Characterization of hydrophobic peptides by atmospheric pressure photoionization-mass spectrometry and tandem mass spectrometry

The use of photoionization at atmospheric pressure shows great potential for the mass analysis of large apolar or hydrophobic peptides. Mass spectra that were obtained using this technique showed mainly singly charged ions. While polar peptides spectra do not produce fragment ions, others lead to B-type or C-type in-source fragmentation. These dissociation reactions, which could involve electron capture dissociation processes in the case of the C-type ions, are observed for hydrophobic peptides. Both the compatibility of this ionization mode with reversed- or normal-phase liquid chromatographic separation and its sensitivity allow liquid chromatography coupling to both mass spectrometry and tandem mass spectrometry for the analyses of hydrophobic peptide mixtures. Atmospheric pressure photoionization seems to be an interesting alternative method to study hydrophobic peptides that are not easily ionizable by more classical ionization techniques such as electrospray ionization and matrix-assisted laser desorption/ionization.     

Multiple sequence comparison — a peptide matching approach

We present in this paper a peptide matching approach to the multiple comparison of a set of protein sequences. This approach consists in looking for all the words that are common to q of these sequences, where q is a parameter.

The comparison between words is done by using as reference an object called a model. In the case of proteins, a model is a product of subsets of the alphabet Σ of the amino acids. These subsets belong to a cover of Σ, that is, their union covers all of Σ. A word is said to be an instance of a model if it belongs to the model.

A further flexibility is introduced in the comparison by allowing for up to e errors in the comparison between a word and a model. These errors may concern gaps or substitutions not allowed by the cover. A word is said to be this time an occurrence of a model if the Levenshtein distance between it and an instance of the model is inferior or equal to e. This corresponds to what we call a Set-Levenshtein distance between the occurrences and the model itself. Two words are said to be similar if there is at least one model of which both are occurrences. In the special case where e = 0, the occurrences of a model are simply its instances. If a model M has occurrences in at least q of the sequences of the set, M is said to occur in the set.

The algorithm presented here is an efficient and exact way of looking for all the models, of a fixed length k or of the greatest possible length k_max, that occur in a set of sequences. It is linear in the total length n of the sequences and proportional to (e + 2)(2e+ 1)k^e+1p^e+1 g^k where k n is a small value in all practical situations, p is the number of sets in the cover and g is related to the latter's degree of nontransitivity.

Models are closely related to what is called a consensus in the biocomputing area, and covers are a good way of representing complex relationships between the amino acids.     

Fuzzy methods for case-based recommendation and decision support

The paper proposes two case-based methods for recommending decisions to users on the basis of information stored in a database. In both approaches, fuzzy sets and related (approximate) reasoning techniques are used for modeling user preferences and decision principles in a flexible manner. The first approach, case-based decision making, can principally be seen as a case-based counterpart to classical decision principles well-known from statistical decision theory. The second approach, called case-based elicitation, combines aspects from flexible querying of databases and case-based prediction. Roughly, imagine a user who aims at choosing an optimal alternative among a given set of options. The preferences with respect to these alternatives are formalized in terms of flexible constraints, the expression of which refers to cases stored in a database. As both types of decision support might provide useful tools for recommender systems, we also place the methods in a broader context and discuss the role of fuzzy set theory in some related fields.     

The role of wingbeat frequency and amplitude in flight power

Body-mounted accelerometers provide a new prospect for estimating power use in flying birds, as the signal varies with the two major kinematic determinants of aerodynamic power: wingbeat frequency and amplitude. Yet wingbeat frequency is sometimes used as a proxy for power output in isolation. There is, therefore, a need to understand which kinematic parameter birds vary and whether this is predicted by flight mode (e.g. accelerating, ascending/descending flight), speed or morphology. We investigate this using high-frequency acceleration data from (i) 14 species flying in the wild, (ii) two species flying in controlled conditions in a wind tunnel and (iii) a review of experimental and field studies. While wingbeat frequency and amplitude were positively correlated, R² values were generally low, supporting the idea that parameters can vary independently. Indeed, birds were more likely to modulate wingbeat amplitude for more energy-demanding flight modes, including climbing and take-off. Nonetheless, the striking variability, even within species and flight types, highlights the complexity of describing the kinematic relationships, which appear sensitive to both the biological and physical context. Notwithstanding this, acceleration metrics that incorporate both kinematic parameters should be more robust proxies for power than wingbeat frequency alone.     

Assessing migratory bottlenecks and escapement of silver eel (Anguilla anguilla) in the highly urbanized North Sea Canal basin,the Netherlands

Habitat fragmentation and migration barriers have attributed to the decline of European eel (Anguilla anguilla). The migration of silver eels through pumping stations, ship locks, and migration facilities within the North Sea Canal basin using acoustic telemetry and overall escapement by mark–recapture was studied. A network of 61 acoustic receivers and three PIT-tag stations was built, and 305 silver eels were tagged with acoustic transmitters and 3923 with PIT-tags. Of all the silver eels that were detected, 55% passed barriers between the polders and the canal and 46% also passed the barrier complex at IJmuiden to sea, mainly via the ship locks. Overall, silver eel escapement to the North Sea per year averaged 81,629 silver eels and 14.3% suffered mortality in the pumping station at IJmuiden. Migration speed was lower for silver eels that initiated their migration upstream compared with silver eels further downstream, higher for silver eels passing barriers later in the migration period, and highest at sea. This study of silver eel movement and escapement in the North Sea canal basin indicated several bottlenecks. Passage success along barriers varied strongly between sites and types of barriers. While at two smaller locations, silver eels migrated through the pedal valves in the ship lock gates, a small passage facility and the pedal valves in a ship lock at complex IJmuiden did not enhance silver eel migration. The barriers and unnatural canal system caused additional delay during silver eel migrations. Mitigation measures for management could include installing fish-friendly pumps, using pumping stations only during the day, and in addition opening ship locks and pedal valves at the beginning of the night.     

Synthesis and SAR Studies of Isoquinoline and Tetrahydroisoquinoline Derivatives as Melatonin Receptor Ligands

In our constant search for new successors of agomelatine, we report herein a new series of compounds resulting from bioisosteric modulation of the naphthalene ring. The isoquinoline and tetrahydroisoquinoline derivatives were synthesized and pharmacologically evaluated. This isosteric replacement of the naphthalene group of agomelatine has led to potent agonist and partial agonist compounds with nanomolar melatonergic binding affinities. Overall, the presence of a nitrogen atom was accompanied with a decrease in the binding affinity toward both MT₁ and MT₂ and the loss of 5HT_2C response, especially for tetrahydroisoquinoline in comparison with the parent compound. Interestingly, due to the presence of this nitrogen atom, a notable improvement in the pharmacokinetic properties was observed for all compounds.