Architectural and historical heritage of the Klein family from the second half of the 19th century

Disertační práce se zaměřuje na stavebně historický odkaz moravské podnikatelské rodiny Kleinů v průběhu 19. století. Soustřeďuje se na mapování významných stavebních realizací v silničním a železničním odvětví, stavbu mostů, rodinných sídel, průmyslových podniků a jiných. Hlavním cílem práce je vytvořit komplexní shrnutí širokého spektra stavebních a podnikatelských aktivit bratří Kleinů, kteří jsou historicky primárně spojováni pouze s výstavbou železniční sítě na území bývalého Rakouského císařství. Práce je strukturovaná do devíti nosných pilířů, kdy osm z nich je zaměřeno na podnikatelskou činnost dělenou dle hlavního oboru zájmu a analyzovanou na primární a sekundární. Součástí textu je i hloubková analýza mezilidských vztahů hlavních představitelů rodiny Franze, Libora, Alberta a Huberta Kleina v kontextu budování prvních železničních tratí na našem území a rozvoje průmyslu od 40. let 19. století. Práce se nesoustřeďuje pouze na zakládající členy významné stavební firmy Gebrüder Klein, ale pokouší se zodpovědět příčiny úpadku podnikatelského impéria ve druhé a třetí generaci rodu.The dissertation covers the architectural heritage of the Moravian entrepreneurial family Klein during the 19th century. The focus is on the coverage of important constructions in the area of road works, railways, bridges, family houses and industrial buildings. The main target is to give a comprehensive overview of the broad spectrum of entrepreneurial and architectural activities of the brothers Klein, who usually are connected to the construction of railways in the former Austrian Empire only. The work is structured into 9 chapters, eight of which focus on the entrepreneurial activities, split by the area of activity, divided into primary and secondary industry. The work also contains an in-depth analysis of the interpersonal relationships between the main personalities of the family, Franz, Libor, Albert and Hubert Klein, in relation to the construction of first railway tracks in our region and the development of the industry of the 1840s. The dissertation does not only cover the founding persons of the construction company Klein Brothers, but expands also to the reasons of the economic downturn of the entrepreneurial imperium in the second and third generation

Transcriptomics and metatranscriptomics in zooplankton: wave of the future?

Abstract Molecular tools have changed the understanding of zooplankton biodiversity, speciation, adaptation, population genetics and global patterns of connectivity. However, the molecular resources needed to capitalize on these advances continue to be limited in comparison with those available for other eukaryotic plankton. This deficiency could be addressed through an Ocean Zooplankton Open 'Omics Project (Ocean ZOOP) that would generate de novo assembled transcriptomes for hundreds of metazoan plankton species. A collection of comparable reference transcriptomes would generate a new framework for ecological and physiological studies. Defining species niches, identifying optimal habitats, assessing adaptive capacity and predicting changes in phenology are just a few examples of how such a resource could transform studies on zooplankton ecology

Diapause vs. reproductive programs: transcriptional phenotypes in a keystone copepod

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Lenz, P. H., Roncalli, V., Cieslak, M. C., Tarrant, A. M., Castelfranco, A. M., & Hartline, D. K. Diapause vs. reproductive programs: transcriptional phenotypes in a keystone copepod. Communications Biology, 4(1), (2021): 426, https://doi.org/10.1038/s42003-021-01946-0.Many arthropods undergo a seasonal dormancy termed “diapause” to optimize timing of reproduction in highly seasonal environments. In the North Atlantic, the copepod Calanus finmarchicus completes one to three generations annually with some individuals maturing into adults, while others interrupt their development to enter diapause. It is unknown which, why and when individuals enter the diapause program. Transcriptomic data from copepods on known programs were analyzed using dimensionality reduction of gene expression and functional analyses to identify program-specific genes and biological processes. These analyses elucidated physiological differences and established protocols that distinguish between programs. Differences in gene expression were associated with maturation of individuals on the reproductive program, while those on the diapause program showed little change over time. Only two of six filters effectively separated copepods by developmental program. The first one included all genes annotated to RNA metabolism and this was confirmed using differential gene expression analysis. The second filter identified 54 differentially expressed genes that were consistently up-regulated in individuals on the diapause program in comparison with those on the reproductive program. Annotated to oogenesis, RNA metabolism and fatty acid biosynthesis, these genes are both indicators for diapause preparation and good candidates for functional studies.This work was supported by National Science Foundation Grants (NSF) OCE-1459235 and OCE-1756767 to P.H.L., D.K.H. and AE Christie and OPP-1746087 to A.M.T

Immunopeptidomics toolkit library (IPTK): a python-based modular toolbox for analyzing immunopeptidomics data

Background The human leukocyte antigen (HLA) proteins play a fundamental role in the adaptive immune system as they present peptides to T cells. Mass-spectrometry-based immunopeptidomics is a promising and powerful tool for characterizing the immunopeptidomic landscape of HLA proteins, that is the peptides presented on HLA proteins. Despite the growing interest in the technology, and the recent rise of immunopeptidomics-specific identification pipelines, there is still a gap in data-analysis and software tools that are specialized in analyzing and visualizing immunopeptidomics data. Results We present the IPTK library which is an open-source Python-based library for analyzing, visualizing, comparing, and integrating different omics layers with the identified peptides for an in-depth characterization of the immunopeptidome. Using different datasets, we illustrate the ability of the library to enrich the result of the identified peptidomes. Also, we demonstrate the utility of the library in developing other software and tools by developing an easy-to-use dashboard that can be used for the interactive analysis of the results. Conclusion IPTK provides a modular and extendable framework for analyzing and integrating immunopeptidomes with different omics layers. The library is deployed into PyPI at https://pypi.org/project/IPTKL/ and into Bioconda at https://anaconda.org/bioconda/iptkl , while the source code of the library and the dashboard, along with the online tutorials are available at https://github.com/ikmb/iptoolkit

Capital Breeding in a Diapausing Copepod: A Transcriptomics Analysis

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Nucleoporation of dendritic cells: efficient gene transfer by electroporation into human monocyte-derived dendritic cells11Disclaimer: The opinions expressed in this article are those of the author and not necessarily those of the Food and Drug Administration or the U.S. Government. The publication of this article should not be construed as an endorsement or approval of either the product or the company.

AbstractDendritic cells (DCs) are ideal accessory cells in the developing field of gene therapy. Although viral transfection of DCs has become widespread, non-viral transfection of DCs has shown disappointing results. Recently, a new technique for transfecting primary cells has become available – the Amaxa Nucleofector™. Here, we describe the use of this device in the successful non-viral transfection of human monocyte-derived DCs. Using enhanced green fluorescent protein as a reporter gene DCs were transfectable with efficiencies approaching 60%, remaining responsive to lipopolysaccharide-stimulated cytokine production in short-term experiments (though long-term functional assays were hampered by loss of viability). Although these data demonstrate the ease and efficiency with which human monocyte-derived DCs can now be non-virally transfected, they also suggest the limitations of this technology due to the gradual loss of cell viability. The potential use of this system in the development of DC-based cell and gene therapies will be hampered until cell viability can be maintained

Characterizing the tumor microenvironment in rare renal cancer histological types

The tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high-grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann-Whitney and Kruskal-Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53-4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22-5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42-3.9]). Spatial analysis revealed CD3+ T-cell and CD20+ B-cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance-dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies

Clinical Post-SARS-CoV-2 Infection Scenarios in Vaccinated and Non-Vaccinated Cancer Patients in Three German Cancer Centers: A Retrospective Analysis.

COVID-19 vaccines have become an integral element in the protection of cancer patients against SARS-CoV-2. To date, there are no direct comparisons of the course of COVID-19 infection in cancer patients between the pre- and post-vaccine era. We analyzed SARS-CoV-2 infections and their impact on cancer in COVID-19 vaccinated and non-vaccinated patients from three German cancer centers. Overall, 133 patients with SARS-CoV-2 were enrolled in pre- and post-vaccine eras: 84 non-vaccinated and 49 vaccinated, respectively. A mild course of COVID-19 was documented more frequently in vaccinated patients (49% vs. 29%), while the frequency of severe and critical courses occurred in approximately one-half of the non-vaccinated patients (22% vs. 42%, p = 0.023). Particularly, patients with hematologic neoplasms benefited from vaccination in this context (p = 0.031). Admissions to intermediate- and intensive-care units and the necessity of non-invasive and invasive respiratory support were reduced by 71% and 50% among vaccinated patients, respectively. The median length of admission was 11 days for non-vaccinated and 5 days for vaccinated patients (p = 0.002). COVID-19 mortality was reduced by 83% in vaccinated patients (p = 0.046). Finally, the median time from SARS-CoV-2 infection to restarting cancer therapy was 12 and 26 days among vaccinated and non-vaccinated groups, respectively (p = 0.002). Although this study does not have enough power to perform multivariate analyses to account for confounders, it provides data on COVID-19 in non-vaccinated and vaccinated cancer patients and illustrates the potential benefits of COVID-19 vaccines for these patients