Arginine 107 of yeast ATP synthase subunit g mediates sensitivity of the mitochondrial permeability transition to phenylglyoxal

Modification with arginine-specific glyoxals modulates the permeability transition (PT) of rat liver mitochondria, with inhibitory or inducing effects that depend on the net charge of the adduct(s). Here, we show that phenylglyoxal (PGO) affects the PT in a species-specific manner (inhibition in mouse and yeast, induction in human and Drosophila mitochondria). Following the hypotheses (i) that the effects are mediated by conserved arginine(s) and (ii) that the PT is mediated by the F-ATP synthase, we have narrowed the search to 60 arginines. Most of these residues are located in subunits alpha, beta, gamma, epsilon, a, and c and were excluded because PGO modification did not significantly affect enzyme catalysis. On the other hand, yeast mitochondria lacking subunit g or bearing a subunit g R107A mutation were totally resistant to PT inhibition by PGO. Thus, the effect of PGO on the PT is specifically mediated by Arg-107, the only subunit g arginine that has been conserved across species. These findings are evidence that the PT is mediated by F-ATP synthase.Peer reviewe

Association between living environmental quality and risk of arthritis in middle-aged and older adults: a national study in China

BackgroundThe association between combined environmental factors and the risk of arthritis is still scarcely studied. The present study performed cross-sectional and cohort studies to explore the association between risk score of living environment quality and the risk of arthritis in middle-aged and older adults in China.MethodsThe study was based on China Health and Retirement Longitudinal Study (CHARLS), and it recruited 17,218 participants in the cross-sectional study and 11,242 participants in the seven-year follow-up study. The living environment quality was measured by household fuel types, household water sources, room temperature, residence types, and ambient concentration of PM2.5. Logistic regression and Cox proportional hazard regression models were utilized to examine the association between the living environment quality and the risk of arthritis. Competing risk models and stratified analyses were applied to further verify our results.ResultsCompared with individuals in the suitable environment group, people who lived in moderate (OR:1.28, 95%CI: 1.14–1.43) and unfavorable environments (OR:1.49, 95%CI:1.31–1.70) showed higher risks of arthritis when considering the multiple living environmental factors (P for trend <0.001) in the cross-sectional analysis. In the follow-up study, similar results (P for trend = 0.021), moderate environment group (HR:1.26, 95%CI:1.01–1.56) and unfavorable environment group (HR: 1.36, 95%CI: 1.07–1.74), were founded.ConclusionInferior living environment might promote the development of arthritis. It is necessary for the public, especially old people, to improve the living environment, which may be the key to the primary prevention of arthritis

Association of long-term triglyceride-glucose index level and change with the risk of cardiometabolic diseases

ObjectiveThe triglyceride-glucose (TyG) index is considered as a pivotal factor for various metabolic, cardiovascular, and cerebrovascular diseases. However, there is currently a paucity of relevant studies on the association between long-term level and change of TyG-index and cardiometabolic diseases (CMDs) risk. We aimed to explore the risk of CMDs in relation to the long-term level and change of TyG-index.MethodsBased on the prospective cohort study, a total of 36359 subjects who were free of CMDs, had complete data of triglyceride (TG) and fasting blood glucose (FBG) and underwent four health check-ups from 2006 to 2012 consecutively were followed up for CMDs until 2021. The associations between long-term level and change of TyG-index and CMDs risk were assessed by Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CIs). The TyG-index was calculated as ln [TG, mg/dL) × FBG, mg/dL)/2].ResultsDuring the median observation period of 8 years, 4685 subjects were newly diagnosed with CMDs. In multivariable-adjusted models, a graded positive association was observed between CMDs and long-term TyG-index. Compared with the Q1 group, subjects with the Q2-Q4 group had increased progressively risk of CMDs, with corresponding HRs of 1.64(1.47-1.83), 2.36(2.13-2.62), 3.15(2.84-3.49), respectively. The association was marginally attenuated, after further adjustment for the baseline TyG level. In addition, compared with stable TyG level, both loss and gain in TyG level were associated with increased CMDs risk.ConclusionsLong-term elevated level and change of TyG-index are risk factors for the incident CMDs. Elevated TyG-index in the early stage remains to exert cumulative effects on the occurrence of CMDs even after accounting for the baseline TyG-index

Regulation of the Mitochondrial Permeability Transition Pore by Arginine Residue(s) and their Role in the Dimerization of F-ATP Synthase

The mitochondrial permeability transition (PT) is a Ca2+-dependent permeability increase of the inner membrane, mediated by the permeability transition pore (PTP). Depending on open time and channel size, the PTP can participate in Ca2+ homeostasis or cell death. In the 1990s, through the use of modifiers of SH groups and of relatively specific histidine and arginine reagents, a few discrete regulatory sites of the PTP have been defined. Recent evidence suggests that PTP forms from F-ATP synthase. The first part of my work was focused on the identification of the arginine residue(s) conferring PTP regulation by glyoxals within the general hypothesis that the PTP originates from F-ATP synthase. Eriksson and co-workers discovered the PTP-modulatory effects of arginine-selective reagents, and focused on the structure-function relationship of arginine-glyoxal adducts in the regulation of PTP opening and closure in rat liver mitochondria. Phenylglyoxal (PGO) is the most extensively used arginine-specific reagent. I have observed for the first time that PGO affects the PT in a species-specific manner (inhibition in mouse and yeast, induction in human and Drosophila mitochondria), indicating that the ability to modulate the PTP by PGO has been conserved but differs across species. I have been able to show that the effect of PGO on the PT is specifically mediated by Arg 107 of subunit g, the only arginine residue of this subunit that has been conserved across species. Yeast mitochondria lacking subunit g or bearing a subunit g R107A mutation were totally resistant to PT inhibition by PGO. Taking advantage of the species-specific differences but conserved reactivity with PGO, I have observed that substitution of yeast subunit g with its human counterpart confers the “human” phenotype to yeast, suggesting that the species-specific effect of PGO is more likely to depend on structural differences between the yeast and human F-ATP synthase than on the R107-PGO adduct as such. This finding is a step forward in the molecular understanding of PTP regulation, and further supports the hypothesis that the PTP forms from F-ATP synthase. The second part of my work was dedicated to reinvestigate the role of Ca2+ as a permissive factor for PTP opening. The most recent hypothesis about the mechanism of PTP formation is that interaction of Ca2+ with the metal binding site of β subunit (which usually contributes to coordinate the binding of Mg-ATP) causes a conformational change that is propagated to the inner membrane through the lateral stalk, which eventually leads to PTP formation. Yet a PT occurred in the absence of added Ca2+ with several inducers including p-hydroxyphenylgloxal (OH-PGO), one of the arginine reagents that favors PTP opening in rat liver mitochondria; and phenylarsine oxide (PhAsO), a dithiol cross-linker that is a potent PTP inducer. I have observed that pore opening can occur in presence of EGTA after the treatment of mitochondria with OH-PGO and PhAsO, but also that the inducing effect is prevented by depletion of matrix Ca2+ with the ionophore A23187 or by chelation of matrix Ca2+ with BAPTA. These observations indicate that in the absence of matrix Ca2+ PTP cannot be activated by OH-PGO and PhAsO. Another part of my work was to test whether charged amino acids of yeast subunits e and g are involved in their interaction, thus playing a role in the dimerization of F-ATP synthase. I have identified Arg 8 of subunit e as a critical residue in mediating e-g interactions, most likely through an electrostatic bond with Glu 83 of subunit g. We have also observed that dimers purified after blue-native electrophoresis from mutants of Arg 8 show decreased PTP channel conductance and activity, indicating that this residue might directly participate in generating the full conductance channel.La transizione di permeabilità mitocondriale (PT) è un aumento Ca2+-dipendente della permeabilità della membrana interna, mediato dal poro di transizione della permeabilità (PTP). A seconda della durata delle aperture e della dimensione del canale, il PTP può partecipare all'omeostasi del Ca2+ o alla morte cellulare. Negli anni '90, attraverso l'uso di modificatori di gruppi SH e di reagenti relativamente specifici di istidina e arginina, sono stati definiti alcuni siti regolatori del PTP. Prove recenti suggeriscono che PTP si forma dalla F-ATP sintasi. La prima parte del mio lavoro è stata dedicata all'identificazione dei residui di arginina che conferiscono la sensibilità del PTP ai gliossali, assumendo che il PTP si formi dalla F-ATP sintasi. Il fenilgliossale (PGO) è il reagente specifico per le arginine più comunemente usato. Ho osservato per la prima volta che il PGO influenza il PTP in modo specie-specifico (causando inibizione in topo e nel lievito, mentre induzione in drosofila e nell’uomo), indicando che, nonostante la sua capacità modulatoria sia diversa tra i vari organismi, la sua reattività è invece conservata. Ho potuto dimostrare che l’effetto del PGO è mediato in modo specifico dalla Arg 107 della subunità g della F-ATP sintasi, peraltro conservata tra le specie. I mitocondri di lievito privi di subunità g o esprimenti una subunità g con la mutazione R107A sono totalmente resistenti all'inibizione del PT da PGO. Questa scoperta è un passo avanti nella comprensione molecolare della regolazione PTP, e supporta ulteriormente l'ipotesi che il PTP si generi dalla F-ATP sintasi. La seconda parte del mio lavoro è stata dedicata a reinvestigare il ruolo del Ca2+ come fattore permissivo per l'apertura del PTP. L'ipotesi più recente sul meccanismo di formazione del PTP è che il legame del Ca2+ al sito di legame del metallo della subunità β (che contribuisce a coordinare il legame di Mg-ATP) causa un cambiamento conformazionale che viene propagato alle subunità inserite nella membrana interna attraverso il gambo laterale, portando all‘apertura del PTP. Eppure la PT si verifica ugualmente in assenza di Ca2+ aggiunto utilizzando diversi induttori compreso il p-idrossifenilgliossale (OH-PGO), uno dei reagenti di arginina che favorisce l'apertura del PTP nei mitocondri del fegato di ratto; e la fenilarsina ossido (PhAsO), un reagente dei ditioli e potente induttore del PTP. Tuttavia, nei miei studi ho osservato che l'apertura del PTP può sì verificarsi in presenza di EGTA dopo il trattamento dei mitocondri con OH-PGO e PhAsO, ma l'effetto di induzione temina con l'esaurimento del Ca2+ di matrice causato dallo ionoforo A23187 o con la chelazione del catione con BAPTA. Queste osservazioni indicano che in assenza del Ca2+ di matrice il PTP non può essere attivato da altri modulatori, confermando il ruolo permissivo e strettamente necessario del catione. Un'altra parte del mio lavoro è stata testare se amminoacidi carichi delle subunità di lievito e e g sono coinvolti nella loro reciproca interazione , svolgendo quindi un ruolo chiave nella dimerizzazione della F-ATP sintasi. Grazie ad una mutagenesi sito specifica, ho identificato la Arg 8 della subunità e come residuo critico per tale interazione, agendo molto probabilmente attraverso legami elettrostatici con la Glu 83 della subunità g. Abbiamo anche osservato che i dimeri purificati da BN gels da mutanti privi dell'Arg 8 mostrano una diminuzione della conduttanza e dell'attività di canale del PTP, indicando che questo residuo potrebbe partecipare direttamente alla generazione di un canale correttamente assemblato

Suitable Tillage Depth Promotes Maize Yields by Changing Soil Physical and Chemical Properties in A 3-Year Experiment in the North China Plain

Rotary tillage is a common farming method because of its ease of operation and low cost in the North China Plain. However, the rotary tillage depth is generally no more than 20 cm, and successive years of rotary tillage harden the root soil layers, which reduces maize’s ability to take root into the deep layer and decreases maize yields. The impact of the different rotary tillage depths and different plow pan thicknesses on maize yields was unclear and needs further study. In this study, a 3-year experiment was conducted, and three rotary tillage depths were designed: 20 cm tillage depth (D20), 25 cm tillage depth (D25), and 30 cm tillage depth (D30). The effects of different rotary tillage depths on soil’s physical and chemical properties, water use efficiency, photosynthetic rate, and maize yields were investigated. The results showed that soil bulk density significantly decreased and field capacity significantly increased in 10–30 cm soil layers by increasing the rotary tillage depths; soil water consumption, photosynthetic rate, and maize yields of D25 significantly increased in comparison to those of D20 and D30; soil bulk density, plow pan thickness, total nitrogen, total phosphorus, and total potassium had an obvious negative correlation with tillage depth and field capacity; the Denitrification–Decomposition (DNDC) model predicted maize yields well; structural equation models (SEM) revealed that rotary tillage depths and soil water consumption played an important role on maize yields; and D25 could increase maize yields by improving maize water use efficiency and photosynthetic rate. The tillage depth of 25 cm is a suitable rotary tillage depth for the increase in maize yields in the North China Plain

Suitable Tillage Depth Promotes Maize Yields by Changing Soil Physical and Chemical Properties in A 3-Year Experiment in the North China Plain

Rotary tillage is a common farming method because of its ease of operation and low cost in the North China Plain. However, the rotary tillage depth is generally no more than 20 cm, and successive years of rotary tillage harden the root soil layers, which reduces maize’s ability to take root into the deep layer and decreases maize yields. The impact of the different rotary tillage depths and different plow pan thicknesses on maize yields was unclear and needs further study. In this study, a 3-year experiment was conducted, and three rotary tillage depths were designed: 20 cm tillage depth (D20), 25 cm tillage depth (D25), and 30 cm tillage depth (D30). The effects of different rotary tillage depths on soil’s physical and chemical properties, water use efficiency, photosynthetic rate, and maize yields were investigated. The results showed that soil bulk density significantly decreased and field capacity significantly increased in 10–30 cm soil layers by increasing the rotary tillage depths; soil water consumption, photosynthetic rate, and maize yields of D25 significantly increased in comparison to those of D20 and D30; soil bulk density, plow pan thickness, total nitrogen, total phosphorus, and total potassium had an obvious negative correlation with tillage depth and field capacity; the Denitrification–Decomposition (DNDC) model predicted maize yields well; structural equation models (SEM) revealed that rotary tillage depths and soil water consumption played an important role on maize yields; and D25 could increase maize yields by improving maize water use efficiency and photosynthetic rate. The tillage depth of 25 cm is a suitable rotary tillage depth for the increase in maize yields in the North China Plain

Calcium and regulation of the mitochondrial permeability transition

Recent years have seen renewed interest in the permeability transition pore, a high conductance channel responsible for permeabilization of the inner mitochondrial membrane, a process that leads to depolarization and Ca2+ release. Transient openings may be involved in physiological Ca2+ homeostasis while long-lasting openings may trigger and/or execute cell death. In this review we specifically focus (i) on the hypothesis that the PTP forms from the F-ATP synthase and (ii) on the mechanisms through which Ca2+ can reversibly switch this energy-conserving nanomachine into an energy-dissipating device. (C) 2017 Elsevier Ltd. All rights reserved

Applicability Evaluation of Multisource Satellite Precipitation Data for Hydrological Research in Arid Mountainous Areas

Global Satellite Mapping of Precipitation (GSMaP), Climate Hazards Group InfraRed Preconception with Station data (CHIRPS), Tropical Rain Measurement Mission Multisatellite Precipitation Analysis (TRMM 3B42 V7) and Rainfall Estimation from Soil Moisture Observations (SM2RAIN) are satellite precipitation products with high applicability, but their applicability in hydrological research in arid mountainous areas is not clear. Based on precipitation and runoff data, this study evaluated the applicability of each product to hydrological research in a typical mountainous basin (the Qaraqash River basin) in an arid region by using two methods: a statistical index and a hydrological model (Soil and Water Assessment Tool, SWAT). Simulation results were evaluated by Nash efficiency coefficient (NS), relative error (PBIAS) and determination coefficient (R2). The results show that: (1) The spatial distributions of precipitation estimated by these four products in the Qaraqash River basin are significantly different, and the multi-year average annual precipitation of GSMaP is 97.11 mm, which is the closest to the weather station interpolation results. (2) On the annual and monthly scales, GSMaP has the highest correlation (R ≥ 0.82) with the observed precipitation and the smallest relative error (BIAS < 6%). On the seasonal scale, the inversion accuracy of GSMaP in spring, summer and autumn is significantly higher than other products. In winter, all four sets of products perform poorly in estimating the actual precipitation. (3) Monthly runoff simulations based on SM2RAIN and GSMaP show good fitting (R2 > 0.6). In daily runoff simulation, GSMaP has the greatest ability to reproduce runoff changes. The study provides a reference for the optimization of precipitation image data and hydrological simulation in data-scarce areas

Advancing Ultra-High Precision in Satellite–Ground Time–Frequency Comparison: Ground-Based Experiment and Simulation Verification for the China Space Station

Establishing an ultra-high-precision link for time–frequency comparisons between satellites and ground stations is critically important. This endeavor is fundamental to the advancement of pioneering space science exploration and the development of a robust space-based time–frequency system featuring ultra-high-precision space atomic clocks. In response to the requirements for assessing the long-term stability of high-precision space atomic clocks, we have designed and implemented a satellite–ground microwave time–frequency comparison system and method based on a three-frequency mode. Ground-based experimental results demonstrate that the equipment layer can achieve a satellite–ground time comparison accuracy better than 0.4 ps (RMS), with the equipment delay stability (ADEV) for all three frequencies being better than 8 × 10−18 at 86,400. By leveraging the ground-based experimental results, we constructed a satellite–ground time–frequency comparison simulation and verification platform. This platform realizes ultra-high-precision satellite–ground time–frequency comparison based on the China Space Station (CSS). After correcting various transmission delay errors, the satellite–ground time comparison achieved an accuracy better than 0.8 ps and an ADEV better than 2 × 10−17 at 86,400. This validation of our novel satellite–ground time–frequency comparison system and method, capable of achieving an 10−17 magnitude stability, is not only a significant contribution to the field of space time–frequency systems but also paves the way for future advancements and applications in space science exploration