Soluble oligomers of amyloid-β peptide disrupt membrane trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor contributing to early synapse dysfunction

β-Amyloid (Aβ), a peptide generated from the amyloid precursor protein, is widely believed to underlie the pathophysiology of Alzheimer disease (AD). Emerging evidences suggest that soluble Aβ oligomers adversely affect synaptic function, leading to cognitive failure associated with AD. The Aβ-induced synaptic dysfunction has been attributed to the synaptic removal of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs). However, the molecular mechanisms underlying the loss of AMPAR induced by Aβ at synapses are largely unknown. In this study we have examined the effect of Aβ oligomers on phosphorylated GluA1 at serine 845, a residue that plays an essential role in the trafficking of AMPARs toward extrasynaptic sites and the subsequent delivery to synapses during synaptic plasticity events. We found that Aβ oligomers reduce basal levels of Ser-845 phosphorylation and surface expression of AMPARs affecting AMPAR subunit composition. Aβ-induced GluA1 dephosphorylation and reduced receptor surface levels are mediated by an increase in calcium influx into neurons through ionotropic glutamate receptors and activation of the calcium-dependent phosphatase calcineurin. Moreover, Aβ oligomers block the extrasynaptic delivery of AMPARs induced by chemical synaptic potentiation. In addition, reduced levels of total and phosphorylated GluA1 are associated with initial spatial memory deficits in a transgenic mouse model of AD. These findings indicate that Aβ oligomers could act as a synaptic depressor affecting the mechanisms involved in the targeting of AMPARs to the synapses during early stages of the disease.     

Extension of sperm motility leads to increased rates of fertilization and hatching in curimba,Prochilodus lineatus

The objective of this study was to evaluate the effects of six activating solutions on duration of sperm motility, fertilization rate (FR), and hatching rate (HR) of Prochilodus lineatus (Valenciennes, 1837). The activating solutions (SA) used were: SA₀ (199 mOsm kg^?1, pH 8.5), SA₁ (138 mOsm kg^?1, pH 7.5), SA₂ (256 mOsm kg^?1, pH 7.5), SA₃ (131 mOsm kg^?1, pH 10), NaCl (92 mOsm kg^?1, pH 7.5) and distilled water (32 mOsm kg^?1, pH 7.5). SA₁ induced the highest motility, FR and HR, compared with the other activating solutions. The lowest motility was obtained with SA₀, with no fertilization or hatching, whereas motility was zero with SA₂ and SA₃. It is possible to conclude that the solution SA₁ can be used for the activation of gametes during fertilization in induced reproduction of curimba to achieve higher fertilization and hatching rates. Thus, it was found that the osmolality and pH of activating solutions, probably with the participation of dissolved substances therein, are the main factors acting on semen motility after activation.     

Attitudes towards Electronic Cigarettes Regulation in Indoor Workplaces and Selected Public and Private Places: A Population-Based Cross-Sectional Study

Background

Currently, there is an intensive debate about the regulation of the use of electronic cigarettes (e-cigarettes) in indoor places. The aim of this study was to assess the attitudes toward e-cigarette use in indoor workplaces and selected public and private venues among the general population in Barcelona (Spain) in 2013–2014.

Methods

This is a cross-sectional study of a representative sample of the population of Barcelona (n = 736). The field work was conducted between May 2013 and February 2014. We computed the prevalence and the adjusted odds ratios (OR) derived from multivariable logistic regression models.

Results

The awareness of e-cigarettes was 82.3%. Forty five percent of respondents did not agree with the use of e-cigarettes in public places and 52.3% in workplaces. The proportion of disapproval of the use of e-cigarettes in indoor places was higher at 71.5% for schools and 65.8% for hospitals and health care centers; while the prevalence of disapproval of e-cigarette use in homes and cars was lower (18.0% and 32.5%, respectively). Respondents who disagreed on the use of e-cigarettes in indoor workplaces were more likely to be older (OR = 1.64 and 1.97 for groups 45–64 and ≧65 years old, respectively), those with a high educational level (OR = 1.60), and never and former smokers (OR = 2.34 and 2.16, respectively). Increased scores in the Fagerström test for cigarette dependence were also related to increased support for their use.

Conclusions

Based on this population based study, half of the general population of Barcelona does not support the use of e-cigarettes in indoor workplaces and public places, with the percentage reaching 65% for use in schools, hospitals and health care centers. Consequently, there is good societal support in Spain for the politicians and legislators to promote policies restricting e-cigarettes use in workplaces and public places, including hospitality venues.     

The lymphocyte receptor CD6 interacts with syntenin-1, a scaffolding protein containing PDZ domains

CD6 is a type I membrane glycoprotein expressed on thymocytes, mature T and B1a lymphocytes, and CNS cells. CD6 binds to activated leukocyte cell adhesion molecule (CD166), and is considered as a costimulatory molecule involved in lymphocyte activation and thymocyte development. Accordingly, CD6 partially associates with the TCR/CD3 complex and colocalizes with it at the center of the mature immunological synapse (IS) on T lymphocytes. However, the signaling pathway used by CD6 is still mostly unknown. The yeast two-hybrid system has allowed us the identification of syntenin-1 as an interacting protein with the cytoplasmic tail of CD6. Syntenin-1 is a PDZ (postsynaptic density protein-95, postsynaptic discs large, and zona occludens-1) domain-containing protein, which functions as an adaptor protein able to bind cytoskeletal proteins and signal transduction effectors. Mutational analyses showed that certain amino acids of the most C-terminal sequence of CD6 (-YDDISAA) and the two postsynaptic density protein-95, postsynaptic discs large, and zona occludens-1 domains of syntenin-1 are relevant to the interaction. Further confirmation of the CD6-syntenin-1 interaction was obtained from pull-down and co-immunoprecipitation assays in mammalian cells. Image analyses also showed that syntenin-1 accumulates at CD6 caps and at the IS. Therefore, we propose that syntenin-1 may function as a scaffolding protein coupling CD6 and most likely other lymphocyte receptors to cytoskeleton and/or signaling effectors during IS maturation.     

Incidencia de la hiponatremia y de sus causas en pacientes neurológicos

IntroductionHyponatremia is considered the most frequent electrolyte disorder found in hospitalized patients and seems to be a prognostic factor during hospitalization.MethodsA prospective observational study was carried out in consecutive neurological patients admitted to our hospital over a 3-month period. Blood and urinary ionogram and osmolality were determined at entry and 3–5 days after admission in all patients with hyponatremia.ResultsOf the 130 patients admitted, 19 (14.6%) had hyponatremia. The causes of hyponatremia were as follows: inappropriate fluid replacement in 4 patients (21%), antihypertensive drugs in 4 (21%), syndrome of inappropriate secretion of antidiuretic hormone in 4 (21%), cerebral salt wasting syndrome in 2 (10%), and edematous status caused by liver disease in one and digestive loss in one (5%) each. Mortality was one (5%) and 0 (0%) among patients with and without hyponatremia, respectively.ConclusionHyponatremia is common in hospitalized neurological patients and can be misdiagnosed as a worsening of the main illness.     

Increased tyrosine phosphorylation in ras transformed fibroblasts occurs prior to manifestation of the transformed phenotype

Murine fibroblasts transformed by ras oncogenes exhibited an increased amount of tyrosine phosphorylated proteins compared to normal cells. The pattern of phosphorylation was similar to that observed in cells chronically stimulated with EGF or PDGF, and is probably due to autocrine stimulation of receptor tyrosine kinases. NIH 3T3 cells transfected with H-ras under the control of a glucocorticoid inducible promoter were used to determine the temporal relationship among expression of p21H-ras oncoprotein, increase in tyrosine phosphorylation and appearance of the transformed morphology. Enhanced tyrosine phosphorylation was observed more than 24 hours before evidence of morphological changes. These results suggest that full transformation by ras oncogenes requires cooperation with tyrosine protein kinases.     

Wild food plants and minor crops in the Ripollès district (Catalonia,Iberian Peninsula): potentialities for developing a local production,consumption and exchange program

Background

Wild food plants (WFP) have always been consumed by humans, first as the main basis of their food and, since the origins of agriculture, as ingredients of normal diets or as an alternative during situations of scarcity. In contemporary industrialized societies their use is for the most part being abandoned, but they may still play an important role. With the purpose of advancing in the ethnobotanical knowledge of one region of the Catalan Pyrenees, the present study reports the findings of a research project conducted in the Ripollès district (Catalonia, Iberian Peninsula), concerning ethnobotanical knowledge and use of wild and semi-wild vascular plants as foods, along with minor crops.

Methods

From August 2004 to July 2014, we performed 104 interviews (93 of which yielded data on food plants) with 163 informants, using the method of semi-structured ethnobotanical interview. We identified the plants quoted and kept herbarium vouchers.

Results

We detected 967 use reports for 80 wild or naturalized taxa, which are or have been consumed in the Ripollès district, the most cited being Taraxacum dissectum, Cynara cardunculus and Origanum vulgare. Certain frequently reported species such as Molopospermum peloponnesiacum and Taraxacum dissectum have only been rarely cited previously or indicated as food plant in very restricted geographical areas. Most cited families included Asteraceae and Lamiaceae, followed by Rosaceae and Apiaceae. Preferred consumed plant parts included leaves, followed by aerial parts, along with fruits and infructescences, while most wild food plants are eaten raw or used as condiments. Demographic factors such as age and locality of informants seem to be more relevant to wild food plant knowledge than gender. Middle-aged people and inhabitants from the Higher Freser River Valley seem to have a greater knowledge of WFP, both in relation to the number of species elicited, as well as the diversity of uses and preparations. To a lesser degree, women seem to have a slightly higher WFP knowledge than men. The consumption of these resources is still fairly alive amongst the populace, yet changes affecting younger generations–in most cases abandonment–have been reported by various participants.

Conclusion

The information provided by this kind of research permits the detection of those traditional species that could constitute the basis for the future development and management of wild edible plant resources along with minor crops. It also helps to determine the factors affecting their use, as well as the distinct target groups that such programmes could be addressed to.

     

C127 cells resistant to transformation by tyrosine protein kinase oncogenes

C127 is a nontumorigenic mouse cell line widely used in in vitro transformation assays due to its normal morphological appearance and its very low levels of spontaneous transformation. We now report that C127 cells are resistant to transformation by tyrosine protein kinase oncogenes derived from growth factor receptors such as the retroviral v-fms and the human trk transforming genes. In contrast, these cells could be efficiently transformed by members of the ras oncogene family and by serine/threonine kinase oncogenes such as v-mos and v-raf. C127 cells were also found to be resistant to transformation by v-src, the prototype of a large family of tyrosine protein kinase oncogenes whose products are associated with the inner side of the plasma membrane. However, morphologically normal C127 cells expressing pp60v-src acquired a transformed phenotype upon continuous passage in vitro. Somatic cell hybrids (neoR, hygroR) obtained by fusion of G418-resistant C127 cells expressing p70trk (neoR) and hygromycin-resistant NIH3T3 cells (hygroR) exhibited transformed properties as determined by their ability to grow in semisolid agar. In contrast, no such growth was observed when these neoR p70trk-containing C127 cells were fused to control hygroR C127 cells. These results indicate that C127 cells may either lack or express insufficient levels of certain critical substrate(s) necessary for the onset of transformation by tyrosine protein kinase oncogenes.     

Characterization of Microbial Mats from a Siliciclastic Tidal Flat (Bahía Blanca Estuary,Argentina)

Biofilms and microbial mats cover the tidal flats of the central zone of the Bahía Blanca estuary (Argentina), creating extensive layers. The objective of this study was to characterize the microphytobenthic communities in these biofilms and mats from sediment cores taken in March, June, September and December 2010. Microorganisms were identified and enumerated by microscopy, and their biomass (chlorophyll a, biovolume) quantified at two different stations in the lower supratidal zone, located ～210 m apart from each other (namely S1 and S2). Additionally, the colloidal carbohydrates produced by these microbial communities were quantified, together with physical parameters such as temperature, granulometry, moisture and organic matter content of the sediment layers that comprise a typical epibenthic mat. On the other hand, changes in biomass and colloidal carbohydrate content were studied through a half-tidal cycle (7 h). There were significant seasonal differences in microphytobenthic biovolume (P < 0.001) with a considerably lower biomass in summer, but no significant differences in microalgal biovolume between stations (P = 0.454). Cyanobacterial biomass (largely composed of the filamentous Microcoleus chthonoplastes) was dominant on all dates at both stations, followed by pennate diatoms. Chlorophyll a and colloidal carbohydrate contents in sediment presented a similar pattern to that of microalgal biovolume; with a 5-fold variation in chlorophyll a for S1 between consecutive sampling events on September and December. There were significant differences between sampling dates in colloidal carbohydrates (P < 0.001) with the lowest values recorded during fall and winter; conversely there were no significant differences between stations (P = 0.324). Silt was the dominant sediment fraction at S1 while sand dominated throughout the uppermost 20 mm at S2. Chlorophyll a contents did not show significant differences throughout a half-tidal cycle, likely the product of vertical migration along the section sampled. Conversely, the content of colloidal carbohydrates varied 5-fold, showing a significant (P < 0.001) and steady increase with time of exposure to air and pointing to the rapid metabolic rates of the community. In conclusion, the microphytobenthic community of the Bahía Blanca estuary presented marked seasonality in its biological parameters and overall physiognomy, also showing elevated metabolic rates when subject to tidal fluctuations.