Biology subjects

Agostini, A.

Publications and source records attributed to Agostini, A..

7 recordsLinked to original sources

bioRxiv2026

Bidirectional Electron Transfer in Far-Red-Light Adapted Photosystem I. Implications for the Photosystem's Functionality

Far-Red (FR) Light Photoacclimation (FaRLiP) enables cyanobacteria to extend photosynthetic activity into the far-red region by extensively remodelling Photosystem I (PSI), including the replacement of several core subunits with paralogs that coordinate the red-shifted chlorophyll f (Chl f). The binding positions of Chls f are still a matter of debate, with the most recent structural findings supporting the location of a single Chl f molecule within the reaction centre (RC) at the so-called A-1B site. This was in turn suggested to strongly affect electron transfer (ET) directionality leading to an almost monodirectional transfer along the B branch in FR-PSI RC. Here, we directly probe ET in FR-PSI by characterising the photogenerated [P700A1-] spin-correlated radical pair using complementary pulse and Time-Resolved (TR) Electron Paramagnetic Resonance (EPR) spectroscopy at cryogenic temperature. Electron spin-echo decay kinetics are distinctly biexponential, indicating the formation of two charge-separated states. Consistently, out-of-phase ESEEM traces are quantitatively described by two modulation frequencies arising from different dipolar interactions, while TR-EPR spectra are accurately simulated by the combined contributions of [P700A1A-] and [P700A1B-] radical pairs. These results provide direct spectroscopic evidence that both the A and B branches remain photochemically active in FR-PSI. The conservation of bidirectional ET, even when considering the presence of a single Chl f molecule in the RC, further implies that the two radical pairs originate from a common primary electron donor. This finding identifies P700 as the most likely primary donor and argues against a mechanism in which the RC Chl f initiates charge separation.

biophysics↗

bioRxiv2026

Multi-omics integration identifies a reproducible inflammatory host-response axis in pediatric sepsis

Sepsis is a major cause of morbidity and mortality in children, yet biological heterogeneity in host responses has limited progress toward targeted therapies and patient stratification. Multiomics integration can combine complementary molecular layers to identify coordinated disease programs not captured by individual assays. Here, we integrated genomic, bulk transcriptomic, proteomic and metabolomic data from blood samples of 22 children with culture-confirmed bacterial sepsis enrolled in the Swiss Pediatric Sepsis Study. Multi-Omics Factor Analysis identified a dominant host-response axis reflecting systemic inflammation. This axis was driven primarily by transcriptomic variation and supported by coordinated proteomic and metabolomic signals, including circulating inflammatory mediators and altered amino-acid metabolism. It was associated with C-reactive protein and a severity score proxy. Projection into an independent pediatric sepsis cohort (n = 22) reproduced the inflammatory and severity-related interpretation of this axis. Single-omic projections showed that the integrated signal could be approximated from individual layers, particularly transcriptomics. In three external pediatric whole-blood transcriptomic datasets, the RNA-derived projection separated septic shock from healthy controls and increased across clinical inflammatory syndromes. These findings define a reproducible inflammatory host-response axis in pediatric sepsis and support multi-omics-guided selection of molecular readouts suitable for clinical translation.

immunology↗

bioRxiv2026

Diet-induced macrophage-driven inflammation fuels pancreatic plasticity and aggressiveness

High-fat diet (HFD) and obesity are increasingly recognized as risk factors of pancreatic ductal adenocarcinoma (PDAC), yet the mechanisms by which dietary fat contribute to oncogenic transformation remain elusive. Using an inducible acinar-specific KrasG12V/Trp53-loss genetically-engineered mouse model of PDAC, we established early-and late-onset protocols to assess age-dependent susceptibility to HFD. Specifically, HFD accelerated tumorigenesis with poorer prognosis in early-onset mice and, strikingly, enabled full PDAC development in late-onset adult mice otherwise resistant to oncogenic transformation. Tumors arising under HFD activated a distinct transcriptional and epigenetic state enriched in pathways or genes related to stemness, plasticity, and metastatic competence, which was maintained even in tumor-derived cell lines. Mechanistically, fatty acid-educated macrophages secreted the cathelicidin antimicrobial peptide (CAMP), activating P2X purinoceptor 7 (P2RX7) signaling in tumor cells to drive a highly plastic, immune-evasive phenotype reinforced by the expression of the peptidoglycan recognition protein 1 (PGLYRP1), further shielding tumor cells from macrophage phagocytosis. Functionally, HFD-induced tumors displayed enhanced metastatic potential independent of host context. Analysis of 164 human PDAC samples revealed that elevated body-mass index (BMI) was associated to a conserved CAMP-P2RX7-CXCR4 signature, maintained despite weight loss during disease progression. Together, these findings uncover a diet-imprinted macrophage-tumor cell circuit that promotes transformation and accelerates PDAC progression, positioning it as a therapeutic vulnerability in obesity-associated pancreatic cancer. Statement of significanceHigh-fat diet induces pancreatic tumorigenesis in adult tissue, driving metastatic competence and a plastic state, and ultimately engages a macrophage-derived CAMP-P2RX7 circuit that reinforces immune evasion and accelerates PDAC progression.

cancer biology↗

bioRxiv2025

Enhanced carotenoid photoprotection in Far-Red light acclimated Chroococcidiopsis thermalis

Oxygenic photosynthesis is mainly driven by visible light in most photosynthetic organisms. However, some cyanobacteria strains can reversibly remodel their photosynthetic apparatus in order to rely exclusively on far-red photons. This acclimation, known as FaRLiP, requires the synthesis of red-shifted pigments, chlorophyll d, chlorophyll f and far-red allophycocyanin, that are incorporated in paralog subunits of the main photosynthetic complexes, namely photosystem II and photosystem I as well as phycobilisomes. In addition, some far-red-acclimating strains were also observed to show a rise in the carotenoid content and in the expression of genes involved in the biosynthesis of UV-shielding molecules, suggesting a counterintuitive photoprotective response concomitant with acclimation to lower energy wavelengths. In this work we investigated the response of Chroococcidiopsis thermalis to far-red light, and identified a robust set of photoprotective mechanisms associated with acclimation. Enhanced carotenoid/chlorophyll content ratios correlated with stronger carotenoid-chlorophyll triplet quenching, particularly pronounced for red-shifted chlorophylls. Non-photochemical quenching was higher and activated more rapidly than in cells grown under simulated solar light, and this was accompanied by enhanced antioxidant activity. Collectively, these findings indicate that the far-red acclimated cells, whose photosynthetic apparatus is not optimal under visible light, exhibit a strong photoprotected state, that we propose to be crucial under fluctuating irradiance conditions and during transitions from shaded to non-shaded environments. HighlightsO_LIFar-red light photoacclimation (FaRLiP) in Chroococcidiopsis thermalis is associated with an increased carotenoid-to-chlorophyll ratio. The relative abundance of myxol-2 fucoside, echinenone and {beta}-carotene increased in cells acclimated to far-red light compared with cells acclimated to simulated solar irradiation. C_LIO_LIUpon establishment of FaRLiP an exceptionally strong chlorophyll triplet quenching by carotenoids was observed, and it was specifically involving red-shifted chlorophylls. C_LIO_LIWhen exposed to the same light treatment, non-photochemical quenching was higher in far-red-acclimated cells than in solar-acclimated. Moreover, following high visible-light stress, far-red-acclimated cells exhibited lower levels of reactive oxygen species. The FaRLiP photosynthetic apparatus is safeguarded by robust mechanisms of photoprotection. C_LI

plant biology↗

bioRxiv2025

The Recombination Triplet State in the Far-Red Light Adapted Photosystem II is Located at the ChlD1 Site and Resides on the Red-Most Chlorophyll of the Reaction Center.

The energetic limits of Photosystem II (PSII) photochemical reactivity required reconsideration after the discovery of far-red light acclimation responses in cyanobacteria. Insights on PSII functionality following the inclusion of the red shifted Chlorophylls d and f can be obtained by extending the current knowledge on spectroscopic and structural properties of its reaction center (RC). The photo-induced triplet states, that represent selective endogenous probes, were therefore investigated in far-red adapted PSII by magnetic resonance techniques. Zero-field splitting tensor analysis combined with spin-polarization dynamics arising from radical pair recombination unambiguously identify an intrinsically low-energy-absorbing chlorophyll participating to charge separation reactions. The triplet-minus-singlet (T-S) spectrum associated to the recombination triplet state, obtained by microwave selection, showed a sharp 725 nm bleaching demonstrating the dominant involvement of this red-shifted chlorophyll in the lowest RC exciton. Moreover, spectral simulations provided strong evidence in favor of its localization at the ChlD1 position, making it the most likely site of primary photochemistry.

biochemistry↗

bioRxiv2024

Origin of the far-red absorbance in eustigmatophyte algae red-shifted Violaxanthin-Chlorophyll a Protein

Photosynthetic organisms harvest light for energy. Some eukaryotic algae have specialized in harvesting far-red light by tuning chlorophyll a absorption through a mechanism still to be elucidated. Here, we combined optically detected magnetic resonance and pulsed electron paramagnetic resonance measurements on red-adapted light-harvesting complexes, rVCP, isolated from the freshwater eustigmatophyte alga Trachydiscus minutus to identify the location of the pigments responsible for this remarkable adaptation. The pigments have been found to belong to an excitonic cluster of chlorophylls a at the core of the complex, close to the central carotenoids in L1/L2 sites. A pair of structural features of the Chl a403/a603 binding site, namely the histidine-to-asparagine substitution in the magnesium-ligation residue and the small size of the amino acid at the i-4 position, are proposed to be the origin of this trait. Phylogenetic analysis of various eukaryotic red antennae identified several potential LHCs that could share this tuning mechanism.

biophysics↗

bioRxiv2022

Transcriptomic dissection of Intraepithelial Papillary Mucinous Neoplasms progression by spatial technologies identified novel markers of pancreatic carcinogenesis.

Intraductal papillary mucinous neoplasms (IPMN) are one of the main precursor lesions of Pancreatic Ductal Adenocarcinoma (PDAC). The number of patients diagnosed with IPMN is constantly increasing. While in most of the cases IPMN present as indolent and nonmalignant entities, some degenerate into PDAC. The main mechanisms behind the IPMN progression to malignancy is still not fully understood. This is mainly due to the technological limit of the analyzes and to cysts heterogeneity whose malignant transformation potential is estimated based on size and degree of dysplasia without take in consideration the transformation time and therefore the real malignancy potential. Moreover, there is a general lack of consensus diagnostic markers to discern the Low-grade nonmalignant from High-grade malignant IPMN. In this study, we used two different Spatial Transcriptomic technologies (Visium, and GeoMx) to investigate the transcriptome of Low-grade dysplasia nonmalignant IPMN, Borderline IPMN, and High-grade dysplasia malignant IPMN to dissect the main mechanism that drives carcingenesis and to find specific markers associated to risk of tumor progression. We performed Visium spatial transcriptomics on two TMAs containing three Low-grade dysplasia nonmalignant IPMN, one Borderline IPMN, two High-grade dysplasia malignant IPMN, and two PDAC. We identified three specific epithelial cell clusters that characterize Low-grade dysplasia IPMN, Borderline IPMN, and High-grade dysplasia malignant IPMN and three transcription factors whose expression is associated with each grade. High-grade malignant IPMN were characterized by high expression levels of NKX6-2 and other markers of gastric isthmus cell lineage such as MUC5AC, PSCA, FERIL6. The SPDEF high IPMN cluster was found in Borderline IPMN and spotted in some regions of High-grade malignant IPMN. This cluster was characterized by high expression levels of SPDEF and other goblet cell lineage markers such as TFF2, AQP5, and MUC6. Low-grade nonmalignant IPMN were characterized by high expression levels of HOXB3, HOXB5, ZNF117. The association of these markers with the different grades was validated by GeoMx spatial transcriptomics on 43 additional IPMN samples divided according to their grade of dysplasia and malignancy. To better understand the transcriptomic changes along IPMN progression we performed spatial trajectory inference and we found that SPDEF high IPMN cluster cells are likely to evolve into NKX6-2 high malignant IPMN, and we found that this switch is characterized by the expression of NKX6-2 and other gastric markers. Taken together, the results presented here not only shed more light in to IPMN and PDAC oncogenesis, but also provided a plethora of novel malignancy-associated markers to be tested in diagnostic routine, to better delineate IPMN progression in patients and improve clinical management.

cancer biology↗