Numerical simulation for a neurotransmitter transport model in the axon terminal of a presynaptic neuron

Neurotransmitters in the terminal bouton of a presynaptic neuron are stored in vesicles, which diffuse in the cytoplasm and, after a stimulation signal is received, fuse with the membrane and release its contents into the synaptic cleft. It is commonly assumed that vesicles belong to three pools whose content is gradually exploited during the stimulation. This article presents a model that relies on the assumption that the release ability is associated with the vesicle location in the bouton. As a modeling tool, partial differential equations are chosen as they allow one to express the continuous dependence of the unknown vesicle concentration on both the time and space variables. The model represents the synthesis, concentration-gradient-driven diffusion, and accumulation of vesicles as well as the release of neuroactive substances into the cleft. An initial and boundary value problem is numerically solved using the finite element method (FEM) and the simulation results are presented and discussed. Simulations were run for various assumptions concerning the parameters that govern the synthesis and diffusion processes. The obtained results are shown to be consistent with those obtained for a compartment model based on ordinary differential equations. Such studies can be helpful in gaining a deeper understanding of synaptic processes including physiological pathologies. Furthermore, such mathematical models can be useful for estimating the biological parameters that are included in a model and are hard or impossible to measure directly.     

Increased Reactive Oxygen Species Production in the Brain After Repeated Low-Dose Pesticide Paraquat Exposure in Rats. A Comparison with Peripheral Tissues

The pesticide paraquat (PQ) was found to be a suitable xenobiotic to model Parkinson’s disease. The reactive oxygen species (ROS) production was suggested to be the main cause of PQ toxicity but very few evidences were found for its generation in the brain in vivo after ip administration. We compared the effects of PQ-induced ROS generation between the brain structures and the peripheral tissues using two different hydroxyl radical generation markers. Repeated but not single ip PQ administration increased the levels of ROS in the striatal homogenates but, when measured in the extracellular microdialysis filtrate, no change was observed. The increased dopamine release was detected in the striatum after the fourth PQ administration and its basal levels were decreased. A single treatment with the pesticide did not influence ROS production in the lungs or kidneys but repeated intoxication decreased its levels. These results suggest that repeated, systemic administration of a low dose of PQ triggers intracellular ROS formation in the brain and can cause slowly progressing degenerative processes, without the toxic effects in the peripheral tissues.     

Can inhibition of angiogenesis and stimulation of immune response be combined into a more effective antitumor therapy?

Cancer initiation and progression is strongly influenced by the tumor microenvironment consisting of various types of host cells (inflammatory cells, vascular cells and fibroblasts), extracellular matrix and non-matrix molecules. Host cells play a defining role in two major processes crucial for tumor growth: angiogenesis and escape from immune surveillance. The interdependence of these processes resemble the principles of Yin and Yang, as the stimulation of tumor angiogenesis inhibits effective immune responses, while angiogenesis inhibition may have the opposite effect. These considerations may be useful in developing anticancer strategies based on the potentially synergistic combinations of antiangiogenic and immunostimulatory drugs.     

Distribution, diversity and biomass of summer zooplankton from the coastal Canadian Beaufort Sea

Composition, abundance, biomass and distribution of zooplankton in the coastal Canadian Beaufort Sea were studied in the summer of 2005 and 2006. Data were collected from two cross-shelf transects (11 stations in each). Sampling was conducted with vertical hauls using a conical net of 153-μm mesh size. Our results revealed that there are three ecological zones, Intense Plume, Diffuse Plume and oceanic, which are primarily shaped by the highly variable Mackenzie River plume. The Intense Plume Grouping was located at stations influenced greatly by the Mackenzie River, where Podon leuckarti, Pseudocalanus spp., Copepoda nauplii and Limnocalanus macrurus were most abundant. The Diffuse Plume Grouping, that was located in the transitional zone between the river plume and the ocean, had the highest diversity. This grouping was characterised by high abundance of Copepoda nauplii, Polychaeta larvae, Pseudocalanus and L. macrurus. The Oceanic Grouping, located farthest from shore beyond the 85-m depth contour, was mainly inhabited by marine taxa—Calanus glacialis, C. hyperboreus, Triconia (Oncea) borealis and Microcalanus spp.—and had the greatest overall zooplankton abundance and biomass of all groupings.     

Response of melon fly (Diptera: Tephritidae) to weathered SPLAT-Spinosad-Cue-Lure

Studies were conducted in Hawaii to measure attraction of male melon fly, Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae), to SPLAT-Cue-Lure (C-L) and SPLAT-Melo-Lure (M-L) (raspberry ketone formate). Direct field comparisons of SPLAT-C-L and SPLAT-M-L at low (5%) and high (20%) concentrations indicated few differences in attraction over a 15-wk period. Subsequently, only SPLAT-Spinosad-C-L (5%) was compared with Min-U-Gel C-L with naled (standard used in California) in weathering studies. Treatments were weathered for 1, 2, 4, and 8 wk in Riverside, CA, and shipped to Hawaii for attraction/toxicity tests under field and semifield conditions by using released males of controlled ages, and for feeding tests in the laboratory. In terms of attraction, SPLAT-Spinosad-C-L compared favorably to, or outperformed the current standard of Min-U-Gel-C-L with naled. In terms of toxicity, the cumulative 24-h mortality did not differ between the two insecticide-containing C-L treatments in field cage studies after 8 wk. However, in feeding studies in which individual males were exposed for 5 min to the different C-L treatments after 4 wk of weathering, SPLAT-Spinosad-C-L demonstrated reduced mortality compared with the Min-U-Gel-C-L with naled, suggesting reduced persistence of the spinosad material. Spinosad has low contact toxicity and when mixed with SPLAT and C-L offers a reduced risk alternative for control of B. cucurbitae and related C-L-responding species, without many of the negative effects to humans and nontargets of broad-spectrum contact poisons such as naled.     

GPRC6A mediates the non-genomic effects of steroids

The identity of the putative G-protein coupled receptor (GPCR) that mediates the non-genomic effects of androgens is unknown. We present in vitro and in vivo evidence that the orphan GPRC6A receptor, a widely expressed calcium and amino acid sensing GPCR, transduces the non-genomic effects of testosterone and other steroids. Overexpression of GPRC6A imparts the ability of extracellular testosterone to illicit a rapid, non-genomic signaling response in HEK-293 cells lacking the androgen receptor. Conversely, testosterone-stimulated rapid signaling and phosphorylation of ERK is attenuated in bone marrow stromal cells derived from GPRC6A(-/-) mice and in 22Rv1 prostate cancer cells after siRNA-mediated knockdown of GPRC6A. Compared with wild-type controls, GPRC6A(-/-) null mice exhibit significantly less ERK activation and Egr-1 expression in both bone marrow and testis in response to pharmacological doses of testosterone in vivo. In addition, testosterone administration results in suppression of luteinizing hormone in wild-type male mice, but paradoxically stimulates serum luteinizing hormone levels in GPRC6A(-/-) null mice. These results suggest that GPRC6A is functionally important in regulating non-genomic effects of androgens in multiple tissues.