Tan, T. | bioRxiv Science

bioRxiv2018

Microtubules Gate Tau Condensation to Spatially Regulate Microtubule Functions

Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimers disease and other dementias, yet the physiological state of tau molecules within cells remains unclear. Using single molecule imaging, we directly observe that the microtubule lattice regulates reversible tau self-association, leading to dynamic condensation of tau molecules on the microtubule surface. Tau condensates form selectively permissible barriers, spatially regulating the activity of MT severing enzymes and the movement of molecular motors through their boundaries. We propose that reversible self-association of tau molecules, controlled by the microtubule, is an important mechanism of taus biological functions, and that oligomerization of tau is a common property shared between the physiological and disease forms of the molecule.\n\nOne Sentence SummaryReversible tau oligomerization regulates microtubule functions.

biophysics↗

bioRxiv2018

Characterisation of carried and invasive Neisseria meningitidis isolates in Shanghai, China from 1950 to 2016: implications for serogroup B vaccine implementation

BackgroundSerogroup B invasive meningococcal disease (IMD) is increasing in China, little is known however, about these meningococci. This study characterises a collection of isolates associated with IMD and carriage in Shanghai and assesses current vaccine strategies.\n\nMethodsIMD epidemiological data in Shanghai from 1950-2016 were obtained from the National Notifiable Diseases Registry System, with 460 isolates collected for analysis including, 169 from IMD and 291 from carriage. Serogroup B meningococcal (MenB) vaccine coverage was evaluated using Bexsero(R) Antigen Sequence Type (BAST).\n\nResultsSeven IMD epidemic periods have been observed in Shanghai since 1950, with incidence peaking from February to April. Analyses were divided according to the period of meningococcal polysaccharide vaccine (MPV) introduction: (i) pre-MPV-A, 1965-1980; (ii) post-MPV-A, 1981-2008; and (iii) post-MPV-A+C, 2009-2016. IMD incidence decreased from 55.4/100,000 to 0.71 then to 0.02, and corresponded with shifts from serogroup A ST-5 complex (MenA:cc5) to MenC:cc4821 then MenB:cc4821. MenB IMD became predominant (63.2%) in the post-MPV-A+C period, of which 50% were caused by cc4821, with the highest incidence in infants (0.45/100,000) and a case-fatality rate of 9.5%. IMD was positively correlated with carriage rates. Data indicate that fewer than 25% of MenB isolates in the post-MPV-A+C period may be covered by the vaccines Bexsero(R), Trumenba(R), or a PorA-based vaccine, NonaMen.\n\nConclusionsA unique IMD epidemiology is found in China, changing periodically from hyperepidemic to low-level endemic disease. MenB IMD now dominates in Shanghai, with isolates harbouring diverse antigenic variants potentially beyond coverage with licenced OMV- and protein-based MenB vaccines.\n\nSummaryMeningococcal disease in Shanghai, China is described and current vaccine approaches evaluated. Since 1950, MenA:cc5 shifted to MenC:cc4821 then MenB:cc4821, with MenB dominating since 2009. Distinct antigens potentially beyond coverage with licensed OMV- and protein-based MenB vaccines were found.

epidemiology↗