João M. Alves

Stoichiometry of benthic invertebrate nutrient recycling: interspecific variation and the role of body mass

Ecological stoichiometry (ES) and allometry offer frameworks for predicting how nutrient recycling varies within and among animal species. Despite the importance of benthic-derived nutrients in most aquatic systems, predictions based on ES and allometry have been poorly tested among benthic invertebrate consumers. Here, we show that the rates and ratios at which three freshwater benthic invertebrate species (a crustacean, an insect, and a polychaeta) recycled nitrogen (N) and phosphorus (P) can be partially predicted by ES and allometry depending on whether data are analyzed intra- or interspecifically. Mass-specific N and P excretion rates were negatively correlated with invertebrate body size both among and within taxa, supporting allometric predictions. However, mass-specific N and P excretion rates were positively and negatively correlated to invertebrate body N and P, respectively, but only when data were analyzed intraspecifically. As a corollary, the mass-specific N:P excretion ratio was positively related to body N:P ratio. Such a contrasting pattern on excretion-mediated N and P recycling suggests that stoichiometric constraints regarding consumer-resource imbalances for the three species utilized in this study may be stronger for P than for N. Our results indicate that the variation in nutrient recycling, which is mediated by taxonomic constraints on stoichiometry and allometry, may substantially help us to understand the importance of benthic detritivorous species to the functioning of aquatic ecosystems.

On the structural plasticity of the human genome: chromosomal inversions revisited.

With the aid of novel and powerful molecular biology techniques, recent years have witnessed a dramatic increase in the number of studies reporting the involvement of complex structural variants in several genomic disorders. In fact, with the discovery of Copy Number Variants (CNVs) and other forms of unbalanced structural variation, much attention has been directed to the detection and characterization of such rearrangements, as well as the identification of the mechanisms involved in their formation. However, it has long been appreciated that chromosomes can undergo other forms of structural changes - balanced rearrangements - that do not involve quantitative variation of genetic material. Indeed, a particular subtype of balanced rearrangement – inversions – was recently found to be far more common than had been predicted from traditional cytogenetics. Chromosomal inversions alter the orientation of a specific genomic sequence and, unless involving breaks in coding or regulatory regions (and, disregarding complex trans effects, in their close vicinity), appear to be phenotypically silent. Such a surprising finding, which is difficult to reconcile with the classical interpretation of inversions as a mechanism causing subfertility (and ultimately reproductive isolation), motivated a new series of theoretical and empirical studies dedicated to understand their role in human genome evolution and to explore their possible association to complex genetic disorders. With this review, we attempt to describe the latest methodological improvements to inversions detection at a genome wide level, while exploring some of the possible implications of inversion rearrangements on the evolution of the human genome.

Aspectos que interferem na construção da acessibilidade em bibliotecas universitárias

Apresenta-se a evolucao do conceito da acessibilidade, inicialmente associado apenas ao projeto livre de barreiras, para o que e hoje conhecido como desenho para todos, envolvendo aspectos tanto do mundo fisico como do mundo digital. Discute-se a importância de as bibliotecas universitarias adotarem criterios de acessibilidade, contribuindo para isso o espaco digital. A partir do estudo de caso feito em uma universidade federal brasileira especifica, focado nos aspectos de acesso a informacao e comunicacao e aspectos atitudinais, sao elaboradas propostas de melhorias para as condicoes de acessibilidade em bibliotecas universitarias

Multiregional Tumor Trees Are Not Phylogenies

Tumor samples most often comprise a mixture of different cell lineages. Multiregional trees built from bulk mutational profiles do not consider this heterogeneity and can potentially lead to erroneous evolutionary inferences, including biased timing of somatic mutations, spurious parallel mutation events, and/or incorrect chronological ordering of metastatic events.

The 8p23 Inversion Polymorphism Determines Local Recombination Heterogeneity across Human Populations

For decades, chromosomal inversions have been regarded as fascinating evolutionary elements as they are expected to suppress recombination between chromosomes with opposite orientations, leading to the accumulation of genetic differences between the two configurations over time. Here, making use of publicly available population genotype data for the largest polymorphic inversion in the human genome (8p23-inv), we assessed whether this inhibitory effect of inversion rearrangements led to significant differences in the recombination landscape of two homologous DNA segments, with opposite orientation. Our analysis revealed that the accumulation of genetic differentiation is positively correlated with the variation in recombination profiles. The observed recombination dissimilarity between inversion types is consistent across all populations analyzed and surpasses the effects of geographic structure, suggesting that both structures (orientations) have been evolving independently over an extended period of time, despite being subjected to the very same demographic history. Aside this mainly independent evolution, we also identified a short segment (350 kb, <10% of the whole inversion) in the central region of the inversion where the genetic divergence between the two structural haplotypes is diminished. Although it is difficult to demonstrate it, this could be due to gene flow (possibly via double-crossing over events), which is consistent with the higher recombination rates surrounding this segment. This study demonstrates for the first time that chromosomal inversions influence the recombination landscape at a fine-scale and highlights the role of these rearrangements as drivers of genome evolution.

Partner selection in co-opetition: a three step model

Purpose – This paper aims to contribute towards a better understanding of the partner selection process, which anticipates a successful co-opetition partnership. Co-opetition partnerships refer to developing cooperation efforts between competitors. The scarcity of studies conducted in this field to date provides limited contribution for the understanding of the partner selection process in this, particularly, paradoxical concept. Design/methodology/approach – This study follows a methodology based on systematic combining for the qualitative analysis of four cases of domestic co-opetition in Portugal. A sample range of eight companies was selected for a series of semi-structured interviews. Testimonials were transcribed and data coded for content analysis. Findings – Results indicate that prior personal relationships between decision-makers are facilitators for the implementation of cooperation partnerships with competitors. Based on these findings, this paper proposes a three-step model to explain the pro...

Biased evolutionary inferences from bulk tumor samples

It is generally agreed that tumors are composed of multiple cell clones defined by different somatic mutations. Characterizing the evolutionary mechanisms driving this intratumor genetic heterogeneity (ITH) is crucial to improve both cancer diagnosis and therapeutic strategies. For that purpose, recent ITH studies have focused on qualitative comparisons of mutational profiles derived from bulk sequencing of multiple tumor samples extracted from the same patient. Here, we show some examples where the naive use of bulk data in multiregional studies may lead to erroneous inferences of the evolutionary trajectories that underlie tumor progression, including biased timing of somatic mutations, spurious parallel mutation events, and/or incorrect chronological ordering of metastatic events. In addition, we analyze three real datasets to highlight how the use of bulk mutational profiles instead of inferred clones can lead to different conclusions about mutational recurrence and population structure.

Reassessing the evolutionary history of the 17q21 inversion polymorphism

A polymorphic inversion that lies on chromosome 17q21 comprises two major haplotype families (H1 and H2) that not only differ in orientation but also in copy-number. Although the processes driving the spread of the inversion-associated lineage (H2) in humans remain unclear, a selective advantage has been proposed for one of its subtypes. Here, we genotyped a large panel of individuals from previously overlooked populations using a custom array with a unique panel of H2-specific single nucleotide polymorphisms and found a patchy distribution of H2 haplotypes in Africa, with North Africans displaying a higher frequency of inverted subtypes, when compared with Sub-Saharan groups. Interestingly, North African H2s were found to be closer to “non-African” chromosomes further supporting that these populations may have diverged more recently from groups outside Africa. Our results uncovered higher diversity within the H2 family than previously described, weakening the hypothesis of a strong selective sweep on all inverted chromosomes and suggesting a rather complex evolutionary history at this locus.

Sensitivity to sequencing depth in single-cell cancer genomics

BackgroundQuerying cancer genomes at single-cell resolution is expected to provide a powerful framework to understand in detail the dynamics of cancer evolution. However, given the high costs currently associated with single-cell sequencing, together with the inevitable technical noise arising from single-cell genome amplification, cost-effective strategies that maximize the quality of single-cell data are critically needed. Taking advantage of previously published single-cell whole-genome and whole-exome cancer datasets, we studied the impact of sequencing depth and sampling effort towards single-cell variant detection.MethodsFive single-cell whole-genome and whole-exome cancer datasets were independently downscaled to 25, 10, 5, and 1× sequencing depth. For each depth level, ten technical replicates were generated, resulting in a total of 6280 single-cell BAM files. The sensitivity of variant detection, including structural and driver mutations, genotyping, clonal inference, and phylogenetic reconstruction to sequencing depth was evaluated using recent tools specifically designed for single-cell data.ResultsAltogether, our results suggest that for relatively large sample sizes (25 or more cells) sequencing single tumor cells at depths > 5× does not drastically improve somatic variant discovery, characterization of clonal genotypes, or estimation of single-cell phylogenies.ConclusionsWe suggest that sequencing multiple individual tumor cells at a modest depth represents an effective alternative to explore the mutational landscape and clonal evolutionary patterns of cancer genomes.

NGS Analysis of Somatic Mutations in Cancer Genomes

The emergence of next-generation sequencing (NGS) technologies has facilitated the accumulation of large genomic datasets for most types of cancer. The analysis of these data has confirmed the early predictions of extensive sequence and structural diversity of cancer genomes, fueling the development of new computational approaches to decipher inter- and intratumoral somatic variation within and among cancer patients. Overall, these techniques have led to a better understanding of the disease as well as to relevant improvements in the diagnosis and therapy of cancer. In this chapter, we review current approaches for the analysis of somatic mutations in cancer genomes using NGS.