The Golgi Outpost Protein TPPP Nucleates Microtubules and Is Critical for Myelination.

Oligodendrocytes extend elaborate microtubule arbors that contact up to 50 axon segments per cell, then spiral around myelin sheaths, penetrating from outer to inner layers. However, how they establish this complex cytoarchitecture is unclear. Here, we show that oligodendrocytes contain Golgi outposts, an organelle that can function as an acentrosomal microtubule-organizing center (MTOC). We identify a specific marker for Golgi outposts-TPPP (tubulin polymerization promoting protein)-that we use to purify this organelle and characterize its proteome. In in vitro cell-free assays, recombinant TPPP nucleates microtubules. Primary oligodendrocytes from Tppp knockout (KO) mice have aberrant microtubule branching, mixed microtubule polarity, and shorter myelin sheaths when cultured on 3-dimensional (3D) microfibers. Tppp KO mice exhibit hypomyelination with shorter, thinner myelin sheaths and motor coordination deficits. Together, our data demonstrate that microtubule nucleation outside the cell body at Golgi outposts by TPPP is critical for elongation of the myelin sheath.

Long-distance mobile mRNA CAX3 modulates iron uptake and zinc compartmentalization.

Iron deficiency in plants can lead to excessive absorption of zinc; however, important details of this mechanism have yet to be elucidated. Here, we report that MdCAX3 mRNA is transported from the leaf to the root, and that MdCAX3 is then activated by MdCXIP1. Suppression of MdCAX3 expression leads to an increase in the root apoplastic pH, which is associated with the iron deficiency response. Notably, overexpression of MdCAX3 does not affect the apoplastic pH in a MdCXIP1 loss-of-function Malus baccata (Mb) mutant that has a deletion in the MdCXIP1 promoter. This deletion in Mb weakens MdCXIP1 expression. Co-expression of MdCAX3 and MdCXIP1 in Mb causes a decrease in the root apoplastic pH. Furthermore, suppressing MdCAX3 in Malus significantly reduces zinc vacuole compartmentalization. We also show that MdCAX3 activated by MdCXIP1 is not only involved in iron uptake, but also in regulating zinc detoxification by compartmentalizing zinc in vacuoles to avoid iron starvation-induced zinc toxicity. Thus, mobile MdCAX3 mRNA is involved in the regulation of iron and zinc homeostasis in response to iron starvation.

Identification of epileptic networks with graph convolutional network incorporating oscillatory activities and evoked synaptic responses.

Stereoelectroencephalography (SEEG) offers unique neural data from in-depth brain structures with fine temporal resolutions to better investigate the origin of epileptic brain activities. Although oscillatory patterns from different frequency bands and functional connectivity computed from the SEEG datasets are employed to study the epileptic zones, direct electrical stimulation-evoked electrophysiological recordings of synaptic responses, namely cortical-cortical evoked potentials (CCEPs), from the same SEEG electrodes are not explored for the localization of epileptic zones. Here we proposed a two-stream model with unsupervised learning and graph convolutional network tailored to the SEEG and CCEP datasets in individual patients to perform localization of epileptic zones. We compared our localization results with the clinically marked electrode sites determined for surgical resections. Our model had good classification capability when compared to other state-of-the-art methods. Furthermore, based on our prediction results we performed group-level brain-area mapping analysis for temporal, frontal and parietal epilepsy patients and found that epileptic and non-epileptic brain networks were distinct in patients with different types of focal epilepsy. Our unsupervised data-driven model provides personalized localization analysis for the epileptic zones. The epileptic and non-epileptic brain areas disclosed by the prediction model provide novel insights into the network-level pathological characteristics of epilepsy.

How to locate the fistula orifice of spinal extradural arachnoid cyst: Surgical experience and clinical outcome.

BACKGROUND: In clinical practice, spinal extradural arachnoid cysts (SEAC) are relatively rare. The key to the treatment of SEAC is recognize and close the dural defects (fistula orifice), but there is currently no convenient method to locate and identify the fistula. We propose a method for predicting the location of lumbar/thoracolumbar SEAC fistula based on surgical experience, subsequently closing the fistula through posterior unilateral interlaminar fenestration. Evaluating its surgical efficacy and investigated its effect on patient prognosis. METHODS: A stepped approach based on clinical experience is proposed. A retrospective analysis was performed on 6 patients diagnosed with thoracolumbar SEAC disease and treated with posterior unilateral interlaminar fenestration through the position by pre-estimated fistula orifice in our hospital's Department of Neurosurgery between January 2017 and January 2022. RESULTS: All patients who received this treatment experienced significantly lower postoperative VAS pain scores and ODI index compared to their corresponding preoperative values (P < 0.01). During the ongoing follow-up after surgery, no unstable vertebral column, adverse effects, or complications were reported. CONCLUSIONS: The use of posterior unilateral interlaminar fenestration for the treatment of large SEAC in the adult lumbar/thoracolumbar segment can reduce spinal cord manipulation and enhance spine stability. The disease can be treated by sealing the fistula orifice through a small fenestra, the position of which is assessed before surgery. This surgical method reduces trauma and improves the prognosis of patients with large SEAC.

RBP differentiation contributes to selective transmissibility of OPT3 mRNAs.

Long-distance mobile mRNAs play key roles in gene regulatory networks that control plant development and stress tolerance. However, the mechanisms underlying species-specific delivery of mRNA still need to be elucidated. Here, the use of grafts involving highly heterozygous apple (Malus) genotypes allowed us to demonstrate that apple (Malus domestica) oligopeptide transporter3 (MdOPT3) mRNA can be transported over a long distance, from the leaf to the root, to regulate iron uptake; however, the mRNA of Arabidopsis (Arabidopsis thaliana) oligopeptide transporter 3 (AtOPT3), the MdOPT3 homolog from A. thaliana, does not move from shoot to root. Reciprocal heterologous expression of the two types of mRNAs showed that the immobile AtOPT3 became mobile and moved from the shoot to the root in two woody species, Malus and Populus, while the mobile MdOPT3 became immobile in two herbaceous species, A. thaliana and tomato (Solanum lycopersicum). Furthermore, we demonstrated that the different transmissibility of OPT3 in A. thaliana and Malus might be caused by divergence in RNA-binding proteins between herbaceous and woody plants. This study provides insights into mechanisms underlying differences in mRNA mobility and validates the important physiological functions associated with this process.

Genetic dynamics of earlier maturity group emergence in south-to-north extension of Northeast China soybeans.

KEY MESSAGE: This population genetic study is characterized with direct comparisons of days to flowering QTL-allele matrices between newly evolved and originally old maturity groups of soybeans to explore its evolutionary dynamics using the RTM-GWAS procedure. The Northeast China (NEC) soybeans are the major germplasm source of modern soybean production in Americas (> 80% of the world total). NEC is a relatively new soybean area in China, expanded after its nomadic status in the seventeenth century. At nine sites of four ecoregions in NEC, 361 varieties were tested for their days to flowering (DTF), a geography-sensitive trait as an indicator for maturity groups (MGs). The DTF reduced obviously along with soybeans extended to higher latitudes, ranging in 41-83 days and MG 000-III. Using the RTM-GWAS (restricted two-stage multi-locus model genome-wide association study) procedure, 81 QTLs with 342 alleles were identified, accounting for 77.85% genetic contribution (R2 = 0.01-7.74%/locus), and other 20.75% (98.60-77.85%, h2 = 98.60%) genetic variation was due to a collective of unmapped QTLs. With soybeans northward, breeding effort made the original MG I-III evolved to MG 0-00-000. In direct comparisons of QTL-allele matrices among MGs, the genetic dynamics are identified with local exotic introduction/migration (58.48%) as the first and selection against/exclusion of positive alleles causing new recombination (40.64%) as the second, while only a few allele emergence/mutation happened (0.88%, limited in MG 0, not in MG 00-000). In new MG emergence, 24 QTLs with 19 candidate genes are the major sources. A genetic potential of further DTF shortening (13-21 days) is predicted for NEC population. The QTL detection in individual ecoregions showed various ecoregion-specific QTLs-alleles/genes after co-localization treatment (removing the random environment shifting ones).

Dynein/dynactin is necessary for anterograde transport of Mbp mRNA in oligodendrocytes and for myelination in vivo.

Oligodendrocytes in the central nervous system produce myelin, a lipid-rich, multilamellar sheath that surrounds axons and promotes the rapid propagation of action potentials. A critical component of myelin is myelin basic protein (MBP), expression of which requires anterograde mRNA transport followed by local translation at the developing myelin sheath. Although the anterograde motor kinesin KIF1B is involved in mbp mRNA transport in zebrafish, it is not entirely clear how mbp transport is regulated. From a forward genetic screen for myelination defects in zebrafish, we identified a mutation in actr10, which encodes the Arp11 subunit of dynactin, a critical activator of the retrograde motor dynein. Both the actr10 mutation and pharmacological dynein inhibition in zebrafish result in failure to properly distribute mbp mRNA in oligodendrocytes, indicating a paradoxical role for the retrograde dynein/dynactin complex in anterograde mbp mRNA transport. To address the molecular mechanism underlying this observation, we biochemically isolated reporter-tagged Mbp mRNA granules from primary cultured mammalian oligodendrocytes to show that they indeed associate with the retrograde motor complex. Next, we used live-cell imaging to show that acute pharmacological dynein inhibition quickly arrests Mbp mRNA transport in both directions. Chronic pharmacological dynein inhibition also abrogates Mbp mRNA distribution and dramatically decreases MBP protein levels. Thus, these cell culture and whole animal studies demonstrate a role for the retrograde dynein/dynactin motor complex in anterograde mbp mRNA transport and myelination in vivo.

Promoting or Prohibiting? Investigating How Time Pressure Influences Innovative Behavior under Stress-Mindset Conditions.

The existing empirical evidence on the relationship between time pressure and innovative behavior is paradoxical. An intriguing yet unresolved question is "When does time pressure promote or prohibit innovative behavior, and how?" We theorize that the paradoxical effect of time pressure on innovative behavior can be elucidated by the moderating role of stress mindset, and we also explore the mediating role of thriving at work. Our research involved a field study of 390 research and development personnel from eight enterprises and research institutes in China to test our proposed model. Results indicated that the stress-is-debilitating mindset negatively moderated the association between time pressure and thriving at work, while the stress-is-enhancing mindset positively moderated the link between time pressure and thriving at work. Furthermore, the findings demonstrated that the stress-is-debilitating mindset negatively moderated the indirect impact of time pressure on employees' innovative behavior through thriving at work, while the stress-is-enhancing mindset positively moderated the indirect effect of time pressure on employees' innovative behavior through thriving at work. The theoretical and practical implications of these findings are also discussed.

How and when Proactive Vitality Management Promotes Undergraduates' Creativity? A Conservation of Resources Perspective.

Despite widely highlighting that creative individuals need to be full of vitality to function optimally, previous research neglects the very real possibility that human beings may also need to proactively manage their vitality to ignite creativity. Drawing on the conservation of resources theory, this study explores the impact of proactive vitality management on undergraduates' creativity through harmonious academic passion, as well as the moderating roles of university creative climate and prevention focus. Evidence from a scenario-based experiment (Study 1) and a multi-wave field survey (Study 2) demonstrated that proactive vitality management positively promoted individual creativity. This relationship was partially mediated by harmonious academic passion. In addition, proactive vitality management enhanced undergraduate students' creativity via harmonious academic passion in a high university creative climate, whereas the indirect effect was weak when prevention focus was high. Theoretical and practical implications are also discussed, along with study limitations and future research directions.

Meaning matters: linking proactive vitality management to subjective well-being.

Prior research has indicated that positive affect, energy, and vitality are positively related to subjective well-being. Unfortunately, most scholars have overlooked the possibility that individuals may proactively manage their energetic, affective, and cognitive resources to boost their subjective well-being. Grounded in social cognitive theory, the current research focuses on explaining why students' proactive vitality management (PVM) leads to positive outcomes (i.e., meaning in life, subjective well-being) and considers how school support climate moderates these effects. One experimental study (Study 1) and a three-wave lagged survey (Study 2) were conducted to examine the benefits of PVM. The results demonstrated that PVM was positively related to students' meaning in life, further promoting their subjective well-being. Moreover, school support climate accentuated PVM's effect on meaning in life and its indirect effect on subjective well-being via meaning in life. Implications for research and practice are also discussed, along with study limitations and future research directions.

Myeloid cell-associated aromatic amino acid metabolism facilitates CNS myelin regeneration.

Regulation of myeloid cell activity is critical for successful myelin regeneration (remyelination) in demyelinating diseases, such as multiple sclerosis (MS). Here, we show aromatic alpha-keto acids (AKAs) generated from the amino acid oxidase, interleukin-4 induced 1 (IL4I1), promote efficient remyelination in mouse models of MS. During remyelination, myeloid cells upregulated the expression of IL4I1. Conditionally knocking out IL4I1 in myeloid cells impaired remyelination efficiency. Mice lacking IL4I1 expression exhibited a reduction in the AKAs, phenylpyruvate, indole-3-pyruvate, and 4-hydroxyphenylpyruvate, in remyelinating lesions. Decreased AKA levels were also observed in people with MS, particularly in the progressive phase when remyelination is impaired. Oral administration of AKAs modulated myeloid cell-associated inflammation, promoted oligodendrocyte maturation, and enhanced remyelination in mice with focal demyelinated lesions. Transcriptomic analysis revealed AKA treatment induced a shift in metabolic pathways in myeloid cells and upregulated aryl hydrocarbon receptor activity in lesions. Our results suggest myeloid cell-associated aromatic amino acid metabolism via IL4I1 produces AKAs in demyelinated lesions to enable efficient remyelination. Increasing AKA levels or targeting related pathways may serve as a strategy to facilitate the regeneration of myelin in inflammatory demyelinating conditions.

Associations between prenatal exposure to polycyclic aromatic hydrocarbons and thyroid hormones in umbilical cord blood.

We explored the association between maternal urinary polycyclic aromatic hydrocarbon (PAH) metabolites and thyroid hormones in umbilical cord blood in 120 pairs of pregnant women and newborns. Maternal urinary PAH metabolites were measured using high-performance liquid chromatography with tandem mass spectrometry. Thyroid hormones were measured using a flow fluorescence assay. The dose-response relationship between PAH metabolites and thyroid hormones was analyzed using the generalized linear model and restricted cubic spline model. Results showed that Æ©OH PAHs in maternal urine had a negative effect on triiodothyronine (T3). Associations between maternal urinary PAH metabolites and thyroid hormones in umbilical cord blood plasma were observed. Prenatal exposure to PAHs could affect neonatal thyroid hormones, thereby disrupting neonatal thyroid function.

Low-frequency repetitive transcranial magnetic stimulation for the treatment of refractory partial epilepsy: a controlled clinical study.

PURPOSE: This study was designed to evaluate the therapeutic effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with refractory partial epilepsy. METHODS: Sixty-four patients with refractory focal epilepsy were screened and 60 patients were randomly divided into two groups by stimulation intensity: 90% (group 1) or 20% (group 2) of resting motor threshold (rMT). Seizure frequency and interictal EEG epileptic discharges were compared between the baseline and follow-up periods. KEY FINDINGS: Seizures significantly decreased following 2-weeks high intensity (90% rMT) rTMS treatment compared with baseline level (p < 0.05). rTMS also decreased interictal epilepsy discharges and improved the scales of Symptom Checklist-90 significantly (p < 0.05). Seizures and spikes in the follow-up period in the patients who received low intensity (20% rMT) rTMS did not show any difference compared with baseline data (p > 0.05, respectively). SIGNIFICANCE: Low-frequency high intensity rTMS (90% rMT) delivered into the epileptogenic zone had a significant antiepileptic effect on patients with refractory partial seizures. rTMS treatment can also reduce the interictal epileptic discharge frequency and improve the psychological condition of these patients.

ER and Golgi trafficking in axons, dendrites, and glial processes.

Both neurons and glia in mammalian brains are highly ramified. Neurons form complex neural networks using axons and dendrites. Axons are long with few branches and form pre-synaptic boutons that connect to target neurons and effector tissues. Dendrites are shorter, highly branched, and form post-synaptic boutons. Astrocyte processes contact synapses and blood vessels in order to regulate neuronal activity and blood flow, respectively. Oligodendrocyte processes extend toward axons to make myelin sheaths. Microglia processes dynamically survey their environments. Here, we describe the local secretory system (ER and Golgi) in neuronal and glial processes. We focus on Golgi outpost functions in acentrosomal microtubule nucleation, cargo trafficking, and protein glycosylation. Thus, satellite ER and Golgi are critical for local structure and function in neurons and glia.

Tobacco smoke exposure and mitochondrial DNA copy number on neurobehavioural performance: A community study.

The influence of tobacco smoke has been a controversial and very questionable subject within the field of neurological behaviours. To examine the dose-response relationships between tobacco smoke and neurological performance, we investigated whether mitochondrial DNA copy number (mtDNAcn) mediates these relationships. We used restricted cubic spline models to estimate the dose-response relationships. A mediation model was also used to detect the mediating effect. Increased cotinine was negatively associated with auditory memory scores and a 0.51 decrease in mtDNAcn. MtDNAcn acts as a mediator between cotinine and auditory memory. Tobacco smoke levels were inversely associated with mtDNAcn and neurobehavioural changes, and there was a mediation effect between cotinine levels and auditory memory by mtDNAcn.

Urinary polycyclic aromatic hydrocarbon metabolites, plasma p-tau231 and mild cognitive impairment in coke oven workers.

BACKGROUND: As a group of environmental pollutants, polycyclic aromatic hydrocarbons (PAHs) may be neurotoxic，especially in high-exposure occupational populations. However, the effect of PAHs on mild cognitive impairment (MCI) is still unclear. OBJECTIVE: We aimed to investigate the relationship between PAH metabolites and MCI and to explore whether plasma p-tau231 can be used as a potential biomarker to reflect MCI in coke oven workers. METHOD: A total of 330 workers were recruited from a coke oven plant as the exposure group, and 234 workers were recruited from a water treatment plant as the control group. The concentrations of eleven PAH metabolites and plasma p-tau231 were determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and ELISA. Cognitive function was measured by the Montreal Cognitive Assessment (MoCA) questionnaire. A multivariate logistic regression model and multiple linear regression model were used to analyze the associations of urinary PAH metabolites with the detection rate of MCI, MoCA scores and plasma p-tau231. The dose-response relationships were evaluated using restricted cubic spline models. RESULTS: We found 146 MCI-positive workers in coke oven plant (44.24%), and 69 MCI-positive workers in water treatment plant (29.49%). In addition, the urinary sum of PAH metabolites (Æ©-OH PAHs) was significantly associated with MCI (OR, 1.371; 95% CI:1.102-1.705). Each one-unit increase in ln-transformed Æ©-OH PAHs was associated with a 0.429 decrease in the sum of MoCA, a 0.281 reduction in the visuospatial/executive function and a 9.416 increase in the level of plasma P-Tau231. We found a negative association between plasma P-Tau231 and visuospatial/executive function (ß = -0.007, 95% CI: -0.011, -0.003). CONCLUSION: Our data indicated that urinary Æ©-OH PAHs levels of workers were positively associated with MCI and the level of plasma P-Tau231.

Transgressive Potential Prediction and Optimal Cross Design of Seed Protein Content in the Northeast China Soybean Population Based on Full Exploration of the QTL-Allele System.

Northeast China is a major soybean production region in China. A representative sample of the Northeast China soybean germplasm population (NECSGP) composed of 361 accessions was evaluated for their seed protein content (SPC) in Tieling, Northeast China. This SPC varied greatly, with a mean SPC of 40.77%, ranging from 36.60 to 46.07%, but it was lower than that of the Chinese soybean landrace population (43.10%, ranging from 37.51 to 50.46%). The SPC increased slightly from 40.32-40.97% in the old maturity groups (MG, MGIII + II + I) to 40.93-41.58% in the new MGs (MG0 + 00 + 000). The restricted two-stage multi-locus genome-wide association study (RTM-GWAS) with 15,501 SNP linkage-disequilibrium block (SNPLDB) markers identified 73 SPC quantitative trait loci (QTLs) with 273 alleles, explaining 71.70% of the phenotypic variation, wherein 28 QTLs were new ones. The evolutionary changes of QTL-allele structures from old MGs to new MGs were analyzed, and 97.79% of the alleles in new MGs were inherited from the old MGs and 2.21% were new. The small amount of new positive allele emergence and possible recombination between alleles might explain the slight SPC increase in the new MGs. The prediction of recombination potentials in the SPC of all the possible crosses indicated that the mean of SPC overall crosses was 43.29% (+2.52%) and the maximum was 50.00% (+9.23%) in the SPC, and the maximum transgressive potential was 3.93%, suggesting that SPC breeding potentials do exist in the NECSGP. A total of 120 candidate genes were annotated and functionally classified into 13 categories, indicating that SPC is a complex trait conferred by a gene network.

Microtubule organization and dynamics in oligodendrocytes, astrocytes, and microglia.

Though much is known about microtubule organization and microtubule-based transport in neurons, the development and function of microtubules in glia are more enigmatic. In this review, we provide an overview of the literature on microtubules in ramified brain cells, including oligodendrocytes, astrocytes, and microglia. We focus on normal cell biology-how structure relates to function in these cells. In oligodendrocytes, microtubules are important for extension of processes that contact axons and for elongating the myelin sheath. Recent studies demonstrate that new microtubules can form outside of the oligodendrocyte cell body off of Golgi outpost organelles. In astrocytes and microglia, changes in cell shape and ramification can be influenced by neighboring cells and the extracellular milieu. Finally, we highlight key papers implicating glial microtubule defects in neurological injury and disease and discuss how microtubules may contribute to invasiveness in gliomas. Thus, future research on the mechanisms underlying microtubule organization in normal glial cell function may yield valuable insights on neurological disease pathology.

Relationships between Parenting Behaviors and Adolescents' Creativity in China: The Mediating Role of Autonomous Motivation.

This study used a two-wave, longitudinal design to examine the relationships between parenting behaviors (parental autonomy support, parental behavioral control, and parental psychological control) and Chinese adolescents' creativity, and the mechanism underlying the relationships. A total of 258 Chinese adolescents (mean age = 13.35, 48% girls) participated in the present study. The study measured the parenting behaviors received by the participants, their autonomous motivation, and creativity using the Parenting Scale, the Self-Regulatory Style Questionnaire-Academic, and the verbal and figural Divergent Thinking Tests, respectively. Structural equation models revealed that parental autonomy support and parental behavioral control had positive effects on Chinese adolescents' creativity one year later, whereas the relationship between parental psychological control and creativity one year later was not significant. In addition, parental autonomy support and parental behavioral control contributed to adolescents' creativity through the mediating effect of autonomous motivation. Findings from the present study help clarify developmental pathways linking parenting behaviors to adolescents' creativity in Chinese culture.

Dose-response relationships between polycyclic aromatic hydrocarbon exposure and blood cell counts among coke oven workers: a sex-stratified analysis.

OBJECTIVES: To explore sex differences and dose-response relationships between nine urinary polycyclic aromatic hydrocarbon (PAH) metabolites and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and complete blood counts among coke oven workers. DESIGN AND SETTING: A cross-sectional study with stratified sex was conducted in Shanxi, China. PARTICIPANTS: A total of 458 male workers and 226 female workers were selected. PRIMARY AND SECONDARY OUTCOME MEASURES: General linear models, p values for trend tests and natural cubic spline models were used to explore the dose-response relationships between nine urinary PAH metabolites and NLR, PLR and complete blood counts. RESULT: Compared with male workers, female workers had lower exposure level of PAH (0.95 ng/mL vs 1.38 ng/mL). Only among female workers did we observe that a 1-unit increase in lg(1-OHPyr) was related to a 0.149 (95% CI: 0.055 to 0.242; p for trend=0.041) and 0.103 (95% CI: 0.025 to 0.181; p for trend=0.007) increase in lg(NLR) and lg(PLR), and a 0.116 (95% CI: -0.179 to -0.054; p for trend=0.007) decrease in lg(lymphocyte counts (LYMs)). A 1-unit increase in lg(2-OHNap) was related to a 0.045 (95% CI: 0.003 to 0.086; p for trend=0.037) increase in lg(PLR) and a 0.029 (95% CI: -0.056 to -0.002; p for trend=0.030) and 0.016 (95% CI: -0.029 to -0.003; p for trend=0.010) decrease in lg(white blood cell counts (WBCs)) and lg(haemoglobin (HGB)). CONCLUSION: Female workers' NLR, PLR, WBCs, HGB and LYMs may be more susceptible than those of male workers when affected by PAH.