Cyclin B1/Cdk1 phosphorylation of mitochondrial p53 induces anti-apoptotic response.

The pro-apoptotic function of p53 has been well defined in preventing genomic instability and cell transformation. However, the intriguing fact that p53 contributes to a pro-survival advantage of tumor cells under DNA damage conditions raises a critical question in radiation therapy for the 50% human cancers with intact p53 function. Herein, we reveal an anti-apoptotic role of mitochondrial p53 regulated by the cell cycle complex cyclin B1/Cdk1 in irradiated human colon cancer HCT116 cells with p53(+/+) status. Steady-state levels of p53 and cyclin B1/Cdk1 were identified in the mitochondria of many human and mouse cells, and their mitochondrial influx was significantly enhanced by radiation. The mitochondrial kinase activity of cyclin B1/Cdk1 was found to specifically phosphorylate p53 at Ser-315 residue, leading to enhanced mitochondrial ATP production and reduced mitochondrial apoptosis. The improved mitochondrial function can be blocked by transfection of mutant p53 Ser-315-Ala, or by siRNA knockdown of cyclin B1 and Cdk1 genes. Enforced translocation of cyclin B1 and Cdk1 into mitochondria with a mitochondrial-targeting-peptide increased levels of Ser-315 phosphorylation on mitochondrial p53, improved ATP production and decreased apoptosis by sequestering p53 from binding to Bcl-2 and Bcl-xL. Furthermore, reconstitution of wild-type p53 in p53-deficient HCT116 p53(-/-) cells resulted in an increased mitochondrial ATP production and suppression of apoptosis. Such phenomena were absent in the p53-deficient HCT116 p53(-/-) cells reconstituted with the mutant p53. These results demonstrate a unique anti-apoptotic function of mitochondrial p53 regulated by cyclin B1/Cdk1-mediated Ser-315 phosphorylation in p53-wild-type tumor cells, which may provide insights for improving the efficacy of anti-cancer therapy, especially for tumors that retain p53

Equation of state of the hot dense matter in a multi-phase transport model

Within the framework of a multi-phase transport model, we study the equation of state and pressure anisotropy of the hot dense matter produced in central relativistic heavy ion collisions. Both are found to depend on the hadronization scheme and scattering cross sections used in the model. Furthermore, only partial thermalization is achieved in the produced matter as a result of its fast expansion

Composite metamaterials with dual-band magnetic resonances in the terahertz frequency regime

Composite metamaterials(CMMs) combining a subwavelength metallic hole array (i.e. one-layer fishnet structure) and an array of split-ring resonators(SRRs) on the same board are fabricated with gold films on silicon wafer. Transmission measurements of the CMMs in the terahertz range have been performed. Dual-band magnetic resonances, namely, a LC resonance at 4.40 THz and an additional magnetic resonance at 8.64 THz originating from the antiparallel current in wire pairs in the CMMs are observed when the electrical field polarization of the incident light is parallel to the gap of the component SRR. The numerical simulations agree well with the experimental results and further clarify the nature of the dual-band magnetic resonances.Comment: 4 figures, 14 page

Telemetric Blood Pressure Assessment in Angiotensin II-Infused ApoE\u3csup\u3e-/-\u3c/sup\u3e Mice: 28 Day Natural History and Comparison to Tail-Cuff Measurements

Abdominal aortic aneurysm (AAA) is a disease of the aortic wall, which can progress to catastrophic rupture. Assessment of mechanical characteristics of AAA, such as aortic distensibility, may provide important insights to help identify at-risk patients and understand disease progression. While the majority of studies on this topic have focused on retrospective patient data, recent studies have used mouse models of AAA to prospectively evaluate the evolution of aortic mechanics. Quantification of aortic distensibility requires accurate measurement of arterial blood pressure, particularly pulse pressure, which is challenging to perform accurately in murine models. We hypothesized that volume/pressure tail-cuff measurements of arterial pulse pressure in anesthetized mice would have sufficient accuracy to enable calculations of aortic distensibility with minimal error. Telemetry devices and osmotic mini-pumps filled with saline or angiotensin-II were surgically implanted in male apolipoprotein-E deficient (ApoE-/-) mice. Blood pressure in the aortic arch was measured continuously via telemetry. In addition, simultaneous blood pressure measurements with a volume/pressure tail-cuff system were performed under anesthesia at specific intervals to assess agreement between techniques. Compared to controls, mice infused with angiotensin-II had an overall statistically significant increase in systolic pressure, with no overall difference in pulse pressure; however, pulse pressure did increase significantly with time. Systolic measurements agreed well between telemetry and tail-cuff (coefficient of variation = 10%), but agreement of pulse pressure was weak (20%). In fact, group-averaged pulse pressure from telemetry was a better predictor of a subject\u27s pulse pressure on a given day than a simultaneous tail-cuff measurement. Furthermore, these approximations introduced acceptable errors (15.1 ± 12.8%) into the calculation of aortic distensibility. Contrary to our hypothesis, we conclude that tail-cuff measures of arterial pulse pressure have limited accuracy. Future studies of aneurysm mechanics using the ApoE-/-/angiotensin-II model would be better in assuming pulse pressure profiles consistent with our telemetry findings instead of attempting to measure pulse pressure in individual mice

The Structure and Morphology of Galaxies during the Epoch of Reionization Revealed by JWST

We analyze 347 galaxies at redshift $4<z<9.5$ using JWST observations from the CEERS program by fitting a two-dimensional parametric model simultaneously to the seven-filter NIRCam images to measure the overall structural parameters and quantify the global properties of the galaxies in the rest-frame optical band. Particular attention is devoted to deriving robust uncertainties that include, among other factors, the influence of cosmological surface brightness dimming and resolution effects. Using the global S\'ersic index ($n < 1.5$) and observed axial ratio ($q < 0.6$) as a guide, we place a conservative lower limit of $\sim 45\%$ on the incidence of galactic disks. Galaxies follow a relation between rest-frame optical luminosity and effective radius in the redshift range $4<z<9.5$, as well as separately over the intervals $4 < z < 5$ and $5 \leq z < 9.5$, with a very similar slope but a marginally lower zero point in the higher redshift bin ($R_e = 0.49 \pm 0.07$ kpc) compared to the lower redshift bin ($R_e = 0.65 \pm 0.12$ kpc). Within the limitations of the current sample size, we find no significant redshift evolution of $n$ or $R_e$ at these early epochs.Comment: 23 pages, 17 figures, 2 tables, accepted for publication in The Astrophysical Journa

Demonstration of Adiabatic Variational Quantum Computing with a Superconducting Quantum Coprocessor

Adiabatic quantum computing enables the preparation of many-body ground states. This is key for applications in chemistry, materials science, and beyond. Realisation poses major experimental challenges: Direct analog implementation requires complex Hamiltonian engineering, while the digitised version needs deep quantum gate circuits. To bypass these obstacles, we suggest an adiabatic variational hybrid algorithm, which employs short quantum circuits and provides a systematic quantum adiabatic optimisation of the circuit parameters. The quantum adiabatic theorem promises not only the ground state but also that the excited eigenstates can be found. We report the first experimental demonstration that many-body eigenstates can be efficiently prepared by an adiabatic variational algorithm assisted with a multi-qubit superconducting coprocessor. We track the real-time evolution of the ground and exited states of transverse-field Ising spins with a fidelity up that can reach about 99%.Comment: 12 pages, 4 figure

iPLA2β Overexpression in Smooth Muscle Exacerbates Angiotensin II-Induced Hypertension and Vascular Remodeling

Calcium independent group VIA phospholipase A(2) (iPLA(2)β) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA(2)β affects vascular morphology and blood pressure is unknown. The current study addresses this question by evaluating the basal- and angiotensin II infusion-induced vascular remodeling and hypertension in smooth muscle specific iPLA(2)β transgenic (iPLA(2)β-Tg) mice.Blood pressure was monitored by radiotelemetry and vascular remodeling was assessed by morphologic analysis. We found that the angiotensin II-induced increase in diastolic pressure was significantly higher in iPLA(2)β-Tg than iPLA(2)β-Wt mice, whereas, the basal blood pressure was not significantly different. The media thickness and media∶lumen ratio of the mesenteric arteries were significantly increased in angiotensin II-infused iPLA(2)β-Tg mice. Analysis revealed no difference in vascular smooth muscle cell proliferation. In contrast, adenovirus-mediated iPLA(2)β overexpression in cultured vascular smooth muscle cells promoted angiotensin II-induced [(3)H]-leucine incorporation, indicating enhanced hypertrophy. Moreover, angiotensin II infusion-induced c-Jun phosphorylation in vascular smooth muscle cells overexpressing iPLA2β to higher levels, which was abolished by inhibition of 12/15 lipoxygenase. In addition, we found that angiotensin II up-regulated the endogenous iPLA(2)β protein in-vitro and in-vivo.The present study reports that iPLA(2)β up-regulation exacerbates angiotensin II-induced vascular smooth muscle cell hypertrophy, vascular remodeling and hypertension via the 12/15 lipoxygenase and c-Jun pathways

Spirulina (Arthrospira) industry in Inner Mongolia of China: current status and prospects

This paper outlines an investigation on current situation of Spirulina (Arthrospira) industry in Inner Mongolia, an internal region of China with temperate continental climate. More than 20 Spirulina plants have been established in Inner Mongolia since 2001, most of which are located at Wulan Town in the Ordos Plateau. By the end of 2009, the total annual production of Spirulina in the Ordos Plateau surpassed 700 t (dw), which account for ca. 80% of the total productivity of Inner Mongolia, and ca. 20% of China. Besides abundant solar radiation and enough freshwater favorable for Spirulina production, the three technical strategies contribute to the prosperity and success of Spirulina industry in the region: (1) reducing the cost or investment by overall advantages of rich local natural resources with low cost for Spirulina production, such as alkaline lakes, coal, electricity, and sandy land; (2) controlling the culture temperature and to avoid contamination by building plastic greenhouses on raceway ponds, (3) reducing investment by simplifying the construction of the ponds and the greenhouses. As the result, the growth period of Spirulina has been prolonged from about 120 to about 165 days, the cost of Spirulina has decreased by 25–30%, and the quality of products has been enhanced substantially. Inner Mongolia is expected to become the largest base for Spirulina production not only in China, but also in the world in the near future