Biology subjects

Lai, H.-Y.

Publications and source records attributed to Lai, H.-Y..

4 recordsLinked to original sources

bioRxiv2023

Comprehensive Assessment of Ischemic Stroke in Nonhuman Primates: Neuroimaging, Behavioral, and Serum Proteomic Analysis

Ischemic strokes, prevalence and impactful, underscore the necessity of advanced research models closely resembling human physiology. O integrating n ur study in nonhuman primates (NHPs) offers a comprehensive exploration of ischemic stroke, integrating neuroimaging data, behavioral outcomes, and serum proteomics to elucidate the complex interplay of factors involved in stroke pathophysiology. We observed a consistent pattern in infarct volume, peaking at 1-month post-middle cerebral artery occlusion (MCAO) and stabilizing thereafter. This trend was closely correlated with notable changes in motor function and working memory performance. Using diffusion tensor imaging (DTI), we detected significant alterations in fractional anisotropy (FA) and mean diffusivity (MD) values, indicative of microstructural changes in the brain. These findings were strongly correlated with the observed neurological and cognitive deficits, highlighting the sensitivity of DTI metrics in stroke assessment. Behaviorally, the monkeys exhibited a reliance on their unaffected limb for compensatory movements, a response commonly observed in stroke impairment. This adaptation, alongside the consistent findings in DTI metrics, suggests a substantial impact of stroke on motor function and spatial perception. Proteomic analysis through MS/MS functional enrichment revealed two distinct groups of proteins with significant changes post-MCAO. Notably, MMP9, THBS1, MB, PFN1, and YWHAZ emerged as potential biomarkers and therapeutic targets in ischemic stroke. Our findings underscore the complex nature of stroke and the potential of an integrated approach, combining neuroimaging, behavioral studies, and proteomics, for advancing our understanding and treatment of this condition.

neuroscience↗

bioRxiv2023

Unveiling interactions of spatial-temporal information in tactile motion perception

The intricate interplay of spatial and temporal information in tactile-motion perception remains elusive. Despite strides in decoding neural signals for direction, speed and texture in tactile perception, nuanced interactions persist as challenges. Addressing this, we investigated direction and speed tactile perception, exploring the intricate spatial-temporal dynamics. Psychophysical experiments manipulated direction and speed parameters using a laboratory-designed fingerpad ball-stimulator. A pivotal discovery includes quadrant-dependent anisotropic distortion in perceived motion direction, expanding the well-known notion of a specific preferred orientation. Spatial features primarily influence inherent responses, while temporal features impact stimulus-specific responses, shedding light on dynamic directional perception. The introduction of a psychometric function improved the modeling of tactile-motion speed perception, incorporating both linear and nonlinear components for a more accurate representation. This study provides intriguing insights into the neural mechanisms in tactile-motion perception, with potential applications for somatosensation in brain-machine interfaces. TeaserThis study unveils the intricate interplay of perceiving tactile motion, shedding light on the mysteries of tactile sensations.

neuroscience↗

bioRxiv2023

Interactions with a phage gene underlie costs of a β-lactamase

The fitness cost of an antibiotic resistance gene (ARG) can differ across host strains creating refuges that allow maintenance of an ARG in the absence of direct selection for its resistance phenotype. Despite the importance of such ARG-host interactions for predicting ARG dynamics, the basis of ARG fitness costs and their variability between hosts are not well understood. We determined the genetic basis of a host-dependent cost of a {beta}-lactamase, blaTEM-116*, that conferred a significant cost in one Escherichia coli strain but was close to neutral in 11 other Escherichia spp. strains. Selection of a blaTEM-116* encoding plasmid in the strain in which it initially had a high cost resulted in rapid and parallel compensation to that cost through mutations in a P1 phage gene, relAP1. When the wildtype relAP1 gene was added to a strain in which it was not present and in which blaTEM-116* was neutral, it caused the ARG to become costly. Thus, relAP1 is both necessary and sufficient to explain blaTEM-116* costs in at least some host backgrounds. To our knowledge, these findings represent the first demonstrated case of the cost of an ARG being influenced by a genetic interaction with a phage gene. The interaction between a phage gene and a plasmid-borne ARG highlights the complexity of selective forces determining the maintenance and spread of ARGs, and, by extension, encoding phage and plasmids, in natural bacterial communities.

evolutionary biology↗

bioRxiv2023

Costs of antibiotic resistance genes depend on host strain and environment and can influence community composition

Antibiotic resistance genes (ARGs) is a major contributor to increasing levels of antibiotic resistance in clinical and agricultural settings. ARGs are strongly selected in environments containing corresponding antibiotics, but it is less clear how ARGs are maintained in environments where antibiotic selection might be weak or sporadic. In particular, few studies have directly estimated the effect of ARGs on host fitness in the absence of direct selection. To the extent that ARGs impose costs, it is not clear if these are fixed or might depend on the host strain, perhaps marking some ARG-host combinations as low-cost reservoirs that can act to maintain ARGs in the absence of antibiotic selection. We quantified the fitness effects of six ARGs in each of 11 diverse Escherichia spp. strains in two environments. While three ARGs (blaTEM-116, cat, and dfrA5, encoding resistance to {beta}-lactam antibiotics, chloramphenicol, and trimethoprim, respectively) imposed an overall cost, all ARGs had an effect in at least one host strain, reflecting a significant ARG effect-by-strain interaction effect. A simulation model predicts that these interactions cause the ecological success of ARGs to depend on available host strains, and, to a lesser extent, for successful host strains to depend on the ARGs present in a community. Together, these results indicate the importance of considering ARG effects over different host strains, especially the potential of reservoir strains that allow resistance to persist in the absence of direct selection, in efforts to understand resistance dynamics. ImportanceAntibiotic resistance is a major and increasing public health concern. Resistance occurs through a variety of mechanisms but commonly involves bacterial strains acquiring antibiotic resistance genes (ARGs) encoded by mobile elements. It is obvious and well-documented that ARGs will be selected in bacteria that are exposed to the antibiotics they confer resistance to. ARGs can also confer costs to bacteria--in environments that do not contain antibiotics, these costs can lead to the loss of ARGs. We show that ARG costs can be significant and that they depend on the host bacterial strain and the environment in which strains are grown. This dependence creates host-environment refuges for many ARGs, allowing them to be maintained in the absence of direct selection.

microbiology↗