On the use of adenovirus dodecahedron as a carrier for glycoconjugate vaccines

Glycoconjugate Journal - Virus-Like Particles (VLPs) have been used as immunogenic molecules in numerous recombinant vaccines. VLPs can also serve as vaccine platform to exogenous antigens, usually...     

Longitudinal Analysis of CCR5 and CXCR4 Usage in a Cohort of Antiretroviral Therapy-Na?ve Subjects with Progressive HIV-1 Subtype C Infection

HIV-1 subtype C (C-HIV) is responsible for most HIV-1 cases worldwide. Although the pathogenesis of C-HIV is thought to predominantly involve CCR5-restricted (R5) strains, we do not have a firm understanding of how frequently CXCR4-using (X4 and R5X4) variants emerge in subjects with progressive C-HIV infection. Nor do we completely understand the molecular determinants of coreceptor switching by C-HIV variants. Here, we characterized a panel of HIV-1 envelope glycoproteins (Envs) (n = 300) cloned sequentially from plasma of 21 antiretroviral therapy (ART)-naïve subjects who experienced progression from chronic to advanced stages of C-HIV infection, and show that CXCR4-using C-HIV variants emerged in only one individual. Mutagenesis studies and structural models suggest that the evolution of R5 to X4 variants in this subject principally involved acquisition of an “Ile-Gly” insertion in the gp120 V3 loop and replacement of the V3 “Gly-Pro-Gly” crown with a “Gly-Arg-Gly” motif, but that the accumulation of additional gp120 “scaffold” mutations was required for these V3 loop changes to confer functional effects. In this context, either of the V3 loop changes could confer possible transitional R5X4 phenotypes, but when present together they completely abolished CCR5 usage and conferred the X4 phenotype. Our results show that the emergence of CXCR4-using strains is rare in this cohort of untreated individuals with advanced C-HIV infection. In the subject where X4 variants did emerge, alterations in the gp120 V3 loop were necessary but not sufficient to confer CXCR4 usage.     

Marine mammal culling programs: review of effects on predator and prey populations

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Co-occurring grass species differ in their associated microbial community composition in a temperate native grassland

Background and aims

Specific associations exist between plant species and the soil microbial community and these associations vary between habitat types and different plant groups. However, there is evidence that the associations are highly specific. Hence, we aimed to determine the specificity of plant-microbe relationships amongst co-occurring grass species in a temperate grassland.

Methods and results

We examined the broad microbial groups of bacteria and fungi as well as a specific fungal group, the arbuscular mycorrhizal community amongst two dominant C₃ and C₄ species and one sub-dominant C₃ species using terminal restriction fragment length polymorphism (T-RFLP) analysis. We found that the two dominant species were more similar to each other in their bacterial and arbuscular mycorrhizal community composition than either was to the sub-dominant species, but not in their fungal community composition. We also found no clear evidence that those differences were directly linked to soil chemical properties.

Conclusions

Our results demonstrate that co-occurring grass species have a distinct soil microbial community and T-RFLP analysis is able to detect plant species effect on the microbial community composition on an extremely local scale, providing an insight into the differences in the response of bacterial, fungal and arbuscular mycorrhizal communities to different, but similar and co-occurring, plant species.     

p53 and Translation Attenuation Regulate Distinct Cell Cycle Checkpoints during Endoplasmic Reticulum (ER) Stress

Cell cycle checkpoints ensure that proliferation occurs only under permissive conditions, but their role in linking nutrient availability to cell division is incompletely understood. Protein folding within the endoplasmic reticulum (ER) is exquisitely sensitive to energy supply and amino acid sources because deficiencies impair luminal protein folding and consequently trigger ER stress signaling. Following ER stress, many cell types arrest within the G₁ phase, although recent studies have identified a novel ER stress G₂ checkpoint. Here, we report that ER stress affects cell cycle progression via two classes of signal: an early inhibition of protein synthesis leading to G₂ delay involving CHK1 and a later induction of G₁ arrest associated both with the induction of p53 target genes and loss of cyclin D1. We show that substitution of p53/47 for p53 impairs the ER stress G₁ checkpoint, attenuates the recovery of protein translation, and impairs induction of NOXA, a mediator of cell death. We propose that cell cycle regulation in response to ER stress comprises redundant pathways invoked sequentially first to impair G₂ progression prior to ultimate G₁ arrest.     

Enhanced hippocampus‐dependent memory and reduced anxiety in mice over‐expressing human catalase in mitochondria

Oxidative stress (OS) and reactive oxygen species (ROS) play a modulatory role in synaptic plasticity and signaling pathways. Mitochondria (MT), a major source of ROS because of their involvement in energy metabolism, are important for brain function. MT‐generated ROS are proposed to be responsible for a significant proportion of OS and are associated with developmental abnormalities and aspects of cellular aging. The role of ROS and MT function in cognition of healthy individuals is relatively understudied. In this study, we characterized behavioral and cognitive performance of 5‐ to 6‐month‐old mice over‐expressing mitochondrial catalase (MCAT). MCAT mice showed enhancements in hippocampus‐dependent spatial learning and memory in the water maze and contextual fear conditioning, and reduced measures of anxiety in the elevated zero maze. Catalase activity was elevated in MCAT mice in all brain regions examined. Measures of oxidative stress (glutathione, protein carbonyl content, lipid peroxidation, and 8‐hydroxyguanine) did not significantly differ between the groups. The lack of differences in these markers of oxidative stress suggests that the differences observed in this study may be due to altered redox signaling. Catalase over‐expression might be sufficient to enhance cognition and reduce measures of anxiety even in the absence of alteration in levels of OS.     

Diversionary feeding and nestling diet of Hen Harriers Circus cyaneus

Capsule: Diversionary feeding reduced Hen Harrier Circus cyaneus nestlings’ natural food intake by half. Red Grouse Lagopus lagopus scotica chicks constituted 0–4% of all nestling food items. Annually, this reduced annual grouse chick production by 0–6%.

Aim: To quantify proportions of diversionary and natural food (including grouse) delivered to Hen Harrier nestlings in relation to brood size, male status and natural prey abundance.

Methods: We recorded diversionary food provisioned to 25 Hen Harrier broods (2008–15) and studied the diet of 15 broods using observations from hides, nest cameras and regurgitated pellet analysis. Variation in nestling diet was analysed using compositional analysis.

Results: Hen Harriers took 76% of diversionary food provided. Depending on assessment method, average nestling diet was 44–53% diversionary food, 39–55% natural prey (including 24–45% passerines, 4–15% small mammals, 0–4% grouse chicks) and 0–9% unknown items. The amount of diversionary food consumed was not influenced by male status, brood size or natural prey abundance. The number of Red Grouse chicks delivered annually was 34–100% lower than expected under unfed conditions, however, the confidence intervals associated with these estimates were large.

Conclusion: Diversionary food influenced Hen Harrier nestling diet and reduced the number of Red Grouse chicks taken relative to modelled predictions. It may help reduce conflict between Hen Harrier conservation and Red Grouse shooting, but only if overall grouse productivity is thereby maintained or increased.     

Association of small ankyrin 1 with the sarcoplasmic reticulum

Small ankyrin 1, or sAnk1, is a small, alternatively spliced product of the erythroid ankyrin gene, ANK1, that is expressed in striated muscle and concentrated in the network sarcoplasmic reticulum (SR) surrounding the Z disks and M lines. We have characterized sAnk1 in muscle homogenates and SR vesicles, and have identified the region that targets it to the network SR. Selective extractions and partitioning into Triton X-114 show that sAnk1 behaves like the SR Ca-ATPase and so is an integral protein of the SR membrane. Mild proteolytic treatment of isolated SR vesicles indicates that sAnk1 is oriented with its hydrophilic, C-terminal sequence exposed to the solution, which is equivalent to the cytoplasmic face of the SR membrane in situ. SDS-PAGE in non-reducing gels suggests that sAnk1 is present as dimers and larger oligomers in the native SR. These results suggest that sAnk1 is oligomeric and oriented with its C-terminus exposed to the cytoplasm, where it may interact with proteins of the contractile apparatus. The N-terminal 29 amino acid hydrophobic sequence of sAnk1, which is predicted to span the SR membrane, is sufficient to target proteins to and anchor them in internal membranes of HEK 293 cells. It also targets reporter proteins to the network SR of skeletal myofibers and is thus the first example of a sequence that targets proteins to a particular compartment of the SR.