Biology subjects

Wilson, W.

Publications and source records attributed to Wilson, W..

4 recordsLinked to original sources

bioRxiv2025

From human joints to bioreactor setups: quantifying mechanical stimuli in cartilage physiology and regeneration

ObjectiveBioreactors are widely used to apply mechanical stimuli to osteochondral (OC) explants and cartilage tissue-engineered (TE) constructs, yet their ability to replicate native joint mechanics is not well quantified. This study benchmarks common bioreactor loading protocols against a finite element (FE) model of the human knee during gait, enabling direct comparison to physiologically relevant mechanical parameters. MethodsA validated FE model of the human knee joint simulating the stance phase of gait was used to characterize physiological mechanical conditions, including maximum principal stress, maximum shear strain, pore pressure, and fluid velocity. These outputs were compared with those generated by representative bioreactor setups: dynamic unconfined compression (10-30%) and combined compression (10%) with ball rotation ({+/-}25{degrees}), which were applied to both OC plugs and TE constructs, and hydrostatic pressure (0.5-50 MPa), which was applied only to TE constructs. FE simulations evaluated spatial and magnitude-based agreement with native cartilage mechanics. ResultsIn OC plugs, 10% unconfined compression generated maximum principal stresses ([~]7.5 MPa) and pore pressures ([~] 4 MPa) closely matching native tissue ([~] 4.5 MPa and [~]5 MPa, respectively). In TE constructs, even at 30% unconfined strain, maximum principal stresses and pore pressures remained around 100 times lower than physiological values, while fluid velocities were 10 times higher. Hydrostatic loading of TE constructs at 5 MPa matched native pore pressures ([~]5 MPa) but induced negligible strains. ConclusionsThis study provides a quantitative framework for evaluating how well bioreactor loading regimens replicate physiological joint mechanics. The findings offer actionable guidance to experimentalists for selecting bioreactor conditions based on specific mechanical targets. This can lead to more effective design of in vitro cartilage studies and support translational strategies in cartilage repair and tissue engineering.

bioengineering↗

bioRxiv2024

Seasonal niche overlap of diverse facultative antagonistic bacteria of diatoms in a productive coastal ecosystem

Biotic interactions between microbes underpin marine ecosystem health, governing the flux of carbon and other nutrients in the ocean. However, studying aquatic microbial interactions is challenging. Model systems can provide in depth understanding of the mechanisms driving such associations. Yet, insights of the prevalence and co-occurrence dynamics of laboratory model systems in natural ecosystems remain limited. By leveraging 16S and 18S metabarcoding combined with phylogenetic analysis, we assessed the environmental presence of facultative bacterial pathogens of one of the most globally abundant phytoplankton groups, the diatoms. Sampling microbial assemblages in a productive coastal ecosystem over the course of an annual cycle, we detected multiple algicidal bacteria that frequently exhibited overlapping co-occurrences. Together, these bacteria positively correlated with members of the potentially toxic genus Pseudo-nitzchia, as well as temperature. Our study indicates that antagonistic bacteria occupy shared temporal niches and demonstrates the need to consider their cumulative impacts on diatom population health, including in future ocean conditions.

ecology↗

bioRxiv2021

Identification of a new family of "megaphages" that are abundant in the marine environment

Megaphages - bacteriophages harbouring extremely large genomes - have recently been found to be ubiquitous, being described from a variety of microbiomes ranging from the animal gut to soil and freshwater systems. However, no complete marine megaphage has been identified to date. Here, using both short and long read sequencing, we assembled >900 high-quality draft viral genomes from water in the English Channel. One of these genomes included a novel megaphage, Mar_Mega_1 at >650 Kb, making it one of the largest phage genomes assembled to date. Utilising phylogenetic and network approaches, we found this phage represents a new family of bacteriophages. Genomic analysis showed Mar_Mega_1 shares relatively few homologues with its closest relatives, but, as with other mega-phages Mar_Mega_1 contained a variety of auxiliary metabolic genes responsible for carbon metabolism and nucleotide biosynthesis, including isocitrate dehydrogenase [NADP] and nicotinamide-nucleotide amidohydrolase [PncC] which have not previously been identified in megaphages. The results of this study indicate that phages containing extremely large genomes can be found in abundance in the marine environment and augment host metabolism by mechanisms not previously described.

microbiology↗

bioRxiv2021

Pathogenic MAST3 variants in the STK domain are associated with epilepsy

ObjectiveThe MAST family of microtubule-associated serine-threonine kinases (STK) have distinct expression patterns in the developing and mature human and mouse brain. To date, only MAST1 has been associated with neurological disease, with de novo variants in individuals with a neurodevelopmental disorder, including a mega corpus callosum. MethodsUsing exome sequencing we identify MAST3 missense variants in individuals with epilepsy. We also assess the effect of these variants on the ability of MAST3 to phosphorylate the target gene product ARPP-16 in HEK293T cells. ResultsWe identify de novo missense variants in the STK domain in 11 individuals, including two recurrent variants p.G510S (n=5) and p.G515S (n=3). All 11 individuals had Developmental and epileptic encephalopathy, with 8 having normal development prior to seizure onset at < 2 years of age. All patients developed multiple seizures types, while 9/11 had seizures triggered by fever and 9/11 had drug-resistant seizures. In vitro analysis of HEK293T cells transfected with MAST3 cDNA carrying a subset of these patient-specific missense variants demonstrated variable but generally lower expression, with concomitant increased phosphorylation of the MAST3 target, ARPP-16, compared to wildtype. These findings suggest the patient-specific variants may confer MAST3 gain-of-function. Moreover, single-nuclei RNA sequencing and immunohistochemistry shows that MAST3 expression is restricted to excitatory neurons in the cortex late in prenatal development and postnatally. InterpretationIn summary, we describe MAST3 as a novel epilepsy-associated gene with a potential gain-of-function pathogenic mechanism that may be primarily restricted to excitatory neurons in the cortex.

genetics↗