Search bioRxiv⌕ Search

Biology subjects

Han, J.-H.

Publications and source records attributed to Han, J.-H..

5 recordsLinked to original sources

AbPACER: parent-aware, affinity-label-blind prioritization of affinity-matured scFv clones from phage-display NGS

Background: Affinity-maturation phage-display next-generation sequencing (NGS) yields more paired single-chain variable fragment clones than can be characterized experimentally, creating a fixed-budget prioritization problem. Read counts provide empirical support rather than direct affinity labels. We developed AbPACER (Antibody Parent-Aware Contextual Evidence Ranker), an affinity-label-blind neural ranker combining parent-relative mutation descriptors, frozen antibody-language-model context, and NGS evidence from related clones. AbPACER is campaign-adaptive rather than zero-shot: for each campaign, it is fitted to paired sequences and round-resolved R1-R3 counts before returning a 384-candidate assay list. We evaluated it in two retrospective phage-display campaigns and separately assessed its supervised mean-squared-error adaptation on AlphaSeq, denoted AbPACER-MSE. Results: From frozen top-5% candidate sets containing 16,323 Fas-associated factor 1 (FAF1) and 7,487 vascular endothelial growth factor receptor (VEGFR) clones, each method ranked the complete target-specific set and selected 384 candidates. In FAF1, AbPACER recovered 2.00 +/- 0.00 of seven retrospective panel clones, recovering two in every seed, compared with 1/7 by total count, 1.00 +/- 0.00 by Ens-Grad CNN, 1.67 +/- 1.15 by A2Binder-HL, and 1.33 +/- 0.58 by AbAffinity. In VEGFR, AbPACER recovered 2.33 +/- 0.58 of three panel clones, the highest observed learned-method mean, whereas total count recovered 3/3. No learned method was uniformly best at broader hypothetical budgets. On the public AlphaSeq common split of 11,670 fixed-test variants, AbPACER-MSE recovered 187.0 +/- 2.6 of the true top-384, closely matching AbAffinity (188.0 +/- 2.6) and exceeding A2Binder (175.7 +/- 6.4) and Ens-Grad CNN (154.0 +/- 6.1). AbPACER-MSE updated 1.378 million task-specific parameters, compared with 651.04 million for AbAffinity, and achieved Pearson 0.687 +/- 0.003 and Spearman 0.652 +/- 0.002. Conclusions: AbPACER provides a campaign-specific, parent-aware framework for fixed-budget prioritization from affinity-label-blind phage-display NGS data. At the 384-candidate endpoint, it showed the highest mean recovery among learned methods in both retrospective campaigns. AbPACER-MSE closely matched AbAffinity in true top-384 recovery while updating substantially fewer task-specific parameters. These results motivate prospective evaluation of sequence-conditioned reranking as a complement to count-based prioritization.

bioinformatics↗

Infantile engram modulates memory formation during adulthood

Infantile amnesia refers to the inability to recall early-life experiences, despite their lasting influence on adult behavior. Recent evidence suggests that memory traces formed during infancy may persist in a silent engram state. However, whether and how these silent engram cells contribute to adult memory formation remains unclear. To address this, we examined whether experiences during infancy affect adult memory formation using contextual fear conditioning in mice. Consistent with previous studies, we observed infantile amnesia 30 days later. Despite amnesia, these mice exhibited memory enhancement upon retraining as adults, suggesting that silent infantile engrams influence adult memory. Notably, this effect was context-specific. Using a cellular tagging system and ablation approaches, we found that infantile engram cells in the infralimbic cortex (IL) were crucial for this memory enhancement. Overall, these findings demonstrate that infant engram cells in the IL are re-recruited into adult memory traces, providing a neural mechanism by which early-life experiences shape adult memory formation through relearning.

neuroscience↗

Repeated experience drives multiscale engram reorganization to shape memory strength and precision

How memories are shaped by repeated experiences remains unclear. Reorganization of memory engram could underlie memory transformation. Here, by combining c-Fos-based engram cell tagging with optogenetics, spine imaging, and reactivation analyses in the dentate gyrus (DG) and medial prefrontal cortex (mPFC), we discovered a distinct system-wide engram reorganization following repeated learning; that is, a reshuffling of engram cells in the DG, as well as the rapid maturation of mPFC engram cells, forming a dual engram distributed within the hippocampal-mPFC network. These mPFC engram cells were crucial for relearning-dependent enhancement of memory precision. In addition, we found that reactivation of DG engram cells during retraining is critical for engram reorganization-dependent memory strengthening. These findings establish a causal link between engram reorganization and memory transformation by relearning.

neuroscience↗

A top-down insular cortex circuit crucial for non-nociceptive fear learning

Understanding how threats drive fear memory formation is crucial to understanding how organisms adapt to environments and treat threat-related disorders like PTSD. While traditional Pavlovian conditioning studies have provided valuable insights, the exclusive reliance on electric shock as a threat stimulus has limited our understanding of diverse threats. To address this, we developed a conditioning paradigm using a looming visual stimulus as an unconditioned stimulus (US) in mice and identified a distinct neural circuit for visual threat conditioning. Parabrachial CGRP neurons were necessary for both conditioning and memory retrieval. Upstream neurons in the posterior insular cortex (pIC) responded to looming stimuli, and their projections to the parabrachial nucleus (PBN) induced aversive states and drove conditioning. However, this pIC-to-PBN pathway was not required for foot-shock conditioning. These findings reveal how non-nociceptive visual stimuli can drive aversive states and fear memory formation, expanding our understanding of aversive US processing beyond traditional models.

neuroscience↗

Importance of the Landlocked Pond Smelt Hypomesus nipponensis as a food resource of the Little Tern Sternula albifrons on inland Andong Lake of Korea: A video image analysis

We carried out the diet study of the little tern on the sandy islet in inland Andong Lake, Korea, during the beeding season (April to July 2018). To identify its diet and examine the importance of the main prey species as a food resource, we set two remote-control video cameras with 4K-resolution on the islet. One thousand two hundred seventy-five still images that the tern had prey in its bill were identified at the species level and measured on a monitor. Then, they were classified to five length-categories and compared among months and breeding stages. Freshwater fishes dominated the diet (100%; eleven species overall), where the landlocked pond smelt Hypomesus nipponensis (80.8%) and largemouth bass Micropterus salmoides (13.7%) were the primary and next essential prey species, respectively. The average prey item length was 51.04 {+/-} 20.89 mm and significantly differed among months and breeding stages (P < 0.001, respectively). 50-75 mm prey length category was the most frequent in the diet (42.2%). In April and May, larger fish >50 mm constituted the greater part of their diet (93.1%, 66.3%, respectively), whereas the diet in June and July consisted of smaller fishes <50 mm (56.2%, 68.8% respectively). The occurrence frequency of prey length categories also varied significantly among the breeding stages (P < 0.001): 1-25 mm and 50-75 mm were overrepresented and underrepresented, respectively, at the chicks in the nest stage. On the other hand, 50-75 mm was preferred for the pre-laying and incubation stages. In terms of the survival condition of pond smelts, the before- and after water surface temperatures of the day when terns flew away showed a significant difference (P = 0.004), where a threshold looks like between 29.11{degrees}C and 30.04{degrees}C. These results support the prey abundance hypothesis that, when cold-water pond smelts might wholly swim down into the deeper lake in the hot summer, the terns might also leave their colony for another foraging place with higher prey availability.

ecology↗