Based on an analysis of the circulation in May associated with the interannual variation of the onset of Yunnan’s rainy season, this study examined the rela-tionship between Arctic Oscillation (AO) and the onset timi...Based on an analysis of the circulation in May associated with the interannual variation of the onset of Yunnan’s rainy season, this study examined the rela-tionship between Arctic Oscillation (AO) and the onset timing of the rainy sea-son by using the NCEP/NCAR reanalysis and observational precipitation data for 1961-2010. The results indicated that, on an interannual time scale, intense Asian summer monsoon and an active EU-pattern wave train circulation in its positive phase, associated with a cold cyclonic cell covering the western part of the East Asian subtropical westerly jet (EASWJ), jointly contributed to the onset of the rainy season in May. Otherwise, the onset might be suppressed. The cold cyclonic cell over East Asia likely led to the southward shift and enhancement of EASWJ as well as its secondary circulation around the jet entrance, which could provide a favorable dynamic and thermal condition for rainfalls in Yunnan as was revealed in previous studies on 10 - 30-day time scale. Further examination showed that the preceding wintertime AO played a significant role in the timing of the onset of the rainy season before the mid-1980s’ by mostly modulating the wave-train-like circulation over East Asia in May. During that time period, when the AO index of the previous winter was positive (negative), Yunnan’s rainy season tended to begin earlier (later) than normal. Correspond-ingly, the precipitation in May was also closely linked to wintertime AO.展开更多
Increased evidence has shown the important role of Atlantic sea surface temperature(SST) in modulating the El Nio-Southern Oscillation(ENSO). Persistent anomalies of summer Madden-Julian Oscillation(MJO) act to link t...Increased evidence has shown the important role of Atlantic sea surface temperature(SST) in modulating the El Nio-Southern Oscillation(ENSO). Persistent anomalies of summer Madden-Julian Oscillation(MJO) act to link the Atlantic SST anomalies(SSTAs) to ENSO. The Atlantic SSTAs are strongly correlated with the persistent anomalies of summer MJO, and possibly affect MJO in two major ways. One is that an anomalous cyclonic(anticyclonic) circulation appears over the tropical Atlantic Ocean associated with positive(negative) SSTA in spring, and it intensifies(weakens) the Walker circulation. Equatorial updraft anomaly then appears over the Indian Ocean and the eastern Pacific Ocean, intensifying MJO activity over these regions. The other involves a high pressure(low pressure) anomaly associated with the North Atlantic SSTA tripole pattern that is transmitted to the mid-and low-latitudes by a circumglobal teleconnection pattern, leading to strong(weak) convective activity of MJO over the Indian Ocean. The above results offer new viewpoints about the process from springtime Atlantic SSTA signals to summertime atmospheric oscillation, and then to the MJO of tropical atmosphere affecting wintertime Pacific ENSO events, which connects different oceans.展开更多
Treatment of Mycobacterium abscessus(Mab)infections is very challenging due to its intrinsic resistance to most available drugs.Therefore,it is crucial to discover novel anti-Mab drugs.In this study,we explored an int...Treatment of Mycobacterium abscessus(Mab)infections is very challenging due to its intrinsic resistance to most available drugs.Therefore,it is crucial to discover novel anti-Mab drugs.In this study,we explored an intrinsic resistance mechanism through which Mab resists echinomycin(ECH).ECH showed activity against Mab at a minimum inhibitory concentration(MIC)of 2μg/ml.A embC strain in which the embC gene was knocked out showed hypersensitivity to ECH(MIC:0.0078-0.0156μg/ml).The MICs of ECH-resistant strains screened with reference to AembC ranged from 0.25 to 1μg/ml.Mutations in EmbB,including D306A,D306N,R350G,V555l,and G581S,increased the Mab's resistance to ECH when overexpressed in AembC individually(MIC:0.25-0.5μg/ml).These EmbB mutants,edited using the CRISPR/Cpf1 system,showed heightened resistance to ECH(MIC:0.25-0.5μg/ml).The permeability of these Mab strains with edited genes and overexpression was reduced,as evidenced by an ethidium bromide accumulation assay,but it remained significantly higher than that of the parent Mab.In summary,our study demonstrates that ECH exerts potent anti-Mab activity and confirms that EmbB and EmbC are implicated in Mab's sensitivity to ECH.Mutation in EmbB may partially compensate foralossof EmbCfunction.展开更多
Depsides and depsidones have attracted attention for biosynthetic studies due to their broad biological activities and structural diversity.Previous structure-activity relationships indicated that triple halogenated d...Depsides and depsidones have attracted attention for biosynthetic studies due to their broad biological activities and structural diversity.Previous structure-activity relationships indicated that triple halogenated depsidones display the best anti-pathogenic activity.However,the gene cluster and the tailoring steps responsible for halogenated depsidone nornidulin(3)remain enigmatic.In this study,we disclosed the complete biosynthetic pathway of the halogenated depsidone through in vivo gene disruption,heterologous expression and in vitro biochemical experiments.We demonstrated an unusual depside skeleton biosynthesis process mediated by both highly-reducing polyketide synthase and nonreducing polyketide synthase,which is distinct from the common depside skeleton biosynthesis.This skeleton was subsequently modified by two in-cluster enzymes DepG and DepF for the ether bond formation and decarboxylation,respectively.In addition,the decarboxylase DepF exhibited substrate promiscuity for different scaffold substrates.Finally,and interestingly,we discovered a halogenase encoded remotely from the biosynthetic gene cluster,which catalyzes triple-halogenation to produce the active end product nornidulin(3).These discoveries provide new insights for further understanding the biosynthesis of depsidones and their derivatives.展开更多
Main observation and conclusion The enzyme AbyU catalyses a Diels-Alder(DA)reaction during abyssomicin C biosynthesis.In this study,AbyU is shown to convert the native substrate of another Diels-Alderase(DAase),AbmU,t...Main observation and conclusion The enzyme AbyU catalyses a Diels-Alder(DA)reaction during abyssomicin C biosynthesis.In this study,AbyU is shown to convert the native substrate of another Diels-Alderase(DAase),AbmU,to a new abyssomicin derivative,abyssomicin 7.展开更多
Discovery and Biosynthesis of Marine Derived Bioactive Natural Products It has been demonstrated that natural products still play a pivotal role in new drug discovery. The novel scaffolds found within nature far exce...Discovery and Biosynthesis of Marine Derived Bioactive Natural Products It has been demonstrated that natural products still play a pivotal role in new drug discovery. The novel scaffolds found within nature far exceed the imagination and synthetic capabilities of chemists, The underexplored marine microorganisms have been recognized as an exciting resource in supplying novel chemoWpes. We are focusing on the screening, fermentation, and discovery of bioactive natural products from marine actinobacteria and fungi, and therefore to obtain fundamentally new, clinically useful drug leads.[1,2]展开更多
文摘Based on an analysis of the circulation in May associated with the interannual variation of the onset of Yunnan’s rainy season, this study examined the rela-tionship between Arctic Oscillation (AO) and the onset timing of the rainy sea-son by using the NCEP/NCAR reanalysis and observational precipitation data for 1961-2010. The results indicated that, on an interannual time scale, intense Asian summer monsoon and an active EU-pattern wave train circulation in its positive phase, associated with a cold cyclonic cell covering the western part of the East Asian subtropical westerly jet (EASWJ), jointly contributed to the onset of the rainy season in May. Otherwise, the onset might be suppressed. The cold cyclonic cell over East Asia likely led to the southward shift and enhancement of EASWJ as well as its secondary circulation around the jet entrance, which could provide a favorable dynamic and thermal condition for rainfalls in Yunnan as was revealed in previous studies on 10 - 30-day time scale. Further examination showed that the preceding wintertime AO played a significant role in the timing of the onset of the rainy season before the mid-1980s’ by mostly modulating the wave-train-like circulation over East Asia in May. During that time period, when the AO index of the previous winter was positive (negative), Yunnan’s rainy season tended to begin earlier (later) than normal. Correspond-ingly, the precipitation in May was also closely linked to wintertime AO.
基金Supported by the National Natural Science Foundation of China(41375059,41690123,41690120,41661144019,and 41375081)China Meteorological Administration(CMA)Special Public Welfare Research Fund(GYHY201306022)+1 种基金State Key Laboratory for Severe Weather Special Fund(2016LASW-B01)Research Fund of CMA Guangzhou Institute of Tropical and Marine Meteorology/Guangdong Provincial Key Laboratory of Regional Numerical Weather Prediction
文摘Increased evidence has shown the important role of Atlantic sea surface temperature(SST) in modulating the El Nio-Southern Oscillation(ENSO). Persistent anomalies of summer Madden-Julian Oscillation(MJO) act to link the Atlantic SST anomalies(SSTAs) to ENSO. The Atlantic SSTAs are strongly correlated with the persistent anomalies of summer MJO, and possibly affect MJO in two major ways. One is that an anomalous cyclonic(anticyclonic) circulation appears over the tropical Atlantic Ocean associated with positive(negative) SSTA in spring, and it intensifies(weakens) the Walker circulation. Equatorial updraft anomaly then appears over the Indian Ocean and the eastern Pacific Ocean, intensifying MJO activity over these regions. The other involves a high pressure(low pressure) anomaly associated with the North Atlantic SSTA tripole pattern that is transmitted to the mid-and low-latitudes by a circumglobal teleconnection pattern, leading to strong(weak) convective activity of MJO over the Indian Ocean. The above results offer new viewpoints about the process from springtime Atlantic SSTA signals to summertime atmospheric oscillation, and then to the MJO of tropical atmosphere affecting wintertime Pacific ENSO events, which connects different oceans.
基金This work was supported by the National Key R&D Program of China(2021YFA1300900)the National Natural Science Foundation of China(21920102003,82022067,and 22037006)+5 种基金the Chinese Academy of Sciences Grants(154144KYSB20190005 and YJKYYQ20210026)the Key R&D Program of Sichuan Provenience(2023YFSY0047)the State Key Laboratory of Respiratory Disease,Guangzhou Institute of Respiratory Diseases,First Affiliated Hospital of Guangzhou Medical University(SKLRD-Z-202414,SKLRD-OP-202324,SKLRD-Z-202301,SKLRD-OP-202113,and SKLRD-Z-202412)Guangzhou Scienceaand Technology Plan-Youth Doctoral"Sail"Project(2024A04J4273)President's International Fellowship Initiative-CAS(2023VBC0015)the National Foreign Young Talent Program(QN2022031002L).
文摘Treatment of Mycobacterium abscessus(Mab)infections is very challenging due to its intrinsic resistance to most available drugs.Therefore,it is crucial to discover novel anti-Mab drugs.In this study,we explored an intrinsic resistance mechanism through which Mab resists echinomycin(ECH).ECH showed activity against Mab at a minimum inhibitory concentration(MIC)of 2μg/ml.A embC strain in which the embC gene was knocked out showed hypersensitivity to ECH(MIC:0.0078-0.0156μg/ml).The MICs of ECH-resistant strains screened with reference to AembC ranged from 0.25 to 1μg/ml.Mutations in EmbB,including D306A,D306N,R350G,V555l,and G581S,increased the Mab's resistance to ECH when overexpressed in AembC individually(MIC:0.25-0.5μg/ml).These EmbB mutants,edited using the CRISPR/Cpf1 system,showed heightened resistance to ECH(MIC:0.25-0.5μg/ml).The permeability of these Mab strains with edited genes and overexpression was reduced,as evidenced by an ethidium bromide accumulation assay,but it remained significantly higher than that of the parent Mab.In summary,our study demonstrates that ECH exerts potent anti-Mab activity and confirms that EmbB and EmbC are implicated in Mab's sensitivity to ECH.Mutation in EmbB may partially compensate foralossof EmbCfunction.
基金funded by the National Natural Science Foundation of China(22037006,U2106207,22077128)Local Innovation and Entrepreneurship Team Project of Guangdong(2019BT02Y262,China)+4 种基金Key Science and Technology Project of Hainan Province(ZDKJ202018,China)Major Project of Basic and Applied Basic Research of Guangdong Province(2019B030302004,China)Key-Area Research and Development Program of Guangdong Province(2020B1111030005,China)Guangdong Provincial Marine Economic Development(Six Major Marine Undertakings,China)Special Fund Project(GDNRC[2021]54,China)Open Program of Shenzhen Bay Laboratory(SZBL2021080601006,China)。
文摘Depsides and depsidones have attracted attention for biosynthetic studies due to their broad biological activities and structural diversity.Previous structure-activity relationships indicated that triple halogenated depsidones display the best anti-pathogenic activity.However,the gene cluster and the tailoring steps responsible for halogenated depsidone nornidulin(3)remain enigmatic.In this study,we disclosed the complete biosynthetic pathway of the halogenated depsidone through in vivo gene disruption,heterologous expression and in vitro biochemical experiments.We demonstrated an unusual depside skeleton biosynthesis process mediated by both highly-reducing polyketide synthase and nonreducing polyketide synthase,which is distinct from the common depside skeleton biosynthesis.This skeleton was subsequently modified by two in-cluster enzymes DepG and DepF for the ether bond formation and decarboxylation,respectively.In addition,the decarboxylase DepF exhibited substrate promiscuity for different scaffold substrates.Finally,and interestingly,we discovered a halogenase encoded remotely from the biosynthetic gene cluster,which catalyzes triple-halogenation to produce the active end product nornidulin(3).These discoveries provide new insights for further understanding the biosynthesis of depsidones and their derivatives.
基金This work was supported by the China NSF(Nos.31670087 and U1706206)the Natural Key Research and Development Program of China(No.2019YFC0312500)+5 种基金the Key Special Project for Introduced Talents Team of Southern Marine Science and Engi-neering Guangdong Laboratory(Guangzhou,No.GML2019ZD0406)the Guangdong NSF(No.2016A030312014)the Guangdong Local Innovation Team Program(No.2019BT02Y262)the Pearl River S&T Nova Program of Guangzhou No.201806010109)the CAS(No.XDA13020302-2)the Guangdong Provincial-Level Special Funds for Promoting High-quality Economic Development(No.2020032).
文摘Main observation and conclusion The enzyme AbyU catalyses a Diels-Alder(DA)reaction during abyssomicin C biosynthesis.In this study,AbyU is shown to convert the native substrate of another Diels-Alderase(DAase),AbmU,to a new abyssomicin derivative,abyssomicin 7.
文摘Discovery and Biosynthesis of Marine Derived Bioactive Natural Products It has been demonstrated that natural products still play a pivotal role in new drug discovery. The novel scaffolds found within nature far exceed the imagination and synthetic capabilities of chemists, The underexplored marine microorganisms have been recognized as an exciting resource in supplying novel chemoWpes. We are focusing on the screening, fermentation, and discovery of bioactive natural products from marine actinobacteria and fungi, and therefore to obtain fundamentally new, clinically useful drug leads.[1,2]