Biology subjects

Fiedler, S.

Publications and source records attributed to Fiedler, S..

12 recordsLinked to original sources

bioRxiv2025

Stone Age anthropogenic impacts to forest development in the interior Scandinavian Peninsula

Forest growth and development is a highly studied phenomenon in which humans have proven to be influential in shaping structure and composition. Delineating the long-term processes of human-environment interactions is crucial for understanding the history and trajectory of landscape formation and vegetation development. Yet, extensive knowledge of the ecological impacts of Stone Age anthropogenic activity is still lacking, particularly from Fennoscandian sites. A sediment core from South Mesna lake from the interior Scandinavian Peninsula was extracted to investigate the long-term evolutionary effects of human-environment interactions following deglaciation (c. 10,500 cal. BP) and initial colonization of the region. Analysis of the core involved microscopic/trace analytical methods, including geochemical analysis, stable isotope analysis, fecal biomarker analysis, and pollen analysis. The combined evidence demonstrates that anthropogenic impacts are prominent shapers of the ecological trajectory and landscape development of the region since the Early Neolithic (c. 5900 cal. BP), which has left a footprint on modern-day land cover. SignificanceAnthropogenic impacts on the environment have been observed to have had notable consequences on global and regional ecological trajectories and environmental development. Yet, how coupled human-environment interactions affect the long-term ecological complexion of boreal landscapes, such as those of the interior Scandinavian Peninsula, is not widely studied. This article presents evidence of early anthropogenic impacts to a forests ecology during the Holocene. Fecal biomarker and pollen analyses make it possible to provide micro-archaeological evidence of human activity and correlate it with noteworthy changes in forest structure. Our data points to a specific co-evolutionary forest development trajectory which is connected to millennial-scale human settlement patterns.

ecology↗

bioRxiv2024

Anthelmintic resistance against benzimidazoles and macrocyclic lactones in strongyle populations on cattle farms in northern Germany

Anthelmintic resistance (AR) in cattle gastrointestinal nematodes (GIN) is an increasing global concern, with low to moderate levels recently documented in Central Europe. This study reports on resistance against both macrocyclic lactones (MLs) and benzimidazoles (BZs), highlighting that AR is spreading. The Fecal Egg Count Reduction Test (FECRT) remains the primary tool for AR assessment, yet differing methodologies and recent guideline updates complicate resistance interpretation across studies. Statistical methods, such as Bayesian approaches used by eggCounts and bayescount, yield varying confidence intervals, further influencing results. Notably, the nemabiome analysis identified Ostertagia ostertagi and Cooperia oncophora as predominant species in the region, though unexpected diversity among farms with additional GIN species occurring sometimes even at high frequency, suggests morphological analysis of coprocultures may underestimate species prevalence. Detecting AR against both drug classes on some farms underscores the urgency of implementing sustainable strategies, such as targeted selective treatment and combinations of anthelmintics with different mode of action, to prevent scenarios of multi-drug resistance observed elsewhere. Effective resistance management requires immediate discussions with veterinarians and stakeholders to steer toward informed, preventive measures in cattle farming.

microbiology↗

bioRxiv2023

Genetic diversity of the Atacama Desert shrub Huidobria chilensis in the context of geography and climate

Survival in hyperarid deserts is a major challenge for plant life, requiring the development of evolutionary strategies. The Atacama Desert presents harsh conditions such as limited rainfall, crusted soils, high soil salinity, high altitude, and intense solar radiation. These conditions, together with paleoclimatic variability since the past millions of years, have influenced the genetic structure and connectivity of plant populations, resulting in a diverse flora with high endemism. However, the diversification of most lineages appears to be relatively recent, in contrast to proposed age of the Atacama Desert and the onset, evolution and expansion of hyperarid conditions since the Late Oligocene and Early Miocene. A prominent exception is the Atacama paleoendemic Huidobria chilensis (Loasaceae), which is thought to be adapted to such conditions since the Eocene. Still, the environmental limits and thresholds for life in the Atacama remain poorly understood. To investigate the genetic structure in relation to the history of the Atacama Desert, we studied 186 individuals from 11 populations using genotyping-by-sequencing (GBS). Genome-wide single nucleotide polymorphisms (SNPs) were analyzed for population structure and genetic diversity. We identified three genetic clusters corresponding to geographic regions: the coastal region south of Tocopilla, the Coastal Cordillera around Chanaral, and the Copiapo watershed in the south. These clusters as well as genetic diversity were analyzed alongside rainfall, altitude, and landscape data. Although the genetic data generally supports isolation by distance as a major factor for genetic variation between populations, the study also reveals the influence of the topography on the distribution of H. chilensis and highlights the role of hydrologically connected watersheds and rivers in plant migration and colonization. This shapes the species evolutionary trajectory and genetic diversity. Understanding these patterns provides insights into the adaptation and survival strategies of plants in extreme desert environments such as the Atacama.

genetics↗

bioRxiv2023

Scale-dependent landscape-biodiversity relationships shape multi-taxa diversity in an oil palm monoculture under restoration

Enhancing biodiversity in monoculture-dominated landscapes is a pressing restoration challenge. Tree islands can enhance biodiversity locally, but the role of scale-dependent processes on local biodiversity remains unclear. Using a multi-scale approach, we explored how scale-dependent processes influence the diversity of seven taxa (woody plants, understory arthropods, birds, herbaceous plants and soil bacteria, fauna, and fungi) within 52 experimental tree islands embedded in an oil palm landscape. We show that local, metacommunity (between islands), and landscape properties shaped above- and below-ground taxa diversity, with the stronger effects on above-ground taxa. The spatial extent that best-predicted diversity ranged from 150 m for woody plants to 700 m for understory arthropods with below-ground taxa responding at large spatial extents. Our results underscore the need for multi-scale approaches to restoration. Additionally, our findings contribute to understanding the complex processes shaping multi-taxa diversity and offer insights for targeted conservation and restoration strategies.

ecology↗

bioRxiv2023

Alpha-synuclein oligomers displace monomeric alpha-synuclein from lipid membranes

Parkinsons disease (PD) is an increasingly prevalent and currently incurable neurodegenerative disorder linked to the accumulation of -synuclein (S) protein aggregates in the nervous system. While S binding to membranes in its monomeric state is correlated to its physiological role, S oligomerisation and subsequent aberrant interactions with lipid bilayers have emerged as key steps in PD-associated neurotoxicity. However, little is known of the mechanisms that govern the interactions of oligomeric S (OS) with lipid membranes and the factors that modulate such interactions. This is in large part due to experimental challenges underlying studies of OS-membrane interactions due to their dynamic and transient nature. Here, we address this challenge by using a suite of microfluidics-based assays that enable in-solution quantification of OS-membrane interactions. We find that OS bind more strongly to highly curved, rather than flat, lipid membranes. By comparing the membrane-binding properties of OS and monomeric S (MS), we further demonstrate that OS bind to membranes with up to 150-fold higher affinity than their monomeric counterparts. Moreover, OS compete with and displace bound MS from the membrane surface, suggesting that disruption to the functional binding of MS to membranes may provide an additional toxicity mechanism in PD. These findings present a unique binding mechanism of oligomers to model membranes, which can potentially be targeted to inhibit the progression of PD. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=62 SRC="FIGDIR/small/533646v2_ufig1.gif" ALT="Figure 1"> View larger version (10K): org.highwire.dtl.DTLVardef@4ab089org.highwire.dtl.DTLVardef@18c0709org.highwire.dtl.DTLVardef@220077org.highwire.dtl.DTLVardef@4c85b9_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2022

Protein secretion zones within the Gram-positive cell wall

Whereas the translocation of proteins across the cell membrane has been thoroughly investigated, it is still unclear how proteins cross the cell wall in Gram positive bacteria, which are widely used for industrial applications. We have studied secretion of -amylase AmyE within two different Bacillus strains. We show that a C-terminal fusion of AmyE with the fluorescent reporter mCherry is secreted via discrete patches with very low dynamics that are visible at many places within the lateral cell wall, for many minutes. Expression from a high copy number plasmid was required to be able to see these structures we term "secretion zones". Zones corresponded to visualized AmyE activity on the surface of cells, and frequently overlapped with SecA signals, but did not necessarily co-localize with the secretion ATPase. Single particle tracking showed much higher dynamics of SecA and of SecDF, involved in AmyE secretion, at the cell membrane than AmyE. These experiments suggest that SecA initially translocates AmyE molecules through the cell membrane, and then diffuses to a different translocon. Single molecule tracking of SecA show changes in distinct diffusion states of SecA, but suggest that AmyE overexpression does not overwhelm the system. Because secretion zones were only found during the transition to and within stationary phase, diffusion rather than passive transport based on cell wall growth from inside to outside, releases AmyE and thus probably secreted proteins in general. Our findings suggest active transport through the cell membrane and slow, passive transition through the cell wall in Gram positive bacteria.

microbiology↗

bioRxiv2022

Antibody affinity and concentration of convalescent sera provide context for reduced SARS-CoV-2 Omicron spike affinity of therapeutic antibodies

We assessed the affinities of the therapeutic monoclonal antibodies (mAbs) cilgavimab, tixagevimab, sotrovimab, casirivimab, and imdevimab to the receptor binding domain (RBD) of wild type, Delta, and Omicron spike. The Omicron RBD affinities of cilgavimab, tixagevimab, casirivimab, and imdevimab decreased by at least two orders of magnitude relative to their wild type equivalents, whereas sotrovimab binding was less severely impacted. These affinity reductions correlate with reduced antiviral activities of these antibodies, suggesting that simple affinity measurements can serve as an indicator for activity before challenging and time-consuming virus neutralization assays are performed. We also compared the properties of these antibodies to serological fingerprints (affinities and concentrations) of wild type RBD specific antibodies in 74 convalescent sera. The affinities of the therapeutic mAbs to wild type and Delta RBD were in the same range as the polyclonal response in the convalescent sera indicative of their high antiviral activities against these variants. However, for Omicron RBD, only sotrovimab retained affinities that were within the range of the polyclonal response, in agreement with its high activity against Omicron. Serological fingerprints thus provide important context to affinities and antiviral activity of mAb drugs and could guide the development of new therapeutics.

biochemistry↗

bioRxiv2021

A GGDEF domain serves as a spatial on-switch for a phosphodiesterase by direct interaction with a polar landmark protein

In bacteria, the monopolar localization of enzymes and protein complexes can result in a bi-modal distribution of enzyme activity between the dividing cells and heterogeneity of cellular behaviors. In Shewanella putrefaciens, the multidomain hybrid diguanylate cyclase/phosphodiesterase PdeB, which degrades the secondary messenger c-di-GMP, is located at the flagellated cell pole. Here we show how PdeB polar recruitment is mediated by direct interaction between the inactive diguanylate cyclase (GGDEF) domain of PdeB and the C-terminal FimV domain of the polar landmark protein HubP. We demonstrate that this interaction is crucial for full function of PdeB as a phosphodiesterase. Thus, the GGDEF domain serves as a spatially controlled on-switch that effectively restricts PdeBs activity to the flagellated cell pole. We further show that PdeB regulates abundance and activity of at least two crucial surface-interaction factors, the BpfA surface adhesion protein and the MSHA type IV pilus. The heterogeneity in c-di-GMP concentrations that is generated by differences in abundance and temporal polar appearance of PdeB as well as by bi-modal distribution after cell fission orchestrates the population behavior with respect to cell-surface interaction and environmental spreading. SignificancePhenotypic heterogeneity benefits the proliferation of microbial populations in changing environments. Such heterogeneity can be created by recruitment of enzymatic activity to specific cellular compartments, e.g., the cell pole. Here we show how a GGDEF domain of a multidomain phosphodiesterase has adopted the function as a spatial on-switch that is specifically activated upon direct interaction with a polar landmark protein.

microbiology↗

bioRxiv2021

Mutations in two SARS-CoV-2 variants of concern reflect two distinct strategies of antibody escape

Understanding the factors that contribute to antibody escape of SARS-CoV-2 and its variants is key for the development of drugs and vaccines that provide broad protection against a variety of virus variants. Using microfluidic diffusional sizing, we determined the dissociation constant (KD) for the interaction between receptor binding domains (RBDs) of SARS-CoV-2 in its original version (WT) as well as alpha and beta variants with the host-cell receptor angiotensin converting enzyme 2 (ACE2). For RBD-alpha, the ACE2-binding affinity was increased by a factor of ten when compared with RBD-WT, while ACE2-binding of RBD-beta was largely unaffected. However, when challenged with a neutralizing antibody that binds to both RBD-WT and RBD-alpha with low nanomolar KD values, RBD-beta displayed no binding, suggesting a substantial epitope change. In SARS-CoV-2 convalescent sera, RBD-binding antibodies showed low nanomolar affinities to both wild-type and variant RBD proteins--strikingly, the concentration of antibodies binding to RBD-beta was half that of RBD-WT and RBD-alpha, again indicating considerable epitope changes in the beta variant. Our data therefore suggests that one factor contributing to the higher transmissibility and antibody evasion of SARS-CoV-2 alpha and beta is a larger fraction of viruses that can form a complex with ACE2. However, the two variants employ different mechanisms to achieve this goal. While SARS-CoV-2 alpha RBD binds with greater affinity to ACE2 and is thus more difficult to displace from the receptor by neutralizing antibodies, RBD-beta is less accessible to antibodies due to epitope changes which increases the chances of ACE2-binding and infection.

biochemistry↗

bioRxiv2021

Understanding the role of memory re-activation and cross-reactivity in the defense against SARS-CoV-2

Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potential beneficial as well as detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be re-activated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Understanding the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be deconvoluted by surface-based assays like enzyme-linked immunosorbent assays (ELISAs) which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody-affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory re-activation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2.

biophysics↗

bioRxiv2020

Restoration ecologists might not get what they want: Global change shifts trade-offs among ecosystem functions

O_LIEcological restoration increasingly aims at improving ecosystem multifunctionality and making landscapes resilient to future threats, especially in biodiversity hotspots such as Mediterranean-type ecosystems. Successful realisation of such a strategy requires a fundamental mechanistic understanding of the link between ecosystem plant composition, plant traits and related ecosystem functions and services, as well as how climate change affects these relationships. An integrated approach of empirical research and simulation modelling with focus on plant traits can allow this understanding. C_LIO_LIBased on empirical data from a large-scale restoration project in a Mediterranean-type climate in Western Australia, we developed and validated the spatially explicit simulation model ModEST, which calculates coupled dynamics of nutrients, water and individual plants characterised by traits. We then simulated all possible combinations of eight plant species with different levels of diversity to assess the role of plant diversity and traits on multifunctionality, the provision of six ecosystem functions (covering three ecosystem services), as well as trade-offs and synergies among the functions under current and future climatic conditions. C_LIO_LIOur results show that multifunctionality cannot fully be achieved because of trade-offs among functions that are attributable to sets of traits that affect functions differently. Our measure of multifunctionality was increased by higher levels of planted species richness under current, but not future climatic conditions. In contrast, single functions were differently impacted by increased plant diversity. In addition, we found that trade-offs and synergies among functions shifted with climate change. C_LIO_LISynthesis and application. Our results imply that restoration ecologists will face a clear challenge to achieve their targets with respect to multifunctionality not only under current conditions, but also in the long-term. However, once ModEST is parameterized and validated for a specific restoration site, managers can assess which target goals can be achieved given the set of available plant species and site-specific conditions. It can also highlight which species combinations can best achieve long-term improved multifunctionality due to their trait diversity. C_LI

ecology↗

bioRxiv2020

In vitro measurements of protein-protein interactions show that antibody affinity governs the inhibition of SARS-CoV-2 spike/ACE2 binding in convalescent serum

The humoral immune response plays a key role in suppressing the pathogenesis of SARS-CoV-2. The molecular determinants underlying the neutralization of the virus remain, however, incompletely understood. Here, we show that the ability of antibodies to disrupt the binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell, the key molecular event initiating SARS-CoV-2 entry into host cells, is controlled by the affinity of these antibodies to the viral antigen. By using microfluidic antibody-affinity profiling, we were able to quantify the serum-antibody mediated inhibition of ACE2-spike binding in two SARS-CoV-2 seropositive individuals. Measurements to determine the affinity, concentration, and neutralization potential of antibodies were performed directly in human serum. Using this approach, we demonstrate that the level of inhibition in both samples can be quantitatively described using the binding energies of the binary interactions between the ACE2 receptor and the spike protein, and the spike protein and the neutralizing antibody. These experiments represent a new type of in-solution receptor binding competition assay, which has further potential areas of application ranging from decisions on donor selection for convalescent plasma therapy, to identification of lead candidates in therapeutic antibody development, and vaccine development.

biochemistry↗