Climate change could fuel urinary schistosomiasis transmission in Africa and Europe.

The freshwater snail Bulinus truncatus is an important intermediate host for trematode parasites causing urogenital schistosomiasis, a tropical disease affecting over 150 million people. Despite its medical importance, uncertainty remains about its global distribution and the potential impacts of climate change on its future spread. Here, we investigate the distribution of B. truncatus, combining the outputs of correlative and mechanistic modelling methods to fully capitalize on both experimental and occurrence data of the species and to create a more reliable distribution forecast than ever constructed. We constructed ensemble correlative species distribution models using 273 occurrence points collected from different sources and a combination of climatic and (bio)physical environmental variables. Additionally, a mechanistic thermal suitability model was constructed, parameterized by recent life-history data obtained through extensive lab-based snail-temperature experiments and supplemented with an extensive literature review. Our findings reveal that the current suitable habitat for B. truncatus encompasses the Sahel region, the Middle East, and the Mediterranean segment of Africa, stretching from Southern Europe to Mozambique. Regions identified as suitable by both methods generally coincide with areas exhibiting high urogenital schistosomiasis prevalence. Model projections into the future suggest an overall net increase in suitable area of up to 17%. New suitable habitat is in Southern Europe, the Middle East, and large parts of Central Africa, while suitable habitat will be lost in the Sahel region. The change in snail habitat suitability may substantially increase the risk of urogenital schistosomiasis transmission in parts of Africa and Southern Europe while reducing it in the Sahel region.

The evolution of thermal performance curves in fungi farmed by attine ant mutualists in aboveground or belowground microclimates.

Fungi are abundant and ecologically important at a global scale, but little is known about whether their thermal adaptations are shaped by biochemical constraints (i.e. the Hotter is Better Model, HBM) or evolutionary tradeoffs (i.e., the Specialist Generalist Model, SGM). We tested these hypotheses by generating thermal performance curves (TPCs) of fungal cultivars farmed by six species of Panamanian fungus-farming 'attine' ants. These fungi represent evolutionary transitions in farming strategies as four cultivars are farmed by ants belowground at stable temperatures near 25°C and two cultivars are farmed aboveground at variable temperatures. We generated TPCs using a common garden experiment confining fungal isolates to different temperatures and then used a Bayesian hierarchical modeling approach to compare competing temperature sensitivity models. Some thermal performance traits differed consistently across farming strategies, with aboveground cultivars having: 1) higher tolerance to low temperatures (CTLmin) and 2) higher maximum growth rate at the optimal temperature (rmax). However, two core assumptions shared by the HBM or SGM were not supported as aboveground cultivars did not show systematic increases in either their optimal temperature (Topt) or thermal tolerance breadth. These results harness ant farming systems as long-term natural experiments to decouple the effects of environmental thermal variation and innate physiological temperature sensitivity on fungal thermal evolution. The results have clear implications for predicting climate warming induced breaking points in animal-microbe mutualisms.

The Novel Oral BET-CBP/p300 Dual Inhibitor NEO2734 Is Highly Effective in Eradicating Acute Myeloid Leukemia Blasts and Stem/Progenitor Cells.

Acute myeloid leukemia (AML) is a disease characterized by transcriptional dysregulation that results in a block in differentiation and aberrant self-renewal. Inhibitors directed to epigenetic modifiers, aiming at transcriptional reprogramming of AML cells, are currently in clinical trials for AML patients. Several of these inhibitors target bromodomain and extraterminal domain (BET) proteins, cyclic AMP response binding protein-binding protein (CBP), and the E1A-interacting protein of 300 kDa (p300), affecting histone acetylation. Unfortunately, single epigenetic inhibitors showed limited efficacy due to appearance of resistance and lack of effective eradication of leukemic stem cells. Here, we describe the efficacy of 2 novel, orally available inhibitors targeting both the BET and CBP/p300 proteins, NEO1132 and NEO2734, in primary AML. NEO2734 and NEO1132 efficiently reduced the viability of AML cell lines and primary AML cells by inducing apoptosis. Importantly, both NEO drugs eliminated leukemic stem/progenitor cells from AML patient samples, and NEO2734 increased the effectiveness of combination chemotherapy treatment in an in vivo AML patient-derived mouse model. Thus, dual inhibition of BET and CBP/p300 using NEO2734 is a promising therapeutic strategy for AML patients, making it a focus for clinical translation.