A Peptide Core Motif for Binding to Heterotrimeric G Protein α Subunits

Recently, in vitro selection using mRNA display was used to identify a novel peptide sequence that binds with high affinity to G{alpha}i1. The peptide was minimized to a 9-residue sequence (R6A-1) that retains high affinity and specificity for the GDP-bound state of G{alpha}i1 and acts as a guanine nucleotide dissociation inhibitor (GDI). Here we demonstrate that the R6A-1 peptide interacts with G{alpha} subunits representing all four G protein classes, acting as a core motif for G{alpha} interaction. This contrasts with the consensus G protein regulatory(GPR) sequence, a 28-mer peptide GDI derived from the GoLoco (G{alpha}i/0-Loco interaction)/GPR motif that shares no homology with R6A-1 and binds only to G{alpha}i1-3 in this assay. Binding of R6A-1 is generally specific to the GDP-bound state of the G{alpha} subunits and excludes association with G{beta}{gamma}. R6A-G{alpha}i1 complexes are resistant to trypsin digestion and exhibit distinct stability in the presence of Mg2+, suggesting that the R6A and GPR peptides exert their activities using different mechanisms. Studies using G{alpha}i1/G{alpha}s chimeras identify two regions of G{alpha}i1 (residues 1–35 and 57–88) as determinants for strong R6A-Gi{alpha}1 interaction. Residues flanking the R6A-1 peptide confer unique binding properties, indicating that the core motif could be used as a starting point for the development of peptides exhibiting novel activities and/or specificity for particular G protein subclasses or nucleotide-bound states

Disclosing Extra-Dyadic Involvement (EDI): Understanding Attitudes, Subjective Norms, and Perceived Behavioral Control

Extra-dyadic involvement (EDI) is a complex issue that affects many individuals, couples, and families. One important, relatively unexplored issue concerns the disclosure of EDI. Despite some scholarly discourse on whether disclosure should be facilitated in a therapeutic context (e.g., Butler et al. in J Marital Fam Ther 35:125–143, 2009; Butler et al. in Am J Fam Ther 36:265–283, 2008), empirical research has not studied the intrapersonal or interpersonal processes related to disclosure. In this study, we explored potential factors involved in the decision to disclose EDI by looking at the relationships among attitudes towards EDI (in terms of perceived justifications and costs), subjective norms (obligation to disclose), and perceived behavioral control (difficulty) associated with EDI disclosure. Our sample included 337 individuals enrolled in at least one university course at one of three geographically distinct universities. Findings indicate that more permissive attitudes towards EDI are not significantly associated to the perceived difficulty in disclosing EDI or the obligation associated with disclosing EDI involving sexual intercourse. However, more permissive attitudes are related to lower felt obligation to disclose EDI that does not involve direct sexual intercourse. Conversely, more restrictive attitudes towards EDI (perceived severity, degree of perceived upset, and how detrimental it is perceived to be to the relationship) predicted greater difficulty but also greater obligation in disclosing all forms of EDI. Specific implications of these findings, including potential implications for therapy, are discussed. Overall, this study provides preliminary information regarding potentially useful factors to consider in understanding the EDI disclosure process that may also be useful in developing intervention points in therapy

University of Minnesota – Twin Cities Modifications to the Montana State University Telemetry System for Stratospheric Eclipse Ballooning

On August 21, 2017, the path of totality of a solar eclipse swept across the continental United States from Oregon to South Carolina. Our team, flying weather balloons near Grand Island, Nebraska, was able to live stream the shadow of the moon from the stratosphere to the ground. The team was able to track our balloons with high accuracy due to new payload software and hardware implemented on the still image telemetry platform developed by the Montana Space Grant. In addition, the modified system allowed the team to relay commands and receive information from individual payloads attached to our balloons, giving live telemetry and control from a new GUI-based ground station control application. Although the eclipse is now over, the system will still be a powerful and useful tool for the University of Minnesota stratospheric ballooning team. The platform could be used for any other application needing real-time, ground-based communication to various payloads on a balloon gondola

C-terminal motif prediction in eukaryotic proteomes using comparative genomics and statistical over-representation across protein families

<p>Abstract</p> <p>Background</p> <p>The carboxy termini of proteins are a frequent site of activity for a variety of biologically important functions, ranging from post-translational modification to protein targeting. Several short peptide motifs involved in protein sorting roles and dependent upon their proximity to the C-terminus for proper function have already been characterized. As a limited number of such motifs have been identified, the potential exists for genome-wide statistical analysis and comparative genomics to reveal novel peptide signatures functioning in a C-terminal dependent manner. We have applied a novel methodology to the prediction of C-terminal-anchored peptide motifs involving a simple z-statistic and several techniques for improving the signal-to-noise ratio.</p> <p>Results</p> <p>We examined the statistical over-representation of position-specific C-terminal tripeptides in 7 eukaryotic proteomes. Sequence randomization models and simple-sequence masking were applied to the successful reduction of background noise. Similarly, as C-terminal homology among members of large protein families may artificially inflate tripeptide counts in an irrelevant and obfuscating manner, gene-family clustering was performed prior to the analysis in order to assess tripeptide over-representation across protein families as opposed to across all proteins. Finally, comparative genomics was used to identify tripeptides significantly occurring in multiple species. This approach has been able to predict, to our knowledge, all C-terminally anchored targeting motifs present in the literature. These include the PTS1 peroxisomal targeting signal (SKL*), the ER-retention signal (K/HDEL*), the ER-retrieval signal for membrane bound proteins (KKxx*), the prenylation signal (CC*) and the CaaX box prenylation motif. In addition to a high statistical over-representation of these known motifs, a collection of significant tripeptides with a high propensity for biological function exists between species, among kingdoms and across eukaryotes. Motifs of note include a serine-acidic peptide (DSD*) as well as several lysine enriched motifs found in nearly all eukaryotic genomes examined.</p> <p>Conclusion</p> <p>We have successfully generated a high confidence representation of eukaryotic motifs anchored at the C-terminus. A high incidence of true-positives in our results suggests that several previously unidentified tripeptide patterns are strong candidates for representing novel peptide motifs of a widely employed nature in the C-terminal biology of eukaryotes. Our application of comparative genomics, statistical over-representation and the adjustment for protein family homology has generated several hypotheses concerning the C-terminal topology as it pertains to sorting and potential protein interaction signals. This approach to background reduction could be expanded for application to protein motif prediction in the protein interior. A parallel N-terminal analysis is presented as supplementary data.</p

SSL: A software specification language

SSL (Software Specification Language) is a new formalism for the definition of specifications for software systems. The language provides a linear format for the representation of the information normally displayed in a two-dimensional module inter-dependency diagram. In comparing SSL to FORTRAN or ALGOL, it is found to be largely complementary to the algorithmic (procedural) languages. SSL is capable of representing explicitly module interconnections and global data flow, information which is deeply imbedded in the algorithmic languages. On the other hand, SSL is not designed to depict the control flow within modules. The SSL level of software design explicitly depicts intermodule data flow as a functional specification

Unitary Averaging with Fault and Loss Tolerance

We consider the impact of the unitary averaging framework on single and two-mode linear optical gates. We demonstrate that this allows a trade-off between the probability of success and gate fidelity, with perfect fidelity gates being achievable for a finite decrease in the probability of success, at least in principle. Furthermore, we show that the encoding and decoding errors in the averaging scheme can also be suppressed up to the first order. We also look at how unitary averaging can work in conjunction with existing error correction schemes. Specifically, we consider how parity encoding might be used to counter the extra loss due to the decreased probability of success, with the aim of achieving fault tolerance. We also consider how unitary averaging might be utilised to expand the parameter space in which fault tolerance may be achievable using standard fault tolerant schemes.Comment: 13 pages, 6 figure

Designed Arginine-Rich RNA-Binding Peptides with Picomolar Affinity

Arginine-rich peptide motifs (ARMs) capable of binding unique RNA structures play critical roles in transcription, translation, RNA trafficking, and RNA packaging. Bacteriophage ARMs necessary for transcription antitermination bind to distinct boxB RNA hairpin sequences with a characteristic induced α-helical structure. Characterization of ARMs from lambdoid phages reveals that the dissociation constant of the P22 bacteriophage model−antitermination complex (P22_(N21)−P22boxB) is 200 ± 56 pM in free solution at physiologic concentrations of monovalent cation, significantly stronger than previously determined by gel mobility shift and polyacrylamide gel coelectophoresis, and 2 orders of magnitude stronger than the tightest known native ARM−RNA interaction at physiological salt. Here, we use a reciprocal design approach to enhance the binding affinity of two separate α-helical ARM−RNA interactions; one derived from the native λ phage antitermination complex and a second isolated using mRNA display selection experiments targeting boxB RNA

Evaluation of spin in the abstracts of systematic reviews regarding the treatment of acne vulgaris

Background: Spin is the misrepresentation of study findings which may positively or negatively influence the reader's interpretation of the results. Little is known regarding the prevalence of spin in abstracts of systematic reviews — specifically systematic reviews pertaining to management and treatment for acne vulgaris.Objective: Our primary objective was to characterize and determine the frequency of the most severe forms of spin in systematic review abstracts, and to evaluate whether various study characteristics were associated with spin.Methods: Using a cross-sectional study design, we searched PubMed and Embase for systematic reviews focusing on the management and treatment of acne vulgaris. Our search returned 316 studies, of which 36 were included in our final sample. To be included, each systematic review must have addressed either pharmacologic or non-pharmacologic treatment of acne vulgaris. These studies were screened and data were extracted in duplicate by two blinded investigators. We analyzed systematic review abstracts for the 9 most severe types of spin.Results: Spin was present in 11 of 36 abstracts (30.56%). Twelve examples of spin were identified in the 11 abstracts containing spin, with one abstract containing two instances of spin. The most common type of spin, selective reporting of or overemphasis on efficacy outcomes or analysis favoring the beneficial effect of the experimental intervention, was identified 5 times (5/12, 41.67%). Sixteen of the 36 (16/36, 44.44%) studies did not report a risk of bias assessment. Of the 11 abstracts containing spin, 6 did not report a risk of bias assessment or performed a risk of bias assessment but did not discuss it (6/11, 54.55%). Spin in abstracts was not significantly associated with a specific intervention type, the use of a medical writer, funding source, journal impact factor, or PRISMA/PRISMA-A journal requirements.Conclusions: Abstracts with evidence of spin have the potential to influence clinical decision making. Therefore, further research is needed to evaluate what types of spin have the greatest influence on clinical practice. To help address the misrepresentation of study findings, we offer recommendations to better educate and improve peer-reviewers' and editors' awareness of, and ability to identify, spin in abstracts of systematic reviews

Using Design Interventions to Develop Communication Solutions for Integrated Pest Management

Iowa State University’s (ISU) Integrated Pest Management (IPM) program partnered with the ISU College of Design (COD) to use Design Thinking and other practical design methodologies and theories to identify and develop approaches to address IPM extension and communication issues. ISU IPM met with agriculture industry, program colleagues, and ISU COD faculty to discuss IPM-related needs in agriculture and to determine the program’s primary challenges. ISU COD faculty developed a two-semester course for undergraduate students, allocating various resources to solve these challenges. Undergraduates in the course, as the primary agents and problem solvers, developed various strategies the IPM program and its colleagues could implement. A model of interdisciplinary collaboration was developed, where design and science may function as equal partners in a design education setting. In our collaboration, the partners bought into a design-led process-based methodology that began with identifying IPM communication needs. This project resulted in unique design interventions to communicate IPM to stakeholders and the public, as well as created a model for interdisciplinary cooperation that can be exported to fields outside of agriculture and IPM