Biology subjects

Cattaneo, G.

Publications and source records attributed to Cattaneo, G..

5 recordsLinked to original sources

bioRxiv2025

Distinguishing Lifelong Individual Differences from Divergent Aging Trajectories of Adult Brain Volumes

Individual differences in the volumes of brain structures are often linked to various conditions, including Alzheimers disease, schizophrenia, and overall brain health. However, it remains unclear to what extent these differences reflect individual levels present from young adulthood or diverging aging trajectories from later ages. In this study, we analyze the aging dynamics of the volumes of six brain structures based on magnetic resonance imaging (MRI) scans from a large cross-cohort longitudinal sample of cognitively healthy adults (n = 8,311 with 18,520 MRIs, ages from 18 to 97 years). From general assumptions about structural brain dynamics and measurement noise, a stochastic dynamical model was fitted to the data to estimate both the variability and persistence of structural changes across adulthood. Using this model, we calculated how much of the variance of volumetric differences between individuals can be attributed to stable levels from young adulthood versus systematic changes at older ages, as well as the theoretical sensitivity of longitudinal studies to detect individual differences in change. The findings were as follows: 1) Before age 60 years, inter-individual differences in neuroanatomical volumes almost exclusively reflect stable differences between individuals, while the influence from systematic differences in rate-of-change increases thereafter; up to 50 % of the variation being due to differences in change at 80 years. In contrast, ventricular volume reflects differences in change from early adulthood. 2) Current brain-age models are unlikely to be sensitive to detect differences in aging trajectories. 3) Imaging studies have low reliability in detecting inter-individual brain changes before age 60. After 60 years, the study reliability increases sharply with longer intervals between scans and more modestly with additional intermediate observations. In conclusion, our results reinforce the view that it is critical to distinguish stable early-adulthood levels from systematic differences in change when studying adult brain aging.

neuroscience↗

bioRxiv2025

Vulnerability to memory decline in aging. A mega-analysis of structural brain change.

Brain atrophy is a key factor behind episodic memory loss in aging, but the nature and ubiquity of this relationship remains poorly understood. This study leveraged 13 longitudinal datasets, including 3,737 cognitively healthy adults (10,343 MRI scans; 13,460 memory assessments), to determine whether brain change-memory change associations are more pronounced with age and genetic risk for Alzheimers Disease. Both factors are associated with accelerated brain decline, yet it remains unclear whether memory loss is exacerbated beyond what atrophy alone would predict. Additionally, we assessed whether memory decline aligns with a global pattern of atrophy or stems from distinct regional contributions. Our mega-analysis revealed a nonlinear relationship between memory decline and brain atrophy, primarily affecting individuals with above-average brain structural decline. The associations were stronger in the hippocampus but also spread across diverse cortical and subcortical regions. The associations strengthened with age, reaching moderate associations in participants in their eighties. While APOE {varepsilon}4 carriers exhibited steeper brain and memory loss, genetic risk had no effect on the change-change associations. These findings support the presence of common biological macrostructural substrates underlying memory function in older age which are vulnerable to multiple age-related factors, even in the absence of overt pathological changes.

neuroscience↗

bioRxiv2024

Releasing the octoPus, an open-source digital tool to promote Integrated Pest Management

Meeting the EU targets to halve chemical pesticide use by 2030 necessitates European farmers to adopt Integrated Pest Management principles as the standard. Decision support systems are valuable tools to meet this target and rely on individual disease models to identify conducive conditions to fungal infections. These models are often proprietary assets of digital startups and agrochemical companies, leading to a lack of transparency for farmers and a bias towards chemical solutions over sustainable practices. We present octoPus, the first free digital tool designed to support the control of primary infections of grapevine downy mildew, and we evaluate its performance and behavior on a wide set of environmental conditions and agricultural contexts. We implemented eight models from scientific articles (Rule310, Laore, EPI, IPI, DMcast, UCSC, Misfits, Magarey, the "tentacles"), and evaluated them across Italian grapevine areas from 2001 to 2020. Model outputs were integrated with phenology and susceptibility models (the "eyes"), which were calibrated using data from regional extension services bulletins. The simulated infections serve as predictors in a Random Forest algorithm ("brain") that elaborates an overall risk level (very low to very high). The Llama large language model is used to generate user-supportive messages (the "mouth"). octoPus is released as an open-source software, which reads weather data, executes the models, and presents outputs in natural language and symbolic syntax. Our results showed reasonable accuracy in simulating grapevine phenology (RMSE = 9-10 days) and seasonal risk (RMSE {approx} 0.75). The infection models consistently identified a moisture and thermal north-south suitability gradient in Italy and accurately detected years with low or high downy mildew pressure. However, the models displayed significant differences in the number and dynamics of simulated infections, with two distinct patterns within the ensemble. By developing and releasing the first free and open-source tool to support the control of grapevine downy mildew, we address a critical gap in the availability and transparency of decision support systems for European farmers. Unlike proprietary models that often lack transparency and may favor agribusiness logic, octoPus provides a comprehensive and accessible alternative that promotes Integrated Pest Management practices. We propose the adoption of octoPus by plant health authorities to identify areas for performance refinement and capabilities expansion.

ecology↗

bioRxiv2024

Disrupting CD38-driven T cell dysfunction restores sensitivity to cancer immunotherapy

A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma1,2. T cell exhaustion, resulting from chronic antigen exposure in the tumour microenvironment, is a major driver of ICB resistance3. Here, we show that CD38, an ecto-enzyme involved in nicotinamide adenine dinucleotide (NAD+) catabolism, is highly expressed in exhausted CD8+ T cells in melanoma and is associated with ICB resistance. Tumour-derived CD38hiCD8+ T cells are dysfunctional, characterised by impaired proliferative capacity, effector function, and dysregulated mitochondrial bioenergetics. Genetic and pharmacological blockade of CD38 in murine and patient-derived organotypic tumour models (MDOTS/PDOTS) enhanced tumour immunity and overcame ICB resistance. Mechanistically, disrupting CD38 activity in T cells restored cellular NAD+ pools, improved mitochondrial function, increased proliferation, augmented effector function, and restored ICB sensitivity. Taken together, these data demonstrate a role for the CD38-NAD+ axis in promoting T cell exhaustion and ICB resistance, and establish the efficacy of CD38 directed therapeutic strategies to overcome ICB resistance using clinically relevant, patient-derived 3D tumour models.

cancer biology↗

bioRxiv2020

Greater TMS-evoked frontoparietal effective connectivity is correlated with better cognitive performance

Fronto-parietal activity has been related to fluid intelligence and flexible cognitive control. However, causal insights on this relation are lacking. We used real-time integration of MRI-guided TMS and EEG to characterize the spatial and temporal properties of signal propagation between these two regions and relate them to cognitive performance. 31 healthy adults (55 {+/-}6 years, 20 female) underwent TMS-EEG and a full cognitive assessment. Local and propagated current from 5 source space-reconstructed scouts ipsilateral to two stimulation sites (pre frontal cortex (PFC) and inferior parietal lobule (IPL)) was quantified in two-time windows (15-40ms and 40-80ms) and related to domain-general (global cognition) and domain-specific (memory, working memory, reasoning, flexibility, lexical access and visuo-spatial) cognitive functions. TMS-evoked activity from stimulation of the PFC and the IPL resulted in local and distributed activity across frontoparietal regions. TMS-evoked activity in local regions was not correlated with cognitive functions. In response to TMS of the PFC, propagated current to the distal superior parietal scout in the first 15-40ms was significantly associated with global cognition ({beta} = 2.63, SE = .898, p = .008, R2 = .31). Similarly, following TMS of the IPL, propagation to the middle prefrontal gyrus scout (15-40ms) was significantly associated with global cognition ({beta} = 2.67, SE = 1.289, p = .025, R2 = .27). In an exploratory step, domain-specific correlations were seen in the PFC condition. Locally evoked activity measured via source space reconstruction from TMS of two association hubs is not associated with cognitive functions. However, the propagation of the TMS pulse through frontoparietal connections is associated with overall cognitive ability. These associations are driven by a number of cognitive domains in the PFC stimulation condition.

neuroscience↗