Mechanism of action of cyclic antimicrobial peptides

This PhD thesis is the result of the combination of experimental and computational techniques with the aim of understanding the mechanism of action of de novo cyclic decapeptides with high antimicrobial activity. By experimental techniques the influence of the replacement of the phenylalanine for tryptophan residue in their antimicrobial activity was tested and the stability in human serum was also analyzed, in order to evaluate their potential therapeutic application as antitumor agents. On the other hand, the interaction amongst the peptide BPC194 c(KKLKKFKKLQ), the best candidate from the whole library of cyclic peptides, and a model anionic membrane was simulated. The results showed a structure-function relationship derived from the stable conformation of the peptides involved in the membrane permeabilization. As a result, a rational design was performed being BPC490 the peptide with best antimicrobial activity compared with the best active peptide from the original library.

Eye movements of beginning and more skilled readers

The present study aimed to analyze and compare the eye movements of beginning (2nd grade) and more skilled (4th grade) readers, during reading words and pseudo-words aloud, that differ in frequency (just for words), regularity and length. In this way, one intends to analyze the process of visual information extraction, by both groups, and detect experience and practice-related changes in the ocular behavior. The eye movements of 34 children were monitored, while these were reading words/pseudo-words lists, and this was accomplished using eye-tracking technology. The results show statistically significant differences between the two groups, in mean and total fixations duration for high-frequency words, in mean fixation duration for regular words and in the mean saccade amplitude in irregular pseudo-words. However, no significant differences were found between the groups on the study of the other variables. Nevertheless, the results suggest that skilled readers tend to show more effective eye movements, what determined a lesser effect of words’ frequency, regularity and length on this group. Moreover, the pseudo-words processing was more difficult than that of words, in both groups.

Memory and power : two movements

The institutions that work with the preservation and diffusion of cultural heritage - be them archive, libraries, museums, art galleries or cultural centres - present a certain discourse about reality. To understand this discourse, composed by sound and silence, by fullness and emptiness, by presence and absence, by remembrance and forgetting, an operation is implied, not only with the enunciation of speech and its gaps, but also the comprehension of that which causes to speak, of who is speaking and of the point whence one speaks. Preservation and destruction, or, in another way, conservation and loss, walk hand in hand in the arteries of life. As suggested by Nietzsche (1999, p.273), it is impossible to live without loss, it is entirely impossible to live avoiding destruction to play its game and drive the dynamics of life on. However, by means of a kind of tautological argument, one often justifies preservation by the imminence of loss and memory by the threat of forgetting. Thus, one ceases to consider that the game and the rules of the game between forgetting and memory are not fed by themselves and that preservation and destruction are not opposed in a deadly duel, but instead they complement one another and are always at the service of subjects that build themselves and are built through social practices. To indicate that memories and forgettings can be sown and cultivated corroborates the importance of working towards the denaturalisation of these concepts and towards the understanding that they result from a construction process also involving other forces, such as: power. Power is a sower, a promoter of memories and forgettings.

Museums, memories and social movements

From modernity to the contemporary world, museums have been acknowledged for their power to produce metamorphoses of meanings and functions, for their ability to adapt historic and social determination, and for their calling for cultural mediation. They derive from creating gestures which bind the symbolic and the material, which bind what is sensitive and what is intelligible. For this very reason the bridge metaphor fits them well, a bridge cast between different times, spaces, individuals, social groups and cultures, a bridge that is built with images and which holds a special place in the imaginary.

Site Safety and Food Affect Movements of Semipalmated Sandpipers (Calidris pusilla) Migrating Through the Upper Bay of Fundy

The upper Bay of Fundy is a critical stopover site for Semipalmated Sandpipers (Calidris pusilla) during their fall migration. However, little is known about factors that influence selection of feeding and roosting sites by these birds, or the extent to which birds move between different sites during their time in the region. Using radio-telemetry, we studied movement patterns, examined habitat use, and tested hypotheses associated with factors influencing foraging and roost-site selection. Movements of radio-tagged sandpipers were tracked in the upper Bay of Fundy in August 2004 and 2005. In 2004, sandpipers from the Minas Basin, Nova Scotia and Chignecto Bay, New Brunswick and Nova Scotia, were tracked, and in 2005, sandpipers were tracked only in Chignecto Bay. Sandpipers were highly mobile in both the Minas Basin 2004 and Chignecto Bay 2005, making daily movements of up to 20 km between foraging and roosting sites, although very little movement was detected in Chignecto Bay in 2004. Migrating sandpipers appeared to select foraging sites based on relative safety, as measured by distance to cover, provided that these sites offered an adequate food supply. Similarly, roosting sandpipers preferred sites that were far from nearby trees that might offer cover to predators. This preference for safe sites became more apparent later in their stay in the Bay of Fundy, when birds were heavier and, therefore, possibly more vulnerable to predation. Semipalmated Sandpipers appear to be flexible during their time in the upper Bay of Fundy, displaying year-to-year and site-to-site variability in movement and mudflat usage. Therefore, multiple, synchronized population counts should be conducted at known roost sites in order to more accurately estimate Semipalmated Sandpiper abundance in this region. Furthermore, in a highly dynamic system where food can be variable, landscape features such as distance to cover may be important factors to consider when selecting candidate sites for shorebird conservation measures.

Movements and Habitat Use by Temperate-Nesting Canada Geese During the Postbreeding Period in Southern Québec

Individual behavior that reduces vulnerability to predation can affect population dynamics of animals. Temperate-nesting Canada Geese (Branta canadensis maxima) have increased steadily throughout the Atlantic flyway and have become a nuisance in some parts of their range. The objective of our study was to describe movements and habitat use during the postbreeding period of Canada Geese recently established in southern Québec. More specifically, we wanted to determine whether geese were using areas where hunting was allowed to assess the potential of harvest to control the number of geese. We tracked a sample of geese fitted with radio or conventional alphanumeric collars throughout the fall in three zones characterized by different habitats and hunting pressure. Before the hunting season, geese left the breeding area where hunting was allowed to reach suburban areas where firearm discharge was prohibited or hunters’ numbers were low. These postbreeding movements occurred when juveniles were approximately three months old. We observed few local movements among zones once migrant geese from northern breeding populations reached the study area. Radio-collared geese used mainly natural habitats (75.4 ± 2.6%), followed by urban (14.4 ± 2.7%), and agricultural habitats (10.3 ± 0.8%). They were located 73.8 ± 6.2% of the time in areas where hunting was prohibited. Geese that attended their juveniles during brood rearing were more prone to use areas where firearm discharge was restricted than geese that had abandoned or lost their brood. This study shows that under the prevailing regulations, the potential of hunting to manage the increasing breeding population of Canada Geese in southern Québec is limited.

Caring at a distance: Gift Theory, aid chains and social movements

This paper takes as its starting point recent work on caring for distant others which is one expression of renewed interest in moral geographies. It examines relationships in aid chains connecting donors/carers in the First World or North and recipients/cared for in the Third World or South. Assuming predominance of relationships between strangers and of universalism as a basis for moral motivation I draw upon Gift Theory in order to characterize two basic forms of gift relationship. The first is purely altruistic, the other fully reciprocal and obligatory within the framework of institutions, values and social forces within specific relationships of politics and power. This conception problematizes donor-recipient relationships in the context of two modernist models of aid chains-the Resource Transfer and the Beyond Aid Paradigms. In the first, donor domination means low levels of reciprocity despite rhetoric about partnership and participation. The second identifies potential for greater reciprocity on the basis of combination between social movements and non-governmental organizations at both national and trans-national levels, although at the risk of marginalizing competencies of states. Finally, I evaluate post-structural critiques which also problematize aid chain relationships. They do so both in terms of bases-such as universals and difference-upon which it might be constructed and the means-such as forms of positionality and mutuality-by which it might be achieved.

Enantioselective Intramolecular Michael Addition of Nitronates onto Conjugated Esters: Access to Cyclic γ-Amino Acids with up to Three Stereocenters

A highly stereoselective synthesis of conformationally constrained cyclic γ-amino acids has been devised. The key step involves an intramolecular cyclization of a nitronate onto a conjugated ester, promoted by a bifunctional thiourea catalyst. This methodology has been successfully applied to generate a variety of γ-amino acids, including some containing three contiguous stereocenters, with very high diastereoselectivity and excellent enantioselectivity. It is postulated that an interaction that is key to the success of the process is the simultaneous coordination of the thiourea functionality to both the conjugated ester and the nitronate. Finally, the synthetic utility of these compounds is demonstrated in the synthesis of two dipeptides derived from the C- and N-termini.

Investigating the practicality of using radio tracking to determine home range and movements of Picathartidae

Radiotelemetry is an important tool used to aid the understanding and conservation of cryptic and rare birds. The two bird species of the family Picathartidae are little-known, secretive, forest-dwelling birds endemic to western and central Africa. In 2005, we conducted a radio-tracking trial of Grey-necked Picathartes Picathartes oreas in the Mbam Minkom Mountain Forest, southern Cameroon, using neck collar (two birds) and tail-mounted (four birds) transmitters to investigate the practicality of radio-tracking Picathartidae. Three birds with tail-mounted transmitters were successfully tracked with the fourth, though not relocated for radio tracking, resighted the following breeding season. Two of these were breeding birds that continued to provision young during radio tracking. One neck-collared bird was found dead three days after transmitter attachment and the other neither relocated nor resighted. As mortality in one bird was potentially caused by the neck collar transmitter we recommend tail-mounted transmitters in future radio-tracking studies of Picathartidae. Home ranges, shown using minimum convex polygon and kernel estimation methods, were generally small (<0.5 km(2)) and centred around breeding sites. A minimum of 60 fixes were found to be sufficient for home range estimation.

Movements, activity patterns and home range of a female brown bear (Ursus arctos, L.) in the Rodopi Mountain Range, Greece

Movements and activity patterns of an adult radio-tagged female brown bear accompanied by her cubs were documented for the first time in Rodopi area (NE Greece) from August 2000 to July 2002. Average daily movements were 2.45 +/- 2.26 SD km, (range 0.15-8.5 km). The longest daily range could be related to human disturbance (hunting activity). The longest seasonal distance (211 km), during Summer 2001 coincided with the dissolution of the family. With cubs, the female was more active during daytime (73 % of all radio-readings) than when solitary (28 %). The female switched to a more crepuscular behaviour, after separation from the yearling (July 2001). According to pooled data from 924 activity - recording sessions, during the whole monitoring period, the female was almost twice as active during day time while rearing cubs (51 % active) than when solitary (23 %). The autumn and early winter home range size of the family was larger (280 km(2)) than after the separation from the cubs (59 km(2)). During the family group phase, home range size varied from 258 km(2) in autumn to 40 km(2) in winter (average denning period lasted 107 days : December 2000-March 2001). The bear hibernated in the Bulgarian part of the Rodopi Range during winters of 2001 and 2002.

A mechanistic study of cyclic siloxane pyrolyses at low pressures

Matrix isolation IR spectroscopy has been used to study the vacuum pyrolysis of hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4) and decamethyl cyclopentasiloxane (D5), and the results interpreted in the context of various kinetic models. In particular, it is shown that the significant pyrolysis products - which include CH3, CH4, C2H2, C2H4, C2H6 and SiO - may be satisfactorily accounted for by radical reactions involving dimethylsiloxane (D1), and estimates are made of the various chain lengths for the proposed reactions based on a range of ambient conditions.

Solvent-induced dynamic single-crystal-to-single-crystal transformation of a synthetic peptide-based cyclic compound

Solvent induced single-crystal-to-single-crystal transformation has been demonstrated indicating the dynamic behavior of one dimensional arrays obtained from a self-assembled new synthetic cyclic peptide.

Anharmonic vibrational levels of the two cyclic isomers of SiC3

Using coupled-cluster approach full six-dimensional analytic potential energy surfaces for two cyclic SiC3 isomers [C-C transannular bond (I) and Si-C transannular bond (II)] have been generated and used to calculate anharmonic vibrational wave functions. Several strong low-lying anharmonic resonances have been found. In both isomers already some of the fundamental transitions cannot be described within the harmonic approximation. Adiabatic electron affinities and ionization energies have been calculated as well. The Franck-Condon factors for the photodetachment processes c-SiC3-(I)-> c-SiC3(I) and c-SiC3-(II)-> c-SiC3(II) are reported. (c) 2006 American Institute of Physics.

Synthesis of fused cyclic systems containing medium-sized rings through tandem ROM-RCM of norbornene derivatives embedded in a carbohydrate template

A general approach for the synthesis of fused cyclic systems containing medium-sized rings (7-9) has been developed. The key steps involve a diastereoface-selective Diels-Alder reaction of the dienophiles 4a-d attached to a furanosugar with cyclopentadiene and ring opening (ROM)-ring closing metathesis (RCM) of the resulting norbornene derivatives 10a-d and 11a-d. Diels-Alder reaction of the dienophiles 4a-d with cyclopentadiene in the absence of a catalyst produced 10a-d as the major product arising through addition of the diene to the unhindered Si-face. The most interesting and new aspect of the Diels-Alder reaction of these dienophiles is the accessibility of the Re-face that was blocked by the alkenyl chains under Lewis acid catalysis producing the diastereoisomers 11a-d exclusively. The reversal of facial selectivity from an uncatalyzed reaction to a catalyzed one is unprecedented. The observed stereochemical dichotomy is attributed to rotation of the enone moiety along the or bond linking the sugar moiety during formation of the chelate 13. This makes the Re-face of the enone moiety in 4a-d unhindered. Diels-Alder reaction of the carbocyclic analogue 15 under Lewis acid catalysis produced a 1: 1 mixture of the adducts 16 and 17 confirming the participation of sugar ring oxygen in chelate formation. Finally ROM-RCM of 10a-d and 11a-d with Grubbs' catalyst afforded the cis-syn-cis and cis-anti-cis bicyclo-annulated sugars 21a-d and 23a-d, respectively, containing 7-9 membered rings.