海南海桑Sonneratia hainanensis KO,E,Y.Chen et W.Y.Chen是我国特有的海桑科红树林濒危植物,仅天然分布于中国的海南岛。海南海桑采用种子育苗。每年6-9月为最佳采种期。洗净的种子应置于含有水的储存缸中,避光、阴凉处储存备用。育...海南海桑Sonneratia hainanensis KO,E,Y.Chen et W.Y.Chen是我国特有的海桑科红树林濒危植物,仅天然分布于中国的海南岛。海南海桑采用种子育苗。每年6-9月为最佳采种期。洗净的种子应置于含有水的储存缸中,避光、阴凉处储存备用。育苗采用配制培养土,育苗过程中应注意补充淡水降低苗床盐度,并注意预防螃蟹、病虫对幼苗的危害。造林可选秋茄(Kandelia candel)等其它树种营造混交林。选用40～80cm高的苗木,株行距规格可为4m×4m,在抚育期内应注意清除藻类及残次林木等。展开更多
Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult hom...Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.展开更多
Abstract： Mechanical properties of clay under high stress are quite different from those under low stress. It is necessary to investi- gate unloading properties of clay under high stress for the design and constructi...Abstract： Mechanical properties of clay under high stress are quite different from those under low stress. It is necessary to investi- gate unloading properties of clay under high stress for the design and construction of deep underground engineering projects. A series of experiments were conducted to investigate the unloading properties of clay under high confining pressures by using a SKA-1 high pressure consolidation instrument designed by us. The stress versus strain relationship and the way that K0 values of clay change during the loading-unloading process were discovered. The results show that there are clear differences in the state of stress and deformation behavior of the clay along different unloading paths.展开更多
From the perspective of analysis-synthesis translation mode,this paper discusses the translator’s responsibility and the translator’s role in the translation of historiography,based on the case of Ko Kung-chen’s Hi...From the perspective of analysis-synthesis translation mode,this paper discusses the translator’s responsibility and the translator’s role in the translation of historiography,based on the case of Ko Kung-chen’s History of Chinese Journalism.Missionary J.S.Roberts believed that translation is the logical combination of two processes of analysis and synthesis.The analysis process is characterized by understanding,emphasizing accurate understanding and professional analysis of the source text,while the synthesis process focuses on the transformation of language and culture.The two processes are dependent,forming the whole process of translation altogether.As the indisputable subject of translation,the translator should assume his own subjective responsibility in the two processes.The translator should be responsible for the fact and professional academics in the analysis process,and language and culture and translation itself in the synthesis process,playing the role of a reviewer,disseminator and translator to ensure that the translation text would be correct,accurate and professional so as to realize the value of himself and translation.展开更多
Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to P...Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc).In a reciprocal manner,LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation.Pharmacological intervention in these diseasemodifying pathways may facilitate the development of novel PD therapeutics,despite the current lack of an established drug evaluation model.As such,we reviewed the feasibility of employing the versatile global Pink1knockout(KO)rat model as a self-sufficient,spontaneous PD model for investigating both disease etiology and drug pharmacology.These rats retain clinical features encompassing basal mitophagic flux changes with PD progression.We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.展开更多
The CRISPR/Cas9 system has been tailored to a revolutionary genetic tool because of its remarkable simplicity and efficacy.While complex genome editing in the mouse since the 1990 s has been dominated by the use of em...The CRISPR/Cas9 system has been tailored to a revolutionary genetic tool because of its remarkable simplicity and efficacy.While complex genome editing in the mouse since the 1990 s has been dominated by the use of embryonic stem（ES） cells,CRISPR/Cas9 now offers a versatile and fast approach to precisely modify virtually any DNA regions directly in mouse zygotes.Yet,this relative simplicity does not preclude a conscientious preparatory work that is often neglected when initiating a project.Here,we describe the key steps leading to successful generation of a double knockout（KO） mouse by simultaneously targeting two homolog genes,Tmem176 a and Tmem176 b,which are located in the same genomic locus.Additionally,we show that similar efficiency can be obtained in a mixed genetic background or directly in the C57BL/6 inbred strain.Thus,presented as a detailed case study that should be helpful to the non-specialists,we focus on the genotyping strategy to anticipate the various possibilities.展开更多
In this paper,we introduce the concept of weakly KKM map on an abstract convex space without any topology and linear structure,and obtain Fan＇s matching theorem and intersection theorem under very weak assumptions on...In this paper,we introduce the concept of weakly KKM map on an abstract convex space without any topology and linear structure,and obtain Fan＇s matching theorem and intersection theorem under very weak assumptions on abstract convex spaces.Finally,we give several minimax inequality theorems as applications.These results generalize and improve many known results in recent literature.展开更多
On Projective Modules with Constant RanksIn this paper,we investigate module structures of rings over which every finitely generated projective module with constant rank is stably free. As applications,we give charact...On Projective Modules with Constant RanksIn this paper,we investigate module structures of rings over which every finitely generated projective module with constant rank is stably free. As applications,we give characterizations of some related rings.展开更多
The H-K-ATPase (HKA), a potassium-dependent proton transporter in the outer medullary collecting duct (OMCD) plays an important role in acid-base homeostasis. The OMCD contains two HKA isoforms;gastric (HKAα1), domin...The H-K-ATPase (HKA), a potassium-dependent proton transporter in the outer medullary collecting duct (OMCD) plays an important role in acid-base homeostasis. The OMCD contains two HKA isoforms;gastric (HKAα1), dominant under normal dietary conditions (ND), and colonic (HKAα2), induced under a K-free diet (KD). The enzymatic activity (EA) of HKA in the OMCD is incompletely understood. The focus of the present study is elucidating the EA of the HKA in HKAα1 and HKAα2 knockout (KO) mice under ND and KD. KO mice were subjected to ND or KD for 10 days. Ten OMCD tubules were extracted, half placed in potassium-free media (Solution 2), half in potassium-containing media (Solution 3). Fluorescence measurements are based on the hydrolysis of ATP to ADP, coupled with the oxidation of NADH. ADP is determined by a decrease in NADH fluorescence. In K presence, NADH fluorescence of HKAα1 KO mice read 13.5 ± 0.7 ppm for ND and 10.3 ± 0.2 ppm for KD, indicating stimulation of the colonic isoform. HKAα2 KO mice averaged 6.8 ± 0.3 ppm for ND and 5.4 ± 0.3 ppm for KD in solution 2 (p p α2 isoform. A significant difference in ATP production in HKAα2 KO mice is likely due to enhanced EA of H-ATPase under potassium depletion.展开更多
Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) was originally identified in patients with seizures. It is densely distributed in the hip-pocampus and amygdala in particular. Because the expression of ...Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) was originally identified in patients with seizures. It is densely distributed in the hip-pocampus and amygdala in particular. Because the expression of Arc/Arg3.1 is regulated by nerve in-puts, it is thought to be an immediate early gene. As shown both in vitro and in vivo, Arc/Arg3.1 is in-volved in synaptic consolidation and regulates some forms of learning and memory in rats and mice [1,2]. Furthermore, a recent study suggests that Arc/Arg3.1 may play a significant role in signal transmission via AMPA-type glutamate receptors [3-5]. Therefore, we conducted a detailed analysis of fear memory in Arc/Arg3.1-deficient mice. As previously reported, the knockout animals exhib-ited impaired fear memory in both contextual and cued test situations. Although Arc/Arg3.1-deficient mice showed almost the same performance as wild-type littermates 4 hr after a conditioning trial, their performance was impaired in the retention test after 24 hr or longer, either with or without reconsolidation. Immunohistochemical analyses showed an abnormal density of GluR1 in the hip-pocampus of Arc/Arg3.1-deficient mice;however, an application of AMPA potentiator did not improve memory performance in the mutant mice. Memory impairment in Arc/Arg3.1-deficient mice is so ro-bust that the mice provide a useful tool for devel-oping treatments for memory impairment.展开更多
H+-K+-ATPase (HKA) is composed of two different subunits: an alpha and a beta subunit. Previous studies have shown that in the kidney gastric HKA (HKA alpha 1) predominates under normal dietary conditions while coloni...H+-K+-ATPase (HKA) is composed of two different subunits: an alpha and a beta subunit. Previous studies have shown that in the kidney gastric HKA (HKA alpha 1) predominates under normal dietary conditions while colonic HKA (HKA alpha 2) predominates under potassium depleted conditions [1]. The purpose of the current study was to elucidate the association between the beta and different alpha subunits from stomach, colon and kidney under normal and potassium depleted conditions. Black Swiss mice were fed a potassium-free diet for 2 weeks, beta subunit expression of HKA in stomach mucosae, colon mucosae and renal outer medulla was examined and compared between normal diet and potassium depleted diet. In wild type (WT) mice, the concentrations of the beta subunit under potassium deficient conditions were found significantly increased compared with normal dietary conditions in colon mucosae (8.27 ± 0.73 vs 6.62 ± 0.55 μg/μl, n = 7, p = 0.0416), whereas in cHKA (HKA alpha 2) mice colon mucosae, the concentrations of the beta subunit were statistically the same (5.05 ± 0.31 vs 4.76 ± 0.37 μg/μl, n = 13, p = 0.2833), and the concentration of the beta subunit stayed the same in renal outer medulla and stomach mucosae as well. The data indicate that potassium deficiency results in a significant increase in the levels of HKA beta subunit concentration in the colonic tissue of WT mice. The results indicate that the HKA beta subunit associates with the cHKA (HKA alpha 2) in order to mediate bicarbonate reabsorption under potassium depletion (hypokalemia)展开更多
文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening （HTS） data for 3 762 distinct global gene knockout （KO） mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type （WT） cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging, ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass： 23 previously reported genes （Calcr, Cebpb, Crtap, Dcstamp, Dkkl, Duoxa2, Enppl, Fgf23, Kissl/Kisslr, Kl （Klotho）, Lrp5, Mstn, Neol, Npr2, Ostml, Postn, Sfrp4, S1c30a5, Sic39a13, Sost, Sumf1, Src, Wnt10b）, five novel genes extensively characterized （Cldn18, Fam20c, Lrrkl, Sgpll, Wnt16）, five novel genes with preliminary characterization （Agpat2, RassfS, Slc10a7, Stc26a7, Slc30a10） and three novel undisclosed genes coding for potential osteoporosis drug targets.
基金Project 50534040 supported by the National Natural Science Foundation of China
文摘Abstract： Mechanical properties of clay under high stress are quite different from those under low stress. It is necessary to investi- gate unloading properties of clay under high stress for the design and construction of deep underground engineering projects. A series of experiments were conducted to investigate the unloading properties of clay under high confining pressures by using a SKA-1 high pressure consolidation instrument designed by us. The stress versus strain relationship and the way that K0 values of clay change during the loading-unloading process were discovered. The results show that there are clear differences in the state of stress and deformation behavior of the clay along different unloading paths.
基金the research result of the provincial quality engineering project“Teaching and Research Section Construction of Applied College English Courses Group”in 2021(Project Number:Guangdong Higher Education[2021]29).
文摘From the perspective of analysis-synthesis translation mode,this paper discusses the translator’s responsibility and the translator’s role in the translation of historiography,based on the case of Ko Kung-chen’s History of Chinese Journalism.Missionary J.S.Roberts believed that translation is the logical combination of two processes of analysis and synthesis.The analysis process is characterized by understanding,emphasizing accurate understanding and professional analysis of the source text,while the synthesis process focuses on the transformation of language and culture.The two processes are dependent,forming the whole process of translation altogether.As the indisputable subject of translation,the translator should assume his own subjective responsibility in the two processes.The translator should be responsible for the fact and professional academics in the analysis process,and language and culture and translation itself in the synthesis process,playing the role of a reviewer,disseminator and translator to ensure that the translation text would be correct,accurate and professional so as to realize the value of himself and translation.
基金supported by the KIZ-CUHK Joint Lab of Bioresources and Molecular Research of Common Diseases(4750378)the VC Discretionary Fund provided to the Hong Kong Branch of Chinese Academy of Science Center for Excellence in Animal Evolution and Genetics(Acc 8601011)partially by the State Key Laboratory CUHKJinan MOE Key Laboratory for Regenerative medicine(2622009)。
文摘Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc).In a reciprocal manner,LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation.Pharmacological intervention in these diseasemodifying pathways may facilitate the development of novel PD therapeutics,despite the current lack of an established drug evaluation model.As such,we reviewed the feasibility of employing the versatile global Pink1knockout(KO)rat model as a self-sufficient,spontaneous PD model for investigating both disease etiology and drug pharmacology.These rats retain clinical features encompassing basal mitophagic flux changes with PD progression.We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.
基金supported by the Labex IGO project(n°ANR11-LABX-0016-01)funded by the "Investissements d'Avenir" French Government program,managed by the French National Research Agency(ANR)+1 种基金the context of the IHU-Cesti project(EXT173947) which received French government financial support managed by the National Research Agency via the "Investment Into The Future program" ANR-10-IBHU-005supported by Nantes Metropole and Region Pays de la Loire. C.L.was supported by Fondation Progreffe
文摘The CRISPR/Cas9 system has been tailored to a revolutionary genetic tool because of its remarkable simplicity and efficacy.While complex genome editing in the mouse since the 1990 s has been dominated by the use of embryonic stem（ES） cells,CRISPR/Cas9 now offers a versatile and fast approach to precisely modify virtually any DNA regions directly in mouse zygotes.Yet,this relative simplicity does not preclude a conscientious preparatory work that is often neglected when initiating a project.Here,we describe the key steps leading to successful generation of a double knockout（KO） mouse by simultaneously targeting two homolog genes,Tmem176 a and Tmem176 b,which are located in the same genomic locus.Additionally,we show that similar efficiency can be obtained in a mixed genetic background or directly in the C57BL/6 inbred strain.Thus,presented as a detailed case study that should be helpful to the non-specialists,we focus on the genotyping strategy to anticipate the various possibilities.
基金Supported by the National Natural Science Foundation of China (Grant No.10361005)
文摘In this paper,we introduce the concept of weakly KKM map on an abstract convex space without any topology and linear structure,and obtain Fan＇s matching theorem and intersection theorem under very weak assumptions on abstract convex spaces.Finally,we give several minimax inequality theorems as applications.These results generalize and improve many known results in recent literature.
文摘On Projective Modules with Constant RanksIn this paper,we investigate module structures of rings over which every finitely generated projective module with constant rank is stably free. As applications,we give characterizations of some related rings.
文摘The H-K-ATPase (HKA), a potassium-dependent proton transporter in the outer medullary collecting duct (OMCD) plays an important role in acid-base homeostasis. The OMCD contains two HKA isoforms;gastric (HKAα1), dominant under normal dietary conditions (ND), and colonic (HKAα2), induced under a K-free diet (KD). The enzymatic activity (EA) of HKA in the OMCD is incompletely understood. The focus of the present study is elucidating the EA of the HKA in HKAα1 and HKAα2 knockout (KO) mice under ND and KD. KO mice were subjected to ND or KD for 10 days. Ten OMCD tubules were extracted, half placed in potassium-free media (Solution 2), half in potassium-containing media (Solution 3). Fluorescence measurements are based on the hydrolysis of ATP to ADP, coupled with the oxidation of NADH. ADP is determined by a decrease in NADH fluorescence. In K presence, NADH fluorescence of HKAα1 KO mice read 13.5 ± 0.7 ppm for ND and 10.3 ± 0.2 ppm for KD, indicating stimulation of the colonic isoform. HKAα2 KO mice averaged 6.8 ± 0.3 ppm for ND and 5.4 ± 0.3 ppm for KD in solution 2 (p p α2 isoform. A significant difference in ATP production in HKAα2 KO mice is likely due to enhanced EA of H-ATPase under potassium depletion.
文摘Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) was originally identified in patients with seizures. It is densely distributed in the hip-pocampus and amygdala in particular. Because the expression of Arc/Arg3.1 is regulated by nerve in-puts, it is thought to be an immediate early gene. As shown both in vitro and in vivo, Arc/Arg3.1 is in-volved in synaptic consolidation and regulates some forms of learning and memory in rats and mice [1,2]. Furthermore, a recent study suggests that Arc/Arg3.1 may play a significant role in signal transmission via AMPA-type glutamate receptors [3-5]. Therefore, we conducted a detailed analysis of fear memory in Arc/Arg3.1-deficient mice. As previously reported, the knockout animals exhib-ited impaired fear memory in both contextual and cued test situations. Although Arc/Arg3.1-deficient mice showed almost the same performance as wild-type littermates 4 hr after a conditioning trial, their performance was impaired in the retention test after 24 hr or longer, either with or without reconsolidation. Immunohistochemical analyses showed an abnormal density of GluR1 in the hip-pocampus of Arc/Arg3.1-deficient mice;however, an application of AMPA potentiator did not improve memory performance in the mutant mice. Memory impairment in Arc/Arg3.1-deficient mice is so ro-bust that the mice provide a useful tool for devel-oping treatments for memory impairment.
文摘H+-K+-ATPase (HKA) is composed of two different subunits: an alpha and a beta subunit. Previous studies have shown that in the kidney gastric HKA (HKA alpha 1) predominates under normal dietary conditions while colonic HKA (HKA alpha 2) predominates under potassium depleted conditions [1]. The purpose of the current study was to elucidate the association between the beta and different alpha subunits from stomach, colon and kidney under normal and potassium depleted conditions. Black Swiss mice were fed a potassium-free diet for 2 weeks, beta subunit expression of HKA in stomach mucosae, colon mucosae and renal outer medulla was examined and compared between normal diet and potassium depleted diet. In wild type (WT) mice, the concentrations of the beta subunit under potassium deficient conditions were found significantly increased compared with normal dietary conditions in colon mucosae (8.27 ± 0.73 vs 6.62 ± 0.55 μg/μl, n = 7, p = 0.0416), whereas in cHKA (HKA alpha 2) mice colon mucosae, the concentrations of the beta subunit were statistically the same (5.05 ± 0.31 vs 4.76 ± 0.37 μg/μl, n = 13, p = 0.2833), and the concentration of the beta subunit stayed the same in renal outer medulla and stomach mucosae as well. The data indicate that potassium deficiency results in a significant increase in the levels of HKA beta subunit concentration in the colonic tissue of WT mice. The results indicate that the HKA beta subunit associates with the cHKA (HKA alpha 2) in order to mediate bicarbonate reabsorption under potassium depletion (hypokalemia)
