New approach to oligotriazoles using a cobalt complex of propargyl azides as a synthetic component

金沢大学医薬保健研究域薬学

Quantification of Local Morphodynamics and Local GTPase Activity by Edge Evolution Tracking

Advances in time-lapse fluorescence microscopy have enabled us to directly observe dynamic cellular phenomena. Although the techniques themselves have promoted the understanding of dynamic cellular functions, the vast number of images acquired has generated a need for automated processing tools to extract statistical information. A problem underlying the analysis of time-lapse cell images is the lack of rigorous methods to extract morphodynamic properties. Here, we propose an algorithm called edge evolution tracking (EET) to quantify the relationship between local morphological changes and local fluorescence intensities around a cell edge using time-lapse microscopy images. This algorithm enables us to trace the local edge extension and contraction by defining subdivided edges and their corresponding positions in successive frames. Thus, this algorithm enables the investigation of cross-correlations between local morphological changes and local intensity of fluorescent signals by considering the time shifts. By applying EET to fluorescence resonance energy transfer images of the Rho-family GTPases Rac1, Cdc42, and RhoA, we examined the cross-correlation between the local area difference and GTPase activity. The calculated correlations changed with time-shifts as expected, but surprisingly, the peak of the correlation coefficients appeared with a 6–8 min time shift of morphological changes and preceded the Rac1 or Cdc42 activities. Our method enables the quantification of the dynamics of local morphological change and local protein activity and statistical investigation of the relationship between them by considering time shifts in the relationship. Thus, this algorithm extends the value of time-lapse imaging data to better understand dynamics of cellular function

Effect of diamagnetic contribution of water on harmonics distribution in a dilute solution of iron oxide nanoparticles measured using high-Tc SQUID magnetometer

The magnetization curve of iron oxide nanoparticles in low-concentration solutions was investigated by a highly sensitive high-Tc superconducting quantum interference device (SQUID) magnetometer. The diamagnetic contribution of water that was used as the carrier liquid was observed in the measured magnetization curves in the high magnetic field region over 100 mT. The effect of the diamagnetic contribution of water on the generation of harmonics during the application of AC and DC magnetic fields was simulated on the basis of measured magnetization curves. Although the diamagnetic effect depends on concentration, a linear relation was observed between the detected harmonics and concentration in the simulated and measured results. The simulation results suggested that improvement could be expected in harmonics generation because of the diamagnetic effect when the iron concentration was lower than 72 μg/ml. The use of second harmonics with an appropriate bias of the DC magnetic field could be utilized for realization of a fast and highly sensitive detection of magnetic nanoparticles in a low-concentration solution

Status Report of Neutral Kaon photo-production study using Neutral Kaon Spectrometer 2 (NKS2) at LNS-Tohoku(I. Nuclear Physics)

The approach described in this paper uses an array of Field Programmable Gate Array (FPGA) devices to implement a fault tolerant hardware system that can be compared to the running of fault tolerant software on a traditional processor. Fault tolerance is achieved is achieved by using FPGA with on the fly partial programmability feature. Major considerations while mapping to the FPGA includes the size of the area to be mapped and communication issues related to their communication. Area size selection is compared to the page size selection in Operating System Design. Communication issues between modules are compared to the software engineering paradigms dealing with module coupling, fan-in, fan-out and cohesiveness. Finally, the overhead associated with the downloading of the reconfiguration files is discussed

The impact of selective HDAC inhibitors on the transcriptome of early mouse embryos

Abstract Background Histone acetylation, which is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), plays a crucial role in the control of gene expression. HDAC inhibitors (HDACi) have shown potential in cancer therapy; however, the specific roles of HDACs in early embryos remain unclear. Moreover, although some pan-HDACi have been used to maintain cellular undifferentiated states in early embryos, the specific mechanisms underlying their effects remain unknown. Thus, there remains a significant knowledge gap regarding the application of selective HDACi in early embryos. Results To address this gap, we treated early embryos with two selective HDACi (MGCD0103 and T247). Subsequently, we collected and analyzed their transcriptome data at different developmental stages. Our findings unveiled a significant effect of HDACi treatment during the crucial 2-cell stage of zygotes, leading to a delay in embryonic development after T247 and an arrest at 2-cell stage after MGCD0103 administration. Furthermore, we elucidated the regulatory targets underlying this arrested embryonic development, which pinpointed the G2/M phase as the potential period of embryonic development arrest caused by MGCD0103. Moreover, our investigation provided a comprehensive profile of the biological processes that are affected by HDACi, with their main effects being predominantly localized in four aspects of zygotic gene activation (ZGA): RNA splicing, cell cycle regulation, autophagy, and transcription factor regulation. By exploring the transcriptional regulation and epigenetic features of the genes affected by HDACi, we made inferences regarding the potential main pathways via which HDACs affect gene expression in early embryos. Notably, Hdac7 exhibited a distinct response, highlighting its potential as a key player in early embryonic development. Conclusions Our study conducted a comprehensive analysis of the effects of HDACi on early embryonic development at the transcriptional level. The results demonstrated that HDACi significantly affected ZGA in embryos, elucidated the distinct actions of various selective HDACi, and identified specific biological pathways and mechanisms via which these inhibitors modulated early embryonic development

Synthesis and evaluation of fluorine-18-labeled SA4503 as a selective sigma1 receptor ligand for positron emission tomography

The [18F]fluoromethyl analog of the sigma1 selective ligand 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride (SA4503) ([18F]FM-SA4503) was prepared and its potential evaluated for the in vivo measurement of sigma1 receptors with positron emission tomography (PET). FM-SA4503 had selective affinity for the sigma1 receptor (Ki for sigma1 receptor, 6.4 nM; Ki for sigma2 receptor, 250 nM) that was compatible with the affinity of SA4503 (Ki for sigma1 receptor, 4.4 nM; Ki for sigma2 receptor, 242 nM). [18F]FM-SA4503 was synthesized by 18F-fluoromethylation of O-demethyl SA4503 in the radiochemical yield of 2.9-16.6% at the end of bombardment with a specific activity of 37.8-283 TBq/mmol at the end of synthesis. In mice, the uptake of [18F]FM-SA4503 in the brain was gradually increased for 30 min after injection, and then decreased. In the blocking study, brain uptake was significantly decreased by co-injection of haloperidol to 32% of control, and FM-SA4503 to 52% of control. In PET study of the monkey brain, high uptake was found in the cerebral cortex, thalamus and striatum. The radioactivity level of [18F]FM-SA4503 in the brain regions gradually increased over a period of 120 min after injection, followed by a stable plateau phase until 180 min after injection. In pretreatment with haloperidol measurement of the monkey brain, the radioactivity level was 22-32% and 11-25% of the baseline at 60 and 180 min, respectively, after injection, suggesting high receptor-specific binding. [18F]FM-SA4503 showed specific binding to sigma1 receptors in mice and monkeys; therefore, [18F]FM-SA4503 has the potential for mapping sigma1 receptors in the brain