Microbial Interactions in Biofilms: Impacts on Homeostasis and Pathogenesis

Microbes in nature or in the human body are predominantly associated with surfaces and living in biofilms. Species diversity, high cell density and close proximity of cells are typical of life in biofilms, where organisms interact with each other and develop complex interactions that can be either competitive or cooperative. Competition between species is a well-recognized ecological force to drive microbial metabolism, diversity and evolution. However, it was not until recently that microbial cooperative activities are also recognized to play important roles in microbial physiology and ecology. Importantly, these microbial interactions in biofilms profoundly affect their overall function, biomass, diversity and pathogenesis. It is now known that every human body contains a personalized microbiome that is essential to maintain host health. Remarkably, the indigenous species in most microbial communities often maintain a relatively stable and harmless relationship with the hosts despite regular exposure to minor environmental perturbations and host defence factors. Such stability or homeostasis results from a dynamic balance of microbial–microbial and microbial–host interactions. Under some circumstances, however, the homeostasis may breakdown, predisposing a site to diseases. The evidence has accumulated that such biofilm or community-based diseases can be prevented or treated not only by targeting putative pathogens, but also by interfering with the processes that drive breakdown of the homeostasis in biofilms

Precise rates in the law of logarithm for i.i.d. random variables

AbstractLet {X, Xn; n ≥ 1} be a sequence of i.i.d. random variables. Set Sn = X1 + X2 + … + Xn and Mn = maxk≤n |Sk|, n ≥ 1. By using the strong approximation method, we obtain that for any −1 < b ≤ 1, lim⁡ε↘0ε2b+2∑n=1∞(log⁡n)bnP(Mn≥εσnlog⁡n)=2E|N|(2b+2)b+1∑k=0∞(−1)k(2k+1)2b+2 if and only if Ex = 0 and Ex2 < ∞, which strengthen and extend the result of Gut and Spǎtaru [1], where N is the standard normal random variable. Furthermore, L2 convergence and a.s. convergence are also discussed

Structural and functional insights into a quorum-sensing signal peptide receptor, the ComD histidine protein kinase of streptococcus mutans

Quorum sensing activation by signal peptide pheromones (SP) in Gram-positive bacteria depends on a membrane-associated histidine kinase receptor, which senses the signal and triggers the signaling cascade for various cell density-dependent activities. However, relatively little is known of peptide pheromone-receptor interactions in these bacteria, largely because of technical challenges in working with membrane-associated proteins in these bacteria. Recently, we have described a genetic approach and several analysis methods to studying membrane topology and structure-function interaction of a quorum sensing pheromone receptor ComD in a Gram-positive bacterium Streptococcus mutans. Using these methods, we confirm that the membrane-spanning domain of the ComD protein forms six transmembrane segments and three extracellular loops, loopA, loopB and loopC. By mutational analyses of these three extracellular loops, we demonstrate that both loopC and loopB are required for signal recognition and quorum sensing activation, while loopA plays little role in signal detection. In particular, a deletion or substitution mutation of four residues NVIP within loopC abolishes signal recognition for quorum sensing activation. Consistent with these findings, the loopC and loopB mutants are completely or partially defective in bacteriocin production. We conclude that both loopC and loopB are required to form the signal peptide receptor and the residues NVIP of loopC are essential for signal recognition and quorum sensing activation in S. mutans

Clinical Features and Genetic Analysis of 20 Chinese Patients with X-Linked Hyper-IgM Syndrome

X-linked hyper-IgM syndrome (XHIGM) is one type of primary immunodeficiency diseases, resulting from defects in the CD40 ligand/CD40 signaling pathways. We retrospectively analyzed the clinical and molecular features of 20 Chinese patients diagnosed and followed up in hospitals affiliated to Shanghai Jiao Tong University School of Medicine from 1999 to 2013. The median onset age of these patients was 8.5 months (range: 20 days–21 months). Half of them had positive family histories, with a shorter diagnosis lag. The most common symptoms were recurrent sinopulmonary infections (18 patients, 90%), neutropenia (14 patients, 70%), oral ulcer (13 patients, 65%), and protracted diarrhea (13 patients, 65%). Six patients had BCGitis. Six patients received hematopoietic stem cell transplantations and four of them had immune reconstructions and clinical remissions. Eighteen unique mutations in CD40L gene were identified in these 20 patients from 19 unrelated families, with 12 novel mutations. We compared with reported mutation results and used bioinformatics software to predict the effects of mutations on the target protein. These mutations reflected the heterogeneity of CD40L gene and expanded our understanding of XHIGM

Magnetic Borophenes from an Evolutionary Search

A computational methodology based on ab initio evolutionary algorithms and spin-polarized density functional theory was developed to predict two-dimensional magnetic materials. Its application to a model system borophene reveals an unexpected rich magnetism and polymorphism. A metastable borophene with nonzero thickness is an antiferromagnetic semiconductor from first-principles calculations, and can be further tuned into a half-metal by finite electron doping. In this borophene, the buckling and coupling among three atomic layers are not only responsible for magnetism, but also result in an out-of-plane negative Poisson\u27s ratio under uniaxial tension, making it the first elemental material possessing auxetic and magnetic properties simultaneously