Publications by authors named "Olivia Osborne"

Article Synopsis
  • The study investigates how cerebral amyloid angiopathy (CAA) affects recovery from ischemic stroke using a 5xFAD mouse model, hypothesizing that amyloid-beta buildup leads to worse outcomes by impairing the blood-brain barrier (BBB).
  • Findings reveal that CAA worsens stroke effects, resulting in narrowed BBB microvessels, decreased cerebral blood flow, and hindered tissue recovery, alongside different gene expression patterns in endothelial cells and neural progenitor cells in the hippocampus.
  • Experiments indicate that disrupting the CXCL12-PIK3C2A-CREB3L2 pathway negatively impacts neurogenesis, but activating the PI3K pathway can restore it
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Advances in biosciences, chemistry, technology, and computer sciences have resulted in the unparalleled development of candidate New Approach Methodologies over the last few years. Many of these are potentially invaluable in the safety assessment of chemicals, but very few have been adopted for regulatory decision making. There is an immediate opportunity to use NAMs in safety assessment where the vision is to be able to predict risk more rapidly, accurately, and efficiently to further assure consumer safety.

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  • Physical particles, specifically fecal particle size (FPS), are influenced by gut microbiomes in humans, highlighting their role as abiotic factors in microbial ecology.
  • A study involving 76 individuals revealed that FPS is highly individualized and not significantly impacted by chewing efficiency or diet, contrary to initial assumptions.
  • Findings indicate that gut microbiota diversity and composition, as well as factors like transit time, are critical in determining FPS, suggesting that the microbiome is essential for efficient digestion and energy extraction in the gastrointestinal tract.
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Occludin (ocln) is one of the main regulatory cells of the blood-brain barrier (BBB). Ocln silencing resulted in alterations of the gene expression signatures of a variety of genes of the innate immunity system, including IFN-stimulated genes (ISGs) and the antiviral retinoic acid-inducible gene-1 (RIG-1) signaling pathway, which functions as a regulator of the cytoplasmic sensors upstream of the mitochondrial antiviral signaling protein (MAVS). Indeed, we observed dysfunctional mitochondrial bioenergetics, dynamics, and autophagy in our system.

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To develop a clinically relevant injectable hydrogel derived from decellularized porcine peripheral nerves and with mechanical properties comparable to native central nervous system (CNS) tissue to be used as a delivery vehicle for Schwann cell transplantation to treat spinal cord injury (SCI).Porcine peripheral nerves (sciatic and peroneal) were decellularized by chemical decellularization using a sodium deoxycholate and DNase (SDD) method previously developed by our group. The decellularized nerves were delipidated using dichloromethane and ethanol solvent and then digested using pepsin enzyme to form injectable hydrogel formulations.

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Article Synopsis
  • Physical particles, specifically fecal particle size (FPS), play an important role in shaping the ecology of microbial communities in the gut.
  • While chewing efficiency and diet influence FPS in non-human vertebrates, a study on humans showed that FPS variability is primarily linked to gut microbiome composition rather than behavior or diet.
  • Findings indicate that gut microbiomes can significantly alter FPS, suggesting that human digestion and microbial interaction have unique processes compared to other mammals.
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  • Disruptions in pericyte and endothelial cell expression can weaken the blood-brain barrier (BBB), leading to neurological disorders; however, current research has mainly focused on tissue homogenates rather than spatial analysis.
  • The study introduces a new microvessel isolation technique that retains RNA integrity, allowing for the visualization of specific RNA in the context of the BBB using RNAscope analysis.
  • Findings from this method on 5XFAD mice, a model for Alzheimer's disease, show reduced pericytes and increased TYROBP mRNA levels, enhancing our understanding of neurovascular interactions and potential therapeutic approaches.
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Perfluorooctanoic acid (PFOA) is a persistent environmental contaminant that can accumulate in the human body due to its long half-life. This substance has been associated with liver, pancreatic, testicular and breast cancers, liver steatosis and endocrine disruption. PFOA is a member of a large group of substances also known as "forever chemicals" and the vast majority of substances of this group lack toxicological data that would enable their effective risk assessment in terms of human health hazards.

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The further optimization of consumer safety through risk assessment of chemicals present in food will require adaptability and flexibility to utilize the accelerating developments in safety science and technology. New Approach Methodologies (NAMs) are gaining traction as a systematic approach to support informed decision making in chemical risk assessment. The vision is to be able to predict risk more accurately, rapidly and efficiently.

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  • - Despite advancements in antiretroviral therapy, around 50% of individuals with HIV experience chronic neurocognitive disorders (HAND), which negatively affect their quality of life due to ongoing central nervous system damage.
  • - Current research suggests that inflammation from latent HIV reservoirs contributes to HAND progression, with BBB pericytes (cells in the blood-brain barrier) playing a crucial role as potential viral reservoirs, although their latent infection is not well understood.
  • - A new study highlights the unique transcriptional profiles of BBB pericytes with active and latent HIV infection, showing that the AKT signaling pathway is vital for the survival of these latent reservoirs, which could inform future treatments targeting these cells.
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For more than a century, clinicians have been aware of the devastating neurological condition called Alzheimer's disease (AD). AD is characterized by the presence of abnormal amyloid protein plaques and tau tangles in the brain. The dominant hypothesis, termed the amyloid hypothesis, attributes AD development to excessive cleavage and accumulation of amyloid precursor protein (APP), leading to brain tissue atrophy.

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Dimensionality reduction techniques are crucial for enabling deep learning driven quantitative structure-activity relationship (QSAR) models to navigate higher dimensional toxicological spaces, however the use of specific techniques is often arbitrary and poorly explored. Six dimensionality techniques (both linear and non-linear) were hence applied to a higher dimensionality mutagenicity dataset and compared in their ability to power a simple deep learning driven QSAR model, following grid searches for optimal hyperparameter values. It was found that comparatively simpler linear techniques, such as principal component analysis (PCA), were sufficient for enabling optimal QSAR model performances, which indicated that the original dataset was at least approximately linearly separable (in accordance with Cover's theorem).

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HIV-1-associated blood brain barrier (BBB) alterations and neurocognitive disorders are frequent clinical manifestations in HIV-1 infected patients. The BBB is formed by cells of the neurovascular unit (NVU) and sealed together by tight junction proteins, such as occludin (ocln). Pericytes are a key cell type of NVU that can harbor HIV-1 infection via a mechanism that is regulated, at least in part, by ocln.

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Article Synopsis
  • * It investigates how HIV-1 infects brain pericytes (a type of cell in the BBB) and the immune response that triggers the expression of certain antiviral genes known as OAS, which help degrade viral RNA.
  • * The findings reveal that occludin modulates the levels of OAS genes and proteins, influencing HIV replication, while the study showed that HIV-1 infection specifically increases the mRNA expression of OAS genes without affecting the RNaseL protein.
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  • The study examines how elevated amyloid beta (Aβ) levels are linked to cognitive issues in Alzheimer's disease and focuses on the role of the blood-brain barrier (BBB) in transferring Aβ to the brain.
  • Researchers investigated how extracellular vesicles (EVs) from the brain's endothelium affect neural progenitor cells (NPCs) when exposed to Aβ, assessing changes in their mitochondrial functions and differentiation.
  • Findings indicate that Aβ can indeed be transferred to NPCs via EVs, causing mitochondrial dysfunction and negatively impacting the NPCs' ability to develop into neurons, which has important implications for learning and memory in Alzheimer's disease.
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While HIV-1 is primarily an infection of CD4 + T cells, there is an emerging interest towards understanding how infection of other cell types can contribute to HIV-associated comorbidities. For HIV-1 to cross from the blood stream into tissues, the virus must come in direct contact with the vascular endothelium, including pericytes that envelope vascular endothelial cells. Pericytes are multifunctional cells that have been recognized for their essential role in angiogenesis, vessel maintenance, and blood flow rate.

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The blood-brain barrier (BBB) is essential for the homeostasis of the central nervous system (CNS). Functions of the BBB are performed by the neurovascular unit (NVU), which consists of endothelial cells, pericytes, astrocytes, microglia, basement membrane, and neurons. NVU cells interact closely and together are responsible for neurovascular coupling, BBB integrity, and transendothelial fluid transport.

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SLOCK is a sweat-based circadian diagnostic platform used for mapping the user's chronobiology cortisol and DHEA. In this work, we have demonstrated the detection capabilities of this sweat-based sensing platform using two electrochemical sensing modalities: Electrochemical Impedance Spectroscopy (EIS) and chronoamperometry. Wicking simulations for vertical horizontal flow patterns under potential bias were evaluated using COMSOL Multiphysics®.

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HIV attacks the body's immune cells, frequently compromises the integrity of the blood-brain barrier (BBB), and infects the CNS in the early stages of infection. Dysfunction of the BBB further potentiates viral replication within the CNS, which can lead to HIV-associated neuropathology. Antiretroviral therapy (ART) significantly improves HIV patient outcomes and reduces mortality rates.

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We have recently shown that the toxicological potential of GaAs and InAs particulates in cells is size- and dissolution-dependent, tending to be more pronounced for nano- vs micron-sized particles. Whether the size-dependent dissolution and shedding of ionic III-V materials also apply to pulmonary exposure is unclear. While it has been demonstrated that micron-sized III-V particles, such as GaAs and InAs, are capable of inducing hazardous pulmonary effects in an occupational setting as well as in animal studies, the effect of submicron particles (e.

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Recent studies suggest that the nanorods consisting of europium hydroxide could promote angiogenesis. In this study, it is sought to determine if additional types of nanoparticles are capable of enhancing angiogenesis and in addition, understand the underlying mechanisms. For this reason, a method is employed that combines a high throughput in vitro cell based screen coupled with an in vivo validation using vascular specific green fluorescent protein reporter transgenic zebrafish for examining proangiogenesis activity.

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Some nanoparticles (NPs) may induce adverse health effects in exposed organisms, but to date the evidence for this in wildlife is very limited. Silver nanoparticles (AgNPs) can be toxic to aquatic organisms, including fish, at concentrations relevant for some environmental exposures. We applied whole mount in-situ hybridisation (WISH) in zebrafish embryos and larvae for a suite of genes involved with detoxifying processes and oxidative stress, including metallothionein (mt2), glutathionine S-transferase pi (gstp), glutathionine S-transferase mu (gstm1), haem oxygenase (hmox1) and ferritin heavy chain 1 (fth1) to identify potential target tissues and effect mechanisms of AgNPs compared with a bulk counterpart and ionic silver (AgNO3).

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We studied adult zebrafish to determine whether the size of 20 and 110 nm citrate-coated silver nanoparticles (AgC NPs) differentially impact the gills and intestines, known target organs for Ag toxicity in fish. Following exposure for 4 h, 4 days, or 4 days plus a 7 day depuration period, we obtained different toxicokinetic profiles for different particle sizes, as determined by Ag content of the tissues. Ionic AgNO3 served as a positive control.

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