Hepatitis B virus(HBV)-induced hepatocellular carcinoma(HCC) is one of the most fre-quently occurring cancers.Hepadnaviral DNA integrations are considered to be essential agents which can promote the process of the he...Hepatitis B virus(HBV)-induced hepatocellular carcinoma(HCC) is one of the most fre-quently occurring cancers.Hepadnaviral DNA integrations are considered to be essential agents which can promote the process of the hepatocarcinogenesis.More and more researches were designed to find the relationship of the two.In this study,we investigated whether HBV DNA integration occurred at sites of DNA double-strand breaks(DSBs),one of the most detrimental DNA damage.An 18-bp I-SceI homing endonuclease recognition site was introduced into the DNA of HepG2 cell line by stable DNA transfection,then cells were incubated in patients’ serum with high HBV DNA copies and at the same time,DSBs were induced by transient expression of I-SceI after transfection of an I-SceI expression vector.By using nest PCR,the viral DNA was detected at the sites of the break.It appeared that integra-tion occurred between part of HBV x gene and the I-SceI induced breaks.The results suggested that DSBs,as the DNA damages,may serve as potential targets for hepadnaviral DNA insertion and the integrants would lead to widespread host genome changes necessarily.It provided a new site to investi-gate the integration.展开更多
DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB r...DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB repair plays dominant roles in safeguarding oocyte quantity and quality. However, little is known regarding the key players of the HR repair pathway in oocytes. Here, we identified oocyte-specific gene Ooep as a novel key component of the HR repair pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia mutated (ATM) kinase activation and Rad51 recombinase (RAD51) focal accumulation at DNA DSBs. Ooep null oocytes were defective in DNA DSB repair and prone to apoptosis upon exogenous DNA damage insults. Moreover, Ooep null oocytes exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving oocyte quantity and quality by maintaining genome stability. Ooep expression decreased with the advance of maternal age, suggesting its involvement in maternal aging.展开更多
Gene targeting technology is an important means to investigate gene functions, but its efficiency of gene targeting is very low, especially for somatic cell targeting. Artificially induced double-strand breaks (DSB)...Gene targeting technology is an important means to investigate gene functions, but its efficiency of gene targeting is very low, especially for somatic cell targeting. Artificially induced double-strand breaks (DSB) and triplex forming oligonucleotide (TFO) are currently developed methods to improve the targeting efficiency. This paper summarized the basic principles, design ideas and application in gene targeting efficiency improvement of these two methods, analyzed and com- pared their characteristics, and finally proposed prospects for their future development.展开更多
The purpose of the study was to investigate if the high gradient strength and slew rate used for long MRI-thermometry monitoring could cause DNA double-stranded breaks (DSBs). To this end, an enzyme-linked immunosorbe...The purpose of the study was to investigate if the high gradient strength and slew rate used for long MRI-thermometry monitoring could cause DNA double-stranded breaks (DSBs). To this end, an enzyme-linked immunosorbent assay (ELISA) was used to quantify γH2AX, a molecular marker for DSBs, in the blood of mice after a 6-hour exposure to magnetic resonance imaging (MRI). Fourteen CF-1 female mice were separated into 4 experimental groups: Untreated negative control, MRI-treated, MRI-Control, and exposed to ionizing radiation positive control. Untreated negative control was used as a baseline for ELISA to quantify γH2AX. MRI-treated consisted of a 6-hour continuous magnetic resonance imaging (MRI) echo planar imaging (EPI) sequence with a slew rate of 192 mT/m/s constituting a significantly longer imaging time than routine clinical imaging. MRI-control mice were maintained under the same conditions outside the MRI scanner for 6-hours. Mice in the irradiation group served as a positive control of DSBs and were exposed to either 2 Gy, 5 Gy or 10 Gy of ionizing radiation. DSBs in the blood lymphocytes from the treatment groups were analyzed using the γH2AX ELISA and compared. Total protein concentration in lysates was determined for each blood sample and averaged 1 ± 0.35 mg/mL. Irradiated positive controls were used to test radiation dose-dependency of the γH2AX ELISA assay where a linear dependency on radiation exposure was observed (r<sup>2</sup> = 0.93) between untreated and irradiated samples. Mean and standard error mean of γH2AX formation were calculated and compared between each treatment group. Repeated measures 1-way ANOVA showed statistically significant differences between the means of irradiated controls and both the MRI-control and MRI-treated groups. There was no statistically significant difference between the MRI-treated samples and the MRI-control groups. Our results show that long MRI exposure at a high slew rate did not cause increased levels of γH2AX when compared to control mice, suggesting that no increase in DSBs was caused by the long MR thermometry imaging session. The novelty of this work contradicts other studies that have suggested MRI may cause DSBs;this work suggests an alternative cause of DNA damage.展开更多
The yield of DNA double-strand breaks (DSBs) is sure to be influenced by theenvironment around DNA molecule. Inverse pulsed-field gel electrophoresis (PIGE) has beenapplied to compare the sensitivity of B16 cells and ...The yield of DNA double-strand breaks (DSBs) is sure to be influenced by theenvironment around DNA molecule. Inverse pulsed-field gel electrophoresis (PIGE) has beenapplied to compare the sensitivity of B16 cells and their DNA in DSBs induced by 75 MeV/u16O8+ beam. Results show that the percentages of DNA released from the plug(PR) in bothkinds of tile samples increase with the dose and approach a similar quasi-threshold of about81%. A simple new equation was presented to calculate the break level of DNA molecules.Within a certain dose, the relationship between the break level and the dose is linear. Theyield of DSBs in deproteinized DNA was 1.11 DSBs/100 Mbp/Gy, while that in intact cells was0.60DSBs/100Mbp/Gy. It is testified that deproteinized DNA is more sensitive to oxygen ionsirradiation than intact cells.展开更多
A submerged cavitation water jet(SCWJ)is an effective method to recycle solid propellant from obsolete solid engines by the breaking method.Solid propellant's breaking modes and mechanical process under SCWJ impac...A submerged cavitation water jet(SCWJ)is an effective method to recycle solid propellant from obsolete solid engines by the breaking method.Solid propellant's breaking modes and mechanical process under SCWJ impact are unclear.This study aims to understand those impact breaking mechanisms.The hydroxyl-terminated polybutadiene(HTPB)propellant was chosen as the research material,and a self-designed test system was used to conduct impact tests at four different working pressures.The high-speed camera characterized crack propagation,and the DIC method calculated strain change during the impact process.Besides,micro and macro fracture morphologies were characterized by scanning electron microscope(SEM)and computed tomography(CT)scanning.The results reveal that the compressive strain concentration region locates right below the nozzle,and the shear strain region distributes symmetrically with the jet axis,which increases to 4% at first 16th ms,the compressive strain rises to 2% and 6% in the axial and transverse direction,respectively.The two tensile cracks formed first at the compression strain concentrate region,and there generate many shear cracks around the tensile cracks,and those shear cracks that develop and aggregate cause the cracks to become wider and cut through the tensile cracks,forming the tensile-shear cracks and the impact parts eventually fail.The HTPB propellant forms a breaking hole shaped conical after impact 10 s.The mass loss increases by 17 times at maximum,with the working pressure increasing by three times.Meanwhile,the damage value of the breaking hole remaining on the surface increases by 7.8 times while 2.9 times in the depth of the breaking hole.The breaking efficiency is closely affected by working pressures.The failure modes of HTPB impacted by SCWJ are classified as tensile crack-dominated and tensile-shear crack-dominated damage mechanisms.展开更多
Biogeographical barriers to gene flow are central to plant phylogeography.In East Asia,plant distribution is greatly influenced by two phylogeographic breaks,the Mekong-Salween Divide and Tanaka-Kaiyong Line,however,f...Biogeographical barriers to gene flow are central to plant phylogeography.In East Asia,plant distribution is greatly influenced by two phylogeographic breaks,the Mekong-Salween Divide and Tanaka-Kaiyong Line,however,few studies have investigated how these barriers affect the genetic diversity of species that are distributed across both.Here we used 14 microsatellite loci and four chloroplast DNA fragments to examine genetic diversity and distribution patterns of 49 populations of Populus rotundifolia,a species that spans both the Mekong-Salween Divide and the Tanaka-Kaiyong Line in southwestern China.Demographic and migration hypotheses were tested using coalescent-based approaches.Limited historical gene flow was observed between the western and eastern groups of P.rotundifolia,but substantial flow occurred across both the Mekong-Salween Divide and Tanaka-Kaiyong Line,manifesting in clear admixture and high genetic diversity in the central group.Wind-borne pollen and seeds may have facilitated the dispersal of P.rotundifolia following prevalent northwest winds in the spring.We also found that the Hengduan Mountains,where multiple genetic barriers were detected,acted on the whole as a barrier between the western and eastern groups of P.rotundifolia.Ecological niche modeling suggested that P.rotundifolia has undergone range expansion since the last glacial maximum,and demographic reconstruction indicated an earlier population expansion around 600 Ka.The phylogeographic pattern of P.rotundifolia reflects the interplay of biological traits,wind patterns,barriers,niche differentiation,and Quaternary climate history.This study emphasizes the need for multiple lines of evidence in understanding the Quaternary evolution of plants in topographically complex areas.展开更多
DNA is the hereditary material in humans and almost all other organisms. It is essential for maintaining accurate transmission of genetic information. In the life cycle, DNA replication, cell division, or genome damag...DNA is the hereditary material in humans and almost all other organisms. It is essential for maintaining accurate transmission of genetic information. In the life cycle, DNA replication, cell division, or genome damage, including that caused by endogenous and exogenous agents, may cause DNA aberrations. Of all forms of DNA damage, DNA double-strand breaks(DSBs) are the most serious. If the repair function is defective, DNA damage may cause gene mutation, genome instability, and cell chromosome loss, which in turn can even lead to tumorigenesis. DNA damage can be repaired through multiple mechanisms. Homologous recombination(HR) and non-homologous end joining(NHEJ) are the two main repair mechanisms for DNA DSBs. Increasing amounts of evidence reveal that protein modifications play an essential role in DNA damage repair.Protein deubiquitination is a vital post-translational modification which removes ubiquitin molecules or polyubiquitinated chains from substrates in order to reverse the ubiquitination reaction. This review discusses the role of deubiquitinating enzymes(DUBs) in repairing DNA DSBs. Exploring the molecular mechanisms of DUB regulation in DSB repair will provide new insights to combat human diseases and develop novel therapeutic approaches.展开更多
DNA double-strand breaks(DSBs)are involved in many cellular mechanisms,including replication,transcription,and genome rearrangements.The recent observation that hot spots of DSBs in human chromosomes delimit DNA domai...DNA double-strand breaks(DSBs)are involved in many cellular mechanisms,including replication,transcription,and genome rearrangements.The recent observation that hot spots of DSBs in human chromosomes delimit DNA domains that possess coordinately expressed genes suggests a strong relationship between the organization of transcription patterns and hot spots of DSBs.In this study,we performed mapping of hot spots of DSBs in a human 43-kb ribosomal DNA(rDNA)repeated unit.We observed that rDNA units corresponded to the most fragile sites in human chromosomes and that these units possessed at least nine specific regions containing clusters of extremely frequently occurring DSBs,which were located exclusively in non-coding intergenic spacer(IGS)regions.The hot spots of DSBs corresponded to only a specific subset of DNase-hypersensitive sites,and coincided with CTCF,PARP1,and HNRNPA2B1 binding sites,and H3K4me3 marks.Our rDNA-4C data indicate that the regions of IGS containing the hot spots of DSBs often form contacts with specific regions in different chromosomes,including the pericentromeric regions,as well as regions that are characterized by H3K27ac and H3K4me3 marks,CTCF binding sites,ChIA-PET and RIP signals,and high levels of DSBs.The data suggest a strong link between chromosome breakage and several different mechanisms of epigenetic regulation of gene expression.展开更多
Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway c...Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining(NHEJ)-mediated DSB repair pathway that rejoins DSB ends.New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination(HR)signaling.This review focuses on the up-and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair,which in turn promotes the sensitivity of poly(ADP-ribose)polymerase inhibitor(PARPi)in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.展开更多
Meiosis is an essential step in gametogenesis which is the key process in sexually reproducing organisms as meiotic aberrations may result in infertility. In meiosis, programmed DNA double-strand break (DSB) formation...Meiosis is an essential step in gametogenesis which is the key process in sexually reproducing organisms as meiotic aberrations may result in infertility. In meiosis, programmed DNA double-strand break (DSB) formation is one of the fundamental processes that are essential for maintaining homolog interactions and correcting segregation of chromosomes. Although the number and distribution of meiotic DSBs are tightly regulated, still abnormalities in DSB formation are known to cause meiotic arrest and infertility. This review is a detailed account of molecular bases of meiotic DSB formation, its evolutionary conservation, and variations in different species. We further reviewed the mutations of DSB formation genes in association with human infertility and also proposed the future directions and strategies about the study of meiotic DSB formation.展开更多
The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)is widely used for targeted genomic and epigenomic modifications and imaging in cells and organisms,and holds trem...The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)is widely used for targeted genomic and epigenomic modifications and imaging in cells and organisms,and holds tremendous promise in clinical applications.The efficiency and accuracy of the technology are partly determined by the target binding affinity and residence time of Cas9-single-guide RNA(sgRNA)at a given site.However,little attention has been paid to the effect of target binding affinity and residence duration on the repair of Cas9-induced DNA double-strand breaks(DSBs).We propose that the choice of DSB repair pathway may be altered by variation in the binding affinity and residence duration of Cas9-sgRNA at the cleaved target,contributing to significantly heterogeneous mutations in CRISPR/Cas9 genome editing.Here,we discuss the effect of Cas9-sgRNA target binding and residence on the choice of DSB repair pathway in CRISPR/Cas9 genome editing,and the opportunity this presents to optimize Cas9-based technology.展开更多
Background It is desirable to minimize the risk of adverse radiation effects associated with percutaneous coronary intervention.The aim of this study was to determine the impact of prolonging the interval between coro...Background It is desirable to minimize the risk of adverse radiation effects associated with percutaneous coronary intervention.The aim of this study was to determine the impact of prolonging the interval between coronary angiography and percutaneous coronary intervention on X-ray-induced DNA double-strand breaks in blood lymphocytes using γ-H2AX immunofluorescence microscopy.Methods Blood samples of eight patients were taken before the first exposure to ionizing radiation,10 minutes,20 minutes,30 minutes,1 hour,and 24 hours after the last exposure to determine the γ-H2AX foci repair kinetics.Fifty-eight patients undergoing percutaneous coronary intervention were randomized to an intermittent radiation exposure group and a continuous radiation exposure group.Blood samples were taken before coronary angiography and 15 minutes after the last exposure.By enumerating γ-H2AX foci,the impact of prolonging the interval on DNA double-strand breaks was investigated.Student t-test was used to compare the difference in DNA double-strand breaks between the two groups.Results An increase in foci was found in all patients received percutaneous coronary intervention.The maximum number of γ-H2AX foci was found 10-20 minutes after the end of the last exposure.There was no statistically significant difference between the two groups in γ-H2AX foci at baseline.On average there were (0.79±0.15) γ-H2AX foci induced by interventional X-rays per lymphocyte in the continuous radiation exposure group and (0.66±0.21) in the intermittent radiation exposure group after exposure (P〈0.05).Conclusions A significant number of γ-H2AX foci develop following the percutaneous coronary intervention procedures.The number of X-ray-induced DNA double-strand breaks may be decreased by prolonging the interval time between coronary angiography and percutaneous coronary intervention to 30 minutes.展开更多
Organic solar cells(OSCs) especially non-fullerene OSCs(NF-OSCs) are promising to become the next-generation of commercial applications and have received great attention from many researchers due to their typical adva...Organic solar cells(OSCs) especially non-fullerene OSCs(NF-OSCs) are promising to become the next-generation of commercial applications and have received great attention from many researchers due to their typical advantages of low cost,light weight,and flexibility [1,2].展开更多
When the traditional drill and blast method is applied to rock crushing projects,it has strong vibration,loud noise and dust pollution,so it cannot be used in densely populated areas such as urban public works.We deve...When the traditional drill and blast method is applied to rock crushing projects,it has strong vibration,loud noise and dust pollution,so it cannot be used in densely populated areas such as urban public works.We developed a supercritical CO_(2)true triaxial pneumatic rock-breaking experimental system,and conducted laboratory and field tests of dry ice powder pneumatic rock-breaking.The characteristics of the blast-induced vibration velocity waveform and the evolution of the vibration velocity and frequency with the focal distance were analyzed and discussed.The fracturing mechanism of dry ice powder pneumatic rock breaking is studied.The research results show that:(1)The vibration velocity induced by dry ice powder pneumatic rock breaking decays as a power function with the increase of the focal distance;(2)The vibration frequency caused by dry ice powder pneumatic rock breaking is mainly distributed in 1–120 Hz.Due to the dispersion effect,the dominant frequency of 10–30 Hz appears abnormally attenuated;(3)The traditional CO_(2)phase change fracturing energy calculation formula is also applicable to dry ice pneumatic rock breaking technology,and the trinitrotoluene(TNT)equivalent of fracturing energy is applicable to the Sadovsky formula;(4)Dry ice powder pneumatic rock breaking is shock wave and highenergy gas acting together to fracture rock,which can be divided into three stages,among which the gas wedge action of high-energy gas plays a dominant role in rock mass damage.展开更多
This study identifies break events of the South China Sea(SCS)summer monsoon(SCSSM)based on 42 years of data from 1979 to 2020,and investigates their statistical characteristics and associated atmospheric anomalies.A ...This study identifies break events of the South China Sea(SCS)summer monsoon(SCSSM)based on 42 years of data from 1979 to 2020,and investigates their statistical characteristics and associated atmospheric anomalies.A total of 214 break events are identified by examining the convection evolution during each monsoon season.It is found that most events occur between June and September and show a roughly even distribution.Short-lived events(3–7 days)are more frequent,accounting for about two thirds of total events,with the residual one third for long-lived events(8–24 days).The SCSSM break is featured by drastic variations in various atmospheric variables.Particularly,the convection and precipitation change from anomalous enhancement in adjoining periods to a substantial suppression during the break,with the differences being more than 60 W m−2 for outgoing longwave radiation(OLR)and 10 mm d−1 for precipitation.This convection/precipitation suppression is accompanied by an anomalous anticyclone in the lower troposphere,corresponding to a remarkable westward retreat of the monsoon trough from the Philippine Sea to the Indochina Peninsula,which reduces the transportation of water vapor into the SCS.Besides,the pseudo-equivalent potential temperature()declines sharply,mainly attributable to the local specific humidity reduction caused by downward dry advection.Furthermore,it is found that the suppressed convection and anomalous anticyclone responsible for the monsoon break form near the equatorial western Pacific and then propagate northwestward to the SCS.展开更多
the laboratories of Prof.Yang Yungui(Beijing Institute of Genomics,Chinese Academy of Sciences)and Prof.Qi Yijun(Center for Plant Biology.School of Life Sciences,Tsinghua University),reported that Ago2 facilitates Rad...the laboratories of Prof.Yang Yungui(Beijing Institute of Genomics,Chinese Academy of Sciences)and Prof.Qi Yijun(Center for Plant Biology.School of Life Sciences,Tsinghua University),reported that Ago2 facilitates RadSl recruitment and DNA double-strand break(DSB)repair by homologous recombination,which was published in Cell Research(2014,24(5):532—541).展开更多
基金supported by grants from National Natural Sciences Foundation of China (No.30872237)the National Basic Research Program of China(No.2007CB512900)
文摘Hepatitis B virus(HBV)-induced hepatocellular carcinoma(HCC) is one of the most fre-quently occurring cancers.Hepadnaviral DNA integrations are considered to be essential agents which can promote the process of the hepatocarcinogenesis.More and more researches were designed to find the relationship of the two.In this study,we investigated whether HBV DNA integration occurred at sites of DNA double-strand breaks(DSBs),one of the most detrimental DNA damage.An 18-bp I-SceI homing endonuclease recognition site was introduced into the DNA of HepG2 cell line by stable DNA transfection,then cells were incubated in patients’ serum with high HBV DNA copies and at the same time,DSBs were induced by transient expression of I-SceI after transfection of an I-SceI expression vector.By using nest PCR,the viral DNA was detected at the sites of the break.It appeared that integra-tion occurred between part of HBV x gene and the I-SceI induced breaks.The results suggested that DSBs,as the DNA damages,may serve as potential targets for hepadnaviral DNA insertion and the integrants would lead to widespread host genome changes necessarily.It provided a new site to investi-gate the integration.
基金supported by the National Key Research and Development Program of China(2017YFC1001102)National Natural Science Foundation of China(81760507)
文摘DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB repair plays dominant roles in safeguarding oocyte quantity and quality. However, little is known regarding the key players of the HR repair pathway in oocytes. Here, we identified oocyte-specific gene Ooep as a novel key component of the HR repair pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia mutated (ATM) kinase activation and Rad51 recombinase (RAD51) focal accumulation at DNA DSBs. Ooep null oocytes were defective in DNA DSB repair and prone to apoptosis upon exogenous DNA damage insults. Moreover, Ooep null oocytes exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving oocyte quantity and quality by maintaining genome stability. Ooep expression decreased with the advance of maternal age, suggesting its involvement in maternal aging.
基金Supported by Shandong Swine Industry Technology System and Science and Technology Planning Program for Basic Research in Qingdao City(12-1-4-14-jch)
文摘Gene targeting technology is an important means to investigate gene functions, but its efficiency of gene targeting is very low, especially for somatic cell targeting. Artificially induced double-strand breaks (DSB) and triplex forming oligonucleotide (TFO) are currently developed methods to improve the targeting efficiency. This paper summarized the basic principles, design ideas and application in gene targeting efficiency improvement of these two methods, analyzed and com- pared their characteristics, and finally proposed prospects for their future development.
文摘The purpose of the study was to investigate if the high gradient strength and slew rate used for long MRI-thermometry monitoring could cause DNA double-stranded breaks (DSBs). To this end, an enzyme-linked immunosorbent assay (ELISA) was used to quantify γH2AX, a molecular marker for DSBs, in the blood of mice after a 6-hour exposure to magnetic resonance imaging (MRI). Fourteen CF-1 female mice were separated into 4 experimental groups: Untreated negative control, MRI-treated, MRI-Control, and exposed to ionizing radiation positive control. Untreated negative control was used as a baseline for ELISA to quantify γH2AX. MRI-treated consisted of a 6-hour continuous magnetic resonance imaging (MRI) echo planar imaging (EPI) sequence with a slew rate of 192 mT/m/s constituting a significantly longer imaging time than routine clinical imaging. MRI-control mice were maintained under the same conditions outside the MRI scanner for 6-hours. Mice in the irradiation group served as a positive control of DSBs and were exposed to either 2 Gy, 5 Gy or 10 Gy of ionizing radiation. DSBs in the blood lymphocytes from the treatment groups were analyzed using the γH2AX ELISA and compared. Total protein concentration in lysates was determined for each blood sample and averaged 1 ± 0.35 mg/mL. Irradiated positive controls were used to test radiation dose-dependency of the γH2AX ELISA assay where a linear dependency on radiation exposure was observed (r<sup>2</sup> = 0.93) between untreated and irradiated samples. Mean and standard error mean of γH2AX formation were calculated and compared between each treatment group. Repeated measures 1-way ANOVA showed statistically significant differences between the means of irradiated controls and both the MRI-control and MRI-treated groups. There was no statistically significant difference between the MRI-treated samples and the MRI-control groups. Our results show that long MRI exposure at a high slew rate did not cause increased levels of γH2AX when compared to control mice, suggesting that no increase in DSBs was caused by the long MR thermometry imaging session. The novelty of this work contradicts other studies that have suggested MRI may cause DSBs;this work suggests an alternative cause of DNA damage.
文摘The yield of DNA double-strand breaks (DSBs) is sure to be influenced by theenvironment around DNA molecule. Inverse pulsed-field gel electrophoresis (PIGE) has beenapplied to compare the sensitivity of B16 cells and their DNA in DSBs induced by 75 MeV/u16O8+ beam. Results show that the percentages of DNA released from the plug(PR) in bothkinds of tile samples increase with the dose and approach a similar quasi-threshold of about81%. A simple new equation was presented to calculate the break level of DNA molecules.Within a certain dose, the relationship between the break level and the dose is linear. Theyield of DSBs in deproteinized DNA was 1.11 DSBs/100 Mbp/Gy, while that in intact cells was0.60DSBs/100Mbp/Gy. It is testified that deproteinized DNA is more sensitive to oxygen ionsirradiation than intact cells.
基金supported by the Program for National Defense Science and Technology Foundation Strengtheningthe Youth Foundation of Rocket Force University of Engineering(Grant No.2021QN-B014)。
文摘A submerged cavitation water jet(SCWJ)is an effective method to recycle solid propellant from obsolete solid engines by the breaking method.Solid propellant's breaking modes and mechanical process under SCWJ impact are unclear.This study aims to understand those impact breaking mechanisms.The hydroxyl-terminated polybutadiene(HTPB)propellant was chosen as the research material,and a self-designed test system was used to conduct impact tests at four different working pressures.The high-speed camera characterized crack propagation,and the DIC method calculated strain change during the impact process.Besides,micro and macro fracture morphologies were characterized by scanning electron microscope(SEM)and computed tomography(CT)scanning.The results reveal that the compressive strain concentration region locates right below the nozzle,and the shear strain region distributes symmetrically with the jet axis,which increases to 4% at first 16th ms,the compressive strain rises to 2% and 6% in the axial and transverse direction,respectively.The two tensile cracks formed first at the compression strain concentrate region,and there generate many shear cracks around the tensile cracks,and those shear cracks that develop and aggregate cause the cracks to become wider and cut through the tensile cracks,forming the tensile-shear cracks and the impact parts eventually fail.The HTPB propellant forms a breaking hole shaped conical after impact 10 s.The mass loss increases by 17 times at maximum,with the working pressure increasing by three times.Meanwhile,the damage value of the breaking hole remaining on the surface increases by 7.8 times while 2.9 times in the depth of the breaking hole.The breaking efficiency is closely affected by working pressures.The failure modes of HTPB impacted by SCWJ are classified as tensile crack-dominated and tensile-shear crack-dominated damage mechanisms.
基金funded by the National Natural Science Foundation of China(grants 41571054 and 31622015)the National Basic Research Program of China(grant 2014CB954100)+1 种基金Sichuan University(Fundamental Research Funds for the Central Universities,SCU2021D006 and SCU2022D003Institutional Research Funds,2021SCUNL102).
文摘Biogeographical barriers to gene flow are central to plant phylogeography.In East Asia,plant distribution is greatly influenced by two phylogeographic breaks,the Mekong-Salween Divide and Tanaka-Kaiyong Line,however,few studies have investigated how these barriers affect the genetic diversity of species that are distributed across both.Here we used 14 microsatellite loci and four chloroplast DNA fragments to examine genetic diversity and distribution patterns of 49 populations of Populus rotundifolia,a species that spans both the Mekong-Salween Divide and the Tanaka-Kaiyong Line in southwestern China.Demographic and migration hypotheses were tested using coalescent-based approaches.Limited historical gene flow was observed between the western and eastern groups of P.rotundifolia,but substantial flow occurred across both the Mekong-Salween Divide and Tanaka-Kaiyong Line,manifesting in clear admixture and high genetic diversity in the central group.Wind-borne pollen and seeds may have facilitated the dispersal of P.rotundifolia following prevalent northwest winds in the spring.We also found that the Hengduan Mountains,where multiple genetic barriers were detected,acted on the whole as a barrier between the western and eastern groups of P.rotundifolia.Ecological niche modeling suggested that P.rotundifolia has undergone range expansion since the last glacial maximum,and demographic reconstruction indicated an earlier population expansion around 600 Ka.The phylogeographic pattern of P.rotundifolia reflects the interplay of biological traits,wind patterns,barriers,niche differentiation,and Quaternary climate history.This study emphasizes the need for multiple lines of evidence in understanding the Quaternary evolution of plants in topographically complex areas.
基金supported by the National Natural Science Foundation of China[grant number 42275025]the Youth Innovation Promotion Association of the Chinese Academy of Sciences[grant number 2023084].
基金supported by the National Natural Science Foundation of China (Nos. 91749115 and 81872298)the Natural Science Foundation of Jiangxi Province (No. 20181BAB205044), China。
文摘DNA is the hereditary material in humans and almost all other organisms. It is essential for maintaining accurate transmission of genetic information. In the life cycle, DNA replication, cell division, or genome damage, including that caused by endogenous and exogenous agents, may cause DNA aberrations. Of all forms of DNA damage, DNA double-strand breaks(DSBs) are the most serious. If the repair function is defective, DNA damage may cause gene mutation, genome instability, and cell chromosome loss, which in turn can even lead to tumorigenesis. DNA damage can be repaired through multiple mechanisms. Homologous recombination(HR) and non-homologous end joining(NHEJ) are the two main repair mechanisms for DNA DSBs. Increasing amounts of evidence reveal that protein modifications play an essential role in DNA damage repair.Protein deubiquitination is a vital post-translational modification which removes ubiquitin molecules or polyubiquitinated chains from substrates in order to reverse the ubiquitination reaction. This review discusses the role of deubiquitinating enzymes(DUBs) in repairing DNA DSBs. Exploring the molecular mechanisms of DUB regulation in DSB repair will provide new insights to combat human diseases and develop novel therapeutic approaches.
基金supported bya grant from the Molecular and Cellular Biology Program of the Russian Academy of Sciences and by grantsfrom the Russian Foundation for Basic Research(#12-04-01416-a,#12-04-01311-a,#14-04-01638-a,and#15-04-00299-a)by a President Grant for Government Support of Young Russian Scientists MK-1934.2014.4.
文摘DNA double-strand breaks(DSBs)are involved in many cellular mechanisms,including replication,transcription,and genome rearrangements.The recent observation that hot spots of DSBs in human chromosomes delimit DNA domains that possess coordinately expressed genes suggests a strong relationship between the organization of transcription patterns and hot spots of DSBs.In this study,we performed mapping of hot spots of DSBs in a human 43-kb ribosomal DNA(rDNA)repeated unit.We observed that rDNA units corresponded to the most fragile sites in human chromosomes and that these units possessed at least nine specific regions containing clusters of extremely frequently occurring DSBs,which were located exclusively in non-coding intergenic spacer(IGS)regions.The hot spots of DSBs corresponded to only a specific subset of DNase-hypersensitive sites,and coincided with CTCF,PARP1,and HNRNPA2B1 binding sites,and H3K4me3 marks.Our rDNA-4C data indicate that the regions of IGS containing the hot spots of DSBs often form contacts with specific regions in different chromosomes,including the pericentromeric regions,as well as regions that are characterized by H3K27ac and H3K4me3 marks,CTCF binding sites,ChIA-PET and RIP signals,and high levels of DSBs.The data suggest a strong link between chromosome breakage and several different mechanisms of epigenetic regulation of gene expression.
文摘Maintenance of cellular homeostasis and genome integrity is a critical responsibility of DNA double-strand break(DSB)signaling.P53-binding protein 1(53BP1)plays a critical role in coordinating the DSB repair pathway choice and promotes the non-homologous end-joining(NHEJ)-mediated DSB repair pathway that rejoins DSB ends.New insights have been gained into a basic molecular mechanism that is involved in 53BP1 recruitment to the DNA lesion and how 53BP1 then recruits the DNA break-responsive effectors that promote NHEJ-mediated DSB repair while inhibiting homologous recombination(HR)signaling.This review focuses on the up-and downstream pathways of 53BP1 and how 53BP1 promotes NHEJ-mediated DSB repair,which in turn promotes the sensitivity of poly(ADP-ribose)polymerase inhibitor(PARPi)in BRCA1-deficient cancers and consequently provides an avenue for improving cancer therapy strategies.
基金This work was supported by the National Key Research and Developmental Program of China(2018YFC1003700,2018YFC1003400,and 2016YFC1000600)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000)+1 种基金the National Natural Science Foundation of China(31890780,31630050,32061143006,82071709,and 31871514)the Fundamental Research Funds for the Central Universities(YD2070002006).
文摘Meiosis is an essential step in gametogenesis which is the key process in sexually reproducing organisms as meiotic aberrations may result in infertility. In meiosis, programmed DNA double-strand break (DSB) formation is one of the fundamental processes that are essential for maintaining homolog interactions and correcting segregation of chromosomes. Although the number and distribution of meiotic DSBs are tightly regulated, still abnormalities in DSB formation are known to cause meiotic arrest and infertility. This review is a detailed account of molecular bases of meiotic DSB formation, its evolutionary conservation, and variations in different species. We further reviewed the mutations of DSB formation genes in association with human infertility and also proposed the future directions and strategies about the study of meiotic DSB formation.
基金supported by the National Natural Science Foundation of China(Nos.31671385 and 31870806)the Zhejiang Provincial Natural Science Foundation of China(Nos.LY18C050001 and LQ20C050004)the Fundamental Research Funds for the Central Universities in China(No.2019QNA7031)。
文摘The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)is widely used for targeted genomic and epigenomic modifications and imaging in cells and organisms,and holds tremendous promise in clinical applications.The efficiency and accuracy of the technology are partly determined by the target binding affinity and residence time of Cas9-single-guide RNA(sgRNA)at a given site.However,little attention has been paid to the effect of target binding affinity and residence duration on the repair of Cas9-induced DNA double-strand breaks(DSBs).We propose that the choice of DSB repair pathway may be altered by variation in the binding affinity and residence duration of Cas9-sgRNA at the cleaved target,contributing to significantly heterogeneous mutations in CRISPR/Cas9 genome editing.Here,we discuss the effect of Cas9-sgRNA target binding and residence on the choice of DSB repair pathway in CRISPR/Cas9 genome editing,and the opportunity this presents to optimize Cas9-based technology.
文摘Background It is desirable to minimize the risk of adverse radiation effects associated with percutaneous coronary intervention.The aim of this study was to determine the impact of prolonging the interval between coronary angiography and percutaneous coronary intervention on X-ray-induced DNA double-strand breaks in blood lymphocytes using γ-H2AX immunofluorescence microscopy.Methods Blood samples of eight patients were taken before the first exposure to ionizing radiation,10 minutes,20 minutes,30 minutes,1 hour,and 24 hours after the last exposure to determine the γ-H2AX foci repair kinetics.Fifty-eight patients undergoing percutaneous coronary intervention were randomized to an intermittent radiation exposure group and a continuous radiation exposure group.Blood samples were taken before coronary angiography and 15 minutes after the last exposure.By enumerating γ-H2AX foci,the impact of prolonging the interval on DNA double-strand breaks was investigated.Student t-test was used to compare the difference in DNA double-strand breaks between the two groups.Results An increase in foci was found in all patients received percutaneous coronary intervention.The maximum number of γ-H2AX foci was found 10-20 minutes after the end of the last exposure.There was no statistically significant difference between the two groups in γ-H2AX foci at baseline.On average there were (0.79±0.15) γ-H2AX foci induced by interventional X-rays per lymphocyte in the continuous radiation exposure group and (0.66±0.21) in the intermittent radiation exposure group after exposure (P〈0.05).Conclusions A significant number of γ-H2AX foci develop following the percutaneous coronary intervention procedures.The number of X-ray-induced DNA double-strand breaks may be decreased by prolonging the interval time between coronary angiography and percutaneous coronary intervention to 30 minutes.
基金the Natural Science Foundation of China (52172048, 52103221, 51873172, 22205130, 12175298)the Shandon Provincial Natural Science Foundation of China (ZR2021QB024, ZR2021QB179, ZR2021ZD06)+2 种基金the Guangdong Natural Science Foundation of China (2023A1515012323, 2023A1515010943, 2022A1515110643)the National Key Research and Development Program of China (2022YFB4200400) funded by MOST of Chinathe Fundamental Research Funds of Shandong University from China。
文摘Organic solar cells(OSCs) especially non-fullerene OSCs(NF-OSCs) are promising to become the next-generation of commercial applications and have received great attention from many researchers due to their typical advantages of low cost,light weight,and flexibility [1,2].
基金supported by the State Key Laboratory Open Fund(No.HKLBEF202004)the Natural Science Foundation of Jiangsu Province(No.BK20201313)+2 种基金the Key Program of National Natural Science Foundation of China(No.51934007)the Major Scientific and Technological Innovation Program in Shandong Province(No.2019JZZY020505)the National Key Research and Development Program of China(No.2022YFC3004700)。
文摘When the traditional drill and blast method is applied to rock crushing projects,it has strong vibration,loud noise and dust pollution,so it cannot be used in densely populated areas such as urban public works.We developed a supercritical CO_(2)true triaxial pneumatic rock-breaking experimental system,and conducted laboratory and field tests of dry ice powder pneumatic rock-breaking.The characteristics of the blast-induced vibration velocity waveform and the evolution of the vibration velocity and frequency with the focal distance were analyzed and discussed.The fracturing mechanism of dry ice powder pneumatic rock breaking is studied.The research results show that:(1)The vibration velocity induced by dry ice powder pneumatic rock breaking decays as a power function with the increase of the focal distance;(2)The vibration frequency caused by dry ice powder pneumatic rock breaking is mainly distributed in 1–120 Hz.Due to the dispersion effect,the dominant frequency of 10–30 Hz appears abnormally attenuated;(3)The traditional CO_(2)phase change fracturing energy calculation formula is also applicable to dry ice pneumatic rock breaking technology,and the trinitrotoluene(TNT)equivalent of fracturing energy is applicable to the Sadovsky formula;(4)Dry ice powder pneumatic rock breaking is shock wave and highenergy gas acting together to fracture rock,which can be divided into three stages,among which the gas wedge action of high-energy gas plays a dominant role in rock mass damage.
基金supported by the National Natural Science Foundation of China(Grant No.42275025).
文摘This study identifies break events of the South China Sea(SCS)summer monsoon(SCSSM)based on 42 years of data from 1979 to 2020,and investigates their statistical characteristics and associated atmospheric anomalies.A total of 214 break events are identified by examining the convection evolution during each monsoon season.It is found that most events occur between June and September and show a roughly even distribution.Short-lived events(3–7 days)are more frequent,accounting for about two thirds of total events,with the residual one third for long-lived events(8–24 days).The SCSSM break is featured by drastic variations in various atmospheric variables.Particularly,the convection and precipitation change from anomalous enhancement in adjoining periods to a substantial suppression during the break,with the differences being more than 60 W m−2 for outgoing longwave radiation(OLR)and 10 mm d−1 for precipitation.This convection/precipitation suppression is accompanied by an anomalous anticyclone in the lower troposphere,corresponding to a remarkable westward retreat of the monsoon trough from the Philippine Sea to the Indochina Peninsula,which reduces the transportation of water vapor into the SCS.Besides,the pseudo-equivalent potential temperature()declines sharply,mainly attributable to the local specific humidity reduction caused by downward dry advection.Furthermore,it is found that the suppressed convection and anomalous anticyclone responsible for the monsoon break form near the equatorial western Pacific and then propagate northwestward to the SCS.
基金support by the National Natural Science Foundation of China(Grant Nos.31225015 and 31370796)the Ministry of Science and Technology of China(Grant Nos.2011CB510103 and2012CB910900)
文摘the laboratories of Prof.Yang Yungui(Beijing Institute of Genomics,Chinese Academy of Sciences)and Prof.Qi Yijun(Center for Plant Biology.School of Life Sciences,Tsinghua University),reported that Ago2 facilitates RadSl recruitment and DNA double-strand break(DSB)repair by homologous recombination,which was published in Cell Research(2014,24(5):532—541).
基金The authors thank Alexandra Surcel and Carey L Hendrix Lord for helpful comments on this manuscript.The work in our laboratory is supported by grants from the National Science Foundation(IBN-0077832,MCB-9896340,MCB-0092075)the National Institutes of Health(R0 1 GM63871)+3 种基金the US Department of Agriculture(2001-35301-10570 and 2003-35301-13313)Wuxing L was partially supported by the Intercollege Graduate Degree Program in Plant PhysiologyHong M gratefully acknowledges the support of the John Simon Guggenheim Foundationthe National Institutes of Health(F33 GM72245-1).
基金This work was supported by grants from the Israel Science Foundation OSF, Grant no. 2021242), the Israel Cancer Association (Grant no. 2019404), the Binational Science Foundation (Grant no. 2023065), the Israel Cancer Research Fund (ICRF, Grant no. 2021_762), and Volkswagen Foundation (Grant no. 2020594). E.R.A.-Z. and S.W.A. are supported by the Council for Higher Education 19 fellowship for outstanding minority M.Sc. and Ph.D. students, respectively. N.A. is supported by the Neubauer Family Foundation.