Characterization of [3H][^3H]Phenobarbital Binding to Rat Brain Membranes

The binding of $[^3H]$phenobarbital to rat brain membranes was studied in order to determine its characteristics and specificity. The binding reaction was rapid and occurred at sites of low affinity. $(K_d = 700 μM)$ and very high density $(B_{max} = 2.7 nmoll/mg protein)$. It was unaffected by temperature changes from O°C to 95°C and was maximal at pH 5. Detergents in low concentrations markedly decreased the binding, apparently without solubilizing the binding sites. It is concluded that the binding of $[^3H]$ phenobarbital is a rather non-specific interaction with the plasma membrane

The historical vanishing of the Blazhko effect of RR Lyr from GEOS and Kepler surveys

RR Lyr is one of the most studied variable stars. Its light curve has been regularly monitored since the discovery of the periodic variability in 1899. Analysis of all observed maxima allows us to identify two primary pulsation states defined as pulsation over a long (P0 longer than 0.56684 d) and a short (P0 shorter than 0.56682 d) primary pulsation period. These states alternate with intervals of 13-16 yr, and are well defined after 1943. The 40.8 d periodical modulations of the amplitude and the period (i.e. Blazhko effect) were noticed in 1916. We provide homogeneous determinations of the Blazhko period in the different primary pulsation states. The Blazhko period does not follow the variations of P0 and suddenly diminished from 40.8 d to around 39.0 d in 1975. The monitoring of these periodicities deserved and deserves a continuous and intensive observational effort. For this purpose we have built dedicated, transportable and autonomous small instruments, Very Tiny Telescopes (VTTs), to observe the times of maximum brightness of RR Lyr. As immediate results the VTTs recorded the last change of P0 state in mid-2009 and extended the time coverage of the Kepler observations, thus recording a maximum O-C amplitude of the Blazhko effect at the end of 2008, followed by the historically smallest O-C amplitude in late 2013. This decrease is still ongoing and VTT instruments are ready to monitor the expected increase in the next few years.Comment: 10 pages, 6 figures. Accepted for publication in MNRAS. Contents of appendix B may be requested to first autho

Genetic Diversity of the Flavohemoprotein Gene of Giardia lamblia: Evidence for High Allelic Heterozygosity and Copy Number Variation

Purpose: The flavohemoprotein (gFlHb) in Giardia plays an important role in managing nitrosative and oxidative stress, and potentially also in virulence and nitroimidazole drug tolerance. The aim of this study was to analyze the genetic diversity of gFlHb in Giardia assemblages A and B clinical isolates. Methods: gFlHb genes from 20 cultured clinical Giardia isolates were subjected to PCR amplification and cloning, followed by Sanger sequencing. Sequences of all cloned PCR fragments from each isolate were analyzed for single nucleotide variants (SNVs) and compared to genomic Illumina sequence data. Identical clone sequences were sorted into alleles, and diversity was further analyzed. The number of gFlHb gene copies was assessed by mining PacBio de novo assembled genomes in eight isolates. Homology models for assessment of SNV’s potential impact on protein function were created using Phyre2. Results: A variable copy number of the gFlHb gene, between two and six copies, depending on isolate, was found. A total of 37 distinct sequences, representing different alleles of the gFlHb gene, were identified in AII isolates, and 41 were identified in B isolates. In some isolates, up to 12 different alleles were found. The total allelic diversity was high for both assemblages (> 0.9) and was coupled with a nucleotide diversity of < 0.01. The genetic variation (SNVs per CDS length) was 4.8% in sub-assemblage AII and 5.4% in assemblage B. The number of non-synonymous (ns) SNVs was high in gFIHb of both assemblages, 1.6% in A and 3.0% in B, respectively. Some of the identified nsSNV are predicted to alter protein structure and possibly function. Conclusion: In this study, we present evidence that gFlHb, a putative protective enzyme against oxidative and nitrosative stress in Giardia, is a variable copy number gene with high allelic diversity. The genetic variability of gFlHb may contribute metabolic adaptability against metronidazole toxicity.Peer Reviewe

Ordered phase in the two-dimensional randomly coupled ferromagnet

True ground states are evaluated for a 2d Ising model with random near neighbor interactions and ferromagnetic second neighbor interactions (the Randomly Coupled Ferromagnet). The spin glass stiffness exponent is positive when the absolute value of the random interaction is weaker than the ferromagnetic interaction. This result demonstrates that in this parameter domain the spin glass like ordering temperature is non-zero for these systems, in strong contrast to the 2d Edwards-Anderson spin glass.Comment: 7 pages; 9 figures; revtex; new version much extende

Ground-state behavior of the 3d +/-J random-bond Ising model

Large numbers of ground states of the three-dimensional $\pm J$ random-bond Ising model are calculated for sizes up to $14^3$ using a combination of a genetic algorithm and Cluster-Exact Approximation. Several quantities are calculated as function of the concentration $p$ of the antiferromagnetic bonds. The critical concentration where the ferromagnetic order disappears is determined using the Binder cumulant of the magnetization. A value of $p_c=0.222\pm 0.005$ is obtained. From the finite-size behavior of the Binder cumulant and the magnetization critical exponents $\nu=1.1 \pm 0.3$ and $\beta=0.2 \pm 0.1$ are calculated.Comment: 8 pages, 11 figures, revte

A new method for analyzing ground-state landscapes: ballistic search

A ``ballistic-search'' algorithm is presented which allows the identification of clusters (or funnels) of ground states in Ising spin glasses even for moderate system sizes. The clusters are defined to be sets of states, which are connected in state-space by chains of zero-energy flips of spins. The technique can also be used to estimate the sizes of such clusters. The performance of the method is tested with respect to different system sizes and choices of parameters. As an application the ground-state funnel structure of two-dimensional +or- J spin glasses of systems up to size L=20 is analyzed by calculating a huge number of ground states per realization. A T=0 entropy per spin of s_0=0.086(4)k_B is obtained.Comment: 10 pages, 11 figures, 35 references, revte

Adenosine receptor agonists: Synthesis and binding affinity of 2-(aryl)alkylthioadenosine derivatives

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The Length and Flexibility of the 2-Substituent of 9-Ethyladenine Derivatives Modulate Affinity and Selectivity for the Human A2A Adenosine Receptor

The A2A adenosine receptor (A2A AR) is a key target for the development of pharmacological tools for the treatment of central nervous system disorders. Previous works have demonstrated that the insertion of substituents at various positions on adenine leads to A2A AR antagonists with affinity in the micromolar to nanomolar range. In this work, a series of 9-ethyladenine derivatives bearing phenylalkylamino, phenylakyloxy or phenylakylthio groups of different lengths at the 2-position were synthesised and tested against the human adenosine receptors. The derivatives showed sub-micromolar affinity for these membrane proteins. The further introduction of a bromine atom at the 8-position has the effect of improving the affinity and selectivity for all ARs and led to compounds that are able bind to the A2A AR subtype at low nanomolar levels. Functional studies confirmed that the new adenine derivatives behave as A2A AR antagonists with half-maximal inhibitory concentration values in the nanomolar range. Molecular modelling studies provide a description of the possible binding mode of these compounds at the A2A AR and an interpretation of the affinity data at this AR subtype