Hydrogen isotope values (δD) of sedimentary aquatic and terrestrial lipid biomarkers, originating from algae, bacteria, and leaf wax, have been used to record isotopic properties of ancient source ...water (i.e., precipitation and/or lake water) in several mid- and high-latitude lacustrine environments. In the tropics, however, where both processes associated with isotope fractionation in the hydrologic system and vegetation strongly differ from those at higher latitudes, calibration studies for this proxy are not yet available. To close this gap of knowledge, we sampled surface sediments from 11 lakes in Cameroon to identify those hydro-climatological processes and physiological factors that determine the hydrogen isotopic composition of aquatic and terrestrial lipid biomarkers. Here we present a robust framework for the application of compound-specific hydrogen isotopes in tropical Africa. Our results show that the δD values of the aquatic lipid biomarker n-C17 alkane were not correlated with the δD values of lake water. Carbon isotope measurements indicate that the n-C17 alkane was derived from multiple source organisms that used different hydrogen pools for biosynthesis. We demonstrate that the δD values of the n-C29 alkane were correlated with the δD values of surface water (i.e., river water and groundwater), which, on large spatial scales, reflect the isotopic composition of mean annual precipitation. Such a relationship has been observed at higher latitudes, supporting the robustness of the leaf-wax lipid δD proxy on a hemispheric spatial scale. In contrast, the δD values of the n-C31 alkane did not show such a relationship but instead were correlated with the evaporative lake water δD values. This result suggests distinct water sources for both leaf-wax lipids, most likely originating from two different groups of plants. These new findings have important implications for the interpretation of long-chain n-alkane δD records from ancient lake sediments. In particular, a robust interpretation of palaeohydrological data requires knowledge of the vegetation in the catchment area as different plants may utilise different water sources. Our results also suggest that the combination of carbon and hydrogen isotopes does help to differentiate between the metabolic pathway and/or growth form of organisms and therefore, the source of hydrogen used during lipid biosynthesis.
Trees and shrubs in tropical Africa use the C-3 cycle as a carbon fixation pathway during photosynthesis, while grasses and sedges mostly use the C-4 cycle. Leaf-wax lipids from sedimentary archives ...such as the long-chain n-alkanes (e.g., n-C-27 to n-C-33) inherit carbon isotope ratios that are representative of the carbon fixation pathway. Therefore, n-alkane delta C-13 values are often used to reconstruct past C-3/C-4 composition of vegetation, assuming that the relative proportions of C-3 and C-4 leaf waxes reflect the relative proportions of C-3 and C-4 plants. We have compared the delta C-13 values of n-alkanes from modern C-3 and C-4 plants with previously published values from recent lake sediments and provide a framework for estimating the fractional contribution (areal-based) of C-3 vegetation cover (f(C3)) represented by these sedimentary archives. Samples were collected in Cameroon, across a latitudinal transect that accommodates a wide range of climate zones and vegetation types, as reflected in the progressive northward replacement of C-3-dominated rain forest by C-4-dominated savanna. The C-3 plants analysed were characterised by substantially higher abundances of n-C-29 alkanes and by substantially lower abundances of n-C-33 alkanes than the C-4 plants. Furthermore, the sedimentary delta C-13 values of n-C-29 and n-C-31 alkanes from recent lake sediments in Cameroon (-37.4%) to 26.5%) were generally within the range of delta C-13 values for C-3 plants, even when from sites where C-4 plants dominated the catchment vegetation. In such cases simple linear mixing models fail to accurately reconstruct the relative proportions of C-3 and C-4 vegetation cover when using the delta C-13 values of sedimentary n-alkanes, overestimating the proportion of C-3 vegetation, likely as a consequence of the differences in plant wax production, preservation, transport, and/or deposition between C-3 and C-4 plants. We therefore tested a set of non-linear binary mixing models using delta C-13 values from both C-3 and C-4 vegetation as end-members. The non-linear models included a sigmoid function (sine-squared) that describes small variations in the f(C3) values as the minimum and maximum delta C-13 values are approached, and a hyperbolic function that takes into account the differences between C-3 and C-4 plants discussed above. Model fitting and the estimation of uncertainties were completed using the Monte Carlo algorithm and can be improved by future data addition. Models that provided the best fit with the observed delta C-13 values of sedimentary n-alkanes were either hyperbolic functions or a combination of hyperbolic and sine-squared functions. Such non-linear models may be used to convert delta C-13 measurements on sedimentary n-alkanes directly into reconstructions of C-3 vegetation cover.
It is well established that axonal Neuregulin 1 type 3 (NRG1t3) regulates developmental myelin formation as well as EGR2‐dependent gene activation and lipid synthesis. However, in peripheral ...neuropathy disease context, elevated axonal NRG1t3 improves remyelination and myelin sheath thickness without increasing Egr2 expression or activity, and without affecting the transcriptional activity of canonical myelination genes. Surprisingly, Pmp2, encoding for a myelin fatty acid binding protein, is the only gene whose expression increases in Schwann cells following overexpression of axonal NRG1t3. Here, we demonstrate PMP2 expression is directly regulated by NRG1t3 active form, following proteolytic cleavage. Then, using a transgenic mouse model overexpressing axonal NRG1t3 (NRG1t3OE) and knocked out for PMP2, we demonstrate that PMP2 is required for NRG1t3‐mediated remyelination. We demonstrate that the sustained expression of Pmp2 in NRG1t3OE mice enhances the fatty acid uptake in sciatic nerve fibers and the mitochondrial ATP production in Schwann cells. In sum, our findings demonstrate that PMP2 is a direct downstream mediator of NRG1t3 and that the modulation of PMP2 downstream NRG1t3 activation has distinct effects on Schwann cell function during developmental myelination and remyelination.
Main Point
PMP2 is a downstream promyelinating mediator of NRG1t3‐mediated remyelination.
Abstract
Myelin sheath thickness is precisely regulated and essential for rapid propagation of action potentials along myelinated axons. In the peripheral nervous system, extrinsic signals from the ...axonal protein neuregulin 1 (NRG1) type III regulate Schwann cell fate and myelination. Here we ask if modulating NRG1 type III levels in neurons would restore myelination in a model of congenital hypomyelinating neuropathy (CHN). Using a mouse model of CHN, we improved the myelination defects by early overexpression of NRG1 type III. Surprisingly, the improvement was independent from the upregulation of Egr2 or essential myelin genes. Rather, we observed the activation of MAPK/ERK and other myelin genes such as peripheral myelin protein 2 and oligodendrocyte myelin glycoprotein. We also confirmed that the permanent activation of MAPK/ERK in Schwann cells has detrimental effects on myelination. Our findings demonstrate that the modulation of axon-to-glial NRG1 type III signaling has beneficial effects and improves myelination defects during development in a model of CHN.
Self-supervised learning (SSL) is at the origin of unprecedented improvements in many different domains including computer vision and natural language processing. Speech processing drastically ...benefitted from SSL as most of the current domain-related tasks are now being approached with pre-trained models. This work introduces LeBenchmark 2.0 an open-source framework for assessing and building SSL-equipped French speech technologies. It includes documented, large-scale and heterogeneous corpora with up to 14,000 h of heterogeneous speech, ten pre-trained SSL wav2vec 2.0 models containing from 26 million to one billion learnable parameters shared with the community, and an evaluation protocol made of six downstream tasks to complement existing benchmarks. LeBenchmark 2.0 also presents unique perspectives on pre-trained SSL models for speech with the investigation of frozen versus fine-tuned downstream models, task-agnostic versus task-specific pre-trained models as well as a discussion on the carbon footprint of large-scale model training. Overall, the newly introduced models trained on 14,000 h of French speech outperform multilingual and previous LeBenchmark SSL models across the benchmark but also required up to four times more energy for pre-training.
•Open-source framework for assessing self-supervised representations in the French language.•14,000 h of heterogeneous speech documented into four datasets.•14 pre-trained self-supervised models for French, ranging from 26 to 965 million neural parameters.•6 standardized tasks for the evaluation of French self-supervised models.
The High Brilliance neutron Source (HBS) is a project for a next generation neutron research facility, based on new concepts and recent technological advancements. As elementary processes it uses ...neither fission nor spallation, but instead low energy nuclear reactions in a very compact Target-ModeratorReflector (TMR) assembly. Our facility design results in very efficient production of neutron beams with high brightness. Key features of HBS are: (i) very competitive instrument performance, (ii) comparatively low construction and operation costs, (iii) resilience, (iv) sustainability, (v) flexibility, (vi) accessibility and (vii) scalability. Here we present the basic layout of the facility, elaborate on the mentioned key features and report on the commissioning of a small test setup.
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