Direct and Conceptual Replications of Burgmer & Englich (2012): Power May Have Little to No Effect on Motor Performance

Burgmer and Englich (2012) have reported that manipulating feelings of power can substantially improve performance on two motor tasks: golf and darts. We conducted two high-powered direct replications of the effects of power on golf, two online conceptual replications using mirror-tracing as a performance measure, and an additional conceptual replication using a cognitive performance measure (word-search). Overall, we found little to no effect of power on motor skill (d = 0.09, 95% CI[-0.07, 0.22], n = 603). We varied task difficulty, re-analyzed data without participants showing weak responses on manipulation checks, and tried adjusting performance scores for age, gender, and initial task skill. None of these secondary analyses revealed a strong effect of power on performance. A meta-analysis integrating our data with Burgmer & Englich leaves open the possibility that manipulating power could provide a modest boost in motor skill (d = 0.19, 95% CI [0.001, 0.38], n = 685). Unfortunately, the pattern of performance changes we observed was unrelated to group differences in perceived and rated power, suggesting that what motor effects do occur with this protocol may not be directly related to the construct of power. [Burgmer, P., &Englich, B. (2012). Bullseye!: How Power Improves Motor Performance. Social Psychological and Personality Science, 4(2), 224–232.]     

Polymer gene delivery vectors encapsulated in thermally sensitive bioreducible shell

Stable, nanosized polyelectrolyte complexes between rationally designed thermally sensitive block copolymers and plasmid DNA (polyplexes) were formed and their in vitro transfection efficiency was tested. The polyplexes were further stabilized through encapsulation into a biodegradable polymer shell. Although reduced as compared to that of the corresponding polyplexes, the encapsulated systems still show acceptable transfection efficiency. That opens the possibility to tune the balance between the safe transport and efficient delivery of DNA into the cells.     

STOCHASTIC TEMPERATURES IMPEDE RNA VIRUS ADAPTATION

Constant environments are often assumed to favor the evolution of specialization whereas exposure to changing environments may favor the evolution of generalists. Here we explored the phenotypic and molecular changes associated with evolving an RNA virus in constant versus fluctuating temperature environments. We used vesicular stomatitis virus (VSV) to determine whether selection at a constant temperature entails a performance trade‐off at an unselected temperature, whether virus populations evolve to be generalists when selected in deterministically changing temperature environments, and whether selection under stochastically changing temperatures prevents evolved generalization, such as by constraining the ability for viruses to adaptively improve. We observed that all VSV lineages evolved at constant temperatures showed fitness gains in their selected temperature with little evidence for trade‐offs in performance in the unselected environment. Evolution in deterministically and stochastically changing temperatures led to populations with the highest and lowest overall fitness gains, respectively. Sequence analysis revealed little evidence for convergent molecular evolution among lineages within the same treatment. Across all temperature treatments, the majority of genome substitutions occurred in the G (glycoprotein) gene, suggesting that this locus for the cell‐binding protein plays a key role in dictating VSV performance under changing temperature.     

Rapid and accurate structure-based therapeutic peptide design using GPU accelerated thermodynamic integration

Peptide-based therapeutics are an alternative to small molecule drugs as they offer superior specificity, lower toxicity, and easy synthesis. Here we present an approach that leverages the dramatic performance increase afforded by the recent arrival of GPU accelerated thermodynamic integration (TI). GPU TI facilitates very fast, highly accurate binding affinity optimization of peptides against therapeutic targets. We benchmarked TI predictions using published peptide binding optimization studies. Prediction of mutations involving charged side-chains was found to be less accurate than for non-charged, and use of a more complex 3-step TI protocol was found to boost accuracy in these cases. Using the 3-step protocol for non-charged side-chains either had no effect or was detrimental. We use the benchmarked pipeline to optimize a peptide binding to our recently discovered cancer target: EME1. TI calculations predict beneficial mutations using both canonical and non-canonical amino acids. We validate these predictions using fluorescence polarization and confirm that binding affinity is increased. We further demonstrate that this increase translates to a significant reduction in pancreatic cancer cell viability.     

Phosphorylation-dependent Regulation of Connecdenn/DENND1 Guanine Nucleotide Exchange Factors

Connecdenn 1/2 are DENN (differentially expressed in normal and neoplastic cells) domain-bearing proteins that function as GEFs (guanine nucleotide exchange factors) for the small GTPase Rab35. Disruption of connecdenn/Rab35 function leads to defects in the recycling of multiple cargo proteins from endosomes with altered cell function, yet the regulation of connecdenn GEF activity is unexplored. We now demonstrate that connecdenn 1/2 are autoinhibited such that the purified, full-length proteins have significantly less Rab35 binding and GEF activity than the isolated DENN domain. Both proteins are phosphorylated with prominent phosphorylation sites between residues 500 and 600 of connecdenn 1. A large scale proteomics screen revealed that connecdenn 1 is phosphorylated at residues Ser-536 and Ser-538 in an Akt-dependent manner in response to insulin stimulation of adipocytes. Interestingly, we find that an Akt inhibitor reduces connecdenn 1 interaction with Rab35 after insulin treatment of adipocytes. Remarkably, a peptide flanking Ser-536/Ser-538 binds the DENN domain of connecdenn 1, whereas a phosphomimetic peptide does not. Moreover, connecdenn 1 interacts with 14-3-3 proteins, and this interaction is also disrupted by Akt inhibition and by mutation of Ser-536/Ser-538. We propose that Akt phosphorylation of connecdenn 1 downstream of insulin activation regulates connecdenn 1 function through an intramolecular interaction.     

Mass Media and the Contagion of Fear: The Case of Ebola in America

Background

In the weeks following the first imported case of Ebola in the U. S. on September 29, 2014, coverage of the very limited outbreak dominated the news media, in a manner quite disproportionate to the actual threat to national public health; by the end of October, 2014, there were only four laboratory confirmed cases of Ebola in the entire nation. Public interest in these events was high, as reflected in the millions of Ebola-related Internet searches and tweets performed in the month following the first confirmed case. Use of trending Internet searches and tweets has been proposed in the past for real-time prediction of outbreaks (a field referred to as “digital epidemiology”), but accounting for the biases of public panic has been problematic. In the case of the limited U. S. Ebola outbreak, we know that the Ebola-related searches and tweets originating the U. S. during the outbreak were due only to public interest or panic, providing an unprecedented means to determine how these dynamics affect such data, and how news media may be driving these trends.

Methodology

We examine daily Ebola-related Internet search and Twitter data in the U. S. during the six week period ending Oct 31, 2014. TV news coverage data were obtained from the daily number of Ebola-related news videos appearing on two major news networks. We fit the parameters of a mathematical contagion model to the data to determine if the news coverage was a significant factor in the temporal patterns in Ebola-related Internet and Twitter data.

Conclusions

We find significant evidence of contagion, with each Ebola-related news video inspiring tens of thousands of Ebola-related tweets and Internet searches. Between 65% to 76% of the variance in all samples is described by the news media contagion model.     

On a Model of Pattern Regeneration Based on Cell Memory

We present here a new model of the cellular dynamics that enable regeneration of complex biological morphologies. Biological cell structures are considered as an ensemble of mathematical points on the plane. Each cell produces a signal which propagates in space and is received by other cells. The total signal received by each cell forms a signal distribution defined on the cell structure. This distribution characterizes the geometry of the cell structure. If a part of this structure is removed, the remaining cells have two signals. They keep the value of the signal which they had before the amputation (memory), and they receive a new signal produced after the amputation. Regeneration of the cell structure is stimulated by the difference between the old and the new signals. It is stopped when the two signals coincide. The algorithm of regeneration contains certain rules which are essential for its functioning, being the first quantitative model of cellular memory that implements regeneration of complex patterns to a specific target morphology. Correct regeneration depends on the form and the size of the cell structure, as well as on some parameters of regeneration.     

Altered ivermectin pharmacology and defective visual system in <Emphasis Type="Italic">Drosophila</Emphasis> mutants for histamine receptor HCLB

The Drosophila gene hclB encodes a histamine-gated chloride channel, which can be activated by the neurotoxin ivermectin when expressed in vitro. We have identified two novel hclB mutants, carrying either a missense mutation (P293S, allele hclB ^T1 ) or a putative null mutation (W111*, allele hclB ^T2 ), as well as a novel splice form of the gene. In survival studies, hclB ^T1 mutants were more sensitive to ivermectin than wild-type, whereas hclB ^T2 were more resistant. Electroretinogram recordings from the two mutants exhibited enlarged peak amplitudes of the transient components, indicating altered synaptic transmission between retinal photoneurons and their target cells. Ivermectin treatment severely affected or completely suppressed these transient components in an allele-specific manner. This suppression of synaptic signals by ivermectin was dose-dependent. These results identify HCLB as an important in vivo target for ivermectin in Drosophila melanogaster, and demonstrate the involvement of this protein in the visual pathway. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An erratum to this article can be found at     

The structure of the carbohydrate backbone of the LPS from Myxococcus xanthus strain DK1622

Gram-negative rod shaped bacterium Myxococcus xanthus DK1622 produces a smooth-type LPS. The structure of the polysaccharide O-chain and the core-lipid A region of the LPS has been determined by chemical and spectroscopic methods. The O-chain was built up of disaccharide repeating units having the following structure: -->6)-alpha-D-Glcp-(1-->4)-alpha-D-GalpNAc6oMe*-(1--> with partially methylated GalNAc residue. The core region consisted of a phosphorylated hexasaccharide, containing one Kdo residue, unsubstituted at O-4, and no heptose residues. The lipid A component consisted of beta-GlcN-(1-->6)-alpha-GlcN1P disaccharide, N-acylated with 13-methyl-C14-3OH (iso-C15-3OH), C16-3OH, and 15-methyl-C16-3OH (iso-C17-3OH) acids. The lipid portion contained O-linked iso-C16 acid.