Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans

Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C.elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.X1144sciescopu

OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research

Online application for survival analysis (OASIS) has served as a popular and convenient platform for the statistical analysis of various survival data, particularly in the field of aging research. With the recent advances in the fields of aging research that deal with complex survival data, we noticed a need for updates to the current version of OASIS. Here, we report OASIS 2 (http://sbi.postech.ac.kr/oasis2), which provides extended statistical tools for survival data and an enhanced user interface. In particular, OASIS 2 enables the statistical comparison of maximal lifespans, which is potentially useful for determining key factors that limit the lifespan of a population. Furthermore, OASIS 2 provides statistical and graphical tools that compare values in different conditions and times. That feature is useful for comparing age-associated changes in physiological activities, which can be used as indicators of "healthspan." We believe that OASIS 2 will serve as a standard platform for survival analysis with advanced and user-friendly statistical tools for experimental biologists in the field of aging research.1127Ysciescopu

Rethinking Annotation: Can Language Learners Contribute?

Researchers have traditionally recruited native speakers to provide annotations for widely used benchmark datasets. However, there are languages for which recruiting native speakers can be difficult, and it would help to find learners of those languages to annotate the data. In this paper, we investigate whether language learners can contribute annotations to benchmark datasets. In a carefully controlled annotation experiment, we recruit 36 language learners, provide two types of additional resources (dictionaries and machine-translated sentences), and perform mini-tests to measure their language proficiency. We target three languages, English, Korean, and Indonesian, and the four NLP tasks of sentiment analysis, natural language inference, named entity recognition, and machine reading comprehension. We find that language learners, especially those with intermediate or advanced levels of language proficiency, are able to provide fairly accurate labels with the help of additional resources. Moreover, we show that data annotation improves learners' language proficiency in terms of vocabulary and grammar. One implication of our findings is that broadening the annotation task to include language learners can open up the opportunity to build benchmark datasets for languages for which it is difficult to recruit native speakers.Comment: ACL 202

Story Visualization by Online Text Augmentation with Context Memory

Story visualization (SV) is a challenging text-to-image generation task for the difficulty of not only rendering visual details from the text descriptions but also encoding a long-term context across multiple sentences. While prior efforts mostly focus on generating a semantically relevant image for each sentence, encoding a context spread across the given paragraph to generate contextually convincing images (e.g., with a correct character or with a proper background of the scene) remains a challenge. To this end, we propose a novel memory architecture for the Bi-directional Transformers with an online text augmentation that generates multiple pseudo-descriptions as supplementary supervision during training, for better generalization to the language variation at inference. In extensive experiments on the two popular SV benchmarks, i.e., the Pororo-SV and Flintstones-SV, the proposed method significantly outperforms the state of the arts in various evaluation metrics including FID, character F1, frame accuracy, BLEU-2/3, and R-precision with similar or less computational complexity.Comment: ICCV 202

Development of Rechargeable Seawater Battery Module

Rechargeable seawater batteries (SWBs) use Na+ ions dissolved in water (seawater or salt-water) as the cathode material. They are attracting attention for marine applications such as light buoys, marine drones, auxiliary power for sailing boats and so on. So far, SWB design has been developed from the coin-type to prismatic-shape cell for research purposes to investigate cell components and electrochemical behaviors. However, for commercial applications, that generally require >12 V and >15 W, the development of an SWB module is required, including cell assembly and packing design. The purpose of this work was to conduct research on the SWB cell assembly method while considering the SWB's properties and minimizing current imbalance. Additionally, a 5 Series (S) 4 Parallel (P) SWB module is constructed and validated using commercially available light buoys (12 V, 15 W)

Dialogue Chain-of-Thought Distillation for Commonsense-aware Conversational Agents

Human-like chatbots necessitate the use of commonsense reasoning in order to effectively comprehend and respond to implicit information present within conversations. Achieving such coherence and informativeness in responses, however, is a non-trivial task. Even for large language models (LLMs), the task of identifying and aggregating key evidence within a single hop presents a substantial challenge. This complexity arises because such evidence is scattered across multiple turns in a conversation, thus necessitating integration over multiple hops. Hence, our focus is to facilitate such multi-hop reasoning over a dialogue context, namely dialogue chain-of-thought (CoT) reasoning. To this end, we propose a knowledge distillation framework that leverages LLMs as unreliable teachers and selectively distills consistent and helpful rationales via alignment filters. We further present DOCTOR, a DialOgue Chain-of-ThOught Reasoner that provides reliable CoT rationales for response generation. We conduct extensive experiments to show that enhancing dialogue agents with high-quality rationales from DOCTOR significantly improves the quality of their responses.Comment: 25 pages, 8 figures, Accepted to EMNLP 202

SREBP and MDT-15 protect C. elegans from glucose-induced accelerated aging by preventing accumulation of saturated fat

Glucose-rich diets shorten the life spans of various organisms. However, the metabolic processes involved in this phenomenon remain unknown. Here, we show that sterol regulatory element-binding protein (SREBP) and mediator-15 (MDT-15) prevent the life-shortening effects of a glucose-rich diet by regulating fat-converting processes in Caenorhabditis elegans. Up-regulation of the SREBP/MDT-15 transcription factor complex was necessary and sufficient for alleviating the life-shortening effect of a glucose-rich diet. Glucose feeding induced key enzymes that convert saturated fatty acids (SFAs) to unsaturated fatty acids (UFAs), which are regulated by SREBP and MDT-15. Furthermore, SREBP/MDT-15 reduced the levels of SFAs and moderated glucose toxicity on life span. Our study may help to develop strategies against elevated blood glucose and free fatty acids, which cause glucolipotoxicity in diabetic patients.112217Ysciescopu

\u3cem\u3eCandida Albicans\u3c/em\u3e Stimulates \u3cem\u3eStreptococcus Mutans\u3c/em\u3e Microcolony Development via Cross-Kingdom Biofilm-Derived Metabolites

Candida albicans is frequently detected with heavy infection of Streptococcus mutans in plaque-biofilms from children affected with early-childhood caries, a prevalent and costly oral disease. The presence of C. albicans enhances S. mutans growth within biofilms, yet the chemical interactions associated with bacterial accumulation remain unclear. Thus, this study was conducted to investigate how microbial products from this cross-kingdom association modulate S. mutans build-up in biofilms. Our data revealed that bacterial-fungal derived conditioned medium (BF-CM) significantly increased the growth of S. mutans and altered biofilm 3D-architecture in a dose-dependent manner, resulting in enlarged and densely packed bacterial cell-clusters (microcolonies). Intriguingly, BF-CM induced S. mutans gtfBC expression (responsible for Gtf exoenzymes production), enhancing Gtf activity essential for microcolony development. Using a recently developed nanoculture system, the data demonstrated simultaneous microcolony growth and gtfB activation in situ by BF-CM. Further metabolites/chromatographic analyses of BF-CM revealed elevated amounts of formate and the presence of Candida-derived farnesol, which is commonly known to exhibit antibacterial activity. Unexpectedly, at the levels detected (25–50 μM), farnesol enhanced S. mutans-biofilm cell growth, microcolony development, and Gtf activity akin to BF-CM bioactivity. Altogether, the data provide new insights on how extracellular microbial products from cross-kingdom interactions stimulate the accumulation of a bacterial pathogen within biofilms

Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans' life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs.1186Ysciescopu