Quantifying the relative roles of selective and neutral processes in defining eukaryotic microbial communities

We have a limited understanding of the relative contributions of different processes that regulate microbial communities, which are crucial components of both natural and agricultural ecosystems. The contributions of selective and neutral processes in defining community composition are often confounded in field studies because as one moves through space, environments also change. Managed ecosystems provide an excellent opportunity to control for this and evaluate the relative strength of these processes by minimising differences between comparable niches separated at different geographic scales. We use next-generation sequencing to characterize the variance in fungal communities inhabiting adjacent fruit, soil and bark in comparable vineyards across 1000 kms in New Zealand. By compartmentalizing community variation, we reveal that niche explains at least four times more community variance than geographic location. We go beyond merely demonstrating that different communities are found in both different niches and locations by quantifying the forces that define these patterns. Overall, selection unsurprisingly predominantly shapes these microbial communities, but we show the balance of neutral processes also have a significant role in defining community assemblage in eukaryotic microbes

Modulation of Aβ(42 )low-n oligomerization using a novel yeast reporter system

BACKGROUND: While traditional models of Alzheimer's disease focused on large fibrillar deposits of the Aβ(42 )amyloid peptide in the brain, recent work suggests that the major pathogenic effects may be attributed to SDS-stable oligomers of Aβ(42). These Aβ(42 )oligomers represent a rational target for therapeutic intervention, yet factors governing their assembly are poorly understood. RESULTS: We describe a new yeast model system focused on the initial stages of Aβ(42 )oligomerization. We show that the activity of a fusion of Aβ(42 )to a reporter protein is compromised in yeast by the formation of SDS-stable low-n oligomers. These oligomers are reminiscent of the low-n oligomers formed by the Aβ(42 )peptide in vitro, in mammalian cell culture, and in the human brain. Point mutations previously shown to inhibit Aβ(42 )aggregation in vitro, were made in the Aβ(42 )portion of the fusion protein. These mutations both inhibited oligomerization and restored activity to the fusion protein. Using this model system, we found that oligomerization of the fusion protein is stimulated by millimolar concentrations of the yeast prion curing agent guanidine. Surprisingly, deletion of the chaperone Hsp104 (a known target for guanidine) inhibited oligomerization of the fusion protein. Furthermore, we demonstrate that Hsp104 interacts with the Aβ(42)-fusion protein and appears to protect it from disaggregation and degradation. CONCLUSION: Previous models of Alzheimer's disease focused on unravelling compounds that inhibit fibrillization of Aβ(42), i.e. the last step of Aβ(42 )assembly. However, inhibition of fibrillization may lead to the accumulation of toxic oligomers of Aβ(42). The model described here can be used to search for and test proteinacious or chemical compounds for their ability to interfere with the initial steps of Aβ(42 )oligomerization. Our findings suggest that yeast contain guanidine-sensitive factor(s) that reduce the amount of low-n oligomers of Aβ(42). As many yeast proteins have human homologs, identification of these factors may help to uncover homologous proteins that affect Aβ(42 )oligomerization in mammals

[PSI+] Maintenance Is Dependent on the Composition, Not Primary Sequence, of the Oligopeptide Repeat Domain

[PSI+], the prion form of the yeast Sup35 protein, results from the structural conversion of Sup35 from a soluble form into an infectious amyloid form. The infectivity of prions is thought to result from chaperone-dependent fiber cleavage that breaks large prion fibers into smaller, inheritable propagons. Like the mammalian prion protein PrP, Sup35 contains an oligopeptide repeat domain. Deletion analysis indicates that the oligopeptide repeat domain is critical for [PSI+] propagation, while a distinct region of the prion domain is responsible for prion nucleation. The PrP oligopeptide repeat domain can substitute for the Sup35 oligopeptide repeat domain in supporting [PSI+] propagation, suggesting a common role for repeats in supporting prion maintenance. However, randomizing the order of the amino acids in the Sup35 prion domain does not block prion formation or propagation, suggesting that amino acid composition is the primary determinant of Sup35's prion propensity. Thus, it is unclear what role the oligopeptide repeats play in [PSI+] propagation: the repeats could simply act as a non-specific spacer separating the prion nucleation domain from the rest of the protein; the repeats could contain specific compositional elements that promote prion propagation; or the repeats, while not essential for prion propagation, might explain some unique features of [PSI+]. Here, we test these three hypotheses and show that the ability of the Sup35 and PrP repeats to support [PSI+] propagation stems from their amino acid composition, not their primary sequences. Furthermore, we demonstrate that compositional requirements for the repeat domain are distinct from those of the nucleation domain, indicating that prion nucleation and propagation are driven by distinct compositional features

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females.

Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. Although these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors have a role in determining treatment outcome. This study analyses the pharmacogenetic association of six polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone (Suboxone) over the course of a 24-week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid-positive urine drug screens over the 24 weeks. In the total sample, no single-nucleotide polymorphisms (SNPs) in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed two intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (P=0.03, relative risk (RR)=1.67, 95% confidence interval (CI) 1.06-2.1). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (P=0.006, RR=2.15, 95% CI 1.3-2.29). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however, confirmation in an independent sample is warranted