Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of PPARα Expression and Inflammatory Interleukin-6 Production by Chronic Glucose Increases Monocyte/Endothelial Adhesion

Objective—We have previously reported increased monocyte adhesion to human aortic endothelial cells (HAECs) cultured in 25 mmol/L glucose (HG) compared with normal glucose (NG) (5.5 mmol/L). In this study, we explored mechanisms that contribute to increased monocyte adhesion by elevated glucose. Methods and Results—We found that HAECs cultured in HG have increased production of the chemokine interleukin-6 (IL-6). We examined whether IL-6 directly modulated monocyte adhesion to EC. Inhibition of IL-6 using a neutralizing antibody significantly reduced glucose-mediated monocyte adhesion by 50%, and addition of IL-6 directly to human EC stimulated monocyte adhesion. PPARα has been reported to negatively regulate expression of IL-6 in vascular cells, so we examined PPARα-associated signaling in EC. A known PPARα agonist, Wy14,643, prevented glucose-mediated IL-6 production by EC and reduced glucose-mediated monocyte adhesion by 40%. HG-cultured HAEC had a 50% reduction in expression of PPARα compared with control EC. Primary aortic EC isolated from PPARα knockout (KO) mice showed increased monocyte adhesion compared with EC isolated from control mice. PPARα KO EC also had increased production of IL-6. Finally, we measured IL-6 levels in diabetic db/db mice and found significant 6-fold elevations in IL-6 levels in db/db EC. Conclusions—These data indicate that IL-6 production is increased in diabetes and contributes to early vascular inflammatory changes. PPARα protects EC from glucose-mediated monocyte adhesion, in part through regulation of IL-6 production.
The pH 6 Antigen Is an Antiphagocytic Factor Produced by Yersinia pestis Independent of Yersinia Outer Proteins and Capsule Antigen

ABSTRACT The pH 6 antigen (pH 6 Ag; PsaA) of Yersinia pestis has been shown to be a virulence factor. In this study, we set out to investigate the possible function of Y. pestis PsaA in a host cell line, RAW264.7 mouse macrophages, in order to better understand the role it might play in virulence. Y. pestis KIM5 derivatives with and without the pCD1 plasmid and their psaA isogenic counterparts and Escherichia coli HB101 and DΗ5α carrying a psaA clone or a vector control were used for macrophage infections. Macrophage-related bacteria and gentamicin-resistant intracellular bacteria generated from plate counting and direct microscopic examinations were used to evaluate these RAW264.7 macrophage infections. Y. pestis psaA isogenic strains did not show any significant difference in their abilities to associate with or bind to mouse macrophage cells. However, expression of psaA appeared to significantly reduce phagocytosis of both Y. pestis and E. coli by mouse macrophages (P < 0.05). Furthermore, we found that complementation of psaA mutant Y. pestis strains could completely restore the ability of the bacteria to resist phagocytosis. Fluorescence microscopy following differential labeling of intracellular and extracellular Y. pestis revealed that significantly lower numbers of psaA-expressing bacteria were located inside the macrophages. Enhanced phagocytosis resistance was specific for bacteria expressing psaA and did not influence the ability of the macrophages to engulf other bacteria. Our data demonstrate that Y. pestis pH 6 Ag does not enhance adhesion to mouse macrophages but rather promotes resistance to phagocytosis.
Tubulin-G protein association stabilizes GTP binding and activates GTPase: cytoskeletal participation in neuronal signal transduction.

It has been suggested that dimeric tubulin can participate in the signal transduction process through its association with the GTP-binding (G) proteins Gs and Gi1. Using the photoaffinity GTP analog, azidoanilido-GTP, it has been shown that the transfer of nucleotide from tubulin to G alpha s and G alpha i1 is the key step of this activation. The binding sites between tubulin and Gs or G alpha i1 appear to involve microtubule polymerization domains, since G protein alpha subunits were demonstrated to inhibit microtubule assembly [Wang, N. , & Rasenick, M. M. (1991) Biochemistry 30, 10957-10965]. In order to understand tubulin-G protein interaction and the nucleotide transfer process in detail, tubulin was labeled with [alpha-32P]GTP or [35S]GTP gamma S and was incubated with recombinant G alpha i1 at increasing molar ratios. Rapid filtration through nitrocellulose was used to determine nucleotide binding in the protein complex. A substantial amount of bound nucleotide was lost from tubulin during the filtration assay. However, the addition of G alpha i1 to [alpha-32P]-GTP-tubulin protected the nucleotide binding in a dose-dependent manner, suggesting a stabilization of GTP binding in the tubulin-G alpha i1 complex. G beta gamma mitigated this effect, and this was not dependent upon the presence of G alpha, suggesting a direct interaction between beta gamma and tubulin. The retinal G protein, transducin, which displayed a much lower affinity for tubulin, did not elicit similar stabilization of GTP binding, and transducin beta gamma did not release GTP from tubulin. (ABSTRACT TRUNCATED AT 250 WORDS)
Airborne Antibiotic Resistant and Nonresistant Bacteria and Fungi Recovered from Two Swine Herd Confined Animal Feeding Operations

Inhalation of microorganisms could be a health concern for workers inside and downwind of animal confinement units. Using the Andersen two-stage viable microbial particle sizing sampler, air samples were collected from locations upwind, inside, and downwind during two visits to two swine herd confined animal feeding operations. Six samples were taken at each location on each site. Bacteria isolated from each site were then tested for antibiotic resistance using the Kirby-Bauer disc diffusion method. Resistant bacterial forms were found inside and downwind of the swine confinement facilities, indicating that resistant organisms were being produced in and released from these facilities. Resistance to a battery of antibiotics including ampicillin, erythromycin, oxytetracycline, penicillin, tetracycline, and tylosin was found in the following bioaerosols: Staphylococcus aureus,Salmonella spp. , and fecal coliforms. The major conclusion reached by this study was that bacteria were recovered inside and downwind of these facilities in levels that previous studies had stated could cause a potential human health hazard.
Diet, body mass and colorectal cancer: A case‐referent study in Stockholm

A population‐based case‐referent study on diet (total energy, protein, fat, dietary fiber), body mass and colorectal cancer was performed in Stockholm in 1986–1988. The study included 1,081 subjects. The relative risks (RR, with a 95% confidence interval, highest versus lowest quintile) for colon cancer were as follows: total energy (1.7, 1. 0–3.0), protein (2.4, 1.5–4.0), total fat (2.2, 1.3–3.6), dietary fiber for men (0.5, 0.2–1.1), dietary fiber for women (1.2, 0.7–2.3) and body mass (2.0, 1.3–3.1). The relative risks for rectal cancer were: total energy (2.4, 1.2–4.7), protein (3.6, 2.0–6.4), total fat (2.5, 1.4 4.6), dietary fiber (0.5, 0.3–0.9), body mass for men (1.7, 0.7–4.0), and body mass for women (1.0, 0.5–1.9). Adjustment for physical activity, body mass (in the diet analysis), the abovementioned dietary factors (in the body mass analysis), and browned meat surface had little or no influence on the results.
Anti-Pseudomonas Activity of Frog Skin Antimicrobial Peptides in a Caenorhabditis elegans Infection Model: a Plausible Mode of Action In Vitro and In Vivo

ABSTRACT The emergence of multidrug-resistant (MDR) microorganisms makes it increasingly difficult to treat infections. These infections include those associated with Pseudomonas aeruginosa, which are hard to eradicate, especially in patients with a compromised immune system. Naturally occurring membrane-active cationic antimicrobial peptides (CAMPs) serve as attractive candidates for the development of new therapeutic agents. Amphibian skin is one of the richest sources for such peptides, but only a few studies on their in vivo activities and modes of action have been reported. We investigated (i) the activity and mechanism underlying the killing of short CAMPs from frog skin (e.g., temporins and esculentin fragments) on an MDR clinical isolate of P. aeruginosa and (ii) their in vivo antibacterial activities and modes of action, using the minihost model of Caenorhabditis elegans. Our data revealed that in vivo, both temporin-1Tb and esculentin(1-18) were highly active in promoting the survival of Pseudomonas-infected nematodes, although temporin-1Tb did not show significant activity in vitro under the experimental conditions used. Importantly, esculentin(1-18) permeated the membrane of Pseudomonas cells within the infected nematode. To the best of our knowledge, this is the first report showing the ability of a CAMP to permeate the microbial membrane within a living organism. Besides shedding light on a plausible mode of action of frog skin CAMPs in vivo, our data suggest that temporins and esculentins would be attractive molecules as templates for the development of new therapeutics against life-threatening infections.
On the mechanism of M‐current inhibition by muscarinic m1 receptors in DNA‐transfected rodent neuroblastoma x glioma cells.

1. Acetylcholine (ACh) produces two membrane current changes when applied to NG108‐15 mouse neuroblastoma x rat glioma hybrid cells transformed (by DNA transfection) to express m1 muscarinic receptors: it activates a Ca(2+)‐dependent K+ conductance, producing an outward current, and it inhibits a voltage‐dependent K+ conductance (the M conductance), thus diminishing the M‐type voltage‐dependent K+ current (IK(M)) and producing an inward current. The present experiments were undertaken to find out how far inhibition of IK(M) might be secondary to stimulation of phospholipase C, by recording membrane currents and intracellular Ca2+ changes with indo‐1 using whole‐cell patch‐clamp methods. 2. Bath application of 100 microM ACh reversibly inhibited IK(M) by 47.3 +/‐ 3.2% (n = 23). Following pressure‐application of 1 mM ACh, the mean latency to inhibition was 420 ms at 35 degrees C and 1.79 s at 23 degrees C. Latencies to inhibition by Ba2+ ions were 148 ms at 35 degrees C and 92 ms at 23 degrees C. 3. The involvement of a G‐protein was tested by adding 0.5 mM GTP‐gamma‐S or 10 mM potassium fluoride to the pipette solution. These slowly reduced IK(M), with half‐times of about 30 and 20 min respectively, and rendered the effect of superimposed ACh irreversible. Effects of ACh were not significantly changed after pretreatment for 24 h with 500 ng ml‐1 pertussis toxin or on adding up to 10 mM GDP‐beta‐S to the pipette solution. 4. The role of phospholipase C and its products was tested using neomycin (to inhibit phospholipase C), inositol 1,4,5‐trisphosphate (InsP3) and inositol 1,3,4,5‐tetrakisphosphate (InsP4), heparin, and phorbol dibutyrate (PDBu) and staurosporin (to activate and inhibit protein kinase C respectively). Both neomycin (1 mM external) and InsP3 (100 microM intrapipette) inhibited the ACh‐induced outward current and/or intracellular Ca2+ transient but did not block ACh‐induced inhibition of IK(M). Intrapipette heparin (1 mM) blocked activation of IK(Ca) and reduced Ach‐induced inhibitions of IK(M), but also reduced inhibition of ICa via endogeneous m4 receptors. PDBu (with or without intrapipette ATP) and staurosporin had no significant effects. (ABSTRACT TRUNCATED AT 400 WORDS)
Dual targeting of tumor vasculature: combining Avastin and vascular disrupting agents (CA4P or OXi4503).

BACKGROUND This study evaluated the therapeutic efficacy of combining vascular disrupting agents with antiangiogenic agents. MATERIALS AND METHODS Human clear cell renal carcinoma (Caki-1) tumors were established in nude mice. Treatments consisted of Avastin (2 mg/kg) administered twice a week; CA4P (100 mg/kg) or OXi4503 (25 mg/kg) administered 3 times a week for a period of 2 weeks; or a combination of Avastin and CA4P or OXi4503. Tumor response was assessed by growth delay. RESULTS The tumor growth delays were 8, 6, and 18 days for Avastin, CA4P, and OXi4503, respectively. When the two therapies were combined, there was a significantly greater tumor response than what was achieved with single-agent treatments. For example, Avastin plus CA4P led to a growth delay of 13 days, and 27 days for Avastin plus OXi4503. CONCLUSION Vascular-directed therapies that include both antiangiogenic and vascular disrupting therapeutics can result in significantly enhanced antitumor effects.
Toll-Like Receptors and Their Function in Innate and Adaptive Immunity

Over the past 3 years our knowledge about how we sense the microbial world has been fundamentally changed. It has been known for decades that microbial products, such as lipopolysaccharide, lipoproteins, or peptidoglycan, have a profound activity on human cells. Whereas the structure of many different pathogenic microbial compounds has been extensively studied and characterized, the molecular basis of their recognition by the cells of the innate immune system remained elusive for a long time. It was Charles Janeway [Cold Spring Harb Symp Quant Biol 1989;54/1:1–13] who developed the idea of microbial structures forming pathogen-associated molecular patterns that would be recognized by pattern recognition receptors. The discovery of the family of Toll receptors in species as diverse as Drosophila and humans, and the recognition of their role in distinguishing molecular patterns that are common to microorganisms have led to a renewed appreciation of the innate immune system. Moreover, it is now clear that the activation of the innate immune system through mammalian Toll-like receptors has also an instructive role for the responses of the adaptive immune response and, thus, may influence allergic diseases such as asthma.
Non‐invasive prediction of the degree of liver fibrosis in patients with hepatitis C using an ultrasound contrast agent. A pilot study

It has been shown that the severity of hepatic fibrosis in patients with hepatitis C can be predicted non‐invasively by measuring intrahepatic circulatory time (IHCT) using a microbubble agent with spectral Doppler analysis. The aim of this study was to assess whether this technique is reproducible using a third‐generation microbubble agent and contrast harmonic imaging, which are becoming the standard ultrasound techniques in all radiology departments. Twenty‐three untreated patients with hepatitis C, who had undergone a recent liver biopsy, were studied prospectively. Based on their histological fibrosis score, patients were divided into four groups (fibrosis levels 1–4). Contrast harmonic imaging was carried out after an intravenous bolus of a microbubble agent (Optison; Amersham Health, Milwaukee, WI, USA). IHCT was calculated by measuring the difference between the hepatic vein and hepatic artery microbubble arrival times. The IHCT was compared with the degree of fibrosis. Significant differences were shown between the groups for IHCT. There were significant differences between fibrosis levels 1 and 3 and between fibrosis levels 1 and 4. This study has shown that calculation of IHCT using a third‐generation microbubble agent and contrast harmonic imaging can differentiate mild fibrosis from more severe degrees of fibrosis in patients with hepatitis C.
Paleobiology of a Neoproterozoic tidal flat/lagoonal complex: the Draken Conglomerate Formation, Spitsbergen

Carbonates and rare shales of the ca 700–800 Ma old Draken Conglomerate Formation, northeastern Spitsbergen, preserve a record of environmental variation within a Neoproterozoic tidal flat/lagoon complex. Forty-two microfossil taxa have been recognized in Draken rocks, and of these, 39 can be characterized in terms of their paleoenvironmental distributions along a gradient from the supratidal zone to permanently submerged lagoons. Supratidal to subtidal trends include: increasing microbenthic diversity, increasing abundance and diversity of included allochthonous (presumably planktonic) elements, decreasing sheath thickness of mat-building organisms (with significant taphonomic consequences), and an increasing sediment/fossil ratio in fossiliferous rocks. Five principal and several minor biofacies can be distinguished. The paleoecological resolution obtainable in the Draken Conglomerate Formation rivals that achieved for most Phanerozoic fossil deposits. It documents the complexity and diversity of Proterozoic coastal ecosystems and indicates that both environment and taphonomy need to be taken into explicit consideration in attempts to understand evolutionary trends in the early fossil record. Three species, Coniunctiophycus majorinum, Myxococcoides distola, and M. chlorelloidea, are described as new; Siphonophycus robustum, Siphonophycus septatum, and Gorgonisphaeridium maximum are proposed as new combinations.
Supratentorial low-grade gliomas in older patients

Background: Low-grade gliomas (LGG) are thought to be very rare in elderly patients (>60 years) and have not been thoroughly studied. Methods: A series of 62 elderly (≥60 years of age) LGG patients were identified in a department database collecting information on pathologically identified adult supratentorial LGG. The clinical, radiologic, pathologic, and therapeutic data of these patients were analyzed and compared to those of 704 younger LGG patients (<60 years). Results: Comparisons between older and younger groups showed that elderly patients more often presented with a clinical deficit (p < 0.0001), a lower Karnofsky performance status (p = 0.0002), a larger tumor on MRI (p = 0.03), and a lower rate of tumor resection (p < 0.0001). Chemotherapy was more often used as first line treatment (p = 0.001). Among the patients who died of progressive disease, 55% of the elderly patients had not received radiotherapy compared to 11% in the younger group (p < 0.0001). Survival was shorter in older patients (p < 0.0001), with a 5-year survival rate of 40%. An astrocytic phenotype (p = 0.0097), increasing age (p = 0.0049), and a tumor crossing the midline (p = 0.028) were negative prognostic factors in the older group. Conclusion: We found that 8% of low-grade gliomas (LGG) occur in older patients (≥60 years of age). The clinical–radiologic picture of LGG in the elderly population differs from younger patients. Although long-term survival occurs, the course is generally more severe because elderly patients accumulate negative prognostic factors and because they are probably undertreated.
SOCIAL CAPITAL, COLLEGE CHOICE, AND COLLEGE PERSISTENCE OF HISPANICS: A CASE OF A PUBLIC UNIVERSITY IN WESTERN PENNSYLVANIA

The purpose of this research study is to identify the social capital factors that help Hispanics in their decision to attend a Predominantly White Institution (henceforth PWI) and those social capital factors that are significant in their college persistence. College persistence is defined as returning a second year and beyond. This case study uses a mixed methodology, specifically an explanatory sequential method. First, a cross-sectional, online survey was sent to participants who self-identified as Hispanics and who were currently enrolled during the spring of 2015 (N=365). The survey was followed-up by four individual semi-structured interviews. The target population is undergraduate Hispanic students who are 18 years old and who are attending the Indiana University of Pennsylvania (IUP).
Medication compliance and clinical outcomes of fixed‐dose combinations vs free combinations of an angiotensin II receptor blocker and a calcium channel blocker in hypertension treatment

Using the National Health Insurance Research Database of Taiwan, the authors identified 1136 patients taking fixed‐dose combination and 4544 patients taking free combinations of an angiotensin II receptor blocker and a dihydropyridine calcium channel blocker from January 2009 to December 2012. At a mean follow‐up of 2.1 years, the fixed‐dose combination was associated with improved medication adherence and persistence and better survival free from major adverse cardiac events and hospitalization for heart failure compared with the free combination regimens.
Identification and Regulation of TPS04/GES, an Arabidopsis Geranyllinalool Synthase Catalyzing the First Step in the Formation of the Insect-Induced Volatile C16-Homoterpene TMTT[W]

Volatile secondary metabolites emitted by plants contribute to plant–plant, plant–fungus, and plant–insect interactions. The C16-homoterpene TMTT (for 4,8,12-trimethyltrideca-1,3,7,11-tetraene) is emitted after herbivore attack by a wide variety of plant species, including Arabidopsis thaliana, and is assumed to play a role in attracting predators or parasitoids of herbivores. TMTT has been suggested to be formed as a degradation product of the diterpene alcohol (E,E)-geranyllinalool. Here, we report the identification of Terpene Synthase 04 (TPS04; At1g61120) as a geranyllinalool synthase (GES). Recombinant TPS04/GES protein expressed in Escherichia coli catalyzes the formation of (E,E)-geranyllinalool from the substrate geranylgeranyl diphosphate. Transgenic Arabidopsis lines carrying T-DNA insertions in the TPS04 locus are deficient in (E,E)-geranyllinalool and TMTT synthesis, a phenotype that can be complemented by expressing the GES gene under the control of a heterologous promoter. GES transcription is upregulated under conditions that induce (E,E)-geranyllinalool and TMTT synthesis, including infestation of plants with larvae of the moth Plutella xylostella and treatment with the fungal peptide alamethicin or the octadecanoid mimic coronalon. Induction requires jasmonic acid but is independent from salicylic acid or ethylene. This study paves the ground to address the contribution of TMTT in ecological interactions and to elucidate the signaling network that regulates TMTT synthesis.
Monitoring dynamic protein expression in living E. coli. Bacterial cells by laser tweezers Raman spectroscopy

Laser tweezers Raman spectroscopy (LTRS) is a novel, nondestructive, and label‐free method that can be used to quantitatively measure changes in cellular activity in single living cells. Here, we demonstrate its use to monitor changes in a population of E. coli cells that occur during overexpression of a protein, the extracellular domain of myelin oligodendrocyte glycoprotein [MOG(1‐120)].
Functionalized Single-Walled Carbon-Nanotube-Blended P3HT-Based Thin-Film Transistors With Multiwalled Carbon-Nanotube Source and Drain Electrodes

We demonstrate the superior performance of thin-film transistors with a functionalized single-walled carbon-nanotube-blended poly(3-hexylthiophene) (F-SWCNT-P3HT) channel and multiwalled CNT source and drain electrodes (MWCNT S/Ds). Compared with transistors with a P3HT channel and gold electrodes, the mobility of transistors with an F-SWCNT-P3HT channel and MWCNT S/Ds is increased by more than one order of magnitude, i.e., from 0.0052 to 0.072 cm2/V·s. This improvement results not only from the well-known fast carrier transport assisted by the blend of F-SWCNTs but also, more importantly, from the reduced contact resistance between P3HT and MWCNT S/Ds.