Structure–Activity Relationship of novel phenylacetic CXCR1 inhibitors

We reported recently the Structure–Activity Relationship (SAR) of a class of CXCL8 allosteric modulators. They invariably share a 2-arylpropionic moiety so far considered a key structural determinant of the biological activity. We show the results of recent SAR studies on a novel series of phenylacetic derivatives supported by a combined approach of mutagenesis experiments and conformational analysis. The results suggest novel insights on the fine role of the propionic/acetic chain in the modulation of CXCL8 receptors.     

Population development of Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae) on different stored products

The lesser grain borer, Rhyzopertha dominica, is an important pest of various stored products around the world. In this study, the development, survival, reproduction, and life table parameters of R. dominica were investigated on six stored products (angelica, jujube, maize, rice, soybean, and wheat). The developmental time of the immature stage of R. dominica was shortest on wheat (40.20 days) and longest on angelica (67.04 days). The survival rate of the immature stage was highest on wheat (76.33%) and lowest on angelica (41.00%). The fecundity level of R. dominica was highest on wheat (246.05 eggs/female) and lowest on angelica (69.38 eggs/female). The net reproductive rate (R₀) and intrinsic rate of increase (r_m) of R. dominica differed significantly among the six stored products. The highest R₀ of R. dominica was on wheat (68.50), followed by rice (41.28), maize (32.32), soybean (27.17), jujube (23.16), and angelica (20.18); the r_m values showed a similar trend, with values of 0.059, 0.046, 0.042, 0.039, 0.036, and 0.033, respectively. Our results indicate that wheat was the most suitable stored product, whereas angelica was the least suitable, for the feeding, development, and population increase of R. dominica. These findings provide basic information about the occurrence trends and characteristics of R. dominica that will be useful for the control of this pest on different stored products. The physicochemical properties of angelica should be further explored for potential application in the control or integrated management of R. dominica.     

Modulation of the endocannabinoid system by focal brain ischemia in the rat is involved in neuroprotection afforded by 17beta-estradiol

Endogenous levels of the endocannabinoid anandamide, and the activities of the synthesizing and hydrolyzing enzymes, i.e. N-acylphosphatidylethanolamine-hydrolyzing phospholipase D and fatty acid amide hydrolase, respectively, were determined in the cortex and the striatum of rats subjected to transient middle cerebral artery occlusion. Anandamide content was markedly increased ( approximately 3-fold over controls; P < 0.01) in the ischemic striatum after 2 h of middle cerebral artery occlusion, but not in the cortex, and this elevation was paralleled by increased activity of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D ( approximately 1.7-fold; P < 0.01), and reduced activity ( approximately 0.6-fold; P < 0.01) and expression ( approximately 0.7-fold; P < 0.05) of fatty acid amide hydrolase. These effects of middle cerebral artery occlusion were further potentiated by 1 h of reperfusion, whereas anandamide binding to type 1 cannabinoid and type 1 vanilloid receptors was not affected significantly by the ischemic insult. Additionally, the cannabinoid type 1 receptor antagonist SR141716, but not the receptor agonist R-(+)-WIN55,212-2, significantly reduced (33%; P < 0.05) cerebral infarct volume detected 22 h after the beginning of reperfusion. A neuroprotective intraperitoneal dose of 17beta-estradiol (0.20 mg x kg(-1)) that reduced infarct size by 43% also minimized the effect of brain ischemia on the endocannabinoid system, in an estrogen receptor-dependent manner. In conclusion, we show that the endocannabinoid system is implicated in the pathophysiology of transient middle cerebral artery occlusion-induced brain damage, and that neuroprotection afforded by estrogen is coincident with a re-establishment of anandamide levels in the ischemic striatum through a mechanism that needs to be investigated further.     

Blood vessel remodeling in pig ovarian follicles during the periovulatory period: an immunohistochemistry and SEM-corrosion casting study

Background  

The present research aims to describe the process of vascular readjustment occurring in pig ovary during the periovulatory phase (from LH surge to ovulation) that drives the transformation of the follicle, a limited blood supplied structure, into the corpus luteum, a highly vascularised endocrine gland required to maintain high levels of progesterone in pregnancy. The swine model was chosen because it is characterized by a long periovulatory window (about 40–44 hrs-similar to human) that permits to recover follicles at a precise endocrinological timing.     

Expression of telomerase reverse transcriptase subunit (TERT) and telomere sizing in pig ovarian follicles.

Telomerase is crucial for chromosome stability because it maintains telomere length. Little is known about telomerase in ovarian follicles, where an intense cell division is crucial to sustain estrous cycle and to drive oocyte development. The present research was performed to detect, by immunohistochemistry, the distribution of telomerase catalytic subunit (TERT) during folliculogenesis and to study the effect of TERT expression on telomeres. To this aim, telomere length has been measured on fluorescence in situ hybridization (FISH)-processed sections either in follicular or in germ cells. In primary and preantral follicles, TERT was observed in granulosa and in germ cells, with a typical nuclear location. During antral differentiation, only somatic cells close to the antrum (antral layer) and cumulus cells maintained TERT expression. The relative oocytes located TERT in the ooplasm independent from the process of meiotic maturation. FISH results indicate that a correlation exists between TERT expression and telomere size. In fact, progressively bigger telomeres were observed from preantral to antral follicles where longer structures were recorded in cells of the cumulus oophorus and of the antral layer than those of the basal one. Stable and elongated telomeres were detected in fully grown oocytes that lost the functional TERT distribution within the nucleus.     

Rinvenimenti floristici in Piemonte

Abstract

New discoveries concerning the Piedmont Flora. – The Author's research on the Piedmont Flora – corried on from 1969 up to 1974 – led to the discovery of new stations of the following entities, that are to be considered of special interest for the Flora in Piedmont. Here they are: Cyperus strigosus L.; Scirpus atrovirens Willd.; Platanus orientalis L.; Ulmus levis Pall.; Rumex paluster Sm. (= Rumex maritimus L. var. limosus (Thuill.); Mollugo verticillata L.; Cardamine flexuosa Wth.; Diplotaxis erucoides DC.; Spiraea japonica L.; Physocarpus opulifolius (L.); Potentilla supina L.; Acer saccarinus L.; Impatiens glandulifera Royle; Euphorbia prostrata Ait.; Euphorbia humifusa W.; Sicyos angulatus L.; Cyclamen hederifolium Aiton; Erigeron karwinskyanus DC. var. mucronalus DC.; Artemisia annua L.; Siegesbekia orientalis L.; Bidens frondosa L.; Ambrosia trifida L.

On the ground of the present contribution it results that some species – considered as rare or at least not very numerous in Piedmont – are probably more frequent than it was known in the past.

The Author's assumption that some of them – seen along the streams – are more widely distributed should proverright.     

Membrane perturbation by the antimicrobial peptide PMAP-23: A fluorescence and molecular dynamics study

Several bioactive peptides exert their biological function by interacting with cellular membranes. Structural data on their location inside lipid bilayers are thus essential for a detailed understanding of their mechanism of action. We propose here a combined approach in which fluorescence spectroscopy and molecular dynamics (MD) simulations were applied to investigate the mechanism of membrane perturbation by the antimicrobial peptide PMAP-23. Fluorescence spectra, depth-dependent quenching experiments, and peptide-translocation assays were employed to determine the location of the peptide inside the membrane. MD simulations were performed starting from a random mixture of water, lipids and peptide, and following the spontaneous self-assembly of the bilayer. Both experimental and theoretical data indicated a peptide location just below the polar headgroups of the membrane, with an orientation essentially parallel to the bilayer plane. These findings, together with experimental results on peptide-induced leakage from large and giant vesicles, lipid flip-flop and peptide exchange between vesicles, support a mechanism of action consistent with the “carpet” model. Furthermore, the atomic detail provided by the simulations suggested the occurrence of an additional, more specific and novel mechanism of bilayer destabilization by PMAP-23, involving the unusual insertion of charged side chains into the hydrophobic core of the membrane.     

Indirect co-culture with tendons or tenocytes can program amniotic epithelial cells towards stepwise tenogenic differentiation

Background

Amniotic epithelial cells (AEC) have potential applications in cell-based therapy. Thus far their ability to differentiate into tenocytes has not been investigated although a cell source providing a large supply of tenocytes remains a priority target of regenerative medicine in order to respond to the poor self-repair capability of adult tendons. Starting from this premise, the present research has been designed firstly to verify whether the co-culture with adult primary tenocytes could be exploited in order to induce tenogenic differentiation in AEC, as previously demonstrated in mesenchymal stem cells. Since the co-culture systems inducing cell differentiation takes advantage of specific soluble paracrine factors released by tenocytes, the research has been then addressed to study whether the co-culture could be improved by making use of the different cell populations present within tendon explants or of the high regenerative properties of fetal derived cell/tissue.

Methodology/Principal Findings

Freshly isolated AEC, obtained from ovine fetuses at mid-gestation, were co-incubated with explanted tendons or primary tenocytes obtained from fetal or adult calcaneal tendons. The morphological and functional analysis indicated that AEC possessed tenogenic differentiation potential. However, only AEC exposed to fetal-derived cell/tissues developed in vitro tendon-like three dimensional structures with an expression profile of matrix (COL1 and THSB4) and mesenchymal/tendon related genes (TNM, OCN and SCXB) similar to that recorded in native ovine tendons. The tendon-like structures displayed high levels of organization as documented by the cell morphology, the newly deposited matrix enriched in COL1 and widespread expression of gap junction proteins (Connexin 32 and 43).

Conclusions/Significance

The co-culture system improves its efficiency in promoting AEC differentiation by exploiting the inductive tenogenic soluble factors released by fetal tendon cells or explants. The co-cultural system can be proposed as a low cost and easy technique to engineer tendon for biological study and cell therapy approach.