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Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease (2020)

Vogel, Jacob W. ; Iturria-Medina, Yasser ; Strandberg, Olof T. ; [et al.]

Springer Nature

In: Nature Communications. 2020; 11(1): 2612. Published 2020 May 26. doi: 10.1038/s41467-020-15701-2.

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Publication Date: 2020-05-26

Description: Tau is a hallmark pathology of Alzheimer’s disease, and animal models have suggested that tau spreads from cell to cell through neuronal connections, facilitated by β-amyloid (Aβ). We test this hypothesis in humans using an epidemic spreading model (ESM) to simulate tau spread, and compare these simulations to observed patterns measured using tau-PET in 312 individuals along Alzheimer’s disease continuum. Up to 70% of the variance in the overall spatial pattern of tau can be explained by our model. Surprisingly, the ESM predicts the spatial patterns of tau irrespective of whether brain Aβ is present, but regions with greater Aβ burden show greater tau than predicted by connectivity patterns, suggesting a role of Aβ in accelerating tau spread. Altogether, our results provide evidence in humans that tau spreads through neuronal communication pathways even in normal aging, and that this process is accelerated by the presence of brain Aβ.

Electronic ISSN: 2041-1723

Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics

Published by Springer Nature

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Majority sensing in synthetic microbial consortia (2020)

Alnahhas, Razan N. ; Sadeghpour, Mehdi ; Chen, Ye ; [et al.]

Springer Nature

In: Nature Communications. 2020; 11(1): 3659. Published 2020 Jul 21. doi: 10.1038/s41467-020-17475-z.

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Publication Date: 2020-07-21

Electronic ISSN: 2041-1723

Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics

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Enhancing photovoltages at p-type semiconductors through a redox-active metal-organic framework surface coating (2020)

Beiler, Anna M. ; McCarthy, Brian D. ; Johnson, Ben A. ; [et al.]

Springer Nature

In: Nature Communications. 2020; 11(1): 5819. Published 2020 Nov 16. doi: 10.1038/s41467-020-19483-5.

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Publication Date: 2020-11-16

Description: Surface modification of semiconductors can improve photoelectrochemical performance by promoting efficient interfacial charge transfer. We show that metal-organic frameworks (MOFs) are viable surface coatings for enhancing cathodic photovoltages. Under 1-sun illumination, no photovoltage is observed for p-type Si(111) functionalized with a naphthalene diimide derivative until the monolayer is expanded in three dimensions in a MOF. The surface-grown MOF thin film at Si promotes reduction of the molecular linkers at formal potentials 〉300 mV positive of their thermodynamic potentials. The photocurrent is governed by charge diffusion through the film, and the MOF film is sufficiently conductive to power reductive transformations. When grown on GaP(100), the reductions of the MOF linkers are shifted anodically by 〉700 mV compared to those of the same MOF on conductive substrates. This photovoltage, among the highest reported for GaP in photoelectrochemical applications, illustrates the power of MOF films to enhance photocathodic operation.

Electronic ISSN: 2041-1723

Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics

Published by Springer Nature

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A neural m6A/Ythdf pathway is required for learning and memory in Drosophila (2021)

Kan, Lijuan ; Ott, Stanislav ; Joseph, Brian ; [et al.]

Springer Nature

In: Nature Communications. 2021; 12(1): 1458. Published 2021 Mar 05. doi: 10.1038/s41467-021-21537-1.

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Publication Date: 2021-03-05

Description: Epitranscriptomic modifications can impact behavior. Here, we used Drosophila melanogaster to study N6-methyladenosine (m6A), the most abundant modification of mRNA. Proteomic and functional analyses confirm its nuclear (Ythdc1) and cytoplasmic (Ythdf) YTH domain proteins as major m6A binders. Assays of short term memory in m6A mutants reveal neural-autonomous requirements of m6A writers working via Ythdf, but not Ythdc1. Furthermore, m6A/Ythdf operate specifically via the mushroom body, the center for associative learning. We map m6A from wild-type and Mettl3 mutant heads, allowing robust discrimination of Mettl3-dependent m6A sites that are highly enriched in 5’ UTRs. Genomic analyses indicate that Drosophila m6A is preferentially deposited on genes with low translational efficiency and that m6A does not affect RNA stability. Nevertheless, functional tests indicate a role for m6A/Ythdf in translational activation. Altogether, our molecular genetic analyses and tissue-specific m6A maps reveal selective behavioral and regulatory defects for the Drosophila Mettl3/Ythdf pathway.

Electronic ISSN: 2041-1723

Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics

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Publisher Correction: A neural m6A/Ythdf pathway is required for learning and memory in Drosophila (2021)

Kan, Lijuan ; Ott, Stanislav ; Joseph, Brian ; [et al.]

Springer Nature

In: Nature Communications. 2021; 12(1): 1743. Published 2021 Mar 15. doi: 10.1038/s41467-021-22219-8.

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Publication Date: 2021-03-15

Description: A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22219-8

Electronic ISSN: 2041-1723

Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics

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Structure of the native pyruvate dehydrogenase complex reveals the mechanism of substrate insertion (2021)

Škerlová, Jana ; Berndtsson, Jens ; Nolte, Hendrik ; [et al.]

Springer Nature

In: Nature Communications. 2021; 12(1): 5277. Published 2021 Sep 06. doi: 10.1038/s41467-021-25570-y.

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Publication Date: 2021-09-06

Description: The pyruvate dehydrogenase complex (PDHc) links glycolysis to the citric acid cycle by converting pyruvate into acetyl-coenzyme A. PDHc encompasses three enzymatically active subunits, namely pyruvate dehydrogenase, dihydrolipoyl transacetylase, and dihydrolipoyl dehydrogenase. Dihydrolipoyl transacetylase is a multidomain protein comprising a varying number of lipoyl domains, a peripheral subunit-binding domain, and a catalytic domain. It forms the structural core of the complex, provides binding sites for the other enzymes, and shuffles reaction intermediates between the active sites through covalently bound lipoyl domains. The molecular mechanism by which this shuttling occurs has remained elusive. Here, we report a cryo-EM reconstruction of the native E. coli dihydrolipoyl transacetylase core in a resting state. This structure provides molecular details of the assembly of the core and reveals how the lipoyl domains interact with the core at the active site.

Electronic ISSN: 2041-1723

Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics

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Sex differences in oncogenic mutational processes (2020)

Li, Constance H. ; Prokopec, Stephenie D. ; Sun, Ren X. ; [et al.]

Springer Nature

In: Nature Communications. 2020; 11(1): 4330. Published 2020 Aug 28. doi: 10.1038/s41467-020-17359-2.

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Publication Date: 2020-08-28

Description: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.

Electronic ISSN: 2041-1723

Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics

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Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples (2020)

Bailey, Matthew H. ; Meyerson, William U. ; Dursi, Lewis Jonathan ; [et al.]

Springer Nature

In: Nature Communications. 2020; 11(1): 4748. Published 2020 Sep 21. doi: 10.1038/s41467-020-18151-y.

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Publication Date: 2020-09-21

Description: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF

Electronic ISSN: 2041-1723

Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General , Physics

Published by Springer Nature

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