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Moller, M.

Publications and source records attributed to Moller, M..

11 recordsLinked to original sources

Phytoplasma mediated transcriptional changes in poinsettia buds suggest MAF3 and bZIP67 transcription factors as potential suppressors of shoot branching

O_LIShoot branching is critical not only in breeding for yield but also for ornamentals architecture. In the ornamental plant poinsettia (Euphorbia pulcherrima), shoot branching has traditionally been induced by phytoplasma (Candidatus Phytoplasma pruni) inoculation. This study aimed to identify regulatory genes that could be leveraged in future breeding-by-genetic engineering efforts to develop phytoplasma-free, branching poinsettia plants. C_LIO_LITo elucidate mechanisms of phytoplasma-induced shoot branching, we performed RNA-sequencing and assembled an axillary bud-specific transcriptome for expression analyses in phytoplasma-infected and -free poinsettia. Phenotyping and RNA-sequencing were also conducted on Arabidopsis mutants and wild-type lines to investigate the transcriptional regulatory effects of candidate genes. C_LIO_LIThe transcription factors EpMAF3 and EpbZIP67 were highly de-regulated in phytoplasma-infected poinsettia. We also found a two-fold increase in primary-stem branching levels of the Arabidopsis maf3 and bzip67 mutants, suggesting the two transcription factors as potential shoot branching suppressors. AtTcp1, a CYC-clade TCP transcription factor, was up-regulated (78x) in leaves of the maf3 mutants. Analyzing previously reported protein-level interactions for the differentially expressed genes (e.g., AtClamt, AtGh3.9/3.15, AtSaur32/36, AtAbi3, AtGamt2, AtTcp3, and AtDwf4) in bzip67 mutants shed light on other shoot branching regulators such as TCPs, PINs, ABIs, DWARF14, and BES1, highlighting two regulatory sub-networks including membrane transport and hormonal signaling. C_LIO_LIThe results open the way to rational engineering of shoot branching in poinsettia by targeted mutagenesis of MAF3 and bZIP67. In that way, the tedious and viral-infection prone process of phytoplasma inoculation can be avoided and poinsettia plants would have more homogenous branching. C_LI One-sentence summaryPhytoplasma infection in poinsettia induces bud-specific repression of the transcription factors EpMaf3 and EpbZip67, consistent with the enhanced stem branching observed in Arabidopsis maf3 and bzip67 mutant lines.

Plant Biology↗

Urban green space exposure reduces subjective stress and physiological arousal

Stress is a major risk factor for mental disorders, and urban living is a key environmental contributor. Nature exposure may promote stress recovery and mental health, but how physiological arousal and subjective stress change across green versus gray space during naturalistic urban mobility is poorly understood. This preregistered study (https://doi.org/10.17605/OSF.IO/HF4RW) employed geolocation-based ambulatory assessment to examine psychophysiological arousal and subjective stress during transitions between urban green and gray environments. Thirty-six healthy urban residents completed a counterbalanced circular walking route in Cologne, Germany, with continuous GPS, cardiovascular, and electrodermal recording alongside ecological momentary assessment of subjective stress, affect, and exertion. Green compared to gray spaces were associated with lower subjective stress and higher affective well-being, with cardiac indices reflecting reduced autonomic arousal during green space exposure. Autonomic changes surrounding environmental transitions persisted beyond the immediate transition window, suggesting that physiological benefits of green space exposure extend into subsequent gray environments. These findings underscore the public health potential of urban green infrastructure for preventing stress-related mental health conditions.

physiology↗

A conserved stripe rust effector elicits variable resistance responses in wheat

Plant resistance (R) and pathogen avirulence (Avr) gene interactions are central to pathogen recognition and disease resistance in crops. Functional characterisation of recognised Avr effectors of Puccinia striiformis f. sp. tritici (Pst) lags other key fungal pathogens of wheat. Here, we used a wheat protoplast-based screen to identify Avr/R interactions via the proxy of effector-induced defence responses in a set of diverse wheat cultivars. We identified an Avr candidate, termed AvrPstB48, that triggers defence responses in 16 out of 24 cultivars tested. AvrPstB48 is hemizygous, and the Pst genome carries four divergent paralogs within a gene cluster. Analysis of these paralogs revealed partial redundancy in their ability to activate wheat defences and enabled us to identify a single amino acid in AvrPstB48 that is necessary but not sufficient for defence activation. Notably, the activation of defence signalling by AvrPstB48 in protoplasts did not directly correlate with disease outcomes. Whole-plant infection assays revealed that some cultivars which exhibited strong defence activation in the protoplast assay are susceptible to the Pst isolate Pst104E137A- from which AvrPstB48 is derived. Comparison of infection dynamics of two wheat cultivars that differ in their AvrPstB48 recognition capacity revealed a delay in disease progression in the recognising cultivar Avocet S compared to the non-recognising cultivar Morocco. While correlative only, our observations, combined with other recent reports, support a recognize-then-suppress model of plant-pathogen interaction where disease outcomes are driven not only by simple Avr/R interactions but also by pathogen effectors that suppress defence signalling downstream of effector recognition.

plant biology↗

Human iPSC derived alveolar macrophages reveal macrophage subtype specific functions of itaconate in M. tuberculosis host defense

Mycobacterium tuberculosis (Mtb) must survive within multiple macrophage populations during infection, including alveolar macrophages (AM) and recruited inflammatory macrophages. In mice, itaconate, produced in macrophages by ACOD1 mediated decarboxylation of aconitate, has direct antimicrobial activity, modulates inflammatory cytokines, and is required for resistance to M. tuberculosis (Mtb) infection. The role of itaconate in human macrophages is less clear and whether itaconate mediates distinct effects in macrophage subtypes is unknown. Here, we investigated the role of itaconate in human iPSC-derived macrophages, either induced by GM-CSF to resemble alveolar macrophages (AM-Like cells), or treated with M-CSF to generate control macrophages (MCDM cells). Both types of human macrophages produce substantially less itaconate than mouse macrophages and AM-Ls produced 4-fold less itaconate than MCDMs. Surprisingly, ACOD1 deficient AM-L macrophages, but not MCDM macrophages, were permissive for Mtb growth. Moreover, itaconate functioned to dampen the Mtb induced inflammatory response in MCDMs, but not AM-L macrophages, affecting both the Type I IFN and TNF pathways. These results indicate that itaconate is involved in human macrophage responses to TB, with distinct roles in different macrophage subsets. These results also show that genetically tractable hiPSC-derived macrophages are a robust and versatile model to dissect cellular host pathogen interactions.

immunology↗

Altered neutrophil extracellular traps in response to Mycobacterium tuberculosis in persons living with HIV with no previous TB and negative TST and IGRA

Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and test persistently negative in tests of immune sensitization tuberculin skin test (TST) and interferon gamma release assays (IGRA) for Mycobacterium tuberculosis (Mtb). This group has been identified and defined as HIV+ persistently TB, tuberculin and IGRA negative (HITTIN). To investigate potential innate mechanisms unique to individuals with the HITTIN phenotype we compared their neutrophil Mtb infection response to that of PLWH, with no TB history, but who test persistently IGRA positive, and tuberculin positive (HIT). Neutrophil samples from 17 HITTIN (PMNHITTIN) and 11 HIT (PMNHIT) were isolated and infected with Mtb H37Rv for 1h and 6h. RNA was extracted and used for RNAseq analysis. At 1h of Mtb infection, PMNHITTIN displayed 151 significantly upregulated and 40 significantly downregulated differentially expressed genes (DEGs) and PMNHIT 98 significantly upregulated and 11 significantly downregulated DEGs. At the 6h timepoint, PMNHITTIN displayed 3106 significantly upregulated and 3548 significantly downregulated DEGs while PMNHIT had 3816 significantly up- and 3794 significantly downregulated DEGs. There was no significant differential transcriptional response at 1h between infected PMNHITTIN and PMNHIT. However, when contrasting the log2FC 6h infection response to Mtb from PMNHITTIN against PMNHIT, 2285 genes showed significant differential response between the two groups. Apoptosis and NETosis were key pathways linked to the enrichment of genes in PMNHITTIN when contrasted to PMNHIT after 6h infection with Mtb. Fluorescence microscopy revealed relatively lower neutrophil extracellular trap formation and cell loss in PMNHITTIN compared to PMNHIT, showing that PMNHITTIN have a distinct response to Mtb.

genetics↗

A highly divergent mitochondrial genome in extant Cape buffalo from Addo Elephant National Park, South Africa

The reduced cost of next-generation sequencing (NGS) has allowed researchers to generate nuclear and mitochondrial genome data to gain deeper insights into the phylogeography, evolutionary history, and biology of non-model species. While the Cape buffalo (Syncerus caffer caffer) has been well-studied across its range with traditional genetic markers over the last 25 years, researchers are building on this knowledge by generating whole genome, population-level data sets to improve understanding of the genetic composition and evolutionary history of the species. Using publicly available NGS data, we assembled 40 Cape buffalo mitochondrial genomes (mitogenomes) from four protected areas in South Africa, expanding the geographical range and almost doubling the number of mitogenomes available for this species. Coverage of the mitogenomes ranged from 154-1,036X. Haplotype and nucleotide diversity for Kruger National Park (n = 15) and Mokala National Park (n = 5) were similar to diversity levels in southern and eastern Africa. Hluhluwe-iMfolozi Park (n = 15) had low levels of genetic diversity, with only four haplotypes detected, reflecting its past bottleneck. Addo Elephant National Park (n = 5) had the highest nucleotide diversity of all populations across Africa, which was unexpected, as it is known from previous studies to have low nuclear diversity. This diversity was driven by a highly divergent mitogenome from one sample, which was subsequently identified in another sample via Sanger sequencing of the cytochrome b gene. Using a fossil-calibrated phylogenetic analysis, we estimated that this lineage diverged from all other Cape buffalo lineages approximately 2.51 million years ago. We discuss several potential sources of this mitogenome but propose that it most likely originated through introgressive hybridisation with an extinct buffalo species, either S. acoelotus or S. antiquus. We conclude by discussing the conservation consequences of this finding for the Addo Elephant National Park population, proposing careful genetic management to prevent inbreeding depression while maintaining this highly unique diversity.

genetics↗

A weakly structured stem for human origins in Africa

While it is now broadly accepted that Homo sapiens originated within Africa, considerable uncertainty surrounds specific models of divergence and migration across the continent. Progress is hampered by a paucity of fossil and genomic data, as well as variability in prior divergence time estimates. Here we use linkage disequilibrium and diversity-based statistics, optimized for rapid, complex demographic inference to discriminate among such models. We infer detailed demographic models for populations across Africa, including representatives from eastern and western groups, as well as 44 newly whole-genome sequenced individuals from the Nama (Khoe-San). Despite the complexity of African population history, contemporary population structure dates back to Marine Isotope Stage (MIS) 5. The earliest population divergence among contemporary populations occurs 120-135ka, between the Khoe-San and other groups. Prior to the divergence of contemporary African groups, we infer long-lasting structure between two or more weakly differentiated ancestral Homo populations connected by gene flow over hundreds of thousands of years (i.e. a weakly structured stem). We find that weakly structured stem models provide more likely explanations of polymorphism that had previously been attributed to contributions from archaic hominins in Africa. In contrast to models with archaic introgression, we predict that fossil remains from coexisting ancestral populations should be morphologically similar. Despite genetic similarity between these populations, an inferred 1-4% of genetic differentiation among contemporary human populations can be attributed to genetic drift between stem populations. We show that model misspecification explains variation in previous divergence time estimates and argue that studying a suite of models is key to robust inferences about deep history.

genomics↗

Dynamics of transposable elements in recently diverged fungal pathogens: lineage-specific transposable element content and efficiency of genome defences

Transposable elements (TEs) impact genome plasticity, architecture and evolution in fungal plant pathogens. The wide range of TE content observed in fungal genomes reflects diverse efficacy of host-genome defence mechanisms that can counter-balance TE expansion and spread. Closely related species can harbour drastically different TE repertoires, suggesting variation in the efficacy of genome defences. The evolution of fungal effectors, which are crucial determinants of pathogenicity, has been linked to the activity of TEs in pathogen genomes. Here we describe how TEs have shaped genome evolution of the fungal wheat pathogen Zymoseptoria tritici and four closely related species. We compared de novo TE annotations and Repeat-Induced Point mutation signatures in thirteen genomes from the Zymoseptoria species-complex. Then, we assessed the relative insertion ages of TEs using a comparative genomics approach. Finally, we explored the impact of TE insertions on genome architecture and plasticity. The thirteen genomes of Zymoseptoria species reflect different TE dynamics with a majority of recent insertions. TEs associate with distinct genome compartments in all Zymoseptoria species, including chromosomal rearrangements, genes showing presence/absence variation and effectors. European Z. tritici isolates have reduced signatures of Repeat-Induced Point mutations compared to Iranian isolates and closely related species. Our study supports the hypothesis that ongoing but moderate TE mobility in Zymoseptoria species shapes pathogen genome evolution.

genomics↗

Genome compartmentalization predates species divergence in the plant pathogen genus Zymoseptoria

BackgroundAntagonistic co-evolution can drive rapid adaptation in pathogens and shape genome architecture. Comparative genome analyses of several fungal pathogens revealed highly variable genomes, for many species characterized by specific repeat-rich genome compartments with exceptionally high sequence variability. Dynamic genome architecture may enable fast adaptation to host genetics. The wheat pathogen Zymoseptoria tritici with its highly variable genome and has emerged as a model organism to study the genomic evolution of plant pathogens. Here, we compared genomes of Z. tritici isolates and genomes of sister species infecting wild grasses to address the evolution of genome composition and structure. ResultsUsing long-read technology, we sequenced and assembled genomes of Z. ardabiliae, Z. brevis, Z. pseudotritici and Z. passerinii, together with two isolates of Z. tritici. We report a high extent of genome collinearity among Zymoseptoria species and high conservation of genomic, transcriptomic and epigenomic signatures of compartmentalization. We identify high gene content variability both within and between species. In addition, such variability is mainly limited to the accessory chromosomes and accessory compartments. Despite strong host specificity and non-overlapping host-range between species, effectors are mainly shared among Zymoseptoria species, yet exhibiting a high level of presence-absence polymorphism within Z. tritici. Using in planta transcriptomic data from Z. tritici, we suggest different roles for the shared orthologs and for the accessory genes during infection of their hosts. ConclusionDespite previous reports of high genomic plasticity in Z. tritici, we describe here a high level of conservation in genomic, epigenomic and transcriptomic signatures of genome architecture and compartmentalization across the genus Zymoseptoria. The compartmentalized genome may reflect purifying selection to retain a functional core genome and relaxed selection on the accessory genome allowing a higher extent of polymorphism.

genomics↗

A sex-stratified genome-wide association study of tuberculosis using a multi-ethnic genotyping array

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a complex disease with a known human genetic component. Males seem to be more affected than females and in most countries the TB notification rate is twice as high in males as in females. While socio-economic status, behaviour and sex hormones influence the male bias they do not fully account for it. Males have only one copy of the X chromosome, while diploid females are subject to X chromosome inactivation. In addition, the X chromosome codes for many immune-related genes, supporting the hypothesis that X-linked genes could contribute to TB susceptibility in a sex-biased manner. We report the first TB susceptibility genome-wide association study (GWAS) with a specific focus on sex-stratified autosomal analysis and the X chromosome. Individuals from an admixed South African population were genotyped using the Illumina Multi Ethnic Genotyping Array, specifically designed as a suitable platform for diverse and admixed populations. Association testing was done on the autosome and X chromosome in a sex stratified and combined manner. SNP association testing was not statistically significant using a stringent cut-off for significance but revealed likely candidate genes that warrant further investigation. A genome wide interaction analysis detected 16 significant interactions. Finally, the results highlight the importance of sex-stratified analysis as strong sex-specific effects were identified on both the autosome and X chromosome.

genetics↗

Fine-scale human population structure in southern Africa reflects ecogeographic boundaries

Recent genetic studies have established that the KhoeSan populations of southern Africa are distinct from all other African populations and have remained largely isolated during human prehistory until about 2,000 years ago. Dozens of different KhoeSan groups exist, belonging to three different language families, but very little is known about their population history. We examine new genome-wide polymorphism data and whole mitochondrial genomes for more than one hundred South Africans from the =Khomani San and Nama populations of the Northern Cape, analyzed in conjunction with 19 additional southern African populations. Our analyses reveal fine-scale population structure in and around the Kalahari Desert. Surprisingly, this structure does not always correspond to linguistic or subsistence categories as previously suggested, but rather reflects the role of geographic barriers and the ecology of the greater Kalahari Basin. Regardless of subsistence strategy, the indigenous Khoe-speaking Nama pastoralists and the N|u-speaking =Khomani (formerly hunter-gatherers) share ancestry with other Khoe-speaking forager populations that form a rim around the Kalahari Desert. We reconstruct earlier migration patterns and estimate that the southern Kalahari populations were among the last to experience gene flow from Bantu-speakers, approximately 14 generations ago. We conclude that local adoption of pastoralism, at least by the Nama, appears to have been primarily a cultural process with limited genetic impact from eastern Africa.\n\nData depositionData files are freely available on the Henn Lab website: http://ecoevo.stonybrook.edu/hennlab/data-software/\n\nSummaryDistinct, spatially organized ancestries demonstrate fine-scale population structure in southern Africa, implying a more complex history of the KhoeSan than previously thought. Southern KhoeSan ancestry in the Nama and =Khomani is shared in a rim around the Kalahari Desert. We hypothesize that there was recent migration of pastoralists from East Africa into southern Africa, independent of the Bantu-expansion, but the spread of pastoralism within southern Africa occurred largely by cultural diffusion.

genetics↗