Moss-m7G: A Motif-Based Interpretable Deep Learning Method for RNA N7-Methlguanosine Site Prediction.

N-7methylguanosine (m7G) modification plays a crucial role in various biological processes and is closely associated with the development and progression of many cancers. Accurate identification of m7G modification sites is essential for understanding their regulatory mechanisms and advancing cancer therapy. Previous studies often suffered from insufficient research data, underutilization of motif information, and lack of interpretability. In this work, we designed a novel motif-based interpretable method for m7G modification site prediction, called Moss-m7G. This approach enables the analysis of RNA sequences from a motif-centric perspective. Our proposed word-detection module and motif-embedding module within Moss-m7G extract motif information from sequences, transforming the raw sequences from base-level into motif-level and generating embeddings for these motif sequences. Compared with base sequences, motif sequences contain richer contextual information, which is further analyzed and integrated through the Transformer model. We constructed a comprehensive m7G data set to implement the training and testing process to address the data insufficiency noted in prior research. Our experimental results affirm the effectiveness and superiority of Moss-m7G in predicting m7G modification sites. Moreover, the introduction of the word-detection module enhances the interpretability of the model, providing insights into the predictive mechanisms.

Heat stress increases carbohydrate oxidation rates and oxygen uptake during prolonged load carriage exercise.

Military missions are conducted in a multitude of environments including heat and may involve walking under load following severe exertion, the metabolic demands of which may have nutritional implications for fueling and recovery planning. Ten males equipped a military pack loaded to 30% of their body mass and walked in 20°C/40% relative humidity (RH) (TEMP) or 37°C/20% RH (HOT) either continuously (CW) for 90 min at the first ventilatory threshold or mixed walking (MW) with unloaded running intervals above the second ventilatory threshold between min 35 and 55 of the 90 min bout. Pulmonary gas, thermoregulatory, and cardiovascular variables were analyzed following running intervals. Final rectal temperature (MW: p < 0.001, g = 3.81, CW: p < 0.001, g = 4.04), oxygen uptake, cardiovascular strain, and energy expenditure were higher during HOT trials (p ≤ 0.05) regardless of exercise type. Both HOT trials elicited higher final carbohydrate oxidation (CHOox) than TEMP CW at min 90 (HOT MW: p < 0.001, g = 1.45, HOT CW: p = 0.009, g = 0.67) and HOT MW CHOox exceeded TEMP MW at min 80 and 90 (p = 0.049, g = 0.60 and p = 0.024, g = 0.73, respectively). There were no within-environment differences in substrate oxidation indicating that severe exertion work cycles did not produce a carryover effect during subsequent loaded walking. The rate of CHOox during 90 minutes of load carriage in the heat appears to be primarily affected by accumulated thermal load.

Load-Velocity Profiles Before and After Heated Resistance Exercise.

ABSTRACT: Sweet, DK, Qiao, J, Rosbrook, P, and Pryor, JL. Load-velocity profiles before and after heated resistance exercise. J Strength Cond Res 38(6): 1019-1024, 2024-This study examined neuromuscular performance using load-velocity (L-V) profiles in men and women before and after resistance exercise (RE) in hot (HOT; 40° C) and temperate (TEMP; 21° C) environments. Sixteen (f = 8, m = 8) resistance-trained individuals completed a single 70-minute whole-body high-volume load (6 exercises, 4 sets of 10 repetitions) RE bout in HOT and TEMP. Before and after RE, rectal temperature (TRE), muscle temperature of the vastus lateralis (TVL) and triceps brachii (TTB), and an L-V profile for the deadlift and bench press were recorded. Thermoregulatory and L-V data were analyzed using separate 2-way repeated measures analysis of variances (ANOVAs; condition [hot, temperate] and time [pre, post]) with significance level set at p ≤ 0.05. Deadlift peak velocity was reduced at 60% 1 repetition maximum (1RM) after RE in HOT but not TEMP. Peak velocity of 40% 1RM bench press was lower in TEMP vs. HOT pre-RE (p < 0.01). Peak velocity was decreased at all loads in the deadlift L-V profile after RE, regardless of condition. Despite elevated TRE (TEMP; 37.58 ± 0.35, HOT; 38.20 ± 0.39° C), TVL (TEMP; 35.24 ± 0.62, HOT; 37.92 ± 0.55° C), and TTB (TEMP; 35.05 ± 0.78, HOT; 38.00 ± 0.16° C) after RE in HOT vs. TEMP (p < 0.01), RE in HOT did not broadly affect L-V profiles. This indicates heated resistance exercise can be performed with high-volume load and high ambient temperature with minimal performance impairment.

Resistance Training in the Heat: Mechanisms of Hypertrophy and Performance Enhancement.

ABSTRACT: Pryor, JL, Sweet, D, Rosbrook, P, Qiao, J, Hess, HW, and Looney, DP. Resistance training in the heat: Mechanisms of hypertrophy and performance enhancement. J Strength Cond Res 38(7): 1350-1357, 2024-The addition of heat stress to resistance exercise or heated resistance exercise (HRE) is growing in popularity as emerging evidence indicates altered neuromuscular function and an amplification of several mechanistic targets of protein synthesis. Studies demonstrating increased protein synthesis activity have shown temperature-dependent mammalian target of rapamycin phosphorylation, supplemental calcium release, augmented heat shock protein expression, and altered immune and hormone activity. These intriguing observations have largely stemmed from myotube, isolated muscle fiber, or rodent models using passive heating alone or in combination with immobilization or injury models. A growing number of translational studies in humans show comparable results employing local tissue or whole-body heat with and without resistance exercise. While few, these translational studies are immensely valuable as they are most applicable to sport and exercise. As such, this brief narrative review aims to discuss evidence primarily from human HRE studies detailing the neuromuscular, hormonal, and molecular responses to HRE and subsequent strength and hypertrophy adaptations. Much remains unknown in this exciting new area of inquiry from both a mechanistic and functional perspective warranting continued research.

Endocrine Responses to Heated Resistance Exercise in Men and Women.

ABSTRACT: Pryor, JL, Sweet, DK, Rosbrook, P, Qiao, J, Looney, DP, Mahmood, S, and Rideout, T. Endocrine responses to heated resistance exercise in men and women. J Strength Cond Res 38(7): 1248-1255, 2024-We examined the endocrine responses of 16 (female = 8) resistance trained volunteers to a single bout of whole-body high-volume load resistance exercise in hot (HOT; 40° C) and temperate (TEMP; 20° C) environmental conditions. Thermoregulatory and heart rate (HR) data were recorded, and venous blood was acquired before and after resistance exercise to assess serum anabolic and catabolic hormones. In men, testosterone increased after resistance exercise in HOT and TEMP ( p < 0.01), but postexercise testosterone was not different between condition ( p = 0.51). In women, human growth hormone was different between condition at pre-exercise ( p = 0.02) and postexercise ( p = 0.03). After controlling for pre-exercise values, the between-condition postexercise difference was abolished ( p = 0.16). There were no differences in insulin-like growth factor-1 for either sex ( p ≥ 0.06). In women, cortisol increased from pre-exercise to postexercise in HOT ( p = 0.04) but not TEMP ( p = 0.19), generating a between-condition difference at postexercise ( p < 0.01). In men, cortisol increased from pre-exercise to postexercise in HOT only ( p < 0.01). Rectal temperature increased to a greater extent in HOT compared with TEMP in both men ( p = 0.01) and women ( p = 0.02). Heart rate increased after exercise under both conditions in men and women ( p = 0.01), but only women experience greater postexercise HR in HOT vs. TEMP ( p = 0.04). The addition of heat stress to resistance exercise session did not overtly shift the endocrine response toward an anabolic or catabolic response. When acute program variables are prescribed to increase postresistance exercise anabolic hormones, adding heat stress is not synergistic but does increase physiologic strain (i.e., elevated HR and rectal temperature).

Plateau in Core Temperature during Shorter but Not Longer Work/Rest Cycles in Heat.

This study compared physiological responses to two work/rest cycles of a 2:1 work-to-rest ratio in a hot environment. In a randomized crossover design, fourteen participants completed 120 min of walking and rest in the heat (36.3 ± 0.6 °C, 30.2 ± 4.0% relative humidity). Work/rest cycles were (1) 40 min work/20 min rest [40/20], or (2) 20 min work/10 min rest [20/10], both completing identical work. Core temperature (Tc), skin temperature (Tsk), heart rate (HR), nude body mass, and perception of work were collected. Comparisons were made between trials at equal durations of work using three-way mixed model ANOVA. Tc plateaued in [20/10] during the second hour of work (p = 0.93), while Tc increased in [40/20] (p < 0.01). There was no difference in maximum Tc ([40/20]: 38.08 ± 0.35 °C, [20/10]: 37.99 ± 0.27 °C, p = 0.22) or end-of-work Tsk ([40/20]: 36.1 ± 0.8 °C, [20/10]: 36.0 ± 0.7 °C, p = 0.45). End-of-work HR was greater in [40/20] (145 ± 25 b·min-1) compared to [20/10] (141 ± 27 b·min-1, p = 0.04). Shorter work/rest cycles caused a plateau in Tc while longer work/rest cycles resulted in a continued increase in Tc throughout the work, indicating that either work structure could be used during shorter work tasks, while work greater than 2 h in duration may benefit from shorter work/rest cycles to mitigate hyperthermia.

NanoCon: contrastive learning-based deep hybrid network for nanopore methylation detection.

MOTIVATION: 5-Methylcytosine (5mC), a fundamental element of DNA methylation in eukaryotes, plays a vital role in gene expression regulation, embryonic development, and other biological processes. Although several computational methods have been proposed for detecting the base modifications in DNA like 5mC sites from Nanopore sequencing data, they face challenges including sensitivity to noise, and ignoring the imbalanced distribution of methylation sites in real-world scenarios. RESULTS: Here, we develop NanoCon, a deep hybrid network coupled with contrastive learning strategy to detect 5mC methylation sites from Nanopore reads. In particular, we adopted a contrastive learning module to alleviate the issues caused by imbalanced data distribution in nanopore sequencing, offering a more accurate and robust detection of 5mC sites. Evaluation results demonstrate that NanoCon outperforms existing methods, highlighting its potential as a valuable tool in genomic sequencing and methylation prediction. In addition, we also verified the effectiveness of our representation learning ability on two datasets by visualizing the dimension reduction of the features of methylation and nonmethylation sites from our NanoCon. Furthermore, cross-species and cross-5mC methylation motifs experiments indicated the robustness and the ability to perform transfer learning of our model. We hope this work can contribute to the community by providing a powerful and reliable solution for 5mC site detection in genomic studies. AVAILABILITY AND IMPLEMENTATION: The project code is available at https://github.com/Challis-yin/NanoCon.

Deep Generative Models in De Novo Drug Molecule Generation.

The discovery of new drugs has important implications for human health. Traditional methods for drug discovery rely on experiments to optimize the structure of lead molecules, which are time-consuming and high-cost. Recently, artificial intelligence has exhibited promising and efficient performance for drug-like molecule generation. In particular, deep generative models achieve great success in de novo generation of drug-like molecules with desired properties, showing massive potential for novel drug discovery. In this study, we review the recent progress of molecule generation using deep generative models, mainly focusing on molecule representations, public databases, data processing tools, and advanced artificial intelligence based molecule generation frameworks. In particular, we present a comprehensive comparison of state-of-the-art deep generative models for molecule generation and a summary of commonly used molecular design strategies. We identify research gaps and challenges of molecule generation such as the need for better databases, missing 3D information in molecular representation, and the lack of high-precision evaluation metrics. We suggest future directions for molecular generation and drug discovery.

Multi-CGAN: Deep Generative Model-Based Multiproperty Antimicrobial Peptide Design.

Antimicrobial peptides are peptides that are effective against bacteria and viruses, and the discovery of new antimicrobial peptides is of great importance to human life and health. Although the design of antimicrobial peptides using machine learning methods has achieved good results in recent years, it remains a challenge to learn and design novel antimicrobial peptides with multiple properties of interest from peptide data with certain property labels. To this end, we propose Multi-CGAN, a deep generative model-based architecture that can learn from single-attribute peptide data and generate antimicrobial peptide sequences with multiple attributes that we need, which may have a potentially wide range of uses in drug discovery. In particular, we verified that our Multi-CGAN generated peptides with the desired properties have good performance in terms of generation rate. Moreover, a comprehensive statistical analysis demonstrated that our generated peptides are diverse and have a low probability of being homologous to the training data. Interestingly, we found that the performance of many popular deep learning methods on the antimicrobial peptide prediction task can be improved by using Multi-CGAN to expand the data on the training set of the original task, indicating the high quality of our generated peptides and the robust ability of our method. In addition, we also investigated whether it is possible to directionally generate peptide sequences with specified properties by controlling the input noise sampling for our model.

Rm-LR: A long-range-based deep learning model for predicting multiple types of RNA modifications.

Recent research has highlighted the pivotal role of RNA post-transcriptional modifications in the regulation of RNA expression and function. Accurate identification of RNA modification sites is important for understanding RNA function. In this study, we propose a novel RNA modification prediction method, namely Rm-LR, which leverages a long-range-based deep learning approach to accurately predict multiple types of RNA modifications using RNA sequences only. Rm-LR incorporates two large-scale RNA language pre-trained models to capture discriminative sequential information and learn local important features, which are subsequently integrated through a bilinear attention network. Rm-LR supports a total of ten RNA modification types (m6A, m1A, m5C, m5U, m6Am, Ψ, Am, Cm, Gm, and Um) and significantly outperforms the state-of-the-art methods in terms of predictive capability on benchmark datasets. Experimental results show the effectiveness and superiority of Rm-LR in prediction of various RNA modifications, demonstrating the strong adaptability and robustness of our proposed model. We demonstrate that RNA language pretrained models enable to learn dense biological sequential representations from large-scale long-range RNA corpus, and meanwhile enhance the interpretability of the models. This work contributes to the development of accurate and reliable computational models for RNA modification prediction, providing insights into the complex landscape of RNA modifications.