Peptides as ‘Drugs’: The Journey so Far

Peptide based drugs are now a day fascinating application areas. This brief review focuses on the history of peptides, synthesis of peptides, their therapeutic applications and the current status of peptides in the market.     

The Scientific Discovery of ‘Natural Capital’: The Production of Catalytic Antibodies

Modern science has undoubtedly become one the principal engines of economic growth, even though the epistemological status of scientific knowledge has been continuously contested. Leaving the philosophical problem of knowledge aside, this paper examines how scientific discovery contributes to the production of wealth. The analysis focuses on a recent achievement at the crossroads of chemistry, immunology and biotechnology: antibody catalysis. For this purpose, we develop a model of entrepreneurial work to explain how the discovery of natural products and processes generates new economic opportunities. The proposed model is based on the assumption that scientists believe that the natural environment is a repository of ‘natural capital’. Natural capital includes goods that are not made by humans but can be used to produce other goods and services. The belief in natural capital induces scientists to search for and identify a natural property that, in the specific cultural context of their work, is recognized as a valuable resource. The selection of such a property forms the initial phase of the discovery process. Certain research methods are then deployed to create novel empirical conditions within which the selected property is transformed into a specific good. The discovery of natural capital thus comprises a historically accountable entrepreneurial endeavour.     

The biological cost of mutational antibiotic resistance: any practical conclusions?

A key parameter influencing the rate and trajectory of the evolution of antibiotic resistance is the fitness cost of resistance. Recent studies have demonstrated that antibiotic resistance, whether caused by target alteration or by other mechanisms, generally confers a reduction in fitness expressed as reduced growth, virulence or transmission. These findings imply that resistance might be reversible, provided antibiotic use is reduced. However, several processes act to stabilize resistance, including compensatory evolution where the fitness cost is ameliorated by additional mutation without loss of resistance, the rare occurrence of cost-free resistance mechanisms and genetic linkage or co-selection between the resistance markers and other selected markers. Conceivably we can use this knowledge to rationally choose and design targets and drugs where the costs of resistance are the highest, and where the likelihood of compensation is the lowest.     

‘To be,or not to be’—The dilemma of ‘silent’ antimicrobial resistance genes in bacteria

Antimicrobial resistance is a serious threat to public health that dramatically undermines our ability to treat bacterial infections. Microorganisms exhibit resistance to different drug classes by acquiring resistance determinants through multiple mechanisms including horizontal gene transfer. The presence of drug resistance genotypes is mostly associated with corresponding phenotypic resistance against the particular antibiotic. However, bacterial communities harbouring silent antimicrobial resistance genes—genes whose presence is not associated with a corresponding resistant phenotype do exist. Under suitable conditions, the expression pattern of such genes often revert and regain resistance and could potentially lead to therapeutic failure. We often miss the presence of silent genes, since the current experimental paradigms are focused on resistant strains. Therefore, the knowledge on the prevalence, importance and mechanism of silent antibiotic resistance genes in bacterial pathogens are very limited. Silent genes, therefore, provide an additional level of complexity in the war against drug-resistant bacteria, reminding us that not only phenotypically resistant strains but also susceptible strains should be carefully investigated. In this review, we discuss the presence of silent antimicrobial resistance genes in bacteria, their relevance and their importance in public health.     

Genetics of resistance to Puccinia graminis tritici in ‘Chris’ and ‘W3746’ wheats

Summary Chris wheat possessed genes Sr5, Sr7a, Sr8a, Sr9g and Sr12. W3746, derived from the cross Chris/Baart, possessed Sr7a and Sr12. The response conferred by Sr7a was influenced by the genetic background. Although Sr7a or Sr12 alone conferred no observable resistance upon adult plants, the adult resistances of Chris and W3746 to predominant pathotypes appeared to be associated with the interaction of Sr7a and Sr12, or genes at closely linked loci.     

The role of Schmidt ‘Antonovka’ in apple scab resistance breeding

??Antonovka?? has long been recognised as a major source of scab (Venturia inaequalis) resistance useful for apple breeding worldwide. Both major gene resistances in the form of the Rvi10 and Rvi17 and quantitative resistance, collectively identified as VA, have been identified in different accessions of ??Antonovka??. Most of the ??Antonovka?? scab resistance used in apple-breeding programmes around the world can be traced back to Schmidt ??Antonovka?? and predominantly its B VIII progenies 33,25 (PI 172623), 34,6 (PI 172633), 33,8 (PI 172612) and 34,5 (PI 172632). Using genetic profile reconstruction, we have identified ??common ??Antonovka?? ?? as the progenitor of the B VIII family, which is consistent with it having been a commercial cultivar in Poland and the single source of scab resistance used by Dr. Martin Schmidt. The major ??Antonovka?? scab resistance genes mapped to date are located either very close to Rvi6, or about 20?C25?cM above it, but their identities need further elucidation. The presence of the 139?bp allele of the CH-Vf1 microsatellite marker known to be associated with Rvi17 (Va1) in most of the ??Antonovka?? germplasm used in breeding suggests that it plays a central role in the resistance. The nature and the genetic relationships of the scab resistance in these accessions as well as a number of apple cultivars derived from ??Antonovka??, such as, ??Freedom??, ??Burgundy?? and ??Angold??, are discussed. The parentage of ??Reglindis?? is unclear, but the cultivar commercialised as ??Reglindis?? was confirmed to be an Rvi6 cultivar.     

The economic approach to ‘theory of mind’

Theory of mind (ToM) is a great evolutionary achievement. It is a special intelligence that can assess not only one''s own desires and beliefs, but also those of others. Whether it is uniquely human or not is controversial, but it is clear that humans are, at least, significantly better at ToM than any other animal. Economists and game theorists have developed sophisticated and powerful models of ToM and we provide a detailed summary of this here. This economic ToM entails a hierarchy of beliefs. I know my preferences, and I have beliefs (a probabilistic distribution) about your preferences, beliefs about your beliefs about my preferences, and so on. We then contrast this economic ToM with the theoretical approaches of neuroscience and with empirical data in general. Although this economic view provides a benchmark and makes useful suggestions about empirical tendencies, it does not always generate a close fit with the data. This provides an opportunity for a synergistic interdisciplinary production of a falsifiable theory of bounded rationality. In particular, a ToM that is founded on evolutionary biology might well be sufficiently structured to have predictive power, while remaining quite general. We sketch two papers that represent preliminary steps in this direction.     

Expression of pAMα1 tetracycline resistance gene inCorynebacterium glutamicum: Segregation of antibiotic resistance due to intramolecular recombination

Summary AnEscherichia coli/Corynebacterium glutamicum chimeric plasmid has been constructed containing the tetracycline resistance (Tc^R) determinant from pAM1 and the kanamycin resistant (Km^R) determinant from pBD10. The paAM1 tetracycline resistance determinant is expressed inC. glutamicum although the transformed population segregates readily into tetracycline and kanamycin resistant populations. The segregation event is the result of an intramolecular recombination between the pAM1 and pUB110 regions of the chimera.     

What are the missing pieces needed to stop antibiotic resistance?

As recognized by several international agencies, antibiotic resistance is nowadays one of the most relevant problems for human health. While this problem was alleviated with the introduction of new antibiotics into the market in the golden age of antimicrobial discovery, nowadays few antibiotics are in the pipeline. Under these circumstances, a deep understanding on the mechanisms of emergence, evolution and transmission of antibiotic resistance, as well as on the consequences for the bacterial physiology of acquiring resistance is needed to implement novel strategies, beyond the development of new antibiotics or the restriction in the use of current ones, to more efficiently treat infections. There are still several aspects in the field of antibiotic resistance that are not fully understood. In the current article, we make a non-exhaustive critical review of some of them that we consider of special relevance, in the aim of presenting a snapshot of the studies that still need to be done to tackle antibiotic resistance.     

Natural selection can favour ‘irrational’ behaviour

Understanding decisions is the fundamental aim of the behavioural sciences. The theory of rational choice is based on axiomatic principles such as transitivity and independence of irrelevant alternatives (IIA). Empirical studies have demonstrated that the behaviour of humans and other animals often seems irrational; there can be a lack of transitivity in choice and seemingly irrelevant alternatives can alter decisions. These violations of transitivity and IIA undermine rational choice theory. However, we show that an individual that is maximizing its rate of food gain can exhibit failure of transitivity and IIA. We show that such violations can be caused because a current option may disappear in the near future or a better option may reappear soon. Current food options can be indicative of food availability in the near future, and this key feature can result in apparently irrational behaviour.