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

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

Antifungal potential and chemical composition of Tagetes lunulata Ort. essential oil for the control of Trichophyton rubrum Malmsten

The essential oils of aromatic and medicinal plants are an important resource used to control several health conditions; however, information about their composition and antimicrobial activity is scarce. This study used a gas chromatography-mass spectrometry (GC-MS) to analyze the composition of the essential oil (EO) of Tagetes lunulata Ort., a Mexican endemic plant, known as wild cempaxúchitl. The major components of the EO include: verbenone (47.17%), α-pinene (10.93%), 1,1,1-Trifluoro-2-hexanone (9.63%), β-caryophyllene (6.10%), germacrene-D (4.99%), L-verbenone (4.89%), and E-tagetone (4.44%). The disk agar diffusion method was used to evaluate the antimicrobial activity of T. lunulata against Trichophyton rubrum (athlete's foot). A significant antimicrobial activity was observed with a ≥60% EO concentration. The dilution method was used to determine the minimum inhibitory concentration (MIC): 200 μg ml-1. The T. lunulata EO recorded a strong antimicrobial activity against T. rubrum; therefore, it is a natural alternative for the control of natural antifungals

Red doméstica de producción de nopal (Nopalea sp.) para exportación

La tenencia de la tierra en Valles Centrales de Oaxaca, México, es minifundista. Muchas familias dependen de las áreas de traspatio para generar ingresos y completar el autoconsumo del hogar

The relevance of the formation of a pharmaceutical chemist biologist: an element of social renponsability of universities

Este estudio de tipo exploratorio, transversal y de campo es solo una fase del proyecto de seguimiento de egresados de la licenciatura en Química Farmacéutico Biológica (QFB) de la Facultad de Estudios Superiores “Zaragoza”. Este proyecto permite retroalimentar el plan curricular, además de establecer el lugar que han ocupado los egresados de esta institución en el mercado laboral, además de detectar las principales áreas de oportunidad en campos profesionales no explorados por los egresados. Así como la determinación de los conocimientos, habilidades, actitudes y valores obtenidos durante su formación y que le han sido indispensables en su desarrollo profesional.This study was exploratory, transversal and field is just one phase of the project following graduates of the FES Zaragoza. This project will provide feedback to the curriculum of the race Pharmaceutical Biological Chemistry (QFB), to establish where they have occupied the graduates of this institution in the labor market, in addition to identifying the main areas of opportunity in professional fields unexplored by the graduates. And the determination of the knowledge, skills, attitudes and values obtained during training and to have been indispensable in their professional development

Social brain, social dysfunction and social withdrawal

The human social brain is complex. Current knowledge fails to define the neurobiological processes underlying social behaviour involving the (patho-) physiological mechanisms that link system-level phenomena to the multiple hierarchies of brain function. Unfortunately, such a high complexity may also be associated with a high susceptibility to several pathogenic interventions. Consistently, social deficits sometimes represent the first signs of a number of neuropsychiatric disorders including schizophrenia (SCZ), Alzheimer's disease (AD) and major depressive disorder (MDD) which leads to a progressive social dysfunction. In the present review we summarize present knowledge linking neurobiological substrates sustaining social functioning, social dysfunction and social withdrawal in major psychiatric disorders. Interestingly, AD, SCZ, and MDD affect the social brain in similar ways. Thus, social dysfunction and its most evident clinical expression (i.e., social withdrawal) may represent an innovative transdiagnostic domain, with the potential of being an independent entity in terms of biological roots, with the perspective of targeted interventions

Are there any risk factors for developing complications with the use of retrievable vena cava filters in orthopaedic surgery?

Background: In high-risk patients, common prophylaxis may be insufficient to prevent thromboembolic events after orthopaedic procedures. In this scenario, a retrievable vena cava filter (VCF) could be considered as an alternative, although it's use remains controversial. Therefore, we asked: (1) what is the overall mechanical complication rate associated with the use of retrievable VCFs in orthopaedic surgery?, (2) what is the association with thromboembolic disease (TED) recurrence, post-thrombotic syndrome and/or major bleeding according to different surgical characteristics?, (3) What is the overall mortality rate attributed to VCF use?Methods: We retrospectively analyzed a cohort of 68 patients who underwent orthopaedic surgery with a previous diagnosis of TED, in whom a retrievable VCF was placed. Permanent filters were excluded. We studied the filter’s mechanical complications and considered as possible outcomes death and 3 hematologic complications: TED recurrence, post-thrombotic syndrome and major bleeding. To estimate association with risk factors, we subclassified surgeries into 5 groups: 1, arthroplasty/non-arthroplasty; 2, primary/revision; 3, elective/urgent; 4, oncologic/non-oncologic; 5, preoperative/postoperative filter.Results: Mechanical complications were 16% and required a filter revision. Sixty-four percent of the revised VCFs developed a mechanical failure and could not be retrieved. Overall prevalence of TED recurrence, post-thrombotic syndrome and hemorrhage was 33%, 15% and 4.5%, respectively. Spinal surgeries were a risk factor for developing TED recurrences.  Only 4% of patients died of a TED recurrence.Conclusions: Orthopaedic procedures had a high risk of mechanical and hematologic complications after using a retrievable VCF. However, mortality was low due to these complications.</p

Binding of Brucella protein, Bp26, to select extracellular matrix molecules

Background: Brucella is a facultative intracellular pathogen responsible for zoonotic disease brucellosis. Little is known about the molecular basis of Brucella adherence to host cells. In the present study, the possible role of Bp26 protein as an adhesin was explored. The ability of Brucella protein Bp26 to bind to extracellular matrix (ECM) proteins was determined by enzyme-linked immunosorbent assay (ELISA) and biolayer interferometry (BLI). Results: ELISA experiments showed that Bp26 bound in a dose-dependent manner to both immobilized type I collagen and vitronectin. Bp26 bound weakly to soluble fibronectin but did not bind to immobilized fibronectin. No binding to laminin was detected. Biolayer interferometry showed high binding affinity of Bp26 to immobilized type I collagen and no binding to fibronectin or laminin. Mapping of Bp26 antigenic epitopes by biotinylated overlapping peptides spanning the entire sequence of Bp26 using anti Bp26 mouse serum led to the identification of five linear epitopes. Collagen and vitronectin bound to peptides from several regions of Bp26, with many of the binding sites for the ligands overlapping. The strongest binding for anti-Bp26 mouse serum, collagen and vitronectin was to the peptides at the C-terminus of Bp26. Fibronectin did not bind to any of the peptides, although it bound to the whole Bp26 protein. Conclusions: Our results highlight the possible role of Bp26 protein in the adhesion process of Brucella to host cells through ECM components. This study revealed that Bp26 binds to both immobilized and soluble type I collagen and vitronectin. It also binds to soluble but not immobilized fibronectin. However, Bp26 does not bind to laminin. These are novel findings that offer insight into understanding the interplay between Brucella and host target cells, which may aid in future identification of a new target for diagnosis and/or vaccine development and prevention of brucellosis