Kristyna Rysava, Jason Espineda, Eva Angela V Silo, Sarah Carino, Ariane Mae Aringo, Rona P Bernales, Florencio F Adonay, Michael J Tildesley and Katie Hampson

Here we investigated the potential for Integrated Bite Case Management (IBCM) to improve rabies detection in Albay province. Using information obtained from animal bite histories combined with phone follow-ups and field investigations, we demonstrated that IBCM resulted in a fourfold increase in case detection over 13 months of study compared to the prior period. Further analysis of the IBCM data suggests that rabies transmission is mostly localized with focal cases from the previous month and current cases in neighbouring villages being most predictive of future rabies occurrence. We conclude that investigations of suspicious biting incidents identified through IBCM have potential to foster intersectoral relationships, and collaborative investments between public health and veterinary services, enabling the One Health ethos to be applied in a more sustainable and equitable way.

Frontiers in Tropical Diseases. March 2022

Finn P. Maloney, Jeremi Kuklewicz, Robin A. Corey, Yunchen Bi, Ruoya Ho, Lukasz Mateusiak, Els Pardon, Jan Steyaert, Phillip J. Stansfeld, Jochen Zimmer 

Hyaluronan is an acidic heteropolysaccharide comprising alternating N-acetylglucosamine and glucuronic acid sugars that is ubiquitously expressed in the vertebrate extracellular matrix. Here we describe five cryo-electron microscopy structures of a viral HAS homologue at different states during substrate binding and initiation of polymer synthesis. Combined with biochemical analyses and molecular dynamics simulations, our data reveal how HAS selects its substrates, hydrolyses the first substrate to prime the synthesis reaction, opens a hyaluronan-conducting transmembrane channel, ensures alternating substrate polymerization and coordinates hyaluronan inside its transmembrane pore. Our research suggests a detailed model for the formation of an acidic extracellular heteropolysaccharide and provides insights into the biosynthesis of one of the most abundant and essential glycosaminoglycans in the human body.

Nature. March 2022

Andrew RJ Murphy, David J Scanlan, Yin Chen, Gary D Bending, John P Hammond, Elizabeth MH Wellington, Ian DEA Lidbury

In pseudomonads, the two-component system regulators CbrAB, NtrBC and PhoBR, are responsible for regulating cellular response to carbon (C), nitrogen (N) and phosphorus (P) respectively. Numerous pseudomonads can use the environmentally abundant phosphonate species 2-aminoethylphosphonate (2AEP) as a source of C, N, or P, but only PhoBR has been shown to play a role in 2AEP utilization. On the other hand, utilization of 2AEP as a C and N source is considered substrate inducible. Here, using the plant-growth-promoting rhizobacterium Pseudomonas putida BIRD-1 we present evidence that 2AEP utilization is under dual regulation and only occurs upon depletion of C, N, or P, controlled by CbrAB, NtrBC, or PhoBR respectively. To our knowledge, this is the first study identifying coordination between global stress response and substrate-specific regulators in phosphonate metabolism.

Environmental Biology. March 2022

Horn, T., Narov, K.D., Panfilio, K.A.

Parental RNA interference (pRNAi) is a powerful and widely used method for gene-specific knockdown. Yet in insects its efficacy varies between species, and how the systemic response is transmitted from mother to offspring remains elusive. Using the beetle Tribolium castaneum, an RT-qPCR strategy to distinguish the presence of double-stranded RNA (dsRNA) from endogenous mRNA is reported. Overall, practical considerations for insect pRNAi against a backdrop of outstanding questions on the molecular mechanism of dsRNA transmission for long-term, systemic knockdown are elucidated.

Advanced Genetics. March 2022

Trystan Leng, Edward M. Hill, Alex Holmes, Emma Southall, Robin N. Thompson, Michael J. Tildesley, Matt J. Keeling & Louise Dyson

A range of measures have been implemented to control within-school SARS-CoV-2 transmission in England, including the self-isolation of close contacts and twice weekly mass testing of secondary school pupils using lateral flow device tests (LFTs). Despite reducing transmission, isolating close contacts can lead to high levels of absences, negatively impacting pupils. To quantify pupil-to-pupil SARS-CoV-2 transmission and the impact of implemented control measures, we fit a stochastic individual-based model of secondary school infection to both swab testing data and secondary school absences data from England, and then simulate outbreaks from 31st August 2020 until 23rd May 2021.

Nature Communications. March 2022

Ravi Prakash, Eram Fauzia, Abu Junaid Siddiqui, Santosh Kumar Yadav, Neha Kumari, Mohammad Tayyab Shams , Abdul Naeem, Prakash P Praharaj , Mohsin Ali Khan , Sujit Kumar Bhutia, Miroslaw Janowski , Johannes Boltze, Syed Shadab Raza

Stem cell therapies have emerged as a promising treatment strategy for various diseases characterized by ischemic injury such as ischemic stroke. Cell survival after transplantation remains a critical issue. We investigated the impact of oxidative stress, being typically present in ischemically challenged tissue, on human dental pulp (hDPSC) and mesenchymal stem cell (hMSC). Our findings contribute to a better understanding of post-transplantation hDPSC and hMSC death and may inform strategies to minimize therapeutic cell loss under oxidative stress.

Stem Cells. March 2022