Dopamine and α-synuclein dysfunction in Smad3 null mice

<p>Abstract</p> <p>Background</p> <p>Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra (SN). Transforming growth factor-β1 (TGF-β1) levels increase in patients with PD, although the effects of this increment remain unclear. We have examined the mesostriatal system in adult mice deficient in Smad3, a molecule involved in the intracellular TGF-β1 signalling cascade.</p> <p>Results</p> <p>Striatal monoamine oxidase (MAO)-mediated dopamine (DA) catabolism to 3,4-dihydroxyphenylacetic acid (DOPAC) is strongly increased, promoting oxidative stress that is reflected by an increase in glutathione levels. Fewer astrocytes are detected in the ventral midbrain (VM) and striatal matrix, suggesting decreased trophic support to dopaminergic neurons. The SN of these mice has dopaminergic neuronal degeneration in its rostral portion, and the pro-survival Erk1/2 signalling is diminished in nigra dopaminergic neurons, not associated with alterations to p-JNK or p-p38. Furthermore, inclusions of α-synuclein are evident in selected brain areas, both in the perikaryon (SN and paralemniscal nucleus) or neurites (motor and cingulate cortices, striatum and spinal cord). Interestingly, these α-synuclein deposits are detected with ubiquitin and P^S129-α-synuclein in a core/halo cellular distribution, which resemble those observed in human Lewy bodies (LB).</p> <p>Conclusions</p> <p>Smad3 deficiency promotes strong catabolism of DA in the striatum (ST), decrease trophic and astrocytic support to dopaminergic neurons and may induce α-synuclein aggregation, which may be related to early parkinsonism. These data underline a role for Smad3 in α-synuclein and DA homeostasis, and suggest that modulatory molecules of this signalling pathway should be evaluated as possible neuroprotective agents.</p

Seasonal Niche Partitioning of Surface Temperate Open Ocean Prokaryotic Communities

Surface microbial communities are exposed to seasonally changing environmental conditions, resulting in recurring patterns of community composition. However, knowledge on temporal dynamics of open ocean microbial communities remains scarce. Seasonal patterns and associations of taxa and oligotypes from surface and chlorophyll maximum layers in the western Mediterranean Sea were studied over a 2-year period. Summer stratification versus winter mixing governed not only the prokaryotic community composition and diversity but also the temporal dynamics and co-occurrence association networks of oligotypes. Flavobacteriales, Rhodobacterales, SAR11, SAR86, and Synechococcales oligotypes exhibited contrasting seasonal dynamics, and consequently, specific microbial assemblages and potential inter-oligotype connections characterized the different seasons. In addition, oligotypes composition and dynamics differed between surface and deep chlorophyll maximum (DCM) prokaryotic communities, indicating depth-related environmental gradients as a major factor affecting association networks between closely related taxa. Taken together, the seasonal and depth specialization of oligotypes suggest temporal dynamics of community composition and metabolism, influencing ecosystem function and global biogeochemical cycles. Moreover, our results indicate highly specific associations between microbes, pointing to keystone ecotypes and fine-tuning of the microbes realized niche.En prens

Dynamic prokaryotic communities in the dark western Mediterranean Sea

Dark ocean microbial dynamics are fundamental to understand ecosystem metabolism and ocean biogeochemical processes. Yet, the ecological response of deep ocean communities to environmental perturbations remains largely unknown. Temporal and spatial dynamics of the meso- and bathypelagic prokaryotic communities were assessed throughout a 2-year seasonal sampling across the western Mediterranean Sea. A common pattern of prokaryotic communities’ depth stratification was observed across the different regions and throughout the seasons. However, sporadic and drastic alterations of the community composition and diversity occurred either at specific water masses or throughout the aphotic zone and at a basin scale. Environmental changes resulted in a major increase in the abundance of rare or low abundant phylotypes and a profound change of the community composition. Our study evidences the temporal dynamism of dark ocean prokaryotic communities, exhibiting long periods of stability but also drastic changes, with implications in community metabolism and carbon fluxes. Taken together, the results highlight the importance of monitoring the temporal patterns of dark ocean prokaryotic communities.Versión del editor2,92

Dynamics of actively dividing prokaryotes in the western Mediterranean Sea

Microbial community metabolism and functionality play a key role modulating global biogeochemical processes. However, the metabolic activities and contribution of actively growing prokaryotes to ecosystem energy fluxes remain underexplored. Here we describe the temporal and spatial dynamics of active prokaryotes in the different water masses of the Mediterranean Sea using a combination of bromodeoxyuridine labelling and 16S rRNA gene Illumina sequencing. Bulk and actively dividing prokaryotic communities were drastically different and depth stratified. Alteromonadales were rare in bulk communities (contributing 0.1% on average) but dominated the actively dividing community throughout the overall water column (28% on average). Moreover, temporal variability of actively dividing Alteromonadales oligotypes was evinced. SAR86, Actinomarinales and Rhodobacterales contributed on average 3–3.4% each to the bulk and 11, 8.4 and 8.5% to the actively dividing communities in the epipelagic zone, respectively. SAR11 and Nitrosopumilales contributed less to the actively dividing than to the bulk communities during all the study period. Noticeably, the large contribution of these two taxa to the total prokaryotic communities (23% SAR11 and 26% Nitrosopumilales), especially in the meso- and bathypelagic zones, results in important contributions to actively dividing communities (11% SAR11 and 12% Nitrosopumilales). The intense temporal and spatial variability of actively dividing communities revealed in this study strengthen the view of a highly dynamic deep ocean. Our results suggest that some rare or low abundant phylotypes from surface layers down to the deep sea can disproportionally contribute to the activity of the prokaryotic communities, exhibiting a more dynamic response to environmental changes than other abundant phylotypes, emphasizing the role they might have in community metabolism and biogeochemical processes.This research has been supported by RADMED-TRES (2015–2019) and ATHAPOC (CTM2014-54374-R) projects, funded by the Spanish Institute of Oceanography and the Spanish Ministry of Economy and Competitiveness, respectively. CM was supported by pre-doctoral FPI fellowship from Conselleria d’Innovació, Recerca i Turisme of the regional Government of the Balearic Islands, co-financed by the European Social Fund as part of the FSE 2014-2020 operational program.Postprin

Phytoplankton Community Structure Is Driven by Stratification in the Oligotrophic Mediterranean Sea

The phytoplankton community composition, structure, and biomass were investigated under stratified and oligotrophic conditions during summer for three consecutive years in the Mediterranean Sea. Our results reveal that the phytoplankton community structure was strongly influenced by vertical stratification. The thermocline separated two different phytoplankton communities in the two layers of the euphotic zone, characterized by different nutrient and light availability. Picoplankton dominated in terms of abundance and biomass at all the stations sampled and throughout the photic zone. However, the structure of the picoplanktonic community changed with depth, with Synechococcus and heterotrophic prokaryotes dominating in surface waters down to the base of the thermocline, and Prochlorococcus and picoeukaryotes contributing relatively more to the community in the deep chlorophyll maximum (DCM). Light and nutrient availability also influenced the communities at the DCM layer. Prochlorococcus prevailed in deeper DCM waters characterized by lower light intensities and higher picophytoplankton abundance was related to lower nutrient concentrations at the DCM. Picoeukaryotes were the major phytoplankton contributors to carbon biomass at surface (up to 80%) and at DCM (more than 40%). Besides, contrarily to the other phytoplankton groups, picoeukaryotes cell size progressively decreased with depth. Our research shows that stratification is a major factor determining the phytoplankton community structure; and underlines the role that picoeukaryotes might play in the carbon flux through the marine food web, with implications for the community metabolism and carbon fate in the ecosystem.En prens

Synthesis and in vitro antiprotozoal activity of some 2- amino-4-phenyloxazole derivatives

Purpose: To prepare some 2-amino-4-(p-substituted phenyl)-oxazole derivatives and to evaluate their in vitro antiprotozoal activity against Giardia lamblia and Trichomonas vaginalis.Methods: The 2-amino-4-(p-substituted phenyl)-oxazoles (a-g) were synthesized by microwave (MW) irradiation of mixtures of p-substituted 2-bromoacetophenones and urea in dimethylformamide (DMF). All compounds were identified by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy and lowand high-resolution mass spectrometry (HRMS). NMR assignments were made based on heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) experiments. Each synthesized compound’s melting point was determined. Antiprotozoal activity against Giardia intestinalis and Trichomonas vaginalis was quantified using a rigorous and sensitive subculture method. The commercial drug, metronidazole, was used as positive control. The 50 % inhibitory concentration (IC50) of the antiprotozoal agents for each protozoa was determined.Results: Seven 2-amino-4-(p-substituted phenyl)-oxazoles (a-g) were synthesized. The most active compounds against G. lamblia was 2-amino-4-(p-benzoyloxyphenyl)-oxazole (3d) with an IC50 of 1.17 μM, while compound 3e (2-amino-4-(p-bromophenyl)-oxazole) showed the highest anti-trichomonal activity (IC50, 1.89 μM).Conclusion: The in vitro antigiardial activity of 2-amino-4-(p-benzoyloxyphenyl) oxazole was higher than that exhibited by metronidazole; however, it is necessary increase the number of synthetic derivatives in order to be able to determine their structure-activity relationship.Keywords: Antiprotozoal, 2-Amino-4-phenyl-oxazoles, Giardia lamblia, Trichomonas vaginali

Circulating Cell-Free DNA-Based Liquid Biopsy Markers for the Non-Invasive Prognosis and Monitoring of Metastatic Pancreatic Cancer

Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue. RAS mutation status in plasma was a strong independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Moreover, RAS MAF in cfDNA was also an independent risk factor for poor OS, and was strongly associated with primary tumours in the body/tail of the pancreas and liver metastases. Higher cfDNA levels and fragmentation were also associated with poorer OS and shorter PFS, body/tail tumors, and hepatic metastases, whereas cfDNA fragmentation positively correlated with RAS MAF. Remarkably, the combination of CA19-9 with MAF, cfDNA levels and fragmentation improved the prognostic stratification of patients. Furthermore, dynamics of RAS MAF better correlated with patients’ outcome than standard CA19-9 marker. In conclusion, our study supports the use of cfDNA-based liquid biopsy markers as clinical tools for the non-invasive prognosis and monitoring of metastatic PDAC patients

Emisiones no-controladas a la atmósfera de gases inorgánicos tóxicos (CO, H2S, HG0 Y NH3) por vertederos en la Isla de Tenerife

Ponencia presentada en: 1er Encuentro sobre Meteorología y Atmósfera de Canarias, celebrado en el Puerto de la Cruz, los días 12,13 y 14 de noviembre de 2003. El encuentro estuvo organizado por el Centro Meteorológico Territorial en Canarias Occidental, con la colaboración del Observatorio Atmosférico de Izaña y del Grupo de Física de la Atmósfera de la Facultad de Física (Universidad de La Laguna

Resultados preliminares de las emisiones COVs generada por el tráfico de vehículos por carretera en Santa Cruz de Tenerife

Ponencia presentada en: 1er Encuentro sobre Meteorología y Atmósfera de Canarias, celebrado en el Puerto de la Cruz, los días 12,13 y 14 de noviembre de 2003. El encuentro estuvo organizado por el Centro Meteorológico Territorial en Canarias Occidental, con la colaboración del Observatorio Atmosférico de Izaña y del Grupo de Física de la Atmósfera de la Facultad de Física (Universidad de La Laguna)Los hidrocarburos emitidos directamente por los vehículos influyen en la salud humana como consecuencia de su toxicidad (e.g. benceno), pero además estos compuestos son precursores de contaminantes atmosféricos secundarios formados por procesos fotoquímicos tales como el ozono. Investigaciones sobre las variaciones espaciales y temporales de compuestos orgánicos volátiles COVs en el interior del túnel de la Avda. Tres de Mayo, SIC de Tenerife, permiten estimar la emisión de COVs generada por el tráfico de vehículos por carretera en SIC de Tenerife. Los resultados preliminares reflejan que las emisiones de específicos COVs tales como el benceno, tolueno, etilbenceno y xilenos (BTEX) generadas por el trafico que entra y sale diariamente de SIC de Tenerife es del orden de decenas de kilogramos por kilómetro recorrido