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Metagenomic time-course studies provide valuable insights into the dynamics of microbial systems and have become increasingly popular alongside the reduction in costs of next-generation sequencing technologies. Normalization is a common but critical preprocessing step before proceeding with downstream analysis. To the best of our knowledge, currently there is no reported method to appropriately normalize microbial time-series data. We propose TimeNorm, a novel normalization method that considers the compositional property and time dependency in time-course microbiome data. It is the first method designed for normalizing time-series data within the same time point (intra-time normalization) and across time points (bridge normalization), separately. Intra- time normalization normalizes microbial samples under the same condition based on common dominant features. Bridge normalization detects and utilizes a group of most stable features across two adjacent time points for normalization. Through comprehensive simulation studies and application to a real study, we demonstrate that TimeNorm outperforms existing normalization methods and boosts the power of downstream differential abundance analysis. [ABSTRACT FROM AUTHOR]

Purpose: Several studies have shown that subcutaneous injections of omalizumab can treat chronic idiopathic/spontaneous urticaria (CIU/CSU) patients by only assessing the efficacy on specific endpoints. This study aimed to quantitatively analyze different doses of omalizumab in CIU/CSU and compare it with ligelizumab. Methods: Literature searches were performed in PubMed, Embase, and Web of Science databases. A model-based meta-analysis (MBMA) was utilized to develop a model incorporating time since the initiation of treatment and dose for omalizumab, with the change from baseline in Urticaria Activity Score (CFB-UAS7) as the primary efficacy endpoint. The time-course and dose-effect relationship throughout the omalizumab treatment period was analyzed, and the findings were compared with those of the investigational ligelizumab. Results: The model equation for the CFB-UAS7 was established as E = –Emax × time/(ET50 + time) × (b0 + b1 × dose). The estimated values of the model parameters E max , ET 50 , b 0 , and b 1 were −1.16, 1.26 weeks, −9.90, and −0.0361 mg−1, respectively. At week 12 after the first dose, the model-predicted CFB-UAS7 for 150 mg and 300 mg of omalizumab were −16.0 (95% CI, −17.2 to −14.8) and −21.7 (95% CI, −22.9 to −20.5), respectively. In the PEARL-1 trial, the CFB-UAS7 for 72 mg and 120 mg of ligelizumab were −19.4 (95% CI, −20.7 to −18.1) and −19.3 (95% CI, −20.6 to −18.0), respectively. In the PEARL-2 trial, these values were −19.2 (95% CI, −20.5 to −17.9) and −20.3 (95% CI, −21.6 to −19.0), respectively. Conclusion: Omalizumab showed a significant dose-dependent effect in the treatment of CSU. Both 72 mg and 120 mg ligelizumab might have the potential to outperform 150 mg (but not 300 mg) omalizumab. [ABSTRACT FROM AUTHOR]

ObjectivesHuman blood gas stability data is limited to small sample sizes and questionable statistical techniques. We sought to determine the stability of blood gases under room temperature and slushed iced conditions in patients using survival analyses.MethodsWhole blood samples from ∼200 patients were stored in plastic syringes and kept at room temperature (22-24 °C) or in slushed ice (0.1-0.2 °C) before analysis. Arterial and venous pO2 (15-150 mmHg), pCO2 (16-72 mmHg), pH (6.73-7.52), and the CO-oximetry panel [total hemoglobin (5.4-19.3 g/dL), percentages of oxyhemoglobin (O2Hb%, 20-99%), carboxyhemoglobin (COHb, 0.1-5.4%) and methemoglobin (MetHb, 0.2-4.6%)], were measured over 5-time points. The Royal College of Pathologists of Australasia's (RCPA's) criteria determined analyte instability. Survival analyses identified storage times at which 5% of the samples for various analytes became unstable.ResultsCOHb and MetHb were stable up to 3 h in slushed ice and at room temperature; pCO2, pH was stable at room temperature for about 60 min and 3 h in slushed ice. Slushed ice shortened the storage time before pO2 became unstable (from 40 to 20 min), and the instability increased when baseline pO2 was ≥60 mmHg. The storage time for pO2, pCO2, pH, and CO-oximetry, when measured together, were limited by the pO2.ConclusionsWhen assessing pO2 in plastic syringes, samples kept in slushed ice harm their stability. For simplicity's sake, the data support storage times for blood gas and CO-oximetry panels of up to 40 min at room temperature if following RCPA guidelines.

Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing the need to elucidate its underlying hepatotoxicity mechanism. This study aimed to capture the alterations in genome-wide expression over time and the subsequent perturbations of corresponding pathways across species. Six data from humans, mice, and rats, including animal liver tissue, human liver microtissues, and two liver cell lines exposed to CsA toxic dose, were used. The microtissue exposed to CsA for 10 d was analyzed to obtain dynamically differentially expressed genes (DEGs). Single-time points data at 1, 3, 5, 7, and 28 d of different species were used to provide additional evidence. Using liver microtissue-based longitudinal design, DEGs that were consistently up- or down-regulated over time were captured, and the well-known mechanism involved in CsA toxicity was elucidated. Thirty DEGs that consistently changed in longitudinal data were also altered in 28-d rat in-house data with concordant expression. Some genes (e.g. TUBB2A, PLIN2, APOB) showed good concordance with identified DEGs in 1-d and 7-d mouse data. Pathway analysis revealed up-regulations of protein processing, asparagine N-linked glycosylation, and cargo concentration in the endoplasmic reticulum. Furthermore, the down-regulations of pathways related to biological oxidations and metabolite and lipid metabolism were elucidated. These pathways were also enriched in single-time-point data and conserved across species, implying their biological significance and generalizability. Overall, the human organoids-based longitudinal design coupled with cross-species validation provides temporal molecular change tracking, aiding mechanistic elucidation and biologically relevant biomarker discovery. [ABSTRACT FROM AUTHOR]

Transcriptional variation has been studied but post-transcriptional modification due to RNA editing has not been investigated in Plasmodium. We investigated developmental stage-specific RNA editing in selected genes in Plasmodium falciparum 3D7. We detected extensive amination- and deamination-type RNA editing at 8, 16, 24, 32, 40, and 46 h in tightly synchronized Plasmodium. Most of the editing events were observed in 8 and 16 h ring-stage parasites. Extensive A-to-G deamination-type editing was detected more during the 16 h ring stage (25%) than the 8 h ring stage (20%). Extensive U-to-C amination-type editing was detected more during the 16 h ring stage (31%) than the 8 h ring stage (22%). In 28S, rRNA editing converted the loop structure to the stem structure. The hemoglobin binding activity of PF3D7_0216900 was also altered due to RNA editing. Among the expressed 28S rRNA genes, PF3D7_0532000 and PF3D7_0726000 expression was higher. Increased amounts of the transcripts of these two genes were found, particularly PF3D7_0726000 in the ring stage and PF3D7_0532000 in the trophozoite and schizont stages. Adenosine deaminase (ADA) expression did not correlate with the editing level. This first experimental report of RNA editing will help to identify the editing machinery that might be useful for antimalarial drug discovery and malaria control. [ABSTRACT FROM AUTHOR]

Prior functional magnetic resonance imaging findings in young adults indicate that recollection-sensitive neural regions dissociate according to the time courses of their respective recollection effects. Here, we examined whether such dissociations are also evident in older adults. Young and older participants encoded a series of word-image pairs, judging which of the denoted objects was the smaller. At the test, participants judged whether each of a series of test words was old or new. If a word was old, the requirement was to recall the associated image and maintain it over a variable delay period. Older adults demonstrated significantly lower associative memory performance than young adults. Transient recollection effects were identified in the left hippocampus, medial prefrontal cortex, and posterior cingulate, while sustained effects were widespread across left lateral cortex and were also evident in the bilateral striatum. Except for those in the left insula, all effects were age-invariant. These findings suggest that both transient and sustained recollection effects are largely stable across much of the healthy adult life span. [ABSTRACT FROM AUTHOR]

Although postoperative neurological events due to brain compression by the swollen temporal muscle are a rare complication, the chronological volume changes of the temporal muscle pedicle and their clinical impact have not yet been documented. This prospective observational study aimed to investigate the chronological volume changes in the temporal muscle pedicle in Moyamoya disease (MMD). Eighteen consecutive combined revascularization procedures using the temporal muscle were performed for symptomatic MMD in 2021. The postoperative pedicle volume was quantified using repeated computed tomography images on postoperative days (PODs) 0, 1, 7, 14, and 30. Postoperative neurological events with radiological evaluations and collateral development evaluated using magnetic resonance angiography obtained 6 months after surgery were studied. On average, the postoperative temporal muscle pedicle volume was most significantly increased by as much as 112% ± 9.6% on POD 7 (P < 0.001) and decreased by as little as 52% ± 21% on POD 30 (P < 0.0001) relative to POD 0. One exceptional patient (overall incidence, 5.6%) demonstrated postoperative transient neurological events due to brain compression by the swollen temporal muscle with decreased focal cerebral blood flow in the adjacent cortical area. The postoperative collateral development via direct and indirect revascularizations was confirmed in 16 (89%) and 12 (67%) hemispheres, respectively. All patients, except for one rebleeding case, showed independent outcomes at the mean latest follow-up period on 290 ± 96 days after surgery. Our observations confirmed the temporal profile of muscle pedicle volume changes after combined revascularization. Through routine attempts to avoid the unfavorable effects of temporal muscle swelling, combined revascularization can provide favorable outcomes in symptomatic MMD.

BackgroundThere are limited data on lactate stability in whole blood. The purpose of this study was to determine whole blood lactate stability at room temperature and in slushed ice conditions.MethodsAn equal number of arterial and venous samples were obtained from 202 subjects hospitalized for various pathophysiological conditions. Whole blood lactate concentration was measured over 5 different times spanning 80-90 min in a blood gas lab at a major hospital center. Samples were stored at room temperature (22-24°C) or in slushed ice conditions (0.1-0.2°C) before analysis.ResultsThe mean increase in lactate concentration was 0.001 mmol/L/min in samples on slushed ice over 90 min. However, at room temperature conditions, the mean increase in lactate concentration was 0.008 mmol/L/min regardless of whether the sample was arterial or venous. An increase in whole blood lactate concentration of ≥ 0.4 mmol/L occured after 45 min at room temperature, with 5% of all whole blood specimens demonstrating a meaningful change at ≤ 20 min. The ≥ 0.4 mmol/L change in whole blood lactate is considered significant based on the College of American Pathologists instrument peer-group standards.ConclusionsConsidering that a change in whole blood lactate concentration of ≥ 0.4 mmol/L is unacceptable instrument peer-group variation as defined by the College of American Pathologists, ice is no longer needed to stabilize whole blood lactate specimens when the draw time to analyze time is < 45 min. Samples remain stable even at 90 min when left on ice.

[Display omitted] • EEG alpha patterns of malevolent creativity mirror conventional creative ideation. • Time-related activity changes during malevolent creativity were observed. • Early frontal alpha increases may reflect conceptual expansion to antisocial ideas. • Mid-stage temporal alpha increases may indicate remote associations of novel harm. • Right-lateralized activity may signal the emotional load of malevolent ideas. On the dark side of creativity, creative ideation is intentionally used to damage others. This first electroencephalogram (EEG) study on malevolent creativity investigated task-related power (TRP) changes in the alpha band while n = 89 participants (52 women, 37 men) generated original ideas for revenge in the psychometric Malevolent Creativity Test. TRP changes were assessed for different stages of the idea generation process and linked to performance indicators of malevolent creativity. This study revealed three crucial findings: 1) Malevolent creativity yielded topographically distinct alpha power increases similar to conventional creative ideation. 2) Time-related activity changes during malevolent creative ideation were reflected in early prefrontal and mid-stage temporal alpha power increases in individuals with higher malevolent creativity performance. This performance-related, time-sensitive pattern of TRP changes during malevolent creativity may reflect early conceptual expansion from prosocial to antisocial perspectives, and subsequent inhibition of dominant semantic associations in favor of novel revenge ideas. 3) The observed, right-lateralized alpha power increases over the entire ideation phase may denote an additional emotional load of creative ideation. Our study highlights the seminal role of EEG alpha oscillations as a biomarker for creativity, also when creative processes operate in a malevolent context. [ABSTRACT FROM AUTHOR]

Speaking involves the preparation of the linguistic content of an utterance and of the motor programs leading to articulation. The temporal dynamics of linguistic versus motor-speech (phonetic) encoding is highly debated: phonetic encoding has been associated either to the last quarter of an utterance preparation time (∼150ms before articulation), or to virtually the entire planning time, simultaneously with linguistic encoding. We (i) review the evidence on the time-course of motor-speech encoding based on EEG/MEG event-related (ERP) studies and (ii) strive to replicate the early effects of phonological-phonetic factors in referential word production by reanalysing a large EEG/ERP dataset. The review indicates that motor-speech encoding is engaged during at least the last 300ms preceding articulation (about half of a word planning lag). By contrast, the very early involvement of phonological-phonetic factors could be replicated only partially and is not as robust as in the second half of the utterance planning time-window. [ABSTRACT FROM AUTHOR]

Guided by the idea that memory retrieval is selective attention turned inward, we report four experiments examining the time-course of focusing attention on memory. We used a novel episodic flanker task that turns the famous perceptual flanker task inward, presenting memory lists followed by probes that asked whether a cued letter had appeared in the same position in the memory list. Like the perceptual flanker task, we manipulated distance to measure the sharpness of the focus of attention on memory, and compatibility to measure the resistance to distraction. To measure the time-course of focusing, we presented a cue indicating the probed position in the interval between the list and the probe and varied the interval between the cue and the probe (0, 250, 500, 750 ms). The main questions were whether the focus would become sharper and resistance to distraction would become stronger as cue–probe delay increased. Experiments 1a and 1b showed strong distance effects and strong cue–probe interval effects but no reliable interaction between them. Experiments 2a and 2b showed robust compatibility effects and cue–probe interval effects but no interaction between them. Thus, there is no evidence that the sharpness of the focus increases and little evidence that the resistance to distraction improves over time. The robust reduction in response time and slight increase in accuracy with cue–probe interval may reflect the time-course of orienting to the cued position in the memory list prior to focusing on the item it contains. [ABSTRACT FROM AUTHOR]

ObjectiveDuring cardiovascular disease progression, molecular systems of myocardium (e.g., a proteome) undergo diverse and distinct changes. Dynamic, temporally-regulated alterations of individual molecules underlie the collective response of the heart to pathological drivers and the ultimate development of pathogenesis. Advances in high-throughput omics technologies have enabled cost-effective, temporal profiling of targeted systems in animal models of human diseases. However, computational analysis of temporal patterns from omics data remains challenging. In particular, bioinformatic pipelines involving unsupervised statistical approaches to support cardiovascular investigations are lacking, which hinders one's ability to extract biomedical insights from these complex datasets.Approach and resultsWe developed a non-parametric data analysis platform to resolve computational challenges unique to temporal omics datasets. Our platform consists of three modules. Module I preprocesses the temporal data using either cubic splines or principal component analysis (PCA), and it simultaneously accomplishes the tasks on missing data imputation and denoising. Module II performs an unsupervised classification by K-means or hierarchical clustering. Module III evaluates and identifies biological entities (e.g., molecular events) that exhibit strong associations to specific temporal patterns. The jackstraw method for cluster membership has been applied to estimate p-values and posterior inclusion probabilities (PIPs), both of which guided feature selection. To demonstrate the utility of the analysis platform, we employed a temporal proteomics dataset that captured the proteome-wide dynamics of oxidative stress induced post-translational modifications (O-PTMs) in mouse hearts undergoing isoproterenol (ISO)-induced hypertrophy.ConclusionWe have created a platform, CV.Signature.TCP, to identify distinct temporal clusters in omics datasets. We presented a cardiovascular use case to demonstrate its utility in unveiling biological insights underlying O-PTM regulations in cardiac remodeling. This platform is implemented in an open source R package (https://github.com/UCLA-BD2K/CV.Signature.TCP).

Transcriptional variation has been studied but post-transcriptional modification due to RNA editing has not been investigated in Plasmodium. We investigated developmental stage-specific RNA editing in selected genes in Plasmodium falciparum 3D7. We detected extensive amination- and deamination-type RNA editing at 8, 16, 24, 32, 40, and 46 h in tightly synchronized Plasmodium. Most of the editing events were observed in 8 and 16 h ring-stage parasites. Extensive A-to-G deamination-type editing was detected more during the 16 h ring stage (25%) than the 8 h ring stage (20%). Extensive U-to-C amination-type editing was detected more during the 16 h ring stage (31%) than the 8 h ring stage (22%). In 28S, rRNA editing converted the loop structure to the stem structure. The hemoglobin binding activity of PF3D7_0216900 was also altered due to RNA editing. Among the expressed 28S rRNA genes, PF3D7_0532000 and PF3D7_0726000 expression was higher. Increased amounts of the transcripts of these two genes were found, particularly PF3D7_0726000 in the ring stage and PF3D7_0532000 in the trophozoite and schizont stages. Adenosine deaminase (ADA) expression did not correlate with the editing level. This first experimental report of RNA editing will help to identify the editing machinery that might be useful for antimalarial drug discovery and malaria control.

Introduction: Soybean (Glycine max) is among the most important crops in the world, and its production can be threatened by biotic diseases, such as anthracnose. Soybean anthracnose is a seed-borne disease mainly caused by the hemibiotrophic fungus Colletotrichum truncatum. Typical symptoms are pre- and post-emergence damping off and necrotic lesions on cotyledons, petioles, leaves, and pods. Anthracnose symptoms can appear early in the field, causing major losses to soybean production. Material and Methods: In preliminary experiments, we observed that the same soybean cultivar can have a range of susceptibility towards different strains of C. truncatum, while the same C. truncatum strain can cause varying levels of disease severity in different soybean cultivars. To gain a better understanding of the molecular mechanisms regulating the early response of different soybean cultivars to different C. truncatum strains, we performed pathogenicity assays to select two soybean cultivars with significantly different susceptibility to two different C. truncatum strains and analyzed their transcriptome profiles at different time points of interaction (0, 12, 48, and 120 h post-inoculation, hpi). Results and Discussion: The pathogenicity assays showed that the soybean cultivar Gm1 is more resistant to C. truncatum strain 1080, and it is highly susceptible to strain 1059, while cultivar Gm2 shows the opposite behavior. However, if only trivial anthracnose symptoms appeared in the more resistant phenotype (MRP; Gm1-1080; Gm2-1059) upon 120 hpi, in the more susceptible phenotype (MSP; Gm-1059; Gm2- 1080) plants show mild symptoms already at 72 hpi, after which the disease evolved rapidly to severe necrosis and plant death. Interestingly, several genes related to different cellular responses of the plant immune system (pathogen recognition, signaling events, transcriptional reprogramming, and defense-related genes) were commonly modulated at the same time points only in both MRP. The list of differentially expressed genes (DEGs) specific to the more resistant combinations and related to different cellular responses of the plant immune system may shed light on the important host defense pathways against soybean anthracnose. [ABSTRACT FROM AUTHOR]

Research indicates that creative cognition depends on both associative and controlled processes, corresponding to the brain's default mode network (DMN) and executive control network (ECN) networks. However, outstanding questions include how the DMN and ECN operate over time during creative task performance, and whether creative cognition involves distinct generative and evaluative stages. To address these questions, we used multivariate pattern analysis (MVPA) to assess how the DMN and ECN contribute to creative cognition over three successive time phases during the production of a single creative idea. Training classifiers to predict trial condition (creative vs non-creative), we used classification accuracy as a measure of the extent of creative activity in each brain network and time phase. Across both networks, classification accuracy was highest in early phases, decreased in mid phases, and increased again in later phases, following a U-shaped curve. Notably, classification accuracy was significantly greater in the ECN than the DMN during early phases, while differences between networks at later time phases were non-significant. We also computed correlations between classification accuracy and human-rated creative performance, to assess how relevant the creative activity in each network was to the creative quality of ideas. In line with expectations, classification accuracy in the DMN was most related to creative quality in early phases, decreasing in later phases, while classification accuracy in the ECN was least related to creative quality in early phases, increasing in later phases. Given the theorized roles of the DMN in generation and the ECN in evaluation, we interpret these results as tentative evidence for the existence of separate generative and evaluative stages in creative cognition that depend on distinct neural substrates. [ABSTRACT FROM AUTHOR]

This article presents data concerning STX18-AS1, a long noncoding RNA gene identified from a Genome-wide association study of Atrial Septal Defect (ASD). The data describes its expression patterns in human tissues and functions in regulating cardiomyocyte differentiation in vitro. STX18-AS1 is a lncRNA with a higher abundance in developing tissues, including hearts. Its transcription distribution within the embryonic hearts during key heart septation stages supports STX18-AS1’s association with risk SNPs for ASD. The CRISPR stem cell pool in which STX18-AS1 was knocked down, showed reduced CM differentiation efficiency and lower expression of key cardiac transcriptional factors. This indicated its regulative role in supporting the lineage specification from cardiac mesoderm into cardiac progenitors and cardiomyocytes. These data can benefit the understanding of human embryonic heart developmental biology, and the time-course changes of cardiac transcriptional factors during in vitro cardiomyocyte differentiation from human embryonic stem cells.

IntroductionSoybean (Glycine max) is among the most important crops in the world, and its production can be threatened by biotic diseases, such as anthracnose. Soybean anthracnose is a seed-borne disease mainly caused by the hemibiotrophic fungus Colletotrichum truncatum. Typical symptoms are pre- and post-emergence damping off and necrotic lesions on cotyledons, petioles, leaves, and pods. Anthracnose symptoms can appear early in the field, causing major losses to soybean production.Material and MethodsIn preliminary experiments, we observed that the same soybean cultivar can have a range of susceptibility towards different strains of C. truncatum, while the same C. truncatum strain can cause varying levels of disease severity in different soybean cultivars. To gain a better understanding of the molecular mechanisms regulating the early response of different soybean cultivars to different C. truncatum strains, we performed pathogenicity assays to select two soybean cultivars with significantly different susceptibility to two different C. truncatum strains and analyzed their transcriptome profiles at different time points of interaction (0, 12, 48, and 120 h post-inoculation, hpi).Results and DiscussionThe pathogenicity assays showed that the soybean cultivar Gm1 is more resistant to C. truncatum strain 1080, and it is highly susceptible to strain 1059, while cultivar Gm2 shows the opposite behavior. However, if only trivial anthracnose symptoms appeared in the more resistant phenotype (MRP; Gm1-1080; Gm2-1059) upon 120 hpi, in the more susceptible phenotype (MSP; Gm-1059; Gm2- 1080) plants show mild symptoms already at 72 hpi, after which the disease evolved rapidly to severe necrosis and plant death. Interestingly, several genes related to different cellular responses of the plant immune system (pathogen recognition, signaling events, transcriptional reprogramming, and defense-related genes) were commonly modulated at the same time points only in both MRP. The list of differentially expressed genes (DEGs) specific to the more resistant combinations and related to different cellular responses of the plant immune system may shed light on the important host defense pathways against soybean anthracnose.

The purpose of the study was to investigate the sensitivity of back squat bar velocity, isometric mid-thigh pull, heart rate variability parameters, perceived recovery scale and step counts for tracking the muscular fatigue time-course (reduction in countermovement jump [CMJ] performance) after strenuous acute lower limb resistance exercise. Sixteen healthy men performed heart rate variability assessment, perceived recovery scale, CMJ, back squat bar velocity, isometric mid-thigh pull, and daily step counts before and 24 h, 48 h and 72 h post a strenuous acute lower limb resistance exercise (8×10 repetitions). The CMJ height decreased at 24 and 48 h after exercise session (p ≤0.017), evidencing the muscular fatigue. The perceived recovery scale presented lower values compared to baseline until 72 h after exercise session (p <0.001 for all). The heart rate variability parameters and step counts were not significantly different across time. At 24 h post, only mean force of mid-thigh pull was decreased (p =0.044), while at 48 h post, only peak force of mid-thigh pull was decreased (p =0.020). On the last day (72 h), only bar velocity (mean) presented reduction (p =0.022). Therefore, the perceived recovery scale was the only variable sensible to tracking muscular fatigue, i. e. presenting a similar time-course to CMJ height. [ABSTRACT FROM AUTHOR]

The root-lesion nematode, Pratylenchus scribneri, is a migratory endo-parasitic nematode that impacts potato production on a large scale. Effective management of this nematode requires an understanding of its population dynamics alongside early detection. Typically, the nematode population estimates are made from infested soil; however, considering the endo-migratory lifestyle of this nematode, it also is crucial to determine the nematode population residing inside the host roots. In this study, a SYBR green-based quantitative real-time PCR (qPCR) assay was developed for detection and quantification of P. scribneri in potato roots. The assay used a previously reported primer pair (ITS-2F/ITS-2R), and it proved to be specific and sensitive, detecting as low as 1/128th equivalents of a P. scribneri individual per 0.2 g of potato roots. The robustness of the assay was reflected in high correlation observed between the P. scribneri densities determined microscopically and the densities detected by qPCR in artificially inoculated (R2 = 0.93) and naturally infected (R2 = 0.73) root samples. A time-course experiment conducted in the greenhouse using qPCR detected P. scribneri in potato roots as early as 5 days after planting. The results correlated well with the microscopic observations (R2 = 0.80) and were complemented further with root staining. Additionally, three P. scribneri reproduction peaks were observed during one 3-month growth cycle of potato. Overall, the assay developed in this study is specific to P. scribneri in DNA extracts of root tissue and allows early detection and understandings of reproduction timings of this important nematode of potato. [ABSTRACT FROM AUTHOR]

Mesenchymal Stem Cells (MSCs) derived from the embryonic mesoderm persist as a viable source of multipotent cells in adults and have a crucial role in tissue repair. One of the most promising aspects of MSCs is their ability to trans-differentiate into cell types outside of the mesodermal lineage, such as neurons. This characteristic positions MSCs as potential therapeutic tools for neurological disorders. However, the definition of a clear MSC signature is an ongoing topic of debate. Likewise, there is still a significant knowledge gap about functional alterations of MSCs during their transition to a neural fate. In this study, our focus is on the dynamic expression of RNA in MSCs as they undergo trans-differentiation compared to undifferentiated MSCs. To track and correlate changes in cellular signaling, we conducted high-throughput RNA expression profiling during the early time-course of human MSC neurogenic trans-differentiation. The expression of synapse maturation markers, including NLGN2 and NPTX1, increased during the first 24 h. The expression of neuron differentiation markers, such as GAP43 strongly increased during 48 h of trans-differentiation. Neural stem cell marker NES and neuron differentiation marker, including TUBB3 and ENO1, were highly expressed in mesenchymal stem cells and remained so during trans-differentiation. Pathways analyses revealed early changes in MSCs signaling that can be linked to the acquisition of neuronal features. Furthermore, we identified microRNAs (miRNAs) as potential drivers of the cellular trans-differentiation process. We also determined potential risk factors related to the neural trans-differentiation process. These factors include the persistence of stemness features and the expression of factors involved in neurofunctional abnormalities and tumorigenic processes. In conclusion, our findings contribute valuable insights into the intricate landscape of MSCs during neural trans-differentiation. These insights can pave the way for the development of safer treatments of neurological disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Metagenomic time-course studies provide valuable insights into the dynamics of microbial systems and have become increasingly popular alongside the reduction in costs of next-generation sequencing technologies. Normalization is a common but critical preprocessing step before proceeding with downstream analysis. To the best of our knowledge, currently there is no reported method to appropriately normalize microbial time-series data. We propose TimeNorm, a novel normalization method that considers the compositional property and time dependency in time-course microbiome data. It is the first method designed for normalizing time-series data within the same time point (intra-time normalization) and across time points (bridge normalization), separately. Intra-time normalization normalizes microbial samples under the same condition based on common dominant features. Bridge normalization detects and utilizes a group of most stable features across two adjacent time points for normalization. Through comprehensive simulation studies and application to a real study, we demonstrate that TimeNorm outperforms existing normalization methods and boosts the power of downstream differential abundance analysis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Lu, Butt, Lytal, Du, Jiang and An.)

The use of protein biomarkers in blood for clinical settings is limited by the cost and accessibility of traditional venipuncture sampling. The dried blood spot (DBS) technique offers a less invasive and more accessible alternative. However, protein stability in DBS has not been well evaluated. Herein, we deployed a quantitative LC-MS/MS system to construct proteomic atlases of whole blood, DBSs, plasma, and blood cells. Approximately 4% of detected proteins' abundance was significantly altered during blood drying into blood spots, with overwhelming disturbances in cytoplasmic fraction. We also reported a novel finding suggesting a decrease in the level of membrane/cytoskeletal proteins (SLC4A1, RHAG, DSC1, DSP, and JUP) and an increase in the level of proteins (ATG3, SEC14L4, and NRBP1) related to intracellular trafficking. Furthermore, we identified 19 temporally dynamic proteins in DBS samples stored at room temperature for up to 6 months. There were three declined cytoskeleton-related proteins (RDX, SH3BGRL3, and MYH9) and four elevated proteins (XPO7, RAN, SLC2A1, and SLC29A1) involved in cytoplasmic transport as representatives. The instability was governed predominantly by hydrophilic proteins and enhanced significantly with an increasing storage time. Our analyses provide comprehensive knowledge of both short- and long-term storage stability of DBS proteins, forming the foundation for the widespread use of DBS in clinical proteomics and other analytical applications.

The hemibiotrophic plant pathogen Phytophthora cinnamomi Rands is the most devastating pathogen of avocado (Persea americana Mill.) and, as such, causes significant annual losses in the industry. Although the molecular basis of P. cinnamomi resistance in avocado and P. cinnamomi virulence determinants have been the subject of recent research, none have yet attempted to compare the transcriptomic responses of both pathogen and host during their interaction. In the current study, the transcriptomes of both avocado and P. cinnamomi were explored by dual RNA sequencing. The basis for partial resistance was sought by the inclusion of both susceptible (R0.12) and partially resistant (Dusa®) rootstocks sampled at early (6, 12 and 24 hours post-inoculation, hpi) and late time-points (120 hpi). Substantial differences were noted in the number of differentially expressed genes found in Dusa® and R0.12, specifically at 12 and 24 hpi. Here, the partially resistant rootstock perpetuated defense responses initiated at 6 hpi, while the susceptible rootstock abruptly reversed course. Instead, gene ontology enrichment confirmed that R0.12 activated pathways related to growth and development, essentially rendering its response at 12 and 24 hpi no different from that of the mock-inoculated controls. As expected, several classes of P. cinnamomi effector genes were differentially expressed in both Dusa® and R0.12. However, their expression differed between rootstocks, indicating that P. cinnamomi might alter the expression of its effector arsenal based on the rootstock. Based on some of the observed differences, several P. cinnamomi effectors were highlighted as potential candidates for further research. Similarly, the receptor-like kinase (RLK) and apoplastic protease coding genes in avocado were investigated, focusing on their potential role in differing rootstock responses. This study suggests that the basis of partial resistance in Dusa® is predicated on its ability to respond appropriately during the early stages following P. cinnamomi inoculation, and that important components of the first line of inducible defense, apoplastic proteases and RLKs, are likely to be important to the observed outcome. [ABSTRACT FROM AUTHOR]

The hemibiotrophic plant pathogen Phytophthora cinnamomi Rands is the most devastating pathogen of avocado (Persea americana Mill.) and, as such, causes significant annual losses in the industry. Although the molecular basis of P. cinnamomi resistance in avocado and P. cinnamomi virulence determinants have been the subject of recent research, none have yet attempted to compare the transcriptomic responses of both pathogen and host during their interaction. In the current study, the transcriptomes of both avocado and P. cinnamomi were explored by dual RNA sequencing. The basis for partial resistance was sought by the inclusion of both susceptible (R0.12) and partially resistant (Dusa®) rootstocks sampled at early (6, 12 and 24 hours post-inoculation, hpi) and late time-points (120 hpi). Substantial differences were noted in the number of differentially expressed genes found in Dusa® and R0.12, specifically at 12 and 24 hpi. Here, the partially resistant rootstock perpetuated defense responses initiated at 6 hpi, while the susceptible rootstock abruptly reversed course. Instead, gene ontology enrichment confirmed that R0.12 activated pathways related to growth and development, essentially rendering its response at 12 and 24 hpi no different from that of the mock-inoculated controls. As expected, several classes of P. cinnamomi effector genes were differentially expressed in both Dusa® and R0.12. However, their expression differed between rootstocks, indicating that P. cinnamomi might alter the expression of its effector arsenal based on the rootstock. Based on some of the observed differences, several P. cinnamomi effectors were highlighted as potential candidates for further research. Similarly, the receptor-like kinase (RLK) and apoplastic protease coding genes in avocado were investigated, focusing on their potential role in differing rootstock responses. This study suggests that the basis of partial resistance in Dusa® is predicated on its ability to respond appropriately during the early stages following P. cinnamomi inoculation, and that important components of the first line of inducible defense, apoplastic proteases and RLKs, are likely to be important to the observed outcome.

Research using zebrafish (Danio rerio) has begun to provide novel information in many fields, including the behavioral pharmacology of drug use and misuse. There have been limited studies on the effects of methamphetamine in adult zebrafish and the parameters of exposure (dose, test session length) have not been well-documented. Behavior following drug exposure is generally measured during relatively short sessions (6–10 min is common) in a novel tank environment. Many procedural variables (isolation, netting, novel tank) elicit anxiety-like behavior that is most apparent during the initial portion of a test session. This anxiety-like behavior might mask the initial effects of methamphetamine. During longer test sessions, these anxiety-like responses would be expected to habituate and drug effects should become more apparent. To test this idea, we measured several locomotor activity responses for 50-min following a range of methamphetamine doses (0.1–3.0 mg/L via immersion in methamphetamine solution). Methamphetamine failed to alter swimming velocity, distance travelled, or freezing time. In contrast, methamphetamine produced a dose-dependent decrease in time spent in the bottom of the tank, an increase in the number of visits to the top of the tank, and an increase in the number of transitions along the sides of the tank. The effects of methamphetamine were apparent 10–20 min following exposure and generally persisted throughout the session. These findings indicate that longer test sessions are required to measure methamphetamine-induced changes in behavior in zebrafish, as has been shown in other laboratory animals. The results also suggest that anxiety-like responses associated with various procedural aspects (netting, isolation, novel test apparatus) likely interfere with the ability to observe many behavioral effects of methamphetamine in zebrafish. Based on the current results, habituation to testing procedures to reduce anxiety-like behaviors is recommended in determining the effects of methamphetamine in zebrafish. • Effects of methamphetamine administered via immersion emerge after 10–15 min. • Effects of methamphetamine persist throughout the 50-min session. • Higher concentrations of methamphetamine are anxiogenic. • An optimal concentration of methamphetamine via immersion is 0.3 mg/L. [ABSTRACT FROM AUTHOR]

Gossypium hirsutum and Gossypium barbadense are the widely cultivated tetraploid cottons around the world, which evolved great differences in the fiber yield and quality due to the independent domestication process. To reveal the genetic basis of the difference, we integrated 90 samples from ten time points during the fiber developmental period for investigating the dynamics of gene expression changes associated with fiber in G. hirsutum acc. TM-1 and G. barbadense cv. Hai7124 and acc. 3-79. Globally, 44,484 genes expressed in all three cultivars account for 61.14% of the total genes. About 61.39% (N = 3,412) of the cotton transcription factors were involved in fiber development, which consisted of 58 cotton TF families. The differential analysis of intraand interspecies showed that 3 DPA had more expression changes. To discover the genes with temporally changed expression profiles during the whole fiber development, 1,850 genes predominantly expressed in G. hirsutum and 1,050 in G. barbadense were identified, respectively. Based on the weighted gene co-expression network and time-course analysis, several candidate genes, mainly involved in the secondary cell wall synthesis and phytohormones, were identified in this study, underlying possibly the transcriptional regulation and molecular mechanisms of the fiber quality differences between G. barbadense and G. hirsutum. The quantitative real-time PCR validation of the candidate genes was consistent with the RNA-seq data. Our study provides a strong rationale for the analysis of gene function and breeding of high-quality cotton. [ABSTRACT FROM AUTHOR]

Background: Exercise elicits a range of adaptive responses in skeletal muscle, which include changes in mRNA expression. To better understand the health benefits of exercise training, it is important to investigate the underlying molecular mechanisms of skeletal muscle adaptation to exercise. However, most studies have assessed the molecular events at only a few time-points within a short time frame post-exercise, and the variations of gene expression kinetics have not been addressed systematically. Methods: We assessed the mRNA expression of 23 gene isoforms implicated in the adaptive response to exercise at six time-points (0, 3, 9, 24, 48, and 72 h post exercise) over a 3-day period following a single session of high-intensity interval exercise. Results: The temporal patterns of target gene expression were highly variable and the expression of mRNA transcripts detected was largely dependent on the timing of muscle sampling. The largest fold change in mRNA expression of each tested target gene was observed between 3 and 72 h post-exercise. Discussion and Conclusions: Our findings highlight an important gap in knowledge regarding the molecular response to exercise, where the use of limited time-points within a short period post-exercise has led to an incomplete understanding of the molecular response to exercise. Muscle sampling timing for individual studies needs to be carefully chosen based on existing literature and preliminary analysis of the molecular targets of interest. We propose that a comprehensive time-course analysis on the exercise-induced transcriptional response in humans will significantly benefit the field of exercise molecular biology. [ABSTRACT FROM AUTHOR]

Background Exercise elicits a range of adaptive responses in skeletal muscle, which include changes in mRNA expression. To better understand the health benefits of exercise training, it is important to investigate the underlying molecular mechanisms of skeletal muscle adaptation to exercise. However, most studies have assessed the molecular events at only a few time-points within a short time frame post-exercise, and the variations of gene expression kinetics have not been addressed systematically. Methods We assessed the mRNA expression of 23 gene isoforms implicated in the adaptive response to exercise at six time-points (0, 3, 9, 24, 48, and 72 h post exercise) over a 3-day period following a single session of high-intensity interval exercise. Results The temporal patterns of target gene expression were highly variable and the expression of mRNA transcripts detected was largely dependent on the timing of muscle sampling. The largest fold change in mRNA expression of each tested target gene was observed between 3 and 72 h post-exercise. Discussion and Conclusions Our findings highlight an important gap in knowledge regarding the molecular response to exercise, where the use of limited time-points within a short period post-exercise has led to an incomplete understanding of the molecular response to exercise. Muscle sampling timing for individual studies needs to be carefully chosen based on existing literature and preliminary analysis of the molecular targets of interest. We propose that a comprehensive time-course analysis on the exercise-induced transcriptional response in humans will significantly benefit the field of exercise molecular biology.

Bissas, A, Paradisis, GP, Nicholson, G, Walker, J, Hanley, B, Havenetidis, K, and Cooke, CB. Development and maintenance of sprint training adaptations: an uphill-downhill study. J Strength Cond Res 36(1): 90–98, 2022—We examined the development of performance adaptations resulting from an uphill-downhill training program and monitored the decline of adaptations during detraining. Twenty-eight men were randomly assigned to 1 of 2 sprint training groups who trained 3 times per week for 6 weeks and a control group (C). The uphill-downhill group (U+D) trained on an 80-m platform with 3° slopes, whereas the horizontal (H) group trained on flat track. Subjects were tested for maximal running speed (MRS), associated kinematics, and leg strength before and after training, with U+D subjects also tested after weeks 2 and 4 of training, and after a 3-week detraining period. The U+D group increased their MRS by 3.7% (from 8.75 ± 0.72 to 9.07 ± 0.64 m·s−1, p < 0.05), their stride rate by 3.1% (from 4.21 ± 0.21 to 4.34 ± 0.18 Hz, p < 0.05), and their knee extensors' maximum isometric force by 21% (from 2,242 ± 489 to 2,712 ± 498 N, p < 0.05) after training. The time course of changes showed declines for weeks 1–4 (1.4–5.1%), but an ascending trend of improvement compensated all losses by the end of week 6 (p < 0.05). During detraining, no decreases occurred. No changes were observed for the H and C groups. The minimum period to produce positive effects was 6 weeks, with a very good standard of performance maintained 3 weeks after training. U+D training will prove useful for all athletes requiring fast adaptations, and it can fit into training mesocycles because of its low time demands. [ABSTRACT FROM AUTHOR]

Abstract Gemcitabine induce thrombocytopenia and thrombocytosis as toxicity. In this report, we show detailed time‐course for platelet fluctuation. Our case emphasis attention to monitor see‐saw‐like toxicity on platelet count.

The auditory efferent system, especially the medial olivocochlear reflex (MOCR), is implicated in both typical auditory processing and in auditory disorders in animal models. Despite the significant strides in both basic and translational research on the MOCR, its clinical applicability remains under-utilized in humans due to the lack of a recommended clinical method. Conventional tests employ broadband noise in one ear while monitoring change in otoacoustic emissions (OAEs) in the other ear to index efferent activity. These methods, (1) can only assay the contralateral MOCR pathway and (2) are unable to extract the kinetics of the reflexes. We have developed a method that re-purposes the same OAE-evoking click-train to also concurrently elicit bilateral MOCR activity. Data from click-train presentations at 80 dB peSPL at 62.5 Hz in 13 young normal-hearing adults demonstrate the feasibility of our method. Mean MOCR magnitude (1.7 dB) and activation time-constant (0.2 s) are consistent with prior MOCR reports. The data also suggest several advantages of this method including, (1) the ability to monitor MEMR, (2) obtain both magnitude and kinetics (time constants) of the MOCR, (3) visual and statistical confirmation of MOCR activation. [ABSTRACT FROM AUTHOR]

The cyanobacterium Synechocystis sp. strain FS 78 was recently isolated from chromium polluted paddy fields in the North of Iran. In the present work, the effect of chromium (VI) was studied at extreme alkaline conditions (pH 11) on the growth, pigment composition, function of photosystems and phycobilisomes. We monitored the cyanobacterium viability in the presence of chromium (VI) from 0.5 to 5 µM every hour up to 6 h inoculation time. An increase in growth, pigment production, photosystems and phycobilisomes activities was observed in cells grown at low concentration (0.5 µM) of chromium (VI). The toxicity of higher chromium concentrations (3.5 and 5 µM) was observed after 1 h of inoculation. Confocal laser microscopy analysis showed the toxic effect of elevated chromium (VI) concentration on viability, probably due to the damage of the photosystem and phycobilisome structures, which on the long-term was able to recover. We concluded that the combination of the three factors (extreme alkaline pH, different concentrations of Cr(VI) and time) can affect cyanobacterial behaviours individually or in combination. [ABSTRACT FROM AUTHOR]

The auditory efferent system, especially the medial olivocochlear reflex (MOCR), is implicated in both typical auditory processing and in auditory disorders in animal models. Despite the significant strides in both basic and translational research on the MOCR, its clinical applicability remains under-utilized in humans due to the lack of a recommended clinical method. Conventional tests employ broadband noise in one ear while monitoring change in otoacoustic emissions (OAEs) in the other ear to index efferent activity. These methods, (1) can only assay the contralateral MOCR pathway and (2) are unable to extract the kinetics of the reflexes. We have developed a method that re-purposes the same OAE-evoking click-train to also concurrently elicit bilateral MOCR activity. Data from click-train presentations at 80 dB peSPL at 62.5 Hz in 13 young normal-hearing adults demonstrate the feasibility of our method. Mean MOCR magnitude (1.7 dB) and activation time-constant (0.2 s) are consistent with prior MOCR reports. The data also suggest several advantages of this method including, (1) the ability to monitor MEMR, (2) obtain both magnitude and kinetics (time constants) of the MOCR, (3) visual and statistical confirmation of MOCR activation.

The gilthead sea bream (Sparus aurata) is a marine fish of great importance for Mediterranean aquaculture. This species has long been considered resistant to Nervous Necrosis Virus (NNV), an RNA virus that causes massive mortalities in several farmed fish animals. However, the recent appearance of RGNNV/SJNNV reassortant strains started to pose a serious threat to sea bream hatcheries, as it is able to infect larvae and juveniles of this species. While host response to NNV has been extensively studied in adult fish, little attention has been devoted to early life history stages, which are generally the most sensitive ones. Here we report for the first time a time-course RNA-seq analysis on 21-day old fish gilthead sea bream larvae experimentally infected with a RGNNV/SJNNV strain. NNV-infected and mock-infected samples were collected at four time points (6 h, 12 h, 24 h, and 48 h post infection). Four biological replicates, each consisting of five pooled larvae, were analysed for each time point and group. A large set of genes were found to be significantly regulated, especially at early time points (6 h and 12 h), with several heat shock protein encoding transcripts being up-regulated (e.g. hspa5, dnaj4, hspa9, hsc70), while many immune genes were down-regulated (e.g. myd88 and irf5 at T06, pik3r1 , stat3 , jak1 , il12b and il6st at T12). A gene set enrichment analysis (GSEA) identified several altered pathways/processes. For instance, the formation of peroxisomes, which are important anti-viral components as well as essential for nervous system homeostasis, and the autophagy pathway were down-regulated at 6 h and 24 h post infection (hpi). Finally, two custom "reactomes" (i.e. significant gene sets observed in other studies) were defined and used. The first reactome integrated the transcriptomic response to NNV in different fish species, while the second one included all genes found to be stimulated either by interferon (IFN) or by IFN and Chikungunya virus in zebrafish. Genes in both reactomes showed predominant up-regulation at 6hpi and 12hpi and a general down-regulation at 24hpi. Such evidence suggest a certain degree of similarity between the response of sea bream and that of other fish species to NNV, while the observed down-regulation of IFN- and viral-stimulated pathways argues for a possible interference of NNV against the host response. • A reassortant NNV strain (RGNNV/SJNNV) poses a serious threat to sea bream hatchery. • Gene expression (GE) changes in 21-day old larvae at 6, 12, 24 and 48 h post infection. • At 6hpi many HSP up-regulated and immune genes down-regulated in infected larvae. • Custom reactomes up-reg at 6, 12hpi and down-reg at 24hpi in infected larvae. • Dynamic GE changes with time suggesting the complexity of host-pathogen interaction. [ABSTRACT FROM AUTHOR]

Introduction: Manganese is important for the endocarditis pathogen Streptococcus sanguinis. Little is known about why manganese is required for virulence or how it impacts the metabolome of streptococci. Objectives: We applied untargeted metabolomics to cells and media to understand temporal changes resulting from manganese depletion. Methods: EDTA was added to a S. sanguinis manganese-transporter mutant in aerobic fermentor conditions. Cell and media samples were collected pre- and post-EDTA treatment. Metabolomics data were generated using positive and negative modes of data acquisition on an LC–MS/MS system. Data were subjected to statistical processing using MetaboAnalyst and time-course analysis using Short Time series Expression Miner (STEM). Recombinant enzymes were assayed for metal dependence. Results: We observed quantitative changes in 534 and 422 metabolites in cells and media, respectively, after EDTA addition. The 173 cellular metabolites identified as significantly different indicated enrichment of purine and pyrimidine metabolism. Further multivariate analysis revealed that the top 15 cellular metabolites belonged primarily to lipids and redox metabolites. The STEM analysis revealed global changes in cells and media in comparable metabolic pathways. Glycolytic intermediates such as fructose-1,6-bisphosphate increased, suggesting that enzymes that utilize them require manganese for activity or expression. Recombinant enzymes were confirmed to utilize manganese in vitro. Nucleosides accumulated, possibly due to a blockage in conversion to nucleobases resulting from manganese-dependent regulation. Conclusion: Differential analysis of metabolites revealed the activation of a number of metabolic pathways in response to manganese depletion, many of which are connected to carbon catabolite repression. [ABSTRACT FROM AUTHOR]

Background: Kinetics, moderators and reference limits for exercise-induced cardiac troponin T (cTnT) elevations are still unclear. Methods: A systematic review of published literature was conducted adhering to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Studies reporting high-sensitivity cardiac troponin T (hs-cTnT) concentrations before and after a bout of exercise in athletes were included and analyzed. The final dataset consisted of 62 estimates from 16 bouts in 13 studies of 5–1,002 athletes (1,421 in total). Meta-analysis was performed using general linear mixed modeling and Bayesian inferences about effect magnitudes. Modifying fixed-effect moderators of gender, age, baseline level, exercise duration, intensity and modalities were investigated. Simulation was used to derive 99th percentile with 95% limits of upper reference ranges for hs-cTnT of athletic populations. Results: The mean and upper reference limits of hs-cTnT before exercise were 4.4 and 19 ng.L−1. Clear increases in hs-cTnT ranging from large to very large (factor changes of 2.1–7.5, 90% compatibility limits, ×/÷1.3) were evident from 0.7 through 25 h, peaking at 2.9 h after the midpoint of a 2.5-h bout of running, when the mean and upper reference limit for hs-cTnT were 33 and 390 ng L−1. A four-fold increase in exercise duration produced a large clear increase (2.4, ×/÷1.7) in post-exercise hs-cTnT. Rowing exercise demonstrated an extremely large clear reduction (0.1 ×/÷2.4). Conclusions: The kinetics of cTnT elevation following exercise, the positive effect of exercise duration, the impact of exercise modality and 99th upper reference limits for athletic populations were reasonably well defined by this meta-analysis. [ABSTRACT FROM AUTHOR]

Increased muscle stiffness of the pectoralis minor (PMi) could deteriorate shoulder function. Stretching is useful for maintaining and improving muscle stiffness in rehabilitation and sport practice. However, the acute and prolonged effect of stretching on the PMi muscle stiffness is unclear due to limited methodology for assessing individual muscle stiffness. Using shear wave elastography, we explored the responses of shear modulus to stretching in the PMi over time. The first experiment (n = 20) aimed to clarify the acute change in the shear modulus during stretching. The shear modulus was measured at intervals of 30 s x 10 sets. The second experiment (n = 16) aimed to observe and compare the prolonged effect of different durations of stretching on the shear modulus. Short and long stretching duration groups underwent 30s x 1 set and 30s x 10 sets, respectively. The assessments of shear modulus were conducted before, immediately after, and at 5, 10, and 15 min post-stretching. In experiment I, the shear modulus decreased immediately after a bout (30 s) of stretching (p < 0.001, change: -2.3 kPa, effect size: r = 0.72) and further decreased after 3 repetitions (i.e., 90 s) of stretching (p = 0.03, change: -1.0 kPa, effect size: r = 0.53). In experiment II, the change in the shear modulus after stretching was greater in the long duration group than in the short duration group (p = 0.013, group mean difference: -2.5 kPa, partial η2 = 0.36). The shear modulus of PMi decreased immediately after stretching, and stretching for a long duration was promising to maintain the decreased shear modulus. The acute and prolonged effects on the PMi shear modulus provide information relevant to minimum and persistent stretching time in rehabilitation and sport practice. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study.Objective: To elucidate the postoperative time course of improvements in physical and mental well-being in patients with cervical spondylotic myelopathy (CSM).Summary Of Background Data: Spinal surgeons should understand the postoperative course in detail. However, data are still needed regarding the time course of improvements in well-being, a fundamental aspect of human life, after cervical surgery for CSM.Methods: One hundred consecutive patients who underwent laminoplasty for CSM, with complete clinical data preoperatively and 3 months and 2 years postoperatively, were enrolled. The Short Form-36 physical component summary (PCS) and mental component summary (MCS) scores were used as parameters of physical and mental well-being, respectively, and 4.0 was defined as the minimal clinically important difference (MCID) for both parameters.Results: On average, PCS and MCS scores were significantly improved after surgery (P < 0.001, P=0.004, respectively). Moreover, 64 and 48 patients achieved meaningful improvement (>MCID) in PCS and MCS scores at 3 months postoperatively, with maintained improvement (to 2 yr) in 46/64 (71.9%) and 34/48 patients (70.8%), respectively (PCS vs. MCS: P = 0.912). Additionally, 15 of 36 patients (41.7%) and 8 of 52 patients (15.4%) achieved late improvement (meaningful improvement at 2 yr but not at 3 months) in PCS and MCS scores, respectively (PCS vs. MCS: P = 0.007). In multivariate regression analysis, improvement in cJOA score was significantly associated with PCS improvement, but not MCS improvement, at both 3 months and 2 years (P = 0.001, P > 0.001, respectively).Conclusion: The overall outcome of physical well-being improvement is decided within 3 months postoperatively, in proportion to the recovery in myelopathy, with a relatively high chance of meaningful improvement over the next 21 months. The outcome of improvement in mental well-being is decided within 3 months postoperatively, independently from the recovery in myelopathy, with a low chance of meaningful improvement over the next 21 months.Level of Evidence: 3. [ABSTRACT FROM AUTHOR]

Eucalyptus rust is caused by the biotrophic fungus, Austropuccinia psidii , which affects commercial plantations of Eucalyptus, a major raw material for the pulp and paper industry in Brazil. In this manuscript we aimed to uncover the molecular mechanisms involved in rust resistance and susceptibility in Eucalyptus grandis. Epifluorescence microscopy was used to follow the fungus development inside the leaves of two contrasting half-sibling genotypes (rust-resistance and rust-susceptible), and also determine the comparative time-course of changes in metabolites and proteins in plants inoculated with rust. Within 24 h of complete fungal invasion, the analysis of 709 metabolomic features showed the suppression of many metabolites 6 h after inoculation (hai) in the rust-resistant genotype, with responses being induced after 12 hai. In contrast, the rust-susceptible genotype displayed more induced metabolites from 0 to 18 hai time-points, but a strong suppression occurred at 24 hai. Multivariate analyses of genotypes and time points were used to select 16 differential metabolites mostly classified as phenylpropanoid-related compounds. Applying the Weighted Gene Co-Expression Network Analysis (WGCNA), rust-resistant and rust-susceptible genotypes had, respectively, 871 and 852 proteins grouped into 5 and 6 modules, of which 5 and 4 of them were significantly correlated to the selected metabolites. Functional analyses revealed roles for photosynthesis and oxidative-dependent responses leading to temporal activity of metabolites and related enzymes after 12 hai in rust-resistance; while the initial over-accumulation of those molecules and suppression of supporting mechanisms at 12 hai caused a lack of progressive metabolite-enzyme responses after 12 hai in rust-susceptible genotype. This study provides some insights on how E. grandis plants are functionally modulated to integrate secondary metabolites and related enzymes from phenylpropanoid pathway and lead to temporal divergences of resistance and susceptibility responses to rust. [ABSTRACT FROM AUTHOR]

Hexaploid spring wheat (Triticum aestivum) may exhibit significant crown rot disease responses to infection by Fusarium pseudograminearum, with a range of susceptibility levels available in commercial cultivars. Dry conditions during grain-fill may lead to the expression of prematurely senescing culms, which typically fail to set grain. Assessment of hexaploid spring wheat plants exhibiting both non-senescent and prematurely senescent culms was performed using visual discolouration, F. pseudograminearum biomass and vascular colonisation in culm sections sampled at three different heights above the crown and at the peduncle. Samples from six commercial cultivars were collected at milk development in 2014 from Narrabri and Tamworth, New South Wales and Wellcamp, Queensland. Prematurely senescent culms exhibited greater visual discolouration, F. pseudograminearum biomass and vascular colonisation than non-senescent culms in each cultivar. A further comparison of the parameters across four time points from milk development, when senescent culms are first observed, to maturity was conducted for cultivar Sunlin. F. pseudograminearum biomass and vascular colonisation were significantly different between culm conditions prior to maturation, while visual discolouration was not significantly different between culm conditions at any single time point. Colonisation of xylem and phloem tissue was extensive in the basal portions of prematurely senescent culms (36 to 99%) prior to maturation, and suggests significant impacts on water and nutrient movement during crown rot disease. Despite a range of resistance ratings being assessed, cultivars were not reliably separated based upon responses to severe disease pressure, demonstrating the continuing need for improved crown rot resistance in commercial wheat. [ABSTRACT FROM AUTHOR]

Abstract Background High-throughput expression profiling experiments with ordered conditions (e.g. time-course or spatial-course) are becoming more common for studying detailed differentiation processes or spatial patterns. Identifying dynamic changes at both the individual gene and whole transcriptome level can provide important insights about genes, pathways, and critical time points. Results We present an R package, Trendy, which utilizes segmented regression models to simultaneously characterize each gene’s expression pattern and summarize overall dynamic activity in ordered condition experiments. For each gene, Trendy finds the optimal segmented regression model and provides the location and direction of dynamic changes in expression. We demonstrate the utility of Trendy to provide biologically relevant results on both microarray and RNA-sequencing (RNA-seq) datasets. Conclusions Trendy is a flexible R package which characterizes gene-specific expression patterns and summarizes changes of global dynamics over ordered conditions. Trendy is freely available on Bioconductor with a full vignette at https://bioconductor.org/packages/release/bioc/html/Trendy.html.

Gemcitabine induce thrombocytopenia and thrombocytosis as toxicity. In this report, we show detailed time‐course for platelet fluctuation. Our case emphasis attention to monitor see‐saw‐like toxicity on platelet count. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: To describe the reliability of blood bicarbonate pharmacokinetics in response to sodium bicarbonate (SB) supplementation across multiple occasions and assess, using putative thresholds, whether individual variation indicated a need for individualized ingestion timings. Methods: Thirteen men (age 27 ± 5 yr; body mass [BM], 77.4 ± 10.5 kg; height, 1.75 ± 0.06 m) ingested 0.3 g·kg−1 BM SB in gelatine capsules on three occasions. One hour after a standardized meal, venous blood was obtained before and every 10 min after ingestion for 3 h, then every 20 min for a further hour. Time to peak (T max), absolute peak (C max), absolute peak change (∆ C max), and area under the curve were analyzed using mixed models, intraclass correlation coefficient, coefficient of variation and typical error. Individual variation in pharmacokinetic responses was assessed using Bayesian simulation with multilevel models with random intercepts. Results: No significant differences between sessions were shown for blood bicarbonate regarding C max, ∆ C max or area under the curve (P > 0.05), although T max occurred earlier in SB2 (127 ± 36 min) than in SB1 (169 ± 54 min, P = 0.0088) and SB3 (159 ± 42 min, P = 0.05). Intraclass correlation coefficient, coefficient of variation, and typical error showed moderate to poor reliability. Bayesian modeling estimated that >80% of individuals from the population experience elevated blood bicarbonate levels above +5 mmol·L−1 between 75 and 240 min after ingestion, and between 90 and 225 min above +6 mmol·L−1. Conclusions: Assessing SB supplementation using discrete values showed only moderate reliability at the group level, and poor reliability at the individual level, whereas T max was not reproducible. However, when analyzed as modeled curves, a 0.3-g·kg−1 BM dose was shown to create a long-lasting window of ergogenic potential, challenging the notion that SB ingestion individualized to time-to-peak is a necessary strategy, at least when SB is ingested in capsules. [ABSTRACT FROM AUTHOR]

The stem cells located in the hair follicle bulge area are critical for skin regeneration and repair. To date, little is known about the evolution of the transcriptome of these cells across time. Here, we have combined genome-wide expression analyses and a variety of in silico tools to determine the age-dependent evolution of the transcriptome of those cells. Our results reveal that the transcriptome of skin stem cells fluctuates extensively along the lifespan of mice. The use of both unbiased and pathway-centered in silico approaches has also enabled the identification of biological programs specifically regulated at those specific time-points. It has also unveiled hubs of highly transcriptionally interconnected genes and transcriptional factors potentially located at the core of those age-specific changes. [ABSTRACT FROM AUTHOR]

Widely different exposure times to endotoxic insults have been employed in reported studies. The current experimental study systematically evaluated the time-course and sex influences of endotoxic insult on survivability and cardiovascular and renal functions. Rats received i.p. lipopolysaccharide (LPS, 5 mg/kg) once or twice (over 2 successive days). Systolic blood pressure (SBP), biomarkers of renal function and inflammation, and vasodilator responsiveness of isolated perfused kidneys to acetylcholine (ACh) or N-ethylcarboxamidoadenosine (NECA) were evaluated 6 hr after first LPS injection or 1, 2, or 6 days later. A single 6-hr LPS challenge caused (i) sex-unrelated elevations in serum urea and creatinine and reductions in NECA, but not ACh, vasodilations, (ii) more increases in renal NF-κB/iNOS expressions in male than in female rats, and (iii) hypotension and tachycardia only in male rats. These parameters, except for hemodynamic changes, were restored to near-control levels 1 day after single LPS dosing. The 2-days dosing with LPS had no effects on renal function biomarkers, but caused hypotension, tachycardia, and increases in renal NF-κB/iNOS expression and NECA and ACh vasodilations in both rat sexes. None of these parameters were different from control values when measured 6 days after the endotoxic insult. Alternatively, the rat mortality was observed during first 2 days of the study and was notably higher in male than in female rats. Our data suggest that the frequency and time elapsed after LPS exposure as well as rat sex are important determinants of the magnitude and direction of detrimental effects of endotoxemia. [ABSTRACT FROM AUTHOR]

This retrospective study highlights the degree of losses and time-course through which the 2015 highly pathogenic avian influenza (HPAI) outbreaks in Ghana were managed. A total of 102 760 birds from 35 farms across five regions in Ghana included in this study were affected. Out of this, 89.3% was from the Greater Accra region. Majority of the birds were culled (94.2%). Adult layers were most affected and destroyed (64.0%), followed by broilers (13.7%). Event initiation to reporting averaged 7.7 ± 1.3 days (range: 1–30 days). Laboratory confirmation to depopulation of birds averaged 2.2 ± 0.5 (0–15) days while depopulation to disinfection took 2.2 ± 0.7 (0–20) days. Overall, some farms took as long as 30 days to report the outbreak to the authorities, 15 days from confirmation to depopulation and 20 days from depopulation to disinfection. On average, outbreak management lasted 12.3 (2–43) days from event initiation to depopulation. The study reveals a significant number of avian losses and delays in HPAI reporting and management by the authorities in Ghana during the 2015 out- break. This poses a high risk of spread to other farms and a threat to public health. Awareness creation for poultry farmers is necessary for early reporting, while further study is required to set thresholds for the management of such outbreaks by veterinary departments. [ABSTRACT FROM AUTHOR]

Abstract Background Stress is a generic term used to describe non-specific responses of the body to all kinds of challenges. A very large variability in the response can be observed across individuals, depending on numerous conditioning factors like genetics, early influences and life history. As a result, there is a wide range of individual vulnerability and resilience to stress, also called robustness. The importance of robustness-related traits in breeding strategies is increasing progressively towards the production of animals with a high level of production under a wide range of climatic conditions and management systems, together with a lower environmental impact and a high level of animal welfare. The present study aims at describing blood transcriptomic, hormonal, and metabolic responses of pigs to a systemic challenge using lipopolysaccharide (LPS). The objective is to analyze the individual variation of the biological responses in relation to the activity of the HPA axis measured by the levels of plasma cortisol after LPS and ACTH in 120 juvenile Large White (LW) pigs. The kinetics of the response was measured with biological variables and whole blood gene expression at 4 time points. A multilevel statistical analysis was used to take into account the longitudinal aspect of the data. Results Cortisol level reaches its peak 4 h after LPS injection. The characteristic changes of white blood cell count to LPS were observed, with a decrease of total count, maximal at t=+4 h, and the mirror changes in the respective proportions of lymphocytes and granulocytes. The lymphocytes / granulocytes ratio was maximal at t=+1 h. An integrative statistical approach was used and provided a set of candidate genes for kinetic studies and ongoing complementary studies focused on the LPS-stimulated inflammatory response. Conclusions The present study demonstrates the specific biomarkers indicative of an inflammation in swine. Furthermore, these stress responses persist for prolonged periods of time and at significant expression levels, making them good candidate markers for evaluating the efficacy of anti-inflammatory drugs.

Aims and objectives/purpose/research questions: Using a modified dot-probe task, the present research examined the time-course of attentional bias for culture-related cues in Mongolian-Chinese bilinguals. Design/methodology/approach: Using a mixed experimental design, children with different language fluency (fluent bilingual, limited bilingual and mandarin monolingual) were recruited (N = 168; 51% boys; Mage = 9.88 years, SD = 0.38 years; 59% Mongolian) to complete a dot-probe task in which they were shown pairs of pictures representing Mongolian and Han culture for short (60 ms) and long (500 ms) exposure durations. The difference between fluent and limited bilinguals lies in their proficiency in Mongolian. Data and analysis: The attentional bias scores (d) were entered into a 2 × 3 mixed design repeated-measures analysis of variance with language fluency (fluent bilingual versus limited bilingual versus monolingual) as a between-subjects variable and the time-course (60 versus 500 ms) as a within-subject variable. Findings/conclusions: In the task, compared with pictures representing Han culture, all students showed preferential attention to pictures conveying Mongolian culture across presentation durations. However, for 60 ms, fluent bilinguals showed a smaller attentional bias than did monolinguals, with no difference between limited bilinguals and monolinguals; there was no significant difference among the three groups at 500 ms. Originality: Relatively less research has been performed on comparative analysis between fluent and non-fluent bilinguals, and most of the culture-related content is measured by subjective methods. This study attempts to directly compare these two bilinguals' attentional bias for culture-related cues using a dot-probe task. Significance/implications: The results of comparative analysis showed that fluent bilinguals were more familiar with Mongolian language and preserved their ethnic culture better, which may indicate a close relationship between language and culture. [ABSTRACT FROM AUTHOR]