Future cooling gap in shared socioeconomic pathways

The extent to which societies will globally be able to adapt to climate change is not well understood. Here we analyze socioeconomic dimensions of adaptive capacity of populations to deal with heat stress and find income, urbanization and income inequality to be important factors in explaining adaptation to heat stress with air conditioning (AC). Using the scenario framework of the Shared Socioeconomic Pathways (SSPs), we estimate the future cooling gap, which represents the difference between the population exposed to heat stress and the population able to protect against heat stress with AC. Depending on the scenario of socioeconomic development, total population affected by the cooling gap may vary between 2 billion and 5 billion people in 2050, with the scenario-dependent range widening further towards the end of the century. Our analysis shows vast regional inequalities in adaptive capacity for one of the most universal manifestations of climate change, underscoring the need to account for the different potential levels of adaptive capacity in assessments of climate change impacts

Overcoming gender inequality for climate resilient development

Gender inequalities are reflected in differential vulnerability, and exposure to the hazards posed by climate change and addressing them is key to increase the adaptive capacities of societies. We provide trajectories of the Gender Inequality Index (GII) alongside the Shared-Socioeconomic Pathways (SSPs), a scenario framework widely used in climate science. Here we find that rapid improvements in gender inequality are possible under a sustainable development scenario already in the near-term. The share of girls growing up in countries with the highest gender inequality could be reduced to about 24% in 2030 compared to about 70% today. Largely overcoming gender inequality as assessed in the GII would be within reach by mid-century. Under less optimistic scenarios, gender inequality may persist throughout the 21st century. Our results highlight the importance of incorporating gender in scenarios assessing future climate impacts and underscore the relevance of addressing gender inequalities in policies aiming to foster climate resilient development

Identification of 2,4-Disubstituted Imidazopyridines as Hemozoin Formation Inhibitors with Fast-Killing Kinetics and In Vivo Efficacy in the Plasmodium falciparum NSG Mouse Model

A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During lead optimization, several issues were flagged such as cross-resistance against the multidrug-resistant K1 strain, in vitro cytotoxicity, and cardiotoxicity and were addressed through structure–activity and structure–property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rγnull (NSG) mouse model. Preliminary mechanistic studies suggest inhibition of hemozoin formation as a contributing mode of action

Towards scenario representation of adaptive capacity for global climate change assessments

Climate change adaptation needs, as well as the capacity to adapt, are unequally distributed around the world. Global models that assess the impacts of climate change and policy options to reduce them most often do not elaborately represent adaptation. When they do, they rarely account for heterogeneity in societies’ adaptive capacities and their temporal dynamics. Here we propose ways to quantify adaptive capacity within the framework of Shared Socioeconomic Pathways, a scenario set widely used by climate impact and integrated assessment models. A large set of indicators spanning different socioeconomic dimensions can be used to assess adaptive capacity and deliver adaptation-relevant, scenario-resolved information that is crucial for more realistic assessment of whether and how climate risks can be reduced by adaptation

Identification of 2,4-disubstituted imidazopyridines as hemozoin formation inhibitors with fast-killing kinetics and in vivo efficacy in the Plasmodium falciparum NSG mouse model

A series of 2,4-disubstituted imidazopyridines, originating from a SoftFocus Kinase library, was identified from a high throughput phenotypic screen against the human malaria parasite Plasmodium falciparum. Hit compounds showed moderate asexual blood stage activity. During lead optimization, several issues were flagged such as cross-resistance against the multidrug-resistant K1 strain, in vitro cytotoxicity, and cardiotoxicity and were addressed through structure-activity and structure-property relationship studies. Pharmacokinetic properties were assessed in mice for compounds showing desirable in vitro activity, a selectivity window over cytotoxicity, and microsomal metabolic stability. Frontrunner compound 37 showed good exposure in mice combined with good in vitro activity against the malaria parasite, which translated into in vivo efficacy in the P. falciparum NOD-scid IL-2Rgamma(null) (NSG) mouse model. Preliminary mechanistic studies suggest inhibition of hemozoin formation as a contributing mode of action