Biology subjects

Garcia, D. A.

Publications and source records attributed to Garcia, D. A..

3 recordsLinked to original sources

bioRxiv2021

Assembling an illustrated family-level tree of life for exploration in mobile devices

Since the concept of the tree of life was introduced by Darwin about a century and a half ago, a considerable fraction of the scientific community has focused its efforts on its reconstruction, with remarkable progress during the last two decades with the advent of DNA sequences. However, the assemblage of a comprehensive tree of life for its exploration has been a difficult task to achieve due to two main obstacles: i) information is scattered into a plethora of individual sources and ii) practical visualization tools for exceptionally large trees are lacking. To overcome both challenges, we aimed to synthetize a family-level tree of life by compiling over 1400 published phylogenetic studies, ensuring that the source trees represent the best phylogenetic hypotheses to date based on a set of objective criteria. Moreover, we dated the synthetic tree by employing over 550 secondary-calibration points, using publicly available sequences for more than 5000 taxa, and by incorporating age ranges from the fossil record for over 2800 taxa. Additionally, we developed a mobile app (Tree of Life) for smartphones in order to facilitate the visualization and interactive exploration of the resulting tree. Interactive features include an easy exploration by zooming and panning gestures of touch screens, collapsing branches, visualizing specific clades as subtrees, a search engine, a timescale to determine extinction and divergence dates, and quick links to Wikipedia. Small illustrations of organisms are displayed at the tips of the branches, to better visualize the morphological diversity of life on earth. Our assembled Tree of Life currently includes over 7000 taxonomic families (about half of the total family-level diversity) and its content will be gradually expanded through regular updates to cover all life on earth at family-level.

evolutionary biology↗

bioRxiv2019

A New Model for Single-Molecule Tracking Analysis of Transcription Factor Dynamics

Single-molecule tracking (SMT) allows the study of transcription factor (TF) dynamics in the nucleus, giving important information regarding the search and binding behaviour of these proteins in the nuclear environment. Dwell time distributions for most TFs have been described by SMT to follow bi-exponential behaviour. This is consistent with the existence of two discrete populations bound to chromatin in vivo, one non-specifically bound to chromatin (i.e. searching mode) and another specifically bound to target sites, as originally defined by decades of biochemical studies. However, alternative models have started to emerge, from multiple exponential components to power-law distributions. Here, we present an analytical pipeline with an unbiased model selection approach based on different statistical metrics to determine the model that best explains SMT data. We found that a broad spectrum of TFs (including glucocorticoid receptor, oestrogen receptor, FOXA1, CTCF) follow a power-law distribution, blurring the temporal line between non-specific and specific binding, and suggesting that productive binding may involve longer binding events than previously thought. We propose a continuum of affinities model to explain the experimental data, consistent with the movement of TFs through complex interactions with multiple nuclear domains as well as binding and searching on the chromatin template.

biophysics↗

bioRxiv2017

Bulk degradation of dendritic cargos requires Rab7-dependent transport in Rab7-positive/LAMP1-negative endosomes to somatic lysosomes.

Regulation of protein homeostasis (\"proteostasis\") is necessary for maintaining healthy cells. Disturbances in proteostasis lead to aggregates, cellular stress and can result in toxicity. There is thus great interest in when and where proteins are degraded in cells. Neurons are very large as well as very long-lived, creating unusually high needs for effective regulation of protein turnover in time and space. We previously discovered that the dendritic membrane proteins Nsg1 and Nsg2 are short-lived with half-lives of less than two hours. Their short half-lives enabled us to ask whether these proteins are degraded by local degradative pathways in dendrites. We discovered a striking spatial gradient of late endosomes/lysosomes in dendrites, with late endosomes (Rab7-positive/LAMP1-negative/cathepsinB-negative) found in distal portion of dendrites, and degradative lysosomes (LAMP1-positive/cathepsinB-positive) being overwhelmingly found in the soma and in the proximal portion of dendrites. Surprisingly, the majority of dendritic Rab7-positive late endosomes do not contain LAMP1, unlike Rab7-positive late endosomes in fibroblasts. Secondly, Rab7 activity is required to mobilize these distal pre-degradative dendritic late endosomes for transport to the soma and degradation. We conclude that the vast majority of dendritic LAMP1-positive endosomes are not degradative lysosomes and that bulk degradation of dendritic cargos, such as Nsg1, Nsg2, and DNER, requires Rab7-dependent transport in late endosomes to somatic lysosomes.

cell biology↗