Biology subjects

Tang, P.-C.

Publications and source records attributed to Tang, P.-C..

3 recordsLinked to original sources

bioRxiv2024

Interactions among Merlin, Arkadia, and SKOR2 mediate NF2-associated Schwann cell proliferation in human.

NF2-Related Schwannomatosis (previously referred to as Neurofibromatosis Type 2, or NF2) is a genetic-associated disease resulting from mutations in the gene, NF2. NF2 encodes the merlin protein, which acts as a tumor suppressor. Bilateral vestibular schwannoma (VS) is a hallmark of NF2. Although the exactly molecular mechanism mediating NF2-driven schwannomatosis remain unclear, it is known that defective Merlin protein functionality leads to abnormal cell proliferation. Herein, we utilized a human induced pluripotent stem cell (hiPSC)-based Schwann cell (SC) model to investigate the role of merlin in human SCs. SCs were derived from hiPSCs carrying a NF2 mutation (c.191 T > C; p. L64P), its isogenic wild-type control cell line, and a NF2 patient-derived hiPSC line. NF2 mutant SCs showed abnormal cellular morphology and proliferation. Proteomic analyses identified novel interaction partners for Merlin - Arkadia and SKOR2. Our results established a new model in which merlin interacts with Arkadia and SKOR2 and this interaction is required for the proper activation of the SMAD-dependent pathway in TGF{beta} signaling.

cell biology↗

bioRxiv2021

Decreased synthesis and variable gene transcripts of oxytocin in a domesticated avian species

The Bengalese finch was domesticated more than 250 years ago from the wild white-rumped munia. Similar to other domesticated species, Bengalese finches show a reduced fear response and have lower corticosterone levels, compared to white-rumped munias. Bengalese finches and munias also have different song types. Since oxytocin (OT) has been found to be involved in stress coping and auditory processing, we tested whether the OT sequence and brain expression pattern and content differ in wild munias and domesticated Bengalese finches. We identified intra-strain variability in the untranslated regions of the OT sequence in Bengalese finches in comparison to the munia OT. Several of these changes fall in specific transcription factor binding sites, which show either a conserved or a relaxed evolutionary trend in the avian lineage, and in vertebrates in general. Although in situ hybridization in several hypothalamic nuclei did not reveal significant differences in the number of cells expressing OT between the two strains, real-time quantitative PCR showed significantly lower OT mRNA expression in the diencephalon of the Bengalese finches relative to munias. Our study thus points to a decreased OT synthesis in the domestic strain compared with the wild strain in birds. This is an opposite pattern from that found in some domesticated mammals, suggesting that different processes of OT function might have occurred in mammals and birds under domestication.

neuroscience↗

bioRxiv2020

The chemotherapeutic drug methotrexate selects for antibiotic resistance

Understanding drivers of antibiotic resistance evolution is fundamental for designing optimal treatment strategies and interventions to reduce the spread of antibiotic resistance. Various cytotoxic drugs used in cancer chemotherapy have antibacterial properties, but how bacterial populations are affected by these selective pressures is unknown. Here we test the hypothesis that the widely used cytotoxic drug methotrexate affects the evolution and selection of antibiotic resistance through the same mechanisms as the antibiotic trimethoprim. We show that methotrexate can select for trimethoprim resistance determinants located on the chromosome or a plasmid in clinical strains of Escherichia coli. Additionally, methotrexate can co-select for virtually any antibiotic resistance determinant when present together with trimethoprim resistance on a multidrug-resistance clinical plasmid. These selective effects occur at concentrations 40- to >320-fold below the methotrexate minimal inhibitory concentration for E. coli, suggesting a selective role of methotrexate chemotherapy for antibiotic resistance in patients that strongly depend on effective antibiotic treatment. Significance statementThe presented data show that methotrexate has the potential to select for virtually any given antibiotic resistance gene when genetically linked to trimethoprim resistance. This study highlights the need for increased awareness of the presence of acquired antibiotic resistance determinants in the gut of patients with impaired immunity undergoing methotrexate treatment to preserve the effects of downstream antibiotic treatments.

microbiology↗