Proton magnetic resonance and polarographic studies of some aminated naphthoquinones

Variable temperature n.m.r. and polarographic measurements have been performed on a series of cyclic secondary aminonaphthoquinones. The results indicate that ring strain is not the only factor which would explain the order of effective electron donation by the various amines to the quinone nucleus

Fully biodegradable and biocompatible emulsion template polymer scaffolds by thiol-acrylate polymerisation of polycaprolactone macropolymers

The emulsion templating process offers a route to highly porous polymers with well-defined morphologies. This study describes the preparation of such porous polymers (polyHIPEs) via the photopolymerization of a multi-functional thiol and polycaprolactone macromonomer. The resulting materials have nominal porosities of 90% and 95%, and are seen to have an interconnected pore morphology, with an average pore diameter of approximately 60 μm. Initial biocompatibility assessments with fibroblast cells (L929) have shown that the polymers are capable of supporting cell growth over 7 days and degradation products are non-toxic to cells up to a concentration of 0.1 mg ml−1

Conformational ensemble of the poliovirus 3CD precursor observed by MD simulations and confirmed by SAXS: A strategy to expand the viral proteome?

The genomes of RNA viruses are relatively small. To overcome the small-size limitation, RNA viruses assign distinct functions to the processed viral proteins and their precursors. This is exemplified by poliovirus 3CD protein. 3C protein is a protease and RNA-binding protein. 3D protein is an RNA-dependent RNA polymerase (RdRp). 3CD exhibits unique protease and RNA-binding activities relative to 3C and is devoid of RdRp activity. The origin of these differences is unclear, since crystal structure of 3CD revealed “beads-on-a-string” structure with no significant structural differences compared to the fully processed proteins. We performed molecular dynamics (MD) simulations on 3CD to investigate its conformational dynamics. A compact conformation of 3CD was observed that was substantially different from that shown crystallographically. This new conformation explained the unique properties of 3CD relative to the individual proteins. Interestingly, simulations of mutant 3CD showed altered interface. Additionally, accelerated MD simulations uncovered a conformational ensemble of 3CD. When we elucidated the 3CD conformations in solution using small-angle X-ray scattering (SAXS) experiments a range of conformations from extended to compact was revealed, validating the MD simulations. The existence of conformational ensemble of 3CD could be viewed as a way to expand the poliovirus proteome, an observation that may extend to other viruses

Poliovirus RNA-dependent RNA polymerase (3D(pol)): Structural, biochemical, and biological analysis of conserved structural motifs A and B

We have constructed a structural model for poliovirus RNA-dependent RNA polymerase (3D(pol)) in complex with a primer-template (sym/sub) and ATP. Residues found in conserved structural motifs A (Asp-238) and B (Asn-297) are involved in nucleotide selection. Asp-238 appears to couple binding of nucleotides with the correct sugar configuration to catalytic efficiency at the active site of the enzyme. Asn-297 is involved in selection of ribonucleoside triphosphates over 2'-dNTPs, a role mediated most likely via a hydrogen bond between the side chain of this residue and the 2'-OH of the ribonucleoside triphosphate. Substitutions at position 238 or 297 of 3D(pol) produced derivatives exhibiting a range of catalytic efficiencies when assayed in vitro for poly(rU) polymerase activity or sym/sub elongation activity. A direct correlation existed between activity on sym/sub and biological phenotypes; a 2.5-fold reduction in polymerase elongation rate produced virus with a temperature-sensitive growth phenotype. These data permit us to propose a detailed, structural model for nucleotide selection by 3D(pol), confirm the biological relevance of the sym/sub system, and provide additional evidence for kinetic coupling between RNA synthesis and subsequent steps in the virus life cycle

Lower Extremity Musculoskeletal Injury in US Military Academy Cadet Basic Training: A Survival Analysis Evaluating Sex, History of Injury, and Body Mass Index

Background: Injury incidence for physically active populations with a high volume of physical load can exceed 79%. There is little existing research focused on timing of injury and how that timing differs based on certain risk factors. Purpose/Hypothesis: The purpose of this study was to report both the incidence and timing of lower extremity injuries during cadet basic training. We hypothesized that women, those with a history of injury, and those in underweight and obese body mass index (BMI) categories would sustain lower extremity musculoskeletal injury earlier in the training period than men, those without injury history, and those in the normal-weight BMI category. Study Design: Cohort study; Level of evidence, 2. Methods: Cadets from the class of 2022, arriving in 2018, served as the study population. Baseline information on sex and injury history was collected via questionnaire, and BMI was calculated from height and weight taken during week 1 at the United States Military Academy. Categories were underweight (BMI <20), middleweight (20-29.99), and obese (≥30). Injury surveillance was performed over the first 60 days of training via electronic medical record review and monitoring. Kaplan-Meier survival curves were used to estimate group differences in time to the first musculoskeletal injury. Cox proportional hazard regression was used to estimate hazard ratios (HRs). Results: A total of 595 cadets participated. The cohort was 76.8% male, with 29.9% reporting previous injury history and 93.3% having a BMI between 20 and 30. Overall, 16.3% of cadets (12.3% of male cadets and 29.7% of female cadets) experienced an injury during the follow-up period. Women experienced significantly greater incident injury than did men (P <.001). Separation of survival curves comparing the sexes and injury history occurred at weeks 3 and 4, respectively. Hazards for first musculoskeletal injury were significantly greater for women versus men (HR, 2.63; 95% CI, 1.76-3.94) and for those who reported a history of injury versus no injury history (HR, 1.76; 95% CI, 1.18-2.64). No differences were observed between BMI categories. Conclusion: Female cadets and those reporting previous musculoskeletal injury demonstrated a greater hazard of musculoskeletal injury during cadet basic training. This study did not observe an association between BMI and injury

Properties of the Lambda(1520) Resonance from High-Precision Electroproduction Data

High-resolution spectrometer measurements of the reaction H(e,e'K+)X at small Q2 are used to extract the mass and width of the Lambda(1520). We investigate the influence of various assumptions used in the extraction. The width appears to be more sensitive to the assumptions than the mass. To reach a width uncertainty about 1 MeV or better, one needs to know the structure of the non-resonant background. Based on the new Jefferson Lab Hall A data, our final values for the Breit-Wigner parameters are M = 1520.4 +- 0.6 (stat) +- 1.5 (syst) MeV, Gamma = 18.6 +- 1.9 (stat) +- 1 (syst) MeV. For the first time, we also estimate the pole position for this resonance and find that both the pole mass and width seem to be smaller than the Breit-Wigner values.Comment: 7 pages, 3 figures; corresponds to the published versio

In search of hair damage using metabolomics?

YesHair fibres are extraordinary materials, not least because they are exquisitely formed by each of the 5 million or so hair follicles on our bodies and have functions that cross from physiology to psychology, but also because they have well known resistance to degradation as seen in hair surviving from archaeological and historical samples [1]. Hair fibres on the head grow at around 1cm each month, together totalling approximately 12km of growth per person per year. Each fibre is incredibly strong for its small diameter; with one fibre typically holding 100g and together a well-formed ponytail [allegedly] has the collective strength to support the weight of a small elephant! Hair – and from here I mean scalp hair – is under constant scrutiny by each of us; whether it be style, split ends, the first few grey hairs or the collection of hairs in the shower that should be firmly attached - leading to the fear that is hair loss

Structure-function relationships of the RNA-dependent RNA polymerase from poliovirus (3Dpol): A surface of the primary oligomerization domain functions in capsid precursor processing and VPg uridylylation

The primary oligomerization domain of poliovirus polymerase, 3Dpol, is stabilized by the interaction of the back of the thumb subdomain of one molecule with the back of the palm subdomain of a second molecule, thus permitting the head-to-tail assembly of 3Dpol monomers into long fibers. The interaction of Arg-455 and Arg-456 of the thumb with Asp-339, Ser-341, and Asp-349 of the palm is key to the stability of this interface. We show that mutations predicted to completely disrupt this interface do not produce equivalent growth phenotypes. Virus encoding a polymerase with changes of both residues of the thumb to alanine is not viable; however, virus encoding a polymerase with changes of all three residues of the palm to alanine is viable. Biochemical analysis of 3Dpol derivatives containing the thumb or palm substitutions revealed that these derivatives are both incapable of forming long fibers, suggesting that polymerase fibers are not essential for virus viability. The RNA binding activity, polymerase activity, and thermal stability of these derivatives were equivalent to that of the wild-type enzyme. The two significant differences observed for the thumb mutant were a modest reduction in the ability of the altered 3CD proteinase to process the VP0/VP3 capsid precursor and a substantial reduction in the ability of the altered 3Dpol to catalyze oriI-templated uridylylation of VPg. The defect to uridylylation was a result of the inability of 3CD to stimulate this reaction. Because 3C alone can substitute for 3CD in this reaction, we conclude that the lethal replication phenotype associated with the thumb mutant is caused, in part, by the disruption of an interaction between the back of the thumb of 3Dpol and some undefined domain of 3C. We speculate that this interaction may also be critical for assembly of other complexes required for poliovirus genome replication

Teaching modern foreign languages in multilingual classrooms: an examination of Key Stage 2 teachers’ experiences

The statutory inclusion of modern foreign languages (MFL) into the Key Stage 2 curriculum in England in 2014 aimed to raise the language skills of younger learners in preparation for their secondary education. This change to the curriculum has occurred at a time in which the linguistic diversity within primary schools across the country has been consistently increasing. This study used Interpretative Phenomenological Analysis to qualitatively examine the impact of the curriculum change on teachers implementing it in multilingual classrooms in Greater Manchester. Six teachers with varying experience in teaching MFL participated in semistructured interviews focussing on different aspects of the curriculum change. This paper focuses on the teaching of MFL, as well as on teachers’ perceptions of English as an Additional Language (EAL) pupils’ aptitude for language learning in comparison to their monolingual peers. The superordinate themes identified from the data included the inconsistent delivery of MFL in primary schools, and the role of multilingual classrooms as opportunities for augmented MFL provision. The findings from this study will have implications for teachers, head teachers, and policy-makers regarding the effectiveness of the initial implementation of MFL into the primary curriculum, with specific reference to the EAL school population