The DarTG toxin-antitoxin system provides phage defense by ADP-ribosylating viral DNA

Toxin-antitoxin (TA) systems are broadly distributed, yet poorly conserved, genetic elements whose biological functions are unclear and controversial. Some TA systems may provide bacteria with immunity to infection by their ubiquitous viral predators, the bacteriophage. To identify TA systems that protect E. coli MG1655 against phage, we searched for those frequently encoded near known phage defense genes in bacterial genomes. Two of the systems tested provide strong protection against phage infection and are homologs of DarTG, a recently discovered family of TA systems whose biological functions and natural activating conditions were unclear. We demonstrate that phage infection triggers the release of DarT toxin, a DNA ADP-ribosyltransferase, to modify viral DNA and prevent replication, thereby blocking the production of mature virions. Phages can evolve to overcome DarTG defense either through mutations to their DNA polymerase or to an anti-DarT factor, gp61.2, encoded by many T-even phages. Collectively, our results indicate that phage defense may be a common function for TA systems and reveal the mechanism by which DarTG systems inhibit phage infection.

Systems of Communication: Aspects of Culture and Structure in Speech Surrogates

The practice of speech surrogacy is used for communication across many cultures. Previous work has historically engaged with the study of speech surrogates as part of anthropological or ethnomusicological inquiry; more recently, scholars have explored aspects of the formal relationship between spoken and surrogate linguistic structures. How speech surrogates function as systems of communication is not yet well understood. Based on evidence from an interdisciplinary corpus of documentation, characteristics of culture and discourse, as well as features of linguistic structure, are shown to play a role in fostering communicability in speech surrogates. Cultural constraints are linked to the development of a speech surrogate-mediated discourse within a community of practice, facilitating comprehension of the surrogate system. Moreover, specific structures including formulas, enphrasing, and framing devices are identified as common to various speech surrogate traditions, suggesting a common function as aids to communication. This analysis points to the need to investigate speech surrogates as linguistic systems within a discursive context.

Using application benchmark call graphs to quantify and improve the practical relevance of microbenchmark suites

Performance problems in applications should ideally be detected as soon as they occur, i.e., directly when the causing code modification is added to the code repository. To this end, complex and cost-intensive application benchmarks or lightweight but less relevant microbenchmarks can be added to existing build pipelines to ensure performance goals. In this paper, we show how the practical relevance of microbenchmark suites can be improved and verified based on the application flow during an application benchmark run. We propose an approach to determine the overlap of common function calls between application and microbenchmarks, describe a method which identifies redundant microbenchmarks, and present a recommendation algorithm which reveals relevant functions that are not covered by microbenchmarks yet. A microbenchmark suite optimized in this way can easily test all functions determined to be relevant by application benchmarks after every code change, thus, significantly reducing the risk of undetected performance problems. Our evaluation using two time series databases shows that, depending on the specific application scenario, application benchmarks cover different functions of the system under test. Their respective microbenchmark suites cover between 35.62% and 66.29% of the functions called during the application benchmark, offering substantial room for improvement. Through two use cases—removing redundancies in the microbenchmark suite and recommendation of yet uncovered functions—we decrease the total number of microbenchmarks and increase the practical relevance of both suites. Removing redundancies can significantly reduce the number of microbenchmarks (and thus the execution time as well) to ~10% and ~23% of the original microbenchmark suites, whereas recommendation identifies up to 26 and 14 newly, uncovered functions to benchmark to improve the relevance. By utilizing the differences and synergies of application benchmarks and microbenchmarks, our approach potentially enables effective software performance assurance with performance tests of multiple granularities.

DyP-Type Peroxidases: Recent Advances and Perspectives

In this review, we chart the major milestones in the research progress on the DyP-type peroxidase family over the past decade. Though mainly distributed among bacteria and fungi, this family actually exhibits more widespread diversity. Advanced tertiary structural analyses have revealed common and different features among members of this family. Notably, the catalytic cycle for the peroxidase activity of DyP-type peroxidases appears to be different from that of other ubiquitous heme peroxidases. DyP-type peroxidases have also been reported to possess activities in addition to peroxidase function, including hydrolase or oxidase activity. They also show various cellular distributions, functioning not only inside cells but also outside of cells. Some are also cargo proteins of encapsulin. Unique, noteworthy functions include a key role in life-cycle switching in Streptomyces and the operation of an iron transport system in Staphylococcus aureus, Bacillus subtilis and Escherichia coli. We also present several probable physiological roles of DyP-type peroxidases that reflect the widespread distribution and function of these enzymes. Lignin degradation is the most common function attributed to DyP-type peroxidases, but their activity is not high compared with that of standard lignin-degrading enzymes. From an environmental standpoint, degradation of natural antifungal anthraquinone compounds is a specific focus of DyP-type peroxidase research. Considered in its totality, the DyP-type peroxidase family offers a rich source of diverse and attractive materials for research scientists.

Trans-acting genetic variation affects the expression of adjacent genes

Gene expression differences among individuals are shaped by trans-acting expression quantitative trait loci (eQTLs). Most trans-eQTLs map to hotspot locations that influence many genes. The molecular mechanisms perturbed by hotspots are often assumed to involve “vertical” cascades of effects in pathways that can ultimately affect the expression of thousands of genes. Here, we report that trans-eQTLs can affect the expression of adjacent genes via “horizontal” mechanisms that extend along a chromosome. Genes affected by trans-eQTL hotspots in the yeast Saccharomyces cerevisiae were more likely to be located next to each other than expected by chance. These paired hotspot effects tended to occur at adjacent genes that also show coexpression in response to genetic and environmental perturbations, suggesting shared mechanisms. Physical proximity and shared chromatin state, in addition to regulation of adjacent genes by similar transcription factors, were independently associated with paired hotspot effects among adjacent genes. Paired effects of trans-eQTLs can occur at neighboring genes even when these genes do not share a common function. This phenomenon could result in unexpected connections between regulatory genetic variation and phenotypes.

Epistêmê Is of What Is

If Plato’s epistemology is indeed objects-based, then he conceives of epistêmê first and foremost as the cognition of a certain kind of object. What is this object? We find a clear answer in the powers argument: epistêmê is of what is, or being. Indeed throughout the dialogues Plato treats this claim as a basic principle, something that everyone will accept. But this may seem an unhelpful answer, for Plato’s talk of being is famously ambiguous, and much debated. I will argue that there is nonetheless a general characterization available: in contexts relevant to the correlation of epistêmê with being, regardless of what ‘being’ or variants mean, the label ‘being’ serves a common function: it privileges certain items above others. The key notion should be understood as the ontologically superior, or of what really is, by contrast with things that have some derivative or inferior status. Epistêmê’s defining object is Being in this sense.

Investigation and analysis of color pragmatics in Beyghami DarabNameh

In the present article, the function of colors in Beyghami DarabNameh has been investigated by descriptive-analytical method. The most frequent colors in this prose work are black and red; the main reason for this frequency is the epic content and the occurrence of successive wars. A common function seen in all colors is the descriptive aspect. In addition, the description of the biological and psychological conditions of the characters, the induction of inner emotions and objectification of abstract concepts has been done with the help of colors. In general, the colors used in DarabNameh are non-symbolic, explicit and direct, and lack multiple layers of meaning, which indicates the realistic and objectivist attitude of the author. The most important weakness of Beyghami in the field of storytelling, which is revealed by analyzing the pragmatics of colors, is the imbalance in its application in the narrative process.

Essays: myths and dead ends of artificial intelligence

The article contains an analysis of the philosophical foundations of the very idea of creating and implementing artificial intelligence via comparison by analogy with the hypothetical concept of "artificial life". The logical and conceptual unfoundedness of common definitions of artificial intelligence is demonstrated. The article offers the understanding of intelligence as an exclusively natural way of solving tasks, and not as a common function that can be implemented on the basis of other technologies. The conclusion is made about the inexpediency of direct replacement of a human with devices with artificial intelligence without a fundamental change in the basic principles of organizing field of activity. The questionableness of the idea of creating general artificial intelligence as a universal local device with a unified architecture in the presence of many specialized devices is substantiated. Doubts are expressed about the effectiveness of the application of evolutionary methods and learning procedures in the design of devices that solve tasks that are considered intelligent.