Perspectives in science最新文献

The rate at which new genes are being sequenced greatly exceeds our ability to correctly annotate the functional properties of the corresponding proteins. Annotations based primarily on sequence identity to experimentally characterized proteins are often misleading because closely related sequences may have different functions, while highly divergent sequences may have identical functions. Our understanding of the principles that dictate the catalytic properties of enzymes, based on protein sequence alone, is often insufficient to correctly annotate proteins of unknown function. To address these problems, we are working to develop a comprehensive strategy for the functional annotation of newly sequenced genes using a combination of structural biology, bioinformatics, computational biology, and molecular enzymology. The power of this multidisciplinary approach for discovering new reactions catalyzed by uncharacterized enzymes has been tested using the amidohydrolase superfamily as a model system.

Thioredoxin, glutaredoxin, and peroxiredoxin systems (collectively called redoxins) play critical roles in a large number of redox-sensitive cellular processes. These systems are linked to each other by coupled redox cycles and by common reaction intermediates into a larger network.

Previous results from a realistic computational model of the Escherichia coli thioredoxin system developed in our group have revealed several modes of kinetic regulation in the system. Amongst others, the coupling of the thioredoxin and peroxiredoxin redox cycles was shown to exhibit the potential for ultrasensitive changes in the thioredoxin concentration and the flux through other thioredoxin-dependent processes in response to changes in the thioredoxin reductase level. Here, we analyse the basis for this ultrasensitive response using kinetic modelling and metabolic control analysis and derive quantitative conditions that must be fulfilled for ultrasensitivity to occur.

The amino acid sequences of primordial enzymes from extinct organisms can be determined by an in silico approach termed ancestral sequence reconstruction (ASR). In the first step of an ASR, a multiple sequence alignment (MSA) comprising extant homologous enzymes is being composed. On the basis of this MSA and a stochastic model of sequence evolution, a phylogenetic tree is calculated by means of a maximum likelihood approach. Finally, the sequences of the ancestral proteins at all internal nodes including the root of the tree are deduced. We present several examples of ASR and the subsequent experimental characterization of enzymes as old as four billion years. The results show that most ancestral enzymes were highly thermostable and catalytically active. Moreover, they adopted three-dimensional structures similar to those of extant enzymes. These findings suggest that sophisticated enzymes were invented at a very early stage of biological evolution.

Dopo una riflessione sulla differenza tra sapere, conoscenza e informazione e sull’equilibrio dei rapporti tra insegnante, allievo e sapere, che una didattica efficace deve garantire, questo lavoro affronta il problema della trasposizione didattica, inteso come il processo attraverso il quale il sapere sapiente può divenire sapere insegnato. Vengono discussi diversi aspetti inerenti la prassi della trasposizione didattica in ambito scientifico e, più specificamente, nella chimica. Tra essi, la trasposizione terminologica, la problematizzazione e la storicizzazione del sapere. In particolare, il lavoro discute criticamente il ruolo della situazione-problema come strumento imprescindibile dell’insegnamento delle scienze al fine di ottenere un apprendimento significativo.

After a short reflection on the discrepancy between (learnt vs. transmitted) knowledge and information and some remarks on the relationships between teacher, student and knowledge, whose good balance should be granted by an effective teaching, the present work tackles the issue of didactic transposition, i.e. the process that translates the scientific knowledge into knowledge taught in the classroom. Different issues related with the praxis of the didactic transposition of scientific knowledge - and, more specifically, of chemical knowledge - are discussed. Amongst them, terminological transposition, problematization, and the historical contextualization of knowledge. More in details, the present work reports a critical analysis of the role of ‘problem situations’ as a peculiar tool for science teaching.

Science standards and textbooks have a huge impact on the manner in which evolution is taught in American classrooms. Standards dictate how much time and what points have to be dedicated to the subject in order to prepare students for state-wide assessments, while the textbooks will largely determine how the subject is presented in the classroom. In the United States both standards and textbooks are determined at the state-level through a political process. Currently there is a tremendous amount of pressure arising from anti-evolutionists in the United States to weaken or omit the teaching of evolution despite recommendations from central institutions such as the National Academy of Science. Results from the Program for International Student Assessment (PISA) showed that not only are American students performing below average, but also that their performance is declining as they scored worse in 2012 than they did in 2010. Interestingly PISA also found that the internal variation within a country is often greater than between countries with a variation of up to 300 points, which is equivalent to seven years of education pointing to the extreme heterogeneous quality of education within a country (OECD, 2012). An implementation of strong standards would not only help to increase the average performance of American students but could also alleviate the vast discrepancy between the highest and lowest scoring groups of American students. Although the Next Generation Science Standards have been in existence since 2013 and A Framework for K-12 Science Education has been available to the public since 2011 many American states still continue to create their own standards that, according to the Fordham study, are well below par (Lerner et al., 2012). Due to the political nature of the adoption procedure of standards and textbooks, there are many opportunities for interested individuals to get involved in the process of improving these fundamental elements of science education.

The number of entries in the sequence databases continues to increase exponentially – the UniProt database is increasing with a doubling time of ∼4 years (2% increase/month). Approximately 50% of the entries have uncertain, unknown, or incorrect function annotations because these are made by automated methods based on sequence homology. If the potential in complete genome sequences is to be realized, strategies and tools must be developed to facilitate experimental assignment of functions to uncharacterized proteins discovered in genome projects. The Enzyme Function Initiative (EFI; previously supported by U54GM093342 from the National Institutes of Health, now supported by P01GM118303) developed web tools for visualizing and analyzing (1) sequence and function space in protein families (EFI-EST) and (2) genome neighbourhoods in microbial and fungal genomes (EFI-GNT) to assist the design of experimental strategies for discovering the in vitro activities and in vivo metabolic functions of uncharacterized enzymes. The EFI developed an experimental platform for large-scale production of the solute binding proteins (SBPs) for ABC, TRAP, and TCT transport systems and their screening with a physical ligand library to identify the identities of the ligands for these transport systems. Because the genes that encode transport systems are often co-located with the genes that encode the catabolic pathways for the transported solutes, the identity of the SBP ligand together with the EFI-EST and EFI-GNT web tools can be used to discover new enzyme functions and new metabolic pathways. This approach is demonstrated with the characterization of a novel pathway for ethanolamine catabolism.

An enormous amount of molecular and phenotypic information of drugs as well as diseases is now available in public repositories. Computational analysis of these datasets is facilitating the acquisition of a systems view of how drugs act on our human organism and interfere with diseases. Here, I highlight recent approaches integrating large-scale information of drugs and diseases that are contributing to change our current view on how drugs interfere with human diseases.

Questa seconda parte illustra un esempio di trasposizione didattica realizzata in Italia, in classi della scuola secondaria di II grado. Oggetto della trasposizione sono i concetti di trasformazione chimica, di reazione chimica e di equazione di reazione; un risultato di questo percorso è l’introduzione della distinzione fra le nozioni di atomo e molecola da parte degli allievi stessi, come ipotesi necessaria per interpretare la fenomenologia osservata. L’approccio adottato in questa sequenza è di tipo storico-epistemologico e la prassi mediante la quale viene realizzata è socio-costruttivista. Lo strumento didattico è la situazione-problema. Nella prima parte di questo articolo vengono presentate le attività che consentono agli studenti di elaborare il concetto di trasformazione chimica a partire dal concetto di identità di una sostanza chimica e dall’utilizzo del modello particellare. Nella seconda parte vengono presentate le attività di apprendimento che partendo dal contrasto fra le idee di Dalton (atomo indivisibile) e quelle di Gay-Lussac (legge di combinazione dei gas) portano alle ipotesi di Avogadro e alla distinzione fra molecole e atomi operata da Cannizzaro.

In the second part of this work, we present an example of didactic transposition carried out in Italy, with high school students. The educational activity is focused on the concepts of chemical transformation, chemical reaction and reaction equation; an achievement of this activity is the introduction of the distinct concepts of atom and molecule by the students themselves, as a hypothesis that allows interpreting the observed phenomenology. This sequence is conceived according to a historical–epistemological approach and it is based on a socio-constructivist praxis. It relies on the problem-situation as a didactic tool. In the first part of this article, we describe the activities that drive students to elaborate the concept of chemical transformation based on the concept of ‘identity of a chemical substance’, and the use of the particle model. In the second part, we describe some learning activities that lead students toward the Avogadro's hypothesis and Cannizzaro's distinction between atoms and molecules, starting from the contrast between Dalton's and Gay-Lussac's positions.

The beginning of the universe, the Big Bang, being an important subdomain in cosmology, marks the very beginning of space and time. Therefore, it has formed the modern scientific worldview. Transferring this to students through science teaching is a frequent request in science literacy discussion (e.g., American Association for the Advancement of Science, 1993, Schecker et al., 2004).

However, it is not yet clear in science education if students’ conceptions about the Big Bang vary by nationality, and therefore, if it is possible to apply the same teaching modules to students from different countries, who may have diverse social and cultural backgrounds and different curricula. These conceptions with which students enter the classroom were investigated in our study. We implemented an open-ended questionnaire survey in Germany, with questions based on recent U.S. studies. The results clearly showed, with high interrater reliabilities, widespread misconceptions like the Big Bang being an explosion of preexisting matter into empty space or the universe having a centre. Furthermore, a comparison of results from researchers in the USA, Sweden and Germany allowed us to identify differences in students’ conceptions between the countries. Our findings appear to indicate that German students have slightly better pre-instructional conceptions about the Big Bang theory.