bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observation of electromyogram and electrocardiogram changes with deqi for the development of an objective evaluation index of the occurrence of deqi
Authors: Miyamoto Nao , Sakaue Yusuke , Okada Shima , Shiozawa Naruhiro 
Published: October 2023

AbstractA unique sensation called “deqi” occurs in acupuncture, which is considered an essential variable in the study of the mechanisms and effects of acupuncture. However, an objective method for evaluating deqi is yet to be established. Therefore, we aimed to create an objective evaluation index for deqi using electromyogram (EMG) and electrocardiogram (ECG), which are expected to present characteristic changes based on the findings of previous studies. This study included 16 healthy adult male subjects. ST36 stimulation was performed three times after a one-week washout (N=48). EMG was used to calculate myopotentials, and ECG was used to calculate the heart rate (HR) immediately after stimulation. The subjects declared whether Deqi occurred, and the characteristic reactions of deqi in EMG and ECG were evaluated. In 48 trials, Deqi occurred 42 times and did not occur 6 times. Myopotentials were significantly higher when deqi occurred than when it did not. Furthermore, a positive correlation was identified between subjective sensation and the rate of change in myopotential. Deqi significantly increased the myopotential levels, indicating that it induced involuntary muscle activity. This involuntary muscle activity may be related to the stretch reflexes and nerve stimulation. For the HR immediately after stimulation, no change with deqi was identified, although a significant decrease in HR was found in cases without deqi. Deqi could induce a transient stress response and inhibit the decrease in the HR caused by acupuncture. The results of this study indicate two characteristics of deqi obtained from EMG and ECG: an increase in myopotential and an inhibition of the decrease in HR expected with acupuncture. These characteristics could provide objective evidence for the occurrence of deqi. Future studies with larger sample sizes are required toto further strengthen the objective assessment of deqi.
Carrageenan-containing nasal spray alleviates allergic symptoms in subjects with grass pollen allergy: A randomized, controlled, crossover clinical trial
Authors: Unger-Manhart Nicole , Morokutti-Kurz Martina , Zieglmayer Petra , Lemell Patrick , Savli Markus , Zieglmayer René , Prieschl-Grassauer Eva 
Published: October 2023

AbstractPurposeNonpharmacological nasal sprays forming a barrier between allergens and the nasal mucosa are used to manage symptoms of allergic rhinitis. We aimed to evaluate the safety and effectiveness of Callergin, a nasal spray containing barrier-forming iota-carrageenan, in the treatment of allergic rhinitis.MethodsIn this randomized, controlled, crossover trial, we assigned adults with grass pollen allergy to receive Callergin, VisAlpin and no treatment in a random order for three consecutive periods, separated by a washout period of 7 days. Subjects prophylactically applied one puff of nasal spray to each nostril 5-10 minutes prior to challenge. The primary endpoint was mean change from baseline in ‘total nasal symptom score’ (TNSS) over 3 hours, a sum of rhinorrhea, itching, sneezing, and congestion scores, recorded every 15 minutes during the challenge period.ResultsA total of 42 subjects underwent randomization. Exposure to grass pollen for 3 hours led to a notable TNSS increase from baseline in all subjects at all times. Mean TNSS was lower when subjects received treatment with Callergin compared to no treatment, although the difference did not reach statistical significance (untreated 6.96 ± 2.30; Callergin 6.59 ± 1.93; difference 0.37 points [95% CI -0.17 to 0.91]; p=0.170). In a post-hoc analysis, mean TNSS at 3 hours was significantly reduced with Callergin treatment compared to no treatment (untreated 8.29 ± 2.64; Callergin 7.70 ± 2.56; difference 0.60 points [95% CI -0.10 to 1.29] p=0.028). While all individual nasal symptoms contributed to this effect, rhinorrhea (p=0.013) and congestion (p=0.076) contributed the most. Consistently, nasal secretion weight was slightly reduced with Callergin (p=0.119). VisAlpin improved nasal symptoms, but not significantly in either analysis.The incidence of adverse events was similar among treatment groups.ConclusionProphylactic treatment with Callergin is safe and alleviates nasal symptoms in adults with grass pollen allergy.Trial registrationNCT04531358
Extracellular modulation of TREK-2 activity with nanobodies provides insight into the mechanisms of K2P channel regulation
Authors: Rödström Karin E.J. , Cloake Alexander , Sörmann Janina , Baronina Agnese , Smith Kathryn H.M. , Pike Ashley C.W. , Ang Jackie , Proks Peter , Schewe Marcus , Holland-Kaye Ingelise , Bushell Simon R. , Elliott Jenna , Pardon Els , Baukrowitz Thomas , Owens Raymond J. , Newstead Simon , Steyaert Jan , Carpenter Elisabeth P. , Tucker Stephen J. 
Published: October 2023

AbstractPotassium channels of the Two-Pore Domain (K2P) subfamily,KCNK1-KCNK18, play crucial roles in controlling the electrical activity of many different cell types and represent attractive therapeutic targets. However, the identification of highly selective small molecule drugs against these channels has been challenging due to the high degree of structural and functional conservation that exists not only between K2P channels, but across the whole K+channel superfamily. To address the issue of selectivity, we generated camelid antibody fragments (nanobodies) against the TREK-2 (KCNK10) K2P K+channel and identified selective binders including several that directly modulate channel activity. X-ray crystallography and CryoEM data of these nanobodies in complex with TREK-2 also reveal insights into their mechanisms of activation and inhibition via binding to the extracellular loops and Cap domain, as well as their suitability for immunodetection. It also facilitated design of a biparatropic inhibitory nanobody with markedly improved affinity and efficacy. These new tools therefore provide important insights into TREK channel gating and suggest alternative, highly selective approach to modulation of K2P channel activity via their extracellular domains.
VRP Assembler: haplotype-resolvedde novoassembly of diploid and polyploid genomes using quantum computing
Authors: Chen Yibo , Huang Jun-Han , Sun Yuhui , Zhang Yong , Li Yuxiang , Xu Xun 
Published: October 2023

AbstractPrecision medicine’s emphasis on individual genetic variants highlights the importance of haplotype-resolved assembly, a computational challenge in bioinformatics given its combinatorial nature. While classical algorithms have made strides in addressing this issue, the potential of quantum computing remains largely untapped. Here, we present the VRP assembler: a novel approach that transforms this task into a vehicle routing problem, a combinatorial optimization problem solvable on a quantum computer. We demonstrate its potential and feasibility through a proof of concept on short synthetic diploid and triploid genomes using a D-Wave quantum annealer. To tackle larger-scale assembly problems, we integrate the VRP assembler with Google’s OR-Tools, achieving a haplotype-resolved assembly across the human major histocompatibility complex (MHC) region. Our results show encouraging performance compared to hifiasm with the phasing accuracy first approaching the theoretical limit, underscoring the promising future of quantum computing in bioinformatics.
The role of positively charged small biomolecules in the aggregation of hyperphosphorylated tau in Alzheimer’s disease
Authors: Lee Jinmin , Lee Kyubin , Kim Min Soo , Kim Min Wook , Lim Manho , Yoo Jejoong , Lee Sang Hak 
Published: October 2023

AbstractTau proteins have recently drawn attention as a possible cause of Alzheimer’s disease (AD)-associated neuronal dementia. Hyperphosphorylated tau proteins detach from microtubules, impairing their stability and leading to neuronal degeneration. The present study focuses on understanding the molecular mechanisms behind the aggregation of hyperphosphorylated tau. Since hyperphosphorylated proteins are highly negatively charged, it is implausible that they create the damaging aggregates in the absence of some counteracting positive charge. This study found such an electrostatic (charge-charge) interaction between tau proteins and polyamines, identifying this interaction as crucial to promoting tau aggregation. In this study, we also directly observed the transition over time from tau protein aggregates to fibril structures. These findings challenge existing theories and offer insights into potential therapeutic targets for AD.
Herb-CMap: Novel Hot Diffusion Algorithm to Identify Bioactive Ingredients from Herbal Medicine Based on Gene Perturbation Profiling
Authors: Wang Yinyin , Sui Yihang , Yao Jiaqi , Hong Jiang , Tian Qimeng , Tang Yun , Tang Jing , Tan Ninghua 
Published: October 2023

AbstractHerbal medicine, especially Traditional Chinese medicine (TCM), is a valuable resource of natural products for drug discovery with obvious therapeutic effects. However, the mechanisms of action (MOAs) of herbal medicine are often unknown due to limited target information and the complexity of multiple ingredients and targets. This study developed a Herb-CMap algorithm to prioritize active ingredients and targets within herbal medicine by integrating transcriptomics- based gene perturbation data with a random walk algorithm. This methodology bridges the gap between gene perturbation of herbal medicine and its therapeutic target. Using the Suhuang antitussive capsule (Suhuang) for treating cough variant asthma (CVA) as a case study, we identify and experimentally verify that quercetin and luteolin directly interact with Il17a, Pik3cb, Pik3cd, Akt1, and Tnf. These interactions inhibit the IL-17 signaling pathway and inactivate PI3K, Akt, and NF- κB, preventing lung inflammation and treating CVA. Our findings demonstrate the potential of the Herb-CMap methodology to provide insights into the molecular MOAs of herbal medicine, thereby advancing drug discovery from herbal medicine.
Screening for links between behaviour and acute hyperthermia and hypoxia resistance in rainbow trout using isogenic lines
Authors: Lagarde H. , Lallias D. , Phocas F. , Goardon L. , Bideau M. , Guyvarc’h F. , Labbé L. , Dupont-Nivet M. , Cousin X. 
Published: October 2023

AbstractIn the context of adaptation to climate change, acute hyperthermia and hypoxia resistance are traits of growing interest in aquaculture. The feasibility of genetic improvement of these resistance traits through selection has been demonstrated in rainbow trout (Oncorhynchus mykiss). The present paper aims to test whether behaviour may be associated with acute hyperthermia and hypoxia resistance to better characterize these resistance phenotypes. For this, six rainbow trout isogenic lines were phenotyped for behaviour variables and for acute hyperthermia and hypoxia resistance, using different individuals for each phenotype. The behaviour variables of the fish were phenotyped using an individual test in a new environment. The experimental design used 150 fish phenotyped per isogenic line for each resistance trait and 18 fish per isogenic line for behavioural traits, distributed in triplicates. Relations between acute hyperthermia and hypoxia resistance phenotypes and behaviour phenotypes were tested at the level of isogenic lines.Significant differences in behaviour between isogenic lines were found, with some behaviour variables being highly associated with hypoxia resistance and moderately associated with acute hyperthermia resistance. Travelling distance, frequency of change between a risky and a safe zone of the tank and the percentage of time in movement in the behaviour test were strongly positively associated with acute hypoxia resistance. Travelling distance and frequency of change between a risky and a safe zone of the tank in the behaviour test were slightly negatively associated with acute hyperthermia resistance. This previously unstudied link between behaviour and resistance phenotypes also suggests that some behaviour variables could be used as predictors for acute hyperthermia and hypoxia resistance in fish. This result could lead to more ethical acute hyperthermia and hypoxia resistance phenotyping protocols, as the current protocols in use are classified as severe by French ethics committees.
Modulation ofα-Synuclein Aggregation Amid Diverse Environmental Perturbation
Authors: Wasim Abdul , Menon Sneha , Mondal Jagannath 
Published: October 2023

AbstractIntrinsically disordered proteinα-Synuclein (αS) is implicated in Parkinson’s disease due to its aberrant aggregation propensity. In a bid to identify the traits of its aggregation, here we computationally simulate the multi-chain association process ofαS in aqueous as well as under diverse environmental perturbations. In particular, the aggregation ofαS in aqueous and varied environmental condition led to marked concentration differences within protein aggregates, resembling liquid-liquid phase separation (LLPS). Both saline and crowded settings enhanced the LLPS propensity. However, the surface tension ofαS droplet responds differently to crowders (entropy-driven) and salt (enthalpy-driven). Conformational analysis reveals that the IDP chains would adopt extended conformations within aggregates and would maintain mutually perpendicular orientations to minimize inter-chain electrostatic repulsions. The droplet stability is found to stem from a diminished intra-chain interactions in the C-terminal regions ofαS, fostering inter-chain residue-residue interactions. Intriguingly, a graph theory analysis identifiessmall-world-like networkswithin droplets across environmental conditions, suggesting the prevalence of a consensus interaction patterns among the chains. Together these findings suggest a delicate balance between molecular grammar and environment-dependent nuanced aggregation behaviour ofαS.
Thiolation-Based Protein-Protein Hydrogels for Improved Wound Healing
Authors: Liu Xing , Wang Jie , Guo Zhao , Shen Wenting , Jia Zhenzhen , Jia Shuang , Li Limiao , Wang Jieqi , Wang Liping , Li Jiaqi , Chen Yufang , Sun Yinan , Zhang Min , Bai Jia , Wang Liyao , Li Xinyu 
Published: October 2023

AbstractThe limitations of protein-based hydrogels, including their insufficient mechanical properties and restricted biological functions, arise from the highly specific functions of proteins as natural building blocks. A potential solution to overcome these shortcomings is the development of protein-protein hydrogels, which integrate structural and functional proteins. In this study, we introduce a protein-protein hydrogel formed by crosslinking bovine serum albumin (BSA) and a genetically engineered intrinsically disordered collagen-like protein (CLP) through Ag-S bonding. Our approach involves thiolating lysine residues of BSA and crosslinking CLP with Ag+ions, utilizing thiolation of BSA and the free-cysteines of CLP. The resulting protein-protein hydrogels exhibit exceptional properties, including notable plasticity, inherent self-healing capabilities, and gel-sol transition in response to redox conditions. Furthermore, in comparison to standalone BSA hydrogels, these protein-protein hydrogels demonstrate remarkable antibacterial properties, enhanced cellular viability, and improved cellular migration. In vivo experiments provide conclusive evidence of accelerated wound healing, observed not only in murine models with streptozotocin (Step)-induced diabetes but also in zebrafish models subjected to UV-burn injuries. Detailed mechanistic insights, combined with assessments of pro-inflammatory cytokines and the expression of epidermal differentiation-related proteins, robustly validate the protein-protein hydrogel’s effectiveness in promoting wound repair. This pioneering approach advances the development of protein-protein hydrogels and serves as a reference for the creation of multifunctional protein-based hydrogels.
Mining the heparinome for cryptic antimicrobial peptides that selectively kill gram-negative bacteria
Authors: Sandín Daniel , Valle Javier , Gómez Jordi , Comas Laura , Nieves Larrosa María , González-López Juan José , Jiménez María Ángeles , Andreu David , Torrent Marc 
Published: October 2023

AbstractGlycosaminoglycan (GAG)-binding proteins regulating essential processes such as cell growth and migration are essential for cell homeostasis. As both GAGs and the lipid A disaccharide core of gram-negative bacteria contain negatively charged disaccharide units, we hypothesized that GAG-binding proteins could also recognize LPS and enclose cryptic antibiotic motifs. Here, we report novel antimicrobial peptides (AMPs) derived from heparin-binding proteins (HBPs), with specific activity against gram-negative bacteria and high LPS binding. We used computational tools to locate antimicrobial regions in 82% of HBPs, most of those colocalizing with putative heparin binding sites. To validate these results, we synthesized five candidates [HBP1-5] that showed remarkable activity against gram-negative bacteria, as well as a strong correlation between heparin and LPS binding. Structural characterization of these AMPs shows that heparin or LPS recognition promotes a conformational arrangement that favors binding. Among all analogs, HBP-5 displayed the highest affinity for both heparin and LPS, with antimicrobial activities against gram-negative bacteria at the nanomolar range. These results suggest that GAG-binding proteins are involved in LPS recognition, which allows them to act also as antimicrobial proteins. Some of the peptides reported here, particularly HBP-5, constitute a new class of AMPs with specific activity against gram-negative bacteria.
Identification of single nucleotide genetic polymorphism sites using machine learning methods
Authors: Yatskou Mikalai M. , Smolyakova Elizabeth V. , Skakun Victor V. , Grinev Vasily V. 
Published: October 2023

AbstractThe paper presents an algorithm for simulation modelling of nucleotide variations in the genomic DNA molecule. To identify single nucleotide genetic polymorphisms, it is proposed to use machine learning methods trained on simulated data. A comparative analysis of the effective classical and machine learning algorithms for identifying single nucleotide polymorphisms was performed on simulated data. The most optimal method for identifying single nucleotide genetic polymorphisms in DNA molecules at various experimental noise levels is the machine learning algorithm CART.
Effects of rumen-bypass protein supplement on growth performance, hepatic mitochondrial protein complexes, and hepatic immune gene expression of beef steers with divergent residual feed intake
Authors: Idowu Modoluwamu , Taiwo Godstime , Sidney Taylor , Treon Emily , Leal Yarahy , Ologunagba Deborah , Eichie Francisca , Pech-Cervantes Andres , Ogunade Ibukun M. 
Published: October 2023

ABSTRACTWe investigated the impact of a rumen-bypass protein supplement on growth performance, plasma and urinary N concentration, hepatic mitochondrial protein complexes, and hepatic mRNA expression of immune genes of beef steers with negative or positive residual feed intake (RFI) phenotype. Forty crossbred beef steers with an average body weight (BW) of 492 ± 36 kg were subjected to a generalized randomized block design over a 42-day experimental period. This study followed a 2 × 2 factorial arrangement of treatments. The factors evaluated were: 1) RFI classification (low-RFI (−2.12 kg/d) vs. high-RFI (2.02 kg/d), and 2) rumen-bypass protein supplement: rumen-bypass protein supplement (RCP; 227 g/steer/d) vs. control diet (CON; 0 g/d), resulting in four distinct treatments: Low-RFI-CON (n = 10), low-RFI-RCP (n = 10), high-RFI-CON (n = 10), and high-RFI-RCP (n = 10). The rumen-bypass protein supplement (84% CP) is a mixture of hydrolyzed feather meal, porcine blood meal, and DL-methionine hydroxy analogue. The beef steers were stratified by BW and randomly assigned to treatments and housed in four pens (1 treatment/pen) equipped with two GrowSafe feed bunks each to measure individual DMI. Body weight was measured every 7 d. Liver tissue samples were collected on d 42 from all the beef steers. These samples were used for mRNA expression analysis of 16 immune-related genes and for evaluating the mitochondrial protein complexes I - V. No significant effects due to RCP supplementation or RFI × RCP interactions (P> 0.05) were observed for ADG and DMI. However, compared to high-RFI steers, low-RFI steers showed a trend towards reduced DMI (12.9 vs. 13.6 kg/d;P= 0.07) but ADG was similar for the two RFI groups. Regardless of RFI status, supplemental RCP increased blood urea nitrogen (BUN) (P= 0.01), with a lower BUN concentration in low-RFI steers compared to high-RFI ones. A tendency for interaction (P= 0.07) between RFI and RCP was detected for urinary N concentrations; feeding RCP diet increased the urinary concentration of urea-N in high-RFI beef steers (209 vs. 124 mM), whereas the concentration was lower than that of the CON group for low-RFI beef steers (86 vs. 131 mM). Interactions of RCP and RFI were observed (P≤ 0.05) for mitochondrial activities of complexes IV, V, and mRNA expressions of some immune genes such asTLR2, TLR3, andIL23A. In conclusion, while RCP supplementation didn’t alter growth performance, its observed effects on hepatic immune gene expression, mitochondrial protein complexes, BUN, and urinary urea nitrogen depended on the beef steers’ RFI phenotype. Further studies are warranted to understand the mechanisms underpinning the interactions between RCP supplementation and RFI status.
Role of the prefrontal cortex in musical and verbal short-term memory: A functional near-infrared spectroscopy study
Authors: Ginzburg Jérémie , Cheylus Anne , Collard Elise , Ferreri Laura , Tillmann Barbara , Moulin Annie , Caclin Anne 
Published: October 2023

AbstractAuditory short-term memory (STM) is a key process in auditory cognition, with evidence for partly distinct networks subtending musical and verbal STM. The delayed matching-to-sample task (DMST) paradigm has been found suitable for comparing musical and verbal STM and for manipulating memory load. In this study, musical and verbal DMSTs were investigated with measures of activity in frontal areas with functional near-infrared spectroscopy (fNIRS): Experiment 1 compared musical and verbal DMSTs with a low-level perception task (that does not entail encoding, retention, or retrieval of information), to identify frontal regions involved in memory processes. Experiment 2 manipulated memory load for musical and verbal materials to uncover frontal brain regions showing parametric changes in activity with load and their potential differences between musical and verbal materials. A FIR model was used to deconvolute fNIRS signals across successive trials without making assumptions with respect to the shape of the hemodynamic response in a DMST. Results revealed the involvement of the dorso-lateral prefrontal cortex (dlPFC) and inferior frontal gyri (IFG), but not of the superior frontal gyri (SFG) in both experiments, in keeping with previously reported neuroimaging data (including fMRI). Experiment 2 demonstrated a parametric variation of activity with memory load in bilateral IFGs during the maintenance period, with opposite directions for musical and verbal materials. Activity in the IFGs increased with memory load for verbal sound sequences, in keeping with previous results with n-back tasks. The decreased activity with memory load observed with musical sequences is discussed in relation to previous research on auditory STM rehearsal strategies. This study highlights fNIRS as a promising tool for investigating musical and verbal STM not only for typical populations, but also for populations with developmental language disorders associated with functional alterations in auditory STM.