SUMMARY Knowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We created an immune map of breast cancer using single-cell RNA-seq data from 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph node. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous tumor-specific phenotypic expansions driven by environmental cues. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer, with important implications for characterizing tumor-infiltrating immune cells.
C arr , A. J. H. (Univ. Coll. Wales, Aberystwyth), and L indsay S. O live . Genetics of Sordaria fimicola. III. Cross compatibility among self‐fertile and self‐sterile cultures. Amer. Jour. Bot. 46(2) : 81‐91. Illis. 1959.—Cross‐compatibility in Sordaria fimicola is shown to be dependent upon a number of factors controlling the sexual process, from hyphal anastomosis and nuclear migration on through to perithecial formation and nuclear compatibility. Fertile cultures which were incompatible through inability to anastomose were induced to cross by the use of a third culture which would anastomose with both. Certain spontaneous or irradiation‐produced sterility mutants were found to be compatible if the sterility genes were at different loci, through complementation by the wild‐type alleles. In some pairings, cross‐karyogamy was preferential, and in one case, only hybrid perithecia were produced. Fully fertile recombinants segregated from these crosses in frequencies which indicated that the sterility loci were unlinked. Certain sterility genes were found to influence hyphal anastomosis, nuclear migration, and the development of fertile sector heterokaryons from the zone of anastomosis. Mutant factors at two loci in a U.V. mutant causing self‐sterility were found also to be responsible for lethality in ascospore germination. Factors in one sterility mutant controlled the production of a sterility‐inducing substance which diffused into the medium. In some crosses, complementation of two sterile cultures towards fertility is shown to require a balanced nuclear ratio. Factors are described which increase the inhibitory effect of one sterility gene, while another factor was found to suppress its effect and thereby make the culture self‐fertile. It is concluded that, since there is recombination between the sterility loci, these results do not represent the derivation of balanced heterothallism from a normally homothallic system, although it may lead by evolutionary progression to such a life cycle. The possible physiologic action of the sterility genes is discussed.
This preliminary study has shown that bracing may improve the cosmetic appearance of a scoliotic back although the underlying curve remains unchanged. Thirty-two patients treated with the Boston brace for adolescent idiopathic scoliosis were assessed both roentgenographically and by integrated shape imaging system scanning before and after treatment. The mean follow-up time was 16 months. Surface shape improved in 41% of the patients, whereas roentgenographic improvement occurred in only 9%. Roentgenographic measurements should, therefore, be considered in conjunction with corresponding surface shape measurements in the assessment of brace treatment of scoliosis.
Abstract Since formulation of the cellular theory in the early 19th century—relatively not so long ago—it has become universally recognized that tissues and organisms are formed and shaped by cells of many different types, all operating in beautiful harmony. Many mechanisms of this orchestration remain largely a mystery to this day, yet are important for us to understand if we are to fully comprehend fundamental processes in disease, especially one as formidable and perplexing as cancer. In the current era of progressive technological advances, many areas of biology are converging, and we now recognize and expect differences between cells, even among those of the same type, but whose origins rest in different tissues. Yet, many core tenets are being universally applied. The detailed cellular composition of tissues is clouded with uncertainty for many tissue types, and this includes the breast. To clarify the cell types in the breast and build a solid foundation for future work, we have meticulously examined a large collection of normal breast tissues, microscopically and by flow cytometry. We developed a complex antibody panel and rigorous gating strategy capable of objectively resolving and sorting each major cell type. We have sequenced mRNAs expressed by even the rarest of cell subpopulations and refined or developed methods for culturing each. This includes: several different luminal and epithelial fractions, myoepithelial cells, adipocytes, leukocytes, pericytes, erythrocytes, adipose-derived mesenchymal stem cells, and both lymphatic and vascular endothelial cells –12 different types in all. Future studies are aimed at developing heterotypic culture models using these cells, but also to use our new knowledge and experience to similarly explore heterogeneity of ductal carcinoma in situ (DCIS) and invasive breast cancers. We will present the development of this method and characterization to date of the sorted cell populations. Citation Format: William Curtis Hines, Ambrose Carr, Kate Thi, Zhenmao Wan, Dana Pe'er, Mina J. Bissell. Cytometric atlas of the human breast: Comprehensive characterization reveals 12 distinct cell populations. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(2_Suppl):Abstract nr A25.
Carr, A. J. H. (Univ. Coll. Wales, Aberystwyth), and Lindsay S. Olive. Genetics of Sordaria fimicola. III. Cross compatibility among self-fertile and self-sterile cultures. Amer. Jour. Bot. 46(2) : 81-91. Illis. 1959.—Cross-compatibility in Sordaria fimicola is shown to be dependent upon a number of factors controlling the sexual process, from hyphal anastomosis and nuclear migration on through to perithecial formation and nuclear compatibility. Fertile cultures which were incompatible through inability to anastomose were induced to cross by the use of a third culture which would anastomose with both. Certain spontaneous or irradiation-produced sterility mutants were found to be compatible if the sterility genes were at different loci, through complementation by the wild-type alleles. In some pairings, cross-karyogamy was preferential, and in one case, only hybrid perithecia were produced. Fully fertile recombinants segregated from these crosses in frequencies which indicated that the sterility loci were unlinked. Certain sterility genes were found to influence hyphal anastomosis, nuclear migration, and the development of fertile sector heterokaryons from the zone of anastomosis. Mutant factors at two loci in a U.V. mutant causing self-sterility were found also to be responsible for lethality in ascospore germination. Factors in one sterility mutant controlled the production of a sterility-inducing substance which diffused into the medium. In some crosses, complementation of two sterile cultures towards fertility is shown to require a balanced nuclear ratio. Factors are described which increase the inhibitory effect of one sterility gene, while another factor was found to suppress its effect and thereby make the culture self-fertile. It is concluded that, since there is recombination between the sterility loci, these results do not represent the derivation of balanced heterothallism from a normally homothallic system, although it may lead by evolutionary progression to such a life cycle. The possible physiologic action of the sterility genes is discussed.
SUMMARY A range of oat species, species hybrids and derived addition lines, varied in their level of race non‐specific resistance to mildew. This resistance prevented attempted primary penetration by a proportion of spores. It was generally expressed more strongly in fifth than in first formed leaves and thus appeared to be a component of adult plant resistance. Penetration was most frequently arrested at the infection peg stage, implicating the papilla formed by the host as a defence mechanism. Epidermal cells close to stomata were more commonly invaded than others, but only in two of ten lines examined was preferential stomatal subsidiary cell infection observed. Where penetration was successful, host resistance could operate by arresting infections prior to the establishment of functional host/pathogen relations. In hybrids between resistant wild species and a susceptible cultivated oat, the level of both forms of resistance was reduced, indicating a similar effect of the susceptible host genome on genes conditioning both resistances.
The standing heights of 40 children with scoliosis and 110 persons from their immediate families were compared with those of a group of 349 contemporary control subjects. Skeletal bone ages and puberty ratings did not differ from normal, but the children with scoliosis were found to be significantly taller than the controls. They were also taller than their unaffected relatives, suggesting that the increased stature is not due to genetic factors alone. Scoliotic children with an affected immediate-family member were of normal height, which suggests that growth is of less etiological importance in children with a strong genetic susceptibility.
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