分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-11
摘要: Caste determination in the honeybee has been demonstrated to be decided by the royalactin in the royal jelly. And the differentially expressed coding genes in caste determination of the worker and queen larvae have also been well studied. Our experiments identified that lncRNAs are also differentially expressed in the caste determination of the larvae, which indicates that lncRNAs are involved in the caste determination. Detailed analysis showed that in the early development of the larvae, lncRNAs play a regulatory role in multicellular organismal development, nervous system development and regulation of transcription by affecting the expression and function of the nearby coding genes.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-05
摘要: Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses. IMPORTANCE Hantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and in multiple biological functions. NP is also the exclusiv
分类: 生物学 >> 生物物理学 提交时间: 2016-05-11
摘要: Enterovirus 71 (EV71), a primary pathogen of hand, foot, and mouth disease (HFMD), affects primarily infants and children. Currently, there are no effective drugs against HFMD. EV71 3C protease performs multiple tasks in the viral replication, which makes it an ideal antiviral target. We synthesized a small set of fluorogenic model peptides derived from cleavage sites of EV71 polyprotein and examined their efficiencies of cleavage by EV71 3C protease. The novel peptide P08 [(2-(N-methylamino)benzoyl) (NMA)-IEALFQGPPK(DNP)FR] was determined to be the most efficiently cleaved by EV71 3C protease, with a kinetic constant k(cat)/K-m of 11.8 +/- 0.82mM(-1) min(-1). Compared with literature reports, P08 gave significant improvement in the signal/background ratio, which makes it an attractive substrate for assay development. A Molecular dynamics simulation study elaborated the interactions between substrate P08 and EV71 3C protease. Arg39, which is located at the bottom of the S2 pocket of EV71 3C protease, may participate in the proteolysis process of substrates. With an aim to evaluate EV71 3C protease inhibitors, a reliable and robust biochemical assay with a Z' factor of 0.87 +/- 0.05 was developed. A novel compound (compound 3) (50% inhibitory concentration [IC50] = 1.89 +/- 0.25 mu M) was discovered using this assay, which effectively suppressed the proliferation of EV 71 (strain Fuyang) in rhabdomyosarcoma (RD) cells with a highly selective index (50% effective concentration [EC50] = 4.54 +/- 0.51 mu M; 50% cytotoxic concentration [CC50] > 100 mu M). This fast and efficient assay for lead discovery and optimization provides an ideal platform for anti-EV71 drug development targeting 3C protease.
分类: 物理学 >> 地球物理学、天文学和天体物理学 提交时间: 2024-01-09 合作期刊: 《Research in Astronomy and Astrophysics》
摘要: The extremely low frequency (f < 40 MHz) is a very important frequency band for modern radio astronomy observations. It is also a key frequency band for solar radio bursts, planetary radio bursts, fast radio bursts detected in the lunar space electromagnetic environment, and the Earth's middle and upper atmosphere with low dispersion values. In this frequency band, the solar stellar activity, the early state of the universe, and the radiation characteristics of the planetary magnetosphere and plasma layer can be explored. Since there are few observations with effective spatial resolution in the extremely low frequency, it is highly possible to discover unknown astronomical phenomena on such a band in the future. In conjunction with low frequency radio observation on the far side of the Moon, we initially set up a novel low-frequency radio array in the Qitai station of Xinjiang Astronomical Observatory deep in Tianshan Mountains, Xinjiang, China on 2021 August 23. The array covers an operating frequency range of 1 ∼ 90 MHz with a sensitivity of −78 dBm/125kHz, a dynamic range of 72 dB, and a typical gain value of 6 dBi, which can realize unattended all-weather observations. The two antennas due south of the Qitai Low-Frequency Radio Array were put into trial observations on 2021 May 28, and the very quiet electromagnetic environment of the station has been confirmed. So far, many solar radio bursts and other foreign signals have been detected. The results show that this novel low frequency radio array has the advantages of good performance, strong direction, and high antenna efficiency. It can play a unique role in Solar Cycle 25, and has a potential value in prospective collaborative observation between the Earth and space for extremely low frequency radio astronomy.
分类: 物理学 >> 核物理学 提交时间: 2023-06-18 合作期刊: 《Nuclear Science and Techniques》
摘要: A Neutron Time-Of-Flight (NTOF) spectrometer, based at the Heavy Ion Research Facility in Lanzhou (HIRFL) was developed for studies of neutron production of proton induced spallation reactions related to the ADS project. After the presentation of comparisons between calculated spallation neutron production double-differential cross sections and the available experimental data, a detailed description of the NTOF spectrometer is given. Test beam results show that the spectrometer works well and data analysis procedures are established. The comparisons of the test beam neutron spectra with those of GEANT4 simulations are presented.