Implication of an Asp residue in the ribonucleolytic activity of hirsutellin A reveals new electrostatic interactions at the active site of ribotoxins

Ribotoxins are fungal extracellular ribonucleases that specifically cleave ribosomes leading to cell-death via apoptosis. α-Sarcin is the ribotoxin studied in deepest detail, and therefore constitutes the referential protein for the whole family. It has been demonstrated that ribotoxin activity depends on a very precise structural microenvironment in which electrostatic interactions among residues in the active site are of the highest importance. Hirsutellin A (HtA) has been recently described as the smallest ribotoxin known to date, encompassing all the abilities of previously characterized members of this family into a shorter sequence. Comparison of HtA and α-sarcin three-dimensional structures suggested that residues presumably forming the catalytic triad of HtA would be His 42, Glu 66, and His 113. Within this same idea, the presence of an Asp residue (Asp 40) in a position equivalent to α-sarcin Tyr 48 is highlighted as a novelty in this field. In this work, substitution mutants H42Q, E66Q and H113Q, as well as double and triple mutants in all possible combinations, are studied regarding their ribonucleolytic activity and cytotoxicity. Implication of these three residues in the ribotoxin activity of HtA is confirmed, though none of them is strictly essential for ribosomal cleavage. Studies with mutants D40N and D40N/E66Q demonstrate an important role for Asp 40 in the activity of HtA and establish a new set of electrostatic interactions different from the one described for already known ribotoxins.     

Landscape Dynamics in Northwestern Amazonia: An Assessment of Pastures,Fire and Illicit Crops as Drivers of Tropical Deforestation

Many studies have identified drivers of deforestation throughout the tropics and, in most cases, have recognised differences in the level of threat. However, only a few have also looked at the temporal and spatial dynamics by which those drivers act, which is critical for assessing the conservation of biodiversity as well as for landscape planning. In this study, we analyse land cover change between 2000 and 2009 in north-western Colombian Amazonia to identify the interactions between the use of fire, cultivation of illicit crops and establishment of pastures, and their impacts on the loss of forest in the region. Yearly analyses were undertaken at randomly selected sample areas to quantify the average areas of transition of land cover types under different landscape compositions: forest-dominated mosaics, pasture mosaics, fire mosaics, and illicit crop mosaics. Our results indicate that despite the fact that forest areas were well-preserved, deforestation occurred at a low annual rate (0.06%). Conversion to pasture was the main factor responsible for forest loss (the area of pastures tripled within forest mosaics over 8 years), and this process was independent of the landscape matrix in which the forests were located. In fire mosaics, burning is a common tool for forest clearing and conversion to pasture. Thus, forests in fire mosaics were highly disturbed and frequently transformed from primary to secondary forests. The use of fire for illicit cropping was not detected, partly due to the small size of common illicit crops. Forest regeneration from pastures and secondary vegetation was observed in areas with large amounts of natural forest. Overall, assuming the continuation of the observed pasture conversion trend and the use of forest fire, we suggest that our results should be incorporated into a spatially explicit and integrated decision support tool to target and focus land-planning activities and policies.     

Future land use effects on the connectivity of protected area networks in southeastern Spain

Land-use change is a major driver of the global biodiversity crisis, mainly via the fragmentation and loss of natural habitat. Although land-use changes will accelerate to meet humankind's growing demand for agricultural products, conservation planning rarely considers future land uses and how they may affect the connectivity of ecological networks. Here, we integrate land-use models with landscape fragmentation and connectivity analyses, to assess the effects of past and future land-use changes on the connectivity of protected area networks for a highly dynamic region in southeast Spain. Our results show a continued geographical polarisation of land use, with agricultural intensification and urban development in the coastal areas, and the abandonment of traditional land use in the mountains (e.g., 1100 km² of natural vegetation are projected to be lost in coastal areas whereas 32 km² of natural vegetation would recover in interior areas from 1991 to 2015). As a result, coastal protected areas will experience increasing isolation. The connectivity analyses reveal that the two protected area networks in place in the study area, the European “Natura 2000” and the Andalusian “RENPA” networks, include many landscape connectors. However, we identify two areas that currently lack protection but contain several important patches for maintaining the region's habitat connectivity: the northwestern and the southwestern slopes of the Sierra Cabrera and Bédar protected area. Our results highlight the importance of considering future land-use trajectories in conservation planning to maintain connectivity at the regional scale, and to improve the resilience of conservation networks.     

Evolutionary history of the European free-tailed bat,a tropical affinity species spanning across the Mediterranean Basin

The Mediterranean Basin is a global biodiversity hotspot, hosting a number of native species belonging to families that are found almost exclusively in tropical climates. Yet, whether or not these taxa were able to survive in the Mediterranean region during the Quaternary climatic oscillations remains unknown. Focusing on the European free-tailed bat (Tadarida teniotis), we aimed to (a) identify potential ancient populations and glacial refugia; (b) determine the post-glacial colonization routes across the Mediterranean; and (c) evaluate current population structure and demography. Mitochondrial and nuclear markers were used to understand T. teniotis evolutionary and demographic history. We show that T. teniotis is likely restricted to the Western Palearctic, with mitochondrial phylogeny suggesting a split between an Anatolian/Middle East clade and a European clade. Nuclear data pointed to three genetic populations, one of which is an isolated and highly differentiated group in the Canary Islands, another distributed across Iberia, Morocco, and France, and a third stretching from Italy to the east, with admixture following a pattern of isolation by distance. Evolutionary and demographic reconstruction supports a pre-Last Glacial Maximum (LGM) colonization of Italy and the Anatolian/Middle East, while the remaining populations were colonized from Italy after the Younger Dryas. We also found support for demographic expansion following the Iberian colonization. The results show that during the LGM T. teniotis persisted in Mediterranean refugia and has subsequently expanded to its current circum-Mediterranean range. Our findings raise questions regarding the physiological and ecological traits that enabled species with tropical affinities to survive in colder climates.     

R-2-hydroxyglutarate attenuates aerobic glycolysis in leukemia by targeting the FTO/m6A/PFKP/LDHB axis

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Genome-wide association study of multiple sclerosis confirms a novel locus at 5p13.1

Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.     

966. CLAVIJA DOMINGENSIS

Clavija domingensis Urb. & Ekman was one of the many Haitian endemics that were described based on collections made by the great Swedish botanist Leonard Ekman between 1924 and 1928. The species is Critically Endangered sensu IUCN (criteria c2a(i); D) and it is currently the focus of conservation initiatives in Jardin Botanique des Cayes (Haiti), Jardín Botánico Nacional Dr. Rafael M. Moscoso (Dominican Republic), and Fairchild Tropical Botanic Garden (U.S.A.). Now known from only six localities from southern Haiti, each locality only represents a single individual. The species is illustrated based on plants grown in Fairchild Tropical Botanic Garden.