The Kunene Complex(KC)represents a very large Mesoproterozoic igneous body,mainly composed of anorthosites and gabbroic rocks that extends from SW Angola to NW Namibia(outcropping 18,000 km^(2),NE-SW trend,and ca.350 ...The Kunene Complex(KC)represents a very large Mesoproterozoic igneous body,mainly composed of anorthosites and gabbroic rocks that extends from SW Angola to NW Namibia(outcropping 18,000 km^(2),NE-SW trend,and ca.350 km long and up to 50 km wide).Little is known about its structure at depth.Here,we use recently acquired aerogeophysical data to accurately determine its hidden extent and to unravel its morphology at depth.These data have been interpreted and modelled to investigate the unexposed KC boundaries,reconstructing the upper crustal structure(between 0 and 15 km depth)overlain by the thin sedimentary cover of the Kalahari Basin.The modelling reveals that the KC was emplaced in the upper crust and extends in depth up to ca.5 km,showing a lobular geometry and following a large NE-SW to NNE-SSW linear trend,presumably inherited from older Paleoproterozoic structures.The lateral continuation of the KC to the east(between 50 and 125 km)beneath the Kalahari Cenozoic sediments suggests an overall size three times the outcropping dimension(about 53,500 km^(2)).This affirmation clearly reinforces the economic potential of this massif,related to the prospecting of raw materials and certain types of economic mineralization(Fe-Ti oxides,metallic sulphides or platinum group minerals).Up to 11 lobes have been isolated with dimensions ranging from 135.5 to 37.3 km in length and 81.9 to 20.7 km in width according to remanent bodies revealed by TMI mapping.A total volume of 65,184 km3 was calculated only for the magnetically remanent bodies of the KC.A long-lasting complex contractional regime,where large strike-slip fault systems were involved,occurred in three kinematic pulses potentially related to a change of velocity or convergence angle acting on previous Paleoproterozoic inherited sutures.The coalescent magmatic pulses can be recognized by means of magnetic anomalies,age of the bodies as well as the lineations inferred in this work:(i)Emplacement of the eastern mafic bodies and granites in a stage of significant lateral extension in a transtensional context between 1500 Ma and 1420 Ma;(ii)Migration of the mantle derived magmas westwards with deformation in a complex contractional setting with shearing structures involving western KC bodies and basement from 1415 Ma to 1340 Ma;(iii)NNW-SSE extensional structures are relocated westwards,involving mantle magmas,negative flower structures and depression that led to the formation of late Mesoproterozoic basins from 1325 Ma to 1170 Ma.Additionally,we detect several first and second order structures to place the structuring of the KC in a craton-scale context in relation to the crustal structures detected in NW Namibia.展开更多
AbstracBteclin-1 is the firstly-identified mammalian protein of the autophagy machinery,which functions as a molecular scaffold for the assembly of PI3KC3(class II phosphatidylinositol 3 kinase)complex,thus controllin...AbstracBteclin-1 is the firstly-identified mammalian protein of the autophagy machinery,which functions as a molecular scaffold for the assembly of PI3KC3(class II phosphatidylinositol 3 kinase)complex,thus controlling autophagy induction and other cellular trafficking events.Notably,there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes,including tumor suppression and progression as well as resistance to cancer therapeutics and CSC(cancer stem-like cell)maintenance.More importantly,Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers.In this review,we provide a comprehensive survey of the structure,functions,and regulations of Beclin-1,and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology.Moreover,we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy,providing novel insights into a promising strategy for regulating Beclin-1 to improvecancer therapeutics in thefuture.展开更多
Human T cell leukemia virus type 1(HTLV-1),an etio-logical factor that causes adult T cell leukemia and lym-phoma(ATL),infects over 20 million people worldwide.About 1 million of HTLV-1-infected patients develop ATL,a...Human T cell leukemia virus type 1(HTLV-1),an etio-logical factor that causes adult T cell leukemia and lym-phoma(ATL),infects over 20 million people worldwide.About 1 million of HTLV-1-infected patients develop ATL,a highly aggressive non-Hodgkin's lymphoma without an effective therapy.The pX region of the HTLV-1 viral genome encodes an oncogenic protein,Tax,which plays a central role in transforming CD4+ T lymphocytes by deregulating oncogenic signaling pathways and promoting cell cycle progression.Expression of Tax following viral entry is critical for promoting survival and proliferation of human T cells and is required for initiation of oncogenesis.Tax exhibits diverse functions in host cells,and this oncoprotein primarily targets IκB kinase complex in the cytoplasm,resulting in persistent activation of NF-κB and upregulation of its responsive gene expressions that are crucial for T cell survival and cell cycle progression.We here review recent advances for the pathological roles of Tax in modulating IκB kinase activity.We also discuss our recent observation that Tax connects the IκB kinase complex to autophagy pathways.Understanding Tax-mediated pathogenesis will provide insights into development of new therapeutics in controlling HTLV-1-associated diseases.展开更多
基金supported by the subsidiary programme“Ayudas Extraordinarias Menciones Excelencia Severo Ochoa”of the CN IGME-CSIC(project AECEX2021,grant 15903)the University of Minnesota and National Science Foundation(award NSF-EAR 2153786)+1 种基金the Portuguese Foundation for Science and Technology(FCT)support,Geosciences Center project UIDB/00073/2020(doi:10.54499/UIDB/00073/2020)University of Coimbra and and GeoBioTec project UIDB/04035/2020(doi:10.54499/UIDB/04035/2020),Nova School of Science and Technology.
文摘The Kunene Complex(KC)represents a very large Mesoproterozoic igneous body,mainly composed of anorthosites and gabbroic rocks that extends from SW Angola to NW Namibia(outcropping 18,000 km^(2),NE-SW trend,and ca.350 km long and up to 50 km wide).Little is known about its structure at depth.Here,we use recently acquired aerogeophysical data to accurately determine its hidden extent and to unravel its morphology at depth.These data have been interpreted and modelled to investigate the unexposed KC boundaries,reconstructing the upper crustal structure(between 0 and 15 km depth)overlain by the thin sedimentary cover of the Kalahari Basin.The modelling reveals that the KC was emplaced in the upper crust and extends in depth up to ca.5 km,showing a lobular geometry and following a large NE-SW to NNE-SSW linear trend,presumably inherited from older Paleoproterozoic structures.The lateral continuation of the KC to the east(between 50 and 125 km)beneath the Kalahari Cenozoic sediments suggests an overall size three times the outcropping dimension(about 53,500 km^(2)).This affirmation clearly reinforces the economic potential of this massif,related to the prospecting of raw materials and certain types of economic mineralization(Fe-Ti oxides,metallic sulphides or platinum group minerals).Up to 11 lobes have been isolated with dimensions ranging from 135.5 to 37.3 km in length and 81.9 to 20.7 km in width according to remanent bodies revealed by TMI mapping.A total volume of 65,184 km3 was calculated only for the magnetically remanent bodies of the KC.A long-lasting complex contractional regime,where large strike-slip fault systems were involved,occurred in three kinematic pulses potentially related to a change of velocity or convergence angle acting on previous Paleoproterozoic inherited sutures.The coalescent magmatic pulses can be recognized by means of magnetic anomalies,age of the bodies as well as the lineations inferred in this work:(i)Emplacement of the eastern mafic bodies and granites in a stage of significant lateral extension in a transtensional context between 1500 Ma and 1420 Ma;(ii)Migration of the mantle derived magmas westwards with deformation in a complex contractional setting with shearing structures involving western KC bodies and basement from 1415 Ma to 1340 Ma;(iii)NNW-SSE extensional structures are relocated westwards,involving mantle magmas,negative flower structures and depression that led to the formation of late Mesoproterozoic basins from 1325 Ma to 1170 Ma.Additionally,we detect several first and second order structures to place the structuring of the KC in a craton-scale context in relation to the crustal structures detected in NW Namibia.
基金supported by the National Natural Science Foundation of China(Grant Nos.22177084 and 82173666)Sichuan Science and Technology Program(Grant No.2022YFQ0054,China)the Open Research Fund of Chengdu University of Traditional Chinese Medicine State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China.
文摘AbstracBteclin-1 is the firstly-identified mammalian protein of the autophagy machinery,which functions as a molecular scaffold for the assembly of PI3KC3(class II phosphatidylinositol 3 kinase)complex,thus controlling autophagy induction and other cellular trafficking events.Notably,there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes,including tumor suppression and progression as well as resistance to cancer therapeutics and CSC(cancer stem-like cell)maintenance.More importantly,Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers.In this review,we provide a comprehensive survey of the structure,functions,and regulations of Beclin-1,and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology.Moreover,we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy,providing novel insights into a promising strategy for regulating Beclin-1 to improvecancer therapeutics in thefuture.
基金supported by a grant from National Institute of Health to H.Cheng.
文摘Human T cell leukemia virus type 1(HTLV-1),an etio-logical factor that causes adult T cell leukemia and lym-phoma(ATL),infects over 20 million people worldwide.About 1 million of HTLV-1-infected patients develop ATL,a highly aggressive non-Hodgkin's lymphoma without an effective therapy.The pX region of the HTLV-1 viral genome encodes an oncogenic protein,Tax,which plays a central role in transforming CD4+ T lymphocytes by deregulating oncogenic signaling pathways and promoting cell cycle progression.Expression of Tax following viral entry is critical for promoting survival and proliferation of human T cells and is required for initiation of oncogenesis.Tax exhibits diverse functions in host cells,and this oncoprotein primarily targets IκB kinase complex in the cytoplasm,resulting in persistent activation of NF-κB and upregulation of its responsive gene expressions that are crucial for T cell survival and cell cycle progression.We here review recent advances for the pathological roles of Tax in modulating IκB kinase activity.We also discuss our recent observation that Tax connects the IκB kinase complex to autophagy pathways.Understanding Tax-mediated pathogenesis will provide insights into development of new therapeutics in controlling HTLV-1-associated diseases.
