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A recent electrocorticographic study by Tan et al. makes an important contribution to understanding the processes involved in mentalizing by adding the temporal dimension to the brain network of mentalizing. Combined with multivariate methods, this approach has the potential to unveil the precise representations underlying mentalizing and their functional interplay. [ABSTRACT FROM AUTHOR]

Live-cell imaging is a powerful method to obtain insights into cellular processes, particularly with respect to their dynamics. This is especially true for meiosis, where chromosomes and other cellular components such as the cytoskeleton follow an elaborate choreography over a relatively short period of time. Making these dynamics visible expands understanding of the regulation of meiosis and its underlying molecular forces. However, the analysis of meiosis by live-cell imaging is challenging; specifically in plants, a temporally resolved understanding of chromosome segregation and recombination events is lacking. Recent advances in live-cell imaging now allow the analysis of meiotic events in plants in real time. These new microscopy methods rely on the generation of reporter lines for meiotic regulators and on the establishment of ex vivo culture and imaging conditions, which stabilize the specimen and keep it alive for several hours or even days. In this review, we combine an overview of the technical aspects of live-cell imaging in plants with a summary of outstanding questions that can now be addressed to promote live-cell imaging in Arabidopsis and other plant species and stimulate ideas on the topics that can be addressed in the context of plant meiotic recombination. [ABSTRACT FROM AUTHOR]

Purpose: The current study investigated the effects of long-term athletic training on the development of the triceps surae muscle-tendon unit in preadolescence. Methods : Eleven preadolescent untrained children and a group of 21 artistic gymnastics athletes of similar age (9 +/- 1.7 yr) and maturity (Tanner stages I and II) participated in the study. The measurements were conducted every 3 months for 1 yr, and training volume and duration of the athletes were documented. Plantar flexor muscle strength, Achilles tendon stiffness, maximum tendon strain, and gastrocnemius medialis morphometrics were measured by integrating kinematics, ultrasonography, and dynamometry. A linear mixed-effects model was used to analyze the investigated parameters. Results : We found greater muscle strength (P < 0.001) in athletes compared with nonathletes but no differences in Achilles tendon stiffness (P = 0.252), indicating a training-induced imbalanced adaptation of muscle strength and tendon stiffness in preadolescent athletes. Although pennation angle (P = 0.490), thickness (P = 0.917), and fascicle length (P = 0.667) did not differ between groups, we found higher fluctuations in pennation angle and muscle strength over 1 yr in athletes. The imbalanced adaptation of muscle strength and tendon stiffness together with greater fluctuations of muscle strength resulted in greater tendon strain fluctuations over 1 yr (P = 0.017) and a higher frequency of athletes with high-level tendon strain (>=9%) compared with nonathletes. Conclusions: The findings indicate an increased mechanical demand for the tendon in preadolescent athletes that could have implications for the risk of tendon overuse injury. Therefore, we recommend the implementation of individual training approaches to preserve a balanced adaptation within the triceps surae muscle-tendon unit in preadolescent athletes. [ABSTRACT FROM AUTHOR]

To achieve successful communication, people should decode not only the literal meaning of an utterance, but also the intended meanings conveyed by the speaker. In the present study, event-related potential (ERP) technique was used to explore how working memory capacity modulates the processes of indirect replies comprehension. Conversations of Speaker A and Speaker B were constructed. Speaker A's question renders Speaker B's reply to be either direct or indirect replies. Participants of high and low working memory span were instructed to read for comprehension. Our results showed that for the high span group, indirect replies elicited a larger P200, a larger P300 and a larger delayed Late Positive Component (LPC) compared with direct replies. While for the low span group, only a delayed LPC effect was elicited by indirect replies. These findings provide evidence that readers' working memory capacity modulates the early detection and immediate processing of indirect replies. [ABSTRACT FROM AUTHOR]

Background: Maternal mRNA provisioning of oocytes regulates early embryogenesis. Maternal transcripts are degraded as zygotic genome activation (ZGA) intensifies, a phenomenon known as the maternal-to-zygotic transition (MZT). Here, we examine gene expression over nine developmental stages in the Pacific rice coral, Montipora capitata, from eggs and embryos at 1, 4, 9, 14, 22, and 36 h-post-fertilization (hpf), as well as swimming larvae (9d), and adult colonies. Results: Weighted Gene Coexpression Network Analysis revealed four expression peaks, identifying the maternal complement, two waves of the MZT, and adult expression. Gene ontology enrichment revealed maternal mRNAs are dominated by cell division, methylation, biosynthesis, metabolism, and protein/RNA processing and transport functions. The first MZT wave occurs from ~4-14 hpf and is enriched in terms related to biosynthesis, methylation, cell division, and transcription. In contrast, functional enrichment in the second MZT wave, or ZGA, from 22 hpf-9dpf, includes ion/peptide transport and cell signaling. Finally, adult expression is enriched for functions related to signaling, metabolism, and ion/peptide transport. Our proposed MZT timing is further supported by expression of enzymes involved in zygotic transcriptional repression (Kaiso) and activation (Sox2), which peak at 14 hpf and 22 hpf, respectively. Further, DNA methylation writing (DNMT3a) and removing (TET1) enzymes peak and remain stable past ~4 hpf, suggesting that methylome programming occurs before 4 hpf. Conclusions: Our high-resolution insight into the coral maternal mRNA and MZT provides essential baseline information to understand parental carryover effects and the sensitivity of developmental success under increasing environmental stress. [ABSTRACT FROM AUTHOR]

Anaphora is the main linguistic means to establish discourse coherence, and anaphora resolution is the psychological process to maintain this coherence. Chinese discourse is characterized with providing multiplicity of linguistic clues to readers by employing various referential apparatuses such as pronoun anaphora, zero anaphora, and so on. As a way of avoiding repeated reference to an object that is mentioned beforehand, zero anaphora is frequently employed in discourse. The production and resolution of zero anaphora largely concerns some constraints underlying psychological mechanisms. We particularly focus on zero anaphora resolution in the present study to try to discover some specific aspects of the underlying mechanism, hoping to find out some factors unique to the resolution process. We designed the first two experiments to probe into the psychological reality when participants were presented with sentences containing either pronoun anaphora or zero anaphora or both under discourse condition with topic continuity in Experiment 1a and topic discontinuity in Experiment 1b. We did not find any significant difference in the reaction time between zero anaphora resolution and pronoun anaphora resolution, indicating that zero anaphora possibly works within the processing mechanism on which pronoun anaphora resolution depends. However, we found significantly longer time in reading the first sentence in any of the discourse, showing that the first-mention effect exists in anaphora resolution. We further explored the time course of zero anaphora resolution by measuring the reaction time during the period when participants read sentences that varied according to the location where zero anaphora occurred under two conditions: topic continuity (Experiment 2a) vs. topic discontinuity (Experiment 2b). The strategies of searching for the referential information were found divergent: the exhaustive searching strategy was adopted when the topics within a discourse were kept continuous and the heuristic searching strategy was employed when the topics were discontinuous. The design of Experiment 5 took the factor of voice type and situation consistency into consideration, investigating in what way do those factors influence the resolution of zero anaphora. The voice type, according to the results, plays a significant role for its exclusively close relationship with the first-mention effect. [ABSTRACT FROM AUTHOR]

• Linear GBCAs exhibited more gadolinium retention in multi-organ/tissue versus macrocyclic GBCAs. • In most case, linear GBCAs show faster accumulation and regression speed in examined tissues than macrocyclic GBCAs. • Linear GBCAs can evoke transient increase of heat hyperalgesia and white blood cells. • Gadodiamide can cause reversible vacuolar changes in the renal tubular epithelial cells. • Long-term injection of gadodiamide induces severe skin lesion in mice tail. As nephrogenic systemic fibrosis (NSF) and increased signal intensities in deep cerebellar nuclei (DCN) were successively discovered in renal insufficiency patients and healthy persons after gadolinium-based contrast agents (GBCAs) exposure, an awareness of potential toxicity with GBCAs exposure has been heightening. Herein, we performed a multi-organ/tissue toxicity assessment after different GBCAs administration with a large number of samples, and long-term, time-course schedule investigation. ICR mice were randomized to five exposure groups (n = 42/group) and received intravenous injection of GBCAs (2.5 mmol Gd/kg) or saline four time a week for 5 consecutive weeks. Gadolinium concentration detection, sensory tests, histological and hematological analyses were performed at corresponding timepoints (4th or 6th or 10th week). Our results showed that (i) gadodiamide could cause reversible vacuolar changes in the renal tubular epithelial cells, which appeared at 6th week and recovered at 10th week, and severe skin lesion in mice tail with consecutive injection for 10 weeks, that (ii) linear GBCAs (gadodiamide and gadopentetate dimeglumine) markedly elevated heat hyperalgesia and white blood cells of mice at 6th week and most of these changes could recovery at 10th week, and that (iii) linear GBCAs exhibited more gadolinium retention in multi-organ/tissue versus macrocyclic GBCAs and in most case, linear GBCAs showed faster accumulation and regression speed in examined tissues than macrocyclic GBCAs excepting gadodiamide in skin which showed slowest regression speed. Collectively, macrocyclic GBCAs presents more stable, lower propensity to release Gd and safer profiles versus linear GBCAs. [ABSTRACT FROM AUTHOR]

The brain's mechanisms for categorizing different odors have long been a research focus. Previous studies suggest that odor categorization may involve multiple neurological processes within the brain with temporal and spatial neuronal activation. However, there is limited evidence regarding temporally mediated mechanisms in humans, especially millisecond odor processing. Such mechanisms may be important because different brain areas may play different roles at a particular activation time during sensory processing. Here, we focused on how the brain categorizes odors at specific time intervals. Using multivariate electroencephalography (EEG) analysis, we found that similarly perceived odors induced similar EEG signals during 50–100, 150–200, and 350–400 ms at the theta frequency. We also found significant activation at 100–150 and 350–400 ms at the gamma frequency. At these two frequencies, significant activation was observed in some olfactory-associated areas, including the orbitofrontal cortex. Our findings provide essential evidence that specific periods may be related to odor quality processing during central olfactory processing. [ABSTRACT FROM AUTHOR]

Previous studies have shown that the human visual system can detect a face and elicit a saccadic eye movement toward it very efficiently compared to other categories of visual stimuli. In the first experiment, we tested the influence of facial expressions on fast face detection using a saccadic choice task. Face‐vehicle pairs were simultaneously presented and participants were asked to saccade toward the target (the face or the vehicle). We observed that saccades toward faces were initiated faster, and more often in the correct direction, than saccades toward vehicles, regardless of the facial expressions (happy, fearful, or neutral). We also observed that saccade endpoints on face images were lower when the face was happy and higher when it was neutral. In the second experiment, we explicitly tested the detection of facial expressions. We used a saccadic choice task with emotional‐neutral pairs of faces and participants were asked to saccade toward the emotional (happy or fearful) or the neutral face. Participants were faster when they were asked to saccade toward the emotional face. They also made fewer errors, especially when the emotional face was happy. Using computational modeling, we showed that this happy face advantage can, at least partly, be explained by perceptual factors. Also, saccade endpoints were lower when the target was happy than when it was fearful. Overall, we suggest that there is no automatic prioritization of emotional faces, at least for saccades with short latencies, but that salient local face features can automatically attract attention. [ABSTRACT FROM AUTHOR]

Background: Fluoride-18 sodium fluoride (18F-NaF) localizes in microcalcifications in atheroma. The microcalcifications may aggregate, passing the resolution threshold to visualize on computed tomography (CT). We evaluated serial NaF positron emission tomography (PET)-CT scans to determine the temporal relationship between vascular NaF uptake and CT evident calcification in the abdominal aorta.Methods: Prostate cancer patients who had at least 3 NaF PET-CT scans over at least 1.5 years were retrospectively enrolled. Regions of interest were traced in the abdominal aorta on both PET and CT images, excluding skeletal NaF activity. The maximum standardized uptake value (SUVmax) of NaF and the density and volume of calcium (exceeding 130 HU) were summed and divided by the number of slices to produce the SUVmax/slice and the mm3·slice-1 of calcium.Results: Of 437 patients, 45 patients met criteria. NaF uptake waxed and waned between scans, while the calcium volume plateaued or increased over time. NaF uptake correlated with calcium volume on the baseline scan (P = .60, < .0001†) and calcium volume increment, especially from 1.0 to 1.5 years (r = .79, P < .0001†). Patients with persistently high NaF uptake showed a higher calcium volume increment (0-1.5 years) than patients with low or transiently high NaF uptake.Conclusions: Abdominal aortic NaF uptake varied over time. NaF uptake on the baseline scans and high NaF uptake on the serial scans preceded an increase in calcium volume, especially by 1.0-1.5 years. Persistently high NaF uptake was associated with a greater increment in calcium volume than patients with transiently elevated or persistently low fluoride uptake. [ABSTRACT FROM AUTHOR]

Low-intensity transcranial ultrasound stimulation (TUS) is a promising non-invasive brain stimulation technique that can modulate the excitability of cortical and deep brain structures with a high degree of focality. Previous human studies showed that TUS decreases motor cortex (M1) excitability measured by transcranial magnetic stimulation (TMS), but whether the effects appear beyond sonication and whether TUS affects the excitability of other interconnected cortical areas is not known. The time course of M1 TUS on ipsilateral and contralateral M1 excitability was investigated in 22 healthy human subjects via TMS-induced motor-evoked potentials. With sonication duration of 500 ms, we found suppression of M1 excitability from 10 ms before to 20 ms after the end of sonication, and the effects were stronger with blocked design compared to interleaved design. There was no significant effect on contralateral M1 excitability. Using ex-vivo measurements, we showed that the ultrasound transducer did not affect the magnitude or time course of the TMS-induced electromagnetic field. We conclude that the online-suppressive effects of TUS on ipsilateral M1 cortical excitability slightly outlast the sonication but did not produce long-lasting effects. The absence of contralateral effects may suggest that there are little tonic interhemispheric interactions in the resting state, or the intensity of TUS was too low to induce transcallosal inhibition.

Gene regulatory network (GRN) inference is an effective approach to understand the molecular mechanisms underlying biological events. Generally, GRN inference mainly targets intracellular regulatory relationships such as transcription factors and their associated targets. In multicellular organisms, there are both intracellular and intercellular regulatory mechanisms. Thus, we hypothesize that GRNs inferred from time-course individual (whole embryo) RNA-Seq during development can reveal intercellular regulatory relationships (signaling pathways) underlying the development. Here, we conducted time-course bulk RNA-Seq of individual mouse embryos during early development, followed by pseudo-time analysis and GRN inference. The results demonstrated that GRN inference from RNA-Seq with pseudo-time can be applied for individual bulk RNA-Seq similar to scRNA-Seq. Validation using an experimental-source-based database showed that our approach could significantly infer GRN for all transcription factors in the database. Furthermore, the inferred ligand-related and receptor-related downstream genes were significantly overlapped. Thus, the inferred GRN based on whole organism could include intercellular regulatory relationships, which cannot be inferred from scRNA-Seq based only on gene expression data. Overall, inferring GRN from time-course bulk RNA-Seq is an effective approach to understand the regulatory relationships underlying biological events in multicellular organisms.

Anaphora is the main linguistic means to establish discourse coherence, and anaphora resolution is the psychological process to maintain this coherence. Chinese discourse is characterized with providing multiplicity of linguistic clues to readers by employing various referential apparatuses such as pronoun anaphora, zero anaphora, and so on. As a way of avoiding repeated reference to an object that is mentioned beforehand, zero anaphora is frequently employed in discourse. The production and resolution of zero anaphora largely concerns some constraints underlying psychological mechanisms. We particularly focus on zero anaphora resolution in the present study to try to discover some specific aspects of the underlying mechanism, hoping to find out some factors unique to the resolution process. We designed the first two experiments to probe into the psychological reality when participants were presented with sentences containing either pronoun anaphora or zero anaphora or both under discourse condition with topic continuity in Experiment 1a and topic discontinuity in Experiment 1b. We did not find any significant difference in the reaction time between zero anaphora resolution and pronoun anaphora resolution, indicating that zero anaphora possibly works within the processing mechanism on which pronoun anaphora resolution depends. However, we found significantly longer time in reading the first sentence in any of the discourse, showing that the first-mention effect exists in anaphora resolution. We further explored the time course of zero anaphora resolution by measuring the reaction time during the period when participants read sentences that varied according to the location where zero anaphora occurred under two conditions: topic continuity (Experiment 2a) vs. topic discontinuity (Experiment 2b). The strategies of searching for the referential information were found divergent: the exhaustive searching strategy was adopted when the topics within a discourse were kept continuous and the heuristic searching strategy was employed when the topics were discontinuous. The design of Experiment 5 took the factor of voice type and situation consistency into consideration, investigating in what way do those factors influence the resolution of zero anaphora. The voice type, according to the results, plays a significant role for its exclusively close relationship with the first-mention effect.

(1) Purpose: This study aimed to explore the time duration of post-activation performance enhancement (PAPE) in elite male sprinters with different strength levels. (2) Methods: Thirteen elite male sprinters were divided into a strong group (relative strength: 1RM squat normalized by body mass of ≥2.5; n = 6) and a weak group (relative strength of n = 7). All sprinters performed one static squat jump (SSJ) at baseline and 15 s, 3 min, 6 min, 9 min, and 12 min following an exercise protocol including three reps of a 90% 1RM back squat. Two force plates were used to determine the vertical jump height, the impulse output, and the power output for all SSJs. (3) Results: Significant improvements in vertical jump height and peak impulse were observed (p < 0.05) at 3, 6, and 9 min, without significant between-group differences. The peak power had a significant increase in 3 min (p < 0.01) and 6 min (p < 0.05), with also no significant difference between-group differences. Moreover, the stronger subjects induced a greater PAPE effect than the weaker counterparts at 3, 6, and 9 min after the intervention. The maximal benefit following the intervention occurred at 6 min and 3 min after the intervention in the stronger and weaker subjects, respectively. (4) Conclusions: The findings indicated that three reps of a 90% 1RM back squat augmented the subsequent explosive movement (SSJ) for 3–9 min in elite male sprinters, especially in stronger sprinters.

Number–color synesthesia is a condition in which synesthetes perceive numbers with concurrent experience of specific, corresponding colors. It has been proposed that synesthetic association exists primarily between representations of Arabic digit graphemes and colors, and a secondary, semantic connection between numerosity and colors is built via repeated co-activation. However, this distinction between the graphemic and semantic pathways of synesthetic number–color connection has not been empirically tested. The current study aims to dissociate graphemic and semantic aspects of color activations in number–color synesthesia by comparing their time courses. We adopted a synesthetic priming paradigm with varied stimuli onset asynchronies (SOAs). A number (2–6, prime) was presented in one of three notations: digit, dice, or non-canonical dot pattern, and a color patch (target) appeared with an SOA of 0, 100, 300, 400, or 800 ms. Participants reported the color as quickly as possible. Using the congruency effect (i.e., shorter reaction time when target color matched the synesthetic color of number prime) as an index of synesthetic color activation level, we revealed that the effect from the graphemic pathway is quick and relatively persistent, while the effect from the semantic pathway unfolds at a later stage and is more transient. The dissociation between the graphemic and semantic pathways of synesthesia implies further functional distinction within “conceptual synesthesia”, which has been originally discussed as a unitary phenomenon. This distinction has been demonstrated by the differential time courses of synesthetic color activations, and suggested that a presumed, single type of synesthesia could involve multiple mechanisms.

Bacillus mycoides SeITE01 is an environmental isolate that transforms the oxyanion selenite (SeO32−) into the less bioavailable elemental selenium (Se0) forming biogenic selenium nanoparticles (Bio-SeNPs). In the present study, the reduction of sodium selenite (Na2SeO3) by SeITE01 strain and the effect of SeO32− exposure on the bacterial cells was examined through untargeted metabolomics. A time-course approach was used to monitor both cell pellet and cell free spent medium (referred as intracellular and extracellular, respectively) metabolites in SeITE01 cells treated or not with SeO32−. The results show substantial biochemical changes in SeITE01 cells when exposed to SeO32−. The initial uptake of SeO32− by SeITE01 cells (3h after inoculation) shows both an increase in intracellular levels of 4-hydroxybenzoate and indole-3-acetic acid, and an extracellular accumulation of guanosine, which are metabolites involved in general stress response adapting strategies. Proactive and defensive mechanisms against SeO32− are observed between the end of lag (12h) and beginning of exponential (18h) phases. Glutathione and N-acetyl-L-cysteine are thiol compounds that would be mainly involved in Painter-type reaction for the reduction and detoxification of SeO32− to Se0. In these growth stages, thiol metabolites perform a dual role, both acting against the toxic and harmful presence of the oxyanion and as substrate or reducing sources to scavenge ROS production. Moreover, detection of the amino acids L-threonine and ornithine suggests changes in membrane lipids. Starting from stationary phase (24 and 48h), metabolites related to the formation and release of SeNPs in the extracellular environment begin to be observed. 5-hydroxyindole acetate, D-[+]-glucosamine, 4-methyl-2-oxo pentanoic acid, and ethanolamine phosphate may represent signaling strategies following SeNPs release from the cytoplasmic compartment, with consequent damage to SeITE01 cell membranes. This is also accompanied by intracellular accumulation of trans-4-hydroxyproline and L-proline, which likely represent osmoprotectant activity. The identification of these metabolites suggests the activation of signaling strategies that would protect the bacterial cells from SeO32− toxicity while it is converting into SeNPs.

This present research investigated variations in lipid profiles and important biomarkers of tissue damage in response to graded concentrations of alcohol administration in male Wistar rats. Group A (control) received distilled water while group B, C and D received 30%, 40% and 50% (v/v) alcohol respectively. Five rats each from groups A-D were sacrificed after day(s) 1, 7, 14, 21 and 28 of administration. A significant increase was observed at day 28 for serum cholesterol by 79% (group B), 78% (group C) and 47% (group D) together with serum phospholipid 58% (group B), 50% (group C) and 92% (group D). Serum triacylglycerol increased by 71% (group B), 43% (group C) and 16% (group D) at day 21, while concentration of serum albumin decreased at day 28 by 40.9% (group B), 50.2% (group C), 53.3% (group D) respectively when compared with control (group A). Serum aminotransferases and alkaline phosphatase specific activities, as well as creatinine and uric acid concentration increased in a concentration-dependent manner, following alcohol administration. Though most of these effects induced by alcohol were time- and concentration-dependent, 40% alcohol appear to be more stable, giving results consistent with alcohol-induced damages, with minimal mortality. This study therefore further validated dyslipidemia and imbalance in clinical biomarkers as hallmarks of tissue damage induced by excessive alcohol consumption with an insight on the time- and concentration-response relationship between alcohol consumption and its toxicity.

Background Serum uric acid (SUA) has been demonstrated as a risk factor for myocardial infarction (MI) and all‐cause mortality; however, the impact of cumulative SUA (cumSUA) remains unclear. We aimed to investigate the association of cumSUA with MI risk and all‐cause mortality, and to further explore the effects of SUA accumulation time course. Methods and Results The study enrolled 53 463 participants without a history of MI, and these participants underwent 3 examinations during 2006 to 2010. cumSUA from baseline to the third examination was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Cox models estimated hazard ratios (HRs) and 95% CIs of MI and all‐cause mortality for cumSUA quartiles, hyperuricemia exposure duration, and SUA accumulation time course. During a median follow‐up of 7.04 years, 476 incident MIs and 2692 deaths occurred. In the fully adjusted model, a higher MI risk was observed in the highest cumSUA quartile (HR, 1.48; 95% CI, 1.10–1.99), in participants with longer hyperuricemia exposure duration (HR, 1.71; 95% CI, 1.06–2.73), and in participants with cumSUA≥median and a negative slope (HR, 1.58; 95% CI, 1.18–2.11). Similar associations persisted for all‐cause mortality. Conclusions The risk of MI and all‐cause mortality increased with higher cumSUA and was affected by the SUA accumulation time course. Early SUA accumulation contributed more to MI risk and all‐cause mortality than later SUA accumulation with the same overall cumulative exposure, emphasizing the importance of optimal SUA control early in life.

Bacillus mycoides SeITE01 is an environmental isolate that transforms the oxyanion selenite ( SeO 3 2 − ) into the less bioavailable elemental selenium (Se0) forming biogenic selenium nanoparticles (Bio-SeNPs). In the present study, the reduction of sodium selenite (Na2SeO3) by SeITE01 strain and the effect of SeO 3 2 − exposure on the bacterial cells was examined through untargeted metabolomics. A time-course approach was used to monitor both cell pellet and cell free spent medium (referred as intracellular and extracellular, respectively) metabolites in SeITE01 cells treated or not with SeO 3 2 − . The results show substantial biochemical changes in SeITE01 cells when exposed to SeO 3 2 − . The initial uptake of SeO 3 2 − by SeITE01 cells (3h after inoculation) shows both an increase in intracellular levels of 4-hydroxybenzoate and indole-3-acetic acid, and an extracellular accumulation of guanosine, which are metabolites involved in general stress response adapting strategies. Proactive and defensive mechanisms against SeO 3 2 − are observed between the end of lag (12h) and beginning of exponential (18h) phases. Glutathione and N-acetyl-L-cysteine are thiol compounds that would be mainly involved in Painter-type reaction for the reduction and detoxification of SeO 3 2 − to Se0. In these growth stages, thiol metabolites perform a dual role, both acting against the toxic and harmful presence of the oxyanion and as substrate or reducing sources to scavenge ROS production. Moreover, detection of the amino acids L-threonine and ornithine suggests changes in membrane lipids. Starting from stationary phase (24 and 48h), metabolites related to the formation and release of SeNPs in the extracellular environment begin to be observed. 5-hydroxyindole acetate, D-[+]-glucosamine, 4-methyl-2-oxo pentanoic acid, and ethanolamine phosphate may represent signaling strategies following SeNPs release from the cytoplasmic compartment, with consequent damage to SeITE01 cell membranes. This is also accompanied by intracellular accumulation of trans-4-hydroxyproline and L-proline, which likely represent osmoprotectant activity. The identification of these metabolites suggests the activation of signaling strategies that would protect the bacterial cells from SeO 3 2 − toxicity while it is converting into SeNPs. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). Methods: In this retrospective–prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. Results: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55–69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89–175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil–lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. Conclusion: Daily values or trends over time of parameters associated with acute organ dysfunction, acid–base derangement, coagulation impairment, or systemic inflammation were associated with patient survival. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is a pivotal target for neuroprotection strategies for traumatic brain injury (TBI). However, comprehensive time-course evaluations of mitochondrial dysfunction are lacking in the pre-clinical penetrating TBI (PTBI) model. The current study was designed to characterize temporal responses of mitochondrial dysfunction from 30 min to 2 weeks post-injury after PTBI. Anesthetized adult male rats were subjected to either PTBI or sham craniectomy (n = 6 animals per group × 7 time points). Animals were euthanized at 30 min, 3 h, 6 h, 24 h, 3 days, 7 days, and 14 days post-PTBI, and mitochondria were isolated from the ipsilateral hemisphere of brain regions near the injury core (i.e., frontal cortex [FC] and striatum [ST]) and a more distant region from the injury core (i.e., hippocampus [HIP]). Mitochondrial bioenergetics parameters were measured in real time using the high-throughput procedures of the Seahorse Flux Analyzer (Agilent Technologies, Santa Clara, CA). The post-injury time course of FC + ST showed a biphasic mitochondrial bioenergetics dysfunction response, indicative of reduced adenosine triphosphate synthesis rate and maximal respiratory capacity after PTBI. An initial phase of energy crisis was detected at 30 min (−42%; p < 0.05 vs. sham), which resolved to baseline levels between 3 and 6 h (non-significant vs. sham). This was followed by a second and more robust phase of bioenergetics dysregulation detected at 24 h that remained unresolved out to 14 days post-injury (−55% to −90%; p < 0.05 vs. sham). In contrast, HIP mitochondria showed a delayed onset of mitochondrial dysfunction at 7 days (−74%; p < 0.05 vs. sham) that remained evident out to 14 days (−51%; p < 0.05 vs. sham) post-PTBI. Collectively, PTBI-induced mitochondrial dysfunction responses were time and region specific, evident differentially at the injury core and distant region of PTBI. The current results provide the basis that mitochondrial dysfunction may be targeted differentially based on region specificity post-PTBI. Even more important, these results suggest that therapeutic interventions targeting mitochondrial dysfunction may require extended dosing regimens to achieve clinical efficacy after TBI. [ABSTRACT FROM AUTHOR]

Abstract Background Bud dormancy is a crucial stage in perennial trees and allows survival over winter to ensure optimal flowering and fruit production. Recent work highlighted physiological and molecular events occurring during bud dormancy in trees. However, they usually examined bud development or bud dormancy in isolation. In this work, we aimed to further explore the global transcriptional changes happening throughout bud development and dormancy onset, progression and release. Results Using next-generation sequencing and modelling, we conducted an in-depth transcriptomic analysis for all stages of flower buds in several sweet cherry (Prunus avium L.) cultivars that are characterized for their contrasted dates of dormancy release. We find that buds in organogenesis, paradormancy, endodormancy and ecodormancy stages are defined by the expression of genes involved in specific pathways, and these are conserved between different sweet cherry cultivars. In particular, we found that DORMANCY ASSOCIATED MADS-box (DAM), floral identity and organogenesis genes are up-regulated during the pre-dormancy stages while endodormancy is characterized by a complex array of signalling pathways, including cold response genes, ABA and oxidation-reduction processes. After dormancy release, genes associated with global cell activity, division and differentiation are activated during ecodormancy and growth resumption. We then went a step beyond the global transcriptomic analysis and we developed a model based on the transcriptional profiles of just seven genes to accurately predict the main bud dormancy stages. Conclusions Overall, this study has allowed us to better understand the transcriptional changes occurring throughout the different phases of flower bud development, from bud formation in the summer to flowering in the following spring. Our work sets the stage for the development of fast and cost effective diagnostic tools to molecularly define the dormancy stages. Such integrative approaches will therefore be extremely useful for a better comprehension of complex phenological processes in many species.

Abstract Background Bacterial cells during many replication cycles accumulate spontaneous mutations, which result in the birth of novel clones. As a result of this clonal expansion, an evolving bacterial population has different clonal composition over time, as revealed in the long-term evolution experiments (LTEEs). Accurately inferring the haplotypes of novel clones as well as the clonal frequencies and the clonal evolutionary history in a bacterial population is useful for the characterization of the evolutionary pressure on multiple correlated mutations instead of that on individual mutations. Results In this paper, we study the computational problem of reconstructing the haplotypes of bacterial clones from the variant allele frequencies observed from an evolving bacterial population at multiple time points. We formalize the problem using a maximum likelihood function, which is defined under the assumption that mutations occur spontaneously, and thus the likelihood of a mutation occurring in a specific clone is proportional to the frequency of the clone in the population when the mutation occurs. We develop a series of heuristic algorithms to address the maximum likelihood inference, and show through simulation experiments that the algorithms are fast and achieve near optimal accuracy that is practically plausible under the maximum likelihood framework. We also validate our method using experimental data obtained from a recent study on long-term evolution of Escherichia coli. Conclusion We developed efficient algorithms to reconstruct the clonal evolution history from time course genomic sequencing data. Our algorithm can also incorporate clonal sequencing data to improve the reconstruction results when they are available. Based on the evaluation on both simulated and experimental sequencing data, our algorithms can achieve satisfactory results on the genome sequencing data from long-term evolution experiments. Availability The program (ClonalTREE) is available as open-source software on GitHub at https://github.com/COL-IU/ClonalTREE.

Static stretching (SS) is widely used to decrease and retain the passive stiffness of the muscle-tendon unit in clinical and athletic settings. It is important to consider the minimum SS duration required to decrease the passive stiffness of the hamstring, from the perspective of injury prevention of the hamstring muscle. The purpose of this study was to investigate the time course of the effect of static stretching (SS) on passive stiffness of the hamstring and to clarify the minimum SS duration required to decrease the passive stiffness. Fifteen healthy males participated in this study. Fifteen healthy and non-athlete male volunteers participated in this study. SS of 60-s session was performed for five sessions with a 30-s rest between sessions. Passive stiffness was measured prior to SS (PRE) and immediately after each SS session to determine the minimum SS duration required to decrease the passive stiffness. The passive stiffness was calculated as the slope of the torque-angle curve corresponding to 50% of the final angle (Nm/°). Passive stiffness after 180, 240, and 300 s of SS was significantly lower than that at PRE. Our results showed that SS for >180 s is recommended to decrease the passive stiffness of the hamstring muscle.

Abstract Background Evidence suggests that early adaptive responses of hepatic mitochondria occur in experimentally induced sepsis. Little is known about both colonic mitochondrial function during abdominal infection and long-term changes in mitochondrial function under inflammatory conditions. We hypothesize that hepatic and colonic mitochondrial oxygen consumption changes time-dependently after sterile laparotomy and in the course of abdominal infection. The aim of the present study was to investigate the hepatic and colonic mitochondrial respiration after sterile laparotomy and abdominal infection over up to 96 h. Methods After approval of the local Animal Care and Use Committee, 95 Wistar rats were randomized into 8 groups (n = 11–12): 1–4 sham (laparotomy only) and 5–8 colon ascendens stent peritonitis (CASP). Healthy, unoperated animals served as controls (n = 9). The mitochondrial respiration in colon and liver homogenates was assessed 24, 48, 72, and 96 h after surgery. Mitochondrial oxygen consumption was determined using a Clark-type electrode. State 2 (oxygen consumption in the presence of the substrates for complexes I and II) and state 3 respiration (ADP dependent) were assessed. The respiratory control ratio (RCR state 3/state 2) and ADP/O ratio (ADP added/oxygen consumed) were calculated for both complexes. Data are presented as means ± SD, two-way ANOVA followed by Tukey’s post hoc test. Results Hepatic RCR was initially (after 24 h) elevated in both operated groups; after 48 h only, the septic group was elevated compared to controls. In CASP groups, the hepatic ADP/O ratio for complex I was elevated after 24 h (vs. controls) and after 48 h (vs. sham) but declined after 72 h (vs. controls). The ADP/O ratio for complex II stayed unchanged over the time period until 96 h. The colonic RCR and ADP/O did not change over time after sham or CASP operation. Conclusion Hepatic, but not colonic, mitochondrial respiration is increased in the initial phase (until 48 h) and normalizes in the longer course of time (until 96 h) of abdominal infection.

Abstract The beneficial effects of exercise training on memory formation are well documented. However, the memory enhancement profile following the time‐course of exercise training remains unknown. In this investigation, changes in the spatial hippocampal memory following a time‐course of swimming exercise training were examined. Young adult Wistar rats were tested for both short‐term and long‐term memories using the radial arm water maize (RAWM) paradigm following 0, 1, 7, 14, and 28 days of swimming exercise training (60 min per day, 5 days/week)s. The mean total errors on RAWM during the learning phase and memory testing remained the same (p > 0.5) after 1 day of swimming exercise. On the other hand, swimming exercise‐induced significant enhancement to the learning phase and memory formation after 7 days of training (p 0.5). Similarly, short‐ and long‐term memories improved after 7 days (p 0.05). The time course of improvement of learning and both short‐ and long‐term memories after swimming exercise were evident after 7 days and plateaued thereafter. Results of the current study could form the base for future utilization of exercises to enhance cognitive function in healthy individuals.

Neurological deterioration (ND) is a devastating complication for patients with ischemic stroke after endovascular recanalization therapy (EVT). We aimed to investigate the time course and clinical relevance of ND after EVT. Consecutive patients with acute ischemic stroke who underwent EVT for large arterial occlusions of the anterior cerebral circulation were enrolled. The National Institutes of Health Stroke Scale (NIHSS) scores were assessed before EVT, at the end of EVT, at 24 h (d1), on day 3 (d3), on day 15 (d15), at discharge and anytime when ND was indicated. ND was defined as an increase of ≥ 4 points in the NIHSS score and was divided into acute ND (AD, within 24 h), subacute ND (SD, d1–d3), and delayed ND (DD, d3–d15 or discharge). Using multivariable logistic regression analysis, we explored predictors and outcomes of ND at different time periods. As a result, of 343 patients, 129 (37.6%) experienced ND, including 90 (26.2%) with AD, 27 (7.9%) with SD and 12 (3.5%) with DD. Multivariable logistic regression analysis revealed that history of hypertension, cardioembolic stroke, lower Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and poor collaterals were significantly associated with an increased risk of AD; history of hypertension, lower ASPECTS, poor collaterals, and unsuccessful recanalization, with SD; and high admission NIHSS score, with DD. In addition, patients who experienced AD (OR = 10.22, P < 0.001), SD (OR = 15.89, P = 0.004), or DD (OR = 8.31, P = 0.015) were more likely to have poor outcomes. ND was a strong predictor of poor stroke outcomes. Management of related risk factors at different ND time periods might improve the prognosis of EVT.

The purpose of this study was to analyze the time course and dose effect from metformin on body mass index (BMI) in children and adolescents by model-based meta-analysis (MBMA). Searching randomized controlled trial (RCT) studies of metformin on BMI in children and adolescents. The change rates of BMI from baseline values were used as indicator of evaluating metformin efficacy. A total of 18 RCT studies, 1,228 children and adolescents, were included for analysis, including patients with obesity, patients with type 1 diabetes mellitus, patients with nonalcoholic fatty liver, and patients with precocity. In order to achieve better effect of metformin on BMI in children and adolescents, the present study recommended that for patients with obesity, 1,000 mg/day metformin was required for at least 15.2 weeks and 60.8 weeks to achieve the plateau of metformin effect; for patients with type 1 diabetes mellitus, 1,000 mg/day metformin was required for at least 25.2 weeks and 100.8 weeks to achieve the plateau of metformin effect; for patients with nonalcoholic fatty liver, 1,000 mg/day metformin was required for at least 6.57 weeks and 26.28 weeks to achieve the plateau of metformin effect; for patients with precocity, 425 mg/day metformin was required for at least 12.4 weeks and 49.6 weeks to achieve the plateau of metformin effect. It was the first time to analyze the time course and dose effect from metformin on BMI and to recommend dosage and duration of treatment for metformin in children and adolescents with different disease types.

Neurological deterioration (ND) is a devastating complication for patients with ischemic stroke after endovascular recanalization therapy (EVT). We aimed to investigate the time course and clinical relevance of ND after EVT. Consecutive patients with acute ischemic stroke who underwent EVT for large arterial occlusions of the anterior cerebral circulation were enrolled. The National Institutes of Health Stroke Scale (NIHSS) scores were assessed before EVT, at the end of EVT, at 24 h (d1), on day 3 (d3), on day 15 (d15), at discharge and anytime when ND was indicated. ND was defined as an increase of ≥ 4 points in the NIHSS score and was divided into acute ND (AD, within 24 h), subacute ND (SD, d1–d3), and delayed ND (DD, d3–d15 or discharge). Using multivariable logistic regression analysis, we explored predictors and outcomes of ND at different time periods. As a result, of 343 patients, 129 (37.6%) experienced ND, including 90 (26.2%) with AD, 27 (7.9%) with SD and 12 (3.5%) with DD. Multivariable logistic regression analysis revealed that history of hypertension, cardioembolic stroke, lower Alberta Stroke Program Early Computed Tomography Score (ASPECTS), and poor collaterals were significantly associated with an increased risk of AD; history of hypertension, lower ASPECTS, poor collaterals, and unsuccessful recanalization, with SD; and high admission NIHSS score, with DD. In addition, patients who experienced AD (OR = 10.22, P < 0.001), SD (OR = 15.89, P = 0.004), or DD (OR = 8.31, P = 0.015) were more likely to have poor outcomes. ND was a strong predictor of poor stroke outcomes. Management of related risk factors at different ND time periods might improve the prognosis of EVT. [ABSTRACT FROM AUTHOR]

Background: Despite recognition that blood donation is an affectively poignant process, many aspects of donors' emotional experiences and their consequences remain unexamined.Purpose: This study tracked the donor's experience of several positive and negative emotions live as they arose during the donation process and tracked the impact of that experience on donor return.Methods: New whole blood donors (N = 414) reported their experience of 10 positive and 10 negative discrete emotions before, during, and after donation. Return behavior of these donors and a business-as-usual control group was tracked over the next 6 months.Results: In total, 46.4% of participants and 43.2% of the control group returned to donate within 6 months. On the basis of established relevance to blood donation and statistical considerations, group-based latent trajectories of three emotions (joy, calm, and stress) were modeled over time, revealing five classes of emotion trajectories. A trajectory of low/increasing joy and calm and high/decreasing stress was associated with significantly lower probability of return (preturn = .28, 95% confidence interval [CI] = 0.20, 0.38) relative to all but one other trajectory group and the control group. A trajectory of medium-high/increasing joy, high calm, and low/decreasing stress was associated with a significantly greater probability of return (preturn = .59, 95% CI = 0.49, 0.69) relative to two other trajectory classes and the control group.Conclusions: By identifying blood donors' emotion trajectories over time and the impact of those trajectories on return behavior, this research paves the way for the development of effective emotion-focused interventions to boost retention. [ABSTRACT FROM AUTHOR]

The beneficial effects of exercise training on memory formation are well documented. However, the memory enhancement profile following the time‐course of exercise training remains unknown. In this investigation, changes in the spatial hippocampal memory following a time‐course of swimming exercise training were examined. Young adult Wistar rats were tested for both short‐term and long‐term memories using the radial arm water maize (RAWM) paradigm following 0, 1, 7, 14, and 28 days of swimming exercise training (60 min per day, 5 days/week)s. The mean total errors on RAWM during the learning phase and memory testing remained the same (p > 0.5) after 1 day of swimming exercise. On the other hand, swimming exercise‐induced significant enhancement to the learning phase and memory formation after 7 days of training (p < 0.01). Errors decreased (p < 0.0001) after 7 days of training and remained lower (p < 0.0001) than baseline without differences between 7, 14, and 28 days (p > 0.5). Similarly, short‐ and long‐term memories improved after 7 days (p < 0.05) of training as compared to the baseline without differences between 7, 14, and 28 days (p > 0.05). The time course of improvement of learning and both short‐ and long‐term memories after swimming exercise were evident after 7 days and plateaued thereafter. Results of the current study could form the base for future utilization of exercises to enhance cognitive function in healthy individuals. [ABSTRACT FROM AUTHOR]

The Cydia pomonella granulovirus (CpGV) has been used as a biological control agent of codling moth (Cydia pomonella), a severe global pest on pome fruit. Despite the economic importance, our knowledge of its molecular biology is still limited and a detailed picture of its gene expression is still missing. Here, we sequenced the transcriptome of codling moth larvae infected with the Mexican isolate CpGV-M and analyzed the expression of viral genes at 12, 48, and 96 h post infection (hpi). The results showed that two genes (p6.9 and pp31/39K) related to DNA binding of virus production, were highly expressed at 48 and 96 hpi. From 48 to 96 hpi, the expression of genes associated with virus replication and dissemination decreased, whereas the expression of genes related to infectious virion production and per os infectivity increased. This study provides a comprehensive view of CpGV gene expression patterns in host larvae. • The first temporal transcriptome of CpGV in host larvae was assessed using RNAseq. • Gene expression pattern of CpGV in host larvae was similar at 48 and 96 hpi. • p6.9 and pp31/39K were top two highly expressed genes and related to replication. • The expression of genes related to replication/dissemination decreased over time. • The expression of genes related to infectious virion production increased over time. [ABSTRACT FROM AUTHOR]

Sleep inertia (SI) refers to a complex psychophysiological phenomenon, observed after awakening, that can be described as the gradual recovery of waking-like status. The time course of cognitive performance dissipation in an everyday life condition is still unclear, especially in terms of the sleep stage at awakening (REM or NREM-stage 2) and the relative effects on performance. The present study aimed to investigate the SI dissipation in different memory performances upon spontaneous morning awakening after uninterrupted nighttime sleep. Eighteen young adults (7 females; mean age 24.9 ± 3.14 years) spent seven non-consecutive nights (one baseline, three REM awakenings and three St2 awakenings) in the laboratory under standard polysomnographic (PSG) control. Participants were tested after three REM awakenings and three St2 awakenings, and three times at 11:00 a.m. as a control condition. In each testing session, participants filled in the Global Vigor and Affect Scale and carried out one memory task (episodic, semantic, or procedural task). For each condition, participants were tested every 10 min within a time window of 80 min. In accordance with previous studies, SI affected subjective alertness throughout the entire time window assessed. Moreover, SI significantly affected performance speed but not accuracy in the semantic task. With reference to this task, the SI effect dissipated within 30 min of awakening from REM, and within 20 min of awakening from St2. No significant SI effect was observed on episodic or procedural memory tasks. [ABSTRACT FROM AUTHOR]

The increasing levels of pesticide resistance in agricultural pests and disease vectors represents a threat to both food security and global health. As insecticide resistance intensity strengthens and spreads, the likelihood of a pest encountering a sub-lethal dose of pesticide dramatically increases. Here, we apply dynamic Bayesian networks to a transcriptome time-course generated using sub-lethal pyrethroid exposure on a highly resistant Anopheles coluzzii population. The model accounts for circadian rhythm and ageing effects allowing high confidence identification of transcription factors with key roles in pesticide response. The associations generated by this model show high concordance with lab-based validation and identifies 44 transcription factors putatively regulating insecticide-responsive transcripts. We identify six key regulators, with each displaying differing enrichment terms, demonstrating the complexity of pesticide response. The considerable overlap of resistance mechanisms in agricultural pests and disease vectors strongly suggests that these findings are relevant in a wide variety of pest species.

Biostimulants are widely used in agriculture because they can improve fruit quality and quantity. Less is known about how biostimulants act over time in plants, in our case peppers, and how they affect the enzyme activity of important enzymes for capsaicinoid synthesis. The biostimulatory effects of amino acids on the activities of phenylalanine ammonia lyase (PAL), capsaicin synthase (CS), and peroxidase (POX) were investigated in the pericarp and placenta of the chili pepper Capsicum baccatum L. cv. “Bishop Crown” over 72 h of application. The PAL and CS activities significantly increased in the placenta after 1 h of biostimulant application, with significant increases of 130% and 16%, respectively. The POX activity remained unchanged over the full 72 h in the placenta but significantly increased after 48 h in the pericarp (+53%). Total capsaicinoids increased in the first hour of biostimulant application, by 4.30 g/kg FW in the placenta (19%) and by 0.94 g/kg FW in the pericarp (+56%). Biostimulant application also increased total and individual capsaicinoids after 48 h in the chili placenta and pericarp. With improved methods for enzymatic determination, we gained new insights into the responses of chilies to biostimulant amino acids.

The main goal of this study was to determine the relationship of cleaved-caspase-3 (C3)-related apoptosis and hepatic proliferation, during the liver repopulation in a living liver donor rat model. Thirty-three animals were randomized into eleven groups and evaluated on postoperative from 3 ​h until 384 ​h after 30%-partial hepatectomy (30%-PHx). Liver sections (5 ​μm) were processed by hematoxylin-eosin, and immunostaining for C3, accompanied by hepatic function test. C3 content and the hepatic lobule enlargement were analyzed by optical density, followed by cell counting. Transient variations of alanine transferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were found. Significant increase in the C3 levels, and cell nuclei number, were detected at 12 ​h and 48 ​h after 30%-PHx, evidencing a correlation of p ​= ​−0.3679. In the 30%-PHx rat model, C3-related apoptosis prevents proliferative pathological conditions during the hepatic lobule re-modeling. [ABSTRACT FROM AUTHOR]

Background: Differences in health effects of dietary α-linolenic acid (ALA) and DHA are mediated at least in part by differences in their effects on oxylipins.Objectives: Time course and sex differences of plasma oxylipins in response to ALA- compared with DHA-rich supplements were examined.Methods: Healthy men and women, aged 19-34 y and BMI 18-28 kg/m2, were provided with capsules containing ∼4 g/d of ALA or DHA in a randomized double-blind crossover study with >6-wk wash-in and wash-out phases. Plasma PUFA and oxylipin (primary outcome) concentrations at days 0, 1, 3, 7, 14, and 28 of supplementation were analyzed by GC and HPLC-MS/MS, respectively. Sex differences, supplementation and time effects, and days to plateau were analyzed.Results: ALA supplementation doubled ALA concentrations, but had no effects on ALA oxylipins after 28 d, whereas DHA supplementation tripled both DHA and its oxylipins. Increases in DHA oxylipins were detected as early as day 1, and a plateau was reached by days 5-7 for 11 of 12 individual DHA oxylipins and for total DHA oxylipins. Nine individual DHA oxylipins reached a plateau in females with DHA supplementation, compared with only 4 in males. A similar time course and sex difference pattern occurred with EPA and its oxylipins with DHA supplementation. DHA compared with ALA supplementation also resulted in higher concentrations of 4 individual arachidonic acids, 1 linoleic acid, and 1 dihomo-γ-linolenic acid oxylipin, despite not increasing the concentrations of these fatty acids, further demonstrating that oxylipins do not always reflect their precursor PUFA.Conclusions: DHA compared with a similar dose of ALA has greater effects on both n-3 and n-6 oxylipins in young, healthy adults, with differences in response to DHA supplementation occurring earlier and being greater in females. These findings can help explain differences in dietary effects of ALA and DHA.This study was registered at clinicaltrials.gov as NCT02317588. [ABSTRACT FROM AUTHOR]

Introduction: This study investigated the time course of attention to pain and examined the moderating effect of attentional control in the relationship between pain catastrophizing and attentional bias in chronic pain patients. Methods: A total of 28 patients with chronic pain and 29 pain-free individuals observed pictures of pain, happy and neutral facial expressions while their gaze behaviour was recorded. Pain intensity and duration, anxiety, depression, stress, attentional control and pain catastrophizing were assessed by questionnaires. Results: In all subjects, the pattern of attention for pain faces was characterized by initial vigilance, followed by avoidance. No significant difference was found between the two groups in terms of orientation towards the stimuli, the duration of first fixation, the average duration of fixation or number of fixations on the pain stimuli. Attentional control moderated the relationship between catastrophizing and overall dwell time for happy faces in pain patients, indicating that those with high attentional control and high catastrophizing focused more on happy faces, whereas the reverse was true for those with low attentional control. Conclusion: This study supported the vigilance–avoidance pattern of attention to painful facial expressions and a moderation effect of attentional control in the association between pain catastrophizing and attentional bias to happy faces among pain patients. [ABSTRACT FROM AUTHOR]

What is known and objectives: Tacrolimus is used to treat patients with lupus nephritis; however, its time course and dose effect on proteinuria in lupus nephritis patients remain unknown. The purpose of this study was to determine the time course and dose effect of tacrolimus on proteinuria in lupus nephritis patients via model‐based meta‐analysis (MBMA). Methods: PubMed, Web of Science, Cochrane Library and ClinicalTrials.gov databases were systematically searched for information on the efficacy of tacrolimus against proteinuria in lupus nephritis patients. Useful data were extracted to build a model for the population studied using a non‐linear mixed‐effect model (NONMEM). This model was applied to simulate time course of tacrolimus on proteinuria using Monte Carlo simulations. Results: Ten clinical studies that recruited 222 patients with lupus nephritis were included. Based on various diagnostic plots, we found that the established model described the observed data reasonably well. In addition, the typical Emax and ET50 of tacrolimus for 24‐hour proteinuria in lupus nephritis patients were −5.88 g and 0.37 months, respectively. The baseline value of 24‐hour proteinuria affected Emax. No significant dose‐response relationship was observed in the range of tacrolimus concentration used in the present study (3‐10 ng/mL), indicating that the effect of tacrolimus on proteinuria depends on effective concentration range and not the dose. However, the time course relationship was obvious; the efficacy of tacrolimus increased over time, reaching a plateau (80% Emax) at approximately 1.48 months from the beginning of treatment. What is new and conclusion: When the concentration range of tacrolimus is maintained at 3‐10 ng/mL, at least 1.48 months of treatment is required to achieve a better outcome with regard to proteinuria in lupus nephritis patients. [ABSTRACT FROM AUTHOR]

During motor imagery, global inhibition and effector-specific inhibition contribute to prevent actual movements. We investigated the decay of inhibition using an action-mode switching paradigm. Participants switched between imagined and executed hand movements. Response–stimulus intervals (RSIs) were varied (200, 700, 1,300, and 2,000 ms). As inhibition (due to imagination) or activation (due to execution) in one trial affects performance in the subsequent trial, we analysed sequential effects. Evidence for the contribution of global inhibition (e.g., switch benefits in execution [E]—imagination [I] sequences compared with I-I sequences) and effector-specific inhibition (e.g., hand repetition costs after an imagination trial) was observed. Sequential effects decreased with increasing RSIs, indicating that both forms of inhibition are subject to decay. However, the decrease of sequential effects was less pronounced for global inhibition than for effector-specific inhibition. This indicates that global inhibition may decay slowly, whereas effector-specific inhibition decays rather quickly. In conclusion, global inhibition may be at least partly implemented in all contexts in which motor imagery has to be performed, whereas effector-specific inhibition may contribute to motor imagery only as soon as the exact movement parameters are known and may decay quickly after the imagined movement has been performed. [ABSTRACT FROM AUTHOR]

Background: Evidence on the longitudinal association of serum uric acid (SUA) with the risk of heart failure (HF) was limited and controversial. This study aimed to investigate the associations of cumulative SUA (cumSUA), incorporating its time course of accumulation, with the risk of HF., Methods: This prospective study enrolled 54,606 participants from the Kailuan study. The magnitude of SUA accumulation was expressed as cumSUA, exposure duration, and cumulative burden from baseline to the third survey, with cumSUA, calculated by multiplying mean values between consecutive examinations by time intervals between visits, as the primary exposure., Results: During a median follow-up of 10.00 years, 1,260 cases of incident HF occurred. A higher risk of HF was observed in participants with the highest versus the lowest quartile of cumSUA (adjusted hazard ratio [aHR], 1.54; 95% confidence interval [CI], 1.29-1.84), 6-years (6 years) versus 0-year exposure duration (aHR, 1.87; 95% CI, 1.43-2.45), cumulative burden >0 versus =0 (aHR, 1.55; 95 CI, 1.29-1.86), and those with a negative versus positive SUA slope (aHR, 1.12; 95% CI, 1.02-1.25). When cumSUA was incorporated with its time course, those with cumSUA≥median and a negative SUA slope had the highest risk of HF (aHR, 1.55; 95% CI, 1.29-1.86)., Conclusions: Incident HF risk was associated with the magnitude and time course of cumSUA accumulation. Early accumulation resulted in a greater risk of HF than later accumulation, indicating the importance of optimal SUA control earlier in life., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Assessing toxicity of complex mixtures of contaminants from industrial sites with historic and ongoing contamination remains a challenge for risk assessors. Groundwater from a pesticide packaging site in Canada containing a complex mixture of known and unknown contaminants was examined in male rats to determine the target organ toxicity. This study determined the time-course of toxicity (7, 14, 28, and 60 days) following ad libitum oral exposure to 0.05% v/v contaminated groundwater compared to tap water (control) in male Sprague Dawley rats (n=5 /group/time). Exposure to groundwater resulted in inflammation, indicated by a statistically significant increase in plasma lymphocyte and neutrophil counts on days 7 and 60, respectively, but a reduction in the plasma alpha 2 macroglobulin levels by day 60. Gonadotoxicity was indicated by a reduced Johnsen score (grading spermatogenesis) in all exposed groups at all time points, while seminiferous epithelial height was reduced on days 7, 14, and 28 compared to controls. Plasma testosterone was reduced in exposed groups on days 7 and 28, accompanied by elevated testicular lipid peroxidation at all time points compared to control. In contrast, lipid peroxidation in the lungs from exposed rats was elevated on days 7, 14, and 28. Plasma symmetric dimethylarginine was elevated on day 14 in the exposed group indicating renal impairment. Taken together, these results indicate that testes, kidney, immune and lung are target organs for the contaminated groundwater from this industrial site. The current study highlights the challenge in hazard assessment for complex mixtures and highlights the need for effects-directed analysis and the continued, albeit limited, use of animal models in toxicity testing., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steve Siciliano reports financial support was provided by Federated Cooperatives Ltd. Rachel Peters reports a relationship with Federated Cooperatives Ltd that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: This study aimed to investigate the time course of cardiac rupture (CR) after acute myocardial infarction (AMI) and the differences among different rupture types., Method: We retrospectively analyzed 145 patients with CR after AMI at Shanxi Cardiovascular Hospital from June 2016 to September 2022. Firstly, according to the time from onset of chest pain to CR, the patients were divided into early CR (≤24 h) ( n  = 61 patients) and late CR (>24 h) ( n  = 75 patients) to explore the difference between early CR and late CR. Secondly, according to the type of CR, the patients were divided into free wall rupture (FWR) ( n  = 55) and ventricular septal rupture (VSR) ( n  = 90) to explore the difference between FWR and VSR., Results: Multivariate logistic regression analysis showed that high white blood cell count (OR = 1.134, 95% CI: 1.019-1.260, P  = 0.021), low creatinine (OR = 0.991, 95% CI: 0.982-0.999, P  = 0.026) were independently associated with early CR. In addition, rapid heart rate (OR = 1.035, 95% CI: 1.009-1.061, P  = 0.009), low systolic blood pressure (OR = 0.981, 95% CI: 0.962-1.000, P  = 0.048), and anterior myocardial infarction (OR = 5.989, 95% CI: 1.978-18.136, P  = 0.002) were independently associated with VSR., Conclusion: In patients with CR, high white blood cell count and low creatinine were independently associated with early CR, rapid heart rate, low systolic blood pressure, and anterior myocardial infarction were independently associated with VSR., 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. The reviewer [CY] declared a shared parent affiliation with the author [XW] to the handling editor at the time of review., (© 2024 Liang, Wang, Yang, Zhao, Li, Wang and Guo.)

Background: Remote ischemic conditioning has been found to be effective in improving functional outcomes in acute ischemic stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to determine whether long-term remote ischemic conditioning duration after stroke onset is associated with better clinical outcomes in ischemic stroke., Methods and Results: Patients from the full analysis set were included in this secondary analysis. The primary outcome was the proportion of patients with an excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. Among the 1776 patients, there were 55 patients in the 1 to 7 days remote ischemic conditioning group, 345 in the 8 to 10 days group, 412 in the 11 to 13 days group, 51 in the 14 to 16 days group, and 913 in the control group. Compared with the control group, a significantly higher proportion of excellent functional outcomes at 90 days was found in the 11 to 13 days remote ischemic conditioning group (adjusted absolute difference, 9.1% [95% CI, 3.7%-14.5%]; P  =0.001), which was attenuated in the other groups (adjusted absolute difference in the 8-10 days group, 2.0% [95% CI, -4.0% to 8.0%]; P =0.51; adjusted absolute difference in the 14-16 days group, 7.4% [95% CI, -5.8% to 20.5%]; P =0.27), but compared to the control group, there was lower proportion of excellent functional outcomes in the 1 to 7 days group (adjusted absolute difference, -14.4% [95% CI, -27.8% to 0.0%]; P =0.05)., Conclusions: Among patients with acute moderate ischemic stroke, a higher likelihood of excellent clinical outcome was found in patients with longer duration of remote ischemic conditioning.

Differences in muscle and tendon responsiveness to mechanical stimuli and time courses of adaptive changes may disrupt the interaction of the musculotendinous unit (MTU), increasing the risk for overuse injuries. We monitored training-induced alterations in muscle and tendon biomechanical properties in elite jumpers over 4 years of athletic training to detect potential non-synchronized adaptations within the triceps surae MTU. A combined cross-sectional and longitudinal investigation over 4 years was conducted by analyzing triceps surae MTU mechanical properties in both legs via dynamometry and ultrasonography in 67 elite track and field jumpers and 24 age-matched controls. Fluctuations in muscle and tendon adaptive changes over time were quantified by calculating individual residuals. The cosine similarity of the relative changes of muscle strength and tendon stiffness between sessions served as a measure of uniformity of adaptive changes. Our cross-sectional study was unable to detect clear non-concurrent differences in muscle strength and tendon stiffness in elite jumpers. However, when considering the longitudinal data over several years of training most of the jumpers demonstrated greater fluctuations in muscle strength and tendon stiffness and hence tendon strain compared to controls, irrespective of training period (preparation vs. competition). Moreover, two monitored athletes with chronic Achilles tendinopathy showed in their affected limb lower uniformity in MTU adaptation as well as higher fluctuations in tendon strain over time. Habitual mechanical loading can affect the MTU uniformity in elite jumpers, leading to increased mechanical demand on the tendon over an athletic season and potentially increased risk for overuse injuries.

Since the emergence of the SARS-CoV-2 pandemic in December 2019 about 500,000 people died within the first 6 months. The virus itself, as well as the related political decisions, intensified an increasing feeling of fear in billions of people worldwide. However, while some people remained unperturbed, others experienced panic over the current situation. In order to investigate individual differences in the perceptions, emotions and behaviors in response to the Coronavirus pandemic, an online survey was conducted between 6th and 27th of March 2020. Participants included 7309 individuals from 96 countries, who provided information on socio-demographics, personality, political orientation and general life satisfaction. To determine the specificity of fear of Coronavirus, we also investigated fear related to two other current political issues: the refugee and the climate crises. Overall, in parallel with the escalation of the pandemic, fear of Coronavirus increased significantly over the 22-day period, with the strongest predictors being the personality variable neuroticism, as well as education, sex and being an at-risk person. A detailed longitudinal analysis of the largest sample, Germany, revealed that political orientation was also an important predictor of fear of Coronavirus. Specifically, conservatives were more afraid of Coronavirus than liberals. However, as the perceived threat of the virus increased, the influence of political orientation disappeared, whereas personality remained a stable predictor. The pattern of results regarding the perceived threat of the refugee and climate crises painted a different picture: political orientation was by far the best predictor, more important even than personality. Conservatives were more worried about the refugees, and liberals about climate change. Cross-cultural analyses showed pronounced differences between countries, dependent on the crisis. Nonetheless, the importance of personality for the prediction of fear of Coronavirus remained stable over time and across the world within the investigated 22-day period.

Abstract To model spatial changes of chromatin mark peaks over time we develop and apply ChromTime, a computational method that predicts peaks to be either expanding, contracting, or holding steady between time points. Predicted expanding and contracting peaks can mark regulatory regions associated with transcription factor binding and gene expression changes. Spatial dynamics of peaks provide information about gene expression changes beyond localized signal density changes. ChromTime detects asymmetric expansions and contractions, which for some marks associate with the direction of transcription. ChromTime facilitates the analysis of time course chromatin data in a range of biological systems.

Abstract Background Division of labor between reproductive queens and workers that perform brood care is a hallmark of insect societies. However, studies of the molecular basis of this fundamental dichotomy are limited by the fact that the caste of an individual cannot typically be experimentally manipulated at the adult stage. Here we take advantage of the unique biology of the clonal raider ant, Ooceraea biroi, to study brain gene expression dynamics during experimentally induced transitions between reproductive and brood care behavior. Results Introducing larvae that inhibit reproduction and induce brood care behavior causes much faster changes in adult gene expression than removing larvae. In addition, the general patterns of gene expression differ depending on whether ants transition from reproduction to brood care or vice versa, indicating that gene expression changes between phases are cyclic rather than pendular. Finally, we identify genes that could play upstream roles in regulating reproduction and behavior because they show large and early expression changes in one or both transitions. Conclusions Our analyses reveal that the nature and timing of gene expression changes differ substantially depending on the direction of the transition, and identify a suite of promising candidate molecular regulators of reproductive division of labor that can now be characterized further in both social and solitary animal models. This study contributes to understanding the molecular regulation of reproduction and behavior, as well as the organization and evolution of insect societies.

Abstract Background Comprehensively understanding the dynamics of biological systems is among the biggest current challenges in biology and medicine. To acquire this understanding, researchers have measured the time-series expression profiles of cell lines of various organisms. Biological technologies have also drastically improved, providing a huge amount of information with support from bioinformatics and systems biology. However, the transitions between the activation and inactivation of gene regulations, at the temporal resolution of single time points, are difficult to extract from time-course gene expression profiles. Results Our proposed method reports the activation period of each gene regulation from gene expression profiles and a gene regulatory network. The correctness and effectiveness of the method were validated by analyzing the diauxic shift from glucose to lactose in Escherichia coli. The method completely detected the three periods of the shift; 1) consumption of glucose as nutrient source, 2) the period of seeking another nutrient source and 3) consumption of lactose as nutrient source. We then applied the method to mouse adipocyte differentiation data. Cell differentiation into adipocytes is known to involve two waves of the gene regulation cascade, and sub-waves are predicted. From the gene expression profiles of the cell differentiation process from ES to adipose cells (62 time points), our method acquired four periods; three periods covering the two known waves of the cascade, and a final period of gene regulations when the differentiation to adipocytes was completed. Conclusions Our proposed method identifies the transitions of gene regulations from time-series gene expression profiles. Dynamic analyses are essential for deep understanding of biological systems and for identifying the causes of the onset of diseases such as diabetes and osteoporosis. The proposed method can greatly contribute to the progress of biology and medicine.

Differences in muscle and tendon responsiveness to mechanical stimuli and time courses of adaptive changes may disrupt the interaction of the musculotendinous unit (MTU), increasing the risk for overuse injuries. We monitored training-induced alterations in muscle and tendon biomechanical properties in elite jumpers over 4 years of athletic training to detect potential non-synchronized adaptations within the triceps surae MTU. A combined cross-sectional and longitudinal investigation over 4 years was conducted by analyzing triceps surae MTU mechanical properties in both legs via dynamometry and ultrasonography in 67 elite track and field jumpers and 24 age-matched controls. Fluctuations in muscle and tendon adaptive changes over time were quantified by calculating individual residuals. The cosine similarity of the relative changes of muscle strength and tendon stiffness between sessions served as a measure of uniformity of adaptive changes. Our cross-sectional study was unable to detect clear non-concurrent differences in muscle strength and tendon stiffness in elite jumpers. However, when considering the longitudinal data over several years of training most of the jumpers demonstrated greater fluctuations in muscle strength and tendon stiffness and hence tendon strain compared to controls, irrespective of training period (preparation vs. competition). Moreover, two monitored athletes with chronic Achilles tendinopathy showed in their affected limb lower uniformity in MTU adaptation as well as higher fluctuations in tendon strain over time. Habitual mechanical loading can affect the MTU uniformity in elite jumpers, leading to increased mechanical demand on the tendon over an athletic season and potentially increased risk for overuse injuries. [ABSTRACT FROM AUTHOR]