Biology subjects

Gonzalez, J. M.

Publications and source records attributed to Gonzalez, J. M..

17 recordsLinked to original sources

bioRxiv2025

Functional redundancy enables emergent metabolic dynamics in marine microbiomes

Understanding how marine microbiomes will respond to ongoing global change is crucial. Functional redundancy, the capacity of different microbes to perform the same function, is considered a key mechanism underpinning the stability and resilience of the ocean microbiome. Although the extent of functional redundancy remains debated, investigating its manifestation in environmentally similar and interconnected microbial communities may provide critical insights into its role in shaping microbial community dynamics. We hypothesized that examining the long-term synchrony and rhythmicity of temperate microbial communities in such locations could provide insight into the role of functional redundancy. High functional redundancy at the community level would manifest as rhythmic and synchronous metabolic functions across sites, even in the absence of synchrony or rhythmicity at finer organizational levels, such as individual genes or taxa, thereby contributing to community resilience. Conversely, low functional redundancy would imply that synchrony and rhythmicity extend to both the contributing genes and taxa, suggesting a greater vulnerability of the community to environmental variability. To test this framework, we analyzed the long-term synchrony and rhythmicity of two marine-coastal microbiomes in the Mediterranean Sea, separated by approximately 150 km and connected by a dominant southwest current. Monthly collected metagenomes from a seven-year period were examined at the levels of metabolic functions (e.g., KEGG pathways), predicted genes (open reading frames), and taxa. We found functions, genes, and taxa exhibiting high, low, or anti-synchrony, as well as displaying rhythmic or non-rhythmic patterns. Although rhythmic behavior was observed on average across all organizational levels, consistent with the seasonal dynamics expected in temperate Mediterranean waters, average synchrony across microbiomes remained low. Focusing specifically on 45 markers of key biogeochemical functions, we revealed that several functions exhibited high synchrony and rhythmicity, in sharp contrast to the low synchrony and rhythmicity among the most abundant genes and taxa contributing to those functions. This suggests that functional redundancy and complementary dynamics at lower organizational levels, with distinct taxa contributing to key metabolic functions at different times, lead to rhythmic and synchronous dynamics at higher levels through emergent self-organization. Together, our results highlight functional redundancy and emergent self-organized dynamics as key mechanisms supporting the stability and resilience of marine microbiomes under environmental change.

ecology↗

bioRxiv2025

Transcriptomic comparison of early onset preeclampsia and placenta accreta identifies inverse trophoblast and decidua functions at the maternal-fetal interface

Early onset preeclampsia is a placental disorder characterized by shallow implantation, whereas placenta accreta spectrum is a placental disorder of deep placental attachment. This study compares the transcriptome of these two obstetric syndromes. By integrating available microarray and single-cell placenta/decidua transcriptomic datasets, we demonstrated that early onset preeclampsia genes are inversely expressed in placenta accreta, with the most marked differences noted in cell types of decidua, endothelial, and extravillous trophoblasts. Our findings highlight the key functions of trophoblast cell migration and invasion, decidua cell signaling, hypoxia pathways, and global growth factor and collagen contributions to these pregnancy disorders. This research provides new insights into the mechanisms of placentation and unifies these clinical siloes of disease by focusing on the fundamental biology of placental development at the maternal-fetal interface.

molecular biology↗

bioRxiv2024

A Multiomics, Spatiotemporal, and Single Cell Atlas for Mapping Cell-Type-Specific Dysregulation at the Maternal-Fetal Interface

The placenta, the first organ to functionally mature, undergoes disordered development in many pregnancy complications. Molecular investigations have been hampered by the extreme cellular heterogeneity of the placenta, and this complexity is further exaggerated at the maternal-fetal interface where maternal and fetal cells co-mingle. We generated the paired single nucleus epigenomes and transcriptome for each of [~]200,000 cells at the human maternal-fetal interface from early pregnancy to term. These data identified cell-type-specific transcriptional regulatory programs and uncovered key transcription factors driving the lineage differentiation of placental cytotrophoblasts. Integrating spatial single cell proteomics profiling, we localized the observed cell types in situ, and characterized the dynamic stages and distinct features of endothelial cells of maternal spiral arteries remodeled by extravillous cytotrophoblasts. Integrative analyses of the single cell data across gestation enabled fine-mapping of the developmental trajectories of cytotrophoblasts and decidual stromal cells, and defining the signature molecular profiles of known and novel cell (sub)types. To demonstrate clinical value, we integrated the reference single cell data with large-scale population genomes from pregnancy complications and identified the most vulnerable maternal and fetal cell types in preeclampsia, preterm birth, and miscarriage. This study presents the most comprehensive placental and decidual single cell resource across gestation to date, reveals new insights into the drivers of normal human placentation, and uncovers the cellular basis of dysfunction associated with common pregnancy complications.

genomics↗

bioRxiv2023

Gene expression response to temperature acclimation in a model photoheterotrophic marine flavobacterium (Dokdonia sp. MED134)

Temperature stands as one of the key factors influencing the community structure and distribution of marine microorganisms. Yet, the physiological adaptations of marine bacteria to rising temperatures remain underexplored. This study examines the transcriptional response of Dokdonia sp. MED134, a proteorhodopsin-based phototrophic organism within the class Flavobacteriia, to a gradient of temperature acclimation conditions from 10 to 34{degrees}C. Light availability during day/night cycles exerted minimal influence on the transcriptional patterns of this strain, with only a few genes mostly related to light sensing, light protecting mechanisms and phototrophy being upregulated during daytime. By contrast, temperature significantly impacted the expression of a large fraction of MED134 genes (>60%), including components of the stress response, cellular translation, DNA replication, and some metabolic pathways such as the anaplerotic carbon fixation and the glyoxylate shunt, suggesting intracellular carbon flow adjustments to temperature. Notably, the expression of some highly expressed TonB transporters, prominent in flavobacteria, was also temperature-sensitive. Our findings provide insights into the transcriptional adjustments of Dokdonia sp. MED134 in response to temperature variations, suggesting potential implications for carbon cycling and organic matter processing in marine environments.

microbiology↗

bioRxiv2023

Systematic assessment of long-read RNA-seq methods for transcript identification and quantification

AbstractThe Long-read RNA-Seq Genome Annotation Assessment Project (LRGASP) Consortium was formed to evaluate the effectiveness of long-read approaches for transcriptome analysis. The consortium generated over 427 million long-read sequences from cDNA and direct RNA datasets, encompassing human, mouse, and manatee species, using different protocols and sequencing platforms. These data were utilized by developers to address challenges in transcript isoform detection and quantification, as well as de novo transcript isoform identification. The study revealed that libraries with longer, more accurate sequences produce more accurate transcripts than those with increased read depth, whereas greater read depth improved quantification accuracy. In well-annotated genomes, tools based on reference sequences demonstrated the best performance. When aiming to detect rare and novel transcripts or when using reference-free approaches, incorporating additional orthogonal data and replicate samples are advised. This collaborative study offers a benchmark for current practices and provides direction for future method development in transcriptome analysis.

genomics↗

bioRxiv2023

Quantifying microbial guilds

The ecological role of microorganisms is of utmost importance due to their multiple interactions with the environment. However, assessing the contribution of individual taxonomic groups has proven difficult despite the availability of high throughput data, hindering our understanding of such complex systems. Here, we propose a quantitative definition of guild that is readily applicable to metagenomic data. Our framework focuses on the functional character of protein sequences, as well as their diversifying nature. First, we discriminate functional sequences from the whole sequence space corresponding to a gene annotation to then quantify their contribution to the guild composition across environments. In addition, we identify and distinguish functional implementations, which are sequence spaces that have different ways of carrying out the function. We demonstrate the value of our approach with two case studies: the ammonia oxidation and polyamine uptake guilds from the Malaspina circumnavigation cruise, revealing novel ecological dynamics of the latter in marine ecosystems. Thus, the quantification of guilds helps to assess the functional role of different taxonomic groups with profound implications on the study of microbial communities.

ecology↗

bioRxiv2021

Cytogenetic evidence supports Avena insularis being closely related to hexaploid oats.

Cytogenetic observations, phylogenetic studies and genome analysis using high-density genetic markers have suggested a tetraploid Avena species carrying the C and D genomes (formerly C and A) to be the donor of all hexaploid oats (AACCDD). However, controversy surrounds which of the three extant CCDD tetraploid species - A. insularis, A. maroccana and A. murphyi - is most closely related to hexaploid oats. The present work describes a comparative karyotype analysis of these three CCDD tetraploid species and two hexaploid species, A. sativa and A. byzantina. This involved the use of FISH with six simple sequence repeats (SSRs) with the motifs CT, AAC, AAG, ACG, ATC and ACT, two repeated ribosomal sequences, and C genome-specific repetitive DNA. The hybridization pattern of A. insularis with oligonucleotide (AC)10 was also determined and compared with those previously published for A. sativa and A. byzantina. Significant differences in the 5S sites and SSR hybridization patterns of A. murphyi compared to the other CCDD species rule out its being directly involved in the origin of the hexaploids. In contrast, the repetitive and SSR hybridization patterns shown by the D genome chromosomes, and by most of the C genome chromosomes of A. maroccana and A. insularis, can be equated with the corresponding chromosomes of the hexaploids. Several chromosome hybridization signals seen for A. insularis, but not for A. maroccana, were shared with the hexaploid oats species, especially with A. byzantina. These diagnostic signals add weight to the idea that the extant A. insularis, or a direct ancestor of it, is the most closely related progenitor of hexaploid oats. The similarity of the chromosome hybridization patterns of the hexaploids and CCDD tetraploids was taken as being indicative of homology. A common chromosome nomenclature for CCDD species based on that of the hexaploid species is proposed.

plant biology↗

bioRxiv2021

A community-driven roadmap to advance research on translated open reading frames detected by Ribo-seq

Ribosome profiling (Ribo-seq) has catalyzed a paradigm shift in our understanding of the translational vocabulary of the human genome, discovering thousands of translated open reading frames (ORFs) within long non-coding RNAs and presumed untranslated regions of protein-coding genes. However, reference gene annotation projects have been circumspect in their incorporation of these ORFs due to uncertainties about their experimental reproducibility and physiological roles. Yet, it is indisputable that certain Ribo-seq ORFs make stable proteins, others mediate gene regulation, and many have medical implications. Ultimately, the absence of standardized ORF annotation has created a circular problem: while Ribo-seq ORFs remain unannotated by reference biological databases, this lack of characterisation will thwart research efforts examining their roles. Here, we outline the initial stages of a community-led effort supported by GENCODE / Ensembl, HGNC and UniProt to produce a consolidated catalog of human Ribo-seq ORFs.

genomics↗

bioRxiv2021

Taxon-specific shifts in bacterial and archaeal transcription of dissolved organic matter cycling genes in a stratified fjord

A considerable fraction of organic matter derived from photosynthesis in the euphotic zone settles into the oceans interior, and under way is degraded by diverse microbial consortia that utilize a suite of extracellular enzymes and membrane transporters. Still, the molecular details that regulate carbon cycling across depths remain little explored. As stratification in fjords has made them attractive models to explore patterns in biological oceanography, we here analyzed bacterial and archaeal transcription in samples from five depth layers in the Gullmar Fjord, Sweden. Transcriptional variation over depth correlated with gradients in chlorophyll a and nutrient concentrations. Differences in transcription between sampling dates (summer and early autumn), were strongly correlated with ammonium concentrations, which potentially was linked with a stronger influence of (micro-)zooplankton grazing in summer. Transcriptional investment in carbohydrate-active enzymes (CAZymes) decreased with depth and shifted toward peptidases, partly a result of elevated CAZyme transcription by Flavobacteriales, Cellvibrionales and Synechococcales at 2-25 m and a dominance of peptidase transcription by Alteromonadales and Rhodobacterales from 50 m and down. In particular, CAZymes for chitin, laminarin, and glycogen were important. High levels of transcription of ammonium transporters by Thaumarchaeota at depth (up to 18% of total transcription), along with the genes for ammonia oxidation and CO2-fixation, indicated that chemolithoautotrophy contributed to the carbon flux in the fjord. The taxon-specific expression of functional genes for processing of the marine DOM pool and nutrients across depths emphasizes the importance of different microbial foraging mechanisms across spatiotemporal scales for shaping biogeochemical cycles. IMPORTANCEIt is generally recognized that stratification in the ocean strongly influences both the community composition and the distribution of ecological functions of microbial communities, which in turn are expected to shape the biogeochemical cycling of essential elements over depth. Here we used metatranscriptomics analyses to infer molecular detail on the distribution of gene systems central to the utilization of organic matter in a stratified marine system. We thereby uncovered that pronounced shifts in transcription of genes encoding CAZymes, peptidases, and membrane transporters occurred over depth among key prokaryotic orders. This implies that sequential utilization and transformation of organic matter through the water column is a key feature that ultimately influences the efficiency of the biological carbon pump.

ecology↗

bioRxiv2020

Endozoochory by parrotfish replenishes reefs with coral-associated microbiome

Sparisoma viride is the most abundant parrotfish in the Caribbean and is considered as the most important excavator due to corallivore behaviour. Parrotfishes are a keystone group that favour the growth and resilience of coral reefs removing macroalgae and structuring the benthic communities. The microbial symbiotic communities are involved in multiple functions related to nutrition and immunity maintaining corals health. Because S. viride scrape coral tissues, the skeleton and the algae on coral, it could be important reservoirs or vectors of microorganism for the corals through the faeces dispersion, however, the role of parrotfishes as reservoirs are poorly studied. Establishing microbial communities present in parrotfish faeces will contribute to understand the ecological impact of parrotfishes in coral resilience. We investigated the composition of disseminated bacteria and the extent to which the cell integrity of dinoflagellate photosymbionts (Symbiodiniaceae) is maintained in the faeces and compare with sediments and water column controls. Then, we analysed diversity and structure of bacterial communities at family level and search similarities between faeces of the study and coral associated microbiome reported in the literature. Similar levels of structural integrity and photosynthetic health of Symbidiodinaceae cells were found in both faeces and reef sediments. Besides, the sediments microbiome echoes the parrotfish faecal microbiome by sharing high diversity and a similar bacterial community composition. Several bacterial families were present in parrotfish faeces and in coral microbiome reported in the literature highlighting the dispersal potential of parrotfishes replenishing coral reefs. Despite the sampling limitations, these findings uncover the potential role of the excavator parrotfish in enriching environmental reservoirs, especially reef sediments, with coral-associated bacteria and photosynthetic microalgae. Parrotfishes could reinforce the coral microbiome and facilitate coral symbiont acquisition, key features critical to maintaining the fitness of one of the most threatened ecosystems on Earth. This finding could be considered as a first step in uncovering a mechanism for reef-microbiome maintenance.

ecology↗

bioRxiv2020

Dog Savior: Immediate Scent-Detection of SARS-COV-2 by Trained Dogs

Molecular tests for viral diagnostics are essential to confront the COVID-19 pandemic, but their production and distribution cannot satisfy the current high demand. Early identification of infected people and their contacts is the key to being able to isolate them and prevent the dissemination of the pathogen; unfortunately, most countries are unable to do this due to the lack of diagnostic tools. Dogs can identify, with a high rate of precision, unique odors of volatile organic compounds generated during an infection; as a result, dogs can diagnose infectious agents by smelling specimens and, sometimes, the body of an infected individual. We trained six dogs of three different breeds to detect SARS-CoV-2 in respiratory secretions of infected patients and evaluated their performance experimentally, comparing it against the gold standard (rRT-PCR). Here we show that viral detection takes one second per specimen. After scent-interrogating 9,200 samples, our six dogs achieved independently and as a group very high sensitivity, specificity, predictive values, accuracy, and likelihood ratio, with very narrow confidence intervals. The highest metric was the negative predictive value, indicating that with a disease prevalence of 7.6%, 99.9% of the specimens indicated as negative by the dogs did not carry the virus. These findings demonstrate that dogs could be useful to track viral infection in humans, allowing COVID-19 free people to return to work safely.

microbiology↗

bioRxiv2020

Structure-guided phylogenetic reconstruction of the superfamily of proteins sharing the metallo-β-lactamase fold

The superfamily of metallo-{beta}-lactamases (MBL) comprises an ancient group of proteins found in all domains of life, sharing a characteristic {beta}{beta} fold and a histidine-rich motif for binding of transition metal ions, with the ability to catalyze a variety of hydrolysis and redox reactions. Herein, structural homology and sequence similarity network (SSN) analysis are used to assist the phylogenetic reconstruction of the MBL superfamily, introducing tanglegrams to evaluate structure-function relationships. SSN neighborhood connectivity is applied for spotting protein families within SSN clusters, showing that 98 % of the superfamily remains to be explored experimentally. Further SSN research is suggested in order to determine their topological properties, which will be instrumental for the improvement of automated sequence annotation methods.

bioinformatics↗

bioRxiv2020

ATR expands embryonic stem cell fate potential in response to replication stress

Unrepaired DNA damage during embryonic development can be potentially inherited by a large population of cells. However, the quality control mechanisms that minimize the contribution of damaged cells to developing embryos remain poorly understood. Here, we uncovered an ATR- and CHK1-mediated transcriptional response to replication stress (RS) in ESCs that induces genes expressed in totipotent two-cell (2C) stage embryos and 2C-like cells. This response is mediated by Dux, a multicopy retrogene defining the cleavage-specific transcriptional program in placental mammals. In response to RS, DUX triggers the transcription of 2C-like markers such as murine endogenous retrovirus-like elements (MERVL) and Zscan4. This response can also be elicited by ETAA1-mediated ATR activation in the absence of RS. ATR-mediated activation of DUX requires GSRF1 dependent post-transcriptional regulation of Dux mRNA. Strikingly, activation of ATR expands ESCs fate potential by extending their contribution to both embryonic and extra{-}embryonic tissues. These findings define a novel ATR dependent pathway involved in maintaining genome stability in developing embryos by controlling ESCs fate in response to RS.

cell biology↗

bioRxiv2019

New peptides with immunomodulatory activity in macrophages and antibacterial activity against multiresistant Staphylococcus aureus

Staphylococcus aureus infections are a common concern world-wide due to the increasing number of bacterial strains with multiresistant properties to existing antibiotics, incrementing the need for novel molecules and therapy approaches for their treatment. This study evaluated the antibacterial and immunomodulatory activity of eight new peptides (AA, KS, NS, RN, AT, GF, KV and LK) as the basis for the search of new antibacterial and therapeutic agents for topic prevention and treatment against S. aureus infections. Here, there are characterized in silico eight new antimicrobial peptides. Their antibacterial activity against S. aureus and cytotoxic activity in mammalian cell lines were evaluated in vitro with the peptides individually and combined. Three of the peptides (GF, AT and AA) immunomodulatory activity was assessed in macrophages and under three scenarios: non-stimulation, Escherichia coli LPS stimulation and S. aureus lysate stimulation. Results showed that three peptides individually showed the best antibacterial activity against the S. aureus bacteria evaluated. The peptides presented immunomodulatory activity in THP-1 macrophages by displaying different profiles, increasing or decreasing four cytokines (IL-1{beta}, TNF-, IL-8 and CCL2 (MCP1)). This activity depended on the peptide concentration and the stimulation in which the macrophages were exposed to. Taken together, these results demonstrate the potential of these peptides to be used in further studies as novel antimicrobial molecules for the prevention and treatment of S. aureus infections.

microbiology↗

bioRxiv2019

Expert Curation of the Human and Mouse Olfactory Receptor Gene Repertoires Identifies Conserved Coding Regions Split Across Two Exons

Olfactory receptor (OR) genes are the largest multi-gene family in the mammalian genome, with over 850 in human and nearly 1500 genes in mouse. The expansion of the OR gene repertoire has occurred through numerous duplication events followed by diversification, resulting in a large number of highly similar paralogous genes. These characteristics have made the annotation of the complete OR gene repertoire a complex task. Most OR genes have been predicted in silico and are typically annotated as intronless coding sequences. Here we have developed an expert curation pipeline to analyse and annotate every OR gene in the human and mouse reference genomes. By combining evidence from structural features, evolutionary conservation and experimental data, we have unified the annotation of these gene families, and have systematically determined the protein-coding potential of each locus. We have defined the non-coding regions of many OR genes, enabling us to generate full-length transcript models. We found that 13 human and 41 mouse OR loci have coding sequences that are split across two exons. These split OR genes are conserved across mammals, and are expressed at the same level as protein-coding OR genes with an intronless coding region. Our findings challenge the long-standing and widespread notion that the coding region of a vertebrate OR gene is contained within a single exon.

genomics↗

bioRxiv2019

Metabolic Architecture of the Deep Ocean Microbiome

The deep sea, the largest compartment of the ocean, is an essential component of the Earth system, but the functional exploration of its microbial communities lags far behind that of other marine realms. Here we analyze 58 bathypelagic microbial metagenomes from the Atlantic, Indian, and Pacific Oceans in an unprecedented sampling effort from the Malaspina Global Expedition, to resolve the metabolic architecture of the deep ocean microbiome. The Malaspina Deep-Sea Gene Collection, 71% of which consists of novel genes, reveals a strong dichotomy between the functional traits of free-living and particle-attached microorganisms, and shows relatively patchy composition challenging the paradigm of a uniform dark ocean ecosystem. Metagenome Assembled Genomes uncovered 11 potential new phyla, establishing references for deep ocean microbial taxa, and revealed mixotrophy to be a widespread trophic strategy in the deep ocean. These results expand our understanding of the functional diversity, metabolic versatility, and carbon cycling in the largest ecosystem on Earth.\n\nOne Sentence SummaryA whole community genomic survey of the deep microbiome sheds light on the microbial and functional diversity of the dark ocean.

microbiology↗

bioRxiv2018

Peripartum cardiomyopathy and hypertensive disorders of pregnancy and cardiovascular events among 1.6 million California pregnancies

BackgroundCardiovascular complications during and soon after pregnancy present an opportunity to assess risk for subsequent cardiovascular disease. We sought to determine whether peripartum cardiomyopathy and hypertensive disorder of pregnancy subtypes predict future myocardial infarction, heart failure, or stroke independent of one another and independent of other risks like gestational diabetes, preterm birth, and intrauterine growth restriction.\n\nMethods and ResultsThe California Healthcare Cost and Utilization Project database was used to identify all hospitalized pregnancies from 2005-2009, with follow-up through 2011, for a retrospective cohort study. Pregnancies, exposures, covariates and outcomes were defined by ICD-9 codes. Among 1.6 million pregnancies (mean age 28y; median follow-up time to event 2.7y), 558 cases of peripartum cardiomyopathy, 123,603 cases of hypertensive disorders of pregnancy, 107,636 cases of gestational diabetes, 116,768 preterm births, and 23,504 cases of intrauterine growth restriction were observed. Using multivariable Cox proportional hazards models, peripartum cardiomyopathy was independently associated with a 13.0-fold increase in myocardial infarction [95%CI, 4.1-40.9], a 39.2-fold increase in heart failure [95%CI, 30.0-51.9], and a 7.7-fold increase in stroke [95%CI, 2.4-24.0]. Hypertensive disorders of pregnancy were associated with a 1.4 [95%CI, 1.0-2.0] to 7.6 [95%CI, 5.4-10.7] fold higher risk of myocardial infarction, heart failure, and stroke. Gestational diabetes, preterm birth, and intrauterine growth restriction had more modest associations with CVD.\n\nConclusionsThese findings support close monitoring of women with cardiovascular pregnancy complications for prevention of early subsequent cardiovascular events and further study of mechanisms underlying their development.

epidemiology↗