Biology subjects

Sala, A.

Publications and source records attributed to Sala, A..

9 recordsLinked to original sources

bioRxiv2026

Ectomycorrhizal networks propagate carbon deficit and drought stress among trees

How plants allocate carbon determines their productivity, responses to stress, and interactions with other organisms. A substantial amount of plant carbon is stored as non-structural carbohydrates (NSC), which sustain turgor via osmoregulation and fuel metabolism when carbon is limited. NSC also support root-colonizing mycorrhizal fungi, thus we hypothesized that under carbon-limiting conditions such as drought, a trade-off between feeding mycorrhizal fungi and maintaining turgor may arise. We reduced carbon allocation to ectomycorrhizal (EcM) networks by girdling Pinus ponderosa trees exposed to drought or ambient conditions and manipulated putative fungal connections between trees by trenching. We show that, in droughted plots, trees putatively connected to girdled trees by EcM networks had 33 % less needle NSC and >10% less turgor than those connected to ungirdled trees. Trees disconnected from the mycorrhizal network by trenching had increased NSC likely from the increased water availability with girdling, but these gains were offset in the presence of networks. Our results demonstrate that the increased carbon demand by EcM fungi in response to reduced carbon inputs from some trees can deplete NSC in neighboring trees via shared mycorrhizal networks. At least in the short term, allocation trade-offs under carbon-limiting conditions may expose networked trees to carbon deficits. This may increase vulnerability to drought, which may be particularly acute given shifts in climate.

ecology↗

bioRxiv2025

A CDCA2 - MYC positive feedback loop controls cancer cells survival

MYC transcription factors are encoded by a small family of genes which include, in addition to the prototype member MYC, MYCN and MYCL. The majority of human cancers display expression alterations of MYC genes and their products, making this group of oncoproteins among the most relevant therapeutic targets in oncology. MYC is regulated at multiple levels, and protein phosphorylation is a critical mechanism used by the cell to modulate MYC stability and activity. Although there is a reasonable knowledge of the kinases required for MYC modifications, the counteracting phosphatases have been relatively understudied. Here we have investigated the role of the chromatin remodelling factor and protein phosphatase 1 (PP1) regulatory subunit CDCA2, also known as RepoMan, in the regulation of MYC proteins in cancer cells. Using RNA interference and regulatable degron-mediated degradation of CDCA2, we demonstrate that the PP1 subunit is required for MYC and MYCN stabilisation and viability of triple negative breast cancer, neuroblastoma and colon cancer cells. Proximity ligation assays indicate that both MYC and MYCN are in close proximity of CDCA2 in vivo. Furthermore, chromatin immunoprecipitation data and promoter mutation studies establish that CDC2A is a bone-fide MYC target gene in cancer cells, revealing a reciprocal regulatory loop that could be exploited for therapeutic purposes.

cell biology↗

bioRxiv2024

Systematic study of hybrid triplex topology and stability suggests a general triplex-mediated regulatory mechanism

By combining in-silico, biophysical and in-cellulo experiments, we decipher the topology, physical and potential biological properties of hybrid-parallel nucleic acids triplexes; an elusive structure at the basis of life. We found that hybrid triplex topology follows a stability order: r(Py)-d(Pu){middle dot}r(Py)> r(Py)-d(Pu){middle dot}d(Py)> d(Py)-d(Pu){middle dot}d(Py)> d(Py)-d(Pu){middle dot}r(Py). The r(Py)-d(Pu){middle dot}d(Py) triplex is expected to be the preferred in the cell as it avoids the need to open the duplex reducing the torsional stress required for triplex formation in the r(Py)-d(Pu){middle dot}r(Py) topology. Upon a massive collection of melting data, we have created the first predictor for hybrid triplex stability. Leveraging this predictor, we conducted a comprehensive scan to assess the likelihood of the human genome and transcriptome to engage in triplex formation. Our findings unveil a remarkable inclination - of both the human genome and transcriptome - to generate hybrid triplex formation, particularly within untranslated (UTRs) and regulatory regions, thereby corroborating the existence of a triplex-mediated regulatory mechanism. Furthermore, we found a correlation between nucleosome linkers and TFS which agree with a putative role of triplexes in arranging chromatin structure and local/global level.

molecular biology↗

bioRxiv2022

DNAffinity: A MACHINE-LEARNING APPROACH TO PREDICT DNA BINDING AFFINITIES OF TRANSCRIPTION FACTORS

We present a physics-based machine learning approach to predict in vitro transcription factor binding affinities from structural and mechanical DNA properties directly derived from atomistic molecular dynamics simulations. The method is able to predict affinities obtained with techniques as different as uPBM, gcPBM and HT-SELEX with an excellent performance, much better than existing algorithms. Due to its nature, the method can be extended to epigenetic variants, mismatches, mutations, or any non-coding nucleobases. When complemented with chromatin structure information, our in vitro trained method provides also good estimates of in vivo binding sites in yeast.

molecular biology↗

bioRxiv2022

Engineered model of t(7;12)(q36;p13) AML recapitulates patient-specific features and gene expression profiles

Acute myeloid leukaemia carrying the translocation t(7;12)(q36;p13) is an adverse-risk leukaemia uniquely observed in infants. Despite constituting up to 30% of cases in under 2-year-olds, it remains poorly understood. Known molecular features are ectopic overexpression of the MNX1 gene and generation of a fusion transcript in 50% of patients. Lack of research models has hindered understanding of t(7;12) biology, which has historically focused on MNX1 overexpression rather than the cytogenetic entity itself. Here, we employed CRISPR/Cas9 to generate t(7;12) in the human K562 cell line, and in healthy CD34+ haematopoietic progenitors where the translocation was not sustained in long-term cultures or through serial replating. In contrast, in K562 cells, t(7;12) was propagated in self-renewing clonogenic assays, with sustained myeloid bias in colony formation and baseline depletion of erythroid signatures. Nuclear localisation analysis revealed repositioning of the translocated MNX1 locus to the interior of t(7;12)-harbouring K562 nuclei - a known phenomenon in t(7;12) patients which associates with ectopic overexpression of MNX1. Crucially, the K562-t(7;12) model successfully recapitulated the transcriptional landscape of t(7;12) patient leukaemia. In summary, we engineered a clinically-relevant model of t(7;12) acute myeloid leukaemia with the potential to unravel targetable molecular mechanisms of disease.

cancer biology↗

bioRxiv2020

Relative water content consistently predicts drought mortality risk in seedling populations with different morphology, physiology, and times to death

Predicted increases in forest drought mortality highlight the need for predictors of incipient drought-induced mortality (DIM) risk that enable proactive large-scale management. Such predictors should be consistent across plants with varying morphology and physiology. Because of their integrative nature, indicators of water status are promising candidates for real time monitoring of DIM, particularly if they standardize morphological differences among plants. We assessed the extent to which differences in morphology and physiology between Pinus ponderosa populations influence time to mortality and the predictive power of key indicators of DIM risk. Time to incipient mortality differed between populations but occurred at the same relative water content (RWC) and water potential (WP). RWC and WP were accurate predictors of drought mortality risk. These results highlight that variables related to water status capture critical thresholds during DIM and the associated dehydration processes. Both WP and RWC are promising candidates for large-scale assessments of DIM risk. RWC is of special interest because it allows comparisons across different morphologies and can be remotely sensed. Our results offer promise for real-time landscape-level monitoring of DIM and its global impacts in the near term.

plant biology↗

bioRxiv2020

Plant carbohydrate depletion spreads via ectomycorrhizal networks impairing plant water relations

Carbon and water relations are fundamental to plant life and strongly interact. Under drought, the ability of plants to assimilate carbon is reduced, which increases their consumption of stored labile carbon in the form of non-structural carbohydrates (NSC). This process may impair plant water relations, but mechanisms are not clear, and we do not know if their effects are independent of water deficit. If so, carbon costs of fungal symbionts could also indirectly influence drought tolerance of plants through stored NSC depletion. We connected well-watered Pinus ponderosa seedling pairs via ectomycorrhizal (EM) networks where one seedling was shaded and the other experienced full light and compared responses to seedling pairs in the light. We measured plant water relations and traced carbon movements using 13CO2 to explore the mechanisms linking stored NSC to water relations, and to identify potential tradeoffs between drought tolerance and maintaining EM fungi under carbon-limiting conditions. We found that even in the absence of drought, mild NSC depletion decreased plant drought tolerance by indirectly impairing osmoregulation capacity and turgor maintenance. This demonstrates that NSC storage influences plant drought tolerance independently of plant water status. We also found that EM networks propagated NSC depletion and its negative effects on drought tolerance from carbon stressed hosts to non-stressed hosts. These results highlight carbon allocation tradeoffs between supporting fungal symbionts and retaining water via stored NSC and have implications for biotic interactions and forest drought responses. Significance StatementThe potential effects of future drought on global carbon cycles, vegetation-climate feedbacks, species distributions and their ecological impacts, urgently call for a clear understanding of factors influencing vegetation tolerance to drought. Key to this is the understanding of mechanisms and processes by which plants tolerate drought and how prevalent plant-fungal interactions may influence these processes. We demonstrate that even mild depletion of plant non-structural carbohydrate (NSC) storage readily decreases plant water retention capacity, therefore decreasing tolerance to drought. Because plant-fungal interactions depend on NSC exchange, plants face carbon-allocation tradeoffs between maintaining drought tolerance and feeding fungal symbionts. The impacts of these tradeoffs extend across plants connected via ectomycorrhizal networks as fungi propagate NSC depletion from NSC-limited plants to non-stressed individuals.

plant biology↗

bioRxiv2020

The Atlas of Inflammation-Resolution (AIR)

Acute inflammation is a protective reaction by the immune system in response to invading pathogens or tissue damage. Ideally, the response should be localized, self-limited, and returning to homeostasis. If not resolved, acute inflammation can result in organ pathologies leading to chronic inflammatory phenotypes. Acute inflammation and inflammation resolution are complex coordinated processes, involving a number of cell types, interacting in space and time. The biomolecular complexity and the fact that several biomedical fields are involved, make a multi and interdisciplinary approach necessary. This Atlas of Inflammation Resolution (AIR) is a web-based resource capturing the state-of-the-art in acute inflammation and inflammation resolution research. The AIR provides an interface for users to search thousands of interactions, arranged in inter-connected multi-layers of process diagrams, covering a wide range of clinically relevant phenotypes. The AIR serves as an open access knowledgebase, including a gateway to numerous public databases. It is furthermore possible for the user to map experimental data onto the molecular interaction maps of the AIR, providing the basis for bioinformatics analyses and systems biology approaches. By mapping experimental data onto the Atlas, it can be used to elucidate drug action as well as molecular mechanisms underlying different disease phenotypes. For the visualization and exploration of information, the AIR uses the Minerva platform, which is a well-established tool for the presentation of disease maps. The molecular details of the AIR are encoded using international standards. The Atlas of Inflammation Resolution was created as a freely accessible resource, supporting research and education in the fields of acute inflammation and inflammation resolution. The AIR connects research communities, facilitates clinical decision making, and supports research scientists in the formulation and validation of hypotheses.

immunology↗

bioRxiv2019

Bottom trawl catch comparison in the Mediterranean Sea: Flexible Turtle Excluder Device (TED) vs traditional gear

The Mediterranean Sea is a hotspot of biodiversity, but the high fishing pressure results in high bycatch rates of protected (sea turtles and cetaceans) and top predator species (sharks). The reduction of bycatch is challenging for fishery scientists, as conservation of these species has become a priority. Among the animals threatened by fishing activities, the loggerhead (Caretta caretta) represents a charismatic species considered as \"vulnerable\" at the global scale by IUCN.\n\nIn the Mediterranean Sea, trawl nets show the highest probabilities of bycatch of protected species, with high rates of mortality. A new flexible Turtle Excluder Device (TED) has been tested for the first time on a commercial scale in the Mediterranean Sea to assess its effectiveness in reducing bycatch. The results did not show any significant ( = 0.05) loss in terms of commercial weight, but a significant reduction of debris in the codend of the nets mounting the TED respect to traditional nets. The catch comparison of the main commercial species showed similar rates without any significant loss of sizes, with the only exception of anglerfishes (Lophius spp.) that showed a loss of the largest individuals by TED. In terms of bycatch, the traditional nets captured mostly rays and sharks, while no turtles were captured, at all. In this regard, the authors were informed by other vessels operating in the same areas at the time of the trials about some accidental catches of loggerhead turtles. Our results demonstrated that the flexible TED represents a practical and effective solution to reduce the bycatch of endangered species in coastal Mediterranean demersal multispecies fisheries, as demonstrated experimentally also in other areas of the world. The measures involving technical modifications of fishing gears require significant investments but are technically feasible and could guarantee the success of the conservation.

ecology↗