Biology subjects

Gonzalez, A.

Publications and source records attributed to Gonzalez, A..

7 recordsLinked to original sources

bioRxiv2018

MyROOT: A novel method and software for the semi-automatic measurement of plant root length

Root analysis is essential for both academic and agricultural research. Despite the great advances in root phenotyping and imaging however, calculating root length is still performed manually and involves considerable amounts of labor and time. To overcome these limitations, we have developed MyROOT, a novel software for the semi-automatic quantification of root growth of seedlings growing directly in agar plates. Our method automatically determines the scale from the image of the plate, and subsequently measures the root length of the individual plants. To this aim, MyROOT combines a bottom-up root tracking approach with a hypocotyl detection algorithm. At the same time as providing accurate root measurements, MyROOT also significantly minimizes the user intervention required during the process. Using Arabidopsis, we tested MyROOT with seedlings from different growth stages. Upon comparing the data obtained using this software with that of manual root measurements, we found that there are no significant differences (t-test, p-value < 0.05). Thus, MyROOT will be of great aid to the plant science community by permitting high-throughput root length measurements while saving on both labor and time.

plant biology↗

bioRxiv2018

American Gut: an Open Platform for Citizen-Science Microbiome Research

Although much work has linked the human microbiome to specific phenotypes and lifestyle variables, data from different projects have been challenging to integrate and the extent of microbial and molecular diversity in human stool remains unknown. Using standardized protocols from the Earth Microbiome Project and sample contributions from over 10,000 citizen-scientists, together with an open research network, we compare human microbiome specimens primarily from the USA, UK, and Australia to one another and to environmental samples. Our results show an unexpected range of beta-diversity in human stool microbiomes as compared to environmental samples, demonstrate the utility of procedures for removing the effects of overgrowth during room-temperature shipping for revealing phenotype correlations, uncover new molecules and kinds of molecular communities in the human stool metabolome, and examine emergent associations among the microbiome, metabolome, and the diversity of plants that are consumed (rather than relying on reductive categorical variables such as veganism, which have little or no explanatory power). We also demonstrate the utility of the living data resource and cross-cohort comparison to confirm existing associations between the microbiome and psychiatric illness, and to reveal the extent of microbiome change within one individual during surgery, providing a paradigm for open microbiome research and education.\n\nImportanceWe show that a citizen-science, self-selected cohort shipping samples through the mail at room temperature recaptures many known microbiome results from clinically collected cohorts and reveals new ones. Of particular interest is integrating n=1 study data with the population data, showing that the extent of microbiome change after events such as surgery can exceed differences between distinct environmental biomes, and the effect of diverse plants in the diet which we confirm with untargeted metabolomics on hundreds of samples.

microbiology↗

bioRxiv2018

Inactivation of NUPR1 promotes cell death by coupling ER-stress responses with necrosis

Genetic inhibition of NUPR1 induces tumor growth arrest. Inactivation of NUPR1 expression in pancreatic cancer cells results in lower ATP production, higher consumption of glucose with a significant switch from OXPHOS to glycolysis followed by necrotic cell death. Importantly, induction of necrosis is independent of the caspase activity. We demonstrated that NUPR1 inactivation triggers a massive release of Ca2+ from the endoplasmic reticulum (ER) to the cytosol and a strong increase in ROS production by mitochondria with a concomitant relocalization of mitochondria to the vicinity of the ER. In addition, transcriptomic analysis of NUPR1-deficient cells shows the induction of an ER stress which is associated to a decrease in the expression of some ER stress response-associated genes. Indeed, during ER stress induced by the treatment with thapsigargin, brefeldin A or tunicamycin, an increase in the mitochondrial malfunction with higher induction of necrosis was observed in NUPR1-defficent cells. Finally, activation of NUPR1 during acute pancreatitis protects acinar cells of necrosis in mice. Altogether, these data enable us to describe a model in which inactivation of NUPR1 in pancreatic cancer cells results in an ER stress that induces a mitochondrial malfunction, a deficient ATP production and, as consequence, the cell death by necrosis.\n\nHighlightsNUPR1 expression promotes pancreatic cancer development and progression\n\nNUPR1-depletion is a promising therapeutic strategy to be used for treating cancers\n\nNUPR1-depletion induces ER stress, mitochondrial malfunction and a significant switch from OXPHOS to glycolysis followed by necrotic cell death\n\nInactivation of NUPR1 antagonizes cell growth by coupling a defective ER-stress response and a caspase-independent necrosis.

cell biology↗

bioRxiv2018

Epigallocatechin-3-Gallate Improves Facial Dysmorphology Associated with Down Syndrome

In Down syndrome (DS), the overall genetic imbalance caused by trisomy of chromosome 21 leads to a complex pleiotropic phenotype that involves a recognizable set of facial traits. Several studies have shown the potential of epigallocatechin-3-gallate (EGCG), a green tea flavanol, as a therapeutic tool for alleviating different developmental alterations associated with DS, such as cognitive impairment, skull dysmorphologies, and skeletal deficiencies. Here we provide for the first time experimental and clinical evidence of the potential benefits of EGCG treatment to facial morphology. Our results showed that mouse models treated with low dose of EGCG during pre- and postnatal development improved facial dysmorphology. However, the same treatment at high dose produced disparate facial morphology changes with an extremely wide and abnormal range of variation. Our observational study in humans revealed that EGCG treatment since early in development is associated with intermediate facial phenotypes and significant facial improvement scores. Overall, our findings suggest a potential beneficial effect of ECGC on facial development, which requires further research to pinpoint the optimal dosages of EGCG that reliably improve DS phenotypes. Current evidence warns against the non-prescribed intake of this supplement as a health-promoting measure.

pathology↗

bioRxiv2017

Patterns of selection reveal shared molecular targets over short and long evolutionary timescales

Standing and de novo genetic variants can both drive adaptation to environmental changes, but their relative contributions and interplay remain poorly understood. Here we investigated the dynamics of drug adaptation in yeast populations with different levels of standing variation by experimental evolution coupled with time-resolved sequencing and phenotyping. We found a doubling of standing variation alone boost the adaptation by 64.1% and 51.5% in hydroxyuea and rapamycin respectively. The causative standing and de novo variants were selected on shared targets of RNR4 in hydroxyurea and TOR1, TOR2 in rapamycin. The standing and de novo TOR variants map to different functional domains and act via distinct mechanisms. Interestingly, standing TOR variants from two domesticated strains exhibited opposite resistance effects, reflecting lineage-specific functional divergence. This study provides a dynamic view on how standing and de novo variants interactively drive adaptation and deepens our understanding of clonally evolving diseases.

genetics↗

bioRxiv2017

Improving the Generation and Selection of Virtual Populations in Quantitative Systems Pharmacology Models

Quantitative systems pharmacology (QSP) models aim to describe mechanistically the pathophysiology of disease and predict the effects of therapies on that disease. For most drug development applications, it is important to predict not only the mean response to an intervention but also the distribution of responses, due to inter-patient variability. Given the necessary complexity of QSP models, and the sparsity of relevant human data, the parameters of QSP models are often not well determined. One approach to overcome these limitations is to develop alternative virtual patients (VPs) and virtual populations (Vpops), which allow for the exploration of parametric uncertainty and reproduce inter-patient variability in response to perturbation. Here we evaluated approaches to improve the efficiency of generating Vpops. We aimed to generate Vpops without sacrificing diversity of the VPs pathophysiologies and phenotypes. To do this, we built upon a previously published approach (Allen, Rieger et al. 2016) by (a) incorporating alternative optimization algorithms (genetic algorithm and Metropolis-Hastings) or alternatively (b) augmenting the optimized objective function. Each method improved the baseline algorithm by requiring significantly fewer plausible patients (precursors to VPs) to create a reasonable Vpop. #ddct #qsp

pharmacology and toxicology↗

bioRxiv2017

Integration And Differentiation Of Neural Information Dissociate Between Conscious Percepts

At any given moment, we experience a perceptual scene as a single whole and yet we may distinguish a variety of objects within it. This phenomenon instantiates two properties of conscious perception: integration and differentiation. Integration to experience a collection of objects as a unitary percept, and differentiation to experience these objects as distinct from each other. Here we evaluated the neural information dynamics underlying integration and differentiation of perceptual contents during bistable perception. Participants listened to a sequence of tones (auditory bistable stimuli) experienced either as a single stream (perceptual integration) or as two parallel streams (perceptual differentiation) of sounds. We computed neurophysiological indices of information integration and information differentiation with electroencephalographic and intracranial recordings. When perceptual alternations were endogenously driven, the integrated percept was associated with an increase in neural information-integration and a decrease in neural differentiation across frontoparietal regions, whereas the opposite pattern was observed for the differentiated percept. However, when perception was exogenously driven by a change in the sound stream (no bistability) neural oscillatory power distinguished between percepts but information measures did not. We demonstrate that perceptual integration and differentiation can be mapped to theoretically-motivated neural information signatures, suggesting a direct relationship between phenomenology and neurophysiology.

neuroscience↗