Biology subjects

Elias, E.

Publications and source records attributed to Elias, E..

7 recordsLinked to original sources

bioRxiv2026

The Red Blood Cell Surface Defines a Distinct Tumor DNA Compartment for Liquid Biopsy

Red blood cells (RBCs) modulate host inflammatory responses by scavenging mitochondrial and pathogen DNA. However, how RBC surface properties govern the capture of tumor-derived DNA remains poorly understood. We show that RBCs tether and retain tumor-derived DNA on their surface, forming a distinct circulating pool of RBC-bound tumor DNA (rtDNA). Desialylation increased DNA capture in a Toll-like receptor 9 (TLR9)-dependent manner, identifying RBC surface sialylation and TLR9 as a regulator of DNA binding. In mice bearing lung cancer xenografts, rtDNA was detected in all animals and its abundance correlated with tumor burden, whereas tumor DNA was undetectable in matched plasma samples. In patients with lung cancer, the majority of detected mutant tumor DNA was associated with RBCs rather than plasma, and RBC-derived mutations were concordant with molecular alterations identified in matched tumor tissue. Collectively, these findings establish the RBC surface as a tunable site of tumor-DNA capture and retention and challenge the plasma-centric paradigm of liquid biopsy by identifying a distinct cellular reservoir of tumor-derived genetic material.

cancer biology↗

bioRxiv2026

Choice of host model and manipulated transcription regulator dictates T6SS effector-mediated toxicity

Type VI secretion system (T6SS), a toxic effector-delivery apparatus primarily studied for its antibacterial properties, has recently emerged as a widespread anti-eukaryotic determinant, particularly in members of the genus Vibrio. Although various anti-eukaryotic effectors have been described, it remains unknown whether effectors target distinct hosts in a similar manner. Moreover, it is unclear whether the entire effector arsenal encoded within a single genome is co-regulated under different conditions and by different regulators. Here, we employ the anti-eukaryotic T6SS3 of Vibrio proteolyticus to address these knowledge gaps. By monitoring toxicity during infection of oyster hemocytes and comparing the results with previous infections of murine macrophages, we find that the effector Tie1 plays a role only in intoxicating murine cells, whereas Tie2 intoxicates both cell models. Furthermore, we show that artificial induction of T6SS3 via deletion of the negative regulator hns1 fails to induce the orphan effector Tie3, whereas overexpression of a T6SS3-specific activator, Ats3, induces all three known effectors. Ats3 overexpression further reveals that Tie3, not only Tie2, participates in hemocyte intoxication. Collectively, these findings indicate that analyses of T6SS-mediated infections must factor in the possibility of partial effector repertoire activation even when the main gene cluster is fully induced, and that the contribution of anti-eukaryotic T6SS effectors to intoxication is host-dependent.

microbiology↗

bioRxiv2025

Far-red light absorption strategies and their structural basis in Photosystem I of Acaryochloris marina NIES-2412

The marine cyanobacterium, Acaryochloris marina, uses the red-shifted chlorophyll d as its primary pigment, allowing it to absorb photons >700 nm. However, the widely studied type strain, A. marina MBIC11017, is atypical compared to most cyanobacteria, due to the absence of low energy chlorophylls ( red forms) within its Photosystem I complex. Consequently, Photosystem I and Photosystem II in the MBIC11017 strain share similar absorption spectra and are incapable of absorbing photons >740 nm. Recently, it has been discovered that the absorption and emission spectra from other A. marina strains are significantly more red-shifted than the MBIC11017 strain. Here, we have combined advanced spectroscopy and high-resolution cryo-EM to characterize Photosystem I from Acaryochloris marina NIES-2412, a red-shifted strain that is more representative of the A. marina species. The structure resolves all 96 chlorophylls and cofactors and indicates the location of the red chlorophyll forms. Spectroscopic analysis reveals two distinct types of red forms: one arising from the classical mechanism of charge transfer-exciton mixing, and the other from purely excitonic interactions. Furthermore, we have identified PsaX2 as a critical subunit that fine-tunes the pigment geometries and energies to enable the formation of these red forms. Together, these findings reveal how NIES-2412 PSI balances far-red light harvesting and energy trapping, highlighting its distinct strategy for adaptation in far-red light environments and redefining A. marina MBIC11017 as an atypical representative of the species.

biophysics↗

bioRxiv2025

Thriving Across Depths: How Blue Light Shapes a Large PSI Supercomplex and Specic Photosynthetic Traits in the seagrass Posidonia oceanica.

Photosynthetic organisms rely on finely tuned mechanisms to optimize photosynthesis under different light conditions. While these processes are well-characterized in land plants, the adaptive strategies of marine plants remain largely unexplored. The Mediterranean seagrass Posidonia oceanica (Alismatales), a key ecosystem engineer thriving from the surface up to 40m depth and one of the largest long-term blue carbon sinks in coastal environments. Here, we investigate how P. oceanica adjusts its photosynthetic apparatus in response to varying light spectra encountered at different seawater depths. Contrary to land plants, P. oceanica maintains a relatively high PSI/PSII ratio and a high content of the major light-harvesting complex II (LHCII), regardless of depth. Notably, the antenna size of the photosystems remains stable across depths, although we document significant depth-dependent reorganization of the thylakoid membrane ultrastructure. Moreover, we identify a novel large PSI-LHCII supercomplex (L-PSI-LHCII) in P. oceanica, characterized by additional Lhca proteins, reduced red-shifted absorption, and increased chlorophyll b content. Ultrafast spectroscopy reveals the distinct energy transfer dynamics within this complex. The presence of a similar supercomplex in other marine plants, such as Zostera marina, suggests a conserved adaptive strategy among seagrasses.

plant biology↗

bioRxiv2025

Early initiation of small intestine neuroendocrine tumors

Small intestine neuroendocrine tumor (SI-NET) is normally diagnosed late in life and has several unusual properties, including low proliferation rate, low mutation burden, lack of driver mutations, and frequent multifocality in the form of polyclonal tumor clusters. This sets SI-NET aside from other adult cancers and raises questions about the timeline of initiation and progression. Here, we investigated the evolutionary history of multifocal and unifocal SI-NET using whole genome sequencing data, obtaining timing information on primary tumors, metastases and key genetic events. Despite the late onset, the results indicated that major genetic alterations and the establishment of advanced metastatic tumor cell clones can often be traced back to childhood or adolescence in SINET. This was validated by re-examination of archival CT/MR scans, allowing longitudinal tracking of individual tumors up to 12 years prior. Metastases were detected at a high degree of consistency in the historical imaging data and estimated growth rates suggested several additional decades of tumor expansion. Collectively, our data support that slow growth of advanced lesions over half a century or more may precede SI-NET diagnosis in late adulthood.

cancer biology↗

bioRxiv2022

Cytoplasmic HIF-2α correlates to proliferation and predicts worse outcome in sympathetic paraganglioma

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs). There are virtually no treatment options, and no cure, for metastatic PCCs and PGLs (PPGLs). Here, we composed a tissue microarray (TMA) consisting of 149 PPGLs, reflecting clinical features and presenting as a useful resource. Mutations in the pseudohypoxic marker EPAS1/HIF-2 correlates to an aggressive tumor phenotype. We show that HIF-2 unexpectedly localized to the cytoplasm in PPGLs. This subcompartmentalized protein expression differed between tumor subtypes, and strongly correlated to proliferation. Half of all sPGLs were metastatic at time of diagnosis. Cytoplasmic HIF-2 was strongly expressed in metastatic sPGLs and predicted poor outcome in this subgroup. We propose that cytoplasmic HIF-2 expression serves as a useful clinical marker to differentiate subtypes and predicting outcome, and hence can be used for improved targeted treatment in PPGLs.

cancer biology↗

bioRxiv2020

Multifocal small intestine neuroendocrine tumors form by independent somatic evolution

BackgroundSmall intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several intestinal tumors centered around a regional lymph node metastasis. Although SI-NET patients often present with metastatic disease at the time of diagnosis, there is an unusual absence of somatic driver mutations explaining tumor initiation and metastatic spread. The evolutionary trajectories that underlie multifocal SI-NET lesions could provide insight into the underlying tumor biology, but this question remains unresolved. Here, we determined the complete genome sequences of 65 tumor and tissue samples from 11 patients with multifocal SI-NET, allowing for elucidation of phylogenetic relationships between tumors within individual patients. Intra-individual comparisons of whole genome sequences revealed a lack of shared somatic single-nucleotide variants and copy number alterations among the sampled intestinal lesions, supporting that they were of independent clonal origin. Furthermore, each metastasis originated from a single intestinal tumor, and in three of the patients, two independent tumors had metastasized. We conclude that primary multifocal SI-NETs generally arise from clonally independent cells, suggesting a contribution from of a cancer-priming local factor.

genomics↗