Biology subjects

Lau, B. Y.

Publications and source records attributed to Lau, B. Y..

3 recordsLinked to original sources

bioRxiv2025

The effects of adolescent stress on adult social behavior and basolateral amygdala GABAergic neurons with perineuronal nets depend on prenatal stress history

Developmental stress is a well-established risk factor for mental health disorders, yet the neural mechanisms underlying these outcomes remain incompletely understood. Inhibitory brain networks, particularly within the amygdala, are disrupted by stress and implicated in stress-related psychopathologies. Using a rodent model, the current study investigated the isolated and combined effects of prenatal and adolescent stress on adult social interactions and GABAergic neurons surrounded by perineuronal nets (PNNs) in the basolateral amygdala (BLA). Male and female rats were exposed to chronic variable stressors (CVS) prenatally (PS), during adolescence (AS), or during both prenatal and adolescent periods (PS+AS). In adulthood, all animals were tested for social behavior with same-sex weight-matched partners, and brains were collected for identification of BLA inhibitory neurons (GAD67 staining) and PNNs (Wisteria Floribunda Agglutinin staining). For social behavior, AS alone robustly increased social investigation in adulthood relative to non-stressed (NS) controls and animals exposed to combined PS+AS. PS+AS subjects did not significantly differ from NS controls, suggesting that prenatal stress exposure prevented adolescent stress-induced increases in adult social investigation. An analogous data pattern was observed in the BLA. AS alone decreased the number GAD67+ neurons surrounded by PNNs (co-labeled) relative to NS controls and subjects exposed to combined PS+AS. When the percentage of total GAD67+ neurons co-labeled with PNNs was assessed, both PS alone and AS alone reduced the proportion of GAD67+ neurons surrounded by PNNs, whereas combined PS+AS had no effect. Overall, these data suggest that prenatal stress exposure prevents adolescent stress-induced disruptions to perineuronal nets surrounding inhibitory neurons in the BLA, potentially conferring resilience to adolescent stress-induced changes in inhibitory function and social behavior. HighlightsO_LIAdolescent stress exposure increased social investigation in adulthood. C_LIO_LIAdolescent stress decreased the number of BLA cells co-labeled with GAD67 and WFA. C_LIO_LIPrenatal or adolescent stress decreased the proportion of inhibitory neurons with PNNs. C_LIO_LIWhen preceded by prenatal stress, effects of adolescent stress were not observed. C_LI

neuroscience↗

bioRxiv2020

Computational front end to diverse therapeutic phage cocktails

New therapies are necessary to combat increasingly antibiotic-resistant bacterial pathogens. We have developed a technology platform of computational, molecular biology, and microbiology tools which together enable on-demand production of phages that target virtually any given bacterial isolate. Two complementary computational tools that identify and precisely map prophages and other integrative genetic elements (IGEs) in bacterial genomes are used to identify prophage-laden bacteria that are close relatives of the target strain. Phage genomes are engineered to disable lysogeny, through use of long amplicon PCR and Gibson assembly. Finally, the engineered phage genomes are introduced into host bacteria for phage production. As an initial demonstration, we used this approach to produce a phage cocktail against the opportunistic pathogen Pseudomonas aeruginosa PAO1. Two prophage-laden P. aeruginosa strains closely related to PAO1 were identified, ATCC 39324 and ATCC 27853. Deep sequencing revealed that mitomycin C treatment of these strains induced seven phages that grow on P. aeruginosa PAO1. The most diverse five of these were engineered for non-lysogeny by deleting the integrase gene (int), which is readily identifiable and typically conveniently located at one end of the prophage. The {Delta}int phages, individually and in cocktails, showed killing of P. aeruginosa PAO1 in vitro as well as in a waxworm (Galleria mellonella) model of infection. SIGNIFICANCE STATEMENTThe antibiotic-resistance crisis in medicine and agriculture has led to renewed interest in phage therapy as an alternative means of treating infection. However, conventional methods for isolating pathogen-specific phage are slow, labor-intensive, and frequently unsuccessful. We have demonstrated that prophages carried by near-neighbor bacteria can serve as starting material for production of engineered phages that kill the target pathogen. Our approach and technology platform offer new opportunity for rapid development of phage therapies against most, if not all, bacterial pathogens, a foundational advance for use of phage in treating infectious disease.

microbiology↗

bioRxiv2020

New candidates for regulated gene integrity revealed through precise mapping of integrative genetic elements

Integrative genetic elements (IGEs) are mobile multigene DNA units that integrate into and excise from host bacterial chromosomes. Each IGE usually targets a specific site within a conserved host gene, integrating in a manner that preserves target gene function. However, a small number of bacterial genes are known to be inactivated upon IGE integration and reactivated upon excision, regulating phenotypes of virulence, mutation rate, and terminal differentiation in multicellular bacteria. The list of regulated gene integrity (RGI) cases has been slow-growing because IGEs have been challenging to precisely and comprehensively locate in genomes. We present software (TIGER) that maps IGEs with unprecedented precision and without attB site bias. TIGER uses a comparative genomic, ping-pong BLAST approach, based on the principle that the IGE integration module (i.e., its int-attP region) is cohesive. The resultant IGEs, along with integrase phylogenetic analysis and gene inactivation tests, revealed 19 new cases of genes whose integrity is regulated by IGEs (including dut, eccCa1, gntT, hrpB, merA, ompN, prkA, tqsA, traG, yifB, yfaT and ynfE), as well as recovering previously known cases (in sigK, spsM, comK, mlrA, and hlb genes). It also recovered known clades of site-promiscuous integrases and identified possible new ones.

bioinformatics↗