Study of the conformation of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein, by fluorescence spectroscopy.

DARPP-32 is a potent inhibitor of protein phosphatase 1 when it is phosphorylated on Thr34 by cAMP-dependent protein kinase. DARPP-32 is also phosphorylated on Ser45 and Ser102 by casein kinase II, resulting in a facilitation of phosphorylation by cAMP-dependent protein kinase. We have studied the conformation of recombinant rat DARPP-32 by steady-state and time-resolved fluorescence. The steady-state emission spectra and quenching of the intrinsic (Trp163) and extrinsic fluorescence (acrylodan or lucifer yellow linked to Cys72) were consistent with a complete exposure of these residues to the aqueous environment. The intrinsic fluorescence of DARPP-32 was resolved into three decay components with lifetimes of 1, 3.4, and 7 ns, with the intermediate lifetime component giving the major contribution. The ratio between the amplitudes associated with the short and long decay constants was decreased upon denaturation. The rotational behavior of DARPP-32 measured by anisotropy decay revealed that Trp163 is located in a highly flexible peptide chain, whereas Cys72 is embedded in a more rigid environment. Phosphorylation by cAMP-dependent protein kinase did not alter any of the fluorescence parameters, whereas only minor effects were associated with casein kinase II phosphorylation. These findings indicate that DARPP-32 contains at least two distinct domains and that phosphorylation has no dramatic effects on its conformation

Transiting Exoplanets with JWST

The era of exoplanet characterization is upon us. For a subset of exoplanets -- the transiting planets -- physical properties can be measured, including mass, radius, and atmosphere characteristics. Indeed, measuring the atmospheres of a further subset of transiting planets, the hot Jupiters, is now routine with the Spitzer Space Telescope. The James Webb Space Telescope (JWST) will continue Spitzer's legacy with its large mirror size and precise thermal stability. JWST is poised for the significant achievement of identifying habitable planets around bright M through G stars--rocky planets lacking extensive gas envelopes, with water vapor and signs of chemical disequilibrium in their atmospheres. Favorable transiting planet systems, are, however, anticipated to be rare and their atmosphere observations will require tens to hundreds of hours of JWST time per planet. We review what is known about the physical characteristics of transiting planets, summarize lessons learned from Spitzer high-contrast exoplanet measurements, and give several examples of potential JWST observations.Comment: 22 pages, 11 figures. In press in "Astrophysics in the Next Decade: JWST and Concurrent Facilities, Astrophysics & Space Science Library, Thronson, H. A., Tielens, A., Stiavelli, M., eds., Springer: Dordrecht (2008)." The original publication will be available at http://www.springerlink.co

Mask formulas for cograssmannian Kazhdan-Lusztig polynomials

We give two contructions of sets of masks on cograssmannian permutations that can be used in Deodhar's formula for Kazhdan-Lusztig basis elements of the Iwahori-Hecke algebra. The constructions are respectively based on a formula of Lascoux-Schutzenberger and its geometric interpretation by Zelevinsky. The first construction relies on a basis of the Hecke algebra constructed from principal lower order ideals in Bruhat order and a translation of this basis into sets of masks. The second construction relies on an interpretation of masks as cells of the Bott-Samelson resolution. These constructions give distinct answers to a question of Deodhar.Comment: 43 page

Parametric Polyhedra with at least kk Lattice Points: Their Semigroup Structure and the k-Frobenius Problem

Given an integral $d \times n$ matrix $A$, the well-studied affine semigroup \mbox{ Sg} (A)=\{ b : Ax=b, \ x \in {\mathbb Z}^n, x \geq 0\} can be stratified by the number of lattice points inside the parametric polyhedra $P_A(b)=\{x: Ax=b, x\geq0\}$. Such families of parametric polyhedra appear in many areas of combinatorics, convex geometry, algebra and number theory. The key themes of this paper are: (1) A structure theory that characterizes precisely the subset \mbox{ Sg}_{\geq k}(A) of all vectors b \in \mbox{ Sg}(A) such that $P_A(b) \cap {\mathbb Z}^n$ has at least $k$ solutions. We demonstrate that this set is finitely generated, it is a union of translated copies of a semigroup which can be computed explicitly via Hilbert bases computations. Related results can be derived for those right-hand-side vectors $b$ for which $P_A(b) \cap {\mathbb Z}^n$ has exactly $k$ solutions or fewer than $k$ solutions. (2) A computational complexity theory. We show that, when $n$, $k$ are fixed natural numbers, one can compute in polynomial time an encoding of \mbox{ Sg}_{\geq k}(A) as a multivariate generating function, using a short sum of rational functions. As a consequence, one can identify all right-hand-side vectors of bounded norm that have at least $k$ solutions. (3) Applications and computation for the $k$-Frobenius numbers. Using Generating functions we prove that for fixed $n,k$ the $k$-Frobenius number can be computed in polynomial time. This generalizes a well-known result for $k=1$ by R. Kannan. Using some adaptation of dynamic programming we show some practical computations of $k$-Frobenius numbers and their relatives

Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics

Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well-orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N-myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe