Biology subjects

Murray, B.

Publications and source records attributed to Murray, B..

6 recordsLinked to original sources

bioRxiv2026

Comprehensive characterization of genomic, transcriptomic and epigenomic artifacts introduced in formalin-fixed, paraffin-embedded tissues.

Genomic, transcriptomic and epigenomic characterization has accelerated the discovery of clinically-relevant alterations in cancer, predominantly using fresh frozen (FF) specimens. However, clinical molecular pathology laboratories prefer formalin-fixed paraffin-embedded (FFPE) methods, known to introduce artifacts at the nucleic acid level, over fresh frozen methods. Extending the multi-platform analysis to FFPE specimens for comprehensive clinical molecular diagnosis requires a thorough understanding of the consequence of formalin-fixation. We present a detailed multi-platform characterization of FFPE preservation using paired FF specimens as the 'gold standard'. DNA and RNA were obtained from 38 patients across 6 cancer types using a FFPE optimized co-isolation. The impact of FFPE on exome sequencing was dependent on filtering, where a minimum coverage or supporting read filter can mitigate FFPE-specific false positives. Copy number alterations, MSI assessment, mutational signatures, and DNA methylation were comparable between FFPE and FF. FFPE biases in RNA expression can be overcome when using biology-relevant genes and we describe a novel consequence of FFPE on miRNA species diversity. Collectively, this data provides a broad view of FFPE artifact and offers best practices for overcome these biases.

bioinformatics↗

bioRxiv2024

Sleep selectively and durably enhances real-world sequence memory

Sleep is thought to play a critical role in the retention of episodic memories. Yet it remains unclear whether and how sleep actively transforms memory for specific experiences. More generally, little is known about sleeps effects on memory for multidimensional real-world experiences, both overnight and in the days to months that follow. In an exception to the law of forgetting, we showed that sleep actively and selectively improves retrieval of a one-time real-world experience (a controlled but immersive art tour) - specifically boosting memory for the order of tour items (sequential associations), but not perceptual details from the tour (featural associations). This above-baseline increase in sequence memory was not evident after a matched period of wakefulness. Moreover, the sleep-induced advantage of sequence over featural memory grew over time up to one-year post-encoding. Finally, overnight polysomnography showed that sleep-related memory enhancement was associated with the duration and neurophysiological hallmarks of slow-wave sleep previously linked to neural replay, particularly spindle-slow wave coupling. These results suggest that sleep serves a crucial and selective role in enhancing sequential organization in episodic memory at the expense of specific details, linking sleep-related neural mechanisms to the transformation and enhancement of memory for complex real-life experiences. Significance StatementSleep affects the retention of episodic memories. Yet, it remains unclear whether sleep active transforms how we remember past experiences, overnight and beyond. We investigated memory for different dimensions underlying a dynamic real-world event - sequential associations versus atemporal featural associations - before and after sleep or wakefulness, and serially up to a year later. Sleep actively and selectively enhanced sequence memory, with this preferential sequence retention growing with time. Overnight memory enhancement is associated with the duration and neurophysiological hallmarks of slow-wave sleep previously linked to sequential neural replay, particularly spindle-slow wave coupling. Our findings support an active role for sleep in transforming different aspects of real-world memory, with sequence structure coming to dominate long-term memory for dynamic real-world experiences.

neuroscience↗

bioRxiv2022

Adaptation of cyanobacteria to the endolithic light spectrum in hyper-arid deserts

In hyper-arid deserts, endolithic microbial communities survive in the pore spaces and cracks of rocks, an environment that enhances water retention and filters UV radiation. The rock colonization zone is enriched in far-red light (FRL) and depleted in visible light. This poses a challenge to cyanobacteria, which are the primary producers of endolithic communities. Many species of cyanobacteria are capable of Far-Red Light Photoacclimation (FaRLiP), a process in which FRL induces the synthesis of specialized chlorophylls and remodeling of the photosynthetic apparatus, providing the ability to grow in FRL. While FaRLiP has been reported in cyanobacteria from various low-light environments, our understanding of light adaptations for endolithic cyanobacteria remains limited. Here, we demonstrated that endolithic Chroococidiopsis isolates from deserts around the world synthesize chlorophyll f, an FRL-specialized chlorophyll when FRL is the sole light source. The metagenome-assembled genomes of these isolates encoded chlorophyll f synthase and all the genes required to implement the FaRLiP response. We also present evidence of FRL-induced changes to the major light-harvesting complexes of a Chroococidiopsis isolate. These findings indicate that endolithic cyanobacteria from hyper-arid deserts use FRL photo-acclimation as an adaptation to the unique light transmission spectrum of their rocky habitat.

microbiology↗

bioRxiv2021

Draft metagenomes of endolithic cyanobacteria and co-habitants from hyper-arid deserts

Cyanobacteria are essential to microbial communities inhabiting translucent rocks in hyper-arid deserts. Metagenomic studies revealed unique adaptations of these cyanobacteria but validation of the corresponding metabolic pathways remained challenging without access to isolates. Here we present high-quality metagenome assembled genomes for cyanobacteria, and their heterotrophic companions, isolated from endolithic substrates.

microbiology↗

bioRxiv2020

Sexually dimorphic responses to MPTP found in microglia, inflammation and gut microbiota in a progressive monkey model of Parkinson's disease

Inflammation has been linked to the development of nonmotor symptoms in Parkinsons disease (PD), which greatly impact patients quality of life and can often precede motor symptoms. Suitable animal models are critical for our understanding of the mechanisms underlying disease and the associated prodromal disturbances. The neurotoxin 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkey model is commonly seen as a "gold standard" model that closely mimics the clinical motor symptoms and the nigrostriatal dopaminergic loss of PD, however MPTP toxicity extends to other nondopaminergic regions. Yet, there are limited reports monitoring the MPTP-induced progressive central and peripheral inflammation as well as other nonmotor symptoms such as gastrointestinal function and microbiota. The main objective of this study is to gain a broader understanding of central and peripheral inflammatory dysfunction triggered by exposure to a neurotoxicant known to degenerate nigral dopaminergic neurons in order to understand the potential role of inflammation in prodromal/pre-motor features of PD-like degeneration in a progressive non-human primate model of the disease. We measured inflammatory proteins in plasma and CSF and performed [18F]FEPPA PET scans to evaluate translocator proteins (TSPO) or microglial activation in a small cohort of rhesus monkeys (n=5) given weekly low doses of MPTP (0.2-0.8 mg/kg, im). Additionally, monkeys were evaluated for working memory and executive function using various behavior tasks and for gastrointestinal hyperpermeability and microbiota composition. Monkeys were also treated with novel TNF inhibitor XPro1595 (10mg/kg, n=3) or vehicle (n=2) every three days starting 11 weeks after the initiation of MPTP to determine whether nonmotor symptoms are tied to TNF signaling and whether XPro1595 would alter inflammation and microglial behavior in a progressive model of PD. Our analyses revealed sex-dependent sensitivity to MPTP that resulted in early microglial activation by PET, acute plasma IL-6 and CSF TNF, and earlier parkinsonism as measured by motor deficits in males compared to female monkeys. Sex differences were also identified in microbiota and their metabolites and targeted short chain fatty acids at both basal levels and in response to MPTP. Both sexes displayed cognitive impairment prior to a significant motor phenotype. Importantly, XPro1595 shifted peripheral and central inflammation, and significantly reduced CD68-immunoreactivity in the colon. As such, our findings revealed a sexually dimorphic inflammatory response to chronic MPTP treatment and suggest that males may have higher vulnerability than females to inflammation-induced degeneration. If these findings reflect potential differences in humans, these sex differences have significant implications for therapeutic development of inflammatory targets in the clinic.

neuroscience↗

bioRxiv2019

Genomic epidemiology of vancomycin 1 resistant Enterococcus faecium (VREfm) in Latin America: Revisiting the global VRE population structure

The prevalence of vancomycin-resistant Enterococcus faecium varies across geographical regions yet little is known about its population structure in Latin America. Here, we provide a complete genomic characterization of 55 representative Latin American VREfm recovered from 1998-2015 in 5 countries. We found that VREfm population in the region is structured into two main clinical clades without geographical clustering. To place our regional findings in context, we reconstructed the global population structure of VREfm by including 285 genomes from 36 countries from 1946-2017. Our results differ from previous studies showing an early branching of animal related isolates and a further split of clinical isolates into two sub-clades, all within clade A. The overall phylogenomic structure was highly dependent on recombination (54% of the genome) and the split between clades A and B is estimated to have occurred more than 3585 years BP. Furthermore, while the branching of animal isolates and clinical clades was predicted to have occur [~]894 years BP, our molecular clock calculations suggest that the split within the clinical clade occurred around [~]371 years BP. By including isolates from Latin America, we present novel insights into the population structure of VREfm and revisit the evolution of this pathogen.

microbiology↗