Human cerebrospinal fluid monoclonal LGI1 autoantibodies increase neuronal excitability

OBJECTIVE: Leucine-rich glioma-inactivated 1 (LGI1) encephalitis is the second most common antibody-mediatedencephalopathy, but insight into the intrathecal B-cell autoimmune response, including clonal relationships, isotype dis-tribution, frequency, and pathogenic effects of single LGI1 antibodies, has remained limited. METHODS: We cloned, expressed, and tested antibodies from 90 antibody-secreting cells (ASCs) and B cells from thecerebrospinalfluid (CSF) of several patients with LGI1 encephalitis. RESULTS: Eighty-four percent of the ASCs and 21% of the memory B cells encoded LGI1-reactive antibodies, whereasreactivities to other brain epitopes were rare. All LGI1 antibodies were of IgG1, IgG2, or IgG4 isotype and had under-gone affinity maturation. Seven of the overall 26 LGI1 antibodies efficiently blocked the interaction of LGI1 with itsreceptor ADAM22 in vitro, and their mean LGI1 signal on mouse brain sections was weak compared to the remaining,non–ADAM22-competing antibodies. Nevertheless, both types of LGI1 antibodies increased the intrinsic cellular excit-ability and glutamatergic synaptic transmission of hippocampal CA3 neurons in slice cultures. Interpretation: Our data show that the patients’intrathecal B-cell autoimmune response is dominated by LGI1 anti-bodies and that LGI1 antibodies alone are sufficient to promote neuronal excitability, a basis of seizure generation.Fundamental differences in target specificity and antibody hypermutations compared to the CSF autoantibody reper-toire in N-methyl-D-aspartate receptor encephalitis underline the clinical concept that autoimmune encephalitides arevery distinct entities

25 Years of Self-organized Criticality: Concepts and Controversies

Introduced by the late Per Bak and his colleagues, self-organized criticality (SOC) has been one of the most stimulating concepts to come out of statistical mechanics and condensed matter theory in the last few decades, and has played a significant role in the development of complexity science. SOC, and more generally fractals and power laws, have attracted much comment, ranging from the very positive to the polemical. The other papers (Aschwanden et al. in Space Sci. Rev., 2014, this issue; McAteer et al. in Space Sci. Rev., 2015, this issue; Sharma et al. in Space Sci. Rev. 2015, in preparation) in this special issue showcase the considerable body of observations in solar, magnetospheric and fusion plasma inspired by the SOC idea, and expose the fertile role the new paradigm has played in approaches to modeling and understanding multiscale plasma instabilities. This very broad impact, and the necessary process of adapting a scientific hypothesis to the conditions of a given physical system, has meant that SOC as studied in these fields has sometimes differed significantly from the definition originally given by its creators. In Bak’s own field of theoretical physics there are significant observational and theoretical open questions, even 25 years on (Pruessner 2012). One aim of the present review is to address the dichotomy between the great reception SOC has received in some areas, and its shortcomings, as they became manifest in the controversies it triggered. Our article tries to clear up what we think are misunderstandings of SOC in fields more remote from its origins in statistical mechanics, condensed matter and dynamical systems by revisiting Bak, Tang and Wiesenfeld’s original papers

Habitat disturbance affects gut microbiota communities differently in wild arboreal and ground-feeding tropical primates

Human exploitation and destruction of natural ecosystems cause extinction of wild animal species on a global scale, and loss of gut ‘micro-biodiversity’ (bacterial and fungal communities) essential for individual nutrition and health is not excluded. While previous investigations have revealed lower gut bacterial diversity in populations living in fragmented compared to intact habitats, no data are available about the other relevant gut component: the fungi (mycobiota). Given their phylogenetic affinity to humans, their conservation status and importance to tropical ecosystems, wild non-human primates make excellent models to investigate the effect of human disturbance on this micro-biodiversity. Thus, to establish whether gut bacterial and fungal communities interact and are affected by diet and/or human disturbance we measured the diversity and composition of gut bacterial and fungal communities in two wild primate species with diverse diets living in human-modified habitats compared to pristine forests within the Udzungwa Mountains of Tanzania. We analysed non-invasively collected samples of 12 groups of Procolobus gordonorum (N = 89), the Udzungwa Red Colobus, endemic and endangered arboreal primates (mainly folivorous), and five groups of Papio cynocephalus (N = 69), the Yellow Baboon of least concern (omnivorous and ground-feeding), using metataxonomic sequencing of the partial 16S rRNA gene and ITS1-ITS2. Despite large intraspecific variability, this study revealed gut bacterial diversities are associated with habitat in both Yellow Baboons and Udzungwa Red Colobus, supporting their usage as sensitive biomarkers of habitat integrity. The details of these associations depend on host physiology and dietary habits. Moreover, gut mycobiota show distinctive traits across hosts and habitat type, resembling patterns found in gut bacterial communities and highlighting the importance of investigating this relatively unexplored gut component