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Tuning beneficial calcineurin phosphatase activation to counterα-synuclein toxicity in a yeast model of Parkinson’s disease

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Neural Regeneration Research 2025年第1期20卷 199-200页

作者： Srishti Chawla Mikael Molin thomas Nystrom Institute for Biomedicine Sahlgrenska AcademyCentre for Ageing and Health-AgeCapUniversity of GothenburgGothenburgSweden department of Life Sciences Chalmers University of TechnologyGothenburgSweden

Calcineurin(CN)is a calcium-and calmodulindependent serine/threonine that has been studied in many model organisms including yeast,filamentous fungi,plants,and *** biological functions range from ion homeostasis and virulence in lower eukaryotes to T-cell activation in humans by human nuclear factors of activated *** is a heterodimeric protein consisting of a catalytic subunit,calcineurin A(Cna1p),which contains an active site with a dinuclear metal center,and a regulatory Ca^(2+) binding subunit called calcineurin B(Cnb1p)required to activate *** calcineurin B subunit has been highly conserved through evolution:For example,the mammalian calcineurin B shows 54%identity with calcineurin B from Saccharomyces cerevisiae.

关键词： activation dinuclear conserved

Microglia:a promising therapeutic target in spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 454-463页

作者： Xiaowei Zha Guoli Zheng thomas Skutella Karl Kiening Andreas Unterberg Alexander Younsi department of Neurosurgery Heidelberg University HospitalHeidelbergGermany department of Neuroanatomy Institute for Anatomy and Cell BiologyHeidelberg UniversityHeidelbergGermany

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal *** a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal *** this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor *** a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive *** review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

关键词： astrocytes cytokines functional recovery immune regulation M1/M2 activation macrophages microglia neuroinflammation spinal cord injury therapy

Sleep as a window to understand and regulate Alzheimer's disease:emerging roles of thalamic reticular nucleus

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Neural Regeneration Research 2025年第6期20卷 1711-1712页

作者： Haoqi Sun Shiqian Shen Robert J.thomas M.Brandon Westover Can Zhang department of Neurology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Center for Translational Pain Research Department of AnesthesiaCritical Care and Pain MedicineMassachusetis General HospitalHarvard Medical SchoolBostonMAUSA division of Pulmonary Critical Care and Sleep MedicineDepartment of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Genetics and Aging Research Unit McCance Center for Brain HealthMass General Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA

Introduction:Alzheimer 's disease(Ad) is a common neurodegenerative disorder and the primary cause of dementia. Considerable evidence supports the “amyloid hypothesis,” stating that the pathogenesis of Ad is primarily caused by the deposition of amyloid-β(Aβ), which drives tau phosphorylation, neuroinflammation, and neurodegeneration in the brain. The amyloid hypothesis is strengthened by the significant and moderate benefit of lecanemab, a humanized antibody through an anti-amyloid mechanism,showing slowed clinical decline(van dyck et al.,2023). The recent positive results of anti-amyloid trials have brought back focus on the amyloid hypothesis through biochemical, genetic, and pharmacological approaches(Zhang, 2023).

关键词： Alzheimer inflammation hypothesis

Phosphatases are involved in modulating the TCA cycle in plants

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Molecular Plant 2021年第7期14卷 1036-1037页

作者： thomas d.Niehaus department of Plant and Microbial Biology University of Minnesota Twin CitiesSaint PaulMNUSA

Phosphorylation is a reversible posttranslational modification that modulates the activities of numerous *** plants,it is known that several mitochondrial proteins can be phosphory-lated,including enzymes of the tricarboxylic acid(TCA)*** kinases and phosphorylases that mediate reversible phosphorylation of TCA cycle enzymes remain largely elusive,as is the impact of protein phosphorylation on the TCA *** this issue of Molecular Plant,Zhang et al.(2021)demonstrate that two phosphatases play important roles in controlling the phosphorylation status of TCA cycle enzymes,which modulates their activities and influences carbon flux through the TCA cycle.

关键词： cycle reversible controlling

High Temperature Effects on Electron and Proton Circuits of Photosynthesis

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Journal of Integrative Plant Biology 2010年第8期52卷 712-722页

作者： thomas d. Sharkey Ru Zhang department of Biochemistry and Molecular Biology Michigan State University East Lansing MI 48824 USA department of Plant Biology Carnegie Institution for Science 260 Stanford CA 94305 USA

Photosynthesis is sensitive to high temperature with reversible declines during moderate stress and irreversible damage with more severe stress. While many studies have focused on the irreversible damage,the reversible changes can tell how photosynthesis tolerates high temperature. Knowing how high temperature is tolerated could lead to ways of extending high temperature tolerance. New analytical methods have been used to probe electron and proton circuits of intact leaves at high temperature. Combined with previous work with isolated systems, it appears that there is a large change in redox distribution among thylakoid components. Photosystem I becomes more reduced but photosystem II and the stroma become more oxidized. Several lines of evidence support the existence of significant cyclic electron flow at high temperature. It is hypothesized that these changes allow for adenosine tri-phosphate homeostasis and maintenance of an energy gradient across the thylakoid membrane, helping to keep it from suffering irreversible damage at high temperature.

关键词： high II

Automated calculation and convergence of defect transport tensors

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npj Computational Materials 2020年第1期6卷 89-95页

作者： thomas d.Swinburne danny Perez Aix-Marseille Université CNRSCINaM UMR 7325Campus de LuminyMarseille 13288France Theoretical division T-1 Los Alamos National LaboratoryLos AlamosNM 87545USA

defect diffusion is a key process in materials science and catalysis,but as migration mechanisms are often too complex to enumerate a priori,calculation of transport tensors typically have no measure of convergence and require significant end-user *** two bottlenecks prevent high-throughput implementations essential to propagate model-form uncertainty from interatomic interactions to predictive *** order to address these issues,we extend a massively parallel accelerated sampling scheme,autonomously controlled by Bayesian estimators of statewide sampling completeness,to build atomistic kinetic Monte Carlo models on a state-space irreducible under exchange and space group *** on isolated defects,we derive analytic expressions for drift and diffusion coefficients,providing a convergence metric by calculating the Kullback–Leibler divergence across the ensemble of diffusion processes consistent with the sampling *** autonomy and efficacy of the method is demonstrated on surface trimers in tungsten and Hexa-interstitials in magnesium oxide,both of which exhibit complex,correlated migration mechanisms.

关键词： convergence diffusion calculation

Multi-regional observations and validation of the M_(3)ocean tide

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Science China Earth Sciences 2023年第10期66卷 2265-2277页

作者： Adam thomas dEVLIN Jiayi PAN déborah IdIER School of Geography and Environment Jiangxi Normal UniversityNanchang330022China Cooperative Institute for Marine and Atmospheric Research School of Ocean and Earth Science and TechnologyUniversity of Hawai’i at MānoaHonoluluHI96822USA department of Oceanography University of Hawai’i at MānoaHonoluluHI96822USA The Chinese University of Hong Kong Hong Kong999077China Key Laboratory of Poyang Lake Wetland and Watershed Research of Ministry of Education Nanchang330022China BRGM Orléans45060France

Improved determinations of the oft-ignored third-degree ocean tides can yield better accuracy for tidal predictions,numerical model solutions,and *** only a small part of tidal range,these components can be larger at certain coastal locations due to shelf resonances and other ***,we discuss observations of the M3lunar terdiurnal tide using 9-year windowed tidal harmonic analyses at 157 tide gauges compares to a global assimilation model(TPXO9v5a),with a focus on the Western Pacific and the European ***9v5a does well in estimating the observed M_(3)amplitudes and phase lags in most regions,though determinations in coastal zones and in morphologically complex areas are coarse and often *** also employ a shallow-water model(MARS)on the European Shelf,which can yield localized improvement over *** five subregions of the European Shelf,regional root-mean-squared-errors(RMSEs)are lower(and thus a better fit)at three locations for TPXO for amplitudes,and three for phase lags,with MARS simulations being a better fit in the other *** also show that some locations have experienced significant long-term increases and/or decreases in the M_(3)amplitude over time,likely related to resonance changes under sea level rise(SLR)which can modulate the oceanic response to astronomical *** hypothesis is explored for Europe using the MARS model by applying various sea level rise scenarios,showing that the directionality(positive or negative)of the long-term changes in M_(3)amplitudes over time match the model results for more than half of our validation stations.

关键词： Third-degree tides M_(3)tide Altimetry Numerical simulation Sea level rise

Larger floods reduce soil CO_(2)efflux during the post-flooding phase in seasonally flooded forests of Western Amazonia

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Pedosphere 2021年第2期31卷 342-352页

作者： Emma M.dOCHERTY Andrew d.thomas department of Geography and Earth Sciences Aberystwyth UniversityAberystwyth SY233DB(UK) School of Geography University of LeedsLeeds LS29JT(UK)

Seasonally flooded várzea forests of Western Amazonia are one of the most productive and biodiverse wetland forests in the ***,data on their soil CO_(2)emissions,soil organic matter decomposition rates,and soil C stocks are *** is a concern because hydrological changes are predicted to lead to increases in the height,extent,and duration of seasonal floods,which are likely to have a significant effect on soil C stocks and ***,with no empirical data,the impact of altered flood regimes on várzea soil C cycles remains *** study quantified the effects of maximum annual flood height and soil moisture on soil CO_(2)efflux rate(R_(s))and soil organic matter decomposition rate(k)in the várzea forests of Pacaya Samiria National Reserve,*** study was conducted between May and August *** results showed that R_(s)(10.6–182.7 mg C m^(-2)h^(-1))and k(0.016–0.078)varied between and within sites,and were considerably lower than the values reported for other tropical *** addition,R_(s)was negatively affected by flood height(Pd soil moisture(Pd it decreased with decreasing river levels post flooding(Pd by any of the above-mentioned *** moisture was the dominant factor influencing R_(s),and it was significantly affected by maximum flood height,even after the floods had subsided(Pded that larger floods will likely lead to reduced R_(s),whilst k could remain unchanged but with decomposition processes becoming more anaerobic.

关键词： C cycle climate change greenhouse gas soil CO_(2)emissions soil moisture soil organic matter decomposition rate tropical forest

Load carrying capacity of a heterogeneous surface bearing

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Friction 2015年第4期3卷 287-293页

作者： Evan thomas Mircea d PASCOVICI Romeo P GLOVNEA Tribology Laboratory Department of Engineering and DesignUniversity of SussexUnited Kingdom Machine Elements and Tribology division Politehnica University of BucharestBucharestRomania

It has been shown before that liquids can slip at a solid boundary,which prompted the idea that parallel-surfaces bearings can be achieved just by alternating slip and non-slip regions in the direction of fluid *** amount of slip at the wall depends on the surface tension at the liquid-solid interface,which in turn depends on the chemical state of the surface and its *** the present study a heterogeneous surface was obtained by coating half of a circular glass disc with a coating repellant to glycerol.A rotating glass disc was placed at a known/calibrated distance and the gap was filled with *** the mobile surface moving from the direction of slip to non-slip region it can be theoretically shown that a pressure build up can be *** pressure gradient in the two regions is constant,similar to that in a Rayleigh step bearing,with the maximum pressure at the separation *** heterogeneous disc was placed on a holder supported by a load cell thus the force generated by this pressure increase can be measured *** were carried out at different sliding speeds and gaps and the load carried was measured and subsequently compared with theoretical *** allowed the slip coefficient to be evaluated.

关键词： bearing slip heterogeneous load