Biology subjects

Almeida, N.

Publications and source records attributed to Almeida, N..

4 recordsLinked to original sources

bioRxiv2026

Functional Assessment of Cardiac Beat Dynamics Under Dynamic Flow: Insights from the Mera Microphysiological System

Cardiac rhythm is a critical clinical indicator for cardiac arrhythmias and adverse events during drug toxicity studies. In vivo, cardiomyocyte responses to pharmacological agents occur within minutes and are strongly influenced by dynamic drug delivery through blood flow. However, conventional 2D and 3D static culture systems fail to replicate these fluid flow kinetics, limiting their physiological relevance for assessing beat rate responses. Here, we present Mera, an advanced microphysiological system (MPS) developed by Hooke Bio, designed for high-throughput, long-term culture and functional analysis of 3D cardiac spheroids composed of human induced pluripotent stem cell-derived cardiomyocytes and cardiac fibroblasts. Mera enables dynamic perfusion, allowing investigation of cardiomyocyte beat rates under physiologically relevant flow conditions. The platform supports up to 640 spheroids per run and integrates automated imaging, fluid handling, and user-friendly software, operating under controlled physiological conditions (37{degrees}C, 5% CO2). Flow rates are tunable between 0 and 12.5 mL/min to mimic in vivo environments. Pharmacological testing with verapamil, isoproterenol, calcium chloride, and propranolol demonstrated real-time, reversible modulation of beat rate under flow, including recovery following drug-induced suppression. System variability was comparable to a temperature-controlled reference platform, supporting robust statistical analysis. Dose-response studies yielded IC values consistent with literature, confirming physiological relevance. Collectively, these results demonstrate that Mera provides a reproducible, scalable, and human-relevant platform for cardiac drug testing. By enabling dynamic drug exposure and automated analysis, Mera represents a powerful new approach methodology (NAM) for improving the predictive assessment of cardiac safety and beat-rate modulation drug responses.

bioengineering↗

bioRxiv2026

MX2 Mediates Collapse of the HIV-1 Capsid

The HIV-1 capsid core encapsulates the viral genome and mediates its delivery into the host cells nucleus. It is composed of multiple copies of the Capsid (CA, p24Gag) protein, assembled into hexamers and pentamers to create a lattice that forms a fullerene-like cone. Myxovirus resistance 2 (MX2) is an HIV-1 restriction factor that binds to the capsid core and blocks nuclear import of the viral genome. Here, we define a minimal region of MX2 required for HIV-1 restriction and produce a corresponding functional recombinant protein. We have used cryo-electron microscopy to determine the structure of this MX2 fragment bound to the tri-hexamer interface of the capsid lattice, revealing a large, buried interface combining electrostatic and hydrophobic interactions. This structure, together with assays that measure capsid core destabilisation, shows that MX2 binding induces conformational rearrangements in the capsid lattice that culminate in a loss of integrity. These results support a model whereby MX2 exerts its antiviral activity by disrupting the capsid lattice, inducing premature fragmentation and preventing HIV-1 nuclear import. By revealing the structural basis for MX2-mediated restriction, this work also provides the framework for the development of anti-HIV molecules that mimic MX2 restriction.

microbiology↗

bioRxiv2025

Bacterial resistance and co-existence with temperate bacteriophages in the human gut

Our understanding of the eco-evolutionary dynamics and consequences of bacteria-phage interactions in nature is limited. By combining longitudinal sampling and analysis of Enterobacterales and associated phages isolated from the human gut, with experimental evolution, our work identifies mechanisms that underpin observed patterns of temperate phage-bacteria co-existence and bacterial resistance in this clinically relevant microbiome. Specifically, we show that limited phage infectivity observed against sympatric and allopatric hosts can be explained by the prevalence of spontaneous prophage induction (SPI) bacterial phenotypes and ecological shifts and turnover in focal host populations at multiple taxonomic levels. Despite the ubiquity of temperate phages in the human gut, these findings challenge the assumption that they are major drivers of within-host bacterial evolution and diversification over short-time scales in this natural ecosystem.

microbiology↗

bioRxiv2021

Glioblastoma remodeling of neural circuits in the human brain decreases survival

Gliomas synaptically integrate into neural circuits. Prior work has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth and gliomas increasing neuronal excitability. In this study we wanted to know how glioma induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. We use intracranial brain recordings during lexical retrieval language tasks in awake humans in addition to site specific tumor tissue biopsies and cell biology experiments. We find that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumor-infiltrated cortex, beyond cortical excitation normally recruited in the healthy brain. Site-directed biopsies from functionally connected regions within the tumor are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumor cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumor regions compared to tumor regions with less functional connectivity. The degree of functional connectivity between glioblastoma and the normal brain negatively impacts both patient survival and language task performance. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumor proliferation and impairs cognition.

cancer biology↗