Peroxynitrite is a highly reactive nitrogen species and a potent inducer of apoptosis and necrosis in somatic cells. Peroxynitrite-induced nitrosative stress has emerged as a major cause of impaired sperm function; ho...Peroxynitrite is a highly reactive nitrogen species and a potent inducer of apoptosis and necrosis in somatic cells. Peroxynitrite-induced nitrosative stress has emerged as a major cause of impaired sperm function; however, its ability to trigger cell death has not been described in human spermatozoa. The objective here was to characterize biochemical and morphological features of cell death induced by peroxynitrite-mediated nitrosative stress in human spermatozoa. For this, spermatozoa were incubated with and without （untreated control） 3-morpholinosydnonimine （SIN-l）, in order to generate peroxynitrite. Sperm viability, mitochondrial permeability transition （MPT）, externalization of phosphatidylserine, DNA oxidation and fragmentation, caspase activation, tyrosine nitration, and sperm ultrastructure were analyzed. The results showed that at 24 h of incubation with SIN-l, the sperm viability was significantly reduced compared to untreated control （P〈 0.001）. Furthermore, the MPT was induced （P〈 0.01） and increment in DNA oxidation （P 〈 0.01）, DNA fragmentation （P 〈 0.01）, tyrosine nitration （P 〈 0.0001） and ultrastructural damage were observed when compared to untreated control. Caspase activation was not evidenced, and although phosphatidylserine externalization increased compared to untreated control （P 〈 0.001）, this process was observed in 〈10% of the cells and the gradual loss of viability was not characterized by an important increase in this parameter. In conclusion, peroxynitrite-mediated nitrosative stress induces the regulated variant of cell death known as MPT-driven necrosis in human spermatozoa. This study provides a new insight into the pathophysiology of nitrosative stress in human spermatozoa and opens up a new focus for developing specific therapeutic strategies to better preserve sperm viability or to avoid cell death.展开更多
The minimally invasive surgery through natural orifices has revolutionized the laparoscopic surgery for abdominal procedures. The use of the vaginal approach is not new for gynecologists but it is a new concept for th...The minimally invasive surgery through natural orifices has revolutionized the laparoscopic surgery for abdominal procedures. The use of the vaginal approach is not new for gynecologists but it is a new concept for the non-gynecological laparoscopic surgeons. The use of this new approach has been used to perform some procedures and to extract specimens after a laparoscopic surgery, but we don’t know exactly the number of procedures performed until today. There are few papers with clinical experience and a lot of philosophical papers about NOTES. Our aim is to know how and how often we are using this new approach for non-gynecological abdominal minimally invasive procedures. With the revision of the PubMed publications we obtained a total of 268 articles, of which 125 were included in the analysis (46.64%). Cholecystectomy was the procedure more usually performed: there is a large clinical experience with a total of 2432 transvaginal cholecystectomies. Bariatric surgery, colectomy and appendectomy have been other surgical procedures with some clinical experience in the use of the transvaginal approach. Analyzing the publications on transvaginal approach, we observed that the use of the vaginal route for non-gynecological abdominal surgery was not anecdotal, with accumulative experience of more than 3000 patients reported in published studies. The use of the vaginal route has shown its safety, obtaining some additional benefits such as the aesthetic and the faster functional recovery. Dyspareunia, one of the most feared, has not been reported in studies as a concern to consider.展开更多
The massively parallel,nonlinear,three-dimensional(3D),toroidal,electrostatic,gyrokinetic,particle-in-cell(PIC),Cartesian geometry UCANcode,with particle ions and adiabatic electrons,has been successfully exercised to...The massively parallel,nonlinear,three-dimensional(3D),toroidal,electrostatic,gyrokinetic,particle-in-cell(PIC),Cartesian geometry UCANcode,with particle ions and adiabatic electrons,has been successfully exercised to identify non-diffusive transport characteristics in present day tokamak discharges.The limitation in applying UCAN to larger scale discharges is the 1D domain decomposition in the toroidal(or z-)direction for massively parallel implementation using MPI which has restricted the calculations to a few hundred ion Larmor radii or gyroradii per plasma minor radius.To exceed these sizes,we have implemented 2D domain decomposition in UCANwith the addition of the y-direction to the processor mix.This has been facilitated by use of relevant components in the P2LIB library of field and particle management routines developed for UCLA’s UPIC Framework of conventional PIC codes.The gyroaveraging specific to gyrokinetic codes is simplified by the use of replicated arrays for efficient charge accumulation and force deposition.The 2D domain-decomposed UCAN2 code reproduces the original 1D domain nonlinear results within round-off.Benchmarks of UCAN2 on the Cray XC30 Edison at NERSC demonstrate ideal scaling when problem size is increased along with processor number up to the largest power of 2 available,namely 131,072 processors.These particle weak scaling benchmarks also indicate that the 1 nanosecond per particle per time step and 1 TFlops barriers are easily broken by UCAN2 with 1 billion particles or more and 2000 or more processors.展开更多
文摘Peroxynitrite is a highly reactive nitrogen species and a potent inducer of apoptosis and necrosis in somatic cells. Peroxynitrite-induced nitrosative stress has emerged as a major cause of impaired sperm function; however, its ability to trigger cell death has not been described in human spermatozoa. The objective here was to characterize biochemical and morphological features of cell death induced by peroxynitrite-mediated nitrosative stress in human spermatozoa. For this, spermatozoa were incubated with and without （untreated control） 3-morpholinosydnonimine （SIN-l）, in order to generate peroxynitrite. Sperm viability, mitochondrial permeability transition （MPT）, externalization of phosphatidylserine, DNA oxidation and fragmentation, caspase activation, tyrosine nitration, and sperm ultrastructure were analyzed. The results showed that at 24 h of incubation with SIN-l, the sperm viability was significantly reduced compared to untreated control （P〈 0.001）. Furthermore, the MPT was induced （P〈 0.01） and increment in DNA oxidation （P 〈 0.01）, DNA fragmentation （P 〈 0.01）, tyrosine nitration （P 〈 0.0001） and ultrastructural damage were observed when compared to untreated control. Caspase activation was not evidenced, and although phosphatidylserine externalization increased compared to untreated control （P 〈 0.001）, this process was observed in 〈10% of the cells and the gradual loss of viability was not characterized by an important increase in this parameter. In conclusion, peroxynitrite-mediated nitrosative stress induces the regulated variant of cell death known as MPT-driven necrosis in human spermatozoa. This study provides a new insight into the pathophysiology of nitrosative stress in human spermatozoa and opens up a new focus for developing specific therapeutic strategies to better preserve sperm viability or to avoid cell death.
文摘The minimally invasive surgery through natural orifices has revolutionized the laparoscopic surgery for abdominal procedures. The use of the vaginal approach is not new for gynecologists but it is a new concept for the non-gynecological laparoscopic surgeons. The use of this new approach has been used to perform some procedures and to extract specimens after a laparoscopic surgery, but we don’t know exactly the number of procedures performed until today. There are few papers with clinical experience and a lot of philosophical papers about NOTES. Our aim is to know how and how often we are using this new approach for non-gynecological abdominal minimally invasive procedures. With the revision of the PubMed publications we obtained a total of 268 articles, of which 125 were included in the analysis (46.64%). Cholecystectomy was the procedure more usually performed: there is a large clinical experience with a total of 2432 transvaginal cholecystectomies. Bariatric surgery, colectomy and appendectomy have been other surgical procedures with some clinical experience in the use of the transvaginal approach. Analyzing the publications on transvaginal approach, we observed that the use of the vaginal route for non-gynecological abdominal surgery was not anecdotal, with accumulative experience of more than 3000 patients reported in published studies. The use of the vaginal route has shown its safety, obtaining some additional benefits such as the aesthetic and the faster functional recovery. Dyspareunia, one of the most feared, has not been reported in studies as a concern to consider.
基金This work was supported in part in the USA by Grant No.DE-FG02-04ER54741 to the University of Alaska,Fairbanks,AK,from the Office of Fusion Energy Sciences,Office of Science,United States Department of EnergyIt was also supported in part at Univer-sidad Carlos III,Madrid,Spain,by Spanish National Project No.ENE2009-12213-C03-03+1 种基金This research used resources of the National Energy Research Scientific Computing Center(NERSC)which is supported by the Office of Science of the U.S.Department of Energy under Contract No.DE-AC02-05CH11231.
文摘The massively parallel,nonlinear,three-dimensional(3D),toroidal,electrostatic,gyrokinetic,particle-in-cell(PIC),Cartesian geometry UCANcode,with particle ions and adiabatic electrons,has been successfully exercised to identify non-diffusive transport characteristics in present day tokamak discharges.The limitation in applying UCAN to larger scale discharges is the 1D domain decomposition in the toroidal(or z-)direction for massively parallel implementation using MPI which has restricted the calculations to a few hundred ion Larmor radii or gyroradii per plasma minor radius.To exceed these sizes,we have implemented 2D domain decomposition in UCANwith the addition of the y-direction to the processor mix.This has been facilitated by use of relevant components in the P2LIB library of field and particle management routines developed for UCLA’s UPIC Framework of conventional PIC codes.The gyroaveraging specific to gyrokinetic codes is simplified by the use of replicated arrays for efficient charge accumulation and force deposition.The 2D domain-decomposed UCAN2 code reproduces the original 1D domain nonlinear results within round-off.Benchmarks of UCAN2 on the Cray XC30 Edison at NERSC demonstrate ideal scaling when problem size is increased along with processor number up to the largest power of 2 available,namely 131,072 processors.These particle weak scaling benchmarks also indicate that the 1 nanosecond per particle per time step and 1 TFlops barriers are easily broken by UCAN2 with 1 billion particles or more and 2000 or more processors.
