Miracle-dz/UniFAR-FTUs huggingface dataset:
C-C Chemokine Ligand 2/Monocyte Chemoattractant Protein-1 Directly Inhibits NKT Cell IL-4 Production and Is Hepatoprotective in T Cell-Mediated Hepatitis in the Mouse1

T cell-mediated liver diseases are associated with elevated serum levels of C-C chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1). However, the extent to which the actions of CCL2/MCP-1 contribute to the pathogenesis of T cell-mediated hepatitis remains incompletely understood. Con A-induced hepatitis is a liver-specific inflammation mediated by activated T cells and is driven by an up-regulation of the hepatic expression of TNF-α, IFN-γ, and IL-4. The present study examined the role of CCL2/MCP-1 in the pathogenesis of T cell-mediated hepatitis induced by Con A administration in the mouse. We demonstrate a novel hepatoprotective role for CCL2/MCP-1 during Con A-induced hepatitis, because CCL2/MCP-1 neutralization strikingly enhanced hepatic injury, both biochemically and histologically, after Con A administration. Furthermore, CCL2/MCP-1 neutralization was associated with a significant reduction in the hepatic levels of TNF-α and IFN-γ, but with a significant increase in hepatic IL-4 levels. Moreover, IL-4 production and CCR2 expression by Con A-stimulated CD3+NK1.1+ T cells was significantly reduced by rMCP-1 treatment in vitro. In summary, we propose that CCL2/MCP-1 fulfills a novel anti-inflammatory role in T cell-mediated hepatitis by inhibiting CD3+NK1.1+ T cell-derived IL-4 production through direct stimulation of its specific receptor CCR2. These findings may have direct clinical relevance to T cell-mediated hepatitis.
Cloning and physical mapping of enteric adenoviruses (candidate types 40 and 41)

We have studied the DNAs of fastidious enteric adenoviruses recovered from the stools of infants with gastroenteritis. By endonuclease analysis, the strains examined represent candidate adenovirus types 40 and 41, which are thought to comprise new adenovirus subgroups F and G. Cloning of DNA from representative enteric adenovirus isolates, together with hybridization and subcleavage analysis, permitted the mapping of restriction enzyme cleavage sites. Although the restriction profiles are different for the two strains, they appear to have several cleavage sites in common. Cross hybridization studies show considerable homology between the subgroup F and G strains but much less homology to adenovirus 2. In addition, regions on both ends of enteric adenovirus genomes (map units, 2.9 to 11.3 and 75 to 100) possess little or no homology to adenovirus 2. Restriction enzyme digests reveal submolar fragments that map to the terminal regions of the genome. Electron micrographic studies of denatured and renatured DNA strands suggest that the submolar fragments may derive from cleavage of defective molecules. Inverted terminal repeat sequences were shown to comprise 0 to 3.2% of the length of complete (greater than or equal to 22 megadaltons) enteric adenovirus DNA molecules but 4 to 69% of incomplete-length (less than 22-megadalton) molecules.
Etidronate prevents, but does not reverse, ectopic mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6−/−)

Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are heritable disorders manifesting with ectopic tissue mineralization. Most cases of PXE and some cases of GACI are caused by mutations in the ABCC6 gene, resulting in reduced plasma pyrophosphate (PPi) levels. There is no effective treatment for these disorders. It has been suggested that administration of bisphosphonates, stable and non-hydrolyzable PPi analogs, could counteract ectopic mineralization in these disorders. In this study we tested the potential efficacy of etidronate, a first generation bisphosphonate, on ectopic mineralization in the muzzle skin of Abcc6−/− mice, a model of PXE. The Abcc6−/− mice received subcutaneous injections of etidronate, 0.283 and 3.40 mg/kg per injection (0.01× and 0.12×), twice a week, in both prevention and reversal studies. Ectopic mineralization in the dermal sheath of vibrissae in muzzle skin was determined by histopathologic analysis and by direct chemical assay for calcium content. Subcutaneous injection of etidronate prevented ectopic mineralization but did not reverse existing mineralization. The effect of etidronate was accompanied by alterations in the trabecular bone microarchitecture, determined by micro-computed tomography. The results suggest that etidronate may offer a potential treatment modality for PXE and GACI caused by ABCC6 mutations. Etidronate therapy should be initiated in PXE patients as soon as the diagnosis is made, with careful monitoring of potential side effects.
b-Blockade improves adjacent regional sympathetic innervation during postinfarction remodeling

Kramer, Christopher M. , Philip D. Nicol, Walter J. Rogers, Philip S. Seibel, Chong S. Park, and Nathaniel Reichek. b-Blockade improves adjacent regional sympathetic innervation during postinfarction remodeling. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1429–H1434, 1999. — The effect of b-blockade on left ventricular (LV) remodeling, when added to angiotensin-converting enzyme inhibition (ACEI) after anterior myocardial infarction (MI), is incompletely understood. On day 2 after coronary ligation-induced anteroapical infarction, 17 sheep were randomized to ramipril (ACEI, n 5 8) or ramipril and metoprolol (ACEI-b, n 5 9). Magnetic resonance imaging was performed before and 8 wk after MI to measure changes in LV end-diastolic, end-systolic, and stroke volume indexes, LV mass index, ejection fraction (EF), and regional percent intramyocardial circumferential shortening. 123I-labeled m-iodobenzylguanidine (MIBG) and fluorescent microspheres before and after adenosine were infused before death at 8 wk post-MI for quantitation of sympathetic innervation, blood flow, and blood flow reserve in adjacent and remote noninfarcted regions. Infarct size, regional blood flow, blood flow reserve, and the increase in LV mass and LV end-diastolic and end-systolic volume indexes were similar between groups. However, EF fell less over the 8-wk study period in the ACEI-b group (213 6 11 vs. 222 6 4% in ACEI, P , 0.05). The ratio of adjacent to remote region 123I-MIBG uptake was greater in ACEI-b animals than in the ACEI group (0.93 6 0.06 vs. 0.86 6 0.07, P , 0.04). When added to ACE inhibition after transmural anteroapical MI, b-blockade improves EF and adjacent regional sympathetic innervation but does not alter LV size.
LRRK2 knockdown in zebrafish causes developmental defects, neuronal loss, and synuclein aggregation

Although mutations in the leucine‐rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinson's disease, their function is largely unknown. LRRK2 is pleiotropic in nature, shown to be involved in neurodegeneration and in more peripheral processes, including kidney functions, in rats and mice. Recent studies in zebrafish have shown conflicting evidence that removal of the LRRK2 WD40 domain may or may not affect dopaminergic neurons and/or locomotion. This study shows that ∼50% LRRK2 knockdown in zebrafish causes not only neuronal loss but also developmental perturbations such as axis curvature defects, ocular abnormalities, and edema in the eyes, lens, and otic vesicles. We further show that LRRK2 knockdown results in significant neuronal loss, including a reduction of dopaminergic neurons. Immunofluorescence demonstrates that endogenous LRRK2 is expressed in the lens, brain, heart, spinal cord, and kidney (pronephros), which mirror the LRRK2 morphant phenotypes observed. LRRK2 knockdown results further in the concomitant upregulation of β‐synuclein, PARK13, and SOD1 and causes β‐synuclein aggregation in the diencephalon, midbrain, hindbrain, and postoptic commissure. LRRK2 knockdown causes mislocalization of the Na+/K+ ATPase protein in the pronephric ducts, suggesting that the edema might be linked to renal malfunction and that LRRK2 might be associated with pronephric duct epithelial cell differentiation. Combined, our study shows that LRRK2 has multifaceted roles in zebrafish and that zebrafish represent a complementary model to further our understanding of this central protein. © 2016 Wiley Periodicals, Inc.
Caspase Inhibition Selectively Reduces the Apoptotic Component of Oxygen-Glucose Deprivation-Induced Cortical Neuronal Cell Death

Cultured mouse cortical neurons undergo apoptosis when exposed to staurosporine. The cell-permeable caspase inhibitor Z-Val-Ala-Asp fluoromethylketone (Z-VAD.FMK) attenuated this death, without altering overall protein synthesis. Z-VAD.FMK also attenuated cortical neuronal apoptosis induced by removal of serum. However, Z-VAD.FMK did not attenuate the excitotoxic necrosis induced by 5-min exposure to 100 microM NMDA, 24-h exposure to 100 microM kainate, or 90-min exposure to oxygen-glucose deprivation. We have previously shown that blockade of the excitotoxic component of oxygen-glucose deprivation-induced neuronal death with glutamate antagonists unmasks an apoptotic death. Treatment with Z-VAD.FMK, but not the cathepsin-B protease inhibitor Z-Phe-Ala fluoromethylketone (Z-FA.FMK), also attenuated this oxygen-glucose deprivation-induced neuronal apoptosis. These data support the idea that brain caspases mediate the apoptotic component of oxygen-glucose deprivation-induced neuronal death and raise the possibility that combining caspase inhibitors with glutamate antagonists might attenuate brain damage induced by hypoxic-ischemic insults in vivo.
Relationship of non-specific airway hyperresponsiveness (AHR) to measures of peak expiratory flow (PEF) variability.

BACKGROUND The relationship between airway hyper-responsiveness (AHR) and clinical asthma remains controversial and unclear. AIMS To test the hypothesis that serial measures of variability of peak expiratory flow rate (PEF) correlate with serial measures of AHR, and to determine which mathematical expression of variability provides the best correlation. METHODS A longitudinal study over 180 days of 20 atopic, moderately severe asthmatics was undertaken. A diary of medication use and morning and evening PEFR before and after beta agonist was kept and AHR (PD20 histamine) was measured at three-weekly intervals. Using group data (128 sets) in PD20 was correlated with various measures of PEF variability over 9 days. RESULTS [Table: see text] Within the group there was a weak but highly statistically significant correlation between AHR and measures of PEF variability--the strongest correlation being with mean morning PEF. Within individual subjects, however, the correlation was not a consistent finding and only four patients had a statistically significant relationship (p < 0.05) between AHR and mean morning PEF. CONCLUSIONS These results suggest that while PEF variability may reflect AHR for the purposes of epidemiologic studies, it is unlikely to be useful as a simple 'non-invasive' means of assessing AHR in individual patients. More complex measures of PEF variability do not have an advantage over simpler measures such as mean morning PEF.
Agreement Between an Ingestible Telemetric Sensor System and a Mercury Thermometer Before and After Linear Regression Correction

Objectives:To evaluate the use of the CorTemp ingestible sensor system to monitor athletes in the prevention of thermal injuries, 3 objectives were established: (1) to determine the agreement between the system and a mercury thermometer and quantify the effect of exceeding the recommended yearly manufacturer calibration, (2) to establish the effect of individual sensor correction on agreement, and (3) to determine the quantity of data required for effective correction. Design:Validation study. Participants:Ninety-four ingestible sensors. Interventions:(1) Five comparisons were made between each sensor and a mercury thermometer across the range of 33 to 41°C. This was performed immediately, and 14 to 18 months, after factory calibration. (2) Linear regression equations were created and used to correct sensor readings at ∼37°C; the corrected value was compared with the mercury thermometer. (3) Linear regression equations were created for each sensor using 2 to 5 data points. Main Outcome Measures:Systematic bias and random error (95%). Results:(1) Systematic bias ± random error (95%) was 0.73% ± 0.23% (≈0.27 ± 0.09°C) and 0.54% ± 0.28% (≈0.22 ± 0.11°C) immediately and 14 to 18 months post factory calibration, respectively. (2) Regression correction improved agreement through reductions in systematic bias. (3) Individualized equations using a minimum of 3 comparisons were required to reduce agreement to ±0.10°C; the use of 5 comparisons minimized the number of readings exceeding ±0.10°C. Conclusions:(1) The CorTemp system inflates temperature measurements compared with a mercury thermometer. (2) Individual sensor calibration is warranted. (3) Correction equations should use a minimum of 3, preferably 5, comparisons. After regression correction, the system displays satisfactory accuracy for preventative monitoring.
An ego-camera based finger-spelling recognition system

This paper describes a portable system for finger-spelling recognition, employing a PC and a video taken by an ego-camera mounted on the body of a person who does finger-spelling. The system is intended to be a useful tool for an orally impaired person to communicate to anyone at any place by carrying it with him/her. The images of the finger-spelling hand of a user who is carrying the system is captured by an ego-camera. The hand is extracted from arbitrary backgrounds by use of a Gaussian mixture model and skin color evaluation: The trimmed and normalized image of the extracted hand is recognized employing the feature space defined by applying the principal component analysis to the learning data containing 45 finger-spelled Japanese Hiragana letters each with 50 samples and the nearest neighbor method. The on-line performance of the proposed system is experimentally shown.
Protein Expression of Matriptase and its Cognate Inhibitor HAI-1 in Human Prostate Cancer: A Tissue Microarray and Automated Quantitative Analysis

Recent studies have suggested that matriptase, a transmembrane serine protease and its cognate inhibitor hepatocyte growth factor activator inhibitor-1 (HAI-1) are important in the progression of many cancers. Limited quantitative data are available on these proteins in prostate cancer. To validate the roles of matriptase and HAI-1 in prostate cancer and its progression, a prostate cancer tissue microarray was constructed. The tissue microarray includes 41 localized prostate cancers (Pca_local), 18 aggressive prostate cancers, 18 metastatic prostate cancers, 24 benign prostate hyperplasias, 18 high-grade intraepithelial neoplasias (HGPIN), and 41 benign prostate tissues. The cellular expression levels of matriptase and HAI-1 were quantified using automated quantitative analysis. We found that matriptase expression levels were significantly higher in Pca_local (P<0.0001) and HGPIN (P<0.05) compared with benign prostate tissue. Matriptase levels were significantly decreased in metastatic cancer when compared with all other tissue types (P<0.05). Compared with benign prostate tissue, HAI-1 expression levels were significantly higher in all proliferative prostate diseases (benign prostate hyperplasia, HGPIN, localized and aggressive cancers, and metastases) (P<0.001); yet, no significant differences were found in HAI-1 expression levels among the diseased tissue types. These results suggest that an increase of matriptase may be useful as a marker for detection of Pca_local, whereas a decrease of matriptase expression may signal prostate cancer progression. HAI-1 seems to be a marker of prostate epithelial cell proliferation.
Circulating Galectin-3 Levels Are Increased in Patients with Ischemic Heart Disease, but Are Not Influenced by Acute Myocardial Infarction

Objectives: Galectin-3 (Gal-3) is involved in cardiac inflammation and fibrosis, and is in use as a biomarker that indicates increased risk in heart failure. This study examined the relationship between Gal-3 levels and acute and old myocardial infarction (MI) in patients assessed by cardiac magnetic resonance (CMR) imaging. Methods: Group 1 consisted of 38 patients with ST-elevation MI and single-vessel disease treated with primary percutaneous coronary intervention (PCI). Group 2 consisted of 52 patients with prior complicated MI. Twenty-two controls were included. CMR was performed in group 1 at 2 days, 1 week, 2 months and 1 year following PCI and in group 2 at >4 years after MI. Results: Median Gal-3 was elevated in patients compared with controls, group 1: 11.93 ng/ml (IQR 6.34-17.52, p = 0.03), group 2: 12.96 (IQR 6.33-19.29, p = 0.03) and controls: 10.16 (IQR 5.59-14.73). Gal-3 levels did not change during acute MI, and there was no relationship between Gal-3 and infarct size, troponin-T, high-sensitivity C-reactive protein, left-ventricular (LV) volumes or LV ejection fraction (LVEF) in group 1. In group 2, Gal-3 correlated modestly with MI size (r = 0.28, p < 0.05), LV end-diastolic volume index (r = 0.40, p < 0.01), LV end-systolic volume index (r = 0.43, p < 0.01) and LVEF (r = -0.39, p < 0.01). Conclusion: There was no relationship between Gal-3 levels and acute ischemic myocardial injury. A significant, modest relationship between Gal-3 levels, MI size and LV remodeling was only found in patients with old MI.
Proteins Exported via the PrsD-PrsE Type I Secretion System and the Acidic Exopolysaccharide Are Involved in Biofilm Formation by Rhizobium leguminosarum

ABSTRACT The type I protein secretion system of Rhizobium leguminosarum bv. viciae encoded by the prsD and prsE genes is responsible for secretion of the exopolysaccharide (EPS)-glycanases PlyA and PlyB. The formation of a ring of biofilm on the surface of the glass in shaken cultures by both the prsD and prsE secretion mutants was greatly affected. Confocal laser scanning microscopy analysis of green-fluorescent-protein-labeled bacteria showed that during growth in minimal medium, R. leguminosarum wild type developed microcolonies, which progress to a characteristic three-dimensional biofilm structure. However, the prsD and prsE secretion mutants were able to form only an immature biofilm structure. A mutant disrupted in the EPS-glycanase plyB gene showed altered timing of biofilm formation, and its structure was atypical. A mutation in an essential gene for EPS synthesis (pssA) or deletion of several other pss genes involved in EPS synthesis completely abolished the ability of R. leguminosarum to develop a biofilm. Extracellular complementation studies of mixed bacterial cultures confirmed the role of the EPS and the modulation of the biofilm structure by the PrsD-PrsE secreted proteins. Protein analysis identified several additional proteins secreted by the PrsD-PrsE secretion system, and N-terminal sequencing revealed peptides homologous to the N termini of proteins from the Rap family (Rhizobium adhering proteins), which could have roles in cellular adhesion in R. leguminosarum. We propose a model for R. leguminosarum in which synthesis of the EPS leads the formation of a biofilm and several PrsD-PrsE secreted proteins are involved in different aspects of biofilm maturation, such as modulation of the EPS length or mediating attachment between bacteria.
Possible association of the DRD4 gene with a history of attention-deficit/hyperactivity disorder in women with bulimia nervosa.

OBJECTIVE Up to one-third of patients with bulimia nervosa (BN) report a history of attention-deficit/hyperactivity disorder (ADHD) symptoms, and the dopaminergic genes, especially the dopamine receptor D4 (DRD4), have been associated independently with both binge eating and ADHD. METHOD The purpose of this study was to (1) compare the frequency of DRD4 exon III VNTR variants in 157 BN probands and equal number of healthy controls; (2) assess transmission of DRD4 alleles in 68 families of patients with BN; and (3) explore the possible role of DRD4 gene in childhood ADHD history in a subgroup of 81 women with BN. RESULTS Our results showed that the BN probands and controls did not differ in DRD4 allele frequency. We also did not find evidence for preferential transmission of any DRD4 variant to the affected offspring with BN. However, the presence of either the 2-repeat or 7-repeat allele was associated with a history of childhood ADHD in BN (p = .038, odds ratio = 3.2). DISCUSSION Our findings suggest that although DRD4 may not be associated with the diagnosis of BN, its variants are associated with a history of childhood ADHD in BN probands. This may have relevance for the understanding, prevention, and treatment of BN that evolves in the context of childhood ADHD.
Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma.

PURPOSE This phase II randomized discontinuation trial evaluated the effects of sorafenib (BAY 43-9006), an oral multikinase inhibitor targeting the tumor and vasculature, on tumor growth in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS Patients initially received oral sorafenib 400 mg twice daily during the initial run-in period. After 12 weeks, patients with changes in bidimensional tumor measurements that were less than 25% from baseline were randomly assigned to sorafenib or placebo for an additional 12 weeks; patients with > or = 25% tumor shrinkage continued open-label sorafenib; patients with > or = 25% tumor growth discontinued treatment. The primary end point was the percentage of randomly assigned patients remaining progression free at 24 weeks after the initiation of sorafenib. RESULTS Of 202 patients treated during the run-in period, 73 patients had tumor shrinkage of > or = 25%. Sixty-five patients with stable disease at 12 weeks were randomly assigned to sorafenib (n = 32) or placebo (n = 33). At 24 weeks, 50% of the sorafenib-treated patients were progression free versus 18% of the placebo-treated patients (P = .0077). Median progression-free survival (PFS) from randomization was significantly longer with sorafenib (24 weeks) than placebo (6 weeks; P = .0087). Median overall PFS was 29 weeks for the entire renal cell carcinoma population (n = 202). Sorafenib was readministered in 28 patients whose disease progressed on placebo; these patients continued on sorafenib until further progression, for a median of 24 weeks. Common adverse events were skin rash/desquamation, hand-foot skin reaction, and fatigue; 9% of patients discontinued therapy, and no patients died from toxicity. CONCLUSION Sorafenib has significant disease-stabilizing activity in metastatic renal cell carcinoma and is tolerable with chronic daily therapy.
Cellular Network Architectures for the Society in Motion

Due to rising mobility worldwide, a growing number of people utilizes cellular network services while on the move. Persistent urbanization trends raise the number of daily commuters, leading to a situation where telecommunication requirements are mainly dictated by two categories of users: 1) Static users inside buildings, demanding instantaneous and virtually bandwidth unlimited access to the Internet and Cloud services; 2) moving users outside, expecting ubiquitous and seamless mobility even at high velocity. While most work on future mobile communications is motivated by the first category of users, we outline in this article a layered cellular network architecture that has the potential to efficiently support both user groups simultaneously. We deduce novel transceiver architectures and derive research questions that need to be tackled to effectively maintain wireless connectivity for the envisioned Society in Motion.