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Grundler, F.

Publications and source records attributed to Grundler, F..

9 recordsLinked to original sources

Effects of long-term fasting: longitudinal epigenetic responses in humans

Prolonged fasting induces marked metabolic adaptations, but whether such time-limited yet intensive interventions engage molecular processes related to biological aging in humans remains unclear. To address this, we investigated physiological and epigenetic responses to a 12-day medically supervised fasting intervention with longitudinal follow-up in 32 participants. Fasting elicited coordinated systemic physiological changes across metabolic and hematological parameters, with partial persistence at one month. Genome-wide DNA methylation analyses revealed modest but detectable CpG-level changes, primarily emerging at follow-up and distributed across genomic contexts. In parallel, epigenetic aging clocks showed clock-specific and time-dependent responses, with substantial inter-individual variability. Lower baseline epigenetic age acceleration was consistently associated with greater fasting-induced weight loss, suggesting a link between epigenetic state and metabolic responsiveness. Together, these findings indicate that prolonged fasting induces coordinated physiological adaptations alongside structured changes in epigenetic aging measures that are not captured by conventional clinical biomarkers. This study highlights epigenetic clocks as integrative molecular readouts for probing aging-related responses to short-term metabolic interventions, while also delineating their current interpretive limits.

genomics↗

Identification of Entomopathogenic Nematode isolates from Nigeria and their pathogenicity against the invasive fall armyworm, Spodoptera frugiperda J.E. Smith (Lepidoptera: Noctuidae)

The fall armyworm (FAW, Spodoptera frugiperda J.E. Smith [Lep.: Noctuidae]), a highly destructive lepidopteran pest, poses a serious threat to maize and other staple crops across sub-Saharan Africa. With growing concerns over resistance to synthetic insecticides, entomopathogenic nematodes (EPNs) have emerged as viable biological control alternative. This study reports the isolation, identification, and virulence evaluation of six indigenous EPN isolates collected from different agroecological zones in Nigeria. Morphological and morphometric assessments, supported by molecular analyses of internal transcribed spacer regions (ITS), D2-D3, and mitochondrial gene regions, identified the isolates as Heterorhabditis bacteriophora, Steinernema carpocapsae, S. feltiae, S. nepalense, and Oscheius myriophilus. Virulence bioassays were conducted against four developmental stages of S. frugiperda (2nd, 4th, 6th instar larvae and pupae) using four dosages (25, 50, 100, and 200 infective juveniles [IJs]/insect). All isolates exhibited dose- and time-dependent pathogenicity, with FAWs 2nd instar larvae showing the highest susceptibility. Heterorhabditis bacteriophora (Ib-CRIN68) caused the highest mortality (82.4 {+/-} 5.6%) and the lowest lethal concentration (LC) and lethal time (LT) values among the tested EPN isolates. Significant effects of isolate, dosage, and exposure time on larval mortality (p < 0.001) were found, particularly in early instars. The findings highlight the high biocontrol potential of these Nigerian EPN isolates and underscore the value of integrating molecular and morphological diagnostics for accurate species identification. This work provides a critical foundation for the future ecological characterization and field deployment of indigenous nematodes in sustainable pest management strategies against S. frugiperda in West Africa.

ecology↗

Farmers awareness and occurrence of Meloidogyne species in tomato production in central Nepal

Tomato (Solanum lycopersicum) is one of the most economically important vegetables in the world. Root-knot nematodes (RKN) form a complex of species that can cause severe losses in tomatoes. Since symptoms and damage depend on the particular nematode species, accurate species identification is critical for implementing potential control measures. Detailed surveys of plant parasitic nematodes in Nepal have not been conducted. Therefore, there is no information on which RKN species occur in key tomato-growing areas. We conducted an initial survey to assess the occurrence and importance of RKN. Nine different districts of Nepal were included: Bhaktapur, Chitwan, Dhading, Dolakha, Kaski, Kathmandu, Kavrepalanchok, Lalitpur, and Lamjung. In the first approach, 70 farmers were interviewed about their awareness and knowledge of RKN. More than 60% of the farmers surveyed knew of RKN and the main signs and symptoms. 40% had limited or no knowledge about it. In a second approach, we conducted a survey of RKN occurrence in tomato fields in the same nine districts. Soil sampling and subsequent analysis in the Kathmandu district revealed RKN infestation at very high levels. Except for Kaski and Chitwan, RKN prevalence was found to be 100% in the districts sampled. The overall prevalence of Meloidogyne species was also 100% in most districts. To identify the species, samples with RKN-infected galls were collected and determined morphologically using perineal patterns and molecularly using specific PCR analyses. Both methods showed that Meloidogyne incognita was the most abundant in the tomato fields, followed by M. arenaria and M. javanica. Our results confirm the importance of RKN in Nepal and suggest that it would be highly beneficial economically to increase farmer awareness of nematode problems and possible control measures.

pathology↗

Long-term fasting remodels gut microbial metabolism and host metabolism

Long-term fasting has become a promising research subject for its potential of treating and preventing metabolic diseases. However, little is known about its impact on the functional capacity of the gut microbiome and the combined effect on the serum metabolome. Here, we demonstrate extensive remodelling of the gut microbial ecosystem in humans (n=92) after an average of 9.8 days of fasting ([~]250 kcal / day). Fasting transiently affected the relative abundance of the majority of bacterial species (306 decreased and 210 increased out of 772). Species changes could largely be explained by their genomic repertoire of carbohydrate-active enzymes (CAZymes), which were investigated here for the first time. Fasting induced extensive abundance changes in CAZyme families, depleting families with dietary fibre substrates and increasing families with host-derived glycan substrates. Likewise, we observed extensive changes in the serum metabolome, with 382 out of 721 metabolites significantly affected (246 increased and 136 decreased). In-depth metagenome-metabolome co-variation analysis suggested Oscillibacter species to be key producers of indole-3-propionic acid, a crucial metabolite for cardiometabolic health. Together, our results provide an unprecedented view on the impact of long-term fasting on gut microbiome composition and function.

microbiology↗

The genome and lifestage-specific transcriptomes of a plant-parasitic nematode and its host reveal susceptibility genes involved in trans-kingdom synthesis of vitamin B.

Plant-parasitic nematodes are a major, and in some cases a dominant, threat to crop production in all agricultural systems. The relative scarcity of classical resistance genes highlights a pressing need to identify new ways to develop nematode-resistant germplasm. Here, we sequence and assemble a high-quality genome of the model cyst nematode Heterodera schachtii to provide a platform for the first system-wide dual analysis of host and parasite gene expression over time, covering all major stages of the interaction. This novel approach enabled the analysis of the hologenome of the infection site, to identify metabolic pathways that were incomplete in the parasite but complemented by the host. Using a combination of bioinformatic, genetic, and biochemical approaches, we show that the highly atypical completion of vitamin B5 biosynthesis by the parasitic animal, putatively enabled by a horizontal gene transfer from a bacterium, is critically important for parasitism. Knockout of either the plant-encoded or the now nematode-encoded steps in the pathway blocks parasitism. Our experiments establish a reference for cyst nematodes, use this platform to further our fundamental understanding of the evolution of plant-parasitism by nematodes, and show that understanding congruent differential expression of metabolic pathways represents a new way to find nematode susceptibility genes, and thereby, targets for future genome editing-mediated generation of nematode-resistant crops.

genetics↗

Glutathione contributes to plant defense against parasitic cyst nematodes

Cyst nematodes (CNs) are an important group of root-infecting sedentary endoparasites that severely damage many crop plants worldwide. An infective CN juvenile enters the hosts roots and migrates towards the vascular cylinder, where it induces the formation of syncytial feeding cells, which nourish the CN throughout its parasitic stages. Here, we examined the role of glutathione (L-{gamma}-glutamyl-L-cysteinylglycine, GSH) in Arabidopsis thaliana upon infection with the CN Heterodera schachtii. Arabidopsis lines with mutations pad2, cad2, or zir1 in the glutamate-cysteine ligase (GSH1) gene, which encodes the first enzyme in the glutathione biosynthetic pathway, displayed enhanced CN susceptibility, but susceptibility was reduced for rax1, another GSH1 allele. Biochemical analysis revealed differentially altered thiol levels in these mutants that was independent of nematode infection. All GSH-deficient mutants exhibited impaired activation of defense marker genes as well as genes for biosynthesis of the antimicrobial compound camalexin early in infection. Further analysis revealed a link between glutathione-mediated plant susceptibility to CN infection and the production of camalexin upon nematode infection. These results suggest that GSH levels affects plant susceptibility to CN by fine-tuning the balance between the cellular redox environment and the production of compounds related to defense against infection.

plant biology↗

Two evolutionary distinct effectors from a nematode and virus target RanGAP1 and 2 via the WPP domain to promote disease

The Gpa2 and Rx1 intracellular immune receptors are canonical CC-NB-LRR proteins belonging to the same R gene cluster in potato. Despite sharing high sequence homology, they have evolved to provide defence against unrelated pathogens. Gpa2 detects Gp-RBP-1 effectors secreted by the potato cyst nematode Globodera pallida whereas Rx1 recognizes the viral coat protein (CP) of Potato Virus X (PVX). How Gpa2 and Rx1 perceive their matching effectors remains unknown. Using a combination of in planta Co-Immunoprecipitation and cellular imaging, we show that both Gp-RBP-1 and PVX-CP physically interact with RanGAP2 and RanGAP1 in the cytoplasm of plant cells. Interestingly, this was also demonstrated for the eliciting variants of Gp-RBP-1 and PVX-CP indicating a role for RanGAP1 and RanGAP2 in pathogenicity independent from Gpa2 and Rx1 recognition. Indeed, knocking down both RanGAP homologs reduce cyst nematode and PVX infection. These findings show that RanGAP1/2 act as common host targets of evolutionary distinct effectors from two plant pathogens with different lifestyles. The involvement of RanGAP1/2 to pathogen virulence is a novel role not yet reported for these key host cell components and as such, their possible role in cyst nematode parasitism and viral pathogenicity are discussed. Moreover, from these findings a model emerges for their possible role as co-factor in pathogen recognition by the potato immune receptors Gpa2/Rx1.

plant biology↗

SIZ1 is a nuclear host target of the nematode effector GpRbp1 from Globodera pallida that acts as a negative regulator of basal plant defense to cyst nematodes

Soil-borne cyst nematodes are obligatory sedentary parasites that cause severe losses to cultivation of major crops such as potato and soybean. Cyst nematodes establish specialised permanent feeding sites within the roots of their host by manipulating plant morphology and physiology through secreted effectors. Here we identified host targets of effector GpRbp-1 and studied their roles in plant-nematode interactions. GpRbp-1 was found to interact in yeast and in planta with the potato and Arabidopsis homologues of Siz/PIAS-type E3 SUMO ligase SIZ1. Our results show that a pathogen effector targets the master regulator SIZ1 in plant cells, which has not been demonstrated earlier to our knowledge. The interaction of GpRbp-1 and SIZ1 localizes to the plant nucleus, suggesting that the nuclear functions of SIZ1 as regulator of plant immunity and physiology may be modulated by GpRbp-1. Furthermore, nematode infection assays and transcriptomic profiling indicate that SIZ1 is required for susceptibility to cyst nematodes. So, these data indicate that E3 SUMO ligases may play an important role in plant-nematode interactions. Based on the prediction of SUMO acceptor and interaction sites in GpRbp-1, a model is proposed in which the effector may recruit SIZ1 to be SUMOylated for full functionality in host cells.\n\nSignificance statementHere we show that a pathogen effector can target SIZ1, a key protein involved in regulating several aspects of plant biology, most likely to manipulate the SUMOylation of host proteins for successful infection of plants.

plant biology↗

Host factors influence the sex of nematodes parasitizing roots of Arabidopsis thaliana

Plant-parasitic cyst nematodes induce hypermetabolic syncytial nurse cells in the roots of their host plants. Syncytia are their only food source. Cyst nematodes are sexually dimorphic, with their differentiation into male or female strongly influenced by host environmental conditions. Under favorable conditions with plenty of nutrients, more females develop, whereas mainly male nematodes develop under adverse conditions such as in resistant plants. Here, we developed and validated a method to predict the sex of beet cyst nematode (Heterodera schachtii) during the early stages of its parasitism in the host plant Arabidopsis thaliana. We collected root segments containing male-associated syncytia (MAS) or female-associated syncytia (FAS), isolated syncytial cells by laser microdissection, and performed a comparative transcriptome analysis. Genes belonging to categories of defense, nutrient deficiency, and nutrient starvation were overrepresented in MAS as compared to FAS. Conversely, gene categories related to metabolism, modification, and biosynthesis of cell walls were overrepresented in FAS. We used {beta}-glucuronidase (GUS) analysis, qRT-PCR, and loss-of-function mutants to characterize FAS- and MAS-specific candidate genes. Our results demonstrated that various plant-based factors, including immune response, nutrient availability, and structural modifications, influence the sexual fate sex determination of cyst the nematodes.

plant biology↗