TDP-43 is a highly conserved and ubiquitously expressed member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family of proteins. Recently, TDP-43 was shown to be a major disease protein in the ubiquitinated inclusions characteristic of most cases of amyotrophic lateral sclerosis (ALS), tau-negative frontotemporal lobar degeneration (FTLD), and inclusion body myopathy. In these diseases, TDP-43 is redistributed from its predominantly nuclear location to ubiquitin-positive, cytoplasmic foci. The extent to which TDP-43 drives pathophysiology is unknown, but the identification of mutations in TDP-43 in familial forms of ALS and FTLD-U suggests an important role for this protein in pathogenesis. Little is known about TDP-43 function and only a few TDP-43 interacting proteins have been previously identified, which makes further insight into both the normal and pathological functions of TDP-43 difficult. Here we show, via a global proteomic approach, that TDP-43 has extensive interaction with proteins that regulate RNA metabolism. Some interactions with TDP-43 were found to be dependent on RNA-binding, whereas other interactions are RNA-independent. Disease-causing mutations in TDP-43 (A315T and M337V) do not alter its interaction profile. TDP-43 interacting proteins largely cluster into two distinct interaction networks, a nuclear/splicing cluster and a cytoplasmic/translation cluster, strongly suggesting that TDP-43 has multiple roles in RNA metabolism and functions in both the nucleus and the cytoplasm. Finally, we found numerous TDP-43 interactors that are known components of stress granules and, indeed, we find that TDP-43 is also recruited to stress granules.

A family of 28 mononuclear Ru(II) complexes have been prepared and characterized by (1)H NMR, electronic absorption, and cyclic voltammetry. These complexes are studied as catalysts for water oxidation. All the catalysts possess one tridentate ligand, closely related to 2,2';6,2''-terpyridine (tpy) and may be divided into two basic types. In the type-1 catalyst, the three remaining coordination sites are occupied by a bidentate closely related to 2,2'-bipyridine (bpy) and a monodentate halogen (Br, Cl, or I) or water molecule. In the type-2 catalyst, the three remaining coordination sites are occupied by two axial 4-picoline molecules and an equatorial halogen or water. In general the type-2 catalysts are more reactive than the type-1. The type-2 iodo-catalyst shows first-order behavior and, unlike the bromo- and chloro-catalysts, does not require water-halogen exchange to show good activity. The importance of steric strain and hindrance around the metal center is examined. The introduction of three t-butyl groups at the 4, 4', and 4'' positions of tpy sometimes improves catalyst activity, but the effect does not appear to be additive.

The occurrence of photoinduced electron transfer in donor-acceptor self-assembled zinc naphthalocyanine (ZnNc) or zinc porphyrin (ZnP) single-wall carbon nanotube (SWNT) nanohybrids has been demonstrated. The nanohybrids were constructed by solubilizing carbon nanotubes by π-π stacking of pyrene functionalized to bear an imidazole moiety, ImPy-SWNT. Through the use of the imidazole ligand of the soluble ImPy-SWNT, donor ZnNc and ZnP entities were axially coordinated to yield ZnNc-ImPy-SWNT and ZnP-ImPy-SWNT donor-acceptor nanohybrids. The nanohybrids thus obtained were fully characterized by using transmission electron microscopy, UV-visible-near infrared spectroscopy, and electrochemical methods. Steady-state and time-resolved emission studies revealed efficient fluorescence quenching of the donor, ZnP, and ZnNc entities in the nanohybrids. Nanosecond transient absorption spectra revealed that the photoexcitation of the ZnNc or ZnP moiety resulted in the one-electron oxidation of the donor unit with a simultaneous one-electron reduction of SWNT. The charge separation yielding ZnNc •+ -ImPy-SWNT •and ZnP •+ -ImPy-SWNT •was further confirmed with the aid of an electron mediator, hexyl-viologen dication (HV 2+ ) and an electron-hole shifter, 1-benzyl-1,4-dihydronicotinamide. As a result of the photoinduced processes, accumulation of the radical cation of HV •+ was observed with 70-90% yields thus demonstrating the importance of the present donor-acceptor nanohybrids in photogeneration of redox products.