The Semiosis of “Side Effects” in Genetic Interventions

Genetic interventions, which include transgenic engineering, gene editing, and other forms of genome modification aimed at altering the information “in” the genetic code, are rapidly increasing in power and scale. Biosemiotics offers unique tools for understanding the nature, risks, scope, and prospects of such technologies, though few in the community have turned their attention specifically in this direction. Bruni (2003, 2008) is an important exception. In this paper, I examine how we frame the concept of “side effects” that result from genetic interventions and how the concept stands up to current perspectives of the role of organism activity in development. I propose that once the role of living systems in constructing and modifying the informational value of their various developmental resources is taken into account, the concept of a “side effect” will need to be significantly revised. Far from merely a disturbance brought about in a senseless albeit complex system, a biosemiotic view would take “side effects” as at least sometimes the organism’s active re-organization in order to accommodate or make use of novelty. This insight is nascent in the work of developmental plasticity and niche construction theory (West-Eberhard 2003; Odling-Smee et al. 2003), but it is brought into sharper focus by the explicitly interpretive perspective offered by biosemiotics. Understanding the “side effects” of genetic interventions depends in part on being able to articulate when and where unexpected consequences are a result of semiotic activity at various levels within the system. While a semiotic interpretation of “side effects” puts into question the naive attitude that would see all unintended side effects as indications of disturbance in system functionality, it certainly does not imply that such side effects are of no concern for the viability of the organisms in the system. As we shall see, the fact that such interventions do not respect the translation of information that occurs in multi-level biological systems ensures that disruption is still likely. But it does unprivilege the human agent as the sole generator of meaning and information in the products of biotechnology, with important consequences on how we understand our relationship with other species.     

Dealing with stochastic environmental variation in space and time: bet hedging by generalist,specialist, and diversified strategies

Building on previous work, we derive an optimization model for a two-state stochastic environment and evaluate the fitnesses of five reproductive strategies across generations. To do this, we characterize spatiotemporal variation and define grain (=patch) size as the scale of fitness autocorrelation. Fitness functions of environmental condition are Gaussian. The strategies include two specialists on each of the environmental conditions; two generalists that each fare equally well under both conditions, but one (a conservative bet hedger) optimizes the shape of the fitness function; and a diversified bet hedger producing an optimal mix of the two specialists within individual broods. When the environment is primarily in one of the two states, the specialist on that state achieves the highest fitness. In the more interesting situation where the two environments are equally prevalent in the long term, with low-moderate environmental variation, a generalist strategy (that copes with both states well) does best. Higher variation favors diversified bet hedgers, or surprisingly, specialists, depending mainly on whether spatial or temporal variation predominates. These strategies reduce variance in fitness and optimize the distribution of offspring among patches differently: specialists by spreading offspring among many independently varying patches, while diversified bet hedgers put all offspring into a few patches or a single patch. We distinguish features consistent with strategies like diversified bet hedgers that spread risk in time from features linked to strategies like specialists that spread risk in space. Finally, we present testable hypotheses arising from this study and suggest directions for future work.     

Reconsidering Darwin’s “Several Powers”

Contemporary textbooks often define evolution in terms of the replication, mutation, and selective retention of DNA sequences, ignoring the contribution of the physical processes involved. In the closing line of The Origin of Species, however, Darwin recognized that natural selection depends on prior more basic living functions, which he merely described as life’s “several powers.” For Darwin these involved the organism’s capacity to maintain itself and to reproduce offspring that preserve its critical functional organization. In modern terms we have come to recognize that this involves the continual generation of complex organic molecules in complex configurations accomplished with the aid of persistent far-from-equilibrium chemical self-organizing and self-assembling processes. But reliable persistence and replication of these processes also requires constantly available constraints and boundary conditions. Organism autonomy further requires that these constraints and co-dependent dynamics are reciprocally produced, each by the other. In this paper I argue that the different constraint-amplifying dynamics of two or more self-organizing processes can be coupled so that they reciprocally generate each other’s critical supportive boundary conditions. This coupling is a higher-order constraint (which can be distributed among components or offloaded onto molecular structures) that effectively constitutes a sign vehicle “interpreted” by the synergistic dynamics of these co-dependent self-organizing process so that they reconstitute this same semiotic-dynamic relationship and its self-reconstituting potential in new substrates. This dynamical co-dependence constitutes Darwin’s “several powers” and is the basis of the biosemiosis that enables evolution.     

The Biosemiotic Concept of the Species

Any biological species of biparental organisms necessarily includes, and is fundamentally dependent on, sign processes between individuals. In this case, the natural category of the species is based on family resemblances (in the Wittgensteinian sense), which is why a species is not a natural kind. We describe the mechanism that generates the family resemblance. An individual recognition window and biparental reproduction almost suffice as conditions to produce species naturally. This is due to assortativity of mating which is not based on certain individual traits, but on the difference between individuals. The biosemiotic model described here explains what holds a species together. It also implies that boundaries of a species are fundamentally fuzzy, and that character displacement occurs in case of sympatry. Speciation is a special case of discretisation that is an inevitable result of any communication system in work. The biosemiotic mechanism provides the conditions and communicative restrictions for the origin and persistence of diversity in the realm of living (communicative and semiotic) systems.     

Adolescent Self-Organization and Adult Smoking and Drinking over Fifty Years of Follow-Up: The British 1946 Birth Cohort

Variations in markers of adolescent self-organization predict a range of economic and health-related outcomes in general population studies. Using a population-based birth cohort study we investigated associations between adolescent self-organization and two common factors over adulthood influencing health, smoking and alcohol consumption. The MRC National Survey of Health and Development (the British 1946 birth cohort) was used to test associations between a dimensional measure of adolescent self-organization derived from teacher ratings, and summary longitudinal measures of smoking and alcohol consumption over the ensuing five decades. Multinomial regression models were adjusted for sex, adolescent emotional and conduct problems, occupational social class of origin, childhood cognition, educational attainment and adult occupational social class. With all covariates adjusted, higher adolescent self-organization was associated with fewer smoking pack years, although not with quitting; there was no association with alcohol consumption across adulthood (none or heavy compared with light to moderate). Adolescent self-organization appears to be protective against smoking, but not against heavy alcohol consumption. Interpretation of this differential effect should be embedded in an understanding of the social and sociodemographic context in which these health behaviours occur over time.     

Dibutyryl-cAMP affecting fat deposition of finishing pigs by decreasing the inflammatory system related to insulin sensitive or lipolysis

Background

The mechanism of db-cAMP regulating fat deposition and improving lean percentage is unclear and needs to be further studied.

Methods

Eighteen 100-day-old Duroc × Landrance × Large White barrows (49.75?±?0.75 kg) were used for experiment 1, and 15 eighteen 135-day-old barrows (78.34?±?1.22 kg) were used for experiment 2 to investigate the effects of dietary dibutyryl-cAMP (db-cAMP) on fat deposition in finishing pigs. Pigs were fed with a corn-soybean meal-based diet supplemented with 0 or 15 mg/kg db-cAMP, and both experiments lasted 35 days, respectively.

Results

The results showed that db-cAMP decreased the backfat thickness, backfat percentage, and diameter of backfat cells without changing the growth performance or carcass characteristics in both experiments, and this effect was more marked in experiment 1 than in experiment 2; db-cAMP enhanced the activity of the growth hormone–insulin-like growth factor-1 (GH-IGF-1) axis and pro-opiomelanocortin (POMC) system in both experiments, which suppressed the accumulation of backfat deposition; microarray analysis showed that db-cAMP suppressed the inflammatory system within the adipose tissue related to insulin sensitivity, which also reduced fat synthesis.

Conclusions

In summary, the effect of db-cAMP on suppressing fat synthesis and accumulation is better in the earlier phase than in the later phase of finishing pigs, and db-cAMP plays this function by increasing the activity of the GH-IGF-1 axis and POMC system, while decreasing the inflammatory system within the adipose tissue related to insulin sensitive or lipolysis.

     

Effect of Hydrothermal Modifications on Functional,Pasting and Structural Properties of False Banana (<Emphasis Type="Italic">Ensete ventricosum</Emphasis>) Starch

Starch extracted from ensete (Ensete ventricosum, Musaceae) also called false banana, was modified by hydrothermal methods of annealing (ANN) and heat moisture treatment (HMT) processes. The effects of treatments on functional, pasting properties, morphology and diffraction pattern of the starch were studied. Swelling power and solubility changed significantly (p < 0.05) with modification. Water absorption (89.3–152.4 %) and oil absorption (105.0–161.3 %) capacities increased significantly (p < 0.05) with ANN and HMT. Alkaline water retention decreased with ANN but increased significantly (p < 0.05) with HMT. Hydrothermal modifications led to reduction in least gelation capacity of ensete starch. In terms of the pasting properties studied, the hydrothermal modifications imparted improved gel strength, increased paste stability, reduced retrogradation tendency and slowed staling rate on ensete starch. Scanning electron micrographs depicted fairly angular and elliptical shapes with diverse sizes for the starch granules. Clustering of granules, mucilage formation, fissures and surface indentation which were gaining prominence with increasing moisture level and temperature of treatment were the hallmarks of modified samples. Native and modified ensete starches showed similar type-B diffraction pattern with maximum peak range of 19.8–20.0^o (2θ). Findings of this work showed that hydrothermally modified ensete starches possess excellent value-added potentials for utilization in pharmaceuticals and food applications.