brk (breast tumor kinase) shows homology to the src family of non-receptor protein-tyrosine kinases and is expressed in breast carcinomas. In order to investigate the role of brk in breast tumor development, we have examined the growth and transformation properties of human mammary epithelial cells engineered to overexpress Brk. Interestingly, like c-Src, overexpression of Brk leads to sensitization to EGF, and also results in a partially transformed phenotype. Further investigation of the latter activity was attempted by mutational analysis, targeting key residues known to affect tyrosine kinase activity in Src-like kinases. Mutation of amino acid residue Lys-219 to Met, by analogy to Src, abolished both kinase activity and transformation capacity. Mutation of amino acid residue Tyr-447 to Phe, however, resulted in a decrease in transforming potential without affecting kinase activity. These results suggest that while Src and Brk share some functional properties, they act differently during transformation. These differences are discussed in the context of the mechanisms underlying breast cancer development.

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Introduction: There is limited real-world evidence surrounding the effectiveness of early, mild-to-moderate COVID-19 treatments following the emergence and dominance of Omicron SARS-CoV-2 subvariants. Here, characteristics and acute clinical outcomes are described for patients with COVID-19 treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or patients at highest risk per NHS criteria but who were untreated. Methods: Retrospective cohort study of non-hospitalised patients who received early treatment for, or were diagnosed with, COVID-19 between 1 December 2021 and 31 May 2022, using data from the Discover dataset in north-west London. Patients were included if aged ≥12 years and treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or were untreated but expected to be eligible for early treatment per NHS highest-risk criteria at time of diagnosis. Outcomes were reported for 28 days from COVID-19 diagnosis (index). Subgroup analyses were conducted in patients with advanced renal disease, those aged 18-64 and ≥65 years and by period of Omicron BA.1, BA.2 and BA.5 (post-hoc exploratory analysis) predominance. Results: A total of 696 patients prescribed sotrovimab, 337 prescribed nirmatrelvir/ritonavir, 470 prescribed molnupiravir and 4,044 eligible high-risk untreated patients were included. A high proportion of patients on sotrovimab had advanced renal disease (29.3%), ≥3 high-risk comorbidities (47.6%) and were aged ≥65 years (36.9%). In total, 5/696 (0.7%) patients on sotrovimab, <5/337 (0.3-1.2%) patients on nirmatrelvir/ritonavir, 10/470 (2.1%) patients on molnupiravir and 114/4,044 (2.8%) untreated patients were hospitalised with COVID-19 as the primary diagnosis. Similar results were observed across all subgroups and during Omicron subvariant periods. Conclusion: Patients who received sotrovimab appeared to show evidence of multiple comorbidities that may increase risk of severe COVID-19. Low hospitalisation rates were observed for all treated cohorts across subgroups and periods of predominant variants of concern. These descriptive results require confirmation with comparative effectiveness analyses adjusting for differences in underlying patient characteristics.

Considerable evidence indicates that radial glial cells play an active role in guiding growing neurites during development of the vertebrate CNS. In this paper we describe subpopulations of radial glial in the spinal cord of the axolotl. Amphibians maintain radial glia throughout life, and subpopulations are described using anatomical criteria following filling of individual cells with horseradish peroxidase and immunocytochemical staining with a range of intermediate filament antibodies. Radial glial cells in specific regions of the spinal cord stain with a range of antibodies specific to human keratins 8 and 18, and to glial fibrillary acid protein (GFAP). Some of these antibodies show selective localized to specific regions of individual glial cell processes. Immunoblotting analysis indicates that two keratins are present in the axolotl CNS corresponding to the two earliest embryonic keratins of vertebrates, keratin 8 and 18. Comparisons of molecular weight indicate that these may correspond to keratins identified in Xenopus laevis, the genes of which have been cloned. Axolotl GFAP is also identified in Western blots and may be present in two forms of differing molecular weight. These results are discussed in terms of the likely role of radial glial cells, and comparisons are drawn between the keratin and GFAP types seen in the axolotl spinal cord and of those in other vertebrate groups.