Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking

Parkinson''s disease (PD) is a neurodegenerative disorder that affects adult people whose treatment is palliative. Thus, we decided to test three dammarane triterpenes 1, 1a, 1b, and we determined that 1 and 1a inhibit β-aggregation through thioflavine T rather than 1b. Since compound 1 was most active, we determined the interaction between α-synuclein and 1 at 50 µM (Kd) through microscale thermophoresis. Also, we observed differences in height and diameter of aggregates, and α-synuclein remains unfolded in the presence of 1. Also, aggregates treated with 1 do not provoke neurites'' retraction in N2a cells previously induced by retinoic acid. Finally, we studied the potential sites of interaction between 1 with α-synuclein fibrils using molecular modelling. Docking experiments suggest that 1 preferably interact with the site 2 of α-synuclein through hydrogen bonds with residues Y39 and T44.     

Can the use of zooplankton dormant stages from natural wetlands contribute to restoration of mined wetlands?

Wetlands are among the most diverse environments on the planet and are strongly threatened by human activities. Their restoration and/or mitigation of human impacts, therefore, relies on information that can aid to the management of impacted wetlands so that they return to a (semi-) natural state. We investigate in this study the relationship between dormant stages of zooplankton and clay removal in areas subjected to mining. We evaluate whether a gradual increase in topsoil addition from donor natural wetlands to the sediment of mined wetlands influenced the zooplankton community. Eight wetlands were sampled in the Sinos River floodplain, four natural and four mined. In the laboratory, four field sediment samples were incubated for zooplankton hatching in five treatments comprising sediments from: mined wetlands, natural wetlands, and three treatments containing mined sediments added with low (5%), medium (20%) and high (40%) quantities of sediment from natural wetlands. Hatching consisted of 61 individuals distributed across eight zooplankton taxa. Copepod nauplii were the most abundant (31.1%) followed by Epiphanes sp. (29.5%) and Ovalona glabra (16.4%). While natural wetlands provided 42.6% of the hatched zooplankton, mined wetlands had just 6.5%. Zooplankton richness and abundance were higher in natural wetland sediments compared with mined and added sediment wetlands. To some degree, the sediment soil donation from natural to mined wetlands was considered viable. As long as prior studies are performed to test the size and quality of the dormant banks present in the sediment of candidate donor wetlands, sediment from donor wetlands may aid in the establishment of a more diverse community in disturbed systems.

     

Arylesterase activity of paraoxonase 1 (PON1) on HDL3 and HDL2: Relationship with Q192R,C-108T,and L55M polymorphisms

BackgroundControversy exists regarding the role of the subfractions of high-density lipoproteins (HDL₂ and HDL₃) in cardiovascular disease. The functionality of these particles, and their protective role, is due in part to the paraoxonase 1 (PON1) presence in them. The polymorphisms rs662 (Q192R, A/G), rs854560 (L55 M, T/A), and rs705379 (C-108T) of the PON1 gene have been related to enzyme activity and, with the anti-oxidative capacity of the HDL. The objective was to determine the arylesterase PON1 activity in HDL₃ and HDL₂ and its relationship with the polymorphisms mentioned, in a young population.MethodsThe polymorphisms were determined through mini-sequencing (SnaPshot). The HDL subpopulations were separated via ionic precipitation, cholesterol was measured with enzymatic methods, and PON1 activity was measured through spectrophotometry.ResultsThe results show that the PON1 polymorphisms do not influence the cholesterol in the HDL. A variation between 40.02 and 43.9 mg/dL was in all the polymorphisms without significant differences. Additionally, PON1 activity in the HDL₃ subfractions was greater (62.83 ± 20 kU/L) than with HDL₂ (35.8 ± 20.8 kU/L) in the whole population and in all the polymorphisms (p < 0.001), and it was independent of the polymorphism and differential arylesterase activity in the Q192R polymorphism (QQ > QR > RR). Thus, 115.90 ± 30.7, 88.78 ± 21.3, 65.29 ± 10.2, respectively, for total HDL, with identical behavior for HDL₃ and HDL₂.ConclusionsPON1 polymorphisms do not influence the HDL_-c, and the PON activity is greater in the HDL₃ than in the HDL₂, independent of the polymorphism, but it is necessary to delve into the functionality of these findings in different populations.     

Evolutionary implications of intron–exon distribution and the properties and sequences of the RPL10A gene in eukaryotes

The RPL10A gene encodes the RPL10 protein, required for joining 40S and 60S subunits into a functional 80S ribosome. This highly conserved gene, ubiquitous across all eukaryotic super-groups, is characterized by a variable number of spliceosomal introns, present in most organisms. These properties facilitate the recognition of orthologs among distant taxa and thus comparative studies of sequences as well as the distribution and properties of introns in taxonomically distant groups of eukaryotes. The present study examined the multiple ways in which RPL10A conservation vs. sequence changes in the gene over the course of evolution, including in exons, introns, and the encoded proteins, can be exploited for evolutionary analysis at different taxonomic levels. At least 25 different positions harboring introns within the RPL10A gene were determined in different taxa, including animals, plants, fungi, and alveolates. Generally, intron positions were found to be well conserved even across different kingdoms. However, certain introns seemed to be restricted to specific groups of organisms. Analyses of several properties of introns, including insertion site, phase, and length, along with exon and intron GC content and exon–intron boundaries, suggested biases within different groups of organisms. The use of a standard primer pair to analyze a portion of the intron-containing RPL10A gene in 12 genera of green algae within Chlorophyta is presented as a case study for evolutionary analyses of introns at intermediate and low taxonomic levels. Our study shows that phylogenetic reconstructions at different depths can be achieved using RPL10A nucleotide sequences from both exons and introns as well as the amino acid sequences of the encoded protein.     

Antibodies recognizing specific Mycobacterium avium subsp. paratuberculosis’s MAP3738c protein in type 1 diabetes mellitus children are associated with serum Th1 (CXCL10) chemokine

Recently Mycobacterium avium subsp. paratuberculosis (Map) was associated to type 1 diabetes mellitus (T1DM). In this study we investigated for Map presence in children affected by T1DM compared to healthy children. A pool of 212 sera from T1DM children at onset was compared to sera from 57 healthy children for humoral immune response towards the Map specific protein MAP3738c by ELISA. Serum concentrations of CXCL10 (pro-Th1) and CCL2 (pro-Th2) chemokines were also measured in both sera pool. Results showed that T1DM children had a stronger seropositivity towards MAP3738c protein compared to healthy children. Data highlighted also the correlation between serum activity of T1DM patients towards the specific protein of Map and the increase of CXCL10 concentration if compared to non-diabetic subjects. In conclusion, an immune response to Map in T1DM patients at onset was observed and this may indicate a role of the bacterium in triggering or precipitating the disease.     

Cryo-electron tomography of the magnetotactic vibrio Magnetovibrio blakemorei: Insights into the biomineralization of prismatic magnetosomes

We examined the structure and biomineralization of prismatic magnetosomes in the magnetotactic marine vibrio Magnetovibrio blakemorei strain MV-1 and a non-magnetotactic mutant derived from it, using a combination of cryo-electron tomography and freeze-fracture. The vesicles enveloping the Magnetovibrio magnetosomes were elongated and detached from the cell membrane. Magnetosome crystal formation appeared to be initiated at a nucleation site on the membrane inner surface. Interestingly, while scattered filaments were observed in the surrounding cytoplasm, their association with the magnetosome chains could not be unequivocally established. Our data suggest fundamental differences between prismatic and octahedral magnetosomes in their mechanisms of nucleation and crystal growth as well as in their structural relationships with the cytoplasm and plasma membrane.     

Mariculture and Natural Production of the Antitumoural (+)-Discodermolide by the Caribbean Marine Sponge Discodermia dissoluta

Biotechnological research on marine organisms, such as ex situ or in situ aquaculture and in vitro cell culture, is being conducted to produce bioactive metabolites for biomedical and industrial uses. The Caribbean marine sponge Discodermia dissoluta is the source of (+)-discodermolide, a potent antitumoural polyketide that has reached clinical trials. This sponge usually lives at depths greater than 30 m, but at Santa Marta (Colombia) there is a shallower population, which has made it logistically possible to investigate for the first time, on ways to supply discodermolide. We thus performed in situ, 6-month fragment culture trials to assess the performance of this sponge in terms of growth and additional discodermolide production and studied possible factors that influence the variability of discodermolide concentrations in the wild. Sponge fragments cultured in soft mesh bags suspended from horizontal lines showed high survivorship (93 %), moderate growth (28 % increase in volume) and an overall rise (33 %) in the discodermolide concentration, equivalent to average additional production of 8 μg of compound per millilitre of sponge. The concentration of discodermolide in wild sponges ranged from 8 to 40 μg mL^?1. Locality was the only factor related to discodermolide variation in the wild, and there were greater concentrations in peripheral vs. basal portions of the sponge, and in clean vs. fouled individuals. As natural growth and regeneration rates can be higher than culture growth rates, there is room for improving techniques to sustainably produce discodermolide.     

Diverging trends of chronic bronchitis and smoking habits between 1998 and 2010

Background

No study has been carried out on the time trend in the prevalence of chronic bronchitis (CB) in recent years, despite its clinical and epidemiological relevance. We evaluated the trend in CB prevalence during the past decade among young Italian adults.

Methods

A screening questionnaire was mailed to general population samples of 20–44 year-old subjects in two cross-sectional surveys: the Italian Study on Asthma in Young Adults (ISAYA) (1998/2000; n = 18,873, 9 centres) and the screening stage of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007/2010; n = 10,494, 7 centres). CB was defined as having cough and phlegm on most days for a minimum of 3 months a year and for at least 2 successive years. The prevalence rates and the risk ratios (RRs) for the association between CB and each potential predictor were adjusted for gender, age, season of response, type of contact, cumulative response rate, and centre.

Results

CB prevalence was 12.5% (95% CI: 12.1-12.9%) in 1998/2000 and 12.6% (95% CI: 11.7-13.7%) in 2007/2010; it increased among never smokers (from 7.6 to 9.1%, p = 0.003), current light smokers (<15 pack-years; from 15.1 to 18.6%, p < 0.001), and unemployed/retired subjects (from 14.3 to 19.1%, p = 0.001). In this decade, the prevalence of current smoking decreased (from 33.6 to 26.9%, p < 0.001), whereas the prevalence of unemployment/premature retirement (from 5.3 to 6.0%, p = 0.005), asthma (from 5.0 to 6.2%, p = 0.003), and allergic rhinitis (from 19.5 to 24.5%, p < 0.001) increased. In both 1998/2000 and 2007/2010, the likelihood of having CB was significantly higher for women, current smokers, asthmatic patients, and subjects with allergic rhinitis. During this period, the strength of the association between CB and current heavy smoking (≥15 pack-years) decreased (RR: from 4.82 to 3.57, p = 0.018), whereas it increased for unemployment/premature retirement (from 1.11 to 1.53, p = 0.019); no change was observed for gender, asthma, and allergic rhinitis.

Conclusions

Despite the significant reduction in current smoking, CB prevalence did not vary among young Italian adults. The temporal pattern of CB prevalence can only be partly explained by the increase of unemployment/premature retirement, asthma and allergic rhinitis, and suggests that other factors could have played a role.