Elucidation of the disulfide folding pathway of hirudin by a topology-based approach

A theoretical model for the folding of proteins containing disulfide bonds is introduced. The model exploits the knowledge of the native state to favour the progressive establishment of native interactions. At variance with traditional approaches based on native topology, not all native bonds are treated in the same way; in particular, a suitable energy term is introduced to account for the special strength of disulfide bonds (irrespective of whether they are native or not) as well as their ability to undergo intra-molecular reshuffling. The model thus possesses the minimal ingredients necessary to investigated the much debated issue of whether the re-folding process occurs through partially structured intermediates with native or non-native disulfide bonds. This strategy is applied to a context of particular interest, the re-folding process of Hirudin, a thrombin-specific protease inhibitor, for which conflicting folding pathways have been proposed. We show that the only two parameters in the model (temperature and disulfide strength) can be tuned to reproduce well a set of experimental transitions between species with different number of formed disulfide. This model is then used to provide a characterisation of the folding process and a detailed description of the species involved in the rate-limiting step of Hirudin refolding.Comment: 14 pages, 9 figure

Circling the Cross: Bridging Native America, Education, and Digital Media

Part of the Volume on Learning Race and Ethnicity: Youth and Digital MediaTo paraphrase a Native elder, any road will get you somewhere. The question for Native America is, where will the information highway take them? As Native Americans continue to face challenges from the legacy of colonialism, new media provide both an opportunity and crises in education. Standardized education policy such as No Child Left Behind and funding cuts in social services inadvertently impact Net access and Indian education, yet alternative programs and approaches exist. It is necessary that programs conceptualize new media learning strategies within a historical context by being sensitive to the political and cultural connotations of literacy and technology in Native American communities. By encouraging the use of new media as a tool for grassroots community media and locally relevant storytelling, this chapter asks educators to consider an alternative epistemology that incorporates non-Western approaches to ecology and knowledge

Agroforestry systems as alternative for conserving native plant species and improving agro-ecological knowledge

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The role of non-verbal communication in second language learner and native speaker discourse

It is undeniable that non-verbal signals exert a profound impact on communication. Many researchers proved that people, when they are hesitating, analyze non-verbal signals to comprehend the meaning of a message (Allen, 1999), because they prioritize non-verbal aspects of communication over the verbal ones. The role of non-verbal communication is much more profound when native/non-native discourse is taken into consideration (Allen, 1999; Gregersen, 2007). The aim of the present paper is to analyze non-verbal communication of a native speaker and a second language learner. The main emphasis is put especially on the differences between the non-verbal signals of second language learners and native speakers. Some of these differences may disturb or prevent the interlocutors from conveying a message in learner/native speaker discourse (Marsh et al., 2003) so it is necessary to raise awareness of cultural differences and underline the tremendous role of non-verbal communication in second language learning. Furthermore, the present paper also covers some suggestions for foreign language teachers in order to improve their knowledge of the body language of their learners in the target language and help them to raise awareness of the significance of non-verbal communication in second language discourse

Conferring resistance to digital disinformation: the innoculating influence of procedural news knowledge

Despite the pervasiveness of digital disinformation in society, little is known about the individual characteristics that make some users more susceptible to erroneous information uptake than others, effectively dividing the media audience into prone and resistant groups. This study identifies and tests procedural news knowledge as a consequential civic resource with the capacity to inoculate audiences from disinformation and close this “resistance gap.” Engaging the persuasion knowledge model, the study utilizes data from two national surveys to demonstrate that possessing working knowledge of how the news media operate aids in the identification and effects of fabricated news and native advertising.Accepted manuscrip

Phonological category quality in the mental lexicon of child and adult learners

• Aims and Objectives: The aim was to identify which criteria children used to decide on the category membership of native and non-native vowels, and to get insight into the organization of phonological representations in the bilingual mind. • Methodology: The study consisted of two cross-language mispronunciation detection tasks, in which L2 vowels were inserted in L1 words, and vice versa. In Experiment 1, 9-12-year-old Dutch-speaking children were presented with Dutch words which were either pronounced with the target Dutch vowel or with an English vowel inserted in the Dutch consonantal frame. Experiment 2 was a mirror of the first, with English words which were pronounced ‘correctly’ or which were ‘mispronounced’ with a Dutch vowel. • Data and Analysis: It was examined to what extent child and adult listeners accepted substitutions of Dutch vowels by English ones, and vice versa, and which vowel substitutions were accepted or rejected. • Findings: The results of Experiment 1 revealed that at that age children have well-established phonological vowel categories in their native language. However, Experiment 2 showed that in the non-native language, children tended to accept mispronounced items which involve sounds from their native language. At the same time, though, they did fully rely on their native phonemic inventory because the children accepted most of the correctly pronounced English items. • Originality: While many studies have examined native and non-native perception by infants, studies on first and second language perception of school-age children are rare. This study adds to the body of literature aimed at expanding our knowledge in this area. • Implications: The study has implications for models of the organization of the bilingual mind: while proficient adult non-native listeners generally have clearly separated sets of phonological representations for their two languages, for non-proficient child learners, the L1 phonology still exerts a big influence on the L2 phonology

Simple models of protein folding and of non--conventional drug design

While all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the three--dimensional, biologically active, native conformation of a protein whose sequence is known. Using insight obtained from simple model simulations of the folding of proteins, in particular of the fact that this phenomenon is essentially controlled by conserved (native) contacts among (few) strongly interacting ("hot"), as a rule hydrophobic, amino acids, which also stabilize local elementary structures (LES, hidden, incipient secondary structures like $\alpha$--helices and $\beta$--sheets) formed early in the folding process and leading to the postcritical folding nucleus (i.e., the minimum set of native contacts which bring the system pass beyond the highest free--energy barrier found in the whole folding process) it is possible to work out a succesful strategy for reading the native structure of designed proteins from the knowledge of only their amino acid sequence and of the contact energies among the amino acids. Because LES have undergone millions of years of evolution to selectively dock to their complementary structures, small peptides made out of the same amino acids as the LES are expected to selectively attach to the newly expressed (unfolded) protein and inhibit its folding, or to the native (fluctuating) native conformation and denaturate it. These peptides, or their mimetic molecules, can thus be used as effective non--conventional drugs to those already existing (and directed at neutralizing the active site of enzymes), displaying the advantage of not suffering from the uprise of resistance

“The thing is, to adapt is traditional”: Environmental Change and its Effects on Traditional Ecological Knowledge in the Eastern United States

In this essay, I examine the transformation of traditional ecological knowledge, particularly that concerning plant knowledge pertaining to medicine. I argue that this transformation is a result of an environmental history influenced by the presence of a colonial population. When the Europeans began to arrive in the Eastern United States in the sixteenth century, they created a domino effect of environmental change. This change occurred because the Europeans had different cultural adaptations when interacting with the environment than the natives did; in other words, they drew from a differently developed form of ecological knowledge. When the colonists utilized this knowledge to interact with their new environment in the Eastern United States, they altered the environment in ways that contradicted how the natives interacted with the same environment. The ecological changes occurring as a result of such alterations fostered changes in native traditional knowledge, because there were now new plants, animals, and people to interact with, as well as transformations of the landscape to contend with

Selecting fast folding proteins by their rate of convergence

We propose a general method for predicting potentially good folders from a given number of amino acid sequences. Our approach is based on the calculation of the rate of convergence of each amino acid chain towards the native structure using only the very initial parts of the dynamical trajectories. It does not require any preliminary knowledge of the native state and can be applied to different kinds of models, including atomistic descriptions. We tested the method within both the lattice and off-lattice model frameworks and obtained several so far unknown good folders. The unbiased algorithm also allows to determine the optimal folding temperature and takes at least 3--4 orders of magnitude less time steps than those needed to compute folding times