https://hdl.handle.net/20.500.14178/908 Mon, 15 Jun 2026 18:17:09 GMT 2026-06-15T18:17:09Z https://hdl.handle.net/20.500.14178/3829 Host Diet Preference Drives Diversity and Composition of Gut Microbiota in Captive Birds Kubovčiak, Jan; Kreisinger, Jakub Gut microbiota (GM) plays a vital role in host physiology, yet our understanding of the factors driving GM variability in birds remains incomplete. Previous research has provided mixed support for different predictors of bird GM variation, possibly due to the high heterogeneity of avian GM combined with the strong influence of environmental factors on its composition. To suppress the role of these confounding factors, we focused on interspecific GM variation in birds from captive populations, with the aim of clarifying the role of diet and phylogeny. Using 16S rRNA amplicon sequencing, we analysed the GM of 36 bird species from 14 orders, focusing on variability in GM diversity and distribution of individual bacterial constituents. We found that host phylogeny only had limited influence on GM diversity and composition. On the other hand, we identified diet preference of host species as a significant predictor of GM diversity and composition, with herbivorous species exhibiting higher GM alpha diversity than carnivorous species. Furthermore, we observed a converging pattern of GM composition among phylogenetically unrelated carnivorous species, driven by increased abundance of microbial taxa that mostly had an undetermined role in host physiology. This contrasts with obligatory anaerobic bacteria from the phylum Bacteroidetes, and other commensal bacteria, observed with increased abundance in hosts preferring carbohydrate-rich vegetarian diets. Overall, our findings emphasise host diet preference as an important factor determining GM diversity in birds, explaining the convergence of GM composition in phylogenetically distant host species. Wed, 01 Jan 2025 00:00:00 GMT https://hdl.handle.net/20.500.14178/3829 2025-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3819 Effectiveness, immunogenicity and safety of human papillomavirus vaccination in non-HIV immunocompromised individuals: a systematic review Kapp, Philipp; Siemens, Waldemar; Gorenflo, Lea; Schulz, Henriette; Chi, Yuan; Röbl-Mathieu, Marianne; Askar, Mona; Brotons, María; Andersen, Peter Henrik; Konopnicki, Deborah; Lynch, Judi; Ruţă, Simona; Saare, Liisa; Swennen, Béatrice; Tachezy, Ruth; Takla, Anja; Učakar, Veronika; Vänskä, Simopekka; Zavadska, Dace; Ali, Karam Adel; Olsson, Kate; Harder, Thomas; Meerpohl, Joerg Johannes Background: Immunocompromised individuals may be at an increased risk for human papillomavirus (HPV)-related diseases and cancers, but the protective benefit of HPV vaccination remains unclear. In this systematic review and meta-analysis we assessed the efficacy, effectiveness, immunogenicity, and safety of HPV vaccination in non-HIV immunocompromised individuals. Methods We searched MEDLINE, Embase and CENTRAL (26 November 2025) for randomised and non-randomised studies comparing vaccinated immunocompromised individuals to unvaccinated immunocompromised individuals (comparison 1). Additionally, we considered studies comparing vaccinated immunocompromised individuals to vaccinated individuals with a different disease or condition (comparison 2) or vaccinated healthy individuals (comparison 3). We assessed the risk of bias (ROBINS-I) and the certainty of evidence (CoE; GRADE) for prioritised outcomes including cervical precancer or cancer, HPV types 16 and 18 immunogenicity, and serious adverse events. We pooled studies using the random-effect meta-analyses model. This study is registered in PROSPERO, CRD42024554574.Findings: We identified 24 non-randomised studies, comprising various immunocompromised populations (e.g. solid organ transplant recipients or autoimmune diseases). One case-control study compared vaccinated immunocompromised with unvaccinated immunocompromised individuals (comparison 1), reporting rate ratios near the null effect for effectiveness against cervical intraepithelial neoplasia (CIN) 2+ (0.96, 95% CI 0.68-1.37) and CIN 3+ (0.96, 95% CI 0.54-1.70), although the CoE was very low. Most studies assessed immunogenicity, generally showing high seropositivity rates (median at 7 months 95.8%, IQR 89.2-99.7; 13 studies) in immunocompromised individuals compared to other immunocompromised or healthy individuals, with a CoE ranging from low to very low (comparisons 2 and 3). Antibody titres were generally high but varied across immunocompromised populations. Serious adverse events were rare and deemed unrelated to vaccination.Interpretation: HPV vaccination appears immunogenic and safe for non-HIV immunocompromised individuals, but the CoE is low to very low and heterogeneity across populations limits generalisability of the findings and pooled analyses. Given the unclear correlate of protection and lack of standardisation of assays for antibody measurement, immunogenicity data should be interpreted cautiously. Future studies should assess HPV-associated precancerous lesions and cancers, and explore subgroups effects, including differences in sex, age, immunosuppressive treatments, and dosing. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3819 2026-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3799 Forward Modeling in ERT Employing Resistor Network - Alternative to Standard Approaches Jirků, Jaroslav; Vilhelm, Jan This paper uses an orthogonal resistor network model instead of traditional finite-difference or finite-element methods to explore an alternative approach to forward modeling in Electrical Resistivity Tomography (ERT). A resistor network is advantageous for modeling high-contrast resistivity environments, particularly in crystalline rock scenarios with thin conductive fractures. The key idea is to represent the resistivity problem as a network of resistors, where each resistor corresponds to a unit cell edge with assigned resistance values. The study compares this approach with existing numerical methods and analytical solutions for 2D conductive dipping faults, showing that the resistor network method produces comparable results for shallow depths while offering better resolution for thin conductive fractures. This study demonstrates that a resistor network can serve as an auxiliary tool for qualitatively assessing the effects of thin conductive fractures in crystalline rock environments or masonry. Wed, 01 Jan 2025 00:00:00 GMT https://hdl.handle.net/20.500.14178/3799 2025-01-01T00:00:00Z https://hdl.handle.net/20.500.14178/3798 CD64-Targeted Polymer-Drug Conjugates Exploit Cathepsin K-Dependent Payload Release for Selective Elimination of Immunosuppressive Macrophages Musil, Dominik; Krhutová, Markéta; Blažková, Kristýna; Kramná, Anežka; Brázdová, Andrea; Výmolová, Barbora; Houdová Megová, Magdalena; Hadzima, Martin; Kryštůfek, Robin; Šubr, Vladimír; Kostka, Libor; Etrych, Tomáš; Ormsby, Tereza; Sácha, Pavel; Ambramson, Jakub; Konvalinka, Jan Selective depletion of immunosuppressive macrophages in the tumor microenvironment is a promising strategy in cancer therapy. CD64 is broadly expressed on myeloid cells, including both pro-inflammatory M1-like and immunosuppressive M2-like macrophages that resemble tumor-associated macrophages (TAMs), and thus represents an attractive entry receptor for targeted payload delivery. We developed HPMA-based CD64-targeted polymer-drug conjugates (CD64-TPDCs) that combine multivalent receptor engagement with enzyme-responsive payload release. These copolymers are decorated with the CD64-binding cyclic peptide cp33 and carry the cytotoxic payload mertansine (DM1) bound via cathepsin-cleavable peptide linkers. Multivalent cp33 presentation on the polymer markedly increased the apparent affinity for human CD64, resulting in subnanomolar binding and selective recognition of CD64-expressing cells, significantly improving the binding potency of monovalent cp33 peptide. In polarized M2-like human monocyte-derived macrophages (MDMs), we showed that cytotoxic Gly-Phe-Leu-Gly-DM1 CD64-TPDCs selectively induced apoptosis. In contrast, M1-like MDMs were largely spared despite expressing higher levels of CD64. In M2-like MDMs, CD64-TPDCs rapidly accumulated in lysosomes, whereas in M1-like cells, they remained largely confined to endosomes. To elucidate the basis of this selectivity, we profiled expression of cathepsins in polarized MDMs. We found that M2-like MDMs display substantially higher levels of cathepsin K, establishing a model in which cathepsin K is the major protease responsible for Gly-Phe-Leu-Gly linker cleavage and DM1 release in M2-like macrophages. These findings demonstrate that CD64-TPDCs can be engineered to exploit subset-specific trafficking and cathepsin K-dependent linker cleavage for the selective elimination of M2-like macrophages. This work provides a generalizable design principle for stimuli-responsive PDCs that may actively target immunosuppressive myeloid cells in tumors. Thu, 01 Jan 2026 00:00:00 GMT https://hdl.handle.net/20.500.14178/3798 2026-01-01T00:00:00Z