The supportive effects of IL-7 on eosinophil progenitors from human bone marrow cells can be blocked by anti-IL-5

Human rIL-7 was studied for its effects on myeloid and erythroid progenitors from human bone marrow cells. IL-7 did not support the granulocytic/monocytic or erythroid lineage but exclusively stimulated eosinophil colony formation (CFU-Eo) (4 ± 3 vs 48 ± 17 CFU-Eo/105 nonadherent fraction-non-T cell (NAF-NT) cells). This supportive effect was not mediated by T cells or monocytes because similar results were obtained with or without T cell or adherent depleted cell fractions. In addition, it was shown that CD34+ sorted cells could be stimulated by IL-7 (0 vs 15 ± 9 CFU-Eo/3 x 103 CD34+ cells). Furthermore studies with IL-3 or granulocyte- macrophage CSF (GM-CSF) demonstrated an additive effect on the IL-7 supported colony formation. Finally, experiments were performed with anti-IL-3, anti- GM-CSF, anti-IL-1, and anti-IL-5 to exclude the possibility that IL-7 indirectly stimulated the eosinophil progenitor cell. Anti-GM-CSF, anti-IL-1, or anti-IL-3 did not influence the supportive effects of IL-7. However, anti- IL-5 did abolish the effects of IL-7 on the eosinophil colony formation (69 ± 15 vs 3 ± 2 CFU-Eo/105 NAF-NT, n = 3). Similar results were obtained with CD34+ sorted cells. Moreover, IL-5 mRNA expression could be demonstrated in IL-7-stimulated NAF-NT cells. These data suggest that the supportive effects of IL-7 on eosinophil precursors are mediated by the endogenous release of IL-5.</p

Promoting physical activity among cancer survivors: meta-analysis and meta-cart analysis of randomized controlled trials

Objective: We conducted a meta-analysis of physical activity interventions among cancer survivors in order to (a) quantify the magnitude of intervention effects on physical activity, and (b) determine what combination of intervention strategies maximizes behavior change. Methods: Out of 32,626 records that were located using computerized searches, 138 independent tests (N = 13,050) met the inclusion criteria for the review. We developed a bespoke taxonomy of 34 categories of techniques designed to promote psychological change, and categorized sample, intervention, and methodological characteristics. Random effects meta-analysis and meta-regressions were conducted; effect size data were also submitted to Meta-CART analysis. Results: The sample-weighted average effect size for physical activity interventions was d+ = .35, equivalent to an increase of 1,149 steps per day. Effect sizes exhibited both publication bias and small sample bias but remained significantly different from zero, albeit of smaller magnitude (d+ ≥ .20), after correction for bias. Meta-CART analysis indicated that the major difference in effectiveness was attributable to supervised versus unsupervised programs (d+ = .49 vs. .26). Greater contact time was associated with larger effects in supervised programs. For unsupervised programs, establishing outcome expectations, greater contact time, and targeting overweight or sedentary participants each predicted greater program effectiveness, whereas prompting barrier identification and providing workbooks were associated with smaller effect sizes. Conclusion: The present review indicates that interventions have a small but significant effect on physical activity among cancer survivors, and offers insights into how the effectiveness of future interventions might be improved

Construction of Red Fox Chromosomal Fragments from the Short-Read Genome Assembly

The genome of a red fox (Vulpes vulpes) was recently sequenced and assembled using next-generation sequencing (NGS). The assembly is of high quality, with 94X coverage and a scaffold N50 of 11.8 Mbp, but is split into 676,878 scaffolds, some of which are likely to contain assembly errors. Fragmentation and misassembly hinder accurate gene prediction and downstream analysis such as the identification of loci under selection. Therefore, assembly of the genome into chromosome-scale fragments was an important step towards developing this genomic model. Scaffolds from the assembly were aligned to the dog reference genome and compared to the alignment of an outgroup genome (cat) against the dog to identify syntenic sequences among species. The program Reference-Assisted Chromosome Assembly (RACA) then integrated the comparative alignment with the mapping of the raw sequencing reads generated during assembly against the fox scaffolds. The 128 sequence fragments RACA assembled were compared to the fox meiotic linkage map to guide the construction of 40 chromosomal fragments. This computational approach to assembly was facilitated by prior research in comparative mammalian genomics, and the continued improvement of the red fox genome can in turn offer insight into canid and carnivore chromosome evolution. This assembly is also necessary for advancing genetic research in foxes and other canids

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or long COVID ), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

The heterogeneity of follicular center cell lymphomas:I. Cytohistologic, immunologic, and enzymehistochemical aspects

Histologic material from 44 patients with follicular center cell lymphomas with a follicular growth pattern was divided into five groups on the basis of the predominating neoplastic cell type(s), i.e., small centrocytes with occasional centroblasts (SCC), centrocytes and few (CBCC/A) or many (CBCC/B) centroblasts, small and large centrocytes (SLCC), and small and large centroblasts (SLCB). Histologic, immunologic, and enzymehistochemical parameters as observed in these groups were compared, and follow-up material and material obtained during staging procedures were studied. Immunologic and enzymehistochemical findings confirmed both the B-cell origin and the neoplastic nature of the lymphomas, but did not yield relevant differences between the various groups. The groups with a predominance of small centrocytes or of small centrocytes and centroblasts showed the most prominent follicular growth and early dissemination to bone marrow and spleen. Histologic transformation in these groups was characterized by an increase in the number of centroblasts and a more diffuse growth pattern. The groups composed of small and large centrocytes or centroblasts tended to a more diffuse growth and had later dissemination and no histological transformation