Sequence, expression and mutational analysis of BAF1, a transcriptional activator and ARS1-binding protein of the yeast Saccharomyces cerevisiae.

We report the cloning and sequence analysis of the yeast BAF1 gene which encodes an abundant protein previously shown to act as a transcription activator in the YPT1-TUB2 intergene region. As predicted from the DNA sequence, the highly hydrophilic BAf1 protein is 731 amino acids long and has a molecular mass of 81 748 daltons. The protein product of the cloned BAF1 gene produced in Escherichia coli is able to form specific complexes with DNA fragments containing the conserved element TCN7ACG. The protein binds also to the ABF1-binding site of the B-domain of ARS1, entertaining the possibility that BAF1 and ABF1 are identical proteins. Extensive deletion studies identified the N-terminal two thirds of the Baf1 protein to be required for specific DNA binding. Amino acid substitutions point to the N-terminal sequence CysX7HisX3HisX4CysX4Cys to form an atypical metal-binding 'finger' structure. Disruption of the BAF1 gene is lethal. The existence of five potential Baf1-protein binding sites in the 5' region of the gene suggests the involvement of the Baf1 protein in transcription regulation of its own gene

TARP as immunotherapeutic target in AML expressed in the LSC compartment

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Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

Ageing and the misperception of words: evidence from eye movements during reading

Research with lexical neighbours (words that differ by a single letter while the number and order of letters are preserved) indicates that readers frequently misperceive a word as its higher frequency neighbour (HFN) even during normal reading. But how this lexical influence on word identification changes across the adult lifespan is largely unknown, although slower lexical processing and reduced visual abilities in later adulthood may lead to an increased incidence of word misperception errors. In particular, older adults may be more likely than younger adults to misidentify a word as its HFN, especially when the HFN is congruent with prior sentence context, although this has not been investigated. Accordingly, to address this issue, young and older adults read sentences containing target words with and without an HFN, where the HFN was either congruent with prior sentence context or not. Consistent with previous findings for young adults, eye movements were disrupted more for words with than without an HFN, especially when the HFN was congruent with prior context. Crucially, however, there was no indication of an adult age difference in this word misperception effect. We discuss these findings in relation to the nature of misperception effects in older age

An Integrated Approach to Testing Dynamic, Multilevel Theory: Using Computational Models to Connect Theory, Model, and Data

Some of the most influential theories in organizational sciences explicitly describe a dynamic, multilevel process. Yet the inherent complexity of such theories makes them difficult to test. These theories often describe multiple subprocesses that interact reciprocally over time at different levels of analysis and over different time scales. Computational (i.e., mathematical) modeling is increasingly advocated as a method for developing and testing theories of this type. In organizational sciences, however, efforts that have been made to test models empirically are often indirect. We argue that the full potential of computational modeling as a tool for testing dynamic, multilevel theory is yet to be realized. In this article, we demonstrate an approach to testing dynamic, multilevel theory using computational modeling. The approach uses simulations to generate model predictions and Bayesian parameter estimation to fit models to empirical data and facilitate model comparisons. This approach enables a direct integration between theory, model, and data that we believe enables a more rigorous test of theory