TDP-43 loss-of-function causes neuronal loss due to defective steroid receptor-mediated gene program switching in Drosophila

TDP-43 proteinopathy is strongly implicated in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative disorders. Whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function is unknown. We increased and decreased expression of TDP-43 (dTDP-43) in Drosophila. Although upregulation of dTDP-43 induced neuronal ubiquitin and dTDP-43-positive inclusions, both up-and downregulated dTDP-43 resulted in selective apoptosis of bursicon neurons and highly similar transcriptome alterations at the pupal-adult transition. Gene network analysis and genetic validation showed that both up-and downregulated dTDP-43 directly and dramatically increased the expression of the neuronal microtubule-associated protein Map205, resulting in cytoplasmic accumulations of the ecdysteroid receptor (EcR) and a failure to switch EcR-dependent gene programs from a pupal to adult pattern. We propose that dTDP-43 neurotoxicity is caused by a loss of its normal function

Overcoming non-radiative losses with AlGaAs PIN junctions for near-field thermophotonic energy harvesting

In a thermophotonic device used in an energy-harvesting configuration, a hot light-emitting diode (LED) is coupled to a photovoltaic (PV) cell by means of electroluminescent radiation in order to produce electrical power. Using fluctuational electrodynamics and the drift-diffusion equations, we optimise a device made of an AlGaAs PIN LED and a GaAs PIN PV cell with matched bandgaps. We find that the LED can work as an efficient heat pump only in the near field, where radiative heat transfer is increased by wave tunnelling. A key reason is that non-radiative recombination rates are reduced compared to radiative ones in this regime. At 10 nm gap distance and for 100 cm.s --1 effective surface recombination velocity, the power output can reach 2.2 W.cm --2 for a 600 K LED, which highlights the potential for low-grade energy harvesting

Methylation profiling RIN3 and MEF2C identifies epigenetic marks associated with sporadic early onset Alzheimer’s disease

A number of genetic loci associate with early onset Alzheimer’s disease (EOAD), however the drivers of this disease remains enigmatic. Genome wide association and in-vivo modelling have shown that loss-of-function e.g. ABCA7, reduced levels of SIRT1, MEFF2C or increases levels of PTK2β confer risk or link to the pathogenies. It is known that DNA methylation can profoundly affect gene expression and can impact on the composition of the proteome, therefore the aim of this study is to assess if genes associated with sporadic EOAD are differentially methylated. Epi-profiles of DNA extracted from blood and cortex were compared using a pyrosequencing platform. We identified significant group-wide hypomethylation in AD blood when compared to controls for 7 CpGs located within the 3’UTR of RIN3 (CpG1 P=0.019, CpG2 p=0.018, CpG3 p=0.012, CpG4 p=0.009, CpG5 p=0.002, CpG6 p=0.018 and CpG7 p=0.013 respectively; AD / Control n=22 / 26; Male / Female, 27 / 21). Observed effects were not gender specific. No group wide significant differences were found in the promoter methylation of PTK2β, ABCA7, SIRT1 or MEF2C, genes known to associate with LOAD. A rare and significant difference in methylation was observed for one CpG located upstream of the MEF2C promoter in one AD individual only (22% reduction in methylation, p=2.0E-10; Control n=26, AD n=25, Male / Female n=29 / 22). It is plausible aberrant methylation may mark sEOAD in blood and may manifest in some individuals as rare epi-variants for genes linked to sEOAD

The best of two worlds: toward large-cale monitoring of biodiversity combining COI metabarcoding and optimized parataxonomic validation

In a context of unprecedented insect decline, it is critical to have reliable monitoring tools to measure species diversity and their dynamic at large-scales. High-throughput DNA-based identification methods, and particularly metabarcoding, were proposed as an effective way to reach this aim. However, these identification methods are subject to multiple technical limitations, resulting in unavoidable false-positive and false-negative species detection. Moreover, metabarcoding does not allow a reliable estimation of species abundance in a given sample, which is key to document and detect population declines or range shifts at large scales. To overcome these obstacles, we propose here a human-assisted molecular identification (HAMI) approach, a framework based on a combination of metabarcoding and image-based parataxonomic validation of outputs and recording of abundance. We assessed the advantages of using HAMI over the exclusive use of a metabarcoding approach by examining 492 mixed beetle samples from a biodiversity monitoring initiative conducted throughout France. On average, 23% of the species are missed when relying exclusively on metabarcoding, this percent being consistently higher in species-rich samples. Importantly, on average, 20% of the species identified by molecular-only approaches correspond to false positives linked to cross-sample contaminations or mis-identified barcode sequences in databases. The combination of molecular methodologies and parataxonomic validation in HAMI significantly reduces the intrinsic biases of metabarcoding and recovers reliable abundance data. This approach also enables users to engage in a virtuous circle of database improvement through the identification of specimens associated with missing or incorrectly assigned barcodes. As such, HAMI fills an important gap in the toolbox available for fast and reliable biodiversity monitoring at large scales

Semantics about soil organic carbon storage: DATA4C+, a comprehensive thesaurus and classification of management practices in agriculture and forestry

Identifying the drivers of soil organic carbon (SOC) stock changes is of the utmost importance to contribute to global challenges like climate change, land degradation, biodiversity loss, or food security. Evaluating the impacts of land use and management practices in agriculture and forestry on SOC is still challenging. Merging datasets or making databases interoperable is a promising way, but still has several semantic challenges. So far, a comprehensive thesaurus and classification of management practices in agriculture and forestry has been lacking, especially while focusing on SOC storage. Therefore, the aim of this paper is to present a first comprehensive thesaurus for management practices driving SOC storage (DATA4C+). The DATA4C+ thesaurus contains 224 classified and defined terms related to land management practices in agriculture and forestry. It is organized as a hierarchical tree reflecting the drivers of SOC storage. It is oriented to be used by scientists in agronomy, forestry, and soil sciences with the aim of uniformizing the description of practices influencing SOC in their original research. It is accessible in Agroportal (http://agroportal.lirmm.fr/ontologies/DATA4CPLUS, last access: 24 March 2022) to enhance its findability, accessibility, interoperability, and reuse by scientists and others such as laboratories or land managers. Future uses of the DATA4C+ thesaurus will be crucial to improve and enrich it, but also to raise the quality of meta-analyses on SOC, and ultimately help policymakers to identify efficient agricultural and forest management practices to enhance SOC storage.</p

The structure of an amyloid precursor protein/talin complex indicates a mechanical basis of Alzheimer’s disease

Misprocessing of amyloid precursor protein (APP) is one of the major causes of Alzheimer’s disease. APP comprises a large extracellular region, a single transmembrane helix and a short cytoplasmic tail containing an NPxY motif (normally referred to as the YENPTY motif). Talins are synaptic scaffold proteins that connect the cytoskeletal machinery to the plasma membrane via binding NPxY motifs in the cytoplasmic tail of integrins. Here, we report the crystal structure of an APP/talin1 complex identifying a new way to couple the cytoskeletal machinery to synaptic sites through APP. Proximity ligation assay (PLA) confirmed the close proximity of talin1 and APP in primary neurons, and talin1 depletion had a dramatic effect on APP processing in cells. Structural modelling reveals APP might form an extracellular meshwork that mechanically couples the cytoskeletons of the pre- and post-synaptic compartments. We propose APP processing represents a mechanical signalling pathway whereby under tension, the cleavage sites in APP have varying accessibility to cleavage by secretases. This leads us to propose a new hypothesis for Alzheimer’s, where misregulated APP dynamics result in loss of the mechanical integrity of the synapse, corruption and loss of mechanical binary data, and excessive generation of toxic plaque-forming Aβ42 peptide