James Nokes Publications
Impact of viral upper respiratory tract infection on the concentration of nasopharyngeal pneumococcal carriage among Kenyan children
Morpeth SC, Munywoki P, Hammitt LL, Bett A, Bottomley C, Onyango CO, Murdoch DR, Nokes DJ, Scott, JAG
Viral upper respiratory tract infection (URTI) predisposes to bacterial pneumonia possibly by facilitating growth of bacteria such as Streptococcus pneumoniae colonising the nasopharynx. We investigated whether viral URTI is temporally associated with an increase in nasopharyngeal pneumococcal concentration. We observed only a small increase in nasopharyngeal pneumococcal concentration during RSV or rhinovirus URTI, relative to natural variation. Other factors, such as host response to viral infection, may be more important than nasopharyngeal pneumococcal concentration in determining risk of invasive disease. Scientific Reports. July 2018
Surveillance of respiratory viruses in the outpatient setting in rural coastal Kenya: baseline epidemiological observations
Joyce Uchi Nyiro, Patrick Munywoki2, Everlyn Kamau, Charles Agoti, Alex Gichuki, Timothy Etyang, Grieven Otieno, D. James Nokes
Endemic and seasonally recurring respiratory viruses are a major cause of disease and death globally, particularly in developing countries.
We report epidemiological data obtained through surveillance of respiratory viruses at nine outpatient health facilities in Kilifi County, coastal Kenya. Respiratory virus infections are common amongst Acute Respiratory Infection outpatients particularly in young children. Rhinovirus predominance warrants further studies on the health and socio-economic implications. Respiratory Syncytial Virus and adenovirus were more commonly associated with severe disease.
Real-time decision-making during emergency disease outbreaks
In the event of a new infectious disease outbreak, mathematical and simulation models are commonly used to inform policy by evaluating which control strategies will minimize the impact of the epidemic. In the early stages of such outbreaks, substantial parameter uncertainty may limit the ability of models to provide accurate predictions, and policymakers do not have the luxury of waiting for data to alleviate this state of uncertainty. For policymakers, however, it is the selection of the optimal control intervention in the face of uncertainty, rather than accuracy of model predictions, that is the measure of success that counts.
Here, we demonstrate the need for both real-time model fitting and generating projections to evaluate alternative control interventions throughout an outbreak. Our results highlight the use of using models at outbreak onset to inform policy and the importance of state-dependent interventions that adapt in response to additional information throughout an outbreak.
Insights into bacterial lipoprotein trafficking from a structure of LolA bound to the LolC periplasmic domain
Kaplan Elise, Greene Nicholas P, Crow Allister, Koronakis Vassilis
The outer membrane of Gram-negative bacteria presents a selectively permeable barrier to the environment and is the first line of defense against antibiotics and other antimicrobial agents. Maintenance of the outer membrane relies on lipoproteins delivered by the LolABCDE system, making the Lol proteins attractive targets for the development of new antimicrobial compounds. During trafficking, lipoproteins are extracted from the cytoplasmic membrane by the LolCDE complex, transported across the periplasm by LolA, and integrated into the outer membrane by LolB. Here, we describe structural features underpinning the interaction between LolA and LolCDE. The structure of LolA bound to the periplasmic domain of LolC provides an arresting molecular snapshot of a key intermediate in the bacterial lipoprotein trafficking pathway.
Laura Green publications
Quantifying the beliefs of key players in the UK sheep industry on the efficacy of two treatments for footrot
JR Winter, LE Green
Clinical trials have demonstrated that sheep with footrot treated with parenteral and topical antibiotic treatment without foot trimming (treatment A), have achieved cure faster than sheep treated with foot trimming and topical antibiotic (treatment B). We investigated how key players in the UK sheep industry recommended treating footrot, and tested whether reviewing the evidence surrounding treatment of footrot changed their beliefs.
Development and assessment of management practices in a flock-specific lameness control plan: A stepped-wedge trial on 44 English sheep flocks
Jessica Witt, Laura Green
Lameness in sheep has economic and welfare implications, including loss of ewe body condition, lower lambing percentages, and poor lamb growth rates. The majority of lameness is caused by the infectious diseases footrot and contagious ovine digital dermatitis, with white line separation, white line abscesses, and toe granulomas also reported by farmers. Most sheep farmers in the UK have other enterprises and care for their flock part-time. A lameness control plan (LCP) consisting of 37 management practices that covered all aspects of control of lameness was developed for part-time sheep farmers. We found that separating lame sheep at treatment, culling sheep lame ≥2 occasions per year, and only using a footbath to treat outbreaks of interdigital dermatitis are flock managements that contribute to improved control of lameness in flocks with part-time farmers.
A re-evaluation of the domestication bottleneck from archaeogenomic evidence
Robin G. Allaby, Roselyn Ware and Logan Kistler
Domesticated crops show a reduced level of diversity that is commonly attributed to the ‘domestication bottleneck’; a drastic reduction in the population size associated with sub‐sampling the wild progenitor species and the imposition of selection pressures associated with the domestication syndrome. A prediction of the domestication bottleneck is a sharp decline in genetic diversity early in the domestication process. Surprisingly, archaeological genomes of three major annual crops do not indicate that such a drop in diversity occurred early in the domestication process. In light of this observation, we revisit the general assumption of the domestication bottleneck concept in our current understanding of the evolutionary process of domestication.
Richard Napier publications
Phyllostictine A : total synthesis, structural verification and determination of substructure responsible for plant growth inhibition
Riemer M, Uzunova VV, Riemeer N, Clarkson GJ, Pereira N, Napier R, Shipman M
The first total synthesis of phyllostictine A (PA) is reported, which confirms the structure of this fungal metabolite and its (6S,7R,8S)-stereochemistry. Both synthetic PA and an analogue containing the 5-methylene-1,5-dihydro-2H-pyrrol-2-one nucleus exhibit μM inhibitory activity in root growth assays against Arabidopsis thaliana, indicating that this heterocyclic subunit is key to the herbicidal activity of the natural product.
It starts with TIRs
Retzer K, Singh G, Napier RM
The canonical auxin receptor complex mediates gene expression, but it is also necessary for responses far too rapid to be mediated by transcription. An innovative setup that uses advanced microscopy and microfluidics can record auxin-induced changes within 30 seconds during root growth.