Biology subjects

Bosch, M.

Publications and source records attributed to Bosch, M..

17 recordsLinked to original sources

bioRxiv2026

Recruitment of intrasegmental and propriospinal interneuron networks of forelimb motor circuitry in chronic cervical contusion spinal cord injury

Cervical spinal cord injury (SCI) disrupts descending supraspinal input and spinal networks controlling upper extremity motor function, making recovery of arm and hand function a major priority for affected individuals. The vast majority of regenerative strategies have been studied during the acute and sub-acute phases following SCI, while therapeutic testing remains limited for chronic injury, when persistent barriers significantly limit circuit remodeling. We asked whether pharmacologic enhancement of neuronal-intrinsic axon growth capacity through PTEN inhibition could promote forelimb motor recovery and circuit plasticity in a rodent model of chronic cervical SCI. Following C5 hemi-contusion, female rats underwent behavioral testing of forelimb motor function and received PTEN antagonist peptide (PAP) beginning at a chronic time point, and the trans-synaptic tracer, pseudorabies virus (PRV), was injected into ipsilesional triceps to trace forelimb-associated motor circuitry. PAP selectively improved forelimb usage during cylinder paw-preference testing, but not strength, sensorimotor, or gait-related forelimb measures. PAP increased recruitment of PRV-traced local-projecting and propriospinal interneuron networks. In addition, PAP enhanced synaptic input to these recruited propriospinal interneurons, raising the possibility that spared descending pathways may contribute to recovery through spinal relay circuits. Lastly, we mapped the supraspinal connectome providing descending input from brainstem to the lower motor neurons innervating forelimb muscle, and we determined how this connectome was impacted both by SCI and PAP. Together, these findings show that, even in chronic SCI, pharmacological PTEN inhibition can promote forelimb functional recovery and significant circuit remodeling, with spinal interneuron networks emerging as a key site of PAP-induced plasticity.

neuroscience↗

bioRxiv2026

APOE4 reduction in vascular-associated fibroblasts decreases cerebral amyloid angiopathy and associated vascular dysfunction

Cerebral amyloid angiopathy (CAA), characterized by cerebrovascular amyloid deposition, is strongly associated with Alzheimers disease, ischemic injury, and lobar hemorrhages. APOE4 is the strongest known genetic risk factor for CAA, yet the cellular sources of APOE4 that drive pathogenic vascular amyloid deposition remain poorly defined. Here, we identify vascular-associated fibroblasts (VAFs) as a key source of APOE4 that mediates CAA and cerebrovascular dysfunction. In post-mortem brain tissue from APOE4/E4 patients with confirmed CAA, APOE colocalizes with COL6 VAFs around A{beta}-laden vessels. Therefore, to study the contribution of APOE4 derived from VAFs in CAA, independently of parenchymal sources, we used 5xFAD mice in which the endogenous mouse Apoe coding exons are replaced with floxed human APOE4 sequences. This enables selective suppression of APOE4 expression in VAFs upon tamoxifen induction of Col1a2-CreERT+. APOE4 reduction in VAFs markedly reduced CAA, with the strongest effects observed in leptomeningeal vessels. Additionally, A{beta}40, which preferentially associates with vascular amyloid, was significantly reduced in the vascular fraction. VAF APOE4 depletion resulted in fewer small microbleeds and an approximately 50% reduction in parenchymal border macrophages within the leptomeningeal compartment, whereas astrocytic reactivity remained unchanged. Functional assessment using in vivo multi-parametric photoacoustic microscopy revealed improved arterial dilation and blood flow in amyloid-laden leptomeningeal arteries. Together, these findings establish VAF-derived APOE4 as a compartment-specific driver of CAA and cerebrovascular dysfunction. One Sentence SummaryVascular-associated fibroblasts are a major source of pathogenic APOE4 that drives vascular dysfunction in cerebral amyloid angiopathy.

neuroscience↗

bioRxiv2026

Defensive lipid droplets are PUFA reservoirs driving bacterial clearance and inflammation

Lipid droplets (LDs) rapidly form in infected cells to participate in the defence against microbes. Here, we investigate the involvement of LD lipids in these immune responses. Comparative shotgun and targeted lipidomics demonstrate that in vivo host LDs accumulate polyunsaturated fatty acids (PUFAs). PUFAs arrive at cells from the bloodstream to be further metabolised into complex PUFAs accrued by LD-triglycerides and -phospholipids. Host lipid metabolism is transcriptionally controlled by rapid, transient, and intricate immune programs initiated by pathogen-associated molecular patterns and relayed by cytokines such as interferons (type I and II), interleukins (IL-1{beta}), and tumour necrosis factor. When this lipid and signalling environment is reproduced in cultured macrophages, newly formed LDs accumulate defensive proteins, coordinate the synthesis of complex PUFAs, and become PUFA reservoirs and suppliers. Among LD-PUFAs, the {omega}-6 arachidonic acid is the most actively metabolised during the initial phases of innate immunity. Released from LDs by adipose triglyceride lipase, arachidonic acid is used by macrophages for prostaglandin synthesis, bacterial phagocytosis, and elimination of microbes. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=163 HEIGHT=200 SRC="FIGDIR/small/711356v2_ufig1.gif" ALT="Figure 1"> View larger version (107K): org.highwire.dtl.DTLVardef@14d65eorg.highwire.dtl.DTLVardef@5ecc1org.highwire.dtl.DTLVardef@fa99e5org.highwire.dtl.DTLVardef@8d9632_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2026

Several plant self-incompatibility systems may be controlled by atypical receptor-ligand interactions

Self-incompatibility (SI) is the single most important mechanism utilized by flowering plants to avoid self-pollination, thus preventing inbreeding and promoting outcrossing. Many plant SI systems are genetically controlled by a multi-allelic S-locus, containing two tightly linked genes that encode the female and male S-determinants. When pollen lands on a "self" pistil, interaction between cognate female and male S-determinants induces an SI signalling response, resulting in the failure of self-fertilization. Here, we review currently known SI systems that utilize receptor-ligand interactions to control pollen rejection on the stigma surface. Although detailed molecular and cellular information is only known for the SI systems in the Brassicaceae and Papaveraceae, it is apparent that the S-determinants of other SI systems (e.g. in the Poaceae and the Convolvulaceae) are likely to also utilize receptor-ligand interactions to prevent self-fertilization. Strikingly, although most of these systems all appear to utilize cysteine rich proteins (CRPs) as ligands to induce an SI response, only one of these receptors is a receptor-like kinase (RLK); the other "receptors" identified to date are proteins of unknown function, which we propose to be atypical receptors (ATRs). Although many of these receptors were identified some time ago, their atypical nature raises many questions, including how they function mechanistically, how they evolved and whether they are found in other plant cell-cell communication systems. Significance StatementSelf-incompatibility involves the precise recognition and rejection of incompatible pollen, often using a receptor-ligand type of interaction between male and female S-determinants. In this review we compare several S-determinants that appear to function as novel, atypical "receptors" (ATRs), with no kinase- or other distinct domains. We propose that the discovery of these novel "receptors" suggests that further, as yet, unidentified ATRs could be more widely utilized in angiosperms than currently appreciated.

plant biology↗

bioRxiv2025

Papaver S-determinants trigger an integrated network of mitochondrially derived ROS and disruption of energy metabolism in incompatible pollen tubes

Many plants use self-incompatibility (SI) mechanisms to prevent inbreeding by inhibiting pollen tube growth in "self" pistils. In Papaver rhoeas, SI is triggered by allele-specific interaction between the pollen and pistil S-determinants, activating a Ca2+-dependent signalling network that leads to rapid reactive oxygen species (ROS) production and eventual programmed cell death (PCD) in incompatible pollen tubes. Expression of the Papaver pollen S-determinant (PrpS) in Arabidopsis thaliana recapitulates Papaver SI when challenged with the cognate pistil ligand (PrsS). Using roGFP2-Orp1, a genetically encoded hydrogen peroxide (H2O2) sensor, combined with measurements of mitochondrial metabolism we have revealed a complex SI response. Within minutes, elevated cytosolic Ca2+ ([Ca2+]cyt) and cytosolic acidification converge to trigger mitochondrial H2O2 production (with consequent cytosolic and plastid H2O2 increase), membrane depolarisation, decreased respiration rate, and ATP depletion. In parallel, oxidative inactivation of cytosolic GAPDH inhibits glycolytic flux, resulting in decreased TCA cycle intermediates and providing a feedback loop to enhance mitochondrial disruption. Preceding production of mitochondrially-sourced ROS, we show that SI rapidly arrests pollen tube growth via inactivation of plasma membrane localised NADPH oxidase (RBOH) mediated superoxide production. Our findings provide new insights into how different ROS signatures from NADPH oxidase and mitochondria drive distinct processes. We demonstrate that mitochondrial disruption is an early and central event in the SI-response, likely driven by positive feedback loops involving altered Ca2+ signalling, cytosolic pH and ROS. Our findings provide novel insights into how SI rapidly disrupts energy metabolism in pollen tubes through interconnected signalling networks centred on mitochondria prior to PCD.

plant biology↗

bioRxiv2025

Sex-dependent neural plasticity in response to damage

Plasticity of intact adult neural tissue in the vicinity of neural damage serves to restore functionality of circuits. Much remains to be learned about the mechanisms regulating this process and the reported sex differences in recovery outcomes. Here, we present the fly gut and its innervation as a simplified model to address these questions. We show that gut damage caused by ingestion of toxic agents resulted in plasticity of the adult enteric neuronal network, manifested as a Reactive Oxygen Species (ROS)-dependent increase in neural tissue, which was reversible after a recovery period. Interestingly, males did not display neural plasticity, and masculinization of neurons in females suppressed the damage-dependent neural growth. Together, these findings position the fly gut as a system to investigate the cellular, molecular, and sex-specific underpinnings of neural plasticity, with implications for therapeutic advancements in neural circuit recovery. SUMMARY STATEMENTThis study establishes the fly gut as a simple system to explore how adult neural tissues differ between sexes in their capacity for plasticity.

neuroscience↗

bioRxiv2024

The mitochondrial unfolded protein response promotes senescence in human microglia by increasing S-adenosylmethionine availability for polyamine synthesis.

Mitochondria have evolved a specialized mitochondrial unfolded protein response (UPRmt) to maintain proteostasis and promote recovery under stress. Studies in simple organisms have shown that UPRmt activation in glial cells supports proteostasis through beneficial noncell-autonomous communication with neurons. However, the role of mitochondrial stress responses in the human brain remains unclear. To address this gap, we investigated the cell type-specific effects of mitochondrial proteotoxic stress using human induced pluripotent stem cell-derived neuronal and glial cultures, as well as brain organoids. We show that mitochondrial proteotoxic stress induces metabolic rewiring in human microglia, marked by depletion of S-adenosylmethionine and lipid remodeling, ultimately leading to a senescent phenotype. Using human neuronal-glial tricultures and microglia-containing brain organoids, we identified the specific contributions of microglia to brain senescence and mitochondrial stress-driven neurodegenerative processes. UPRmt activation disrupts microglial communication with neighboring cells, triggering inflammatory signaling and impairing proteostasis. Together, these findings reveal how impaired mitochondrial proteostasis alters intercellular networks and identify a critical role for the UPRmt in neurodegenerative disease pathogenesis.

neuroscience↗

bioRxiv2023

Identifying environmental factors affecting the production of pea aphid dispersal morphs in field populations

O_LIMany species of insects show phenotypically plastic dispersal traits in response to suboptimal environmental conditions. These polyphenetic traits can have large impacts on the population dynamics of the dispersing insects. Therefore, it is important to understand what environmental factors affect the development of dispersal traits and how these factors affect population dynamics via immigration/emigration. C_LIO_LIPea aphids (Acyrthosiphon pisum) exhibit a polyphenetic wing dimorphism in which individuals are either winged (alate) or not (apterous). The production of alate offspring is determined by environmental cues experienced by the mother. Environmental factors associated with these cues have been intensively studied, with crowding, host plant quality, natural enemies, and fungal infection being shown to affect the production of pea aphid alates under controlled laboratory conditions. Nonetheless, environmental factors affecting alate production have rarely been studied in field populations of pea aphids. C_LIO_LIUsing data from a three-year study of alate production in 5-9 alfalfa (lucerne) fields, we examined the effects of (i) pea aphid abundance, (ii) host plant maturity, (iii) temperature, (iv) predator and herbivore abundance, (v) parasitism, and (vi) entomopathic fungal incidence. In twice-weekly samples taken over the growing season, alate production ranged from 0 to 83% of the nymphal population. C_LIO_LIPea aphid abundance, temperature, and alfalfa maturity together explained 67% of the variation in alate production. The other factors we investigated explained little variation. These results suggest there is a limited number of key environmental factors that consistently predict changes in alate production in field populations, while many factors identified in lab studies may be unimportant. Our results highlight the value of investigating factors affecting the expression of plastic traits in insect species at a broad spatiotemporal scale and under natural conditions. C_LI

ecology↗

bioRxiv2022

Proteostatic regulation of caveolins avoids premature oligomerisation and preserves ER homeostasis

Caveolin-1 (CAV1) and CAV3 are membrane sculpting proteins driving formation of plasma membrane caveolae. Caveola formation is unique as it requires oligomerisation of newly synthesised caveolins through the biosynthetic-secretory pathway. Here, we combine structural, biochemical, and microscopy analyses to examine the early proteostasis of caveolin family members and mutants. We describe striking trafficking differences between newly synthesised caveolins, with CAV1 rapidly exported to the Golgi but CAV3 showing ER retention and targeting to lipid droplets. Only monomeric/low oligomeric caveolins are efficiently exported from the ER, with oligomers assembling beyond the cis-Golgi and disease-causing mutations leading to detrimental non-functional complexes. Caveolins in the ER are maintained at low levels by active proteasomal degradation, avoiding premature oligomerisation and ER stress. Increasing lipid availability, cholesterol for CAV1 and fatty acids for CAV3, enhances trafficking and reduces proteasomal degradation. In conclusion, we identify proteostatic mechanisms that modulate stability and trafficking of newly synthesised caveolins, protecting cells against ER stress but perturbed in caveolin-related disease. SummaryUnderstanding the unique proteostasis of caveolins has important implications for cell biology and physiopathology. Combining structural, microscopy, and biochemical analyses, we uncover new insights into the mechanisms that differentiate the early biosynthetic steps of caveolin family members, isoforms, and pathogenic mutants.

cell biology↗

bioRxiv2022

Regulation of adult neurogenesis and neuronal differentiation by Neural Cell Adhesion Molecule 2 (NCAM2)

Adult neurogenesis persists in mammals in the neurogenic zones where newborn neurons are incorporated into existing neuronal circuits. Relevant molecular elements of the neurogenic niches include the family of Cell Adhesion Molecules (CAM), which participate in signal transduction and regulate radial glial progenitors (RGPs) survival, division and differentiation. The Neural Cell Adhesion Molecule 2 (NCAM2) is expressed in brain development and in adult stages, and controls dendrite arborisation and synaptic formation and maintenance during development. Nevertheless, the role of NCAM2 in neurogenesis and lineage progression is not well understood. Here we analyse the functions of NCAM2 in the regulation of RGPs in adult neurogenesis in the dentate gyrus and during corticogenesis, by using different lentiviral-mediated genetic approaches to modulate its expression, both in vivo and in vitro. First, we characterized the expression of NCAM2 among the main actors of the neurogenic process revealing different levels of NCAM2 amid the progression of RGPs and the formation of juvenile neurons. Further, we show that overexpression of NCAM2 arrest infected cells in a RGP-like state, with characteristic morphological, immunocytochemical and electron microscopy features. In contrast, NCAM2 overexpression in embryonic cortical progenitors does not seems to alter cell fate, but causes transient migration deficits. These results reveal a differential role of NCAM2 in the regulation of adult and embryonic RGPs, and specifically, a significant implication of NCAM2 in the regulation and progression of RGPs during adult neurogenesis in the hippocampus.

neuroscience↗

bioRxiv2021

GPI anchor remodeling by the plant PGAP1 ortholog HLD1 is essential for Papaver self-incompatibility

In eukaryotes, glycosylphosphatidylinositol anchored proteins (GPI-APs) are tethered to the outer leaflet of the plasma membrane where they function as key regulators of a plethora of biological processes. Self-incompatibility (SI) plays a pivotal role regulating fertilization in higher plants through recognition and rejection of self pollen. Here we used Arabidopsis thaliana lines engineered to be self-incompatible by expression of Papaver SI determinants for an SI suppressor screen. We identify HLD1, an ortholog of human GPI-inositol deacylase PGAP1, whose mutation completely abolishes the SI response. We show that HLD1 functions as a GPI-inositol deacylase and that this GPI-remodeling activity is essential for SI. Using GFP-SKU5 as a representative GPI-AP, we show that HLD1 mutation does not affect GPI-AP production and targeting, but alters the configuration of mature GPI-APs. This prevents GPI-AP release from the plasma membrane, suggesting that this process plays a critical role in the regulation of SI. Our data not only identify GPI anchoring as a new pathway of SI providing new directions to investigate SI mechanisms, but identifies for the first time a function for GPI-AP remodeling by inositol deacylation in plants. One sentence summaryThe Papaver self-incompatibility response requires GPI-anchor modification by HLD1, an ortholog of the mammalian PGAP1.

plant biology↗

bioRxiv2020

Evaluating urban greening scenarios for urban heat mitigation: a spatially-explicit approach

Urban green infrastructure, especially trees, are widely regarded as one of the most effective ways to reducing urban temperatures in extreme heat events, and alleviate its adverse impacts on human health and well-being. Nevertheless, urban planners and decision-makers are still lacking methods and tools to spatially evaluate the cooling effects of urban green spaces and exploit them to assess greening strategies at the urban agglomeration scale. This article introduces a novel spatially-explicit approach to simulate urban greening scenarios by increasing the tree canopy cover in the existing urban fabric, and evaluating their heat mitigation potential. The latter is achieved by applying the InVEST urban cooling model to the synthetic land use/land cover maps generated for the greening scenarios. A case study in the urban agglomeration of Lausanne, Switzerland, illustrates the development of tree canopy scenarios following distinct spatial distribution strategies. The spatial pattern of the tree canopy strongly influences the human exposure to the highest temperatures, and small increases in the abundance of tree canopy cover with the appropriate spatial configuration can have major impacts on human health and well-being. The proposed approach supports urban planning and the design of nature-based solutions to enhance climate resilience.

ecology↗

bioRxiv2020

eEF1A2 controls local translation and actin dynamics in structural synaptic plasticity

Synaptic plasticity involves structural modifications in dendritic spines. Increasing evidence suggests that structural plasticity is modulated by local protein synthesis and actin remodeling in a synapsis-specific manner. However, the precise molecular mechanisms connecting synaptic stimulation to these processes in dendritic spines are still unclear. In the present study, we demonstrate that the configuration of phosphorylation sites in eEF1A2, an essential translation elongation factor in neurons, is a key modulator of structural plasticity in dendritic spines. A mutant that cannot be phosphorylated stimulates translation but reduces actin dynamics and spine density. By contrast, the phosphomimetic variant loosens its association with F-actin and becomes inactive as a translation elongation factor. Metabotropic glutamate receptor signaling triggers a transient dissociation of eEF1A2 from its GEF protein in dendritic spines, in a phospho-dependent manner. We propose that eEF1A2 establishes a crosstalk mechanism that coordinates local translation and actin dynamics during spine remodeling.

neuroscience↗

bioRxiv2019

Photocontrol of endogenous glycine receptors in vivo

Glycine receptors (GlyRs) are indispensable to maintain excitatory/inhibitory balance in neuronal circuits controlling reflex and rhythmic motor behaviors. Here we have developed Glyght, the first GlyR ligand controlled with light. It is selective over other cys-loop receptors, active in vivo, and displays an allosteric mechanism of action. The photomanipulation of glycinergic neurotransmission opens new avenues to understand inhibitory circuits in intact animals, and to develop drug-based phototherapies.

neuroscience↗

bioRxiv2019

PyLandStats: An open-source Pythonic library to compute landscape metrics

Quantifying the spatial pattern of landscapes has become a common task of many studies in landscape ecology. Most of the existing software to compute landscape metrics is not well suited to be used in interactive environments such as Jupyter notebooks nor to be included as part of automated computational workflows. This article presents PyLandStats, an open-source Python library to compute landscape metrics within the scientific Python stack. The PyLandStats package provides a set of methods to undertake recurrent approaches to quantify landscape patterns, such as the analysis of the spatiotemporal patterns of land use/land cover change or gradient analysis. The implementation is based on the prevailing Python libraries for geospatial data analysis in a way that they can be forthwith integrated into complex computational workflows. Notably, the provided methods offer a large variety of options so that users can employ PyLandStats in the way that best supports their needs. The source code is publicly available, and is organized in a modular object-oriented structure that enhances its maintainability and extensibility.

ecology↗

bioRxiv2019

Spatiotemporal patterns of urbanization in three Swiss urban agglomerations: insights from landscape metrics, growth modes and fractal analysis

Urbanization is currently a global phenomenon that has become the most important form of landscape change and is increasingly affecting biodiversity and ecosystem functions. In order to evaluate the impacts of urbanization and inform urban planning, it is important to understand the spatiotemporal patterns of land use change associated to urbanization. This paper exploits three different frameworks, namely landscape metrics, urban growth modes and fractal analysis to characterize the spatiotemporal patterns of urbanization of the Swiss urban agglomerations of Zurich, Bern and Lausanne. The land use inventory provided by the Swiss Federal Statistical Office was used to assemble four temporal snapshots from 1980 to 2016 at the extent of the urban agglomerations. The time series of landscape metrics generally supports the diffusion and coalescence model of urban growth, with Zurich exhibiting most characteristics of coalescence while Bern and Lausanne seem to be at the transition between diffusion and coalescence. Nevertheless, the analysis of the urban growth modes suggest that leapfrog development occurs at all periods, which contributes to an increasing fragmentation of natural patches and maintains the fractal configuration of the landscape. The discussion reviews potential explanations for the observed landscape changes, and concludes with some planning implications.

ecology↗

bioRxiv2019

Reversible silencing of endogenous receptors in intact brain tissue using two-photon pharmacology

The physiological activity of proteins is often studied with loss-of-function genetic approaches, but the corresponding phenotypes develop slowly and can be confounding. Photopharmacology allows direct, fast and reversible control of endogenous protein activity, with spatiotemporal resolution set by the illumination method. Here, we combine a photoswitchable allosteric modulator (alloswitch) and two-photon excitation (2PE) using pulsed near-infrared lasers to reversibly silence mGlu5 receptor activity in intact brain tissue. Endogenous receptors can be photoactivated in neurons and astrocytes with pharmacological selectivity and with an axial resolution between 5 and 10 m. Thus, two-photon pharmacology (2PP) using alloswitch allows investigating mGlu5-dependent processes in wild type animals, including synaptic formation and plasticity, and signaling pathways from intracellular organelles.

pharmacology and toxicology↗