Epithelioid sarcoma(EpS)is a high-grade malignancy of unknown histogenesis first described in 1970[1],characterized by high rates of relapse and metastasis,with 5-year survival rates of 60%-75%[2].The only Food and Dr...Epithelioid sarcoma(EpS)is a high-grade malignancy of unknown histogenesis first described in 1970[1],characterized by high rates of relapse and metastasis,with 5-year survival rates of 60%-75%[2].The only Food and Drug Administration(FDA)-approved targeted therapy,the enhancer of zeste homology 2(EZH2)inhibitor tazemetostat,achieved transient responses in only 15%of patients[2].展开更多
A series of palladium-modified(Pd-modified)CuO-ZnO-Al_(2)O_(3)(CZA)catalysts with various Pd loadings(0.3 wt%to 2.4 wt%)were prepared using the wetness impregnation method,on two CZA supports with different structures...A series of palladium-modified(Pd-modified)CuO-ZnO-Al_(2)O_(3)(CZA)catalysts with various Pd loadings(0.3 wt%to 2.4 wt%)were prepared using the wetness impregnation method,on two CZA supports with different structures that are CZA-aged precursor composed of a mixture of zincian-malachite and hydrotalcite-like phases(CZA-zH),and CuO-ZnO-Al_(2)O_(3)metal oxide nanoparticles(CZA-MO).Enhancement on catalytic activity can be observed on both Pd-modified CZA catalysts in a temperature range of 180-240℃for methanol synthesis via CO_(2)hydrogenation.Pd/CZA-zH catalysts exhibited a more efficient and stable production of methanol at a relatively low reaction temperature of 180℃for 100 hrs of reaction.The improvement of activity is mainly ascribed to a higher surface area and abundant oxygen-containing functional groups(e.g.,-OH)of CZA-zH support,which is beneficial for better adsorption and distribution of Pd promoter.Hydrogen temperature programmed reduction and X-ray photoelectron spectroscopy results demonstrated a better interaction between Pd and Cu on Pd/CZA-zH catalysts via enhanced reducibility of CuO,and peak shift of Cu to a lower binding energy.The difference in the efficient utilization of hydrogen spillover effect of Pd promoter over two CZA supports resulted in the different performances for methanol synthesis under mild reaction co℃nditions.展开更多
To sustain plant growth,development,and crop yield,sucrose must be transported from leaves to distant parts of the plant,such as seeds and roots.To identify genes that regulate sucrose accumulation and transport in ma...To sustain plant growth,development,and crop yield,sucrose must be transported from leaves to distant parts of the plant,such as seeds and roots.To identify genes that regulate sucrose accumulation and transport in maize(Zea mays),we isolated carbo/iydrafe part/f/ofi/ngf defecf/Ve33(cpd33),a recessive mutant that accumulated excess starch and soluble sugars in mature leaves.The cpd33 mutants also exhibited chlorosis in the leaf blades,greatly diminished plant growth,and reduced fertility.Cpd33 encodes a protein containing multiple C2 domains and transmembrane regions.Subcellular localization experiments showed the CPD33 protein localized to plasmodesmata(PD),the plasma membrane,and the endoplasmic reticulum.We also found that a loss-of-function mutant of the CPD33 homolog in Arabidopsis,QUIRKY,had a similar carbohydrate hyperaccumulation phenotype.Radioactively labeled sucrose transport assays showed that sucrose export was significantly lower in cpd33 mutant leaves relative to wild-type leaves.However,PD transport in the adaxial-abaxial direction was unaffected in cpd33 mutant leaves.Intriguingly,transmission electron microscopy revealed fewer PD at the companion cell-sieve element interface in mutant phloem tissue,providing a possible explanation for the reduced sucrose export in mutant leaves.Collectively,our results suggest that CPD33 functions to promote symplastic transport into sieve elements.展开更多
Dear Editor,The Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)and CRISPR-associated protein 9(Cas9)(CRISPR/Cas9)-mediated generation of somatically genetically engineered mouse models have emerged a...Dear Editor,The Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)and CRISPR-associated protein 9(Cas9)(CRISPR/Cas9)-mediated generation of somatically genetically engineered mouse models have emerged as a new approach for in vivo modeling of cancer[1].Here,we describe a novel DNA-free,easy,rapid,flexible,multiplexable,and robust method to model endometrial neoplasia by CRISPR/Cas9 ribonucleoprotein(RNP)electroporation into the uterus of mice.展开更多
Synaptic vesicles can undergo several modes of exocytosis,endocytosis,and trafficking within individual synapses,and their fates may be linked to different vesicular protein compositions.Here,we mapped the intrasynapt...Synaptic vesicles can undergo several modes of exocytosis,endocytosis,and trafficking within individual synapses,and their fates may be linked to different vesicular protein compositions.Here,we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron microscopy.SV2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active zone.In contrast,SV2A was found in all domains of the synapse and was slightly enriched near the active zone.SV2B and SV2A were found on the membrane in the peri-active zone,suggesting the recycling from both clusters of vesicles.SV2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency stimulation.Our data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial gradients.The almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found more important for vesicle release.展开更多
基金supported by a grant from the SMARCB1 associationsupported by grants from the Dr.Rolf M.Schwiete foundation(2021-007,2022-031)+11 种基金the Matthias-Lackas foundationthe Dr.Leopold und Carmen Ellinger foundationthe Deutsche Forschungsgemeinschaft(DFG 458891500)the Cancer Grand Challenges project PROTECTthe German Cancer Aid(DKH-7011411,DKH-70114278,DKH-70115315,DKH-70115914)the Ministry of Education and Research(BMBF,SMART-CARE and HEROES-AYA)the KiKa foundation(#486)the Fight Kids Cancer foundation(FKC-NEWtargets)the KiTZ-Foundation in memory of Kirstin Diehl,the KiTZPMC twinning programthe German Cancer Consortium(DKTK,PRedictAHR)the Barbara and Wilfried Mohr foundationThe laboratory of Thomas G.P.Grünewald is co-funded by the European Union(ERC,CANCERHARAKIRI,101122595).
文摘Epithelioid sarcoma(EpS)is a high-grade malignancy of unknown histogenesis first described in 1970[1],characterized by high rates of relapse and metastasis,with 5-year survival rates of 60%-75%[2].The only Food and Drug Administration(FDA)-approved targeted therapy,the enhancer of zeste homology 2(EZH2)inhibitor tazemetostat,achieved transient responses in only 15%of patients[2].
基金supported in part by the U.S.Department of Energy through contracts DE-FE0031909 and DE-FE0031909.
文摘A series of palladium-modified(Pd-modified)CuO-ZnO-Al_(2)O_(3)(CZA)catalysts with various Pd loadings(0.3 wt%to 2.4 wt%)were prepared using the wetness impregnation method,on two CZA supports with different structures that are CZA-aged precursor composed of a mixture of zincian-malachite and hydrotalcite-like phases(CZA-zH),and CuO-ZnO-Al_(2)O_(3)metal oxide nanoparticles(CZA-MO).Enhancement on catalytic activity can be observed on both Pd-modified CZA catalysts in a temperature range of 180-240℃for methanol synthesis via CO_(2)hydrogenation.Pd/CZA-zH catalysts exhibited a more efficient and stable production of methanol at a relatively low reaction temperature of 180℃for 100 hrs of reaction.The improvement of activity is mainly ascribed to a higher surface area and abundant oxygen-containing functional groups(e.g.,-OH)of CZA-zH support,which is beneficial for better adsorption and distribution of Pd promoter.Hydrogen temperature programmed reduction and X-ray photoelectron spectroscopy results demonstrated a better interaction between Pd and Cu on Pd/CZA-zH catalysts via enhanced reducibility of CuO,and peak shift of Cu to a lower binding energy.The difference in the efficient utilization of hydrogen spillover effect of Pd promoter over two CZA supports resulted in the different performances for methanol synthesis under mild reaction co℃nditions.
文摘To sustain plant growth,development,and crop yield,sucrose must be transported from leaves to distant parts of the plant,such as seeds and roots.To identify genes that regulate sucrose accumulation and transport in maize(Zea mays),we isolated carbo/iydrafe part/f/ofi/ngf defecf/Ve33(cpd33),a recessive mutant that accumulated excess starch and soluble sugars in mature leaves.The cpd33 mutants also exhibited chlorosis in the leaf blades,greatly diminished plant growth,and reduced fertility.Cpd33 encodes a protein containing multiple C2 domains and transmembrane regions.Subcellular localization experiments showed the CPD33 protein localized to plasmodesmata(PD),the plasma membrane,and the endoplasmic reticulum.We also found that a loss-of-function mutant of the CPD33 homolog in Arabidopsis,QUIRKY,had a similar carbohydrate hyperaccumulation phenotype.Radioactively labeled sucrose transport assays showed that sucrose export was significantly lower in cpd33 mutant leaves relative to wild-type leaves.However,PD transport in the adaxial-abaxial direction was unaffected in cpd33 mutant leaves.Intriguingly,transmission electron microscopy revealed fewer PD at the companion cell-sieve element interface in mutant phloem tissue,providing a possible explanation for the reduced sucrose export in mutant leaves.Collectively,our results suggest that CPD33 functions to promote symplastic transport into sieve elements.
基金supported by the Spanish Ministry of Science,Innovation and Universities(grant code PID2019-104734RB-I00)and the Spanish Association Against Cancer(grant code LABAE19004LLOB).This work was also funded by the Institute of Health Carlos III(MS17/00063)(co-founded by the European Social Fund[ESF]“investing in your future”).
文摘Dear Editor,The Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)and CRISPR-associated protein 9(Cas9)(CRISPR/Cas9)-mediated generation of somatically genetically engineered mouse models have emerged as a new approach for in vivo modeling of cancer[1].Here,we describe a novel DNA-free,easy,rapid,flexible,multiplexable,and robust method to model endometrial neoplasia by CRISPR/Cas9 ribonucleoprotein(RNP)electroporation into the uterus of mice.
基金supported by grants from Deutsche Forschungsgemeinschaft(DFG)(SFB1089,SCHO 820/4-1,SCHO 820/6-1,SCHO 820/7-1,SCHO 820/5-2,and SPP1757 to S.S.,SFB1089,SPP1757,INST117215,DI853/3-5&7,and INST 217/785-1 to D.D.),the BONFOR program of the University of Bonn Medical Center(S.S.and D.D.),and UCB Pharma.
文摘Synaptic vesicles can undergo several modes of exocytosis,endocytosis,and trafficking within individual synapses,and their fates may be linked to different vesicular protein compositions.Here,we mapped the intrasynaptic distribution of the synaptic vesicle proteins SV2B and SV2A in glutamatergic synapses of the hippocampus using three-dimensional electron microscopy.SV2B was almost completely absent from docked vesicles and a distinct cluster of vesicles found near the active zone.In contrast,SV2A was found in all domains of the synapse and was slightly enriched near the active zone.SV2B and SV2A were found on the membrane in the peri-active zone,suggesting the recycling from both clusters of vesicles.SV2B knockout mice displayed an increased seizure induction threshold only in a model employing high-frequency stimulation.Our data show that glutamatergic synapses generate molecularly distinct populations of synaptic vesicles and are able to maintain them at steep spatial gradients.The almost complete absence of SV2B from vesicles at the active zone of wildtype mice may explain why SV2A has been found more important for vesicle release.
