更新于：2024-05-01

DNAL1

dynein axonemal light chain 1

更新于：2024-05-01

基本信息

别名

1700010H15RiK、C14orf168、CILD16

+ [4]

简介

Part of the multisubunit axonemal ATPase complexes that generate the force for cilia motility and govern beat frequency (By similarity). Component of the outer arm dynein (ODA). May be involved in a mechanosensory feedback mechanism controlling ODA activity based on external conformational cues by tethering the outer arm dynein heavy chain (DNAH5) to the microtubule within the axoneme (By similarity). Important for ciliary function in the airways and for the function of the cilia that produce the nodal flow essential for the determination of the left-right asymmetry (PubMed:21496787).

关联

100 项与 DNAL1 相关的临床结果

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100 项与 DNAL1 相关的转化医学

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0 项与 DNAL1 相关的专利（医药）

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492

项与 DNAL1 相关的文献（医药）

2024-03-01·Biochemistry and biophysics reports

Analysis of Achyranthes aspera leaf extract and acute toxicity study on fingerlings of Nile tilapia, Oreochromis niloticus

Article

作者: Mandefro, Belayhun ; Fereja, Workineh Mengesha ; Fremichael, Dawit ; Mereta, Seid Tiku ; Ambelu, Argaw

Schistosomiasis is a debilitating chronic disease with great socioeconomic and public health impact affecting the poor rural populations who lack access to sanitation, and safe water supply. The high cost of synthetic molluscicides, their toxicity to non-target organisms, and their persistence in the environment have forced the research of plant-derived molluscicides. Although plant molluscicides are cheap, biodegradable, ecofriendly and less toxic to higher animals, unregulated applications could affect non-target organisms. Therefore, ecotoxicological studies are essential to assess the toxicity of these substances to economically and ecologically significant fish species and to establish safe dosage level. This study is intended to investigate the acute toxicity of a molluscicidal plant Achyranthes aspera to Nile tilapia fingerlings, Oreochromis niloticus (O. niloticus) (n = 7) were exposed to serial dilutions of A. aspera leaf aqueous extract using maceration method for 96 h in triplicate setup. Phytoconstituents were identified by GC-MS. Mortality data were analyzed by probit regression to determine lethal concentrations. The NOAEC was ascertained through hypothesis testing based on survival data. The respective piscicidal LC₁ and LC₁₀ values were 897.43 and 1063.87 mg/L while the LC₅₀ is 1310.74 mg/L. In addition, the NOAEC was 1100 mg/L (p > 0.05). This piscicidal toxicity is much lower than its molluscicidal potency may be due to the presence of rotenones and triterpenoides which are commonly found in piscicidal natural products. The GC-MS analysis revealed 12 phytoconstituents including a monoterpene. This study indicates that A. aspera has low toxicity to Nile tilapia could be due to monoterpenes are nontoxic. The findings of this study demonstrate that, at this dose, the plant is safe to the test fish. Thus it can be effective, eco-friendly and sustainable alternative for the development of molluscicides for snail control.

2024-02-15·Ecotoxicology and environmental safety

Diesel exhaust particle exposure exacerbates ciliary and epithelial barrier dysfunction in the multiciliated bronchial epithelium models.

Article

作者: Eunsook Park ; Bu-Yeo Kim ; Seahyoung Lee ; Kuk Hui Son ; Jihye Bang ; Se Hyang Hong ; Joong Won Lee ; Kyung-Ok Uhm ; Hyun-Jeong Kwak ; Hyun Joung Lim

Airway epithelium, the first defense barrier of the respiratory system, facilitates mucociliary clearance against inflammatory stimuli, such as pathogens and particulates inhaled into the airway and lung. Inhaled particulate matter 2.5 (PM_2.5) can penetrate the alveolar region of the lung, and it can develop and exacerbate respiratory diseases. Although the pathophysiological effects of PM_2.5 in the respiratory system are well known, its impact on mucociliary clearance of airway epithelium has yet to be clearly defined. In this study, we used two different 3D in vitro airway models, namely the EpiAirway-full-thickness (FT) model and a normal human bronchial epithelial cell (NHBE)-based air-liquid interface (ALI) system, to investigate the effect of diesel exhaust particles (DEPs) belonging to PM_2.5 on mucociliary clearance. RNA-sequencing (RNA-Seq) analyses of EpiAirway-FT exposed to DEPs indicated that DEP-induced differentially expressed genes (DEGs) are related to ciliary and microtubule function and inflammatory-related pathways. The exposure to DEPs significantly decreased the number of ciliated cells and shortened ciliary length. It reduced the expression of cilium-related genes such as acetylated α-tubulin, ARL13B, DNAH5, and DNAL1 in the NHBEs cultured in the ALI system. Furthermore, DEPs significantly increased the expression of MUC5AC, whereas they decreased the expression of epithelial junction proteins, namely, ZO1, Occludin, and E-cadherin. Impairment of mucociliary clearance by DEPs significantly improved the release of epithelial-derived inflammatory and fibrotic mediators such as IL-1β, IL-6, IL-8, GM-CSF, MMP-1, VEGF, and S100A9. Taken together, it can be speculated that DEPs can cause ciliary dysfunction, hyperplasia of goblet cells, and the disruption of the epithelial barrier, resulting in the hyperproduction of lung injury mediators. Our data strongly suggest that PM2.5 exposure is directly associated with ciliary and epithelial barrier dysfunction and may exacerbate lung injury.

2024-01-31·Archives of disease in childhood

Stepwise genetic approach for the diagnosis of primary ciliary dyskinesia in highly consanguineous populations.

Article

作者: Dvir Gatt ; Inbal Golan Tripto ; Eran Levanon ; Noga Arwas ; Guy Hazan ; Soliman Alkrinawi ; Aviv D Goldbart ; Micha Aviram

BACKGROUND:

The American Thoracic Society guidelines for the diagnosis of primary ciliary dyskinesia (PCD) consider the presence of a bi-allelic pathogenic variant confirmatory for the diagnosis of PCD, with genetic testing recommended when other confirmatory diagnostic tests are less accessible. We present our experience with genetic testing as first line with a proposed algorithm for high consanguinity populations.

METHODS:

Patients with a suspected diagnosis of PCD underwent genetic testing according to a diagnostic algorithm composed of three steps: (1) patients with a previously known causative familial/Bedouin tribal pathogenic variant completed direct testing for a single variant; (2) if the initial test was negative or there was no known pathogenic variant, a PCD genetic panel was completed; (3) if the panel was negative, whole exome sequencing (WES) was completed.

RESULTS:

Since the implementation of the protocol, diagnosis was confirmed by genetic testing in 21 patients. The majority of them were of Bedouin origin (81%) and had a positive history of consanguinity (65%). Nine patients (43%) had a sibling with a confirmed diagnosis. Most patients (15/21, 71%) were diagnosed by direct pathogenic variant testing and the remainder by genetic panel (19%) and WES (10%). Disease-causing variants were found in nine genes, with DNAL1 (24%) and DNAAF3, DNAAF5, ZMYND10 (14% each) as the most prevalent ones.

CONCLUSIONS:

In highly consanguineous regions, a stepwise genetic testing approach is recommended. This approach may be particularly useful in areas where the ability to obtain confirmatory diagnostic tests through other modalities is less accessible.

项与 DNAL1 相关的新闻（医药）

2024-04-02

·佰傲谷BioValley

自身免疫性疾病“微环境”

不少自身免疫病都伴有皮肤病变（简述26种自身免疫性疾病）。作为免疫系统的第一道屏障，皮肤也存在影响疾病进展的免疫微环境。人类和小鼠皮肤中的免疫细胞类型Mucosal Immunol 15, 551–561 (2022)皮肤中的先天免疫细胞群皮肤中的APC包括：肥大细胞，尤其是在肢端部位。皮肤巨噬细胞：包括胚胎来源和招募的单核细胞衍生亚群。先天淋巴细胞(ILC)：1型(如NK细胞)，2型和3型ILC都存在于皮肤中，但ILC2尤其普遍。虽然皮肤ILC与其他粘膜组织中的ILC一样，主要是局部维持和扩张的组织驻留型细胞，但它们表达独特的受体模式，并且特别依赖于IL-18和TSLP的激活和功能。Immunity. 2021 Oct 12;54(10):2305-2320.e11.真皮中的其他DC亚群包括：经典树突状细胞(cDC)：cDC1型：在人皮肤中表达CD141，在小鼠皮肤中表达CD103；cDC2型：在人皮肤中表达CD1c，在小鼠皮肤中表达CD11b。在小鼠真皮中，也有CD103- CD11b-的“双阴性”DC细胞亚群。CD123+浆细胞样DC：在健康皮肤中的含量很少，但在各种疾病的情况下可以显着增加。单核细胞来源的DC细胞(moDCs)：经典单核细胞在进入组织后经过获得II类表达分化而来。人皮肤中表达CD14,小鼠皮肤中表达CD11b和CD64。朗格汉斯细胞(LCs)：主要存在于表皮中，通过延伸其树突以捕获皮肤表面附近的抗原。最近的研究表明，LC实际上是胚胎来源的组织驻留巨噬细胞的一个子集。其特点包括：在皮肤炎症期间，骨髓来源的单核细胞有助于增强朗格汉斯细胞的免疫特性。朗格汉斯细胞已被证明可以促进皮肤中的效应和调节性T细胞反应。最近研究鉴定了两个人类皮肤中的朗格汉斯细胞亚群LC1和LC2，二者的主要分化调节途径之一是EGR1和Notch信号。LC1在炎症微环境下保持稳定，而LC2容易被激活并表现出免疫抑制分子的表达升高。皮肤淋巴细胞：皮肤也是T细胞的密集储存库，整个表皮中约含有2×10^10个。以组织驻留的记忆亚型居多。在小鼠皮肤中，Vγ5Vδ1树突状表皮T细胞（DETC）在妊娠晚期就驻留在表皮中，与朗格汉斯细胞形成稳定的相互作用并产生细胞因子，有助于角质形成细胞的稳态增殖和伤口愈合。人类表皮缺乏DETC，但含有更多的CD8+CD103+ αβ T细胞群，这些细胞可能执行类似的功能。CD4+T细胞占人和小鼠皮肤中αβ T细胞的大部分。这些细胞优先存在于真皮中，但也可以存在于表皮和皮下。具有驻留记忆表型的Tregs占健康成人皮肤CD4+T细胞群的10-30%。皮肤Tregs中可能包含相当比例的胸腺来源Tregs。真皮中还含有丰富的非经典淋巴细胞亚群：真皮γδ T细胞群(小鼠皮肤中比例较人更高）、粘膜相关的不变性T(MAIT)细胞等。在稳定状态下，少量中性粒细胞，单核细胞和αβ T细胞负责检查真皮中的病原体；在炎症刺激下，皮肤驻留DC、巨噬细胞前体细胞、中性粒细胞、T细胞等免疫细胞收到招募，在细胞外基质(ECM)中迅速积聚。γδ T细胞、MAIT细胞和CD4+ Th17细胞则是皮肤IL-17A的主要来源。不同于肠道免疫微环境，使用靶向生物制剂的IL-17与上皮完整性的损害无关。抗IL-17疗法现在是治疗银屑病的主要手段。角质形成细胞则在表皮免疫微环境中表达几种不同的模式识别受体，并在炎症时产生多种细胞因子，包括胸腺基质淋巴生成素(TSLP)、TNF和IL-33等IL-1家族成员。这些细胞因子是激活皮肤免疫细胞和免疫细胞募集到皮肤所必需的。自身免疫病的表皮免疫微环境影响皮肤炎症伴有皮肤先天免疫细胞的显着变化，包括：巨噬细胞、树突状细胞、肥大细胞和ILC显著扩张；新细胞亚群募集，例如嗜酸性粒细胞和中性粒细胞；细胞活化，导致关键表面标志物表达模式改变。在不同类型的自身免疫病中，皮肤中可能存在的APC也有所不同。接触性超敏反应(CHS)：皮肤DC细胞、肥大细胞、嗜碱性粒细胞、血液内皮细胞、抗辐射细胞或朗格汉斯细胞；移植物宿主病(GvHD)：朗格汉斯细胞或角质细胞；银屑病：皮肤DC或朗格汉斯细胞。CHS：在CHS的诱发中，真皮DC是其中最重要的APC。真皮DC捕获的半抗原被呈现给皮肤中的效应T细胞。活化的效应T细胞产生IFNγ并引起皮肤炎症。同时，角质形成细胞收到诱导产生IL-1α，从而激活位于毛细血管后小静脉周围的M2型巨噬细胞。活化的巨噬细胞产生CXCL2，促进真皮DC的积累。银屑病：近期研究发现，表皮免疫微环境(epidermal immune microenvironment)在银屑病的发展中起主导作用。银屑病真皮中，表达CD1c和CD11b的DC2s在预启动阶段迁移到病灶周围皮肤区域，迅速取代EpCAM+++++CD11c low LC细胞，并引发炎症。表皮CD141 cDC1、CD1c cDC2、CD14 moDC和BDCA2 pDC可协调银屑病炎症。CCR2+ CD11c+hi LC在银屑病表皮中释放IL-23。CD5 T细胞在银屑病表皮和真皮中产生IL-17A和TNF-α的能力增强。CD4+CD25+Foxp3+Treg被认为在维持免疫稳态和通过抑制免疫应答调节局部组织炎症方面起重要作用。在银屑病中，Treg抑制功能受损导致辅助性T17/Treg平衡改变。不过Tregs在银屑病发病机制中的确切功能仍不清楚。Cell Mol Immunol (2022)参考文献：1.Zhang, C., Merana, G.R., Harris-Tryon, T. et al. Skin immunity: dissecting the complex biology of our body’s outer barrier. Mucosal Immunol 15, 551–561 (2022). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41385-022-00505-y2.Zhou, Y., Xu, F., Chen, XY. et al. The epidermal immune microenvironment plays a dominant role in psoriasis development, as revealed by mass cytometry. Cell Mol Immunol (2022). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41423-022-00940-83.Kabashima, K., Honda, T., Ginhoux, F. et al. The immunological anatomy of the skin. Nat Rev Immunol 19, 19–30 (2019). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41577-018-0084-54.Liu X, Zhu R, Luo Y, Wang S, Zhao Y, Qiu Z, Zhang Y, Liu X, Yao X, Li X, Li W. Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation. Immunity. 2021 Oct 12;54(10):2305-2320.e11. doi: 10.1016/j.immuni.2021.08.012. Epub 2021 Sep 10. PMID: 34508661.本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处···

临床研究免疫疗法细胞疗法

2022-11-27

·佰傲谷BioValley

自身免疫病的皮肤“免疫微环境”

不少自身免疫病都伴有皮肤病变（简述26种自身免疫性疾病）。作为免疫系统的第一道屏障，皮肤也存在影响疾病进展的免疫微环境。人类和小鼠皮肤中的免疫细胞类型Mucosal Immunol 15, 551–561 (2022)皮肤中的先天免疫细胞群皮肤中的APC包括：肥大细胞，尤其是在肢端部位。皮肤巨噬细胞：包括胚胎来源和招募的单核细胞衍生亚群。先天淋巴细胞(ILC)：1型(如NK细胞)，2型和3型ILC都存在于皮肤中，但ILC2尤其普遍。虽然皮肤ILC与其他粘膜组织中的ILC一样，主要是局部维持和扩张的组织驻留型细胞，但它们表达独特的受体模式，并且特别依赖于IL-18和TSLP的激活和功能。Immunity. 2021 Oct 12;54(10):2305-2320.e11.真皮中的其他DC亚群包括：经典树突状细胞(cDC)：cDC1型：在人皮肤中表达CD141，在小鼠皮肤中表达CD103；cDC2型：在人皮肤中表达CD1c，在小鼠皮肤中表达CD11b。在小鼠真皮中，也有CD103- CD11b-的“双阴性”DC细胞亚群。CD123+浆细胞样DC：在健康皮肤中的含量很少，但在各种疾病的情况下可以显着增加。单核细胞来源的DC细胞(moDCs)：经典单核细胞在进入组织后经过获得II类表达分化而来。人皮肤中表达CD14,小鼠皮肤中表达CD11b和CD64。朗格汉斯细胞(LCs)：主要存在于表皮中，通过延伸其树突以捕获皮肤表面附近的抗原。最近的研究表明，LC实际上是胚胎来源的组织驻留巨噬细胞的一个子集。其特点包括：在皮肤炎症期间，骨髓来源的单核细胞有助于增强朗格汉斯细胞的免疫特性。朗格汉斯细胞已被证明可以促进皮肤中的效应和调节性T细胞反应。最近研究鉴定了两个人类皮肤中的朗格汉斯细胞亚群LC1和LC2，二者的主要分化调节途径之一是EGR1和Notch信号。LC1在炎症微环境下保持稳定，而LC2容易被激活并表现出免疫抑制分子的表达升高。皮肤淋巴细胞：皮肤也是T细胞的密集储存库，整个表皮中约含有2×10^10个。以组织驻留的记忆亚型居多。在小鼠皮肤中，Vγ5Vδ1树突状表皮T细胞（DETC）在妊娠晚期就驻留在表皮中，与朗格汉斯细胞形成稳定的相互作用并产生细胞因子，有助于角质形成细胞的稳态增殖和伤口愈合。人类表皮缺乏DETC，但含有更多的CD8+CD103+ αβ T细胞群，这些细胞可能执行类似的功能。CD4+T细胞占人和小鼠皮肤中αβ T细胞的大部分。这些细胞优先存在于真皮中，但也可以存在于表皮和皮下。具有驻留记忆表型的Tregs占健康成人皮肤CD4+T细胞群的10-30%。皮肤Tregs中可能包含相当比例的胸腺来源Tregs。真皮中还含有丰富的非经典淋巴细胞亚群：真皮γδ T细胞群(小鼠皮肤中比例较人更高）、粘膜相关的不变性T(MAIT)细胞等。在稳定状态下，少量中性粒细胞，单核细胞和αβ T细胞负责检查真皮中的病原体；在炎症刺激下，皮肤驻留DC、巨噬细胞前体细胞、中性粒细胞、T细胞等免疫细胞收到招募，在细胞外基质(ECM)中迅速积聚。γδ T细胞、MAIT细胞和CD4+ Th17细胞则是皮肤IL-17A的主要来源。不同于肠道免疫微环境，使用靶向生物制剂的IL-17与上皮完整性的损害无关。抗IL-17疗法现在是治疗银屑病的主要手段。角质形成细胞则在表皮免疫微环境中表达几种不同的模式识别受体，并在炎症时产生多种细胞因子，包括胸腺基质淋巴生成素(TSLP)、TNF和IL-33等IL-1家族成员。这些细胞因子是激活皮肤免疫细胞和免疫细胞募集到皮肤所必需的。自身免疫病的表皮免疫微环境影响皮肤炎症伴有皮肤先天免疫细胞的显着变化，包括：巨噬细胞、树突状细胞、肥大细胞和ILC显著扩张；新细胞亚群募集，例如嗜酸性粒细胞和中性粒细胞；细胞活化，导致关键表面标志物表达模式改变。在不同类型的自身免疫病中，皮肤中可能存在的APC也有所不同。接触性超敏反应(CHS)：皮肤DC细胞、肥大细胞、嗜碱性粒细胞、血液内皮细胞、抗辐射细胞或朗格汉斯细胞；移植物宿主病(GvHD)：朗格汉斯细胞或角质细胞；银屑病：皮肤DC或朗格汉斯细胞。CHS：在CHS的诱发中，真皮DC是其中最重要的APC。真皮DC捕获的半抗原被呈现给皮肤中的效应T细胞。活化的效应T细胞产生IFNγ并引起皮肤炎症。同时，角质形成细胞收到诱导产生IL-1α，从而激活位于毛细血管后小静脉周围的M2型巨噬细胞。活化的巨噬细胞产生CXCL2，促进真皮DC的积累。银屑病：近期研究发现，表皮免疫微环境(epidermal immune microenvironment)在银屑病的发展中起主导作用。银屑病真皮中，表达CD1c和CD11b的DC2s在预启动阶段迁移到病灶周围皮肤区域，迅速取代EpCAM+++++CD11c low LC细胞，并引发炎症。表皮CD141 cDC1、CD1c cDC2、CD14 moDC和BDCA2 pDC可协调银屑病炎症。CCR2+ CD11c+hi LC在银屑病表皮中释放IL-23。CD5 T细胞在银屑病表皮和真皮中产生IL-17A和TNF-α的能力增强。CD4+CD25+Foxp3+Treg被认为在维持免疫稳态和通过抑制免疫应答调节局部组织炎症方面起重要作用。在银屑病中，Treg抑制功能受损导致辅助性T17/Treg平衡改变。不过Tregs在银屑病发病机制中的确切功能仍不清楚。Cell Mol Immunol (2022)参考文献：1.Zhang, C., Merana, G.R., Harris-Tryon, T. et al. Skin immunity: dissecting the complex biology of our body’s outer barrier. Mucosal Immunol 15, 551–561 (2022). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41385-022-00505-y2.Zhou, Y., Xu, F., Chen, XY. et al. The epidermal immune microenvironment plays a dominant role in psoriasis development, as revealed by mass cytometry. Cell Mol Immunol (2022). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41423-022-00940-83.Kabashima, K., Honda, T., Ginhoux, F. et al. The immunological anatomy of the skin. Nat Rev Immunol 19, 19–30 (2019). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41577-018-0084-54.Liu X, Zhu R, Luo Y, Wang S, Zhao Y, Qiu Z, Zhang Y, Liu X, Yao X, Li X, Li W. Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation. Immunity. 2021 Oct 12;54(10):2305-2320.e11. doi: 10.1016/j.immuni.2021.08.012. Epub 2021 Sep 10. PMID: 34508661.近期热门视频更多精彩视频，尽在佰傲谷视频号，欢迎关注~本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀点亮在看，传递信息♥

临床研究细胞疗法