The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense

Trypanosoma brucei gambiense causes 97% of all cases of African sleeping sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome, such as T. b. brucei, are unable to infect humans due to the trypanolytic serum protein apolipoprotein-L1 (APOL1) delivered via two trypanosome lytic factors (TLF-1 and TLF-2). Understanding how T. b. gambiense overcomes these factors and infects humans is of major importance in the fight against this disease. Previous work indicated that a failure to take up TLF-1 in T. b. gambiense contributes to resistance to TLF-1, although another mechanism is required to overcome TLF-2. Here, we have examined a T. b. gambiense specific gene, TgsGP, which had previously been suggested, but not shown, to be involved in serum resistance. We show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T. b. gambiense renders the parasites sensitive to human serum and recombinant APOL1. Deletion of TgsGP in T. b. gambiense modified to uptake TLF-1 showed sensitivity to TLF-1, APOL1 and human serum. Reintroducing TgsGP into knockout parasite lines restored resistance. We conclude that TgsGP is essential for human serum resistance in T. b. gambiense

Piper betle L. Piperaceae

Artanthe hexagyna Miq.; Betela mastica Raf.; Chavica betle (L.) Miq.; Chavica blumei Miq.; Chavica chuvya Miq.; Chavica densa Miq.; Chavica siriboa (L.) Miq.; Cubeba melamiri Miq.; Cubeba seriboa Miq.; Macropiper potamogetonifolium (Opiz) Miq.; Piper anisodorum Blanco; Piper bathicarpum C.DC.; Piper bidentatum Stokes; Piper blancoi Merr.; Piper blumei (Miq.) Backer; Piper canaliculatum Opiz; Piper carnistilum C.DC.; Piper densum Blume; Piper fenixii C.DC.; Piper macgregorii C.DC.; Piper malamiri Blume; Piper malamiris L.; Piper malarayatense C.DC.; Piper marianum Opiz; Piper philippinense C.DC.; Piper pinguispicum C.DC. & Koord.; Piper potamogetonifolium Opiz; Piper puberulinodum C.DC.; Piper rubroglandulosum Chaveer. & Mokkamul; Piper saururus Burm.; Piper siriboa L.; Piperi betlum (L.) St.-Lag

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

The global abundance of tree palms

Aim: Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change. Location: Tropical and subtropical moist forests. Time period: Current. Major taxa studied: Palms (Arecaceae). Methods: We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure. Results: On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work. Conclusions: Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests

Database modeling and design: logical design

Database systems and database design technology have undergone significant evolution in recent years. The relational data model and relational database systems dominate business applications; in turn, they are extended by other technologies like data warehousing, OLAP, and data mining. How do you model and design your database application in consideration of new technology or new business needs? In the extensively revised fifth edition, you'll get clear explanations, lots of terrific examples and an illustrative case, and the really practical advice you have come to count on--with design rule

Database modeling and design: logical design

Database systems and database design technology have undergone significant evolution in recent years. The relational data model and relational database systems dominate business applications; in turn, they are extended by other technologies like data warehousing, OLAP, and data mining. How do you model and design your database application in consideration of new technology or new business needs? In the extensively revised fourth edition, you'll get clear explanations, lots of terrific examples and an illustrative case, and the really practical advice you have come to count on--with design ru