Report of the Subsidiary Body for Implementation on its forty-seventh session, held in Bonn from 6 to 15 November 2017.

Report of the Subsidiary Body for Scientific and Technological Advice on its forty-seventh session, held in Bonn from 6 to 15 November 2017.

Nepal. Report of the technical assessment of the proposed forest reference emission level of Nepal submitted in 2017.

Report of the Conference of the Parties serving as the meeting of the Parties to the Kyoto Protocol on its thirteenth session, held in Bonn from 6 to 18 November 2017. Part one: Proceedings

Report of the Conference of the Parties serving as the meeting of the Parties to the Paris Agreement on the second part of its first session, held in Bonn from 6 to 18 November 2017

Report of the Conference of the Parties serving as the meeting of the Parties to the Kyoto Protocol on its thirteenth session, held in Bonn from 6 to 18 November 2017. Addendum. Part two: Action taken by the Conference of the Parties serving as the meeting of the Parties to the Kyoto Protocol at its thirteenth session

Report of the Conference of the Parties on its twenty-third session, held in Bonn from 6 to 18 November 2017. Addendum. Part two: Action taken by the Conference of the Parties at its twenty-third session

Report of the Conference of the Parties on its twenty-third session, held in Bonn from 6 to 18 November 2017. Addendum. Part two: Action taken by the Conference of the Parties at its twenty-third session

Report of the Conference of the Parties on its twenty-third session, held in Bonn from 6 to 18 November 2017. Part one: Proceedings

Report of the Ad Hoc Working Group on the Paris Agreement on the fourth part of its first session, held in Bonn from 7 to 18 November 2017.

Hungary. Report on the individual review of the annual submission of Hungary submitted in 2017. Note by the expert review team.

Capacity-building work of bodies established under the Convention and its Kyoto Protocol. Compilation and synthesis report by the secretariat.

Adaptation in human settlements: key findings and way forward. Report by the secretariat.

Provisional agenda and annotations. Note by the Executive Secretary.

Provisional agenda and annotations. Note by the Executive Secretary.

Technical workshop on ways to increase the efficiency and transparency of the budget process. Report by the secretariat.

Côte d'Ivoire. Report of the technical assessment of the proposed forest reference emission level of Côte d'Ivoire submitted in 2017.

Agenda and annotations. Note by the Executive Secretary.

Iceland. Report on the individual review of the annual submission of Iceland submitted in 2017. Note by the expert review team.

Papua New Guinea. Report of the technical assessment of the proposed forest reference level of Papua New Guinea submitted in 2017.

United Kingdom of Great Britain and Northern Ireland. Report on the individual review of the annual submission of the United Kingdom of Great Britain and Northern Ireland submitted in 2017. Note by the expert review team.

Greece. Report on the individual review of the annual submission of Greece submitted in 2017. Note by the expert review team.

Capacity-building work of bodies established under the Convention and its Kyoto Protocol. Compilation and synthesis report by the secretariat. Addendum. Compilation of capacity-building activities undertaken by bodies established under the Convention and its Kyoto Protocol

Initial draft of the technology framework. Informal document by the Chair

Slovakia. Report on the individual review of the annual submission of Slovakia submitted in 2017. Note by the expert review team.

The 33rd meeting of the Least Developed Countries Expert Group. Report by the secretariat.

Draft elements of the modalities, work programme and functions of the forum on the impact of the implementation of response measures under the Paris Agreement . Informal document by the Chairs.

Implementation of the framework for capacity-building in developing countries. Synthesis report by the secretariat.

Arrangements for Intergovernmental Meetings. Note by the Executive Secretary.

Monaco. Report on the individual review of the annual submission of Monaco submitted in 2017. Note by the expert review team.

Monaco. Report on the review of the report to facilitate the calculation of the assigned amount for the second commitment period of the Kyoto Protocol of Monaco.

Czechia. Report on the individual review of the annual submission of Czechia submitted in 2017. Note by the expert review team.

Outcomes of work under the Nairobi work programme on impacts, vulnerability and adaptation to climate change since May 2016. Synthesis report by the secretariat.

Cambodia. Report of the technical assessment of the proposed forest reference level of Cambodia submitted in 2017.

China. Technical analysis of the first biennial update report of China submitted on 12 January 2017.

United Nations Environment Programme response to the independent review of the Climate Technology Centre and Network.

New Zealand. Report on the individual review of the annual submission of New Zealand submitted in 2017. Note by the expert review team.

Status of submission and review of seventh national communications and third biennial reports. Note by the secretariat.

Where businesses are fighting to survive, agility is the name of the game, says Mignon Reynecke.

Después de 28 años bajo el gobierno de Paul Biya, Camerún se encuentra en una situación de inestabilidad grave que no sólo podría echar a perder las próximas elecciones presidenciales en 2011, sino que también pone en riesgo su papel como principal pilar de estabilidad en África Central.

On 15 June 2011 the Congolese Parliament adopted, after nearly three months of de-bate, the new electoral law. The Senate, or upper house, controlled by the opposition, and the National Assembly, or lower house, controlled by the ruling coalition, both voted for an electoral law which ultimately remains very similar to that governing the 2006 elections. Parliament took three months of debate to reject most of the amend-ments proposed by the ruling party (PPRD). In doing so it demonstrated that the ex-ecutive could not simply trump its interests.

Trois semaines après la réélection contestée de Joseph Kabila en République démocratique du Congo (RDC), Thierry Vircoulon, responsable de l'Afrique centrale à l'International Crisis Group dresse un premier bilan des élections congolaises.

En Centrafrique, la course aux élections qui prévoit des scrutins présidentiel et législatif avant la fin de l’année est aussi irréaliste que dangereuse. Alors que le plan initial de la transition a complètement déraillé, l’obstination des internationaux, et plus particulièrement de la France, à faire voter les Centrafricains à l’ombre des groupes armés, avec une administration territoriale squelettique et des haines inter-communautaires tenaces ressemble plus à une fuite en avant qu’à un processus de transition accompli.

This article, published ahead of print on 28 July 2008, has been withdrawn by the authors. Although moderate synergy between P2-RANTES and C peptides can be observed with high statistical significance in cell fusion assays, this synergy was not able to be verified in HIV viral assays. The authors regret the overstatement of synergy and will revise the paper for publication at a later date.

Leishmania major is the causative agent of cutaneous leishmaniasis (CL). No human vaccine is available for CL and current drug regimens present several drawbacks such as emerging resistance, severe toxicity, medium effectiveness, and/or high cost. Thus, the need for better treatment options against CL is a priority. In the present study, we validate the enzyme methionine aminopeptidase-1 (MetAP1), a metalloprotease that catalyzes the removal of N-terminal methionine from peptides and proteins, as a chemotherapeutic target against CL infection. The in vitro antileishmanial activity of eight novel MetAP1 inhibitors (OJT001-OJT008) were investigated. Three compounds OJT006, OJT007, and OJT008 demonstrated potent anti-proliferative effect in macrophages infected with L. major amastigotes and promastigotes at submicromolar concentrations, with no cytotoxicity against host cells. Importantly, the leishmanicidal effect was diminished by almost 10-fold in transgenic L. major promastigotes overexpressing MetAP1_LM in comparison to wild-type promastigotes. Furthermore, the in vivo activity of OJT006, OJT007, and OJT008 were investigated in L. major-infected BALB/c mice. In comparison to the control group, OJT008 significantly decreased footpad parasite load by 86%, and exhibited no toxicity against in treated mice. We propose MetAP1 inhibitor OJT008 as a potential chemotherapeutic candidate against CL infection caused by L. major infection.

The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct acting-antivirals (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.5 cells stably harboring a subgenomic genotype 1b replicon. A dose-dependent decrease of HCV RNA levels was observed upon MK-571 administration, with an EC₅₀ of 9±0.3 μM and a maximum HCV RNA level reduction of approximatively 1 Log₁₀. MK-571 also reduced the replication of the HCV full-length J6/JFH1 model in a dose-dependent manner. However, probenecid and apigenin homodimer (APN), two specific inhibitors of MRP-1, had no effect on HCV replication. In contrast, the CysLTR1 antagonists SR2640 increased HCV-SGR RNA levels in a dose-dependent manner, with a maximum increase of 10-fold. In addition, a combination of natural CysLTR1 agonist (LTD4) or antagonists (zafirlukast, cinalukast, and SR2640) with MK-571 completely reversed its antiviral effect, suggesting its anti-HCV activity is related to CysLTR1 rather to MRP-1 inhibition. In conclusion, we showed that MK-571 inhibits HCV replication in hepatoma cell cultures by acting as a CysLTR1 receptor antagonist, thus unraveling a new host-virus interaction in the HCV life cycle.

β-lactam resistance in Staphylococcus aureus limits treatment options. Stp1 and Stk1, a serine-threonine phosphatase and kinase respectively, mediate serine-threonine kinase (STK) signaling. Loss of function point mutations in stp1 were detected among laboratory passaged, β-lactam resistant S. aureus strains lacking mecA and blaZ, the major determinants of β-lactam resistance in the bacteria. Loss of Stp1 function facilitates β-lactam resistance of the bacteria.

Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo β-lactamase (MBL) families. The recent introduction of SBL carbapenemase-inhibitors has provided alternative therapeutic options. Unfortunately, there are no approved inhibitors of MBL-mediated carbapenem-resistance and treatment options for infections caused by MBL-producing Gram-negatives are limited. Here, we present ZN148, a zinc-chelating MBL-inhibitor capable of restoring the bactericidal effect of meropenem and in vitro clinical susceptibility to carbapenems in >98% of a large international collection of MBL-producing clinical Enterobacterales strains (n=234). Moreover, ZN148 was able to potentiate the effect of meropenem against NDM-1-producing Klebsiella pneumoniae in a murine neutropenic peritonitis model. ZN148 showed no inhibition of the human zinc-containing enzyme glyoxylase II at 500 μM and no acute toxicity was observed in an in vivo mouse model with cumulative dosages up to 128 mg/kg. Biochemical analysis showed a time-dependent inhibition of MBLs by ZN148 and removal of zinc ions from the active site. Addition of exogenous zinc after ZN148 exposure only restored MBL activity by ~30%, suggesting an irreversible mechanism of inhibition. Mass-spectrometry and molecular modelling indicated potential oxidation of the active site Cys221 residue. Overall, these results demonstrate the therapeutic potential of a ZN148-carbapenem combination against MBL-producing Gram-negative pathogens and that ZN148 is a highly promising MBL inhibitor, capable of operating in a functional space not presently filled by any clinically approved compound.