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- Lu, Lu, 1984-, et al.
(författare)
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MEPicides : α,β-Unsaturated Fosmidomycin N-acyl Analogsas inhibitors that selectively target DXR from Plasmodium falciparum, the deadliest causative parasite of human Malaria
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Fosmidomycin and FR-9000098 have been confirmed to show parasiticidal activity against Plasmodium falciparum, targeting DXR involved in the MEP pathway. We designed a construct of PfDXR that has successfully been overexpressed in E. coli BL21(DE3) C43, and purified by IMAC and SEC, with the final yield of 1.2 mg/ 8 L culture. PfDXR was concentrated to 20 mg/ml, and co-crystallized with previously tested inhibitors in the FR-9000098 scaffold in the presence of Mn2+. Three FR-9000098 analogues with double-bonded Ca-Cband/or a phenyl ring with various lengths to N1, showed inhibitory activities with IC50s roughly 50 nM. Three crystals were in triclinic P1space group, with similar dimensions in the unit cell (51Å, 56Å, 86Å, 103°, 103°, 101°). All four complex structures have been crystallographically determined at resolutions in the range 1.86 Å, 2.45 Å, 2.13Å, 2.05 Å. Given the high similarity in structures, the initial phases were determined by rigid body refinement with search model PfDXR-FN3 complex, followed by restrained refinement in refmac5. Subsequently, the ligands and surrounding amino acid residues were manually rebuilt with theqdstools in O. the Ca-Cbbonds of the three ligands were altered from a single to double bond based on the structure of FR9000098. In addition, two ligands were extended at the Cdwith a phenyl group, and with the benzyl group connected by two carbons. N-terminal NADPH binding domains from four complexes undergo minor rigid body movement, and more details of conformational changes in the flap region are discussed.
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- Yang, Kunlong, et al.
(författare)
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Merged acquisition-processing system based on a photoelectrical neural network
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In brain-inspired computing, one of the most attractive fields of study currently, new issues are emerging despite its booming development. From the systems perspective, the performances of the existing systems are hindered by inadequate hardware support, particularly the unavoidable data acquisition and transmission between the sensor module and the data processing module. In this work, we break this bottleneck by proposing a photoelectrical neural network (PNN) that merges the new sensing function into the processing network. Benefitting from its high-parallel structure and minimized hardware consumption, a novel merged acquisition-processing (MAP) system with very high efficiency and very low cost has been developed. As the key component of the MAP system, a dual-mode photoelectrical synapse (DMPS) is carefully designed and developed. It has advantages in terms of both function and performance as compared to the existing artificial synapses, which make it the best candidate for the proposed system. This work will initiate an entirely new field of unconventional neuromorphic systems.
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- Ålund, Murielle, et al.
(författare)
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Reproductive -omics of a wild avian speciation model unveils candidate genes for gamete interaction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The complex nature of interspecific interactions contributing to reproductive isolation means that we still know little about their molecular basis. Male reproductive traits are notorious for their fast evolution at the phenotypic and genotypic level, and divergence in components of the ejaculate can lead to incompatibilities between closely related species. Making use of recent advances of molecular tools and the extensive knowledge on the biology and ecology of young sister species, here the pied (Ficedula hypoleuca) and collared flycatcher (F. albicollis), allows the identification of candidate phenotypes and the underlying genotypes maintaining species boundaries. Pied flycatcher females can avoid costly production of sterile hybrids when mated to collared flycatchers by cryptically favouring conspecific sperm. Here, we describe the testes transcriptome and sperm proteome of both species, confirm the complexity of avian sperm development and functions and identify several candidate genes for interactions between sperm and the female reproductive tract, using multiple independent measures of divergence between the species. We show that divergence at the transcriptional and translational levels can potentially lead to the evolution of reproductive incompatibilities despite low levels of sequence divergence, and suggest that integrating several -omics techniques with knowledge of the biology of naturally hybridizing species will greatly improve our understanding of the molecular basis of speciation in the near future.
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