Secretion systems enable bacteria to import and secrete large macromolecules including DNA and proteins. While most components of these systems have been identified, the molecular mechanisms of macromolecular transport remain poorly understood. Recent findings suggest that various bacterial secretion systems make use of the translocation ratchet mechanism for transporting polymers across the cell envelope. Translocation ratchets are powered by chemical potential differences generated by concentration gradients of ions or molecules that are specific to the respective secretion systems. (...) Bacteria employ these potential differences for biasing Brownian motion of the macromolecules within the conduits of the secretion systems. Candidates for this mechanism include DNA import by the type II secretion/type IV pilus system, DNA export by the type IV secretion system, and protein export by the type I secretion system. Here, we propose that these three secretion systems employ different molecular implementations of the translocation ratchet mechanism. Brownian ratchets are often discussed in the context of directed molecular movement. Bacterial secretion systems transport molecules through membranes in a directed fashion. Here, we focus on recent experiments supporting a role of translocation ratchets in the secretion and import of proteins and DNA. (shrink)

The translocation of tRNAs through the ribosome proceeds through numerous small steps in which tRNAs gradually shift their positions on the small and large ribosomal subunits. The most urgent questions are: (i) whether these intermediates are important; (ii) how the ribosomal translocase, the GTPase elongation factor G (EF‐G), promotes directed movement; and (iii) how the energy of GTP hydrolysis is coupled to movement. In the light of recent advances in biophysical and structural studies, we argue that intermediate states of (...) translocation are snapshots of dynamic fluctuations that guide the movement. In contrast to current models of stepwise translocation, kinetic evidence shows that the tRNAs move synchronously on the two ribosomal subunits in a rapid reaction orchestrated by EF‐G and GTP hydrolysis. EF‐G combines the energy regimes of a GTPase and a motor protein and facilitates tRNA movement by a combination of directed Brownian ratchet and power stroke mechanisms. (shrink)

I argue for the existence of a ‘ratcheting-up effect’: the behavior of moral saints serves to increase the level of moral obligation the rest of us face. What we are morally obligated to do is constrained by what it would be reasonable for us to believe we are morally obligated to do. Moral saints provide us with a special kind of evidence that bears on what we can reasonably believe about our obligations. They do this by modeling the level of (...) sacrifice a person can realistically bear. Exposure to moral saints thus ‘ratchets-up’ our obligations by combating a type of ignorance that would otherwise defeat those obligations. (shrink)

Recent research on agricultural innovation has outlined social networks’ role in diffusing agricultural knowledge; however, so far, it has broadly neglected the socio-spatial dimensions of innovation processes. Against this backdrop, we apply a spatially explicit translocal network perspective in order to investigate the role of migration-related translocal networks for adaptive change in a small-scale farming community in Northeast Thailand. By means of formal social network analysis we map the socio-spatial patterns of advice sharing regarding changes in sugarcane and rice farming (...) over a period of five years. We find that, in translocally connected and mobile rural communities, a substantial share of advice originates from translocal levels. Translocal advice is dominantly provided through weak and formal ties with extension agencies and shared by few highly central larger-scale farmers within sparse local networks. This draws the picture of top-down translocal innovation flows driven by extension agencies and brokered through elite farmers. A closer look on institutional context and key actors of particular changes, however, suggests the potential of migration-related translocal networks and migration experience in fostering bottom-up innovations. Migration-related innovations transfers can promote adaptive capacity also among less favorably connected actors, especially if changes are geared towards limited household resources and are compatible with social practices of small-scale farming. We conclude that a translocal network perspective is instructive for research and extension interested in leveraging more inclusive agricultural innovation. (shrink)

This article explores the process by which intelligent transport system technologies have further advanced a data-driven culture in public transport and traffic control. Based on 12 interviews with transport engineers and fieldwork visits to three control rooms, it follows the implementation of Real-Time Passenger Information in Dublin and the various technologies on which it is dependent. It uses the concept of ‘data ratcheting’ to describe how a new data-driven rational order supplants a gradualist, conservative ethos, creating technological dependencies that pressure (...) organisations to take control of their own data and curate accessibility to outside organisations. It is argued that the implementation of Real-Time Passenger Information forms part of a changing landscape of urban technologies as cities move from a phase of opening data silos and expanded communication across departments and with citizens towards one in which new streams of digital data are recognised for their value in stabilising novel forms of city administration. (shrink)

We hypothesize that as one of the most consequential events in evolution, primary endosymbiosis accelerates lineage divergence, a process we refer to as the endosymbiotic ratchet. Our proposal is supported by recent work on the photosynthetic amoeba, Paulinella, that underwent primary plastid endosymbiosis about 124 Mya. This amoeba model allows us to explore the early impacts of photosynthetic organelle (plastid) origin on the host lineage. The current data point to a central role for effective population size (Ne) in accelerating (...) divergence post‐endosymbiosis due to limits to dispersal and reproductive isolation that reduce Ne, leading to local adaptation. We posit that isolated populations exploit different strategies and behaviors and assort themselves in non‐overlapping niches to minimize competition during the early, rapid evolutionary phase of organelle integration. The endosymbiotic ratchet provides a general framework for interpreting post‐endosymbiosis lineage evolution that is driven by disruptive selection and demographic and population shifts. Also see the video abstract here: https://youtu.be/gYXrFM6Zz6Q. (shrink)

Protein translocation across biological membranes is of fundamental importance for the biogenesis of organelles and in protein secretion. We will give an overview of the recent achievements in the understanding of protein translocation across mitochondrial membranes(1‐5). In particular we will focus on recently identified components of the mitochondrial import apparatus.

This paper examines the social and organizational innovation processes undertaken by small-scale producers engaged in short food supply chains in the North Swedish region of Västerbotten. The study uses the notion of proximity to empirically analyse and conceptually explore these phenomena. The paper illustrates the ‘new associationalism’ mobilized by producers in order to promote knowledge exchange and learning and highlights the role of translocal practices in sustaining this transition. The study found that open and trusted interactions with consumers are central (...) to the development of ‘quasi-organic’ practices, and that producers belong to numerous motley associations of food professionals facilitating the creation of collective meanings about near-produced quality food. The paper contributes to the rapprochement between agri-food studies and human geography to understand the formation of local food systems from an evolutionary and relational perspective. (shrink)

From island biogeography theory, the ethic of organic diversity was posited as a precept to guide applied biogeography. It states that humanity must act in such a way as to reduce the rate of worldwide species extinction for an indefinite period of time. Almost 50 years later, the ethic of organic diversity remains relevant in the context of the debate over species translocation practices. Ultimately, matters of biodiversity conservation are too complex to expect an exceptionless moral framework to determine (...) whether species translocation is acceptable in every situation. Instead, individual cases should be judged based on the adequacy of their decision-making processes. (shrink)

Transport through the nuclear pore complex (NPC), a keystone of the eukaryotic building plan, is known to involve a large channel and an abundance of phenylalanine–glycine (FG) protein domains serving as binding sites for soluble nuclear transport receptors and their cargo complexes. However, the conformation of the FG domains in vivo, their arrangement in relation to the transport channel and their function(s) in transport are still vividly debated. Here, we revisit a number of representative transport models—specifically Brownian affinity gating, selective (...) phase gating, reversible FG domain collapse, and reduction of dimensionality (ROD)—in the light of new data obtained by optical single transporter recording, optical superresolution microscopy, artificial nanopores, and many other techniques. The analysis suggests that a properly adapted, simplified version of the ROD model accounts well for the available data. This has implications for nucleocytoplasmic transport in general. (shrink)

What we consider “nature” is always historical and relational, shaped in contingent configurations of representational and social practices. In the early twentieth century, the English ecologist A.G. Tansley lamented the pervasive problem of international misunderstandings concerning the nature of “nature.” In order to create some consensus on the concepts and language of ecological plant geography, Tansley founded the International Phytogeographical Excursion, which brought together leading plant geographers and botanists from North America and Europe. The first IPE in August 1911 started (...) with the Norfolk Broads. It was led by Marietta Pallis, Tansley’s former student at Cambridge. This trip and the work of Pallis, neglected in other accounts of this early period of the history of ecology, influenced the relations between Tansley and important American ecologists H.C. Cowles and F.E. Clements. Understanding “place” as a network of relations, our regional focus shows how taking international dialogue, travel and interchange into account enriches understanding of ecological practice. (shrink)

Under the influence of recurrent deleterious mutation and selection, asexual and sexual populations reach a deterministic equilibrium with individuals carrying 0,1,2,. . . harmful mutations. When a favourable mutation (aA) occurs in an asexual population it will usually occur in an individual who has one or more (k) deleterious mutations. Muller's ratchet then applies as A will thereafter never occur in an individual with less than k mutations. If the selective advantage of A is less than the selective disadvantage (...) of k harmful mutations then A will not spread. If it is greater it may spread carrying k deleterious mutations to fixation. Sexual populations are not affected in this way. A will spread through the population experiencing genomes with 0,1,2,. . . deleterious mutations in accordance with the deterministic equilibrium. (shrink)

We suggest a new view of secretory and membrane protein folding that emphasizes the role of pathways of biogenesis in generating functional and conformational heterogeneity. In this view, heterogeneity results from action of accessory factors either directly binding specific sequences of the nascent chain, or indirectly, changing the environment in which a particular domain is synthesized. Entrained by signaling pathways, these variables create a combinatorial set of necessary‐but‐not‐sufficient conditions that enhance synthesis and folding of particular alternate, functional, conformational forms. We (...) therefore propose that protein conformation is productively regulated by the cell during translocation across the endoplasmic reticulum (ER), a concept that may account for currently poorly understood aspects of physiological function, natural selection, and disease pathogenesis. BioEssays 24:741–748, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

It has been unclear why certain defined DNA regions are consistently sites of chromosomal translocations. Some of these are simply sequences of recognition by endogenous recombination enzymes, but most are not. Recent progress indicates that some of the most common fragile sites in human neoplasm assume non‐B DNA structures, namely deviations from the Watson–Crick helix. Because of the single strandedness within these non‐B structures, they are vulnerable to structure‐specific nucleases. Here we summarize these findings and integrate them with other recent (...) data for non‐B structures at sites of consistent constitutional chromosomal translocations. BioEssays 28: 480–494, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Graphical AbstractA cell translocation mechanism displaces sporadic mutant cells from normal, suppressive epithelial environment during early steps of tumor initiation. This epithelial cell translocation process exerts a selective pressure on early mutant cells to survive and grow in new microenvironment outside of their native niches.

The article Do translocal networks matter for agricultural innovation? A case study on advice sharing in small scale farming communities in Northeast Thailand, written by Till Rockenbauch, Patrick Sakdapolrak and Harald Sterly, was originally published electronically on the publisher’s internet portal on 10 April 2019 without open access.

Under the influence of deleterious mutation and selection a population will reach equilibrium and contain individuals with [0, 1, 2 - - mutations.] This deterministic equilibrium distribution is exactly the same for asexual and sexual populations. The size of the optimal class , i.e. the class with the smallest number of mutations, is determined by the genome mutation rate and the average selective disadvantage of the mutations. A large U and small s gives a very small n o. If n (...) o is small in an asexual population it will be lost by drift and this causes a reduction in the mean fitness of the population . It is argued that diploidy increases U and reduces s. Values of U and s observed from Drosophila indicate a diploid would have a vanishingly small n o. The argument suggests Muller's ratchet is more powerful than previously accepted in asexual species derived from diploid sexual ancestors. (shrink)

Despite the propensity of species introductions to disrupt ecosystems through community disassembly, the use of species translocations is becoming more widely accepted. In this paper, we examine ethical investigations into human migration in an attempt to evaluate how translocation may be justified. Previous attempts to make the analogy between human and species migration have been prone to black and white thinking. We argue that the disagreement between nativist and cosmopolitan approaches to introduced species can be defused by extending the (...) analogy through the migration ethics literature. Additionally, by extending the discussion to the special status of refugees, we are able to develop a theoretical framework for species migrations that acknowledges the risk of species introduction while recognising that special obligations towards endangered species may necessitate the use of translocations. (shrink)

Perhaps the most contentious part of the response to the Covid-19 pandemic has been the decision by governments to mandate—or effectively mandate—the shutdown of certain businesses. The justification for doing so is broadly consequentialist. The public health costs of not shutting down are so great that potential benefits from allowing businesses to open are dwarfed. Operating within this consequentialist framework, this paper identifies an underappreciated set of social costs that are a product of the present public policy that pairs mandated (...) shutdowns with government subsidies. Such policy is prone to being an instance of what Robert Higgs calls the ratchet effect. Given that ratchets tend to be both costly and sticky, it is best to avoid allowing them to come into existence. This paper identifies a way of circumventing this particular ratchet; namely, by replacing governmental subsidies with support from private charitable funds like The Barstool Fund. (shrink)

How do social movements respond to the ecological crisis? In this paper, we reframe social movements as ‘more-than-social movements’ to highlight the fact that many contemporary mobilisations do much more than target recognised social institutions and political governance; indeed, they are practically transforming eco-societies with and within both the human and the nonhuman world. What constitutes the core of more-than-social movements’ action is the capacity to set up alternative ecologies of existence, or ‘alterontologies’, as we call them in the paper. (...) In what follows, we engage with the imaginaries and practices of agroecology, AIDS treatment activism and permaculture in order to rethink what autonomy and justice might look like in the context of today's ecological crisis. (shrink)

A model is proposed that deals with the observed collinearities (spatial, temporal and quantitative) of Hox gene expression during pattern formation along the primary and secondary axes of vertebrates. In particular, in the proximodistal axis of the developing limb, it is assumed that a morphogen gradient is laid down with its source at the distal tip of the bud. The extracellular signals in every cell of the morphogenetic field are transduced and uniformly amplified so that molecules are produced in the (...) nucleus with appropriate physicochemical properties. These molecules can exert a concentration‐dependent force on the Hox cluster. It is assumed that, before activation, the Hox cluster is packaged as an elongated rigid body inside the chromatin and is covered by a coat that prevents the transcription factors reaching the genes of the cluster. The transcription factors are confined to the interchromatin domain and their density decreases with their distance from the chromatin surface. A gradual increase in the extracellular morphogen concentration causes a corresponding increase in the number of the nuclear molecules and the resulting bigger force pushes the Hox cluster toward the interchromatin domain. The step‐by‐step translocations of the Hox cluster initiate the consecutive exposure of genes to their transcription factors. The model explains how gene activation is triggered and it describes spatial, temporal and quantitative collinearities at the initial stages of gene expression. Some recent experiments of Hox deletions and duplications are accounted for by the model. BioEssays 26:189–195, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

At first glance the three eukaryotic protein translocation machineries – the ER‐associated degradation (ERAD) transport apparatus of the endoplasmic reticulum, the peroxisomal importomer and SELMA, the pre‐protein translocator of complex plastids – appear quite different. However, mechanistic comparisons and phylogenetic analyses presented here suggest that all three translocation machineries share a common ancestral origin, which highlights the recycling of pre‐existing components as an effective evolutionary driving force.Editor's suggested further reading in BioEssays ERAD ubiquitin ligases Abstract.

I investigate the structure of an argument that culture cannot be maintained in a population if each individual learns only from a single person. This appears to conflict with many models of cultural transmission and real-world cases. I resolve the first problem by showing that one of the models central to the argument is conceptually analogous and mathematically equivalent to one used to investigate the evolution of sexual reproduction. I resolve the second by arguing that probabilistic models of epistemological coherence (...) can be reinterpreted as models of support between cultural variants—illustrating the idea with a new model. (shrink)

First performed in June 2011, Paulista used fixed and mobile streaming technology to create a translocal, musical and sonic performance linking SARC (Belfast/Northern Ireland), LAMI (São Paulo/Brazil) and Paulista Avenue, in the heart of São Paulo’s city centre. By discussing the performative and compositional strategies employed in this work, we aim at highlighting the central role played by the network in articulating notions of liveness and dramaturgy, as well as fostering new ideas and processes to engage dislocated spaces in shared (...) musical practice. (shrink)

Ascorbic acid is a redox regulator in many physiological processes. Besides its antioxidant activity, many intriguing functions of ascorbic acid in the expression of immunoregulatory genes have been suggested. Ascorbic acid acts as a co‐factor for the Fe+2‐containing α‐ketoglutarate‐dependent Jumonji‐C domain‐containing histone demethylases (JHDM) and Ten eleven translocation (TET) methylcytosine dioxygenasemediated epigenetic modulation. By influencing JHDM and TET, ascorbic acid facilitates the differentiation of double negative (CD4−CD8−) T cells to double positive (CD4+CD8+) T cells and of T‐helper cells to (...) different effector subsets. Ascorbic acid modulates plasma cell differentiation and promotes early differentiation of hematopoietic stem cells (HSCs) to NK cells. These findings indicate that ascorbic acid plays a significant role in regulating both innate and adaptive immune cells, opening up new research areas in Immunonutrition. Being a water‐soluble vitamin and a safe micro‐nutrient, ascorbic acid can be used as an adjunct therapy for many disorders of the immune system. (shrink)

H. sapiens stands out from other primates along many social dimensions; however, none seems as prominent and important as the capacity of our species for cumulative cultural evolution or, as Tomasello calls it, “the ratchet.” Although other primate species show evidence of cultural variation, there is little evidence of cumulative cultural evolution, i.e., the gradual accumulation, modification, and refinement of traditions and skills over historical time, in any primate species other than our own. This is clearly an extremely significant (...) component of the human phenotype, responsible for our unparalleled cultural, social, political, and technological achievements. However, it remains extremely controversial what sorts of cognitive capacities are necessary to trigger cumulative cultural evolution and whether any currently proposed candidates are really distinctive of humans. Furthermore, the ratchet raises a bootstrapping problem: before complex skills and technologies are present and necessary for biological success, there appear to be few advantages to high-fidelity social learning; however, without such high-fidelity social learning, it is unclear how traditions capable of generating complex skills and technologies could arise in the first place. In this chapter, we survey relevant empirical research in comparative and developmental psychology, integrating it with a novel theoretical analysis of the bootstrapping problem to defend a hypothesis about the minimal cognitive preconditions on the ratchet. (shrink)

Ensuring that research is of high quality and is based on sound ethical principles is not easy; it requires a fine balance between adequate oversight and suitable facilitation. The current state of research ethics governance is an ideal environment to maintain a governance ‘ratchet’ rather than produce a well-organized and carefully thought out ‘dial’.

The variation and selection form of explanationcan be prescinded from the evolutionary biologyhome ground in which it was discovered and forwhich it has been most developed. When this isdone, variation and selection explanations arefound to have potential application to a widerange of phenomena, far beyond the classicalbiological ground and the contemporaryextensions into epistemological domains. Itappears as the form of explanation most suitedto phenomena of fit. It is also found toparticipate in multiple interestingrelationships with other forms of explanation. We proceed with (...) an examination of multiplekinds of phenomena, interrelationships withother members of the family of forms ofexplanation, and some novel applications evenwithin the home ground of evolutionary biology. (shrink)

The processes of post-socialist transformation, especially large-scale migration from Eastern Europe to the Western hemisphere, are creating an ‘expansion of space’ from the local to the supra-local. This process involves the expansion of personal-, familial- and friendship-based networking practices which acquire significance as transnational mobile livelihoods and as significant dimensions of urban dynamics in global cities like Chicago. What are the networks, attachments and social bonds of Eastern European migrants in Chicago? Ethnographic fieldwork conducted in Chicago in 2013 among recent (...) Lithuanian immigrants brought out the importance of a cultural identity of East European-ness involving contested loyalties and limited integration. While living locally, Lithuanian immigrants are expected both to be bound to the ethnic community and to be immersed in the multicultural life-style of the mega city. However the research has shown that livelihoods and social relations among ‘one’s own people’ are involved in trans-ethnic networks and that the bonds of intimacy and the alliances among ‘one’s own people’ run through homeland roots and patrimonial linkages rather than through the citizenship loyalties of the state (the United States and/or Lithuania). The circle of ‘one’s own people’ implies extensive reciprocity and social networking among ‘friends’ and co-workers based on ‘one’s own resourcefulness’ a kind of social capital. Thus, ‘sharing important acquaintances’ ought to involve ‘doing favours’ and livelihood experiences transplanted from oversees are practised in Chicago as ‘local’ life-styles and are used for transnational networking, securing in the process the social status of those involved. (shrink)

If the general arguments concerning theinvolvement of variation and selection inexplanations of ``fit'' are valid, then variationand selection explanations should beappropriate, or at least potentiallyappropriate, outside the paradigm historisticdomains of biology and knowledge. In thisdiscussion, I wish to indicate some potentialroles for variation and selection infoundational physics – specifically inquantum field theory. I will not be attemptingany full coherent ontology for quantum fieldtheory – none currently exists, and none islikely for at least the short term future. Instead, I wish to (...) engage in some partiallyspeculative interpretations of some interestingresults in this area with the aim ofdemonstrating that variation and selectionnotions might play a role even here. Ifvariation and selection can survive in even asinhospitable and non-paradigmatic a terrain asfoundational physics, then it can surviveanywhere. (shrink)

Why the DNA‐containing organelles, chloroplasts, and mitochondria, are inherited maternally is a long standing and unsolved question. However, recent years have seen a paradigm shift, in that the absoluteness of uniparental inheritance is increasingly questioned. Here, we review the field and propose a unifying model for organelle inheritance. We argue that the predominance of the maternal mode is a result of higher mutational load in the paternal gamete. Uniparental inheritance evolved from relaxed organelle inheritance patterns because it avoids the spread (...) of selfish cytoplasmic elements. However, on evolutionary timescales, uniparentally inherited organelles are susceptible to mutational meltdown (Muller's ratchet). To prevent this, fall‐back to relaxed inheritance patterns occurs, allowing low levels of sexual organelle recombination. Since sexual organelle recombination is insufficient to mitigate the effects of selfish cytoplasmic elements, various mechanisms for uniparental inheritance then evolve again independently. Organelle inheritance must therefore be seen as an evolutionary unstable trait, with a strong general bias to the uniparental, maternal, mode. (shrink)

Studies on Neurospora chromosome segment duplications (Dps) performed since the publication of Perkins's comprehensive review in 1997 form the focus of this article. We present a brief summary of Perkins's seminal work on chromosome rearrangements, specifically, the identification of insertional and quasiterminal translocations that can segregate Dp progeny when crossed with normal sequence strains (i.e., T × N). We describe the genome defense process called meiotic silencing by unpaired DNA that renders Dp‐heterozygous crosses (i.e., Dp × N) barren, which provides (...) a basis for identifying Dps, and discuss whether other processes also might contribute to the barren phenotype of Dp × N and Dp × Dp crosses. We then turn to studies suggesting that large Dps (i.e., >300 kbp) can allow smaller gene‐sized duplications to escape another genome defense process called repeat‐induced point mutation (RIP), possibly by titration of the RIP machinery. Finally, we assess whether in natural populations dominant RIP suppressor Dps provide an “RIP‐free” niche for evolution of new genes following the duplication of existing genes. (shrink)

The recent explosion of philosophical papers on Confederate and Colonialist statues centers on a central question: When, if ever, is it permissible to admire a person? This paper contends it’s not just Confederates and slavers whose reputations are on the line, but also pacifists like Martin Luther King, Jr., and Daisy Bates whose commitments to pacifism meant they were unwilling to save others using defensive violence, including others they talked into endangering themselves for the sake of racial equality. Other things (...) being equal, that’s gravely immoral if pacifism is false, and we shouldn’t admire people guilty of grave immorality. So, it appears that we shouldn’t admire Bates or King, which is counterintuitive. To solve this problem, I explore several possibilities: that only selective traits of Bates and King are admirable, that Bates and King are admirable despite their grave immorality, and that Bates and King are admirable by virtue of their integrity. However, each of these proposals fails: the first because it inadequately captures our moral phenomenology (we admire people, not just their traits), the second because it ignores the extent to which gravely immoral commitments are constitutive of a person’s moral character, and the third because we ought not to admire people for acting on their immoral beliefs. The paper concludes, first, that either pacifists like Bates and King aren’t admirable or they are, and the latter presupposes the truth of pacifism. Second, I borrow from Vanessa Carbonell’s ratcheting-up argument from moral sainthood to argue that pacifists like Bates and King provide epistemic defeaters to the objection that pacifism is unreasonably costly. Thus, not only are pacifists admirable only if they’re right—they are right. (shrink)