A hyper-mutant of the unusual σ70-Pr promoter bypasses synergistic ppGpp/DksA co-stimulation

The activities of promoters can be temporally and conditionally regulated by mechanisms other than classical DNA-binding repressors and activators. One example is the inherently weak σ70-dependent Pr promoter that ultimately controls catabolism of phenolic compounds. The activity of Pr is up-regulated through the joint action of ppGpp and DksA that enhance the performance of RNA polymerase at this promoter. Here, we report a mutagenesis analysis that revealed substantial differences between Pr and other ppGpp/DksA co-stimulated promoters. In vitro transcription and RNA polymerase binding assays show that it is the T at the −11 position of the extremely suboptimal −10 element of Pr that underlies both poor binding of σ70-RNAP and a slow rate of open complex formation—the process that is accelerated by ppGpp and DksA. Our findings support the idea that collaborative action of ppGpp and DksA lowers the rate-limiting transition energy required for conversion between intermediates on the road to open complex formation

Ebola Virion Attachment and Entry into Human Macrophages Profoundly Effects Early Cellular Gene Expression

Zaire ebolavirus (ZEBOV) infections are associated with high lethality in primates. ZEBOV primarily targets mononuclear phagocytes, which are activated upon infection and secrete mediators believed to trigger initial stages of pathogenesis. The characterization of the responses of target cells to ZEBOV infection may therefore not only further understanding of pathogenesis but also suggest possible points of therapeutic intervention. Gene expression profiles of primary human macrophages exposed to ZEBOV were determined using DNA microarrays and quantitative PCR to gain insight into the cellular response immediately after cell entry. Significant changes in mRNA concentrations encoding for 88 cellular proteins were observed. Most of these proteins have not yet been implicated in ZEBOV infection. Some, however, are inflammatory mediators known to be elevated during the acute phase of disease in the blood of ZEBOV-infected humans. Interestingly, the cellular response occurred within the first hour of Ebola virion exposure, i.e. prior to virus gene expression. This observation supports the hypothesis that virion binding or entry mediated by the spike glycoprotein (GP1,2) is the primary stimulus for an initial response. Indeed, ZEBOV virions, LPS, and virus-like particles consisting of only the ZEBOV matrix protein VP40 and GP1,2 (VLPVP40-GP) triggered comparable responses in macrophages, including pro-inflammatory and pro-apoptotic signals. In contrast, VLPVP40 (particles lacking GP1,2) caused an aberrant response. This suggests that GP1,2 binding to macrophages plays an important role in the immediate cellular response

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Pain Neuroscience Education: State of the Art and Application in Pediatrics

Chronic pain is a widespread problem in the field of pediatrics. Many interventions to ameliorate pain-related dysfunction have a biobehavioral focus. As treatments for chronic pain (e.g., increased movement) often stand in stark contrast to treatments for an acute injury (e.g., rest), providing a solid rationale for treatment is necessary to gain patient and parent buy-in. Most pain treatment interventions incorporate psychoeducation, or pain neuroscience education (PNE), as an essential component, and in some cases, as a stand-alone approach. The current topical review focuses on the state of pain neuroscience education and its application to pediatric chronic pain. As very little research has examined pain neuroscience education in pediatrics, we aim to describe this emerging area and catalyze further work on this important topic. As the present literature has generally focused on adults with chronic pain, pain neuroscience education merits further attention in the realm of pediatric pain in order to be tailored and implemented in this population

COMPOUND HYDRO-KINETIC SUBMERSIBLE TURBINE

This project investigates the concept of a compound hydrokinetic turbine, a device that can extract energy from flowing fluids such as ocean currents, channels or rivers. The compound turbine operates without delivering a reaction force to its supporting structure or mooring. Conceptually the device could also operate in air and thus be an alternative configuration to the conventional wind turbine. Also reviewed is availability of energy from ocean currents, the performance of airfoils developed for wind turbine use in water rather than air and various systems for mooring hydrokinetic devices in deep water

SLATE Ambulance: Designing an Interior Storage System for Improved Sanitation

The purpose of this Major Qualifying Project is to design a sanitary medical equipment storage system that protects contents from contaminants such as pathogens, waste, organisms, and fumes in the patient compartment. The team evaluates the storage and workspace environment of an ambulance patient compartment and identifies the challenges to protect ambulance occupants and accessories from contaminants. A list containing the quantity, weight and size of all tools, pharmaceuticals, and consumables in the patient compartment is compiled. The design incorporates a high density polyethylene outer surface, which proves easier to clean and disinfect than the current materials used. The proposed vending machine provides an opportunity to protect, clean, and reduce contamination effectively

Recent measles outbreaks in the United States: A look at the causes and responses

As measles cases continue to rise in the United States and elsewhere, public health officials, health care providers and elected officials alike are facing critical questions of how to protect the health of the public from current and future vaccine preventable disease outbreaks while still preserving the religious and personal autonomy of the populations they serve. As measles cases are being examined and carefully managed, public health officials are also tasked with revisiting vaccination policies and agendas to determine the best evidence-based interventions to control this epidemic. To determine the best course of action for the public's interest, research and current literature must be examined to protect and promote the health and wellbeing of those currently affected by the measles outbreak and those yet to be exposed. </jats:p