Expression profiling of snoRNAs in normal hematopoiesis and AML

Key Points A subset of snoRNAs is expressed in a developmental- and lineage-specific manner during human hematopoiesis. Neither host gene expression nor alternative splicing accounted for the observed differential expression of snoRNAs in a subset of AML.</jats:p

Mechanisms of aging in senescence-accelerated mice

BACKGROUND: Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and hippocampus in two rare inbred mouse models of accelerated neurological senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J). RESULTS: The majority of age-related gene expression changes were strain-specific, with only a few common pathways found for normal and accelerated neurological aging. Polymorphism screening led to the identification of mutations that could have a direct impact on important disease processes, including a mutation in a fibroblast growth factor gene, Fgf1, and a mutation in and ectopic expression of the gene for the chemokine CCL19, which is involved in the inflammatory response. CONCLUSION: We show that combining the study of inbred mouse strains with interesting traits and gene-expression profiling can lead to the discovery of genes important for complex phenotypes. Furthermore, full-genome polymorphism detection, sequencing and gene-expression profiling of inbred mouse strains with interesting phenotypic differences may provide unique insights into the molecular genetics of late-manifesting complex diseases

Lunar Lander Offloading Operations Using a Heavy-Lift Lunar Surface Manipulator System

This study investigates the feasibility of using a heavy-lift variant of the Lunar Surface Manipulator System (LSMS-H) to lift and handle a 12 metric ton payload. Design challenges and requirements particular to handling heavy cargo were examined. Differences between the previously developed first-generation LSMS and the heavy-lift version are highlighted. An in-depth evaluation of the tip-over risk during LSMS-H operations has been conducted using the Synergistic Engineering Environment and potential methods to mitigate that risk are identified. The study investigated three specific offloading scenarios pertinent to current Lunar Campaign studies. The first involved offloading a large element, such as a habitat or logistics module, onto a mobility chassis with a lander-mounted LSMS-H and offloading that payload from the chassis onto the lunar surface with a surface-mounted LSMS-H. The second scenario involved offloading small pressurized rovers with a lander-mounted LSMS-H. The third scenario involved offloading cargo from a third-party lander, such as the proposed ESA cargo lander, with a chassis-mounted LSMS-H. In all cases, the analyses show that the LSMS-H can perform the required operations safely. However, Chariot-mounted operations require the addition of stabilizing outriggers, and when operating from the Lunar surface, LSMS-H functionality is enhanced by adding a simple ground anchoring system

Assessment of habitat‐specific competition for oral rabies vaccine baits between raccoons and opossums

Throughout the eastern United States, the National Rabies Management Program (NRMP) distributes oral rabies vaccine (ORV) baits to manage rabies virus circulation in raccoon (Procyon lotor) populations. The consumption of vaccine baits by non‐target species including Virginia opossums (Didelphis virginiana) may reduce the effectiveness of ORV programs, but competition for baits remains poorly quantified in many areas of the southeastern United States. We distributed placebo ORV baits injected with a biomarker across 4 land cover types (bottomland hardwood, upland pine, riparian, isolated wetland) on the Savannah River Site in South Carolina, USA, 2017–2019. We then trapped and collected whiskers from 247 raccoons and 78 opossums to assess biomarker presence using fluorescent microscopy. Our data revealed greater bait uptake probability by raccoons (estimated x̅= 0.30, 95% CI = 0.19–0.44) compared to opossums (estimated x̅ = 0.11, 95% CI = 0.05–0.23) across all cover types surveyed. Probability of bait consumption was not affected by cover type or the abundance of raccoons or opossums. Among raccoons, males were more likely to consume baits than females (estimated x̅ = 0.28, 95% CI = 0.17–0.44 for males and 0.14, 95% CI = 0.05–0.31 for females) and probability of consumption increased by 0.08 with each additional day trapped during the 10‐day trapping session. Uptake rates for raccoons were relatively low compared to other studies and not influenced by competition with opossums. These low consumption rates indicate that additional research addressing the roles of baiting season, bait density, and resource selection will be important to maximize ORV bait uptake by target species in these southeastern landscapes

Influence of landscape attributes on Virginia opossum density

TheVirginia opossum (Didelphis virginiana), North America\u27s only marsupial, has a range extending from southern Ontario, Canada, to the Yucatan Peninsula, Mexico, and from the Atlantic seaboard to the Pacific. Despite the Virginia opossum\u27s taxonomic uniqueness in relation to other mammals in North America and rapidly expanding distribution, its ecology remains relatively understudied. Our poor understanding of the ecology of this important mesopredator is especially pronounced in the rural southeastern United States. Our goal was to estimate effects of habitat on opossum density within an extensive multiyear spatial capture‐recapture study. Additionally, we compared the results of this spatial capture‐recapture analysis with a simple relative abundance index. Opossum densities in the relatively underdeveloped regions of the southeastern United States were lower compared to the more human‐dominated landscapes of the Northeast and Midwest. In the southeastern United States, Virginia opossums occurred at a higher density in bottomland swamp and riparian hardwood forest compared to upland pine (Pinus spp.) plantations and isolated wetlands. These results reinforce the notion that the Virginia opossum is commonly associated with land cover types adjacent to permanent water (bottomland swamps, riparian hardwood). The relatively low density of opossums at isolated wetland sites suggests that the large spatial scale of selection demonstrated by opossums gives the species access to preferable cover types within the same landscape

Functional and epigenetic phenotypes of humans and mice with DNMT3A Overgrowth Syndrome

Germline mutations in the DNMT3A gene can cause an overgrowth syndrome associated with behavioural and hematopoietic phenotypes. Here the authors describe a mouse model of this syndrome that recapitulates many of these features, including conserved alterations in DNA methylation in the blood cells of both species

Genomic landscape of TP53-mutated myeloid malignancies

TP53-mutated myeloid malignancies are associated with complex cytogenetics and extensive structural variants, which complicates detailed genomic analysis by conventional clinical techniques. We performed whole-genome sequencing (WGS) of 42 acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS) cases with paired normal tissue to better characterize the genomic landscape of TP53-mutated AML/MDS. WGS accurately determines TP53 allele status, a key prognostic factor, resulting in the reclassification of 12% of cases from monoallelic to multihit. Although aneuploidy and chromothripsis are shared with most TP53-mutated cancers, the specific chromosome abnormalities are distinct to each cancer type, suggesting a dependence on the tissue of origin. ETV6 expression is reduced in nearly all cases of TP53-mutated AML/MDS, either through gene deletion or presumed epigenetic silencing. Within the AML cohort, mutations of NF1 are highly enriched, with deletions of 1 copy of NF1 present in 45% of cases and biallelic mutations in 17%. Telomere content is increased in TP53-mutated AMLs compared with other AML subtypes, and abnormal telomeric sequences were detected in the interstitial regions of chromosomes. These data highlight the unique features of TP53-mutated myeloid malignancies, including the high frequency of chromothripsis and structural variation, the frequent involvement of unique genes (including NF1 and ETV6) as cooperating events, and evidence for altered telomere maintenance