Quinolinic Acid Amyloid-like Fibrillar Assemblies Seed α-Synuclein Aggregation

Quinolinic acid (QA), a downstream neurometabolite in the kynurenine pathway, the biosynthetic pathway of tryptophan, is associated with neurodegenerative diseases pathology. Mutations in genes encoding kynurenine pathway enzymes, which control the level of QA production, are linked with elevated risk of developing Parkinson's disease. Recent findings have revealed the accumulation and deposition of QA in post-mortem samples, as well as in cellular models of Alzheimer's disease and related disorders. Furthermore, intrastriatal inoculation of mice with QA results in increased levels of phosphorylated α-synuclein and neurodegenerative pathological and behavioral characteristics. However, the cellular and molecular mechanisms underlying the involvement of QA accumulation in protein aggregation and neurodegeneration remain elusive. We recently established that self-assembled ordered structures are formed by various metabolites and hypothesized that these “metabolite amyloids” may seed amyloidogenic proteins. Here we demonstrate the formation of QA amyloid-like fibrillar assemblies and seeding of α-synuclein aggregation by these nanostructures both in vitro and in cell culture. Notably, α-synuclein aggregation kinetics was accelerated by an order of magnitude. Additional amyloid-like properties of QA assemblies were demonstrated using thioflavin T assay, powder X-ray diffraction and cell apoptosis analysis. Moreover, fluorescently labeled QA assemblies were internalized by neuronal cells and co-localized with α-synuclein aggregates. In addition, we observed cell-to-cell propagation of fluorescently labeled QA assemblies in a co-culture of treated and untreated cells. Our findings suggest that excess QA levels, due to mutations in the kynurenine pathway, for example, may lead to the formation of metabolite assemblies that seed α-synuclein aggregation, resulting in neuronal toxicity and induction of Parkinson's disease.     

Review of the genus Laelaspisella Marais & Loots,with the description of a new species from Iran (Acari,Laelapidae)

A new species of mite is described from Iran, Laelaspisella elsae sp. n. (Acari: Laelapidae). The new species was collected from bark of elm trees in Isfahan province. A revised diagnosis for Laelaspisella, as well as a key to the world species of the genus, are presented. Two species groups of Laelaspisella are proposed: those with seta pd3 on genu I and those without pd3 on genu I. Pseudoparasitus (Gymnolaelaps) tonsilis Karg, 1989a is transferred to Laelaspisella, based on its hypertrichous holodorsal shield, metasternal setae st4 absent and genu IV with ten setae. The problems with Laelaspisella canestrinii are explained and Laelaspisella canestrinii sensu Berlese (1903), (1904) and Costa (1962) is provided with a new name, Laelaspisella berlesei Joharchi, nom. n.     

Development of Molecularly Imprinted Olanzapine Nano-particles: <Emphasis Type="Italic">In Vitro</Emphasis> Characterization and <Emphasis Type="Italic">In Vivo</Emphasis> Evaluation

Molecularly imprinted nano-particles (MINPs) selective for olanzapine were prepared using methacrylic acid (MA) as monomer, ethylene glycol dimethacrylate (EGDMA) as a cross-linker, and 2,2-azobis (2-isobutyronitrile) (AIBN) as the initiator in 36 different ratios. The reaction runs with considerable fine powder formation were selected for further binding and selectivity studies. The MINP with the best selectivity (MINP-32) was chosen for further structural characterization by Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), adsorption-desorption isotherm for specific surface area, volume and average pore diameter determination. All characterization methods confirmed the successful formation of MINP. The optimum conditions for maximum template loading on the MINP-32 were found by experimental design using response surface methodology (RSM) and choosing absorbent amount, pH, and time as the main factors. MINPs with maximum template loading also indicated significant selectivity between template and its analog (clozapine). The release profile demonstrated a maximum release of about 95% after 288 h for MINP-32 in comparison with about 94% after 120 h for non-MINP-32. The same slow release of drug from MINP-32 was also observed during animal study of the plasma level of template, 20–28 μg/ml versus 5–10 μg/ml. The MINP-32 of this study represents a desirable ability to keep the memory of the template with significant selectivity and good capability to control the release of template in vitro and in vivo and hence could be a promising drug delivery system.     

Field evaluation of two biorational compounds in the control of pear psylla,Cacopsylla pyricola (Förster), on pear trees

Cacopsylla pyricola (Förster) (Hemiptera: Psyllidae) is an important pest of commercial pear in all pear-growing regions of Iran. In the scope of an integrated pest management, a research was carried out on the impact of treatment with biorational compounds in comparison with conventional chemical insecticides for controlling the pear psyllid. The experiments were done with five treatments consisted of diflubenzuron and lufenuron as biorational insecticides and thiacloprid and diazinon as conventional chemical insecticides and untreated check. The trials were set up in a randomised complete block design. The treatments were replicated four times. Samplings were carried out one day before spraying and 3, 7, 15, 30 and 45 days after spraying through clipping 15 leaves in each replicate and counting the number of pear psyllid live nymphs. Mortality percentage was calculated using Henderson–Tilton formula. The data were subjected to analysis of variance (ANOVA) and the means comparison was performed using Duncan’s multiple range test. The results indicated that the highest mortality in diflubenzuron and lufenuron treatments occurred after 15 days, with 82.09% and 71.01% mortality, respectively. In comparison with conventional chemical insecticides, the efficacy of biorational compounds was higher or not significantly different. The results of the trials are discussed in terms of improving management of the populations of pear psylla.     

Vasoactive intestinal peptide receptor activity in human fetal enterocytes

Functional and specific receptors for vasoactive intestinal peptide (VIP) (determined by their capacity to bind ¹²⁵I-VIP and activate adenylate cyclase) and cyclic AMP-dependent phosphodiesterase activities were characterized in enterocytes of human fetal small intestine between 18 and 23 weeks of gestation. Half-maximal stimulation of the cyclase and inhibition of ¹²⁵I-VIP binding in membrane preparations were respectively observed at 1.4 and 5 × 10⁻¹⁰ M VIP. The peptides structurally related to VIP activated the cyclic AMP generating system at pharmacological doses (10⁻⁷M and above) in the following order of potency: VIP> PHI> GRF> secretin. Other peptides or test substances, including GIP, pancreatic glucagon, somatostatin-14, gastrin, CCK, neurotensin, pancreatic polypeptide, PYY, substance P, histamine and isoproterenol are inactive in this system, while the ubiquitous adenylate cyclase activators NaF, forskolin and prostaglandins were effective. These results, combined with the appearance of intestinal VIP in nerve fibers at 8 weeks and with the morphological and enzymatic maturation at 9–12 weeks of the intestinal mucosa, indicate that this neuropeptide may regulate either the differentiation or function of enterocytes during the early development of human intestinal mucosa.