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Alternative lengthening of telomeres (ALT) is a DNA recombination pathway which grants replicative immortality in approximately 10% of all cancers. Despite the high prevalence of ALT in cancer, the genetics and mechanism by which cells activate this pathway are largely not understood. A major challenge in dissecting ALT is the extremely low frequency of ALT induction in genetically tractable human cell systems. Guided by the genetic lesions that have been associated with ALT from cancer sequencing studies, we genetically engineered primary human cells to deterministically induce ALT. Using this system, we demonstrate that disruption of the p53 and Rb pathways in combination with ATRX loss-of-function is, in a cell type-specific manner, sufficient to induce all hallmarks of ALT and results in functional immortalization. We demonstrate that ALT can be induced in the presence of telomerase, is neither dependent on telomere shortening nor crisis, but is rather the consequence of epigenetic changes induced by differentiation of ATRX-deficient cells.

Social relationships are shaped by ecological conditions, giving rise to diverse societies even among related species. Among elephants, females exhibit close, often familial bonds with some degree of philopatry and fission–fusion dynamics. Forest elephant sociality is the least studied among elephant species, and their ecology differs from that of savannah and Asian elephants. We use over 15 years of data from an individually identified population using the Dzanga Bai forest clearing in Central African Republic to characterize social patterns of adult female elephants in two contexts, when entering the forest clearing and within the clearing. Social properties were nonrandom and highly stable over the study period in both contexts. Composition of aggregations within the clearing indicated considerable mixing among females, while association in groups entering the bai together were limited in composition, likely representing core social units. The co-entry data set exhibited distinct communities that were not apparent in the co-occurrence data set. In contrast to savannah elephants, network centrality and age were negatively correlated, suggesting a muted or absent matriarch social hub role in forest elephants at a broader level than family units. Temporal and community analyses indicated that bai co-entry and co-occurrence contexts may represent distinct processes, with the former social and the latter driven by shared resource use. Our results point to social patterns potentially driven by the need for families to fission into small units because of resource competition and highlight the importance of aggregation context in interpreting association indices.

Summary African forest elephants Loxodonta cyclotis are experiencing persistent declines driven by illegal killing and range loss. Despite the importance for policy debates regarding elephant trade managed through the Convention on International Trade in Endangered Species (CITES), little is known about forest elephant demography and, consequently, the impacts of offtake and subsequent population recovery potential. Using 23 years of individually based demographic data from Dzanga, Central African Republic, we found low reproductive potential resulting from annual birth rates averaging 4·3% (SD: 1·4%), a median inter-birth interval of 68 months and a median primiparous age of 23 years. Average mortality was 3·1% per year (SD: 1·0%) during the study, with approximately 1·4% of that attributed to human killing. This population of forest elephants demonstrated concerningly slow growth rates, with a doubling time of nearly 60 years under current conditions (41 years excluding human impacts), amounting to three times that reported for savanna elephants. As such, forest elephants appear to be significantly more sensitive to human-induced mortality than their congeneric species. Such slow intrinsic growth challenges current perceptions of historic and contemporary ivory trade impacts on forest elephants, highlighting the urgent need to stem poaching and institute long-term protective measures. Policy implications. Debates regarding the sustainability of the ivory trade for the species appear to have overestimated growth rates of forest elephants. The information presented here indicates that sustainable offtake models for forest elephants need reassessment.

SUMMARYSyngamid strongylids of the genusMammomonogamusundoubtedly belong among the least known nematodes with apparent zoonotic potential and the real diversity of the genus remains hard to evaluate without extensive molecular data. Eggs ofMammomonogamussp. are frequently found in feces of African forest elephants (Loxodonta cyclotis) and western lowland gorillas (Gorilla gorilla gorilla) in Dzanga-Sangha Protected Areas. Using sedimentation-based coproscopic techniques, we found the eggs ofMammomonogamusin 19·7% elephant and 54·1% gorilla fecal samples with 8–55 and 1–24 eggs per gram of fecal sediment for elephants and gorillas, respectively. We used a combination of light microscopy, scanning electron microscopy and analysis of cytochromecoxidase subunit I (cox1) and a partial sequence of 18S rDNA isolated from single eggs to test the hypothesis of possibleMammomonogamusconspecificity in gorillas and elephants. Whereas 18S rDNA sequences were identical in both gorillas and elephants, we distinguished seven different haplotypes within thecox1. Two haplotypes were found in both gorillas and elephants suggesting sharing ofMammomonogamus.Assignment of the parasite toM. loxodontisis proposed. Provided sequences represent the first genomic data onMammomonogamusspp.

Ewing sarcoma is a malignant bone cancer that primarily occurs in children and adolescents. Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene. Previously, we demonstrated that an interaction between EWS/FLI1 and wild-type EWS led to the inhibition of EWS activity and mitotic dysfunction. Although defective mitosis is considered to be a critical step in cancer initiation, it is unknown how interference with EWS contributes to Ewing sarcoma formation. Here, we demonstrate that EWS/FLI1- and EWS-knockdown cells display a high incidence of defects in the midzone, a midline structure located between segregating chromatids during anaphase. Defects in the midzone can lead to the failure of cytokinesis and can result in the induction of aneuploidy. The similarity among the phenotypes of EWS/FLI1- and EWS siRNA-transfected HeLa cells points to the inhibition of EWS as the key mechanism for the induction of midzone defects. Supporting this observation, the ectopic expression of EWS rescues the high incidence of midzone defects observed in Ewing sarcoma A673 cells. We discovered that EWS interacts with Aurora B kinase, and that EWS is also required for recruiting Aurora B to the midzone. A domain analysis revealed that the R565 in the RGG3 domain of EWS is essential for both Aurora B interaction and the recruitment of Aurora B to the midzone. Here, we propose that the impairment of EWS-dependent midzone formation via the recruitment of Aurora B is a potential mechanism of Ewing sarcoma development.

Presented at the 9th international wildlife ranching symposium: wildlife - the key to prosperity for rural communities, held on 12-16 September 2016 at Hotel Safari & the Safari Court, Windhoek, Namibia in conjuction with the IUCN 2nd African Buffalo Symposium., Understanding the social organization of elusive forest-dwelling ungulates may have important conservation and management implications. We present a comparison of grouping patterns in forest buffalo across different sites and through time in Central African rainforest. We examined five sites: Mbeli Bai and Bonye Bai (Nouabalé-Ndoki National Park, Republic of Congo), Dzanga Bai and Bai-Hokou (Dzanga-Ndoki National Park, C.A.R.) and Lopé-Okanda National Park (Gabon).Buffalo showed high site fidelity to open areas, including forest clearings. Forest buffalo herds (mean 12 ind. ± SD; range 3-24) were much smaller than records of savanna buffalo herds (mean 350 ind. ± SD; range 12-1500>), but also showed frequently fission-fusion patterns. Data from Mbeli Bai collected from 2012 to 2016confirm a stable presence of two buffalo herds (range 9-10 ind.) with occasional visits by lone individuals. Observations from Dzanga Bai over a period of 10 years (2006-2016) confirm the occurrence of only one buffalo herd (range 8-10ind.). In Bai-Hokou site, a single buffalo herd increased from 16 to 24 individuals during a three year period (2001-2004). Finally in Lopé National Park (a mosaic of savanna and forest fragments), the mean group size for 18 herds monitored from2002 to 2004 was 12±2 ind. (range of means=3–24). We analysed if herd size and herd stability are affected by clearing size, clearing type (e.g. marsh or land) and grass coverage across different sites and through time.

The Dzanga-Sangha landscape consists of a national park surrounded by production forest. It is subject to an integrated conservation and development project (ICDP). In collaboration with the ICDP personnel, a participatory model was constructed to explore wildlife conservation and industrial logging scenarios for the landscape. Three management options for the landscape's production forest were modelled: (I) 'predatory logging', exploitation by a logging company characterised by a lack of long-term plans for staying in the landscape, (II) sustainable exploitation by a certified logging company, and (III) conservation concession with no commercial timber harvesting. The simulation outcomes indicate the extreme difficulties to achieve progress on either conservation or development scenarios. Both logging scenarios give best outcomes for development of the local population. However, the depletion of bushmeat under the predatory logging scenario negatively impacts the population, especially the BaAka pygmy minority who most strongly depend on hunting for their income. The model suggests that conservation and development outcomes are largely determined by the level of economic activity, both inside and outside the landscape. Large investments in the formal sector in the landscape without any measures for protecting wildlife (Scenario I) leads to some species going nearly extinct, while investments in the formal sector including conservation measures (Scenario II) gives best outcomes for maintaining wildlife populations. The conservation concession at simulated investment levels does not reduce poverty, defined here in terms of monetary income. Neither does it seem capable of maintaining wildlife populations since the landscape is already filled with settlers lacking economic opportunities as alternatives to poaching, We would like to thank the Livelihoods and Landscapes initiative of the International Union for Conservation of Nature (IUCN) and the Center for International Forestry Research (CIFOR) for financing part of this research

Ewing sarcoma is the second most common skeletal (bone and cartilage) cancer in adolescents, and it is characterized by the expression of the aberrant chimeric fusion gene EWS/FLI1. Wild-type EWS has been proposed to play a role in mitosis, splicing and transcription. We have previously shown that EWS/FLI1 interacts with EWS, and it inhibits EWS activity in a dominant manner. Ewing sarcoma is a cancer that specifically develops in skeletal tissues, and although the above data suggests the significance of EWS, its role in chondrogenesis/skeletogenesis is not understood. To elucidate the function of EWS in skeletal development, we generated and analyzed a maternal zygotic (MZ) ewsa/ewsa line because the ewsa/wt and ewsa/ewsa zebrafish appeared to be normal and fertile. Compared with wt/wt, the Meckel’s cartilage of MZ ewsa/ewsa mutants had a higher number of craniofacial prehypertrophic chondrocytes that failed to mature into hypertrophic chondrocytes at 4 days post-fertilization (dpf). Ewsa interacted with Sox9, which is the master transcription factor for chondrogenesis. Sox9 target genes were either upregulated (ctgfa, ctgfb, col2a1a, and col2a1b) or downregulated (sox5, nog1, nog2, and bmp4) in MZ ewsa/ewsa embryos compared with the wt/wt zebrafish embryos. Among these Sox9 target genes, the chromatin immunoprecipitation (ChIP) experiment demonstrated that Ewsa directly binds to ctgfa and ctgfb loci. Consistently, immunohistochemistry showed that the Ctgf protein is upregulated in the Meckel’s cartilage of MZ ewsa/ewsa mutants. Together, we propose that Ewsa promotes the differentiation from prehypertrophic chondrocytes to hypertrophic chondrocytes of Meckel’s cartilage through inhibiting Sox9 binding site of the ctgf gene promoter. Because Ewing sarcoma specifically develops in skeletal tissue that is originating from chondrocytes, this new role of EWS may provide a potential molecular basis of its pathogenesis.

Le comportement social des antilopes n'est pas bien connu dans les forets tropicales denses. Le bongo (Tragelaphus eurycerus Ogilby), la plus grande antilope de foret d'Afrique, est social et forme souvent des groupes de plus de 10 animaux. Pour etudier la composition des groupes, leur dimension et certains aspects du comportement social du bongo, des observations directes ont ete effectuees dans la grande clairiere naturelle de Dzanga du Parc national de Dzanga, Republique Centrafricaine. La taille moyenne des groupes etait de 13.3, plus grande qu'ailleurs en Afrique. Nos resultats suggerent que les groupes de bongos peuvent changer avec le temps, par contre que des sous-groupes peuvent former des unites fixes. L'unite sociale qu'on rencontre en majorite est constituee de femelles accompagnees de leurs jeunes, et dans plus de 50 % des cas, accompagnees d'un mâle adulte. Cette etude montre que des lieux ouverts, comme Dzanga, permettent de reunir de nombreuses informations, surtout pour les especes forestieres, qui sont assez difficiles a observer pendant des periodes prolongees.

Individual identification of the relatively cryptic forest elephant (Loxodonta cyclotis) at forest clearings currently provides the highest quality monitoring data on this ecologically important but increasingly threatened species. Here we present baseline data from the first 20 years of an individually based study of this species, conducted at the Dzanga Clearing, Central African Republic. A total of 3,128 elephants were identified over the 20-year study (1,244 adults; 675 females, 569 males). It took approximately four years for the majority of elephants visiting the clearing to be identified, but new elephants entered the clearing every year of the study. The study population was relatively stable, varying from 1,668 to 1,864 individuals (including juveniles and infants), with increasingly fewer males than females over time. The age-class distribution for females remained qualitatively unchanged between 1995 and 2010, while the proportion of adult males decreased from 20% to 10%, likely reflecting increased mortality. Visitation patterns by individuals were highly variable, with some elephants visiting monthly while others were ephemeral users with visits separated by multiple years. The number of individuals in the clearing at any time varied between 40 and 100 individuals, and there was little evidence of a seasonal pattern in this variation. The number of elephants entering the clearing together (defined here as a social group) averaged 1.49 (range 1-12) for males and 2.67 (range 1-14) for females. This collation of 20 years of intensive forest elephant monitoring provides the first detailed, long term look at the ecology of bai visitation for this species, offering insight to the ecological significance and motivation for bai use, social behavior, and threats to forest elephants. We discuss likely drivers (rainfall, compression, illegal killing, etc.) influencing bai visitation rates. This study provides the baseline for future demographic and behavioral studies of this population.

The rapid disruption of tropical forests probably imperils global biodiversity more than any other contemporary phenomenon(1-3). With deforestation advancing quickly, protected areas are increasingly becoming final refuges for threatened species and natural ecosystem processes. However, many protected areas in the tropics are themselves vulnerable to human encroachment and other environmental stresses(4-9). As pressures mount, it is vital to know whether existing reserves can sustain their biodiversity. A critical constraint in addressing this question has been that data describing a broad array of biodiversity groups have been unavailable for a sufficiently large and representative sample of reserves. Here we present a uniquely comprehensive data set on changes over the past 20 to 30 years in 31 functional groups of species and 21 potential drivers of environmental change, for 60 protected areas stratified across the world's major tropical regions. Our analysis reveals great variation in reserve `health': about half of all reserves have been effective or performed passably, but the rest are experiencing an erosion of biodiversity that is often alarmingly widespread taxonomically and functionally. Habitat disruption, hunting and forest-product exploitation were the strongest predictors of declining reserve health. Crucially, environmental changes immediately outside reserves seemed nearly as important as those inside in determining their ecological fate, with changes inside reserves strongly mirroring those occurring around them. These findings suggest that tropical protected areas are often intimately linked ecologically to their surrounding habitats, and that a failure to stem broad-scale loss and degradation of such habitats could sharply increase the likelihood of serious biodiversity declines.

African forest elephants- taxonomically and functionally unique-are being poached at accelerating rates, but we lack range-wide information on the repercussions. Analysis of the largest survey dataset ever assembled for forest elephants (80 foot-surveys; covering 13,000 km; 91,600 person-days of fieldwork) revealed that population size declined by ca. 62% between 2002-2011, and the taxon lost 30% of its geographical range. The population is now less than 10% of its potential size, occupying less than 25% of its potential range. High human population density, hunting intensity, absence of law enforcement, poor governance, and proximity to expanding infrastructure are the strongest predictors of decline. To save the remaining African forest elephants, illegal poaching for ivory and encroachment into core elephant habitat must be stopped. In addition, the international demand for ivory, which fuels illegal trade, must be dramatically reduced.