糖心TV

Zuyu Yang, Heather Davies, Jane Clapham, Liza Lopez, Holly B Bratcher, Audrey Tong, Xavier Didelot, Martin C.J. Maiden, Philip E. Carter, Xiaoyun Ren

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD), a form of bacterial meningitis and septicaemia, leading to isolated cases, outbreaks, and epidemics worldwide. Between 1991 and 2008, Aotearoa/New Zealand (NZ) experienced a prolonged hyperendemic group B IMD outbreak caused by the NZMenB epidemic strain. To understand NZMenB origin and initiation we used phylodynamic tools to analyse approximately 97鈥�% of all NZMenB isolates submitted to the NZ Meningococcal Reference Laboratory from 1990 to 2019.. Our evidence from molecular dating and clonal expansion analysis suggests that NZMenB was circulating and had expanded before the epidemic. Comparison with international data showed multiple importations and re-introductions of NZMenB into NZ, while not suggesting close relationships with international variants. We propose the NZMenB epidemic may have been triggered by increasing societal inequality and household crowding resulting from government policies at the time.

Huazhen Liu, Lakshminarayan M. Iyer, Paul Norris, Ruiying Liu, Keshun Yu, Murray Grant, L. Aravind, Aardra Kachroo & Pradeep Kachroo

Dietary consumption of lysine in humans leads to the biosynthesis of 螖¹-piperideine-6-carboxylic acid (P6C), with elevated levels linked to the neurological disorder epilepsy. Here we demonstrate that P6C biosynthesis is also a critical component of lysine catabolism in Arabidopsis thaliana. P6C regulates vitamin B6 homeostasis, and increased P6C levels deplete B6 vitamers, resulting in compromised plant immunity. We further establish a key role for pyridoxal and pyridoxal-5-phosphate biosynthesis in plant immunity. Our analysis indicates that P6C metabolism probably evolved through combining select lysine and proline metabolic enzymes horizontally acquired from diverse bacterial sources at different points during evolution. More generally, certain enzymes from the lysine and proline metabolic pathways were probably recruited in evolution as potential guardians of B6 vitamers and for semialdehyde detoxification.

Emma Short, Robert T.R. Huckstepp et al

It is paramount that the language used in the scienitifc and medical literature is clear and unambiguous to ensure shared understanding amongst researchers, clinicians, and policymakers. The aim of the ICCARP is to develop a systematic and comprehensive classifcation system for ageingrelated changes including pathologies, diseases, and syndromes. Currently, the ICCARP is in the process of identifying all phenomena that meet the criteria for ageing-related pathologies, to develop proposals for grouping and naming them within a comprehensive classification system. We expect that these defnitions, and subsequent classifcations, will contribute to improving discourse, research methodologies, clinical diagnostics, and public health planning.

Alexander R Kaye, Giorgio Guzzetta, Michael J Tildesley

For many infectious diseases, the risk of outbreaks varies seasonally. If a pathogen is usually absent from a host population, a key public health policy question is whether the pathogen鈥檚 arrival will initiate local transmission, which depends on the season in which arrival occurs. This question can be addressed by estimating the 鈥減robability of a major outbreak鈥� (the probability that introduced cases will initiate sustained local transmission). We have devised an approach for inferring outbreak risks for seasonal pathogens (involving calculating the Threshold Epidemic Risk; TER). Estimation of the TER involves calculating the probability that introduced cases will initiate a local outbreak in which a threshold number of cumulative infections is exceeded before outbreak extinction. For simple seasonal epidemic models, such as the stochastic Susceptible-Infectious-Removed model, the TER can be calculated numerically (without model simulations). For more complex models, such as stochastic host-vector models, the TER can be estimated using model simulations.

Tohidul Islam et al, including Emily Hill & Mark J Wall

Patients with Alzheimer鈥檚 disease (AD) with little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those with advanced NFTs. The formation of NFTs can be prevented by targeting the intermediate soluble tau assemblies (STAs). However, biochemical understanding and biomarkers of STAs are lacking. Our findings inform about the status of early-stage tau aggregation, reveal aggregation-relevant phosphorylation epitopes in tau and offer a diagnostic biomarker and targeted therapeutic opportunities for AD.

Press Release

Sarbjit Nijjar, Deborah Brotherton, Jack Butler, Valentin-Mihai Dospinescu, Harry G Gannon, Victoria Linthwaite, Martin Cann, Alexander Cameron, Nicholas Dale 

CO₂ directly modifies the gating of connexin26 (Cx26) gap junction channels and hemichannels. This gating depends upon Lys125, and the proposed mechanism involves carbamylation of Lys125 to allow formation of a salt bridge with Arg104 on the neighbouring subunit. We demonstrate via carbamate trapping and tandem mass spectrometry that five Lys residues within the cytoplasmic loop, including Lys125, are indeed carbamylated by CO₂ . Our findings directly demonstrate carbamylation in connexins, provide further insight into the differential action of CO₂ on Cx26 hemichannels and gap junction channels, and increase support for the role of the N-terminus in gating the Cx26 channel. KEY POINTS: Direct evidence of carbamylation of multiple lysine residues in the cytoplasmic loop of Cx26. Concentration-dependent carbamylation at lysines 108, 122 and 125. Only carbamylation of lysine 125 is essential for hemichannel opening to CO₂. Carbamylation of lysine 108 along with lysine 125 is essential for CO₂-dependent gap junction channel closure.