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)

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)

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)

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.

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.

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)

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)

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)

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)

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)

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)

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.

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.

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)

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)

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)

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)

Bacterial pathogens deliver effector proteins into host cells by deploying sophisticated secretion systems. This effector translocation during host‐pathogen interactions is a prerequisite for the manipulation of host cells and organisms and is important for pathogenesis. Analyses of dynamics and kinetics of translocation, subcellular localization, and cellular targets of effector proteins lead to understanding the mode of action and function of effector proteins in host‐pathogen interplay. This review provides an overview of biochemical and genetic tools that have been developed (...) to study protein effector translocation qualitatively or quantitatively. After introducing the challenges of analyses of effector translocation during host‐pathogen interaction, we describe various methods ranging from static visualization in fixed cells to dynamic live‐cell imaging of effector protein translocation. We show the main findings enabled by the approaches, emphasize the advantages and limitations of the methods, describe recent approaches that allow real‐time tracking of effector proteins in living cells on a single molecule level, and highlight open questions in the field to be addressed by application of new methods. (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)

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)

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)

In dialogue with Bishop and Phillips’ (2013) concern to establish what the category of the urban might mean in the context of megacities, this piece offers four provocations in the spirit of developing their analysis. The first is the need to attend to the specifics of megacities; the second insists on the importance of including those who navigate them in the analysis; the third is a concern to unwind different forms of urban traction, and the fourth is a need to (...) be mindful of the intersecting logics of translocality. Drawing on my own empirical research into the urban translocalities drawn by the flip-flop trail, it concludes that globalization is less solid and more fragile and shifting than many of its theorists suggest. (shrink)

Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and rapidly transported into the organelle by a complex machinery. The data gathered in recent years suggest that this machinery operates through a syringe-like mechanism, in which the shuttling receptor PEX5 − the “plunger” − pushes a newly synthesized protein all the way through a peroxisomal transmembrane protein complex − the “barrel” − into the matrix of the organelle. Notably, insertion of cargo-loaded receptor into the “barrel” is an ATP-independent process, whereas extraction (...) of the receptor back into the cytosol requires its monoubiquitination and the action of ATP-dependent mechanoenzymes. Here, we review the main data behind this model. The peroxin PEX5 is the peroxisomal matrix protein receptor. It shuttles between the cytosol and the organelle membrane, where it gets inserted into the docking/translocation module, thus pushing the cargo-protein into the peroxisome lumen. Resetting the system involves PEX5 monoubiquitination and its extraction from the membrane by the AAA-ATPases, PEX1/PEX6. (shrink)

Wildlife translocations often raise concerns about the purpose and impact among people living in target locations. We applied the integrated impact assessment in planning the reintroduction of wild forest reindeer in Finland. We investigated the variety of expected socioecological impacts, the relative importance of these impacts and local willingness to participate in local-level reintroduction activities. The reintroduction project organised interactive forums in 2013 and 2016 in each of the four regions suitable for wild forest reindeer. The variety of recognised potential (...) impacts was high, but the relative importance given to the expected impacts varied relatively little from forum to forum. Importantly, we found a contextual and relational value of wild forest reindeer that extended beyond their intrinsic and instrumental value. The results indicate high local acceptance of reintroduction and willingness to participate in it. (shrink)

Local foodshed proponents in the United States seek to change the food system through campaigns to “buy local” and to rediscover “good food” in the local foodshed. Presumably, common sense dictates that the word “local” signifies spatial proximity to the consumer. For some populations, however, both the terms “local” and “local food” signify various different meanings. The local food definition generally used by scholars and activists alike as “geographically proximate food” is unhelpfully narrow. Localist rhetoric often does not incorporate the (...) food choices and practices of immigrants, migrants, and refugees. In this paper, I report the various characterizations of local food among Filipino immigrants in San Diego, California: (1) geography-based local food; (2) (US) America-based local food; (3) community-based local food; and (4) immigrant identity-based local food. Local foodshed proponents should acknowledge those who have a starkly different definition of “local”—those who possess translocal subjectivities, for whom “local-ness” is both mobile and embodied. My study underscores how the movement of food—or its containment within a geographic space—cannot be viewed in isolation from the movement of people. (shrink)

The translocation of proteins across membranes is a central problem in biology. Regardless of the system in question, delivering proteins across a given membrane relies on many of the same basic themes. At the same time, however, each membrane translocation system, beit signal‐gated or signal‐assembled, makes use of components unique to that system. The latest findings on protein translocation across a variety of biological membranes have been presented in a recent review article.1 BioEssays 25:1154–1157, 2003. © 2003 (...) Wiley Periodicals, Inc. (shrink)

Given immunity’s general role in the organism’s economy—both in terms of its internal environment as well as mediating its external relations—immune theory has expanded its traditional formulation of preserving individual autonomy to one that includes accounting for nutritional processes and symbiotic relationships that require immune tolerance. When such a full ecological alignment is adopted, the immune system becomes the mediator of both defensive and assimilative environmental intercourse, where a balance of immune rejection and tolerance governs the complex interactions of the (...) organism’s ecological relationships. Accordingly, immunology, which historically had affiliated with the biology of individuals, now becomes a science concerned with the biology of communities. With this translocation, the ontological basis of the organism is undergoing a profound change. Indeed, the recent recognition of the ubiquity of symbiosis has challenged the traditional notions of biological individuality and requires a shift in the metaphysics undergirding biology, in which a philosophy of the organism must be characterized by ecological dialectics “all-the-way-down.”. (shrink)

As the final installment of Public Culture’s Millennial Quartet, Cosmopolitanism assesses the pasts and possible futures of cosmopolitanism—or ways of thinking, feeling, and acting beyond one’s particular society. With contributions from distinguished scholars in disciplines such as literary studies, art history, South Asian studies, and anthropology, this volume recenters the history and theory of translocal political aspirations and cultural ideas from the usual Western vantage point to areas outside Europe, such as South Asia, China, and Africa. By examining new archives, (...) proposing new theoretical formulations, and suggesting new possibilities of political practice, the contributors critically probe the concept of cosmopolitanism. On the one hand, cosmopolitanism may be taken to promise a form of supraregional political solidarity, but on the other, these essays argue, it may erode precisely those intimate cultural differences that derive their meaning from particular places and traditions. Given that most cosmopolitan political formations—from the Roman empire and European imperialism to contemporary globalization—have been coercive and unequal, can there be a noncoercive and egalitarian cosmopolitan politics? Finally, the volume asks whether cosmopolitanism can promise any universalism that is not the unwarranted generalization of some Western particular. Contributors. Ackbar Abbas, Arjun Appadurai, Homi K. Bhabha, T. K. Biaya, Carol A. Breckenridge, Dipesh Chakrabarty, Ousame Ndiaye Dago, Mamadou Diouf, Wu Hung, Walter D. Mignolo, Sheldon Pollock, Steven Randall. (shrink)

According to the somatic mutation theory (SMT), cancer begins with a genetic change in a single cell that passes it on to its progeny, thereby generating a clone of malignant cells. It is strongly supported by observations of leukemias that bear specific chromosome translocations, such as Burkitt's lymphoma, in which a translocation activates the c‐myc gene, and chronic myeloid leukemia (CML), in which the Philadelphia chromosome causes production of the BCR‐ABL oncoprotein. Although the SMT has been modified and extended (...) to encompass tumor suppressor genes, epigenetic inheritance, and tumor progression through accumulation of further mutations, perhaps the strongest validation comes from the successful treatment of certain malignancies with drugs that directly target the product of the mutant gene.magnified imageDavid Vaux is at the Walter and Eliza Hall Institute and La Trobe Institute for Molecular Science, Melbourne, Australia. (shrink)

In this article I provide a critical perspective on governing the global corporation. While the papers in the 2009 special issue of Business Ethics Quarterly explore the political role of corporations I argue that they lack a sophisticated analysis of power acrossinstitutional and actor networks. The argument that corporate engagement with deliberative democracy can enhance the legitimacy of corporations does not take into account the effects of institutional, material and discursive forms of power that determine legitimacycriteria. As a result corporate (...) versions of citizenship mediate versions of social responsibility and morality, which are reflected in the institutional and political economic norms that are produced by this power/knowledge. In order to overcome the limits of corporate social responsibility there is a need to develop more democratic forms of global governance of corporations. A radical revisioning of democratic governance would also need to overcome the limits posed by sovereignty and would require new forms of multi-actor and multi-level translocal governance arrangements in an attempt to create forms of power that are more compatible with the principles of economic democracy. (shrink)

The centrality of trust in traditional doctor–patient relationships has been criticized as inordinately paternalistic, yet in today's discussions about medical ethics—mostly in response to disruptive innovation in healthcare—trust reappears as an asset to enable empowerment. To turn away from paternalistic trust‐based doctor–patient relationships and to arrive at an empowerment‐based medical model, increasing reference is made to the importance of nurturing trust in technologies that are supposed to bring that empowerment. In this article we stimulate discussion about why the move towards (...) patient empowerment may not be able to keep clear of the criticism of trust in traditional patient–doctor relationships. First, we explore how such a shift in trust dynamics might corrode patient empowerment in the name of patient empowerment. Second, we examine how a translocation of trust may at best push the “trust issue” elsewhere and at worst make it harder to evaluate trustworthiness. (shrink)

Agriculture occupies 38% of the planet’s terrestrial surface, using 70% of freshwater resources. Its modern practice is dominated by an industrial–productivist discourse, which has contributed to the simplification and degradation of human and ecological systems. As such, agricultural transformation is essential for creating more sustainable food systems. This paper focuses on discursive change. A prominent discursive alternative to industrial–productivist agriculture is regenerative agriculture. Regenerative discourses are emergent, radically evolving and diverse. It is unclear whether they have the potential to generate (...) the changes required to shift industrial–productivist agriculture. This paper presents a literature-based discourse analysis to illustrate key thematic characteristics of regenerative agricultural discourses. The analysis finds that such discourses: situate agricultural work within nested, complex living systems; position farms as relational, characterised by co-evolution between humans and other landscape biota; perceive the innate potential of living systems as place-sourced; maintain a transformative openness to alternative thinking and practice; believe that multiple regenerative cultures are necessary for deeply regenerative agriculture; and depart from industrialism to varying degrees. The paper concludes by reviewing three transformative opportunities for regenerative discourses—discourse coalitions, translocal organising and collective learning. (shrink)

“Flat pre-semantics” lets each parameter of truth (etc.) be considered sepa-rately and equally, and without worrying about grammatical complications. This allows one to become a little clearer on a variety of philosophical-logical points, such as the use fulness of Carnapian tolerance and the deep relativity of truth. A more definite result of thinking in terms of flat pre-semantics lies in the articulation of some instructive ways of categorizing operations on meanings in purely logical terms in relation to various parame- ters (...) of truth (etc.); namely, closing vs. leaving open, local vs. translocal, and anchored vs. unanchored. Basic relations among these categories are established. (shrink)

D‐amino acids are being recognized as functionally important molecules in mammals. We recently identified endogenous D‐cysteine in mammalian brain. D‐cysteine is present in neonatal brain in substantial amounts (mM) and decreases with postnatal development. D‐cysteine binds to MARCKS and a host of proteins implicated in cell division and neurodevelopmental disorders. D‐cysteine decreases phosphorylation of MARCKS in neural progenitor cells (NPCs) affecting its translocation. D‐cysteine controls NPC proliferation by inhibiting AKT signaling. Exogenous D‐cysteine inhibits AKT phosphorylation at Thr 308 and (...) Ser 473 in NPCs. D‐cysteine treatment of NPCs led to 50% reduction in phosphorylation of Foxo1 at Ser 256 and Foxo3a at Ser 253. We hypothesize that in the developing brain endogenous D‐cysteine is as a physiologic regulator of NPC proliferation by inhibiting AKT signaling mediated by Foxo1 and Foxo3a. Endogenous D‐cysteine may regulate mammalian neurodevelopment with roles in schizophrenia and Alzheimer's disease (AD). (shrink)

One of the near-to-invariant hallmarks of early apoptosis (programmed cell death) is mitochondrial membrane permeabilization (MMP). It appears that mitochondria fulfill a dual role during the apoptotic process. On the one hand, they integrate multiple different pro-apoptotic signal transducing cascades into a common pathway initiated by MMP. On the other hand, they coordinate the catabolic reactions accompanying late apoptosis by releasing soluble proteins that are normally sequestered within the intermembrane space. In a recent study,(1) Li et al. described a nuclear (...) transcription factor (Nur77/TR1/NGFI-B) that can translocate to mitochondrial membranes to induce MMP. Moreover, two groups(2,3) identified a novel intermembrane protein (Smac/DIABLO) that specifically neutralizes the inhibitor of apoptosis (IAP) proteins, thereby facilitating the activation of caspases, a class of proteases activated during apoptosis. These findings refine our knowledge how MMP connects to the cellular suicide machinery. BioEssays 23:111–115, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

The language of Buddhist teaching is Janus‐faced. One face looks towards the local and responds to shifting historical, institutional, cultural, and personal conditions. The other face looks towards the translocal: to that which is stable and persists across time. In this chapter, the author reconsiders the comparatively neglected former face of Buddhist teaching, by asking after the ways in which Buddhist intellectuals have historically thematized the contribution to philosophy of what the author calls responsiveness. Responsiveness to context ineluctably shapes the (...) forms of speech that we study, as well as the forms of speech that we ourselves use. To deny this shaping role in either domain is to opt for a needlessly shuttered vision of what Buddhist philosophy has been and what it might yet be. (shrink)

Many of the recent advances in the history of science have come from local microstudies, but with the unintended by‐product of a typically “postmodern” fragmentation of knowledge. The question for us post‐postmodernists is how to write a broader “general” history of science—a history for all of us specialists—without losing the advantages of case study. One way, this essay suggests, is to structure case studies around the activities or issues that are common to knowledge production generally: for example, issues of common (...) practices, role and identity, credibility and trust, fairness in participation and reward, and translocal circulation. Such studies would be particular and local yet transcend the singularities of period, place, and discipline. They would facilitate productive contest over the general meaning of science in its diversely varied forms. (shrink)

During evolution, the genomes of eukaryotic cells have undergone major restructuring to meet the new regulatory challenges associated with compartmentalization of the genetic material in the nucleus and the organelles acquired by endosymbiosis (mitochondria and plastids). Restructuring involved the loss of dispensable or redundant genes and the massive translocation of genes from the ancestral organelles to the nucleus. Genomics and bioinformatic data suggest that the process of DNA transfer from organelles to the nucleus still continues, providing raw material for (...) evolutionary tinkering in the nuclear genome. Recent reconstruction of these events in the laboratory has provided a unique tool to observe genome evolution in real time and to study the molecular mechanisms by which plastid genes are converted into functional nuclear genes. Here, we summarize current knowledge about plastid‐to‐nuclear gene transfer in the context of genome evolution and discuss new insights gained from experiments that recapitulate endosymbiotic gene transfer in the laboratory. BioEssays 30:556–566, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Loss of the Y‐chromosome is a common feature of species with chromosomal sex determination. However, our understanding of why some lineages frequently lose Y‐chromosomes while others do not is limited. The fragile Y hypothesis proposes that in species with chiasmatic meiosis the rate of Y‐chromosome aneuploidy and the size of the recombining region have a negative correlation. The fragile Y hypothesis provides a number of novel insights not possible under traditional models. Specifically, increased rates of Y aneuploidy may impose positive (...) selection for (i) gene movement off the Y; (ii) translocations and fusions which expand the recombining region; and (iii) alternative meiotic segregation mechanisms (achiasmatic or asynaptic). These insights as well as existing evidence for the frequency of Y‐chromosome aneuploidy raise doubt about the prospects for long‐term retention of the human Y‐chromosome despite recent evidence for stable gene content in older non‐recombining regions. (shrink)

The role of membrane receptors is regarded as being to transduce the signal represented by ligand binding from the external cell surface across the membrane into the cell. Signals are subsequently conveyed from the cytoplasm to the nucleus through a combination of second-messenger molecules, kinase/phosphorylation cascades, and transcription factor (TF) translocation to effect changes in gene expression. Mounting evidence suggests that through direct targeting to the nucleus, polypeptide ligands and their receptors may have an important additional signaling role. Ligands (...) such as those of the platelet-derived and fibroblast growth factor classes, as well as cytokines such as interferon-γ and interleukins-1 and -5, have been found to localize in the nucleus through the action of nuclear localization sequences (NLSs). Where tested, these NLSs appear to be essential for full signaling activity and may be responsible for cotranslocating receptors to the nucleus in complexes with their ligands. The implication is that, subsequent to endocytosis at the membrane, particular polypeptide ligands or their receptors, or both, may translocate to the nucleus to participate directly in gene regulation. BioEssays 20:400–411, 1998.© 1998 John Wiley & Sons Inc. (shrink)

Numerous humans - in my opinion, far too many - continue to live apart from nature, rather than as a part of nature. In this personal essay I discuss various aspects of traditional science and suggest that holistic and heart-driven compassionate science needs to replace reductionist and impersonal science. I argue that creative proactive solutions drenched in deep caring, respect, and love for the universe need to be developed to deal with the broad range of problems with which we are (...) confronted. Simply put, I have had enough. I want the world to be a better place for all of its inhabitants and time is not on our side. I feel a deep sense of urgency and passionate impatience. We are worrying about wildness as it is disappearing right in front of our eyes - as I write and we discuss. Thus, I am willing to open myself to criticism, to be vulnerable for expressing views that are not part of main-stream science. Rather than take a doomsday view that the world will not even exist in 100 years if we fail to accept our unique responsibilities, it is more disturbing to imagine a world in which humans and other life coexist in the absence of any intimacy and interconnectedness. Surely we do not want to be remembered as the generation that killed nature. To illustrate some of my points, I discuss various aspects of translocation studies in which animals are moved about from one place to another in humans' attempts to "redecorate" nature. In these projects interdisciplinary collaboration is necessary and disciplinary boundaries must be trespassed. I also emphasize the importance of teaching children well for their and our futures rest on their developing a deeply-rooted caring ethic. My vision is to create a world-wide community in which humans perceive themselves as a part of nature and not apart from her, in which humans who are overwhelmed and whose spirits and souls have been robbed and squelched by living in and amongst steel, concrete, asphalt, noise, and a multitude of invasions of their private space reconnect with raw nature - with the wind in their faces, the odors of wild flowers, and the sounds, sights, odors, and touch of other animals and inanimate environs. A world in which sensing is feeling. Nature is our unconditional friend and reconnecting with nature can help overcome alienation and loneliness. The power of love must not be underestimated as we forge ahead to reconnect with nature. (shrink)