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 Third, the initial unstable membrane, composed of prebiotically available fatty acids, should have been superseded quite early by a more stable membrane (e.g., composed of phospholipids, like modern cells).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

Urbano non urbano. Progetto di centro intermodale a Castelvetrano

La proposta progettuale si colloca in un\u2019area di circa 120.000 mq in prossimit\ue0 della stazione ferroviaria di Castelvetrano, tra l\u2019attuale linea ferrata e l\u2019ex sede ferroviaria; una zona che presenta un indebolimento della forma urbana conseguente all\u2019espansione della citt\ue0 dentro il territorio agricolo. Il progetto mira alla riqualificazione di tale area e dove possibile anche alla rifunzionalizzazione di alcuni edifici dismessi appartenenti alla ferrovia. Nell\u2019ambito di un\u2019 eventuale pi\uf9 ampia proposta progettuale di collocare lungo la linea ferrata gli edifici di un centro intermodale volto alla valorizzazione delle vocazioni produttive del comune di Castelvetrano, nonch\ue9 dei comuni limitrofi, un ruolo chiave \ue8 assunto dalla testata di tale centro intermodale, che si collocher\ue0 proprio in quella parte dell\u2019area di progetto particolarmente ibrida, che si pone a cerniera tra il tessuto consolidato e la campagna. Qui trover\ue0 posto il centro direzionale di tale sistema, un edificio che oltre ad avere una funzione pi\uf9 espressamente amministrativa, conterr\ue0 alcuni servizi volti al pubblico, quali una sala conferenze, un ristorante, un cinema, un bar, alcuni negozi; servizi, dunque, volti a un\u2019utenza non necessariamente legata al centro intermodale, ma piuttosto punto di partenza per una progressiva urbanizzazione di tale area. La collocazione planimetrica del centro direzionale si lega inoltre ad un forte elemento strutturante del tessuto urbano di Castelvetrano, costituito dal sistema Villa Comunale - Convento di S. Francesco - Viale Vittorio Veneto e che si spinge in basso fino alla Piazza antistante la Stazione ferroviaria, ponendosi in questo modo come ideale proseguimento del Viale e collegamento tra due parti di citt\ue0 in realt\ue0 divisi dal forte segno della linea ferrata. Proprio l\u2019orientamento di tale asse viario diventa, assieme a quello costituito dalla linea ferrata, elemento generatore della forma dell\u2019edificio che ospiter\ue0 il centro direzionale e della piazza antistante; quest\u2019ultima, in posizione sopraelevata rispetto alla vallata, diventa una sorta di terrazza urbana sulla valle del Belice. Il centro direzionale si presenta come un edificio ibrido, in quanto sistema di elementi funzionali relativamente autonomi e identificabili; esso \ue8 costituito in particolare da tre elementi. Un primo elemento parallelo alla linea ferrata, presenta un corpo basso adibito in parte a magazzino intermodale e in parte a snodo tra i diversi sistemi di circolazione interni all\u2019edificio ed una torre. Questa, in continuit\ue0 rispetto al magazzino, ma con il lato Sud inclinato secondo l\u2019asse del Viale Vittorio Veneto, ospiter\ue0 gli uffici amministrativi, nonch\ue9 una sala conferenze ed un ristorante che occuper\ue0 gli ultimi due livelli. La parte basamentale di questo sistema non presenta soluzioni di continuit\ue0, cosicch\ue8 un ipotetico utente, accedendo dalla zona d\u2019ingresso posta nell\u2019angolo Sud-Est dell\u2019edificio, attraverser\ue0 tutto il primo livello trovando in sequenza l\u2019ampia scalinata di accesso al secondo livello, il centro informazioni, il magazzino intermodale e un\u2019ampia zona di snodo a doppia altezza dalla quale \ue8 possibile accedere al Bar e al cinema, i quali, assieme ad alcuni uffici, occupano il secondo elemento di cui si compone l\u2019edificio. Questo, si pone perpendicolarmente rispetto al sistema torre-magazzino e si sviluppa su tre livelli, delimitando l\u2019ampia piazza antistante, che in parte verr\ue0 coperta dal profondo aggetto della sala cinematografica. Un terzo elemento ospiter\ue0 una serie di negozi ai quali si accede dalla quota della strada che occupa il tracciato dell\u2019ex sede ferroviaria; quest\u2019ultimo elemento si pone in parte parallelamente al primo, ma piega, seguendo l\u2019inclinazione della strada, in corrispondenza della piazza, alla quale si accede mediante un\u2019ampia scalinata, posta lungo il marciapiede alberato antistante i negozi. Completano il progetto la sistemazione a verde delle zone adiacenti all\u2019edificio e la creazione di un parcheggio nell\u2019area antistante l\u2019accesso alla torre

Intrinsic Properties of tRNA Molecules as Deciphered via Bayesian Network and Distribution Divergence Analysis

The identity/recognition of tRNAs, in the context of aminoacyl tRNA synthetases (and other molecules), is a complex phenomenon that has major implications ranging from the origins and evolution of translation machinery and genetic code to the evolution and speciation of tRNAs themselves to human mitochondrial diseases to artificial genetic code engineering. Deciphering it via laboratory experiments, however, is difficult and necessarily time- and resource-consuming. In this study, we propose a mathematically rigorous two-pronged in silico approach to identifying and classifying tRNA positions important for tRNA identity/recognition, rooted in machine learning and information-theoretic methodology. We apply Bayesian Network modeling to elucidate the structure of intra-tRNA-molecule relationships, and distribution divergence analysis to identify meaningful inter-molecule differences between various tRNA subclasses. We illustrate the complementary application of these two approaches using tRNA examples across the three domains of life, and identify and discuss important (informative) positions therein. In summary, we deliver to the tRNA research community a novel, comprehensive methodology for identifying the specific elements of interest in various tRNA molecules, which can be followed up by the corresponding experimental work and/or high-resolution position-specific statistical analyses

Epigenetics and Evolution: Transposons and the Stochastic Epigenetic Modification Model

In addition to genetic variation, epigenetic variation and transposons can greatly affect the evolutionary fitnesses landscape and gene expression. Previously we proposed a mathematical treatment of a general epigenetic variation model that we called Stochastic Epigenetic Modification (SEM) model. In this study we follow up with a special case, the Transposon Silencing Model (TSM), with, once again, emphasis on quantitative treatment. We have investigated the evolutionary effects of epigenetic changes due to transposon (T) insertions; in particular, we have considered a typical gene locus A and postulated that (i) the expression level of gene A depends on the epigenetic state (active or inactive) of a cis- located transposon element T, (ii) stochastic variability in the epigenetic silencing of T occurs only in a short window of opportunity during development, (iii) the epigenetic state is then stable during further development, and (iv) the epigenetic memory is fully reset at each generation. We develop the model using two complementary approaches: a standard analytical population genetics framework (di usion equations) and Monte-Carlo simulations. Both approaches led to similar estimates for the probability of fixation and time of fixation of locus TA with initial frequency P in a randomly mating diploid population of effective size Ne. We have ascertained the e ect that ρ, the probability of transposon Modification during the developmental window, has on the population (species). One of our principal conclusions is that as ρ increases, the pattern of fixation of the combined TA locus goes from "neutral" to "dominant" to "over-dominant". We observe that, under realistic values of ρ, epigenetic Modifications can provide an e cient mechanism for more rapid fixation of transposons and cis-located gene alleles. The results obtained suggest that epigenetic silencing, even if strictly transient (being reset at each generation), can still have signi cant macro-evolutionary effects. Importantly, this conclusion also holds for the static fitness landscape. To the best of our knowledge, no previous analytical modeling has treated stochastic epigenetic changes during a window of opportunity

Concepts and Applications of Information Theory to Immuno-Oncology

Recent successes of immune-modulating therapies for cancer have stimulated research on information flow within the immune system and, in turn, clinical applications of concepts from information theory. Through information theory, one can describe and formalize, in a mathematically rigorous fashion, the function of interconnected components of the immune system in health and disease. Specifically, using concepts including entropy, mutual information, and channel capacity, one can quantify the storage, transmission, encoding, and flow of information within and between cellular components of the immune system on multiple temporal and spatial scales. To understand, at the quantitative level, immune signaling function and dysfunction in cancer, we present a methodology-oriented review of information-theoretic treatment of biochemical signal transduction and transmission coupled with mathematical modeling

Combined Action of a Bacterial Monooxygenase and a Fungal Laccase for the Biodegradation of Mono- and Poly-Aromatic Hydrocarbons

The combined action of a wide substrate range toluene o-xylene monooxygenase from Pseudomonas sp. OX1, able to convert many aromatic compounds into mono- and di-hydroxylated derivatives, and fungal laccases from Pleurotus ostreatus which oxidize these hydroxylated products yielding polymers with reduced toxicity is described. This strategy permits to overcome many of the substrate specificity problems and dead end toxic products formation generally encountered in complex bacterial biodegradation pathways. Toluene and naphthalene degradations were tested as representative of mono- and poly-aromatic pollutants. The combined biological action was optimized in micellar and microemulsion systems able to increase the bioavailability of the hydrophobic aromatic pollutants. This approach allows efficient hydroxylations of hydrophobic substrates thus favoring the further action of fungal oxidases

Palermo e il suo mare

L’articolo descrive un progetto per il concorso di “Riqualificazione urbana di Mondello”, luogo di balneazione nella città di Palermo. Il progetto di riqualificazione che nasce dall’idea che il waterfront possa costituire un punto d’incontro tra città e mare, articola diversi spazi della città, dall’isolato di Valdesi alla passeggiata a mare fino alla piazza di Mondello. L’intervento progettuale, che stabilisce un corretto rapporto tra architettura e preesistenza, si basa su un profondo senso della misura, intendendo con questo termine la capacità di dosare il gesto architettonico rispetto alle condizioni di contorno che sono assunte come prioritarie nell’intervento