Biology subjects

Ortiz, R.

Publications and source records attributed to Ortiz, R..

At least 19 recordsLinked to original sources

bioRxiv2026

A novel matrix multiplication framework for modeling genotype-by-environment interaction in genomic prediction

Accurate modeling of genotype-by-environment (GxE) interaction is critical for genomic prediction in plant breeding but remains challenging due to complex interaction structures. Conventional models often use the Hadamard product of genotype and environment covariance matrices to capture joint similarity, which may not fully represent GxE complexity. Here we propose a novel framework that derives covariance structures from the matrix multiplication of genotype and environment kernels, decomposing these into symmetric components incorporated as random effects in mixed models. Evaluated for 11 wheat and rice multi-environment datasets and across, this approach consistently outperformed the traditional Hadamard-based model, improving prediction accuracy by up to 13.2% in Pearsons correlation and enhancing top-selection accuracy. Combining both methods yielded the highest performance, indicating complementary information capture. This framework offers a flexible, interpretable, and computationally feasible extension for modeling GxE interaction, potentially enhancing genomic selection effectiveness under diverse environmental conditions.

genetics↗

bioRxiv2026

Stools and stool-derived extracellular vesicles from patients with Parkinson`s disease show alpha-4 synuclein seeding activity

BackgroundParkinsons disease (PD) is a neurodegenerative disorder for which there is currently no cure or reliable biomarker for early detection or for evaluating the effectiveness of potential treatments. PD pathology is driven by misfolding and subsequent accumulation of alpha-synuclein (Syn) protein into pathological aggregates within neurons and glial cells. Seed amplification assay (SAA) is a highly sensitive and specific diagnostic tool developed to detect pathological Syn species in the cerebrospinal fluid (CSF) of PD patients. However, Syn aggregates are present in multiple tissues and biosamples, including stools. In this study, we aimed to investigate the potential diagnostic value of SAA using stool samples from PD patients and healthy controls (HC). MethodsStool samples from PD patients (n=45) and healthy controls (n=35) were analysed for the presence of Syn species using slot blot assays with a panel of six Syn antibodies, and ELISA assays. Samples were subjected to SAA, and the end-point products (SAA EP) were characterised using transmission electron microscopy (TEM). Extracellular vesicles (EVs) were isolated from the subset of samples (n=5 per group) using size exclusion chromatography and characterized by TEM. The seeding activity of isolated EVs was evaluated using SAA, followed by TEM analysis of SAA EP. ResultsProtein extracts from both PD and HC stool samples revealed pathological Syn species in the slot blot assay using the phosphorylated Syn antibody, pS129 and conformation-specific antibodies, MJFR-14 and 5G4. ELISA showed significantly elevated total Syn levels in PD samples compared to HC, although no differences in aggregated Syn levels were detected. In stool protein extracts, SAA demonstrated 55.6% sensitivity and 60% specificity. When applied to stool-derived EVs from PD patients and controls, sensitivity increased to 100%, while specificity remained at 60%. Notably, SAA applied to stool-derived EVs pre-incubated with recombinant monomeric Syn achieved 100% sensitivity and 100% specificity. ConclusionThese findings suggest that SAA applied to EVs isolated from stool samples, particularly after pre-incubation with recombinant monomeric Syn, may serve as a valuable, non-invasive screening tool for the diagnosis of PD.

neuroscience↗

bioRxiv2025

Fronto-Parietal Oscillatory Dynamics of Emotion Regulation as a Function of Adult Attachment Orientations

Emotion regulation enables individuals to modulate emotional experiences and behaviors according to situational demands. Within attachment theory, individual differences in attachment anxiety and avoidance are conceived as interpersonal dispositions that influence the quality and efficiency of emotion regulation strategies, potentially shaping the underlying neural dynamics. This study examined cortical oscillatory activity during two regulation strategies--cognitive reappraisal and expressive suppression--focusing on theta (4-8 Hz) and beta (15-30 Hz) bands at the source level. Forty adults (21 male, 18 female, 1 gender-unspecified; M = 27.58 years, SD = 8.71) performed an emotion regulation task involving emotionally evocative images from the International Affective Picture System (IAPS) while EEG was recorded. Cortical sources were reconstructed using standardized low-resolution brain electromagnetic tomography (sLORETA). Linear mixed-effects models (LMMs) assessed the effects of condition, region of interest (ROI), and attachment orientations on oscillatory power. Results showed that higher attachment anxiety predicted reduced theta power in the right dorsolateral prefrontal cortex (dlPFC) during reappraisal, indicating attenuated recruitment of cognitive control mechanisms. In the beta band, suppression reduced activity in the right parietal lobe/precuneus -- a region involved in self-referential and attentional processes -- across participants, while during reappraisal, attachment anxiety was linked to lower beta power and attachment avoidance to higher beta power in the left dlPFC. Together, these findings indicate that cognitive reappraisal and expressive suppression engage distinct cortical oscillatory systems, and that interpersonal dispositions modulate their neural implementation. Frontal theta appears to index top-down control during reappraisal, whereas beta activity shows a dual pattern: frontal beta variations reflect differences in control stability associated with attachment orientations, and parietal beta decreases during suppression suggest attentional disengagement from self-referential processing.

neuroscience↗

bioRxiv2025

Population structure and diversity of common bean (Phaseolus vulgaris L.) landraces in the Peruvian Amazon

Common bean (Phaseolus vulgaris L.) is a globally important legume with significant nutritional and agronomic value. Genetic diversity in Amazonian landraces remains undercharacterized, limiting their utilization in breeding programs. Here we analyzed 647 accessions from the Peruvian Amazon using 18 morphological traits and 23,050 high-quality DArTseq single nucleotide polymorphisms (SNPs). Our results revealed two major genetic groups corresponding to Andean and Mesoamerican gene pools, each subdivided into distinct subgroups, exhibiting high allelic richness and structured diversity. Despite abundant polymorphic loci, observed heterozygosity was low, consistent with the species self-pollinating nature. These findings highlight the Peruvian Amazon as a reservoir of unique genetic variation, underscoring the need for integrated in situ and ex situ conservation strategies. This germplasm offers valuable resources for breeding programs targeting tropical adaptation and resilience, contributing to sustainable agriculture and food security.

plant biology↗

bioRxiv2025

Persistent cortical excitatory neuron dysregulation in adult Chd8 haploinsufficient mice.

CHD8 mutations cause autism spectrum disorder, cognitive deficits, and macrocephaly. Chd8+/- mouse models exhibit macrocephaly and transcriptional pathology, with inconsistent findings regarding neurogenesis, neuron function, and behavior. Via stereology and single nucleus transcriptomics (snRNA-seq), we found increased Chd8+/- cortical volume was not explained by increase in neuron number. Differential expression (DE) was present across cortical cell types, with excitatory neurons exhibiting high DE burden and shared and subclass-specific DE signatures. Bulk RNA-seq DE of constitutive Chd8+/- and conditional Camk2a-Cre Chd8+/-mice identified shared transcriptional pathology. DE in synaptosomal versus nuclear mRNA identified overlapping DEGs, but also significant differences and exaggerated synaptosomal changes. Building on DE findings implicating glutamatergic neurons, we found Chd8+/-mice exhibited altered excitatory neuron spine density and dynamics, decreased GCaMP activity correlation, and sleep perturbation. Thus, Chd8 haploinsufficiency causes lasting excitatory neuron dysfunction, perturbs RNA regulation beyond transcription, and impacts neuronal properties, cortical microcircuits, and behavior.

genomics↗

bioRxiv2025

Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats.

Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of psilocybin in fully awake, drug naive rats. Female and male rats were given IP injections of vehicle or psilocybin in doses of 0.03 mg/kg, 0.3 mg/kg, and 3.0 mg/kg while fully awake during the imaging session. Changes in BOLD signal were recorded over a 20 min window. Data for resting state functional connectivity were collected approximately 35 min post injection All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific changes in global brain activity and changes in functional connectivity. Treatment with psilocybin resulted in a significant dose-dependent increase in positive BOLD signal. The areas most affected by the acute presentation of psilocybin were the somatosensory cortex, basal ganglia and thalamus. Females were significantly more sensitive to the 0.3 mg/kg dose of psilocybin than males. There was a significant dose-dependent global increase in functional connectivity, highlighted by hyperconnectivity to the cerebellum. Brain areas hypothesized to be involved in loss of sensory filtering and organization of sensory motor stimuli such as the claustrum and the cortico-basal ganglia-thalamic-cortical loop were all affected by psilocybin in a dose-dependent manner. Indeed, the general neuroanatomical circuitry associated with the psychedelic experience was affected but the direction of the BOLD signal and pattern of activity between neural networks was inconsistent with the human literature.

neuroscience↗

bioRxiv2024

Evaluating the Biocontrol Potential of Pythium oligandrum and Serratia proteamaculans in Controlling Phytophthora plurivora in European beech (Fagus sylvatica)

In recent years, the plant pathogen Phytophthora plurivora has caused severe damage to beech forests in many European countries, including Sweden. In many affected areas, few protective measures are in place due to fears about potential negative impacts on the ecosystem or public health. The research presented in this article assesses the biocontrol potential of the oomycete Pythium oligandrum and the bacterium Serratia proteamaculans against P. plurivora, with experiments performed under both in vitro and greenhouse conditions, which could represent a step forward in developing a safe treatment for European beech forests. The in vitro results revealed that P. oligandrum and S. proteamaculans significantly inhibited pathogen growth and stimulated a shift in the hyphal growth pattern towards shorter, branched hyphae with many hyphal swellings and thickened cell walls. The experiments conducted in greenhouses showed that treating three-month-old beech seedlings with P. oligandrum and S. proteamaculans counteracts the P. plurivora pathogen and reduces disease symptoms on the aerial and underground parts of the plant. GC-MS analysis detected the volatile organic compounds alpha-pinene, 2,5-dimethyl-pyrazine, and 3-methyl-1-butanol from S. proteamaculans; these compounds have the potential to inhibit pathogen growth. The disease suppression demonstrated by these biocontrol agents could thus be related to the synergistic effect of competition for nutrients with the secretion of hydrolytic enzymes and VOCs; moreover, induced systemic resistance may be triggered under greenhouse conditions. In conclusion, using P. oligandrum and S. proteamaculans could represent an environmentally friendly strategy for effectively controlling the disease caused by P. plurivora in beech.

pathology↗

bioRxiv2024

HAdV-5 infection dysregulates cysteine, purine, and unsaturated fatty acid metabolism in fibroblasts

Viral infections can cause cellular dysregulation of metabolic reactions. Viruses alter host metabolism to meet their replication needs. The impact of viruses on specific metabolic pathways is not well understood, even for a well-studied virus-like human adenovirus. Adenoviral infection is known to affect cellular glycolysis and respiration, however, global effects on cellular metabolic pathways in response to adenoviral infection are lacking, particularly in normally quiescent structural cells, such as fibroblasts. Further, few studies have employed an untargeted approach with an emphasis on viral dosage and duration of infection. To address this, we employed untargeted metabolomics to quantify the dynamic metabolic shifts in fibroblasts infected with human adenovirus serotype 5 (HAdV-5) at three dosages (0.5, 1.0, and 2.0 multiplicity of infection [MOI]) and across four time points (6, 12, 24, and 36 h post-infection [HPI]). The greatest differences in individual metabolites were observed at 6- and 12-hours post-infection. In addition to its effects on glycolysis and respiration, adenoviral infection downregulated cysteine and unsaturated fatty acid metabolism, while upregulated purine metabolism. These results reveal the specific metabolic pathways that are perturbed by adenoviral infection and the associated dynamic shifts in metabolism, suggesting that viral infections alter energetics via profound changes in protein, lipid, and nucleic acid metabolism. The results revealed previously unconsidered metabolic pathways disrupted by HAdV-5 that can alter cells, even in non-excitable structural cells, such as fibroblasts. ImportanceHuman adenoviruses overtake the DNA replication machinery of the infected host, rewiring mitotic events and leading to effects on cellular respiration and glycolysis. Fibroblast lineages are normally quiescent cells that display a repertoire of responses to certain agonists. While metabolism often begins with glucose breakdown in the form of aerobic glycolysis, additional pathways are important for the overall functioning of the cell. Data on shifts in the metabolism of fibroblast cells in response to human adenoviral infection are lacking. We used an untargeted metabolomic approach to better understand the dynamic metabolic changes in human kidney cells in response to three viral dosages across four time points post infection. Profound shifts were observed for the cysteine, purine, and unsaturated fatty acid metabolites. This analysis provides a global perspective and highlights previously underappreciated aspects of how human adenoviruses alter host metabolism.

microbiology↗

bioRxiv2024

Plant Development Drives Dynamic Shifts in the Root Compartment Microbiomes of Wild and Domesticated Finger Millet Cultivars

BackgroundPlant-microbe interactions in two root compartments - the rhizosphere and endosphere - play vital roles in maintaining plant health and ecosystem dynamics. The microbial communities in these niches are shaped in complex ways by factors including the plants developmental stage and cultivar, and the compartment where the interactions occur. Different plant cultivars provide distinct nutritional and ecological niches and may selectively enrich specific microbial populations through the secretion of root exudates. This gives rise to complex and dynamic plant-microbe interactions; some cultivars promote the recruitment of beneficial symbionts while others may deter pathogens. To clarify these processes, this work investigated the structure of the endosphere and rhizosphere microbial communities of wild type finger millet and five domesticated cultivars across two plant developmental stages. ResultsOur results showed that the plant developmental stage, compartment, and cultivar have varying degrees of impact on root-associated microbiomes. The dominant bacterial phyla in all samples were Proteobacteria, Actinobacteria, and Bacteroidetes, while the dominant fungal phyla were Ascomycota and Basidiomycota. All of these phyla exhibited pronounced variations in abundance. In general, an increased abundance of Actinobacteria in the endosphere was accompanied by a reduced abundance of Proteobacteria. The most pronounced changes in microbial community structure were observed in the rhizosphere during the flowering stage. Changes in the microbiome patterns of the rhizosphere were driven predominantly by the genus Pseudomonas. Moreover, the host plants developmental stage strongly influenced the microbial communities, suggesting that plants can recruit specific taxa based on their need for particular soil consortia. ConclusionsOur results show that both host developmental stage and domestication strongly affect the assembly and structure of the plant microbiome. Moreover, plant root compartments can selectively recruit specific taxa from associated core microbial communities to fulfill their needs in a manner that depends on both the plants developmental stage and the specific root compartment that is involved. These findings show that deterministic selection pressures exerted by plants during their growth and development can significantly affect their microbial communities and have important implications for efforts to create tools for manipulating the microbiome to sustainably improve primary productivity.

microbiology↗

bioRxiv2024

Extracellular biosynthesis of silver nanoparticles using cell suspension of Rhodococcus fascians

Biosynthesis of metallic nanoparticles using biological systems such as bacteria has become an important nanobiotechnology area. In this report, we present the first extracellular biosynthesis of silver nanoparticles (AgNPs) using the gram-positive bacterium Rhodococcus fascians. The AgNPs underwent characterization through various analytical techniques, encompassing UV-visible spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM). UV-visible spectroscopy revealed the emergence of an absorbance peak at 430 nm due to the synthesis of AgNPs. R. fascians started producing AgNPs after 12 h of incubation, with the highest yield after 48 h. The extent of synthesis was higher when cultures were grown in the dark than in the light. According to TEM and SEM, the AgNPs had a uniform spherical morphology of diameter 10-80 nm. The AgNPs exhibited antifungal efficacy against the virulent filamentous fungi Rhizoctonia solani, Botrytis cinerea, and Fusarium graminearum, which cause root rot, soft rot and head blight on plants, respectively. This research provides evidence on the ability of R. fascians to generate AgNPs from silver nitrate, as well as their subsequent assembly and potential for controlling vascular wilt disease.

microbiology↗

bioRxiv2023

Dilated cardiomyopathy-associated RNA Binding Motif Protein 20 regulates long pre-mRNAs in neurons

Precise coordination of molecular programs and neuronal growth govern the formation, maintenance, and adaptation of neuronal circuits. RNA metabolism has emerged as a key regulatory node of neural development and nervous system pathologies. To uncover cell-type-specific RNA regulators, we systematically investigated expression of RNA recognition motif-containing proteins in the mouse neocortex. Surprisingly, we found RBM20, an alternative splicing regulator associated with dilated cardiomyopathy, to be expressed in cortical parvalbumin interneurons and mitral cells of the olfactory bulb. Genome-wide mapping of RBM20 target mRNAs revealed that neuronal RBM20 binds pre-mRNAs in distal intronic regions. Loss of neuronal RBM20 has only modest impact on alternative splice isoforms but results in a significant reduction in an array of mature mRNAs in the neuronal cytoplasm. This phenotype is particularly pronounced for genes with long introns that encode synaptic proteins. We hypothesize that RBM20 ensures fidelity of pre-mRNA splicing by suppressing non-productive splicing events in long neuronal genes. This work highlights a common requirement for RBM20-dependent transcriptome regulation in cardiomyocytes and neurons and demonstrates that a major genetic risk factor of heart disease impacts neuronal gene expression.

neuroscience↗

bioRxiv2023

VLP-mediated delivery of structure-selected neoantigens demonstrates immunogenicity and antitumoral activity in mice

BackgroundNeoantigens are patient- and tumor-specific peptides that arise from somatic mutations. They stand as promising targets for personalized therapeutic cancer vaccines. The identification process for neoantigens has evolved with the use of next-generation sequencing technologies and bioinformatic tools in tumor genomics. However, in silico strategies for selecting immunogenic neoantigens still have very low accuracy rates, since they mainly focus on predicting peptide binding to Major Histocompatibility Complex (MHC) molecules, which is key but not the sole determinant for immunogenicity. MethodsWe developed a novel neoantigen selection pipeline based on existing software combined with a novel prediction method, the Neoantigen Optimization Algorithm (NOAH), which takes into account structural features of the peptide/MHC-I interaction in its prediction strategy. Moreover, to maximize neoantigens therapeutic potential, neoantigen-based vaccines should be manufactured in an optimal delivery platform that elicits robust de novo immune responses and bypasses central and peripheral tolerance. ResultsWe generated a highly immunogenic vaccine platform based on engineered HIV-1 Gag-based Virus-Like Particles (VLPs) expressing a high copy number of each in silico selected neoantigen. We tested different neoantigen-loaded VLPs (neoVLPs) in a B16-F10 melanoma mouse model to evaluate their capability to generate new immunogenic specificities. NeoVLPs were used in in vivo immunogenicity and tumor challenge experiments. ConclusionsNeoVLPs can promote the generation of de novo antitumor-specific immune responses, resulting in a delay in tumor growth. Vaccination with the neoVLP platform is a robust alternative to current therapeutic vaccine approaches and a promising candidate for future personalized immunotherapy. WHAT IS ALREADY KNOWN ON THIS TOPICIdentification of highly immunogenic neoantigens is still challenging, currently available pipelines base their prediction on MHC-I binding affinity. Moreover, neoantigen-based vaccine delivery needs to be improved to increase the potency of anti-tumor immune response. WHAT THIS STUDY ADDSNOAH is a novel pipeline for the identification and selection of neoantigens that combines binding affinity and structural features of the peptide/MHC-I interaction. Preclinical studies show highly immunogenic vaccine platform based on HIV-1 Gag based VLPs (neoVLPs) generates antitumor-specific immune responses, delaying tumor growth. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYThe combination of NOAH and neoVLP platform represents an alternative to current therapeutic vaccine approaches and a promising candidate for future personalized immunotherapy.

immunology↗

bioRxiv2023

Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant.

Most COVID-19 vaccines are based on the SARS-CoV-2 Spike glycoprotein (S) or their subunits. However, the S shows some structural instability that limits its immunogenicity and production, hampering the development of recombinant S-based vaccines. The introduction of the K986P and V987P (S-2P) mutations increases the production of the recombinant S trimer and, more importantly, its immunogenicity, suggesting that these two parameters are related. However, S-2P still shows some molecular instability and it is produced with low yield. Thus, S-2P production can be further optimized. Here we described a novel set of mutations identified by molecular modelling and located in the S2 region of the Spike that increase S-2P production up to five-fold. Besides their immunogenicity, the efficacy of two representative S-2P-based mutants, S-29 and S-21, protecting from a heterologous SARS-CoV-2 Beta variant challenge was assayed in K18-hACE2 mice (an animal model of severe SARS-CoV-2 disease) and golden Syrian hamsters (GSH) (a moderate disease model). S-21 induced higher level of WH1 and Delta variants neutralizing antibodies than S-2P in K18-hACE2 mice three days after challenge. Viral load in nasal turbinate and oropharyngeal samples were reduced in S-21 and S-29 vaccinated mice. Despite that, only the S-29 protein protected 100% of K18-hACE2 mice from severe disease. When GSH were analyzed, all immunized animals were protected from disease development irrespectively of the immunogen they received. Therefore, the higher yield of S-29, as well as its improved immunogenicity and efficacy protecting from the highly pathogenic SARS-CoV-2 Beta variant, pinpoint the S-29 spike mutant as an alternative to the S-2P protein for future SARS-CoV-2 vaccine development. Authors summaryThe rapid development of SARS-CoV-2 vaccines have been pivotal in the control of the COVID-19 pandemic worldwide. Most of these vaccines include the S glycoprotein as the main immunogen since this protein, and particularly its receptor binding domain (RBD), is the major target of neutralizing antibodies. SARS-CoV-2 have been evolving from the beginning of the pandemic and several variants with increased transmissibility, pathogenicity or resistance to infection- or vaccine-induced immunity have emerged. Different strategies have been adopted to improve vaccine protection including additional booster doses or the adaptation of the S immunogens to the novel SARS-CoV-2 variants. As a complementary strategy we have identified a combination of non-proline mutations that increase S production by 5-fold (S-29 protein). Despite the sequence of this novel S-29 immunogen is based on the ancestral SARS-CoV-2 WH1 variant, it effectively protects animal model from the highly pathogenic and neutralization resistant SARS-CoV-2 Beta variant. Thus, we describe a novel set of mutations that can increase the production and efficacy of S-based COVID-19 vaccines.

immunology↗

bioRxiv2023

KIS counteracts PTBP2 and regulates alternative exon usage in neurons

Alternative RNA splicing is an essential and dynamic process to control neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here we show that KIS, a brain-enriched kinase with a domain shared by splicing factors, controls exon usage in differentiated neurons at a genome-wide level. KIS phosphorylates the splicing regulator PTBP2 complex and markedly counteracts its role in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from key co-regulators and hinders its RNA-binding capacity. Taken together, our data provide new insights into the post-translational control of splicing regulators and uncover an essential role of KIS in setting alternative exon usage in neurons.

molecular biology↗

bioRxiv2023

Targeting ABCB4 using mRNA-LNP for the treatment of rare liver diseases

Mutations in the ABCB4 gene lead to a wide-spectrum of rare liver diseases including progressive familial intrahepatic cholestasis type 3 (PFIC3) and low-phospholipid associated cholelithiasis (LPAC) syndrome. PFIC3 patients develop symptoms during late infancy, including severe itching, jaundice, and failure to thrive. The condition may progress to liver failure during childhood or adulthood. This is a highly unmet medical condition where liver transplantation is the only option to correct this disease. Recently, exciting data suggested that restoration of the ABCB4 function via gene replacement could rescue liver phenotypes associated with ABCB4 dysfunction in a preclinical PFIC3 mouse model. Here, we used mRNA LNP platform to determine expression and durability of ABCB4 in the liver of wildtype mice. In addition, we generated Abcb4-/- mice to study the efficacy of systemic delivery of ABCB4 mRNA LNP. We observed a robust and durable expression of hABCB4 up to 72 hours post systemic dosing in the liver of wild-type mice. Systemic administration of hABCB4 mRNA achieved a remarkable restoration of phosphatidylcholine levels in bile, a significant decrease in liver stiffness as measured by shear wave elastography, and amelioration of liver histopathology including fibrosis and ductular reaction. We conclude that administration of hABCB4 mRNA LNPs was sufficient to ameliorate fibrosis markers in the PFIC3 mouse model. Our data suggests that gene replacement using mRNA LNP modality could provide an excellent opportunity for patients with biliary diseases.

molecular biology↗

bioRxiv2023

Comparative Transcriptome Profiling Provides Insights into the Growth Promotion Activity of Pseudomonas fluorescens strain SLU99 in Tomato and Potato Plants

The use of biocontrol agents with plant growth-promoting activity has emerged as an approach to support sustainable agriculture. During our field evaluation of potato plants treated with biocontrol rhizobacteria, four bacteria were associated with increased plant height. Using two important solanaceous crop plants, tomato and potato, we carried out a comparative analysis of the growth-promoting activity of the four bacterial strains: Pseudomonas fluorescens SLU99, Serratia plymuthica S412, S. rubidaea AV10, and S. rubidaea EV23. Greenhouse and in vitro experiments showed that P. fluorescens SLU99 promoted plant height, biomass accumulation, and yield of potato and tomato plants, while EV23 promoted growth in potato but not in tomato plants. SLU99 induced the expression of plant hormone-related genes in potato and tomato, especially those involved in maintaining homeostasis of auxin, cytokinin, gibberellic acid and ethylene. Our results reveal potential mechanisms underlying the growth promotion and biocontrol effects of these rhizobacteria and suggest which strains may be best deployed for sustainably improving crop yield.

plant biology↗

bioRxiv2022

Trans-cellular control of synapse properties by a cell type-specific splicing regulator

The recognition of synaptic partners and specification of synaptic properties are fundamental for the function of neuronal circuits. Terminal selector transcription factors coordinate the expression of terminal gene batteries that specify cell type-specific properties. Moreover, pan-neuronal alternative splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell type-specific loss-of-function studies to uncover the contribution of the nuclear RNA binding protein SLM2 to hippocampal synapse specification. Focusing on hippocampal pyramidal cells and SST-positive GABAergic interneurons, we find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins, thereby generating cell type-specific isoforms. In the absence of SLM2, cell type-specification, differentiation, and viability are unaltered and neuronal populations exhibit normal intrinsic properties. By contrast, cell type-specific loss of SLM2 results in highly selective, non-cell autonomous synaptic phenotypes, altered synaptic transmission, and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner.

neuroscience↗

bioRxiv2022

Modeling genotype environment interaction for single- and multi-trait genomic prediction in potato (Solanum tuberosum L.)

In this study we extend research on genomic prediction (GP) to polysomic polyploid plant species with the main objective to investigate single trait (ST) versus multi-trait (MT) for multi-environment (ME) models for the combination of three locations in Sweden (Helgeg[a]rden [HEL], Mosslunda [MOS], Ume[a] [UM]) over two year-trials (2020, 2021) of 253 potato cultivars and breeding clones for five tuber weight traits and two tuber flesh quality characteristics. This research investigated the GP of four genome-based prediction models with genotype xenvironment interactions (GE): (1) single trait reaction norm model (M1), (2) single trait model considering covariances between environments (M2), (3) single trait M2 extended to include a random vector that utilizes the environmental covariances (M3) and (4) multi-trait model with GE (M4). Several prediction problems were analyzed for each of the GP accuracy of the four models. Results of the prediction of traits in HEL, the high yield potential testing site in 2021, show that the best predicted traits were tuber flesh starch (%), weight of tuber above 60 or below 40 mm in size, and total tuber weight. In terms of GP, accuracy model M4 gave the best prediction accuracy in three traits, namely tuber weight of 40-50 or above 60 mm in size, and total tuber weight and very similar in the starch trait. For MOS in 2021, the best predictive traits were starch, weight of tuber above 60, 50-60, or below 40 mm in size, and total tuber weight. MT model M4 was the best GP model based on its accuracy when some cultivars are observed in some traits. For GP accuracy of traits in UM in 2021, the best predictive traits were weight of tuber above 60, 50-60, or below 40 mm in size and the best model was MT M4 followed by models ST M3 and M2.

plant biology↗