分类: 生物学 >> 生物物理学 提交时间: 2016-05-11
摘要: Emerging evidence indicates that the neuronal guidance molecule SLIT plays a role in tumor suppression, as SLIT-encoding genes are inactivated in several types of cancer, including lung cancer; however, it is not clear how SLIT functions in lung cancer. Here, our data show that SLIT inhibits cancer cell migration by activating RhoA and that myosin 9b (Myo9b) is a ROBO-interacting protein that suppresses RhoA activity in lung cancer cells. Structural analyses revealed that the RhoGAP domain of Myo9b contains a unique patch that specifically recognizes RhoA. We also determined that the ROBO Intracellular domain interacts with the Myo9b RhoGAP domain and inhibits its activity; therefore, SLIT-dependent activation of RhoA is mediated by ROBO inhibition of Myo9b. In a murine model, compared with control lung cancer cells, SLIT-expressing cells had a decreased capacity for tumor formation and lung metastasis. Evaluation of human lung cancer and adjacent nontumor tissues revealed that Myo9b is upregulated in the cancer tissue. Moreover, elevated Myo9b expression was associated with lung cancer progression and poor prognosis. Together, our data identify Myo9b as a key player in lung cancer and as a ROBO-interacting protein in what is, to the best of our knowledge, a newly defined SLIT/ROBO/Myo9b/RhoA signaling pathway that restricts lung cancer progression and metastasis. Additionally, our work suggests that targeting the SLIT/ROBO/Myo9b/RhoA pathway has potential as a diagnostic and therapeutic strategy for lung cancer.
分类: 物理学 >> 核物理学 提交时间: 2023-10-23
摘要: The pseudo-rapidity distributions of the charged particles produced in the asymmetric collision systems p+Al, p+Au and $^3$He+Au at $ sqrt{s_{NN}} = 200$ GeV are evaluated in the framework of a fireball model with Tsallis thermodynamics. The fireball model assumes that the experimentally measured particles are produced by fireballs following the Tsallis distribution and it can effectively describe the experimental data. Our results as well as previous results for d+Au collisions at $ sqrt{s_{NN}} = 200$ GeV and p+Pb collisions at $ sqrt{s_{NN}} = 5.02$ TeV validate that the fireball model based on Tsallis thermodynamics can provide a universal framework for pseudo-rapidity distribution of the charged particles produced in asymmetric collision systems. We predict the centrality dependence of the total charged particle multiplicity in the p+Al, p+Au and $^3$He+Au collisions. Additionally, the dependences of the fireball model parameters ($y_{0a}$, $y_{0A}$, $ sigma_{a}$ and $ sigma_{A}$) on the centrality and system size are studied.
分类: 物理学 >> 核物理学 提交时间: 2024-01-18
摘要: Very high-energy electrons (VHEE) are potential candidates for FLASH radiotherapy for deep-seated tumors. We proposed a compact VHEE facility based on an X-band high-gradient high-power technique. In this study, we investigated and realized the first X-band backward traveling wave (BTW) accelerating structure as the buncher for a VHEE facility. A method for calculating the parameters of single cells from the field distribution was introduced to simplify the design of the BTW structure. Time-domain circuit equations were applied to calculate the transient beam parameters of the buncher in the unsteady state. A prototype of the BTW structure with a thermionic-cathode diode electron gun was designed, fabricated, and tested at high power at the Tsinghua X-band High-power test stand. The structure successfully operated with 5-MW microwave pulses from the pulse compressor and outputted electron bunches with an energy of 8 MeV and a pulsed current of 108 mA.
提交时间: 2017-05-02
摘要: Laterally coupled indium-zinc-oxide electric-double-layer [EDL] transistors gated by solution-processed sodium alginate electrolyte films are self-assembled on glass substrates. Due to the strong EDL effect, a low-operation voltage of 1.5 V, a high-curren
提交时间: 2017-05-02
摘要: Indium-zinc-oxide [IZO]-based electric double layer [EDL] transistors gated by solution-processed chitosan electrolyte films are fabricated on glass substrates and used for mimicking synaptic plasticity. The conductance of the self-assembled IZO channel t
分类: 生物学 >> 生物物理学 >> 肿瘤学 提交时间: 2016-05-12
摘要: Originally discovered in neuronal guidance, the Slit-Robo pathway is emerging as an important player in human cancers. However, its involvement and mechanism in colorectal cancer (CRC) remains to be elucidated. Here, we report that Slit2 expression is reduced in CRC tissues compared with adjacent noncancerous tissues. Extensive promoter hypermethylation of the Slit2 gene has been observed in CRC cells, which provides a mechanistic explanation for the Slit2 downregulation in CRC. Functional studies showed that Slit2 inhibits CRC cell migration in a Robo-dependent manner. Robo-interacting ubiquitin-specific protease 33 (USP33) is required for the inhibitory function of Slit2 on CRC cell migration by deubiquitinating and stabilizing Robo1. USP33 expression is downregulated in CRC samples, and reduced USP33 mRNA levels are correlated with increased tumor grade, lymph node metastasis and poor patient survival. Taken together, our data reveal USP33 as a previously unknown tumor-suppressing gene for CRC by mediating the inhibitory function of Slit-Robo signaling on CRC cell migration. Our work suggests the potential value of USP33 as an independent prognostic marker of CRC.
分类: 生物学 >> 生物物理学 >> 基因表达调控与表观遗传学 提交时间: 2016-05-11
摘要: FUS-proteinopathies, a group of heterogeneous disorders including ALS-FUS and FTLD-FUS, are characterized by the formation of inclusion bodies containing the nuclear protein FUS in the affected patients. However, the underlying molecular and cellular defects remain unclear. Here we provide evidence for mitochondrial localization of FUS and its induction of mitochondrial damage. Remarkably, FTLD-FUS brain samples show increased FUS expression and mitochondrial defects. Biochemical and genetic data demonstrate that FUS interacts with a mitochondrial chaperonin, HSP60, and that FUS translocation to mitochondria is, at least in part, mediated by HSP60. Down-regulating HSP60 reduces mitochondrially localized FUS and partially rescues mitochondrial defects and neurodegenerative phenotypes caused by FUS expression in transgenic flies. This is the first report of direct mitochondrial targeting by a nuclear protein associated with neurodegeneration, suggesting that mitochondrial impairment may represent a critical event in different forms of FUS-proteinopathies and a common pathological feature for both ALS-FUS and FTLD-FUS. Our study offers a potential explanation for the highly heterogeneous nature and complex genetic presentation of different forms of FUS-proteinopathies. Our data also suggest that mitochondrial damage may be a target in future development of diagnostic and therapeutic tools for FUS-proteinopathies, a group of devastating neurodegenerative diseases.
提交时间: 2017-05-02
摘要: Proton-conducting graphene oxide electrolyte films with very high electric-double-layer capacitance are used as the gate dielectrics for oxide-based neuron transistor fabrication. Paired-pulse facilitation, dendritic integration, and orientation tuning ar