Consensus of self-driven agents with avoidance of collisions

In recent years, many efforts have been addressed on collision avoidance of collectively moving agents. In this paper, we propose a modified version of the Vicsek model with adaptive speed, which can guarantee the absence of collisions. However, this strategy leads to an aggregated state with slowly moving agents. We therefore further introduce a certain repulsion, which results in both faster consensus and longer safe distance among agents, and thus provides a powerful mechanism for collective motions in biological and technological multi-agent systems.Comment: 8 figures, and 7 page

Integral membrane protein structure determination using pseudocontact shifts.

Obtaining enough experimental restraints can be a limiting factor in the NMR structure determination of larger proteins. This is particularly the case for large assemblies such as membrane proteins that have been solubilized in a membrane-mimicking environment. Whilst in such cases extensive deuteration strategies are regularly utilised with the aim to improve the spectral quality, these schemes often limit the number of NOEs obtainable, making complementary strategies highly beneficial for successful structure elucidation. Recently, lanthanide-induced pseudocontact shifts (PCSs) have been established as a structural tool for globular proteins. Here, we demonstrate that a PCS-based approach can be successfully applied for the structure determination of integral membrane proteins. Using the 7TM α-helical microbial receptor pSRII, we show that PCS-derived restraints from lanthanide binding tags attached to four different positions of the protein facilitate the backbone structure determination when combined with a limited set of NOEs. In contrast, the same set of NOEs fails to determine the correct 3D fold. The latter situation is frequently encountered in polytopical α-helical membrane proteins and a PCS approach is thus suitable even for this particularly challenging class of membrane proteins. The ease of measuring PCSs makes this an attractive route for structure determination of large membrane proteins in general.This work was supported by the Biotechnology and Biological Sciences Research Council BBSRC [BB/K01983X/1].This paper was originally published in the Journal of Bimolecular NMR (Crick DJ, Wang JX, Graham B, Swarbrick JD, Mott HR, Nietlispach D, Journal of Biomolecular NMR 2015, doi:10.1007/s10858-015-9899-6)

Mitochondrial GTP metabolism controls reproductive aging in C. elegans

Healthy mitochondria are critical for reproduction. During aging, both reproductive fitness and mitochondrial homeostasis decline. Mitochondrial metabolism and dynamics are key factors in supporting mitochondrial homeostasis. However, how they are coupled to control reproductive health remains unclear. We report that mitochondrial GTP (mtGTP) metabolism acts through mitochondrial dynamics factors to regulate reproductive aging. We discovered that germline-only inactivation of GTP-but not ATP-specific succinyl-CoA synthetase (SCS) promotes reproductive longevity in Caenorhabditis elegans. We further identified an age-associated increase in mitochondrial clustering surrounding oocyte nuclei, which is attenuated by GTP-specific SCS inactivation. Germline-only induction of mitochondrial fission factors sufficiently promotes mitochondrial dispersion and reproductive longevity. Moreover, we discovered that bacterial inputs affect mtGTP levels and dynamics factors to modulate reproductive aging. These results demonstrate the significance of mtGTP metabolism in regulating oocyte mitochondrial homeostasis and reproductive longevity and identify mitochondrial fission induction as an effective strategy to improve reproductive health

Zhi-Bai-Di-Huang-Wan, a classic Chinese medicinal formula in relieving menopausal symptoms: A multi-centre and controlled trial from UK and China

Background: To explore the effects of Zhi-Bai-Di-Huang-Wan (ZBDHW), a classic formula of Chinese  medicinal herbs in relieving menopausal symptoms in British and Chinese women.Methods and Materials: Between May 2011 and May 2013, 224 Chinese and British women were  divided into a ZBDHW group with 115 cases and a control group with 109 cases. The clinical menopausal  symptoms were assessed by the modified Kupperman Index Scale. The serum levels of follicle stimulating hormone (FSH) and estradiol (E2) were respectively detected before and after the treatment. Results: After 12 weeks of treatment, both groups’ Kupperman index scores markedly decreased  (P<0.05) and no significant difference existed between them (P>0.05). The serum levels of FSH did not change  significantly after the treatment (P>0.05) and no significant difference existed between them (P>0.05). The  serum levels of E2 significantly increased in both of the two groups (P<0.05) and it increased more in the comparison group (P<0.05). No side-effect of the treatment was reported in both of the two groups during the  period of the treatment.Conclusion: The classic Chinese medicinal formula, ZBDHW, showed promise in relieving menopausal  symptoms.Key words: Chinese medicinal herb; Zhi-Bai-Di-Huang-Wan (ZBDHW); menopausal symptom

Binding Mechanism of Metal⋅NTP Substrates and Stringent-Response Alarmones to Bacterial DnaG-Type Primases

SummaryPrimases are DNA-dependent RNA polymerases found in all cellular organisms. In bacteria, primer synthesis is carried out by DnaG, an essential enzyme that serves as a key component of DNA replication initiation, progression, and restart. How DnaG associates with nucleotide substrates and how certain naturally prevalent nucleotide analogs impair DnaG function are unknown. We have examined one of the earliest stages in primer synthesis and its control by solving crystal structures of the S. aureus DnaG catalytic core bound to metal ion cofactors and either individual nucleoside triphosphates or the nucleotidyl alarmones, pppGpp and ppGpp. These structures, together with both biochemical analyses and comparative studies of enzymes that use the same catalytic fold as DnaG, pinpoint the predominant nucleotide-binding site of DnaG and explain how the induction of the stringent response in bacteria interferes with primer synthesis

Genome wide screens in yeast to identify potential binding sites and target genes of DNA-binding proteins

Knowledge of all binding sites for transcriptional activators and repressors is essential for computationally aided identification of transcriptional networks. The techniques developed for defining the binding sites of transcription factors tend to be cumbersome and not adaptable to high throughput. We refined a versatile yeast strategy to rapidly and efficiently identify genomic targets of DNA-binding proteins. Yeast expressing a transcription factor is mated to yeast containing a library of genomic fragments cloned upstream of the reporter gene URA3. DNA fragments with target-binding sites are identified by growth of yeast clones in media lacking uracil. The experimental approach was validated with the tumor suppressor protein p53 and the forkhead protein FoxI1 using genomic libraries for zebrafish and mouse generated by shotgun cloning of short genomic fragments. Computational analysis of the genomic fragments recapitulated the published consensus-binding site for each protein. Identified fragments were mapped to identify the genomic context of each binding site. Our yeast screening strategy, combined with bioinformatics approaches, will allow both detailed and high-throughput characterization of transcription factors, scalable to the analysis of all putative DNA-binding proteins

The Acute Liver Injury in Mice Caused by Nano-Anatase TiO2

Although it is known that nano-TiO2or other nanoparticles can induce liver toxicities, the mechanisms and the molecular pathogenesis are still unclear. In this study, nano-anatase TiO2(5 nm) was injected into the abdominal cavity of ICR mice for consecutive 14 days, and the inflammatory responses of liver of mice was investigated. The results showed the obvious titanium accumulation in liver DNA, histopathological changes and hepatocytes apoptosis of mice liver, and the liver function damaged by higher doses nano-anatase TiO2. The real-time quantitative RT-PCR and ELISA analyses showed that nano-anatase TiO2can significantly alter the mRNA and protein expressions of several inflammatory cytokines, including nucleic factor-κB, macrophage migration inhibitory factor, tumor necrosis factor-α, interleukin-6, interleukin-1β, cross-reaction protein, interleukin-4, and interleukin-10. Our results also implied that the inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity