Biology subjects

Lutz, M.

Publications and source records attributed to Lutz, M..

8 recordsLinked to original sources

bioRxiv2026

Contrasting controls on tree methane emissions in upland and wetland forests

Trees can produce, consume, transport, and emit methane (CH), yet the environmental controls and mechanisms underlying these fluxes remain poorly understood. We combined 1,640 stem-chamber observations (2023-2025) with tower-based meteorology, soil moisture and temperature networks, water table monitoring, and non-destructive tomography to test how hydrology, energy balance, species identity, and internal wood condition regulate stem CH flux. Wetland trees emitted approximately 40-fold more CH than upland trees (1.96 vs. 0.05 nmol m-{superscript 2} s-{superscript 1}). At the wetland, a three-way interaction between soil temperature, water table depth, and species explained 65% of flux variance, consistent with soil-derived CH transport through stems. The wetland specialist Nyssa sylvatica emitted an order of magnitude more CH than co-occurring generalists, likely reflecting flood-tolerance adaptations that enhance gas transport. In contrast, upland fluxes showed minimal environmental control (R{superscript 2} < 9%), with most variance occurring as unexplained temporal variation within individual trees--a pattern suggesting competing methanogenic and methanotrophic processes operating near equilibrium. Internal wood condition, assessed via acoustic and electrical resistance tomography, had opposite effects across sites: decay increased emissions in upland trees, likely by creating anaerobic microsites for in situ production, while decay decreased net emissions in wetland trees, likely by impairing transport of soil-derived CH more than it enhanced in situ production. Together, these results indicate that the dominant controls on tree CH flux differ fundamentally between wetland and upland forests, underscoring the need to represent hydrologic setting, species composition, and tree condition when scaling forest CH contributions to regional budgets.

ecology↗

bioRxiv2025

1,2,4-Triazole-based first-in-class non-nucleoside inhibitors of bacterial enzyme MraY

MraY, a bacterial enzyme crucial for the synthesis of peptidoglycans, represents a promising yet underexplored target for the development of effective antibacterial agents. Nature has provided several classes of nucleoside inhibitors of MraY and scientists have modified these structures further to obtain natural product-like inhibitors of MraY. The natural products and their synthetic analogs suffer from non-optimal in vivo efficacy, and the synthetic complexity of the structures renders the synthesis and structure-activity relationship (SAR) studies of these molecules particularly challenging. In this study, we present our findings on the discovery of first-in-class 1,2,4-triazole-based MraY inhibitors that are not nucleoside-derived. A series of 1,2,4-triazole analogous were identified by a structure-activity-relationship (SAR) study using a structure-based drug design strategy. Compound 1, with an IC50 of 171 {micro}M against MraY from Staphylococcus aureus (MraYSA), was optimized to compound 12a, exhibiting an IC50 of 25 {micro}M. Molecular docking studies against MraYSA provided insights into these compounds binding interactions and activity. Furthermore, screening against the ESKAPE bacterial panel was also conducted, through which we discovered compounds demonstrating broad-spectrum antibacterial activity against E. faecium, methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococci (VRE) strains and Mycobacterium tuberculosis. The novel, first-in-class non-nucleoside inhibitors of MraY highlighted in this work provide a strong proof-of-concept of how to leverage structural information of the protein to develop future antibacterial agents targeting MraY. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=168 SRC="FIGDIR/small/635793v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@14b1f84org.highwire.dtl.DTLVardef@1024f45org.highwire.dtl.DTLVardef@a246d0org.highwire.dtl.DTLVardef@1d70e52_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

The enigmatic fungal genus Ceraceosorus provides a theoretical framework for studying intragenomic variation in ribosomal DNA sequences

Multicopy nuclear ribosomal (rDNA) genes have been used as markers for fungal identification for three decades. The rDNA sequences in a genome are thought to be homogeneous due to concerted evolution. However, intragenomic variation of rDNA sequences has recently been observed in many fungi, which cause problems in fungal identification and species abundance estimation. Various sequence-based methods have been used to demonstrate rDNA sequence heterogeneity, but there is no technical assessment of the comparability of results from these methods. In this article, we sampled smut fungi representing all major lineages of subphylum Ustilaginomycotina as a system to examine sequence heterogeneity in the rDNA repeats. Three methods were used: PCR-cloning-Sanger sequencing, targeted amplicon high-throughput sequencing, and WGS high-throughput sequencing. Based on our analyses, Ceraceosorus is the only sampled fungal genus in Ustilaginomycotina showing intragenomic variation, with up to 27 nucleotide variant sites in the ITS1-5.8S-ITS2 region and 2.6% divergence among analyzed ITS haplotypes. We found many conflicting patterns across the three detection methods, with up to 28 conflicting variant sites in one sample. Surprisingly, at least 40% of these conflicts are due to PCR-cloning-sequencing errors, as the corresponding variant sites were not observed in the other methods. Based on our data and the literature, we evaluated the characteristics and advantages/disadvantages of each detection method. A model for how intragenomic variation may arise in the rDNA region is presented. Finally, we describe the fourth known species of Ceraceosorus, C. americanus, isolated from an asymptomatic rosemary leaf collected in Louisiana, USA. We anticipate that our study will provide a framework for future research in rDNA regions as well as other similar multicopy genes. Author SummaryRibosomal DNA (rDNA) genes are one of the most ancient multicopy genes in cellular organisms. They function as a part of the protein synthesis machinery in a cell. The rDNA sequences have also been used in species identification and microbial community profiling. Despite these utilities, little is known how the rDNA genes have evolved. Biologists initially thought the sequences among rDNA copies are homogeneous, but many recent cases illustrated rDNA sequence heterogeneity. In this article, we utilized the fungal genus Ceraceosorus together with allied smut fungi as a system to study sequence heterogeneity in the rDNA genes using various detection methods. Our system found rDNA sequence homogeneity as a common form, while sequence heterogeneity is taxon-specific. Based on our data and literature review, we explained possible sources for sequence heterogeneity in the rDNA genes. Our study also noticed result discrepancies across variant detection methods. These include artefactual variants from the PCR-cloning-sequencing method, inconsistent detected variants from the independent runs of high-throughput sequencing, and technical errors in bioinformatic analyses. We therefore emphasize the importance of methodological choices which have different pros and cons for studying intragenomic variation of rDNA genes, as well as other multicopy gene families.

genomics↗

bioRxiv2023

A Continuous Extension of Gene Set Enrichment Analysis using the Likelihood Ratio Test Statistics Identifies VEGF as a Candidate Pathway for Alzheimers disease

BackgroundAlzheimers disease involves brain pathologies such as amyloid plaque depositions and hyperphosphorylated tau tangles and is accompanied by cognitive decline. Identifying the biological mechanisms underlying disease onset and progression based on quantifiable phenotypes will help understand the disease etiology and devise therapies. ObjectiveOur objective was to identify molecular pathways associated with AD biomarkers (Amyloid-{beta} and tau) and cognitive status (MMSE) accounting for variables such as age, sex, education, and APOE genotype. MethodsWe introduce a novel pathway-based statistical approach, extending the gene set likelihood ratio test to continuous phenotypes. We first analyzed independently each of the three phenotypes (Amyloid-{beta}, tau, cognition), using continuous gene set likelihood ratio tests to account for covariates, including age, sex, education, and APOE genotype. The analysis involved a large sample size with data available for all three phenotypes, allowing for the identification of common pathways. ResultsWe identified 14 pathways significantly associated with Amyloid-{beta}, 5 associated with tau, and 174 associated with MMSE. Surprisingly, the MMSE outcome showed a larger number of significant pathways compared to biomarkers. A single pathway, vascular endothelial growth factor receptor binding (VEGF-RB), exhibited significant associations with all three phenotypes. ConclusionsThe studys findings highlight the importance of the VEGF signaling pathway in aging in AD. The complex interactions within the VEGF signaling family offer valuable insights for future therapeutic interventions.

genetics↗

bioRxiv2020

Autonomous termination of proliferation in the Drosophila wing disc is TORC1 dependent

Cells in a developing organ stop proliferating when the organ reaches a correct, final size. The underlying mechanisms are not understood. Although many signaling pathways and cell cycle components are required to sustain cell proliferation, which one of these turns off to terminate proliferation is not known. Here we study proliferation termination using Drosophila wing discs. We extend larval development to provide wing discs a constant growth-sustaining environment, allowing them to terminate proliferation autonomously. We find that the wing pouch, which forms the adult wing blade, terminates proliferation in the absence of brinker or warts, indicating that neither Dpp signaling nor Hippo/Yorkie signaling control final wing size. Instead, termination of proliferation coincides with reduced TORC1 activity and is bypassed by reactivating TORC1. Hence proliferation ceases due to reduced cell growth. Experimental manipulation of Dpp or Yki signaling can bypass proliferation termination in hinge and notum regions, suggesting that the mechanisms regulating proliferation termination may be distinct in different regions of the disc. One Sentence SummaryUsing Drosophila, Strassburger et al. investigate the termination of proliferation of an organ when it reaches its final size, and show this occurs due to a drop in TORC1 signaling.

developmental biology↗

bioRxiv2020

Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F

Tetraspanins are ubiquitous eukaryotic membrane proteins that contribute to a variety of signaling processes by spatially organizing partner-receptor molecules in the plasma membrane. How tetraspanins bind and cluster partner receptors into so-called tetraspanin-enriched microdomains is unknown. Here we present crystal structures of the large extracellular loop of CD9 in complex with nanobodies 4C8 and 4E8; and, the cryo-EM structure of 4C8-bound CD9 in complex with its prototypical partner EWI-F. The CD9 - EWI-F complex displays a tetrameric arrangement with two centrally positioned EWI-F molecules, dimerized through their ectodomains, and two CD9 molecules, one bound to each EWI-F single-pass transmembrane helix through CD9-helices h3 and h4. In the crystal structures, nanobodies 4C8 and 4E8 bind CD9 at the C and D loop, in agreement with 4C8 binding at the ends of the CD9 - EWI-F cryo-EM complex. Overall, the 4C8 - CD9 - EWI-F - EWI-F - CD9 - 4C8 complexes varied from nearly two-fold symmetric (i.e. with the two CD9 - 4C8 copies in nearly anti-parallel orientation) to ca. 50{degrees} bent arrangements. Since membrane helices h1 and h2 and the EC2 D-loop have been previously identified as sites for tetraspanin homo-dimerization, the observed linear but flexible arrangement of CD9 - EWI-F with potential CD9 - CD9 homo-dimerization at either end provides a new concatenation model for forming short linear or circular assemblies, which may explain the occurrence of tetraspanin-enriched microdomains.

biophysics↗

bioRxiv2020

Network analysis of workshop activities reveals increasing transdisciplinarity of German biodiversity research community

Boundary spanning activities in the biodiversity science-policy interface are urgently needed. Effective science communication and uptake of scientific findings by policymakers is crucial for a successful, cross-scale policy implementation. For this, national platforms promoting knowledge exchange between different stakeholder groups are key. Established in 2009, the Network-Forum on Biodiversity Research Germany (NeFo) until 2018 has organized more than 40 workshops bringing together actors from science, policy and society. In this paper, we present a network and cluster analysis of these NeFo workshops. Based on this, we discuss the importance of science-policy interface projects and networks as knowledge brokers and boundary organizations, as well as challenges in using network analysis as a tool for evaluating workshop impacts. Based on the network analysis outcomes as well as experiences in the conduction of workshops, recommendations to strengthen the innovation impact of networking efforts are drawn.

scientific communication and education↗

bioRxiv2019

A secreted Echinococcus multilocularis activin A homologue promotes regulatory T cell expansion

BackgroundAlveolar echinococcosis (AE), caused by the metacestode larval stage of the fox-tapeworm Echinococcus multilocularis, is a chronic zoonosis associated with significant modulation of the host immune response. A role of regulatory T-cells (Treg) in generating an immunosuppressive environment around the metacestode during chronic disease has been reported, but the molecular mechanisms of Treg induction by E. multilocularis remain elusive so far.\n\nMethodology/Principal findingsWe herein demonstrate that excretory/secretory (E/S) products of the E. multilocularis metacestode promote the formation of Foxp3+ Treg from CD4+ T-cells in vitro in a TGF-{beta}-dependent manner. We also show that host T-cells secrete elevated levels of the immunosuppressive cytokine IL-10 in response to metacestode E/S products. Within the E/S fraction of the metacestode we identified an E. multilocularis activin A homolog (EmACT) that displays significant similarities to mammalian Transforming Growth Factor-{beta} (TGF-{beta})/activin subfamily members. EmACT obtained from heterologous expression promoted host TGF-{beta}-driven CD4+ Foxp3+ Treg conversion in vitro. Furthermore, like in the case of metacestode E/S products, EmACT-treated CD4+ T-cells secreted higher levels of IL-10. These observations suggest a contribution of EmACT in the in vitro expansion of Foxp3+ Treg by the E. multilocularis metacestode. Using infection experiments we show that intraperitoneally injected metacestode tissue expands host Foxp3+ Treg, confirming the expansion of this cell type in vivo during parasite establishment.\n\nConclusions/SignificanceIn conclusion, we herein show that E. multilocularis larvae secrete a factor with clear structural and functional homologies to mammalian activin A. Like its mammalian homolog, this protein induces the secretion of IL-10 by T-cells and contributes to the expansion of TGF-{beta}-driven Foxp3+ Treg, a cell type that has been reported crucial for generating a tolerogenic environment to support parasite establishment and proliferation.\n\nAUTHOR SUMMARYThe metacestode larval stage of the tapeworm E. multilocularis grows infiltratively, like a malignant tumor, within the organs of its human host, thus causing the lethal disease alveolar echinococcosis (AE). Immunosuppression plays an important role in both survival and proliferation of the metacestode, which mainly depends on factors that are released by the parasite. These parasite-derived molecules are potential targets for developing new anti-echinococcosis drugs and/or improving the effectiveness of current therapies. Additionally, an optimized use of such factors could help minimize pathologies resulting from over-reactive immune responses, like allergies and autoimmune diseases. The authors herein demonstrate that the E. multilocularis metacestode releases a protein, EmACT, with significant homology to activin A, a cytokine that might support host TGF-{beta} in its ability to induce the generation of immunosuppressive regulatory T-cells (Treg) in mammals. Like its mammalian counterpart, EmACT was associated with the expansion of TGF-{beta}-induced Treg and stimulated the release of elevated amounts of immunosuppressive IL-10 by CD4+ T-cells. The authors also demonstrate that Treg are locally expanded by the metacestode during an infection of mice. These data confirm an important role of Treg for parasite establishment and growth during AE and suggest a potential role of EmACT in the expansion of these immunosuppressive cells around the parasite.

immunology↗