Biology subjects

Baumann, L.

Publications and source records attributed to Baumann, L..

5 recordsLinked to original sources

bioRxiv2026

L1CAMxCD3 bispecific antibodies exert potent anti-tumor effects in preclinical pancreatic cancer models with representation of the complex tumor microenvironment

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment (TME) with pancreatic myofibroblasts (PMF) and macrophages being two prominent cell populations essentially impairing tumor responses to (immuno)therapies. L1 cell adhesion molecule (L1CAM) is upregulated in PDAC cells in primary and metastatic tissues and associated with tumor progression and therapy resistance. Using L1CAM as tumor-associated antigen, two bispecific antibodies (bsAB) targeting L1CAM and CD3 were developed in the IgG-(L)-ScFv format and their anti-tumorigenic activity was investigated in different preclinical PDAC models. In 2D models, both L1-bsAB exerted L1CAM-specific anti-PDAC cell activity when co-cultured with activated CD8+ T cells. Strong anti-PDAC cell effects along with elevated release of T cell effector molecules were also observed upon co-culture with peripheral blood mononuclear cells (PMBC) from healthy donors and PDAC patients. Of note, both L1-bsAB were also effective in 3D PDAC cell spheroids and neither impaired by PMF nor macrophages. Finally, application of L1-bsAB on organotypic tissue slice cultures from PDAC tissues comprising the entire complex TME also induced PDAC cell apoptosis and release of T cell effector molecules. Overall, our results highlight relevant anti-PDAC cell activity of L1-bsAB in immunosuppressive contexts supporting their potential as immunotherapeutic strategy for PDAC.

cancer biology↗

bioRxiv2025

Topology control by a conserved cysteine pair in the OMM-protein CCDC127 enables MICOS interaction

Mitochondrial disulfide relay substrates beyond the canonical substrates remain incompletely defined. Revisiting the human MIA40 interactome with enhanced depth, we identified CCDC127 as a previously unrecognized substrate candidate. CCDC127 contains a single transmembrane segment and a conserved C-terminal helical bundle domain (CHB). Comprehensive proteomic and biochemical analyses revealed that, contrary to earlier reports, CCDC127 adopts an Nout-Cin topology in the outer mitochondrial membrane (OMM) with its CHB residing in the intermembrane space (IMS). CCDC127 undergoes oxidation by the disulfide relay, forming a long-range intramolecular disulfide bond between C174 and C219. Loss of these cysteines disrupts correct OMM insertion, inverts transmembrane topology and triggers proteasome-dependent degradation, establishing the disulfide as a key determinant of CCDC127 maturation. Interactome analyses identified MICOS components--particularly the MIC60/MIC19 module--as major partner proteins required for the stability of large oligomeric CCDC127 complexes. CCDC127 deficiency impaired cellular proliferation, influenced phospholipid levels, and caused grossly altered cristae morphology. Together, CCDC127 emerges as a MICOS-associated OMM protein essential for mitochondrial membrane organization and lipid homeostasis.

biochemistry↗

bioRxiv2025

Interdependent Dynamics of mRNA Expression and HIV-1 Viral Load: Insights from Transcriptomics and Mendelian Randomization

The interaction between HIV-1 and the host immune system plays a crucial role in the natural control and progression of the infection. Previous studies have identified APOBEC3G, Tetherin, SAMHD1, and SERINC5 as HIV-1 host restriction factors, which are counteracted by the viral proteins Vif, Vpu, and Nef, respectively. The blood expression levels of some of these host proteins are correlated with HIV load, suggesting that interindividual differences in the spontaneous control of HIV infection might lead to the identification of novel HIV restriction factors. Our study enrolled 150 participants from the Swiss HIV Cohort Study with human genome-wide genotyping data, pre-antiretroviral treatment peripheral blood mononuclear cells (PBMC) aliquots and HIV load measurements. Using BrB-seq, we quantified mRNA expression of all protein-coding genes and found significant associations between 792 genes and HIV load. Pathway analysis revealed that higher viral load associated with the upregulation of innate immune response, proteasome complex, mitochondrial and cell-cycle related activity, and with the downregulation of ribosomal transcripts and genes involved in cytokine-cytokine receptor interaction, including IL4R, IL7R, and TCF7. Mendelian Randomization confirmed the viral restriction activity of TRABD2A and identified new candidates as potential restriction factors. These findings provide novel insights into the host-virus interplay and suggest additional genes that may contribute to the natural control of HIV-1 infection.

immunology↗

bioRxiv2018

Mycoplasma genitalium incidence, persistence, concordance between partners and progression: systematic review and meta-analysis

BackgroundMycoplasma genitalium is increasingly seen as an emerging sexually transmitted pathogen, and has been likened to Chlamydia trachomatis, but its natural history is poorly understood. The objectives of this systematic review were to determine M. genitalium incidence, persistence, concordance between sexual partners, and the risk of pelvic inflammatory disease (PID).\n\nMethodsWe searched Medline, EMBASE, LILACS, IndMed and African Index Medicus from 1 January 1981 until 17 March 2018. Two independent researchers screened studies for inclusion and extracted data. We examined results in forest plots, assessed heterogeneity and conducted meta-analysis where appropriate. Risk of bias was assessed for all studies.\n\nResultsWe screened 4634 records and included 17 studies; five (4100 women) reported on incidence, five (636 women) on persistence, 10 (1346 women and men) on concordance and three (5139 women) on PID. Incidence in women in two very highly developed countries was 1.07 per 100 person-years (95% CI, 0.61 to 1.53, I2 0%). Median persistence of M. genitalium was estimated from one to three months in four studies but 15 months in one study. In ten studies measuring M. genitalium infection status in couples, 39-50% of male or female sexual partners of infected participants also had M. genitalium detected. In prospective studies, the incidence of PID was higher in women with M. genitalium than those without (RR 1.68, 95% CI 0.59 to 2.77, I2 0%, 2 studies).\n\nDiscussionBased on findings from this and our linked review of prevalence, concordant M. genitalium might be less common than for C. trachomatis and the age distributions of the infections differ. The synthesised data about prevalence, incidence and persistence of M. genitalium infection are inconsistent. Taken together with evidence about antimicrobial resistance in the two infections, M. genitalium is not the new chlamydia.\n\nRegistration NumbersPROSPERO: CRD42015020420, CRD42015020405\n\nKEY MESSAGESO_LIThere are calls for widespread screening for Mycoplasma genitalium, but the natural history of this emerging sexually transmitted pathogen is poorly understood.\nC_LIO_LIM. genitalium incidence was 1.07 (95% confidence intervals, CI 0.61 to 1.53) per 100-person years in women in highly developed countries, 39-50% of infected individuals had a heterosexual partner with M. genitalium and the risk ratio for pelvic inflammatory disease was 1.68 (95% CI 0.59 to 2.77).\nC_LIO_LIThe duration of untreated M. genitalium infection is probably longer than persistent detection of M. genitalium, as measured in most cohort studies, in which inadvertent treatment cannot be ruled out.\nC_LIO_LIThe results of this systematic review and other evidence sources show important differences in the epidemiology and dynamics of M. genitalium and Chlamydia trachomatis infection.\nC_LI

epidemiology↗

bioRxiv2017

Prevalence of Mycoplasma genitalium in different population groups: systematic review and meta-analysis

BackgroundMycoplasma genitalium is a common cause of non-gonococcal non-chlamydial urethritis and cervicitis. Testing of asymptomatic populations has been proposed, but prevalence rates in asymptomatic populations are not well established. We aimed to estimate the prevalence of M. genitalium in adults in the general population, in clinic-based samples, pregnant women, men who have sex with men (MSM) and female sex workers (FSW).\n\nMethodsWe searched Embase, Medline, IndMED, AIM and LILACS from 1 January 1991 to 12 July 2016 without language restrictions. We included studies with 500 participants or more. We screened and selected studies and extracted data in duplicate. We examined eligible studies in forest plots and conducted random effects meta-analysis to estimate prevalence, if appropriate. Between study heterogeneity was examined using the I2 statistic and meta-regression.\n\nResultsOf 3,316 screened records, 63 were included. In randomly selected samples from the general population, the summary prevalence estimate was 1.3% (95% confidence intervals, CI 1.0 to 1.8%, I2 41.5%, 3 studies) in countries with higher levels of development and 3.9% (95% CI 2.2 to 6.7, I2 89.2%, 3 studies) in countries with lower levels. Prevalence estimates were similar in women and men (p=0.47). In clinic-based samples prevalence estimates were higher, except in asymptomatic patients (0.8%, 95% CI 0.4 to 1.4, I2 0.0%, 3 studies). Summary prevalence estimates were: pregnant women 0.9% (95% CI 0.6 to 1.4%, I2 0%, 4 studies); MSM in the community 3.2% (95% CI 2.1 to 5.1, I2 78.3%, 5 studies); FSW in the community 15.9% (95% CI 13.5 to 18.9, I2 =79.9%, 4 studies).\n\nDiscussionThis systematic review can inform testing guidelines for M. genitalium infection. The low estimated prevalence of M. genitalium in the general population, pregnant women and asymptomatic attenders at clinics does not support expansion of testing to asymptomatic people in these groups.\n\nRegistration Numbers\n\nPROSPERO: CRD42015020420

epidemiology↗