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Biology subjects

Sanchez, B.

Publications and source records attributed to Sanchez, B..

8 recordsLinked to original sources

Thille, a chromosome-level type B avocado genome, and the structural and allelic variation at candidate flowering-type loci

Avocado (Persea americana Mill.) is heterodichogamous: each flower opens first as female and then as male, and cultivars fall into two complementary flowering types, A and B, determined by the transcription factor SDMYB, whose dominant allele confers type A. Avocado genomes have so far come from type A cultivars. Here we report a chromosome-level genome of Thille, a type B cultivar used in breeding. From 72.2 Gb of PacBio HiFi reads (81x coverage) and Omni-C data, the assembly places 859.8 Mb, 96% of the expected 896 Mb genome, in 12 chromosomes with an NG50 of 84.5 Mb, a consensus quality of QV 69.95, and 97.3% complete BUSCO genes; repeats occupy 64.0% of the assembly, and 35,386 protein-coding genes were predicted. We compared Thille with the type A cultivars Hass and Puebla, a predominantly Guatemalan hybrid, and with a West Indian (WI) accession, a Lowland botanical group variety of unreported flowering type. The assemblies differ by large rearrangements, including an 18.8 Mb inversion on chromosome 12 specific to Hass. Using phased reads and haplotype assemblies, we reconstructed the alleles of candidate flowering genes from a type A versus type B Fst scan. Both WI haplotypes carry the recessive SDMYB allele found in Thille; based on this study and the previous study of SDMYB, we predict the WI accession to be type B. Six genes, including SDMYB, carry an allele shared by all three type A cultivars and absent from Thille and WI. The genome and HiFi reads are available under BioProject PRJNA1142556.

genomics↗

Spatial transcriptomics reveals organizational properties of mouse spinal cord and alterations in neuropathic pain

The spinal cord integrates diverse somatosensory inputs and executes motor outputs through anatomically and functionally distinct circuits. Here, we employed spatially resolved single-cell transcriptomic profiling of the adult mouse spinal cord to gain insights into the organizational logic of the spinal cord. Our results reveal distinct spatial and laminar distributions of neuronal subtypes, including axial level and sex-specific differences. Many neuronal subtypes exhibit close spatial proximity, implicating regionally specific patterns of connectivity and circuit functions. Additionally, neuronal subtypes within the dorsal horn exhibit a wide range of predicted cell-cell communication motifs, as assessed by the spatial distribution of neuropeptide-and other ligand-receptor pairs. Finally, we identified several neuronal subtypes with altered transcriptomic and predicted cell-cell communications in a model of neuropathic pain. This spatially resolved cellular and molecular map of the spinal cord will facilitate the decoding of circuit mechanisms underlying somatosensory and motor functions in health and disease.

neuroscience↗

A Multitrait Genome-Wide Association Study Reveals a Requirement for the Strigolactone Receptor DWARF14 in Optimal GOLVEN10 Signaling

GOLVEN/ROOT MERISTEM GROWTH FACTOR family of signaling peptides have been shown to control root lateral organ number, density and positioning in plants, although the signaling pathways involved remain obscure. A diverse set of 171 Medicago truncatula HapMap accessions with variation in responses to the GOLVEN 10 peptide, GLV10, were used to identify 74 significant loci controlling seven traits related to nodule formation and root architecture. Importantly, a single nucleotide polymorphism (SNP) in the upstream region of the MtGLV10 peptide-inducible strigolactone receptor gene, MtDWARF14 was significantly associated with insensitivity of nodule density to GLV10, suggesting a link between strigolactone signaling and GLV10 responsiveness. Three independent d14 mutants of the DWARF14 gene were found to hypernodulate, while overexpression of the gene led to reduction in nodule number, phenocopying GLV10. A null mutant, mtd14-1, remained sensitive to GLV10s effect on nodule density. However, at the transcriptional level, the mutant failed to effectively induce the expression of the GOLVEN marker genes, MtPLETHORA3 and MtPINLIKES2. Our study uncovers a hitherto unknown link between the strigolactone and GLV peptide signaling pathways using genotype x environment analysis of Medicago HapMap lines and provides a putative molecular mechanism for recovery from frost damage to fine roots.

plant biology↗

Three-dimensional reconstructions of mechanosensory end organs suggest a unifying mechanism underlying dynamic, light touch

Specialized mechanosensory end organs within mammalian skin--hair follicle-associated lanceolate complexes, Meissner corpuscles, and Pacinian corpuscles--enable our perception of light, dynamic touch1. In each of these end organs, fast-conducting mechanically sensitive neurons, called A{beta} low-threshold mechanoreceptors (A{beta} LTMRs), associate with resident glial cells, known as terminal Schwann cells (TSCs) or lamellar cells, to form complex axon ending structures. Lanceolate-forming and corpuscle-innervating A{beta} LTMRs share a low threshold for mechanical activation, a rapidly adapting (RA) response to force indentation, and high sensitivity to dynamic stimuli1-6. How mechanical stimuli lead to activation of the requisite mechanotransduction channel Piezo27-15 and A{beta} RA-LTMR excitation across the morphologically dissimilar mechanosensory end organ structures is not understood. Here, we report the precise subcellular distribution of Piezo2 and high-resolution, isotropic 3D reconstructions of all three end organs formed by A{beta} RA-LTMRs determined by large volume enhanced Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) imaging. We found that within each end organ, Piezo2 is enriched along the sensory axon membrane and is minimally or not expressed in TSCs and lamellar cells. We also observed a large number of small cytoplasmic protrusions enriched along the A{beta} RA-LTMR axon terminals associated with hair follicles, Meissner corpuscles, and Pacinian corpuscles. These axon protrusions reside within close proximity to axonal Piezo2, occasionally contain the channel, and often form adherens junctions with nearby non-neuronal cells. Our findings support a unified model for A{beta} RA-LTMR activation in which axon protrusions anchor A{beta} RA-LTMR axon terminals to specialized end organ cells, enabling mechanical stimuli to stretch the axon in hundreds to thousands of sites across an individual end organ and leading to activation of proximal Piezo2 channels and excitation of the neuron.

neuroscience↗

Application of synthetic peptide CEP1 increases nutrient uptake rates along plant roots

The root system of a plant provides vital functions including resource uptake, storage, and anchorage in soil. Uptake from the soil of macro-nutrients like nitrogen (N), phosphorus (P), potassium (K), and sulphur (S) is critical for plant growth and development. Small signaling peptide (SSP) hormones are best known as potent regulators of plant growth and development with a few also known to have specialized roles in macronutrient utilization. Here we describe a high-throughput screen of SSP effects on root uptake of multiple nutrients. The SSP, MtCEP1 enhanced nitrate uptake rate per unit root length in Medicago truncatula plants deprived of N. MtCEP1 and AtCEP1 enhanced uptake not only of nitrate, but also phosphate and sulfate in both Medicago and Arabidopsis. Transcriptome analysis of Medicago roots treated with different MtCEP1 encoded peptide domains revealed that hundreds of genes respond to these peptides, including several nitrate transporters and a sulfate transporter that may mediate the uptake of these macronutrients downstream of CEP1 signaling. Likewise, several putative signaling pathway genes were induced in roots by CEP1 treatment. Thus, a scalable method has been developed for screening synthetic peptides of potential use in agriculture, with CEP1 shown to be one such peptide.

plant biology↗

Reconstruction of a catalogue of genome-scale metabolic models with enzymatic constraints using GECKO 2.0

Genome-scale metabolic models (GEMs) have been widely used for quantitative exploration of the relation between genotype and phenotype. Streamlined integration of enzyme constraints and proteomics data into GEMs was first enabled by the GECKO method, allowing the study of phenotypes constrained by protein limitations. Here, we upgraded the GECKO toolbox in order to enhance models with enzyme and proteomics constraints for any organism with an available GEM reconstruction. With this, enzyme-constrained models (ecModels) for the budding yeasts Saccharomyces cerevisiae, Yarrowia lipolytica and Kluyveromyces marxianus were generated, aiming to study their long-term adaptation to several stress factors by incorporation of proteomics data. Predictions revealed that upregulation and high saturation of enzymes in amino acid metabolism were found to be common across organisms and conditions, suggesting the relevance of metabolic robustness in contrast to optimal protein utilization as a cellular objective for microbial growth under stress and nutrient-limited conditions. The functionality of GECKO was further developed by the implementation of an automated framework for continuous and version-controlled update of ecModels, which was validated by producing additional high-quality ecModels for Escherichia coli and Homo sapiens. These efforts aim to facilitate the utilization of ecModels in basic science, metabolic engineering and synthetic biology purposes.

systems biology↗

Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps

COVID-2019 has progressed in around 10-15% of patients to an acute respiratory distress syndrome characterized by extensive pulmonary inflammation and elevated production of pro-inflammatory cytokines. Neutrophil activation seems to be crucial in the initiation and perpetuation of this exacerbated lung inflammation. However, the precise mechanisms by which this activation occurs remain yet elusive. To this end, this in silico study tried to identify potential proinflammatory inducing peptides (PIPs) produced by the action of the elastase released in neutrophil-extracellular traps over SARS-CoV-2 particles. We found nine potential PIPs exclusive from the SARS-CoV-2, showing homology against T cell recognition epitopes. Moreover, 78 percent of these exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, suggesting that high PIP concentrations might be released following SARS-CoV-2 huge replication rate. Therefore, these PIPs might play a role in the exacerbated inflammatory response observed in some patients. HighlightsO_LINine potential PIPs were predicted exclusive from the SARS-CoV-2. C_LIO_LISARS-CoV-2 PIPs showed homology against T cell recognition epitopes. C_LIO_LIMost of PIPs were produced by enzymatic cleavage of the spike glycoproteins. C_LIO_LIThe release of these PIPs might be related to the increased inflammatory response observed in the patients. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/072439v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1cd2c3forg.highwire.dtl.DTLVardef@113f8b7org.highwire.dtl.DTLVardef@2df78eorg.highwire.dtl.DTLVardef@1d7c946_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

Activation of WNT signaling restores the facial deficits in a zebrafish with defects in cholesterol metabolism.

BackgroundInborn errors of cholesterol metabolism occur as a result of mutations in the cholesterol synthesis pathway (CSP). Although mutations in the CSP cause a multiple congenital anomaly syndrome, craniofacial abnormalities are a hallmark phenotype associated with these disorders. Previous studies have established that mutation of the zebrafish hmgcs1 gene (Vu57 allele), which encodes the first enzyme in the CSP, causes defects in craniofacial development and abnormal neural crest cell (NCC) differentiation. However, the molecular mechanisms by which the products of the CSP disrupt NCC differentiation are not completely known. Cholesterol is known to regulate the activity of WNT signaling, an established regulator of NCC differentiation. We hypothesized that defects in cholesterol synthesis reduce WNT signaling, consequently resulting in abnormal craniofacial development. MethodsTo test our hypothesis we performed a combination of pharmaceutical inhibition, gene expression assays, and targeted rescue experiments to understand the function of CSP and WNT signaling during craniofacial development. ResultsWe demonstrate reduced expression of axin2, a WNT downstream target gene in homozygous carriers of the Vu57 allele and in larvae treated with Ro-48-8071, which inhibits the synthesis of cholesterol. Moreover, activation of WNT signaling via treatment with a WNT agonist completely restored the craniofacial defects present in the Vu57 allele. ConclusionsCollectively, these data suggest interplay between the CSP and WNT signaling during craniofacial development.

developmental biology↗