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Nicotiana benthamiana is increasingly used for transient gene expression to produce antibodies, vaccines, and other pharmaceutical proteins but transient gene expression is low in fully developed, 6–8‐week old plants. This low gene expression is thought to be caused by the perception of the cold shock protein (CSP) of Agrobacterium tumefaciens . The CSP receptor is contested because both Nb CSPR and Nb CORE have been claimed to perceive CSP. Here, we demonstrate that CSP perception is abolished in 6‐week‐old plants silenced for Nb CORE but not Nb CSPR. Importantly, older Nb CORE‐silenced plants support a highly increased level of GFP fluorescence and protein upon agroinfiltration. The drastic increase in transient protein production in Nb CORE‐depleted plants offers new opportunities for molecular farming, where older plants with larger biomass can now be used for efficient protein expression.

The clinical phenotypes of human CoQ10‐deficiency caused by COQ2 mutations range from fatal neonatal disease to adult‐onset multisystem atrophy. So far, treatment options for these diseases are unsatisfactory. Here, we demonstrate that supplementation of 4‐hydroxybenzoic acid (4‐HBA) fully restores endogenous CoQ10‐biosynthesis in COQ2‐deficient cell lines. This was accompanied by increased protein expression of CoQ10‐biosynthesis‐enzymes as well as a rescue of cell viability during stress conditions. In silico analysis suggested a ligand transportation path for 4‐HBA through the COQ2 protein towards the mitochondrial matrix side. This process is apparently hindered by disease‐causing mutations, which can be overcome by increasing 4‐HBA concentrations.

The role of T cells in autoimmune encephalitis syndromes with autoantibodies against cell surface antigens is still enigmatic. Here we analyzed the T cell receptor repertoires of CD8+ and CD4+ T cells in a patient with “idiopathic” gamma‐aminobutyric‐acid‐A receptor (GABAA‐R) encephalitis by next‐generation sequencing and single‐cell analyses. We identified a CD8+ T cell clone that was strongly expanded in the cerebrospinal fluid and in the hippocampus but not in the operculo‐insular cortex. By contrast, CD4+ T cells were polyclonal in these tissues. Such a strong clonal expansion suggests that CD8+ T cells may play a significant role in the pathogenesis.

Arising from J. D. Bowman, A. E. E. Rogers, R. A. Monsalve, T. J. Mozdzen & N. Mahesh Nature 555, 67-70 (2018); https://doi.org/10.1038/nature25792 It is predicted1 that the spectrum of radio emission from the whole sky should show a dip arising from the action of the light from the first stars on the hydrogen atoms in the surrounding gas, which causes the 21-cm line to appear in absorption against the cosmic microwave background. Since the proposed 21-cm absorption profile does not match theoretical expectations in either shape or amplitude, it is not clear why it should be preferred to the other forms of signal explored here or to the many more that can be found in the degenerate space between signal and foreground model. [...]although our analysis does not prove that the feature identified by Bowman et al.2 is absent from their data, we believe the issues that we have raised are such that the evidence for its presence falls well short of the level required to invoke new physics for its explanation. Richard Hills1·, Girish Kulkami2'3'7, P. Daniel Meerburg2'3'4'5'6 & Ewald Puchwein2'3'8 1Cavendish Laboratory, University of Cambridge, Cambridge, UK. 2Institute of Astronomy, University of Cambridge, Cambridge, UK. 3Kavli Institute for Cosmology, University of Cambridge, Cambridge, UK. 4Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, UK. 5Kapteyn Astronomical Institute, University of Groningen, Groningen, The Netherlands. 6Van Swinderen Institute for Particle Physics and Gravity, University of Groningen, Groningen, The Netherlands. 7Present address: Department of Theoretical Physics, Tata Institute of Fundamental Research, Mumbai, India. 8Present address:

The prevalence of autism spectrum disorders (ASDs), which affect over 1% of the population, has increased twofold in recent years. Reduced expression of GABAA receptors has been observed in postmortem brain tissue and neuroimaging of individuals with ASDs. We found that deletion of the gene for the α5 subunit of the GABAA receptor caused robust autism‐like behaviors in mice, including reduced social contacts and vocalizations. Screening of human exome sequencing data from 396 ASD subjects revealed potential missense mutations in GABRA5 and in RDX, the gene for the α5GABAA receptor‐anchoring protein radixin, further supporting a α5GABAA receptor deficiency in ASDs.

We have developed a novel real‐time quaking‐induced conversion RT‐QuIC‐based assay to detect alpha‐synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha‐synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT‐QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha‐synucleinopathies.

Studies using 16S rRNA and shotgun metagenomics typically yield different results, usually attributed to PCR amplification biases. We introduce Greengenes2, a reference tree that unifies genomic and 16S rRNA databases in a consistent, integrated resource. By inserting sequences into a whole-genome phylogeny, we show that 16S rRNA and shotgun metagenomic data generated from the same samples agree in principal coordinates space, taxonomy and phenotype effect size when analyzed with the same tree. A comprehensive microbial resource reconciles genomic and 16S rRNA data in a single tree.

As structure prediction methods are generating millions of publicly available protein structures, searching these databases is becoming a bottleneck. Foldseek aligns the structure of a query protein against a database by describing tertiary amino acid interactions within proteins as sequences over a structural alphabet. Foldseek decreases computation times by four to five orders of magnitude with 86%, 88% and 133% of the sensitivities of Dali, TM-align and CE, respectively. Foldseek speeds up protein structural search by four to five orders of magnitude.