Over-the-counter analgesics during pregnancy : a comprehensive review of global prevalence and offspring safety

Funding This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC)/EASTBIO studentship to A.Z. (Grant Number: 1942576). RTM is supported by UKRI Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health is supported by MRC Centre Grant (MR/N022556/1).Peer reviewedPostprin

Pre-service Teachers’ Impact on Student Learning: Planning, Teaching, and Assessing during Professional Practice

This paper reports a pilot study to investigate four pre-service teachers’ reports of their impact on student learning while they completed a four-week professional experience block. We used Hiebert, Morris, Berk, and Jansen’s (2007) framework for teacher preparation to analyse the how the participants planned, assessed and reflected on a lesson sequence. Data collected were the pre-service teachers’ learning diary entries completed during the four-week block and an online questionnaire and interview completed at the end of the teaching block. Results indicate that the pre-service teachers struggled to identify clear learning goals for students which adversely impacted their ability to plan their lessons and assess students’ learning. Implications for teacher education programs are discussed

Maternal over-the-counter analgesics use during pregnancy and adverse perinatal outcomes : Cohort study of 151,141 singleton pregnancies

Funding: This work is supported by the Biotechnology and Biological Sciences Research council (BBSRC) funding the lead author under the EASTBIO doctoral training programme and to PAF, the EU Horizon 2020 project FREIA (Grant Number 825100). RTM is supported by MRC Centre for Reproductive Health Grant MR/N022556/1. The funders had no role in study design, data collection, data analysis, decision to publish, or manuscript preparation.Peer reviewedPublisher PD

Infectious Diseases, Climate Influences, and Nonstationarity

Cazelles and Hales discuss a new study that uses a range of mathematical tools to illustrate a clear relationship between climatic variables and the dynamics of cutaneous leishmaniasis

Genetic diversity among pandemic 2009 influenza viruses isolated from a transmission chain

BACKGROUND: Influenza viruses such as swine-origin influenza A(H1N1) virus (A(H1N1)pdm09) generate genetic diversity due to the high error rate of their RNA polymerase, often resulting in mixed genotype populations (intra-host variants) within a single infection. This variation helps influenza to rapidly respond to selection pressures, such as those imposed by the immunological host response and antiviral therapy. We have applied deep sequencing to characterize influenza intra-host variation in a transmission chain consisting of three cases due to oseltamivir-sensitive viruses, and one derived oseltamivir-resistant case. METHODS: Following detection of the A(H1N1)pdm09 infections, we deep-sequenced the complete NA gene from two of the oseltamivir-sensitive virus-infected cases, and all eight gene segments of the viruses causing the remaining two cases. RESULTS: No evidence for the resistance-causing mutation (resulting in NA H275Y substitution) was observed in the oseltamivir-sensitive cases. Furthermore, deep sequencing revealed a subpopulation of oseltamivir-sensitive viruses in the case carrying resistant viruses. We detected higher levels of intra-host variation in the case carrying oseltamivir-resistant viruses than in those infected with oseltamivir-sensitive viruses. CONCLUSIONS: Oseltamivir-resistance was only detected after prophylaxis with oseltamivir, suggesting that the mutation was selected for as a result of antiviral intervention. The persisting oseltamivir-sensitive virus population in the case carrying resistant viruses suggests either that a small proportion survive the treatment, or that the oseltamivir-sensitive virus rapidly re-establishes itself in the virus population after the bottleneck. Moreover, the increased intra-host variation in the oseltamivir-resistant case is consistent with the hypothesis that the population diversity of a RNA virus can increase rapidly following a population bottleneck

1918 Influenza Pandemic and Highly Conserved Viruses with Two Receptor-Binding Variants

The “Spanish influenza pandemic swept the globe in the autumn and winter of 1918–19, and resulted in the deaths of approximately 40 million people. Clinically, epidemiologically, and pathologically, the disease was remarkably uniform, which suggests that similar viruses were causing disease around the world. To assess the homogeneity of the 1918 pandemic influenza virus, partial hemagglutinin gene sequences have been determined for five cases, including two newly identified samples from London, United Kingdom. The strains show 98.9% to 99.8% nucleotide sequence identity. One of the few differences between the strains maps to the receptor-binding site of hemagglutinin, suggesting that two receptor-binding configurations were co-circulating during the pandemic. The results suggest that in the early stages of an influenza A pandemic, mutations that occur during replication do not become fixed so that a uniform “consensus” strain circulates for some time

Protein motions and dynamic effects in enzyme catalysis

The role of protein motions in promoting the chemical step of enzyme catalysed reactions remains a subject of considerable debate. Here, a unified view of the role of protein dynamics in dihydrofolate reductase catalysis is described. Recently the role of such motions has been investigated by characterising the biophysical properties of isotopically substituted enzymes through a combination of experimental and computational analyses. Together with previous work, these results suggest that dynamic coupling to the chemical coordinate is detrimental to catalysis and may have been selected against during DHFR evolution. The full catalytic power of Nature's catalysts appears to depend on finely tuning protein motions in each step of the catalytic cycle

Loop Interactions during Catalysis by Dihydrofolate Reductase fromMoritella profunda

Dihydrofolate reductase (DHFR) is often used as a model system to study the relation between protein dynamics and catalysis. We have studied a number of variants of the cold-adapted DHFR from Moritella profunda (MpDHFR), in which the catalytically important M20 and FG loops have been altered, and present a comparison with the corresponding variants of the wellstudied DHFR from Escherichia coli (EcDHFR). Mutations in the M20 loop do not affect the actual chemical step of transfer of hydride from reduced nicotinamide adenine dinucleotide phosphate to the substrate 7,8-dihydrofolate in the catalytic cycle in either enzyme; they affect the steady state turnover rate in EcDHFR but not in MpDHFR. Mutations in the FG loop also have different effects on catalysis by the two DHFRs. Despite the two enzymes most likely sharing a common catalytic cycle at pH 7, motions of these loops, known to be important for progression through the catalytic cycle in EcDHFR, appear not to play a significant role in MpDHFR