Course Of Evolution Research Articles

Study of Inter-Species Social Interactions Among Bacterial Cells Using Computer Vision and Zeta Potential Analysis.

The interplay between the growth patterns of two or more bacterial species in a co-culture system is often overlooked in traditional microbiology. Analysing the behaviour of pathogens as part of a cohort of bacterial species becomes important because when under a high degree of stress or in large populations, bacterial species can develop mutants. However, the factors affecting the course of such social evolution remain unexplored. In this article, we have attempted to systematically study the social interaction in paired and triplet mixed cultures of Escherichia coli, Salmonella enterica serovar Typhimurium and Staphylococcus aureus. The method is based on computer vision analysis of selective agar plating of both pure and mixed cultures (plated after co-incubation) followed by Zeta potential measurements. Primarily, the social interactions between bacterial species, whether synergetic or antagonistic, are mediated through the exchange of electrical charges. The density of charges which are present on the bacterial surface can be characterised by measuring the Zeta potential. Studying the Zeta potential of co-cultures in various volume ratios aims at probing the effect of mixing of species on the resultant surface charge of the cells in the cohort. Based on the results, we explore how certain species electrically dominate over others in co-cultures, yet they co-exist. Most importantly, the surface charge modifications arising due to the social interactions can severely affect the bactericidal action of antimicrobial agents. To confirm this, the last section of the manuscript is dedicated to the antimicrobial susceptibility tests performed using the disc diffusion method on pure samples and consortia. The results are presented for eleven different antibiotics indicating significant alterations in the efficacy of some of the antimicrobial agents when used against co-cultures.

Revisiting the cosmological phase transitions on the inflationary gravitational waves with BKP18

The effects of the electroweak and the quark-gluon plasma phase transitions are considered in the course of evolution of the universe and the resulting spectrum of primordial gravitational waves normalized with the BICEP/Keck and Planck joint data is obtained. The QGP index n=0.203 leads to a step reduction of ∼17.6% in the amplitude and a step of ∼35% in the energy density spectrum for frequency >1.36×10−8Hz. On the other hand, the EW index w=0.0147 leads to a step of ∼1.47% in the amplitude and a step of ∼2.9% in the energy density spectrum for frequency >10−5Hz. The combined effect of phase transitions on the inflationary gravitational waves leads to about ∼19% reduction in the amplitude and an overall reduction of ∼38% in the energy density as compared to the spectrum without considering these phase transitions. The resulting spectrum for R2 inflation model is found to be well within the BBN bound and its potential detectability is tested with the power-law integrated sensitivity curves of the future LISA, DECIGO, BBO, SKA and IPTA experiments.

The universal Sua5/TsaC family evolved different mechanisms for the synthesis of a key tRNA modification.

TsaC/Sua5 family of enzymes catalyzes the first step in the synthesis of N6-threonyl-carbamoyl adenosine (t6A) one of few truly ubiquitous tRNA modifications important for translation accuracy. TsaC is a single domain protein while Sua5 proteins contains a TsaC-like domain and an additional SUA5 domain of unknown function. The emergence of these two proteins and their respective mechanisms for t6A synthesis remain poorly understood. Here, we performed phylogenetic and comparative sequence and structure analysis of TsaC and Sua5 proteins. We confirm that this family is ubiquitous but the co-occurrence of both variants in the same organism is rare and unstable. We further find that obligate symbionts are the only organisms lacking sua5 or tsaC genes. The data suggest that Sua5 was the ancestral version of the enzyme while TsaC arose via loss of the SUA5 domain that occurred multiple times in course of evolution. Multiple losses of one of the two variants in combination with horizontal gene transfers along a large range of phylogenetic distances explains the present day patchy distribution of Sua5 and TsaC. The loss of the SUA5 domain triggered adaptive mutations affecting the substrate binding in TsaC proteins. Finally, we identified atypical Sua5 proteins in Archaeoglobi archaea that seem to be in the process of losing the SUA5 domain through progressive gene erosion. Together, our study uncovers the evolutionary path for emergence of these homologous isofunctional enzymes and lays the groundwork for future experimental studies on the function of TsaC/Sua5 proteins in maintaining faithful translation.

Managing anxiety disorders in bipolar patients

Anxiety disorders are among the main comorbidities encountered in patients with bipolar disease. Numerous clinical and epidemiological studies show an increased prevalence of anxiety pathologies (generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder, panic disorder, and post-traumatic stress disorder) in bipolar subjects compared to the frequencies in the general population. Anxiety disorders are not without consequences on the evolutionary course of the mood disorder, including a significant reduction in euthymia time and less sensitivity to conventional medicinal therapies.

The Iconicity Ring Hypothesis Bridges the Gap Between Symbol Grounding and Linguistic Relativity.

Kemmerer captured the drastic change in theories of word meaning representations, contrasting the view that word meaning representations are amodal and universal, with the view that they are grounded and language-specific. However, he does not address how language can be simultaneously grounded and language-specific. Here, we approach this question from the perspective of language acquisition and evolution. We argue that adding a new element-iconicity-is critically beneficial and offer the iconicity ring hypothesis, which explains how language-specific, secondary iconicity might emerge from biologically grounded and universally shared iconicity in the course of language acquisition and evolution.

Towards an Interdisciplinary Approach in Public Legal Research

The article raises the question of the need to expand interdisciplinary links of legal science and its output beyond the socio-cultural context, in which the state-legal phenomena are most often studied. On the example of the data of evolutionary biology, cognitive and evolutionary psychology, as well as a number of other directions of modern scientific knowledge, the issues that can and should become a subject of reflection for legal scientists are outlined. At the same time, attention is drawn to the relevance of the principle of transdisciplinarity in the knowledge of the world around, including the study of law and state.Some perspective directions of interdisciplinary research of human legal behavior and state-legal regulation are defined. In particular, the influence of the system of intuitive inferences is developed in the course of biological evolution and is not controlled by consciousness on the process of selection and perception of meaningful information (including predisposition to learning morality), on the ability of a person to form various associations and innate mechanisms of recognizing social alliances (coalitions) and control over loyalty to them, on the built-in in the mind patterns of exchange and sense of justice are outlined.

Endocrine communication of endoplasmic reticulum stress.

Cellular stress is caused by a multitude of environmental factors, which over the course of evolution have led to the development of molecular resistance programs.[1] Many of these are linked to the endoplasmic reticulum (ER), as the ER is the central platform for cellular lipid and protein synthesis. The unfolded protein response (UPR) is activated when partially folded or misfolded proteins accumulate in the lumen of the ER, typically referred to as ER stress. Through specific sensor proteins in the ER membrane, the cell can restore normal proteostasis by means of halted protein translation and enhanced folding machinery. However, if ER stress remains unresolved, sustained activation of UPR will ultimately result in cell death. In this issue of BioEssays, Watt et al. discuss UPR activation and the formation of bioactive lipids, proposing an endocrine role for ceramides in propagating UPR signaling to distant tissues.[2] There is evidence that ER stress is transmitted from stressed cells to healthy neighbors,[3] but the general view in the field is that cellular stress is communicated by cytokines (Figure 1). Undoubtedly, ER stress is associated with tissue inflammation and several lipid mediators are implicated in both initiation and resolution of inflammation. Over the past years, several bioactive lipids implicated in cell signaling have been described. Among these, ceramides are known to play a role in a variety of diseases, such as obesity, diabetes, hypertension, cancer, and COVID-19, where plasma and tissue levels of this sphingolipid are elevated. The detrimental effects of ceramides are associated with the disruption of intracellular signaling and induction of pro-inflammatory cytokine release. In terms of endocrine activity, ceramide action in the pathophysiology of diseases remains to be elucidated. This is complex because how ceramides are released or transported in the circulation is not well understood. Furthermore, dissociating ceramide action from inflammatory signaling might be difficult. It is noteworthy that while Watt et al. focus on discussing UPR as the main program combating ER stress,[2] proteostasis and the prevention and resolution of ER stress are critically dependent on the interplay of UPR, ER-associated protein degradation (ERAD), ubiquitin-proteasome system (UPS), and autophagy in a cell type-specific fashion.[1] It is still unclear how each of these programs compensate for each other but there is evidence that failure of one activates the others. For example, when UPS function is compromised, UPR and autophagy are activated, but this response is insufficient to restore proteostasis in the context of metabolic adaptation. Interestingly, failure of the UPS is associated with increased susceptibility to reactive oxygen species (ROS) and oxidative stress.[4] Especially in lipid-rich tissues or under conditions of dysregulated lipid metabolism such as obesity, ER stress could promote lipid peroxidation and local or distant tissue damage. In this context, one needs to consider that protein folding, one of the critical processes in the ER, is carried out in an oxidative environment to ensure the correct formation of disulfide bonds, which is very sensitive to changes in redox homeostasis. When ER stress is sustained, the increasing production of ROS drives the cell toward a state of oxidative stress. The unchecked production of ROS leads to the creation of oxilipid species, which have been described to have signaling functions,[5] but are also linked to ferroptosis, a non-apoptotic form of cell death induced by iron-dependent lipid peroxidation. Whether ER stress is directly linked to ferroptosis is poorly explored, but it is conceivable that sustained unresolved ER stress would promote ferroptosis. In fact, it has been recently shown that dysfunctional proteostasis is associated with increased susceptibility to ferroptosis.[4] How this local tissue damage response would be communicated in an endocrine fashion is unknown, but the hypothesis that ceramides or oxilipids play a role as lipokines here is intriguing. In conclusion, Watt et al. propose that bioactive lipids are extracellular communicators of ER stress. While this hypothesis is valid, more work is needed to provide causal proof of this concept. However, even if these lipids turn out to be biomarkers instead of causal lipokines they might still be useful for the early detection of diabetes and other diseases caused or promoted by ER stress. This article comments in the hypothesis paper by Nicole Watt, Anna McGrane, and Lee Roberts, https://doi.org/10.1002/bies.202300029. Alba Mena Gómez wrote the manuscript and created the figure with the help of Alexander Bartelt. All authors read and commented on the manuscript. Alexander Bartelt was supported by the German Center for Cardiovascular Research (DZHK), the DFG SPP2306 on ferroptosis, and the ERC Starting Grant PROTEOFIT. We apologize to colleagues whose work we could not cite due to space limitations. The authors declare no conflicts of interest.

Two Millennia of Climate History for the Russian Altai: Integrated Reconstruction from Lake Sediment Data

Abstract—A continuous history of annual air temperatures in the Russian Altai for the past 2000 years has been reconstructed for the first time by integrating climate archives stored in the bottom sediments of four lakes in Gorny Altai (Teletskoye, Kucherla, Lower Multa, and Middle Multa). The integrated chronology comprises all known climate events of the two millennia time span: Roman warm epoch (~200 to 500 AD), Dark Age cold epoch (~500 to 750 AD), medieval warming (~750 to 1300 AD), and Little Ice Age (~1300 to 1850 AD). The events distinguished in the integrated climate reconstruction agree perfectly in number and time with the events reconstructed from other climate proxies for the Altai and adjacent areas of West Siberia, Tyva, and West Mongolia. Therefore, the temperature patterns represent a common course of the 2000-year climate evolution over a large part of Central Asia. Similar synchronicity is observed with the available quantitative climate reconstructions for the Northern Hemisphere and its different regions. It means that the climate change in Central Asia over the past two millennia has followed the general global scenario.

The effects of religious views and creationism on teleological reasoning, acceptance and understanding of natural selection: a preliminary mixed-methods study

BackgroundCreationist religious views have a large influence on the public’s views and learning related to evolution, especially human evolution. Creationism has been shown to reinforce students’ design teleological stance, which creates a challenging conceptual obstacle for learning evolution. The purpose of the current study was to determine if students with creationist views responded differently to education intended to directly challenge design teleological reasoning in the context of a human evolution course, compared to students with naturalist views. In a convergent mixed methods design this study combined pre- and post-semester quantitative survey data (N = 48) on student endorsement of teleological reasoning, acceptance of evolution (Inventory of Student Evolution Acceptance), and understanding of natural selection (Conceptual Inventory of Natural Selection), with a thematic analysis of student reflective writing on their understanding and acceptance of natural selection and teleological reasoning.ResultsThis study found that students with creationist views had higher levels of design teleological reasoning and lower levels of acceptance of evolution at the beginning of the semester, compared to students with naturalist views (p < 0.01). Students with creationist views experienced significant (p < 0.01) improvements in teleological reasoning and acceptance of human evolution. While the changes in teleological reasoning, understanding and acceptance experienced by students with creationist views were similar in magnitude to changes in students with naturalist views, creationists never achieved levels of evolution understanding and acceptance seen in students with naturalist views. Multiple linear regression showed that student religiosity was a significant predictor of understanding of evolution, while having creationist views was a predictor of acceptance of evolution. Thematic analysis revealed that more students believed that religion and evolution are incompatible than compatible. However, more than one-third of students expressed openness to learning about evolution alongside their religious views.ConclusionsStudents with creationist views made gains on nearly all measures, but significantly underperformed their counterparts with natural views. For many students, religiosity and creationism challenge their thinking about evolution. This paper describes pedagogical practices to help students understand their own teleological reasoning and support students with creationist views who are learning about evolution.

Cell wall thickness has phylogenetically consistent effects on the photosynthetic nitrogen-use efficiency of terrestrial plants.

Leaf photosynthetic nitrogen-use efficiency (PNUE) diversified significantly among C3 species. To date, the morpho-physiological mechanisms and interrelationships shaping PNUE on an evolutionary time scale remain unclear. In this study, we assembled a comprehensive matrix of leaf morpho-anatomical and physiological traits for 679 C3 species, ranging from bryophytes to angiosperms, to comprehend the complexity of interrelationships underpinning PNUE variations. We discovered that leaf mass per area (LMA), mesophyll cell wall thickness (Tcwm ), Rubisco N allocation fraction (PR ), and mesophyll conductance (gm ) together explained 83% of PNUE variations, with PR and gm accounting for 65% of those variations. However, the PR effects were species-dependent on gm , meaning the contribution of PR on PNUE was substantially significant in high-gm species compared to low-gm species. Standard major axis (SMA) and path analyses revealed a weak correlation between PNUE and LMA (r2 = 0.1), while the SMA correlation for PNUE-Tcwm was robust (r2 = 0.61). PR was inversely related to Tcwm , paralleling the relationship between gm and Tcwm , resulting in the internal CO2 drawdown being only weakly proportional to Tcwm . The coordination of PR and gm in relation to Tcwm constrains PNUE during the course of evolution.

Teleonomy in living systems: an overview

Abstract An introduction, overview and discussion are provided for this special issue of the Biological Journal of the Linnean Society, entitled ‘Teleonomy in Living Systems’. The introduction offers a brief account of the origin of Colin Pittendrigh’s notion of teleonomy, in many ways comparable to Dobzhansky’s later proposal of ‘internal teleology’, and a subsequent externalist interpretation of the concept by Ernst Mayr which, unfortunately, has remained influential. As part of the growing movement that places organismic purpose, goal-directedness and agency back at the centre of biology, in June 2021 a 2-day online international meeting was organized by the authors through the Linnean Society of London, under the title Evolution ‘On Purpose’: Teleonomy in Living Systems. Our overview provides a summary, with some commentary, for each of 15 papers presented here. Together with a complementary volume of 18 papers published by MIT Press, they form a selected and extended proceedings. These papers represent scientifically founded views of evolutionary biologists and philosophers of science who seriously question the adequacy of the neo-Darwinian Modern Synthesis to account for the purposive nature of living systems. Like any other phenomena associated with life, purposive and teleonomic behaviours demand evolutionary explanations and context. Without any recourse to supernatural or non-material processes, various approaches to trying to understand how this goal-directed, teleonomic property of life has influenced the course of evolution are explored.

Abstract A078: Identifying and targeting the genetic determinants of immune suppression and immunotherapy failure in prostate cancer

Abstract The advent of immunotherapies such as immune checkpoint blockade (ICB) has greatly expanded the therapeutic options available to patients with treatment-refractory solid tumors. However, patients with castration-resistant prostate cancer (CRPC) generally remain unresponsive to ICB therapy due to an immunologically “cold” prostate tumor microenvironment (TME) with limited accessibility to cytotoxic lymphocytes such as Natural Killer (NK) and T cells that can mediate potent anti-tumor immunity. During the course of tumor evolution, CRPCs acquire many genomic alterations and copy number changes that can influence therapy outcomes. Yet the impact of such genetic alterations on the immune TME and response to ICB remains largely unknown, in part due to the lack of models to functionally study them in an immune competent setting. To this end, we previously developed a novel electroporation-based genetically engineered mouse model (EPO-GEMM) to rapidly generate genetically defined prostate tumors de novo within an intact prostate TME (Leibold*, Ruscetti* et al., Cancer Discovery 2020). Here, we applied the EPO-GEMM approach to characterize the immune landscapes of distinct genetic subtypes of CRPC and subsequently identify and target tumor intrinsic mediators of immune suppression for prostate cancer immunotherapy. Using transposon systems to overexpress the MYC oncogene and CRISPR/Cas9 vectors to inactivate tumor suppressor genes (TSGs) commonly altered in CRPC (Pten, P53, Rb1, Apc), we generated a suite of genetically distinct prostate cancer-bearing EPO-GEMMs. Histological analysis revealed genotype-specific immune infiltrates, with MYC-driven tumors generally lacking cytotoxic CD8+ T cells and harboring increased numbers of regulatory T cells (Tregs). A similar correlation was also observed between MYC levels and cytotoxic lymphocyte suppression in CRPC patient samples. In particular, tumors with compound MYC overexpression and p53 loss (MP) displayed drastic NK cell suppression. Cytokine and RNA-seq profiling of primary EPO-GEMM CRPCs, tumor-derived cell lines, and isogenic Myc-CaP cells engineered with TSG losses revealed that MP alterations led to not only inhibition of inflammatory cytokine and interferon signaling and antigen presentation/processing gene expression, but also induction of VEGF signaling and increased angiogenesis in the prostate TME. Treatment of MP tumors with a VEGFR2 antibody to block VEGF signaling significantly reduced tumor growth and increased NK and CD8+T cell infiltration and activation, indicating a phenotypic switch from a traditionally “cold” TME. Our results demonstrate that the genetic configuration of prostate cancer shapes its surrounding TME. Additionally, targeting VEGF signaling may be a mechanism to overcome ICB resistance in prostate cancer. More broadly, we believe that by understanding the tumor intrinsic mechanisms driving immune suppression, we can identify rational immunotherapy combinations for CRPC based on the genetic fingerprint of a patient’s tumor for precision medicine. Citation Format: Katherine C. Murphy, Kelly DeMarco, Yvette Lopez-Diaz, Lin Zhou, Marcus Ruscetti. Identifying and targeting the genetic determinants of immune suppression and immunotherapy failure in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A078.

Subtelomeres: hotspots of genome variation.

Eukaryotic cells contain multiple types of duplicated sequences. Typical examples are tandem repeat sequences including telomeres, centromeres, rDNA genes and transposable elements. Most of these sequences are unstable; thus, their copy numbers or sequences change rapidly in the course of evolution. In this review, I will describe roles of subtelomere regions, which are located adjacent to telomeres at chromosome ends, and recent discoveries about their sequence variation.

Getting athletes back in the game

Movement is an essential characteristic that has developed over the course of human evolution. With the inclusion of various populations in sports activities, sports have become an important part of people’s daily lives. Knee injuries are common among athletes, with knee joint being the most vulnerable to various injuries. Knee injuries require appropriate treatment to allow the athlete to return to their sports activities. Additionally, this study aimed to increase awareness of the importance of preventing knee injuries in sports and to highlight the potential impact of such injuries on an athlete’s ability to participate in their sport.A cross-sectional study was conducted to evaluate the functional outcomes of athletes with knee injuries. The study included 38 patients with knee injuries (ACL, meniscal injuries, collateral ligament injuries) out of which 21 were physically active athletes, 9 were not, but they were athletes who were not involved in sports at the time of the testing and 8 were recreational athletes. The majority of respondents (76%) reported that they sustained the injury during sports activities. Knee pain was reported as at least once a week by most respondents. The study highlights the importance of proper knee injury prevention measures during sports activities and the need for prompt and effective rehabilitation for those who do suffer injuries. Overall, these findings have important implications for the treatment and management of knee injuries among athletes and individuals seeking to maintain an active lifestyle.

The Biological Applications of Metals and Metal Complexes

Over the course of biological evolution, approximately 25 to 30 elements have been recognized as essential for the proper functioning of biological systems since the emergence of life [...]

Clinical Course, Nosocomial, and Opportunistic Infections Among Kidney Transplant Recipients with COVID-19: A Retrospective Single Center Study

We report the results of an observational study, analyzing the clinical course of kidney transplant patients hospitalized for COVID-19 and comparing it with a control to determine if outcomes, nosocomial, and opportunistic infections were different between groups. An observational, retrospective, case-control, single-center study, including a group of kidney transplant adults diagnosed with COVID-19, from March 2020 to April 2022. Transplant patients hospitalized for COVID-19 comprised the cases. The control group consisted of non-transplanted adults, without immunosuppressive treatment, hospitalized for COVID-19, and matched by age, sex, and month at diagnosis of COVID-19. Study variables were collected, including demographic/clinical, epidemiologic, clinical/biological at diagnosis, evolutive, and outcome variables. Fifty-eight kidney transplant recipients were included. Thirty required hospital admission. Ninety controls were included. Transplant recipients had a higher frequency of intensive care unit (ICU) admission, ventilatory support, and death. The relative risk for death was 2.45. When adjusted by baseline estimated glomerular filtration rate (eGFR) and comorbidity, only the risk for opportunistic infection remained high. Variables independently associated with death were dyslipidemia, eGFR at admission, MULBSTA score, and ventilatory support. Pneumonia by Klebsiella oxytoca was the most frequent nosocomial infection. Pulmonary aspergillosis was the most frequent opportunistic infection overall. Pneumocystosis and cytomegalovirus colitis were more frequent among transplant patients. The relative risk for opportunistic infection in this group was 1.88. Baseline eGFR, serum interleukin 6 level, and coinfection were independently associated with it. Evolutive course of COVID-19 requiring hospitalization in renal transplant recipients was primarily determined by comorbidity and baseline kidney function. At equal comorbidity and renal function, there were no differences in mortality, ICU admission, nosocomial infection, and hospital stay. However, the risk for opportunistic infection remained high.

A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics

BackgroundMitochondria have a central role in cellular functions, aging, and in certain diseases. They possess their own genome, a vestige of their bacterial ancestor. Over the course of evolution, most of the genes of the ancestor have been lost or transferred to the nucleus. In humans, the mtDNA is a very small circular molecule with a functional repertoire limited to only 37 genes. Its extremely compact nature with genes arranged one after the other and separated by short non-coding regions suggests that there is little room for evolutionary novelties. This is radically different from bacterial genomes, which are also circular but much larger, and in which we can find genes inside other genes. These sequences, different from the reference coding sequences, are called alternatives open reading frames or altORFs, and they are involved in key biological functions. However, whether altORFs exist in mitochondrial protein-coding genes or elsewhere in the human mitogenome has not been fully addressed.ResultsWe found a downstream alternative ATG initiation codon in the + 3 reading frame of the human mitochondrial nd4 gene. This newly characterized altORF encodes a 99-amino-acid-long polypeptide, MTALTND4, which is conserved in primates. Our custom antibody, but not the pre-immune serum, was able to immunoprecipitate MTALTND4 from HeLa cell lysates, confirming the existence of an endogenous MTALTND4 peptide. The protein is localized in mitochondria and cytoplasm and is also found in the plasma, and it impacts cell and mitochondrial physiology.ConclusionsMany human mitochondrial translated ORFs might have so far gone unnoticed. By ignoring mtaltORFs, we have underestimated the coding potential of the mitogenome. Alternative mitochondrial peptides such as MTALTND4 may offer a new framework for the investigation of mitochondrial functions and diseases.

Nothing in evolution makes sense except in the light of code biology

This article highlights the potential contribution of biological codes to the course and dynamics of evolution. The concept of organic codes, developed by Marcello Barbieri, has fundamentally changed our view of how living systems function. The notion that molecular interactions built on adaptors that arbitrarily link molecules from different “worlds” in a conventional, i.e., rule-based way, departs significantly from the law-based constraints imposed on livening things by physical and chemical mechanisms. In other words, living entities and non-living things behave like rules and laws, respectively, but this important distinction is rarely considered in current evolutionary theory. The many known codes allow quantification of codes that relate to a cell, or comparisons between different biological systems and may pave the way to a quantitative and empirical research agenda in code biology. A starting point for such an endeavour is the introduction of a simple dichotomous classification of structural and regulatory codes. This classification can be used as a tool to analyse and quantify key organising principles of the living world, such as modularity, hierarchy, and robustness, based on organic codes. The implications for evolutionary research are related to the unique dynamics of codes, or 'Eigendynamics' (self-momentum) and how they determine the behaviour of biological systems from inside, whereas physical constraints are imposed mainly from outside. A speculation on the drivers of macroevolution in light of codes is followed by the conclusion that a meaningful and comprehensive understanding of evolution depends on including codes into the equation of life.

Cellular Protein Aggregates: Formation, Biological Effects, and Ways of Elimination.

The accumulation of protein aggregates is the hallmark of many neurodegenerative diseases. The dysregulation of protein homeostasis (or proteostasis) caused by acute proteotoxic stresses or chronic expression of mutant proteins can lead to protein aggregation. Protein aggregates can interfere with a variety of cellular biological processes and consume factors essential for maintaining proteostasis, leading to a further imbalance of proteostasis and further accumulation of protein aggregates, creating a vicious cycle that ultimately leads to aging and the progression of age-related neurodegenerative diseases. Over the long course of evolution, eukaryotic cells have evolved a variety of mechanisms to rescue or eliminate aggregated proteins. Here, we will briefly review the composition and causes of protein aggregation in mammalian cells, systematically summarize the role of protein aggregates in the organisms, and further highlight some of the clearance mechanisms of protein aggregates. Finally, we will discuss potential therapeutic strategies that target protein aggregates in the treatment of aging and age-related neurodegenerative diseases.

Amyloids and prions in the light of evolution.

Functional amyloids have been identified in a wide variety of organisms including bacteria, fungi, plants, and vertebrates. Intracellular and extracellular amyloid fibrils of different proteins perform storage, protective, structural, and regulatory functions. The structural organization of amyloid fibrils determines their unique physical and biochemical properties. The formation of these fibrillar structures can provide adaptive advantages that are picked up by natural selection. Despite the great interest in functional and pathological amyloids, questions about the conservatism of the amyloid properties of proteins and the regularities in the appearance of these fibrillar structures in evolution remain almost unexplored. Using bioinformatics approaches and summarizing the data published previously, we have shown that amyloid fibrils performing similar functions in different organisms have been arising repeatedly and independently in the course of evolution. On the other hand, we show that the amyloid properties of a number of bacterial and eukaryotic proteins are evolutionarily conserved. We also discuss the role of protein-based inheritance in the evolution of microorganisms. Considering that missense mutations and the emergence of prions cause the same consequences, we propose the concept that the formation of prions, similarly to mutations, generally causes a negative effect, although it can also lead to adaptations in rare cases. In general, our analysis revealed certain patterns in the emergence and spread of amyloid fibrillar structures in the course of evolution.