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Biology subjects

Lucas, K.

Publications and source records attributed to Lucas, K..

6 recordsLinked to original sources

Ontogeny of escape response and body shape in Threespine Stickleback (Gasterosteus aculeatus L.)

Escape responses in fishes provide insight into accelerative motions and behavioral response times of these animals, linking numerous fitness-related traits. We sought to connect escape response performance to genotype and phenotype across ontogenetic stages within a single population of Threespine Stickleback (Gasterosteus aculeatus L.), to determine if a gene of major effect (Ectodysplasin; Eda) on adaptive lateral armour plate phenotype and fitness conveys a performance advantage in brackish and saltwater environments. We predicted that possession of one or more low-plated alleles would result in better escape performance in brackish environments across ontogeny, and that Eda genotype would result in variation in shape phenotype that would be predictive of escape performance before the completion of lateral plate development. We assessed three kinematic variables derived from C-start escape responses in wild-caught, F1 juvenile, and F1 adults, and found that Eda genotypes did not directly impact maximum velocity or curvature coefficient, but linked phenotypes contributed to an increase in total distance traveled in F1 adults. We further showed that Eda genotype impacted growth, producing variation in size which in turn influenced escape performance variables across age groups, with a particular focus on total distance traveled. The influence of Eda genotype on shape was confounded by sexual dimorphism, indicating that further sex-specific studies on shape and performance are needed. The presence of at least one low-plated allele conferred a growth advantage, particularly in a freshwater rearing environment, consistent with known pleiotropic effects of Eda, including on skeletal development, that may be modulating anti-predator responses before plate phenotype is fully expressed. Altogether, more ontogenic studies are needed to ensure the influence of development on adaptive traits is more clearly understood.

evolutionary biology↗

Rapid Assessment of Biomarkers on Single Extracellular Vesicles Using 'Catch and Display' on Ultrathin Nanoporous Silicon Nitride Membranes

Extracellular vesicles (EVs) are particles secreted by all cells that carry bioactive cargo and facilitate intercellular communication with roles in normal physiology and disease pathogenesis. EVs have tremendous diagnostic and therapeutic potential and accordingly, the EV field has grown exponentially in recent years. Bulk assays lack the sensitivity to detect rare EV subsets relevant to disease, and while single EV analysis techniques remedy this, they are undermined by complicated detection schemes often coupled with prohibitive instrumentation. To address these issues, we propose a microfluidic technique for EV characterization called catch and display for liquid biopsy (CAD-LB). CAD-LB rapidly captures fluorescently labeled EVs in the similarly-sized pores of an ultrathin silicon nitride membrane. Minimally processed sample is introduced via pipette injection into a simple microfluidic device which is directly imaged using fluorescence microscopy for a rapid assessment of EV number and biomarker colocalization. In this work, nanoparticles were first used to define the accuracy and dynamic range for counting and colocalization by CAD-LB. Following this, the same assessments were made for purified EVs and for unpurified EVs in plasma. Biomarker detection was validated using CD9 in which Western blot analysis confirmed that CAD-LB faithfully recapitulated differing expression levels among samples. We further verified that CAD-LB captured the known increase in EV-associated ICAM-1 following the cytokine stimulation of endothelial cells. Finally, to demonstrate CAD-LBs clinical potential, we show that EV biomarkers indicative of immunotherapy responsiveness are successfully detected in the plasma of bladder cancer patients undergoing immune checkpoint blockade.

bioengineering↗

A platform for the recombinant production of Group A Streptococcus glycoconjugate vaccines

Strep A is a human-exclusive bacterial pathogen killing annually more than 500,000 patients, and no current licensed vaccine exists. Strep A bacteria are highly diverse, but all produce an essential, abundant, and conserved surface carbohydrate, the Group A Carbohydrate, which contains a rhamnose polysaccharide (RhaPS) backbone. RhaPS is a validated universal vaccine candidate in a glycoconjugate prepared by chemical conjugation of the native carbohydrate to a carrier protein. We engineered the Group A Carbohydratte biosynthesis pathway to enable recombinant production using the industry standard route to couple RhaPS to selected carrier proteins within E. coli cells. The structural integrity of the produced recombinant glycoconjugate vaccines was confirmed by NMR spectroscopy and mass spectrometry. Purified RhaPS glycoconjugates elicited carbohydrate-specific antibodies in mice and rabbits and bound to the surface of multiple Strep A strains of diverse M-types, confirming the recombinantly produced RhaPS glycoconjugates as valuable vaccine candidates.

microbiology↗

Ceylon cinnamon and its major compound Cinnamaldehyde can limit overshooting inflammatory signaling and angiogenesis in vitro: implications for COVID-19 treatment

Overshooting immune reactions can occur during inflammatory responses that accompany severe infections, such as COVID-19. Cytokines, damage-associated molecular patterns (DAMPs), and reactive oxygen and nitrogen species can generate positive feedback loops of inflammation, leading to long-term complications such as vascular endothelialitis, thrombosis, endothelial dysfunction, neurological impairments, and chronic fatigue. Dexamethasone can limit inflammation by inhibiting the activation of pro-inflammatory transcription factors. High dose dexamethasone, however, has undesirable side effects. Here, we show that Ceylon cinnamon and its major compound cinnamaldehyde can mitigate inflammatory signaling in vitro. Cinnamaldehyde interferes with the dimerization of toll-like receptor 4 (TLR4), which can be activated by DAMPs like HSP60 and HMGB1. Our results suggest that supplementary treatment with Ceylon cinnamon may allow administration of lower doses of dexamethasone to avoid high dose steroid side effects. Moreover, preliminary results indicate that Ceylon cinnamon modulates angiogenesis, which is a reactive phenomenon in COVID-19.

immunology↗

Primitive and modern swimmers solve the challenges of turning similarly to achieve high maneuverability

Animal swimmers alter trajectories - or turn - for a variety of critical life functions such as feeding, mating and avoiding predation. Yet turning represents a fundamental dilemma based in rotational dynamics: the torque powering a turn is favored by an expanded body configuration, yet minimizing the resistance to a turn (the moment of inertia) is favored by a contracted body configuration. How do animals balance these opposing demands to achieve high maneuverability? By noninvasively measuring fluid and body motions, we found that both jellyfish (Aurelia aurita) and fish (Danio rerio) initially maximized torque using previously undescribed, rapid body movements. Both species then minimized resistance to turning by bending their bodies to reduce their moment of inertia. Use of this sequential solution by such distantly related animals as an invertebrate and a vertebrate suggests strong selection for these turning dynamics that may extend to other swimmers and inform future vehicle designs.

zoology↗

Tangential flow microfluidics for the capture and release of nanoparticles and extracellular vesicles on conventional and ultrathin membranes

Membranes have been used extensively for the purification and separation of biological species. A persistent challenge is the purification of species from concentrated feed solutions such as extracellular vesicles (EVs) from biological fluids. We investigated a new method to isolate micro- and nano-scale species termed tangential flow for analyte capture (TFAC), which is an extension of traditional tangential flow filtration (TFF). Initially, EV purification from plasma on ultrathin nanomembranes was compared between both normal flow filtration (NFF) and TFF. NFF resulted in rapid formation of a protein cake which completely obscured any captured EVs and also prevented further transport across the membrane. On the other hand, TFF showed capture of CD63 positive EVs with minimal contamination. We explored the use of TFF to capture target species over membrane pores, wash and then release in a physical process that does not rely upon affinity or chemical interactions. This process of TFAC was studied with model particles on both ultrathin nanomembranes and conventional thickness membranes (polycarbonate track-etch). Successful capture and release of model particles was observed using both membranes. Ultrathin nanomembranes showed higher efficiency of capture and release with significantly lower pressures indicating that ultrathin nanomembranes are well-suited for TFAC of delicate nanoscale particles such as EVs.

bioengineering↗