Biology subjects

Monteiro, F.

Publications and source records attributed to Monteiro, F..

8 recordsLinked to original sources

bioRxiv2026

Unraveling grapevine taxonomic and functional soil microbiome under different edaphic conditions within a vineyard plot.

Grapevine, mainly Vitis vinifera, occupies an elite position among crops worldwide. Soil and plant rhizosphere microbiomes are known to act as promoters of plant growth and health status. Plant root systems can select microbial communities through root exudates, while soil physicochemical parameters influence the structure and composition of the microbial community. In this work, we characterize the taxonomic composition and potential functional microbiome in combination with a large set of physicochemical parameters from the same soil samples collected at short distance (250 m) within a conventionally managed commercial vineyard plot. Metabarcoding and metagenome analysis, using amplicon and shotgun sequencing, allowed us to explore the structure and composition of the microbiomes and their functional activity. Soil microbial structure and functionality, as well as physicochemical parameters, differed between the two locations. Levels of locations elevation, boron, and sodium showed high correlation with the sample distribution of microbial community and functional genes suggesting they could affect directly the microbial community and their interaction with grapevine roots. Elevation variable, which includes a set of stochastic and deterministic factors, could have exacerbated further the differences in the microbial community and functionality. As a result, Burkholderia-Caballeronia-Paraburkholderia, Pseudomonas, Pseudoxanthomonas, and Streptomyces genera, which were described to effectively improve plant growth and resistance to abiotic stresses, were significantly more abundant in one location presenting lower levels of boron, zinc and active limestone and higher levels of sodium (within safe ranges). Microbial activity points out to have higher positive plant interactions in the same location registering genes associated with biofilm formation and quorum sensing pathways together with lipopolysaccharide biosynthesis and membrane transport. Altogether this data contributes to a better understanding of complex systems such as grapevine soil since soil physicochemical properties and microbial communities present significant variation within the vineyard, which can eventually impact wine quality.

microbiology↗

bioRxiv2023

Bi-allelic variants in WDR47 lead to neuronal loss causing a rare neurodevelopmental syndrome with corpus callosum dysgenesis in humans.

The corpus callosum (CC) is the largest interhemispheric connection that is largely formed by the axons of layer 2/3 callosal projection neurons (CPNs) through a series of tightly regulated cellular events, including neuronal specification, migration, axon extension and branching. Defects in any of those steps may prevent the proper development of the corpus callosum resulting in a spectrum of disorders collectively referred to as corpus callosum dysgenesis (CCD). Here, we report four unrelated families carrying bi-allelic variants in WDR47 presenting with CCD together with other neuroanatomical phenotypes such as microcephaly, cerebellar abnormalities and hydrocephalus. Using a combination of in vitro and in vivo mouse models and complementation assays, we show that independently from its previously identified functions in neuronal migration and axonal extension, WDR47 is required for survival of callosal neurons by contributing to the maintenance of mitochondrial and microtubule homeostasis. We further provide evidence that severity of the CCD phenotype is determined by the degree of the loss of function caused by the human variants. Taken together, we identify WDR47 as a causative gene of a new neurodevelopmental syndrome characterized by corpus callosum abnormalities and other neuroanatomical malformations.

neuroscience↗

bioRxiv2021

The power of dying slowly - persistence as unintentional dormancy

Persistence is a state of bacterial dormancy where cells with low metabolic activity and growth rates are phenotypically tolerant to antibiotics and other cytotoxic substances. Given its obvious advantage to bacteria, several researchers have been looking for the genetic mechanism behind persistence. However, other authors argue that there is no such mechanism and that persistence results from inadvertent cell errors. In this case, the persistent population should decay according to a power-law with a particular exponent of -2. Studying persisters decay is, therefore, a valuable way to understand persistence. Here we simulated the fate of susceptible cells in laboratory experiments in the context of indirect resistance. Eventually, under indirect resistance, detoxifying drug-resistant cells save the persister cells that leave the dormant state and resume growth. The simulations presented here show that, by assuming a power-law decline, the exponent is close to -2, which is the expected value if persistence results from unintentional errors. Whether persisters are cells in a moribund state or, on the contrary, result from a genetic program, should impact the research of anti-persistent drugs. Author SummaryPersistence, a form of bacterial dormancy, was discovered in the early days of the antibiotic era. Thanks to dormancy, these cells often evade antibiotic therapy and the immune system. However, despite its clinical importance, this phenotypes nature is still under debate. Arguably, the prevailing view is that persistence is an evolved (selected for) bet-hedging mechanism to survive in the presence of cytotoxic agents such as antibiotics. In that case, the persister population should decay exponentially, although at a much slower pace than the non-persister population. A few authors recently advanced an alternative hypothesis: bacterial persistence results from many malfunctions and cell division errors. In this case, persistent populations should decay according to a power-law with exponent of -2, that is, according to 1/t2. Here we simulated the fate of susceptible bacterial cells in the presence of bactericidal antibiotics in the context of indirect resistance based on laboratory experiments performed earlier. By showing that the dynamics of persister cells is consistent with 1/t2, our results corroborate the hypothesis that the phenomenon of bacterial persistence is an accidental consequence of inadvertent cell problems and errors. If confirmed, this conclusion should impact the research strategies of anti-persistent drugs. O_QD"The following day, no one died. This fact, being absolutely contrary to lifes rules, provoked enormous and, in the circumstances, perfectly justifiable anxiety in peoples minds, for we have only to consider that in the entire forty volumes of universal history there is no mention, not even one exemplary case, of such a phenomenon ever having occurred..." Death with interruptions Jose Saramago (2005) Nobel Prize for Literature 1998 C_QD

microbiology↗

bioRxiv2020

Role for the Na+/K+ ATPase α 3 subunit in folding and lamination of the human neocortex

Osmotic equilibrium and membrane potential in animal cells depend on concentration gradients of sodium (Na+) and potassium (K+) ions across the plasma membrane, a function that is catalyzed by the Na,K-ATPase alpha subunit. In vertebrates, four paralogous genes, ATP1A1-4, encode distinct alpha subunit isoforms (a1-a4), three of which (a1, a2, a3) are expressed in the brain, and two (a1, a3) predominantly in neurons. The a3 isoform, encoded by ATP1A3, is critical to neuronal physiology, and a growing spectrum of neurological diseases are associated with ATP1A3 pathogenic variants, with ages of onset ranging from early childhood to adulthood. Here, we describe ATP1A3 variants encoding dysfunctional a3 subunits in children affected by polymicrogyria, a developmental malformation of the cerebral cortex characterized by abnormal folding and laminar organization. To gain cell-biological insights into the spatiotemporal dynamics of prenatal ATP1A3 expression, we established a transcriptional atlas of ATP1A3 expression during cortical development using mRNA in situ hybridization and transcriptomic profiling of ~125,000 individual cells with single-cell RNA sequencing (Drop-Seq) from various areas of the midgestational human neocortex. We find that fetal expression of ATP1A3 is restricted to a subset of excitatory neurons carrying transcriptional signatures of neuronal activity and maturation characteristic of the developing subplate. Furthermore, by performing Drop-Seq on ~52,000 nuclei from four different areas of an infant human neocortex, we show that ATP1A3 expression persists throughout early postnatal development, not only within excitatory neurons across all cortical layers, but also and more predominantly in inhibitory neurons, with specific enrichment in fast-spiking basket cells. In addition, we show that ATP1A3 expression, both in fetal and postnatal neurons, tends to be higher in frontal cortical areas than in occipital areas, in a pattern consistent with the rostro-caudal maturation gradient of the human neocortex. Finally, we discover distinct co-expression patterns linking catalytic subunit isoforms (ATP1A1,2,3) and auxiliary isoforms (ATP1B1,2,3), suggesting the ATPase pump may form non-redundant, cell-type specific -{beta} combinations. Together, the importance of the developmental phenotypes and dynamic expression patterns of ATP1A3 point to a key role for a3 in the development and function of human cortex.

neuroscience↗

bioRxiv2020

Gene transmission and antibiotic usage are the key factors responsible for the positive correlation between antibiotic resistance gene diversity and virulence gene diversity in human metagenomes

1.This study aims to understand the cause of the recent observation that humans with a higher diversity of virulence genes in their metagenomes tend to be precisely those with higher diversity of antibiotic-resistance genes. We simulated the transferring of virulence and antibiotic-resistance genes in a community of interacting people where some take antibiotics. The diversities of the two genes types became positively correlated whenever the contagion probability between two people was higher than the probability of losing resistant genes. However, no such positive correlations arise if no one takes antibiotics. This finding holds even under changes of several simulations parameters, such as the relative or total diversity of virulence and resistance genes, the contagion probability between individuals, the loss rate of resistance genes, or the social network type. Because the loss rate of resistance genes may be shallow, we conclude that the contagion between people and antibiotic usage is the leading cause of establishing the positive correlation mentioned above. Therefore, antibiotic use and something as prosaic as the contagion between people may facilitate the emergence of virulent and multi-resistant bacteria in peoples metagenomes with a high diversity of both gene types. These superbugs may then circulate in the community.

microbiology↗

bioRxiv2019

Measuring glycolytic flux in single yeast cells with an orthogonal synthetic biosensor

Metabolic heterogeneity between individual cells of a population harbors offers significant challenges for fundamental and applied research. Identifying metabolic heterogeneity and investigating its emergence requires tools to zoom into metabolism of individual cells. While methods exist to measure metabolite levels in single cells, we lack capability to measure metabolic flux, i.e. the ultimate functional output of metabolic activity, on the single-cell level. Here, combining promoter engineering, computational protein design, biochemical methods, proteomics and metabolomics, we developed a biosensor to measure glycolytic flux in single yeast cells, by drawing on the robust cell-intrinsic correlation between glycolytic flux and levels of fructose-1,6-bisphosphate (FBP), and by transplanting the B. subtilis FBP-binding transcription factor CggR into yeast. As proof of principle, using fluorescence microscopy, we applied the sensor to identify metabolic subpopulations in yeast cultures. We anticipate that our biosensor will become a valuable tool to identify and study metabolic heterogeneity in cell populations.

synthetic biology↗

bioRxiv2019

The Arabidopsis thaliana pan-NLRome

Disease is both among the most important selection pressures in nature and among the main causes of yield loss in agriculture. In plants, resistance to disease is often conferred by Nucleotide-binding Leucine-rich Repeat (NLR) proteins. These proteins function as intracellular immune receptors that recognize pathogen proteins and their effects on the plant. Consistent with evolutionarily dynamic interactions between plants and pathogens, NLRs are known to be encoded by one of the most variable gene families in plants, but the true extent of intraspecific NLR diversity has been unclear. Here, we define the majority of the Arabidopsis thaliana species-wide "NLRome". From NLR sequence enrichment and long-read sequencing of 65 diverse A. thaliana accessions, we infer that the pan-NLRome saturates with approximately 40 accessions. Despite the high diversity of NLRs, half of the pan-NLRome is present in most accessions. We chart the architectural diversity of NLR proteins, identify novel architectures, and quantify the selective forces that act on specific NLRs, domains, and positions. Our study provides a blueprint for defining the pan-NLRome of plant species.

plant biology↗

bioRxiv2018

Yellow fever virus is susceptible to sofosbuvir both in vitro and in vivo

Yellow fever virus (YFV) is a member of the Flaviviridae family, that causes major mortality. In Brazil, YFV activity increased in the last years. It has been registered that sylvatic, instead of urban, yellow fever (YF) leads our contemporary public health concern. Low vaccinal coverage leaves the human population near the jangle vulnerable to the outbreak, making it necessary to identify therapeutic options. Repurposing of clinically approved antiviral drugs represents an alternative for such identification. Other Flaviviruses, such Zika (ZIKV) and dengue (DENV) viruses, are susceptible to Sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Moreover, sofosbuvir has a safety record on critically ill hepatic patients, making it an attractive option. Our data show that YFV RNA polymerase uses conserved amino acid resides for nucleotide binding to dock sofosbuvir. This drug inhibited YFV replication in different lineages of human hepatoma cells, Huh-7 and HepG2, with EC50 value of 4.8 {micro}M. Sofosbuvir protected YFV-infected neonatal Swiss mice from mortality and weight loss. Our pre-clinical results indicate that sofosbuvir could represent an option against YFV.

microbiology↗