Structure and stability of pertussis toxin studied by in situ atomic force microscopy

AbstractPertussis toxin, both complete and the B-oligomer, were imaged by atomic force miroscopy (AFM), using specimens prepared by simple surface adsorption on mica without further manipulation. The spatial arrangement of the subunits of the B-oligomer was clearly resolved, representing the first protein quaternary structure obtained by AFM in situ. The results suggest that the B-oligomer is a flat pentamer with the two large subunits located next to each other, and the catalytic A-subunit situated at the center above. We found that the B-pentamer was structurally stable for temperatures up to 60°C and within the pH range of 4.5–9.5. It is also demonstrated that the AFM was capable of resolving features down to 0.5 nm on the B-oligomers, indicating its great potential for structural determination

Learning Granularity-Unified Representations for Text-to-Image Person Re-identification

Text-to-image person re-identification (ReID) aims to search for pedestrian images of an interested identity via textual descriptions. It is challenging due to both rich intra-modal variations and significant inter-modal gaps. Existing works usually ignore the difference in feature granularity between the two modalities, i.e., the visual features are usually fine-grained while textual features are coarse, which is mainly responsible for the large inter-modal gaps. In this paper, we propose an end-to-end framework based on transformers to learn granularity-unified representations for both modalities, denoted as LGUR. LGUR framework contains two modules: a Dictionary-based Granularity Alignment (DGA) module and a Prototype-based Granularity Unification (PGU) module. In DGA, in order to align the granularities of two modalities, we introduce a Multi-modality Shared Dictionary (MSD) to reconstruct both visual and textual features. Besides, DGA has two important factors, i.e., the cross-modality guidance and the foreground-centric reconstruction, to facilitate the optimization of MSD. In PGU, we adopt a set of shared and learnable prototypes as the queries to extract diverse and semantically aligned features for both modalities in the granularity-unified feature space, which further promotes the ReID performance. Comprehensive experiments show that our LGUR consistently outperforms state-of-the-arts by large margins on both CUHK-PEDES and ICFG-PEDES datasets. Code will be released at https://github.com/ZhiyinShao-H/LGUR.Comment: Accepted by ACM Multimedia 202

Epigenetic Profiling of H3K4Me3 Reveals Herbal Medicine Jinfukang-Induced Epigenetic Alteration Is Involved in Anti-Lung Cancer Activity

Traditional Chinese medicine Jinfukang (JFK) has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P<0.05). Gene Ontology analysis indicates that these genes are involved in tumor-related pathways, including pathway in cancer, basal cell carcinoma, apoptosis, induction of programmed cell death, regulation of transcription (DNA-templated), intracellular signal transduction, and regulation of peptidase activity. In particular, we found that the levels of H3K4Me3 at the promoters of SUSD2, CCND2, BCL2A1, and TMEM158 are significantly altered in A549, NCI-H1975, NCI-H1650, and NCI-H2228 cells, when treated with JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci

Responses of photosynthetic characteristics of oat flag leaf and spike to drought stress

Raising crops production via improving photosynthesis has always been focused. Recently excavating and increasing the photosynthetic capacity of non-leaf organs becomes an important approach to crops yield increase. Here we studied the photosynthetic characteristics of the flag leaf and the non-leaf organs including the sheath, the glume and the lemma under greenhouse. The relative water content (RWC), the stomatal characteristics, the photosynthetic pigment contents, the enzyme activities in C3 and C4 pathway and the malate content of the flag leaf and the non-leaf organs on 7, 14, 21, and 28 days after anthesis (denoted by 7DAA, 14DAA, 21DAA, and 28DAA) were determined under well-watered (CK) and water-stressed (D) treatments. Drought stress significantly reduced the RWC of the flag leaf and the non-leaf organs, while the variation of RWC in the glume and the lemma was lower than in the flag leaf. The chlorophyll a content, the chlorophyll b content, the total chlorophyll content and the xanthophyll content in the flag leaf were significantly decreased under D. However, drought stress significantly increased the photosynthetic pigment contents in the glume at the late stage (21DAA and 28DAA). In addition, the induced activities of PEPC, NADP-MDH, NADP-ME, NAD-ME, and PPDK in non-leaf organs under drought stress suggested that the C4 photosynthetic pathway in non-leaf organs compensated the limited C3 photosynthesis in the flag leaf. Non-leaf organs, in particular the glume, showed the crucial function in maintaining the stable photosynthetic performance of oat

IgM, Fc mu Rs, and malarial immune evasion

IgM is an ancestral Ab class found in all jawed vertebrates, from sharks to mammals. This ancient ancestry is shared by malaria parasites (genus Plasmodium) that infect all classes of terrestrial vertebrates with whom they coevolved. IgM, the least studied and most enigmatic of the vertebrate Igs, was recently shown to form an intimate relationship with the malaria parasite Plasmodium falciparum. In this article, we discuss how this association might have come about, building on the recently determined structure of the human IgM pentamer, and how this interaction could affect parasite survival, particularly in light of the just-discovered Fc mu R localized to B and T cell surfaces. Because this parasite may exploit an interaction with IgM to limit immune detection, as well as to manipulate the immune response when detected, a better understanding of this association may prove critical for the development of improved vaccines or vaccination strategies

Characterization of DNA Methylation Associated Gene Regulatory Networks During Stomach Cancer Progression

DNA methylation plays a critical role in tumorigenesis through regulating oncogene activation and tumor suppressor gene silencing. Although extensively analyzed, the implication of DNA methylation in gene regulatory network is less characterized. To address this issue, in this study we performed an integrative analysis on the alteration of DNA methylation patterns and the dynamics of gene regulatory network topology across distinct stages of stomach cancer. We found the global DNA methylation patterns in different stages are generally conserved, whereas some significantly differentially methylated genes were exclusively observed in the early stage of stomach cancer. Integrative analysis of DNA methylation and network topology alteration yielded several genes which have been reported to be involved in the progression of stomach cancer, such as IGF2, ERBB2, GSTP1, MYH11, TMEM59, and SST. Finally, we demonstrated that inhibition of SST promotes cell proliferation, suggesting that DNA methylation-associated SST suppression possibly contributes to the gastric cancer progression. Taken together, our study suggests the DNA methylation-associated regulatory network analysis could be used for identifying cancer-related genes. This strategy can facilitate the understanding of gene regulatory network in cancer biology and provide a new insight into the study of DNA methylation at system level

Self-assembling subnanometer pores with unusual mass-transport properties

A long-standing aim in molecular self-assembly is the development of synthetic nanopores capable of mimicking the mass-transport characteristics of biological channels and pores. Here we report a strategy for enforcing the nanotubular assembly of rigid macrocycles in both the solid state and solution based on the interplay of multiple hydrogen-bonding and aromatic π − π stacking interactions. The resultant nanotubes have modifiable surfaces and inner pores of a uniform diameter defined by the constituent macrocycles. The self-assembling hydrophobic nanopores can mediate not only highly selective transmembrane ion transport, unprecedented for a synthetic nanopore, but also highly efficient transmembrane water permeability. These results establish a solid foundation for developing synthetically accessible, robust nanostructured systems with broad applications such as reconstituted mimicry of defined functions solely achieved by biological nanostructures, molecular sensing, and the fabrication of porous materials required for water purification and molecular separations