Biology subjects

Argyropoulos, C.

Publications and source records attributed to Argyropoulos, C..

3 recordsLinked to original sources

bioRxiv2025

Structural polymorphism of ex-vivo ALECT2 amyloid fibrils revealed by cryo-EM

ALECT2 amyloidosis is a rare systemic disease characterized by the pathological deposition of leukocyte cell-derived chemotaxin-2 (LECT2) as amyloid fibrils, primarily affecting the kidneys and liver. The molecular mechanisms underlying LECT2 aggregation remain poorly defined, hindering diagnostic and therapeutic development. Here, we present cryo-electron microscopy structures of ex-vivo ALECT2 fibrils extracted from a patients kidney. We identified three fibril polymorphs: a predominant single-protofilament morphology and two minor double-protofilament morphologies. The dominant single-protofilament morphology comprises the full-length 133-residue LECT2 protein and retains all three native disulfide bonds. Low-resolution reconstructions of double-protofilament morphologies suggest they adopt a similar fold to the single protofilament morphology, but form paired assemblies with different inter-filament interfaces. Mass spectrometry also reveals acetylation within the fibrils. These findings offer critical insights into the structural basis of ALECT2 amyloid formation and identify molecular features that could inform future diagnostic and therapeutic approaches.

biophysics↗

bioRxiv2022

To make a short story long: simultaneous short and long RNA profiling on Nanopore devices

Sequencing of long coding RNAs informs about the abundance and the novelty in the transcriptome, while sequencing of short coding RNAs (e.g., microRNAs) or long non-coding RNAs informs about the epigenetic regulation of the transcriptome. Currently, each of these goals is addressed by separate sequencing experiments given the different physical characteristics of RNA species from biological samples. Sequencing of both short and long RNAs from the same experimental run has not been reported for long-read Nanopore sequencing to date and only recently has been achieved for short-read (Illumina) methods. We propose a library preparation method capable of simultaneously profiling short and long RNA reads in the same library on the Nanopore platform and provide the relevant bioinformatics workflows to support the goals of RNA quantification. Using a variety of synthetic samples we demonstrate that the proposed method can simultaneously detect short and long RNAs in a manner that is linear over 5 orders of magnitude for RNA abundance and three orders of magnitude for RNA length. In biological samples the proposed method is capable of profiling a wider variety of short and long non-coding RNAs when compared against the existing Smart-seq protocols for Illumina and Nanopore sequencing.

molecular biology↗

bioRxiv2018

Surveillance of CKD epidemiology in the US -- a joint analysis of NHANES and KEEP

Chronic Kidney Disease (CKD), is highly prevalent in the United States. Epidemiological systems for surveillance of CKD rely on data that are based solely on the NHANES survey, which does not include many patients with the most severe and less frequent forms of CKD. We investigated the feasibility of estimating CKD prevalence from the large-scale community disease detection Kidney Early Evaluation and Program (KEEP, n = 127,149). We adopted methodologies from the field of web surveys to address the self-selection bias inherent in KEEP. Primary outcomes studied were CKD Stage 3-5 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2, and CKD Stage 4-5 (eGFR <30 mL/min/1.73m2). The unweighted prevalence of Stage 4-5 CKD was higher in KEEP (1.00%, 95%CI: 0.94-1.05%) than in NHANES (0.51%, 95% CI: 0.43-0.59%). Application of a selection model with IPW of variables related to demographics, recruitment and socio-economic factors resulted in estimates similar to NHANES (0.55%, 95% CI: 0.50-0.60%). Weighted prevalence of Stages 3-5 CKD in KEEP was 6.45% (95% CI: 5.70 7.28%) compared to 6.73% (95% CI: 6.30-7.19%) for NHANES. Application of methodologies that address the self-selection bias in the KEEP program may allow the use of this large, geographically diverse dataset for CKD surveillance.

epidemiology↗