Biology subjects

Richter, V.

Publications and source records attributed to Richter, V..

7 recordsLinked to original sources

bioRxiv2026

The First Experience of Accelerator-based Lithium Neutron Capture Therapy in vivo

Boron neutron capture therapy (BNCT) is one of the promising treatment methods for cancer. BNCT is based on the unique high ability of the non-radioactive boron-10 (10B) nucleus to absorb thermal neutrons. The absorption of a neutron by boron results in a nuclear reaction 10B(n,)7Li with 84% of the energy being released within the cell, thereby inducing cancer cell death. We propose a novel approach based on using lithium instead of boron in neutron capture therapy: the neutron capture reaction cross-section for lithium is 4 times smaller than that of boron, while the energy release is 2 times higher, and the primary advantage of lithium is that 100% of the energy is released inside the cell. A series of in vivo neutron irradiation experiments using the murine B16 skin melanoma model demonstrated the efficacy of lithium neutron capture therapy (LiNCT). Higher lithium concentrations in the tumor achieved through intraperitoneal administration, compared to the oral route, contributed to a significant increase in animal survival and a significant decrease in tumor growth. The results of our study provide entirely new opportunities for the development of neutron capture therapy, both with lithium and with a possible lithium-boron combination.

biophysics↗

bioRxiv2026

The 3D micro- and nanostructure of the apical extracellular matrix in Drosophila

The apical extracellular matrix (aECM) serves as a dynamic scaffold, orchestrating tissue growth, cellular communication, and wound repair, and thus functions as a powerful biomaterial. In this study, we explored the intricate three-dimensional landscape of the Drosophila larval aECM using advanced 3D Volume electron microscopy. This technique opens a window into understanding and mimicking the diversity of aECM surfaces and architectures of the exoskeletal cuticles. We reconstructed the striking forms of denticles, hairs, and sensory organs, including double sensilla and Keils organs, at the epidermal surface. Our reconstructions brought the larval tracheal system and the sponge-like felt chamber (Filzkorper) of the spiracles into sharp relief, revealing a labyrinth of tiny cavities surrounding a central tube that extends from the posterior opening to the tracheal lumen. When examining the ultrastructure of transport-active anal pad cells, we discovered an inverted pattern of cuticular pore-canal structures, which supports their suggested role in osmoregulation across the aECM. Our findings further suggest that ordinary epidermal cells weave an intricate network of pore canals, enabling the orchestration of material distribution throughout the entire aECM. Moreover, we reconstructed tendon cells and chordotonal organs that form a branching network of numerous filamentous intracuticular fibers that weave through the aECM, linking the exoskeleton to muscles and sensory organs. By thoroughly mapping the intricate ultrastructural features of the aECM, this study opens new avenues for exploring how its protective, mechanical, and sensory roles intertwine, inspiring the next generation of tailor-made biomimetic materials.

developmental biology↗

bioRxiv2026

Octopamine receptors at a glance: from expression and anatomical maps to their role in development and behavior in the Drosophila melanogaster larva

Octopamine is involved in a variety of different physiological and behavioral mecha-nisms in Drosophila melanogaster. Throughout the life cycle of the fruit fly, from the larva to the adult, octopaminergic neurons in both the central and the peripheral nerv-ous system target a multitude of neurons and even non-neuronal tissues, making it challenging to analyze individual mechanisms of octopamine function. One approach to deconstructing this complex system is to examine the postsynaptic components of signal transmission. In Drosophila, octopamine interacts with six distinct G-protein-coupled receptors. For some of these receptors, expression maps and functional im-plications have been described. In contrast, other receptors have been neglected, partly due to the lack of suitable genetic tools. Here, for the first time, we compiled a complete set of mutant lines of all known octopamine receptors, all generated using the same genetic tool, the recently established Trojan Exon system. It integrates the Gal4/UAS binary expression strategy while simultaneously impairing receptor func-tion. This enabled us to generate a comprehensive anatomical map of receptor ex-pression in the larva and, at the same time, analyze the function of individual octopa-mine receptors during larval development, chemosensory perception and locomotion. All octopamine receptors (Oamb, Oct2R, Oct{beta}1R, Oct{beta}2R, Oct{beta}3R, and Oct-TyrR) showed extensive signal in the central nervous system. The same was found for the peripheral nervous system, with the exception of Oct{beta}2R, which showed pronounced expression in the somatic muscles. We also observed a previously undescribed role of Oct{beta}1R, Oct{beta}3R, and Oct-TyrR in larval hatching and in the survival of larvae and pupae. Molecular evaluation of the Trojan Exon octopamine lines supports our analy-sis. In addition, we combined the experimental results with gene expression data from the different development stages of Drosophila melanogaster and from different tis-sues and cell populations throughout the body. Overall, we compiled, analyzed and validated a complete set of octopamine lines which, together with gene expression analysis, provides a basis for further functional studies on the larval octopaminergic system.

neuroscience↗

bioRxiv2025

Aptamer-Fortified VV-GMCSF-Lact for Systemic Glial Tumor Virotherapy

Virotherapy represents a promising approach for cancer treatment. However, when administered intravenously, oncolytic viruses are often hampered by neutralization from antibodies, reducing their antitumor efficacy. Aptamers offer a potential solution by shielding viral particles from neutralizing antibodies and prevent viral particle aggregation. In this study, human glioblastoma xenografts were orthotopically implanted in immunocompromised ICR mice. The therapeutic agents (VV-GMCSF-Lact-Apt1, VV-GMCSF-Lact-Apt2 or VV-GMCSF-Lact) were administered intravenously. Using magnetic resonance imaging, we observed a decrease in tumor growth in all experimental groups. Using the Kaplan-Meier method, it was shown that the mouse survival in the VV-GMCSF-Lact-Apt1, VV-GMCSF-Lact-Apt2 groups was higher than in the control group. The level of key cytokines (IL-1, IL-10, TNF-alpha) in mouse plasma was measured using ELISA. A study of cytokine levels (IL-1, IL-10, and TNF-) showed that the aptamers shift the immune response from a pro-inflammatory systemic response, by reducing IL-1, to an anti-tumor one, with an increase in TNF-. In histological analysis, the most destructive changes in tumor tissue were observed in the VV-GMCSF-Lact-Apt2 group, while the morphology of organ tissues (spleen, liver, kidneys and lungs) did not differ between the control and experimental groups. Thus, our results demonstrate a synergistic antitumor effect of the aptamer in combination with the oncolytic virus against glioblastoma tumor xenografts.

cancer biology↗

bioRxiv2025

Morphology and ultrastructure of pharyngeal sense organs of Drosophila larvae

This study provides a comprehensive ultrastructural analysis of the pharyngeal sensory system in Drosophila melanogaster larvae, focusing on the four major pharyngeal sense organs: the ventral pharyngeal sensilla (VPS), dorsal pharyngeal sensilla (DPS), dorsal pharyngeal organ (DPO), and posterior pharyngeal sensilla (PPS). Our analysis revealed 15 sensilla across these organs, comprising four mechanosensory, nine chemosensory, and two dual-function sensilla. We identified 35 Type I neurons (six mechanosensory and 29 chemosensory) and six Type II neurons with putative chemosensory functions. Additional sensory structures, including papilla sensilla and chordotonal organs in the cephalopharyngeal region, were characterized. This detailed mapping and classification of pharyngeal sensory structures completes their structural characterization and provides a foundation for future anatomical and functional studies of sensory perception in insects. This work represents a significant step towards a complete analysis of the larval sensory system, providing new opportunities for investigating how an organism processes sensory information to navigate and interact with its environment.

neuroscience↗

bioRxiv2023

Morphology and ultrastructure of external sense organsof Drosophila larvae

Sensory perception is the ability through which an organism is able to process sensory stimuli from the environment. This stimulus is transmitted from the peripheral sensory organs to the central nervous system, where it is interpreted. Drosophila melanogaster larvae possess peripheral sense organs on their head, thoracic, and abdominal segments. These are specialized to receive diverse environmental information, such as olfactory, gustatory, temperature or mechanosensory signals. In this work, we complete the description of the morphology of external larval sensilla and provide a comprehensive map of the ultrastructure of the different types of sensilla that comprise them. This was achieved by 3D electron microscopic analysis of partial and whole body volumes, which contain high-resolution and complete three-dimensional data of the anatomy of the sensilla and adjacent ganglia. Our analysis revealed three main types of sensilla on thoracic and abdominal segments: the papilla sensillum, the hair sensillum and the knob sensillum. They occur solitary or organized in compound sensilla such as the thoracic keilins organ or the terminal sensory cones. We present a spatial map defining these sensilla by their position on thoracic and abdominal segments. Further, we identify and name the sensilla at the larval head and the last fused abdominal segments. We show that mechanosensation dominates in the larval peripheral nervous system, as most sensilla have corresponding structural properties. The result of this work, the construction of a complete structural and neuronal map of the external larval sensilla, provides the basis for following molecular and functional studies to understand which sensory strategies the Drosophila larva employs to orient itself in its natural environment.

neuroscience↗

bioRxiv2022

Somatic copy number variant load in neurons of healthy controls and Alzheimer's disease patients

BackgroundThe possible role of somatic copy number variations (CNVs) in Alzheimers disease (AD) aetiology has been controversial. Although cytogenetic studies suggested increased CNV loads in AD brains, a recent single-cell whole-genome sequencing (scWGS) experiment, studying frontal cortex brain samples, found no such evidence. Here we readdressed this issue using lowcoverage scWGS on pyramidal neurons dissected using laser capture microdissection (LCM) across five brain regions: entorhinal cortex, temporal cortex, hippocampal CA1, hippocampal CA3, and the cerebellum. ResultsAmong reliably detected somatic CNVs identified in 1301 cells obtained from the brains of 13 AD patients and 7 healthy controls, deletions were more frequent compared to duplications. Interestingly, we observed slightly higher frequencies of CNV events in cells from AD compared to similar numbers of cells from controls (4.1% vs. 1.4%, or 0.9% vs. 0.7%, using different filtering approaches), although the differences were not statistically significant. We also observed that LCM-isolated cells show higher within-cell read depth variation compared to cells isolated with fluorescence activated cell sorting (FACS), which we argue may have both biological and technical causes. Furthermore, we found that LCM-isolated neurons in AD harbour slightly more read depth variability than neurons of controls, which might be related to the reported hyperploid profiles of some AD-affected neurons. We also propose a principal component analysis-based denoising approach that significantly reduces within-cell read depth variation in scWGS data. ConclusionsWe find slightly higher somatic CNV frequencies in the brains of AD patients, and higher sequencing coverage variability, although the effects measured do not reach statistical significance. The results call for improved experimental protocols to determine the possible role of CNVs in AD pathogenesis.

bioinformatics↗