@article{rutschlin_unexpected_2026,

title = {Unexpected Dual Function of Plant YUCCA Enzymes Links Chlorophyll Catabolism to Auxin Homeostasis},

author = {Sina Rütschlin and Lei Zhang and Cornelia A. Karg and Michael Zwerger and Johanna M. Gostner and Simone Moser and Robin Teufel},

doi = {10.1002/anie.202525568},

issn = {1521-3773},

year  = {2026},

date = {2026-01-01},

journal = {Angewandte Chemie},

pages = {e25568},

abstract = {Chlorophyll (Chl) metabolism is pivotal to both photosynthesis and plant senescence and represents one of the most fundamental biological processes on Earth with an estimated annual turnover of 1 billion tons. During Chl degradation, only early catabolites and corresponding enzymes are well characterized, whereas for late-stage degradation products it remains often unclear if their formation involves specific enzymes. Here, we report that the ubiquitous YUCCA10 enzymes from the YUCCA flavin-containing monooxygenase (FMOs) family in land plants, normally implicated in the biosynthesis of indole-3-acetic acid (IAA) as the primary form of auxin, surprisingly catalyze the production of several predominant Chl catabolites via mechanistically distinct Baeyer-Villiger oxidation and subsequent hydrolytic γ-lactam-forming deformylation reactions. These historically postulated but hitherto undiscovered Chl degradation steps on several high molecular weight chl catabolites were verified for YUCCA10 from Vitis vinifera and Coffea arabica, while YUCCA10 from Arabidopsis thaliana lacked this activity. In contrast, all three homologs were able to catalyze the rate-limiting key step in IAA biosynthesis, akin to other YUCCA enzymes. Interestingly, Chl catabolites at physiological concentrations impaired IAA formation by YUCCA10 in vitro, suggesting a key role in leaf senescence through enzymatic feedback regulation of auxin levels.},

note = {Place: International ed. in English},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{parrakova_validated_2026,

title = {A Validated Method for the Simultaneous Measurement of Tryptophan, Kynurenine, Phenylalanine, and Tyrosine by High-Performance Liquid Chromatography–Ultraviolet/Fluorescence Detection in Human Plasma and Serum},

author = {Lucia Parráková and Cornelia A. Karg and Stefanie Hofer and Pablo Monfort-Lanzas and Celina Wilgermein and Kevin Allmer and Sabine Scholl-Bürgi and Anita Siller and Harald Schennach and Simon Geisler and Dietmar Fuchs and Thomas K. Felder and Johanna M. Gostner},

url = {https://doi.org/10.1021/acsomega.5c07457},

doi = {10.1021/acsomega.5c07457},

year  = {2026},

date = {2026-01-01},

urldate = {2026-01-19},

journal = {ACS Omega},

abstract = {Aromatic amino acids are precursors of neurotransmitters and immunomodulatory molecules, and their catabolism is dysregulated in various disorders associated with inflammation. This dysregulation often correlates with disease stage, symptom severity, comorbidities, quality of life, and cognitive performance, making its measurement valuable for research, diagnostics, and personalized monitoring. We developed a rapid, reliable, and cost-effective HPLC method for the simultaneous quantification of phenylalanine, tyrosine, tryptophan, and kynurenine in human serum and plasma. After protein precipitation, analytes were separated on a reversed-phase C18 column under isocratic conditions. Detection was performed based on intrinsic fluorescence for tryptophan, phenylalanine, and tyrosine and on UV absorption for kynurenine and the internal standard nitrotyrosine. The method showed linearity (R2 > 0.99) over 0.31–20 μM for kynurenine, 1.56–200 μM for phenylalanine, 0.08–200 μM for tryptophan, and 0.78–200 μM tyrosine. Limits of detection were 0.01 μM for tryptophan,0.08 μM, 0.08 μM for tyrosine and kynurenine, and 0.39 μM for phenylalanine. Precision and accuracy were within 15%, and recovery rates ranged from 98 to 100%. Samples remained stable after processing and after three freeze–thaw cycles. Interlaboratory testing confirmed the reproducibility of the results. This validated method enables sensitive, accurate, and simultaneous quantification of key aromatic amino acids, providing a practical alternative to LC–MS/MS for routine diagnostics and biomarker studies.},

note = {Publisher: American Chemical Society},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{robertson_increased_2025,

title = {Increased immune activation in people living with HIV on antiretroviral therapy but not when compared with persons on HIV preexposure prophylaxis},

author = {Josefina Robertson and Arvid Edén and Aylin Yilmaz and Lars-Magnus Andersson and Lars Hagberg and Kristina Nyström and Staffan Nilsson and Carl-Johan Treutiger and Petra Tunbäck and Johanna M. Gostner and Henrik Zetterberg and Magnus Gisslén},

url = {https://www.tandfonline.com/doi/full/10.1080/23744235.2025.2515157},

doi = {10.1080/23744235.2025.2515157},

issn = {2374-4235, 2374-4243},

year  = {2025},

date = {2025-11-01},

urldate = {2026-01-26},

journal = {Infectious Diseases},

volume = {57},

number = {11},

pages = {1028–1035},

abstract = {BACKGROUND: Residual immune activation is common in people living with HIV (PWH) despite antiretroviral therapy (ART) and may be associated with HIV-specific, as well as lifestyle-related factors. 

OBJECTIVE: We aimed to investigate markers of immune activation and neuronal injury in PWH on ART compared with controls with similar lifestyle. 

METHODS: Cerebrospinal fluid (CSF) and blood were collected from 50 men who have sex with men (MSM) with HIV on ART, 50 HIV-negative MSM on preexposure prophylaxis (PrEP), and 25 HIV-negative controls without PrEP. β2-microglobulin, neopterin, and neurofilament light protein (NfL) were analyzed. Cytomegalovirus and herpes simplex virus-2 serostatus, as well as sexually transmitted bacterial infections were registered. 

RESULTS: Serum and CSF β2-microglobulin and neopterin did not differ significantly between MSM with HIV and MSM on PrEP. However, both groups had significantly higher serum levels of β2-microglobulin and neopterin compared with HIV-negative controls without PrEP. Age-adjusted CSF NfL levels were also similar in MSM with HIV and MSM on PrEP, but higher than in controls without PrEP. A recent syphilis infection was associated with increased immune activation in CSF and blood. 

CONCLUSION: Increased levels of immune activation and neuronal injury markers were found in virologically suppressed MSM with HIV and MSM on PrEP compared with controls. These findings imply that other factors than HIV contribute to the residual immune activation and impact on neurons observed in MSM with HIV on ART, and emphasize the importance of appropriate controls with similar lifestyle in studies of biomarkers in PWH.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hammerle_photoprotective_2025,

title = {Photoprotective mycosporine-like amino acids in different organs of Baltic flatfish species revealed by targeted and untargeted metabolomics analyses},

author = {Fabian J. Hammerle and Romina Schöpf and Cornelia A. Karg and Uwe Krumme and Johanna M. Gostner and Ulf Karsten and Markus Ganzera},

url = {https://www.frontiersin.org/journals/marine-science/articles/10.3389/fmars.2025.1688685/full},

doi = {10.3389/fmars.2025.1688685},

issn = {2296-7745},

year  = {2025},

date = {2025-10-01},

urldate = {2025-10-26},

journal = {Frontiers in Marine Science},

volume = {12},

abstract = {Coastal marine organisms are often exposed to high levels of biologically harmful ultraviolet radiation (UVR), the most photochemically reactive waveband of sunlight. It is well known that marine organisms at higher trophic levels, such as fish, enhance their UV protection by accumulating UV-protective metabolites from their diet, as primary producers can effectively synthesize these compounds. Among the best studied natural UV-sunscreens in marine organisms are mycosporine-like amino acids (MAAs). They are known for their high molar extinction coefficients in the UVR-region along with pronounced photo- and thermal stability. In the present study we investigated the qualitative and quantitative MAA distribution in organs (eyes, gills, heart, intestine, kidneys, liver, skin, and stomach) of three flatfish species from the Baltic Sea, the benthivorous European flounder (Platichthys flesus) and European plaice (Pleuronectes platessa), and the piscivorous turbot (Scophthalmus maximus), using state-of-the-art analytical methods. Most of the analyzed organ samples contained the MAAs palythine, asterina-330, porphyra-334, usujirene, and palythene at concentrations sufficient for reliable detection and quantification using an established HPLC-UV method. Additionally, in a few samples also shinorine and mycosporine-methylamine-threonine were found. The highest MAA contents (0.04 to 0.25 mg g-1 dry weight) occurred in the eyes of the three fish species, while the other organs exhibited much lower but still detectable concentrations. Our data support the assumed trophic transfer of MAAs from primary producers via the food web to fish. For the first time we show that MAAs are not only found in the eyes but also in internal organs that possibly represent transfer points from the digestive tract to UV-sensitive tissues. The underlying mechanisms are, however, still unknown.},

note = {Publisher: Frontiers},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nadegger_characterization_2025,

title = {Characterization of Phyllobilins in Hops: Antioxidant and Potentially Bitter Senescence-Related Metabolites},

author = {Christian Nadegger and Patricia Frei and Christian A. Elvert and Cornelia A. Karg and Johanna M. Gostner and Jonathan S. Lindsey and Christoph R. Kreutz and Stefan Schwaiger and Thomas Müller and Simone Moser},

url = {https://pubs.acs.org/doi/10.1021/acs.jafc.5c03549},

doi = {10.1021/acs.jafc.5c03549},

issn = {0021-8561, 1520-5118},

year  = {2025},

date = {2025-07-01},

urldate = {2026-01-26},

journal = {Journal of Agricultural and Food Chemistry},

volume = {73},

number = {28},

pages = {17637–17645},

abstract = {Hops is of high relevance to the food sector, and increasingly valued as medicinal plant. Its complex phytochemistry includes phenolic compounds and bitter prenylated polyketides, but phyllobilins─bioactive linear tetrapyrroles from chlorophyll catabolism─remain underexplored. In this work, several dioxobilin-type phylloleucobilins (DPleBs) and phylloxanthobilins (DPxBs) were identified in yellowish leaves of common hops (Humulus lupulus). Isolation from 107 g of leaves yielded 0.24 mg of Hl-DPleB-28 and 0.80 mg of Hl-DPxB-31. Structural elucidation via UV/vis, HR-MS2, and NMR confirmed those as new phyllobilins, featuring an unusual hydroxylation motif, indicating an uncharacterized metabolic pathway. Hl-DPxB constituted about 40% of HPLC peak areas at 420 nm in yellow leaves, suggesting its significant role in the visual senescence of hops. Hl-DPxB-31 possessed high antioxidative activity, comparable to quercetin. A virtual tool predicted over 60% bitterness probability. These findings expand the phytochemical profile of hops and highlight potential for upcycling leaf waste.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{seizer_case_2025,

title = {Case Report: Endocrine, immune and disease dynamics in a patient with rheumatoid arthritis during flare and medication change},

author = {Lennart Seizer and Johanna M. Gostner and Christoph Garbers and Melina Licht and Sebastian Sager and Andreas Brandl and Christian Schubert},

url = {https://www.frontiersin.org/articles/10.3389/fimmu.2025.1491475/full},

doi = {10.3389/fimmu.2025.1491475},

issn = {1664-3224},

year  = {2025},

date = {2025-05-01},

urldate = {2026-01-26},

journal = {Frontiers in Immunology},

volume = {16},

pages = {1491475},

abstract = {Objective 

 Rheumatoid arthritis (RA) is a chronic autoimmune disease of mostly unknown etiology and pathophysiology. In this integrative single-case study on a patient with RA, we had the unique opportunity to closely monitor the individual dynamics of endocrine, immune and disease variables during a naturally occurring flare-up and subsequent medication change. 

 Methods 

 The 59-year-old female RA patient collected her entire urine over 30 days in 12-h intervals (60 consecutive measurements in total). Subsequently, cortisol, interleukin-6 (IL-6), orosomucoid-2 (ORM-2), neopterin and creatinine levels were determined in the urine samples. Further, each morning and evening, the patient completed the DIARI, a set of questionnaires on variables such as perceived pain, perceived RA disease activity and emotional states. Once a week, the patient was interviewed online and had an appointment with her rheumatologist, in which several indices of RA disease activity were determined: SDAI, CDAI and DAS28. From these data various time series were constructed for statistical analysis. 

 Results 

 RA disease state increased from low to high activity during the first 12 study days. Thereupon, the medication was changed, which proved effective in reducing RA disease activity. However, the levels of urinary neopterin, urinary IL-6 and urinary ORM-2 did not show any response, neither to the increasing disease activity nor the medication change. The patient’s daily reports on pain, RA disease activity, emotional states and body temperature, however, mirrored the course of the rheumatologic indices. 

 Conclusion 

 This integrative single-case study clearly demonstrated the importance of process analysis for the evaluation of therapeutic measures in RA. In the studied patient, urinary levels of neopterin, IL-6 and ORM-2 were not found to be appropriate biomarkers of short-term fluctuations in RA disease activity. Instead, the results reported by the patient proved to be a useful tool for ambulatory and longitudinal monitoring of RA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hofer_myrobalan_2025,

title = {Myrobalan Fruit Extracts Modulate Immunobiochemical Pathways In Vitro},

author = {Stefanie Hofer and Marcel Jenny and Angela Klein and Kathrin Becker and Lucia Parráková and Florian Überall and Markus Ganzera and Dietmar Fuchs and Hubert Hackl and Pablo Monfort-Lanzas and Johanna M. Gostner},

url = {https://www.mdpi.com/2076-3921/14/3/350},

doi = {10.3390/antiox14030350},

issn = {2076-3921},

year  = {2025},

date = {2025-03-01},

urldate = {2026-01-26},

journal = {Antioxidants},

volume = {14},

number = {3},

pages = {350},

abstract = {Myrobalan fruits are important ingredients of traditional remedies, such as the Ayurvedic formulation Triphala or the Tibetan formulation Bras bu 3. Myrobalan-containing remedies are described to have positive effects on metabolism, the cardiovascular system, and the immune system. The chemical composition of botanical mixtures can be very complex, and it is often impossible to identify individual compounds as specific active ingredients, which suggests a multi-target mode of action. In this in vitro study, the effect of myrobalan extracts in human cell models was investigated to gain more information about the molecular mechanism of action and to find possible synergistic effects. Direct and indirect antioxidant effects were investigated, and the activation of immunobiochemical metabolic pathways involved in the cellular immune response was examined in cell lines treated with extracts of the fruits of Phyllanthus emblica, Terminalia chebula and Terminalia bellirica, as well as a combination of them. In particular, a synergistic effect on the activation of the endogenous antioxidant defence system was observed with the combined treatment of the three fruit extracts. An integrated transcriptome analysis of cells treated with a combination of fruit extracts confirmed an effect on immune pathways, oxidative stress, and detoxification processes. This study shows the modulation of various signalling pathways and cellular processes that may be part of the multi-target mechanism of individual and combined myrobalan fruit extracts. Although the results are limited to in vitro data, they contribute to a better understanding of how botanical mixtures work and provide hypotheses for further research.},

note = {Place: Switzerland},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ulfhammer_asymptomatic_2025,

title = {Asymptomatic Cerebrospinal Fluid HIV-1 Escape: Incidence and Consequences.},

author = {Gustaf Ulfhammer and Aylin Yilmaz and Åsa Mellgren and Erika Tyrberg and Erik Sörstedt and Lars Hagberg and Johanna Gostner and Dietmar Fuchs and Henrik Zetterberg and Staffan Nilsson and Kristina Nyström and Arvid Edén and Magnus Gisslén},

doi = {10.1093/infdis/jiae555},

issn = {1537-6613 0022-1899},

year  = {2025},

date = {2025-02-01},

journal = {The Journal of infectious diseases},

volume = {231},

number = {2},

pages = {e429–e437},

abstract = {BACKGROUND: The incidence and clinical relevance of asymptomatic cerebrospinal fluid escape (CSFE) during antiretroviral therapy (ART) is uncertain. We examined the impact and incidence of asymptomatic CSFE in a Swedish HIV cohort. METHODS: Neuroasymptomatic people with HIV (PWH) who have been on ART for at least 6 months with suppressed plasma viral load were followed longitudinally. CSFE was defined as either increased CSF HIV-1 RNA with concurrent plasma suppression or CSF HIV-1 RNA exceeding that in plasma when both were quantifiable. Paired CSF and plasma were analyzed for HIV-1 RNA, neopterin, neurofilament light protein (NfL), white blood cell (WBC) count, and albumin ratio. RESULTS: Asymptomatic CSFE (cutoff 50 copies/mL) was found in 4 of 173 PWH (2%) and 5 of 449 samples (1%). The corresponding proportions were 8% of PWH and 4% for samples using a 20 copies/mL cutoff for CSF HIV-1 RNA. CSFE samples (cutoff 20 copies/mL) had a 25% higher geometric mean of CSF neopterin (P = .01) and 8% higher albumin ratio (P = .04) compared to samples without CSFE. No differences were observed in CSF NfL levels (P = .8). The odds ratio for increased CSF WBC (≥ 3 cells/μL) in samples with CSFE was 3.9 (P = .004), compared to samples without elevated CSF viral load. CONCLUSIONS: Asymptomatic CSFE was identified in only 4 (2%) PWH, with no cases of continuous CSFE observed. Increased CSF HIV-1 RNA was associated with biomarkers of CNS immune activation and blood-brain barrier impairment, but not with biomarkers of neuronal injury.},

note = {Place: United States},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{burtscher_interplay_2025,

title = {The interplay of NAD and hypoxic stress and its relevance for ageing},

author = {Johannes Burtscher and Vanna Denti and Johanna M. Gostner and Alexander Kh Weiss and Barbara Strasser and Katharina Hüfner and Martin Burtscher and Giuseppe Paglia and Martin Kopp and Tobias Dünnwald},

url = {https://linkinghub.elsevier.com/retrieve/pii/S1568163724004641},

doi = {10.1016/j.arr.2024.102646},

issn = {15681637},

year  = {2025},

date = {2025-02-01},

urldate = {2026-01-26},

journal = {Ageing Research Reviews},

volume = {104},

pages = {102646},

abstract = {Nicotinamide adenine dinucleotide (NAD) is an essential regulator of cellular metabolism and redox processes. NAD levels and the dynamics of NAD metabolism change with increasing age but can be modulated via the diet or medication. Because NAD metabolism is complex and its regulation still insufficiently understood, achieving specific outcomes without perturbing delicate balances through targeted pharmacological interventions remains challenging. NAD metabolism is also highly sensitive to environmental conditions and can be influenced behaviorally, e.g., by exercise. Changes in oxygen availability directly and indirectly affect NAD levels and may result from exposure to ambient hypoxia, increased oxygen demand during exercise, ageing or disease. Cellular responses to hypoxic stress involve rapid alterations in NAD metabolism and depend on many factors, including age, glucose status, the dose of the hypoxic stress and occurrence of reoxygenation phases, and exhibit complex time-courses. Here we summarize the known determinants of NAD-regulation by hypoxia and evaluate the role of NAD in hypoxic stress. We define the specific NAD responses to hypoxia and identify a great potential of the modulation of NAD metabolism regarding hypoxic injuries. In conclusion, NAD metabolism and cellular hypoxia responses are strongly intertwined and together mediate protective processes against hypoxic insults. Their interactions likely contribute to age-related changes and vulnerabilities. Targeting NAD homeostasis presents a promising avenue to prevent/treat hypoxic insults and - conversely - controlled hypoxia is a potential tool to regulate NAD homeostasis.},

note = {Place: England},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{gostner_41th_2025,

title = {41th International Winter-Workshop Clinical, Chemical and Biochemical Aspects of Pteridines and Related Topics Innsbruck, Austria, February 5th to 7th, 2025},

author = {Johanna M. Gostner and Simone Moser and Thomas K. Felder and Andrea Griesmacher and Günter Weiss and Bohuslav Melichar},

url = {https://www.degruyterbrill.com/document/doi/10.1515/pteridines-2025-0058/html?utm_source=researchgate.net&utm_medium=article},

doi = {10.1515/pteridines-2025-0058},

issn = {2195-4720},

year  = {2025},

date = {2025-01-01},

urldate = {2026-01-19},

journal = {Pteridines},

volume = {36},

number = {1},

abstract = {Article 41th International Winter-Workshop Clinical, Chemical and Biochemical Aspects of Pteridines and Related Topics Innsbruck, Austria, February 5th to 7th, 2025 was published on January 1, 2025 in the journal Pteridines (volume 36, issue 1).},

note = {Publisher: De Gruyter},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{allmer_validated_2025,

title = {Validated HPLC-MS/MS quantification of melatonin in human breast milk from mothers of preterm infants confirms circadian rhythmicity},

author = {Kevin Allmer and Johanna Pichler and Emma Lanzinger and Johanna M. Gostner and Silke Häusler and Thomas K. Felder},

url = {https://www.degruyterbrill.com/document/doi/10.1515/pteridines-2025-0059/html?utm_source=researchgate.net&utm_medium=article},

doi = {10.1515/pteridines-2025-0059},

issn = {2195-4720},

year  = {2025},

date = {2025-01-01},

urldate = {2026-01-19},

journal = {Pteridines},

volume = {36},

number = {1},

abstract = {Melatonin in human breast milk follows a circadian rhythmicity and serves as a crucial chronobiological signal for neonatal development. Preterm infants are particularly vulnerable to melatonin deficiency due to the immature pineal gland function. Accurate analytical methods are essential for characterizing temporal patterns and assessing clinical relevance. We developed and validated a sensitive LC-MS/MS method for melatonin quantification in breast milk using liquid-liquid extraction with ethyl acetate. The method employed melatonin-d4 as internal standard and scheduled multiple reaction monitoring. Validation followed Eurachem and FDA guidelines and the method was applied to paired daytime and nighttime breast milk samples from mothers of preterm infants ( n = 80). The method demonstrated excellent analytical performance with an LLOQ of 4.8 pg/ml, intraday and interday precision <5 %, and 97 % extraction efficiency. Nighttime melatonin concentrations (27.5 ± 16.8 pg/ml) were significantly higher than daytime levels (9.0 ± 10.0 pg/ml, p < 0.0001). Circadian variation was maintained across all lactational stages (colostrum, transitional, and mature milk). This validated LC-MS/MS method enables reliable quantification of physiological melatonin concentrations in breast milk and confirms circadian rhythmicity across lactation stages. The simplified sample preparation and robust performance make it suitable for clinical studies investigating chrononutrition and neonatal chronobiological development.},

note = {Publisher: De Gruyter},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{karg_extracellular_2025b,

title = {Extracellular spermidine attenuates tryptophan breakdown in mitogen-stimulated peripheral human mononuclear blood cells},

author = {Cornelia A. Karg and Rebecca Lisandrelli and Günther Schider and Pablo Monfort-Lanzas and Anita Siller and Harald Schennach and Simone Moser and Dietmar Fuchs and Johanna M. Gostner},

url = {https://www.degruyterbrill.com/document/doi/10.1515/pteridines-2025-0054/html},

doi = {10.1515/pteridines-2025-0054},

issn = {2195-4720},

year  = {2025},

date = {2025-01-01},

urldate = {2025-10-17},

journal = {Pteridines},

volume = {36},

number = {1},

abstract = {Polyamines, particularly spermidine, play a vital role in regulating cellular functions and influencing processes such as proliferation, ageing, and immune modulation. This study explores the effects of spermidine on the immunoregulatory pathway of tryptophan breakdown, which is mediated by indoleamine 2,3-dioxygenase 1 (IDO-1), as well as on neopterin synthesis, in peripheral blood mononuclear cells. Spermidine treatment was found to suppress IDO-1 activity in mitogen-stimulated cells in a dose-dependent manner without affecting neopterin synthesis. This suppressive effect on tryptophan breakdown contributes to the debate surrounding the health-promoting antioxidant properties of spermidine. However, the divergent regulation of the two immunobiochemical pathways investigated, which share common upstream signalling events, requires further exploration.},

note = {Publisher: De Gruyter},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{karg_extracellular_2025,

title = {Extracellular spermidine attenuates tryptophan breakdown in mitogen-stimulated peripheral human mononuclear blood cells},

author = {Cornelia A. Karg and Rebecca Lisandrelli and Günther Schider and Pablo Monfort-Lanzas and Anita Siller and Harald Schennach and Simone Moser and Dietmar Fuchs and Johanna M. Gostner},

url = {https://www.degruyterbrill.com/document/doi/10.1515/pteridines-2025-0054/html},

doi = {10.1515/pteridines-2025-0054},

issn = {2195-4720},

year  = {2025},

date = {2025-01-01},

urldate = {2025-10-17},

journal = {Pteridines},

volume = {36},

number = {1},

abstract = {Polyamines, particularly spermidine, play a vital role in regulating cellular functions and influencing processes such as proliferation, ageing, and immune modulation. This study explores the effects of spermidine on the immunoregulatory pathway of tryptophan breakdown, which is mediated by indoleamine 2,3-dioxygenase 1 (IDO-1), as well as on neopterin synthesis, in peripheral blood mononuclear cells. Spermidine treatment was found to suppress IDO-1 activity in mitogen-stimulated cells in a dose-dependent manner without affecting neopterin synthesis. This suppressive effect on tryptophan breakdown contributes to the debate surrounding the health-promoting antioxidant properties of spermidine. However, the divergent regulation of the two immunobiochemical pathways investigated, which share common upstream signalling events, requires further exploration.},

note = {Publisher: De Gruyter},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{monfort-lanzas_modeling_2025,

title = {Modeling omics dose-response at the pathway level with DoseRider},

author = {Pablo Monfort-Lanzas and Johanna M. Gostner and Hubert Hackl},

doi = {10.1016/j.csbj.2025.04.004},

issn = {2001-0370},

year  = {2025},

date = {2025-01-01},

journal = {Computational and Structural Biotechnology Journal},

volume = {27},

pages = {1440–1448},

abstract = {The generation of omics data sets has become an important approach in modern pharmacological and toxicological research as it can provide mechanistic and quantitative information on a large scale. Analyses of these data frequently revealed a non-linear dose-response relationship underscoring the importance of the modeling process to infer biological exposure limits. A number of tools have been developed for dose-response modeling and various thresholds have been defined as a quantitative representation of the effect of a substance, such as effective concentrations or benchmark doses (BMD). Here we present DoseRider an easy-to-use web application and a companion R package for linear and non-linear dose-response modeling and assessment of BMD at the level of biological pathways or signatures using generalized mixed effect models. This approach allows to analyze custom or provided multi-omics data such as RNA sequencing or metabolomics data and its annotation of a collection of pathways and gene sets from various species. Moreover, we introduce the concept of the trend change doses (TCDs) as a numerical descriptor of effects derived from complex dose-response curves. The usability of DoseRider was demonstrated by analyses of RNA sequencing data of bisphenol AF (BPAF) treatment of a human breast cancer cell line (MCF-7) at 8 different concentrations using gene sets for chemical and genetic perturbations (MSigDB). The BMD for BPAF and a set of genes upregulated by estrogen in breast cancer was 0.2 µM (95 %-CI 0.1-0.5 µM) and the lowest TCD (TCD1) was 0.003 µM (95 %-CI 0.0006-0.01 µM). The comprehensive presentation of the results underlines the suitability of the system for pharmacogenomics, toxicogenomics, and applications beyond.},

note = {Place: Netherlands},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kyvelidou_dendritic_2024,

title = {Dendritic cells under the control of the preimplantation embryo secretome: an in vitro study},

author = {Christiana Kyvelidou and Sofia Haselrieder and Maria Von Gierke and Johanna M. Gostner and Wolfgang Biasio and Barbara Wirleitner and Christine Heufler and Bettina Toth and Susanne Hofer-Tollinger},

url = {https://rbej.biomedcentral.com/articles/10.1186/s12958-024-01319-2},

doi = {10.1186/s12958-024-01319-2},

issn = {1477-7827},

year  = {2024},

date = {2024-11-01},

urldate = {2026-01-26},

journal = {Reproductive Biology and Endocrinology},

volume = {22},

number = {1},

pages = {150},

abstract = {Abstract 

 Objective 

 To study the crosstalk between maternal immune cells and the developing embryo by investigating the immunogenic properties of human blastocyst spent media (SM) on dendritic cells. 

 Methods 

 In this prospective multicenter experimental study, human preimplantation embryo spent media were collected after blastocyst formation, grouped based on successful or unsuccessful implantation, and analyzed by protein array or used to stimulate monocyte derived dendritic cells (moDC). The immunomodulatory properties of SM on moDC were investigated by analyzing changes in phenotype, cytokine secretion, indoleamine 2,3-dioxygenase (IDO) activity, and ability to activate T cells. 

 Results 

 A plethora of cytokines and growth factors secreted from preimplantation embryos was detected. Exposure to embryo SM altered the phenotype of moDC in a manner dependent on the implantation outcome. Specifically, SM from non-implanted embryos increased the expression of co-stimulatory molecules and activation markers on moDC. Furthermore, SM treated dendritic cells secreted low levels of cytokines and growth factors and were able to stimulate naïve T cells. Activation of IDO was decreased in moDC after stimulation with SM. 

 Conclusions 

 Our findings show that human preimplantation embryos secrete an abundance of molecules with the ability to significantly affect and even regulate immune cells in their environment.},

note = {Place: England},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hu_changes_2024-1,

title = {Changes in cerebrospinal fluid proteins across the spectrum of untreated and treated chronic HIV-1 infection.},

author = {Zicheng Hu and Paola Cinque and Ameet Dravid and Lars Hagberg and Aylin Yilmaz and Henrik Zetterberg and Dietmar Fuchs and Johanna Gostner and Kaj Blennow and Serena S. Spudich and Laura Kincer and Shuntai Zhou and Sarah Beth Joseph and Ronald Swanstrom and Richard W. Price and Magnus Gisslén},

doi = {10.1371/journal.ppat.1012470},

issn = {1553-7374 1553-7366},

year  = {2024},

date = {2024-09-01},

journal = {PLoS pathogens},

volume = {20},

number = {9},

pages = {e1012470},

abstract = {Using the Olink Explore 1536 platform, we measured 1,463 unique proteins in 303 cerebrospinal fluid (CSF) specimens from four clinical centers contributed by uninfected controls and 12 groups of people living with HIV-1 infection representing the spectrum of progressive untreated and treated chronic infection. We present three initial analyses of these measurements: an overview of the CSF protein features of the sample; correlations of the CSF proteins with CSF HIV-1 RNA and neurofilament light chain protein (NfL) concentrations; and comparison of CSF proteins in HIV-associated dementia (HAD) and neurosymptomatic CSF escape (NSE). These reveal a complex but coherent picture of CSF protein changes with highest concentrations of many proteins during CNS injury in the HAD and NSE groups and variable protein changes across the course of systemic HIV-1 progression that included two common patterns, designated as lymphoid and myeloid patterns, related to principal involvement of their underlying inflammatory cell lineages. Antiretroviral therapy reduced CSF protein perturbations, though not always to control levels. The dataset of these CSF protein measurements, along with background clinical information, is posted online. Extended studies of this unique dataset will supplement this report to provide more detailed characterization of the dynamic impact of HIV-1 infection on the CSF proteome across the spectrum of HIV-1 infection, advancing the mechanistic understanding of HIV-1-related CNS pathobiology.},

note = {Place: United States},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hargitai_chemical_2024,

title = {Chemical respiratory sensitization—Current status of mechanistic understanding, knowledge gaps and possible identification methods of sensitizers},

author = {Rita Hargitai and Lucia Parráková and Tünde Szatmári and Pablo Monfort-Lanzas and Valentina Galbiati and Karine Audouze and Florence Jornod and Yvonne C. M. Staal and Sabina Burla and Aline Chary and Arno C. Gutleb and Katalin Lumniczky and Rob J. Vandebriel and Johanna M. Gostner},

url = {https://www.frontiersin.org/articles/10.3389/ftox.2024.1331803/full},

doi = {10.3389/ftox.2024.1331803},

issn = {2673-3080},

year  = {2024},

date = {2024-07-01},

urldate = {2026-01-26},

journal = {Frontiers in Toxicology},

volume = {6},

pages = {1331803},

abstract = {Respiratory sensitization is a complex immunological process eventually leading to hypersensitivity following re-exposure to the chemical. A frequent consequence is occupational asthma, which may occur after long latency periods. Although chemical-induced respiratory hypersensitivity has been known for decades, there are currently no comprehensive and validated approaches available for the prospective identification of chemicals that induce respiratory sensitization, while the expectations of new approach methodologies (NAMs) are high. A great hope is that due to a better understanding of the molecular key events, new methods can be developed now. However, this is a big challenge due to the different chemical classes to which respiratory sensitizers belong, as well as because of the complexity of the response and the late manifestation of symptoms. In this review article, the current information on respiratory sensitization related processes is summarized by introducing it in the available adverse outcome pathway (AOP) concept. Potentially useful models for prediction are discussed. Knowledge gaps and gaps of regulatory concern are identified.},

note = {Place: Switzerland},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{monfort-lanzas_exonsurfer_2024,

title = {ExonSurfer: a web-tool to design primers at exon–exon junctions},

author = {Pablo Monfort-Lanzas and Elena Cristina Rusu and Lucia Parrakova and Cornelia A. Karg and Dorina-Elina Kernbichler and Dietmar Rieder and Peter Lackner and Hubert Hackl and Johanna M. Gostner},

url = {https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-024-10456-2},

doi = {10.1186/s12864-024-10456-2},

issn = {1471-2164},

year  = {2024},

date = {2024-06-01},

urldate = {2026-01-26},

journal = {BMC Genomics},

volume = {25},

number = {1},

pages = {594},

abstract = {Abstract 

 Background 

 Reverse transcription quantitative PCR (RT-qPCR) with intercalating dyes is one of the main techniques to assess gene expression levels used in basic and applied research as well as in diagnostics. However, primer design for RT-qPCR can be complex due to the high demands on primer quality. Primers are best placed on exon junctions, should avoid polymorphic regions, be specific to the target transcripts and also prevent genomic amplification accurately, among others. Current software tools manage to meet all the necessary criteria only insufficiently. Here, we present ExonSurfer, a novel, user-friendly web-tool for qPCR primer design. 

 Results 

 ExonSurfer combines the different steps of the primer design process, encompassing target selection, specificity and self-complementarity assessment, and the avoidance of issues arising from polymorphisms. Amplification of potentially contaminating genomic DNA is avoided by designing primers on exon-exon junctions, moreover, a genomic alignment is performed to filter the primers accordingly and inform the user of any predicted interaction. In order to test the whole performance of the application, we designed primer pairs for 26 targets and checked both primer efficiency, amplicon melting temperature and length and confirmed the targeted amplicon by Sanger sequencing. Most of the tested primers accurately and selectively amplified the corresponding targets. 

 Conclusion 

 ExonSurfer offers a comprehensive end-to-end primer design, guaranteeing transcript-specific amplification. The user interface is intuitive, providing essential specificity and amplicon details. The tool can also be used by command line and the source code is available. Overall, we expect ExonSurfer to facilitate RT-qPCR set-up for researchers in many fields.},

note = {Place: England},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{wagner_crpneopterin_2024,

title = {CRP/Neopterin Ratio and Neuropsychiatric Symptoms in Patients with Different Forms of Pneumonia: Results of a Pilot Study.},

author = {Katharina Konstanze Lilly Wagner and Daniele Corda and Andreas Steinmayr and Francesco Burkert and Dietmar Fuchs and Johanna Gostner and Stefanie Hofer and Lucia Parrakova and Irina Gasslitter and Günter Weiss and Christian Irsara and Sarah Maier and Andrea Griesmacher and Rosa Bellmann-Weiler and Katharina Kurz},

doi = {10.3390/microorganisms12061099},

issn = {2076-2607},

year  = {2024},

date = {2024-05-01},

journal = {Microorganisms},

volume = {12},

number = {6},

abstract = {BACKGROUND: Pneumonia is one of the most common infectious diseases, mostly caused by viruses or bacteria. In response to bacteria or viruses which are different but which also are partly overlapping, innate and adaptive immune responses are induced, which can be quantified using the determination of specific biomarkers. Among these, C-reactive protein (CRP) has been established as a marker of innate immune function, whereas Neopterin, which is mainly produced upon stimulation with interferon-gamma, reflects cellular immune activation. AIM: We investigated inflammation markers in patients with microbiologically confirmed viral or bacterial pneumonia, and studied the potential of CRP, Neopterin, and the CRP/Neopterin ratio to distinguish between viral and bacterial pathogenesis. Furthermore, we examined, how often neuropsychiatric symptoms occur in patients suffering from different kinds of pneumonia. PATIENTS AND METHOD: A total of 194 patients diagnosed with either coronavirus disease 2019 (COVID-19) (n = 63), bacterial pneumonia (n = 58), Influenza infection (n = 10), Influenza and a bacterial superinfection (n = 9), and COVID-19 patients with a bacterial superinfection (n = 54) were included in our pilot study. Clinical as well as laboratory parameters were determined shortly after admission. RESULTS: We found significantly higher CRP/Neopterin ratios in patients with bacterial pneumonia (median: 0.34) and lower CRP/Neopterin ratios in patients hospitalized with COVID-19 infection (median: 0.03; p < 0.001). Both in men and in women, the CRP/Neopterin ratio was able to distinguish between viral and bacterial pathogens, but also was able to detect bacterial super-infection (BSI) in subjects with initial viral pneumonia (p < 0.001). Patients with BSI presented with significantly lower CRP/Neopterin ratios (median 0.08) than patients with bacterial infection only (median 0.34; p < 0.001). Interestingly, COVID-19 patients had a decreased physical functioning (as reflected in the ECOG score) and a higher frequency of fatigue (84.1%) and neurological symptoms (54.8%) than patients with pneumonia, due to other underlying pathogens. Patients that reported fatigue during viral and bacterial pneumonia presented with lower CRP concentrations than patients without it. CONCLUSIONS: The CRP/Neopterin ratio is useful to differentiate between viral and bacterial pathogenesis. The occurrence of neuropsychiatric symptoms in pneumonia appears to depend on the kind of pathogen causing the infection. Lower CRP concentrations at admission appear to be related to fatigue during acute viral and bacterial infection.},

note = {Place: Switzerland},

keywords = {},

pubstate = {published},

tppubtype = {article}

}