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Biology subjects

Mina, M.

Publications and source records attributed to Mina, M..

7 recordsLinked to original sources

Loss of competitive strength in European conifer species under climate change

Climate change is expected to alter species assemblages by affecting the outcome of competition between species. Investigating processes of competition remains challenging particularly in tree communities, as they unfold over extensive spatio-temporal scales. Here, we developed a deep-learning approach to leverage a novel database of 135 million simulated local-scale tree responses to climate across continental Europe to investigate changes in the competitiveness of nine major tree species under different scenarios of climate change. Specifically, we trained a Deep Neural Network on local process model projections to investigate climate change effects on indicators of competitive strength and species dominance. We found decreasing competitive strength for all investigated evergreen coniferous species across their distribution, while major deciduous broadleaved species such as Quercus robur and Fagus sylvatica increased in competitiveness. Changes in tree species competition with climate differed locally, but most investigated species lost competitive strength at their warm range edges. As a consequence of these changes, up to 19% of Europes forests could experience a change in the dominant tree species until the end of the 21st century. Our results suggest a profound climate-induced reassembly of Europes forests and identify areas that may require specific attention in forest policy and management.

ecology↗

Naturalness of forest composition affects vulnerability to climate change and disturbances in Alpine mountain landscapes

European mountain forests have been strongly shaped by past human activities, which have influenced their structure and composition. Assessing the natural tree-species composition of current forest landscapes is essential for evaluating their biodiversity potential and for informing management prioritization. High levels of compositional naturalness are often associated with greater ecosystem functioning, but it remains unclear whether forest landscapes that are closer to their potential forest composition are also less vulnerable to future climate change and natural disturbances. Using a process-based forest landscape model, we quantified the naturalness and the vulnerability to disturbances across a large forested area in the Italian Alps. We developed a spatially-explicit index to evaluate how closely current tree species composition matches potential forest composition. We then simulated future forest dynamics under multiple climate change and disturbance scenarios, using two different initial vegetation conditions on the same landscape - potential vs. current forest - and compared their vulnerability based on changes in species dominance, vegetation structure, and height heterogeneity. Results indicate that current forests exhibit generally low naturalness compared with their potential forest composition, reflecting historical management and agro-silvopastoral practices. The naturalness score changed depending on elevation across the landscape: forests at low (<1500 m a.s.l.) and high (>2100 m a.s.l.) elevations had low naturalness, while those in the mid-elevation range (1500-2100 m) exhibited medium to high levels of naturalness. Vulnerability to disturbances under climate change differed markedly between the two initial vegetation conditions. Current forest was more susceptible to bark beetle outbreaks, driven by past promotion of Norway spruce and further amplified by warming. In contrast, the potential forest was more vulnerable to wind disturbance, likely due to old-growth characteristics, such as greater height heterogeneity and canopy roughness, that increase blowdown susceptibility. This study provides the first assessment of forest naturalness using spatially explicit dynamic landscape modelling. Given the projected intensification of natural disturbances under future climates, our findings suggest that promoting more natural forest conditions alone may not guarantee higher resilience to climate-induced disturbances. Instead, management approaches should aim at increasing landscape-level structural and compositional heterogeneity in a balanced manner to minimizing future disturbance vulnerability.

ecology↗

Tissue specificity and chromosomal alterations shape divergent immune programs in HRD tumors

Homologous recombination deficiency (HRD) activates pro-inflammatory cGAS/STING signaling, positioning it as a biomarker for combining immune checkpoint blockade (ICB) and PARP inhibition (PARPi). However, the consequences of HRD on the immune landscape across cancers remain unclear. Here, we applied a pan-cancer HRD classifier to >10,000 tumors from The Cancer Genome Atlas and uncovered striking heterogeneity in immune activity. Compared to HR-proficient tumors, HRD tumors showed elevated inflammation in breast, ovarian, and endometrial cancers. These tumors exhibited robust activation of innate and adaptive immune pathways (IFN, NF-{kappa}B) and transcriptional hallmarks of senescence, angiogenesis, and adenosine signaling. In contrast, lung, head and neck, and melanoma HRD tumors displayed suppressed inflammation and evidence of immune escape through large-scale loss-of-heterozygosity (LOH) at IFNA/B, STING, and other loci. These tumors also frequently presented HLA LOH and oncogene amplifications, suggesting selection under immune pressure and replication stress. Together, our study resolves HRD tumors into two immune archetypes, immune-inflamed and immune-evasive, linked to chromosomal instability and lineage, informing biomarker-driven evaluation of immune checkpoint blockade/PARPi combinatorial therapies.

genomics↗

Reliability of canopy photography for forest ecology and biodiversity studies

Understory is a key component of forest biodiversity. The structure of the forest stand and the horizontal composition of the canopy play a major role on the light regime of the understory, which in turn affects the abundance and the diversity of the understory plant community. Reliable assessments of canopy structural attributes are essential for forest research and biodiversity monitoring programs, as well as to study the relationship between canopy and understory plant communities. Canopy photography is a widely used method but it is still not clear which photographic techniques is better suited to capture canopy attributes at stand-level that can be relevant in forest biodiversity studies. For this purpose, we collected canopy structure and understory plant diversity data on 51 forest sites in the north-eastern Italian Alps, encompassing a diversity of forest types. Canopy images were acquired using both digital cover (DCP) and hemispherical (DHP) photography. Canopy structural attributes were then compared to tree species composition data to evaluate whether they were appropriate to differentiate between forest types. Additionally, we tested what canopy attributes derived from DCP and DHP best explained the species composition of vascular plants growing in the understory. We found that hemispherical canopy photography was most suitable to capture differences in forest types, which was best expressed by variables such as leaf inclination angle and canopy openness. On our sites, DHP-based canopy attributes were also able to better distinguish between different conifer forests. Leaf clumping was the most important attribute for determining plant species distribution of the understory, indicating that diverse gap structures create different microclimate conditions enhancing diverse plant species with different ecological strategies. This study supports the reliability of canopy photography in forest ecology and biodiversity monitoring, but also provide insights for increasing understory diversity in managed forests of high conservation value. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/610276v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@15b706forg.highwire.dtl.DTLVardef@329571org.highwire.dtl.DTLVardef@f13605org.highwire.dtl.DTLVardef@11b816_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

Peptidergic modulation of motor neuron output via CART signaling at C bouton synapses

The intensity of muscle contraction, and therefore movement vigour, needs to be adaptable to enable complex motor behaviors. This can be achieved by adjusting the properties of motor neurons, which form the final common pathway for all motor output from the central nervous system. Here we identify novel roles for a neuropeptide, Cocaine and Amphetamine Regulated Transcript (CART), in the control of movement vigour. We reveal distinct, but parallel mechanisms by which CART and acetylcholine, both released at C bouton synapses on motor neurons, selectively amplify the output of subtypes of motor neurons that are recruited during intense movement. We find that mice with broad genetic deletion of CART or selective elimination of acetylcholine from C boutons exhibit deficits in behavioral tasks that require higher levels of motor output. Overall, these data uncover novel spinal modulatory mechanisms that control movement vigour to support movements that require a high degree of muscle force.

neuroscience↗

Longitudinal characterisation of phagocytic and neutralisation functions of anti-Spike antibodies in plasma of patients after SARS-CoV-2 infection.

Phagocytic responses by effector cells to antibody or complement-opsonised viruses have been recognized to play a key role in anti-viral immunity. These include antibody dependent cellular phagocytosis mediated via Fc-receptors, phagocytosis mediated by classically activated complement-fixing IgM or IgG1 antibodies and antibody independent phagocytosis mediated via direct opsonisation of viruses by complement products activated via the mannose-binding lectin pathway. Limited data suggest these phagocytic responses by effector cells may contribute to the immunological and inflammatory responses in SARS-CoV-2 infection, however, their development and clinical significance remain to be fully elucidated. In this cohort of 62 patients, acutely ill individuals were shown to mount phagocytic responses to autologous plasma-opsonised SARS-CoV-2 Spike protein-coated microbeads as early as 10 days post symptom onset. Heat inactivation of the plasma prior to use as an opsonin caused 77-95% abrogation of the phagocytic response, and pre-blocking of Fc-receptors on the effector cells showed only 18-60% inhibition. These results suggest that SARS-CoV-2 can provoke early phagocytosis, which is primarily driven by heat labile components, likely activated complements, with variable contribution from anti-Spike antibodies. During convalescence, phagocytic responses correlated significantly with anti-Spike IgG titers. Older patients and patients with severe disease had significantly higher phagocytosis and neutralisation functions when compared to younger patients or patients with asymptomatic, mild, or moderate disease. A longitudinal study of a subset of these patients over 12 months showed preservation of phagocytic and neutralisation functions in all patients, despite a drop in the endpoint antibody titers by more than 90%. Interestingly, surface plasmon resonance showed a significant increase in the affinity of the anti-Spike antibodies over time correlating with the maintenance of both the phagocytic and neutralisation functions suggesting that improvement in the antibody quality over the 12 months contributed to the retention of effector functions. Author SummaryLimited data suggest antibody dependent effector functions including phagocytosis may contribute to the immunological and inflammatory responses in SARS CoV-2 infection, however, their development, maintenance, and clinical significance remain unknown. In this study we show: O_LIPatients with acute SARS CoV-2 infection can mount phagocytic responses as early as 10 days post symptom onset and these responses were primarily driven by heat labile components of the autologous plasma. These results indicate that the current approach of studying phagocytosis using purified or monoclonal antibodies does not recapitulate contribution by all components in the plasma. C_LIO_LIIn convalescent patients, high phagocytic responses significantly correlated with increasing age, increasing disease severity, high neutralisation functions and high anti-Spike antibody titers, particularly IgG1. C_LIO_LILongitudinal study of convalescent patients over a 12-month period showed maintenance of phagocytic and neutralisation functions, despite a drop in the anti-Spike endpoint antibody titers by more than 90%. However, we found significant increase in the affinity of the anti-Spike antibodies over the 12-month period and these correlated with the maintenance of functions suggesting that improvement in the antibody quality over time contributed to the retention of effector functions. Clinically, measuring antibody titers in sera but not the quality of antibodies is considered a gold standard indicator of immune protection following SARS-CoV 2 infection or vaccination. Our results challenge this notion and recommends change in the current clinical practice. C_LI

immunology↗

Evolutionary dynamics and molecular features of intra-tumor heterogeneity

The systematic assessment of intra-tumor heterogeneity is still limited and often unfeasible. In silico investigations of large tumor cohorts can be used to decipher how multiple clones emerge and organize into complex architectures. Here, we addressed this challenge by integrating mathematical modeling of cancer evolution with algorithmic inference of clonal phylogenies in 2,600 human tumors from 15 tumor types. Through numerical simulations, we could discriminate between observable and hidden intra-tumor heterogeneity, the latter characterized by clones that are missed by DNA sequencing of human samples. To overcome this limitation in human tumors, we show that population frequencies of detectable clones can be used to estimate the extent of hidden heterogeneity. Overall, simulated and human clonal architectures were highly concordant and showed that high numbers of clones invariably emerge through branching lineages. Interestingly, high numbers of alterations were not necessarily associated with high intra-tumor heterogeneity. Indeed, tumors with alterations in proliferation-associated genes exhibited high numbers of clonal mutations, but few clones. Instead, mutations of chromatin remodeling genes characterized tumors with high numbers of subclonal alterations and multiple clones. Our results identify evolutionary and genetic determinants of tumor clonal architectures to guide functional investigations of intra-tumor heterogeneity.

cancer biology↗