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C9ORF72hexanucleotide repeat expansion is the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). One pathogenic mechanism is the accumulation of toxic dipeptide repeat (DPR) proteins like poly-GA, GP and GR, produced by the noncanonical translation of the expanded RNA repeats. However, how different DPRs are synthesized remains elusive. Here, we use single-molecule imaging techniques to directly measure the translation dynamics of different DPRs. Besides initiation, translation elongation rates vary drastically between different frames, with GP slower than GA and GR the slowest. We directly visualize frameshift events using a two-color single-molecule translation assay. The repeat expansion enhances frameshifting, but the overall frequency is low. There is a higher chance of GR-to-GA shift than in the reversed direction. Finally, the ribosome-associated protein quality control (RQC) factors ZNF598 and Pelota modulate the translation dynamics, and the repeat RNA sequence is important for invoking the RQC pathway. This study reveals that multiple translation steps modulate the final DPR production. Understanding repeat RNA translation is critically important to decipher the DPR-mediated pathogenesis and identify potential therapeutic targets in C9ORF72-ALS/FTD.

 

In paleoceanography, carbon and oxygen stable isotope ratios from benthic foraminifera are used as tracers of physical and biogeochemical properties of the deep ocean. We present the first version of the Ocean Carbon Cycling working group database,  of stable isotope ratios of oxygen and carbon from benthic foraminifera from deep ocean sediment cores from the Last Glacial Maximum (LGM, 23-20 ky before present (BP)) to the Holocene (<10 ky BP) with a particular focus on the early last deglaciation (20-15 ky BP). It includes 287 globally distributed coring sites, with metadata, isotopic and chronostratigraphic information, and age models. A quality check was performed for all data and age models. Sites with at least millennial resolution were preferred, because the main goal is to resolve ocean changes associated with the last deglaciation on at least millennial timescales. Software tools were produced to access and analyze the data, and are included with this publication. Deep water mass structure as well as differences between the early deglaciation and LGM are captured by the data in the compilation, even though its coverage is still sparse in many ocean regions. We find high correlations among time series calculated with different age models at sites that allow such analysis. The database provides a useful dynamical approach to map physical and biogeochemical changes of the ocean throughout the last deglaciation.

Custom python scripts to read and analyze the data base may be found in https://github.com/juanmuglia/OC3-python-scripts and in OC3-python-scripts.zip in this repository. plots_d13c.pdf and plots_d18o.pdf contain time series for all sites and available age models. 

We present the first version of the Ocean Circulation and Carbon Cycling (OC3) working group database, of oxygen and carbon stable isotope ratios from benthic foraminifera in deep ocean sediment cores from the Last Glacial Maximum (LGM, 23-19 ky) to the Holocene (<10 ky) with a particular focus on the early last deglaciation (19-15 ky BP). It includes 287 globally distributed coring sites, with metadata, isotopic and chronostratigraphic information, and age models. A quality check was performed for all data and age models, and sites with at least millennial resolution were preferred. Deep water mass structure as well as differences between the early deglaciation and LGM are captured by the data, even though its coverage is still sparse in many regions. We find high correlations among time series calculated with different age models at sites that allow such analysis. The database provides a useful dynamical approach to map physical and biogeochemical changes of the ocean throughout the last deglaciation.

 

Antibodies are indispensable tools used for a large number of applications in both foundational and translational bioscience research; however, there are drawbacks to using traditional antibodies generated in animals. These include a lack of standardization leading to problems with reproducibility, high costs of antibodies purchased from commercial sources, and ethical concerns regarding the large number of animals used to generate antibodies. To address these issues, we have developed practical methodologies and tools for generating low-cost, high-yield preparations of recombinant monoclonal antibodies and antibody fragments directed to protein epitopes from primary sequences. We describe these methods here, as well as approaches to diversify monoclonal antibodies, including customization of antibody species specificity, generation of genetically encoded small antibody fragments, and conversion of single chain antibody fragments (e.g. scFv) into full-length, bivalent antibodies. This study focuses on antibodies directed to epitopes important for mitosis and kinetochore function; however, the methods and reagents described here are applicable to antibodies and antibody fragments for use in any field. 

The Nd isotope composition of seawater has been used to reconstruct past changes in the contribution of different water masses to the deep ocean. In the absence of contrary information, the Nd isotope compositions of endmember water masses are usually assumed constant during the Quaternary. Here we show that the Nd isotope composition of North Atlantic Deep Water (NADW), a major component of the global overturning ocean circulation, was significantly more radiogenic than modern during the Last Glacial Maximum (LGM), and shifted towards modern values during the deglaciation. We propose that weathering contributions of unradiogenic Nd modulated by the North American Ice Sheet dominated the evolution of the NADW Nd isotope endmember. If water mass mixing dominated the distribution of deep glacial Atlantic Nd isotopes, our results would imply a larger fraction of NADW in the deep Atlantic during the LGM and deglaciation than reconstructed with a constant northern endmember.

 

Nutrient allocation is an important aspect of plant resource uptake and use, which is related to life‐history strategies. Although to date considerable attention has focused on plant allocation of nitrogen and phosphorus, comparatively little information is available on the allocation of various other nutrients and their up‐scaling from the species to community level.

We measured 10 nutrient elements in the leaves, branches and fine roots of 551 plant species growing in eight forest ecosystems in China, ranging from cold temperate to subtropical forests. We estimated the scaling relationship of multiple nutrients among plant organs at the species level and scaled‐up the relationship to the community level by combining this information with that of community structure.

Nutrient allocation among plant organs was conserved in different functional groups and biomes across broad environmental gradients. Nutrient partitioning between organs with similar function tended to be isometric, whereas partitioning between organs with distinct functions tended to be allometric. The scaling relationship between above‐ and below‐ground organs remained consistent, whereas the scaling relationship within above‐ground organs changed after scaling up from the species to the community level, with the relative change in nutrients being consistently smaller in the more active organs.

Synthesis. The pattern of multiple nutrient allocation among organs showed a degree of conservatism across plant functional groups and biomes, with disproportional changes in nutrient content between functionally distinct organs and a lower relative change in more active organs. This conservative strategy implies the existence of general rules that constrain plant nutrient allocation.