Ivermectin-dependent release of IL-1beta in response to ATP by peritoneal macrophages from P2X<Subscript>7</Subscript>-KO mice

The response to ATP of peritoneal macrophages from wild-type (WT) and P2X₇-invalidated (KO) mice was tested. Low concentrations (1–100 μM) of ATP transiently increased the intracellular concentration of calcium ([Ca²⁺]_i) in cells from both mice. The inhibition of the polyphosphoinositide-specific phospholipase C with U73122 inhibited this response especially in WT mice suggesting that the responses coupled to P2Y receptors were potentiated by the expression of P2X₇ receptors. One millimolar ATP provoked a sustained increase in the [Ca²⁺]_i only in WT mice. The response to 10 μM ATP was potentiated and prolonged by ivermectin in both mice. One millimolar ATP increased the influx of extracellular calcium, decreased the intracellular concentration of potassium ([K⁺]_i) and stimulated the secretion of interleukin-1β (IL-1β) only in cells from WT mice. Ten micromolar ATP in combination with 3 μM ivermectin reproduced these responses both in WT and KO mice. The secretion of IL-1β was also increased by nigericin in WT mice and the secretory effect of a combination of ivermectin with ATP in KO mice was suppressed in a medium containing a high concentration of potassium. In WT mice, 150 μM BzATP stimulated the uptake of YOPRO-1. Incubation of macrophages from WT and KO mice with 10 μM ATP resulted in a small increase of YOPRO-1 uptake, which was potentiated by addition of 3 μM ivermectin. The uptake of this dye was unaffected by pannexin-1 blockers. In conclusion, prolonged stimulation of P2X₄ receptors by a combination of low concentrations of ATP plus ivermectin produced a sustained activation of the non-selective cation channel coupled to this receptor. The ensuing variations of the [K⁺]_i triggered the secretion of IL-1β. Pore formation was also triggered by activation of P2X₄ receptors. Higher concentrations of ATP elicited similar responses after binding to P2X₇ receptors. The expression of the P2X₇ receptors was also coupled to a better response to P2Y receptors.     

Characterization of the oligosaccharide moiety of VIP receptor from the human pancreatic cell line BxPC-3

The human pancreatic cell line BxPC-3 displays two classes of binding sites with high and low affinity for VIP. The order of potency of VIP-related peptides in inhibiting either [¹²⁵I]VIP or [¹²⁵I]N-AcPACAP27 binding and in stimulating cAMP production was typical of the human VIP receptor. By combining affinity labeling with glycosidase treatments, we have characterized the VIP receptor as a M_r = 68,200 glycoprotein, consisting of a M_r = 39,300 polypeptide core with at least three N-linked oligosaccharide chains. In addition, our results revealed the presence of a low amount of sialic acid residues in the carbohydrate moiety of receptor.     

Diet of upper paleolithic modern humans: Evidence from microwear texture analysis

This article presents the results of the occlusal molar microwear texture analysis of 32 adult Upper Paleolithic modern humans from a total of 21 European sites dating to marine isotope stages 3 and 2. The occlusal molar microwear textures of these specimens were analyzed with the aim of examining the effects of the climatic, as well as the cultural, changes on the diets of the Upper Paleolithic modern humans. The results of this analysis do not reveal any environmentally driven dietary shifts for the Upper Paleolithic hominins indicating that the climatic and their associated paleoecological changes did not force these humans to significantly alter their diets in order to survive. However, the microwear texture analysis does detect culturally related changes in the Upper Paleolithic humans' diets. Specifically, significant differences in diet were found between the earlier Upper Paleolithic individuals, i.e., those belonging to the Aurignacian and Gravettian contexts, and the later Magdalenian ones, such that the diet of the latter group was more varied and included more abrasive foods compared with those of the former. Am J Phys Anthropol 153:570–581, 2014. © 2014 Wiley Periodicals, Inc.     

Cultural transmission and the evolution of human behaviour: a general approach based on the Price equation

Transmitted culture can be viewed as an inheritance system somewhat independent of genes that is subject to processes of descent with modification in its own right. Although many authors have conceptualized cultural change as a Darwinian process, there is no generally agreed formal framework for defining key concepts such as natural selection, fitness, relatedness and altruism for the cultural case. Here, we present and explore such a framework using the Price equation. Assuming an isolated, independently measurable culturally transmitted trait, we show that cultural natural selection maximizes cultural fitness, a distinct quantity from genetic fitness, and also that cultural relatedness and cultural altruism are not reducible to or necessarily related to their genetic counterparts. We show that antagonistic coevolution will occur between genes and culture whenever cultural fitness is not perfectly aligned with genetic fitness, as genetic selection will shape psychological mechanisms to avoid susceptibility to cultural traits that bear a genetic fitness cost. We discuss the difficulties with conceptualizing cultural change using the framework of evolutionary theory, the degree to which cultural evolution is autonomous from genetic evolution, and the extent to which cultural change should be seen as a Darwinian process. We argue that the nonselection components of evolutionary change are much more important for culture than for genes, and that this and other important differences from the genetic case mean that different approaches and emphases are needed for cultural than genetic processes.     

The influence of postnatal nutrition on lipoprotein lipase activity and hormone sensitive lipolysis in vitro of rat adipose tissue

In rats grown up in small and large nests the lipolytic activity of adipose tissue was studied in vitro in dependence on age. Independent of age and sex a significantly higher lipoprotein lipase activity as well as a lower basal or norepinephrine stimulated lipolysis and reesterification (absolute) occurred in rats from small nests compared with rats from large nests. The calculated degree of reesterification was independent of the nest size, but decreased from 80% to 30% from one month to one year of age. The marked differences in the lipolytic activities of adipose tissue emphasize the distinct influence of the post-natal nutrition on metabolic functions in the later life and lead to the conclusion that the metabolism of adipose tissue of animals from small nests is directed towards a long-term increased storage of lipids.     

Influence of Magnetic Field on Brain Activity During Administration of Caffeine

The aim of the present work is to evaluate the effect of caffeine, the world’s most popular psychoactive drug, on the electric activity of the rat’s brain that exposed to extremely low-frequency magnetic field (ELF-MF), during 15 days. The obtained results showed that administration of caffeine in a group of rats by dose of 10 mg/kg (equivalent to human daily consumption) caused a reduction in the mean power amplitude of electroencephalogram (EEG) trace for almost all frequency bands especially α (8–12 Hz). It was observed that the influence of caffeine was more evident in motor cortex than in visual cortex. While the exposure of another group to ELF-MF of intensity 0.2 mT during the same period caused an enhancement in the mean power amplitude of most EEG frequency bands; this was more observed in the right hemisphere of the brain than that of the left hemisphere. The administration of caffeine while rats were exposed to ELF-MF, led, after 5 days of exposure, to a great increase in the mean power amplitude of α band at all places of recording electrodes. It may be concluded that caffeine administration was more effective in reducing the hazardous of ELF-MF in motor cortex than in visual cortex.     

Clinical significance of plasma MMP‐2 and MMP‐9 levels as biomarkers for tumor expression in breast cancer patients in Egypt

Matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9) are involved in the breakdown of extracellular matrix in normal physiological processes as well as in disease processes, such as cancer metastasis. We conducted this work to study the role of MMP-2 and MMP-9 in breast cancer by measuring their plasma concentrations before and after surgery. Also, to examine if their levels can reflect the stage of disease and prognosis. Forty-eight breast cancer patients and 13 patients with benign breast diseases were included in the study. MMP-2 and MMP-9 levels were measured by ELISA and semi-quantitative real-time PCR. MMP-2 and MMP-9 levels in plasma were determined by ELISA immediately before surgery and during 6 to 12 months after curative surgery. We observed a significant increase in the level of MMP-9 mRNA expression in breast cancer patients in comparison to their normal breast tissues and to tissues of benign breast disease. In all TNM tumor stages, the plasma levels of MMP-2 and MMP-9 were increased significantly before curative surgery in the studied patients with breast carcinoma and decreased significantly after surgery. Both MMP-2 and MMP-9 may be used as a possible marker for follow-up or as a marker that reflects the response of the disease to treatment.

     

Long-Term Effect of Forskolin on the Activation of Adenylyl Cyclase in Astrocytes

Abstract: Long-term (48-h) forskolin treatment of rat astroglial cells led to a slight decrease (30–40%) in the response to isoproterenol, vasoactive-intestinal peptide, guanyl 5'-(βγ-imido)diphosphate, guanosine 5'- O -(3-thiotriphosphate) [GTP(S)], and AIF₄⁻ in crude membrane fractions. In contrast, the acute stimulatory effect of forskolin was increased by 1.25–1.5-fold. These two opposite effects of forskolin were mediated by a cyclic AMP-dependent mechanism. No changes in G_sα, G_iα, or Gβ protein levels could be determined by immunoblotting using specific antisera. No significant differences were observed in the ability of G proteins extracted from control and forskolin-treated cells to reconstitute a full adenylyl cyclase activity in membranes from S49 cyc⁻ cells, lacking G_sα protein. G_sα proteins were detected in two pools of membranes, one in the heavy sucrose fractions and the other in light sucrose fractions. Forskolin treatment of the cells shifted G_sα protein toward the light-density membranes. We did not find any significant change in the distribution of adenylyl cyclase. In contrast to the decreased stimulation of adenylyl cyclase activity by agonists acting via G_sα, observed in the crude membrane fraction, the responses of adenylyl cyclase to forskolin as well as to GTP(S) were increased in the purified plasma membrane fractions. These results may indicate that sensitization of the catalyst appears to be the dominant component in the astroglial cell response to long-term treatment by forskolin.     

Interplay Between Side Chain Pattern,Polymer Aggregation,and Charge Carrier Dynamics in PBDTTPD:PCBM Bulk‐Heterojunction Solar Cells

Poly(benzo[1,2‐b:4,5‐b′]dithiophene–alt–thieno[3,4‐c]pyrrole‐4,6‐dione) (PBDTTPD) polymer donors with linear side‐chains yield bulk‐heterojunction (BHJ) solar cell power conversion efficiencies (PCEs) of about 4% with phenyl‐C₇₁‐butyric acid methyl ester (PC₇₁BM) as the acceptor, while a PBDTTPD polymer with a combination of branched and linear substituents yields a doubling of the PCE to 8%. Using transient optical spectroscopy it is shown that while the exciton dissociation and ultrafast charge generation steps are not strongly affected by the side chain modifications, the polymer with branched side chains exhibits a decreased rate of nongeminate recombination and a lower fraction of sub‐nanosecond geminate recombination. In turn the yield of long‐lived charge carriers increases, resulting in a 33% increase in short circuit current (J _sc). In parallel, the two polymers show distinct grazing incidence X‐ray scattering spectra indicative of the presence of stacks with different orientation patterns in optimized thin‐film BHJ devices. Independent of the packing pattern the spectroscopic data also reveals the existence of polymer aggregates in the pristine polymer films as well as in both blends which trap excitons and hinder their dissociation.