Molecular epidemiology of methicillin-resistant Staphylococcus aureus.

Subtyping methicillin- resistant Staphylococcus aureus (MRSA) isolates and tracking nosocomial infections have evolved from phenotypic to genotypic approaches; most laboratories now depend on pulsed-field gel electrophoresis (PFGE). We discuss the limitations of current image-based genotyping methods, including PFGE, and the advantages (including ease of entering data into a database) of using DNA sequence analysis to control MRSA infections in health-care facilities

Lithium suppression of tau induces brain iron accumulation and neurodegeneration

Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer’s disease), and may explain lithium-associated motor symptoms in susceptible patients

The Tempo and Mode of Gene Regulatory Programs During Bacterial Infection

Innate immune recognition of bacterial pathogens is a key determinant of the ensuing systemic response, and host or pathogen heterogeneity in this early interaction can impact the course of infection. To gain insight into host response heterogeneity, we investigate macrophage inflammatory dynamics using primary human macrophages infected with Group B Streptococcus. Transcriptomic analysis reveals discrete cellular states within responding macrophages, one of which consists of four sub-states, reflecting inflammatory activation. Infection with six additional bacterial species—Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, Yersinia pseudotuberculosis, Shigella flexneri, and Salmonella enterica—recapitulates these states, though at different frequencies. We show that modulating the duration of infection and the presence of a toxin impacts inflammatory trajectory dynamics. We provide evidence for this trajectory in infected macrophages in an in vivo model of Staphylococcus aureus infection. Our cell-state analysis defines a framework for understanding inflammatory activation dynamics in response to bacterial infection

Methicillin-Resistant Staphylococcus aureus USA300 Clone in Long-Term Care Facility

We performed a longitudinal analysis of 661 methicillin-resistant Staphylococcus aureus (MRSA) isolates obtained from patients in a long-term care facility. USA300 clone increased from 11.3% of all MRSA isolates in 2002 to 64.0% in 2006 (p<0.0001) and was mostly recovered from skin or skin structures (64.3% vs. 27.0% for non-USA300 MRSA; p<0.0001)

Sustainable building assessment of colonial shophouses after adaptive reuse in Kuala Lumpur

© 2017 by the authors. Kuala Lumpur, as a major capital city, has undergone a drastic transformation in the past ten years. Many heritage buildings have been sacrificed for urban renewal projects. Those located in the touristic heritage zones within Kuala Lumpur were being converted by their owners into hotels and cafés to meet current demands to sustain their incomes. This approach, however, creates several physical and environmental issues within the new adaptation. The aim of this study is to evaluate the building performance of heritage shophouses that were adapted into budget hotels. The research focuses on two case studies in a strategic and historical location of Jalan Sultan, Kuala Lumpur. At the initial stage, interviews and physical surveys were done to determine the context of this study. The authors of this research then used a triangulation method through indoor environmental condition assessment, measurements of indoor environmental conditions and occupant survey to determine the indoor building performance after the adaption. Results showed that adaptive reuse heritage buildings can perform and meet new indoor environmental requirements, but many sensitive design judgments need to be made before the adaptive reuse renovation. The research found that the use of natural light, natural ventilation, recycled materials and water efficiency have been neglected and thus, they should be prioritized and preserved to ensure a successful change of use. Conserving existing heritage buildings, while incorporating new usages with acceptable comfort, is in line with the principle of sustainability

Transcription-Replication Interactions Reveal Bacterial Genome Regulation

Organisms determine the transcription rates of thousands of genes through a few modes of regulation that recur across the genome1. In bacteria, the relationship between the regulatory architecture of a gene and its expression is well understood for individual model gene circuits2,3. However, a broader perspective of these dynamics at the genome scale is lacking, in part because bacterial transcriptomics has hitherto captured only a static snapshot of expression averaged across millions of cells4. As a result, the full diversity of gene expression dynamics and their relation to regulatory architecture remains unknown. Here we present a novel genome-wide classification of regulatory modes based on the transcriptional response of each gene to its own replication, which we term the transcription-replication interaction profile (TRIP). Analysing single-bacterium RNA-sequencing data, we found that the response to the universal perturbation of chromosomal replication integrates biological regulatory factors with biophysical molecular events on the chromosome to reveal the local regulatory context of a gene. Whereas the TRIPs of many genes conform to a gene dosage-dependent pattern, others diverge in distinct ways, and this is shaped by factors such as intra-operon position and repression state. By revealing the underlying mechanistic drivers of gene expression heterogeneity, this work provides a quantitative, biophysical framework for modelling replication-dependent expression dynamics