Biology subjects

Metzger, S.

Publications and source records attributed to Metzger, S..

24 records · Page 2Linked to original sources

bioRxiv2022

Nitrogen and phosphorus deficiencies alter primary and secondary metabolites of soybean roots

Nitrogen (N) and phosphorus (P) are two essential plant macronutrients that can limit plant growth by different mechanisms. We aimed to shed light on how soybean respond to low nitrogen (LN), low phosphorus (LP) and their combined deficiency (LNP). Generally, these conditions triggered changes in gene expression of the same processes, including cell wall organization, defense response, response to oxidative stress, and photosynthesis, however, response was different in each condition. A typical primary response to LN and LP was detected also in soybean, i.e., the enhanced uptake of N and P, respectively, by upregulation of genes for the corresponding transporters. The regulation of genes involved in cell wall organization showed that in LP roots tended to produce more casparian strip, in LN more secondary wall biosynthesis occurred, and in LNP reduction in expression of genes involved in secondary wall production accompanied by cell wall loosening was observed. Flavonoid biosynthesis also showed distinct pattern of regulation in different conditions: more anthocyanin production in LP, and more isoflavonoid production in LN and LNP, which we confirmed also on the metabolite level. Interestingly, in soybean the nutrient deficiencies reduced defense response by lowering expression of genes involved in defense response, suggesting a role of N and P nutrition in plant disease resistance. In conclusion, we provide detailed information on how LN, LP, and LNP affect different processes in soybean roots on the molecular and physiological levels.

plant biology↗

bioRxiv2021

Metabolic analysis of a bacterial synthetic community from maize roots provides new mechanistic insights into microbiome stability

Stability is a desirable property for agricultural microbiomes, but there is a poor understanding of the mechanisms that mediate microbial community stability. Recently, a representative bacterial synthetic community from maize roots has been proposed as a model system to study microbiome stability (Niu 2017, PNAS, 114:E2450). This SynCom assembles stably when all seven members are present, but community diversity collapses without the keystone E. cloacae strain. The aim of this study was to assess the role of metabolites for the stability of this SynCom, by defining the metabolic niches occupied by each strain, as well as their cross-feeding phenotypes and B-vitamin dependencies. We show that the individual member strains occupy complementary metabolic niches, measured by the depletion of distinct metabolites in exometabolomic experiments, as well as contrasting growth phenotypes on diverse carbon substrates. Minimal medium experiments show that the established seven-member community comprises a mixture of prototrophic and auxotrophic strains. Correspondingly, experimental cross-feeding phenotypes showed that spent media harvested from the prototrophic strains can sustain growth of two auxotrophs. We suggest that the metabolic mechanisms exhibited by this SynCom could serve as design principles to inform the rational assembly of stable plant-associated microbial communities.

microbiology↗

bioRxiv2021

Latent neural dynamics encode temporal context in speech

Direct neural recordings from human auditory cortex have demonstrated encoding for acoustic-phonetic features of consonants and vowels. Neural responses also encode distinct acoustic amplitude cues related to timing, such as those that occur at the onset of a sentence after a silent period or the onset of the vowel in each syllable. Here, we used a group reduced rank regression model to show that distributed cortical responses support a low-dimensional latent state representation of temporal context in speech. The timing cues each capture more unique variance than all other phonetic features and exhibit rotational or cyclical dynamics in latent space from activity that is widespread over the superior temporal gyrus. We propose that these spatially distributed timing signals could serve to provide temporal context for, and possibly bind across time, the concurrent processing of individual phonetic features, to compose higher-order phonological (e.g. word-level) representations.

neuroscience↗

bioRxiv2021

Universal amyloidogenicity of patient-derivedimmunoglobulin light chains

The deposition of immunoglobulin light chains (IgLCs) in the form of amorphous aggregates or amyloid fibrils in different tissues of patients can lead to severe and potentially fatal organ damage, requiring transplantation in some cases. There has been great interest in recent years to elucidate the origin of the very different in vivo solubilities of IgLCs, as well as the molecular determinants that drive either the formation of ordered amyloid fibrils or disordered amorphous aggregates. It is commonly thought that the reason of this differential aggregation behaviour is to be found in the amino acid sequences of the respective IgLCs, i.e. that some sequences display higher intrinsic tendencies to form amyloid fibrils. Here we perform in depth Thermodynamic and Aggregation Fingerprinting (ThAgg-Fip) of 9 multiple myeloma patient-derived IgLCs, the amino acid sequences of all of which we have solved by de novo protein sequencing with mass spectrometry. The latter technique was also used for one IgLc from a patient with AL amyloidosis. We find that all samples also contain proteases that fragment the proteins under physiologically relevant mildly acidic pH conditions, leading to amyloid fibril formation in all cases. Our results suggest that while every pathogenic IgLC has a unique ThAgg fingerprint, all sequences have comparable amyloidogenic potential. Therefore, extrinsic factors, in particular presence of, and susceptibility to, proteolytic cleavage is likely to be a strong determinant of in vivo aggregation behaviour. The important conclusion, which is corroborated by systematic analysis of our sequences, as well as many sequences of IgLCs from amyloidosis patients reported in the literature, challenges the current paradigm of the link between sequence and amyloid fibril formation of pathogenic light chains.

biophysics↗

bioRxiv2020

Leprosy in wild chimpanzees

Humans are considered the main host for Mycobacterium leprae, the aetiologic agent of leprosy, but spill-over to other mammals such as nine-banded armadillos and red squirrels occurs. Although naturally acquired leprosy has also been described in captive nonhuman primates, the exact origins of infection remain unclear. Here, we report on leprosy-like lesions in two wild populations of western chimpanzees (Pan troglodytes verus) in the Cantanhez National Park, Guinea-Bissau, and the Tai National Park, Cote dIvoire, West Africa. Longitudinal monitoring of both populations revealed the progression of disease symptoms compatible with advanced leprosy. Screening of faecal and necropsy samples confirmed the presence of M. leprae as the causative agent at each site and phylogenomic comparisons with other strains from humans and other animals show that the chimpanzee strains belong to different and rare genotypes (4N/O and 2F). The independent evolutionary origin of M. leprae in two geographically distant populations of wild chimpanzees, with no prolonged direct contact with humans, suggests multiple introductions of M. leprae from an unknown animal or environmental source.

evolutionary biology↗

bioRxiv2019

Vascular Progenitors Generated from Tankyrase Inhibitor-Regulated Diabetic Induced Pluripotent Stem Cells Potentiate Efficient Revascularization of Ischemic Retina

Vascular regenerative therapies with conventional human induced pluripotent stem cells (hiPSC) currently remain limited by high interline variability of differentiation and poor efficiency for generating functionally transplantable vascular progenitors (VP). Here, we report the advantage of tankyrase inhibitor-regulated naive hiPSC (N-hiPSC) for significantly improving vascular cell therapies. Conventional hiPSC reprogrammed from type-1 diabetic donor fibroblasts (DhiPSC) were stably reverted to naive epiblast-like state with high functional pluripotency with a cocktail of LIF and three small molecules inhibiting the tankyrase, MEK, and GSK3{beta} signaling pathways (LIF-3i). Naive diabetic VP (N-DVP) differentiated from naive DhiPSC (N-DhiPSC) expanded more efficiently, possessed higher proliferation, possessed more stable genomic integrity and displayed higher in vitro vascular functionality than primed diabetic VP (DVP) generated from isogenic conventional DhiPSC. Moreover, N-DVP survived, migrated, and engrafted in vivo into the deep vasculature of the neural retinal layers with significantly higher efficiencies than isogenic primed DVP in a murine model of ischemic retinopathy. Epigenetic analyses of CpG DNA methylation and histone configurations at developmental promoters of N-hiPSC revealed tight regulation of lineage-specific gene expression and a de-repressed naive epiblast-like epigenetic state that was highly poised for multi-lineage transcriptional activation. We propose that reprogramming of patient donor cells to a tankyrase inhibitor-regulated N-hiPSC may more effectively erase epigenetic aberrations sustained from chronic diseases such as diabetes for subsequent regenerative therapies. More broadly, tankyrase inhibitor-regulated N-hiPSC represent a new class of human stem cells with high epigenetic plasticity, improved multi-lineage functionality, and potentially high impact for regenerative medicine.

developmental biology↗