Human endogenous retroviruses form a reservoir of T cell targets in hematological cancers

Human endogenous retroviruses (HERV) form a substantial part of the human genome, but mostly remain transcriptionally silent under strict epigenetic regulation, yet can potentially be reactivated by malignant transformation or epigenetic therapies. Here, we evaluate the potential for T cell recognition of HERV elements in myeloid malignancies by mapping transcribed HERV genes and generating a library of 1169 potential antigenic HERV-derived peptides predicted for presentation by 4 HLA class I molecules. Using DNA barcode-labeled MHC-I multimers, we find CD8+ T cell populations recognizing 29 HERV-derived peptides representing 18 different HERV loci, of which HERVH-5, HERVW-1, and HERVE-3 have more profound responses; such HERV-specific T cells are present in 17 of the 34 patients, but less frequently in healthy donors. Transcriptomic analyses reveal enhanced transcription of the HERVs in patients; meanwhile DNA-demethylating therapy causes a small and heterogeneous enhancement in HERV transcription without altering T cell recognition. Our study thus uncovers T cell recognition of HERVs in myeloid malignancies, thereby implicating HERVs as potential targets for immunotherapeutic therapies

Scientific understanding of East African climate change from the HyCRISTAL project

Integrating Hydro-Climate Science into Policy Decisions for Climate-Resilient Infrastructure and Livelihoods in East Africa (HyCRISTAL) is a Future Climate for Africa (FCFA) project funded to deliver new understanding of East African climate change and its impacts, and to demonstrate use of climate change information in long-term decision-making in the region. Here, we briefly summarise key findings from HyCRISTAL so far on climate change, as well as key findings from the pan-African FCFA project “IMPALA” relevant to East Africa, both in the context of previous literature on the topic

Scientific understanding of East African climate change from the HyCRISTAL project

Integrating Hydro-Climate Science into Policy Decisions for Climate-Resilient Infrastructure and Livelihoods in East Africa (HyCRISTAL) is a Future Climate for Africa (FCFA) project funded to deliver new understanding of East African climate change and its impacts, and to demonstrate use of climate change information in long-term decision-making in the region. Here, we briefly summarise key findings from HyCRISTAL so far on climate change, as well as key findings from the pan-African FCFA project “IMPALA” relevant to East Africa, both in the context of previous literature on the topic

Advances, gaps and way forward in provision of climate services over the Greater Horn of Africa

The Greater Horn of Africa is prone to extreme climatic conditions, thus, making climate services increasingly important in supporting decision-making processes across a range of climate sensitive sectors. This study aims to provide a comprehensive review of the recent advances, gaps and challenges in the provision of climate services over the region, for each of the components of the Global Framework for Climate Services. The study explores various milestones that have been achieved toward climate service delivery. The achievements include improvement of station network coverage, and enhancing the capacity of member states to utilize various tools in data analysis and generate routine climate products. The advancement in science, and availability of High-Performance Computing has made it possible for forecast information to be provided from nowcasting to seasonal timescales. Moreover, operationalizing of the objective forecasting method for monthly and seasonal forecasts has made it possible to translate tercile forecasts for applications models. Additionally, innovative approaches to user engagement through co-production, communication channels, user-friendly interfaces, and dissemination of climate information have also been developed. Despite the significant progress that has been made in the provision of climate services, there are still many challenges and gaps that need to be overcome in order to ensure that these services are effectively meeting the needs of users. The research of the science underpinning climate variability, capacity building and stakeholder engagement, as well as improved data management and quality control processes are some of the gaps that exist over the region. Additionally, communication and dissemination of climate information, including timely warnings and risk communication, require improvement to reach diverse user groups effectively. Addressing these challenges will require strengthened partnerships, increased investment in capacity building, enhanced collaboration between the climate information producers and stakeholders, and the development of user-friendly climate products. Bridging these gaps will foster greater resilience to climate-related hazards and disasters in the Greater Horn of Africa and support sustainable development in the region

RNA splicing alterations induce a cellular stress response associated with poor prognosis inAcute Myeloid Leukemia.

Purpose: RNA splicing is a fundamental biological process that generates protein diversity from a finite set of genes. Recurrent somatic mutations of splicing factor genes are common in some hematologic cancers but are relatively uncommon in acute myeloid leukemia (AML, < 20% of patients). We examined whether RNA splicing differences exist in AML, even in the absence of splicing factor mutations.Experimental Design: We developed a bioinformatics pipeline to study alternative RNA splicing in RNA-sequencing data from large cohorts of patients with AML.Results: We have identified recurrent differential alternative splicing between patients with poor and good prognosis. These splicing events occurred even in patients without any discernible splicing factor mutations. Alternative splicing recurrently occurred in genes with specific molecular functions, primarily related to protein translation. Developing tools to predict the functional impact of alternative splicing on the translated protein, we discovered that approximately 45% of the splicing events directly affected highly conserved protein domains. Several splicing factors were themselves misspliced and the splicing of their target transcripts were altered. Studying differential gene expression in the same patients, we identified that alternative splicing of protein translation genes in ELNAdv patients resulted in the induction of an integrated stress response and upregulation of inflammation-related genes. Finally, using machine learning techniques, we identified a splicing signature of four genes which refine the accuracy of existing risk prognosis schemes and validated it in a completely independent cohort.Conclusions: Our discoveries therefore identify aberrant alternative splicing as a molecular feature of adverse AML with clinical relevance

The RNA Atlas expands the catalog of human non-coding RNAs

Existing compendia of non-coding RNA (ncRNA) are incomplete, in part because they are derived almost exclusively from small and polyadenylated RNAs. Here we present a more comprehensive atlas of the human transcriptome, which includes small and polyA RNA as well as total RNA from 300 human tissues and cell lines. We report thousands of previously uncharacterized RNAs, increasing the number of documented ncRNAs by approximately 8%. To infer functional regulation by known and newly characterized ncRNAs, we exploited pre-mRNA abundance estimates from total RNA sequencing, revealing 316 microRNAs and 3,310 long non-coding RNAs with multiple lines of evidence for roles in regulating protein-coding genes and pathways. Our study both refines and expands the current catalog of human ncRNAs and their regulatory interactions. All data, analyses and results are available for download and interrogation in the R2 web portal, serving as a basis for future exploration of RNA biology and function