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Tale of mitochondria and mitochondria-associated ER membrane in patient-derived neuronal models of Wolfram syndrome

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Neural Regeneration Research 2025年第9期20卷 2587-2588页

作者： Laetitia Aubry timothy Barrett Sovan Sarkar I-STEM CECSCorbeil-EssonnesFrance UniversitéParis-Saclay Universitéd’EvryINSERMI-STEMUMR861Corbeil-EssonnesFrance Institute of Cancer and genomic Sciences Institute of Biomedical ResearchCollege of Medical and Dental SciencesUniversity of BirminghamEdgbastonBirminghamUK Department of Endocrinology Birmingham Women’s and Children’s HospitalSteelhouse LaneBirminghamUK

Mitochondria and mitochondria-associated endoplasmic reticulum membrane in neurodegenerative diseases:Mitochondria generate most of the chemical energy needed to power the biochemical reactions of cells,and thus are often referred to as the"powerhouse"of the ***,this organelle is also involved in a pleth,ora of different cellular functions such as calcium(Ca^(2+))homeostasis,apoptosis,oxidative stress,and several metabolic pathways including oxidative phosphorylation,tricarboxylic acid cycle,andβ-oxidation of fatty acids.

关键词： oxidative cycle carboxylic

The paternal epigenome and embryogenesis： poising mechanisms for development

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Asian Journal of Andrology 2011年第1期13卷 76-80页

作者： timothy g Jenkins Douglas T Carrell Andrology and IVF Laboratories Department of Surgery University of Utah Salt Lake City UT 84108 USA Department of Obstetrics and gynecology University of Utah School of Medicine Salt Lake City UT 84108 USA Department of Physiology University of Utah School of Medicine Salt Lake City UT 84108 USA

The scope of paternal contributions during early embryonic development has long been considered limited. Dramatic changes in chromatin structure throughout spermatogenesis have been thought to leave the sperm void of complex layers of epigenetic regulation over the DNA blueprint, thus leaving the balance of that regulation to the oocyte. However, recent work in the fields of epigenetics and male factor infertility has placed this long-held, and now controversial dogma, in a new light. Elegant studies investigating chromatin and epigenetic modifications in the developing sperm cell have provided new insights that may establish a more critical role for the paternal epigenome in the developing embryo. DNA methylation, histone tail modifications, targeted histone retention and protamine incorporation into the chromatin have great influence in the developing sperm cell. Perturbations in the establishment and/or maintenance of any of these epigenetic marks have been demonstrated to affect fertility status, ranging in severity from mild to catastrophic. Sperm require this myriad of chromatin structural changes not only to serve a protective role to DNA throughout spermatogenesis and future delivery to the egg, but also, it appears, to contribute to the developmental program of the future embryo. This review will focus on our current understanding of the epigenetics of sperm. We will discuss sperm-specific chromatin modifications that result in genes essential to development being poised for activation early in embryonic development, the disruption of which may result in reduced fecundity.

关键词： chromatin DNA methylation embryogenesis epigenetics histone modification male infertility

Plate tectonics in relation to mantle temperatures and metamorphic properties

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Science China Earth Sciences 2020年第5期63卷 634-642页

作者： timothy KUSKY State Key Laboratory of geological Processes and Mineral Resources Center for Global TectonicsSchool of Earth SciencesChina University of GeosciencesWuhan 430074China Three gorges Research Center for geohazards China University of GeosciencesWuhan 430074China

When plate tectonics emerged and how it has evolved over Earth history are two of the most fundamental challenges in Earth *** questions are tackled using a holistic approach to analyze tectonic styles in the history of Earth,giving rise to the interpretation of two styles of plate tectonics since the *** these interpretations,there are different styles of deformation and metamorphism between early times dominated by warm subduction,and later times preferring cold *** two styles of plate tectonics are recorded by different properties of regional metamorphism at convergent plate boundaries,which are linked to the differences in mantle temperature between the Archean and Phanerozoic.A transition to modern plate tectonics is recorded by the signature of blueschist facies metamorphism developed in the *** is consistent with geological evidence for the operation of ancient plate tectonics since the early *** temporal cooling of the mantle explains the geochemical trends of mantle-derived melts,the likely change from numerous small plates to fewer but larger plates,changes in thickness and preservation of oceanic crust and lithosphere in accretionary and collisional orogens,and led to the oxygenation of the surface environment providing the environments needed to foster life.

关键词： Plate tectonics Precambrian Accretionary orogen Mantle temperature Metamorphic facies series

Analysis of the design and performance characteristics of pumpable roof supports

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International Journal of Mining Science and Technology 2017年第1期27卷 91-99页

作者： Batchler timothy NIOSH Office of Mine Safety and Health ResearchPittsburghPA 15236USA

Pumpable roof supports are currently being used to provide a safe working environment for longwall mining. Because different pumpable supports are visually similar and installed fundamentally in the same manner as other supports, there is a tendency to believe they all perform the same way. However, there are several design parameters that can affect their performance, including the cementitious material properties and the bag construction practices that influence the degree of confinement provided. A full understanding of the impact of these design parameters is necessary to optimize the support application and to provide a foundation for making further improvements in the support performance. This paper evaluates the impact of various support design parameters by examining full-scale performance tests conducted using the National Institute for Occupational Safety and Health(NIOSH) Mine Roof Simulator(MRS) as part of manufacturers' developmental and quality control testing. These tests were analyzed to identify correlations between the support design parameters and the resulting performance. Based on more than 160 tests over 7 years, quantifiable patterns were examined to assess the correlation between the support dimensions, cementitious material type, wire pitch, and single-wall vs. dualwalled bag designs to the support capacity, stiffness, load shedding events, and yield characteristics.

关键词： Pumpable Roofsuppo Performance characteristics Secondary support

graph-theoretic algorithms for cyber-physical vulnerability analysis of power grid with incomplete information

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Journal of Modern Power Systems and Clean Energy 2018年第5期6卷 887-899页

作者： Anurag K.SRIVASTAVA timothy A.ERNSTER Ren LIU Vignesh g.KRISHNAN Department of Electrical Engineering and Computer Science Washington State University U.S. Army Corps of Engineers Dominion Power

A key focus recently has been on assessing therisk of a coordinated cyber-physical attack and minimizing the impact of a successful attack. Most of the cyberattackers will have limited system information and conventional power grid N-1 security analysis cannot be extended to assess the risk. Centrality measures are widely used in the network science and an attacker with incomplete information can use it to identify power system vulnerabilities by defining the system as a complex network but without real-time system measurements. This paper presents a graph theory based centrality indices for vulnerability assessment of the power system due to various bus and branch contingencies using limited system information and provides a preliminary defense mechanism to prevent such an attack. Proposed work answers the fundamental question of possible attack scenarios by balancing risk(limited information with low risk to get caught orhigh risk attack to access more system information) and impact(identifying contingencies with maximal impact on system operation). Statistical comparisons are made between the graph theory measures compared to the corresponding DC power flow based N-X linear sensitivity measures. A unified N-X centrality based performance index is proposed and validated against the AC power flow based performance index by doing the real-time simulations of an N-3 attack scenario. Defensive mechanisms using topology-based performance indices are also presented.

关键词： Cyber-physical security graph theory Transmission system Contingency Defense mechanism Incomplete information

growth of continental crust in intra-oceanic and continental-margin arc systems: Analogs for Archean systems

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Science China Earth Sciences 2022年第9期65卷 1615-1645页

作者： timothy KUSKY Lu WANg State Key Lab for geological Processes and Mineral Resources Center for Global TectonicsSchool of Earth SciencesChina University of GeosciencesWuhan 430074China Badong National Observatory and Research Station for geohazards China University of GeosciencesWuhan 430074China

Earth’s continental crust has grown and been recycled throughout geologic history along convergent plate *** main locus of continental crustal growth is in intra-oceanic and continental-margin arc systems in Archean time. In arc systems, oceanic lithosphere is subducted to the deeper mantle, and together with its overlying sedimentary sequence is in some cases off-scraped to form accretionary prisms. Fluids are released from the subducting slab to chemically react with the mantle wedge, forming mafic-ultramafic metasomatites, whose partial melting generates mafic melts that rise up to form arcs. In intraoceanic arcs, they produce dominantly basaltic lavas, with a mid-crust that includes variably-developed vertically-walled intermediate plutons and higher-level dikes and sills. In continental-margin arcs, different petrogenetic processes cause assimilation and fractionation of basaltic magmas, partial melting/reworking of juvenile basaltic rocks, and mixing of mantle-and crust-derived melts, so they produce andesitic calc-alkaline melts but still have a mid-crust dominated by vertically-walled felsic plutons, which form 3-D dome-and-basin structures, akin to those in some Archean terranes such as parts of the Pilbara and Zimbabwe cratons. Notably, the continental crust of Archean times is dominated by tonalite-trondhjemite-granodiorite(TTg)plutons, similar to that of the mid-crust of these arc systems, suggesting that early continental crust may have formed largely by the amalgamation of multiple arc systems. The patterns of magmatism, in terms of petrogenesis, rock types, duration of magmatic and accretionary events, and the spatial scales of deformation and magmatism have remained essentially the same throughout geological history, demonstrating that plate tectonic processes characterized by subduction and arc magmatism have been in operation at least as long as recorded by the preserved geologic record, since the Eoarchean. However, the early Earth was dom

关键词： Oceanic arc Continental arc Accretionary orogen Archean Crustal growth

Performance-based seismic design of nonstructural building components:The next frontier of earthquake engineering

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Earthquake Engineering and Engineering Vibration 2014年第S1期13卷 17-46页

作者： Andre Filiatrault timothy Sullivan Dept.of Civil Structural and Environmental Engineering University at BuffaloState University of New York Dept.of Civil Engineering & Architecture University of Pavia Assistant Professor

With the development and implementation of performance-based earthquake engineering,harmonization of performance levels between structural and nonstructural components becomes vital. Even if the structural components of a building achieve a continuous or immediate occupancy performance level after a seismic event,failure of architectural,mechanical or electrical components can lower the performance level of the entire building system. This reduction in performance caused by the vulnerability of nonstructural components has been observed during recent earthquakes worldwide. Moreover,nonstructural damage has limited the functionality of critical facilities,such as hospitals,following major seismic events. The investment in nonstructural components and building contents is far greater than that of structural components and framing. Therefore,it is not surprising that in many past earthquakes,losses from damage to nonstructural components have exceeded losses from structural damage. Furthermore,the failure of nonstructural components can become a safety hazard or can hamper the safe movement of occupants evacuating buildings,or of rescue workers entering buildings. In comparison to structural components and systems,there is relatively limited information on the seismic design of nonstructural components. Basic research work in this area has been sparse,and the available codes and guidelines are usually,for the most part,based on past experiences,engineering judgment and intuition,rather than on objective experimental and analytical results. Often,design engineers are forced to start almost from square one after each earthquake event: to observe what went wrong and to try to prevent repetitions. This is a consequence of the empirical nature of current seismic regulations and guidelines for nonstructural components. This review paper summarizes current knowledge on the seismic design and analysis of nonstructural building components,identifying major knowledge gaps that w

关键词： nonstructural building components performance-based earthquake engineering seismic design and analysis

Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

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World Journal of gastroenterology 2014年第39期20卷 14105-14125页

作者： Paul J Kennedy John F Cryan timothy g Dinan gerard Clarke 1.15 Biosciences Institute Department of Psychiatry Alimentary Pharmabiotic Centre University College Cork Cork Ireland Department of Anatomy and Neuroscience Alimentary Pharmabiotic CentreUniversity College CorkCork Ireland

Irritable bowel syndrome(IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions.

关键词： Irritable bowel syndrome Microbiome Anxiety Tryptophan Abdominal pain gastrointestinal motility Cognition

Comparison of Results of Recent Seismic Profiles with Tectonic Models of the North China Craton

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Journal of Earth Science 2011年第2期22卷 250-259页

作者： timothy M Kusky State Key Laboratory of geological Processes and Mineral Resources Three Gorges Research Center for Geo-hazardMinistry of EducationChina University of Geosciences

The geometry and timing of amalgamation of the North China craton（NCC） have been controversial,with three main models with significantly different interpretations of regional structure,geochronology,and geological *** model of Zhao g C et *** that the eastern and western blocks of the NCC formed separately in the Archean,and an active margin was developed on the eastern block between 2.5 and 1.85 ga,when the two blocks collided above an east dipping subduc-tion *** model of Kusky et *** that the eastern block rifted from an unknown larger continent at circa 2.7 ga,and experienced a collision with an arc（perhaps attached to the western block） above a west-dipping subduction zone at 2.5 ga,and the 1.85 ga metamorphism is related to a collision along the northern margin of the craton when the NCC joined the Columbia *** model of Faure et *** two collisions in the central orogenic belt,at 2.1 and 1.88 *** seismic results support both the models of Kusky et *** Faure et al.,showing that subduction be-neath the central orogenic belt（COB） was west-directed,and that there is a second,west-dipping pa-leosubduction zone located to the east of the COB dipping beneath the western block（Ordos craton）.The boundaries identified through geophysics do not correlate with the boundaries of the Trans-North China orogen suggested in the Zhao et ***,and the subduction polarity is opposite that predicted by that *** seismic profiles are consistent with an Archean collision above a west-dipping sub-duction zone beneath the COB predicted by the models of Kusky et al.,and the second west-dipping subduction zone is consistent with the two events suggested in the Faure et ***.

关键词： North China craton Archean tectonics geophysics.