Emerging therapies for severe asthma

Many patients with asthma have poorly controlled symptoms, and particularly for those with severe disease, there is a clear need for improved treatments. Two recent therapies licensed for use in asthma are omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, and bronchial thermoplasty, which involves the delivery of radio frequency energy to the airways to reduce airway smooth muscle mass. In addition, there are new therapies under development for asthma that have good potential to reach the clinic in the next five years. These include biological agents targeting pro-inflammatory cytokines such as interleukin-5 and interleukin-13, inhaled ultra long-acting β2-agonists and once daily inhaled corticosteroids. In addition, drugs that block components of the arachidonic acid pathway that targets neutrophilic asthma and CRTH2 receptor antagonists that inhibit the proinflammatory actions of prostaglandin D2 may become available. We review the recent progress made in developing viable therapies for severe asthma and briefly discuss the idea that development of novel therapies for asthma is likely to increasingly involve the assessment of genotypic and/or phenotypic factors

Replacement Of Pyrite Framboids By Magnetite In Limestone And Implications For Paleomagnetism

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62750/1/345611a0.pd

DNA sequencing and CRISPR-Cas9 gene editing for target validation in mammalian cells

Identification and validation of drug-resistant mutations can provide important insights into the mechanism of action of a compound. Here we demonstrate the feasibility of such an approach in mammalian cells using next-generation sequencing of drug-resistant clones and CRISPR-Cas9-mediated gene editing on two drug-target pairs, 6-thioguanine-HPRT1 and triptolide-ERCC3. We showed that disrupting functional HPRT1 allele or introducing ERCC3 point mutations by gene editing can confer drug resistance in cell

Chapter 5 Feeding and Food Processing in Antarctic Krill (Euphausia superba Dana)

Euphausia superba is exceptional among euphausiids for the large filtering surface of the feeding basket and its fine mesh size (2–3 μm), which remain into adulthood. This enables them to feed efficiently on nano- and microplankton, and to reach substantial growth rates with food concentrations as low as 0.5 μg Chlorophyll a L �1. Even though phytoplankton – in particular diatoms – are their staple food, protozoans and small copepods are ingested simultaneously and represent an important supplementary food source year-round. However, krill feeding behaviour is more complex than just filter-feeding in the water column, it includes raptorial capture of larger zooplankton, handling of ‘giant’ diatoms, scraping algae from beneath sea ice and lifting detritus from the seabed. High mobility and physiological robustness enable krill to explore three feeding grounds – the water column, the sea ice and the benthos. Variability in access and productivity of these feeding grounds leads to fundamental differences in krill overwintering across their habitats. Gut passage time, absorption efficiency and fecal pellet density vary with food concentration and nutritional needs. Therefore krill fecal pellets have a dual role; some promote the export of carbon and nutrients while others facilitate the recycling of material in the upper water column. Krill grazing can suppress phytoplankton blooms, but this tends to be a localised phenomenon where krill abundances are exceptionally high. Conversely, krill appear to have major conditioning effects due to nutrient supply (e.g. ammonium, iron), although their role in Southern Ocean biogeochemical cycles is only starting to be discovered