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Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients.
Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post-heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day-14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN-gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man
Propagation of coherent waves in elastically scattering media
A general method for calculating statistical properties of speckle patterns
of coherent waves propagating in disordered media is developed. It allows one
to calculate speckle pattern correlations in space, as well as their
sensitivity to external parameters. This method, which is similar to the
Boltzmann-Langevin approach for the calculation of classical fluctuations,
applies for a wide range of systems: From cases where the ray propagation is
diffusive to the regime where the rays experience only small angle scattering.
The latter case comprises the regime of directed waves where rays propagate
ballistically in space while their directions diffuse. We demonstrate the
applicability of the method by calculating the correlation function of the wave
intensity and its sensitivity to the wave frequency and the angle of incidence
of the incoming wave.Comment: 19 pages, 5 figure
Improved estimates for the role of grey matter volume and GABA in bistable perception
they provide a method for studying the internal mechanisms of the brain while ensuring an unchanging external stimulus. In recent years, several studies have reported correlations between perceptual dynamics during bistable perception and particular brain characteristics such as the grey matter volume of areas in the superior parietal lobule (SPL) and the relative GABA concentration in the occipital lobe. Here, we attempt to replicate previous results using similar paradigms to those used in the studies first reporting the correlations. Using the original findings as priors for Bayesian analyses, we found strong support for the correlation between structure-from-motion percept duration and anterior SPL grey matter volume. Correlations between percept duration and other parietal areas as well as occipital GABA, however, were not directly replicated or appeared less strong than previous studies suggested. Inspection of the posterior distributions (current “best guess” based on new data given old data as prior) revealed that several original findings may reflect true relationships although no direct evidence was found in support of them in the current sample. Additionally, we found that multiple regression models based on grey matter volume at 2–3 parietal locations (but not including GABA) were the best predictors of percept duration, explaining approximately 35% of the inter-individual variance. Taken together, our results provide new estimates of correlation strengths, generally increasing confidence in the role of the aSPL while decreasing confidence in some of the other relationships
IL-12p40 Homodimer Ameliorates Experimental Autoimmune Arthritis
IL-23 is the key cytokine that induces the expansion of Th17 cells. It is composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to the receptor of IL-23 and blocks its activity. Our aim was to assess the preventive and therapeutic effect of the IL-12p40 homodimer (p40)(2) subunit in autoimmune arthritis animal models. In the current study, using IL-1R antagonist-knockout mice and a collagen-induced arthritis model, we investigated the suppressive effect of (p40)(2) on inflammatory arthritis. We demonstrated that the recombinant adenovirus-expressing mouse (p40)(2) model prevented the development of arthritis when given before the onset of arthritis. It also decreased the arthritis index and joint erosions in the mouse model if transferred after arthritis was established. (p40)(2) inhibited the production of inflammatory cytokines and Ag-specific T cell proliferation. It also induced CD4(+)CD25(+)Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the generation of retinoic acid receptor-related organ receptor gamma t and Th17 cells was suppressed. The induction of Treg cells and the suppression of Th17 cells were mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)(2) suppressed inflammatory arthritis successfully. This could be a useful therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance and IL-23 signaling.1156Ysciescopu
A rapid, efficient, and facile solution for dental hypersensitivity: The tannin–iron complex
Dental hypersensitivity due to exposure of dentinal tubules under the enamel layer to saliva is a very popular and highly elusive technology priority in dentistry. Blocking water flow within exposed dentinal tubules is a key principle for curing dental hypersensitivity. Some salts used in "at home" solutions remineralize the tubules inside by concentrating saliva ingredients. An "in-office" option of applying dense resin sealants on the tubule entrance has only localized effects on well-defined sore spots. We report a self-assembled film that was formed by facile, rapid (4 min), and efficient (approximately 0.5 g/L concentration) dip-coating of teeth in an aqueous solution containing a tannic acid-iron(III) complex. It quickly and effectively occluded the dentinal tubules of human teeth. It withstood intense tooth brushing and induced hydroxyapatite remineralisation within the dentinal tubules. This strategy holds great promise for future applications as an effective and user-friendly desensitizer for managing dental hypersensitivity.111310Ysciescopu
RNA-DNA differences are rarer in proto-oncogenes than in tumor suppressor genes
It has long been assumed that DNA sequences and corresponding RNA transcripts are almost identical; a recent discovery, however, revealed widespread RNA-DNA differences (RDDs), which represent a largely unexplored aspect of human genome variation. It has been speculated that RDDs can affect disease susceptibility and manifestations; however, almost nothing is known about how RDDs are related to disease. Here, we show that RDDs are rarer in proto-oncogenes than in tumor suppressor genes; the number of RDDs in coding exons, but not in 3′UTR and 5′UTR, is significantly lower in the former than the latter, and this trend is especially pronounced in non-synonymous RDDs, i.e., those cause amino acid changes. A potential mechanism is that, unlike proto-oncogenes, the requirement of tumor suppressor genes to have both alleles affected to cause tumor ‘buffers' these genes to tolerate more RDDs
Inflation on the Brane with Vanishing Gravity
Many existing models of brane inflation suffer from a steep irreducible
gravitational potential between the branes that causes inflation to end too
early. Inspired by the fact that point masses in 2+1 D exert no gravitational
force, we propose a novel unwarped and non-supersymmetric setup for inflation,
consisting of 3-branes in two extra dimensions compactified on a sphere. The
size of the sphere is stabilized by a combination of a bulk cosmological
constant and a magnetic flux. Computing the 4D effective potential between
probe branes in this background, we find a non-zero contribution only from
exchange of level-1 KK modes of the graviton and radion. Identifying antipodal
points on the 2-sphere projects out these modes, eliminating entirely the
troublesome gravitational contribution to the inflationary potential.Comment: 19 pages, 11 figures, JHEP forma
Manipulating infrared photons using plasmons in transparent graphene superlattices
Superlattices are artificial periodic nanostructures which can control the
flow of electrons. Their operation typically relies on the periodic modulation
of the electric potential in the direction of electron wave propagation. Here
we demonstrate transparent graphene superlattices which can manipulate infrared
photons utilizing the collective oscillations of carriers, i.e., plasmons of
the ensemble of multiple graphene layers. The superlattice is formed by
depositing alternating wafer-scale graphene sheets and thin insulating layers,
followed by patterning them all together into 3-dimensional
photonic-crystal-like structures. We demonstrate experimentally that the
collective oscillation of Dirac fermions in such graphene superlattices is
unambiguously nonclassical: compared to doping single layer graphene,
distributing carriers into multiple graphene layers strongly enhances the
plasmonic resonance frequency and magnitude, which is fundamentally different
from that in a conventional semiconductor superlattice. This property allows us
to construct widely tunable far-infrared notch filters with 8.2 dB rejection
ratio and terahertz linear polarizers with 9.5 dB extinction ratio, using a
superlattice with merely five graphene atomic layers. Moreover, an unpatterned
superlattice shields up to 97.5% of the electromagnetic radiations below 1.2
terahertz. This demonstration also opens an avenue for the realization of other
transparent mid- and far-infrared photonic devices such as detectors,
modulators, and 3-dimensional meta-material systems.Comment: under revie
Peptidoglycan-Targeted [<sup>18</sup>F]3,3,3-Trifluoro-d-alanine Tracer for Imaging Bacterial Infection
\ua9 2024 The Authors. Published by American Chemical Society. Imaging is increasingly used to detect and monitor bacterial infection. Both anatomic (X-rays, computed tomography, ultrasound, and MRI) and nuclear medicine ([111In]-WBC SPECT, [18F]FDG PET) techniques are used in clinical practice but lack specificity for the causative microorganisms themselves. To meet this challenge, many groups have developed imaging methods that target pathogen-specific metabolism, including PET tracers integrated into the bacterial cell wall. We have previously reported the d-amino acid derived PET radiotracers d-methyl-[11C]-methionine, d-[3-11C]-alanine, and d-[3-11C]-alanine-d-alanine, which showed robust bacterial accumulation in vitro and in vivo. Given the clinical importance of radionuclide half-life, in the current study, we developed [18F]3,3,3-trifluoro-d-alanine (d-[18F]-CF3-ala), a fluorine-18 labeled tracer. We tested the hypothesis that d-[18F]-CF3-ala would be incorporated into bacterial peptidoglycan given its structural similarity to d-alanine itself. NMR analysis showed that the fluorine-19 parent amino acid d-[19F]-CF3-ala was stable in human and mouse serum. d-[19F]-CF3-ala was also a poor substrate for d-amino acid oxidase, the enzyme largely responsible for mammalian d-amino acid metabolism and a likely contributor to background signals using d-amino acid derived PET tracers. In addition, d-[19F]-CF3-ala showed robust incorporation into Escherichia coli peptidoglycan, as detected by HPLC/mass spectrometry. Based on these promising results, we developed a radiosynthesis of d-[18F]-CF3-ala via displacement of a bromo-precursor with [18F]fluoride followed by chiral stationary phase HPLC. Unexpectedly, the accumulation of d-[18F]-CF3-ala by bacteria in vitro was highest for Gram-negative pathogens in particular E. coli. In a murine model of acute bacterial infection, d-[18F]-CF3-ala could distinguish live from heat-killed E. coli, with low background signals. These results indicate the viability of [18F]-modified d-amino acids for infection imaging and indicate that improved specificity for bacterial metabolism can improve tracer performance
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