热休克蛋白47 (HSP47)是一种内质网(ER)的常驻分子伴侣,对前胶原蛋白的正确折叠至关重要。HSP47表达的增加与纤维化等胶原相关疾病有关,例如肝、肺、消化道肿瘤等器官纤维化疾病。有研究表明,慢性心力衰竭患者心肌HSP47表达随心功能下...热休克蛋白47 (HSP47)是一种内质网(ER)的常驻分子伴侣,对前胶原蛋白的正确折叠至关重要。HSP47表达的增加与纤维化等胶原相关疾病有关,例如肝、肺、消化道肿瘤等器官纤维化疾病。有研究表明,慢性心力衰竭患者心肌HSP47表达随心功能下降而升高,与左室舒张末期内径呈正相关,而与左室射血分数呈负相关,本文就HSP47结构,表达调控,与胶原蛋白的相互作用,及在心力衰竭等各类纤维化疾病中的作用进行描述。Heat shock protein 47 (HSP47) is a resident molecular chaperone of the endoplasmic reticulum (ER) that is essential for the proper folding of procollagen. The increase in expression of HSP47 is associated with collagen-related diseases such as organ fibrosis in the liver, lungs, and gastrointestinal tract tumors. Studies have shown that cardiac HSP47 expression in patients with chronic heart failure decreases and increases in spontaneous function, which is positively correlated with left ventricular end-diastolic diameter, while negatively correlated with left ventricular ejection fraction. This paper describes the structure, expression regulation, interaction with collagen of HSP, and its role in various fibrotic diseases such as heart failure.展开更多
Osteogenesis imperfecta(OI)is a group of diseases caused by defects in type I collagen processing which result in skeletal fragility.While these disorders have been regarded as defects in osteoblast function,the role ...Osteogenesis imperfecta(OI)is a group of diseases caused by defects in type I collagen processing which result in skeletal fragility.While these disorders have been regarded as defects in osteoblast function,the role of matrix-embedded osteocytes in OI pathogenesis remains largely unknown.Homozygous human SP7(c.946 C>T,R316C)mutation results in a recessive form of OI characterized by fragility fractures,low bone mineral density and osteocyte dendrite defects.To better understand how the OI-causing R316C mutation affects the function of SP7,we generated Sp7^(R342C)knock-in mice.Consistent with patient phenotypes,Sp7^(R342C/R342C)mice demonstrate increased cortical porosity and reduced cortical bone mineral density.Sp7^(R342C/R342C)mice show osteocyte dendrite defects,increased osteocyte apoptosis,and intracortical bone remodeling with ectopic intracortical osteoclasts and elevated osteocyte Tnfsf11 expression.展开更多
VACHERON CONSTANTIN 江诗丹顿 寻迹时光,致敬时光 9月17日,为回溯270载制表臻途,江诗丹顿重磅呈献里程碑之作--La Quête du Temps寻迹时光座钟,并沿用该座钟的4项专利技术打造灵感新作--Métiers d’Art艺术大师系列致敬时光...VACHERON CONSTANTIN 江诗丹顿 寻迹时光,致敬时光 9月17日,为回溯270载制表臻途,江诗丹顿重磅呈献里程碑之作--La Quête du Temps寻迹时光座钟,并沿用该座钟的4项专利技术打造灵感新作--Métiers d’Art艺术大师系列致敬时光臻途腕表。La Quête du Temps座钟由江诗丹顿携手动偶大师François Junod、瑞士高端时钟制造商L’Épée 1839及日内瓦天文台专家历经七年协作研发,凝聚6,293枚零件、23项复杂功能、144种动偶姿态于一体,搭载陀飞轮、万年历、恒星时、三维逆跳月相等精密机制,并申请15项专利,堪称突破制表疆域的机械艺术巨制。其核心装置由天文学家动偶指示时间,伴随乐音奏响,演绎人类探索宇宙的浪漫诗篇。展开更多
将基于最优插值（OI）的同化并行模块植入全谱空间的第三代海浪模式 WAVEWATCH III ver-sion3.14,建立数据同化的海浪模式预报系统,并通过实际的预报个例对同化系统进行检验。个例实验是以5°S以北的印度洋海域为目标计算区域,海面...将基于最优插值（OI）的同化并行模块植入全谱空间的第三代海浪模式 WAVEWATCH III ver-sion3.14,建立数据同化的海浪模式预报系统,并通过实际的预报个例对同化系统进行检验。个例实验是以5°S以北的印度洋海域为目标计算区域,海面风场强迫采用业务单位的中尺度天气预报模式WRF （weather research and forecast）提供的逐时海面风场预报产品。模式积分过程中连续同化2010年12月15日、16日和17日过境北印度洋的Jason-2卫星高度计沿轨有效波高（SWH）数据（需要指出的是,每次同化得到新的SWH分析场后需重构相应的二维海浪谱用于谱模式）。SWH同化分析值和无同化的对照组分别与高度计沿轨观测数据比较发现,就日平均统计来看,同化较无同化使SWH分析值的均方根误差减小约25%-50%。以 SWH同化分析场作为初始场的预报表明,同化对预报影响的时效性可延长至48-60 h。本研究目的是通过将高度计测量的SWH数据同化到海浪模式进一步提升海浪数值预报的准确度。展开更多
文摘热休克蛋白47 (HSP47)是一种内质网(ER)的常驻分子伴侣,对前胶原蛋白的正确折叠至关重要。HSP47表达的增加与纤维化等胶原相关疾病有关,例如肝、肺、消化道肿瘤等器官纤维化疾病。有研究表明,慢性心力衰竭患者心肌HSP47表达随心功能下降而升高,与左室舒张末期内径呈正相关,而与左室射血分数呈负相关,本文就HSP47结构,表达调控,与胶原蛋白的相互作用,及在心力衰竭等各类纤维化疾病中的作用进行描述。Heat shock protein 47 (HSP47) is a resident molecular chaperone of the endoplasmic reticulum (ER) that is essential for the proper folding of procollagen. The increase in expression of HSP47 is associated with collagen-related diseases such as organ fibrosis in the liver, lungs, and gastrointestinal tract tumors. Studies have shown that cardiac HSP47 expression in patients with chronic heart failure decreases and increases in spontaneous function, which is positively correlated with left ventricular end-diastolic diameter, while negatively correlated with left ventricular ejection fraction. This paper describes the structure, expression regulation, interaction with collagen of HSP, and its role in various fibrotic diseases such as heart failure.
基金support from the National Institute of Health(K99AR081897,R00AR081897)M.N.W.acknowledges funding support from the National Institute of Health(P01DK011794,R01DK116716)+1 种基金the Smith Family Foundation Odyssey Award,and the Chen Institute Massachusetts General Hospital Research Scholar(2024-2029)awardμCT and bone histomorphometry were performed by the Center for Skeletal Research at Massachusetts General Hospital,a NIH-funded program(P30AR066261 and AR075042)led by Mary Bouxsein and Marie Demay.
文摘Osteogenesis imperfecta(OI)is a group of diseases caused by defects in type I collagen processing which result in skeletal fragility.While these disorders have been regarded as defects in osteoblast function,the role of matrix-embedded osteocytes in OI pathogenesis remains largely unknown.Homozygous human SP7(c.946 C>T,R316C)mutation results in a recessive form of OI characterized by fragility fractures,low bone mineral density and osteocyte dendrite defects.To better understand how the OI-causing R316C mutation affects the function of SP7,we generated Sp7^(R342C)knock-in mice.Consistent with patient phenotypes,Sp7^(R342C/R342C)mice demonstrate increased cortical porosity and reduced cortical bone mineral density.Sp7^(R342C/R342C)mice show osteocyte dendrite defects,increased osteocyte apoptosis,and intracortical bone remodeling with ectopic intracortical osteoclasts and elevated osteocyte Tnfsf11 expression.
文摘VACHERON CONSTANTIN 江诗丹顿 寻迹时光,致敬时光 9月17日,为回溯270载制表臻途,江诗丹顿重磅呈献里程碑之作--La Quête du Temps寻迹时光座钟,并沿用该座钟的4项专利技术打造灵感新作--Métiers d’Art艺术大师系列致敬时光臻途腕表。La Quête du Temps座钟由江诗丹顿携手动偶大师François Junod、瑞士高端时钟制造商L’Épée 1839及日内瓦天文台专家历经七年协作研发,凝聚6,293枚零件、23项复杂功能、144种动偶姿态于一体,搭载陀飞轮、万年历、恒星时、三维逆跳月相等精密机制,并申请15项专利,堪称突破制表疆域的机械艺术巨制。其核心装置由天文学家动偶指示时间,伴随乐音奏响,演绎人类探索宇宙的浪漫诗篇。
文摘将基于最优插值（OI）的同化并行模块植入全谱空间的第三代海浪模式 WAVEWATCH III ver-sion3.14,建立数据同化的海浪模式预报系统,并通过实际的预报个例对同化系统进行检验。个例实验是以5°S以北的印度洋海域为目标计算区域,海面风场强迫采用业务单位的中尺度天气预报模式WRF （weather research and forecast）提供的逐时海面风场预报产品。模式积分过程中连续同化2010年12月15日、16日和17日过境北印度洋的Jason-2卫星高度计沿轨有效波高（SWH）数据（需要指出的是,每次同化得到新的SWH分析场后需重构相应的二维海浪谱用于谱模式）。SWH同化分析值和无同化的对照组分别与高度计沿轨观测数据比较发现,就日平均统计来看,同化较无同化使SWH分析值的均方根误差减小约25%-50%。以 SWH同化分析场作为初始场的预报表明,同化对预报影响的时效性可延长至48-60 h。本研究目的是通过将高度计测量的SWH数据同化到海浪模式进一步提升海浪数值预报的准确度。
