Biology subjects

Andres, J.

Publications and source records attributed to Andres, J..

9 recordsLinked to original sources

bioRxiv2026

Mechanophenotype of synovial fibroblasts correlates with patients' pathotypes and treatment response in Rheumatoid Arthritis

The mechanical features of synovial fibroblasts may encode clinically relevant information for the management of rheumatoid arthritis. Indeed, it remains poorly understood the links between cellular and microenvironment mechanics with patient stratification and therapeutic response. Here we show that combining organotypic synovial cultures with multimodal mechanophenotyping and transcriptomics identifies distinct ''soft'' and ''stiff'' fibroblast states. Healthy and rheumatoid arthritis fibroblasts were cultured in two or three dimensions (organotypic cell cultures), alone or with endothelial cells, and characterized by high-throughput nanoindentation, picobalance measurements, digital holographic microscopy, Brillouin microscopy and RNA sequencing. Three-dimensional culture reduced single-cell Young's modulus and total mass while increasing dry-mass surface density; endothelial co-culture increased fibroblast stiffness and the longitudinal modulus of intact organotypic cultures. Stiffness-based grouping revealed transcriptional programmes related to extracellular-matrix remodelling, cytoskeletal contractility, and TGF-beta, WNT, and Hippo signalling. Mapping these signatures to publicly available rheumatoid arthritis clinical transcriptomic datasets associated the ''stiff'' state with fibrotic and myeloid-fibrotic pathotypes and treatment-refractory programmes, whereas the ''soft'' state aligned with lymphoid pathotypes and rituximab- or tocilizumab-responsive programmes. These findings support mechanophenotype-associated transcriptional signatures as potential biomarkers for rheumatoid arthritis stratification.

biophysics↗

bioRxiv2026

Population genetics meets precision-cut kidney slices: Nephrotoxicity modelled ex vivo in the founder strains of the BXD mouse consortium

Acute kidney injury (AKI) affects millions of patients annually and is associated with high morbidity and mortality, to date no curative treatment exists. Drug-induced nephrotoxicity accounts for up to 25% of AKI cases, but individual susceptibility remains hard to predict. While genetic factors are suspected to play a part in this variability, the pharmacogenomics of nephrotoxin-induced kidney injury remain largely unknown. To investigate genetically determined susceptibility, we used precision-cut kidney slices (PCKS) from the two founder strains of the BXD mouse consortium, C57BL/6J and DBA/2J. PCKS preserves tissue architecture and cell-cell interaction, allowing close experimental control while maintaining the renal microenvironment. Slices were exposed to cyclosporine A (80 nM for 6h, 20nM for 24h and 48h) and Tunicamycin (1 {micro}M for 6h and for 24h) as well as normoxia (4{degrees}C for 20h) and hyperoxia (4{degrees}C for 20h and 4h in incubator). Slices were then analysed using histopathological scoring, TUNEL staining, ATP quantification and bulk RNA sequencing. We found that the main source of variation was experimental duration. Nevertheless, a subtle difference between the strains could be observed for both cyclosporine A and Tunicamycin, with DBA/2J showing a stronger response to nephrotoxic stress, including lower ATP levels, higher proportion of apoptotic cells and a more pronounced transcriptomic response. For both strains, normoxia was the least harmful condition. These findings support the hypothesis that the BXD founder strains differ in their susceptibility to nephrotoxic kidney injury and support the use of PCKS as a relevant ex vivo model for studying early renal stress response. This provides the foundation to extend this approach to a broader spectrum of the BXD population to identify genetic loci and candidate genes involved in genetic susceptibility to nephrotoxins.

pharmacology and toxicology↗

bioRxiv2026

DNA Damage Response Proteins Are Involved in the Formation of Defective HIV-1 Proviruses

Latent HIV-1 proviruses remain the major barrier to curing HIV infection. Although many of these proviruses are defective, with large internal deletions and hypermutations, the mechanisms underlying their formation are still poorly understood. In this study, we applied CRISPR/Cas9 knockout screens to identify DNA damage response (DDR) proteins that contribute to the formation of defective HIV-1 proviruses carrying large internal deletions. Using an HIV-1-based dual-fluorophore vector as a model, we distinguished cells harbouring intact proviruses from those carrying large internal deletions by flow cytometry and cell sorting. We then validated top candidates using CRISPR-mediated gene activation and small interfering RNA-mediated knockdown. Across these approaches, the helicase-like transcription factor HLTF emerged as a consistent modulator of large internal deletions: increased HLTF expression raised the proportion of cells carrying defective proviruses, whereas reduced HLTF expression had the opposite effect. Additional repair factors, including RAD1, RAD18, TREX2, and ZRANB3, also influenced the balance between intact and defective proviruses, suggesting that multiple DNA repair pathways cooperate in this process. Our data indicate that several DNA damage response proteins, including HLTF, are involved in the generation of defective proviruses and may constitute a previously undescribed host defence mechanism against HIV-1.

molecular biology↗

bioRxiv2025

Environmental DNA monitoring of waterfowl reveals community changes during migration

Large-scale visual surveys are an integral part of waterfowl conservation and management programs. In this paper we explore the possibility of using environmental DNA-based surveys as a cost-efficient, complementary tool to estimate populations of North American waterfowl species. To achieve this, we first evaluated the performance of all currently available avian metabarcoding primers and compared them to newly designed primers targeting the mitochondrial ND2 gene within the Anatidae tribes of North America. All the existing avian assays showed strong cross-priming amplification with other vertebrates. In contrast, in-silico analyses of our waterfowl targeted assays showed a high degree (>90%) of avian specificity, encompassing all the 132 Anatidae species sequenced thus far. We used this targeted metabarcoding approach to track the temporal variation in the relative abundance of waterfowl species during the fall migration at Montezuma National Wildlife Refuge, New York, a major resting area for waterfowl on their journey to and from North American nesting areas. We compared eDNA results with visual surveys conducted by us and from those reported on eBird. Our results showed that eDNA detected all waterfowl species (n= 25) during fall migration. Positive correlations existed between standardized eDNA read counts and the relative abundance of waterfowl species as reported in eBird on the day of sampling and up to five days prior. However, this approach did not provide a good metric for absolute abundance of waterfowl species: only 8 out of 25 waterfowl species showed significant correlations between the number of eDNA reads and the total abundance of birds. Overall, while eDNA-targeted metabarcoding has not yet been applied to study bird communities extensively, our results demonstrate that this technique can be used as an effective complementary tool for assessing species composition of waterfowl communities and estimating relative abundance of species within those communities.

genetics↗

bioRxiv2025

FvFT1-FvTFL1 epistasis drives flowering time adaptation in woodland strawberry

Floral transition and flower bud development during autumn and winter are common in plants inhabiting temperate and cold climates. However, our understanding of the natural variation and underlying molecular mechanisms of such life-history strategy remain largely limited to Brassicaceae model species. To address this gap, we investigated flowering time variation across a broad geographical and bioclimatic range in Fragaria vesca (woodland strawberry), a perennial herb from the Rosaceae family. We found that the timing of floral transition and subsequent flowering in F. vesca populations is primarily shaped by population structure, reflecting postglacial colonization patterns from distinct refugia, and is further modulated by adaptations to winter temperatures. The association of increasing expression of FvFT1, the strawberry ortholog of FLOWERING LOCUS T, with delayed flowering in accessions from diverse climatic and genetic backgrounds suggested FvFT1 as a major candidate gene regulating flowering time variation. We further demonstrated how distinct florigen and antiflorigen roles of FvFT1 are dependent on functional alleles of F. vesca TERMINAL FLOWER1 (FvTFL1) and how the epistatic relationship between FvFT1 and FvTFL1 controls adaptive flowering time variation by adjusting sensitivity to floral inductive photoperiod and vernalization. Our findings reveal a major molecular basis of how timing of floral transition has adapted to temperature in a Rosaceae model inhabiting multiple climatic zones and highlight lineage-specific adaptive mechanisms underlying convergent life-history strategy. Significance statementMolecular mechanisms underlying flowering time adaptation have been primarily investigated in annual plants that transit to flowering in spring. However, many perennial plant species in temperate climates form flower buds in autumn and winter to flower in the following spring. We uncover wide geographical and climatic patterns of flowering time adaptation in the perennial model species woodland strawberry. We report that natural variation in the expression of strawberry FLOWERING LOCUS T (FvFT1) gene originating ice ages ago and further driven by local temperature adaptations control flowering time variation in this species. Finally, we show how FvFT1 may function as both flowering promoter and repressor depending on the genetic background, thus revealing a novel mechanism of flowering time adaptation.

plant biology↗

bioRxiv2022

bHLH heterodimer complex variations shape meristems in Arabidopsis thaliana by affecting target gene specificity

The main regions of cell proliferation in plants are the root and shoot apical meristems during primary growth and the vascular cambia as lateral meristems during secondary thickening. A number of unique regulators have been described in each of these meristems, suggesting that these different meristems might have independently evolved dedicated transcriptional networks to balance cell proliferation. Here, we show that the basic Helix Loop Helix (bHLH) transcription factor complexes formed by TARGET OF MONOPTEROS5 (TMO5), LONESOME HIGHWAY (LHW) and their close homologs are broadly expressed throughout plant development and operate as general regulators of cell proliferation in all meristems. Yet, genetic and expression analyses indicate that these complexes have specific functions in distinct meristems mediated by heterodimer complex variations between members of the TMO5 and LHW subclades. We determine that this is primarily due to their expression domains limiting the possible combinations of heterodimer complexes within a certain meristem, and to a certain extent to the absence of some members in a given meristem. We further demonstrate target gene specificity for heterodimer complexes, suggesting that spatial differences in transcriptional responses through heterodimer diversification allow a common bHLH heterodimer complex module to contribute to the control of cell proliferation in multiple meristems.

developmental biology↗

bioRxiv2022

A chromosome-length genome assembly and annotation of blackberry (Rubus argutus, cv. Hillquist)

BackgroundBlackberries (Rubus spp.) are the fourth most economically important berry crop worldwide. Genome assemblies and annotations have been developed for Rubus species in subgenus Idaeobatus, including black raspberry (R. occidentalis), red raspberry (R. idaeus), and R. chingii, but very few genomic resources exist for blackberries and their relatives in subgenus Rubus. FindingsHere we present a chromosome-length assembly and annotation of the diploid blackberry germplasm accession Hillquist (R. argutus). Hillquist is the only known source of primocane-fruiting (annual-fruiting) in tetraploid fresh-market blackberry breeding programs and is represented in the pedigree of many important cultivars worldwide. The Hillquist assembly, generated using PacBio long reads scaffolded with Hi-C sequencing, consisted of 298 Mb, of which 270 Mb (90%) was placed on seven chromosome-length scaffolds with an average length of 38.6 Mb. Approximately 52.8% of the genome was composed of repetitive elements. The genome sequence was highly collinear with a novel maternal haplotype-resolved linkage map of the tetraploid blackberry selection A-2551TN and genome assemblies of R. chingii and red raspberry. A total of 38,503 protein-coding genes were predicted using the assembly and Iso-Seq and RNA-seq data, of which 72% were functionally annotated. ConclusionsThe utility of the Hillquist genome has been demonstrated here by the development of the first genotyping-by-sequencing based linkage map of tetraploid blackberry and the identification of several possible candidate genes for primocane-fruiting within the previously mapped locus. This chromosome-length assembly will facilitate future studies in Rubus biology, genetics, and genomics and strengthen applied breeding programs.

genomics↗

bioRxiv2021

Natural variation in the control of flowering and shoot architecture in diploid Fragaria species

In perennial fruit and berry crops of the Rosaceae family, flower initiation occurs in late summer or autumn after downregulation of a strong repressor TERMINAL FLOWER1 (TFL1) and flowering and fruiting takes place the following growing season. Rosaceous fruit trees typically form two types of axillary shoots, short flower-bearing shoots called spurs and long shoots that are respectively analogous to branch crowns and stolons in strawberry. However, regulation of flowering and shoot architecture differs between species and environmental and endogenous controlling mechanisms have just started to emerge. In woodland strawberry (Fragaria vesca L.), long days maintain vegetative meristems and promote stolon formation by activating TFL1 and GIBBERELLIN 20-OXIDASE4 (GA20ox4), respectively, while silencing of these factors by short days and cool temperatures induces flowering and branch crown formation. We characterized flowering responses of 14 accessions of seven diploid Fragaria species native to diverse habitats in the northern hemisphere, and selected two species with contrasting environmental responses, F. bucharica Losinsk. and F. nilgerrensis Schlecht. ex J. Gay for detailed studies together with F. vesca. Similar to F. vesca, F. bucharica was induced to flower in short days at 18{degrees}C and regardless of photoperiod at 11{degrees}C after silencing of TFL1. F. nilgerrensis maintained higher TFL1 expression level and likely required cooler temperatures or longer exposure to inductive treatments to flower. We also found that high expression of GA20ox4 was associated with stolon formation in all three species, and its downregulation by short days and cool temperature caused branch crown formation in F. vesca and F. nilgerrensis, although the latter did not flower. F. bucharica, in contrast, rarely formed branch crowns, regardless of flowering or GA20ox4 expression level. Our findings highlighted diploid Fragaria species as a rich source of genetic variation controlling flowering and plant architecture, with potential applications in breeding of Rosaceous crops.

plant biology↗

bioRxiv2019

GENETIC BASES OF APOSEMATIC TRAITS: INSIGHTS FROM THE SKIN TRANSCRIPTIONAL PROFILES OF Oophaga POISON FROGS

AO_SCPLOWBSTRACTC_SCPLOWAposematic organisms advertise their defensive toxins to predators using a variety of warning signals, including bright coloration. While most Neotropical poison frogs (Dendrobatidae) rely on crypsis to avoid predators, Oophaga poison frogs from South America advertise their chemical defenses, a complex mix of diet-derived alkaloids, by using conspicuous hues. The present study aimed to characterize the skin transcriptomic profiles of the South American clade of Oophaga poison frogs (O. anchicayensis, O. solanensis, O. lehmanni and O. sylvatica). Our analyses showed very similar transcriptomic profiles for these closely related species in terms of functional annotation and relative abundance of gene ontology terms expressed. Analyses of expression profiles of Oophaga and available skin transcriptomes of cryptic anurans allowed us to propose possible mechanisms for the active sequestration of alkaloid-based chemical defenses and to highlight some genes that may be potentially involved in resistance mechanisms to avoid self-intoxication and skin coloration. In doing so, we provide an important molecular resource for the study of warning signals that will facilitate the assembly and annotation of future poison frog genomes.

molecular biology↗