Publications

Peptide-based vaccines offer a modular and readily manufacturable platform for both prophylactic and therapeutic immunization. However, their broader translation has been constrained by the limited capacity to predict protective immunity directly from sequence-level features. Recent advances in systems vaccinology and high-throughput immune profiling have substantially expanded the experimental evidence, while generative artificial intelligence now enables de novo design of peptide immunogens and multi-epitope antigens under precisely controlled constraints. This review approaches how these complementary developments are transforming peptide vaccine research, moving beyond classical reverse vaccinology and conventional epitope prediction toward integrated, data-driven design frameworks. We discuss key generative model architectures and conditioning strategies aligned with vaccine objectives, including approaches that account for structural presentation, antigen processing and population-level human leukocyte antigen (HLA) diversity. Central to this perspective is the requirement for rigorous experimental validation and for strengthening the computational–experimental feedback loop through iterative in vitro and in vivo testing informed by systems-level immune readouts. We highlight representative applications spanning infectious diseases, cancer immunotherapy and vector-borne vaccinology, and we outline major technical and translational challenges that must be addressed to enable robust real-world deployment. Finally, we propose future directions for precision peptide vaccinology, emphasizing standardized functional benchmarks, the development of richer curated datasets linking sequence space to immune outcomes, and the early incorporation of formulation and delivery constraints into generative design pipelines.

The concept of “Smart Secondary Metabolites” is introduced here to describe a privileged class of natural products defined by structural originality, biosynthetic adaptability, and broad interaction potential with biological systems. Elatol, a halogenated sesquiterpene chiefly produced by Laurencia red seaweeds and occasionally accumulated by their consumers, exemplifies this concept with remarkable clarity. Its biosynthesis unfolds from farnesyl diphosphate via γ-bisabolane cations, bromochlorination, and stereoselective cyclization to chamigrene scaffolds, generating both (+)- and (–)-enantiomers, two metabolites with clearly distinct potential ecological roles and pharmacological profiles. This review synthesizes the current state of knowledge on elatol’s distribution, biosynthetic origins, ecological relevance, and therapeutic potential. Elatol serves as a multifunctional chemical mediator, fulfilling defensive, communicative, and regulatory roles whose intensity shifts in response to herbivory, biofouling, temperature, and salinity. In parallel, its potent activities against infectious, metabolic, and neoplastic diseases highlight its growing value as a drug lead, reflected in a rising number of patent claims. Altogether, elatol emerges as a model Smart Secondary Metabolite whose ecological sophistication and biochemical versatility position it as a promising scaffold for marine-derived drug discovery.

The concept of “Smart Secondary Metabolites” is introduced here to describe a privileged class of natural products defined by structural originality, biosynthetic adaptability, and broad interaction potential with biological systems. Elatol, a halogenated sesquiterpene chiefly produced by Laurencia red seaweeds and occasionally accumulated by their consumers, exemplifies this concept with remarkable clarity. Its biosynthesis unfolds from farnesyl diphosphate via γ-bisabolane cations, bromochlorination, and stereoselective cyclization to chamigrene scaffolds, generating both (+)- and (–)-enantiomers, two metabolites with clearly distinct potential ecological roles and pharmacological profiles. This review synthesizes the current state of knowledge on elatol’s distribution, biosynthetic origins, ecological relevance, and therapeutic potential. Elatol serves as a multifunctional chemical mediator, fulfilling defensive, communicative, and regulatory roles whose intensity shifts in response to herbivory, biofouling, temperature, and salinity. In parallel, its potent activities against infectious, metabolic, and neoplastic diseases highlight its growing value as a drug lead, reflected in a rising number of patent claims. Altogether, elatol emerges as a model Smart Secondary Metabolite whose ecological sophistication and biochemical versatility position it as a promising scaffold for marine-derived drug discovery.

Cathelicidins, a diverse family of host defence peptides (HDPs) in vertebrates, are recognized for their potential in combating resistant microorganisms and their varied biological functions. While extensive studies have focused on mammalian cathelicidins, those in reptiles remain largely unexplored. In this study, we conducted a genome mining analysis that identified 287 cathelicidin genes across reptilian orders Testudines and Squamata. Of these genes, we identified 219 complete cathelicidin protein sequences and 68 cathelicidin-like gene copies that appear to be pseudogenes or gene fragments lacking intact open reading frames. We established for the first time a classification for reptile cathelicidins of the cited orders based on their sequence and structure, observing six types for Testudines and six for Squamata, suggesting a common ancestral lineage. Furthermore, we investigated the genomic arrangement of these cathelicidin genes, uncovering that they are grouped into clusters with variability in the gene number and in their organization. Cathelicidin derived mature peptides were classified into nine groups based on their sequences and physicochemical properties. This comprehensive study enhances the understanding of the cathelicidin family in reptiles, clarifying their genomic organization and describing the different types present. These classifications pave the way for future studies on the functions and specialization of each identified cathelicidin group. Moreover, they enable potential structure-activity studies of the peptides, establishing a foundation for differentiating their key features.

Endemism, a hallmark of island biodiversity, reaches its lowest levels among bryophytes compared with other land plants. Whether this pattern reflects low diversification rates, and why, or whether it is a result of loss of endemicity due to extinctions or subsequent continental (back-)colonization, is examined here through a review of available evidence in the Macaronesian flora. Significant genetic differentiation (GST, based on allele frequencies) was consistently found between Macaronesian and continental populations, ruling out the hypothesis that intense migrations necessarily hamper differentiation. A significant phylogeographical signal in the data (NST > GST; where NST is a GST analog incorporating phylogenetic relationships among alleles), involving higher mutation rates than dispersal rates and evidencing incipient speciation, was further found in more than 1/3 of the species investigated. The significantly higher average NST between extra-European regions and Macaronesia compared to Europe and Macaronesia suggests, however, that incipient speciation is more likely to occur between distant (Macaronesian versus extra-European) than closer (Macaronesian versus European) populations. In line with this, ancestral area estimations in Macaronesian endemic bryophyte species revealed that at least 50% of them have an extra-European origin, in contrast with the almost exclusively (>90%) European/Mediterranean origin of Macaronesian endemic spermatophytes. Allopatric speciation via long-distance dispersal and subsequent divergence of a single endemic species prevails in island bryophytes, wherein sympatric radiations virtually never occur. Such a speciation mode does not trigger high rates of endemism, in contrast to radiations in Macaronesian spermatophytes, which contribute to 56% of the total number of endemics. Several mechanisms may explain the failure of island bryophytes to diversify in situ, including the fact that oceanic islands are too small or insufficiently isolated from each other or from continents to promote sympatric speciation, the lack of key innovations, and phylogenetic niche conservatism for stable habitats not prone to trigger radiations. In comparison with spermatophytes, continental (back-)colonization further largely prevails in bryophytes and, unlike in many instances in angiosperms, is not followed by in situ speciation on the mainland. The consequent loss of the endemic status of species that did speciate on islands but subsequently enlarged their range further accounts for the low rates of endemism among island bryophyte floras and invalidates the use of endemism rates as a proxy of speciation rates in this group.

A practical and efficient regio- and stereoselective hydrophosphorylation of propiolates, as well as a multicomponent reaction incorporating an aldehyde component, is reported. Both processes proceed with atom economy in very straightforward experimental procedures. The reactions are catalyzed by DABCO (1,4-diazabicyclo[2.2.2]octane) and use readily available H-phosphonates as the phosphorylating agent.

Reactive oxygen species (ROS) are context-dependent mediators that function as second messengers at low, localized flux and as drivers of damage when production overruns buffering capacity. Outcomes are dictated by source identity, subcellular compartment and pulse kinetics—the “where–when–how much” rule. We synthesize advances (2015–2025) across principal generators—mitochondrial electron transport, NADPH oxidases, xanthine oxidoreductase and ER/peroxisomal oxidoreductases—to show how compartmental H2O2 microgradients encode reversible cysteine signaling, while iron-rich niches pivot chemistry toward peroxynitrite, Fenton-derived ·OH, lipid peroxidation and regulated cell death (apoptosis, ferroptosis, parthanatos). We integrate these mechanisms with endothelial dysfunction, innate immune priming, ECM remodeling and barrier failure across cardiovascular, metabolic, neurodegenerative, oncologic, pulmonary, renal and critical-illness contexts, emphasizing crosstalk with RNS/RSS and iron metabolism as key modulators. Methodologically, we advocate species-resolved, compartment-aware assessment—e.g., DHE → 2-OH-E⁺ HPLC for O2·−, targeted HyPer/roGFP-Orp for H2O2 and peroxiredoxin redox state—embedded in composite panels that pair flux with damage footprints and iron/ferroptosis metrics for attribution and trial guidance. Therapeutically, we argue against indiscriminate antioxidant loading in favor of node-specific, compartment-targeted modulation (NOX/NOS tuning, mitochondrial QC/RET tempering, ER redox control, iron/ferroptosis management, calibrated sulfur-axis support), implemented as time-staged sequences and titrated to biomarkers. Clarifying which species arise, where and when, reframes ROS from generic toxicity to precision redox modulation with translational impact.

Key Biodiversity Areas (KBAs) are sites that contribute significantly to the global persistence of biodiversity. Distinct genetic diversity has been introduced as one of the metrics to estimate whether a site holds a threshold proportion of a species' global genetic diversity during the KBA identification process. However, genetic data has so far not been applied in KBA identification due to the lack of thoroughly tested methods and guidance. We tested the suitability of six analytical methods for identification of KBAs based upon genetic data: allelic overlap, Analyses of Molecular Variance (AMOVA), average taxonomic distinctness (AvTD, Δ+), effective population size (Ne), the genetic differentiation index (Dest), and the diversity index Simpson's λ. We conclude that Δ+, a measure that was developed to measure taxonomic distinctness of biotic communities, performs best in the context of KBA identification as it reflects the unique nature of a species' genetic diversity, is based on simple allele frequencies, and can be easily applied and calculated. AMOVA, Ne, allelic overlap, and our modified version of λ were difficult to apply, interpret, or both. Dest is easily applied for measuring genetic distinctiveness but not genetic diversity. For this reason, it may not be suitable for prioritising areas for the long-term protection of the species.

Dedicated to the memory of Dra. Celina García, whose mentorship was essential to the development of this project. The authors express their deep gratitude to Prof. Víctor S. Martín, recently retired, for his generous contribution and financial support in the design of the synthesized products. Leishmaniasis and Chagas disease are parasitic infections with limited treatment options due to drug toxicity and rising resistance. Leishmaniasis, caused by Leishmania spp., often manifests in a cutaneous form and is treated with drugs like amphotericin B and miltefosine, which can cause severe side effects. Chagas disease, caused by Trypanosoma cruzi, is endemic in the Americas and classified by the WHO as a neglected tropical disease. Existing treatments are effective mainly in the acute phase but have significant limitations. In search of new therapies, this study explored diversity-oriented synthesis to generate a library of β,γ-unsaturated carboxylic acid derivatives. From 23 synthesized compounds −12 reported for the first time– several showed promising antiparasitic activity. Four compounds were effective against Leishmania amazonensis, with three also targeting the amastigote form. Two compounds showed activity against Trypanosoma cruzi, outperforming reference drugs in selectivity. Signs of parasite apoptosis, including mitochondrial damage and ROS accumulation, suggest strong therapeutic potential for these derivatives.

The earliest documentation of hundreds of ancient settlements in South Asia, including some of the most famous and significant sites, lies in largely unacknowledged subaltern hands. Operating during the British colonial period, teams employed by the Survey of India systematically mapped the colonial dominions and produced high-quality maps that depicted topography and land use across vast areas. Systematic analysis of these map sheets combined with ground-truthing is demonstrating that these teams documented thousands of mound features, and a significant number of these are (or sadly in many cases were) archaeological sites. Members of the original survey teams were for the most part not in a position to contribute their thoughts to the historical narrative, but the legacy of what they documented has long been hidden in plain sight. The collaborative Mapping Archaeological Heritage in South Asia (MAHSA) project is systematically documenting this archaeological heritage. Its work is demonstrating that the teams carrying out the Survey of India topographic surveys incidentally conducted the first systematic survey of archaeological sites in South Asia. This was potentially the world’s most extensive (albeit incidental) archaeological survey.