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B7-1 and B7-2 are homologous costimulatory ligands expressed on the surfaces of antigen-presenting cells. Their interactions with CD28/CTLA-4 receptors expressed on T cell surfaces are crucial for the proper regulation of T cell activity. B7-1 and B7-2 display distinct roles in immune regulation, although they are usually considered to have redundant functions. Here, we report the crystal structure of the receptor-binding (Ig V-type) domain of human B7-2 at 2.7-Å resolution. Structures of unliganded and liganded B7-1 and B7-2 suggest a physical-chemical basis for the observed functional similarities and differences between these two costimulatory ligands. Of particular note, whereas the majority of the residues mediating B7-1 dimerization are hydrophobic, the B7-2 dimer observed in the B7-2/CTLA-4 complex displays a very hydrophilic dimer interface. These differences provide a mechanism for preventing the formation of B7-1/B7-2 heterodimers. The divergence at the putative dimer interface is also consistent with the lower tendency of B7-2 to dimerize, as shown by the monomeric state of unliganded B7-2 both in solution and crystalline form, and may result in detailed differences in signaling mechanisms associated with B7-1 and B7-2. [ABSTRACT FROM AUTHOR]

Presents an experiment to examine the cell surface organization and signal transduction that regulates T-cell activity. Methods; Results; Conclusion that the direct observation of the network formed by the T-cell surface receptor CTLA-4 and the B7-2 ligand provides a model for the periodic organization of these molecules within the immunological synapse.

The article looks at a study which report two cryo-EM structures of Munc18-1 bound to cross-linked syntaxin-1 and synaptobrevin. It mentions structures allow visualization of how syntaxin-1 opens and reveal how part of the syntaxin-1 amino-terminal region can help nucleate interactions between the amino termini of the syntaxin-1 and synaptobrevin SNARE motifs. It also mentions SNARE complex assembly experiments, and fusion assays with reconstituted proteoliposomes.

The article discusses the challenges associated with insulin therapy for treating type 1 diabetes, including insulin fibrillation, which reduces therapeutic efficacy and can lead to insulin-derived amyloidosis. It explores the use of cryo-electron microscopy (cryo-EM) to characterize the structures of full-length insulin fibrils and provides insights into the mechanisms of insulin fibrillation.

The article presents a study which explores the inhibition of FAM46/TENT5 activity by BCCIP-alpha adopting a unique fold. It mentions the results of the study showcase the unique fold of BCCIPα underlies its interaction with and functional regulation of FAM46. It discusses the regulatory mechanisms of FAM46.

Plexins are semaphorin receptors that play essential roles in mammalian neuronal axon guidance and in many other important mammalian biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism and is modulated by small GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations, we showed that RND1 reinforces the plexin dimerization interface, whereas RhoD destabilizes it due to their differential interaction with the cell membrane. Upon binding plexin at the Rho-GTPase-binding domain (RBD), RND1 and RhoD interact differently with the inner leaflet of the cell membrane and exert opposite effects on the dimerization interface via an allosteric network involving the RBD, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively charged membrane interface. [ABSTRACT FROM AUTHOR]

Subcritical water extraction (SWE) is an environment-friendly and energy-efficient technology. However, the coupling of ultrasound and SWE for peptides production is not reported. In this study, we performed a two-step strategy to obtain optimal peptide extraction from Spirulina platensis. Firstly, by improving extraction kettle in the original SWE equipment, the extraction rate was increased from 10.30% to 40.20%; Secondly, by coupling SWE with ultrasound and subsequent process optimization, the extraction rate was elevated to 74% under the process conditions: temperature 153 °C, power 221 W, time 64 min. Notably, the extraction rate was 45.80% using traditional ultrasound + freeze-thaw method, and the longer time (at least 16 h) was required. Moreover, the molecular weight distribution indicated that the traditional ultrasound + freeze-thaw method primarily extracted proteins (>5000 Da), while the newly developed ultrasound + subcritical water method primarily extracted peptides (180–5000 Da). This provides a one-step method to obtain peptides without enzyme hydrolysis. [ABSTRACT FROM AUTHOR]

TFCP2L1 (transcription factor CP2-like 1) is a transcriptional regulator critical for maintaining mouse and human embryonic stem cell (ESC) pluripotency. However, the direct TFCP2L1 target genes are uncharacterized. Here, using gene overexpression, immunoblotting, quantitative real-time PCR, ChIP, and reporter gene assays, we show that TFCP2L1 primarily induces estrogen-related receptor β (Esrrb) expression that supports mouse ESC identity and also selectively enhances Kruppel-like factor 4 (Klf4) expression and thereby promotes human ESC self-renewal. Specifically, we found that in mouse ESCs, TFCP2L1 binds directly to the Esrrb gene promoter and regulates its transcription. Esrrb knockdown impaired Tfcp2l1's ability to induce interleukin 6 family cytokine (leukemia inhibitory factor)-independent ESC self-renewal and to reprogram epiblast stem cells to naïve pluripotency. Conversely, Esrrb overexpression blocked differentiation induced by Tfcp2l1 down-regulation. Moreover, we identified Klf4 as a direct TFCP2L1 target in human ESCs, bypassing the requirement for activin A and basic fibroblast growth factor in short-term human ESC self-renewal. Enforced Klf4 expression recapitulated the self-renewal-promoting effect of Tfcp2l1, whereas Klf4 knockdown eliminated these effects and caused loss of colony- forming capability. These findings indicate that TFCP2L1 functions differently in naïve and primed pluripotency, insights that may help elucidate the different states of pluripotency. [ABSTRACT FROM AUTHOR]

In this work, a simple, rapid and sensitive analytical method for the determination of rhodamine B in chili-containing foodstuffs is described. The dye is extracted from samples with methanol and analysed without further cleanup procedure by high-performance liquid chromatography (HPLC) coupled to fluorescence detection (FLD). The influence of matrix fluorescent compounds (capsaicin and dihydrocapsaicin) on the analysis was overcome by the optimisation of mobile-phase composition. The limit of determination (LOD) and limit of quantification (LOQ) were 3.7 and 10 μg/kg, respectively. Validation data show a good repeatability and within-lab reproducibility with relative standard deviations <10%. The overall recoveries are in the range of 98-103% in chili powder and in the range of 87-100% in chili oil depending on the concentration of rhodamine B in foodstuffs. This method is suitable for the routine analysis of rhodamine B due to its sensitivity, simplicity, reasonable time and cost. [ABSTRACT FROM AUTHOR]

4',5,7-Trihydroxy-8-methoxyflavone is an anticancer monomer component isolated from the traditional Chinese medicine Sorbaria sorbifolia . 4',5-Dihydroxy-7-piperazinemethoxy-8-methoxy flavonoids (DMF) with good solubility and anti-tumor effects was obtained by chemical modification in the early stage. This study explored the mechanism by which DMF regulates the mitochondrial apoptosis of human hepatoma cells through Bcl-2-associated transcription factor 1 (Bclaf1). DMF inhibited the proliferation of human hepatoma cells in a concentration- and time-dependent manner and induced cell mitochondrial apoptosis. The molecular docking and cell assay results demonstrated that DMF inhibits Bclaf1 expression by binding to its active site. Lentivirus transfection was used to construct cells with stable knockout and overexpression of Bclaf1, and a Hep3B xenograft model was constructed in nude mice. The mechanism by which DMF induced the mitochondrial apoptosis of human hepatoma cells through Bclaf1 was further verified in vitro and in vivo . These findings indicated that DMF induced human hepatoma cell mitochondrial apoptosis through Bclaf1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Cheng, Bai, Wang, Fu, Hao, Wang, Xuewu.)