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Hwang, W. S.

Publications and source records attributed to Hwang, W. S..

4 recordsLinked to original sources

Parsing digital or analogue TCR performance through piconewton forces

{beta} T-cell receptors (TCRs) recognize aberrant peptides bound to major histocompatibility complex molecules (pMHCs) on unhealthy cells, amplifying specificity and sensitivity through physical load placed on the TCR-pMHC bond during immunosurveillance. To understand this mechanobiology, TCRs stimulated by abundantly and sparsely arrayed epitopes (NP366-374 /Db and PA224-233/Db, respectively) following in vivo influenza A virus infection were studied with optical tweezers. While certain NP repertoire CD8 T lymphocytes require many ligands for activation, others are digital, needing just few. Conversely, all PA TCRs perform digitally, exhibiting pronounced bond lifetime increases through sustained, energizing volleys of structural transitioning. Optimal digital performance is superior in vivo, correlating with ERK phosphorylation, CD3 loss, and activation marker upregulation in vitro. Given neoantigen array paucity, digital TCRs are likely critical for immunotherapies. One Sentence SummaryQuality of ligand recognition in a T-cell repertoire is revealed through application of physical load on clonal T-cell receptor (TCR)-pMHC bonds

immunology↗

Chromosome-aware phylogenomics of Assassin Bugs (Hemiptera: Reduvioidea) elucidates ancient gene conflict

Though the phylogenetic signal of loci on sex chromosomes can differ from those on autosomes, chromosomal-level genome assemblies for non-vertebrates are still relatively scarce and conservation of chromosomal gene content across deep phylogenetic scales has therefore remained largely unexplored. We here assemble a uniquely large and diverse set of samples (17 Anchored Hybrid Enrichment [AHE], 24 RNA-Seq, and 70 whole-genome sequencing [WGS] samples of variable depth) for the medically important assassin bugs (Reduvioidea). We assess the performance of genes based on multiple features (e.g., nucleotide vs. amino acid, nuclear vs. mitochondrial, and autosomal vs. X chromosomal) and employ different methods (concatenation and coalescence analyses) to reconstruct the unresolved phylogeny of this diverse ([~]7,000 spp.) and old (>180 MYA) group. Our results show that genes on the X chromosome are more likely to have discordant phylogenies than those on autosomes. We find that the X chromosome conflict is driven by high gene substitution rates that impact accuracy of phylogenetic inference. However, gene tree clustering showed strong conflict even after discounting variable third codon positions. Alternative topologies were not particularly enriched for sex chromosome loci, but spread across the genome. We conclude that binning genes to autosomal or sex chromosomes may result in a more accurate picture of the complex evolutionary history of a clade.

genomics↗

Global convergence of dominance and neglect in flying insect diversity

Most of arthropod biodiversity is unknown to science. For this reason, it has been unclear whether insect communities around the world are dominated by the same or different taxa. This question can be answered through standardized sampling of biodiversity followed by estimation of species diversity and community composition with DNA sequences. This approach is here applied to flying insects sampled by 39 Malaise traps placed in five biogeographic regions, eight countries, and numerous habitats (>220,000 specimens belonging to >25,000 species in 463 families). Unexpectedly, we find that 20 insect families account for >50% of local species diversity regardless of continent, climatic region, and habitat type. These consistent differences in family-level dominance explain two-thirds of variation in community composition despite massive levels of species turnover, with most species (>97%) in the top 20 families encountered at a single site only. Alarmingly, the same families that dominate global insect diversity also suffer from extreme taxonomic neglect with little signs of increasing activities in recent years. Tackling the biodiversity of these "dark taxa" thereby emerges as an urgent priority because the arthropod groups comprising most of the global flying insect diversity are particularly poorly known.

ecology↗

Sphingosine-1-Phosphate (S1P) analogue Phyto-sphingosine-1-Phosphate (P1P) improves the in vitro maturation efficiency of porcine oocytes via regulation of oxidative stress and apoptosis

Phytosphingosine-1-Phosphate (P1P) is a signaling sphingolipid regulating various physiological activities. Yet, little is known of the effect of P1P in the context of reproduction. As such, we aimed to investigate the influence of P1P on oocyte maturation during porcine in vitro maturation (IVM). Here we report the expression of S1PR1-3 among P1P receptors (S1PR1-4) in cumulus cells and oocytes. When P1P was treated by concentrations 10 nM, 50 nM, 100 nM, and 1000 nM during IVM, Metaphase II rate was significantly increased in 1000 nM (=1 M) P1P treatment group. Maturation rate improvement by P1P supplementation was only observed in the presence of EGF. Oocytes under the influence of P1P decreased intracellular ROS levels yet did not show significant differences in GSH levels. In our molecular studies, P1P treatment up-regulated gene expressions involved in cumulus expansion (Has2 and EGF), antioxidant enzyme (SOD3 and Cat), and developmental competence (Oct4) while activating ERK1/2 and Akt signaling. P1P treatment also influenced oocyte survival by shifting the ratio of Bcl-2 to Bax, while inactivating JNK signaling. We further demonstrated that oocytes matured with P1P significantly displayed not only higher developmental competence (cleavage and blastocyst formation rate), but also greater blastocyst quality (total cell number and the ratio of apoptotic cells) when activated via parthenogenetic activation (PA) and in vitro fertilization (IVF). Despite low levels of endogenous P1P found in animals, exogenous P1P was able to influence animal reproduction as shown by increased porcine oocyte maturation as well as preimplantation embryo development.

developmental biology↗