Prospects for resolving the Hubble constant tension with standard sirens

The Hubble constant ($H_0$) estimated from the local Cepheid-supernova (SN) distance ladder is in 3-$\sigma$ tension with the value extrapolated from cosmic microwave background (CMB) data assuming the standard cosmological model. Whether this tension represents new physics or systematic effects is the subject of intense debate. Here, we investigate how new, independent $H_0$ estimates can arbitrate this tension, assessing whether the measurements are consistent with being derived from the same model using the posterior predictive distribution (PPD). We show that, with existing data, the inverse distance ladder formed from BOSS baryon acoustic oscillation measurements and the Pantheon SN sample yields an $H_0$ posterior near-identical to the Planck CMB measurement. The observed local distance ladder value is a very unlikely draw from the resulting PPD. Turning to the future, we find that a sample of $\sim50$ binary neutron star "standard sirens" (detectable within the next decade) will be able to adjudicate between the local and CMB estimates

Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

How and why DNA barcodes underestimate the diversity of microbial eukaryotes

Background: Because many picoplanktonic eukaryotic species cannot currently be maintained in culture, direct sequencing of PCR-amplified 18S ribosomal gene DNA fragments from filtered sea-water has been successfully used to investigate the astounding diversity of these organisms. The recognition of many novel planktonic organisms is thus based solely on their 18S rDNA sequence. However, a species delimited by its 18S rDNA sequence might contain many cryptic species, which are highly differentiated in their protein coding sequences. Principal Findings: Here, we investigate the issue of species identification from one gene to the whole genome sequence. Using 52 whole genome DNA sequences, we estimated the global genetic divergence in protein coding genes between organisms from different lineages and compared this to their ribosomal gene sequence divergences. We show that this relationship between proteome divergence and 18S divergence is lineage dependant. Unicellular lineages have especially low 18S divergences relative to their protein sequence divergences, suggesting that 18S ribosomal genes are too conservative to assess planktonic eukaryotic diversity. We provide an explanation for this lineage dependency, which suggests that most species with large effective population sizes will show far less divergence in 18S than protein coding sequences. Conclusions: There is therefore a trade-off between using genes that are easy to amplify in all species, but which by their nature are highly conserved and underestimate the true number of species, and using genes that give a better description of the number of species, but which are more difficult to amplify. We have shown that this trade-off differs between unicellular and multicellular organisms as a likely consequence of differences in effective population sizes. We anticipate that biodiversity of microbial eukaryotic species is underestimated and that numerous ''cryptic species'' will become discernable with the future acquisition of genomic and metagenomic sequences

CLU: A new algorithm for EST clustering

BACKGROUND: The continuous flow of EST data remains one of the richest sources for discoveries in modern biology. The first step in EST data mining is usually associated with EST clustering, the process of grouping of original fragments according to their annotation, similarity to known genomic DNA or each other. Clustered EST data, accumulated in databases such as UniGene, STACK and TIGR Gene Indices have proven to be crucial in research areas from gene discovery to regulation of gene expression. RESULTS: We have developed a new nucleotide sequence matching algorithm and its implementation for clustering EST sequences. The program is based on the original CLU match detection algorithm, which has improved performance over the widely used d2_cluster. The CLU algorithm automatically ignores low-complexity regions like poly-tracts and short tandem repeats. CONCLUSION: CLU represents a new generation of EST clustering algorithm with improved performance over current approaches. An early implementation can be applied in small and medium-size projects. The CLU program is available on an open source basis free of charge. It can be downloaded fro

Interest in healthy living outweighs presumed cultural norms for obesity for Ghanaian women

BACKGROUND: Cultural norms indicate that obesity reflects increased wealth and prosperity. Yet obesity is linked to serious medical illnesses. The purpose of this study was to determine if Ghanaian women would change their body image if it meant a healthier life. METHODS: A questionnaire was administered to 305 Ghanaian women waiting for clinic appointments at Korle Bu Teaching Hospital, Accra Ghana. This survey included questions on current health, selection of figural stimuli, decision making on health and social determinants and 5 questions on self-perception of health from SF-36. Anthropometric measures were taken and body mass index calculated. Women were also provided with health related information at the conclusion of the interview. RESULTS: The majority of all women surveyed would reduce their current body image if it meant that they would have an overall healthier life and reduce the risks of obesity-linked illnesses and complications. Currently obese women were significantly more likely than non-obese women to reduce their body image to reduce the risk of hypertension (OR 2.03 [1.64 – 2.51],<0.001); cardiovascular accident (OR 1.96 [1.61 – 2.38],<0.001); diabetes (OR 2.00 [1.63 – 2.44],<0.001); myocardial infarction (OR 2.27 [1.80 – 2.86],<0.001); if requested by a spouse(OR 2.64 [1.98 – 3.52],<0.001); and to improve overall health (OR 1.95 [1.60 – 2.37], <0.001). There was no association with current body image and responses to SF-36. The decision to select a new body image was not influenced by education, income, marital status or parity. Age 50 years old and less was significantly associated with the body image size reduction to reduce the risk of hypertension, diabetes, and a cardiovascular accident. CONCLUSION: The Ghanaian women interviewed in this study are interested in living a healthy life and are willing to reduce their body size to reduce the risk of obesity-linked illnesses. The target group for any interventional studies and measures to reduce obesity appears to be women age 50 and younger