bluuebunny/crossref_metadata_2025_split huggingface dataset:
Menstrual cycle associated alteration of vastus lateralis motor unit function
Authors: Piasecki Jessica , Guo Yuxiao , Jones Eleanor J. , Phillips Bethan E. , Stashuk Daniel W. , Atherton Philip J. , Piasecki Mathew 
Published: March 2023

AbstractEstrogen and progesterone are the primary female sex hormones and have net excitatory and inhibitory effects, respectively, on neuronal function. Fluctuating concentrations across the menstrual cycle has led to several lines of research in relation to neuromuscular function, yet evidence from animal and cell culture models have yet to be demonstrated in human motor units (MU) coupled with quantification of circulating hormones.Intramuscular electromyography (iEMG) was applied to record MU potentials (MUP) and corresponding MUP trains (MUPT) from the vastus lateralis of eumenorrheic females during the early follicular, ovulation and mid luteal phases of the menstrual cycle, alongside assessments of neuromuscular performance. Multi-level regression models were applied to explore effects of time and of contraction level. Statistical significance was accepted as p<0.05.Knee extensor maximum voluntary contraction (MVC), jump power, force steadiness, and balance did not differ across the menstrual phases (all p>0.4). Firing rate of low threshold MU (10% MVC) was reduced during phases of high progesterone (β=-0.82Hz, p<0.001), with no difference in MUPs analysed from 25% MVC contractions. MUPs were more complex during ovulation and mid luteal phase (p<0.03), with no change in neuromuscular junction transmission instability (p>0.3).Assessments of neuromuscular performance did not differ across the menstrual cycle. The suppression of low threshold MU firing rate during periods of increased progesterone may suggest a potential inhibitory effect and an alteration of recruitment strategy, however this had no discernible effect on performance. These findings highlight contraction level dependent modulation of VL MU function over the eumenorrheic cycle.
Exploring the Spatiotemporal Influence of Climate on American Avian Migration with Random Forests
Authors: Bick I. Avery , Bakkestuen Vegar , Pedersen Marius , Raja Kiran , Sethi Sarab 
Published: March 2023

AbstractNorth and South American Birds have adapted to climatic and ecological patterns to inform their Spring and Fall migration timings. Temperature and precipitation patterns are shifting under anthropogenic climate change, causing downstream effects on plant flowering cycles, insect populations, and habitat availability. Understanding how these cues trigger migration could improve the effectiveness and timing of bird surveys, as well as informing habitat protection and creation efforts to lessen biodiversity loss due to climate change. Here, we employ a modeling approach to explore how climate spatiotemporally affects accuracy of predicting bird occurrence. Specifically, we train an ensemble of random forests on subsets of North and South American climate data to predict distributions of historical bird occurrence probability for passerine bird species in a North American forested region on eBird citizen science surveys from 2008-2018. We further investigate the relevance of each feature, region, and temporal lag for predicting the observed bird occurrence in a forested region in Northeast America, finding that both temperature and precipitation facilitate accurate prediction. For predicting species in October, when many passerines have begun their southward winter migration, we achieve more accurate predictions of bird occurrence using lagged, rather than current, climate features alone to predict communities in October. We also note significant higher random forest feature importance for some lagged North American climate features than South American features. These results suggest that machine learning models may be useful for identifying spatiotemporal climatic cues that affect migratory behavior. Lastly, we explore the application and limitations of random forests for prediction of future bird occurrence using 2021-2040 climate projections.
Reducing squalene epoxidase by the aging-dependent intra-tissue cholesterol accumulation is associated with increased colorectal cancer patient severity in high-risk populations
Authors: Jun Soo Young , Yoon Hyang Ran , Yoon Ji-Yong , Lee Jeong-Ju , Kim Jin-Man , Kim Nam-Soon 
Published: March 2023

ABSTRACTObjectiveRecently, we demonstrated cholesterol accelerating colorectal cancer (CRC) progression via squalene epoxidase (SQLE) reduction, activating the β-catenin oncogenic pathway while downregulating the p53 pathway, mediated by the inhibition of GSK3β activity (GSK3βpS9). However, the interrelationship between cholesterol increase and CRC progression with aging has never been determined.DesignWe utilized case data from public databases and human specimens to assess the relationship between cholesterol accumulation and CRC progression with aging. Digital image analysis-machine learning with multiplex fluorescence-immunohistochemistry evaluated the effects of SQLE, p53WT, p53MT, and GSK3βpS9(hereafter candidates) on the survival of CRC patients. Also, the prognostic and diagnostic abilities were assessed by a time-dependent receiver operating characteristic (timeROC) and a ROC curve with and without the discriminant score for the candidates as a single or whole, respectively.ResultsWe found an accumulation of cholesterol and cholesteryl ester in tissues with aging, which led to the acceleration of CRC progression through substantial decreases of SQLE, p53WT, p53MTexpressions and inhibition of GSK3β activity in advanced CRCs. Retrospective studies demonstrated that SQLE significantly impacted the shortened progression-free survival of the population with progressive pathological severity and high CRC risk beyond the age of 50. Clinical assays further showed the excellent prognostic and diagnostic abilities of SQLE and GSK3βpS9but also the substantial diagnostic potential of the combined candidate for the aged high-risk CRC population.ConclusionWe provide new insights into the relationship between cholesterol increase and CRC progression with aging and identify valuable biomarkers for aged populations with high-risk CRC.
Rapid and scalable preclinical evaluation of personalized antisense oligonucleotide therapeutics using organoids derived from rare disease patients
Authors: Means John C. , Louiselle Daniel A. , Farrow Emily G. , Pastinen Tomi , Younger Scott T. 
Published: March 2023

AbstractPersonalized antisense oligonucleotides (ASOs) have achieved positive results in the treatment of rare genetic disease. As clinical sequencing technologies continue to advance, the ability to identify rare disease patients harboring pathogenic genetic variants amenable to this therapeutic strategy will likely improve. Here, we describe a scalable platform for generating patient-derived cellular models and demonstrate that these personalized models can be used for preclinical evaluation of patient-specific ASOs. We establish robust protocols for delivery of ASOs to patient-derived organoid models and confirm reversal of disease-associated phenotypes in cardiac organoids derived from a Duchenne muscular dystrophy (DMD) patient harboring a structural deletion in the dystrophin gene amenable to treatment with existing ASO therapeutics. Furthermore, we design novel patient-specific ASOs for two additional DMD patients (siblings) harboring a deep intronic variant in the dystrophin gene that gives rise to a novel splice acceptor site, incorporation of a cryptic exon, and premature transcript termination. We show that treatment of patient-derived cardiac organoids with patient-specific ASOs results in restoration of DMD expression and reversal of disease-associated phenotypes. The approach outlined here provides the foundation for an expedited path towards the design and preclinical evaluation of personalized ASO therapeutics for a broad range of rare diseases.
Long-term stress shapes dynamic reconfiguration of functional brain networks across multi-task demands
Authors: Gao Hongyao , Zeng Yimeng , Tian Ting , Liu Chao , Wu Jianhui , Wu Haitao , Qin Shaozheng 
Published: March 2023

AbstractExposure to sustained stress can have a profound impact on the brain, emotion and cognition, with either adaptive or maladaptive effects. Human functional brain networks are dynamically organized to enable rapid and flexible adaptation to meet ever-changing task demands. Yet, little is known about how long-term stress alters the dynamic reconfiguration of functional brain networks across multi-task demands. Here we show prominent changes in the dynamic reconfiguration of large-scale brain networks during resting-state, emotional and working-memory processing under long-term stress. Hidden Markov Model analysis detected several latent brain states and switching processes involving the default mode, emotional salience and executive-control networks that are dominant to rest, emotion and working memory, respectively. Critically, long-term stress increased persistent time on brain states relevant to goal-directed demands and cognitive control, with more frequent transitions to these brain states when compared to controls. Furthermore, long-term stress led to higher correlations of the occupancy and persistency of brain states linked to psychological distress and behavioral performance. Our findings provide a neurocognitive framework whereby long-term stress shapes the way the brain adapts to varying task demands and increases the sensitivity of functional brain networks to psychological and behavioral responses. These changes can be both adaptive and maladaptive, reflecting the complex effects of long-term stress on brain function.
A visual paired associate learning (vPAL) paradigm to study memory consolidation during sleep
Authors: Schmidig J.F. , Geva-Sagiv M. , Falach R. , Yakim S. , Gat Y. , Sharon O. , Fried I. , Nir Y. 
Published: March 2023

AbstractThe hippocampus helps transform an experience into an enduring memory by associating its multiple aspects. Sleep improves the consolidation of the newly formed associations, leading to stable long-term memory. Most research on human declarative memory and its consolidation during sleep uses word-pair associations requiring exhaustive learning. Here we present the visual paired association learning (vPAL) paradigm, in which participants learn new associations between images of celebrities and animals. vPAL associations are based on a one-shot exposure that resembles learning in natural conditions. We tested if vPAL can reveal a role for sleep in memory consolidation by assessing the specificity of memory recognition, and the cued recall performance, before and after sleep. We found that a daytime nap improved the stability of recognition memory and discrimination abilities compared to identical intervals of wakefulness. By contrast, cued recall of associations did not exhibit significant sleep-dependent effects. High-density EEG during naps further revealed an association between sleep spindle density and stability of recognition memory. Thus, the vPAL paradigm opens new avenues for future research on sleep and memory consolidation across ages and heterogeneous populations in health and disease.
Antibacterial activity of solid surfaces is critically dependent on relative humidity, inoculum volume and organic soiling
Authors: Kaur Harleen , Rosenberg Merilin , Kook Mati , Danilian Dmytro , Kisand Vambola , Ivask Angela 
Published: March 2023

AbstractAntimicrobial surface materials potentially prevent pathogen transfer from contaminated surfaces. Efficacy of such surfaces is assessed by standard methods using wet exposure conditions known to overestimate antimicrobial activity compared to dry exposure. Some dry test formats have been proposed but semi-dry exposure scenariose.g.,oral spray or water droplets exposed to ambient environment, are less studied. We aimed to determine the impact of environmental test conditions on antibacterial activity against the model speciesEscherichia coliandStaphylococcus aureus. Surfaces based on copper, silver, and quaternary ammonium with known or claimed antimicrobial properties were tested in conditions mimicking microdroplet spray or larger water droplets exposed to variable relative air humidity in the presence or absence of organic soiling. All the environmental parameters critically affected antibacterial activity of the tested surfaces from no effect in high-organic dry conditions to higher effect in low-organic humid conditions but not reaching the effect size demonstrated in the ISO 22169 wet format. Copper was the most efficient antibacterial surface followed by silver and quaternary ammonium based coating. Antimicrobial testing of surfaces using small droplet contamination in application-relevant conditions could therefore be considered as one of the worst-case exposure scenarios relevant to dry use surfaces.Featured image + One Sentence summaryAntibacterial activity of copper and silver surfaces is highly dependent on environmental testing conditions with maximum efficiency in low-organic wet conditions to no antibacterial activity in high-organic dry conditions indicating the need to test antimicrobial surface materials in application-relevant test formats as opposed to current standards.
Wnt-Ror-Dvl signalling and the dystrophin complex organize planar-polarized membrane compartments inC. elegansmuscles
Authors: Peysson Alice , Zariohi Noura , Gendrel Marie , Chambert-Loir Amandine , Frébault Noémie , Cheynet Elise , Andrini Olga , Boulin Thomas 
Published: March 2023

ABSTRACTCell polarity mechanisms allow the formation of specialized membrane domains with unique protein compositions, signalling properties, and functional characteristics. By analysing the localization of potassium channels and proteins belonging to the dystrophin-associated protein complex, we reveal the existence of distinct planar-polarized membrane compartments at the surface ofC. elegansmuscle cells. We find that muscle polarity is controlled by a non-canonical Wnt signalling cascade involving the ligand EGL-20/Wnt, the receptor CAM-1/Ror, and the intracellular effector DSH-1/Dishevelled. Interestingly, classical planar cell polarity proteins are not required for this process. Using time-resolved protein degradation, we demonstrate that –while it is essentially in place by the end of embryogenesis– muscle polarity is a dynamic state, requiring continued presence of DSH-1 throughout post-embryonic life. Our results reveal the unsuspected complexity of theC. elegansmuscle membrane and establish a novel genetically tractable model system to study cellular polarity and membrane compartmentalizationin vivo.
A parasitoid serpin gene that disrupts host immunity shows adaptive evolution of alternative splicing
Authors: Yan Zhichao , Fang Qi , Yang Lei , Xiao Shan , Wang Jiale , Ye Gongyin 
Published: March 2023

AbstractAlternative splicing (AS) is a major source of protein diversity in eukaryotes, but less is known about its evolution compared to gene duplication (GD). How AS and GD interact is also largely understudied. By constructing the evolutionary trajectory of a serpin gene PpSerpin-1 (Pteromalus puparumserpin 1) in parasitoids and other insects, we found that both AS and GD jointly contribute to serpin protein diversity. These two processes are negatively correlated and show divergent features in both protein and regulatory sequences. Furthermore, parasitoid wasps exhibit higher numbers of serpin protein/domains than nonparasitoids, resulting from more GD but less AS in parasitoids. Nevertheless, PpSerpin-1 shows an exon expansion of AS compared to other parasitoids. We find that several isoforms of PpSerpin-1 are involved in the wasp immune response, have been recruited to both wasp venom and larval saliva, and suppress host immunity. In summary, we report the differential features of AS and GD in the evolution of insect serpins and their associations with the parasitic life strategy, and we provide an example of how a parasitoid serpin gene adapts to parasitism through AS.
Implantation of engineered adipocytes that outcompete tumors for resources suppresses cancer progression
Authors: Nguyen Hai P. , Sheng Rory , Murray Elizabeth , Ito Yusuke , Bruck Michael , Biellak Cassidy , An Kelly , Lynce Filipa , Dillon Deborah A. , Magbanua Mark Jesus M. , Huppert Laura A. , Hammerlindl Heinz , Esserman Laura , Rosenbluth Jennifer M. , Ahituv Nadav 
Published: March 2023

AbstractTumors acquire an increased ability to obtain and metabolize nutrients. Here, we engineered and implanted adipocytes to outcompete tumors for nutrients and show that they can substantially reduce cancer progression. Growing cells or xenografts from several cancers (breast, colon, pancreas, prostate) alongside engineered human adipocytes or adipose organoids significantly suppresses cancer progression and reduces hypoxia and angiogenesis. Transplanting modulated adipocyte organoids in pancreatic or breast cancer mouse models nearby or distal from the tumor significantly suppresses its growth. To further showcase therapeutic potential, we demonstrate that co-culturing tumor organoids derived from human breast cancers with engineered patient-derived adipocytes significantly reduces cancer growth. Combined, our results introduce a novel cancer therapeutic approach, termed adipose modulation transplantation (AMT), that can be utilized for a broad range of cancers.
A Retina-Inspired Computational Model for Stimulation Efficacy Characterization and Implementation Optimization of Implantable Optogenetic Epi-Retinal Neuro-Stimulators
Authors: Yousefi Tayebeh , Kassiri Hossein 
Published: March 2023

AbstractIn this paper, a biologically-informed computational framework is developed to model the efficacy and to optimize the implementation of an implantable epi-retinal prosthesis that performs optogenetic stimulation through aμLED array. The developed model is capable of translating visual stimulus inputs into corresponding signals evoked in the transfected retinal cells through optogenetic stimulation, calculating the subsequent neuronal activities of the following retinal layers, and estimating the resulted brain’s visual perception. As such, it can model and quantitatively analyze the impact of optical stimulation parameters (intensity, frequency, directivity, wavelength, etc.) and theμLED array’s physical specifications (array size, density, pitch, implantation location, etc.) on the efficacy of the stimulation.Using this model, we compared optical and electrical stimulations in terms of the structural similarity between their induced visual perception in the brain and the visual stimulus input. We showed that thanks to the cell-type specificity of optogenetic stimulation, it can induce more relevant visual perception qualities than electrical stimulation. We also showed that its resulted visual perception substantially improves with scaling the stimulator’s array size. The model was also used to qualitatively and quantitatively analyze the impact of parameters such as implantation location, light intensity, single- and dual-wavelength stimulation, and illumination divergence angle on the quality of the optical-stimulation-induced visual perception. In each case, the simulation results were followed by our interpretation from a biological point of view. More importantly, in each case, we discussed how the results could be used for optimizing different parameters of an implantable optogenetic stimulator to achieve maximum efficacy and energy efficiency. Keywords: Retinal prosthesis, optogenetics, visual perception, optical stimulation,μLED array, computational model, spatial resolution, pathway-specific stimulation.
Prediction of the Human Pharmacokinetics of 30 Modern Antibiotics Using the ANDROMEDA Software
Authors: Fagerholm Urban , Hellberg Sven , Alvarsson Jonathan , Spjuth Ola 
Published: March 2023

ABSTRACTThe ANDROMEDA software, based on machine learning, conformal prediction and a new physiologically-based pharmacokinetic model, was used to predict and characterize the human clinical pharmacokinetics of 30 selected modern small antibiotic compounds (investigational and marketed drugs). A majority of clinical pharmacokinetic data was missing. ANDROMEDA successfully filled this gap. Most antibiotics were predicted and measured to have limited permeability, good metabolic stability and multiple elimination pathways. According to predictions, most of the antibiotics are mainly eliminated renally and biliary and every other antibiotic is mainly eliminated via the renal route. Mean prediction errors for steady state volume of distribution, unbound fraction in plasma, renal and total clearance, oral clearance, fraction absorbed, fraction excreted renally, oral bioavailability and half-life were 1.3- to 2.3-fold. The overall median and maximum prediction errors were 1.5- and 4.8-fold, respectively, and 92 % of predictions had <3-fold error. Results are consistent with those obtained in previous validation studies and are better than with the best laboratory-based prediction methods, which validates ANDROMEDA for predictions of human clinical pharmacokinetics of modern antibiotic drugs, which to a great extent demonstrate pharmacokinetic characteristics challenging for laboratory methods (metabolic stability, limited permeability, efflux and multiple elimination pathways). Advantages with ANDROMEDA include that results are produced without the use of animals and cells and that predictions and decision-making can be done already at the design stage.
Potential of LocalBacillusspp. Isolates as Wilt Disease Biocontrol Agents forFusarium(Fusarium oxysporumf. sp.cepae) on Wakegi Onions (Allium×wakegiAraki)
Authors: Asrul Asrul 
Published: March 2023

AbstractThe use of biological agents as a biocontrol against plant pathogens was often ineffective because it worked slowly. The objective of this research was to examine the potential of local isolates of Bacillus spp. as a biocontrol agent in suppressing Fusarium wilt disease (Fusarium oxysporumf. sp.cepae) on wakegi onions. The research was designed using a completely randomized design with the treatment of rhizosphere bacterial isolates. The treatments consisted of control (without isolate application), isolates KP17, KP5, DB9, DB12, DB18, DG4, and DG11 so that the number of treatments was eight. Each treatment was repeated 5 times and each replication consisted of 10 wakegi onion plants. This research was divided into 2 stages, namely laboratory research which included isolation, characterization of colony morphology of rhizosphere bacterial isolates, and in vitro testing of the inhibitory power of biocontrol agents against pathogens. The test in the greenhouse was in the form of a disease case suppression test. The results obtained seven candidate isolates of biocontrol from 46 isolates obtained from the rhizosphere of the wakegi onion. These isolates had similarities with Bacillus spp. based on colony morphology, physiology, and biochemistry characteristics. Among the isolates found, the DB12 isolate had the potential to be developed as a biocontrol agent compared to other isolates.