Biology subjects

Porter, T.

Publications and source records attributed to Porter, T..

12 recordsLinked to original sources

bioRxiv2026

Stabilizing gas in aqueous liquids with metal-organic frameworks for persistent acoustic transduction

Gas is the most efficient mediator of acoustic energy owing to its high compressibility, yet its thermodynamic instability in aqueous environments makes it inherently transient, limiting sustained ultrasound-biological interfacing. Here, we show that gas can be stabilized, confined, and manipulated in the liquid phase to function as a persistent acoustic transducer. By trapping gas within designed microporous metal-organic framework (MOF) nanocrystals, interfacial forces establish a stable ternary-phase equilibrium that suppresses water intrusion and prevents gas collapse, enabling reversible, non-destructive oscillations under ultrasound stimulation and providing design principles for stabilizing gas in liquid environments. By leveraging high-resolution ultra-high-speed digital image correlation (DIC), we unveil the previously inaccessible spatiotemporal dynamics of confined gas oscillations within these nanotransducers under ultrasound stimulation, revealing localized amplification of the surrounding acoustic field and establishing a quantitative structure-function relationship for programmable acoustic transduction. These aqueous-phase gas nanotransducers exhibit sustained acoustic amplification over millions of excitation cycles and remain functional after prolonged storage (>2 years) under physiological conditions. In vitro and in vivo, this platform enables long-term ultrasound imaging and sustained, non-invasive neuromodulation by converting confined gas oscillations into persistent and amplified mechanical actuation. Our findings establish a generalizable design framework for stabilizing gas in liquid environments to achieve persistent and programmable acoustic transduction, thereby enabling sustained ultrasound-biological interfacing and opening opportunities for gas-based therapeutics.

bioengineering↗

bioRxiv2026

FlyAnatoView: Visualization of Drosophila Single-cell RNA-seq Datasets on Anatomographs

Single-cell RNA sequencing (scRNA-seq) is a powerful approach for measuring the transcriptomic landscape at single-cell resolution. However, while scRNA-seq data reveals what genes each cell expresses, they do not indicate where that cell was located within the tissue or organ, anatomically. We developed FlyAnatoView (https://www.flyrnai.org/tools/rna_seq_base/web/svg_files/), a resource that projects scRNA-seq data onto anatomical diagrams, restoring this missing spatial context.

bioinformatics↗

bioRxiv2026

Probing the Glymphatic System Using Optical Imaging and Mathematical Modeling

The glymphatic system is a macroscopic waste clearance pathway in the central nervous system (CNS), crucial to maintaining neural homeostasis through the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF). Impairments in this system have been associated with neurodegenerative diseases such as Alzheimers and Parkinsons, emphasizing the need to understand and potentially improve glymphatic clearance. We investigate tracer diffusion and transport in the glymphatic system by combining optical imaging in rats and mathematical modeling using a partial differential equation of advection-diffusion type. The experimental conditions differ in the levels of isoflurane-induced anesthesia (1.5, 2 and 3%) and the molecular weight of the tracer compounds (1 and 160 kDa). The optimal parameters show a close clustering of the diffusion coefficients and a wider spread of the flow velocities of the cerebrospinal fluid. Our work contributes to a better understanding of flow processes in the brain parenchyma during sleep.

neuroscience↗

bioRxiv2025

A spatiotemporal cancer cell trajectory underlies glioblastoma heterogeneity

Cancer cells display highly heterogeneous and plastic states in glioblastoma, an incurable brain tumour. However, how these malignant states arise and whether they follow defined cellular trajectories across tumours is poorly understood. Here, we generated a deep single cell and spatial multi-omic atlas of human glioblastoma that pairs transcriptomic, epigenomic and genomic profiling of 12 tumours across multiple regions. We identify that glioblastoma heterogeneity is driven by spatially-patterned transitions of cancer cells from developmental-like states towards those defined by a glial injury response and hypoxia. This cellular trajectory regionalises tumours into distinct tissue niches and manifests in a molecularly conserved manner across tumours as well as genetically distinct tumour subclones. Moreover, using a new deep learning framework to map cancer cell states jointly with clones in situ, we show that tumour subclones are finely spatially intermixed through glioblastoma tissue niches. Finally, we show that this cancer cell trajectory is intimately linked to myeloid heterogeneity and unfolds across regionalised myeloid signalling environments. Our findings define a stereotyped trajectory of cancer cells in glioblastoma and unify glioblastoma tumour heterogeneity into a tractable cellular and tissue framework.

cancer biology↗

bioRxiv2025

Improving retention time of Indocyanine Green for in vivo two-photon microscopy using liposomal encapsulation

We propose a technique for improving the retention time of Indocyanine Green (ICG), an FDA-approved, widely available, near infrared (NIR) probe for in vivo imaging of the cerebrovascular structure in rodents. We present a synthesis process for liposomal nanoparticles that, when used to encapsulate ICG, significantly increase the circulation time of the vascular label. Further, we conduct in vivo imaging experiments with unencapsuated (free) ICG and liposomal ICG (L-ICG) and compare the retention of ICG in the vascular network. Our work tackles one of the most fundamental limitations in using ICG i.e. rapid clearance, for the purpose of two-photon microscopy.

neuroscience↗

bioRxiv2024

Accurate estimation of SNP genotypes and genetic relatedness from DNA methylation data

Epigenome-wide association studies (EWAS) are susceptible to widespread confounding caused by population structure and genetic relatedness. Nevertheless, kinship estimation is challenging in EWAS without genotyping data. We propose MethylGenotyper, a method that for the first time enables accurate genotyping at thousands of SNPs directly from commercial DNA methylation microarrays. We model the intensities of methylation probes near SNPs with a mixture of three beta distributions corresponding to different genotypes and estimate parameters with an expectation-maximization algorithm. We conduct extensive simulations to demonstrate the performance of the method. When applying MethylGenotyper to Infinium EPIC array data of 4,662 Chinese, we obtain genotypes at 4,319 SNPs with a concordance rate of 98.26%, enabling the identification of 255 pairs of close relatedness. Furthermore, we show that MethylGenotyper allows for the estimation of both population structure and cryptic relatedness among 702 Australians of diverse ancestry. We have implemented MethylGenotyper in a publicly available R package to facilitate future large-scale EWAS.

bioinformatics↗

bioRxiv2024

The Impact of Anesthesia on Ultrasonic Glymphatic Perturbation Protocol: Alertness, and Glymphatic Influx

We have recently discovered that transcranial low-intensity focused ultrasound can enhance glymphatic transport, which facilitates the removal of waste metabolites from the brain in a preclinical rat model [1]. The central hypothesis was that ultrasound, functioning as a pressure wave, has the potential to influence the convective forces generated by arterial pulsations, which are also pressure waves, serving as the primary mechanism for glymphatic transport. Importantly, our data revealed that (i) the ultrasound protocol (650 kHz at 0.2MPa for 10 minutes to the entire brain) is safe, as histological evaluations showed no parenchymal damage and no difference in levels of neuronal degeneration or astrocytic activation 72 hours after the intervention, and (ii) the required pressure is significantly low, 10 times below FDA-approved limits for diagnostic ultrasound, and can be achieved using existing FDA-approved clinical transcranial focused ultrasound systems, suggesting its ease of translation into clinical applications. However, the study was conducted under specific physiological states with approximately 2.5% isoflurane-induced anesthesia. There is a limitation in fully understanding the potential bioeffects of ultrasound within the glymphatic space across various physiological conditions, primarily because the glymphatic transports efficiency fluctuates with anesthetically induced physiological states. Hence, establishing standardized protocols of ultrasonic glymphatic transport at optimal physiological state is crucial for ensuring consistent, reliable results across research laboratories during the preclinical development of this technique. The primary objective of this study is to evaluate how ultrasonically manipulated glymphatic transport is influenced by different levels of isoflurane-induced anesthetic conditions, including 3% (just above 2.5%), 2% (slightly below 2.5%), and 1.5% (quasi-awake state, resembling the existing clinical practice of ultrasound treatment). Results show that the impact of ultrasound during glymphatic transport depends on the level of anesthesia. It increases alertness in lightly anesthetized animals and improves glymphatic transport, while it induces drowsiness in heavily anesthetized animals, leading to reduced glymphatic transport. The results suggest that lighter anesthesia is beneficial for efficient ultrasonic glymphatic transport, making it more in line with the awake state in current clinical ultrasound treatments, thus advancing the technology closer to clinical translation.

bioengineering↗

bioRxiv2022

Investigating neurotrophin genetics and hippocampal volume

As individuals get older, the structural integrity of brain regions becomes progressively diminished. Neurotrophic function might aid in preventing such losses through increased synaptogenesis and neurogenesis, particularly in the hippocampus, a brain structure relevant for cognitive function. However, the carriage of certain genetic alleles for genes involved in neurotrophic function might restrain the effectiveness of neurotrophin signalling, hindering neuroprotection. Yet, research on the contribution of single nucleotide polymorphisms (SNPs) within genes coding for neurotrophins and their receptors to hippocampal volumes is scarce, with the exception of rs6265 within the brain-derived neurotrophic factor gene. Therefore, the aim of this study was to identify SNPs within genes involved neurotrophic function that are associated with hippocampal volume in a sample of 23,776 cognitively normal older adults from the UK Biobank. We found that, in individuals older than 50, homozygote carriage of the major alleles rs4839435-A within nerve growth factor gene and rs56405676-T within the neurotrophic receptor tyrosine kinase 2 gene, were associated with increase hippocampal volumes, compared to carriage of 1 or 2 copies of the minor alleles. However, only rs56405676-T was significantly associated with greater hippocampal volumes in individuals older than 60. Hence this study might serve to identify populations at higher risk of hippocampal attrition and cognitive decline.

genetics↗

bioRxiv2021

Single cell mRNA signals reveal a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia

Infant B-cell acute lymphoblastic leukemia (B-ALL) has not followed the increasing trend towards cure seen in other childhood B-ALLs. The prognosis for infants with KMT2A gene fusions is especially poor, and the origins of this aggressive leukemia remain unknown. Here, we investigated the developmental state of KMT2A-rearranged infant B-ALL within hematopoietic hierarchies of human fetal bone marrow, using bulk mRNA meta-analysis of childhood leukemia and examination of single lymphoblast transcriptomes. KMT2A-rearranged infant B-ALL was uniquely dominated by an early lymphocyte precursor (ELP) state. Direct comparison of infant lymphoblasts with ELP cells distilled the core oncogenic transcriptome of cancer cells which harboured potentially targetable hybrid myeloid-lymphoid features. Overall our quantitative molecular analyses demonstrate a distinct developmental state of KMT2A-rearranged infant B-ALL.

genomics↗

bioRxiv2021

Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro

The endometrium, the mucosal lining of the uterus, undergoes dynamic changes throughout the menstrual cycle in response to ovarian hormones. We have generated single-cell and spatial reference maps of the human uterus and 3D endometrial organoid cultures. We dissect the signalling pathways that determine cell fate of the epithelial lineages in the lumenal and glandular microenvironments. Our benchmark of the endometrial organoids highlights common pathways regulating the differentiation of secretory and ciliated lineage in vivo and in vitro. We show in vitro that downregulation of WNT or NOTCH pathways increases the differentiation efficiency along the secretory and ciliated lineages, respectively. These mechanistic insights provide a platform for future development of treatments for a range of common endometrial disorders including endometriosis and carcinoma.

genomics↗

bioRxiv2019

Studying ecosystems with DNA metabarcoding: lessons from aquatic biomonitoring

An ongoing challenge for ecological studies has been the collection of data with high precision and accuracy at a sufficient scale to detect effects relevant to management of critical global change processes. A major hurdle for many workflows has been the time-consuming and challenging process of sorting and identification of organisms, but the rapid development of DNA metabarcoding as a biodiversity observation tool provides a potential solution. As high-throughput sequencing becomes more rapid and cost-effective, a big data revolution is anticipated, based on higher and more accurate taxonomic resolution, more efficient detection, and greater sample processing capacity. These advances have the potential to amplify the power of ecological studies to detect change and diagnose its cause, through a methodology termed Biomonitoring 2.0.\n\nDespite its promise, the unfamiliar terminology and pace of development in high-throughput sequencing technologies has contributed to a growing concern that an unproven technology is supplanting tried and tested approaches, lowering trust among potential users, and reducing uptake by ecologists and environmental management practitioners. While it is reasonable to exercise caution, we argue that any criticism of new methods must also acknowledge the shortcomings and lower capacity of current observation methods. Broader understanding of the statistical properties of metabarcoding data will help ecologists to design, test and review evidence for new hypotheses.\n\nWe highlight the uncertainties and challenges underlying DNA metabarcoding and traditional methods for compositional analysis, focusing on issues of taxonomic resolution, sample similarity, taxon misidentification, sample contamination, and taxon abundance. Using the example of freshwater benthic ecosystems, one of the most widely-applied non-microbial applications of DNA metabarcoding to date, we explore the ability of this new technology to improve the quality and utility of ecological data, recognising that the issues raised have widespread applicability across all ecosystem types.

ecology↗

bioRxiv2019

Watered-down biodiversity? A comparison of metabarcoding results from DNA extracted from matched water and bulk tissue biomonitoring samples

Biomonitoring programs have evolved beyond the sole use of morphological identification to determine the composition of invertebrate species assemblages in an array of ecosystems. The application of DNA metabarcoding in freshwater systems for assessing benthic invertebrate communities is now being employed to generate biological information for environmental monitoring and assessment. A possible shift from the extraction of DNA from net-collected bulk benthic samples to its extraction directly from water samples for metabarcoding has generated considerable interest based on the assumption that taxon detectability is comparable when using either method. To test this, we studied paired water and benthos samples from a taxon-rich wetland complex, to investigate differences in the detection of taxa from each sample type. We demonstrate that metabarcoding of DNA extracted directly from water samples is a poor surrogate for DNA extracted from bulk benthic samples, focusing on key bioindicator groups. Our results continue to support the use of bulk benthic samples as a basis for metabarcoding-based biomonitoring, with nearly three times greater total richness in benthic samples compared to water samples. We also demonstrated that few arthropod taxa are shared between collection methods, with a notable lack of key bioindicator EPTO taxa in the water samples. Although species coverage in water could likely be improved through increased sample replication and/or increased sequencing depth, benthic samples remain the most representative, cost-effective method of generating aquatic compositional information via metabarcoding.

ecology↗