Proliferation tracing with single-cell mass cytometry optimizes generation of stem cell memory-like T cells.

Selective differentiation of naive T cells into multipotent T cells is of great interest clinically for the generation of cell-based cancer immunotherapies. Cellular differentiation depends crucially on division state and time. Here we adapt a dye dilution assay for tracking cell proliferative history through mass cytometry and uncouple division, time and regulatory protein expression in single naive human T cells during their activation and expansion in a complex ex vivo milieu. Using 23 markers, we defined groups of proteins controlled predominantly by division state or time and found that undivided cells account for the majority of phenotypic diversity. We next built a map of cell state changes during naive T-cell expansion. By examining cell signaling on this map, we rationally selected ibrutinib, a BTK and ITK inhibitor, and administered it before T cell activation to direct differentiation toward a T stem cell memory (TSCM)-like phenotype. This method for tracing cell fate across division states and time can be broadly applied for directing cellular differentiation

Establishment of the Jesuit order in Poland and the Grand Duchy of Lithuania (before the beginning of the 1570s)

The process of inviting the Jesuit Order to Poland and the Grand Duchy of Lithuania is considered. Definitely the role of Nuncio D.F. Camendoni, Bishop of Warmia S. Gozi, Bishop of Vilnо V. Protasevich, as well as King and Grand Duke Sigismund II Augustus. The еmphasis is placed on the analysis of the creation of the Vilnо Jesuit Collegium. It is noted that its emergence was caused not only by confrontation with Protestants, but also by the desire to prevent the organization of a secular Catholic university like the Krakow Academy in the capital. The opening of Jesuit collegiums in Brunsberg, Pultusk, Yaroslavl and Poznan at the specified time was also mentioned.Разгледжаны працэс запрашэння езуіцкага ордэну ў Польшчу і ВКЛ. Вызначана роля ў гэтай справе нунцыя Д.Ф. Камендоні, біскупа вармійскага С. Гозія, біскупа віленскага В. Пратасевіча, а таксама караля і вялікага князя Жыгімонта ІІ Аўгуста. Акцэнт зроблены на аналізе стварэння Віленскага езуіцкага калегіўма. Адзначана, што яго ўзнікненне было выклікана не толькі супрацьстаяннем з пратэстантамі, але і жаданнем перадухіліць арганізацыю ў сталіцы ВКЛ свецкага каталіцкага ўніверсітэта накшталт Кракаўскай акадэміі. Таксама згадана адкрыццё ў азначаны час езуіцкіх калегіўмаў у Брунсбергу, Пултуску, Яраславе і Познані

The formation of the basic principles of the educational activity of the Jesuit order in the 1550s

In the scientific article, for the first time in national historiography, the initial steps of the Jesuits to develop general approaches to the organization of educational affairs were considered. The relevant activity of the rector of collegiums in Messina and Rome, I. Nadal, was noted. The "Constitution of the Jesuit Order" of 1558 was studied in detail, the IV part of which was fully devoted to the functioning of the order's educational institutions.У навуковым артыкуле ўпершыню ў айчыннай гістарыяграфіі разгледжаны першапачатковыя захады езуітаў па выпрацоўцы агульных падыходаў да арганізацыі адукацыйнай справы. Адзначана адпаведная дзейнасць рэктара калегіўмаў у Месіне і Рыме І. Надаля. Падрабязна вывучаны “Канстытуцыі езуіцкага ордэну” 1558 г., IV частка якіх была цалкам прысвечана пытанням функцыянавання навучальных устаноў ордэна

Evolutionarily new sequences expressed in tumors

BACKGROUND: Earlier we suggested the concept of the positive evolutionary role of tumors. According to this concept, tumors provide conditions for the expression of evolutionarily new and/or sleeping genes in their cells. Thus, tumors are considered as evolutionary proving ground or reservoir of expression. To support this concept we have previously characterized in silico and experimentally a new class of human tumor-related transcribed sequences. RESULTS: In this article we describe results of further studies of previously described tumor-related sequences. The results of molecular phylogeny studies, Southern hybridization experiments and computational comparison with genomes of other species are presented. CONCLUSION: These results suggest that these previously described tumor-related human transcripts are also relatively evolutionarily new

Aphasia Taxonomy – the Classification Criteria and the Types of Disorders

The article summarizes the important criteria for aphasia divisions, which present different methods of approaching the disease. Discussed: classical forms of aphasia, non-classical forms of aphasia, aphasia division by the positions of selected authors. Each adopted criterion has been enriched with descriptions of the most important properties of a given type of aphasia, encountered in speech therapy. A contemporary approach to the diagnosis and therapy of the above disorder is also presented.W artykule zestawiono istotne kryteria podziałów afazji, które prezentują różne metody podejścia do schorzenia. Omówiono klasyczne postacie afazji, nieklasyczne postacie afazji oraz podział afazji ze względu na stanowiska wybranych autorów. Każde przyjęte kryterium zostało wzbogacone o opisy najważniejszych właściwości danego typu afazji, spotykanych w praktyce logopedycznej. Przedstawiono także współczesne podejście do diagnozy i terapii tego zaburzenia

Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front.

Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. We identified nine conserved, distinct cellular neighborhoods (CNs)-a collection of components characteristic of the CRC iTME. Enrichment of PD-1+CD4+ T cells only within a granulocyte CN positively correlated with survival in a high-risk patient subset. Coupling of tumor and immune CNs, fragmentation of T cell and macrophage CNs, and disruption of inter-CN communication was associated with inferior outcomes. This study provides a framework for interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions of cells and spatial domains

GateFinder: projection-based gating strategy optimization for flow and mass cytometry

Motivation: High-parameter single-cell technologies can reveal novel cell populations of interest, but studying or validating these populations using lower-parameter methods remains challenging.Results: Here, we present GateFinder, an algorithm that enriches high-dimensional cell types with simple, stepwise polygon gates requiring only two markers at a time. A series of case studies of complex cell types illustrates how simplified enrichment strategies can enable more efficient assays, reveal novel biomarkers and clarify underlying biology

Foetal macrosomia — incidence, determinants and neonatal outcomes: 10-years retrospective review, 2010–2019

Objectives: Prevalence of macrosomia differs worldwide according to studied population and has been variable over last few decades. The objective of the study was to determine the trends in incidence and clinical characteristics of infants with macrosomia born in two diverse Polish neonatal centres from 2010–2019. Material and methods: Trends in the incidence of macrosomia, maternal age, delivery mode and neonatal complications were analysed over a 10 year period based on birth medical records. Results: The total number of 43 165 term neonates were analysed with macrosomia incidence of 16.63% (n = 7179). The prevalence of macrosomia was stable from 2010–2019 irrespectively of referentiality and geographical area. Mean maternal age increased over the decade with higher age of mothers of macrosomic neonates. Recognizability of gestation diabetes among pregnant women increased from 9.61% in 2010 to 15.27% in 2019 and it was comparable in mothers of macrosomic infants. The percentage of caesarean sections was higher in macrosomic neonates and gradually increased over last decade. The highest percentage of birth injuries was observed in the first grade of macrosomia (4000–4499 g). The number of neonatal complications including lower Apgar score, respiratory and cardiology symptoms correlated with severity of macrosomia, with highest morbidity in children above 5000 g. Conclusions: The prevalence of macrosomia in the studied cohort remained invariable over the last decade. Macrosomia is associated with an increased rate of caesarean sections, higher maternal age and increased neonatal morbidity. A higher macrosomia grade is related to a worse neonatal outcome. Further studies on other risk factors of macrosomia are needed

Testing for differential abundance in mass cytometry data.

When comparing biological conditions using mass cytometry data, a key challenge is to identify cellular populations that change in abundance. Here, we present a computational strategy for detecting 'differentially abundant' populations by assigning cells to hyperspheres, testing for significant differences between conditions and controlling the spatial false discovery rate. Our method (http://bioconductor.org/packages/cydar) outperforms other approaches in simulations and finds novel patterns of differential abundance in real data.This work was supported by Cancer Research UK (core funding to J.C.M., award no. A17197), the University of Cambridge and Hutchison Whampoa Limited. J.C.M. was also supported by core funding from EMBL

Reconstruction of functional networks from multiparametric high-throughput screens

Hazelton Ind. USA1 over White River 1921. Wooden trestle shown supporting the construction of two concrete piers. Two cranes are shown on top of the trestle deck. Formwork for a concrete pier is shown in left background