Biology subjects

Sales, G.

Publications and source records attributed to Sales, G..

13 recordsLinked to original sources

bioRxiv2026

Grass wars: how native and non-indigenous Sporobolus battle heatwaves in salt marshes

O_LIHeatwaves are increasing in frequency and intensity and may alter competitive interactions between native and non-indigenous plant species. C_LIO_LIWe compared the responses of the native Sporobolus maritimus and the non-indigenous Sporobolus anglicus to a simulated 5-day heatwave using an integrative approach combining morphological, physiological, biochemical, transcriptomic, and metabolomic analyses. C_LIO_LIS. maritimus showed reduced survival, greater physiological damage, and no recovery, indicating high sensitivity to heat stress. Conversely, S. anglicus exhibited a rapid and coordinated response, limited damage to the photosynthetic apparatus, and full recovery after stress. C_LIO_LIThese results highlight the greater resilience of S. anglicus and suggest a potential decline of the native species in the Venetian salt marshes under increasing heat stress. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/728445v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1579ffeorg.highwire.dtl.DTLVardef@1c8e490org.highwire.dtl.DTLVardef@15cbadorg.highwire.dtl.DTLVardef@ef024b_HPS_FORMAT_FIGEXP M_FIG C_FIG We investigated the effects of heatwaves on a native and NIS Sporobolus species from the Venice Lagoon using an integrative, multi-level approach during a simulated 5-day heatwave and recovery phase. The native species showed reduced survival, pronounced physiological damage, and no recovery, indicating high sensitivity to heat stress. Conversely, the NIS exhibited a rapid response, limited impairment of the photosynthetic apparatus, and full recovery. These findings indicate greater resilience of the NIS and suggest a potential decline of the native species in the Venice Lagoon under increasing heat stress. Image created with BioRender (www.biorender.com).

plant biology↗

bioRxiv2026

An AI-driven pipeline for the discovery of hidden peptides in plant proteomes: the CLE family as a case study

Plant proteomes contain evolutionarily conserved peptides with poorly conserved primary sequences, often hindering their identification and classification into families. Homology-based approaches and conventional annotation pipelines frequently fail to detect these family members, particularly in poorly characterized, but agronomically relevant plant species. CLE peptides (CLAVATA3/EMBRYO SURROUNDING REGION-related peptides) constitute a large and evolutionarily conserved family of plant signaling molecules, yet their characterization remains incomplete. Beyond a limited number of well-studied members, a substantial number of CLE peptides remain uncharacterized due to functional redundancy and the intrinsic features of CLE genes, which encode short pre-propeptides with only a small 12-residue conserved motif. Here, we present a novel framework leveraging state-of-the-art Protein Language Models (pLMs) to discover CLE peptides directly from 13 plant proteomes. By coupling sequence embeddings trained on large evolutionary datasets (ESM2 and ProtT5) with supervised machine learning, our dual-model approach captures deep semantic features of the CLE family that are missed by traditional alignment methods. The pipeline demonstrated robust generalization, achieving high classification accuracy (98.9-99.4%) on a held-out set of CLE peptides not used during training. Consequently, we identified a set of high-confidence, previously unannotated CLE candidates prioritized through a stringent consensus-based filtering strategy. This work demonstrates how AI-driven proteome analysis can overcome the limitations of homology-based methods and provides a scalable strategy for uncovering previously unidentified peptide-mediated signaling molecules across plant lineages. HighlightLeveraging Protein Language Models, our AI framework uncovers "hidden" signaling peptides missed by standard tools, revealing the elusive diversity of CLE regulators across plant proteomes.

plant biology↗

bioRxiv2025

Benchmarking large-scale single-cell RNA-seq analysis

The increasing size of single-cell RNA sequencing (scRNA-seq) datasets poses major computational challenges. This work benchmarks the scalability, efficiency, and accuracy of five widely used analysis frameworks (Seurat, OSCA, scrap-per, Scanpy, and rapids singlecell), focusing on the impact of algorithmic and infrastructural choices on performance. We performed a systematic comparison of these workflows using representative datasets, including a 1.3 million mouse brain cell dataset for scalability and three smaller datasets (BE1, scMixology, and cord blood CITE-seq) with ground truth labels to assess clustering accuracy. Principal Component Analysis (PCA) was used as a paradigmatic step to evaluate the computational performance of six SVD algorithms (exact, ARPACK, IRLBA, randomized, Jacobi, and incremental PCA) across multiple data representations (dense, sparse, HDF5) and hardware configurations (CPU vs GPU). All methods showed high concordance in PCA results, with negligible loss of accuracy in truncated approaches. GPU-based computation using rapids singlecell provided a 15x speed-up over the best CPU methods, with moderate memory usage. On CPU, ARPACK and IRLBA were the most efficient for sparse matrices, while randomized SVD performed best for HDF5-backed data. Among full pipelines, rapids singlecell was the fastest, whereas OSCA and scrapper achieved the highest clustering accuracy (ARI up to 0.97) in datasets with known cell identities. Performance differences were largely driven by the choice of highly variable genes (HVGs) and PCA implementation. The study highlights that scalability in scRNA-seq analysis depends critically on both algorithmic and infrastructural factors. GPU acceleration and optimized BLAS/LAPACK configurations markedly enhance performance, while Bioconductor-based pipelines remain robust in accuracy. The provided benchmarks offer practical guidelines for efficient and reliable analysis of large-scale single-cell datasets.

bioinformatics↗

bioRxiv2025

CD300e Controls Macrophage Lipid Handling and Safeguards Adipose Tissue Function in Obesity

Previous studies in monozygotic twins discordant for body mass index (BMI) revealed that obese individuals exhibit elevated expression of the immune receptor CD300e in white adipose tissue (WAT). Notably, CD300e levels decreased following weight loss, implicating its involvement in adipose tissue remodeling and metabolic regulation. To elucidate the functional role of CD300e, we employed a Cd300e knockout (Cd300e-/-) mouse model subjected to a high-fat diet (HFD). Our findings demonstrate that CD300e deficiency exacerbates obesity-associated metabolic dysfunction, including increased weight gain, adipocyte hypertrophy, hepatic steatosis, and impaired glucose and insulin sensitivity. Adipose tissue macrophages (ATMs) lacking CD300e displayed reduced lipid and glucose uptake, alongside diminished mitochondrial respiration--a phenotype consistent with a broader metabolic impairment, as evidenced by proteomic profiling. These metabolic deficits were genotype-dependent and persisted after 16 weeks of HFD. Concurrently, adipocytes from Cd300e-/- mice exhibited enhanced lipogenesis and attenuated lipolysis. Remarkably, the impaired metabolic fitness exhibited by Cd300e-/- mouse macrophages was recapitulated in human cells upon gene silencing. Collectively, these results establish CD300e as essential for ATM metabolic activation, positioning it as a key regulator of adipose tissue homeostasis and a critical mediator of obesity-induced metabolic dysfunction. Given its pivotal role, CD300e emerges as a promising therapeutic target for modulating adipose tissue function and improving metabolic health in obesity.

immunology↗

bioRxiv2024

Generative Models Validation via Manifold Recapitulation Analysis

Comparing empirical distributions is central to generative model evaluation, hypothesis testing and data augmentation in high-dimensional biological data. Established methods such as energy distance summarize each point's relationship to the opposing distribution through a single expected distance, providing sensitivity to location shifts. We introduce Signature Distance (SD), a statistical distance that compares empirical distributions through the mean absolute difference of their sorted pointwise distance profiles. SD is a structural generalization of energy distance and matches its quadratic pairwise-distance cost, with an additional sorting step. In controlled experiments and on TCGA pan-cancer transcriptomic data, we show that (1) SD detects density changes with greater sensitivity than energy distance in the tested scale-contraction scenarios; (2) per-point mean-distance and signature-profile landscapes reveal the geometric mechanisms behind their different penalties; (3) linearly interpolated biological samples that receive no increased penalty from energy distance are penalized by SD; (4) SD provides a direct differentiable potential energy for model-free Langevin data expansion, with a bootstrap resampling protocol to assess the stopping epoch; and (5) SD is directly usable as a differentiable generative training loss. Code to reproduce all experiments is available at github.com/lazzaronico/signature-distance.

bioinformatics↗

bioRxiv2024

PAK6 promotes neuronal autophagy by regulating TFEB nuclear translocation.

Autophagy is a highly conserved homeostatic process essential for the bulk degradation of cytoplasmic components and aggregated proteins. Multiple evidence indicates that impairment of (macro)autophagy leads to neurodegeneration, such as Parkinson disease (PD). Our previous work showed that p21 activated kinase 6 (PAK6) interacts with the PD-associated leucine-rich repeat kinase (LRRK2) to promote neurite outgrowth in the mouse striatum; still the function of PAK6 in the brain is largely unknown. Here, we found that downregulation of neuronal but not glial mbt, the D. melanogaster homolog of PAK6, impairs autophagy-lysosomal function. PAK6 overexpression in cells and in C. elegans increases transcription factor EB (TFEB) nuclear translocation in a kinase activity-dependent manner. Mechanistically, PAK6 forms a complex with TFEB to regulate its nuclear localization in a manner dependent on phosphorylation of and binding to 14-3-3 proteins and phosphorylation of TFEB at S467. In line with its ability to promote neuronal autophagy, mbt downregulation exacerbates alpha-synuclein toxicity in Drosophila dopaminergic neurons. Moreover, PAK6 overexpression in the substantia nigra of mutant LRRK2 mice reduces the burden of phosphorylated alpha-synuclein in dopaminergic neurons. Altogether, our study uncovers a novel role of PAK6 as a positive regulator of autophagy via TFEB and suggests that modulating its activity may represent a way to selectively turn on autophagy in neurons, with implications for the treatment of neurodegenerative disorders.

neuroscience↗

bioRxiv2024

miR-210 is essential to retinal homeostasis in fruit flies and mice

miR-210 is one of the most evolutionarily conserved microRNAs. Recent studies in Drosophila melanogaster have unveiled that the absence of miR-210 leads to a progressive retinal degeneration characterized by the accumulation of lipid droplets and disruptions in lipid metabolism. Further investigation into lipid anabolism and catabolism revealed significant alterations in gene expression within these pathways. We provide the first morphological characterization of miR-210 KO mice retinas, highlighting a significant photoreceptor degeneration. While exploring potential parallels between miR-210 KO models in flies and mice, we examined mice lipid metabolism, circadian behaviour, and retinal transcriptome yet found no resemblances, suggesting divergent mechanisms of retinal degeneration between the two species. Simultaneously, analysis of the transcriptome in the brains of miR-210 KO flies revealed the potential existence of a shared upstream mechanism contributing to retinal degeneration in both fruit flies and mammals.

genetics↗

bioRxiv2021

NewWave: a scalable R/Bioconductor package for the dimensionality reduction and batch effect removal of single-cell RNA-seq data

SummaryWe present NewWave, a scalable R/Bioconductor package for the dimensionality reduction and batch effect removal of single-cell RNA sequencing data. To achieve scalability, NewWave uses mini-batch optimization and can work with out-of-memory data, enabling users to analyze datasets with millions of cells. Availability and implementationNewWave is implemented as an open-source R package available through the Bioconductor project at https://bioconductor.org/packages/NewWave/ Supplementary informationSupplementary data are available at Bioinformatics online.

genomics↗

bioRxiv2021

Low dose/dose rate γ irradiation protects Drosophila melanogaster chromosomes from double strand breaks and telomere fusions by modulating the expression of Loquacious.

It is still continuously debated whether the low-dose/dose-rate (LDR) of ionizing radiation represents a hazard for humans. Model organisms, such as fruit flies, are considered valuable systems to reveal insights into this issue. We found that, in wild-type Drosophila melanogaster larval neuroblasts, the frequency of Chromosome Breaks (CBs), induced by acute {gamma}-irradiation, is significantly reduced when flies are previously exposed to a protracted dose of 0.4Gy delivered at a dose rate of 2.5mGy/h. This indicates that this exposure, which is associated with an increased expression of DNA damage response proteins, induces a radioadaptive response (RAR) that protects Drosophila from extensive DNA damage. Interestingly, the same exposure reduces the frequency of telomere fusions (TFs) from Drosophila telomere capping mutants suggesting that the LDR can generally promote a protective response on chromatin sites that are recognized as DNA breaks. Deep RNA sequencing revealed that RAR is associated with a reduced expression of Loquacious D (Loqs-RD) gene that encodes a well-conserved dsRNA binding protein required for esiRNAs biogenesis. Remarkably, loss of Loqs mimics the LDR-mediated chromosome protection as it decreases the IR-induced CBs and TF frequency. Thus, our molecular characterization of RAR identifies Loqs as a key factor in the cellular response to LDR and unveils unprecedented epigenetic routes involved in radioresistance.

genetics↗

bioRxiv2021

The most comprehensive annotation of the Krill transcriptome provides new insights for the study of physiological processes and environmental adaptation

The krill species Euphausia superba plays a critical role in the food chain of the Antarctic ecosystem, as the abundance of its biomass affects trophic levels both below it and above. Major changes in climate conditions observed in the Antarctic Peninsula region in the last decades have already altered the distribution of the krill population and its reproductive dynamics. A deeper understanding of the adaptation capabilities of this species, and of the molecular mechanisms behind it are urgently needed. The availability of a large body of RNA-seq assays gave us the opportunity to extend the current knowledge of the krill transcriptome, considerably reducing errors and redundancies. Our study covered the entire developmental process, from larval stages to adult individuals, providing information of central relevance for ecological studies. Here we describe the KrillDB2 database, a resource combining the latest annotation of the krill transcriptome with a series of analyses specifically targeting genes and molecular processes relevant to krill physiology. KrillDB2 provides in a single resource the most complete collection of experimental data and bioinformatic annotations: it includes an extended catalog of krill genes; an atlas of their expression profiles over all RNA-seq datasets publicly available; a study of differential expression across multiple conditions such as developmental stages, geographical regions, seasons, and sexes. Finally, it provides initial indications about non-coding RNAs, a class of molecules whose contribute to krill physiology has never been reported before.

ecology↗

bioRxiv2021

A species-specific retrotransposon drives a conserved Cdk2ap1 isoform essential for preimplantation development

Retrotransposons mediate gene regulation in multiple developmental and pathological processes. Here, we characterized the transient retrotransposon induction in preimplantation development of eight mammalian species. While species-specific in sequences, induced retrotransposons exhibit a similar preimplantation profile, conferring gene regulatory activities particularly through LTR retrotransposon promoters. We investigated a mouse-specific MT2B2 retrotransposon promoter, which generates an N-terminally truncated, preimplantation-specific Cdk2ap1{Delta}N isoform to promote cell proliferation. Cdk2ap1{Delta}N functionally contrasts to the canonical Cdk2ap1, which represses cell proliferation and peaks in mid-gestation stage. The mouse-specific MT2B2 element is developmentally essential, as its deletion abolishes Cdk2ap1{Delta}N, reduces cell proliferation and impairs embryo implantation. Intriguingly, Cdk2ap1{Delta}N is evolutionarily conserved across mammals, driven by species-specific promoters. The distinct preimplantation Cdk2ap1{Delta}N expression across different mammalian species correlates with their different duration in preimplantation development. Hence, species-specific transposon promoters can yield evolutionarily conserved, alternative protein isoforms, bestowing them with new functions and species-specific expression to govern essential biological divergence. One Sentence SummaryIn mammalian preimplantation embryos, retrotransposon promoters generate conserved gene isoforms, confer species-specific expression, and perform essential developmental functions.

developmental biology↗

bioRxiv2020

TGS1 controls snRNA 3' end processing, prevents neurodegeneration and ameliorates SMN-dependent neurological phenotypes in vivo

Trimethylguanosine synthase 1 (TGS1) is a highly conserved enzyme that converts the 5 mono-methylguanosine cap of snRNAs to a trimethylguanosine cap. Here, we show that loss of TGS1 in C. elegans, D. melanogaster and D. rerio results in neurological phenotypes similar to those caused by Survival Motor Neuron (SMN) deficiency. Importantly, expression of human TGS1 ameliorates the SMN-dependent neurological phenotypes in both flies and worms, revealing that TGS1 can partly counteract the effects of SMN deficiency. TGS1 loss in HeLa cells leads to the accumulation of immature U2 and U4atac snRNAs with long 3 tails that are often uridylated. snRNAs with defective 3 terminations also accumulate in Drosophila Tgs1 mutants. Consistent with defective snRNA maturation, TGS1 and SMN mutant cells also exhibit partially overlapping transcriptome alterations that include aberrantly spliced and readthrough transcripts. Together, these results identify a neuroprotective function for TGS1 and reinforce the view that defective snRNA maturation affects neuronal viability and function.

genetics↗

bioRxiv2020

Allelic expression analysis of Imprinted and X-linked genes from bulk and single-cell transcriptomes

Genomic imprinting and X chromosome inactivation (XCI) are two prototypical epigenetic mechanisms whereby a set of genes is expressed mono-allelically in order to fine-tune their expression levels. Defects in genomic imprinting have been observed in several neurodevelopmental disorders, in a wide range of tumours and in induced pluripotent stem cells (iPSCs). Single Nucleotide Variants (SNVs) are readily detectable by RNA-sequencing allowing determination of whether imprinted or X-linked genes are aberrantly expressed from both alleles, although standardised analysis methods are still missing. We have developed a tool, named BrewerIX, that provides comprehensive information about the allelic expression of a large, manually-curated set of imprinted and X-linked genes. BrewerIX does not require programming skills, runs on a standard personal computer, and can analyze both bulk and single-cell transcriptomes of human and mouse cells directly from raw sequencing data. BrewerIX confirmed previous observations regarding the bi-allelic expression of some imprinted genes in naive pluripotent cells and extended them to preimplantation embryos. BrewerIX identified also misregulated imprinted genes in breast cancer cells and in human organoids and identified new genes escaping XCI in human somatic cells. We believe BrewerIX will be useful for the study of genomic imprinting and XCI during development and reprogramming, and for detecting aberrations in cancer, iPSCs and organoids. Due to its ease of use to non-computational biologists, its implementation could become standard practice during sample assessment, thus raising robustness and reproducibility of future studies.

bioinformatics↗