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1.
J Cell Physiol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31674013

RESUMO

MicroRNA-142-3p (miR-142-3p) was previously investigated in various cancers, whereas, it's role in breast cancer (BC) remains far from understood. In this study, we found that miR-142-3p was markedly decreased both in cell lines and BC tumor tissues. Elevated miR-142-3p expression suppressed growth and metastasis of BC cell lines via gain-of-function assay in vitro and in vivo. Mechanistically, miR-142-3p could regulate the ras-related C3 botulinum toxin substrate 1 (RAC1) expression in protein level, which simultaneously suppressed the epithelial-to-mesenchymal transition related protein levels and the activity of PAK1 phosphorylation, respectively. In addition, rescue experiments revealed RAC1 overexpression could reverse tumor-suppressive role of miR-142-3p. Our results showed miR-142-3p could function as a tumor suppressor via targeting RAC1/PAK1 pathway in BC, suggesting a potent therapeutic target for BC treatment.

2.
Cell Death Dis ; 10(11): 825, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672961

RESUMO

C-X-C motif chemokine receptor 7 (CXCR7), which mediates the immune response in the brain, was recently reported to regulate neurological functions. However, the role of CXCR7 in epilepsy remains unclear. Here, we found that CXCR7 was upregulated in the hippocampal dentate gyrus (DG) of mice subjected to kainic acid (KA)-induced epilepsy and in the brain tissues of patients with temporal lobe epilepsy. Silencing CXCR7 in the hippocampal DG region exerted an antiepileptic effect on the KA-induced mouse model of epilepsy, whereas CXCR7 overexpression produced a seizure-aggravating effect. Mechanistically, CXCR7 selectively regulated N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic neurotransmission in hippocampal dentate granule cells by modulating the cell membrane expression of the NMDAR subunit2A, which requires the activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Thus, CXCR7 may regulate epileptic seizures and represents a novel target for antiepileptic treatments.

3.
J Clin Immunol ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31686315

RESUMO

PURPOSE: Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that mediates cellular responses to interferons (IFNs) and other cytokines and growth factors in diverse cell types. STAT1 gain-of-function (GOF) mutations result in an unexpectedly wide range of clinical features. It remains unclear why STAT1 GOF mutations result in such a broad spectrum of phenotypes. METHODS: We analyzed the clinical, molecular, and phenotypic characteristics of nine Chinese patients with STAT1 GOF mutations. RESULTS: This study enrolled nine patients with STAT1 GOF mutations including five novel mutations. We discuss the molecular and phenotypic characterization such as unique Penicillium marneffei lymphadenitis. Patients with STAT1 GOF mutations had defects in both innate and adaptive immunity, including impaired T cell receptor (TCR) diversity; reduced numbers of naïve and effector memory CD4+ T cells, memory B cells, and NK cells; and defects in the production of IL-17A and IFN-γ. In addition, experiments with primary immune cells revealed that enhanced STAT1 phosphorylation resulted from not only lower rates of STAT1 dephosphorylation but also increased total STAT1 expression. CONCLUSIONS: Our report provides the first comprehensive overview of the molecular genetics, clinical heterogeneity, and underlying immunological abnormalities of patients with STAT1 GOF mutations in China. In further study, to find the relationship between different STAT1 GOF mutations and clinical phenotype as well as the mechanism of increased total STAT1 expression will be needed.

4.
Org Lett ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31686514

RESUMO

An efficient in situ Pd-NHC catalytic system for regioselective arylation of B(3,6)-H bonds of o-carborane has been developed for the first time. A series of symmetric and unsymmetric 3,6-diaryl-o-carboranes anchored with active groups have been synthesized with moderate to good yields under mild conditions. This work offers an efficient protocol for selective activation of B(3,6)-H bonds and has important value in design coupling reactions for selective functionalization of o-carboranes.

5.
Pharmacol Res ; : 104501, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31689520

RESUMO

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide that afflicts human health. With the in-depth study of the disease, its pathogenesis has gradually become clear. Although great breakthroughs have been made in the research of ALD, the research and development of drugs related to ALD has lagged behind seriously. However, natural products have always inspired the development of drugs. Meanwhile, there is evidence that some natural products can also play a certain role in the treatment of ALD. Thus, we reviewed the natural products, extracts and formulations with potential anti-ALD activities by consulting the relevant data in the databases of PubMed, Web of Science and CNKI databases, in order to elucidate the regulated mechanism of these natural products. Sum up, the insights provided in present review will be needed for further exploration of botanical drugs in the development of ALD therapy.

6.
Medicine (Baltimore) ; 98(45): e17844, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702641

RESUMO

BACKGROUND: Several treatments are beneficial for patients with cancer-related pain (CRP), and there are numbers of systematic reviews evaluating the effectiveness and safety of these treatments. However, the overall quality of the evidence has not been quantitatively assessed. The aim of this study is to overcome the inconclusive evidence about the interventions of CRP. METHODS: We will perform an umbrella systematic review to identify eligible randomised controlled trials (RCTs). A comprehensive literature search will be conducted in MEDLINE, EMBASE, and the Cochrane library for systematic reviews, meta-analyses and RCTs. We will describe the general information of the RCTs for participants, interventions, outcome measurements, comparisons, and results. Network meta-analysis will be developed to determine the comparative effectiveness of the treatments. RESULTS: The result of this network meta-analysis will provide direct and indirect evidence of treatments for CRP. CONCLUSION: The conclusion of our study will help clinicians and CRP patients to choose suitable treatment options. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as the data are not individualized. The findings of this systematic review will be disseminated in a peer-reviewed publication and/or presented at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42019131721.

7.
J Sex Med ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31668731

RESUMO

INTRODUCTION: Acellular dermal matrix (ADM) is a common filler used widely in clinical practice to increase penile girth for cosmetic reasons, but there are few studies on its complications. AIM: The aim of this study was to investigate and analyze the complications of penile girth enhancement (PGE) with ADM. METHODS: The medical records of 78 patients who underwent PGE with ADM between June 2016 and January 2019 were retrospectively reviewed. MAIN OUTCOME MEASURE: Related complications and their subsequent management were summarized and analyzed. RESULTS: 78 patients (mean age 31.14 years [21-66 years]) received PGE with ADM. At the 3-month follow-up, the penile circumference was increased by 1.1 (0.5-2.1) cm on average. There were 47 patients with erectile discomfort, 12 with delayed healing, 10 with unobvious augmentation effect, 8 with wound hematoma, 7 with prepuce edema, 4 with wound infection, and 3 patients with skin necrosis of the dorsal side. 7 patients eventually underwent ADM removal. CLINICAL IMPLICATIONS: These adverse complications indicate that ADM should be used with caution for PGE. STRENGTH & LIMITATIONS: This study adds important data, as there are few published reports on the complications of PGE with ADM. However, this study did not compare postoperative complications with ADM to those seen with other filler material. CONCLUSION: Even with standardized surgical methods and rigorous postoperative care, complications of PGE using ADM are severe, which indicates that it is not an ideal or safe method for PGE. Xu T, Zhang G, Bai W, et al. Complications and Management of Penile Girth Enhancement with Acellular Dermal Matrix. J Sex Med 2019;XX:XXX-XXX.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31581102

RESUMO

Uterine cancer (also known as endometrial cancer) can seriously affect the female reproductive system, and histopathological image analysis is the gold standard for diagnosing endometrial cancer. Due to the limited ability to model the complicated relationships between histopathological images and their interpretations, existing computer-aided diagnosis (CADx) approaches using traditional machine learning algorithms often failed to achieve satisfying results. In this study, we develop a CADx approach based on a convolutional neural network (CNN) and attention mechanisms, called HIENet. In the ten-fold cross-validation on ~3,300 hematoxylin and eosin (H&E) image patches from ~500 endometrial specimens, HIENet achieved a 76.91 ± 1.17% (mean ± s. d.) accuracy for four classes of endometrial tissue, i.e., normal endometrium, endometrial polyp, endometrial hyperplasia, and endometrial adenocarcinoma. Also, HIENet obtained an area-under-the-curve (AUC) of 0.9579 ± 0.0103 with an 81.04 ± 3.87% sensitivity and 94.78 ± 0.87% specificity in a binary classification task that detected endometrioid adenocarcinoma. Besides, in the external validation on 200 H&E image patches from 50 randomly-selected female patients, HIENet achieved an 84.50% accuracy in the four-class classification task, as well as an AUC of 0.9829 with a 77.97% (95% confidence interval, CI, 65.27%~87.71%) sensitivity and 100% (95% CI, 97.42%~100.00%) specificity. The proposed CADx method outperformed three human experts and five CNN-based classifiers regarding overall classification performance. It was also able to provide pathologists better interpretability of diagnoses by highlighting the histopathological correlations of local pixel-level image features to morphological characteristics of endometrial tissue.

9.
Nat Methods ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31641286

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

10.
Biomed Res Int ; 2019: 7368627, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662995

RESUMO

Brucellar spondylodiscitis, the most prevalent and significant osteoarticular presentation of human Brucellosis, is difficult to diagnose and usually yields irreversible neurologic deficits and spinal deformities. However, no animal models of Brucellar spondylodiscitis exist, allowing for preclinical investigations. The present study investigated whether intraosseous injection of attenuated Brucella melitensis vaccine into rabbits' lumbar vertebrae imitates the radiographic and histopathological characteristics of human Brucellar spondylodiscitis. Radiographic and histopathological analyses at 8 weeks postoperatively revealed radiographic changes within vertebral bodies and intervertebral discs, abscesses formation within the paravertebral soft tissue, and typical prominent inflammation response without caseous necrosis, which were largely comparable to human Brucellar spondylodiscitis. Such a medium-sized, surgically feasible rabbit model provides a promising in vivo setting for further preclinical investigation of Brucellar spondylodiscitis.

11.
Med Sci Monit ; 25: 7882-7888, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31634342

RESUMO

BACKGROUND Because facet joints move with the disc, changes in vertebral bodies occur simultaneously with progression of degeneration of cervical facet joints. This study investigated age-related differences in cervical facet joint abnormalities and multi-dimensional characteristics of MCs in patients with cervical spondylotic myelopathy. MATERIAL AND METHODS Forty-five patients underwent both magnetic resonance imaging (MRI) and computed tomography (CT) of the cervical spine. Axial and sagittal parameter changes from C3 to C7, including facet orientation (FO) and facet tropism (FT), and Modic changes (MCs), were evaluated and documented preoperatively, and we also measured the heights and diameters of MCs and performed correlation analysis and established linear regression models. RESULTS The axial facet orientation increased slightly from C3 66.5 (11.4) to C7 89.9 (19). The sagittal facet orientation and facet tropism increased between C3-C4 and C6-C7, but it decreased between C4 to C6. The MCs volume decreased from C3 to C4 and increased from C4 to C7. There was a gradual decrease of FO and FT from C3 to C5 and a gradual increase of these 2 angles from C5 to C7 in all age groups. The lowest values of FO and FT were detected at C5, while the highest values of FO and FT were detected at C7. CONCLUSIONS Age was negatively correlated with the axial, sagittal, and coronal cervical facet orientation, especially at C4/5 level. The FT with respect to the axial and sagittal plane from C5 to C6 increased with age.

12.
Life Sci ; 237: 116978, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31644893

RESUMO

AIMS: The activation of NLRP3 inflammasome, which initiates an inflammatory cascade and triggers inflammatory death, plays a crucial role in the pathogenesis of spinal cord injury (SCI). Echinacoside (ECH) is a phenylethanoid glycoside possessing prominent anti-inflammatory effects and various neuroprotective properties in the central nervous system, but the effect of ECH on SCI was rarely studied. Therefore, the purpose of this experiment was to look into the therapeutic effects of ECH on SCI and the underlying mechanisms. MAIN METHODS: Basso-Beattie-Bresnahan (BBB) locomotion scale, Nissl staining, and hematoxylin-eosin (HE) staining was employed to examine the therapeutic effects of ECH on SCI. In addition, reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP) in BV-2 cells stimulated with lipopolysaccharides and adenosine 5'-triphosphate were examined. The expression levels of proteins involving NLRP3 inflammasome-related pathway were measured. KEY FINDINGS: The in vivo experiment indicated that administration of ECH significantly enhanced the BBB scores, reduced the neuron loss, and ameliorated the tissue architecture after SCI. Additionally, ECH dramatically inhibited NLRP3 inflammasome activation in the rat SCI model. In vitro study indicated that ECH significantly reduced ROS level, improved the MMP, blocked activation of NF-κB, and inhibited the NLRP3 inflammasome signaling pathway. The effect of ECH on inhibition of NLRP3 inflammasome signaling pathway was partially governed by suppression of the generation of ROS and activation of NF-κB. SIGNIFICANCE: ECH can accelerate motor function recovery in rats following SCI by inhibiting NLRP3 inflammasome-related signaling pathway, suggesting that ECH may serve as a potential therapeutic agent for treating SCI.

13.
Molecules ; 24(20)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614601

RESUMO

To develop new anti-inflammatory agents, a series of 7-O-amide hesperetin derivatives was designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. All compounds showed inhibitory effect on LPS-induced NO production. Among them, 7-O-(2-(Propylamino)-2-oxoethyl)hesperetin (4d) and 7-O-(2-(Cyclopentylamino)-2-oxoethyl)hesperetin (4k) with hydrophobic side chains exhibited the most potent NO inhibitory activity (IC50 = 19.32 and 16.63 µM, respectively), showing stronger inhibitory effect on the production of pro- inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) than indomethacin and celecoxib at 10 µM. The structure-activity relationships (SARs) suggested that the 7-O-amide unit was buried in a medium-sized hydrophobic cavity of the bound receptor. Furthermore, compound 4d could also significantly suppress the expression of inducible nitric oxide synthase enzymes (iNOS) and cyclooxygenase-2 (COX-2), through the nuclear factor-kappa B (NF-κB) signaling pathway.

14.
J Exp Bot ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31616940

RESUMO

Soluble carbohydrates not only directly affect crop growth and development but also act as signal molecules, enhancing the cold tolerance of plants. For example, raffinose family oligosaccharides (RFOs) play an important role in abiotic stress tolerance. The following experiments were performed to determine whether galactinol, a key limiting factor in RFOs biosynthesis, functions as a signal molecule triggering cold tolerance. Exposure to low temperatures induced the expression of galactinol synthase (AnGolS1) in Ammopiptanthus nanus, which is a desert plant that survives temperatures between -30°C to 47°C. AnGolS1 has a greater catalytic activity than tomato galactinol synthase (SlGolS2). Moreover, SlGolS2 was expressed only at low levels. Expression of AnGolS1 in tomato enhanced cold tolerance and led to changes in the sugar composition of the tomato seeds and seedlings. AnGolS1 transgenic tomato lines exhibited an enhanced capacity for ethylene (ET) signaling. The application of galactinol abolished the repression of the ET signaling pathway by 1-methylcyclopropene during seed germination. Moreover, the expression of ERF transcription factors was increased. Galactinol may therefore act as a signal molecule affecting the ET pathway.

15.
Sleep Med ; 2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-31607435

RESUMO

OBJECTIVE: Cataplexy is a pathognomonic symptom of narcolepsy type 1. This study was conducted to clarify the clinical characteristics of cataplexy by staging, and to further analyse the correlations of clinical features and cataplectic stages in patients with narcolepsy type 1 (NT1). METHODS: We experimentally triggered patients with NT1 into cataplexy while under video-polysomnography (v-PSG) monitoring in the sleep lab. The most serious cataplectic attack from each patient was analysed. Each cataplectic episode was segmented into four stages according to the v-PSG. Correlations were analysed between cataplectic stages in pairs, and between cataplectic stages and other clinical features. RESULTS: We observed 81 cataplectic episodes in 21 patients with diverse triggers, including humorous or exciting videos, tickling, recalling horrible memories and exercising. Nine patients (43%) went through complete cataplectic attacks while the others experienced partial attacks. Four cataplectic stages (ie, triggering, resisting, atonic, and recovering) were identified according to clinical and electromyograms characteristics. Resisting stage is predominant (56.4%) in cataplexy, while atonic stage is most related with the total duration of cataplexy. The Epworth Sleepiness Scale score (ESS) has a positive correlation with the total duration of cataplexy. Both duration of cataplexy and ESS score are negatively correlated with disease course. However, medication history seems have no influence on either cataplexy duration or ESS score. CONCLUSION: Four-stage segmentation shows the dynamic process of the cataplectic attack, which is different from the traditional classification of complete or partial cataplexy. Resisting stage is necessary for every cataplexy and might reflect the compensation mechanism, while atonic stage may be omitted in some patients. The severity of narcolepsy reduces with the extension of natural course regardless of medication history.

16.
Nat Methods ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31611693

RESUMO

Super-resolution correlative light and electron microscopy (SR-CLEM) is a powerful approach for imaging specific molecules at the nanoscale in the context of the cellular ultrastructure. Epon epoxy resin embedding offers advantages for SR-CLEM, including ultrastructural preservation and high quality sectioning. However, Epon embedding eliminates fluorescence from most fluorescent proteins. We describe a photocontrollable fluorescent protein, mEosEM, that can survive Epon embedding after osmium tetroxide (OsO4) treatment for improved SR-CLEM.

17.
Medicine (Baltimore) ; 98(39): e16774, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574793

RESUMO

BACKGROUND: Total hip arthroplasty (THA) relieves pain and restores function in patients with severe rheumatoid arthritis and osteoarthritis. Over the past few decades, several authors have attempted to assess the efficacy and safety of simultaneous bilateral THA compared with staged bilateral THA. The purpose of this meta-analysis is to compare the mortalities and complications between simultaneous bilateral THA and staged bilateral THA. METHODS: A literature search to identify eligible studies was undertaken to identify all relevant articles published until August 2018. We included studies that compared simultaneous bilateral THA and staged bilateral THA and their effects on mortality and complications. The outcomes included mortality, the occurrence of deep venous thrombosis (DVT), the occurrence of pulmonary embolism (PE), respiratory complications, cardiovascular complications, digestive system complications and the occurrence of dislocation. Stata 12.0 was used for the meta-analysis. RESULTS: Nineteen studies involving 59,257 patients were identified; among them, 16,758 patients were selected for treatment with simultaneous bilateral THA, and 42,499 patients were chosen for the purpose of staged bilateral THA. The meta-analysis results demonstrated that there was no significant difference between simultaneous bilateral THA and staged bilateral THA in terms of mortality (risk ratio [RR] = 1.15, 95% CI = 0.76, 1.74; P = .520). Compared with staged bilateral THA, simultaneous bilateral THA was associated with a reduction in the occurrence of DVT, PE and respiratory complications (P < .05). There were no significant differences in the cardiovascular complications, digestive system complications or the occurrence of dislocation and infection (P = .057). CONCLUSIONS: We observed that the prevalence of DVT, PE and respiratory complications was considerably lower with the use of simultaneous bilateral THA than with the use of staged bilateral THA. Thus, simultaneous bilateral THA is a considerably safer procedure than staged bilateral THA in selected THA patients.


Assuntos
Artrite Reumatoide/cirurgia , Artroplastia de Quadril/efeitos adversos , Artroplastia de Quadril/métodos , Osteoartrite do Quadril/cirurgia , Complicações Pós-Operatórias/epidemiologia , Artroplastia de Quadril/mortalidade , Doenças do Sistema Digestório/epidemiologia , Cardiopatias/epidemiologia , Humanos , Luxações Articulares/epidemiologia , Prevalência , Embolia Pulmonar/epidemiologia , Transtornos Respiratórios/epidemiologia , Trombose Venosa/epidemiologia
18.
Medicine (Baltimore) ; 98(40): e17409, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577752

RESUMO

Lower urinary tract symptoms (LUTS) have detrimental impact on health-related quality of life. This study has 2 aims: first to identify the optimum model for LUTS study and then to explore the potential associated factors of LUTS and bother LUTS with the optimum model among adult women in China.The survey was conducted in 6 regions of China between February and July 2006. A modified Chinese Bristol Female LUTS questionnaire was administered. The number of LUTS was the main outcome measure. The fitting goodness was compared to identify the optimum model with likelihood ratio test statistics. Zero-inflated negative binomial (ZINB) model was used to explore the potential associated factors of LUTS and bother LUTS.Of all 18,992 respondents, 55.5% of respondents reported one (any LUTS) or more LUTS (mixed LUTS) and 36.5% of respondents reported one or more bother LUTS. With the largest log likelihood and smallest AIC and BIC, ZINB model showed the best goodness of fit. In the ZINB model, we identified multiple associated factors for any LUTS and mixed LUTS; older age (ß≥0.2), overweight [ß = 0.059, 95%CI (0.016∼0.102)], obese [ß = 0.143, 95%CI (0.087∼0.198)], postmenopausal status [ß = 0.099, 95%CI (0.023∼0.175)], prolonged labor [ß = 0.188, 95%CI (0.104∼0.272)], constipation [ß = 0.309, 95%CI (0.262∼0.357)], coexisting pelvic organ prolapse (POP) [ß = 0.348, 95%CI (0.224∼0.473)], diabetes (ß = 0.178, 95%CI (0.100∼0.257), hypertension [ß = 0.092, 95%CI (0.041∼0.143)], smoking (ß = 0.192, 95%CI (0.127∼0.258) and alcohol consumption [ß = 0.063, 95%CI (0.001∼0.126)] increased the odds of mixed LUTS. We identified multiple associated factors for bother LUTS and mixed LUTS; older age (ß ≥ 0.1), prolonged labor [ß = 0.153, 95%CI (0.031∼0.275)], constipation [ß = 0.359, 95%CI (0.292∼0.426)] coexisting POP (ß = 0.212, [95%CI (0.031∼0.393)], diabetes [ß = 0.154, 95%CI (0.030∼0.278)], and smoking [ß = 0.169, 95%CI (0.076∼0.262)] increased the odds of bother mixed LUTS.ZINB model was the optimum model to explore the potential associated factors of LUTS. Older age, coexisting POP and constipation were both closely related to any and bother LUTS, also the severity of LUTS. Compared to nulliparity, single or multiple deliveries and women who had perineal laceration had nothing to do with the severity of LUTS.


Assuntos
Sintomas do Trato Urinário Inferior/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Comorbidade , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Pessoa de Meia-Idade , Modelos Estatísticos , Prevalência , Qualidade de Vida , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
19.
Sci Adv ; 5(9): eaax2166, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31579823

RESUMO

RNA binding proteins are key players in posttranscriptional regulation and have been implicated in neurodevelopmental and neuropsychiatric disorders. Here, we report a significant burden of heterozygous, likely gene-disrupting variants in CSDE1 (encoding a highly constrained RNA binding protein) among patients with autism and related neurodevelopmental disabilities. Analysis of 17 patients identifies common phenotypes including autism, intellectual disability, language and motor delay, seizures, macrocephaly, and variable ocular abnormalities. HITS-CLIP revealed that Csde1-binding targets are enriched in autism-associated gene sets, especially FMRP targets, and in neuronal development and synaptic plasticity-related pathways. Csde1 knockdown in primary mouse cortical neurons leads to an overgrowth of the neurites and abnormal dendritic spine morphology/synapse formation and impaired synaptic transmission, whereas mutant and knockdown experiments in Drosophila result in defects in synapse growth and synaptic transmission. Our study defines a new autism-related syndrome and highlights the functional role of CSDE1 in synapse development and synaptic transmission.

20.
Nat Commun ; 10(1): 4765, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628366

RESUMO

Spin-orbit coupling (SOC) has gained much attention for its rich physical phenomena and highly promising applications in spintronic devices. The Rashba-type SOC in systems with inversion symmetry breaking is particularly attractive for spintronics applications since it allows for flexible manipulation of spin current by external electric fields. Here, we report the discovery of a giant anisotropic Rashba-like spin splitting along three momentum directions (3D Rashba-like spin splitting) with a helical spin polarization around the M points in the Brillouin zone of trigonal layered PtBi2. Due to its inversion asymmetry and reduced symmetry at the M point, Rashba-type as well as Dresselhaus-type SOC cooperatively yield a 3D spin splitting with αR ≈ 4.36 eV Å in PtBi2. The experimental realization of 3D Rashba-like spin splitting not only has fundamental interests but also paves the way to the future exploration of a new class of material with unprecedented functionalities for spintronics applications.

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