Luspatercept diminishes the need for red blood cell replacement in transfusion-dependent β-thalassemia patients

A clinical decision report appraising: Cappellini MD, Viprakasit V, Taher AT, et al. A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia. N Engl J Med. 2020;382(13):1219-1231. https://doi.org/10.1056/NEJMoa1910182 for a patient with transfusion-dependent beta-thalassemia

Reply to Engelthaler and Meyer, "Furthering the Continental Drift Speciation Hypothesis in the Pathogenic Cryptococcus Species Complexes".

We thank and compliment Engelthaler and Meyer for their letter (1), which provides new information extending our hypothesis that continental drift was a major influence in driving speciation within the Cryptococcus species complexes (2). Their map superimposing the four major current Cryptococcus gattii molecular types/ species (VGI, VGII, VGIII, and VGIV) on the map of Pangea sheds light on possible origins of Asian, Indian, and Iberian isolates and clearly delineates areas that are unexplored and in need of sampling. We are encouraged by the notion that viewing cryptococcal speciation in the larger context of continental drift is already stimulating new thought, and we hope that it also catalyzes new experimental work to separate ancient speciation events in deep geologic time from more recent introductions of isolates in defined geographic areas

Reply to Engelthaler and Meyer, "Furthering the Continental Drift Speciation Hypothesis in the Pathogenic Cryptococcus Species Complexes".

We thank and compliment Engelthaler and Meyer for their letter (1), which provides new information extending our hypothesis that continental drift was a major influence in driving speciation within the Cryptococcus species complexes (2). Their map superimposing the four major current Cryptococcus gattii molecular types/ species (VGI, VGII, VGIII, and VGIV) on the map of Pangea sheds light on possible origins of Asian, Indian, and Iberian isolates and clearly delineates areas that are unexplored and in need of sampling. We are encouraged by the notion that viewing cryptococcal speciation in the larger context of continental drift is already stimulating new thought, and we hope that it also catalyzes new experimental work to separate ancient speciation events in deep geologic time from more recent introductions of isolates in defined geographic areas

Continental Drift and Speciation of the Cryptococcus neoformans and Cryptococcus gattii Species Complexes.

Genomic analysis has placed the origins of two human-pathogenic fungi, the Cryptococcus gattii species complex and the Cryptococcus neoformans species complex, in South America and Africa, respectively. Molecular clock calculations suggest that the two species separated ~80 to 100 million years ago. This time closely approximates the breakup of the supercontinent Pangea, which gave rise to South America and Africa. On the basis of the geographic distribution of these two species complexes and the coincidence of the evolutionary divergence and Pangea breakup times, we propose that a spatial separation caused by continental drift resulted in the emergence of the C. gattii and C. neoformans species complexes from a Pangean ancestor. We note that, despite the spatial and temporal separation that occurred approximately 100 million years ago, these two species complexes are morphologically similar, share virulence factors, and cause very similar diseases. Continuation of these phenotypic characteristics despite ancient separation suggests the maintenance of similar selection pressures throughout geologic ages