Search Results (85)

Phosphatidate phosphatase (PAP) governs a critical branchpoint in glycerolipid synthesis by catalyzing the Mg²⁺-dependent dephosphorylation of phosphatidate (PA) to diacylglycerol (DAG), thereby controlling the partitioning of lipid flux between membrane phospholipid synthesis and triacylglycerol (TAG) storage. While the structure, regulation, and function of ScPah1 have been extensively characterized in the non-oleaginous yeast Saccharomyces cerevisiae, far less is known about its ortholog in the oleaginous yeast Yarrowia lipolytica. This review provides a comparative analysis of Pah1 between the two yeasts, encompassing domain architecture, phosphorylation-dependent regulation, enzymatic characterization, and genetic and multi-omics studies. ScPah1 and YlPah1 share a conserved HAD-like catalytic core but diverge substantially in their regulatory domains: YlPah1 features compressed intrinsically disordered regions, an attenuated regulation of phosphorylation (RP) domain, and a massively expanded acidic tail. Unlike ScPah1, which is hyperphosphorylated and cytosolically sequestered during growth, YlPah1 maintains membrane association and increasing protein levels throughout growth. Deletion of PAH1 in Y. lipolytica produces a moderate reduction in TAG levels with evidence of metabolic redundancy, contrasting with the near-complete TAG loss observed in S. cerevisiae. Total PAP activity in Y. lipolytica peaks during exponential growth and does not correlate temporally with TAG accumulation, a dissociation attributable to the contributions of non-Pah1 PAP enzymes. Whether the Nem1–Spo7 homologs in Y. lipolytica form a functional phosphatase complex and the individual contributions of all PAP-encoding genes to lipid homeostasis remain important unresolved questions. Full article

Alpha-band activity has been widely associated with sensory and cognitive processing, yet the functional role of non-phase-locked alpha modulation during early sensory stages remains incompletely understood. In particular, it is unclear whether such activity reflects modality-specific neural mechanisms and to what extent its characterization depends on the frequency range used for its estimation. The present study investigated phase-locked and non-phase-locked alpha activity during visual and auditory oddball tasks, focusing on their temporal dynamics and topographical organization. In addition, we examined whether the observed effects depend on the definition of the alpha band by comparing a conventional frequency range (8–13 Hz), subdivided bands (8–10.5 Hz and 10.5–13 Hz), and individualized frequency ranges based on the individual alpha frequency (IAF). Results revealed clear modality-dependent differences, with shorter latencies for auditory responses and a dissociation between anterior and posterior regions, with auditory activity predominating in central areas and visual activity in parieto-occipital regions. Non-phase-locked alpha activity showed a spatial distribution similar to phase-locked activity but with opposite polarity. Importantly, these patterns were consistent across all frequency definitions, indicating that early alpha modulation is primarily determined by sensory modality and cortical organization, rather than frequency definition. Full article

Background: Autism spectrum disorder (ASD) is characterized by widespread aberrations in brain scalp-level synchronization. Phase-amplitude coupling (PAC), which reflects cross-frequency neuronal oscillatory interactions, serves as a crucial metric for assessing functional brain integration. However, the specific patterns of PAC at both intra-region and inter-region scalp levels in young children with ASD, as well as their precise associations with clinical symptoms, remain unclear. Methods: This study enrolled 237 children with ASD aged 3–9 years and 201 age-matched typically developing (TD) children. Resting-state electroencephalography (EEG) data were acquired from all participants. The analysis systematically examined low-frequency oscillation phase (δ, θ, α) modulation of high-frequency oscillation amplitude (β and low γ) from both intra-region and inter-region dimensions. The PAC strength was quantified using the modulation index (MI). Multiple comparisons were corrected using the Bonferroni method. Finally, correlations between PAC metrics and Autism Behavior Checklist (ABC) scores were analyzed. Results: Compared to the control group, children with ASD exhibited significant frequency-specific PAC abnormalities: (1) Multi-regional γ hyper-coupling: There was a significant enhancement in the modulation of γ amplitude by δ/θ/α phase across the measured scalp regions, suggesting abnormal high-frequency synchronization. (2) Dissociated β modulation patterns: The ASD group showed increased δ–β coupling (predominantly in frontal, temporal, and occipital lobes) alongside significantly reduced α–β coupling (localized to frontal and central regions). This reflects both an abnormal locking of slow-wave activity to the β band and a diminished regulatory role of α oscillations. (3) Clinical correlation: Notably, abnormally elevated PAC strength (particularly in the δ/θ/α–γ bands) showed a negative correlation with clinical symptom severity—that is, stronger coupling was associated with lower scores on the ABC. Conclusions: Leveraging a large-sample dataset, this study characterizes the landscape of aberrant cross-frequency interactions in young children with ASD. Our findings indicate that the neuroelectrical activity in ASD goes beyond mere connectivity anomalies by demonstrating altered PAC strength at both the intra-region and inter-region levels. Notably, the strength of this aberrant intra-region PAC is correlated with clinical symptoms. Full article

Phosphene-based visual neuroprostheses require encoding schemes that preserve task-relevant information while remaining feasible under safety-constrained stimulation. This study proposes a stress-based evaluation framework that reframes phosphene encoder assessment as a tri-objective operating-envelope problem rather than a single-metric comparison. Four representative encoders—rate, sparse, temporal, and optim—were evaluated under structured perturbations using two simulated prosthetic-vision(SPV) benchmarks: EMNIST Letters for symbolic recognition and a COCO-derived balanced subset for a reduced four-class COCO-derived image-level classification task. The final experimental configuration used 20,000/3000/3000 train/validation/test samples for EMNIST and 4000/1000/1000 for the COCO-derived benchmark. The framework combined structured stress sweeps, residual proxy safety-burden analysis, topology-based representation metrics, and stress-integrated utility summaries within a simulation-based evaluation setting. The results showed that clean-conditioning accuracy alone was insufficient to predict encoder behavior under stress. EMNIST exhibited broad operator-dependent degradation, whereas the COCO-derived benchmark showed a lower but more compressed performance regime. Residual proxy safety burden was only loosely aligned with performance, with moderate dissociation between performance and residual proxy safety burden in EMNIST and weaker alignment between these two axes in the COCO-derived benchmark. In the point-estimate utility summaries, the sparse encoder tended to yield comparatively favorable tri-objective utility values within the present single-run simulation-based framework, simplified SPV percept-synthesis operator, and fixed benchmark-specific decoder setting, primarily because it maintained an almost negligible residual proxy safety burden while preserving competitive performance and topology-based representation metrics. Topology-based analysis further indicated that topology-based representation metrics largely tracked task degradation in EMNIST, whereas topology-based representation metrics showed larger relative variation than decoder accuracy within the evaluated simulation setting under degraded COCO-derived conditions. Taken together, these findings provide an exploratory, benchmark-specific assessment suggesting that phosphene encoder evaluation may benefit from a multi-axis operating-envelope-oriented analysis that jointly considers stressed functional performance, residual proxy safety burden, and topology-based representation metrics within the present simplified SPV and fixed-decoder evaluation setting. These results should therefore be interpreted as simulation-level, configuration-dependent observations under a simplified SPV percept-synthesis operator, with safety-related quantities treated as residual proxy safety-burden summaries rather than as direct physiological, electrochemical, clinical, or implant-specific safety measurements. Full article

Reaction time (RT) is widely used as a fundamental indicator of central nervous system processing speed. Numerous studies have shown that RT increases with age, generally interpreted as a decline in information processing efficiency. However, most previous studies have focused on absolute RT values, and it remains unclear whether aging also alters the relative relationships between responses under different task conditions. The present study investigated whether aging affects the relative difference between inside and outside pedal reaction times in a Foot Psychomotor Vigilance Test (Foot PVT). A total of 44 participants were analyzed, including 20 younger adults (24 ± 3 years) and 24 older adults (73 ± 5 years). Participants responded to visual stimuli by pressing either the left or right pedal with the right foot. The difference between inside and outside RT (dRT) was calculated for each participant as an index of relative response structure. Group comparisons and correlation analyses were conducted to examine associations with age, height, physical activity level (PAL), and sleep-related factors. As expected, RTs were consistently longer in older adults across conditions. In contrast, dRT did not differ significantly between younger and older groups, with negligible effect sizes (|d| < 0.1). Furthermore, dRT showed no significant correlations with height, PAL, or sleep-related indices. These findings indicate that while aging affects the overall speed of motor responses, the relative temporal structure between response conditions is preserved. This dissociation between global slowing and stable response structure may represent a fundamental characteristic of neuromotor aging. Full article

Age-related deterioration of the dermal extracellular matrix is driven primarily by fibroblast dysfunction, leading to loss of collagen integrity, elasticity, and structural support. In aesthetic dermatology, injectable and biostimulatory interventions increasingly target qualitative dermal remodelling, with collagen reorganisation widely adopted as a histological endpoint. Picrosirius red (PSR) staining under polarised light remains the most frequently used method for visualising collagen architecture; however, its birefringence colour patterns are often misinterpreted as proxies for collagen subtype shifts, particularly between types I and III. This conceptual review examines the methodological basis of such interpretations. We summarise the biological roles of major dermal collagens and compare current histochemical, immunohistochemical, ultrastructural and molecular methods for collagen assessment. We propose an interpretative framework that separates architectural collagen remodelling from molecular collagen synthesis and addresses the temporal dissociation between early fibre reorganisation and later subtype-specific expression as a plausible explanation for between-study discrepancies. Practical guidance is provided to support responsible interpretation and reporting of PSR-based collagen analyses. PSR is best regarded as a complementary tool for assessing collagen architecture rather than a definitive method for collagen subtype identification. Full article

Background/Objectives: While the descriptive trajectory of COVID-19 is well-documented, there is a methodological gap in quantifying the precise magnitude of risk reduction across multi-year pandemic phases in Brazilian subnational units. This study aimed to fill this gap by applying Generalized Linear Models (GLMs) to quantify the temporal transition of epidemiological risks (Incidence, Mortality, and Case Fatality) in Ceará (2020–2023), using the first year of the pandemic as a statistical baseline. Methods: Ecological time-series study was conducted using official surveillance data. We employed GLMs with Poisson distribution to calculate Rate Ratios (RRs) and 95% Confidence Intervals, allowing for a robust comparative risk modeling between 2020 (reference) and subsequent years (2021–2023). Results: Modeling revealed a significant epidemiological dissociation between transmission and severity. While the risk of incidence remained high through 2022 (RR = 1.42), the mortality risk showed an earlier and more drastic decline, with a 68% reduction as early as 2022 (RR = 0.32) and 99% in 2023 (RR = 0.01). The Case Fatality Rate (CFR) risk decreased consistently from 2021 onwards, reaching its lowest point in 2023 (RR = 0.09; 91% reduction). Conclusions: Between 2020 and 2023, Ceará transitioned to reduced COVID-19 severity. Despite ecological design and data limitations, these findings underscore the importance of resilient health systems and equitable immunization. Full article

This study aimed to determine the absolute bioavailability of quercetin and quantitatively evaluate its pharmacokinetic–pharmacodynamic (PK-PD) relationship regarding acute glucose-lowering effects in normoglycemic and alloxan-induced diabetic rats, addressing whether its in vivo efficacy is driven by the free aglycone or its biotransformed intermediates. Healthy and diabetic rats received single doses of quercetin either orally (75 mg/kg) or intravenously (38 mg/kg). Plasma concentrations of free quercetin were quantified using a validated HPLC-DAD method, and temporal PK-PD relationships between systemic exposure and the percentage variation of glycemia were mathematically evaluated employing Pearson correlation analysis. The absolute bioavailability of free quercetin was significantly impaired by the pathophysiological state, dropping from 59.7% in healthy rats to 40.9% in diabetic subjects. Despite this diminished systemic exposure, oral administration elicited significant hypoglycemic responses. Crucially, the Pearson correlation analysis revealed a pronounced temporal dissociation: the onset of glycemic reduction occurred independently of the maximal circulating concentration of free quercetin. Furthermore, intravenous delivery bypassed first-pass barriers and induced a markedly faster and deeper hypoglycemic effect (up to −47% in diabetic rats). Finally, the diminished bioavailability under diabetic conditions and the stark PK-PD temporal dissociation strongly suggest that quercetin’s acute antihyperglycemic effect is driven by rapid hepatic Phase II biotransformation, implicating conjugated metabolites (rather than the free aglycone) as the principal pharmacological effectors. Full article

Background: Hypertrophic olivary degeneration (HOD) is a rare neurological condition resulting from trans-synaptic degeneration of the inferior olivary nucleus (ION) following disruption of the dentato-rubro-olivary pathway, also known as the Guillain–Mollaret triangle (GMT). Although the clinical and radiologic features of HOD have been previously described, the precise temporal correlation between clinical symptom onset and manifestations on magnetic resonance imaging (MRI) remains difficult to establish, and the factors contributing to accelerated disease progression are poorly understood. Case Presentation: A 43-year-old male presented with intracerebral hemorrhage involving the left midbrain, bilateral pons, and cerebellum. Serial MRI was prospectively performed starting four weeks post-hemorrhage, at which time no signal abnormalities were detected in the ION. However, at 9 weeks, T2 hyperintensity first emerged in the bilateral ION. Approximately 2 weeks after this finding, the patient developed characteristic palatal and lingual tremors, accompanied by a dissociated vertical pendular nystagmus that was predominantly monocular (right eye). In addition, severe dysphagia was also noted, with videofluoroscopic swallowing study (VFSS) showing aspiration across all diets. A subsequent MRI obtained at 13 weeks post-insult (two weeks after tremor onset) revealed newly developed bilateral ION hypertrophy, with the maximal diameter increasing from a 5 mm baseline to 7 mm. Follow-up MRI at 17 weeks post-hemorrhage revealed further progression with increased hypertrophy and signal intensity. Dysphagia persisted throughout the clinical course, ultimately necessitating percutaneous endoscopic gastrostomy (PEG) tube insertion. Conclusions: This case provides rare, longitudinal documentation of the clinico-radiologic progression of HOD, facilitated by a pre-insult baseline MRI and prospective serial imaging. Our findings provide a detailed timeline of the transition from signal abnormality to hypertrophy in correlation with clinical symptom emergence. Full article

Background: Sleep deprivation is one of the major public health and performance risk factors, with documented effects on vigilance, executive function, emotional regulation, and safety-critical behaviour. This review examines how event-related potentials (ERPs)—which provide millisecond-level resolution of cognitive processing stages—can clarify which neural processes are most affected by sleep loss, from early sensory encoding to later evaluative and control-related stages. Materials and Methods: This study was conducted as a systematic review of human studies on sleep deprivation and ERPs. Eligible studies included human participants, focused primarily on acute/total sleep deprivation, and reported ERP outcomes (e.g., amplitude, latency, topography, or related event-locked EEG measures). Searches were performed in major biomedical/psychology databases using sleep deprivation and ERP terms, with additional forward/backward citation searching. Data was extracted in a structured format (participant characteristics, deprivation protocol, ERP methods, behavioural outcomes, ERP findings, and recovery/countermeasure effects). Due to substantial heterogeneity in paradigms, protocols, and ERP methods, findings were synthesised narratively rather than meta-analysed. Risk of bias was assessed with RoB 2 and ROBINS-I. Results: The search identified 854 records, of which 82 studies were included following deduplication, screening, full-text review, and citation chasing. Samples were typically small, highly selected, and dominated by healthy young adults, with frequent attrition related to prolonged wakefulness and EEG data-quality constraints. Across studies, sleep deprivation produced stage-specific and task-dependent ERP effects rather than a single uniform pattern. The most consistent findings involved mid-to-late components. These components typically showed prolonged latency and reduced amplitude. In some cases, amplitude increases were observed and interpreted as compensatory recruitment. Early sensory/pre-attentive components (e.g., P1/N1/MMN/P50) were often relatively preserved, but showed selective vulnerability, including latency slowing, reduced filtering/gating, or decreased phase locking. A recurring observation was a behaviour–ERP dissociation, where ERP abnormalities were detectable even when behavioural impairment was modest, indicating covert neural inefficiency or compensation. Recovery sleep, naps, and countermeasures (e.g., modafinil, caffeine) produced partial, component-specific recovery, with amplitude and latency often recovering at different rates. Conclusions: The evidence indicates that sleep deprivation primarily disrupts higher-order, late-stage, and temporally coordinated neural processing, while earlier sensory processing is often preserved but becomes slower and less stable. Among ERP markers, the P300/P3 family is the most robust and informative signature of sleep loss effects and recovery. ERPs are therefore a sensitive tool for detecting neural dysfunction and compensation under sleep deprivation, including changes that may precede overt behavioural decline. Future research must improve the generalisability and reproducibility of ERP findings by employing larger, more diverse samples, alongside more standardised methodological, recording, and reporting practices. Full article

Background/Objectives: The oscillatory dynamics underlying stage-specific processing in working memory (WM) remain incompletely characterized, particularly under varying memory loads. We examined the load-dependent modulation of theta (4–7 Hz), lower alpha (8–10 Hz), and upper alpha (11–13 Hz) absolute power during encoding, maintenance, and retrieval using quantitative EEG in a modified Sternberg task that temporally dissociates these stages. Methods: Forty-five healthy young adults performed trials with memory sets of three, five, or six uppercase consonants, followed by a lowercase probe. EEG data were analyzed using cluster-based permutation testing, and brain–behavior relationships were assessed using regression models. Results: Fronto-central theta power increased with memory load and was significantly higher during retrieval than during encoding or maintenance. Greater theta power during retrieval predicted faster reaction times in the three-letter condition. Alpha oscillations showed robust stage effects. Lower alpha power was higher during maintenance than retrieval across loads and exhibited a load effect during maintenance (three > six letters) in occipital regions. Upper alpha power was consistently maximal during maintenance across all loads, involving bilateral fronto-central, parietal, and occipital regions. Critically, under moderate load (five letters), higher upper alpha power predicted a greater probability of correct responses across task stages. Conclusions: These findings demonstrate a functional dissociation between oscillatory bands across temporally separated WM stages: theta activity was retrieval-dominant and associated with response speed, whereas alpha, particularly upper alpha, was maintenance-dominant and supported accuracy under increased mnemonic demand. Full article

This study evaluated whether the complexity and temporal dynamics of environmental enrichment during the nursery phase are associated with piglets’ threat-related responses and affective state using a multimodal approach. We combined an Attentional Bias Test (ABT) with bioacoustic measures, Qualitative Behavior Assessment (QBA), and biomarkers (hair cortisol and serum BDNF). In a commercial nursery setting, 675 piglets were allocated to three treatments: UNI (single continuous item: chains), ALT (chains plus an additional object rotated weekly), and SIM (continuous simultaneous provision of multiple objects). A subsample of 32 piglets underwent the ABT (UNI, n = 10; ALT, n = 11; SIM, n = 11). Most ABT measures related to threat-directed attention and space use showed no detectable treatment differences under the present protocol, and feeding latency was affected by stimulus exposure but not by treatment. In contrast, treatments differed in coping-related responses: UNI showed a higher frequency of excretions, ALT showed a longer standing-inactive duration, and SIM showed more escape attempts. Vocalizations were restricted to harsh grunts, with ALT showing longer harsh-grunt duration and higher total vocal output. QBA and biomarkers further differentiated treatments: SIM showed calmer/less tense expressive profiles, whereas UNI showed higher post-exposure hair cortisol and lower serum BDNF than the more complex conditions. Overall, enrichment-related differences were more consistently detected in coping-related behavior, QBA, and biomarkers than in ABT attentional measures, suggesting that enrichment implementation (stable vs. rotational) shapes partially dissociable behavioral and physiological adaptation profiles, and that both more complex strategies showed a more favorable biological profile than UNI. Full article

This study compares the breadth and temporal dynamics of positive and negative priming effects depending on the depth of stimulus processing. Two experiments were conducted using a Naming task (shallow processing) and a semantic Categorisation task into “living/non-living” (deep processing) with varying categorical proximity of the prime and probe. A dissociation between the patterns of positive and negative priming was observed. Positive priming emerged exclusively in the Categorisation task, demonstrated graded sensitivity to categorical proximity, and increased with longer response times, consistent with spreading activation models. Negative priming, by contrast, was observed in both tasks: in the Naming task, it appeared as a stable effect independent of categorical proximity, whereas in the Categorisation task, it manifested as a short-lived effect restricted to fast responses. These findings support the early automatic inhibition account and contradict the predictions of episodic retrieval models. Overall, the results indicate functional differences between positive and negative priming under the present conditions: whereas positive priming appears to implement fine-grained semantic tuning, negative priming serves as a coarse, early inhibitory mechanism operating at the level of generalised representations. Full article

Background: Hemodynamic failure remains a major determinant of mortality in critical illness, yet its detection is often delayed because conventional monitoring relies predominantly on Eulerian measurements that quantify pressure and flow magnitude without resolving the spatial and temporal organization of circulation. Consequently, clinically significant states of dysfunction may persist despite apparently stable hemodynamic indices. The Geometry of Shock is a conceptual and hypothesis-generating multi-scale framework intended to integrate established cardiovascular physiology with emerging computational approaches for the analysis of circulatory dysfunction. Framework: The proposed framework combines Guytonian venous return physiology and cardiopulmonary interactions with Lagrangian flow topology, geometric representations of circulatory equilibrium, topological data analysis, and physics-constrained inverse modeling. Rather than focusing exclusively on static thresholds of pressure and flow, the framework proposes a structural interpretation of circulation centered on the dynamic organization and coherence of blood transport across cardiovascular domains. Within this paradigm, under-recognized hemodynamic phenotypes—including stressed volume failure, oscillatory shock during spontaneous breathing, macro–microcirculatory decoupling, and pulmonary vascular pressure–flow dissociation—may emerge from disrupted coupling between vascular, cardiac, pulmonary, and microcirculatory systems. These states may represent reversible structural transitions in venous return geometry and cardiopulmonary interaction preceding overt circulatory collapse. Conclusions: By reframing shock as a disorder of circulatory structure and coherence rather than solely a deficit in flow, this framework proposes a mechanistic foundation that may support future approaches aimed at earlier recognition of instability, improved physiological characterization of hemodynamic phenotypes, and future development and prospective validation of physiology-informed computational decision-support strategies in critical care. These concepts remain exploratory and hypothesis-generating rather than clinically validated. Full article

Background: Radio Electric Asymmetric Conveyer (REAC) neurobiological modulation is proposed as an approach designed to interact with endogenous bioelectrical processes involved in cortical regulation. However, its electrophysiological correlates in physiologically preserved neural systems remain insufficiently characterized. The present study explored whether a standardized REAC Brain Wave Optimization Gamma (BWO-G_B) protocol is associated with measurable changes in resting-state EEG activity in healthy adults. Methods: Nine neurologically healthy participants completed a standardized REAC BWO-G_B protocol consisting of 18 sessions administered over six consecutive days. Resting-state EEG recordings were obtained before and after the intervention. Spectral power was analyzed across the 1–100 Hz range. Multivariate organization of cortical activity was explored using Principal Component Analysis (PCA) and Canonical Discriminant Analysis (CDA), with CDA used only as a descriptive visualization of within-dataset multivariate organization. Cross-correlation analysis was applied to evaluate changes in inter-regional temporal synchronization. Individual-level non-parametric testing (Wilcoxon signed-rank test) was conducted only to characterize within-subject directional spectral modulation across the recorded montage. Results: Post-intervention EEG recordings showed a consistent redistribution of spectral power across cortical regions, predominantly within frequencies below approximately 20 Hz. This pattern was observed across subjects at the individual level. Multivariate analysis revealed a dissociation between PCA, which showed partial overlap between conditions, and CDA, which descriptively showed within-dataset separability between baseline and post-intervention cortical states. Cross-correlation analysis indicated a spatially differentiated redistribution of temporal synchronization across cortical regions. At the individual level, descriptive Wilcoxon analyses indicated broadband spectral differences in seven of nine participants (p < 0.05), with consistent directional trends across all subjects; these p-values should not be interpreted as confirmatory statistical evidence. Conclusions: The findings indicate the presence of a reproducible electrophysiological pattern observed after completion of the REAC BWO-G_B protocol in healthy adults. The observed combination of spectral redistribution, descriptive multivariate organization, and changes in temporal synchronization is consistent with a structured post-intervention modification of cortical activity organization within the present dataset. However, given the exploratory design, small sample size, absence of a control condition, and absence of objective vigilance monitoring, these results should be interpreted cautiously and should not be considered as evidence of intervention-specific effects. Further controlled studies are required to determine specificity, underlying mechanisms, and potential functional relevance. Full article