Role of RGS14(414) in object recognition memory and regulation of synaptic plasticity in perirhinal cortex

Participation of perirhinal and frontal cortices in processing of object recognition memory has long been recognized, however, recently our laboratory extended this to area V2 of visual cortex. We observed that RGS14414-mediated activation of area V2 neurons leads to an enormous increase in object recognition memory. This memory enhancement was of such extent that it converted short term memory of 45 minutes into long lasting long-term memory that could be traced even after many months. Here, we have tested the memory enhancer effect of RGS14414 in perirhinal cortex, an area intimately involved in processing of object memory. A relationship of behavioral performance of RGS14414-treated rats with electrophysiological synaptic plasticity was investigated. Stimulation of perirhinal cortex with RGS14414 produced an equally robust increase in object recognition memory as was observed in area V2. Further, we found that RGS14414-mediated activation of perirhinal cortex, (i) blocked the depotentiation induced by 1Hz stimulation during 10min; (ii) blocked the LTP induced by 20Hz stimulation while showed no effect at 100Hz stimulation; and (iii) reduced the LTD induced by the application of 20µM carbachol, a cholinergic receptor agonist, during 10min, however no effect was observed at a higher concentration (50µM). Furthermore, we also observed that phosphorylated isoforms of AMPA receptor 1 and 2 (iGluR1 & iGluR2) were significantly reduced. Thus, our results indicate that iGluRs reflects the level of synaptic plasticity (LTP and LTD) observed in RGS-animals but lack this correlation with enhanced memory behavior. This work was supported by projects from MINECO, Junta de Andalucía y NIH.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Essential requirement for sphingosine kinase activity in eNOS-dependent NO release and vasorelaxation

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts both as an extracellular ligand for endothelial differentiation gene receptor family and as an intracellular second messenger. Cellular levels of S1P are low and tightly regulated by sphingosine kinase (SPK). Recent studies have suggested that eNOS pathway may function as a downstream target for the biological effects of receptor-mediated S1P. Here we have studied the possible interplay between intracellular SIP generation and the eNOS activation pathway. S1P causes an endothelium-dependent vasorelaxation in rat aorta that is PTX sensitive, inhibited by L-NAME that involves eNOS phosphorylation, and mainly dependent on hsp90. When rat aorta rings were incubated with the SPK inhibitor DL-threo-dihydrosphingosine (DTD), there was a concentration-dependent reduction of Ach-induced vasorelaxation, implying a consistent contribution of sphingolipid pathway through intracellular sphingosine release and phosphorylation. Co-immunoprecipitation experiments consistently showed increased association of hsp90 with eNOS after exposure of cells to S1P as well to BK or calcium ionophore A-23187. Interestingly, as opposite to A-23187, BK and S1P effect were significantly inhibited by pretreatment with the SPK inhibitor DTD. In conclusion, our data demonstrate that an interplay exists among eNOS, hsp90, and intracellularly generated S1P where eNOS coupling to hsp90 is a major determinant for NO release as confirmed by our functional and molecular studies

Fluorescent Transgenic Zebrafish Tg(nkx2.2a:mEGFP) Provides a Highly Sensitive Monitoring Tool for Neurotoxins

10.1371/journal.pone.0055474PLoS ONE82

Neutral high-generation phosphorus dendrimers inhibit macrophage-mediated inflammatory response in vitro and in vivo

Inflammation is part of the physiological response of the organism to infectious diseases caused by organisms such as bacteria, viruses, fungi, or parasites. Innate immunity, mediated by mono nuclear phagocytes, including monocytes and macrophages, is a first line of defense against infectious diseases and plays a key role triggering the delayed adaptive response that ensures an efficient defense against pathogens. Monocytes and macrophages stimu lation by pathogen antigens results in activation of different signaling pathways leading to the release of proinflammatory cyto kines. However, inflammation can also participate in the pathogenesis of several diseases, the autoimmune diseases that represent a relevant burden for human health. Dendrimers are branched, multivalent nanoparticles with a well-defined structure that have a high potential for biomedical applications. To explore new approaches to fight against the negative aspects of inflammation, we have used neutral high-generation phosphorus dendrimers bearing 48 (G3) or 96 (G4) bisphosphonate groups on their surface. These dendrimers show no toxicity and have good solubility and chemical stability in aqueous solutions. Here, we present data indicating that neutral phosphorus dendrimers show impressive antiinflammatory activities both in vitro and in vivo. In vitro, these dendrimers reduced the secretion of proinflammatory cytokines from mice and human monocyte derived macrophages. In addition, these molecules present efficient antiinflammatory activity in vivo in a mouse model of subchronic inflammation. Taken together, these data suggest that neutral G3- G4 phosphorus dendrimers have strong potential applications in the therapy of inflammation and, likely, of autoimmune diseases.info:eu-repo/semantics/publishedVersio

Seasonal anestrus of sheep flocks

Objective: To determine seasonal anestrus in relation to the season of the year, feeding type, breed, and social environment variables of sheep production systems in Singuilucan, Hidalgo, Mexico. Design/Methodology/Approach: Based on n41 semi-structured surveys applied to the producers of the study area, a logistic regression analysis was carried out to determine the influence of the study variables on the seasonal anestrus of sheep production systems. Results: Thirty-nine production units with seasonal anestrus periods were identified. Seasonal anestrus was influenced by the season of the year, feeding type, breed, and social environment variables (P0.05). The anestrus periods were influenced (P0.05) by spring (season of the year), range and shed system with concentrate feeding (feeding type), wool sheep (breeds), and the presence or absence of rams in the flock (social environment). Study Limitations/Implications: Determining which variables influence seasonal anestrus will help to develop sheep reproductive programs. Findings/Conclusions: Wool sheep have a seasonal anestrus in spring. The season of the year, feeding type, breed, and social environment variables influenced the seasonal anestrus of sheep production systems in Singuilucan, Hidalgo, Mexico

Morphological, biochemical and nutritional variations in a Mexican purslane (Portulaca oleracea L.) variety exposed to salt stress during the vegetative stage

Salt stress limits productivity of crop plants, and differential responses may be observed among genotypes. Herein we analyzed the effects of saline stress induced by the application of different concentrations of sodium chloride (0.00, 0.25, 0.50, 0.75, and 1.00 M NaCl) in a local Mexican variety of purslane (Portulaca oleracea L.) named ‘Atlapulco’ in vegetative stage. The NaCl concentrations were applied in the Hoagland nutrient solution used in irrigation for 14 days under greenhouse conditions, using perlite as a substrate. Analysis of variance and comparison of means were carried out with the data obtained. NaCl concentrations from 0.50 M reduced canopy coverage 36.8% and stem diameter by almost 21%, while all NaCl doses reduced the leaf area by 28.2%, on average, as compared to the control. Dry stem biomass and chlorophyll b were reduced by the saline gradient. Secondary stems and root length increased with 1.00 M by 23 and 29%, respectively. Proline concentration both in leaves and stems increased by 223.9 and 138%, respectively, when applying 1.00 M NaCl, compared to the control. Applying 0.75 and 1.00 M NaCl reduced N concentrations by 47 and 28.8% in leaf tissues, respectively, compared to the control. The concentrations of P and K in leaves, and K in roots also decreased with the saline treatments, while those of Ca and Mg were not affected in any of the analyzed tissues. The highest concentrations of Na in leaves were observed in doses 0.50 and 0.75 M NaCl, surpassing the control by 67.5 and 73.1%, respectively. The findings reported herein are very useful to propose programs for the recovery of saline soils in the region and design environmental policies aimed at mitigating the effects of climate change on food production

Heterogeneity of LSU rDNA sequences and morphology of Gymnodinium catenatum dinoflagellate strains in Bahía Concepción, Gulf of California, Mexico

We report the large subunit (LSU) rDNA sequences and morphology of several Gymnodinium catenatum dinoflagellate strains isolated from Bahía Concepción, Mexico. PCR amplifications of the D1–D2 fragment of the nuclear LSU rDNA gene resulted in a single product of 889 bp. A phylogenetic tree was constructed from the partial LSU rDNA (350 bp) sequences from six strains of G. catenatum isolated from the bay and 12 isolates from around the world. Strains from the bay grouped within the G. catenatum clade; however, a constant characteristic of G. catenatum strains from the bay is that, at position ≈453, a single nucleotide polymorphism was observed, presenting cytosine instead of guanine. This single base polymorphism could indicate a mutation or genetic isolation from other G. catenum populations. It is suggested that the Western Pacific could be the ancestral population of this species. Significant differences were found between cell length (CL), cell width (CW) and CW/CL ratios in laboratory cultures in the late exponential growth phase. Average CL varied between 41 and 53.69 µm, with a range between 26.94 and 69.99 µm; average CW varied between 33.75 and 40.68 µm, with a range between 25.04 and 54.73 µm; the average CW/CL varied between 0.76 and 0.97 µm, with a range between 0.49 and 1.27 µm. Cingulum thickness was between 3 and 4.11 µm, with a range between 1.97 and 6.74 µm. Cell size varied with the length of the chain and position in the chain.Instituto Politécnico Nacional (IPN). Centro Interdisciplinario de Ciencias MarinasCiencias marinasPD

UV-Casting on methacrylated PCL for the production of a peripheral nerve implant containing an array of porous aligned microchannels

Peripheral nerves are basic communication structures guiding motor and sensory information from the central nervous system to receptor units. Severed peripheral nerve injuries represent a large clinical problem with relevant challenges to successful synthetic nerve repair scaffolds as substitutes to autologous nerve grafting. Numerous studies reported the use of hollow tubes made of synthetic polymers sutured between severed nerve stumps to promote nerve regeneration while providing protection for external factors, such as scar tissue formation and inflammation. Few approaches have described the potential use of a lumen structure comprised of microchannels or microfibers to provide axon growth avoiding misdirection and fostering proper healing. Here, we report the use of a 3D porous microchannel-based structure made of a photocurable methacrylated polycaprolactone, whose mechanical properties are comparable to native nerves. The neuro-regenerative properties of the polymer were assessed in vitro, prior to the implantation of the 3D porous structure, in a 6-mm rat sciatic nerve gap injury. The manufactured implants were biocompatible and able to be resorbed by the host’s body at a suitable rate, allowing the complete healing of the nerve. The innovative design of the highly porous structure with the axon guiding microchannels, along with the observation of myelinated axons and Schwann cells in the in vivo tests, led to a significant progress towards the standardized use of synthetic 3D multichannel-based structures in peripheral nerve surgery

Multilocus phylogeny and historical biogeography of <i>Hypostomus</i> shed light on the processes of fish diversification in La Plata Basin

Distribution history of the widespread Neotropical genus Hypostomus was studied to shed light on the processes that shaped species diversity. We inferred a calibrated phylogeny, ancestral habitat preference, ancestral areas distribution, and the history of dispersal and vicariance events of this genus. The phylogenetic and distribution analyses indicate that Hypostomus species inhabiting La Plata Basin do not form a monophyletic clade, suggesting that several unrelated ancestral species colonized this basin in the Miocene. Dispersal to other rivers of La Plata Basin started about 8 Mya, followed by habitat shifts and an increased rate of cladogenesis. Amazonian Hypostomus species colonized La Plata Basin several times in the Middle Miocene, probably via the Upper Parana and the Paraguay rivers that acted as dispersal corridors. During the Miocene, La Plata Basin experienced marine incursions, and geomorphological and climatic changes that reconfigured its drainage pattern, driving dispersal and diversification of Hypostomus . The Miocene marine incursion was a strong barrier and its retraction triggered Hypostomus dispersal, increased speciation rate and ecological diversification. The timing of hydrogeological changes in La Plata Basin coincides well with Hypostomus cladogenetic events, indicating that the history of this basin has acted on the diversification of its biota.Facultad de Ciencias Naturales y MuseoLaboratorio de Sistemática y Biología Evolutiv