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Casal, J.

Publications and source records attributed to Casal, J..

10 recordsLinked to original sources

TDP-43 expression in the cytoplasm leads to early synaptic and mitochondrial abnormalities in an inducible mouse model of ALS/FTD

TDP-43 proteinopathy is the primary pathology associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), indicating that these neurodegenerative diseases have common underlying mechanisms. We have previously shown that transgenic (Tg) mice conditionally overexpressing a cytoplasmic form of human TDP-43 protein (TDP-43-{Delta}NLS) in forebrain neurons replicate key features of FTD/ALS, including altered cognitive, motor and social behaviors. These behavioral phenotypes and changes in plasticity-related gene expression can be detected as early as 1 month after Tg induction, before overt neurodegeneration occurs. To assess early ultrastructural features in this model, we performed Transmission Electron Microscopy (TEM) analysis in the cortex (Ctx) and hippocampus (Hp) of Tg animals and their non-Tg controls. TEM evaluation of Ctx and Hp revealed that synaptic density was significantly decreased and synapse length was increased in both regions of Tg animals. Synaptic cleft thickness was increased and post-synaptic density thickness was decreased only in the Ctx of Tg mice, revealing differential regional effects in synaptic morphology. We analysed mitochondrial density and we found an increase in the Ctx and a decrease in the Hp of Tg animals, with preserved individual mitochondrial area. Lastly, transcriptomic and proteomic analysis from both transgenic TDP-43-{Delta}NLS mice and human proteinopathy showed widespread decreased expression of synaptic structure and function genes. The alterations in synaptic density and architecture reported here, combined with the mRNA/protein expression data, suggest that TDP-43-{Delta}NLS mice may exhibit abnormal synaptic transmission and that ultrastructural changes play a role in the early behavioral deficits observed in this model. HighlightsO_LICytoplasmic TDP-43 expression in vivo causes early synaptic and mitochondrial abnormalities. C_LIO_LIReduced synaptic density observed in cortical and hippocampal regions of TDP-43-{Delta}NLS mice. C_LIO_LISynaptic ultrastructure altered, including increased cleft width and reduced PSD thickness. C_LIO_LIRegion-specific mitochondrial density changes: increased in cortex, decreased in hippocampus. C_LIO_LIFindings link TDP-43 mislocalization to early structural and functional brain deficits. C_LI

neuroscience↗

What Large Language Models Know About Plant Molecular Biology

Large language models (LLMs) are rapidly permeating scientific research, yet their capabilities in plant molecular biology remain largely uncharacterized. Here, we present MOBIPLANT, the first comprehensive benchmark for evaluating LLMs in this domain, developed by a consortium of 112 plant scientists across 19 countries. MOBIPLANT comprises 565 expert-curated multiple-choice questions and 1,075 synthetically generated questions, spanning core topics from gene regulation to plant-environment interactions. We benchmarked seven leading chat-based LLMs using both automated scoring and human evaluation of open-ended answers. Models performed well on multiple-choice tasks (exceeding 75% accuracy), although most of them exhibited a consistent bias towards option A. In contrast, expert reviews exposed persistent limitations, including factual misalignment, hallucinations, and low self-awareness. Critically, we found that model performance strongly correlated with the citation frequency of source literature, suggesting that LLM knowledge inherits the visibility distribution of the underlying scientific corpus. Consequently, models tend to be more reliable on consolidated topics and less reliable on under-cited or recently emerging ones. We also benchmarked agents equipped with web-search and additional tools in more complex tasks involving DNA sequence analysis. These agents were outperformed by domain specific models in sequence classification and regression tasks, indicating an opportunity for joint agentic systems that combine both the reasoning power of LLMs and the dedicated processing of DNA models. This understanding is key to guiding both the development of next-generation models and the informed use of current tools in the everyday work of plant researchers. MOBIPLANT is publicly available online in this link.

plant biology↗

Wild boar trade and African swine fever risk of introduction into new territories: A quantitative release assessment with retrospective data of wild boar shipments to France and Spain (2010-2017).

Wild boar (WB) (Sus scrofa) farming and trade in EU countries consistently developed at the end of the last century, primarily for repopulating hunting estates within the sport hunting industry. Since the introduction of African swine fever (ASF) in the Caucasus in 2007 and its subsequent spread from Eastern to Central Europe, international WB trade increased the risk of ASF introduction into new territories. In order to prevent such events, the EU veterinary authorities decided to ban WB trade in June 2018. In our study, we documented retrospective WB trade movements to France and Spain between 2010 and 2017, and used this data to undertake a quantitative risk assessment for ASF introduction resulting from those shipments. A total of 127 trade events introducing live WB into France (n=93) and Spain (n=34) from Eastern EU countries were recorded between 2010 and 2017, encompassing a total of 5567 animals. Hungary was the main exporter to both countries while Poland was the main exporter to France. The highest annual risk of ASF release was related to shipments from Poland to France after 2014 coinciding with an epidemic phase of ASF in that country. During the same period, the risk of ASFV introduction from Hungary to France was much smaller but gradually increased, coinciding with outbreaks in adjacent Ukraine territory during 2015 onward. Despite no outbreaks in France nor Spain were detected to date, quantified values of ASF introduction risk into Western Europe were very high, suggesting that prohibiting international WB trade in 2018 was well justified. Our study highlights the relevance to monitor and supervise more closely legal wildlife production within the EU countries. Our results are an interesting example on how to use trade data to design and implement risk reduction strategies to reduce the spread of pathogens in the wildlife trade sector. Highlights This is the first documented report of the legal trade of live WB between EU countries during the last decade (2010-2017) prior to the EU Commissions decision to prohibit shipments of live wild pigs from ASF-infected areas in June 2018. It provides insight into the level of trade between Eastern and Southern EU countries between 2010 and 2017. Results highlight that the risks of disease introduction and dissemination of African swine fever through the legal wildlife trade during the study period were very high and measures taken by banning WB trade in June 2018 were totally justified. Our data suggest that collecting and sharing information on wildlife production and trade can be beneficial for identifying and managing disease risks. This work served as a good example of a risk assessment exercise with potential applications for other infectious pathogens as well as wildlife production and trade situations such as promoting cross-sector collaboration between animal health, agricultural and wildlife authorities or strengthening the design and implementation of regulations in the surveillance of captive wild animals

zoology↗

Planar cell polarity: intracellular asymmetry and supracellular gradients of Dachsous

The slope of a supracellular molecular gradient has long been thought to orient and coordinate planar cell polarity (PCP). Here we demonstrate and measure that gradient. Dachsous (Ds) is a conserved and elemental molecule of PCP; Ds forms intercellular bridges with another cadherin molecule, Fat (Ft), an interaction modulated by the Golgi protein Four- jointed (Fj). Using genetic mosaics and tagged Ds we measure Ds in vivo in membranes of individual cells over a whole metamere of the Drosophila abdomen. We find: 1. A supracellular gradient that rises from head to tail in the anterior compartment (A) and then falls in the posterior compartment (P). 2. There is more Ds in the front than the rear membranes of all cells in the A compartment, except that compartments most anterior and most posterior cells. There is more Ds in the rear than in the front membranes of all cells of the P compartment 3. The loss of Fj removes intracellular asymmetry anteriorly in the segment and reduces it elsewhere. Additional experiments show that Fj makes PCP more robust. Using Dachs (D) as a molecular indicator of polarity, we confirm that opposing gradients of PCP meet slightly out of register with compartment boundaries.

developmental biology↗

Day length-dependent thermal COP1 dynamics integrate conflicting seasonal cues in the control of Arabidopsis elongation

As the summer approaches, plants experience enhanced light inputs and elevated temperatures, two environmental cues with an opposite morphogenic impact. How plants integrate this conflicting information throughout seasons remains unclear. Key components of the plant response to light and temperature include phytochrome B (phyB), PHYTOCROME INTERACTING FACTOR 4 (PIF4), EARLY FLOWERING 3 (ELF3) and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). Here, we used hypocotyl lengths of single and double mutant/over-expression lines to fit a mathematical model incorporating known interactions of these genes. The fitted model recapitulates day length-dependent thermoelongation of all lines studied, and correctly predicts temperature responsiveness of new genotypes. Whilst previous works pointed to a lightindependent thermal function of COP1, simulations of our model suggested that COP1 has a role in temperature-signaling only during daytime. Based on by this prediction, we show that COP1 overexpression increases thermal response in continuous white light, while it has little effect in darkness. Defective thermal response of cop1-4 mutants is epistatic to phyB-9 and elf3-8, indicating that COP1 activity is essential to the transduction of phyB and ELF3 thermosensory function. Our model accurately captures phyB, ELF3 and PIF4 dynamics, providing an excellent toolbox for identification of best allelic combinations towards optimized crops resilience to climate change at different geographical latitudes.

plant biology↗

How do Dachsous and Fat polarise cells in the larval abdomen of Drosophila?

We investigate the mechanisms of planar cell polarity (PCP) in the Drosophila larva. The epidermis displays an intricate pattern of polarity and is excellent for the study of one system of PCP, the Dachsous/Fat system; partly because the Starry Night/Frizzled system plays no discernable role in the larva. Measurements of the amount of Dachsous reveal a peak near the rear of the anterior compartment. Localisation of Dachs and orientation of ectopic denticles reveal the polarity of every cell in the segment. We discuss how well these findings evidence our gradient model of Dachsous activity. Several groups have proposed that Dachsous and Fat fix the direction of PCP via oriented microtubules that transport PCP proteins to one side of the cell. We test this proposition in the larval cells and find that most microtubules grow perpendicularly to the axis of PCP. We find no meaningful bias in the polarity of those microtubules aligned close to that axis. We also reexamine published data from the pupal abdomen and fail to find evidence supporting the hypothesis that microtubular orientation draws the arrow of PCP.

developmental biology↗

Shade-avoidance responses become more aggressive in warm environments

When exposed to neighbour signals, competitive plants increase the growth of the stem to reduce the degree of current or future shade. Plants can experience similar neighbour cues under different weather conditions and the aim of this work is to investigate the impact of daily average temperature and irradiance and thermal amplitude on the magnitude of shade-avoidance responses in Arabidopsis thaliana. For this purpose, we first generated a growth database and elaborated under controlled conditions a model that predicts hypocotyl growth during the photoperiod as a function of the light-modulated activity of the main photo-sensory receptors (phytochromes A and B, cryptochromes 1 and 2), temperature-modulated activity of phytochrome B and an independent temperature input. Thermal amplitude (lower temperatures during the morning and afternoon that at midday) reduced growth of genotypes with normally fast morning growth, and this effect was incorporated to the model. Thermal amplitude also decreased the abundance of the growth-promoting transcription factor PHYTOCHROME-INTERACTING FACTOR 4. The model predicted growth in the field through different seasons with reasonable accuracy. Then, we used the model in combination with a worldwide dataset of current and future whether conditions. The analysis predicted enhanced shade-avoidance responses as a result of higher temperatures due to the geographical location or global warming. Irradiance and thermal amplitude had no effects. These trends were also observed for our local growth measurements. We conclude that, if water and nutrients do not become limiting, warm environments enhance the shade avoidance response.

plant biology↗

A survey of biosecurity measures applied on dairy cattle farms in Spain

Attention to biosecurity has been highlighted as the most important measure to reduce and prevent the introduction of diseases to farms. There is little published information about the biosecurity of dairy cattle in Spain. We therefore aimed to assess and characterize the current application of biosecurity measures on dairy cattle farms in Spain, and relate these to bovine viral diarrhea and infectious bovine rhinotracheitis. From July 2017 to April 2018, data on biosecurity measures for 124 dairy herds were collected using a questionnaire. We also assessed the sanitary status of these farms (efficacy of measures implemented against both diseases using antibody ELISA. Data were analyzed descriptively, and using multiple correspondence analysis and a two-step cluster analysis. Measures to prevent disease introduction were often poorly implemented. Three main clusters of farms were identified: Clusters 1 and 2 included herds of small and intermediate sizes, respectively. These, particularly cluster 1, showed the most deficiencies in the control of vehicles and visitors. However, individual purchases usually involved low numbers of animals, especially in cluster 2, and animals were tested for bovine viral diarrhea and infectious bovine rhinotracheitis at their places of origin or on arrival at farms. Farms in clusters 1 and 2 were frequently under voluntary control programs. Cluster 3 had the largest herd sizes, with somewhat better biosecurity control of vehicles and visitors. However, farms in this cluster also purchased the most animals, sometimes without testing, and hired external workers most often. Farms in cluster 1 showed the best sanitary level, followed by clusters 2 and 3. Collecting data such as these is an important first step to identification of biosecurity shortcomings, and to structuring of adequate follow-up to ensure that measures are implemented correctly on farms in Spain.

epidemiology↗

A refutation to ‘A new A-P compartment boundary and organizer in holometabolous insect wings.’

We respond to a recent report by Abbasi and Marcus who present two main findings: first they argue that there is an organiser and a compartment boundary within the posterior compartment of the butterfly wing. Second, they present evidence for a previously undiscovered lineage boundary near wing vein 5 in Drosophila, a boundary that delineates a \"far posterior\" compartment. Clones of cells were marked with the yellow mutation and they reported that these clones always fail to cross a line close to vein 5 on the Drosophila wing. In our hands yellow proved an unusable marker for clones in the wing blade and therefore we reexamined the matter. We marked clones of cells with multiple wing hairs or forked and found a substantial proportion of these clones cross the proposed lineage boundary near vein 5, in conflict with their findings and conclusion. As internal controls we showed that these same clones respect the other two well established compartment boundaries: the anteroposterior compartment boundary is always respected. The dorsoventral boundary is mostly respected, and is crossed only by clones that are induced early in development, consistent with many reports. We question the validity of Abbasi and Marcus conclusions regarding the butterfly wing but present no new data.\n\nArising from: R. Abbasi and J. M. Marcus Sci. Rep. 7, 16337 (2017); https://doi.org/10.1038/s41598-017-16553-5

developmental biology↗

Planar Cell Polarity: What Does The prickle Gene Do?

Epithelial cells are polarised within the plane of the epithelium, forming oriented structures whose coordinated and consistent polarity (planar cell polarity, PCP) relates to the principal axes of the body or organ. In Drosophila at least two separate molecular systems generate and interpret intercellular polarity signals: Dachsous/Fat, and the \"core\" or Stan system. Here we study the prickle gene and its protein products Prickle and Spiny leg. Much research on PCP has focused on the asymmetric localisation of core proteins in the cell and as a result prickle was placed in the heart of the Stan system. Here we ask if this view is correct and how the prickle gene relates to the two systems. We find that prickle can affect, separately, both systems -- however, neither Pk nor Sple are essential components of the Ds/Ft or the Stan system, nor do they act as a functional link between the two systems.

developmental biology↗