Anticancer Potential of Compounds from the Brazilian Blue Amazon.

"Blue Amazon" is used to designate the Brazilian Economic Exclusive Zone, which covers an area comparable in size to that of its green counterpart. Indeed, Brazil flaunts a coastline spanning 8000 km through tropical and temperate regions and hosting part of the organisms accredited for the country's megadiversity status. Still, biodiversity may be expressed at different scales of organization; besides species inventory, genetic characteristics of living beings and metabolic expression of their genes meet some of these other layers. These metabolites produced by terrestrial creatures traditionally and lately added to by those from marine organisms are recognized for their pharmaceutical value, since over 50% of small molecule-based medicines are related to natural products. Nonetheless, Brazil gives a modest contribution to the field of pharmacology and even less when considering marine pharmacology, which still lacks comprehensive in-depth assessments toward the bioactivity of marine compounds so far. Therefore, this review examined the last 40 years of Brazilian natural products research, focusing on molecules that evidenced anticancer potential-which represents ~ 15% of marine natural products isolated from Brazilian species. This review discusses the most promising compounds isolated from sponges, cnidarians, ascidians, and microbes in terms of their molecular targets and mechanisms of action. Wrapping up, the review delivers an outlook on the challenges that stand against developing groundbreaking natural products research in Brazil and on a means of surpassing these matters.

Developing a two-dimensional landscape model of opportunities for penetrative passing in association football - Stage I.

This study investigated a method for modelling a landscape of opportunities for penetrative passing completed on the ground by ball carriers in association football. Analysis of video footage of competitive, professional football performance was undertaken, identifying a sample (n = 20) of attacking sub-phases of gameplay which ended in a penetrative pass being made between defenders to a receiver. Players' relative co-positioning during performance was modelled using bi-dimensional x and y coordinates of each player recorded at 25 fps. Data on player movements during competitive interactions were captured using an automatic video tracking system, recording player co-locations emerging over time, as well as current and estimated running velocities. Results revealed that the half spaces between the midfield and both sidelines were the key locations on field providing most affordances for penetrating passes in the competitive performance sample analysed. Due to the dynamics of players' co-adaptive performance behaviours, it was expected that opportunities for penetrative passing by ball carriers would not display a homogeneous space-time spread across the entire field. Results agreed with these expectations, showing how a landscape of opportunities for penetrative passing might be specified by information emerging from continuous player interactions in competitive performance.

Pathoarchitectonics of the cerebral cortex in chorea-acanthocytosis and Huntington's disease.

AIMS: Quantitative estimation of cortical neurone loss in cases with chorea-acanthocytosis (ChAc) and its impact on laminar composition. METHODS: We used unbiased stereological tools to estimate the degree of cortical pathology in serial gallocyanin-stained brain sections through the complete hemispheres of three subjects with genetically verified ChAc and a range of disease durations. We compared these results with our previous data of five Huntington's disease (HD) and five control cases. Pathoarchitectonic changes were exemplarily documented in TE1 of a 61-year-old female HD-, a 60-year-old female control case, and ChAc3. RESULTS: Macroscopically, the cortical volume of our ChAc cases (ChAc1-3) remained close to normal. However, the average number of neurones was reduced by 46% in ChAc and by 33% in HD (P = 0.03 for ChAc & HD vs. controls; P = 0.64 for ChAc vs. HD). Terminal HD cases featured selective laminar neurone loss with pallor of layers III, V and VIa, a high density of small, pale, closely packed radial fibres in deep cortical layers VI and V, shrinkage, and chromophilia of subcortical white matter. In ChAc, pronounced diffuse astrogliosis blurred the laminar borders, thus masking the complete and partial loss of pyramidal cells in layer IIIc and of neurones in layers III, V and VI. CONCLUSION: ChAc is a neurodegenerative disease with distinct cortical neurodegeneration. The hypertrophy of the peripheral neuropil space of minicolumns with coarse vertical striation was characteristic of ChAc. The role of astroglia in the pathogenesis of this disorder remains to be elucidated.

Boronated tartrolon antibiotic produced by symbiotic cellulose-degrading bacteria in shipworm gills.

Shipworms are marine wood-boring bivalve mollusks (family Teredinidae) that harbor a community of closely related Gammaproteobacteria as intracellular endosymbionts in their gills. These symbionts have been proposed to assist the shipworm host in cellulose digestion and have been shown to play a role in nitrogen fixation. The genome of one strain of Teredinibacter turnerae, the first shipworm symbiont to be cultivated, was sequenced, revealing potential as a rich source of polyketides and nonribosomal peptides. Bioassay-guided fractionation led to the isolation and identification of two macrodioloide polyketides belonging to the tartrolon class. Both compounds were found to possess antibacterial properties, and the major compound was found to inhibit other shipworm symbiont strains and various pathogenic bacteria. The gene cluster responsible for the synthesis of these compounds was identified and characterized, and the ketosynthase domains were analyzed phylogenetically. Reverse-transcription PCR in addition to liquid chromatography and high-resolution mass spectrometry and tandem mass spectrometry revealed the transcription of these genes and the presence of the compounds in the shipworm, suggesting that the gene cluster is expressed in vivo and that the compounds may fulfill a specific function for the shipworm host. This study reports tartrolon polyketides from a shipworm symbiont and unveils the biosynthetic gene cluster of a member of this class of compounds, which might reveal the mechanism by which these bioactive metabolites are biosynthesized.

Genomic and phenotypic attributes of novel salinivibrios from stromatolites, sediment and water from a high altitude lake.

BACKGROUND: Salinivibrios are moderately halophilic bacteria found in salted meats, brines and hypersaline environments. We obtained three novel conspecific Salinivibrio strains closely related to S. costicola, from Socompa Lake, a high altitude hypersaline Andean lake (approx. 3,570 meters above the sea level). RESULTS: The three novel Salinivibrio spp. were extremely resistant to arsenic (up to 200 mM HAsO42-), NaCl (up to 15%), and UV-B radiation (19 KJ/m2, corresponding to 240 minutes of exposure) by means of phenotypic tests. Our subsequent draft genome ionsequencing and RAST-based genome annotation revealed the presence of genes related to arsenic, NaCl, and UV radiation resistance. The three novel Salinivibrio genomes also had the xanthorhodopsin gene cluster phylogenetically related to Marinobacter and Spiribacter. The genomic taxonomy analysis, including multilocus sequence analysis, average amino acid identity, and genome-to-genome distance revealed that the three novel strains belong to a new Salinivibrio species. CONCLUSIONS: Arsenic resistance genes, genes involved in DNA repair, resistance to extreme environmental conditions and the possible light-based energy production, may represent important attributes of the novel salinivibrios, allowing these microbes to thrive in the Socompa Lake.

Polyketide synthase gene diversity within the microbiome of the sponge Arenosclera brasiliensis, endemic to the Southern Atlantic Ocean.

Microbes associated with marine sponges are considered important producers of bioactive, structurally unique polyketides. The synthesis of such secondary metabolites involves type I polyketide synthases (PKSs), which are enzymes that reach a maximum complexity degree in bacteria. The Haplosclerida sponge Arenosclera brasiliensis hosts a complex microbiota and is the source of arenosclerins, alkaloids with cytotoxic and antibacterial activity. In the present investigation, we performed high-throughput sequencing of the ketosynthase (KS) amplicon to investigate the diversity of PKS genes present in the metagenome of A. brasiliensis. Almost 4,000 ketosynthase reads were recovered, with about 90% annotated automatically as bacterial. A total of 235 bacterial KS contigs was rigorously assembled from this sequence pool and submitted to phylogenetic analysis. A great diversity of six type I PKS groups has been consistently detected in our phylogenetic reconstructions, including a novel and A. brasiliensis-exclusive group. Our study is the first to reveal the diversity of type I PKS genes in A. brasiliensis as well as the potential of its microbiome to serve as a source of new polyketides.

The chemistry and biology of organic guanidine derivatives.

The chemistry and biology of organic natural guanidines are reviewed, including the isolation, structure determination, synthesis, biosynthesis and biological activities of alkaloids, non-ribosomal peptides, guanidine-bearing terpenes, polyketides and shikimic acid derivatives from natural sources.

Illustrating changes in landscapes of passing opportunities along a set of competitive football matches.

This study aims to illustrate the landscape of passing opportunities of a football team across a set of competitive matches. To do so positional data of 5 competitive matches was used to create polygons of pass availability. Passes were divided into three types depending on the hypothetical threat they may pose to the opposing defense (penetrative, support, and backwards passes). These categories were used to create three heatmaps per match. Moreover, the mean time of passing opportunities was calculated and compared across matches and for the three categories of passes. Due to the specificity of player's interactive behavior, results showed heatmaps with a variety of patterns. Specifically the fifth match was very dissimilar to the other four. However, characterizing a football match in terms of passing opportunities with a single heatmap dismisses the variety of dynamics that occur throughout a match. Therefore, three temporal heatmaps over windows of 10 min were presented highlighting on-going dynamical changes in pass availability. Results also display that penetrative passes were available over shorter periods of time than backward passes that were available shorter than support passes. The results highlight the sensibility of the model to different task constrains that emerge within football matches.

Migraine and motion sickness independently contribute to visual discomfort.

The objective of this study was to evaluate, in patients with migraine and healthy volunteers, with and without a history of motion sickness, the degree of discomfort elicited by drifting striped patterns. Eighteen healthy volunteers (HV) and 30 migraine patients participated in the study. Discomfort was greater in migraine patients than in HV, and in individuals with a history of motion sickness than in those without, but the effect of history of migraine was independent of history of motion sickness. Generalized Estimating Equations models for binary correlated data revealed that these differences did not depend on levels of duty cycle, spatial and temporal frequencies. Visual discomfort in migraine patients was associated with worse performance. There was a significant correlation between median degree of discomfort across conditions and number of migraine attacks in the past month. Discomfort to drifting striped patterns may be related to central sensitization in migraine patients.

Characterization of the biocompatible magnetic colloid on the basis of Fe3O4 nanoparticles coated with dextran, used as contrast agent in magnetic resonance imaging.

The magnetic resonance imaging contrast agent, the so-called Endorem colloidal suspension on the basis of superparamagnetic iron oxide nanoparticles (mean diameter of 5.5 nm) coated with dextran, were characterized on the basis of several measurement techniques to determine the parameters of their most important physical and chemical properties. It is assumed that each nanoparticle is consisted of Fe3O4 monodomain and it was observed that its oxidation to gamma-Fe2O3 occurs at 253.1 degrees C. The Mössbauer spectroscopy have shown a superparamagnetic behavior of the magnetic nanoparticles. The Magnetic Resonance results show an increase of the relaxation times T1, T2, and T2* with decreasing concentration of iron oxide nanoparticles. The relaxation effects of SPIONs contrast agents are influenced by their local concentration as well as the applied field strength and the environment in which these agents interact with surrounding protons. The proton relaxation rates presented a linear behavior with concentration. The measured values of thermo-optic coefficient dn/dT, thermal conductivity kappa, optical birefringence delta n0, nonlinear refractive index n2, nonlinear absorption beta' and third-order nonlinear susceptibility |chi(3)| are also reported.

Characterization of superparamagnetic iron oxide coated with silicone used as contrast agent for magnetic resonance image for the gastrointestinal tract.

The present work is a report of the characterization of superparamagnetic iron oxide nanoparticles coated with silicone used as a contrast agent in magnetic resonance imaging of the gastrointestinal tract. The hydrodynamic size of the contrast agent is 281.2 nm, where it was determined by transmission electron microscopy and a Fe3O4 crystalline structure was identified by X-ray diffraction, also confirmed by Mössbauer Spectroscopy. The blocking temperature of 190 K was determined from magnetic measurements based on the Zero Field Cooled and Field Cooled methods. The hysteresis loops were measured at different temperatures below and above the blocking temperature. Ferromagnetic resonance analysis indicated the superparamagnetic nature of the nanoparticles and a strong temperature dependence of the peak-to-peak linewidth deltaH(pp), giromagnetic factor g, number of spins N(s) and relaxation time T2 were observed. This behavior can be attributed to an increase in the superexchange interaction.

Secondary Metabolism in the Gill Microbiota of Shipworms (Teredinidae) as Revealed by Comparison of Metagenomes and Nearly Complete Symbiont Genomes.

Shipworms play critical roles in recycling wood in the sea. Symbiotic bacteria supply enzymes that the organisms need for nutrition and wood degradation. Some of these bacteria have been grown in pure culture and have the capacity to make many secondary metabolites. However, little is known about whether such secondary metabolite pathways are represented in the symbiont communities within their hosts. In addition, little has been reported about the patterns of host-symbiont co-occurrence. Here, we collected shipworms from the United States, the Philippines, and Brazil and cultivated symbiotic bacteria from their gills. We analyzed sequences from 22 shipworm gill metagenomes from seven shipworm species and from 23 cultivated symbiont isolates. Using (meta)genome sequencing, we demonstrate that the cultivated isolates represent all the major bacterial symbiont species and strains in shipworm gills. We show that the bacterial symbionts are distributed among shipworm hosts in consistent, predictable patterns. The symbiotic bacteria harbor many gene cluster families (GCFs) for biosynthesis of bioactive secondary metabolites, only <5% of which match previously described biosynthetic pathways. Because we were able to cultivate the symbionts and to sequence their genomes, we can definitively enumerate the biosynthetic pathways in these symbiont communities, showing that ∼150 of ∼200 total biosynthetic gene clusters (BGCs) present in the animal gill metagenomes are represented in our culture collection. Shipworm symbionts occur in suites that differ predictably across a wide taxonomic and geographic range of host species and collectively constitute an immense resource for the discovery of new biosynthetic pathways corresponding to bioactive secondary metabolites.IMPORTANCE We define a system in which the major symbionts that are important to host biology and to the production of secondary metabolites can be cultivated. We show that symbiotic bacteria that are critical to host nutrition and lifestyle also have an immense capacity to produce a multitude of diverse and likely novel bioactive secondary metabolites that could lead to the discovery of drugs and that these pathways are found within shipworm gills. We propose that, by shaping associated microbial communities within the host, the compounds support the ability of shipworms to degrade wood in marine environments. Because these symbionts can be cultivated and genetically manipulated, they provide a powerful model for understanding how secondary metabolism impacts microbial symbiosis.

Latin American Brain Mapping Network (LABMAN).

On March 8, 2008 in Havana, the Latin American Network for Brain Mapping (LABMAN) was created with participants from Argentina, Brazil, Colombia, Cuba and Mexico. The focus of LABMAN is to promote neuroimaging and systems neuroscience in the region through the implementation of training and exchange programs, and to increase public awareness of the Latin American potential to contribute both to basic and applied research in human brain mapping.

Integrating Computational Methods to Investigate the Macroecology of Microbiomes.

Studies in microbiology have long been mostly restricted to small spatial scales. However, recent technological advances, such as new sequencing methodologies, have ushered an era of large-scale sequencing of environmental DNA data from multiple biomes worldwide. These global datasets can now be used to explore long standing questions of microbial ecology. New methodological approaches and concepts are being developed to study such large-scale patterns in microbial communities, resulting in new perspectives that represent a significant advances for both microbiology and macroecology. Here, we identify and review important conceptual, computational, and methodological challenges and opportunities in microbial macroecology. Specifically, we discuss the challenges of handling and analyzing large amounts of microbiome data to understand taxa distribution and co-occurrence patterns. We also discuss approaches for modeling microbial communities based on environmental data, including information on biological interactions to make full use of available Big Data. Finally, we summarize the methods presented in a general approach aimed to aid microbiologists in addressing fundamental questions in microbial macroecology, including classical propositions (such as "everything is everywhere, but the environment selects") as well as applied ecological problems, such as those posed by human induced global environmental changes.

In vitro study of CD133 human stem cells labeled with superparamagnetic iron oxide nanoparticles.

Superparamagnetic iron oxide nanoparticles (SPIONs) are applied in stem cell labeling because of their high magnetic susceptibility as compared with ordinary paramagnetic species, their low toxicity, and their ease of magnetic manipulation. The present work is the study of CD133+ stem cell labeling by SPIONs coupled to a specific antibody (AC133), resulting in the antigenic labeling of the CD133+ stem cell, and a method was developed for the quantification of the SPION content per cell, necessary for molecular imaging optimization. Flow cytometry analysis established the efficiency of the selection process and helped determine that the CD133 cells selected by chromatographic affinity express the transmembrane glycoprotein CD133. The presence of antibodies coupled to the SPION, expressed in the cell membrane, was observed by transmission electron microscopy. Quantification of the SPION concentration in the marked cells using the ferromagnetic resonance technique resulted in a value of 1.70 x 10(-13) mol iron (9.5 pg) or 7.0 x 10(6) nanoparticles per cell (the measurement was carried out in a volume of 2 muL containing about 6.16 x 10(5) pg iron, equivalent to 4.5 x 10(11) SPIONs).

The gill-associated microbiome is the main source of wood plant polysaccharide hydrolases and secondary metabolite gene clusters in the mangrove shipworm Neoteredo reynei.

Teredinidae are a family of highly adapted wood-feeding and wood-boring bivalves, commonly known as shipworms, whose evolution is linked to the acquisition of cellulolytic gammaproteobacterial symbionts harbored in bacteriocytes within the gills. In the present work we applied metagenomics to characterize microbiomes of the gills and digestive tract of Neoteredo reynei, a mangrove-adapted shipworm species found over a large range of the Brazilian coast. Comparative metagenomics grouped the gill symbiont community of different N. reynei specimens, indicating closely related bacterial types are shared. Similarly, the intestine and digestive gland communities were related, yet were more diverse than and showed no overlap with the gill community. Annotation of assembled metagenomic contigs revealed that the gill symbiotic community of N. reynei encodes a plethora of plant cell wall polysaccharides degrading glycoside hydrolase encoding genes, and Biosynthetic Gene Clusters (BGCs). In contrast, the digestive tract microbiomes seem to play little role in wood digestion and secondary metabolites biosynthesis. Metagenome binning recovered the nearly complete genome sequences of two symbiotic Teredinibacter strains from the gills, a representative of Teredinibacter turnerae "clade I" strain, and a yet to be cultivated Teredinibacter sp. type. These Teredinibacter genomes, as well as un-binned gill-derived gammaproteobacteria contigs, also include an endo-ß-1,4-xylanase/acetylxylan esterase multi-catalytic carbohydrate-active enzyme, and a trans-acyltransferase polyketide synthase (trans-AT PKS) gene cluster with the gene cassette for generating ß-branching on complex polyketides. Finally, we use multivariate analyses to show that the secondary metabolome from the genomes of Teredinibacter representatives, including genomes binned from N. reynei gills' metagenomes presented herein, stands out within the Cellvibrionaceae family by size, and enrichments for polyketide, nonribosomal peptide and hybrid BGCs. Results presented here add to the growing characterization of shipworm symbiotic microbiomes and indicate that the N. reynei gill gammaproteobacterial community is a prolific source of biotechnologically relevant enzymes for wood-digestion and bioactive compounds production.

Endophytic fungus Pseudofusicoccum stromaticum produces cyclopeptides and plant-related bioactive rotenoids.

In the present study, we integrated liquid chromatography high-resolution mass spectrometry (LC-HRMS) and high-throughput DNA sequencing for prospecting cytotoxic specialized metabolites from Pseudofusicoccum stromaticum, an endophytic fungus associated to the medicinal plant Myracrodruon urundeuva. LC-HRMS profiling allowed identifying putatively eleven compounds in the ethyl acetate extract from P. stromaticum broth. Additionally, a chemical fractionation guided by cytotoxicity combined with spectrometric analysis resulted in the isolation of three compounds: the cyclopeptide cyclo-l-Phe-d-Leu-l-Leu-l-Leu-l-lle along with the known rotenoids rotenolone and tephrosin. MTT assay showed that tephrosin (IC50 0.51 µg mL-1) has strong cytotoxic effect and may be pointed out as the compound responsible for the antiproliferative activity of P. stromaticum. Next Generation Sequencing (NGS) and genome mining of P. stromaticum draft genome revealed 56 contigs codifying specialized metabolites biosynthesis-related enzymes. Nearly half of such genes (44.6%) could be mapped to orphan Biosynthetic Gene Clusters (BGCs) of related plant pathogens belonging to family Botryosphaeriaceae. Also, screening for rotenoids biosynthetic enzymes led to characterization of a putative chalcone isomerase-like (CHI-like) protein. This is the first report of rotenoids biosynthesized by a fungus, unveiling a unique ability of P. stromaticum.

Coordinated brain development: exploring the synchrony between changes in grey and white matter during childhood maturation.

Brain development during childhood and early adolescence is characterized by global changes in brain architecture. Neuroimaging studies have revealed overall decreases in cortical thickness (CT) and increases in fractional anisotropy (FA). Furthermore, previous studies have shown that certain cortical regions display coordinated growth during development. However, there is significant heterogeneity in the timing and speed of these developmental transformations, and it is still unclear whether white and grey matter changes are co-localized. In this multimodal neuroimaging study, we investigated the relationship between grey and white matter developmental changes and asynchronous maturation within brain regions in 249 normally developing children between the ages 7-14. We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to analyze CT and FA, respectively, as well as their covariance across development. Consistent with previous studies, we observed overall cortical thinning with age, which was accompanied by increased FA. We then compared the coordinated development of grey and white matter as indexed by covariance measures. Covariance between grey matter regions and the microstructure of white matter tracts connecting those regions were highly similar, suggesting that coordinated changes in the cortex were mirrored by coordinated changes in their respective tracts. Examining within-brain divergent trajectories, we found significant structural decoupling (decreased covariance) between several brain regions and tracts in the 9- to 11-year-old group, particularly involving the forceps minor and the regions that it connects to. We argue that this decoupling could reflect a developmental pattern within the prefrontal region in 9- and 11-year-old children, possibly related to the significant changes in cognitive control observed at this age.

Magnetic resonance diffusion tensor imaging for the pedunculopontine nucleus: proof of concept and histological correlation.

The pedunculopontine nucleus (PPN) has been proposed as target for deep brain stimulation (DBS) in patients with postural instability and gait disorders due to its involvement in muscle tonus adjustments and control of locomotion. However, it is a deep-seated brainstem nucleus without clear imaging or electrophysiological markers. Some studies suggested that diffusion tensor imaging (DTI) may help guiding electrode placement in the PPN by showing the surrounding fiber bundles, but none have provided a direct histological correlation. We investigated DTI fractional anisotropy (FA) maps from in vivo and in situ post-mortem magnetic resonance images (MRI) compared to histological evaluations for improving PPN targeting in humans. A post-mortem brain was scanned in a clinical 3T MR system in situ. Thereafter, the brain was processed with a special method ideally suited for cytoarchitectonic analyses. Also, nine volunteers had in vivo brain scanning using the same MRI protocol. Images from volunteers were compared to those obtained in the post-mortem study. FA values of the volunteers were obtained from PPN, inferior colliculus, cerebellar crossing fibers and medial lemniscus using histological data and atlas information. FA values in the PPN were significantly lower than in the surrounding white matter region and higher than in areas with predominantly gray matter. In Nissl-stained histologic sections, the PPN extended for more than 10 mm in the rostro-caudal axis being closely attached to the lateral parabrachial nucleus. Our DTI analyses and the spatial correlation with histological findings proposed a location for PPN that matched the position assigned to this nucleus in the literature. Coregistration of neuroimaging and cytoarchitectonic features can add value to help establishing functional architectonics of the PPN and facilitate neurosurgical targeting of this extended nucleus.