Johannes Boltze publications
Status dystonicus in adult patients with anti-N-methyl-D-1 aspartate-acid receptor encephalitis
Zhang Y., Cui L., Chen W., Huang H., Liu G., Su Y., Boltze J.
Status dystonicus (SD) is a severe movement disorder (MD) and has rarely been recognized in anti-N-methyl-D-aspartate-acid receptor (NMDAR) encephalitis, particularly in adult patients. We aimed to explore the clinical characteristics and outcome of SD in anti-NMDAR encephalitis. A total of 172 patients with anti-NMDAR encephalitis admitted to Xuanwu Hospital from July 2013 to December 2019 were prospectively enrolled.. Eighty patients (presented with movement disorder, 14 of whom suffered from SD, which manifested as chorea orofacial dyskinesia, generalized dystonia, tremor, stereotypies, and catatonia of the trunk and limbs. All SD patients exhibited disturbed consciousness and central hypoventilation, requiring intensive care. SD patients also had high cerebrospinal fluid NMDAR antibody titers, a higher proportion of ovarian teratoma, higher mRS scores upon enrollment, longer duration to recover, and poorer outcomes at 6 (P < 0.05) but not at 12 months as compared to non-SD patients. Journal of Neurology. February 2023
MCC950 regulates stem cells destiny through modulating SIRT3-NLRP3 inflammasome dynamics during oxygen glucose deprivation-induced oxidative and inflammatory stress
Prakash R., Kumari N., Siddiqui A.J., Khan A.Q., Khan M.A., Khan R., Haque R., Robertson A.A.B., Boltze J., Raza S.S.
This study examines the influence of oxidative and inflammatory pathological events associated with experimental ischemic stroke (oxygen glucose deprivation (OGD)) on the stem cell population (human Dental Pulp Stem Cells, and human Mesenchymal Stem Cells) through the involvement of the NLRP3 inflammasome. We explored the destiny of the above-mentioned stem cells in the stressed micro (-environment) and the ability of MCC950 to reverse the magnitudes. In brief, we discovered that MCC950 inhibits NLRP3-mediated inflammation by inhibiting the NLRP3 inflammasome and increasing SIRT3. To conclude, according to our findings, inhibiting NLRP3 activation while enhancing SIRT3 levels with MCC950 reduces oxidative and inflammatory stress in stem cells under OGD-induced stress. These findings shed light on the causes of hDPSC and hMSC demise following transplantation and point to strategies to lessen therapeutic cell loss under ischemic-reperfusion stress.
The impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England
Matt J. Keeling, Samuel Moore, Bridget S. Penman & Edward M. Hill
In late 2020, the Joint Committee on Vaccination and Immunisation, which provides advice to the Department of Health and Social Care, England made two important recommendations for the initial roll-out of the COVID-19 vaccine. The first was that vaccines should be targeted to older and vulnerable people, with the aim of maximally preventing disease rather than infection. The second was to increase the interval between first and second doses from 3 to 12 weeks. Here, we re-examine these recommendations through a mathematical model of SARS-CoV-2 infection in England. We show that targeting the most vulnerable had the biggest immediate impact. The 12-week delay was also highly beneficial, estimated to have averted between 32-72 thousand hospital admissions and 4-9 thousand deaths over the first ten months of the campaign depending on the assumed interaction between dose interval and efficacy.
Soil colloidal particles in a subtropical savanna: Biogeochemical significance and influence of anthropogenic disturbances
Qian Zhang, Thomas W Boutton, Che-Jen Hsiao, Ryan M Mushinski, Liming Wang, Roland Bol, Erwin Klumpp
Soil colloids (diameter < 1000 nm) are comprised mainly of clay minerals and organic matter, and play major roles in determining ion exchange capacity and in regulating key biogeochemical processes. Consequently, it is important to understand how soil colloids and their functions are influenced by land cover and anthropogenic disturbances. In grasslands, savannas, and other dryland ecosystems across the globe, woody plants are encroaching due to livestock grazing, fire suppression, elevated CO2 concentrations, and climate change. These major land cover changes could influence soil colloidal properties, with implications for soil C, N, and P cycles. We assessed how woody encroachment, livestock grazing, and fire interact to influence soil colloidal properties in a juniper-oak savanna. Moderate grazing did not affect the retention of colloidal P, while heavy grazing potentially increased the loss risk of colloidal P. Fire accelerated soil P loss from colloid fractions only in woody areas. Our findings highlight that woody encroachment strengthens the retention of OC and P by soil colloids, consequently increasing overall C and P pools in savanna soils.
Structural basis for membrane attack complex inhibition by CD59
Emma C. Couves, Scott Gardner, Tomas B. Voisin, Jasmine K. Bickel, Phillip J. Stansfeld, Edward W. Tate & Doryen Bubeck
CD59 is an abundant immuno-regulatory receptor that protects human cells from damage during complement activation. Here we show how the receptor binds complement proteins C8 and C9 at the membrane to prevent insertion and polymerization of membrane attack complex (MAC) pores. We present cryo-electron microscopy structures of two inhibited MAC precursors known as C5b8 and C5b9. We discover that in both complexes, CD59 binds the pore-forming β-hairpins of C8 to form an intermolecular β-sheet that prevents membrane perforation. While bound to C8, CD59 deflects the cascading C9 β-hairpins, rerouting their trajectory into the membrane. Preventing insertion of C9 restricts structural transitions of subsequent monomers and indirectly halts MAC polymerization. We combine our structural data with cellular assays and molecular dynamics simulations to explain how the membrane environment impacts the dual roles of CD59 in controlling pore formation of MAC, and as a target of bacterial virulence factors which hijack CD59 to lyse human cells.
The mammalian purine salvage pathway as an exploitable route for cerebral bioenergetic support after brain injury
Philipp Gessner, Jenni Lum, Bruno G Frenguelli
Purine-based molecules play ancient, fundamental, and evolutionarily-conserved roles across life on Earth, ranging from DNA and RNA, to the universal energy currency, ATP. Having previously shown that hippocampal cellular ATP and adenosine release can be increased by supplying substrates for the PSP (d-ribose and adenine), we now explore the expression of DNPB and PSP enzymes in hippocampal neurons and astrocytes based on available transcriptomic data. We find that key enzymes of the PSP are expressed at higher levels than those in the DNPB pathway, and that PSP enzymes are expressed at higher levels in neurons than in astrocytes. These data reflect the importance of the PSP in the mammalian brain and imply that pharmacological targeting of the PSP may be particularly beneficial to neurons at times of metabolic stress.
Tipburn Resilience in Lettuce (Lactuca spp.) – The Importance of Germplasm Resources and Production System-Specific Assays
Andrew M Beacham, Paul Hand, Graham R Teakle, Guy C Barker, David A C Pink and James M Monaghan
Tipburn is a physiological disorder of lettuce (Lactuca spp.) that causes discolouration and collapse of leaf margins, leading to unsaleable crops in both and outdoor production systems. Phenotyping for tipburn resilience requires diverse germplasm resources and to date limited material has been investigated for this condition. Using a Lactuca Diversity Fixed Foundation Set (DFFS) under glasshouse conditions, we identified a significant genotypic effect on tipburn resilience across both the entire population and across lines belonging to the cultivated species, L. sativa, alone. The results reflect the benefit of phenotyping under production system-specific conditions for the examination of environmentally sensitive traits and highlight genetic markers and germplasm resources for the development of tipburn resilient lines for use in both protected and outdoor lettuce production.
Journal of the Science of Food and Agriculture. February 2023