Redox-Responsive Polymeric Nanogels as Efficient mRNA Delivery Vehicles in .

Efficient delivery of sensitive nucleic acid payloads, including mRNA, in remains challenging, especially with traditional, labor-intensive transgenesis methods. We addressed these challenges using polymeric nanogels (NGs) as an advanced platform for mRNA delivery in . These polymeric delivery vehicles can be engineered to suit desired applications owing to their chemical versatility, resulting from the ability to conjugate multiple functional groups onto the same backbone.

Dissecting the genetic landscape of GPCR signaling through phenotypic profiling in C. elegans.

G protein-coupled receptors (GPCRs) mediate responses to various extracellular and intracellular cues. However, the large number of GPCR genes and their substantial functional redundancy make it challenging to systematically dissect GPCR functions in vivo. Here, we employ a CRISPR/Cas9-based approach, disrupting 1654 GPCR-encoding genes in 284 strains and mutating 152 neuropeptide-encoding genes in 38 strains in C.

Visualizing the Replisome, Chromosome Breaks, and Replication Restart in Bacillus subtilis.

Research over the last two decades has revealed that bacterial genomes are highly organized and that bacteria have sophisticated mechanisms in place to ensure their correct replication and segregation into progeny cells. Here we discuss techniques that can be used with live bacterial cells to analyze DNA replisome dynamics, double-strand chromosome breaks, and restart of repaired replication forks.

Conformation control of the histidine kinase BceS of Bacillus subtilis by its cognate ABC-transporter facilitates need-based activation of antibiotic resistance.

Bacteria closely control gene expression to ensure optimal physiological responses to their environment. Such careful gene expression can minimize the fitness cost associated with antibiotic resistance. We previously described a novel regulatory logic in Bacillus subtilis enabling the cell to directly monitor its need for detoxification.

A widespread toxin-antitoxin system exploiting growth control via alarmone signaling.

Under stressful conditions, bacterial RelA-SpoT Homolog (RSH) enzymes synthesize the alarmone (p)ppGpp, a nucleotide second messenger. (p)ppGpp rewires bacterial transcription and metabolism to cope with stress, and, at high concentrations, inhibits the process of protein synthesis and bacterial growth to save and redirect resources until conditions improve. Single-domain small alarmone synthetases (SASs) are RSH family members that contain the (p)ppGpp synthesis (SYNTH) domain, but lack the hydrolysis (HD) domain and regulatory C-terminal domains of the long RSHs such as Rel, RelA, and SpoT.

The structural basis for dynamic DNA binding and bridging interactions which condense the bacterial centromere.

The ParB protein forms DNA bridging interactions around to condense DNA and earmark the bacterial chromosome for segregation. The molecular mechanism underlying the formation of these ParB networks is unclear. We show here that while the central DNA binding domain is essential for anchoring at , this interaction is not required for DNA condensation.

Crystal structure of NucB, a biofilm-degrading endonuclease.

Bacterial biofilms are a complex architecture of cells that grow on moist interfaces, and are held together by a molecular glue of extracellular proteins, sugars and nucleic acids. Biofilms are particularly problematic in human healthcare as they can coat medical implants and are thus a potential source of disease. The enzymatic dispersal of biofilms is increasingly being developed as a new strategy to treat this problem.

Probing Chromosome Dynamics in Bacillus subtilis.

Research over the last two decades has revealed that bacterial genomes are, in fact, highly organized. The goal of future research is to understand the molecular mechanisms underlying bacterial chromosome architecture and dynamics during the cell cycle. Here we discuss techniques that can be used with live cells to analyze chromosome structure and segregation in the gram-positive model organism Bacillus subtilis.

Condensin- and Replication-Mediated Bacterial Chromosome Folding and Origin Condensation Revealed by Hi-C and Super-resolution Imaging.

Chromosomes of a broad range of species, from bacteria to mammals, are structured by large topological domains whose precise functional roles and regulatory mechanisms remain elusive. Here, we combine super-resolution microscopies and chromosome-capture technologies to unravel the higher-order organization of the Bacillus subtilis chromosome and its dynamic rearrangements during the cell cycle. We decipher the fine 3D architecture of the origin domain, revealing folding motifs regulated by condensin-like complexes.

Multiple regulatory systems coordinate DNA replication with cell growth in Bacillus subtilis.

In many bacteria the rate of DNA replication is linked with cellular physiology to ensure that genome duplication is coordinated with growth. Nutrient-mediated growth rate control of DNA replication initiation has been appreciated for decades, however the mechanism(s) that connects these cell cycle activities has eluded understanding. In order to help address this fundamental question we have investigated regulation of DNA replication in the model organism Bacillus subtilis.

Ocular trauma injuries: a 1-year surveillance study in the University of Malaya Medical Centre, Malaysia. 2008.

Purpose: To describe the epidemiology of ocular injuries presenting to the University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia.

Design: Prospective analysis of all ocular trauma injuries presenting to the Department of Ophthalmology in UMMC from 1 January 2008 to 31 December 2008.

Participants: A total of 603 eyes of 546 patients were recruited for the study.

Inhibitor of p42/44 mitogen-activated protein kinase, but not p38 MAPK, attenuated antigen challenge of guinea pig airways in vitro.

Upon cross-linking of the high-affinity IgE receptors on mast cells, a family of mitogen-activated protein kinases (MAPKs) is activated. The present study examined the effects of p42/44 MAPK kinase inhibitor U0126 and p38 MAPK inhibitors SB220025 and PD169316 on ovalbumin (OVA)-induced anaphylactic contraction of isolated guinea pig bronchi and release of histamine and peptidoleukotrienes from lung fragments. Guinea pigs were actively sensitized by OVA.