NF-κBp50/p52 double knockout （dKO） and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have os...NF-κBp50/p52 double knockout （dKO） and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function, are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50/p52 dKO, RANK KO, Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths. We found that growth plates in p50/p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone. This growth plate abnormality disappears when animals become older, but their dwarfism persists. Op/Op or Src KO mice have relatively normal growth plate morphology. In-situ hybridization study of long bones from pS0/ p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen-expressing chondrocytes. Treatment of micro-mass chondrocyte cultures with RANKL did not affect expression levels of type 2 collagen and Sox9, markers for proliferative chondrocytes, but RANKL reduced the number of type 10 collagen-expressing hypertrophic chondrocytes. Thus, RANK/NF-κB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice.展开更多
Dwarfism is an important plant architecture trait in crop breeding（Peng et al.,1999;Sasaki el al.,2002）.In cucurbits.the compact plant type was proposed to develop new varieties for the once-over mechanical harvest ...Dwarfism is an important plant architecture trait in crop breeding（Peng et al.,1999;Sasaki el al.,2002）.In cucurbits.the compact plant type was proposed to develop new varieties for the once-over mechanical harvest for concentrated fruit set and higher densities（Li et al.,2011;Mondal et al.,2011）.展开更多
BACKGROUND There are many factors that lead to dwarfism,and the mechanism has not yet been elucidated.Next-generation sequencing may identify candidate-related gene mutations,which may clarify the molecular cause.AIM ...BACKGROUND There are many factors that lead to dwarfism,and the mechanism has not yet been elucidated.Next-generation sequencing may identify candidate-related gene mutations,which may clarify the molecular cause.AIM To analyze genetic variation by using a constructed panel related to dwarfism by utilizing next-generation sequencing platform sequencing analysis to screen candidate-related gene mutations.METHODS Physical and laboratory characteristics,including clinical examination,growth hormone drug challenge test,serum insulin-like growth factor-1(IGF-1),IGF binding protein 3,other related tests,imaging examination,and chromosome karyotyping,were analyzed.Next-generation sequencing was performed to analyze pathogenicity variability.RESULTS In the 39 dwarfism patients,10 had pathogenicity variability.Gene variation was found in the OBSL1,SLC26A2,PTPN11,COL27AI,HDAC6,CUL7,FGFR3,DYNC2H1,GH1,and ATP7B genes.Of the 10 patients with pathogenicity variability,the related physical characteristics included double breast development and growth hormone deficiency,enuresis and indirect inguinal hernia on the left,two finger distance of 70.2 cm,head circumference of 49.2 cm,ischium/lower body length of 1.8 cm,weak limb muscles,and partial growth hormone deficiency.After 6 mo of growth hormone therapy,the concentrations of IGF-1 and IGF binding protein 3 increased from 215.2±170.3 to 285.0±166.0 and 3.9±1.4 to 4.2±1.1,respectively.CONCLUSION OBSL1,SLC26A2,PTPN11,COL27AI,HDAC6,CUL7,FGFR3,DYNC2H1,GH1,and ATP7B genes may be related to the incidence of dwarfism,and more research needs to be performed to elucidate the mechanism.展开更多
The island rule,a general pattern of dwarfism in large species to gigantism in small species on islands relative to mainland,is typically seen as a macroevolutionary phenomenon.However,whether the ecological processes...The island rule,a general pattern of dwarfism in large species to gigantism in small species on islands relative to mainland,is typically seen as a macroevolutionary phenomenon.However,whether the ecological processes associated with abiotic and biotic factors generate a pattern of plant size variation similar to the island rule remains unknown.We measured plant height for 29,623 individuals of 50 common woody plant species across 43 islands in the Zhoushan Archipelago(8500 years old and yet to undergo major evolutionary adaptation)and the adjacent mainlands in China.We found pronounced variations in plant height,similar to those of the island rule.Interestingly,islands with low resource availability,such as low soil organic matter content and low precipitation,had a high degree of dwarfism;islands experiencing high environmental stress,such as high soil pH,had a high degree of dwarfism;and islands experiencing less planteplant competition had a high degree of gigantism.The magnitude of plant dwarfism was higher on small and remote islands than on larger and nearer islands.These results highlight the importance of ecological processes associated with abiotic and biotic conditions in shaping the island rule-like patterns of plant size variation.Since our studied archipelago is too young to undergo major evolution,ecological processes likely played a prominent role in generating the observed pattern,challenging the notion that the evolutionary process is the dominant factor underlying the island rule.Future studies on the island rule need to perform experiments to disentangle evolutionary from ecological mechanisms.展开更多
Cinnamoyl CoA reductase （CCR） and cinnamyl alcohol dehydrogenase （CAD） catalyze the last steps of mono- lignol biosynthesis. In Arabidopsis, one CCR gene （CCR1, Atlg15950） and two CAD genes （CAD C At3g19450 and...Cinnamoyl CoA reductase （CCR） and cinnamyl alcohol dehydrogenase （CAD） catalyze the last steps of mono- lignol biosynthesis. In Arabidopsis, one CCR gene （CCR1, Atlg15950） and two CAD genes （CAD C At3g19450 and CAD D At4g34230） are involved in this pathway. A triple cad c cad d ccrl mutant, named ccc, was obtained. This mutant displays a severe dwarf phenotype and male sterility. The lignin content in ccc mature stems is reduced to 50% of the wild-type level. In addition, stem lignin structure is severely affected, as shown by the dramatic enrichment in resistant inter-unit bonds and incorporation into the polymer of monolignol precursors such as coniferaldehyde, sinapaldehyde, and ferulic acid. Male sterility is due to the lack of lignification in the anther endothecium, which causes the failure of anther de- hiscence and of pollen release. The cc~ hypolignified stems accumulate higher amounts of flavonol glycosides, sinapoyl malate and feruloyl malate, which suggests a redirection of the phenolic pathway. Therefore, the absence of CAD and CCR, key enzymes of the monolignol pathway, has more severe consequences on the phenotype than the individual absence of each of them. Induction of another CCR （CCR2, Atlg80820） and another CAD （CAD1, At4g39330） does not compensate the absence of the main CCR and CAD activities. This lack of CCR and CAD activities not only impacts lignification, but also severely affects the development of the plants. These consequences must be carefully considered when trying to reduce the lignin content of plants in order to facilitate the lignocellulose-to-bioethanol conversion process.展开更多
小于胎龄儿(small for gestational age,SGA)成年期发生身材矮小的概率比正常出生体质量儿高5~7倍,且代谢性疾病风险增加。近年来,重组人生长激素(recombinant human growth hormone,rhGH)用于改善2~4岁追赶生长不足的SGA儿童身高,经过...小于胎龄儿(small for gestational age,SGA)成年期发生身材矮小的概率比正常出生体质量儿高5~7倍,且代谢性疾病风险增加。近年来,重组人生长激素(recombinant human growth hormone,rhGH)用于改善2~4岁追赶生长不足的SGA儿童身高,经过3~7年治疗,成年身高可改善6.9~12.6 cm。安全性总体良好,常见的不良反应包括注射部位局部疼痛、红肿,多可自行缓解;少数患儿可能出现一过性血糖升高、甲状腺功能减退等代谢异常。展开更多
目的研究基因重组人生长激素治疗特发性矮小症患儿的效果及对IGF-1水平、糖脂代谢的影响。方法选取2021年1月至2024年1月本院收治的120例特发性矮小症患儿作为研究对象,将其随机分为对照组和观察组,各60例。对照组采用常规治疗,观察组...目的研究基因重组人生长激素治疗特发性矮小症患儿的效果及对IGF-1水平、糖脂代谢的影响。方法选取2021年1月至2024年1月本院收治的120例特发性矮小症患儿作为研究对象,将其随机分为对照组和观察组,各60例。对照组采用常规治疗,观察组在对照组基础上增加基因重组人生长激素治疗。比较两组的临床疗效、生长指标、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白3(IGFBP-3)水平、糖脂代谢指标及不良反应发生情况。结果观察组的治疗总有效率高于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组的身高、生长速度均高于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组的IGF-1、IGFBP-3水平高于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)水平比较,差异无统计学意义(P>0.05)。两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论基因重组人生长激素治疗特发性矮小症患儿的效果显著,可促进身高生长,提高IGF-1水平,不影响糖脂代谢过程,且治疗安全性良好。展开更多
Plant height(PH)is one of the most important components of the plant ideotype,and it affects plant biomass,yield,lodging resistance,and the ability to use mechanized harvesting.Since many complex pathways controlling ...Plant height(PH)is one of the most important components of the plant ideotype,and it affects plant biomass,yield,lodging resistance,and the ability to use mechanized harvesting.Since many complex pathways controlling plant growth and development remain poorly understood,we are still unable to obtain the most ideal plants solely through breeding efforts.PH can be influenced by genotype,plant hormonal regulation,environmental conditions,and interactions with other plants.Here,we comprehensively review the factors influencing PH,including the regulation of PH-related developmental processes,the genetics and QTLs contributing to PH,and the hormone-regulated molecular mechanisms for PH.Additionally,the symbiotic influence of grafting on PH is discussed,focusing on the molecular regulation of gene expression and genetics.Finally,we propose strategies for applying recent findings to breeding for better PH,highlight some knowledge gaps,and suggest potential directions for future studies.展开更多
EPSPS is a key gene in the shikimic acid synthesis pathway that has been widely used in breeding crops with herbicide resistance.However,its role in regulating cell elongation is poorly understood.Through the overexpr...EPSPS is a key gene in the shikimic acid synthesis pathway that has been widely used in breeding crops with herbicide resistance.However,its role in regulating cell elongation is poorly understood.Through the overexpression of EPSPS genes,we generated lines resistant to glyphosate that exhibit an unexpected dwarf phenotype.A representative line,DHR1,exhibits a stable dwarf phenotype throughout its entire growth period.Except for plant height,the other agronomic traits of DHR1 are similar to its transgenic explants ZM24.Paraffin section observations showed that DHR1 internodes are shortened due to reduced elongation and division of the internode cells.Exogenous hormones confirmed that DHR1 is not a classical brassinolide(BR)-or gibberellin(GA)-related dwarfing mutant.Hybridization analysis and fine mapping confirmed that the EPSPS gene is the causal gene for dwarfism,and the phenotype can be inherited in different genotypes.Transcriptome and metabolome analyses showed that genes associated with the phenylpropanoid synthesis pathway are enriched in DHR1 compared with ZM24.Flavonoid metabolites are enriched in DHR1,whereas lignin metabolites are reduced.The enhancement of flavonoids likely results in differential expression of auxin signal pathway genes and alters the auxin response,subsequently affecting cell elongation.This study provides a new strategy for generating dwarfs and will accelerate advancements in light simplification in the cultivation and mechanized harvesting of cotton.展开更多
基金supported by research grants from the National Institutes of Health PHS awards(AR48697 and AR63650 to LX,AR055915 to DC,and AR43510 and AR49305 to BFB)
文摘NF-κBp50/p52 double knockout （dKO） and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function, are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50/p52 dKO, RANK KO, Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths. We found that growth plates in p50/p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone. This growth plate abnormality disappears when animals become older, but their dwarfism persists. Op/Op or Src KO mice have relatively normal growth plate morphology. In-situ hybridization study of long bones from pS0/ p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen-expressing chondrocytes. Treatment of micro-mass chondrocyte cultures with RANKL did not affect expression levels of type 2 collagen and Sox9, markers for proliferative chondrocytes, but RANKL reduced the number of type 10 collagen-expressing hypertrophic chondrocytes. Thus, RANK/NF-κB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice.
基金supported by funding from the National Natural Science Foundation of China(No.31225025)the National Basic Research Program of China(973 Program) (No.2012CB113900)+3 种基金the National High-tech R&D Program (863 Program)(No.2012AA100101)the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-AGISCAAS)the leading talents of Guangdong province Program(No. 00201515)supported by the Shenzhen Municipal and Dapeng District governments
文摘Dwarfism is an important plant architecture trait in crop breeding（Peng et al.,1999;Sasaki el al.,2002）.In cucurbits.the compact plant type was proposed to develop new varieties for the once-over mechanical harvest for concentrated fruit set and higher densities（Li et al.,2011;Mondal et al.,2011）.
基金Quanzhou Science and Technology Bureau,No.2018Z072。
文摘BACKGROUND There are many factors that lead to dwarfism,and the mechanism has not yet been elucidated.Next-generation sequencing may identify candidate-related gene mutations,which may clarify the molecular cause.AIM To analyze genetic variation by using a constructed panel related to dwarfism by utilizing next-generation sequencing platform sequencing analysis to screen candidate-related gene mutations.METHODS Physical and laboratory characteristics,including clinical examination,growth hormone drug challenge test,serum insulin-like growth factor-1(IGF-1),IGF binding protein 3,other related tests,imaging examination,and chromosome karyotyping,were analyzed.Next-generation sequencing was performed to analyze pathogenicity variability.RESULTS In the 39 dwarfism patients,10 had pathogenicity variability.Gene variation was found in the OBSL1,SLC26A2,PTPN11,COL27AI,HDAC6,CUL7,FGFR3,DYNC2H1,GH1,and ATP7B genes.Of the 10 patients with pathogenicity variability,the related physical characteristics included double breast development and growth hormone deficiency,enuresis and indirect inguinal hernia on the left,two finger distance of 70.2 cm,head circumference of 49.2 cm,ischium/lower body length of 1.8 cm,weak limb muscles,and partial growth hormone deficiency.After 6 mo of growth hormone therapy,the concentrations of IGF-1 and IGF binding protein 3 increased from 215.2±170.3 to 285.0±166.0 and 3.9±1.4 to 4.2±1.1,respectively.CONCLUSION OBSL1,SLC26A2,PTPN11,COL27AI,HDAC6,CUL7,FGFR3,DYNC2H1,GH1,and ATP7B genes may be related to the incidence of dwarfism,and more research needs to be performed to elucidate the mechanism.
基金supported by the State Key Program of National Natural Science Foundation of China(Grant No.32030068)the“Lump-sum System”Project of Chongqing Talent Plan(Grant No.cstc2022ycjh-bgzxm0204).
文摘The island rule,a general pattern of dwarfism in large species to gigantism in small species on islands relative to mainland,is typically seen as a macroevolutionary phenomenon.However,whether the ecological processes associated with abiotic and biotic factors generate a pattern of plant size variation similar to the island rule remains unknown.We measured plant height for 29,623 individuals of 50 common woody plant species across 43 islands in the Zhoushan Archipelago(8500 years old and yet to undergo major evolutionary adaptation)and the adjacent mainlands in China.We found pronounced variations in plant height,similar to those of the island rule.Interestingly,islands with low resource availability,such as low soil organic matter content and low precipitation,had a high degree of dwarfism;islands experiencing high environmental stress,such as high soil pH,had a high degree of dwarfism;and islands experiencing less planteplant competition had a high degree of gigantism.The magnitude of plant dwarfism was higher on small and remote islands than on larger and nearer islands.These results highlight the importance of ecological processes associated with abiotic and biotic conditions in shaping the island rule-like patterns of plant size variation.Since our studied archipelago is too young to undergo major evolution,ecological processes likely played a prominent role in generating the observed pattern,challenging the notion that the evolutionary process is the dominant factor underlying the island rule.Future studies on the island rule need to perform experiments to disentangle evolutionary from ecological mechanisms.
文摘Cinnamoyl CoA reductase （CCR） and cinnamyl alcohol dehydrogenase （CAD） catalyze the last steps of mono- lignol biosynthesis. In Arabidopsis, one CCR gene （CCR1, Atlg15950） and two CAD genes （CAD C At3g19450 and CAD D At4g34230） are involved in this pathway. A triple cad c cad d ccrl mutant, named ccc, was obtained. This mutant displays a severe dwarf phenotype and male sterility. The lignin content in ccc mature stems is reduced to 50% of the wild-type level. In addition, stem lignin structure is severely affected, as shown by the dramatic enrichment in resistant inter-unit bonds and incorporation into the polymer of monolignol precursors such as coniferaldehyde, sinapaldehyde, and ferulic acid. Male sterility is due to the lack of lignification in the anther endothecium, which causes the failure of anther de- hiscence and of pollen release. The cc~ hypolignified stems accumulate higher amounts of flavonol glycosides, sinapoyl malate and feruloyl malate, which suggests a redirection of the phenolic pathway. Therefore, the absence of CAD and CCR, key enzymes of the monolignol pathway, has more severe consequences on the phenotype than the individual absence of each of them. Induction of another CCR （CCR2, Atlg80820） and another CAD （CAD1, At4g39330） does not compensate the absence of the main CCR and CAD activities. This lack of CCR and CAD activities not only impacts lignification, but also severely affects the development of the plants. These consequences must be carefully considered when trying to reduce the lignin content of plants in order to facilitate the lignocellulose-to-bioethanol conversion process.
文摘小于胎龄儿(small for gestational age,SGA)成年期发生身材矮小的概率比正常出生体质量儿高5~7倍,且代谢性疾病风险增加。近年来,重组人生长激素(recombinant human growth hormone,rhGH)用于改善2~4岁追赶生长不足的SGA儿童身高,经过3~7年治疗,成年身高可改善6.9~12.6 cm。安全性总体良好,常见的不良反应包括注射部位局部疼痛、红肿,多可自行缓解;少数患儿可能出现一过性血糖升高、甲状腺功能减退等代谢异常。
文摘目的研究基因重组人生长激素治疗特发性矮小症患儿的效果及对IGF-1水平、糖脂代谢的影响。方法选取2021年1月至2024年1月本院收治的120例特发性矮小症患儿作为研究对象,将其随机分为对照组和观察组,各60例。对照组采用常规治疗,观察组在对照组基础上增加基因重组人生长激素治疗。比较两组的临床疗效、生长指标、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白3(IGFBP-3)水平、糖脂代谢指标及不良反应发生情况。结果观察组的治疗总有效率高于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组的身高、生长速度均高于对照组,差异具有统计学意义(P<0.05)。治疗后,观察组的IGF-1、IGFBP-3水平高于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的空腹血糖(FBG)、餐后2 h血糖(2 h PG)、总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)水平比较,差异无统计学意义(P>0.05)。两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论基因重组人生长激素治疗特发性矮小症患儿的效果显著,可促进身高生长,提高IGF-1水平,不影响糖脂代谢过程,且治疗安全性良好。
基金supported by the Major Science and Technology Project of Plant Breeding in Zhejiang Province,China(2021C02065-2)the Science&Technology Specific Projects in Agricultural High-tech Industrial Demonstration Area of the Yellow River Delta,China(2022SZX36)+1 种基金the“Pioneer”and“Leading Goose”R&D Program of Zhejiang,China(2022C02051)the National Natural Science Foundation of China(32202511,31972221,32002048,32172595).
文摘Plant height(PH)is one of the most important components of the plant ideotype,and it affects plant biomass,yield,lodging resistance,and the ability to use mechanized harvesting.Since many complex pathways controlling plant growth and development remain poorly understood,we are still unable to obtain the most ideal plants solely through breeding efforts.PH can be influenced by genotype,plant hormonal regulation,environmental conditions,and interactions with other plants.Here,we comprehensively review the factors influencing PH,including the regulation of PH-related developmental processes,the genetics and QTLs contributing to PH,and the hormone-regulated molecular mechanisms for PH.Additionally,the symbiotic influence of grafting on PH is discussed,focusing on the molecular regulation of gene expression and genetics.Finally,we propose strategies for applying recent findings to breeding for better PH,highlight some knowledge gaps,and suggest potential directions for future studies.
基金supported by funding from the Natural Science Foundation of Henan Province,China(232300421010)the Key Research and Development Project of Henan Province,China(231111110400)+4 种基金the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City,China(320LH045)the Hainan Yazhou Bay Seed Laboratory,China(B21HJ0215)the Fundamental Research Funds of State Key Laboratory of Cotton Biology,China(2021CBE03)the Central Public-interest Scientific Institution Basal Research Fund,China(Y2023XK16)the Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ASTIPIVFCAAS to F.G.L)。
文摘EPSPS is a key gene in the shikimic acid synthesis pathway that has been widely used in breeding crops with herbicide resistance.However,its role in regulating cell elongation is poorly understood.Through the overexpression of EPSPS genes,we generated lines resistant to glyphosate that exhibit an unexpected dwarf phenotype.A representative line,DHR1,exhibits a stable dwarf phenotype throughout its entire growth period.Except for plant height,the other agronomic traits of DHR1 are similar to its transgenic explants ZM24.Paraffin section observations showed that DHR1 internodes are shortened due to reduced elongation and division of the internode cells.Exogenous hormones confirmed that DHR1 is not a classical brassinolide(BR)-or gibberellin(GA)-related dwarfing mutant.Hybridization analysis and fine mapping confirmed that the EPSPS gene is the causal gene for dwarfism,and the phenotype can be inherited in different genotypes.Transcriptome and metabolome analyses showed that genes associated with the phenylpropanoid synthesis pathway are enriched in DHR1 compared with ZM24.Flavonoid metabolites are enriched in DHR1,whereas lignin metabolites are reduced.The enhancement of flavonoids likely results in differential expression of auxin signal pathway genes and alters the auxin response,subsequently affecting cell elongation.This study provides a new strategy for generating dwarfs and will accelerate advancements in light simplification in the cultivation and mechanized harvesting of cotton.
