Tracking property: A viability approach

Background: Identification of drug-target interaction is essential in drug discovery. It is beneficial to predict unexpected therapeutic or adverse side effects of drugs. To date, several computational methods have been proposed to predict drug-target interactions because they are prompt and low-cost compared with traditional wet experiments. Methods: In this study, we investigated this problem in a different way. According to KEGG, drugs were classified into several groups based on their target proteins. A multi-label classification model was presented to assign drugs into correct target groups. To make full use of the known drug properties, five networks were constructed, each of which represented drug associations in one property. A powerful network embedding method, Mashup, was adopted to extract drug features from above-mentioned networks, based on which several machine learning algorithms, including RAndom k-labELsets (RAKEL) algorithm, Label Powerset (LP) algorithm and Support Vector Machine (SVM), were used to build the classification model. Results and Conclusion: Tenfold cross-validation yielded the accuracy of 0.839, exact match of 0.816 and hamming loss of 0.037, indicating good performance of the model. The contribution of each network was also analyzed. Furthermore, the network model with multiple networks was found to be superior to the one with a single network and classic model, indicating the superiority of the proposed model.

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Conflict of Laws and the Return of Indigenous Peoples’ Cultural Property: A Latin American Perspective

International Journal of Cultural Property ◽

10.1017/s0940739119000341 ◽

2019 ◽

Vol 26 (4) ◽

pp. 437-456

Author(s):

María Julia Ochoa Jiménez

Keyword(s):

Human Rights ◽

Indigenous Peoples ◽

Latin American ◽

National Level ◽

Cultural Property ◽

Cultural Value ◽

Property A ◽

American Perspective ◽

International Instruments ◽

Conflict Of Law

Abstract:In Latin America, conflict-of-law norms have not appropriately considered the cultural diversity that exists in their legal systems. However, developments towards the recognition of Indigenous peoples’ human rights, at the international and national levels, impose the task of considering such diversity. In that regard, within the conflict-of-law realm, interpersonal law offers a useful perspective. This article proposes a conflict-of-law rule that can contribute to clarity and legal certainty, offering a sound way of dealing at the national level with Indigenous peoples’ claims for restitution of property with a cultural value for them, which is framed in international instruments on human rights.

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Naphthalimide-Containing BP100 Leads to Higher Model Membranes Interactions and Antimicrobial Activity

Biomolecules ◽

10.3390/biom11040542 ◽

2021 ◽

Vol 11 (4) ◽

pp. 542

Author(s):

Gustavo Penteado Battesini Carretero ◽

Greice Kelle Viegas Saraiva ◽

Magali Aparecida Rodrigues ◽

Sumika Kiyota ◽

Marcelo Porto Bemquerer ◽

...

Keyword(s):

Anticancer Agents ◽

Biological Activities ◽

Biological Effects ◽

Membrane Surface ◽

Helical Structure ◽

Helical Conformation ◽

Property A ◽

Cellular Processes ◽

Double Stranded Dna ◽

Low Toxicity

In a large variety of organisms, antimicrobial peptides (AMPs) are primary defenses against pathogens. BP100 (KKLFKKILKYL-NH2), a short, synthetic, cationic AMP, is active against bacteria and displays low toxicity towards eukaryotic cells. BP100 acquires a α-helical conformation upon interaction with membranes and increases membrane permeability. Despite the volume of information available, the action mechanism of BP100, the selectivity of its biological effects, and possible applications are far from consensual. Our group synthesized a fluorescent BP100 analogue containing naphthalimide linked to its N-terminal end, NAPHT-BP100 (Naphthalimide-AAKKLFKKILKYL-NH2). The fluorescence properties of naphthalimides, especially their spectral sensitivity to microenvironment changes, are well established, and their biological activities against transformed cells and bacteria are known. Naphthalimide derived compounds are known to interact with DNA disturbing related processes as replication and transcription, and used as anticancer agents due to this property. A wide variety of techniques were used to demonstrate that NAPHT-BP100 bound to and permeabilized zwitterionic POPC and negatively charged POPC:POPG liposomes and, upon interaction, acquired a α-helical structure. Membrane surface high peptide/lipid ratios triggered complete permeabilization of the liposomes in a detergent-like manner. Membrane disruption was driven by charge neutralization, lipid aggregation, and bilayer destabilization. NAPHT-BP100 also interacted with double-stranded DNA, indicating that this peptide could also affect other cellular processes besides causing membrane destabilization. NAPHT-BP100 showed increased antibacterial and hemolytic activities, compared to BP100, and may constitute an efficient antimicrobial agent for dermatological use. By conjugating BP100 and naphthalimide DNA binding properties, NAPHT-BP100 bound to a large extent to the bacterial membrane and could more efficiently destabilize it. We also speculate that peptide could enter the bacteria cell and interact with its DNA in the cytoplasm.

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