Biology subjects

Meltzer, J.

Publications and source records attributed to Meltzer, J..

4 recordsLinked to original sources

bioRxiv2026

Characterisation and genomic analysis of bacterial nutritional endosymbionts in Australian ticks from shotgun metagenomic sequencing

Ticks are obligate hematophagous arthropods and feed exclusively on blood. As blood is nutrient-poor, ticks rely on bacterial endosymbionts to synthesise nutrients, yet the diversity and functional roles of these symbionts in Australian ticks remain largely uncharacterised. This is critical to address as these ticks are of high medical importance in Australia. In this study, shotgun metagenomic sequencing was performed on Bothriocroton concolor, Bothriocroton hydrosauri, Haemaphysalis longicornis and Ixodes holocyclus, enabling the recovery of six complete or partial metagenome-assembled genomes (MAGs). These comprised Coxiella-like endosymbionts (CLE), a facultative Rickettsia symbiont, and two Midichloria mitochondrii strains (Ixholo1 and Ixholo2). Functional annotation of these taxon-specific symbionts revealed the absence of virulence factors and the presence of B-vitamin and/or heme biosynthesis genes, indicative of nutritional mutualism, which is essential for tick hematophagy. The CLEs additionally harbour genes of the shikimate pathway, which modulate blood feeding in ticks by regulating serotonin biosynthesis. Furthermore, functional annotation and pangenomic analysis of Midichloria spp. found evidence that the genus may encompass multiple species, as well as the retention of genes potentially associated with an intramitochondrial lifestyle in M. mitochondrii Ixholo2. Tick microbiomes are dominated by non-pathogenic microorganisms, which are often overshadowed by pathogens. These include the endosymbionts, which can influence host biology and pathogen transmission, and are fundamental for the development of diagnostic tools and taxon-specific tick biocontrols.

microbiology↗

bioRxiv2026

Utilizing a cell culture based novel cellular thermal shift assay to understand the isoform-dependent thermal stability of ApoE variants

Apolipoprotein E (ApoE) is the primary genetic risk modifier of late-onset Alzheimers disease, with the {varepsilon}4 allele increasing risk up to 15-fold relative to {varepsilon}3. The structural differences between isoforms are thought to underlie their distinct effects on lipid transport, receptor binding, and disease risk. ApoE4 exhibits reduced thermodynamic stability compared to ApoE3, but prior characterisation has relied on purified recombinant protein, leaving open whether these differences are preserved in native cellular environments and how they relate to rare disease-associated variants. Here, we employed the cellular thermal shift assay (CETSA) and a bioluminescence-based thermal stability assay (BiTSA) to systematically characterise ApoE thermal stability across isoforms and variants. Using CETSA on brain tissue from humanised APOE knock-in mice and post-mortem human brain, we confirm that ApoE4 exhibits significantly reduced thermal stability compared to ApoE3 in native tissue, with this difference conserved across species despite variation in absolute melting temperatures. We developed BiTSA, which leverages a split-luciferase HiBiT tag to quantify soluble ApoE across a thermal gradient in living cells, providing a higher-throughput platform that faithfully recapitulates isoform stability differences. Applying BiTSA to rare AD-associated variants, we found that L28P exerts divergent, isoform-dependent effects, destabilising ApoE3 while paradoxically stabilising ApoE4--a finding supported by AlphaFold modelling revealing isoform-specific differences in helix 1 architecture. These results establish BiTSA as a robust cellular tool for ApoE variant characterisation and demonstrate that isoform background critically modulates the structural consequences of rare mutations.

neuroscience↗

bioRxiv2025

Phase-locking saccades to posterior alpha oscillations improves the neural representation of visual objects during memory formation

Visual memory formation begins with the intake and neural processing of discrete samples provided by gaze fixations and saccades. Past research has highlighted a functional relationship between the timing of saccades and oscillations in neural activity over posterior brain areas: saccades phase-lock to alpha oscillations (8-12 Hz) and the degree of phase-locking, in natural scenes, has been associated with subsequent recognition memory. Here, we tested the hypothesis that the putative memory encoding benefit arises due to improved neuronal processing and, ultimately, better neural representation of foveated items, when saccades are locked to alpha phase. In a co-registered magnetoencephalography (MEG) and eye-tracking paradigm, participants executed saccades from central fixation to images that appeared in the periphery, attempting to remember those images for later testing. Replicating past results, saccades to subsequently remembered images were preceded by greater inter-trial phase coherence in the alpha frequency band, at posterior MEG channels, consistent with the notion that the eye movements were phase-locked. Across participants, the degree of saccade phase-locking was positively correlated with how well visual and semantic properties of the images were represented in neural activity, within 200 ms of their foveation. This relationship was evident in responses localized to the left parieto-occipital and ventral temporal cortex, where greater saccade phase-locking was associated with improved visual and semantic representations, respectively. These results support the hypothesis that phase-locking saccades to alpha oscillations leads to improved neuronal representation of foveated stimuli, providing new mechanistic insight into how episodic memories are formed from discrete visual samples. Significance StatementVisual memories begin with discrete samples provided by eye movements and gaze fixations, from which the brain must extract information that is integrated into a coherent memory trace. This work examined the neural mechanisms that support this memory formation process, one eye movement at a time. The results identified a functioning coupling between saccade timing and neuronal oscillations in the alpha frequency band: when saccades are phase-locked to alpha oscillations, the brain can better process the visual information provided by gaze fixations. This indicates that precise coordination of saccade timing, with respect to neuronal oscillations, promotes more veridical neural representation of the resulting visual samples, from which accurate episodic memories can be constructed.

neuroscience↗

bioRxiv2025

An Asgard archaeon from a modern analog of ancient microbial mats

It has been proposed that eukaryotic cells evolved via symbiosis between sulfate-reducing bacteria and hydrogen-producing archaea. Here we describe a highly enriched culture of a novel Asgard archaeon, Nerearchaeum marumarumayae, with a bacterium Stromatodesulfovibrio nilemahensis from a stromatolite-associated microbial mat. The N. marumarumayae genome indicates it produces H2, acetate, formate, and sulfite, while S. nilemahensis synthesizes amino acids and vitamins, which can be exchanged in a syntrophic partnership. Electron cryotomography revealed N. marumarumayae cells produce chains of budded envelope vesicles attached to the coccoid cell body by extracellular fibers, and intracellular tube- and cage-like structures. Furthermore, the two species were observed interacting via intercellular nanotubes assembled by the bacterium. These characteristics and interactions may reflect an early step in the symbiotic evolution of eukaryotic cells.

microbiology↗