Biology subjects

Silva, C.

Publications and source records attributed to Silva, C..

23 records · Page 2Linked to original sources

bioRxiv2020

The genetic structure and adaptation of Andean highlanders and Amazonian dwellers is influenced by the interplay between geography and culture

Western South America was one of the worldwide cradles of civilization. The well known Inca Empire was the tip of the iceberg of a cultural and biological evolutionary process that started 14-11 thousand years ago. Genetic data from 18 Peruvian populations reveal that: (1) The between-population homogenization of the central-southern Andes and its differentiation with respect to Amazonian populations of similar latitudes do not extend northward. Instead, longitudinal gene flow between the northern coast of Peru, Andes and Amazonia accompanied cultural and socioeconomic interactions revealed by archeological studies. This pattern recapitulates the environmental and cultural differentiation between the fertile north, where altitudes are lower; and the arid south, where the Andes are higher, acting as a genetic barrier between the sharply different environments of the Andes and Amazonia (2). The genetic homogenization between the populations of the arid Andes is not only due to migration during the Inca Empire or the subsequent colonial period. It started at least during the earlier expansion of the pre-Inca Wari Empire (600-1000 YBP) (3) This demographic history allowed for cases of positive natural selection in the high and arid Andes vs. the low Amazon tropical forest: in the Andes, HAND2-AS1 (heart and neural crest derivatives expressed 2 antisense RNA1, related with cardiovascular function) and DUOX2 (dual oxidase 2, related to thyroid function and innate immunity) genes; in the Amazon, the gene encoding for the CD45 protein, essential for antigen recognition by T/B lymphocytes in viral-host interaction, consistent with the host-virus arms race hypothesis.

evolutionary biology↗

bioRxiv2019

Alcohol intake triggers aberrant synaptic pruning leading to synapse loss and anxiety-like behavior

Alcohol use adversely impacts the life of millions of people worldwide. Deficits in synaptic transmission and in microglial function are common findings in human alcohol users and in animal models of alcohol intoxication. Here, we show that alcohol intake over ten consecutive days resulted in substantial loss of excitatory synapse in the prefrontal cortex, a consequence of aberrant synaptic pruning, which led to increased anxiety-like behavior. Mechanistically, these effects of alcohol intake were mediated by a detrimental increase of microglia engulfment capacity via Src-dependent activation of NFkB and consequent TNF production. Accordingly, pharmacological blockade of Src activation or TNF production by microglia, genetic ablation of TNF, or diphtheria toxin-mediated conditional ablation of microglia attenuated aberrant synaptic pruning preventing excitatory synapse loss and anxiety-like behavior. Overall, our data suggest that aberrant pruning of excitatory synapses by microglia might disrupt synaptic transmission during alcohol use.

neuroscience↗

bioRxiv2019

Molecular mechanisms of Evening Complex activity in Arabidopsis

The Evening Complex (EC), composed of the DNA-binding protein LUX ARRHYTHMO (LUX) and two additional proteins, EARLY FLOWERING 3 (ELF3) and ELF4, is a transcriptional repressor complex and a core component of the plant circadian clock. In addition to maintaining oscillations in clock gene expression, the EC also participates in temperature and light entrainment and regulates important clock output genes such as PHYTOCHROME INTERACTING FACTOR 4 (PIF4), a key transcription factor involved in temperature dependent plant growth. These properties make the EC an attractive target for altering plant development through targeted mutations to the complex. However, the molecular basis for EC function was not known. Here we show that binding of the EC requires all three proteins and that ELF3 decreases the ability of LUX to bind DNA whereas the presence of ELF4 restores interaction with DNA. To be able to manipulate this complex, we solved the structure of the DNA-binding domain of LUX bound to DNA. Using structure-based design, a LUX variant was constructed that showed decreased in vitro binding affinity but retained specificity for its cognate sequences. This designed LUX allele modulates hypocotyl elongation and flowering. These results demonstrate that modifying the DNA-binding affinity of LUX can be used to titrate the repressive activity of the entire EC, tuning growth and development in a predictable manner.\n\nSignificance StatementCircadian gene expression oscillates over a 24 hr. period and regulates many genes critical for growth and development. In plants, the Evening Complex (EC), a three-protein repressive complex made up of LUX ARRYTHMO, EARLY FLOWERING 3 and EARLY FLOWERING 4, acts as a key component of the circadian clock and is a regulator of thermomorphogenic growth. However, the molecular mechanisms of complex formation and DNA-binding have not been identified. Here we determine the roles of each protein in the complex and present the structure of the LUX DNA-binding domain in complex with DNA. Based on these data, we used structure-based protein engineering to produce a version of the EC with altered in vitro and in vivo activity. These results demonstrate that the EC can be modified to alter plant growth and development at different temperatures in a predictable manner.

plant biology↗

bioRxiv2019

Carnivore endozoochory of a dry fruited tree can benefit quarry passive restoration

As more work assert passive restoration as a complementary approach to technical reclamation, it is imperative to know its drivers. Although the consequences of endozoochory are crucial to predict passive restoration success, few experimental studies assess the use of heavily disturbed sites by seed dispersers such as carnivores and how the seeds they bring in emerge and survive. Using an indoor sowing experiment conducted in situ, we examined for the first time how carnivore endozoochorous seeds collected in a quarry potentially influence its passive restoration, through effects on plant emergence and survival. Also, we tested whether sowing date and water soaking, relevant factors when sowings are to be carried out, would affect seedling emergence and survival rates when compared with the effect of endozoochory. Most interesting in our analysis were the results for Carob tree (Ceratonia siliqua), a dry-fruited species being used in an ongoing action of artificial revegetation of this quarry located within a natural park in Portugal. Irrespective of the carnivore species, endozoochorous carob seeds collected in the quarry performed similarly to untreated seeds regarding emergence rates. Endozoochorous carob seedlings showed greater mortality rates but the net result for the plant can still be the colonization of recently vacant habitats by a large proportion of viable seeds. The later carob seeds were sown, the faster seedlings emerged, including endozoochorous seedlings. As expected, water soaking implied faster emergences. Broadly, plantings, sowings with previous soaking, and carnivore-mediated seed dispersal of this dry-fruited tree can jointly enhance quarry restoration. Implications for practiceO_LIRestorers can undertake pilot sowing experiments similar to ours prior to large scale revegetation campaigns to identify which species can benefit the most from endozoochory. C_LIO_LICarnivores in the surroundings of a quarry contribute a large proportion of viable seeds, likely assisting quarry passive restoration. C_LIO_LICarnivores ingesting carob seeds later in the fruiting season may assist quarry passive revegetation more readily as seeds ingested around that time emerge earlier. C_LIO_LIImmersion in tap water seems to be a simple, inexpensive, and a highly efficient method to break physical dormancy when carob seed sowings are to be carried out in degraded sites. C_LI

ecology↗

bioRxiv2016

Mocap: Large-scale inference of transcription factor binding sites from chromatin accessibility

Differential binding of transcription factors (TFs) at cis-regulatory loci drives the differentiation and function of diverse cellular lineages. Understanding the regulatory interactions that underlie cell fate decisions requires characterizing TF binding sites (TFBS) across multiple cell types and conditions. Techniques, e.g. ChIP-Seq can reveal genome-wide patterns of TF binding, but typically requires laborious and costly experiments for each TF-cell-type (TFCT) condition of interest. Chromosomal accessibility assays can connect accessible chromatin in one cell type to many TFs through sequence motif mapping. Such methods, however, rarely take into account that the genomic context preferred by each factor differs from TF to TF, and from cell type to cell type. To address the differences in TF behaviors, we developed Mocap, a method that integrates chromatin accessibility, motif scores, TF footprints, CpG/GC content, evolutionary conservation and other factors in an ensemble of TFCT-specific classifiers. We show that integration of genomic features, such as CpG islands improves TFBS prediction in some TFCT. Further, we describe a method for mapping new TFCT, for which no ChIP-seq data exists, onto our ensemble of classifiers and show that our cross-sample TFBS prediction method outperforms several previously described methods.

bioinformatics↗