Assessment of the nucleotide modifications in the high-resolution cryo-electron microscopy structure of the Escherichia coli 50S subunit.

Post-transcriptional ribosomal RNA (rRNA) modifications are present in all organisms, but their exact functional roles and positions are yet to be fully characterized. Modified nucleotides have been implicated in the stabilization of RNA structure and regulation of ribosome biogenesis and protein synthesis. In some instances, rRNA modifications can confer antibiotic resistance. High-resolution ribosome structures are thus necessary for precise determination of modified nucleotides' positions, a task that has previously been accomplished by X-ray crystallography. Here, we present a cryo-electron microscopy (cryo-EM) structure of the Escherichia coli 50S subunit at an average resolution of 2.2 Å as an additional approach for mapping modification sites. Our structure confirms known modifications present in 23S rRNA and additionally allows for localization of Mg2+ ions and their coordinated water molecules. Using our cryo-EM structure as a testbed, we developed a program for assessment of cryo-EM map quality. This program can be easily used on any RNA-containing cryo-EM structure, and an associated Coot plugin allows for visualization of validated modifications, making it highly accessible

Vitamin D supplementation does not improve human skeletal muscle contractile properties in insufficient young males

Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function

Smallholder farmers’ access to credit in the Amathole District Municipality, Eastern Cape Province, South Africa

Provision of credit has being identified as an important instrument for improving the welfare of smallholder farmers directly and for enhancing productive capacity through financing investment by the farmers in their human and physical capital. This study investigated the individual and household characteristics that influence credit market access in Amathole District Municipality, Eastern Cape Province, South Africa, using a cross sectional data from smallholder farmers’ household survey. The aim is to provide a better understanding of the households’ level socio-economic characteristics, not only because they influence household’s demand for credit but also due to the fact that potential lenders are most likely to base their assessment of borrowers’ creditworthiness on such characteristics. The results of the logistic regression suggest that credit market access was significantly influenced by variables such as gender, education, households’ income, value of assets, savings, dependency ratio, repayment capacity and social capital. Implications for rural credit delivery are discussed

Recent advances in the application of stable isotope ratio analysis in forensic chemistry

This review paper updates the previous literature in relation to the continued and developing use of stable isotope ratio analysis in samples which are relevant to forensic science. Recent advances in the analysis of drug samples, explosive materials, and samples derived from human and animal samples are discussed. The paper also aims to put the use of isotope ratio mass spectrometry into a forensic context and discuss its evidential potential

Population screening for colorectal cancer means getting FIT:the past, present, and future of colorectal cancer screening using the fecal immunochemical test for hemoglobin (FIT)

Fecal immunochemical tests for hemoglobin (FIT) are changing the manner in which colorectal cancer (CRC) is screened. Although these tests are being performed worldwide, why is this test different from its predecessors? What evidence supports its adoption? How can this evidence best be used? This review addresses these questions and provides an understanding of FIT theory and practices to expedite international efforts to implement the use of FIT in CRC screening

Is there a reliable taphonomic clock in the temperate North Atlantic? An example from a North Sea population of the mollusc Arctica islandica

Two hundred and seventy-seven shells of the long-lived bivalve mollusc Arctica islandica, collected from the Fladen Ground, northern North Sea, were radiocarbon dated and their taphonomic condition assessed, in order to determine whether taphonomic condition might provide a reliable indication of time since the death of the animal. With nine stations from across the Fladen Ground sampled, some strong geographic biases in 14C ages were apparent, with living and modern (post-bomb pulse) material found in the northern part of the Fladen Ground while older material (first half of the last millennium and Early Holocene/Lateglacial) was concentrated in the central and western sites. Samples from the south and east Fladen Ground were sparse and were dominated by material from the second half of the last millennium. This south-north distribution is interpreted as the result of environmental change over millennial time-scales in the North Sea causing a gradual northward shift of living A. islandica populations and is not thought to be related to post mortem transport of shells to the south and east. Taphonomic condition, assessed using discriminant analysis and principal component analysis of five characteristics (amount of remaining periostracum, presence and condition of the ligament, extent of erosion at the shell margin, amount of bioerosion, and nacre condition), appeared to be a generally unreliable indicator of time since the death of the animal. Based on these five taphonomic characteristics, discriminant analysis placed 81.1% of post-bomb shells, 39.6% of shells from the period 0–500 yr BP, 68.0% of shells from the period 500–1000 yr BP and 20.0% of shells from the Early Holocene/Lateglacial group into the correct radiocarbon age grouping, providing no support for the idea that this method can be used to triage shells for chronology construction as an alternative to radiometric dating

Multi-modal analysis of courtship behaviour in the old world leishmaniasis vector Phlebotomus argentipes

BACKGROUND: The sand fly Phlebotomus argentipes is arguably the most important vector of leishmaniasis worldwide. As there is no vaccine against the parasites that cause leishmaniasis, disease prevention focuses on control of the insect vector. Understanding reproductive behaviour will be essential to controlling populations of P. argentipes, and developing new strategies for reducing leishmaniasis transmission. Through statistical analysis of male-female interactions, this study provides a detailed description of P. argentipes courtship, and behaviours critical to mating success are highlighted. The potential for a role of cuticular hydrocarbons in P. argentipes courtship is also investigated, by comparing chemicals extracted from the surface of male and female flies. PRINCIPAL FINDINGS: P. argentipes courtship shared many similarities with that of both Phlebotomus papatasi and the New World leishmaniasis vector Lutzomyia longipalpis. Male wing-flapping while approaching the female during courtship predicted mating success, and touching between males and females was a common and frequent occurrence. Both sexes were able to reject a potential partner. Significant differences were found in the profile of chemicals extracted from the surface of males and females. Results of GC analysis indicate that female extracts contained a number of peaks with relatively short retention times not present in males. Extracts from males had higher peaks for chemicals with relatively long retention times. CONCLUSIONS: The importance of male approach flapping suggests that production of audio signals through wing beating, or dispersal of sex pheromones, are important to mating in this species. Frequent touching as a means of communication, and the differences in the chemical profiles extracted from males and females, may also indicate a role for cuticular hydrocarbons in P. argentipes courtship. Comparing characteristics of successful and unsuccessful mates could aid in identifying the modality of signals involved in P. argentipes courtship, and their potential for use in developing new strategies for vector control

Circulating levels of anti-angiogenic VEGF-A isoform (VEGF-Axxxb) in colorectal cancer patients predicts tumour VEGF-A ratios

Purpose: Bevacizumab as an adjunct to chemotherapy improves survival for some patients with metastatic colorectal cancer. Immunohistochemical staining of samples from the registration ECOG E3200 trial of bevacizumab with FOLFOX demonstrated that only patients with carcinomas expressing low levels of VEGF-A(165)b, an anti-angiogenic splice variant of the Vascular Endothelial Growth Factor family of proteins, benefited from bevacizumab treatment. To identify a more useful biomarker of response we tested the hypothesis that circulating VEGF-A(165)b levels correlate with immunohistochemical staining. Experimental Design: 17 patients with biopsy proven colorectal adenocarcinoma had pre-operative blood samples drawn. They underwent resection and had post-resection blood drawn. The plasma was analysed for levels of VEGF-A(xxx)b using enzyme-linked immunosorbent assay (ELISA) and the tumour blocks stained for VEGF-A(xxx)b and pan-VEGF-A. The normalised ratio of VEGF-A(xxx)b expression to that of panVEGF-A expression scored by IHC was calculated and correlated with plasma VEGF-A(165)b levels. Results: Plasma levels of VEGF-A(xxx)b significantly correlated with the VEGF-A(xxx)b:panVEGF-A ratio (r=0.594, P<0.02) in colorectal cancers. Median plasma VEGF-A(xxx)b levels were 151 pg/ml. The mean (1.5±0.17) and median, IQR (1.8, 1-2) IHC scores of the patients with greater than median plasma VEGF-A(xxx)b were significantly greater than those with less than median plasma VEGF-A(xxx)b levels (mean ± SEM=0.85±10.12, median, IQR=1, 0.54-1). Conclusion: These results suggest that plasma VEGF-A(xxx)b levels could be an effective biomarker of response to Bevacizumab. These results indicate that a prospective trial is warranted to explore the use of plasma VEGF-A(xxx)b levels to stratify patients for colorectal cancer treatment by bevacizumab