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Faithful transfer of parental histones to newly replicated daughter DNA strands is critical for inheritance of epigenetic states. Although replication proteins that facilitate parental histone transfer have been identified, how intact histone H3-H4 tetramers travel from the front to the back of the replication fork remains unknown. Here, we use AlphaFold-Multimer structural predictions combined with biochemical and genetic approaches to identify the Mrc1/CLASPIN subunit of the replisome as a histone chaperone. Mrc1 contains a conserved histone-binding domain that forms a brace around the H3-H4 tetramer mimicking nucleosomal DNA and H2A-H2B histones, is required for heterochromatin inheritance, and promotes parental histone recycling during replication. We further identify binding sites for the FACT histone chaperone in Swi1/TIMELESS and DNA polymerase α that are required for heterochromatin inheritance. We propose that Mrc1, in concert with FACT acting as a mobile co-chaperone, coordinates the distribution of parental histones to newly replicated DNA.
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Chromatin-based epigenetic memory relies on the symmetric distribution of parental histones to newly synthesized daughter DNA strands, aided by histone chaperones within the DNA replication machinery. However, the mechanism of parental histone transfer remains elusive. Here, we reveal that in fission yeast, the replisome protein Mrc1 plays a crucial role in promoting the transfer of parental histone H3-H4 to the lagging strand, ensuring proper heterochromatin inheritance. In addition, Mrc1 facilitates the interaction between Mcm2 and DNA polymerase alpha, two histone-binding proteins critical for parental histone transfer. Furthermore, Mrc1's involvement in parental histone transfer and epigenetic inheritance is independent of its known functions in DNA replication checkpoint activation and replisome speed control. Instead, Mrc1 interacts with Mcm2 outside of its histone-binding region, creating a physical barrier to separate parental histone transfer pathways. These findings unveil Mrc1 as a key player within the replisome, coordinating parental histone segregation to regulate epigenetic inheritance.
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Chromatin-based epigenetic memory relies on the accurate distribution of parental histone H3-H4 tetramers to newly replicated DNA strands. Mcm2, a subunit of the replicative helicase, and Dpb3/4, subunits of DNA polymerase ε, govern parental histone H3-H4 deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here, using fission yeast heterochromatin inheritance systems that eliminate interference from initiation pathways, we show that a Mcm2 histone binding mutation severely disrupts heterochromatin inheritance, while mutations in Dpb3/4 cause only moderate defects. Surprisingly, simultaneous mutations of Mcm2 and Dpb3/4 stabilize heterochromatin inheritance. eSPAN (enrichment and sequencing of protein-associated nascent DNA) analyses confirmed the conservation of Mcm2 and Dpb3/4 functions in parental histone H3-H4 segregation, with their combined absence showing a more symmetric distribution of parental histone H3-H4 than either single mutation alone. Furthermore, the FACT histone chaperone regulates parental histone transfer to both strands and collaborates with Mcm2 and Dpb3/4 to maintain parental histone H3-H4 density and faithful heterochromatin inheritance. These results underscore the importance of both symmetric distribution of parental histones and their density at daughter strands for epigenetic inheritance and unveil distinctive properties of parental histone chaperones during DNA replication.
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Histonas , Schizosaccharomyces , Histonas/metabolismo , Chaperonas de Histonas/genética , Chaperonas de Histonas/metabolismo , Heterocromatina/genética , Replicación del ADN/genética , ADN/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Epigénesis GenéticaRESUMEN
BACKGROUND: This study aimed to investigate the efficacy of circuits-based paired associative stimulation (PAS) in adults with amnestic mild cognitive impairment (aMCI). METHODS: We conducted a parallel-group, randomised, controlled clinical trial. Initially, a cohort of healthy subjects was recruited to establish the cortical-hippocampal circuits by tracking white matter fibre connections using diffusion tensor imaging. Subsequently, patients diagnosed with aMCI, matched for age and education, were randomly allocated in a 1:1 ratio to undergo a 2-week intervention, either circuit-based PAS or sham PAS. Additionally, we explored the relationship between changes in cognitive performance and the functional connectivity (FC) of cortical-hippocampal circuits. RESULTS: FCs between hippocampus and precuneus and between hippocampus and superior frontal gyrus (orbital part) were most closely associated with the Auditory Verbal Learning Test (AVLT)_N5 score in 42 aMCI patients, thus designated as target circuits. The AVLT_N5 score improved from 2.43 (1.43) to 5.29 (1.98) in the circuit-based PAS group, compared with 2.52 (1.44) to 3.86 (2.39) in the sham PAS group (p=0.003; Cohen's d=0.97). A significant decrease was noted in FC between the left hippocampus and left precuneus in the circuit-based PAS group from baseline to postintervention (p=0.013). Using a generalised linear model, significant group×FC interaction effects for the improvements in AVLT_N5 scores were found within the circuit-based PAS group (B=3.4, p=0.017). CONCLUSIONS: Circuit-based PAS effectively enhances long-term delayed recall in adults diagnosed with aMCI, which includes individuals aged 50-80 years. This enhancement is potentially linked to the decreased functional connectivity between the left hippocampus and left precuneus. TRIAL REGISTRATION NUMBER: ChiCTR2100053315; Chinese Clinical Trial Registry.
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The objectives of the study were to systematically evaluate the rehabilitation effect of noninvasive brain stimulation (NIBS) on upper extremity motor function and activities of daily living in stroke patients and to prioritize various stimulation protocols for reliable evidence-based medical recommendations in patients with upper extremity motor dysfunction after stroke. Web of Science, PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, and CBM were searched to collect all randomized controlled trials (RCTs) of NIBS to improve upper extremity motor function in stroke patients. The retrieval time was from the establishment of all databases to May 2023. According to the Cochrane system evaluation manual, the quality of the included studies was evaluated, and the data were extracted. Statistical analysis was carried out by using RevMan 5.3, R 4.3.0, and Stata 17.0 software. Finally, 94 RCTs were included, with a total of 5546 patients. Meta-analysis showed that NIBS improved the Fugl-Meyer assessment (FMA) score (mean difference (MD) = 6.51, 95% CI 6.20 ~ 6.82, P < 0.05), MBI score (MD = 7.69, 95% CI 6.57 ~ 8.81, P < 0.05), ARAT score (MD = 5.06, 95% CI 3.85 ~ 6.27, P < 0.05), and motor evoked potential (MEP) amplitude. The modified Ashworth scale score (MD = - 0.37, 95% CI - 0.60 to - 0.14, P < 0.05), National Institutes of Health Stroke Scale score (MD = - 2.17, 95% CI - 3.32 to - 1.11, P < 0.05), incubation period of MEP (MD = - 0.72, 95% CI - 1.06 to - 0.38, P < 0.05), and central motor conduction time (MD = - 0.90, 95% CI - 1.29 to - 0.50, P < 0.05) were decreased in stroke patients. Network meta-analysis showed that the order of interventions in improving FMA scores from high to low was anodal-transcranial direct current stimulation (tDCS) (surface under the cumulative ranking curve (SUCRA) = 83.7%) > cathodal-tDCS (SUCRA = 80.2%) > high-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (SUCRA = 68.5%) > low-frequency (LF)-rTMS (SUCRA = 66.5%) > continuous theta burst stimulation (cTBS) (SUCRA = 54.2%) > bilateral-tDCS (SUCRA = 45.2%) > intermittent theta burst stimulation (iTBS) (SUCRA = 34.1%) > sham-NIBS (SUCRA = 16.0%) > CR (SUCRA = 1.6%). In terms of improving MBI scores, the order from high to low was anodal-tDCS (SUCRA = 88.7%) > cathodal-tDCS (SUCRA = 85.4%) > HF-rTMS (SUCRA = 63.4%) > bilateral-tDCS (SUCRA = 56.0%) > LF-rTMS (SUCRA = 54.2%) > iTBS (SUCRA = 32.4%) > sham-NIBS (SUCRA = 13.8%) > CR (SUCRA = 6.1%). NIBS can effectively improve upper extremity motor function and activities of daily living after stroke. Among the various NIBS protocols, anodal-tDCS demonstrated the most significant intervention effect, followed by cathodal-tDCS and HF-rTMS.
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Actividades Cotidianas , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Extremidad Superior , Humanos , Extremidad Superior/fisiopatología , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/terapia , Metaanálisis en Red , Recuperación de la Función/fisiología , Estimulación Magnética Transcraneal/métodos , Estimulación Transcraneal de Corriente Directa/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The most challenging aspect of rehabilitation is the repurposing of residual functional plasticity in stroke patients. To achieve this, numerous plasticity-based clinical rehabilitation programs have been developed. This study aimed to investigate the effects of motor imagery (MI)-based brain-computer interface (BCI) rehabilitation programs on upper extremity hand function in patients with chronic hemiplegia. DESIGN: A 2010 Consolidated Standards for Test Reports (CONSORT)-compliant randomized controlled trial. METHODS: Forty-six eligible stroke patients with upper limb motor dysfunction participated in the study, six of whom dropped out. The patients were randomly divided into a BCI group and a control group. The BCI group received BCI therapy and conventional rehabilitation therapy, while the control group received conventional rehabilitation only. The Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score was used as the primary outcome to evaluate upper extremity motor function. Additionally, functional magnetic resonance imaging (fMRI) scans were performed on all patients before and after treatment, in both the resting and task states. We measured the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), z conversion of ALFF (zALFF), and z conversion of ReHo (ReHo) in the resting state. The task state was divided into four tasks: left-hand grasping, right-hand grasping, imagining left-hand grasping, and imagining right-hand grasping. Finally, meaningful differences were assessed using correlation analysis of the clinical assessments and functional measures. RESULTS: A total of 40 patients completed the study, 20 in the BCI group and 20 in the control group. Task-related blood-oxygen-level-dependent (BOLD) analysis showed that when performing the motor grasping task with the affected hand, the BCI group exhibited significant activation in the ipsilateral middle cingulate gyrus, precuneus, inferior parietal gyrus, postcentral gyrus, middle frontal gyrus, superior temporal gyrus, and contralateral middle cingulate gyrus. When imagining a grasping task with the affected hand, the BCI group exhibited greater activation in the ipsilateral superior frontal gyrus (medial) and middle frontal gyrus after treatment. However, the activation of the contralateral superior frontal gyrus decreased in the BCI group relative to the control group. Resting-state fMRI revealed increased zALFF in multiple cerebral regions, including the contralateral precentral gyrus and calcarine and the ipsilateral middle occipital gyrus and cuneus, and decreased zALFF in the ipsilateral superior temporal gyrus in the BCI group relative to the control group. Increased zReHo in the ipsilateral cuneus and contralateral calcarine and decreased zReHo in the contralateral middle temporal gyrus, temporal pole, and superior temporal gyrus were observed post-intervention. According to the subsequent correlation analysis, the increase in the FMA-UE score showed a positive correlation with the mean zALFF of the contralateral precentral gyrus (r = 0.425, P < 0.05), the mean zReHo of the right cuneus (r = 0.399, P < 0.05). CONCLUSION: In conclusion, BCI therapy is effective and safe for arm rehabilitation after severe poststroke hemiparesis. The correlation of the zALFF of the contralateral precentral gyrus and the zReHo of the ipsilateral cuneus with motor improvements suggested that these values can be used as prognostic measures for BCI-based stroke rehabilitation. We found that motor function was related to visual and spatial processing, suggesting potential avenues for refining treatment strategies for stroke patients. TRIAL REGISTRATION: The trial is registered in the Chinese Clinical Trial Registry (number ChiCTR2000034848, registered July 21, 2020).
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Interfaces Cerebro-Computador , Imágenes en Psicoterapia , Imagen por Resonancia Magnética , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Extremidad Superior , Humanos , Masculino , Rehabilitación de Accidente Cerebrovascular/métodos , Femenino , Persona de Mediana Edad , Extremidad Superior/fisiopatología , Imágenes en Psicoterapia/métodos , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/complicaciones , Anciano , Adulto , Imaginación/fisiología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatologíaRESUMEN
The Marine Predator Algorithm (MPA) has unique advantages as an important branch of population-based algorithms. However, it emerges more disadvantages gradually, such as traps to local optima, insufficient diversity, and premature convergence, when dealing with complex problems in practical industrial engineering design applications. In response to these limitations, this paper proposes a novel Improved Marine Predator Algorithm (IMPA). By introducing an adaptive weight adjustment strategy and a dynamic social learning mechanism, this study significantly improves the encounter frequency and efficiency between predators and preys in marine ecosystems. The performance of the IMPA was evaluated through benchmark functions, CEC2021 suite problems, and engineering design problems, including welded beam design, tension/compression spring design, pressure vessel design, and three-bar design. The results indicate that the IMPA has achieved significant success in the optimization process over other methods, exhibiting excellent performance in both solving optimal parameter solutions and optimizing objective function values. The IMPA performs well in terms of accuracy and robustness, which also proves its efficiency in successfully solving complex industrial engineering design problems.
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The rich information underlying graphs has inspired further investigation of unsupervised graph representation. Existing studies mainly depend on node features and topological properties within static graphs to create self-supervised signals, neglecting the temporal components carried by real-world graph data, such as timestamps of edges. To overcome this limitation, this paper explores how to model temporal evolution on dynamic graphs elegantly. Specifically, we introduce a new inductive bias, namely temporal translation invariance, which illustrates the tendency of the identical node to keep similar labels across different timespans. Based on this assumption, we develop a dynamic graph representation framework CLDG that encourages the node to maintain locally consistent temporal translation invariance through contrastive learning on different timespans. Except for standard CLDG which only considers explicit topological links, our further proposed CLDGï¼ï¼additionally employs graph diffusion to uncover global contextual correlations between nodes, and designs a multi-scale contrastive learning objective composed of local-local, local-global, and global-global contrasts to enhance representation capabilities. Interestingly, by measuring the consistency between different timespans to shape anomaly indicators, CLDG and CLDGï¼ï¼are seamlessly integrated with the task of spotting anomalies on dynamic graphs, which has broad applications in many high-impact domains, such as finance, cybersecurity, and healthcare. Experiments demonstrate that CLDG and CLDGï¼ï¼both exhibit desirable performance in downstream tasks including node classification and dynamic graph anomaly detection. Moreover, CLDG significantly reduces time and space complexity by implicitly exploiting temporal cues instead of complicated sequence models. The code and data are available at https://github.com/yimingxu24/CLDG.
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Redes Neurales de la Computación , Algoritmos , Factores de Tiempo , Humanos , Gráficos por ComputadorRESUMEN
Background: Brachial plexus injury is a common severe peripheral nerve injury with high disability. At present, the bibliometric analysis of brachial plexus injury is basically unknown. Methods: This article analyzes the data retrieved to the web of science and uses the R language (version 4.2), Citespace (version 6.1.R3 Advanced), Vosviewer (Lei deng university) to make a scientific map. Specifically, we analyze the main publication countries, institutions, journals where the article is published, and the cooperative relationship between different institutions, the relationship between authors, main research directions in this field, and current research hotspots. Results: From 1980 to 2022, the total number of publications is 1542. In terms of countries where articles were published, 551 records were published in the United States, accounting for 35% of the total. With 74 articles, Fudan University ranks first in the world in terms of the number of articles issued by the institution, followed by 72 articles from Mayo Clinic. The magazine with the largest number of articles is JOURNAL OF HAND SURGERY-AMERICAN VOLUME, which has published 87 articles in total. GU YD (Gu Yu-Dong) team (Fudan University) and spinner RJ (Robert J Spinner) team (Mayo clinic) are in a leading position in this field. Nerve transfer and nerve reconstruction have been a hot topic of brachial plexus injury. "Spinal nerve root repair and reimplantation of avulsed ventral roots into the spinal cord after brachial plexus injury" has the strongest citation bursts. Conclusion: Research on brachial plexus injury shows a trend of increasing heat. At present, there is a lack of communication and cooperation between scholars from different countries. Nerve transfer and nerve reconstruction are the current and future research directions in the treatment of brachial plexus injury.
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BACKGROUND: Recent studies have indicated that depression is associated with persistent postoperative pain and decreased satisfaction following foot and ankle surgery. This study aimed to evaluate the effect of perioperative duloxetine on postoperative outcomes of anterior talofibular ligament (ATFL) surgical repair for chronic ankle instability (CAI) in patients with depression. We further sought to evaluate patients' satisfaction and side effects related to duloxetine. MATERIAL AND METHODS: Patients undergoing ATFL repair were screened for depression preoperatively with the Patient Health Questionnaire (PHQ-9). Among 249 patients who underwent arthroscopic or open surgical Brostrom repair of the ATFL, 120 patients were identified as being "possibly depressed" and were included in the study. Sixty patients were randomly assigned to the duloxetine group (one day preoperatively and for 6 weeks postoperatively), and the other sixty were randomized to the placebo group. Painkillers and opioid consumption, pain scores, and patient satisfaction were recorded at 12, 24, 48, and 72hours postoperatively and at follow-up visits 1, 3, and 6 months after surgery. Patient-reported outcome measures (PROMs) were assessed preoperatively and at 3, 6, 12 and 24 months postoperatively. Duloxetine-related side effects such as nausea/vomiting and fatigue were also recorded. RESULTS: The patients in the duloxetine group reported a significantly longer time to rescue analgesic and reduced opioid requirements (including celecoxib, pregabalin, acetaminophen, and tramadol). The patients experienced decreased pain intensity and greater satisfaction with their pain management at 24, 48, 72h and 1 and 3 months after surgery (p<0.05). The duloxetine group also had significantly better clinical and functional outcomes at 3 and 6 months of follow-up compared to the placebo group (p<0.05). The occurrence and rate of symptoms of duloxetine side effects were not significant. DISCUSSION: Depression is an important factor to consider and address because its presence before surgery can predict poor postoperative outcomes, including more severe postoperative pain, persistent postoperative pain, and increased consumption of painkillers and opioids. CONCLUSION: Perioperative administration of duloxetine following ATFL repair for CAI in patients with depression increased the time to first postoperative rescue analgesic request and reduced both opioid consumption and postoperative pain. This approach also led to a high level of patient satisfaction. In addition, duloxetine improved the quality of recovery without leading to significant side effects. LEVEL OF EVIDENCE: I; prospective randomized controlled trial.
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AIMS: The present study aimed to explore the effect of cortico-cortical paired-associative stimulation (ccPAS) in modulating hyperdirect pathway and its influence on balance performance. METHODS: Forty healthy participants were randomly allocated to the active ccPAS group (n = 20) or the sham ccPAS group (n = 20). The primary motor cortex and subthalamic nucleus were stimulated sequentially with ccPAS. Unlike the active ccPAS group, one wing of coil was tilted to form a 90° angle with scalp of stimulation locations for the sham ccPAS group. Magnetic resonance imaging, functional reach test (FRT), timed up and go (TUG) test, and limit of stability (LOS) test were performed, and correlation between them was also analyzed. RESULTS: Three participants in the sham ccPAS group were excluded because of poor quality of NIfTI images. The active group had strengthened hyperdirect pathway, increased functional connectivity (FC) between orbital part of frontal cortex and bilateral precuneus, and decreased FC among basal ganglia (all p < 0.05). Regional network properties of triangular and orbital parts of IFG, middle cingulate cortex, and hippocampus increased. The active group performed better in FRT and LOS (all p < 0.05). FRT positively correlated with FC of the hyperdirect pathway (r = 0.439, p = 0.007) and FCs between orbital part of frontal cortex and bilateral precuneus (all p < 0.05). CONCLUSION: The ccPAS enhanced balance performance by promotion-like plasticity mechanisms through the hyperdirect pathway.
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Encéfalo , Núcleo Subtalámico , Humanos , Encéfalo/diagnóstico por imagen , Cuero Cabelludo , Ganglios Basales , Lóbulo FrontalRESUMEN
Introduction: Chronic lower back pain (cLBP), frequently attributed to lumbar disk herniation (LDH), imposes substantial limitations on daily activities. Despite its prevalence, the neural mechanisms underlying lower back pain remain incompletely elucidated. Functional magnetic resonance imaging (fMRI) emerges as a non-invasive modality extensively employed for investigating neuroplastic changes in neuroscience. In this study, task-based and resting-state fMRI methodologies are employed to probe the central mechanisms of lower back pain. Methods: The study included 71 chronic lower back pain patients (cLBP group) due to LDH and 80 age, gender, and education-matched healthy volunteers (HC group). The subjects are mainly middle-aged and elderly individuals. Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopedic Association Scores (JOA) were recorded. Resting-state and task-based fMRI data were collected. Results/discussion: No significant differences were observed in age, gender, and education level between the two groups. In the cLBP group during task execution, there was diffuse and reduced activation observed in the primary motor cortex and supplementary motor area. Additionally, during resting states, notable changes were detected in brain regions, particularly in the frontal lobe, primary sensory area, primary motor cortex, precuneus, and caudate nucleus, accompanied by alterations in Amplitude of Low Frequency Fluctuation, Regional Homogeneity, Degree Centrality, and functional connectivity. These findings suggest that chronic lower back pain may entail reduced excitability in sensory-motor areas during tasks and heightened activity in the sensory-motor network during resting states, along with modified functional connectivity in various brain regions.
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BACKGROUND: The review highlights recent advancements and innovative uses of nerve transfer surgery in treating dysfunctions caused by central nervous system (CNS) injuries, with a particular focus on spinal cord injury (SCI), stroke, traumatic brain injury, and cerebral palsy. METHODS: A comprehensive literature search was conducted regarding nerve transfer for restoring sensorimotor functions and bladder control following injuries of spinal cord and brain, across PubMed and Web of Science from January 1920 to May 2023. Two independent reviewers undertook article selection, data extraction, and risk of bias assessment with several appraisal tools, including the Cochrane Risk of Bias Tool, the JBI Critical Appraisal Checklist, and SYRCLE's ROB tool. The study protocol has been registered and reported following PRISMA and AMSTAR guidelines. RESULTS: Nine hundred six articles were retrieved, of which 35 studies were included (20 on SCI and 15 on brain injury), with 371 participants included in the surgery group and 192 in the control group. These articles were mostly low-risk, with methodological concerns in study types, highlighting the complexity and diversity. For SCI, the strength of target muscle increased by 3.13 of Medical Research Council grade, and the residual urine volume reduced by more than 100 ml in 15 of 20 patients. For unilateral brain injury, the Fugl-Myer motor assessment (FMA) improved 15.14-26 score in upper extremity compared to 2.35-26 in the control group. The overall reduction in Modified Ashworth score was 0.76-2 compared to 0-1 in the control group. Range of motion (ROM) increased 18.4-80° in elbow, 20.4-110° in wrist and 18.8-130° in forearm, while ROM changed -4.03°-20° in elbow, -2.08°-10° in wrist, -2.26°-20° in forearm in the control group. The improvement of FMA in lower extremity was 9 score compared to the presurgery. CONCLUSION: Nerve transfer generally improves sensorimotor functions in paralyzed limbs and bladder control following CNS injury. The technique effectively creates a 'bypass' for signals and facilitates functional recovery by leveraging neural plasticity. It suggested a future of surgery, neurorehabilitation and robotic-assistants converge to improve outcomes for CNS.
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Transferencia de Nervios , Traumatismos de la Médula Espinal , Humanos , Transferencia de Nervios/métodos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/fisiopatología , Lesiones Traumáticas del Encéfalo/cirugía , Lesiones Traumáticas del Encéfalo/complicaciones , Nervios Periféricos/cirugía , Nervios Periféricos/trasplante , Parálisis Cerebral/cirugíaRESUMEN
Inheritance of epigenetic information is critical for maintaining cell identity. The transfer of parental histone H3-H4 tetramers, the primary carrier of epigenetic modifications on histone proteins, represents a crucial yet poorly understood step in the inheritance of epigenetic information. Here, we show the lagging strand DNA polymerase, Pol δ, interacts directly with H3-H4 and that the interaction between Pol δ and the sliding clamp PCNA regulates parental histone transfer to lagging strands, most likely independent of their roles in DNA synthesis. When combined, mutations at Pol δ and Mcm2 that compromise parental histone transfer result in a greater reduction in nucleosome occupancy at nascent chromatin than mutations in either alone. Last, PCNA contributes to nucleosome positioning on nascent chromatin. On the basis of these results, we suggest that the PCNA-Pol δ complex couples lagging strand DNA synthesis to parental H3-H4 transfer, facilitating epigenetic inheritance.
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ADN Polimerasa III , Replicación del ADN , Epigénesis Genética , Histonas , Antígeno Nuclear de Célula en Proliferación , Antígeno Nuclear de Célula en Proliferación/metabolismo , Antígeno Nuclear de Célula en Proliferación/genética , Histonas/metabolismo , ADN Polimerasa III/metabolismo , ADN Polimerasa III/genética , Nucleosomas/metabolismo , Nucleosomas/genética , ADN/metabolismo , Humanos , Unión Proteica , Mutación , Cromatina/metabolismo , Cromatina/genéticaRESUMEN
BACKGROUND: The volumes of the hippocampal subfields are related to poststroke cognitive dysfunctions. However, it remains unclear whether contralesional hippocampal subfield volume contributes to cognitive impairment. This study aimed to investigate the volumetric differences in the contralesional hippocampal subfields between patients with left and right hemisphere strokes (LHS/RHS). Additionally, correlations between contralesional hippocampal subfield volumes and clinical outcomes were explored. METHODS: Fourteen LHS (13 males, 52.57 ± 7.10 years), 13 RHS (11 males, 51.23 ± 15.23 years), and 18 healthy controls (11 males, 46.94 ± 12.74 years) were enrolled. Contralesional global and regional hippocampal volumes were obtained with T1-weighted images. Correlations between contralesional hippocampal subfield volumes and clinical outcomes, including the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), were analyzed. Bonferroni correction was applied for multiple comparisons. RESULTS: Significant reductions were found in contralesional hippocampal as a whole (adjusted p = .011) and its subfield volumes, including the hippocampal tail (adjusted p = .005), cornu ammonis 1 (CA1) (adjusted p = .002), molecular layer (ML) (adjusted p = .004), granule cell and ML of the dentate gyrus (GC-ML-DG) (adjusted p = .015), CA3 (adjusted p = .009), and CA4 (adjusted p = .014) in the RHS group compared to the LHS group. MoCA and MMSE had positive correlations with volumes of contralesional hippocampal tail (p = .015, r = .771; p = .017, r = .763) and fimbria (p = .020, r = .750; p = .019, r = .753) in the LHS group, and CA3 (p = .007, r = .857; p = .009, r = .838) in the RHS group, respectively. CONCLUSION: Unilateral stroke caused volumetric differences in different hippocampal subfields contralesionally, which correlated to cognitive impairment. RHS leads to greater volumetric reduction in the whole contralesional hippocampus and specific subfields (hippocampal tail, CA1, ML, GC-ML-DG, CA3, and CA4) compared to LHS. These changes are correlated with cognitive impairments, potentially due to disrupted neural pathways and interhemispheric communication.
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Disfunción Cognitiva , Hipocampo , Imagen por Resonancia Magnética , Accidente Cerebrovascular , Humanos , Masculino , Persona de Mediana Edad , Femenino , Hipocampo/patología , Hipocampo/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/patología , Adulto , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/etiología , Lateralidad Funcional/fisiología , Cognición/fisiología , Anciano , Pruebas de Estado Mental y DemenciaRESUMEN
Background: The chronic pain arising from knee osteoarthritis (KOA) is a prevalent clinical manifestation. As a traditional Chinese approach, electroacupuncture (EA) has a positive influence in relieving chronic pain from KOA. The study aims to explore functional connectivity (FC) and effective connectivity (EC) alterations induced by EA in anterior cruciate ligament transection (ACLT) rat model of KOA using resting-state functional magnetic resonance imaging (fMRI). Methods: After the establishment of ACLT, rats were randomly divided into the EA group and the sham-EA group. The EA group received EA intervention while the sham-EA group received sham-intervention for 3 weeks. Mechanical pain threshold (MPT) assessment was performed before and after intervention, and fMRI was conducted after intervention. Results: EA intervention effectively relieved pain in post-ACLT rats. Results of rest-state functional connectivity (rs-FC) analysis revealed that compared with the sham-EA group, the EA group had higher FC between the right raphe and the left auditory cortex, the left caudate_ putamen and the left internal capsule (IC), as well as the right zona incerta (ZI) and the left piriform cortex, but lower FC between the right raphe and the left hippocampus ventral, as well as the right septum and the left septum. Furthermore, Granger causality analysis (GCA) found the altered EC between the right septum and the left septum, as well as the left IC and the right septum. Conclusion: The results confirmed the effect of EA on analgesia in post- ACLT rats. The alterations of FC and EC, mainly involving basal ganglia and limbic system neural connections, might be one of the neural mechanisms underlying the effect of EA, providing novel information about connectomics plasticity of EA following ACLT.
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BACKGROUND: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. METHODS AND RESULTS: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. CONCLUSION: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.
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Electroacupuntura , Infarto de la Arteria Cerebral Media , Imagen por Resonancia Magnética , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Electroacupuntura/métodos , Masculino , Ratas , Daño por Reperfusión/fisiopatología , Daño por Reperfusión/terapia , Daño por Reperfusión/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/terapia , Infarto de la Arteria Cerebral Media/fisiopatología , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Isquemia Encefálica/terapia , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/diagnóstico por imagen , Modelos Animales de Enfermedad , Red Nerviosa/fisiopatología , Red Nerviosa/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Hipocampo/diagnóstico por imagen , Hipocampo/fisiopatologíaRESUMEN
Background: Long-term skill learning can lead to structure and function changes in the brain. Different sports can trigger neuroplasticity in distinct brain regions. Volleyball, as one of the most popular team sports, heavily relies on individual abilities such as perception and prediction for high-level athletes to excel. However, the specific brain mechanisms that contribute to the superior performance of volleyball athletes compared to non-athletes remain unclear. Method: We conducted a study involving the recruitment of ten female volleyball athletes and ten regular female college students, forming the athlete and novice groups, respectively. Comprehensive behavioral assessments, including Functional Movement Screen and audio-visual reaction time tests, were administered to both groups. Additionally, resting-state magnetic resonance imaging (MRI) data were acquired for both groups. Subsequently, we conducted in-depth analyses, focusing on the amplitude of low-frequency fluctuations (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) in the brain for both the athlete and novice groups. Results: No significant differences were observed in the behavioral data between the two groups. However, the athlete group exhibited noteworthy enhancements in both the ALFF and ReHo within the visual cortex compared to the novice group. Moreover, the functional connectivity between the visual cortex and key brain regions, including the left primary sensory cortex, left supplementary motor cortex, right insula, left superior temporal gyrus, and left inferior parietal lobule, was notably stronger in the athlete group than in the novice group. Conclusion: This study has unveiled the remarkable impact of volleyball athletes on various brain functions related to vision, movement, and cognition. It indicates that volleyball, as a team-based competitive activity, fosters the advancement of visual, cognitive, and motor skills. These findings lend additional support to the early cultivation of sports talents and the comprehensive development of adolescents. Furthermore, they offer fresh perspectives on preventing and treating movement-related disorders. Trial registration: Registration number: ChiCTR2400079602. Date of Registration: January 8, 2024.
RESUMEN
Tongue coating affects cognition, and cognitive decline at early stage also showed relations to functional and structural remodeling of superior temporal sulcus (STS) in amnestic mild cognitive impairment (aMCI). The potential correlation between disparate cognitive manifestations in aMCI patients with different tongue coatings, and corresponding mechanisms of STS remodeling remains uncharted. In this case-control study, aMCI patients were divided into thin coating (n = 18) and thick coating (n = 21) groups. All participants underwent neuropsychological evaluations and multimodal magnetic resonance imaging. Group comparisons were conducted in clinical assessments and neuroimaging measures of banks of the STS (bankssts). Generalized linear models were constructed to explore relationships between neuroimaging measures and cognition. aMCI patients in the thick coating group exhibited significantly poorer immediate and delayed recall and slower information processing speed (IPS) (P < 0.05), and decreased functional connectivity (FC) of bilateral bankssts with frontoparietal cortices (P < 0.05, AlphaSim corrected) compared to the thin coating group. It was found notable correlations between cognition encompassing recall and IPS, and FC of bilateral bankssts with frontoparietal cortices (P < 0.05, Bonferroni's correction), as well as interaction effects of group × regional homogeneity (ReHo) of right bankssts on the first immediate recall (P < 0.05, Bonferroni's correction). aMCI patients with thick coating exhibited poor cognitive performance, which might be attributed to decreased FC seeding from bankssts. Our findings strengthen the understanding of brain reorganization of STS via which tongue coating status impacts cognition in patients with aMCI.
Asunto(s)
Disfunción Cognitiva , Imagen por Resonancia Magnética , Lóbulo Temporal , Lengua , Humanos , Disfunción Cognitiva/fisiopatología , Masculino , Femenino , Anciano , Lóbulo Temporal/fisiopatología , Lóbulo Temporal/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Lengua/fisiopatología , Estudios de Casos y Controles , Persona de Mediana Edad , Pruebas Neuropsicológicas , Amnesia/fisiopatología , Amnesia/diagnóstico por imagen , Recuerdo Mental/fisiologíaRESUMEN
Aberrant DNA methylation patterns have been used for cancer detection. However, DNA hemi-methylation, present at about 10% CpG dinucleotides, has been less well studied. Here we show that a majority of differentially hemi-methylated regions (DHMRs) in liver tumor DNA or plasma cells free (cf) DNA do not overlap with differentially methylated regions (DMRs) of the same samples, indicating that DHMRs could serve as independent biomarkers. Furthermore, we analyzed the cfDNA methylomes of 215 samples from individuals with liver or brain cancer and individuals without cancer (controls), and trained machine learning models using DMRs, DHMRs or both. The models incorporated with both DMRs and DHMRs show a superior performance compared to models trained with DMRs or DHMRs, with AUROC being 0.978, 0.990, and 0.983 in distinguishing control, liver and brain cancer, respectively, in a validation cohort. This study supports the potential of utilizing both DMRs and DHMRs for multi-cancer detection.