Migrating pyramidal neurons require DSCAM to bypass the border of the developing cortical plate.

During mammalian neocortex development, nascent pyramidal neurons migrate along radial glial cells and overtake earlier-born neurons to terminate at the front of the developing cortical plate (CP), leading to the outward expansion of the CP border. While much has been learned about the cellular and molecular mechanisms that underlie the migration of pyramidal neurons, how migrating neurons bypass the preceding neurons at the end of migration to reach their final positions remains poorly understood. Here, we report that Down syndrome cell adhesion molecule (DSCAM) is required for migrating neurons to bypass their post-migratory predecessors during the expansion of the upper cortical layers. DSCAM is a type I transmembrane cell adhesion molecule. It has been linked to Down syndrome through its location in the Down syndrome critical region of Chromosome 21 trisomy and to autism spectrum disorders through loss-of-function mutations. Ex vivo time-lapse imaging demonstrates that DSCAM is required for migrating neurons to bypass their post-migratory predecessors, crossing the CP border to expand the upper cortical layers. In DSCAM-deficient cortices, migrating neurons stop prematurely under the CP border, leading to thinner and denser upper cortical layers. We further show that DSCAM weakens cell adhesion mediated by N-cadherin in the upper cortical plate, allowing migrating neurons to traverse the CP border and expand the CP. These findings suggest that DSCAM is required for proper migratory termination and final positioning of nascent pyramidal neurons, which may provide insight into brain disorders that exhibit thinner upper layers of the cerebral cortex without neuronal loss.SIGNIFICANCE STATEMENTNewly born neurons in the developing mammalian neocortex migrate outward towards the cortical surface, bypassing earlier born neurons to expand the developing cortex. How migrating neurons bypass the preceding neurons and terminate at the front of the expanding cortex remains poorly understood. We demonstrate that Down syndrome cell adhesion molecule (DSCAM), linked to Down syndrome and autism spectrum disorder, is required by migrating neurons to bypass their post-migratory predecessors and terminate migration in the outwardly expanding cortical layer. Migrating neurons deficient in DSCAM stop prematurely, failing to expand the cortex. We further show that DSCAM likely mediates migratory termination by weakening cell-adhesion mediated by N-cadherin.

Novel insights into molecular signatures and pathogenic cell populations shared by systemic lupus erythematosus and vascular dementia.

Although vascular dementia (VD) and systemic lupus erythematosus (SLE) may share immune-mediated pathophysiologic processes, the underlying mechanisms are unclear. This study investigated shared gene signatures in SLE versus VD, as well as their potential molecular mechanisms. Bulk RNA sequencing (RNAseq) and single-cell or single-nucleus RNAseq (sc/snRNAseq) datasets from SLE blood samples and VD brain samples were obtained from Gene Expression Omnibus. The identification of genes associated with both SLE and VD was performed using the weighted gene co-expression network analysis (WGCNA) and machine learning algorithms. For the sc/snRNAseq data, an unbiased clustering pipeline based on Seurat and CellChat was used to determine the cellular landscape profile and examine intracellular communication, respectively. The results were subsequently validated using a mice model of SLE with cognitive dysfunction (female MRL/lpr mice). WGCNA and machine learning identified C1QA, LY96, CD163, and MS4A4A as key genes for SLE and VD. sc/snRNAseq analyses revealed that CD163 and MS4A4A were upregulated in mononuclear phagocytes (MPs) from SLE and VD samples and were associated with monocyte-macrophage differentiation. Intriguingly, LGALS9-associated molecular pathway, as the only signaling pathway common between SLE and VD via CellChat analysis, exhibited significant upregulation in cortical microglia of MRL/lpr mice. Our analyses identified C1QA, LY96, CD163, and MS4A4A as potential biomarkers for SLE and VD. Moreover, the upregulation of CD163/MS4A4A and activation of LGALS9 signaling in MPs may contribute to the pathogenesis of VD with SLE. These findings offer novel insight into the mechanisms underlying VD in SLE patients.

Microglial mTOR is Neuronal Protective and Antiepileptogenic in the Pilocarpine Model of Temporal Lobe Epilepsy.

Excessive activation of mammalian target of rapamycin (mTOR) signaling is epileptogenic in genetic epilepsy. However, the exact role of microglial mTOR in acquired epilepsy remains to be clarified. In the present study, we found that mTOR is strongly activated in microglia following excitatory injury elicited by status epilepticus. To determine the role of microglial mTOR signaling in excitatory injury and epileptogenesis, we generated mice with restrictive deletion of mTOR in microglia. Both male and female mice were used in the present study. We found that mTOR-deficient microglia lost their typical proliferative and inflammatory responses to excitatory injury, whereas the proliferation of astrocytes was preserved. In addition, mTOR-deficient microglia did not effectively engulf injured/dying neurons. More importantly, microglial mTOR-deficient mice displayed increased neuronal loss and developed more severe spontaneous seizures. These findings suggest that microglial mTOR plays a protective role in mitigating neuronal loss and attenuating epileptogenesis in the excitatory injury model of epilepsy.SIGNIFICANCE STATEMENT The mammalian target of rapamycin (mTOR) pathway is strongly implicated in epilepsy. However, the effect of mTOR inhibitors in preclinical models of acquired epilepsy is inconsistent. The broad presence of mTOR signaling in various brain cells could prevent mTOR inhibitors from achieving a net therapeutic effect. This conundrum has spurred further investigation of the cell type-specific effects of mTOR signaling in the CNS. We found that activation of microglial mTOR is antiepileptogenic. Thus, microglial mTOR activation represents a novel antiepileptogenic route that appears to parallel the proepileptogenic route of neuronal mTOR activation. This may explain why the net effect of mTOR inhibitors is paradoxical in the acquired models of epilepsy. Our findings could better guide the use of mTOR inhibitors in preventing acquired epilepsy.

The effect of interface angle on the thermal conductivity of Si/Ge superlattices.

Si/Ge superlattices (SLs) are good candidates for thermoelectric materials because of their remarkable thermal insulating performance compared with their bulk counterparts. In this paper, the non-equilibrium molecular dynamics (NEMD) simulation method was applied to investigate the thermal conductivity of Si/Ge SLs containing tilted interfaces. It was found that the thermal conductivity will be 4-5 times higher than that of other angles when the period length is 4-8 atomic layers and the interface angle is 45°. This phenomenon can be attributed to the smooth arrangement of the 45° interface which induces phonon coherent transport. Meanwhile, the thermal conductivity has not been improved due to the phonon localization although the phonons satisfy the coherent transport when the interface angle is 90°. Interestingly, the thermal conductivity is almost unchanged with the increasing interface angle when the period length is large enough which exceeds 20 atomic layers. The main reason for the unchanged thermal conductivity is due to the period length which is greater than the phonon coherence length inducing the phonon incoherent transport.

Incidental para-ureteral aggressive angiomyxoma: a rare case report and literature review.

BACKGROUND: Aggressive angiomyxoma (AA) is a rare tumor that typically occurs in the pelvis and perineum, most commonly in women of reproductive age. However, no para-ureteral AA has been reported according to the literature. Case presentation We herein describe the first case of para-ureteral AA. A 62-year-old male presented to our institute in March 2017 with a para-ureteral mass that was 15 mm in diameter incidentally. No symptom was observed and laboratory analysis was unremarkable. Magnetic resonance and computed tomography imaging showed a non-enhancing mass abutting the left ureter without causing obstruction. Laparoscopic resection of the mass was performed without injury to the ureter. Pathologic and immunohistochemical results were consistent with AA. Till now, no recurrence was noticed. CONCLUSIONS: We reported a rare case of para-ureteral AA, along with a literature review. Early diagnosis, proper surgical plan and long-term close follow-up is recommended for its high risk of recurrence and malignant potential.

Influence of extending expansive open-door laminoplasty to C1 and C2 on cervical sagittal parameters.

BACKGROUND: For patients with spinal canal stenosis in the upper cervical spine who undergo C3-7 laminoplasty alone, it remains impossible to achieve full decompression due to its limited range. This study explores the extension of expansive open-door laminoplasty (EODL) to C1 and C2 for the treatment of cervical spinal stenosis of the upper cervical spine and its effects on cervical sagittal parameters. METHODS: A retrospective analysis of 33 patients presenting with symptoms of cervical spondylosis myelopathy (CSM) and ossification in the posterior longitudinal ligament (OPLL) of the upper cervical spine from February 2013 to December 2015 was performed. Furthermore, the changes in the C0-2 Cobb angle, C1-2 Cobb angle, C2-7 Cobb angle, C2-7 SVA, and T1-Slope in lateral X-rays of the cervical spine were measured before, immediately after, and 1 year after the operation. JOA and NDI scores were used to evaluate spinal cord function. RESULTS: The C0-2 and C1-2 Cobb angles did not significantly increase (P = 0.190 and P = 0.081), but the C2-7 Cobb angle (P = 0.001), C2-7 SVA (P < 0.001), and T1-Slope (P < 0.001) significantly increased from preoperative to 1 year postoperative. In addition, C2-7 SVA was significantly correlated with the T1-Slope (Pearson = 0.376, P < 0.001) and C0-2 Cobb angle (Pearson = 0.287, P = 0.004), and the C2-7 SVA was negatively correlated with the C2-7 Cobb angle (Pearson = - 0.295, P < 0.001). The average preoperative and postoperative JOA scores were 8.3 ± 1.6 and 14.6 ± 1.4 points, respectively, indicating in a postoperative neurological improvement rate of approximately 91.6%. The average preoperative and final follow-up NDI scores were 12.62 ± 2.34 and 7.61 ± 1.23. CONCLUSIONS: The sagittal parameters of patients who underwent EODL extended to C1 and C2 included loss of cervical curvature, increased cervical anteversion and compensatory posterior extension of the upper cervical spine to maintain visual balance in the field of vision. However, the changes in cervical spine parameters were far less substantial than the alarm thresholds reported in previous studies. We believe that EODL extended to C1 and C2 for the treatment of patients with spinal canal stenosis in the upper cervical spine is a feasible and safe procedure with excellent outcomes.

Association between T-182C, G1287A polymorphism in NET gene and suicidality in major depressive disorder in Chinese patients.

Objective: Previous studies have implicated norepinephrine transporter gene (NET) polymorphisms in the etiology of major depressive disorder (MDD). A functional NET T-182C polymorphism (rs2242446) in the promoter region and a synonymous polymorphisms G1287A in the exon 9 (rs5569) were associated with MDD in different populations. However, few studies have focused on the relationship between these polymorphisms and MDD patients with suicidality. The objective of the present study was to examine whether the two polymorphisms are associated with MDD patients with suicidality in the Han Chinese population. Methods: Two hundred and sixty-three suicidal depressed patients and 241 non-suicidal depressed patients who met DSM-IV criteria for MDD were recruited from our hospital. Three hundred and three unrelated, age- and sex-matched healthy control subjects participated in this case-control study. Suicidality was assessed using Mini International Neuropsychiatric Interview (MINI) and the Hamilton rating scale for depression (HAMD). Genotypes of T-182C polymorphism (rs2242446) and G1287A (rs5569) were screened by polymerase chain reaction. Results: No statistical significant differences between patients and controls were found for any of the analysed polymorphisms, either in the genotype or allele distribution. Conclusions: Our results suggest that the investigated polymorphisms are not major susceptibility factors in the etiology of MDD with suicidality. However, the results must be verified in larger samples and different ethnicities.

Two new fatty acids esters were detected in ginseng stems by the application of azoxystrobin and the increasing of antioxidant enzyme activity and ginsenosides content.

Panax ginseng C.A. Meyer is a valuable herb in China that has also gained popularity in the West because of its pharmacological properties. The constituents isolated and characterized in ginseng stems include ginsenosides, fatty acids, amino acids, volatile oils, and polysaccharides. In this study, the effects of fungicide azoxystrobin applied on antioxidant enzyme activity and ginsenosides content in ginseng stems was studied by using Panax ginseng C. A. Mey. cv. (the cultivar of Ermaya) under natural environmental conditions. The azoxystrobin formulation (25% SC) was sprayed three times on ginseng plants at different doses (150ga.i./ha and 225ga.i./ha), respectively. Two new fatty acids esters (ethyl linoleate and methyl linolenate) were firstly detected in ginseng stems by the application of azoxystrobin as foliar spray. The results indicated that activities of enzymatic antioxidants, the content of ginsenosides and two new fatty acids esters in ginseng stems in azoxystrobin-treated plants were increased. Azoxystrobin treatments to ginseng plants at all growth stages suggest that the azoxystrobin-induced delay of senescence is due to an enhanced antioxidant enzyme activity protecting the plants from harmful active oxygen species (AOS). The activity of superoxide dismutase (SOD) in azoxystrobin-treated plants was about 1-3 times higher than that in untreated plants. And the effects was more significant (P=0.05) when azoxystrobin was applied at dose of 225ga.i./ha. This work suggests that azoxystrobin plays an important role in delaying of senescence by changing physiological and biochemical indicators and increasing ginsenosides content in ginseng stems.

Jak/Stat signaling stimulates zebrafish optic nerve regeneration and overcomes the inhibitory actions of Socs3 and Sfpq.

The regenerative failure of mammalian optic axons is partly mediated by Socs3-dependent inhibition of Jak/Stat signaling (Smith et al., 2009, 2011). Whether Jak/Stat signaling is part of the normal regenerative response observed in animals that exhibit an intrinsic capacity for optic nerve regeneration, such as zebrafish, remains unknown. Nor is it known whether the repression of regenerative inhibitors, such as Socs3, contributes to the robust regenerative response of zebrafish to optic nerve damage. Here we report that Jak/Stat signaling stimulates optic nerve regeneration in zebrafish. We found that IL-6 family cytokines, acting via Gp130-coupled receptors, stimulate Jak/Stat3 signaling in retinal ganglion cells after optic nerve injury. Among these cytokines, we found that CNTF, IL-11, and Clcf1/Crlf1a can stimulate optic axon regrowth. Surprisingly, optic nerve injury stimulated the expression of Socs3 and Sfpq (splicing factor, proline/glutamine rich) that attenuate optic nerve regeneration. These proteins were induced in a Jak/Stat-dependent manner, stimulated each other's expression and suppressed the expression of regeneration-associated genes. In vivo, the injury-dependent induction of Socs3 and Sfpq inhibits optic nerve regeneration but does not block it. We identified a robust induction of multiple cytokine genes in zebrafish retinal ganglion cells that may contribute to their ability to overcome these inhibitory factors. These studies not only identified mechanisms underlying optic nerve regeneration in fish but also suggest new molecular targets for enhancing optic nerve regeneration in mammals.

A role for the rap GTPase YlRsr1 in cellular morphogenesis and the involvement of YlRsr1 and the ras GTPase YlRas2 in bud site selection in the dimorphic yeast Yarrowia lipolytica.

Yarrowia lipolytica is a dimorphic yeast species that can grow in the ovoid yeast form or in the elongated pseudohyphal or hyphal form depending on the growth conditions. Here, we show that the Rap GTPase Rsr1 of Y. lipolytica (YlRsr1) plays an important role in cellular morphogenesis in this microorganism. Cells deleted for YlRSR1 exhibited impaired polarized growth during yeast-form growth. Pseudohyphal and hyphal development were also abnormal. YlRsr1 is also important for cell growth, since the deletion of YlRSR1 in cells lacking the Ras GTPase YlRas2 caused lethality. Y. lipolytica cells bud in a bipolar pattern in which the cells produce the new buds at the two poles. YlRsr1 plays a prominent role in this bud site selection process. YlRsr1's function in bud site selection absolutely requires the cycling of YlRsr1 between the GTP- and GDP-bound states but its function in cellular morphogenesis does not, suggesting that the two processes are differentially regulated. Interestingly, the Ras GTPase YlRas2 is also involved in the control of bud site selection, as Ylras2Δ cells were severely impaired in bipolar bud site selection. The GTP/GDP cycling and the plasma membrane localization of YlRas2 are important for YlRas2's function in bud site selection. However, they are not essential for this process, suggesting that the mechanism by which YlRas2 acts is different from that of YlRsr1. Our results suggest that YlRsr1 is regulated by the GTPase-activating protein (GAP) YlBud2 and partially by YlCdc25, the potential guanine nucleotide exchange factor (GEF) for YlRas2.

[The correlation study on syndrome differentiation of rheumatoid arthritis and joint high frequency ultrasound performance].

OBJECTIVE: To observe the differential effect of joint ultrasound on the syndrome differentiation of rheumatoid arthritis (RA) by observing the high frequency ultrasound performances among inactive stage and different syndromes in active stage. METHODS: Totally 83 RA patients in the active stage were assigned to the dampness heat syndrome group (DHS, 59 cases)and the cold dampness syndrome group (CDS, 24 cases) according to Chinese medicine (CM) syndrome typing. Besides, 20 RA patients in the remission stage were recruited as the control group (abbreviated as the remission group). By using high frequency ultrasound and power Doppler ultrasound technology, a comparative observation of synovitis, tenosynovitis, synovial blood flow, and bone erosion in the 2nd-5th metacarpophalangeal (MCP) joints, proximal interphalangeal (PIP) joints, wrist joints, knee joints, the second and the fifth metatarsophalangeal (MTP) joints (a total of 24 joints) was performed in all patients. Correlation analyses were performed between the ultrasound performance, laboratory indices, and the disease activity. Ultrasound data of each RA patient were analyzed by their total scores. Χ2 test was used for enumeration data. The measurement data was expressed as x ± s. One-way ANOVA was used for data of normal distribution, while non- parametric test was used for data of non-normal distribution. Correlation analysis of two variables was performed for clinical indicators and ultrasound indicators. Its significance was detected using Pearson correlation. RESULTS: Compared with the remission group, the severity degree of synovitis, tenosynovitis, synovial blood flow, and bone erosion significantly increased in the DHS group (P < 0.01). There was statistical difference in ESR, CRP, anti-CCP, DAS28 score, and the positive rate of RF (P < 0.05, P < 0.01). There was statistical difference in the severity degree of synovitis and synovial blood flow, and DAS28 score in the CDS group (P < 0.05). Compared with the CDS group, there was statistical difference in the four ultrasound indices (P < 0.05, P < 0.01), ESR, CRP, anti-CCP, DAS28 score, and the positive rate of RF in the DHS group (P < 0.05, P < 0.01). There was no statistical difference in G, IgG, IgA, or IgM among the three groups (P > 0.05). There existed positive correlation between ESR and the synovitis degree, synovial blood flow, and bone erosion in the DHS group (r = 0.444, 0.397, 0.486, P < 0.05).There existed positive correlation between ESR and the synovitis degree, bone erosion, and synovial blood flow in the DHS group (r = 0.378, 0.270, P < 0.05). There existed positive correlation between the DAS28 score and the synovitis degree and synovial blood flow in the DHS group (r = 0.304, 0.351, P < 0.05). CONCLUSIONS: The inflammation degree was the most severe in RA patients of DHS. High frequency ultrasound could provide better evidence for Chinese medical syndrome differentiation of RA patients.

Roles of the three Ras proteins in the regulation of dimorphic transition in the yeast Yarrowia lipolytica.

Ras proteins in the budding yeast Saccharomyces cerevisiae are essential for growth and dimorphic transition. The dimorphic yeast Yarrowia lipolytica is distantly related to S. cerevisiae. Its genome encodes three Ras proteins. Here, we show that the three Ras proteins in Y. lipolytica are critical for dimorphic transition but are dispensable for growth. Among the three Ras proteins, YlRas2 plays a major role in the regulation of dimorphic transition, whereas YlRas1 plays a minor role in this process. The additional Ras protein, YlRas3, which resembles mammalian K-Ras4B at the C-terminus, does not seem to have a significant role in dimorphic transition. Thus, the three Ras proteins do not act equally in the regulation of dimorphic transition. We also show that the expression of YlRAS2 was increased dramatically at the transcriptional level during yeast-to-hypha transition, consistent with a major role of YlRas2 in the regulation of dimorphic transition. YlRas2's function in dimorphic transition depends on the active GTP-bound form of YlRas2 and its localization to the plasma membrane. YlRas2 could also partially function on the endomembranes. In addition, we identified the transcription factor Mhy1 as a potential signal transducer downstream of YlRas2 in the control of dimorphic transition. This finding suggests that novel signaling pathway controlled by Ras proteins regulating dimorphic transition may exist in Y. lipolytica.

Ascl1a/Dkk/beta-catenin signaling pathway is necessary and glycogen synthase kinase-3beta inhibition is sufficient for zebrafish retina regeneration.

Key to successful retina regeneration in zebrafish are Müller glia (MG) that respond to retinal injury by dedifferentiating into a cycling population of retinal progenitors. Although recent studies have identified several genes involved in retina regeneration, the signaling mechanisms underlying injury-dependent MG proliferation have remained elusive. Here we report that canonical Wnt signaling controls the proliferation of MG-derived retinal progenitors. We found that injury-dependent induction of Ascl1a suppressed expression of the Wnt signaling inhibitor, Dkk, and induced expression of the Wnt ligand, Wnt4a. Genetic and pharmacological inhibition of Wnt signaling suppressed injury-dependent proliferation of MG-derived progenitors. Remarkably, in the uninjured retina, glycogen synthase kinase-3ß (GSK-3ß) inhibition was sufficient to stimulate MG dedifferentiation and the formation of multipotent retinal progenitors that were capable of differentiating into all major retinal cell types. Importantly, Ascl1a expression was found to contribute to the multipotential character of these progenitors. Our data suggest that Wnt signaling and GSK-3ß inhibition, in particular, are crucial for successful retina regeneration.

Efficacy and safety of electroacupuncture for insomnia: A systematic review and meta-analysis.

BACKGROUND: Electroacupuncture is often used to treat insomnia. OBJECTIVE: To evaluate the efficacy and safety of electroacupuncture for insomnia. SEARCH STRATEGY: Databases including PubMed, Cochrane Library, Embase, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang Data and VIP Full-text e-Journals Database were searched up to January 15, 2023. INCLUSION CRITERIA: Randomized clinical trials were included if they compared the clinical efficacy and safety of electroacupuncture with sham acupuncture, no treatment or usual care (UC) and general acupuncture. DATA EXTRACTION AND ANALYSIS: The full texts of the studies were reviewed to remove ineligible literature. The extracted data included authors, publication year, diagnostic criteria, sample size, population characteristics, interventions and outcomes. The above steps were performed independently by two reviewers and the data were cross-checked. Stata15.0 software was used to analyze the extracted outcome data. For continuous data (Pittsburgh Sleep Quality Index [PSQI] score and Insomnia Severity Index score), weighted mean difference (WMD) was calculated and 95% confidence interval (CI) was reported when the same scale was applied. For dichotomous variables (clinical response rate and adverse events), a meta-analysis was performed using risk ratio (RR) as the effect indicator. RESULTS: Thirty-one trials with 2226 subjects were included. The meta-analysis suggested that electroacupuncture was more effective in improving insomnia compared with the control group (sham acupuncture, no treatment, UC and general acupuncture) (RR = 1.21; 95% CI: [1.16, 1.27]), significantly reducing the PSQI score in insomnia patients after treatment and at follow-up (WMD = -3.23; 95% CI: [-4.29, -2.17]; P < 0.001). There was no significant difference in the incidence of adverse events between the EA and control groups (sham acupuncture and no treatment or UC. RR = 1.48; 95% CI: [0.91, 2.40]; P = 0.117). In addition, the regression results revealed that receiving electroacupuncture for seven to nine weeks provided the best efficacy (P < 0.05). CONCLUSION: Electroacupuncture can significantly promote better sleep quality in insomnia patients and is suitable for the treatment of various types of insomnia. However, the articles included were single-center trials with small sample sizes, and some articles were of poor quality. Therefore, further research is still needed to confirm these findings. Please cite this article as: Xu HY, Wu LN, Zhang Y, Ba T, Zhao XF. Efficacy and safety of electroacupuncture for insomnia: A systematic review and meta-analysis. J Integr Med. 2024; Epub ahead of print.

Structure and function of Semaphorin-5A glycosaminoglycan interactions.

Integration of extracellular signals by neurons is pivotal for brain development, plasticity, and repair. Axon guidance relies on receptor-ligand interactions crosstalking with extracellular matrix components. Semaphorin-5A (Sema5A) is a bifunctional guidance cue exerting attractive and inhibitory effects on neuronal growth through the interaction with heparan sulfate (HS) and chondroitin sulfate (CS) glycosaminoglycans (GAGs), respectively. Sema5A harbors seven thrombospondin type-1 repeats (TSR1-7) important for GAG binding, however the underlying molecular basis and functions in vivo remain enigmatic. Here we dissect the structural basis for Sema5A:GAG specificity and demonstrate the functional significance of this interaction in vivo. Using x-ray crystallography, we reveal a dimeric fold variation for TSR4 that accommodates GAG interactions. TSR4 co-crystal structures identify binding residues validated by site-directed mutagenesis. In vitro and cell-based assays uncover specific GAG epitopes necessary for TSR association. We demonstrate that HS-GAG binding is preferred over CS-GAG and mediates Sema5A oligomerization. In vivo, Sema5A:GAG interactions are necessary for Sema5A function and regulate Plexin-A2 dependent dentate progenitor cell migration. Our study rationalizes Sema5A associated developmental and neurological disorders and provides mechanistic insights into how multifaceted guidance functions of a single transmembrane cue are regulated by proteoglycans.

Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration.

In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate ß-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to ß-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. Here, we demonstrate that protection of the inflamed vasculature promotes immune-mediated RGC regeneration. In the absence of microglia, leakiness of the blood-retina barrier increases, pro-inflammatory neutrophils are elevated, and RGC regeneration is reduced. Functional ablation of the complement receptor 3 (CD11b/integrin-αM), but not the complement components C1q-/- or C3-/-, reduces ocular inflammation, protects the blood-retina barrier, and enhances RGC regeneration. Selective targeting of neutrophils with anti-Ly6G does not increase axogenic neutrophils but protects the blood-retina barrier and enhances RGC regeneration. Together, these findings reveal that protection of the inflamed vasculature promotes neuronal regeneration.

Sarm1 is not necessary for activation of neuron-intrinsic growth programs yet required for the Schwann cell repair response and peripheral nerve regeneration.

Upon peripheral nervous system (PNS) injury, severed axons undergo rapid SARM1-dependent Wallerian degeneration (WD). In mammals, the role of SARM1 in PNS regeneration, however, is unknown. Here we demonstrate that Sarm1 is not required for axotomy induced activation of neuron-intrinsic growth programs and axonal growth into a nerve crush site. However, in the distal nerve, Sarm1 is necessary for the timely induction of the Schwann cell (SC) repair response, nerve inflammation, myelin clearance, and regeneration of sensory and motor axons. In Sarm1-/- mice, regenerated fibers exhibit reduced axon caliber, defective nerve conduction, and recovery of motor function is delayed. The growth hostile environment of Sarm1-/- distal nerve tissue was demonstrated by grafting of Sarm1-/- nerve into WT recipients. SC lineage tracing in injured WT and Sarm1-/- mice revealed morphological differences. In the Sarm1-/- distal nerve, the appearance of p75NTR+, c-Jun+ SCs is significantly delayed. Ex vivo, p75NTR and c-Jun upregulation in Sarm1-/- nerves can be rescued by pharmacological inhibition of ErbB kinase. Together, our studies show that Sarm1 is not necessary for the activation of neuron intrinsic growth programs but in the distal nerve is required for the orchestration of cellular programs that underlie rapid axon extension.

The TEA/ATTS transcription factor YlTec1p represses the yeast-to-hypha transition in the dimorphic yeast Yarrowia lipolytica.

Tec1p in the budding yeast Saccharomyces cerevisiae is important for dimorphic transition. In this study, we identified a homologue of Tec1p, YlTec1p, in the distantly related dimorphic yeast Yarrowia lipolytica. YlTec1p contains an evolutionarily conserved TEA/ATTS DNA-binding domain. Expression of YlTEC1 in S. cerevisiae tec1Δ cells rescued the invasive growth defect and activated a FLO11-lacZ reporter, indicating that YlTec1p is functionally related to Tec1p. However, YlTEC1 expression failed to activate an FRE-lacZ reporter, suggesting that these two transcription factors are different. YlTEC1 plays a negative role in the yeast-to-hypha transition in Y. lipolytica based on gene deletion and overexpression studies. We show that YlTec1p activates rather than represses gene expression in Y. lipolytica by yeast one-hybrid assay, and YlTec1p is critical for the activation of FLO11-lacZ in Y. lipolytica. In addition, YlTec1p localized to the nucleus and its nuclear localization decreased during hyphal growth. We speculate that YlTec1p may normally regulate the expression of a set of target genes that may prevent rather than promote hyphal development in Y. lipolytica. Our study also suggests that YlTEC1 may not be largely regulated by the cAMP-protein kinase A pathway.

[Species, Habitat Characteristics, and Screening Suggestions of Cadmium Hyperaccumulators in China].

Phytoremediation, as a green and effective in-situ remediation technology for heavy metal-contaminated soil, has attracted the attention of Chinese scholars and has resulted in a series of achievements over the past 20 years. In this study, the species characteristics, distribution of field discovery sites in various vegetation zones, habitat characteristics, habitat geological characteristics, and geochemistry of cadmium (Cd) of the Cd hyperaccumulators in China reported in the relevant literature from the past 20 years (from 2002 to 2021) were summarized by searching for related keywords. Finally, suggestions were proposed for the screening of new Cd hyperaccumulators. The results showed that a total of 45 species of Cd hyperaccumulators in China have been reported so far. In terms of plant species, they belonged to 22 families and 36 genera, among which Compositae with 14 species was the most abundant. There were 25 species discovered through the field investigation, which were mainly distributed in the subtropical broadleaf evergreen forest region of southern China. Additionally, the Cd hyperaccumulators discovered by field surveys were mainly found in high Cd-concentrated soils surrounding lead-zinc mines. In conclusion, abundant plant resources, high concentrations of heavy metal soils, and long-term domestication jointly promoted the formation of hyperaccumulators. Therefore, the region with these three points could be considered a high probability region for the presence of hyperaccumulators, and the screening of hyperaccumulators could be carried out around this. We proposed that the screening of new hyperaccumulators can be carried out through the following six steps:the identification and investigation of high probability areas, the enrichment capability test, the enrichment capability test in low concentration levels, the enrichment capability test between different ecotypes, the succession of enrichment capability, and the test of remediation proficiency.

Identifying spatial agglomeration and driving forces of land use by green industries: a case study of Jiangsu Province, China.

In response to China's aims of becoming "carbon-neutral," the development of green industries such as renewable energy and recycling has flourished. Based on 2015 and 2019 data, this study uses spatial autocorrelation to analyze the evolution of land use by the green industries in Jiangsu Province. The Geodetector model was also applied to identify the driving factors underlying these spatial patterns. The spatial variability of green industrial land use in Jiangsu Province is significant, with the land-use area gradually decreasing from Southern to Northern Jiangsu. In terms of spatial-temporal changes, there is an increase in land use and a trend of expansion in the central and northern regions of Jiangsu. Land use by green industries in the province exhibits a more significant spatial clustering pattern but with a weakened clustering effect. The clustering types are mainly H-H and L-L, with the H-H type distributed mainly in the Su-Xi-Chang region and the L-L type distributed mainly in the Northern Jiangsu region. The levels of technology, economic development, industrialization, and industrial diversification are important individual driving factors, and the interaction among the different factors enhances their driving forces. This study suggests that spatial spillover effects should be focused to promote the coordinated development of regional energy-saving and environmental protection industries. At the same time, joint efforts should be made from the aspects of resources, government, economy, and related industries to promote the agglomeration of land for energy-saving and environmental protection industries.