Biological Channeling of a Reactive Intermediate in the Bifunctional Enzyme DmpFG

It has been hypothesized that the bifunctional enzyme DmpFG channels its intermediate, acetaldehyde, from one active site to the next using a buried intermolecular channel identified in the crystal structure. This channel appears to switch between an open and a closed conformation depending on whether the coenzyme NAD(+) is present or absent. Here, we applied molecular dynamics and metadynamics to investigate channeling within DmpFG in both the presence and absence of NAD(+). We found that substrate channeling within this enzyme is energetically feasible in the presence of NAD(+) but was less likely in its absence. Tyr-291, a proposed control point at the channel's entry, does not appear to function as a molecular gate. Instead, it is thought to orientate the substrate 4-hydroxy-2-ketovalerate in DmpG before reaction occurs, and may function as a proton shuttle for the DmpG reaction. Three hydrophobic residues at the channel's exit appear to have an important role in controlling the entry of acetaldehyde into the DmpF active site

Biological Channeling of a Reactive Intermediate in the Bifunctional Enzyme DmpFG

AbstractIt has been hypothesized that the bifunctional enzyme DmpFG channels its intermediate, acetaldehyde, from one active site to the next using a buried intermolecular channel identified in the crystal structure. This channel appears to switch between an open and a closed conformation depending on whether the coenzyme NAD+ is present or absent. Here, we applied molecular dynamics and metadynamics to investigate channeling within DmpFG in both the presence and absence of NAD+. We found that substrate channeling within this enzyme is energetically feasible in the presence of NAD+ but was less likely in its absence. Tyr-291, a proposed control point at the channel's entry, does not appear to function as a molecular gate. Instead, it is thought to orientate the substrate 4-hydroxy-2-ketovalerate in DmpG before reaction occurs, and may function as a proton shuttle for the DmpG reaction. Three hydrophobic residues at the channel's exit appear to have an important role in controlling the entry of acetaldehyde into the DmpF active site

Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool.

Funder: Oxford Martin School, University of OxfordThe response of the global virus genomics community to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unprecedented, with significant advances made towards the 'real-time' generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude of more genomes than previously available. Here, we present and describe Phylogenetic Assignment of Named Global Outbreak Lineages (pangolin), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme. To date, nearly two million virus genomes have been submitted to the web-application implementation of pangolin, which has facilitated the SARS-CoV-2 genomic epidemiology and provided researchers with access to actionable information about the pandemic's transmission lineages

Scoping studies to establish the capability and utility of a real-time bioaerosol sensor to characterise emissions from environmental sources

A novel dual excitation wavelength based bioaerosol sensor with multiple fluorescence bands called Spectral Intensity Bioaerosol Sensor (SIBS) has been assessed across five contrasting outdoor environments. The mean concentrations of total and fluorescent particles across the sites were highly variable being the highest at the agricultural farm (2.6 cm−3 and 0.48 cm−3, respectively) and the composting site (2.32 cm−3 and 0.46 cm−3, respectively) and the lowest at the dairy farm (1.03 cm−3 and 0.24 cm−3, respectively) and the sewage treatment works (1.03 cm−3 and 0.25 cm−3, respectively). In contrast, the number-weighted fluorescent fraction was lowest at the agricultural site (0.18) in comparison to the other sites indicating high variability in nature and magnitude of emissions from environmental sources. The fluorescence emissions data demonstrated that the spectra at different sites were multimodal with intensity differences largely at wavelengths located in secondary emission peaks for λex 280 and λex 370. This finding suggests differences in the molecular composition of emissions at these sites which can help to identify distinct fluorescence signature of different environmental sources. Overall this study demonstrated that SIBS provides additional spectral information compared to existing instruments and capability to resolve spectrally integrated signals from relevant biological fluorophores could improve selectivity and thus enhance discrimination and classification strategies for real-time characterisation of bioaerosols from environmental sources. However, detailed lab-based measurements in conjunction with real-world studies and improved numerical methods are required to optimise and validate these highly resolved spectral signatures with respect to the diverse atmospherically relevant biological fluorophores

A behavioral comparison of male and female adults with high functioning autism spectrum conditions

Autism spectrum conditions (ASC) affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome). Of the 83 (45 males and 38 females) participants, 62 (33 males and 29 females) met Autism Diagnostic Interview-Revised (ADI-R) cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036), fewer current socio-communication difficulties (p = 0.001), and more self-reported autistic traits (p = 0.012) than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001), a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males

Author correction : Divergence across mitochondrial genomes of sympatric members of the 'Schistosoma indicum' group and clues into the evolution of 'Schistosoma spindale'

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Evaluating deterministic motif significance measures in protein databases

<p>Abstract</p> <p>Background</p> <p>Assessing the outcome of motif mining algorithms is an essential task, as the number of reported motifs can be very large. Significance measures play a central role in automatically ranking those motifs, and therefore alleviating the analysis work. Spotting the most interesting and relevant motifs is then dependent on the choice of the right measures. The combined use of several measures may provide more robust results. However caution has to be taken in order to avoid spurious evaluations.</p> <p>Results</p> <p>From the set of conducted experiments, it was verified that several of the selected significance measures show a very similar behavior in a wide range of situations therefore providing redundant information. Some measures have proved to be more appropriate to rank highly conserved motifs, while others are more appropriate for weakly conserved ones. Support appears as a very important feature to be considered for correct motif ranking. We observed that not all the measures are suitable for situations with poorly balanced class information, like for instance, when positive data is significantly less than negative data. Finally, a visualization scheme was proposed that, when several measures are applied, enables an easy identification of high scoring motifs.</p> <p>Conclusion</p> <p>In this work we have surveyed and categorized 14 significance measures for pattern evaluation. Their ability to rank three types of deterministic motifs was evaluated. Measures were applied in different testing conditions, where relations were identified. This study provides some pertinent insights on the choice of the right set of significance measures for the evaluation of deterministic motifs extracted from protein databases.</p

Comparisons of the factor structure and measurement invariance of the Spence children’s anxiety scale - parent version in children with autism spectrum disorder and typically developing anxious children

The Spence Children’s Anxiety Scale - Parent version (SCAS-P) is often used to assess anxiety in children with autism spectrum disorder (ASD), however, little is known about the validity of the tool in this population. The aim of this study was to determine whether the SCAS-P has the same factorial validity in a sample of young people with ASD (n=285), compared to a sample of typically developing young people with anxiety disorders (n=224). Poor model fit with all of the six hypothesised models precluded invariance testing. Exploratory factor analysis indicated that different anxiety phenomenology characterises the two samples. The findings suggest that cross-group comparisons between ASD and anxious samples based on the SCAS-P scores may not always be appropriat