Reduced NMDA receptor tyrosine phosphorylation in PTPalpha-deficient mouse synaptosomes is accompanied by inhibition of four src family kinases and Pyk2: an upstream role for PTPalpha in NMDA receptor regulation

Mice lacking protein tyrosine phosphatase alpha (PTPalpha) exhibited defects in NMDA receptor (NMDAR)-associated processes such as learning and memory, hippocampal neuron migration, and CA1 hippocampal long-term potentiation (LTP). In vivo molecular effectors linking PTPalpha and the NMDAR have not been reported. Thus the involvement of PTPalpha as an upstream regulator of NMDAR tyrosine phosphorylation was investigated in synaptosomes of wild-type and PTPalpha-null mice. Tyrosine phosphorylation of the NMDAR NR2A and NR2B subunits was reduced upon PTPalpha ablation, indicating a positive effect of this phosphatase on NMDAR phosphorylation via intermediate molecules. The NMDAR is a substrate of src family tyrosine kinases, and reduced activity of src, fyn, yes and lck, but not lyn, was apparent in the absence of PTPalpha. In addition, autophosphorylation of proline-rich tyrosine kinase 2 (Pyk2), a tyrosine kinase linked to NMDAR signaling, was also reduced in PTPalpha-deficient synaptosomes. Altered protein tyrosine phosphorylation was not accompanied by altered expression of the NMDAR or the above tyrosine kinases at any stage of PTPalpha-null mouse development examined. In a human embryonic kidney (HEK) 293 cell expression system, PTPalpha enhanced fyn-mediated NR2A and NR2B tyrosine phosphorylation by several-fold. Together, these findings provide evidence that aberrant NMDAR-associated functions in PTPalpha-null mice are due to impaired NMDAR tyrosine phosphorylation resulting from the reduced activity of probably more than one of the src family kinases src, fyn, yes and lck. Defective NMDAR activity in these mice may also be linked to the loss of PTPalpha as an upstream regulator of Pyk2.     

Worldwide invasion of vector mosquitoes: present European distribution and challenges for Spain

An Asiatic mosquito species, Aedes albopictus, began to spread worldwide in the 1970s thanks to marine transport of tires and other goods, leading to colonization of many areas of the world. This species is a vector of major human diseases such as Dengue, Yellow Fever and the West Nile virus. In Europe, it was established in Albania and Italy and has been detected in other countries such as France; no records exist for Spain as yet. Colonization by Aedes albopictus is a major public health concern considering that the West Nile virus and several other viruses are known to circulate sporadically in the Mediterranean. Additionally, the parent species Aedes aegypti was the vector causing severe outbreaks of Dengue and Yellow Fever two centuries ago. Although Ae. aegypti was also introduced, it was eradicated from Spain. Both mosquitoes shared habitat types, diseases transmitted and many bionomic data. This article contains a review of the present Ae. albopictusdistribution range worldwide and discusses the likelihood of an establishment in Spain in view of climatological and geographical data. This revised version was published online in July 2006 with corrections to the Cover Date.     

Regulation of the p19Arf/p53 pathway by histone acetylation underlies neural stem cell behavior in senescence‐prone SAMP8 mice

Brain aging is associated with increased neurodegeneration and reduced neurogenesis. B1/neural stem cells (B1‐NSCs) of the mouse subependymal zone (SEZ) support the ongoing production of olfactory bulb interneurons, but their neurogenic potential is progressively reduced as mice age. Although age‐related changes in B1‐NSCs may result from increased expression of tumor suppressor proteins, accumulation of DNA damage, metabolic alterations, and microenvironmental or systemic changes, the ultimate causes remain unclear. Senescence‐accelerated‐prone mice (SAMP8) relative to senescence‐accelerated‐resistant mice (SAMR1) exhibit signs of hastened senescence and can be used as a model for the study of aging. We have found that the B1‐NSC compartment is transiently expanded in young SAMP8 relative to SAMR1 mice, resulting in disturbed cytoarchitecture of the SEZ, B1‐NSC hyperproliferation, and higher yields of primary neurospheres. These unusual features are, however, accompanied by premature loss of B1‐NSCs. Moreover, SAMP8 neurospheres lack self‐renewal and enter p53‐dependent senescence after only two passages. Interestingly, in vitro senescence of SAMP8 cells could be prevented by inhibition of histone acetyltransferases and mimicked in SAMR1 cells by inhibition of histone deacetylases (HDAC). Our data indicate that expression of the tumor suppressor p19, but not of p16, is increased in SAMP8 neurospheres, as well as in SAMR1 neurospheres upon HDAC inhibition, and suggest that the SAMP8 phenotype may, at least in part, be due to changes in chromatin status. Interestingly, acute HDAC inhibition in vivo resulted in changes in the SEZ of SAMR1 mice that resembled those found in young SAMP8 mice.     

Changes in the level of endogenous cytokinins in apical buds ofChenopodium rubrum L.

CCC (2-chloroethyl)trimethylammonium chloride applied to plants ofChenopodium rubrum during floral induction led to an increase in the level of endogenous cytokinins in the apical buds. Application of gibberellic acid or indole-3-acetic acid at concentrations reversing the effect of CCC reduced the level of cytokinins. After simultaneous treatment with both CCC and one of the growth substances this reduction was less pronounced. From the comparison bf the present results, as well as of those published in previous papers it follows that in apical buds ofChenopodium rubrum there exists a mutual interaction between gibberellins and cytokinins. Under certain conditions both these groups of hormones may substitute for each other in flowering. IAA seems to affect flowering by regulating the level of both gibberellins and cytokinins.     

Early peritoneal immune response during Echinococcus granulosus establishment displays a biphasic behavior

Background

Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice.

Principal Findings

Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4⁺ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13).

Conclusions

Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies based on stimulation of effective responses and blockade of evasion mechanisms.     

Simulation of habituation to simple and multiple stimuli

Within the psychological literature there are a number of models that reproduce the defining properties of habituation to a single stimulus. However, most of them do not reproduce the phenomenon of dishabituation shown in empirical studies, consisting in the recovery of a stimulus previously habituated upon the appearance of a novel stimulus. The present work offers a model of habituation which, in addition to reproducing the basic properties of habituation to a stimulus, also does so when more than one stimulus is presented, and thus includes the dishabituation phenomenon. This model consists of two functions, one called "activation" and the other "availability", and is tested by means of simulation of the responses in the context of different stimulus patterns. The results of the simulation show a good qualitative fit to the empirical results on the phenomena of habituation, including dishabituation. In addition, the model is suitable for inclusion in associative models that reproduce classical conditioning, which will make it possible in the future to incorporate into these in a simple way the influence that the habituation of each stimulus may have on its association with other stimuli.     

Supercritical methodologies applied to the production of biopesticides: a review

Supercritical technologies are new, environmentally friendly, advanced separation techniques that have attracted the attention of both industry and academy in their aspirations of producing safer products with cleaner processes. In the field of biopesticides, supercritical fluids are being used in different stages, from the extraction of active ingredients from natural matrices to the encapsulation of blends during the formulation of the final commercial pesticide. This review summarizes different supercritical processes that arise in literature comprising supercritical fluid extraction, supercritical antisolvent fractionation or extraction, supercritical assisted atomization, particle from gas saturated solutions and supercritical solvent impregnation among others. The aim of this work is to give a general view of supercritical fluids in the field of biopesticides production, optimization and formulation, emphasizing in the extraction, fractionation and encapsulation and highlighting their importance when green, solvent free processes have to be designed.