Academic cooperation to foster research and advocacy competences in the occupied Palestinian territory (West Bank)

Palestinians living in the West Bank, a territory occupied by the State of Israel according to International Law, face deprived access to land and a limited ability to move freely which pertains to the presence of Israeli settlements and other infrastructure (closures, restricted or forbidden roads, etc.). This confinement has significant impacts on their economic and social livelihoods, and it is even worsening with the on-going construction of a 709 km long Barrier which mainly runs inside the West Bank. With regard to this situation, there is a clear need to strengthen the capacity of civil society and its representatives to apply sound research processes as a basis for improved advocacy for Palestinian human rights. Monitoring processes and tools are needed to assess the impacts of the Palestinians’ confinement, particularly in relation to the Barrier’s construction. Reliable data has also to be collected, managed, and above all, shared. These challenges have been addressed within the Academic Cooperation Palestine Project (ACPP) that brings together academic partners from the occupied Palestinian territory (oPt) West Bank (WB), and Switzerland as well as other international academic institutions and Palestinian governmental and non-governmental agencies. ACPP started in early 2011 and is designed as a large cooperation networking platform involving researchers, students, public servants and experts from the oPt WB. A large set of actions have already been developed during the first year of the project, including courses, training, and research actions. First relevant results and impacts of the different actions are presented in this paper. Taken as a whole, the project produces valuable results for all partners: useful advocacy material for the Palestinian partners, and a unique “real-scale laboratory” where investigations are jointly conducted to develop novel confinement and change indicators.

EU trade agreements and their impacts on human rights: study commissioned by the German Federal Ministry for Economic Cooperation and Development (BMZ)

The European Union’s (EU) trade policy has a strong influence on economic development and the human rights situation in the EU’s partner countries, particularly in developing countries. The present study was commissioned by the German Federal Ministry for Economic Cooperation and Development (BMZ) as a contribution to further developing appropriate methodologies for assessing human rights risks in development-related policies, an objective set in the BMZ’s 2011 strategy on human rights. The study offers guidance for stakeholders seeking to improve their knowledge of how to assess, both ex ante and ex post, the impact of Economic Partnership Agreements on poverty reduction and the right to food in ACP countries. Currently, human rights impacts are not yet systematically addressed in the trade sustainability impact assessments (trade SIAs) that the European Commission conducts when negotiating trade agreements. Nor do they focus specifically on disadvantaged groups or include other benchmarks relevant to human rights impact assessments (HRIAs). The EU itself has identified a need for action in this regard. In June 2012 it presented an Action Plan on Human Rights and Democracy that calls for the inclusion of human rights in all impact assessments and in this context explicitly refers to trade agreements. Since then, the EU has begun to slightly adapt its SIA methodology and is working to define more adequate human rights–consistent procedures. It is hoped that readers of this study will find inspiration to help contribute to this process and help improve human rights consistency of future trade options.

Fluorinated olefinic peptide nucleic acid: synthesis and pairing properties with complementary DNA

The fluorinated olefinic peptide nucleic acid (F-OPA) system was designed as a peptide nucleic acid (PNA) analogue in which the base carrying amide moiety was replaced by an isostructural and isoelectrostatic fluorinated C-C double bond, locking the nucleobases in one of the two possible rotameric forms. By comparison of the base-pairing properties of this analogue with its nonfluorinated analogue OPA and PNA, we aimed at a closer understanding of the role of this amide function in complementary DNA recognition. Here we present the synthesis of the F-OPA monomer building blocks containing the nucleobases A, T, and G according to the MMTr/Acyl protecting group scheme. Key steps are a selective desymmetrization of the double bond in the monomer precursor via lactonization as well as a highly regioselective Mitsunobu reaction for the introduction of the bases. PNA decamers containing single F-OPA mutations and fully modified F-OPA decamers and pentadecamers containing the bases A and T were synthesized by solid-phase peptide chemistry, and their hybridization properties with complementary parallel and antiparallel DNA were assessed by UV melting curves and CD spectroscopic methods. The stability of the duplexes formed by the decamers containing single (Z)-F-OPA modifications with parallel and antiparallel DNA was found to be strongly dependent on their position in the sequence with T(m) values ranging from +2.4 to -8.1 degrees C/modification as compared to PNA. Fully modified F-OPA decamers and pentadecamers were found to form parallel duplexes with complementary DNA with reduced stability compared to PNA or OPA. An asymmetric F-OPA pentadecamer was found to form a stable self-complex (T(m) approximately 65 degrees C) of unknown structure. The generally reduced affinity to DNA may therefore be due to an increased propensity for self-aggregation

Trust, Competition and Cooperation in Autism Spectrum Disorder

Objective: Impaired social interactions and repetitive behavior are key features of autism spectrum disorder (ASD). In the present study we compared social decision-making in subjects with and without ASD. Subjects performed five social decision-making games in order to assess trust, fairness, cooperation & competition behavior and social value orientation. Methods: 19 adults with autism spectrum disorder and 17 controls, matched for age and education, participated in the study. Each subject performed five social decision-making tasks. In the trust game, subjects could maximize their gain by sharing some of their money with another person. In the punishment game, subjects played two versions of the Dictator’s Dilemma. In the dictator condition they could share an amount of 0-100 points with another person. In the punishment condition, the opponent was able to punish the subject if he/she was not satisfied with the amount of points received. In the cooperation game, subjects played with a small group of 3 people. Each of them could (anonymously) select an amount of 5, 7.5 or 10 Swiss francs. The goal of the game was to achieve a high group minimum. In the competition game, subjects performed a dexterity task. Before performing the task, they were asked whether they wanted to compete (winner takes it all) or cooperation (sharing the joint achieved amount of points) with a randomly selected person. Lastly, subjects performed a social value orientation task where they were playing for themselves and for another person. Results: There was no overall difference between healthy controls an ASD subjects in investment in the trust game. However, healthy controls increased their investment over number of trials whereas ASD subjects did not. A similar pattern was found for the punishment game. Furthermore, ASD subjects revealed a decreased investment in the dictator condition of the punishment game. There were no mean differences in competition behavior and social value orientation. Conclusions: The results provide evidence for differences between ASD subjects and healthy controls in social decision-making. Subjects with ASD showed a more consistent behavior than healthy controls in the trust game and the dictator dilemma. The present findings provide evidence for impaired social learning in ASD.

Synthesis of cyclopentane amide DNA (cpa-DNA) and its pairing properties

We recently reported on the synthesis and pairing properties of the DNA analogue bicyclo[3.2.1]amide DNA (bca-DNA). In this analogue the nucleobases are attached via a linear, 4-bond amide-linker to a structurally preorganized sugar-phosphate backbone unit. To define the importance of the degree of structural rigidity of the bca-backbone unit on the pairing properties, we designed the structurally simpler cyclopentane amide DNA (cpa-DNA), in which the bicyclo[3.2.1]-scaffold was reduced to a cyclopentane unit while the base-linker was left unchanged. Here we present a synthetic route to the enantiomerically pure cpa-DNA monomers and the corresponding phosphoramidites containing the bases A and T, starting from a known, achiral precursor in 9 and 12 steps, respectively. Fully modified oligodeoxynucleotides were synthesized by standard solid-phase oligonucleotide chemistry, and their base-pairing properties with complementary oligonucleotides of the DNA-, RNA-, bca-DNA-, and cpa-DNA-backbones were assessed by UV melting curves and CD-spectroscopic methods. We found that cpa-oligoadenylates form duplexes with complementary DNA that are less stable by -2.7 degrees C/mod. compared to DNA. The corresponding cpa-oligothymidylates do not participate in complementary base-pairing with any of the investigated backbone systems except with its own (homo-duplex). As its congener bca-DNA, cpa-DNA seems to prefer left-handed helical duplex structures with DNA or with itself as indicated by the CD spectra

Synthesis of a cyclopentane amide DNA analogue and its base pairing properties

cpa-DNA monomers containing the bases adenine and thymine have been synthesized starting from the known compound 1 in 12 steps. Partially and fully modified cpa-thymidine and cpa-adenosine containing oligodeoxynucleotides were synthesized by standard oligonucleotide chemistry. Fully modified homo-cpa-A sequences lead to duplex destabilization by -1.4 degrees C/mod. relative to DNA. As its congener bca-DNA, cpa-DNA prefers left-handed duplex formation where possible

Watson-Crick base-pairing properties of tricyclo-DNA

Tricyclo-DNA belongs to the family of conformationally restricted oligodeoxynucleotide analogues. It differs structurally from DNA by an additional ethylene bridge between the centers C(3') and C(5') of the nucleosides, to which a cyclopropane unit is fused for further enhancement of structural rigidity. The synthesis of the hitherto unknown tricyclodeoxynucleosides containing the bases cytosine and guanine and of the corresponding phosphoramidite building blocks is described, as well as a structural description of a representative of an alpha- and a beta-tricyclodeoxynucleoside by X-ray analysis. Tricyclodeoxynucleoside building blocks of all four bases were used for the synthesis of fully modified mixed-base oligonucleotides. Their Watson-Crick pairing properties with complementary DNA, RNA, and with itself were investigated by UV melting curves, CD spectroscopy, and molecular modeling. Tricyclo-DNA was found to be a very stable Watson-Crick base-pairing system. A UV melting curve analysis of the decamers tcd(pcgtgacagtt) and tcd(paactgtcacg) showed increased thermal stabilities of up to DeltaT(m)/mod. = +1.2 degrees C with complementary DNA and +2.4 degrees C with complementary RNA. With itself, tricyclo-DNA showed an increase in stability of +3.1 degrees C/base pair relative to DNA. Investigations into the thermodynamic properties of these decamers revealed an entropic stabilization and an enthalpic destabilization for the tricyclo-DNA/DNA duplexes. CD spectroscopic structural investigations indicated that tricyclo-DNA containing duplexes preferrably exist in an A-conformation, a fact which is in agreement with results from molecular modeling

Bicyclo[3.2.1]amide-DNA: a chiral, non-chiroselective base-pairing system

The design, synthesis and base-pairing properties of bicyclo[3.2.1]amide-(bca)DNA, a novel phosphodiester based DNA analogue, is reported. This analogue consists of a conformationally constrained backbone entity which emulates a B-DNA geometry, to which the nucleobases were attached via an extended, acyclic amide linker. Homobasic adenine-containing bca-decamers form duplexes with complementary oligonucleotides containing the bca-, the DNA the RNA and, surprisingly, also the L-RNA backbone. UV- and CD-spectroscopic investigations revealed the duplexes with D- or L-complement to be of similar stability and enantiomorphic in structure. Bca-oligonucleotides containing all four bases form strictly antiparallel, left-handed complementary duplexes with itself and complementary DNA but not with RNA. Base-mismatch discrimination is comparable to that of DNA while the overall thermal stabilities of bca-oligonucleotide duplexes are inferior relative to that of DNA or RNA. A detailed molecular modeling study of left- and right-handed bca-DNA containing duplexes showed only minor changes in the backbone structure and revealed a structural switch around the base-linker unit to be responsible for the generation of enantiomorphic duplex structures. The obtained data are discussed with respect to the structural and energetic role of the ribofuranose entities in DNA and RNA association