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Franco, A.

Publications and source records attributed to Franco, A..

11 recordsLinked to original sources

SenoQuant: One-stop AI software for senescence marker analysis and prediction

Senescent cells accumulate with age and contribute to tissue dysfunction, yet their identification in tissues is challenging due to low abundance, heterogeneous phenotypes, and the lack of specific markers. Senescence-associated features span multiple subcellular compartments, including nuclear DNA damage foci, cytosolic protein changes, and perinuclear alterations, each requiring tailored detection strategies. To overcome these challenges, we developed SenoQuant (https://github.com/HaamsRee/senoquant), a versatile software designed for comprehensive, accurate, and unbiased spatial quantification and prediction of senescence markers across diverse tissue contexts. Utilizing AI models, SenoQuant enables precise nuclear and cytoplasmic segmentation and detection of senescence markers across low- and high-plex imaging modalities, applicable to cultured cells and tissue sections from mice and humans. The platform also supports custom AI models; for example, we built SenCeption, a proof-of-concept predictor of single-cell p21 status from DAPI-stained nuclei in human skin. Available as a free napari plugin, SenoQuant is widely accessible to researchers. By providing a unified approach to senescence analysis and prediction, SenoQuant opens new opportunities for exploring the complex biology of senescence and its impacts on aging and disease.

Cell Biology↗

Monitoring jumping ability and subjective recovery in women's volleyball: acute effects of match play on countermovement jump and well-being

PurposeJumping ability is a crucial element for success in volleyball. Monitoring it helps optimize performance and prevent injuries. The countermovement jump (CMJ) is a reliable, non-invasive, and quick tool to periodically assess neuromuscular fatigue and performance, which, in combination with subjective measures, can offer a comprehensive view of fatigue/recovery status. The study aimed to: a) analyze changes in CMJ after a womens volleyball match based on playing time and b) evaluate the temporal recovery of subjective variables TQR (perceived recovery) and HI (well-being). It was hypothesized that players would recover baseline values of CMJ and subjective variables 48 hours post-match. MethodsA descriptive, longitudinal, and repeated-measures design was proposed. Twelve volleyball players were evaluated for changes in CMJ before and after a match, and at 24-, 48-, and 72-hours post-match. Outcome variables (jump height and RSImod), kinetic variables (concentric impulse), and jump strategy variables (contraction time and time to peak power) were analyzed. TQR and HI scales assessed perceived recovery and well-being. ResultsSignificant changes were observed in jump height, concentric impulse, and RSImod between pre-match and 48 hours post-match in players with less playing time. Subjective variables TQR and HI did not show significant differences during the study period. ConclusionCompetition did not significantly affect CMJ variables, suggesting that volleyball does not reduce jumping ability immediately after competing, which has direct implications for microcycle structure. The study highlights the importance of continuous monitoring of performance and recovery in volleyball.

physiology↗

HBN-EEG: The FAIR implementation of the Healthy Brain Network (HBN) electroencephalography dataset

The Child Mind Institute (CMI) Healthy Brain Network (HBN) project has recorded phenotypic, behavioral, and neuroimaging data from [~]5,000 children and young adults between the ages of 5 and 21. Here, we present HBN-EEG, the "analysis-ready" data from its high-density (128-channel) electroencephalographic (EEG) recording sessions formatted as Brain Imaging Data Structure (BIDS) datasets. HBN-EEG also includes behavioral and task-condition events annotated using Hierarchical Event Descriptors (HED), making the datasets analysis-ready for many purposes without forensic search for unreported details. We also ensured data consistency and event integrity and marked inconsistencies. HBN-EEG sessions include six tasks, three with no participant behavioral input (passive tasks) and three including button press responses following task instructions (active tasks). Openly available participant information includes age, gender, and four psychopathology dimensions (internalizing, externalizing, attention, and p-factor) derived from a bifactor model of questionnaire data. Currently, HBN-EEG data from more than 2,600 participants is freely available on NEMAR (nemar.org) and OpenNeuro in the form of nine dataset releases, with further dataset releases to follow.

neuroscience↗

A human mitofusin 2 mutation causes mitophagic cardiomyopathy

Cardiac muscle has the highest mitochondrial density of any human tissue, but mitochondrial dysfunction is not a recognized cause of isolated cardiomyopathy. Here, we determined that the rare mitofusin (MFN) 2 R400Q mutation is ~20x over-represented in clinical cardiomyopathy, whereas this specific mutation is not reported as a cause of the MFN2 mutant-induced peripheral neuropathy, Charcot-Marie-Tooth disease type 2A (CMT2A). Accordingly, we interrogated the enzymatic, biophysical and functional characteristics of MFN2 Q400 versus wild-type and representative CMT2A-causing MFN2 mutants. All MFN2 mutants we studied suppressed mitochondrial fusion, the canonical MFN2 function. Compared to CMT2A mutants MFN2 R94Q and T105M that lacked catalytic GTPase activity and exhibited normal activation-induced changes in conformation, MFN2 Q400 had normal GTPase activity with impaired conformational shifting. GTPase-defective MFN2 mutants, but not MFN2 Q400, suppressed mitochondrial motility, provoked mitochondrial depolarization and reduced mitochondrial respiration. By contrast, MFN2 Q400 was uniquely defective in recruiting Parkin to mitochondria. CRISPR editing of the R400Q mutation into the mouse Mfn2 gene induced perinatal cardiomyopathy with no other organ involvement. RNA sequencing and metabolomics of cardiomyopathic Mfn2 Q400 hearts revealed signature abnormalities recapitulating experimental mitophagic cardiomyopathy. Indeed, cardiomyoblasts expressing MFN2 Q400 exhibited multiple mitophagy defects, but normal mitochondrial respiration. MFN2 Q400 is the first known natural mitophagy- and shape change-defective MFN2 mutant. Its unique profile of dysfunction evokes mitophagic cardiomyopathy, suggesting a mechanism for its enrichment in clinical cardiomyopathy.

developmental biology↗

Myosin II regulatory light chain phosphorylation and formin availability modulate cytokinesis upon changes in carbohydrate metabolism.

Cytokinesis, which achieves the separation of daughter cells after mitosis completion, relies in animal cells on a contractile actomyosin ring (CAR), made of actin and class II myosins, whose activity is heavily influenced by regulatory light chain (RLC) phosphorylation. However, in simple eukaryotes such as fission yeast Schizosaccharomyces pombe, regulation of CAR dynamics by RLC phosphorylation seems dispensable. We found that redundant phosphorylation at Ser35 of the S. pombe RLC homolog Rlc1 by the p21-activated kinases Pak1 and Pak2, modulates Myosin II Myo2 activity and becomes essential for cytokinesis and cell growth during respiration. Previously, we showed that the Stress Activated Protein Kinase Pathway (SAPK) MAPK Sty1 controls fission yeast CAR integrity by downregulating formin For3 levels (Gomez-Gil et al.,2020). Here we report that reduced availability of formin For3-nucleated actin filaments for the CAR is the main reason for the required control of myosin II contractile activity by RLC phosphorylation during respiration-induced oxidative stress. Hence, recovery of For3 levels with antioxidants bypasses the control of Myosin II function regulated by RLC phosphorylation to allow cytokinesis and cell proliferation during respiration. Therefore, a fine-tuned interplay between Myosin II function by Rlc1 phosphorylation and environmentally controlled actin filament availability is critical for a successful cytokinesis in response to a switch to a respiratory carbohydrate metabolism.

cell biology↗

Visual Perception of 3D Space and Shape in Time - Part I: 2D Space Perception by 2D Linear Translation

Visual perception plays a critical role in navigating space and extracting useful semantic information crucial to survival. To identify distant landmarks, we constantly shift gaze vectors through saccades, while still maintaining the visual perception of stable allocentric space. How can we sustain stable allocentric space so effortlessly? To solve this question, we have developed a new concept of NHT (Neural Holography Tomography). This model states that retinotopy is invisible (not available to consciousness) and must be converted to a time code by traveling alpha brainwaves to perceive objects consciously. According to this framework, if identical alpha phases are continually assigned to a landmark, we perceive its exact and consistent allocentric location. To test this hypothesis, we designed reaction time (RT) experiments to observe evidence of the predicted space-to-time conversion. Various visual stimuli were generated at a wide range of eccentricities either on a large TV (up to 40{degrees}) or by LED strips on a hemispherical dome (up to 60{degrees}). Participants were instructed to report the observed patterns promptly under either covert (no eye movement) or overt (with eye movement) conditions. As predicted, stimuli presented at the center of fixation always produced the fastest RTs. The additional RT delay was precisely proportional to the eccentricity of the peripheral stimulus presentation. Furthermore, both covert and overt attention protocols created the same RT delays, and trajectories of saccadic eye motions were in parallel to the overt RT vs. eccentricity. These findings strongly support our NHT model, in which the observed RT-eccentricity dependence is indicative of the spatiotemporal conversion required for maintaining a stable allocentric frame of reference. That is, we perceive space by time.

neuroscience↗

Moving Beyond Processing and Analysis-Related Variation in Neuroscience

When fields lack consensus standard methods and accessible ground truths, reproducibility can be more of an ideal than a reality. Such has been the case for functional neuroimaging, where there exists a sprawling space of tools and processing pipelines. We provide a critical evaluation of the impact of differences across five independently developed minimal preprocessing pipelines for functional MRI. We show that even when handling identical data, inter-pipeline agreement was only moderate, critically shedding light on a factor that limits cross-study reproducibility. We show that low inter-pipeline agreement mainly becomes appreciable when the reliability of the underlying data is high, which is increasingly the case as the field progresses. Crucially, we show that when inter-pipeline agreement is compromised, so too are the consistency of insights from brainwide association studies. We highlight the importance of comparing analytic configurations, as both widely discussed and commonly overlooked decisions can lead to marked variation.

neuroscience↗

Evidence of structural rearrangements and variability in pESI(like) megaplasmids of S.Infantis by resolving the pESI-like-blaCTX-M-1 positive variant.

The increasing prevalence of pESI(like)-positive, multidrug-resistant (MDR) S. Infantis in Europe is a cause of major concern. As previously demonstrated, the pESI(like) megaplasmid is not only a carrier of antimicrobial resistant (AMR) genes (at least tet, dfr and sul genes), but also harbours several virulence and fitness genes, and toxin/antitoxin systems that enhance its persistence in the S. Infantis host. In this study, five prototype pESI(like) plasmids, of either CTX-M-1 or CTX-M-65 ESBL producing strains, were long-read sequenced using Oxford Nanopore Technology (ONT) and their complete sequences were resolved. Comparison of the structure and gene content of the five sequenced plasmids, and further comparison with previously published pESI(like) sequences, indicated that although the sequence of such pESI(like) "mosaic" plasmids remains almost identical, their structures appear different and composed of regions inserted or transposed after different events. The results obtained in this study are essential to better understand the plasticity and the evolution of the pESI(like) megaplasmid, and therefore to better address risk management options and policy decisions to fight against AMR and MDR in Salmonella and other food-borne pathogens.

microbiology↗

Relative Concentration of Brain Iron (rcFe) Derived from Standard Functional MRI.

Brain iron plays key roles in catecholaminergic neurotransmitter synthesis and early life brain development. It is also central to cellular energetics and neurotransmitter metabolism throughout the lifespan. Disturbances in brain iron have been implicated in a growing number of psychiatric and late-life neurodegenerative disorders. Additionally, brain iron accumulations are thought to play a deleterious role in neuroinflammatory processes in later life. Despite its importance, the role of brain iron in development, aging, and psychiatric disorders remains comparatively understudied. This is partly due to technical challenges inherent in implementation and analysis of formal iron imaging protocols and practical constraints on scan session durations. Here, we introduce a method to estimate relative brain iron concentrations that is 1) computationally simple, 2) shows excellent correspondence with formal iron imaging in-vivo, 3) replicates clinically-relevant findings from formal iron imaging, 4) yields novel insights into brain iron and cognition across the lifespan, and 5) leverages a widely available and frequently shared brain imaging modality: functional MRI. The computationally simple nature of the measure, coupled with the availability of fMRI datasets across the lifespan and disorders, has the potential to transform our understanding of the complex and critical relationship between iron and brain health.

neuroscience↗

First report of enhanced contents of nine macro- and micronutrients in gymnosperms via arbuscular mycorrhizal fungi

Traditionally, it is thought that arbuscular mycorrhizae establish a mutualist symbiosis only with the roots of angiosperm plants. In this mutualism, fungi receive carbon from the plants, and angiosperms receive nutrients through the external mycelium of the arbuscular mycorrhizal fungi (AMF). However, the enhanced contents of macro- and micronutrients in gymnosperm plants, and therefore the mutualistic relationship, with AMF has not been reported so far. The present work evaluated whether arbuscular mycorrhizae were able to establish and enhance 9 nutrient contents in the neotropical Pinaceae species Pinus greggii. The tree seedlings were inoculated with three consortia of AMF isolated from an agricultural site, a forest of Cupressus lusitanica and a forest of Pinus hartwegii. The effect of AMF inoculation on plant growth and nutrient enhancement, in addition to colonization, was evaluated. There was evidence of enhancement of plant growth and 9 macro- and micronutrients in plants inoculated with the three evaluated consortia. After 7 months, the translocation was greater for Mg, Mn and Zn in plants inoculated with the consortium of AMF from pine forest. The presence of hyphae, vesicles and arbuscules was detected in the roots of the Pinus greggii plants inoculated with the AMF consortia. In addition to these positive effects, colonization of 10 to 15% and 20 to 38% was observed depending on the AMF consortia after 2 and 7 months, respectively. The presence of arbuscules which is the translocation structure among involved symbionts was also recorded; and photographed for the first time. In the present work, we report for the first time that arbuscular mycorrhiza affects the mobilization of N, P, K, Ca, Mg, Fe, Mn, Zn, Cu and B in gymnosperms, indicating that this mycorrhizal symbiosis is more complex than previously believed.

ecology↗

Unsupervised Extraction of Epidemic Syndromes from Participatory Influenza Surveillance Self-reported Symptoms

Seasonal influenza surveillance is usually carried out by sentinel general practitioners who compile weekly reports based on the number of influenza-like illness (ILI) clinical cases observed among visited patients. This practice for surveillance is generally affected by two main issues: i) reports are usually released with a lag of about one week or more, ii) the definition of a case of influenza-like illness based on patients symptoms varies from one surveillance system to the other, i.e. from one country to the other. The availability of novel data streams for disease surveillance can alleviate these issues; in this paper, we employed data from Influenzanet, a participatory web-based surveillance project which collects symptoms directly from the general population in real time. We developed an unsupervised probabilistic framework that combines time series analysis of symptoms counts and performs an algorithmic detection of groups of symptoms, hereafter called syndromes. Symptoms counts were collected through the participatory web-based surveillance platforms of a consortium called Influenzanet which is found to correlate with Influenza-like illness incidence as detected by sentinel doctors. Our aim is to suggest how web-based surveillance data can provide an epidemiological signal capable of detecting influenza-like illness temporal trends without relying on a specific case definition. We evaluated the performance of our framework by showing that the temporal trends of the detected syndromes closely follow the ILI incidence as reported by the traditional surveillance, and consist of combinations of symptoms that are compatible with the ILI definition. The proposed framework was able to predict quite accurately the ILI trend of the forthcoming influenza season based only on the available information of the previous years. Moreover, we assessed the generalisability of the approach by evaluating its potentials for the detection of gastrointestinal syndromes. We evaluated the approach against the traditional surveillance data and despite the limited amount of data, the gastrointestinal trend was successfully detected. The result is a real-time flexible surveillance and prediction tool that is not constrained by any disease case definition.\n\nAuthor summaryThis study suggests how web-based surveillance data can provide an epidemiological signal capable of detecting influenza-like illness temporal trends without relying on a specific case definition. The proposed framework was able to predict quite accurately the ILI trend of the forthcoming influenza season based only on the available information of the previous years. Moreover, we assessed the generalisability of the approach by evaluating its potentials for the detection of gastrointestinal syndromes. We evaluated the approach against the traditional surveillance data and despite the limited amount of data, the gastrointestinal trend was successfully detected. The result is a real-time flexible surveillance and prediction tool that is not constrained by any disease case definition.

epidemiology↗