Robust self-replication of combinatorial information via crystal growth and scission

Understanding how a simple chemical system can accurately replicate combinatorial information, such as a sequence, is an important question for both the study of life in the universe and for the development of evolutionary molecular design techniques. During biological sequence replication, a nucleic acid polymer serves as a template for the enzyme-catalyzed assembly of a complementary sequence. Enzymes then separate the template and complement before the next round of replication. Attempts to understand how replication could occur more simply, such as without enzymes, have largely focused on developing minimal versions of this replication process. Here we describe how a different mechanism, crystal growth and scission, can accurately replicate chemical sequences without enzymes. Crystal growth propagates a sequence of bits while mechanically-induced scission creates new growth fronts. Together, these processes exponentially increase the number of crystal sequences. In the system we describe, sequences are arrangements of DNA tile monomers within ribbon-shaped crystals. 99.98% of bits are copied correctly and 78% of 4-bit sequences are correct after two generations; roughly 40 sequence copies are made per growth front per generation. In principle, this process is accurate enough for 1,000-fold replication of 4-bit sequences with 50% yield, replication of longer sequences, and Darwinian evolution. We thus demonstrate that neither enzymes nor covalent bond formation are required for robust chemical sequence replication. The form of the replicated information is also compatible with the replication and evolution of a wide class of materials with precise nanoscale geometry such as plasmonic nanostructures or heterogeneous protein assemblies

Required Skills for Teachers: Information Literacy at the Top

European Conference on Information Literacy (ECIL) 2017: Information Literacy in the Workplace, held in Saint Malo, France, 18-21 SeptemberThis study seeks to contribute to a reflection on teachers’ training and professional development in the field of information literacy, in Portugal. Aspects regarding teacher training and their role as spreaders of knowledge and multipliers of good practices are problematized. UNESCO’s curriculum for teachers and ACRL guidelines are used methodologically as the central thread of this interpretation. From here we seek to explain how a higher education institution – an Institute of Education -, which is devoted to the professional development of educators, including teachers, has engaged in information literacy actions through training interventions, in recent years. The study concludes that through sharing and dialogue within the librarian profession, but also within the sphere of education professionals - teachers and trainers - the best training practices in university libraries can be consolidated. Finally, certain points for reflection and debate concerning this theme are proposed.info:eu-repo/semantics/publishedVersio

Eosinophils downregulate lung alloimmunity by decreasing TCR signal transduction

Despite the accepted notion that granulocytes play a universally destructive role in organ and tissue grafts, it has been recently described that eosinophils can facilitate immunosuppression-mediated acceptance of murine lung allografts. The mechanism of eosinophil-mediated tolerance, or their role in regulating alloimmune responses in the absence of immunosuppression, remains unknown. Using lung transplants in a fully MHC-mismatched BALB/c (H2d) to C57BL/6 (H2b) strain combination, we demonstrate that eosinophils downregulate T cell-mediated immune responses and play a tolerogenic role even in the absence of immunosuppression. We further show that such downregulation depends on PD-L1/PD-1-mediated synapse formation between eosinophils and T cells. We also demonstrate that eosinophils suppress T lymphocyte responses through the inhibition of T cell receptor/CD3 (TCR/CD3) subunit association and signal transduction in an inducible NOS-dependent manner. Increasing local eosinophil concentration, through administration of intratracheal eotaxin and IL-5, can ameliorate alloimmune responses in the lung allograft. Thus, our data indicate that eosinophil mobilization may be utilized as a novel means of lung allograft-specific immunosuppression

Antarctic sediment chronology by programmed-temperature pyrolysis : methodology and data treatment

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 9 (2008): Q04005, doi:10.1029/2007GC001816.We report a detailed programmed-temperature pyrolysis/combustion methodology for radiocarbon (14C) dating of Antarctic sub-ice shelf sediments. The method targets the autochthonous organic component in sediments that contain a distribution of acid-insoluble organic components from several sources of different ages. The approach has improved sediment chronology in organic-rich sediments proximal to Antarctic ice shelves by yielding maximum age constraints significantly younger than bulk radiocarbon dates from the same sediment horizons. The method proves adequate in determining isotope ratios of the pre-aged carbon end-member; however, the isotopic compositions of the low-temperature measurements indicate that no samples completely avoided mixing with some proportion of pre-aged organic material. Dating the unresolved but desired young end-member must rely on indirect methods, but a simple mixing model cannot be developed without knowledge of the sedimentation rate or comparable constraints. A mathematical approach allowing for multiple mixing components yields a maximum likelihood age, a first-order approximation of the relative proportion of the autochthonous component, and the temperature at which allochthonous carbon begins to volatilize and mix with the autochthonous component. It is likely that our estimation of the cutoff temperature will be improved with knowledge of the pyrolysis kinetics of the major components. Chronology is improved relative to bulk acid-insoluble organic material ages from nine temperature interval dates down to two, but incorporation of inherently more pre-aged carbon in the first division becomes more apparent with fewer and larger temperature intervals.The project was paid for in part by NSF research grants OPP 02-30089 and OPP 03-38142 to Hamilton College (E. Domack) and NSF Cooperative Agreement OCE- 0228996 to Woods Hole Oceanographic Institution

Anti-Fas Induces Hepatic Chemokines and Promotes Inflammation by an NF-κB-independent, Caspase-3-dependent Pathway

Agonistic antibodies against the Fas receptor, when administered to mice in vivo, cause significant apoptosis in the liver. In this study we show that anti-Fas antibody not only causes apoptosis of liver cells but also provokes hepatic inflammation. Two hours after injection of anti-Fas, when mice displayed evidence of caspase-3 activation and apoptosis, we found significant hepatic induction of the CXC chemokines macrophage inflammatory protein-2 and KC. Coincident with the chemokine induction was infiltration of the hepatic parenchyma by neutrophils. Neutralization experiments identified that chemokines were the cause of Fas-induced hepatic inflammation, with KC having the predominant effect. Chemokine induction in the livers of anti-Fas-treated mice was not associated with activation of NF-kappa B. Instead, it coincided with nuclear translocation of activator protein-1 (AP-1). AP-1 activation in liver was detected 1-2 h after anti-Fas treatment, suggesting a connection to the onset of apoptosis. When apoptosis was prevented by pretreating mice with a caspase-3 inhibitor, AP-1 activation and hepatic chemokine production were both significantly reduced. Hepatic inflammation was also reduced by 70%. Taken together, these findings indicate that Fas ligation can induce inflammation in the liver in vivo. Inflammation does not arise from Fas-mediated signaling through NF-kappa B; rather, it represents an indirect effect, requiring activation of caspase-3 and nuclear translocation of AP-1

Quantitative Analysis of Protein Phosphorylations and Interactions by Multi-Colour IP-FCM as an Input for Kinetic Modelling of Signalling Networks

BACKGROUND: To understand complex biological signalling mechanisms, mathematical modelling of signal transduction pathways has been applied successfully in last few years. However, precise quantitative measurements of signal transduction events such as activation-dependent phosphorylation of proteins, remains one bottleneck to this success. METHODOLOGY/PRINCIPAL FINDINGS: We use multi-colour immunoprecipitation measured by flow cytometry (IP-FCM) for studying signal transduction events to unrivalled precision. In this method, antibody-coupled latex beads capture the protein of interest from cellular lysates and are then stained with differently fluorescent-labelled antibodies to quantify the amount of the immunoprecipitated protein, of an interaction partner and of phosphorylation sites. The fluorescence signals are measured by FCM. Combining this procedure with beads containing defined amounts of a fluorophore allows retrieving absolute numbers of stained proteins, and not only relative values. Using IP-FCM we derived multidimensional data on the membrane-proximal T-cell antigen receptor (TCR-CD3) signalling network, including the recruitment of the kinase ZAP70 to the TCR-CD3 and subsequent ZAP70 activation by phosphorylation in the murine T-cell hybridoma and primary murine T cells. Counter-intuitively, these data showed that cell stimulation by pervanadate led to a transient decrease of the phospho-ZAP70/ZAP70 ratio at the TCR. A mechanistic mathematical model of the underlying processes demonstrated that an initial massive recruitment of non-phosphorylated ZAP70 was responsible for this behaviour. Further, the model predicted a temporal order of multisite phosphorylation of ZAP70 (with Y319 phosphorylation preceding phosphorylation at Y493) that we subsequently verified experimentally. CONCLUSIONS/SIGNIFICANCE: The quantitative data sets generated by IP-FCM are one order of magnitude more precise than Western blot data. This accuracy allowed us to gain unequalled insight into the dynamics of the TCR-CD3-ZAP70 signalling network

Effect of Stalling after Mismatches on the Error Catastrophe in Nonenzymatic Nucleic Acid Replication

The frequency of errors during genome replication limits the amount of functionally important information that can be passed on from generation to generation. During the origin of life, mutation rates are thought to have been quite high, raising a classic chicken-and-egg paradox: could nonenzymatic replication propagate sequences accurately enough to allow for the emergence of heritable function? Here we show that the theoretical limit on genomic information content may increase substantially as a consequence of dramatically slowed polymerization after mismatches. As a result of postmismatch stalling, accurate copies of a template tend to be completed more rapidly than mutant copies and the accurate copies can therefore begin a second round of replication more quickly. To quantify this effect, we characterized an experimental model of nonenzymatic, template-directed nucleic acid polymerization. We found that most mismatches decrease the rate of primer extension by more than 2 orders of magnitude relative to a matched (Watson-Crick) control. A chemical replication system with this property would be able to propagate sequences long enough to have function. Our study suggests that the emergence of functional sequences during the origin of life would be possible even in the face of the high intrinsic error rates of chemical replication

'Upon the gears and upon the wheels':terror convergence and total administration in the neoliberal university

University governance is becoming increasingly autocratic as marketization intensifies. Far from the classical ideal of a professional collegium run according to academic norms, today’s universities feature corporate cultures and senior leadership teams disconnected from both staff and students, and intolerant of dissenting views. This is not a completely new phenomenon. In 1960s America, senior leaders developed a technocratic and managerialist model of the university, in keeping with theories around the ‘convergence’ of socio-economic systems towards a pluralist ‘industrial society’. This administrative-managerial vision was opposed by radical students, triggering punitive responses that reflected how universities’ control measures were at the time mostly aimed at students. Today, their primary target is academics. Informed by Critical Theory and based on an autoethnographic account of a university restructuring programme, we argue that the direction of convergence in universities has not been towards liberal, pluralist, democracy but towards neo-Stalinist organizing principles. Performance measurements – ‘targets and terror’ – are powerful mechanisms for the expansion of managerial power or, in Marcuse’s words, ‘total administration’. Total administration in the contemporary university damages teaching, learning, workplace democracy and freedom of speech on campus, suggesting that the critique of university autocracy by 1960s students and scholars remains highly relevant.</p

Computer Simulation on the Cooperation of Functional Molecules during the Early Stages of Evolution

It is very likely that life began with some RNA (or RNA-like) molecules, self-replicating by base-pairing and exhibiting enzyme-like functions that favored the self-replication. Different functional molecules may have emerged by favoring their own self-replication at different aspects. Then, a direct route towards complexity/efficiency may have been through the coexistence/cooperation of these molecules. However, the likelihood of this route remains quite unclear, especially because the molecules would be competing for limited common resources. By computer simulation using a Monte-Carlo model (with “micro-resolution” at the level of nucleotides and membrane components), we show that the coexistence/cooperation of these molecules can occur naturally, both in a naked form and in a protocell form. The results of the computer simulation also lead to quite a few deductions concerning the environment and history in the scenario. First, a naked stage (with functional molecules catalyzing template-replication and metabolism) may have occurred early in evolution but required high concentration and limited dispersal of the system (e.g., on some mineral surface); the emergence of protocells enabled a “habitat-shift” into bulk water. Second, the protocell stage started with a substage of “pseudo-protocells”, with functional molecules catalyzing template-replication and metabolism, but still missing the function involved in the synthesis of membrane components, the emergence of which would lead to a subsequent “true-protocell” substage. Third, the initial unstable membrane, composed of prebiotically available fatty acids, should have been superseded quite early by a more stable membrane (e.g., composed of phospholipids, like modern cells). Additionally, the membrane-takeover probably occurred at the transition of the two substages of the protocells. The scenario described in the present study should correspond to an episode in early evolution, after the emergence of single “genes”, but before the appearance of a “chromosome” with linked genes