Elucidating the inhibition of peptidoglycan biosynthesis in Staphylococcus aureus by albocycline, a macrolactone isolated from Streptomyces maizeus.

Antibiotic resistance is a serious threat to global public health, and methicillin-resistant Staphylococcus aureus (MRSA) is a poignant example. The macrolactone natural product albocycline, derived from various Streptomyces strains, was recently identified as a promising antibiotic candidate for the treatment of both MRSA and vancomycin-resistant S. aureus (VRSA), which is another clinically relevant and antibiotic resistant strain.

Noncoding RNAs: Regulators of the Mammalian Transcription Machinery.

Transcription by RNA polymerase II (Pol II) is required to produce mRNAs and some noncoding RNAs (ncRNAs) within mammalian cells. This coordinated process is precisely regulated by multiple factors, including many recently discovered ncRNAs. In this perspective, we will discuss newly identified ncRNAs that facilitate DNA looping, regulate transcription factor binding, mediate promoter-proximal pausing of Pol II, and/or interact with Pol II to modulate transcription.

Infection by Herpes Simplex Virus 1 Causes Near-Complete Loss of RNA Polymerase II Occupancy on the Host Cell Genome.

Unlabelled: Lytic infection by herpes simplex virus 1 (HSV-1) triggers a change in many host cell programs as the virus strives to express its own genes and replicate. Part of this process is repression of host cell transcription by RNA polymerase II (Pol II), which also transcribes the viral genome. Here, we describe a global characterization of Pol II occupancy on the viral and host genomes in response to HSV-1 infection using chromatin immunoprecipitation followed by deep sequencing (ChIP-seq).

Small-molecule inhibitors of Staphylococcus aureus RnpA-mediated RNA turnover and tRNA processing.

New agents are urgently needed for the therapeutic treatment of Staphylococcus aureus infections. In that regard, S. aureus RNase RnpA may represent a promising novel dual-function antimicrobial target that participates in two essential cellular processes, RNA degradation and tRNA maturation.

LpxC inhibitors as new antibacterial agents and tools for studying regulation of lipid A biosynthesis in Gram-negative pathogens.

Unlabelled: The problem of multidrug resistance in serious Gram-negative bacterial pathogens has escalated so severely that new cellular targets and pathways need to be exploited to avoid many of the preexisting antibiotic resistance mechanisms that are rapidly disseminating to new strains. The discovery of small-molecule inhibitors of LpxC, the enzyme responsible for the first committed step in the biosynthesis of lipid A, represents a clinically unprecedented strategy to specifically act against Gram-negative organisms such as Pseudomonas aeruginosa and members of the Enterobacteriaceae. In this report, we describe the microbiological characterization of LpxC-4, a recently disclosed inhibitor of this bacterial target, and demonstrate that its spectrum of activity extends to several of the pathogenic species that are most threatening to human health today.

Drug-eluting cements for hard tissue repair: a comparative study using vancomycin and RNPA1000 to inhibit growth of Staphylococcus aureus.

Bone cement used in orthopaedic applications can become colonized with bacterial biofilms, resulting in severe medical complications. Consequently, bone cements are often loaded with antibiotics in an effort to prevent bacterial colonization. However, current formulations may not release antibiotics into the environment at sufficient and sustained concentrations required to impede bacterial growth or may be incompatible with antibiotics that are effective against the colonizing organism.

RNA decay: a novel therapeutic target in bacteria.

The need for novel antibiotics is greater now than perhaps any time since the pre-antibiotic era. Indeed, the recent collapse of most pharmaceutical antibacterial groups, combined with the emergence of hypervirulent and pan-antibiotic-resistant bacteria have, in effect, created a 'perfect storm' that has severely compromised infection treatment options and led to dramatic increases in the incidence and severity of bacterial infections. To put simply, it is imperative that we develop new classes of antibiotics for the therapeutic intervention of bacterial infections.

Inflammation mediates varying effects in neurogenesis: relevance to the pathogenesis of brain injury and neurodegenerative disorders.

Brain inflammation is a complex cellular and molecular response to stress, injury or infection of the CNS in attempt to defend against insults, clear dead and damaged neurons and return the CNS to a normal state. Inflammation in the CNS is driven by the activation of resident microglia, astrocytes and infiltrating peripheral macrophages, which release a plethora of anti- and pro-inflammatory cytokines, chemokines, neurotransmitters and reactive oxygen species. This inflammatory state inadvertently causes further bystander damage to neurons and produces both detrimental and favorable conditions for neurogenesis.

Cadmium exposures in fathead minnows: are there sex-specific differences in mortality, reproductive success, and Cd accumulation?

The primary goal of this experiment was to determine whether cadmium (Cd) exposure has sex-specific effects on the reproductive success of fathead minnows as measured by time to first spawn, spawning frequency, clutch size, fecundity, fertilization success, hatching success, and offspring mortality to 2 d post hatch. Prior to breeding, minnows were either exposed to 50 microg/L Cd or sham exposed for 21 d. After exposures, minnows were paired (male x female) into one of four breeding groups-control x control (C x C), control x exposed (C x E), exposed x control (E x C) or exposed x exposed (E x E).