A fluorescent molecular imaging probe with selectivity for soluble tau aggregated protein

Soluble forms of aggregated tau misfolded protein, generally termed oligomers, are considered to be the most toxic species of the different assembly states that are the pathological components of neurodegenerative disorders. Therefore, a critical biomedical need exists for imaging probes that can identify and quantify them. We have designed and synthesized a novel fluorescent probe, pTP-TFE for which binding and selectivity profiles towards aggregated tau and Aβ proteins were assessed. Our results have shown pTP-TFE to be selective for early forms of soluble tau aggregates, with high affinity of dissociation constants (K_d) = 66 nM, and tenfold selectivity over mature tau fibrils. Furthermore, we found that pTP-TFE is selective for tau over Aβ aggregates and had good cell permeability. This selectivity of pTP-TFE towards early forms of aggregated tau protein ex vivo was also supported with studies on human brain tissue containing tau and Aβ pathology. To the best of our knowledge, this is the first fluorescent molecule to be reported to have this form of selectivity profile, which suggests that pTP-TFE is a unique probe candidate for imaging-based detection of early stages of Alzheimer''s disease and other tauopathies.

pTP-TFE imaging probe can distinguish soluble tau aggregated proteins from other aggregated proteins enabling earlier detection of neurodegenerative diseases.     

Intramolecular electron transfer in nitrite reductases.

The copper- and heme-containing nitrite reductases (NiRs) are key enzymes in denitrification. Their subunits contain two distinct redox-active metal centers, an electron-accepting site and a nitrite-reducing site, to carry out the single-electron reduction of nitrite to nitric oxide. Catalytic cycles of both enzyme families employ intramolecular electron transfer that can be rate-determining for their activity. Herein, we report results comparing these two enzyme families in order to resolve the different mechanisms controlling intramolecular electron transfer in these proteins.     

Pulse radiolysis and fourier transform infrared study of neopentyl peroxy radicals in the gas phase at 297 K

The ultraviolet absorption spectrum of the neopentyl peroxy radical (CH₃)₃CCH₂O₂, and the kinetics and products of its self reaction have been studied in the gas phase at 298 K. Absorption cross sections were quantified over the wavelength range 230–290 nm. The measured cross section at 250 nm was; Errors represent statistical (2σ) together with our estimate of potential systematic errors(15%). The kinetics of the decay of the UV absorption following the generation of the neopentyl peroxy radicals was complicated by the rapid decomposition of the (CH₃)₃CCH₂O radicals formed in channel (4a). By measuring the yield of t-butyl peroxy radicals, the branching ratio k_4a/(k_4a + k_4b) was determined to be 0.39 ± 0.03. The rate constant for the self reaction of neopentyl peroxy radicals was k₄ = (1.07 ± 0.22) × 10^?12 cm³ molecule^?1 s^?1. Quoted errors represent 2σ. These results are discussed with respect to the available literature data. © John Wiley & Sons, Inc.     

Single crystal Raman study of potassium oxalate monohydrate,K2C2O4. H2O,and potassium oxalate monodeuterate,K2C2O4. D2O

Raman spectra of poly crystalline and single crystal K₂C₂O₄. H₂O and K₂C₂O₄. D₂O have been recorded at room temperature. From an earlier neutron diffraction study it is known that the space group is C⁶₂h. The water molecule occupies a C₂ site and the oxalate ion a C₁ site. The assigned water vibrations show small factor group splitting between g modes (Raman active) and u modes (IR active). The internal oxalate vibrations are found to have wavenumbers in good agreement with those reported from Raman studies of other oxalates.     

How to synthesize macrocycles efficiently by using virtual combinatorial libraries

The selection of different diimines 4 a-c by alkaline earth ions from a virtual combinatorial library (VCL) is described. The products were stabilized by reduction to the diamines 6 a-c; this allowed easy analysis. The library can be directed toward different target molecules 6 a-c upon addition of alkaline earth ions with different radii. Competition experiments show the possibility of synthesizing the macrocycles 6 a, 6 b, and 6 c simultaneously when using Mg(2+), Ca(2+), and Ba(2+) as template ions. The scope of this thermodynamically controlled, reversible approach for macrocycle syntheses is illustrated.     

Fermionic solution of the Andrews-Baxter-Forrester model. II. Proof of Melzer's polynomial identities

We compute the one-dimensional configuration sums of the ABF model using the fermionic technique introduced in part I of this paper. Combined with the results of Andrews, Baxter, and Forrester, we prove polynomial identities for finitizations of the Virasoro characters as conjectured by Melzer. In the thermodynamic limit these identities reproduce Rogers-Ramanujan-type identities for the unitary minimal Virasoro characters conjectured by the Stony Brook group. We also present a list of additional Virasoro character identities which follow from our proof of Melzer's identities and application of Bailey's lemma.Dedicated to the memory of Piet Kasteleyn.     

Muffin-tin orbital Wannier-like functions for insulators and metals.

Herein, we outline a method that is able to generate truly minimal basis sets that accurately describe either a group of bands, a band, or even just the occupied part of a band. These basis sets are the so-called NMTOs, muffin-tin orbitals of order N. For an isolated set of bands, symmetrical orthonormalization of the NMTOs yields a set of Wannier functions that are atom-centered and localized by construction. They are not necessarily maximally localized, but may be transformed into those Wannier functions. For bands that overlap others, Wannier-like functions can be generated. It is shown that NMTOs give a chemical understanding of an extended system. In particular, orbitals for the pi and sigma bands in an insulator, boron nitride, and a semimetal, graphite, will be considered. In addition, we illustrate that it is possible to obtain Wannier-like functions for only the occupied states in a metallic system by generating NMTOs for cesium. Finally, we visualize the pressure-induced s-->d transition.     

Alkali—SCl2 chemiluminescence: Vibrational population inversion in the B state of S2

S₂(B-X) chemiluminescence, primarily from ν′ = 0 and 1, has been observed in alkali atom—SCl₂ reactions. The addition of He or Ar buffer gas to the reaction chamber alters the reaction dynamics, and at certain buffer gas pressures the S₂ emission originates exclusively from the ν′ = 6–9 vibrational levels of the B(³Σ_u^?) state.