Clinical, biological, and prognostic implications of SF3B1 co-occurrence mutations in very low/low- and intermediate-risk MDS patients

SF3B1 is a highly mutated gene in myelodysplastic syndrome (MDS) patients, related to a specific subtype and parameters of good prognosis in MDS without excess blasts. More than 40% of MDS patients carry at least two myeloid-related gene mutations but little is known about the impact of concurrent mutations on the outcome of MDS patients. In applying next-generation sequencing (NGS) with a 117 myeloid gene custom panel, we analyzed the co-occurrence of SF3B1 with other mutations to reveal their clinical, biological, and prognostic implications in very low/low- and intermediate-risk MDS patients. Mutations in addition to those of SF3B1 were present in 80.4% of patients (median of 2 additional mutations/patient, range 0–5). The most frequently mutated genes were as follows: TET2 (39.2%), DNMT3A (25.5%), SRSF2 (10.8%), CDH23 (5.9%), and ASXL1, CUX1, and KMT2D (4.9% each). The presence of at least two mutations concomitant with that of SF3B1 had an adverse impact on survival compared with those with the SF3B1 mutation and fewer than two additional mutations (median of 54 vs. 87 months, respectively: p = 0.007). The co-occurrence of SF3B1 mutations with specific genes is also linked to a dismal prognosis: SRSF2 mutations were associated with shorter overall survival (OS) than SRSF2wt (median, 27 vs. 75 months, respectively; p = 0.001), concomitant IDH2 mutations (median OS, 11 [mut] vs. 75 [wt] months; p = 0.001), BCOR mutations (median OS, 11 [mut] vs. 71 [wt] months; p = 0.036), and NUP98 and STAG2 mutations (median OS, 27 and 11 vs. 71 months, respectively; p = 0.008 and p = 0.002). Mutations in CHIP genes (TET2, DNMT3A) did not significantly affect the clinical features or outcome. Our results suggest that a more comprehensive NGS study in low-risk MDS SF3B1mut patients is essential for a better prognostic evaluation.This work was supported by grants from the following: Contrato Rio Hortega, CM17/00171; Gerencia Regional de Salud (Castilla y León) para proyectos de investigación año 2018, 1850/A/18; Spanish Fondo de Investigaciones Sanitarias, PI15/01471, PI18/01500; Instituto de Salud Carlos III (ISCIII); European Regional Development Fund (ERDF) “Una manera de hacer Europa”; Consejería de Educación, Junta de Castilla y León (SA271P18); Proyectos de Investigación del SACYL, Spain, GRS1847/A/18, GRS1653/A17; SYNtherapy, Synthetic Lethality for Personalized Therapy-based Stratification In Acute Leukemia (ERAPERMED2018–275); ISCIII (AC18/00093), co-funded by ERDF/ESF, “Investing in your future”, by grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC) (RD12/0036/0069) and Centro de Investigación Biomédica en Red de Cáncer (CIBERONC CB16/12/00233). JMHS is supported by a research grant from Fundación Española de Hematología y Hemoterapia. MM is currently supported by an Ayuda predoctoral de la Junta de Castilla y León from the Fondo Social Europeo (JCYL- EDU/556/2019 PhD scholarship)

Modern insulation materials for warming of walls

Biodiversity hotspots understandably attract considerable conservation attention. However, deserts are rarely viewed as conservation priority areas, due to their relatively low productivity, yet these systems are home to unique species, adapted to harsh and highly variable environments. While global attention has been focused on hotspots, the world's largest tropical desert, the Sahara, has suffered a catastrophic decline in megafauna. Of 14 large vertebrates that have historically occurred in the region, four are now extinct in the wild, including the iconic scimitar-horned oryx (Oryx dammah). The majority has disappeared from more than 90% of their Saharan range, including addax (Addax nasomaculatus), dama gazelle (Nanger dama) and Saharan cheetah (Acinonyx jubatus hecki) - all now on the brink of extinction. Greater conservation support and scientific attention for the region might have helped to avert these catastrophic declines. The Sahara serves as an example of a wider historical neglect of deserts and the human communities who depend on them. The scientific community can make an important contribution to conservation in deserts by establishing baseline information on biodiversity and developing new approaches to sustainable management of desert species and ecosystems. Such approaches must accommodate mobility of both people and wildlife so that they can use resources most efficiently in the face of low and unpredictable rainfall. This is needed to enable governments to deliver on their commitments to halt further degradation of deserts and to improve their status for both biodiversity conservation and human well-being. Only by so-doing will deserts be able to support resilient ecosystems and communities that are best able to adapt to climate change. © 2013 John Wiley & Sons Ltd

Splitting or lumping? A conservation dilemma exemplified by the critically endangered Dama Gazelle (Nanger dama)

Managers of threatened species often face the dilemma of whether to keep populations separate to conserve local adaptations and minimize the risk of outbreeding, or whether to manage populations jointly to reduce loss of genetic diversity and minimise inbreeding. In this study we examine genetic relatedness and diversity in three of the five last remaining wild populations of dama gazelle and a number of captive populations, using mtDNA control region and cytochrome b data. Despite the sampled populations belonging to the three putative subspecies, which are delineated according to phenotypes and geographical location, we find limited evidence for phylogeographical structure within the data and no genetic support for the putative subspecies. In the light of these data we discuss the relevance of inbreeding depression, outbreeding depression, adaptive variation, genetic drift, and phenotypic variation to the conservation of the dama gazelle and make some recommendations for its future conservation management. The genetic data suggest that the best conservation approach is to view the dama gazelle as a single species without subspecific divisions

The first reintroduction project for mhorr gazelle (Nanger dama mhorr) into the wild: Knowledge and experience gained to support future conservation actions

Reintroductions continue to be an important conservation action for endangered species. Until this, all reintroduction projects for Mhorr gazelle (Nanger dama mhorr) had remained at the stage where the animals live in fenced protected areas of different sizes. This study describes the first experience of reintroduction of a group of 24 Mhorr gazelle into the wild in the Safia Reserve, in Southern Morocco. The reintroduction was carried out in two phases: in the first one, the entire group was released; then, after an unexpected dogs attack event, part of them were kept safe until this problem was solved. Seven of the gazelles were monitored with telemetry collars, providing previously unavailable data on time allocation, daily rhythm of activity and social organization for the species in the wild. In addition, post-release movements revealed three patterns: during the first few days after release, small daily movements (average 2.78 km) close to the fence, followed by long-distance exploratory movements (up to 50 km) until establish territories; and finally, daily movements between established territories (average 8.39 km). Exceptional long distances (>50 km/day) were traveled after a poaching event. The study has also revealed the ability of the species to select and settle territories in favorable areas, after being kept for generations under captive or semi-captive conditions. However, their inability to recognize predators was demonstrated in an unexpected attack by dogs, resulting in the death of seven released gazelles. This mortality following the dog attack was favored, in part, because the released gazelle remained close to the fence, and therefore suggests that the release procedure should be revised, especially when there are predators in the release site. This study has confirmed that dogs as predators and poaching continue to be the main threat to reintroduction projects in Southern Morocco.This project has been funded by UNESCO/MaB (no 4500261532), HCEFLCD and the National Spanish Research Council (CSIC OTT 2005X0269). Emilio Rodriguez Caballero would like to acknowledge the Spanish Ministry for Economy and Competitiveness for the Juan de la Cierva-Incorporación grant (IJCI-2016-29274) and the University of Almeria for the Hipatia-UAL postdoctoral fellowshi

Armed conflicts and wildlife decline: Challenges and recommendations for effective conservation policy in the Sahara-Sahel

Increasing conflicts and social insecurity are expected to accelerate biodiversity decline and escalate illegal wildlife killing. Sahara‐Sahel megafauna has experienced recent continuous decline due to unsustainable hunting pressure. Here, we provide the best available data on distribution and population trends of threatened, large vertebrates, to illustrate how escalating regional conflict (565% growth since 2011) is hastening population decline in areas that were formerly refugia for megafauna. Without conservation action, the unique and iconic biodiversity of Earth's largest desert will be forever lost. We recommend: (1) establishing strong commitments for change in global attitude toward nature; (2) engraining a culture of environmental responsibility among all stakeholders; (3) fostering environmental awareness to drive societal change; (4) reinforcing regional security and firearms control; and (5) implementing local research and wildlife monitoring schemes. We identify relevant international partners needed to tackle these challenges and to make strong policy change for biodiversity conservation and regional stability

Armed conflicts and wildlife decline: Challenges and recommendations for effective conservation policy in the Sahara-Sahel

Increasing conflicts and social insecurity are expected to accelerate biodiversity decline and escalate illegal wildlife killing. Sahara‐Sahel megafauna has experienced recent continuous decline due to unsustainable hunting pressure. Here, we provide the best available data on distribution and population trends of threatened, large vertebrates, to illustrate how escalating regional conflict (565% growth since 2011) is hastening population decline in areas that were formerly refugia for megafauna. Without conservation action, the unique and iconic biodiversity of Earth's largest desert will be forever lost. We recommend: (1) establishing strong commitments for change in global attitude toward nature; (2) engraining a culture of environmental responsibility among all stakeholders; (3) fostering environmental awareness to drive societal change; (4) reinforcing regional security and firearms control; and (5) implementing local research and wildlife monitoring schemes. We identify relevant international partners needed to tackle these challenges and to make strong policy change for biodiversity conservation and regional stability