Biology subjects

Gonzalez, R.

Publications and source records attributed to Gonzalez, R..

44 records · Page 3Linked to original sources

bioRxiv2019

Quantification of malaria antigens PfHRP2 and pLDH by quantitative suspension array technology in whole blood, dried blood spot and plasma

BackgroundMalaria diagnostics by rapid diagnostic tests (RDTs) relies primarily on the qualitative detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and Plasmodium sp lactate dehydrogenase (pLDH). As novel RDTs with increased sensitivity are being developed and implemented as point of care diagnostics, highly sensitive laboratory based assays are needed for evaluating RDTs performance. Here, a quantitative suspension array technology (qSAT) was developed, validated and applied for the simultaneous detection of PfHRP2 and pLDH in a variety of clinical samples (whole blood, plasma and dried blood spots) from different endemic countries.\n\nResultsThe qSAT was specific for the target antigens, with analytical ranges of 6.8 to 762.8 pg/ml for PfHRP2 and 78.1 to 17076.6 pg/ml for P. falciparum (Pf-LDH). The assay detected P. vivax LDH (Pv-LDH) at a lower sensitivity than Pf-LDH (analytical range of 1093.20 to 187288.5 pg/ml). Both PfHRP2 and pLDH levels determined using the qSAT showed to positively correlate with parasite densities determined by quantitative PCR (Spearman r=0.59 and 0.75, respectively) as well as microscopy (Spearman r=0.40 and 0.75, respectively), suggesting the assay to be a good predictor of parasite density.\n\nConclusionThis immunoassay can be used as a reference test for the detection and quantification of PfHRP2 and pLDH, and could serve for external validation of RDTs performance, to determine antigen persistence after parasite clearance, as well as a complementary tool to assess malaria burden in endemic settings.

microbiology↗

bioRxiv2019

Role of host genetic diversity for susceptibility-to-infection in the evolution of virulence of a plant virus

Predicting viral emergence is difficult due to the stochastic nature of the underlying processes and the many factors that govern pathogen evolution. Environmental factors affecting the host, the pathogen and the interaction between both are key in emergence. In particular, infectious disease dynamics are affected by spatiotemporal heterogeneity in their environments. A broad knowledge of these factors will allow better estimating where and when viral emergence is more likely to occur. Here we investigate how the population structure for susceptibility-to-infection genes of the plant Arabidopsis thaliana shapes the evolution of Turnip mosaic virus (TuMV). For doing so we have evolved TuMV lineages in two radically different host population structures: (i) multiple genetically homogeneous A. thaliana subpopulations and (ii) a single maximally genetically heterogeneous population. We found faster adaptation of TuMV to homogeneous than to heterogeneous host populations. However, viruses evolved in heterogeneous host populations were more pathogenic and infectious than viruses evolved in the homogeneous population. Furthermore, the viruses evolved in homogeneous populations showed stronger signatures of local specialization than viruses evolved in heterogeneous populations. These results illustrate how the genetic diversity of hosts in an experimental ecosystem favors the evolution of virulence of a pathogen.

evolutionary biology↗

bioRxiv2019

Land-use and related pressures have reduced biotic integrity more on islands than on mainlands

Tracking progress towards biodiversity targets requires indicators that are sensitive to changes at policy-relevant scales, can easily be aggregated to any spatial scale and are simple to understand. The Biodiversity Intactness Index (BII), which estimates the average abundance of a diverse set of organisms in a given area relative to their reference populations, was proposed in 2005 in response to this need. A new implementation of BII was developed as part of the PREDICTS project in 2016 and has been adopted by GEO BON, IPBES and CBD. The previous global models for BII estimation could not account for pressures having different effects in different settings. Islands are a setting of particular interest: many are home to a disproportionate number of endemic species; oceanic islands may have relatively low overall species diversity because of their isolation; and the pattern and timing of human pressures can be very different from that seen on mainlands. Here, we test whether biotic integrity - as estimated by BII - has decreased more severely on islands than mainlands. We update methods previously used to estimate BII globally (Newbold et al., 2016) to allow pressure effects to differ between islands and mainlands, while also implementing some other recent improvements in modelling. We estimate BII for islands and mainlands by combining global models of how two aspects of biodiversity - overall abundance, and compositional similarity to minimally-impacted sites - have been affected by human pressures. We use these models to project high-resolution ([~]1km2) global maps of BII for the year 2005. We calculate average BII for island and mainland biomes, countries, IPBES regions and biodiversity hotspots; and repeat our analyses using a richness-based version of BII. BII on both islands and mainlands has fallen below the values proposed as safe limits across most regions, biomes and biodiversity hotspots. Our BII estimates are lower than those published in 2016, globally, within all biodiversity hotspots and within most biomes, and show greater spatial heterogeneity; detailed analysis of these differences shows that they arise mostly from a combination of improvements to the modelling framework. Average BII does not strongly differ between islands and mainlands, but richness-based BII has fallen by more on islands. It seems native species are more negatively affected by rising human population density and road development on islands than mainlands, and islands have seen more land conversion. Our results highlight the parlous state of biodiversity native to islands.

ecology↗

bioRxiv2019

Pancreatic tumor organoids for modeling in vivo drug response and discovering clinically-actionable biomarkers

Patient-derived models are transforming translational cancer research. It is not clear if the emergence of patient-derived organoid (PDO) models can extend the utility of the widely used patient-derived xenograft (PDX). In addition, the utility of PDO models for serum biomarker discovery is not known. Here, we demonstrate that PDO models recapitulate the genomics, cell biology, glycomics and drug responses observed in PDX models. Furthermore, we demonstrate the applicability of PDO models for identification of N-glycans that are enriched in the glycome of pancreatic ductal adenocarcinoma (PDAC). Surprisingly, among all the glycans observed in PDX and PDOs, a core set of 57 N-glycans represent 50-94% of the relative abundance of all N-glycans detected, suggesting that only a subset of glycans dominate the cell surface landscape in PDAC. In addition, we outline a tumor organoid-based pipeline to identify surface proteins in extracellular vesicles (EV) from media supernatant of PDO cultures. When combined with the affinity-based validation platform, the EV surface proteins discovered in PDOs are effective in differentiating patients with PDAC from those with benign pancreatitis in the clinic, identifying PDO as powerful discovery platform for serum biomarkers. Thus, PDOs extend the utility of the archival collections of PDX models for translational research and function as a powerful platform for identification of clinically-actionable biomarkers in patients blood. Significance statementTumor organoids extend the utility of PDX models as platforms for investigating drug response, glycosylation changes and function as new platforms for discovering blood-based biomarkers

cancer biology↗

bioRxiv2018

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.\n\nHighlightsO_LIAn overview of the MRI processing pipeline for the ABCD Study\nC_LIO_LIA discussion on the challenges of large, multisite population studies\nC_LIO_LIA methodological reference for users of publicly shared data from the ABCD Study\nC_LI

neuroscience↗

bioRxiv2018

Pitch perception is adapted to species-specific cochlear filtering

Pitch perception is critical for recognizing speech, music and animal vocalizations, but its neurobiological basis remains unsettled, in part because of divergent results from different species. We used a combination of behavioural measurements and cochlear modelling to investigate whether species-specific differences exist in the cues used to perceive pitch and whether these can be accounted for by differences in the auditory periphery. Ferrets performed a pitch discrimination task well whenever temporal envelope cues were robust, but not when resolved harmonics only were available. By contrast, human listeners exhibited the opposite pattern of results on an analogous task, consistent with previous studies. Simulated cochlear responses in the two species suggest that the relative salience of the two types of pitch cues can be attributed to differences in cochlear filter bandwidths. Cross-species variation in pitch perception may therefore reflect the constraints of estimating a sounds fundamental frequency given species-specific cochlear tuning.

neuroscience↗

bioRxiv2018

Worldwide impacts of past and projected future land-use change on local species richness and the Biodiversity Intactness Index

Although people have modified the world around us throughout human history, the Great Acceleration has seen drivers such as land conversion, exploitation of natural populations, species introductions, pollution and human-induced climate change placing biodiversity under increasing pressure. In this paper we examine 1) how terrestrial species communities have been impacted over the last thousand years of human development and 2) how plausible futures defined by alternative socio-economic scenarios are expected to impact species communities in the future. We use the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) database to model impacts of land-use change and human population on local species richness, community abundance, and biodiversity intactness using a mixed-effects modelling structure. Historical impacts are inferred through projection of model results onto maps of historical land use, provided by the land-use harmonization project, and gridded human population density (HYDE 3.1). Future impacts are explored using the Shared Socio-economic Pathway (SSP) scenarios. These scenarios detail five plausible global futures based upon socio-economic factors such as wealth, population, education, technology, and reliance on fossil fuels, and can be combined with Representative Concentration Pathway (RCP) scenarios to consider climate mitigation strategies. We project model results onto the gridded outputs of six SSP/RCP scenario combinations: SSP1/RCP2.6, SSP2/RCP4.5, SSP3/RCP7.0, SSP4/RCP3.4, SSP4/RCP6.0, and SSP5/RCP8.5. Historical trend lines show that most losses in local biodiversity are relatively recent, with 75% of all loss in both abundance-based Biodiversity Intactness Index and species richness occurring post-1800. Stark regional differences emerge in all future scenarios, with biodiversity in African regions undergoing greater losses than Oceania, North America and the European regions. Although climate change is expected to have severe detrimental impacts to biodiversity - which are not quantified in these results - it is important to consider how the climate change mitigation itself may also impact biodiversity. Our results suggest that strong climate change mitigation through biofuel production will detrimentally impact biodiversity: SSP4/RCP3.4 (with high biofuel mitigation) is predicted to see two times the decrease in abundance-based biodiversity intactness and three times the decrease in local species richness between 2015-2100 as is predicted for SSP4/RCP6.0 (with lower levels of mitigation). SSP4/RCP3.4 forecasts the greatest impact to average local species richness of all the SSP/RCP combinations with an average loss of 13% of local species richness projected to have occurred by 2100. SSP3/RCP7.0 - a scenario describing a globally segregated, and economically protectionist future with low climate change mitigation - has the worst impacts on abundance-based biodiversity intactness with an average loss of 26% of intactness by 2100. However, a brighter future is possible; SSP1/RCP2.6 describes a more sustainable future, where human populations are provided for without further jeopardising environmental integrity - in this scenario we project that biodiversity will recover somewhat, with gains in biodiversity intactness and species richness in many regions of the world by 2100.

ecology↗

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↗