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.     

Adaptation of the 3H-Leucine Incorporation Technique to Measure Heterotrophic Activity Associated with Biofilm on the Blades of the Seaweed Sargassum spp.

The ecological interaction between microorganisms and seaweeds depends on the production of secondary compounds that can influence microbial diversity in the water column and the composition of reef environments. We adapted the ³H-leucine incorporation technique to measure bacterial activity in biofilms associated with the blades of the macroalgae Sargassum spp. We evaluated (1) if the epiphytic bacteria on the blades were more active in detritus or in the biofilm, (2) substrate saturation and linearity of ³H-leucine incorporation, (3) the influence of specific metabolic inhibitors during ³H-leucine incorporation under the presence or absence of natural and artificial light, and (4) the efficiency of radiolabeled protein extraction. Scanning electron microscopy showed heterogeneous distribution of bacteria, diatoms, and polymeric extracellular secretions. Active bacteria were present in both biofilm and detritus on the blades. The highest ³H-leucine incorporation was obtained when incubating blades not colonized by macroepibionts. Incubations done under field conditions reported higher ³H-leucine incorporation than in the laboratory. Light quality and sampling manipulation seemed to be the main factors behind this difference. The use of specific metabolic inhibitors confirmed that bacteria are the main group incorporating ³H-leucine but their association with primary production suggested a symbiotic relationship between bacteria, diatoms, and the seaweed.     

Polymorphism of the Human Immunodeficiency Virus Type 1 in Brazil: genetic characterization of the nef gene and implications for vaccine design

Most of the Brazilian HIV-1 samples have been characterized based on the structural genes (env, gag and pol) and no data concerning the variability of the accessory genes such as nef have been available so far. Considering the role of the nef on virus biology and the inclusion of this region in some HIV/AIDS vaccine products under testing, the purpose of this study was to document the genetic diversity of the nef gene in third-four HIV-1 Brazilian samples previously subtyped based on the env C2-V3 region. Although only few non-subtype B samples have already been analyzed so far, the cytotoxic Tlymphocyte epitopes encoded in this region were relatively conserved among the subtypes, with some amino acid signatures mainly in the subtype C samples. Considering the increasing of the non-B HIV-1 subtypes worldwide, in special the subtype C, more data should be generated concerning the genetic and antigenic variability of these subtypes, as well as the study of the impact of such polymorphism in HIV/AIDS vaccine design and testing.     

TP53: a key gene in human cancer

TP53 is mutated in most types of human cancers and is one of the most popular genes in cancer research. The p53 protein is a sensor of multiple forms of genotoxic, oncogenic and non-genotoxic stress. It suppresses growth and controls survival of stressed cells, and as such, is the focal point of selection pressures in tissues exposed to carcinogens or to oncogenic changes. Thus, the clonal expansion of cells with mutations in TP53 may be seen as the result of a selection process intrinsic to the natural history of cancer. In this review, we discuss the nature of these various forms of selection pressure. We present a hypothesis to explain why TP53 is often mutated as either an early or a late event in cancer. Furthermore, we also summarise current knowledge on the molecular consequences of mutation for loss of wild-type protein function, dominant-negative activity, and a possible gain of oncogenic function.     

Relationship among Medical Student Resilience,Educational Environment and Quality of Life

Context

Resilience is a capacity to face and overcome adversities, with personal transformation and growth. In medical education, it is critical to understand the determinants of a positive, developmental reaction in the face of stressful, emotionally demanding situations. We studied the association among resilience, quality of life (QoL) and educational environment perceptions in medical students.

Methods

We evaluated data from a random sample of 1,350 medical students from 22 Brazilian medical schools. Information from participants included the Wagnild and Young’s resilience scale (RS-14), the Dundee Ready Educational Environment Measure (DREEM), the World Health Organization Quality of Life questionnaire – short form (WHOQOL-BREF), the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI).

Results

Full multiple linear regression models were adjusted for sex, age, year of medical course, presence of a BDI score ≥ 14 and STAI state or anxiety scores ≥ 50. Compared to those with very high resilience levels, individuals with very low resilience had worse QoL, measured by overall (β=-0.89; 95% confidence interval =-1.21 to -0.56) and medical-school related (β=-0.85; 95%CI=-1.25 to -0.45) QoL scores, environment (β=-6.48; 95%CI=-10.01 to -2.95), psychological (β=-22.89; 95%CI=-25.70 to -20.07), social relationships (β=-14.28; 95%CI=-19.07 to -9.49), and physical health (β=-10.74; 95%CI=-14.07 to -7.42) WHOQOL-BREF domain scores. They also had a worse educational environment perception, measured by global DREEM score (β=-31.42; 95%CI=-37.86 to -24.98), learning (β=-7.32; 95%CI=-9.23 to -5.41), teachers (β=-5.37; 95%CI=-7.16 to -3.58), academic self-perception (β=-7.33; 95%CI=-8.53 to -6.12), atmosphere (β=-8.29; 95%CI=-10.13 to -6.44) and social self-perception (β=-3.12; 95%CI=-4.11 to -2.12) DREEM domain scores. We also observed a dose-response pattern across resilience level groups for most measurements.

Conclusions

Medical students with higher resilience levels had a better quality of life and a better perception of educational environment. Developing resilience may become an important strategy to minimize emotional distress and enhance medical training.     

Diet and seed dispersal by five marsupials (Didelphimorphia: Didelphidae) in a Brazilian cerrado reserve

The food habits and seed dispersal promoted by five didelphid marsupials, were investigated through fecal analysis in a cerrado reserve located in the central part of the Espinhaço mountain range in Minas Gerais state, southeastern Brazil. The studied species presented a remarkable constancy in their diets and just for C. philander a seasonal change in diet seems to be present with a high consumption of fruits during the wetter season. Arthropods such as hymenopterans, coleopterans and homopterans were the main food resource detected but seeds belonging to pioneer plants were found with high frequencies in samples of all didelphids. Fruits of pioneer plants belonging to the families Melastomataceae (Clidemia urceolata and Miconia holocericea) and Rubiaceae (Psychotria barbiflora and P. capitata) present high germination rates and were among the mostly consumed. In spite of the differences observed in food preferences, all of the didelphids studied must be considered effective seed dispersers of pioneer plants.