Dispersal traits and dispersal patterns in an oro-Mediterranean thorn cushion plant formation of the eastern High Atlas, Morocco

This study describes the dispersal traits and dispersal patterns of 51 perennial plant species belonging to 19 families in an oro-Mediterranean thorn cushion plant formation on the High Atlas, Morocco. Diaspore type, mass, number, antitelechoric mechanisms and dispersal time were studied with respect to growth forms, dispersal modes and spatial dispersal. Species spanned 10⁵ range of diaspore mass, which coincided with those found in other high mountain regions. Diaspore mass was significantly higher in trees and shrubs than in semi-shrubs and perennial herbs. Barochorous and zoochorous species are more likely to have heavy diaspores, whereas anemochorous and ballistic species have a medium diaspore mass and semachorous and ombro-hydrochorous species have low diaspore mass. Diaspore number was significantly higher in trees and shrubs than in semi-shrubs and perennial herbs. The barochorous, ombro-hydrochorous and zoochorous species tended to produce higher diaspore numbers than species with other dispersal modes. Bradyspory was well-developed by trees and large shrubs dispersed by biotic vectors. Synaptospermy was represented by its long dispersal component. Myxospermy was significantly associated with semi-shrubs and perennial herbs with restricted spatial dispersal. It seems that ombro-hydrochory combined with myxospermy and a high number of light seeds is an efficient mechanism that ensures successful establishment of the most typical and endemic thorn cushion plant species, such as Alyssum, Vella and Ormenis. In our study area, the highest dispersal availability was synchronized with the dry summer season (July–August) and the beginning of the rainy months (September). The dispersal peak for the wind-dispersed species, which is the most effective primary dispersal mode, occurs during the dry season, while dispersal for the biotic-dispersed species takes place throughout the year.     

Endogenous morphine in SH-SY5Y cells and the mouse cerebellum

Background

Morphine, the principal active agent in opium, is not restricted to plants, but is also present in different animal tissues and cell types, including the mammalian brain. In fact, its biosynthetic pathway has been elucidated in a human neural cell line. These data suggest a role for morphine in brain physiology (e.g., neurotransmission), but this hypothesis remains a matter of debate. Recently, using the adrenal neuroendocrine chromaffin cell model, we have shown the presence of morphine-6-glucuronide (M6G) in secretory granules and their secretion products, leading us to propose that these endogenous alkaloids might represent new neuroendocrine factors. Here, we investigate the potential function of endogenous alkaloids in the central nervous system.

Methodology and Principal Findings

Microscopy, molecular biology, electrophysiology, and proteomic tools were applied to human neuroblastoma SH-SY5Y cells (i) to characterize morphine and M6G, and (ii) to demonstrate the presence of the UDP-glucuronyltransferase 2B7 enzyme, which is responsible for the formation of M6G from morphine. We show that morphine is secreted in response to nicotine stimulation via a Ca²⁺-dependent mechanism involving specific storage and release mechanisms. We also show that morphine and M6G at concentrations as low as 10⁻¹⁰ M are able to evoke specific naloxone-reversible membrane currents, indicating possible autocrine/paracrine regulation in SH-SY5Y cells. Microscopy and proteomic approaches were employed to detect and quantify endogenous morphine in the mouse brain. Morphine is present in the hippocampus, cortex, olfactory bulb, and cerebellum at concentration ranging from 1.45 to 7.5 pmol/g. In the cerebellum, morphine immunoreactivity is localized to GABA basket cells and their termini, which form close contacts on Purkinje cell bodies.

Conclusions/Significance

The presence of morphine in the brain and its localization in particular areas lead us to conclude that it has a specific function in neuromodulation and/or neurotransmission. Furthermore, its presence in cerebellar basket cell termini suggests that morphine has signaling functions in Purkinje cells that remain to be discovered.     

Analysis of polymorphism of the interleukin-4 gene of healthy and HIV-infected persons

The distribution of the allel variants of the promoter area (C = 590T) of the interleukin-4 (IL-4) gene in HIV-infected and relatively healthy representatives of the Caucasoid population has been studied. The relationship between the genotypes of this polymorphism and the production of IL-4 by mononuclear cells of peripheral blood as well as distribution of IL-4 genotypes among males and females is analyzed. The occurrence of the homozygous combination of the allel variant C/C of the promoter of IL-4 has been shown to prevail almost twofold over the occurrence of the variant C/T among healthy donors and HIV-infected patients. Sexual differences play an essential role in the character of inheriting the allel variants of the genes of IL-4, the presence of the homozygous variant C/C or T/T being a risk factor of HIV infection in males. As revealed in this study, in the peripheral blood of healthy donors mononuclear cells having genotype C/C differ from cells with the heterozygous variant C/T in higher spontaneous production of IL-4 and, simultaneously, in lower capacity for the activation of its production in response to stimulation with mitogen. In HIV-infected patients mononuclear cells differ in higher spontaneous production of IL-4 in comparison with controls. We may thus infer that the human genotype controlling the initial level of the production of IL-4 by lymphocytes Th2 may influence the intensity of antibody production in the process of infection.     

Production of glycolipids containing biosurfactant by Pseudomonas species

Microorganisms, that degrade hydrocarbon were isolated and screened for their biosurfactant activity. A total of 68 strains were isolated and tested for their glycolipid activity of which 4 isolates showed good glycolipid activity. Isolate K10 gave the maximum biosurfactant production in medium A (containing kerosene as a sole carbon source) as compared to medium B (containing glucose as a sole carbon source). Characterization of isolate K10 showed that it belongs to Pseudomonas species.     

Modelling the Brain for Rotational Loading: Shear Effects and Other Complications

This study considers modelling the brain due to rotation of the skull where, at lower frequencies, the shear property of the material is important. Investigations reported here cover the effect of elastic and viscoelastic (lossy) cerebral material, the effect of the Falx protruding into the brain, the gap around the Falx and the brain filled with non viscous fluid in addition to different models of the Falx with bending or membrane stiffness. Analytical benchmark formulations are also described for the simple 2D plane strain in a cylinder produced by a half-sine rotation on the outer periphery which allows numerical (Finite Element) models to be validated. The results show the importance of the material properties, duration of loading and amplitude of loading as well as the influence of the partition. The results are shown for predicted maximum Principal strains in the models, as this may well be indicative of whether damage of the brain tissue occurs.     

Effect of Costus spiralis (Jacq.) Roscoe Leaves,Methanolic Extract and Guaijaverin on Blood Glucose and Lipid Levels in a Type II Diabetic Rat Model

This study aimed to isolate and identify flavonoids with hypoglycemic activity in Costus spiralis leaves. The methanolic extract (ME) was rich in flavonoids, while the powdered leaves (PL) contained considerable amounts of macro‐ and microelements. Oral acute treatment of streptozotocin (STZ)‐induced diabetic rats for 18 h with the C. spiralis PL, ME and isolated guaijaverin (GUA) lowered glycemia, improved oral glucose tolerance and inhibited liver lipid peroxidation. GUA and ME lowered plasma levels of low‐density and non‐high density lipoproteins; GUA also lowered total cholesterol levels. PL, ME and GUA did not significantly alter the plasma levels of triglycerides, high‐density lipoproteins, very low‐density lipoproteins, creatinine and aspartate transaminase, and the total protein levels in the kidney and liver tissues. Therefore, C. spiralis leaves are promising raw materials and rich sources of bioactive flavonoids for the development of novel antidiabetic drugs due to their hypoglycemic, antidyslipidemic and antioxidant actions.     

Biodistribution study of nanometric hybrid gadolinium oxide particles as a multimodal SPECT/MR/optical imaging and theragnostic agent

Nanometric hybrid gadolinium oxide particles (Gado-6Si-NP) for diagnostic and therapeutic applications (mean diameter 3-4 nm) were obtained by encapsulating Gd(2)O(3) cores within a polysiloxane shell, which carries organic fluorophore (Cy 5) and is derivatized by a hydrophilic carboxylic layer. As residency time in the living body and methods of waste elimination are crucial to defining a good nanoparticle candidate and moving forward with steps for validation, this study was aimed at evaluating the biodistribution of these multimodal Gado-6Si-NP in rodents. Gado-6Si-NP were imaged following intravenous injection in control Wistar rats and mice using MRI (7 T), optical fluorescent imaging, and SPECT. A clear correlation was observed among MRI, optical imaging, and SPECT regarding the renal elimination. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles circulated freely in the blood pool and were rapidly cleared by renal excretion without accumulation in liver and RES uptake. These results demonstrate that Gado-6Si-NP display optimal biodistribution properties, enabling them to be developed as multimodal agents for in vivo imaging and theragnostics, especially in oncological applications.     

Insights into the inhibitory mechanism of triazole-based small molecules on phosphatidylinositol-4,5-bisphosphate binding pleckstrin homology domain

BackgroundPhosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] is an important regulator of several cellular processes and a precursor for other second messengers which are involved in cell signaling pathways. Signaling proteins preferably interact with PI(4,5)P₂ through its pleckstrin homology (PH) domain. Efforts are underway to design small molecule-based antagonist, which can specifically inhibit the PI(4,5)P₂/PH-domain interaction to establish an alternate strategy for the development of drug(s) for phosphoinositide signaling pathways.MethodsSurface plasmon resonance, molecular docking, circular dichroism, competitive Förster resonance energy transfer, isothermal titration calorimetric analyses and liposome pull down assay were used.ResultsIn this study, we employed 1,2,3-triazol-4-yl methanol containing small molecule (CIPs) as antagonists for PI(4,5)P₂/PH-domain interaction and determined their inhibitory effect by using competitive-surface plasmon resonance analysis (IC₅₀ ranges from 53 to 159 nM for PI(4,5)P₂/PLCδ1-PH domain binding assay). We also used phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P₃], phosphatidylinositol 3,4-bisphosphate [PI(3,4)P₂], PI(4,5)P₂ specific PH-domains to determine binding selectivity of the compounds. Various physicochemical analyses showed that the compounds have weak affect on fluidity of the model membrane but, strongly interact with the phospholipase C δ1 (PLCδ1)-PH domains. The 1,2,3-triazol-4-yl methanol moiety and nitro group of the compounds are essential for their exothermic interaction with the PH-domains. Potent compound can efficiently displace PLCδ1-PH domain from plasma membrane to cytosol in A549 cells.ConclusionsOverall, our studies demonstrate that these compounds interact with the PIP-binding PH-domains and inhibit their membrane recruitment.General significanceThese results suggest specific but differential binding of these compounds to the PLCδ1-PH domain and emphasize the role of their structural differences in binding parameters. These triazole-based compounds could be directly used/further developed as potential inhibitor for PH domain-dependent enzyme activity.     

Changes in the vertical distribution of hyporheic and benthic fauna associated with low flow conditions in the headwaters of the Tafna river (northwest Algeria)

Limnology - This study investigated temporal changes in the vertical distribution of invertebrates during periods of low flows in the Tafna wadi, a semi-arid Mediterranean river characterised by a...     

Development of liver microtissues with functional biliary ductular network

Liver tissue engineering aims to create transplantable liver grafts that can serve as substitutes for donor's livers. One major challenge in creating a fully functional liver tissue has been to recreate the biliary drainage in an engineered liver construct through integration of bile canaliculi (BC) with the biliary ductular network that would enable the clearance of bile from the hepatocytes to the host duodenum. In this study, we show the formation of such a hepatic microtissue by coculturing rat primary hepatocytes with cholangiocytes and stromal cells. Our results indicate that within the spheroids, hepatocytes maintained viability and function for up to 7 days. Viable hepatocytes became polarized by forming BC with the presence of tight junctions. Morphologically, hepatocytes formed the core of the spheroids, while cholangiocytes resided at the periphery forming a monolayer microcysts and tubular structures extending outward. The spheroids were subsequently cultured in clusters to create a higher order ductular network resembling hepatic lobule. The cholangiocytes formed functional biliary ductular channels in between hepatic spheroids that were able to collect, transport, and secrete bile. Our results constitute the first step to recreate hepatic building blocks with biliary drainage for repopulating the whole liver scaffolds to be used as transplantable liver grafts.