Biology subjects

Nagel, A.

Publications and source records attributed to Nagel, A..

5 recordsLinked to original sources

bioRxiv2026

Signatures of Hebbian plasticity in the nanoscale morphodynamics of cortical spines

The size, shape, and nanoscale organization of synaptic spines are predictive of physiological synaptic strength and thus key to connectome-based neural circuit models. In the intact brain, spine size and shape undergo continuous morphological remodeling. While these nanoscale morphodynamics are not well understood, it is clear that morphological changes that strongly impact synaptic strength should modify spine head and neck in a coordinated manner and that such coordinated remodeling can be triggered by spike-timing-dependent synaptic plasticity. Here we demonstrate unambiguous signatures of such coordinated spine remodeling from in vivo long-term nanoscopy of cortical spines. We infer data-driven generative models of synaptic spine morphodynamics. These models imply that although coordinated remodeling represents the smallest component of ongoing morphodynamic fluctuations, this component causes massive fluctuations in instantaneous synaptic strength. Despite these fluctuations, synaptic strengths exhibit a synapse-specific long-term persistent component that results from spine fluctuations exploring only a limited subregion of accessible spine morphospace. Our results suggest that nanoscale morphodynamic spine remodeling injects substantial fluctuations of instantaneous synaptic strength into the operation of cortical circuits. Connectome-based neural circuit models thus need to consider features of spine organization beyond spine head size and should be augmented by data-driven generative models of spine morphodynamics.

neuroscience↗

bioRxiv2025

Characterization of real B0 shim fields generated by higher order B0 shim systems of whole body human 3T and 7T MRI systems

PurposeEnsuring optimal homogeneity of the static magnetic field (B0) is critically important for significantly enhancing the image quality, spectral resolution, and overall diagnostic accuracy of magnetic resonance imaging (MRI) and magnetic resonance spectroscopy/spectroscopic imaging (MRS/MRSI), especially at high and ultra-high field strengths. Achieving this goal relies on the deployment of advanced, higher-order shim hardware, which is indispensable for effective and precise B0 shimming. MethodsIn this study, we acquired B0 field maps to characterize the performance of each shim channel of vendor-provided B0 shim hardware integrated into whole body human 7T MRI system. To rigorously evaluate and compare the B0 field homogeneity achievable using these devices, we utilized spherical harmonic expansions to fit the measured B0 distributions for each shim channel in each of the investigated built-in B0 shim systems. This methodology enabled a systematic assessment of shim field "purity" and the effectiveness of different B0 shim configurations. ResultsWhile our analysis confirmed that the linear-order shim terms provided by the gradient coils maintained high purity, certain second-order shim terms and all third-order B0 shim coils of all vendors 7T whole body human MRI systems exhibit a high level of impurity and more specifically introduce substantial linear field components. These unintended linear contributions interfere with the linear shim fields provided by the gradient coils negating their corrective influence. As a result, the 3rd order B0 shim coils and some 2nd order B0 shim coil elements compromised the overall effectiveness of the B0 shimming process rather than improving it. Although pure higher order B0 shim fields were previously shown to substantially improve B0 field inhomogeneity, the vendor implemented versions of higher order B0 shim systems in current 7T whole-body human MRI scanners cannot achieve the desired level of uniformity and partly perform worse than first order B0 shimming. Substantial deviations between 2nd order and especially 3rd order real shim fields versus ideal shim fields demonstrate the necessity of real shim field calibration and call for improvement of future 2nd and 3rd order B0 shim coil design for human whole-body MRI scanners. Our findings offer valuable guidance for optimizing B0 shimming strategies at high and ultra-high field strengths, ultimately enhancing image quality. ConclusionRecent evaluations have demonstrated that certain second- and third-order shim coils, as implemented in current commercial 7T human whole-body MRI systems, introduce unintended lower-order (linear) field components. These field "impurities" substantially deviate from the desired higher-order spatial harmonics, thereby diminishing the orthogonality of the higher order B0 shim system. This in turn largely compromises the effectiveness of higher-order B0 shimming at whole-body 7T MRI scanners. These findings emphasize the necessity of conducting accurate shim field calibration to best utilize the current 7T B0 shim system configurations on one hand. On the other hand, improving the purity of these commercial B0 shim systems in the design phase to ensure that the higher-order terms accurately match their intended spherical harmonic profiles, particularly for the third-order shim terms--would largely enhance the achievable B0 field homogeneity at 7T. This improvement has directly clinically significant outcomes.

bioengineering↗

bioRxiv2025

The Aspergillus nidulans transcription factor SclB governs the transition from vegetative to asexual development

Asexual reproduction in filamentous fungi is a common, efficient and fast differentiation process, for producing large numbers of asexual spores (conidia), which can be distributed through the air to colonize new environments. The whole process is tightly controlled by specific regulatory proteins. Among those major regulators is the zinc-finger domain protein of SclB (Sclerotia like B), known to influence various aspects of asexual growth and secondary metabolism in Aspergillus nidulans as well as other filamentous fungi. Two different growth conditions of A. nidulans were compared to obtain a mechanistic overview for the role of SclB, mainly during the transition of the fungus from vegetative to asexual growth. Chromatin immunoprecipitation was coupled with next generation sequencing (ChIP-seq) and combined with transcriptomic analyses (RNA-seq). SclB coordinates this developmental shift mainly by controlling the expression of genes encoding for few, however, prominent regulators of conidiation. They include the transcription factors BrlA, VelB and SclB and the pheromone oxygenase PpoC. Association of SclB to promoter regions requires the newly identified SclB response element (SRE) with a nine base-pair DNA motif. Scl2 is the corresponding protein in the fungal plant pathogen Verticillium dahliae and partially complements the {Delta}sclB A. nidulans asexual deficiency. This supports a conserved function of this regulator among different fungal species. In summary, SclB coordinates transition from vegetative growth to asexual reproduction in A. nidulans through in vivo transcriptional control over genes coding for established players of conidia formation. ImportanceFungi constantly adapt to environmental changes in their various habitats. Asexual spore formation allows to quickly leave an unfriendly habitat through dispersal into the air. The asexual developmental program of fungi ensures large number of spores, in a short period of time and in energetically efficient manner. SclB transcription factor is a key regulator of asexual growth and secondary metabolism in numerous fungal species. The mechanism through which SclB orchestrates the transition of the Aspergillus nidulans filamentous fungus from the vegetative to the asexual growth was revealed. This regulator directly controls in vivo itself as well as expression of master genes for the asexual program such as brlA for transcriptional control or ppoC for pheromone production. This study enhances the molecular understanding, how fungal asexual differentiation is initiated and coordinated, which supports the development of better strategies to control fungal pathogens, improving human health, safety and crop management.

molecular biology↗

bioRxiv2025

A Chemostat-Based Model for Growing Bacterial Biofilms

Biofilms are groups of microbes that live together in dense communities, often attached to a surface. They play an outsized role in all aspects of microbial life, from chronic infections to biofouling to dental decay. In recent decades, appreciation for the diversity of roles that biofilms play in the environment has grown. Yet, most bacterial studies still rely upon approaches developed in the 19th century and center on planktonic populations alone. Here we present a chemostat-based experimental platform to investigate not only biofilms themselves, but how they interact with their surrounding environments. Our results show that biofilms grow to larger sizes in chemostats as opposed to flasks. In addition, we show that biofilms may be a consistent source of migrants into planktonic populations. We also show that secondary biofilms rapidly develop, although these may be more susceptible to environmental conditions. Taken together, our data suggest that chemostats may be a flexible and insightful platform for the study of biofilms in vitro. IMPORTANCEBiofilms are the predominant way that bacteria live in natural environments and are characterized by three emergent properties: ubiquity, resilience, and impact. They can be found across all environments, both natural and human-made, and across all of recorded time, dating back at least 3.5 billion years. Biofilms also represent a major economic impact of over $5 trillion annually. Yet, most of what is known about bacteria is the result of studies using planktonically growing liquid cultures under laboratory conditions. Here, we propose a comprehensive experimental platform that allows for study of biofilms on the molecular, organismal, and community levels using chemostats.

microbiology↗

bioRxiv2020

V. longisporum elicits media-dependent secretome responses with a further capacity to distinguish between plant-related environments

Verticillia cause a vascular wilt disease affecting a broad range of economically valuable crops. The fungus enters its host plants through the roots and colonizes the vascular system. It requires extracellular proteins for a successful plant colonization. The exoproteome of the allodiploid Verticillium longisporum was analyzed upon cultivation in different media. Secreted fungal proteins were identified by label free LC-MS/MS screening. V. longisporum induced two main secretion patterns. One response pattern was elicited in various non-plant related environments. The second pattern includes the exoprotein responses to the plant-related media, pectin-rich simulated xylem medium and pure xylem sap, which exhibited similar but additional distinct features. These exoproteomes include a shared core set of 223 secreted and similarly enriched fungal proteins. The pectin-rich medium significantly induced the secretion of 144 proteins including a number of pectin degrading enzymes, whereas xylem sap triggered a smaller but unique fungal exoproteome pattern with 32 enriched proteins. The latter pattern included proteins with domains of known effectors, metallopeptidases and carbohydrate-active enzymes. The most abundant and uniquely enriched proteins of these different groups are the necrosis and ethylene inducing-like proteins Nlp2 and Nlp3, the cerato-platanin proteins Cp1 and Cp2, the metallopeptidases Mep1 and Mep2 and the CAZys Gla1, Amy1 and Cbd1. Deletion of the majority of the corresponding genes caused no phenotypic changes during ex planta growth or invasion and colonization of tomato plants. However, we discovered that the NLP2 and NLP3 deletion strains were compromised in plant infections. Overall, our exoproteome approach revealed that the fungus induces specific secretion responses in different environments. The fungus has a general response to non-plant related media whereas it is able to fine-tune its exoproteome in the presence of plant material. Importantly, the xylem sap-specific exoproteome pinpointed Nlp2 and Nlp3 as single effectors required for successful V. dahliae colonization. Author SummaryVerticillium spp. infect hundreds of different plants world-wide leading to enormous economic losses. Verticillium wilt is a disease of the vasculature. The fungus colonizes the xylem of its host plant where it exploits the vascular system to colonize the whole plant. Therefore, the fungus spends part of its lifetime in this nutrient-low and imbalanced environment where it is inaccessible for disease control treatments. This lifestyle as well requires the fungus to react to plant defense responses by secreting specific effector molecules to establish a successful infection. We addressed the differences in media-dependent secretion responses of Verticillium longisporum. We identified a broad response pattern induced by several media, and a similar response (but with some distinct differences) for the plant-related environments: the pectin-rich medium SXM and xylem sap from the host rapeseed. Importantly, we show that the necrosis and ethylene inducing-like proteins Nlp2 and Nlp3 are xylem sap-specific proteins that are required for full V. dahliae pathogenicity on tomato. These factors play a role during the colonization phase and represent potential targets for new control strategies for Verticillium wilt.

genetics↗