ToM

成釉细胞瘤
  • 文章类型: Journal Article
    在植物中,通过与TOC(外叶绿体膜上的转位子)和TOM(外线粒体膜上的转位子)复合物的特定受体结合,将在细胞质中翻译的数千种核编码蛋白分选到叶绿体和线粒体中,以导入这些细胞器。这些受体的降解途径尚不清楚。这里,我们发现了一个融合的泛素-蛋白酶体途径降解拟南芥TOC和TOM尾部锚定受体。受体被E3连接酶泛素化,并被AAA+腺苷三磷酸酶CDC48从外膜拉扯,之后是以前未表征的细胞溶质蛋白,尾锚定外膜蛋白(TTOP)的跨膜结构域(TMD)结合蛋白,在受体和CDC48的C末端与暴露的TMD结合,并将这些复合物递送至26S蛋白酶体。
    In plants, thousands of nucleus-encoded proteins translated in the cytosol are sorted to chloroplasts and mitochondria by binding to specific receptors of the TOC (translocon on the outer chloroplast membrane) and the TOM (translocon on the outer mitochondrial membrane) complexes for import into those organelles. The degradation pathways for these receptors are unclear. Here, we discovered a converged ubiquitin-proteasome pathway for the degradation of Arabidopsis thaliana TOC and TOM tail-anchored receptors. The receptors are ubiquitinated by E3 ligase(s) and pulled from the outer membranes by the AAA+ adenosine triphosphatase CDC48, after which a previously uncharacterized cytosolic protein, transmembrane domain (TMD)-binding protein for tail-anchored outer membrane proteins (TTOP), binds to the exposed TMDs at the C termini of the receptors and CDC48, and delivers these complexes to the 26S proteasome.
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  • 文章类型: Journal Article
    脂质双层的全干涉反射荧光(TIRF)显微镜是研究单个完整膜蛋白的横向运动和离子通道活性的有效技术。在这里,我们描述了如何将线粒体外膜前蛋白转位酶TOM-CC及其β桶蛋白传导通道Tom40整合到支持的脂质双层中,以确定运动和通道活性之间的可能关系。我们建议我们的方法可以很容易地应用于膜蛋白通道,其中与膜近端或膜内结构的瞬时束缚伴随着通道渗透的变化。
    Total interference reflection fluorescence (TIRF) microscopy of lipid bilayers is an effective technique for studying the lateral movement and ion channel activity of single integral membrane proteins. Here we describe how to integrate the mitochondrial outer membrane preprotein translocase TOM-CC and its β-barrel protein-conducting channel Tom40 into supported lipid bilayers to identify possible relationships between movement and channel activity. We propose that our approach can be readily applied to membrane protein channels where transient tethering to either membrane-proximal or intramembrane structures is accompanied by a change in channel permeation.
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  • 文章类型: Journal Article
    尽管社会认知障碍是精神分裂症的核心特征,其子组件之间的关系不太清楚。对19例精神分裂症患者和20名匹配的健康对照进行了情绪识别测试,以及移情和心理理论(ToM)的认知和情感子成分。患者在认知移情和ToM的两个子组成部分上的得分明显低于对照组。当情感识别作为协变量时,认知移情和情感ToM的群体差异消失了。我们的结果表明,情绪识别是精神分裂症较高社会认知水平缺陷的重要因素。
    Although impairments in social cognition are a core feature in schizophrenia, the relationship between its subcomponents is less clear. Nineteen schizophrenia patients and 20 matched healthy controls were tested for emotion recognition, and for the cognitive and affective subcomponents of empathy and theory of mind (ToM). Patients scored significantly worse than controls on cognitive empathy and both subcomponents of ToM. Group differences disappeared for cognitive empathy and affective ToM when emotion recognition was included as a covariate. Our results indicate that emotion recognition is an important factor involved in the deficits on higher levels of social cognition in schizophrenia.
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  • 文章类型: Published Erratum
    [这修正了文章DOI:10.3389/freur.2023.1208638。].
    [This corrects the article DOI: 10.3389/fneur.2023.1208638.].
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  • 文章类型: Journal Article
    帕金森病(PD)患者表现出社会认知缺陷,特别是在心理理论(ToM)能力方面。目前尚不清楚它们是否与PD相关的多巴胺缺乏相关,并由左旋多巴替代疗法调节。
    共有15名PD患者和13名健康对照(HC)参与了研究。他们执行不同的神经心理任务,包括假发识别测试(FPRT),评估认知ToM的不同维度(例如,检测,不适当,意图),和阅读心灵中的眼睛测试(RMET)作为情感ToM的指标。PD患者接受了两次测试,一次在常规治疗下,另一次在左旋多巴戒断至少18小时后(MED-ON和MED-OFF,分别)。无论哪种情况,测量血清药物水平和运动症状严重程度[统一帕金森病评定量表(UPDRS)]。
    PD患者的MED-ON和MED-OFF状况通过前者的血清药物水平高于后者状态以及相应的运动缺陷改善得到证实。这样做,在任何与ToM相关的任务中,没有发现左旋多巴治疗的功能差异.一般来说,患者在情感和认知ToM测试中的表现均比对照组差。
    PD患者在认知和情感ToM方面存在缺陷。多巴胺替代,有效改善电机状况,似乎并不能抵消这些功能障碍。
    UNASSIGNED: Patients with Parkinson\'s disease (PD) exhibit deficits in social cognition, particularly with respect to Theory of Mind (ToM) capacities. It is unclear whether they are associated with PD-related dopamine deficiency and modulated by levodopa replacement therapy.
    UNASSIGNED: A total of 15 persons with PD and 13 healthy controls (HC) participated in the study. They performed different neuropsychological tasks, including the Faux Pas Recognition Test (FPRT), assessing different dimensions of cognitive ToM (e.g., detection, inappropriateness, intentions), and the Reading the Mind in the Eyes Test (RMET) as an index of affective ToM. Persons with PD were tested twice, once under their regular treatment and another time after at least 18 h of levodopa withdrawal (MED-ON and MED-OFF, respectively). On either occasion, serum drug levels and motor symptom severity [Unified Parkinson\'s Disease Rating Scale (UPDRS)] were measured.
    UNASSIGNED: MED-ON and MED-OFF conditions in patients with PD were confirmed by higher serum drug levels in the former than in the latter state and a corresponding amelioration of the motor deficit. In so doing, no performance difference in any ToM-related task was identified as a function of the levodopa therapy. Generally, patients performed worse than controls in both affective and cognitive ToM tests.
    UNASSIGNED: Patients with PD have deficits in cognitive and affective ToM. Dopamine replacement, effective for improving the motor condition, does not appear to counteract these dysfunctions.
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  • 文章类型: Journal Article
    幽灵虾(甲壳类:Decapoda)表现出显着的生态位选择和栖息地多样性水平。由于他们神秘的生活方式,鬼虾组合与可能影响其局部分布的环境参数之间的相互作用知之甚少。在本研究中,对波斯湾(PG)和阿曼湾(GO)的幽灵虾组合进行了调查,以评估主要驱动因素,这些驱动因素决定了它们在广泛的生态位类型和大的地理范围内的组合结构。在三次大规模海洋探险中,用于生物和理化分析的沉积物样品由箱式取芯器(0.1m2)从62个站点收集。收集的样品的空间分布是根据粒度获得的沉积物参数进行评估的,总有机物含量(TOM)和碳酸盐,以及包括pH在内的水参数,温度,深度,溶解氧,叶绿素α和盐度。我们的结果表明,在PG的西北部和GO的东部,幽灵虾的生物多样性热点。Aqaballianassaehsani是本研究中最常见的物种。DistLM分析表明,该地区鬼虾的丰度与TOM和Sand显着相关。此外,逐步回归模型强调,每种幽灵虾都受到特定环境因素的影响。我们的发现为两个Michaelcallianassa同类物的利基偏好提供了新的见解。尽管水和沉积物参数在确定M.persica的栖息地偏好中起着至关重要的作用,只有沉积物参数指定了M.indica的有利生态位。
    Ghost shrimps (Crustacea: Decapoda) demonstrate remarkable levels of niche selection and habitat diversity. Due to their cryptic life style, interactions between ghost shrimp assemblages and environmental parameters that potentially shape their local distribution are poorly understood. In the present study, ghost shrimp assemblages from the Persian Gulf (PG) and the Gulf of Oman (GO) were investigated to assess the main drivers determining their assemblage structure along a wide niche type and at a large geographic scale. During three large-scale oceanographic expeditions, sediments samples for biological and physicochemical analysis were collected by box corer (0.1 m2) from 62 stations. The spatial distribution of collected samples was evaluated based on sediment parameters obtained on grain size, total organic content (TOM) and carbonate, as well as water parameters including pH, temperature, depth, dissolved oxygen, chlorophyll α and salinity. Our results indicated a biodiversity hotspot for ghost shrimp in the north-western part of PG and the eastern part of GO. Aqaballianassa ehsani is the most frequent species in this research. DistLM analysis revealed that the abundance of ghost shrimps in the region is significantly corelated with TOM and Sand. Furthermore, a step-wise regression model highlighted that each ghost shrimp species is influenced by specific environmental factors. Our findings provide new insight in niche preferences of the two Michaelcallianassa congeners. While water and sediment parameters play a crucial role in determining the habitat preference of M. persica, only sediment parameters specify the favored niche of M. indica.
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  • 文章类型: Journal Article
    心理理论(ToM)理解并将精神状态归因于自己和他人的能力,在多发性硬化症(MS)中可能受损,一种影响年轻人的神经退行性疾病。考虑到ToM与MS中的生活质量(QoL)严格相关,并且可以增强社会支持网络-这对该人群尤为重要-,我们旨在设计和实施一种新颖的ToM康复训练。为了使培训尽可能生态化,我们设计了一种协议,通过描述现实世界条件的刺激来增强ToM(从电影电影拍摄的视频剪辑,文学小说,和音频声音)。我们在13名受试者的样本中测试训练对ToM的认知和情感成分的影响,随机分配到ToM培训组和对照组。执行了以下ToM任务:阅读眼中的思想(RMET),奇怪的故事任务,假假任务和错误信念第一和第二阶任务(FBII和III阶)。我们还通过多伦多述情障碍量表(TAS-20)进行了心理行为评估。结果表明,我们新颖的ToM训练可用于增强由以下任务测量的ToM能力:RMET(情感任务,p=0.015)和FBII订单任务(FB,认知任务,p=0.032)。我们的ToM训练对TAS-20量表的总分(p=0.018)及其“困难描述情感分量表”(p=0.018)也有显着影响,表明述情障碍特征减少。未来使用更大样本的工作可以研究更具代表性的MS群体中的ToM训练有效性。
    Theory of Mind (ToM), the ability to understand and attribute mental states to ourselves and others, could be impaired in Multiple Sclerosis (MS), a neurodegenerative disease affecting young adults. Considering that ToM is strictly connected to Quality of Life (QoL) in MS and that could enhance the social support network -which is particularly important for this population-, we aimed to design and implement a novel ToM rehabilitation training. To make the training as much ecological as possible, we have devised a protocol enhancing ToM through stimuli depicting real-world conditions (video-clips taken from cinema movies, literary fictions, and audio voices). We test training\'s effect on both cognitive and affective components of ToM in a sample of 13 subjects, randomly assigned to the ToM training Group and to the Control Group. The following ToM tasks were administered: the Reading the Mind in the Eyes (RMET), the Strange Stories task, the Faux Pas Task and the False Belief First- and Second - Order Task (FB II and III order). We also administered a psycho-behavioral assessment through the Toronto Alexithymia Scale (TAS-20). Results show that our novel ToM training is useful in enhancing ToM abilities measured by the following tasks: the RMET (affective task, p = 0.015) and the FB II-order task (FB, cognitive task, p = 0.032). Our ToM training had also a significant effect on the total score of the TAS-20 Scale (p = 0.018) and on its \"Difficulty Describing Feelings subscale\" (p = 0.018), indicating a reduction of the alexithymia traits. Future works with larger samples could investigate the ToM training effectiveness in a more representative MS populations.
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  • 文章类型: Journal Article
    用于注释基因功能的改进的生物信息学工具变得越来越可用,但是这些信息必须被认为是理论上的,直到进一步的实验证据证明它。在这里报道的工作中,叶绿体(Toc)和线粒体(Tom)的外膜的主要成分的基因,包括N.benthamiana的前蛋白受体和蛋白质传导通道,已确定。与功能注释序列(例如拟南芥的序列)的序列同一性搜索和系统发育关系表明,N.benthamiana直向同源物主要作为最近重复的基因座存在。仅发现Toc34直系同源物(NbToc34),而Toc159受体家族由四个直向同源物组成,但与拟南芥有些不同。除NbToc90外,其余(NbToc120、NbToc159A和NbToc159B)具有约150kDa的分子量和相似长度的酸性结构域。只有两个Tom20受体的直系同源物,发现了NbTom20-1和NbTom20-2。N.benthamiana中Toc和Tom受体同工型的数量与先前在番茄中报道的数量以及我们在烟草属和茄属其他物种的BLAST搜索中发现的数量相当。克隆后,研究了N.benthamiana直系同源物的亚细胞定位,结果与拟南芥受体相同。沉默后的表型分析以及根中的相对表达分析,茎和叶显示,除了Toc和Tom通道形成成分(NbToc75和NbTom40)和NbToc34外,在Toc159或线粒体受体中都可以观察到功能冗余。最后,通过两种替代技术证实了NbToc34和NbToc159家族受体之间的异二聚体形成,表明可以组装不同的Toc复合物。需要解决其他工作,以了解这是否会导致每个Toc复合体的功能专业化。
    Improved bioinformatics tools for annotating gene function are becoming increasingly available, but such information must be considered theoretical until further experimental evidence proves it. In the work reported here, the genes for the main components of the translocons of the outer membrane of chloroplasts (Toc) and mitochondria (Tom), including preprotein receptors and protein-conducting channels of N. benthamiana, were identified. Sequence identity searches and phylogenetic relationships with functionally annotated sequences such as those of A. thaliana revealed that N. benthamiana orthologs mainly exist as recently duplicated loci. Only a Toc34 ortholog was found (NbToc34), while Toc159 receptor family was composed of four orthologs but somewhat different from those of A. thaliana. Except for NbToc90, the rest (NbToc120, NbToc159A and NbToc159B) had a molecular weight of about 150 kDa and an acidic domain similar in length. Only two orthologs of the Tom20 receptors, NbTom20-1 and NbTom20-2, were found. The number of the Toc and Tom receptor isoforms in N. benthamiana was comparable to that previously reported in tomato and what we found in BLAST searches in other species in the genera Nicotiana and Solanum. After cloning, the subcellular localization of N. benthamiana orthologs was studied, resulting to be identical to that of A. thaliana receptors. Phenotype analysis after silencing together with relative expression analysis in roots, stems and leaves revealed that, except for the Toc and Tom channel-forming components (NbToc75 and NbTom40) and NbToc34, functional redundancy could be observed either among Toc159 or mitochondrial receptors. Finally, heterodimer formation between NbToc34 and the NbToc159 family receptors was confirmed by two alternative techniques indicating that different Toc complexes could be assembled. Additional work needs to be addressed to know if this results in a functional specialization of each Toc complex.
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  • 文章类型: Journal Article
    线粒体疾病是一组异质性的遗传疾病,由编码调节线粒体功能的基因产物的致病变异引起。这些基因位于线粒体或核基因组中。TOMM7基因编码线粒体外膜(TOM)复合物转位酶的调节亚基,该调节亚基在核编码的线粒体蛋白易位到线粒体中起重要作用。我们报告了一个在TOMM7中具有纯合变体的个体(c.73T>C,p.Trp25Arg)表现为综合征性身材矮小,骨骼异常,肌肉张力减退,微泡肝脂肪变性,和发育迟缓。对小鼠模型的分析强烈提示所鉴定的变体是低形态的,因为对于该变体纯合的小鼠显示出比具有纯合Tomm7缺失的小鼠更温和的表型。这些Tomm7突变小鼠表现出与线粒体功能障碍一致的病理变化,包括生长缺陷,严重的脂肪萎缩,和肝脏中的脂质积累。这些小鼠在其生命的最后一周内快速进行性体重减轻后过早死亡。Tomm7缺乏导致线粒体功能的独特改变;尽管生物能量缺乏,突变细胞显示增加的氧消耗与电子传递链(ETC)抑制剂的正常反应,这表明Tomm7缺乏导致氧化和ATP合成之间的解偶联,而不会损害三羧酸循环代谢或ETC的功能。这项研究提供了证据,表明编码TOM复合物亚基的基因之一的低态变体会导致线粒体疾病。
    Mitochondrial diseases are a heterogeneous group of genetic disorders caused by pathogenic variants in genes encoding gene products that regulate mitochondrial function. These genes are located either in the mitochondrial or in the nuclear genome. The TOMM7 gene encodes a regulatory subunit of the translocase of outer mitochondrial membrane (TOM) complex that plays an essential role in translocation of nuclear-encoded mitochondrial proteins into mitochondria. We report an individual with a homozygous variant in TOMM7 (c.73T>C, p.Trp25Arg) that presented with a syndromic short stature, skeletal abnormalities, muscle hypotonia, microvesicular liver steatosis, and developmental delay. Analysis of mouse models strongly suggested that the identified variant is hypomorphic because mice homozygous for this variant showed a milder phenotype than those with homozygous Tomm7 deletion. These Tomm7 mutant mice show pathological changes consistent with mitochondrial dysfunction, including growth defects, severe lipoatrophy, and lipid accumulation in the liver. These mice die prematurely following a rapidly progressive weight loss during the last week of their lives. Tomm7 deficiency causes a unique alteration in mitochondrial function; despite the bioenergetic deficiency, mutant cells show increased oxygen consumption with normal responses to electron transport chain (ETC) inhibitors, suggesting that Tomm7 deficiency leads to an uncoupling between oxidation and ATP synthesis without impairing the function of the tricarboxylic cycle metabolism or ETC. This study presents evidence that a hypomorphic variant in one of the genes encoding a subunit of the TOM complex causes mitochondrial disease.
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  • 文章类型: Journal Article
    UNASSIGNED:心理理论(ToM)是识别的能力,理解,并考虑自己和他人的心理状态和观点来预测和解释行为和动机。人们普遍认为,自闭症谱系障碍(ASD)的儿童在ToM方面遇到困难。然而,还有一些研究结果表明,患有发育性语言障碍(DLD)的儿童的ToM能力也可能受到损害。
    UNASSIGNED:评估三组儿童的ToM能力:1。无语言困难的ASD;2.DLD,以他们的语言障碍而闻名;3.TD没有语言问题。
    UNASSIGNED:根据以前的临床报告和标准化的希伯来语语言评估工具,共检查了41名5至6岁的学龄前儿童,并将其分配到三组之一。通过标准化测试建立非语言智商,以验证平均范围内的放置(>75智商)。使用希伯来语版本的ToM任务电池和父母问卷(ToMI)检查了ToM技能。
    UNASSIGNED:与DLD儿童相比,ASD儿童的ToM评分明显较低,和TD。DLD儿童的ToM得分与TD儿童的得分相似。根据家长的调查问卷,与TD同龄人相比,ASD儿童和DLD儿童的ToM技能都较少。
    UNASSIGNED:目前的研究结果表明,患有ASD的儿童在ToM方面有一个基本的困难,这与他们的语言能力无关。患有DLD的儿童在涉及ToM的日常社交互动中表现出困难。ASD和语言障碍都可能影响ToM发育,这表明不同的发育路线会影响ToM的获得。
    UNASSIGNED: Theory of mind (ToM) is the ability to recognize, comprehend, and consider oneself\'s and others\' mental states and perspectives to predict and explain behaviors and motivations. It is widely accepted that children with autism spectrum disorder (ASD) experience difficulties with ToM. However, there are also findings suggesting that ToM abilities might also be compromised in children with Developmental Language Disorders (DLD).
    UNASSIGNED: To assess ToM abilities in three groups of children: 1. ASD with no language difficulties; 2. DLD, known for their language disorder; and 3. TD with no language issues.
    UNASSIGNED: A total of 41 preschool children aged 5-to-6 were examined and assigned to one of the three groups based on previous clinical reports and a standardized Hebrew language assessment tool. Nonverbal IQ was established with a standardized test to verify within average range placement (>75 IQ). ToM skills were examined with a Hebrew version of the ToM Task Battery and parent\'s questionnaire (ToMI).
    UNASSIGNED: Children with ASD had significantly lower ToM scores compared to the children with DLD, and TD. The ToM scores of the children with DLD were similar to the scores of the TD children. According to the parents\' questionnaires, both the ASD children and the DLD children had less developed ToM skills compared to their TD peers.
    UNASSIGNED: The present findings suggest that children with ASD have a fundamental difficulty in ToM that is independent of their language abilities. Children with DLD show difficulties in everyday social interactions that involve ToM. It is possible that both ASD and language disorders influence ToM development, suggesting that different developmental routes affect the acquisition of ToM.
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