‐α represent a key cytokine combination for epidermal integrity during infection with Candida albicans
2011-04-06

Abstract T cells exercise their full impact on target cells through a combination of secreted cytokines. The recently described T helper cell subset Th22 is characterized by a combinatorial secretion of IL‐22 and TNF‐α. Here, we demonstrate that IL‐22 increases the TNF‐α‐dependent induction and secretion of several immune‐modulatory molecules such as initial complement factors C1r and C1s, antimicrobial peptides S100A7 and HBD‐2 (human β defensin 2), and antimicrobial chemokines CXCL‐9/‐10/‐11 in primary human keratinocytes. The synergism of IL‐22 and TNF‐α is transmitted intracellularly by MAP kinases and downstream by transcription factors of the AP‐1 family. The induction of innate immunity is relevant in an in vitro infection model, where keratinocytes stimulated with Th22 supernatants or recombinant IL‐22 plus TNF‐α effectively inhibit the growth of Candida albicans and maintain survival of epithelia. Accordingly, the combinatorial stimulation of keratinocytes with IL‐22 and TNF‐α most efficiently conserves the integrity of the epidermal barrier in a three‐dimensional skin infection model as compared with IFN‐γ, IL‐17, IL‐22 or TNF‐α alone. In summary, we demonstrate that IL‐22 and TNF‐α represent a potent, synergistic cytokine combination for cutaneous immunity.
Identification and characterization of human leukocyte antigen class I ligands in renal cell carcinoma cells
2011-04-06

Abstract The presentation of tumor antigen‐derived peptides by human leukocyte antigen (HLA) class I surface antigens on tumor cells is a key prerequisite to trigger effective T‐cell responses in cancer patients. Multiple complementary strategies like cDNA and serological expression cloning, reverse immunology and different ‘ome’‐based methods have been employed to identify potential T‐cell targets. This report focuses on a ligandomic profiling approach leading to the identification of 49 naturally processed HLA class I peptide ligands presented on the cell surface of renal cell carcinoma (RCC) cells. The source proteins of the defined HLA ligands are classified according to their biological function and subcellular localization. Previously established cDNA microarray data of paired tissue specimen of RCC and renal epithelium assessed the transcriptional regulation for 28 source proteins. In addition, HLA‐A2‐restricted, peptide‐specific T cells directed against a HLA ligand derived from sulfiredoxin‐1 (SRXN1) were generated, which were able to recognize and lyse ligand‐presenting target cells in a HLA class I‐restricted manner. Furthermore, tumor‐infiltrating T cells isolated from a RCC patient were also able to kill SRXN1 expressing tumor cells. Thus, this experimental strategy might be suited to define potential candidate biomarkers and novel targets for T‐cell‐based immunotherapies of this disease.
Jarosite in a Pleistocene East African saline-alkaline paleolacustrine deposit: Implications for Mars aqueous geochemistry
2011-04-06

Jarosite occurs within altered tephra from the saline‐alkaline paleolake deposits of Pliocene‐Pleistocene Olduvai Gorge, Tanzania. Zeolites (mainly phillipsite), authigenic K‐feldspar, and Mg/Fe‐smectites dominate the mineral assemblage, indicating salinealkaline diagenetic conditions (pH &amp;gt; 9). As jarosite is ordinarily an indicator of acidic conditions on Earth and Mars, its association with such undisputed high‐pH indicators is unexpected. Of 55 altered tephra samples collected from the paleolake basin and margin deposits, eleven contained jarosite detectable by X‐ray Diffraction (XRD) (&amp;gt;0.15%). M&amp;ouml;ssbauer spectroscopy, Fourier Transform Infrared Reflectance (FTIR), Electron Probe Microanalysis (EPMA), X‐ray Fluorescence (XRF), and Scanning Electron Microscopy (SEM) analyses confirm the presence and nature of the jarosite. This paper documents this occurrence and presents mechanisms that could produce this unusual and contradictory mineral assemblage. We favor a mechanism by which jarosite formed recently, perhaps as modern ground and meteoric water interacted with and oxidized paleolacustrine pyrite, providing local and temporary acidic conditions. However, local groundwater (at modern springs) has a pH &amp;gt; 9. In recent studies of Mars, the presence of jarosite or other Fe or Mg sulfates is often used to indicate dominantly acidic conditions. Regardless, the current study shows that jarosite can form in sediments dominated by alkaline minerals and solutions. Its coexistence with Mg/Fe smectites in particular makes it relevant to recent observations of Martian paleolakes.
The E. coli Siderophores Enterobactin and Salmochelin Form Six‐Coordinate Silicon Complexes at Physiological pH
2011-04-06

Not limited to iron: The high affinity of the bacterial iron siderophores enterobactin and salmochelin for Fe3+ ions, which are bound through chelating catecholate groups, is well known. These two siderophores have now been found to also bind silicon ions with high affinity, giving the first examples of silicon complexes of natural products stable under physiological conditions. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cell-Sorting at the A/P Boundary in the Drosophila Wing Primordium: A Computational Model to Consolidate Observed Non-Local Effects of Hh Signaling
2011-04-07

Non-intermingling, adjacent populations of cells define compartment boundaries; such boundaries are often essential for the positioning and the maintenance of tissue-organizers during growth. In the developing wing primordium of Drosophila melanogaster, signaling by the secreted protein Hedgehog (Hh) is required for compartment boundary maintenance. However, the precise mechanism of Hh input remains poorly understood. Here, we combine experimental observations of perturbed Hh signaling with computer simulations of cellular behavior, and connect physical properties of cells to their Hh signaling status. We find that experimental disruption of Hh signaling has observable effects on cell sorting surprisingly far from the compartment boundary, which is in contrast to a previous model that confines Hh influence to the compartment boundary itself. We have recapitulated our experimental observations by simulations of Hh diffusion and transduction coupled to mechanical tension along cell-to-cell contact surfaces. Intriguingly, the best results were obtained under the assumption that Hh signaling cannot alter the overall tension force of the cell, but will merely re-distribute it locally inside the cell, relative to the signaling status of neighboring cells. Our results suggest a scenario in which homotypic interactions of a putative Hh target molecule at the cell surface are converted into a mechanical force. Such a scenario could explain why the mechanical output of Hh signaling appears to be confined to the compartment boundary, despite the longer range of the Hh molecule itself. Our study is the first to couple a cellular vertex model describing mechanical properties of cells in a growing tissue, to an explicit model of an entire signaling pathway, including a freely diffusible component. We discuss potential applications and challenges of such an approach.
Sandwich Immunoassay for Soluble Glycoprotein VI in Patients with Symptomatic Coronary Artery Disease
2011-04-07

BACKGROUND Platelet glycoprotein VI (pGPVI) expression is increased in acute coronary syndrome (ACS), reflecting platelet activation. There is no reliable method available to measure pGPVI. Our aim was to develop a bead-based sandwich immunoassay to measure soluble GPVI (sGPVI). METHODS Based on antibodies for sGPVI developed earlier, we established and validated a bead-based sandwich immunoassay in 2438 consecutive patients with stable angina pectoris (SAP; n = 1371), non–ST-elevation myocardial infarction (NSTEMI; n = 724), and ST-elevation MI (STEMI; n = 343). In a subgroup (n = 1011), we measured surface expression of pGPVI using flow cytometry. RESULTS The assay revealed a working range of 8–500 ng/L. Intra- and interassay imprecision was &amp;lt;7% and &amp;lt;14%, respectively. Patients with NSTEMI and STEMI showed significantly lower mean sGPVI concentrations than patients with SAP [mean (SD), 8.4 (3.6) μg/L and 8.6 (4.1) μg/L vs 9.8 (4.8) μg/L; P = 0.002], whereas subgroup analysis revealed significantly enhanced pGPVI in NSTEMI (n = 276) and STEMI (n = 80) patients compared with SAP (n = 655) [mean fluorescence intensity (SD), 21.2 (8.1) and 19.8 (6.8) vs 18.5 (7.7); P = 0.002 and P = 0.018]. pGPVI and sGPVI were inversely correlated (r = −0.076; P = 0.023). Area under the ROC curve was 0.716, 95% CI 0.681–0.751, for sGPVI, distinguishing patients with SAP from those with ACS, and was superior (P = 0.044) to the curve of subgroup analysis for pGPVI (0.624, 95% CI 0.586–0.662). sGPVI (P = 0.023) and pGPVI (P = 0.028) had better association with the development of ACS than troponin I (P = 0.055) in the very early stage of disease, based on logistic regression analysis. CONCLUSIONS This sandwich immunoassay reliably measures sGPVI and may help to identify patients with ACS earlier than other laboratory markers.
Exobasidium darwinii, a new Hawaiian species infecting endemic Vaccinium reticulatum in Haleakala National Park
2011-04-07

Hawaii is one of the most isolated archipelagos in the world, situated about 4,000 km from the nearest continent, and never connected with continental land masses. Two Hawaiian endemic blueberries, Vaccinium calycinum and V. reticulatum, are infected by Exobasidium species previously recognized as Exobasidium vaccinii. However, because of the high host-specificity of Exobasidium, it seems unlikely that the species infecting Vaccinium calycinum and V. reticulatum belongs to Exobasidium vaccinii, which in the current circumscription is restricted to Vaccinium vitis-idaea. We collected a fresh specimen of Exobasidium on Vaccinium reticulatum in Haleakala National Park, and analysed it by a combined morphological and molecular approach. The morphological and phylogenetic analyses (based on the LSU and the concatenated ITS+LSU sequence data) showed that Exobasidium on Vaccinium reticulatum belongs to an undescribed species, distinct from Exobasidium vaccinii and any other species. The name Exobasidium darwinii is proposed for this novel taxon. This species is characterized among others by the production of peculiar witches' brooms with bright red leaves on the infected branches of Vaccinium reticulatum. Relevant characters of Exobasidium darwinii are described and illustrated, additionally phylogenetic relationships of the new species are discussed.
A simple, diversity oriented synthesis of highly substituted pyridines
2011-04-07

Abstract A particularly straightforward and efficient protocol for the synthesis of highly substituted pyridines, based on a condensation reaction of β‐aminocrotonitrile and easily accessible ( E )‐2‐oxo‐4‐aryl‐but‐3‐enoic acids and ( E )‐4‐oxo‐4‐aryl‐but‐2‐enoic acids is described. J. Heterocyclic Chem., (2011).
Closing the sensorimotor loop: haptic feedback facilitates decoding of motor imagery
2011-04-08

The combination of brain-computer interfaces (BCIs) with robot-assisted physical therapy constitutes a promising approach to neurorehabilitation of patients with severe hemiparetic syndromes caused by cerebrovascular brain damage (e.g. stroke) and other neurological conditions. In such a scenario, a key aspect is how to reestablish the disrupted sensorimotor feedback loop. However, to date it is an open question how artificially closing the sensorimotor feedback loop influences the decoding performance of a BCI. In this paper, we answer this issue by studying six healthy subjects and two stroke patients. We present empirical evidence that haptic feedback, provided by a seven degrees of freedom robotic arm, facilitates online decoding of arm movement intention. The results support the feasibility of future rehabilitative treatments based on the combination of robot-assisted physical therapy with BCIs.
Meteorological profiling of the lower troposphere using the research UAV "M2AV Carolo"
2011-04-08

Abstract. Vertical profiles of temperature, humidity and wind up to a height of 1500 m a.g.l. (above ground level) were measured with the automatically operating small unmanned research aircraft M2AV (Meteorological Mini Aerial Vehicle) during the LITFASS-2009 LIndenberg-To-Falkenberg: Aircraft, Scintillometer and large-eddy Simulation) experiment. The campaign took place in July 2009 over the heterogeneous landscape around the Meteorological Observatory Lindenberg – Richard-Aßmann-Observatory in the eastern part of Germany. Due to a high vertical resolution of about 10 cm the M2AV data show details of the turbulent structure of the atmospheric boundary layer (ABL). One profile took about 10–15 min allowing for a continuous monitoring of certain phases of ABL development by successive ascents and descents during one flight (50–60 min duration). Two case studies of measurements performed during the morning and evening ABL transition periods are discussed in detail. Comparison of the aircraft-based temperature, humidity and wind profiles with tower, sodar/RASS, wind profiler/RASS, radiosoundings and microwave radiometer profiler measurements show good agreement taking into account the different sampling strategies of these measurement systems.
Multiple Peptide Resistance Factor (MprF)-mediated Resistance of Staphylococcus aureus against Antimicrobial Peptides Coincides with a Modulated Peptide Interaction with Artificial Membranes Comprising Lysyl-Phosphatidylglycerol
2011-04-08

Modification of the membrane lipid phosphatidylglycerol (PG) of Staphylococcus aureus by enzymatic transfer of a l-lysine residue leading to lysyl-PG converts the net charge of PG from -1 to +1 and is thought to confer resistance to cationic antimicrobial peptides (AMPs). Lysyl-PG synthesis and translocation to the outer leaflet of the bacterial membrane are achieved by the membrane protein MprF. Consequently, mutants lacking a functional mprF gene are in particular vulnerable to the action of AMPs. Hence, we aim at elucidating whether and to which extent lysyl-PG modulates membrane binding, insertion, and permeabilization by various AMPs. Lysyl-PG was incorporated into artificial lipid bilayers, mimicking the cytoplasmic membrane of S. aureus. Moreover, we determined the activity of the peptides against a clinical isolate of S. aureus strain SA113 and two mutants lacking a functional mprF gene and visualized peptide-induced ultrastructural changes of bacteria by transmission electron microscopy. The studied peptides were: (i) NK-2, an α-helical fragment of mammalian NK-lysin, (ii) arenicin-1, a lugworm β-sheet peptide, and (iii) bee venom melittin. Biophysical data obtained by FRET spectroscopy, Fourier transform infrared spectroscopy, and electrical measurements with planar lipid bilayers were correlated with the biological activities of the peptides. They strongly support the hypothesis that peptide-membrane interactions are a prerequisite for eradication of S. aureus. However, degree and mode of modulation of membrane properties such as fluidity, capacitance, and conductivity were unique for each of the peptides. Altogether, our data support and underline the significance of lysyl-PG for S. aureus resistance to AMPs.
Surface Chemistry Study of the Interactions of Benzalkonium Chloride with Films of Meibum, Corneal Cells Lipids, and Whole Tears
2011-04-08

The surface chemistry approach used in this study provided molecular-scale insights into the detrimental effect of BAC on TF, which well explain the TF instability and corneal epithelial barrier dysfunction after exposure to BAC in the in vivo human eye.
ImageStream cytometry extends the analysis of phagocytosis and oxidative burst
2011-04-08

We describe a simple whole blood image-based method for measuring bacterial phagocytosis and oxidative burst. ImageStream cytometry provides the spatial resolution to determine the number of bacteria ingested and the sub-cellular localization and trafficking patterns that enables a more complete evaluation of the phagocytic process.
Acquisition vs. Memorization Trade-Offs Are Modulated by Walking Distance and Pattern Complexity in a Large-Scale Copying Paradigm
2011-04-08

In a "block-copying paradigm", subjects were required to copy a configuration of colored blocks from a model area to a distant work area, using additional blocks provided at an equally distant resource area. Experimental conditions varied between the inter-area separation (walking distance) and the complexity of the block patterns to be copied. Two major behavioral strategies were identified: in the memory-intensive strategy, subjects memorize large parts of the pattern and rebuild them without intermediate visits at the model area. In the acquisition-intensive strategy, subjects memorize one block at a time and return to the model after having placed this block. Results show that the frequency of the memory-intensive strategy is increased for larger inter-area separations (larger walking distances) and for simpler block patterns. This strategy-shift can be interpreted as the result of an optimization process or trade-off, minimizing combined, condition-dependent costs of the two strategies. Combined costs correlate with overall response time. We present evidence that for the memory-intensive strategy, costs correlate with model visit duration, while for the acquisition-intensive strategy, costs correlate with inter-area transition (i.e., walking) times.