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Biology subjects

Binder, S.

Publications and source records attributed to Binder, S..

9 recordsLinked to original sources

DIRTNet: Enabling Root Phenotyping with Fiber Bragg Grating Sensors

Non-destructive methods for real-time phenotyping of root growth and development are essential to accelerate the breeding of climate-resilient crops. We present DIRTNet (Digital Investigations of Root Traits Net), a hybrid deep learning model that interprets in-soil signals collected by Fiber Bragg Grating (FBG) sensors. We first evaluated DIRTNet in a controlled simulation study in which metal rods of varying diameters were inserted into soil to emulate root growth. Using augmented training data with an 80:20 train-test split, DIRTNet surpassed baseline models, achieving 0.97 accuracy for root depth prediction and 0.94 for root diameter prediction. We then applied the best-performing models to maize (Zea mays) roots monitored by six FBG sensors placed at different soil location and depths. A control trial and a drought-stress trial yielded 192 samples, split 80:20 into training and holdout sets; the hold-out portion was divided equally into validation and test sets. Augmentation was applied only to the training data. On real maize root data, DIRTNet achieved 0.92 accuracy for both root depth and root width prediction across variable growth periods, covering root mass lengths up to 20 cm and diameters up to 10 cm. The prediction accuracy is independent of the soil moisture and drought condition. In a fixed-interval analysis, accuracy reached 0.97 for days 25-42 after planting and 0.93 for days 25-48, demonstrating robust performance as root complexity increased.

plant biology↗

A comparative framework for neocortical sulcal anatomy in pinnipeds

The transition of pinnipeds from terrestrial ancestors into marine environments provides a unique opportunity to examine how cortical organisation has changed with adaptation to life in water. Here, we examined neocortical sulcal anatomy in nine species representing all three extant pinniped families using cortical surfaces reconstructed from post-mortem MRI. Building on a standardised framework previously established for land-dwelling (fissiped) carnivorans, we developed identification criteria for major pinniped sulci and compared their configurations with those observed across fissipeds. Major sulci were broadly conserved, but pinnipeds exhibited characteristic modifications, including a complex, highly branched pseudosylvian configuration and distinct frontoparietal sulcal patterns, with further family-level variation in both territories. This observed variation in sulcal patterns may reflect pronounced differences in locomotor, tactile, and vocal specialisations, generating hypotheses about how cortical organisation may vary with adaptation to marine environments. Together, these findings establish a common anatomical framework across Carnivora for investigating how cortical organisation diversified in relation to behaviour and ecology.

neuroscience↗

Ciliary sensing in tanycytes couples nutrient availability to metabolic regulation

Body homeostasis relies on accurate communication between the brain and the periphery. Disruption of this communication can contribute to disease. Tanycytes are located at the interface of the cerebrospinal fluid (CSF), bloodstream, and hypothalamus, where they sense circulating nutrients and regulate neuroendocrine axes and metabolism. However, the mechanisms by which they sense CSF signals remain largely unclear. Recent evidence that tanycytes possess primary cilia -- key sensory organelles -- led us to hypothesize that tanycytic cilia function as sensory antennae that detect metabolic cues in the CSF. Here, we demonstrate that tanycytic cilia exhibit distinct morphologies across subtypes and physiological states. They respond dynamically to hormonal and nutrient availability; notably, excess oleic acid shortens cilia, promotes lipid droplet accumulation, and reduces Ca{superscript 2} responses to ATP and glucose. Disrupting cilia via knockdown of intraflagellar transport (IFT) genes produced similar defects and impaired autophagy. Finally, selective Ift88 knockout in tanycytes increased body weight and reduced thermogenic activity in female mice. These findings identify tanycytic cilia as key sensors regulating energy balance.

neuroscience↗

Tissue architecture and immune niches govern ctDNA release in colorectal cancer

Circulating tumor DNA (ctDNA) is central to liquid biopsy-based cancer detection, yet its release into the bloodstream varies widely and remains poorly understood. To define the tissue-level determinants of ctDNA shedding in colorectal cancer (CRC), we integrated tumor-informed plasma sequencing with detailed histopathology, immunophenotyping, spatial transcriptomics, and in situ mutation detection in resectable stages (I-III). ctDNA detectability increased with tumor burden, and high ctDNA shedders exhibited a distinct architectural and microenvironmental phenotype characterized by expanded necrotic pseudolumina, frequent epithelial barrier disruption, and dense myeloid infiltration. Spatial profiling revealed stress-associated malignant programs and a myeloid-rich immune-luminal niche. In situ sequencing confirmed plasma-detected mutations within pseudoluminal debris, identifying these structures as focal reservoirs of shed DNA. These findings provide a mechanistic framework linking tissue architecture, immune remodelling, and spatially organized cell death to ctDNA release with implications for refining liquid biopsy applications.

cancer biology↗

Fiber Bragg grating based sensing system for non-destructive root phenotyping using ResNet prediction

Real-time measurements of crop root architecture can overcome limitations faced by plant breeders when developing climate-resilient plants. Due to current measurement methods failing to continuously monitor root growth in a non-destructive and scalable fashion, we propose a first in-soil sensing system based on fiber Bragg gratings (FBG). The sensing system logs three-dimensional strain generated by a growing pseudo-root. Two ResNet models confirm the utility of in-soil FBG sensors by predicting pseudo-root width and depth with accuracies of 92% and 93%, respectively. To analyze model robustness, a preliminary experiment was performed where FBGs logged strain generated from a corn plants roots for 30 days. The models were then retrained on new data where they achieved accuracies of 98% and 96%, respectively. Our presented prototype has potential prospects to go beyond measuring root parameters and sense its surrounding soil environment.

plant biology↗

Implementation and testing of a biohybrid transitionmicroelectrode array for neural recording and modulation

Recent advances in microtissue engineered neural networks have opened avenues for the fabrication of biohybrid intracortical brain implants. To date, however, the experimental validation of these biohybrid implants has been restricted to singularly positioned electrodes, with the functionality confined to optical neuromodulation and neural recording. We present for the first time a biohybrid transition microelectrode array (TMEA) comprising a 4x4 matrix of biohybrid electrodes. These electrodes are expected to project axons into the brain, thereby establishing synaptic connections for electrical readout and excitation. Our device thus offers a promising pathway to leverage organic, endogenous materials in intracortical implants to enhance their biocompatibility as well as their functionality. In particular with respect to functionality, we assume that the spatiotemporal resolution of recorded neural signals may be significantly increased using this technology owing to the size ratios of these biohybrid microelectrodes compared to abiotic ones. Future investigations will therefore focus on the exploitation of the electrode density to further advance brain-computer interface technology.

neuroscience↗

Engineering the biological conversion of formate into crotonate in Cupriavidus necator

To advance the sustainability of the biobased economy, our society needs to develop novel bioprocesses based on truly renewable resources. The C1-molecule formate is increasingly proposed as carbon and energy source for microbial fermentations, as it can be efficiently generated electrochemically from CO2 and renewable energy. Yet, its biotechnological conversion into value-added compounds has been limited to a handful of examples. In this work, we engineered the natural formatotrophic bacterium C. necator as cell factory to enable biological conversion of formate into crotonate, a platform short-chain unsaturated carboxylic acid of biotechnological relevance. First, we developed a small-scale (150-mL working volume) cultivation setup for growing C. necator in minimal medium using formate as only carbon and energy source. By using a fed-batch strategy with automatic feeding of formic acid, we could increase final biomass concentrations 15-fold compared to batch cultivations in flasks. Then, we engineered a heterologous crotonate pathway in the bacterium via a modular approach, where each pathway section was assessed using multiple candidates. The best performing modules included a malonyl-CoA bypass for increasing the thermodynamic drive towards the intermediate acetoacetyl-CoA and subsequent conversion to crotonyl-CoA through partial reverse {beta}-oxidation. This pathway architecture was then tested for formate-based biosynthesis in our fed-batch setup, resulting in a two-fold higher titer, three-fold higher productivity, and five-fold higher yield compared to the strain not harboring the bypass. Eventually, we reached a maximum product titer of 148.0 {+/-} 6.8 mg/L. Altogether, this work consists in a proof-of-principle integrating bioprocess and metabolic engineering approaches for the biological upgrading of formate into a value-added platform chemical.

synthetic biology↗

The NLRP3/eIF2 axis drives cell cycle progression in acute myeloid leukemia

Aberrant activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome mediates numerous inflammatory diseases. Oncogenes can activate the NLRP3 inflammasome and thereby promote myeloproliferative neoplasia, suggesting a crucial role of NLRP3 in the malignant transformation of hematopoietic cells. Here, we show that bone marrow-derived mononuclear cells of AML patients display enhanced expression of NLRP3, IL-1{beta} and IL-18 and that high-level expression of NLRP3 is linked to poor survival of AML patients. Pharmacological and genetic inhibition of NLRP3 inflammasome activation attenuated cell proliferation of MOLM-13 AML cells in vitro. In vivo, genetic inhibition of NLRP3 in MOLM-13 AML cells resulted in reduced engraftment potential in xenografts, along with reduced splenomegaly and organ infiltration. Differential proteomic analysis revealed the eIF2 pathway as potential target of NLRP3 in AML, with a significant increase of eIF2 phosphorylation upon NLRP3 inhibition. NLRP3 inhibition also caused a strong decrease in cyclin - dependent kinases CDK4 and CDK6, accompanied by an upregulation of the CDK inhibitor p21 (CDKN1A) and a marked arrest of cell cycle progression in the G0/G1 phase, consistent with the role of eIF2 phosphorylation as negative cell cycle regulator. Taken together, we show that inhibition of the NLRP3 inflammasome reduces AML cell proliferation by promoting eIF2 phosphorylation, which in turn enhances the expression of cell cycle arrest genes such as p21. Thus, the study uncovers the NLRP3/eIF2 axis as new driver of AML proliferation and proposes a novel therapeutic treatment of AML by targeted inhibition of NLRP3 activation.

immunology↗

Rescue Ebola Patients in silico

Ebola, one of the most pathogenic and lethal viruses, repeatedly leads to severe outbreaks with large numbers of casualties. By integration of data of fatal, non-fatal and asymptomatic cases, we developed a mathematical model of the immune response to Ebola infections and found that TNF- can explain subsequent cytokine responses and allows to quantitatively stratify patients into survivors and fatal cases. The model further suggests that antibodies provide the key resolving mechanism in survivors while IFN-{gamma} is the key defense mechanism in fatal cases. Exogenous IFN-{gamma} and inhibition of excessive inflammation have the potential to rescue fatal Ebola infections in silico. In view of the high mortality of this disease, limited real life studies, and the unforeseeable next outbreak, our in silico analysis is meant as a guide for future research by the determination of the most efficient strategies for Ebola treatment.

systems biology↗