GRO.publications
Not a member yet
137257 research outputs found
Sort by
The Odd Couple: Oxidative Coupling of an Iridium(III) Phenylimido Complex
No full textCatalytic arylnitrene transfer often results in catalyst decay via aromatic coupling reactions. We here report a case study for the oxidative coupling of an in situ formed iridium(III) phenyimido complex with a triplet ground state. The nitrenoid species is inherently unstable towards oxidative coupling in para ‐position to give a dinuclear, diphenoquinone‐diiminato bridged Ir II /Ir II complex. Thermochemical, kinetic, and computational examinations show that the CC coupling is driven by abstraction of the weak CH bonds
Antihypertensive medication is not associated with increased disease severity in atopic dermatitis in the TREATgermany registry
No full textBimekizumab plus topical photochemotherapy effective in palmoplantar pustulosis in a patient with hidradenitis suppurativa
No full textModeling immune responses of cattle to Mycobacterium bovis using magnetic bioprinted granulomas
No full textABSTRACT Tuberculosis (TB) remains a threat for human and livestock health. Mycobacteria causing TB are host-adapted pathogens that occasionally spill over into other species. Mycobacterium bovis causes bovine TB, a well-known zoonosis. Mycobacterium tuberculosis is adapted to humans and can occasionally trigger symptomatic infection in cattle. However, immunocompetent cattle are resistant to experimental infection with M. tuberculosis . Hallmarks of TB in susceptible hosts are organized multicellular tissue lesions termed granulomas. In the absence of suitable in vitro systems that enable investigations of bovine tuberculous granuloma, we developed a three-dimensional granuloma model using bovine leukocytes and magnetic cell labeling. This model was termed the in vitro granuloma-like structure (IVGLS). We generated stable IVGLS resembling TB granulomas at the innate stage, composed of macrophages, and at adaptive stages, containing lymphocytes in addition. M. bovis Bacillus Calmette-Guérin (BCG) replicated within IVGLS and triggered the progression of macrophages to foamy phenotypes. Within the IVGLS, the lymphocytes accelerated BCG-induced apoptotic cell death over time. IVGLS released abundant chemoattractants and Th1-associated cytokines and adopted a glycolytically polarized metabolism. Magnetic bioprinted bovine granulomas recapitulate features of TB granulomas and thus facilitate the study of immune responses to mycobacteria, including spatial and temporal mapping, as well as establishing precise cell death patterns within multicellular microenvironments. Deciphering protective immune responses within IVGLS can contribute to vaccine development for bovine TB, and elucidation of resistance mechanisms can facilitate the design of novel interventions for human TB. IMPORTANCE Mycobacterial infections, including bovine tuberculosis (TB), have a profound impact on global health. This is exemplified by zoonotic TB in humans and animal TB, which is a life-threatening disease in livestock and wildlife. Mycobacteria cause the formation of granulomas, which significantly impact disease progression. Therefore, decoding granulomas is essential for an in-depth understanding of immune responses to mycobacteria. Conventional mouse models frequently fail to develop organized granulomas, and the procurement of samples from granulomatous lesions in cattle and humans is challenging, offering limited insights into the course of infection. Most in vitro TB research is confined to two-dimensional cell cultures, which neglect the spatial characteristics and cellular architecture of granulomas in vivo . To address this gap in knowledge, we have developed a novel multicellular in vitro model for TB. Our spheroid granuloma model, derived from bovine leukocytes using nanotechnologies, offers an adaptable platform for deciphering immune events within granulomas.Mycobacterial infections, including bovine tuberculosis (TB), have a profound impact on global health. This is exemplified by zoonotic TB in humans and animal TB, which is a life-threatening disease in livestock and wildlife. Mycobacteria cause the formation of granulomas, which significantly impact disease progression. Therefore, decoding granulomas is essential for an in-depth understanding of immune responses to mycobacteria. Conventional mouse models frequently fail to develop organized granulomas, and the procurement of samples from granulomatous lesions in cattle and humans is challenging, offering limited insights into the course of infection. Most in vitro TB research is confined to two-dimensional cell cultures, which neglect the spatial characteristics and cellular architecture of granulomas in vivo . To address this gap in knowledge, we have developed a novel multicellular in vitro model for TB. Our spheroid granuloma model, derived from bovine leukocytes using nanotechnologies, offers an adaptable platform for deciphering immune events within granulomas.ABSTRACT Tuberculosis (TB) remains a threat for human and livestock health. Mycobacteria causing TB are host-adapted pathogens that occasionally spill over into other species. Mycobacterium bovis causes bovine TB, a well-known zoonosis. Mycobacterium tuberculosis is adapted to humans and can occasionally trigger symptomatic infection in cattle. However, immunocompetent cattle are resistant to experimental infection with M. tuberculosis . Hallmarks of TB in susceptible hosts are organized multicellular tissue lesions termed granulomas. In the absence of suitable in vitro systems that enable investigations of bovine tuberculous granuloma, we developed a three-dimensional granuloma model using bovine leukocytes and magnetic cell labeling. This model was termed the in vitro granuloma-like structure (IVGLS). We generated stable IVGLS resembling TB granulomas at the innate stage, composed of macrophages, and at adaptive stages, containing lymphocytes in addition. M. bovis Bacillus Calmette-Guérin (BCG) replicated within IVGLS and triggered the progression of macrophages to foamy phenotypes. Within the IVGLS, the lymphocytes accelerated BCG-induced apoptotic cell death over time. IVGLS released abundant chemoattractants and Th1-associated cytokines and adopted a glycolytically polarized metabolism. Magnetic bioprinted bovine granulomas recapitulate features of TB granulomas and thus facilitate the study of immune responses to mycobacteria, including spatial and temporal mapping, as well as establishing precise cell death patterns within multicellular microenvironments. Deciphering protective immune responses within IVGLS can contribute to vaccine development for bovine TB, and elucidation of resistance mechanisms can facilitate the design of novel interventions for human TB. IMPORTANCE Mycobacterial infections, including bovine tuberculosis (TB), have a profound impact on global health. This is exemplified by zoonotic TB in humans and animal TB, which is a life-threatening disease in livestock and wildlife. Mycobacteria cause the formation of granulomas, which significantly impact disease progression. Therefore, decoding granulomas is essential for an in-depth understanding of immune responses to mycobacteria. Conventional mouse models frequently fail to develop organized granulomas, and the procurement of samples from granulomatous lesions in cattle and humans is challenging, offering limited insights into the course of infection. Most in vitro TB research is confined to two-dimensional cell cultures, which neglect the spatial characteristics and cellular architecture of granulomas in vivo . To address this gap in knowledge, we have developed a novel multicellular in vitro model for TB. Our spheroid granuloma model, derived from bovine leukocytes using nanotechnologies, offers an adaptable platform for deciphering immune events within granulomas.Mycobacterial infections, including bovine tuberculosis (TB), have a profound impact on global health. This is exemplified by zoonotic TB in humans and animal TB, which is a life-threatening disease in livestock and wildlife. Mycobacteria cause the formation of granulomas, which significantly impact disease progression. Therefore, decoding granulomas is essential for an in-depth understanding of immune responses to mycobacteria. Conventional mouse models frequently fail to develop organized granulomas, and the procurement of samples from granulomatous lesions in cattle and humans is challenging, offering limited insights into the course of infection. Most in vitro TB research is confined to two-dimensional cell cultures, which neglect the spatial characteristics and cellular architecture of granulomas in vivo . To address this gap in knowledge, we have developed a novel multicellular in vitro model for TB. Our spheroid granuloma model, derived from bovine leukocytes using nanotechnologies, offers an adaptable platform for deciphering immune events within granulomas.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Land Mecklenburg-Vorpommer
Longitudinal development and clinical predictors of financial toxicity among radiation oncology patients: final results of the SOCOFIN study
No full textAbstract Purpose Financial toxicity (FT) associated with cancer and its treatment has become increasingly important. This study investigated factors associated with the development of FT during radiation therapy (RT). SOCOFIN was the first longitudinal prospective study to systematically evaluate FT in the context of RT. Methods Financial toxicity was measured with the Comprehensive Score for Financial Toxicity (COST-12) at RT initiation, completion, and at 3 months afterwards. Secondary endpoints included socioeconomic factors, health-related quality of life (EORTC QLQ-C30), depression (PHQ-9), coping mechanisms, and sense of coherence. The data were collected digitally; missing data were estimated using multiple imputation with chained equations. Results Between July 2023 and June 2024, 230 patients were recruited. Analyses were performed on 170 records. During RT, FT did not increase; a slight overall decrease was descriptively observed. Of seven tumor groups, the highest difference in FT at baseline was measured between prostate (median 33) and pelvic cancer patients (median 19), reaching statistical significance (Kruskal–Wallis test, p = 0.01). Nonetheless, tumor entity was not found to be a significant predictor of FT following RT in multivariate linear regression models. While factors associated with FT differed between timepoints, financial difficulties at baseline predicted the occurrence of FT most strongly ( p < 10 −13 ) and persistently. Conclusion Predictors of FT were predominantly socioeconomic, such as baseline financial difficulties, net income, employment stability, and sense of coherence, which superseded tumor- or treatment-specific variables. The findings of this study underscore the necessity of multifactorial, early screening before RT to mitigate FT among radiation oncology patients
Transmission electron microscopy analysis of UV laser implanted gold nanoparticles and their influence on photoluminescence enhancement from silicon nanocrystals
No full textAbstract The photoluminescence of silicon nanocrystals is significantly enhanced via laser-based implantation of gold nanoparticles into silicon suboxide. This study is to explore in detail the nanoscale interactions between silicon nanocrystals embedded in the oxide matrix and gold nanoparticles through transmission electron microscopy. The influence of gold nanoparticle size and distance from the silicon nanocrystals is investigated and correlated with photoluminescence enhancement. A more than threefold enhancement in photoluminescence of silicon nanocrystals is observed, depending on the size and separation distance of the gold nanoparticles, demonstrating the efficiency of this straightforward and rapid laser-based method
Scattering-based super-resolution optical fluctuation imaging
No full textSuper-resolution optical imaging has become a prominent tool in life and material sciences, allowing one to decipher structures at increasingly greater spatial detail. Among the utilized techniques in this field, super-resolution optical fluctuation imaging (SOFI) has proved to be a valuable approach. A major advantage of SOFI is its less restrictive requirements for generating super-resolved images of neighboring nano-structures or molecules, as it only assumes that the detected fluctuating light from neighboring emitters is statistically uncorrelated, but not necessarily separated in time. While most optical super-resolution microscopies depend on signals obtained from fluorescence, they are limited by photobleaching and phototoxicity. An alternative source for optical signals can be acquired by detecting the light scattered from molecules or nanoparticles. However, the application of coherent scattering-based imaging modalities for super-resolution imaging has been considerably limited compared to fluorescence-based modalities. Here, we develop scattering-based super-resolution optical fluctuation imaging (sSOFI), where we utilize the rotation of anisotropic particles as a source of fluctuating optical signals. We discuss the differences in the application of SOFI algorithms for coherent and incoherent imaging modalities and utilize interference microscopy to demonstrate super-resolution imaging of rotating nanoparticle dimers. We present a theoretical analysis of the relevant model systems and discuss the possible effects of cusp artifacts and electrodynamic coupling between nearby nano-scatterers. Finally, we apply sSOFI as a label-free novelty filter that highlights regions with higher activity of biomolecules and demonstrates its use by imaging membrane protrusions of live cells. Overall, the development of optical super-resolution approaches for coherent scattering-based imaging modalities, as described here, could potentially allow for the investigation of biological processes at temporal resolutions and acquisition durations previously inaccessible in fluorescence-based imaging.HORIZON EUROPE European Research Council http://dx.doi.org/10.13039/100019180Israel Science Foundation http://dx.doi.org/10.13039/501100003977National Science Foundation http://dx.doi.org/10.13039/10000000
Donor Variability and Seeding Density Shape NK-Cell Proliferation and Surface Receptor Expression: Insights from an Integrated Phenotypic and Genetic Analysis
No full textNatural killer (NK) cells are promising candidates for adoptive immunotherapy, but their clinical application requires standardized expansion protocols that yield functional cells in sufficient numbers. This study examined how initial seeding density and donor-intrinsic variability affect NK cell proliferation and receptor phenotype during in vitro expansion in a G-Rex® 24-well plate under IL-2 stimulation. NK cells from healthy donors were analyzed longitudinally by flow cytometry, and targeted SNP sequencing of selected receptor genes (IL2RA, IL2RB, FCGR3A, NCR1, KLRK1, and ICAM-1) was performed to assess potential genetic contributions. A seeding density of 2.0 × 106 cells/cm2 promoted high expansion rates and favorable expression of activating receptors including CD16a, NKp46, and NKG2D. Nonetheless, marked inter-donor differences were observed. Some donors exhibited impaired proliferation and aberrant receptor expression, possibly associated with high-priority SNPs and distinct haplotype structures. Others showed robust proliferation despite the absence of identifiable genetic drivers, suggesting the involvement of variants in other genes or non-genetic mechanisms such as epigenetic priming or adaptive NK-cell differentiation. These results highlight the influence of both culture conditions and donor-intrinsic factors on NK-cell expansion outcomes. Integrating phenotypic and genetic analyses may improve the reproducibility and personalization of NK-cell-based manufacturing protocols for therapeutic use
CRISPR/Cas13-Based Anti-RNA Viral Approaches
No full textRNA viruses pose significant threats to global health, causing diseases such as COVID-19, HIV/AIDS, influenza, and dengue. These viruses are characterized by high mutation rates, rapid evolution, and the ability to evade traditional antiviral therapies, making effective treatment and prevention particularly challenging. In recent years, CRISPR/Cas13 has emerged as a promising antiviral tool due to its ability to specifically target and degrade viral RNA. Unlike conventional antiviral strategies, Cas13 functions at the RNA level, providing a broad-spectrum and programmable approach to combating RNA viruses. Its flexibility allows for rapid adaptation of guide RNAs to counteract emerging viral variants, making it particularly suitable for highly diverse viruses such as SARS-CoV-2 and HIV. This review discusses up-to-date applications of Cas13 in targeting a wide range of RNA viruses, including SARS-CoV-2, HIV, dengue, influenza, and other RNA viruses, focusing on its therapeutic potential. Preclinical studies have demonstrated Cas13’s efficacy in degrading viral RNA and inhibiting replication, with applications spanning prophylactic interventions to post-infection treatments. However, challenges such as collateral cleavage, inefficient delivery, potential immunogenicity, and the development of an appropriate ethical framework must be addressed before clinical translation. Future research should focus on optimizing crRNA design, improving delivery systems, and conducting rigorous preclinical evaluations to enhance specificity, safety, and therapeutic efficacy. With continued advancements, Cas13 holds great promise as a revolutionary antiviral strategy, offering novel solutions to combat some of the world’s most persistent viral threats
The HETDEX Survey: Probing Neutral Hydrogen in the Circumgalactic Medium of ∼88,000 Ly α Emitters
No full textAbstract We explore the neutral hydrogen (H i ) gas around 1.9 < z < 3.5 Lyman alpha emitters (LAEs) from the Hobby–Eberly Telescope Dark Energy Experiment using faint Ly α absorption. This absorption is the result of H i in the halo of the LAE scattering Ly α photons from the integrated light of background galaxies along the line of sight. We stack millions of spectra from regions around ∼88,000 LAEs, in order to focus on the physics of the gas at large radii. The extensive number of fiber spectra contributing to the stacks ensures a sufficient signal-to-noise ratio to detect the faint Ly α absorption, which would otherwise be buried within the noise. We detect absorption out to a projected ∼350 kpc around an average LAE at z ∼ 2.5. We use these results to create an empirical radial W λ (Ly α ) profile around LAEs. Comparison with numerical simulations reveals a profile similar to the empirical one within this region. Compared to previous studies, the profile is similar but modestly higher. We also outline a simple physical picture motivated by the observed trends in the data. We plan to quantify this radial profile as a function of redshift, local density, and Ly α luminosity, to explore the relationship between LAE environments and H i distribution.Karl Gebhard