TDP‐43 is an RNA‐binding protein active in splicing that concentrates into membraneless ribonucleoprotein granules and forms aggregates in amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. Although best known for its predominantly disordered C‐terminal domain which mediates ALS inclusions, TDP‐43 has a globular N‐terminal domain (NTD). Here, we show that TDP‐43 NTD assembles into head‐to‐tail linear chains and that phosphomimetic substitution at S48 disrupts TDP‐43 polymeric assembly, discourages liquid–liquid phase separation (LLPS) in vitro, fluidizes liquid–liquid phase separated nuclear TDP‐43 reporter constructs in cells, and disrupts RNA splicing activity. Finally, we present the solution NMR structure of a head‐to‐tail NTD dimer comprised of two engineered variants that allow saturation of the native polymerization interface while disrupting higher‐order polymerization. These data provide structural detail for the established mechanistic role of the well‐folded TDP‐43 NTD in splicing and link this function to LLPS. In addition, the fusion‐tag solubilized, recombinant form of TDP‐43 full‐length protein developed here will enable future phase separation and in vitro biochemical assays on TDP‐43 function and interactions that have been hampered in the past by TDP‐43 aggregation.

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Highly fluorescent carbon dots (CDs) exhibiting molecular fluorescence were synthesized and successfully used for sensing ferricyanide based on fluorescence quenching. We conducted dialysis to purify the CDs and found that the dialysate is also fluorescent. From the mass spectra and quantum yield analyses of the dialysate, it is demonstrated that molecular fluorophores were also synthesized during the synthesis of CDs. By the comparison of fluorescence spectra between CDs and dialysate, it is established that the fluorescence emission of CDs partly originates from fluorophores that are attached to CDs’ surface. The fluorescence quenching caused by ferricyanide is proved to be the overlap of absorption spectra between ferricyanide and CDs. The changes of the absorbance and fluorescence spectra are combined to enhance the detection sensitivity, and the limit of detection is calculated to be 1.7 μM. A good linear response of fluorescence-absorbance combined sensing toward ferricyanide is achieved in the range of 5–100 µM. This method is highly selective to ferricyanide among other common cations and anions, and it is also successfully applied in detecting ferricyanide in real water samples.