Mouse models to investigate in situ cell fate decisions induced by p53.

Investigating how transcription factors control complex cellular processes requires tools that enable responses to be visualised at the single-cell level and their cell fate to be followed over time. For example, the tumour suppressor p53 (also called TP53 in humans and TRP53 in mice) can initiate diverse cellular responses by transcriptional activation of its target genes: Puma to induce apoptotic cell death and p21 to induce cell cycle arrest/cell senescence. However, it is not known how these processes are regulated and initiated in different cell types.

Putting the STING back into BH3-mimetic drugs for TP53-mutant blood cancers.

TP53-mutant blood cancers remain a clinical challenge. BH3-mimetic drugs inhibit BCL-2 pro-survival proteins, inducing cancer cell apoptosis. Despite acting downstream of p53, functional p53 is required for maximal cancer cell killing by BH3-mimetics through an unknown mechanism.

Epstein-Barr Virus and the Pathogenesis of Diffuse Large B-Cell Lymphoma.

Epstein-Barr virus (EBV), defined as a group I carcinogen by the World Health Organization (WHO), is present in the tumour cells of patients with different forms of B-cell lymphoma, including Burkitt lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and, most recently, diffuse large B-cell lymphoma (DLBCL). Understanding how EBV contributes to the development of these different types of B-cell lymphoma has not only provided fundamental insights into the underlying mechanisms of viral oncogenesis, but has also highlighted potential new therapeutic opportunities. In this review, we describe the effects of EBV infection in normal B-cells and we address the germinal centre model of infection and how this can lead to lymphoma in some instances.

Identification of Nanoparticle Properties for Optimal Drug Delivery across a Physiological Cell Barrier.

Nanoparticles (NPs) represent an attractive strategy to overcome difficulties associated with the delivery of therapeutics. Knowing the optimal properties of NPs to address these issues could allow for improved in vivo responses. This work investigated NPs prepared from 5 materials of 3 sizes and 3 concentrations applied to a cell barrier model.

S100B dysregulation during brain development affects synaptic SHANK protein networks via alteration of zinc homeostasis.

Autism Spectrum Disorders (ASD) are caused by a combination of genetic predisposition and nongenetic factors. Among the nongenetic factors, maternal immune system activation and zinc deficiency have been proposed. Intriguingly, as a genetic factor, copy-number variations in S100B, a pro-inflammatory damage-associated molecular pattern (DAMP), have been associated with ASD, and increased serum S100B has been found in ASD.

A blood biomarker and clinical correlation cohort study protocol to diagnose sports-related concussion and monitor recovery in elite rugby.

Introduction: In professional rugby, sports-related concussion (SRC) remains the most frequent time loss injury. Therefore, accurately diagnosing SRC and monitoring player recovery, through a multi-modal assessment process, is critical to SRC management. In this protocol study, we aim to assess SRC over multiple time points post-injury to determine the value of multi-modal assessments to monitor player recovery.

The effect of serum starvation on tight junctional proteins and barrier formation in Caco-2 cells.

Assessing the ability of pharmaceutics to cross biological barriers and reach the site-of-action requires faithful representation of these barriers . Difficulties have arisen in replicating resistance . This paper investigated serum starvation as a method to increase Caco-2 barrier stability and resistance.

Mechanical characterisation of the human dura mater, falx cerebri and superior sagittal sinus.

The cranial meninges have been shown to play a pivotal role in traumatic brain injury mechanopathology. However, while the mechanical response of the brain and its many subregions have been studied extensively, the meninges have conventionally been overlooked. This paper presents the first comparative mechanical analysis of human dura mater, falx cerebri and superior sagittal sinus tissues.

On the association between circulating biomarkers and atherosclerotic calcification in a cohort of arterial disease participants.

Background And Aims: Atherosclerotic calcification is a powerful predictor of cardiovascular disease. This study aims to determine whether circulating levels of a local/systemic calcification inhibitor or a marker of bone formation correlate with measures of coronary or extracoronary calcification.

Methods And Results: Clinical computed tomography (CT) was performed on 64 arterial disease participants undergoing carotid and lower extremity endarterectomy.

Comparing nanoparticles for drug delivery: The effect of physiological dispersion media on nanoparticle properties.

Delivering therapeutics to disease sites is a challenge facing modern medicine. Nanoparticle delivery systems are of considerable interest to overcome this challenge, but these systems suffer from poor clinical translation. It is believed this is, in part, due to incomplete understanding of nanoparticle physico-chemical properties in vivo.

Drug delivery across the blood-brain barrier: recent advances in the use of nanocarriers.

The blood-brain barrier (BBB) has a significant contribution to homeostasis and protection of the CNS. However, it also limits the crossing of therapeutics and thereby complicates the treatment of CNS disorders. To overcome this limitation, the use of nanocarriers for drug delivery across the BBB has recently been exploited.

Standardization of research methods employed in assessing the interaction between metallic-based nanoparticles and the blood-brain barrier: Present and future perspectives.

Treating diseases of the central nervous system (CNS) is complicated by the presence of the blood-brain barrier (BBB), a semipermeable boundary layer protecting the CNS from toxins and homeostatic disruptions. However, this layer also excludes almost 100% of therapeutics, impeding the treatment of CNS diseases. The advent of nanoparticles, in particular metallic-based nanoparticles, presents the potential to overcome this barrier and transport drugs into the CNS.

Regional mechanical and biochemical properties of the porcine cortical meninges.

The meninges are pivotal in protecting the brain against traumatic brain injury (TBI), an ongoing issue in most mainstream sports. Improved understanding of TBI biomechanics and pathophysiology is desirable to improve preventative measures, such as protective helmets, and advance our TBI diagnostic/prognostic capabilities. This study mechanically characterised the porcine meninges by performing uniaxial tensile testing on the dura mater (DM) tissue adjacent to the frontal, parietal, temporal, and occipital lobes of the cerebellum and superior sagittal sinus region of the DM.