Fire mediated patterns of population densities in mountain big sagebrush bird communities

We employed a chronosequence approach to evaluate patterns of bird abundance in relation to post-fire vegetation recovery in mountain big sagebrush (Artemisia tridentata vaseyana). We estimated population density for 12 species of birds within the perimeters of 4 fires that had undergone 8–20 years of vegetation recovery and on adjacent unburned areas in the northwestern Great Basin, USA. Six species showed negative responses to fire persisting up to 20 years. Two species showed positive responses with effects persisting for <20 years. Understory vegetation was similar between burned and unburned areas irrespective of recovery time, and shrub canopy cover was similar between burned and unburned sites after 20 years of recovery. Persistent reductions in bird densities lead us to conclude that shrub canopy cover alone is not a sufficient metric for predicting recovery of songbird abundances following disturbance in mountain big sagebrush. © 2013 The Wildlife Society.     

Neil3 and NEIL1 DNA Glycosylases Remove Oxidative Damages from Quadruplex DNA and Exhibit Preferences for Lesions in the Telomeric Sequence Context

The telomeric DNA of vertebrates consists of d(TTAGGG)_n tandem repeats, which can form quadruplex DNA structures in vitro and likely in vivo. Despite the fact that the G-rich telomeric DNA is susceptible to oxidation, few biochemical studies of base excision repair in telomeric DNA and quadruplex structures have been done. Here, we show that telomeric DNA containing thymine glycol (Tg), 8-oxo-7,8-dihydroguanine (8-oxoG), guanidinohydantoin (Gh), or spiroiminodihydantoin (Sp) can form quadruplex DNA structures in vitro. We have tested the base excision activities of five mammalian DNA glycosylases (NEIL1, NEIL2, mNeil3, NTH1, and OGG1) on these lesion-containing quadruplex substrates and found that only mNeil3 had excision activity on Tg in quadruplex DNA and that the glycosylase exhibited a strong preference for Tg in the telomeric sequence context. Although Sp and Gh in quadruplex DNA were good substrates for mNeil3 and NEIL1, none of the glycosylases had activity on quadruplex DNA containing 8-oxoG. In addition, NEIL1 but not mNeil3 showed enhanced glycosylase activity on Gh in the telomeric sequence context. These data suggest that one role for Neil3 and NEIL1 is to repair DNA base damages in telomeres in vivo and that Neil3 and Neil1 may function in quadruplex-mediated cellular events, such as gene regulation via removal of damaged bases from quadruplex DNA.     

Insecticidal Activity of Bacillus thuringiensis Cry1Bh1 against Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae) and Other Lepidopteran Pests

Bacillus thuringiensis is an important source of insect resistance traits in commercial crops. In an effort to prolong B. thuringiensis trait durability, insect resistance management programs often include combinations of insecticidal proteins that are not cross resistant or have demonstrable differences in their site of action as a means to mitigate the development of resistant insect populations. In this report, we describe the activity spectrum of a novel B. thuringiensis Cry protein, Cry1Bh1, against several lepidopteran pests, including laboratory-selected B. thuringiensis-resistant strains of Ostrinia nubilalis and Heliothis virescens and progeny of field-evolved B. thuringiensis-resistant strains of Plutella xylostella and Spodoptera frugiperda. Cry1Bh1 is active against susceptible and B. thuringiensis-resistant colonies of O. nubilalis, P. xylostella, and H. virescens in laboratory diet-based assays, implying a lack of cross-resistance in these insects. However, Cry1Bh1 is not active against susceptible or Cry1F-resistant S. frugiperda. Further, Cry1Bh1 does not compete with Cry1Fa or Cry1Ab for O. nubilalis midgut brush border membrane binding sites. Cry1Bh1-expressing corn, while not completely resistant to insect damage, provided significantly better leaf protection against Cry1Fa-resistant O. nubilalis than did Cry1Fa-expressing hybrid corn. The lack of cross-resistance with Cry1Ab and Cry1Fa along with independent membrane binding sites in O. nubilalis makes Cry1Bh1 a candidate to further optimize for in-plant resistance to this pest.     

Interactions between Fengycin and Model Bilayers Quantified by Coarse-Grained Molecular Dynamics

Bacteria, particularly of the genus Bacillus, produce a wide variety of antifungal compounds. They act by affecting the lipid bilayers of fungal membranes, causing curvature-induced strain and eventual permeabilization. One class of these, known as fengycins, has been commercialized for treating agricultural infections and shows some promise as a possible antifungal pharmaceutical. Understanding the mechanism by which fengycins damage lipid bilayers could prove useful to the future development of related antifungal treatments. In this work, we present multi-microsecond-long simulations of fengycin interacting with different lipid bilayer systems. We see fengycin aggregation and uncover a clear aggregation pattern that is partially influenced by bilayer composition. We also quantify some local bilayer perturbations caused by fengycin binding, including curvature of the lipid bilayer and local electrostatic-driven reorganization.     

A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains

All influenza viral neuraminidases (NA) of both type A and B viruses have only one universally conserved sequence located between amino acids 222–230. A monoclonal antibody against this region has been previously reported to provide broad inhibition against all nine subtypes of influenza A NA; yet its inhibitory effect against influenza B viral NA remained unknown. Here, we report that the monoclonal antibody provides a broad inhibition against various strains of influenza B viruses of both Victoria and Yamagata genetic lineage. Moreover, the growth and NA enzymatic activity of two drug resistant influenza B strains (E117D and D197E) are also inhibited by the antibody even though these two mutations are conformationally proximal to the universal epitope. Collectively, these data suggest that this unique, highly-conserved linear sequence in viral NA is exposed sufficiently to allow access by inhibitory antibody during the course of infection; it could represent a potential target for antiviral agents and vaccine-induced immune responses against diverse strains of type B influenza virus.     

Getting to the guts of the matter: The status and potential of ‘omics’ research of parasitic protists of the human gastrointestinal system

Parasitic protists are a major cause of diarrhoeal illnesses in humans globally. Collectively, enteric pathogens exceed all other forms of infectious disease, in terms of their estimated global prevalence and socioeconomic impact. They have a disproportionately high impact on children in impoverished communities, leading to acute (diarrhoea, vomiting, dehydration and death) and chronic disease (malabsorption, malnutrition, physical and cognitive stunting and predisposition to chronic, non-communicable disease) consequences. However, historically, investment in research and disease control measures has been disproportionately poor, leading to their current classification as neglected pathogens. A sound understanding of their biology is essential in underpinning detection, treatment and control efforts. One major tool in rapidly improving our knowledge of these parasites is the use of biological systems, including ‘omic’ technologies. In recent years, these tools have shown significant success when applied to enteric protists. This review summarises much of this knowledge and highlights the significant remaining knowledge gaps. A major focus of the present review was to provide a perspective on a way forward to address these gaps using advanced biotechnologies.     

Investigation of an F-18 oxytocin receptor selective ligand via PET imaging

The compound 1-(1-(2-(2-(2-fluoroethoxy)-4-(piperidin-4-yloxy)phenyl)acetyl)piperidin-4-yl)-3,4-dihydroquinolin-2(1H)-one (1) was synthesized and positively evaluated in vitro for high potency and selectivity with human oxytocin receptors. The positron emitting analogue, [F-18]1, was synthesized and investigated in vivo via PET imaging using rat and cynomolgus monkey models. PET imaging studies in female Sprague–Dawley rats suggested [F-18]1 reached the brain and accumulated in various regions of the brain, but washed out too rapidly for adequate quantification and localization. In vivo PET imaging studies in a male cynomolgus monkey suggested [F-18]1 had limited brain penetration while specific uptake of radioactivity significantly accumulated within the vasculature of the cerebral ventricles in areas representative of the choroid plexus.     

Stalking the wild Tetrahymena

We live on a microbial planet. Microorganisms dominate in terms of numbers of lineages, numbers of organisms, biomass and evolutionary innovations. Yet much remains to be learned about our microbial neighbours. We have gotten to know a few species that have been transformed into ‘laboratory rats’ (i.e. model organisms), but even here our understanding of the natural history of these lineages remains inadequate as there are few data from populations living in natural habitats. Zufall et al. (2013) move beyond this trend by providing insights into the natural history of Tetrahymena thermophila, a ciliate that has been used in many studies of cellular and molecular biology. Characterization of T. thermophila sampled from numerous ponds across this ciliate's range in Eastern North America reveals the following: (i) considerable differentiation among isolates, with the greatest diversity among lineages in New England, and (ii) a relatively small effective population size for this model ciliate. Such population data are fundamental for inferences about the origins of the numerous remarkable features of T. thermophila.     

A 2,6,9-hetero-trisubstituted purine inhibitor exhibits potent biological effects against multiple myeloma cells

A focused library of hetero-trisubstituted purines was developed for improving the cell penetrating and biological efficacy of a series of anti-Stat3 protein inhibitors. From this SAR study, lead agent 22e was identified as being a promising inhibitor of MM tumour cells (IC₅₀’s <5 μM). Surprisingly, biophysical and biochemical characterization proved that 22e was not a Stat3 inhibitor. Initial screening against the kinome, prompted by the purine scaffold’s history for targeting ATP binding pockets, suggests possible targeting of the JAK family kinases, as well for ABL1 (nonphosphorylated F317L) and AAK1.