The timing and ecological consequences of Pleistocene megafaunal decline in the eastern Andes of Colombia (article)

This is the final version. Available on open access from Cambridge University Press via the DOI in this recordData availability: The data supporting this publication are openly available from the NERC Data repository or can be accessed by contacting the corresponding author(s).Examining the ecological consequences of the late Quaternary megafaunal extinctions within biodiversity hotspots is crucial for our understanding of the potential consequences of contemporary extinctions. We present the first multi-species record of spores of coprophilous fungi (SCF) from Monquentiva and the high-Andean forests of Colombia to reconstruct Late Pleistocene and Holocene megafaunal abundance. Fossilised pollen and charcoal are used to examine the consequences of megafaunal declines on the surrounding vegetation and fire activity. Our SCF record indicates the presence of Pleistocene megafauna at least since 30,290 BP, with two waves of megafaunal decline at ca. 22,900 BP and 10,990 BP. At Monquentiva, megafaunal decline in the Early Holocene resulted in transitional non-analogue vegetation, loss of some herbivore-dispersed plant taxa, an encroachment of palatable and woody flora, and a rise in fire activity. Differences with other published South-American records suggest that ecological consequences of megafaunal declines were habitat-specific. Overall, we show that ecosystems in the eastern Colombian Cordillera were highly sensitive to the decline of megafaunal populations. Under the current biodiversity crisis, management and conservation efforts must account for the effects of local herbivore declines on plant dispersal, on fire activity, and the potential loss of ecosystem services.Natural Environment Research Council (NERC)Arts and Humanities Research Council (AHRC

High Content Phenotypic Cell-Based Visual Screen Identifies Mycobacterium tuberculosis Acyltrehalose-Containing Glycolipids Involved in Phagosome Remodeling

The ability of the tubercle bacillus to arrest phagosome maturation is considered one major mechanism that allows its survival within host macrophages. To identify mycobacterial genes involved in this process, we developed a high throughput phenotypic cell-based assay enabling individual sub-cellular analysis of over 11,000 Mycobacterium tuberculosis mutants. This very stringent assay makes use of fluorescent staining for intracellular acidic compartments, and automated confocal microscopy to quantitatively determine the intracellular localization of M. tuberculosis. We characterised the ten mutants that traffic most frequently into acidified compartments early after phagocytosis, suggesting that they had lost their ability to arrest phagosomal maturation. Molecular analysis of these mutants revealed mainly disruptions in genes involved in cell envelope biogenesis (fadD28), the ESX-1 secretion system (espL/Rv3880), molybdopterin biosynthesis (moaC1 and moaD1), as well as in genes from a novel locus, Rv1503c-Rv1506c. Most interestingly, the mutants in Rv1503c and Rv1506c were perturbed in the biosynthesis of acyltrehalose-containing glycolipids. Our results suggest that such glycolipids indeed play a critical role in the early intracellular fate of the tubercle bacillus. The unbiased approach developed here can be easily adapted for functional genomics study of intracellular pathogens, together with focused discovery of new anti-microbials

The timing and ecological consequences of Pleistocene megafaunal decline in the eastern Andes of Colombia

Examining the ecological consequences of Late-Quaternary megafaunal extinctions within biodiversity hotspots is crucial for our understanding of the potential consequences of contemporary extinctions. This research presents the first multi-species record of spores of coprophilous fungi (SCF) from Monquentiva and the high Andean forests of Colombia to reconstruct the Late-Pleistocene and Holocene megafaunal abundance. Fossilised pollen and charcoal are used to examine the consequences of megafaunal declines on the history of the study region. The SCF record indicated the presence of megafauna since at least 30,290 BP; with two periods of megafauna decline at ca. 22,900 and 10,990 BP. At Monquentiva, megafaunal decline in the Early-Holocene resulted in transitional non-analogue vegetation, a loss of some herbivore-dispersed taxa, an encroachment of some palatable and woody flora, and a rise in fire activity. Overall, this research shows that ecosystems in the eastern Colombian Cordillera were highly sensitive to the decline of megafaunal populations. Under the current biodiversity crisis, management and conservation efforts must account for the effect of local herbivore declines on the dispersal of certain plant species, on fire activity and the potential loss of ecosystem services.Natural Environment Research Council (NERC

Manipulation of BCG vaccine: a double-edged sword.

Mycobacterium bovis Bacillus Calmette-Guérin (BCG), an attenuated vaccine derived from M. bovis, is the only licensed vaccine against tuberculosis (TB). Despite its protection against TB in children, the protective efficacy in pulmonary TB is variable in adolescents and adults. In spite of the current knowledge of molecular biology, immunology and cell biology, infectious diseases such as TB and HIV/AIDS are still challenges for the scientific community. Genetic manipulation facilitates the construction of recombinant BCG (rBCG) vaccine that can be used as a highly immunogenic vaccine against TB with an improved safety profile, but, still, the manipulation of BCG vaccine to improve efficacy should be carefully considered, as it can bring in both favourable and unfavourable effects. The purpose of this review is not to comprehensively review the interaction between microorganisms and host cells in order to use rBCG expressing M. tuberculosis (Mtb) immunodominant antigens that are available in the public domain, but, rather, to also discuss the limitations of rBCG vaccine, expressing heterologous antigens, during manipulation that pave the way for a promising new vaccine approach