Acute Encephalopathy Associated with Influenza A Infection in Adults

We report acute encephalopathy associated with influenza A infection in 3 adults. We detected high cerebrospinal fluid (CSF) and plasma concentrations of CXCL8/IL-8 and CCL2/MCP-1 (CSF/plasma ratios >3), and interleukin-6, CXCL10/IP-10, but no evidence of viral neuroinvasion. Patients recovered without sequelae. Hyperactivated cytokine response may play a role in pathogenesis

Applications Of Genomics To Plantation Forestry With Kelampayan In Sarawak

Wood-based industries in Sarawak are increasingly encouraged to adapt to “new wood” from planted forests composed of fast-growing species such as Kelampayan with short rotation cycle (6-8 years). The rationale is that natural forests at the most produce about 3m3 /ha/yr of commercial timber, whereas plantations can produce annually from 10m3 /ha to 30m3 /ha of commercial timber. It is estimated at least 30 million seedlings are required for annual planting or reforestation programmes to meet the increasing global demand for raw materials. To date, several molecular genetics studies have been completed for Kelampayan. These include genetic diversity of Kelampayan, genetic marker (SSRs) development, ‘Touch-incubate-PCR’ approach for preparing plant tissues for high throughput genotyping, and transcriptomics and bioinformatics on wood formation of Kelampayan. This information provides a useful resource for genomic selection of Kelampayan aiming at the production of high value forests for maximum returns

EPO does not promote interaction between the erythropoietin and beta-common receptors

A direct interaction between the erythropoietin (EPOR) and the beta-common (βc) receptors to form an Innate Repair Receptor (IRR) is controversial. On one hand, studies have shown a functional link between EPOR and βc receptor in tissue protection while others have shown no involvement of the βc receptor in tissue repair. To date there is no biophysical evidence to confirm a direct association of the two receptors either in vitro or in vivo. We investigated the existence of an interaction between the extracellular regions of EPOR and the βc receptor in silico and in vitro (either in the presence or absence of EPO or EPO-derived peptide ARA290). Although a possible interaction between EPOR and βc was suggested by our computational and genomic studies, our in vitro biophysical analysis demonstrates that the extracellular regions of the two receptors do not specifically associate. We also explored the involvement of the βc receptor gene (Csf2rb) under anaemic stress conditions and found no requirement for the βc receptor in mice. In light of these studies, we conclude that the extracellular regions of the EPOR and the βc receptor do not directly interact and that the IRR is not involved in anaemic stress.Karen S. Cheung Tung Shing, Sophie E. Broughton, Tracy L. Nero, Kevin Gillinder, Melissa D. Ilsley, Hayley Ramshaw, Angel F. Lopez, Michael D. W. Griffin, Michael W. Parker, Andrew C. Perkins, Urmi Dhaga

Genomics studies on plantation tree species in Sarawak

Rapid socio-economic changes in the world are having profound impacts on all sectors, including forestry. The increase in global demand for wood requires increase in forest productivity. The alternative is to farm trees in plantations composed of fast-growing species with short rotation cycles (6–8 y). The rationale is that natural forests at the most produce about 3 m3 ha y-1 of commercial timber, whereas plantations can produce annually from 10 m3 ha y-1 of hardwoods to 30 m3 ha-1 of softwoods and thus, decrease the effects of human pressure on our ecosystems while increasing the competitiveness of Sarawak’s forest industry. This is in line with the state government’s aspiration to establish one million hectares of planted forests by year 2020 to meet the increasing demand from both domestic and international markets for raw materials. It is estimated at least 30 million seedlings are required for annual planting or reforestation programmes. In this regard, forest genomics research will help respond to the need to develop adequate tools that enable us to produce quality planting materials that are of faster growth, high yield and high wood quality, and also adapted to local conditions, so that we may achieve economic benefits of great significance. Realizing the need, we have centred our research on the development of tools via biotechnological innovations for tree breeders. Over the years, we have successfully developed: 1) simple sequence repeat (SSR) 173 DNA markers specific for identifying the genetic make-up of two fastgrowing indigenous tree species, i.e. kelampayan and sawih; 2) the ‘Touch-incubate-PCR’ approach for preparing plant tissues for high throughput genotyping, and 3) a kelampayan tree transcriptome database (NcdbEST aka CADAMOMICS) for wood formation. These tools will greatly facilitate the selection of quality planting materials for planted forest development in Sarawak as well as long-term tree improvement activities by integrating genomics into our breeding programme via association mapping. The overall benefit of genomics application to tree improvement programme will be in terms of greater certainty in the outcome of results, specifically the performance of the forest plantations, as well as the savings in time and cost in the production and supply of quality planting materials

Distinct Assemblies of Heterodimeric Cytokine Receptors Govern Stemness Programs in Leukemia

Published first May 16, 2023Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, and recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological and clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels are a constant yet puzzling feature, as this receptor lacks tyrosine kinase activity. Here, we show that the heterodimeric IL3Rα/βc receptor assembles into hexamers and dodecamers through a unique interface in the 3D structure, where high IL3Rα/βc ratios bias hexamer formation. Importantly, receptor stoichiometry is clinically relevant as it varies across the individual cells in the AML hierarchy, in which high IL3Rα/βc ratios in LSCs drive hexamer-mediated stemness programs and poor patient survival, while low ratios mediate differentiation. Our study establishes a new paradigm in which alternative cytokine receptor stoichiometries differentially regulate cell fate, a signaling mechanism that may be generalizable to other transformed cellular hierarchies and of potential therapeutic significance.Winnie L. Kan, Urmi Dhagat, Kerstin B. Kaufmann, Timothy R. Hercus, Tracy L. Nero, Andy G.X. Zeng, John Toubia, Emma F. Barry, Sophie E. Broughton, Guillermo A. Gomez, Brooks A. Benard, Mara Dottore, Karen S. Cheung Tung Shing, Héléna Boutzen, Saumya E. Samaraweera, Kaylene J. Simpson, Liqing Jin, Gregory J. Goodall, C. Glenn Begley, Daniel Thomas, Paul G. Ekert, Denis Tvorogov, Richard J. D, Andrea, John E. Dick, Michael W. Parker, and Angel F. Lope

Mangroves give cause for conservation optimism, for now

No abstract available

Messing with beta c: a unique receptor with many goals

Our understanding of the biological role of the βc family of cytokines has evolved enormously since their initial identification as bone marrow colony stimulating factors in the 1960's. It has become abundantly clear over the intervening decades that this family of cytokines has truly astonishing pleiotropic capacity, capable of regulating not only hematopoiesis but also many other normal and pathological processes such as development, inflammation, allergy and cancer. As noted in the current pandemic, βc cytokines contribute to the cytokine storm seen in acutely ill COVID-19 patients. Ongoing studies to discover how these cytokines activate their receptor are revealing insights into the fundamental mechanisms that give rise to cytokine pleiotropy and are providing tantalizing glimpses of how discrete signaling pathways may be dissected for activation with novel ligands for therapeutic benefit.Winnie L. Kan, Karen S. Cheung Tung Shing, Tracy L. Nero, Timothy R. Hercus, Denis Tvorogov, Michael W. Parker, Angel F. Lope