Biology subjects

Weber, B.

Publications and source records attributed to Weber, B..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

ECgo: All-Optical Induction of Single Endothelial Cell Injury and Capillary Occlusion in the Brain

The ability to induce endothelial cell (EC) damage in the mouse brain with high spatial precision is invaluable for mechanistic studies of brain capillary injury and repair. Here, we introduce an optical method, termed ECgo, that utilizes a new two-photon-excitable porphyrin-based photosensitizer (Ps2P) to selectively obliterate single ECs within the brain microvascular network. Using the developed approach, we were able to induce occlusions of single capillaries with high spatiotemporal control, while preserving the surrounding tissue. Combined with longitudinal two-photon imaging, ECgo enables studies of morphological and functional consequences of targeted single capillary EC injury in vivo under healthy and diseased conditions. SIGNIFICANCE STATEMENTBrain capillary injury is a common feature of aging and many neurological disorders. While a single capillary lesion may appear inconsequential, the cumulative effect of repeated and spatially dispersed capillary insults can lead to substantial brain dysfunction. Understanding how single capillary injuries contribute cumulatively to long-term brain damage requires tools that can precisely target individual capillaries in the living brain. Here, we introduce an optical method that uses a new light-activatable compound to selectively injure single brain capillaries with high spatial accuracy. Our method enables detailed, longitudinal studies of capillary repair, blood flow recovery, local oxygen dynamics, and glial responses following microvascular injury.

neuroscience↗

bioRxiv2025

APOE genotype-dependent differences in human astrocytic energy metabolism

The main genetic risk factor for Alzheimers disease (AD) is the presence of the apolipoprotein E4 (APOE4) allele. While APOE4 increases the risk of developing AD, the APOE2 allele is protective and APOE3 is risk-neutral. In the brain, APOE is primarily expressed by astrocytes and plays a key role in various processes including cholesterol and lipid transport, neuronal growth, synaptic plasticity, immune response and energy metabolism. Disruptions in brain energy metabolism are considered a major contributor to AD pathophysiology, raising a key question about how different APOE isoforms affect the energy metabolism of human astrocytes. In this study, we generated astrocytes (iAstrocytes) from APOE-isogenic human induced pluripotent stem cells (iPSCs), expressing either APOE2, APOE3, APOE4 or carrying an APOE knockout (APOE-KO), and investigated APOE genotype-dependent changes in energy metabolism. ATP Seahorse assay revealed a reduced mitochondrial and glycolytic ATP production in APOE4 iAstrocytes. In contrast, proteomic GO enrichment analysis and mitochondrial stress tests indicated increased mitochondrial respiration and activity in APOE4 iAstrocytes, accompanied with elevated proton leak, while mitochondrial fusion and fission protein levels remain unchanged. Glycolysis stress tests also demonstrated enhanced glycolysis and glycolytic capacity in APOE4 iAstrocytes while genetically encoded nanosensor-based FLIM analysis revealed that APOE does not affect lactate dynamics. Mass spectrometry-based metabolomic analysis identified various energy and glucose metabolism-related pathways that were differentially regulated in APOE4 compared to the other genotypes, including mitochondrial electron transport chain and glycolysis. In general, APOE2 and APOE-KO iAstrocytes showed a very similar phenotype in all functional assays and differences between APOE2/APOE-KO and APOE4 were stronger than between APOE3 and APOE4. Our study provides evidence for APOE genotype-dependent effects on astrocyte energy metabolism and highlights alterations in the bioenergetic processes of the brain as important pathomechanisms in AD.

neuroscience↗

bioRxiv2025

Volatile-Mediated Plant Defense Networks: Field Evidence for Isoprene as a Short-Distance Immune Signal

Isoprene, the most abundant hydrocarbon emitted by vegetation, protects photosynthesis against oxidative and thermal stress and significantly impacts atmospheric chemistry. While laboratory studies suggest a role for isoprene in plant defense, its function in plant-plant communication under natural conditions remains unclear. Here, we demonstrate that isoprene acts as a signaling molecule, triggering systemic immune responses in neighboring plants against bacterial pathogens under field conditions. We established an experimental system using wild-type and transgenic silver birch (Betula pendula) lines engineered to emit varying levels of isoprene. Over two growing seasons, we examined the effects of birch-emitted volatile organic compounds on neighboring Arabidopsis thaliana, including wild-type and immune signaling mutants (llp1: legume lectin-like protein 1; jar1: jasmonate resistant 1). Isoprene emission rates positively correlated with systemic resistance in receiver plants, with higher emissions enhancing inhibition of Pseudomonas syringae growth. This immune response occurred independently of jasmonate signaling but required functional LLP1, suggesting a specific recognition pathway. By combining Arabidopsis mutant responses with birch volatile profiles, we confirmed that isoprene, rather than other terpenoids, mediates this effect. These findings reveal an unrecognized ecological function of isoprene as an airborne immune signal, establishing transgenic birch as a robust model for studying volatile-mediated plant defense networks in natural environments. Our results provide new insights into the molecular mechanisms underlying plant volatile perception and expand our understanding of chemical communication in terrestrial ecosystems. Significance StatementIsoprene, the most abundant volatile organic compound released by plants, protects against abiotic stress. Here, we demonstrate that isoprene also functions under ambient atmosphere as a short-distance immune signal, enhancing neighboring plants resistance to bacterial pathogens. This finding reveals a putative ecological role of isoprene in plant defense networks and suggests strategies for sustainable agriculture and forest management under environmental stress.

plant biology↗

bioRxiv2024

A low-cost FPGA-based approach for pile-up corrected high-speed in vivo FLIM imaging

Intensity-based two-photon microscopy (2PM) is a cornerstone of biomedical research but lacks the ability to measure concentrations, a pivotal task for longitudinal studies and quantitative comparisons. Fluorescence Lifetime Imaging (FLIM) based on Time-Correlated Single Photon Counting (TCSPC) can overcome those limits but suffers from "pile-up" distortions at high photon count rates, severely limiting acquisition speed. We introduce the "laser period blind time" (LPBT) method to correct pile-up distortions in photon counting electronics, enabling reliable low-cost TCSPC-FLIM at high count rates. The correction was implemented on low-cost hardware based on a field programable gate array (FPGA) and validated using a combination of in silico simulations and in vitro, ex vivo and in vivo measurements. The LBPT approach achieves <3% error in lifetime measurements at count rates more than ten times higher than traditional limits, allowing robust FLIM imaging of sub-second metabolite dynamics with subcellular resolution. Our work enables high-precision, cost-effective FLIM imaging at rates comparable to commercial systems and at a fraction of the cost, facilitating the adoption of FLIM across all areas of research needing affordable, quantitative live imaging solutions.

neuroscience↗

bioRxiv2024

Overactivation of prefrontal astrocytes impairs cognition through the metabolic pathway of central kynurenines

Astrocyte dysfunctions have long been implicated in psychiatric and cognitive disorders, yet the precise mechanisms underlying this association remain elusive. Here, we show that chemogenetic activation of prefrontal astrocytes in mice impairs short-term memory and sensorimotor gating and attenuates the activation of parvalbumin (PV) interneurons in the prefrontal cortex. These alterations are accompanied by increases in prefrontal levels of kynurenic acid (KYNA), a key metabolite of the kynurenine (KYN) pathway, known to be produced by astrocytes, which serves as an endogenous antagonist of NMDA receptors. Pharmacological inhibition of kynurenine aminotransferase II, the key enzyme mediating the transamination of KYN to KYNA, reinstates the astrocyte-mediated impairments in short-term memory and sensorimotor gating, and normalizes the deficits in prefrontal PV interneuron activation. Our study identifies a mechanistic link between overactivation of prefrontal astrocytes, increased production of KYNA, and cognitive as well as cellular dysfunctions involved in major psychiatric disorders and beyond.

neuroscience↗

bioRxiv2024

A structural MRI marker predicts individual differences in impulsivity and classifies patients with behavioral-variant frontotemporal dementia from matched controls

Impulsive decision-making is a symptom across many neuropsychiatric and neurological disorders. Yet, it is still unknown whether impulsivity can be predicted based on individual differences in brain structure. Here, we used machine-learning to develop a structural MRI signature of impulsivity, tested its validity in several independent samples, and assessed its diagnostic value in patients with behavioral variant frontotemporal dementia (bvFTD)--a neurodegenerative disease characterized by high impulsivity. The resulting whole-brain grey matter density pattern--the Structural Impulsivity Signature (SIS)--showed a good prediction-outcome correlation of r=0.35 (out-of-sample, p=0.0028) in the training sample of healthy adults (N=117) and significantly predicted individual differences in impulsivity in four other, independent studies (total N=626), including healthy and clinical participants with neuropsychiatric and neurological conditions. Further, the SIS separated bvFTD patients from controls with high accuracy (81% correct, p=0.002) and predicted impulsivity-related symptom severity among patients. The spatial distribution of weights in the SIS brain pattern highlights the key role of brain regions associated with affective processing in impulsivity. Together, these results provide evidence for a new structural neuromarker of individual differences in impulsivity that can be easily applied to new samples. Future studies can further assess its predictive value towards better prevention, diagnosis and treatment of mental disorders associated with impulsivity symptoms.

neuroscience↗

bioRxiv2024

Deciphering plant-beneficial fungal interactions: Unravelling metabolic diversity that underpins communication between Laccaria bicolor and Trichoderma

With over 250 known species, the genus Trichoderma (Ascomycota, Hypocreaceae) is found in various soils, on plant surfaces and as plant endophytes. While Trichoderma species are known as mycoparasites, their antagonistic behaviour can also negatively affect other beneficial fungi, such as mycorrhizal fungi. To gain insight into the metabolic signals involved in the interactions between the ectomycorrhizal fungus (ECM) Laccaria bicolor (Basidomycota, Hydnangiaceae), and different mycoparasitic Trichoderma spp. (T. harzianum strains WM24a1, MS8a1 and ES8g1, and T. atrobrunneum), we performed in vitro dual-confrontation experiments. We studied the volatile organic compounds (VOCs), hyphal metabolomes and soluble metabolites released by each of the fungi in various co-cultivation scenarios. The results revealed an altered growth of the mycelia depending on the degree of contact: When Trichoderma spp. and L. bicolor shared only the same headspace, Trichoderma spp. growth was at least partially inhibited, whereas in direct contact the growth of L. bicolor was impaired. Distinct strain- and species-specific changes in hyphal metabolites, in exudates and volatile emission were revealed from each of the studied fungi. We identified both core metabolite profiles and interaction-specific metabolic responses that were related to carbohydrate, lipid, nucleotide, energy and amino acid metabolisms. Volatile and soluble metabolites revealed temporal and spatial adjustments in dual cultures compared to solitary cultures, suggesting rapid contact-dependent adaptations and demonstrating the dynamic communication mechanisms between Trichoderma spp. and the ECM. These results suggest a central role for both emitted and secreted fungal metabolites in the fungal non-self-recognition and in interaction with each other.

microbiology↗

bioRxiv2024

Lactate-carried Mitochondrial Energy Overflow

We addressed the question of mitochondrial lactate metabolism using genetically-encoded sensors. The organelle was found to contain a dynamic lactate pool that leads to dose- and time-dependent protein lactylation. In neurons, mitochondrial lactate reported blood lactate levels with high fidelity. The exchange of lactate across the inner mitochondrial membrane was found to be mediated by a high affinity H+-coupled transport system involving the mitochondrial pyruvate carrier MPC. Assessment of electron transport chain activity and determination of lactate flux showed that mitochondria are tonic lactate producers, a phenomenon driven by energization and stimulated by hypoxia. We conclude that an overflow mechanism caps the redox level of mitochondria, while saving energy in the form of lactate. One Sentence SummaryMitochondrial lactate production

biochemistry↗

bioRxiv2024

Astrocytes adopt a progenitor-like migratory strategy for regeneration in adult brain

Mature astrocytes become activated upon non-specific tissue damage and contribute to glial scar formation. Proliferation and migration of adult reactive astrocytes after injury is considered very limited. However, the regenerative behavior of individual astrocytes following selective astroglial loss, as seen in astrocytopathies, such as neuromyelitis optica spectrum disorder, remains unexplored. Here, we performed longitudinal in vivo imaging of cortical astrocytes after focal astrocyte ablation in mice. We discovered that perilesional astrocytes develop a remarkable plasticity for efficient lesion repopulation. A subset of mature astrocytes transforms into reactive progenitor-like (REPL) astrocytes that not only undergo multiple asymmetric divisions but also remain in a multinucleated interstage. This regenerative response facilitates efficient migration of newly formed daughter cell nuclei towards unoccupied astrocyte territories. Our findings define the cellular principles of astrocyte plasticity upon focal lesion, unravelling the REPL phenotype as a fundamental regenerative strategy of mature astrocytes to restore astrocytic networks in the adult mammalian brain. Promoting this regenerative phenotype bears therapeutic potential for neurological conditions involving glial dysfunction.

neuroscience↗

bioRxiv2024

Exogenous stimulation of Tanacetum vulgare roots with pipecolic acid leads to tissue-specific responses in terpenoid composition

Tanacetum vulgare L., known as tansy, is a perennial plant with a highly variable terpenoid composition, with mono- and sesquiterpenoids being the most abundant. The high diversity of terpenoids is known to play an important role in mediating ecological interactions. However, the distribution of terpenoids in different tissues and the inducibility of terpenoids in these tissues by biotic stress are poorly understood. In this study, we investigated the changes in terpenoid profiles and concentrations in different plant organs following treatment of roots with pipecolic acid (Pip). Pipecolic acid is a non-proteinogenic amino acid that triggers defense responses in plants. It is often used to induce systemic resistance (SAR) in plants under controlled conditions. Examination of the tissues showed that the leaves and midribs contained mainly monoterpenoids, while the coarse and fine roots of the plants contained mainly sesquiterpenoids. The rhizomes occupied an intermediate position by presenting the terpenoid profiles of both the midribs and roots but also the unique compounds of its own. Treatment with pipecolic acid led to an increase in the concentration of mono- and sesquiterpenoids in all tissues except rhizomes. However, a significantly higher amount of sesquiterpenoids was formed in root tissues in response to Pip compared to shoots. The metabolic atlas for terpenoids presented here shows that there is an exceptionally strong differentiation of terpenoid patterns and terpenoid contents in the different tissues of tansy. This, together with the differential inducibility by biotic stress, suggests that the chemical diversity of terpenoids may play an important role in the ecological interactions of tansy and in the defense against biotic stressors that feed on the below- and above-ground organs of the plant.

ecology↗

bioRxiv2024

Bessel Beam Optical Coherence Microscopy Enables Multiscale Assessment of Cerebrovascular Network Morphology and Function

Understanding the morphology and function of large-scale cerebrovascular networks is crucial for studying brain health and disease. However, reconciling the demands for imaging on a broad scale with the precision of high-resolution volumetric microscopy has been a persistent challenge. In this study, we introduce Bessel beam optical coherence microscopy with an extended focus to capture the full cortical vascular hierarchy in mice over 1000 x 1000 x 360 m3 field-of-view at capillary level resolution. The post-processing pipeline leverages a supervised deep learning approach for precise 3D segmentation of high-resolution angiograms, hence permitting reliable examination of microvascular structures at multiple spatial scales. Coupled with high-sensitivity Doppler optical coherence tomography, our method enables the computation of both axial and transverse blood velocity components as well as vessel-specific blood flow direction, facilitating a detailed assessment of morpho-functional characteristics across all vessel dimensions. Through graph-based analysis, we deliver insights into vascular connectivity, all the way from individual capillaries to broader network interactions, a task traditionally challenging for in vivo studies. The new imaging and analysis framework extends the frontiers of research into cerebrovascular function and neurovascular pathologies.

bioengineering↗

bioRxiv2024

L-Type calcium channels and TRPC3 channels shape brain pericyte calcium signaling and hemodynamics throughout the arteriole to capillary network in vivo

Pericytes play a crucial role in regulating cerebral blood flow (CBF) through processes like vasomotion and neurovascular coupling (NVC). Recent work has identified different pericyte types at distinct points in the cerebrovascular network, such as the arteriole-capillary transition zone (ACT) and distal capillaries, sparking debate about their functional roles in blood flow control. Part of this discussion has comprised the possible mechanisms that may regulate pericyte Ca2+ signaling. Using in vivo two-photon Ca2+ imaging and a pharmacological approach with Ca2+ channel blockers (nimodipine and Pyr3), we assessed the contribution of L-type voltage-gated Ca2+ channels (VGCC) and transient receptor potential canonical 3 (TRPC3) channels to Ca2+ signaling in different pericyte types, ensheathing and capillary pericytes. We also measured local hemodynamics such as vessel diameter, blood cell velocity and flux during vasomotion, and following somatosensory stimulation to evoke NVC. We report that VGCC and TRPC3 channels underlie spontaneous fluctuations in ensheathing pericyte Ca2+ that trigger vasomotor contractions, but the contribution of each of these mechanisms to vascular tone depends on the specific branch of the ACT. Distal capillary pericytes also express L-type VGCCs and TRPC3 channels and they mediate spontaneous Ca2+ signaling in these cells. However, only TRPC3 channels maintain resting capillary tone, possibly by a receptor-operated Ca2+ entry mechanism. By applying the Ca2+ channel blockers during NVC, we found a significant involvement of L-type VGCCs in both pericyte types, influencing their ability to dilate during functional hyperemia. These findings provide new evidence of VGCC and TRPC3 activity in pericytes in vivo and establish a clear distinction between brain pericyte types and their functional roles, opening avenues for innovative strategies to selectively target their Ca2+ dynamics for CBF control. Significance StatementAlthough brain pericytes contribute to the regulation of CBF, there is uncertainty about how different types of pericytes are involved in this process. Ca2+ signaling is believed to be important for the contractility and tone of pericytes, but there is a limited understanding of the Ca2+ pathways in specific pericyte types. Here, we demonstrate that both VGCC and TRPC3 channels are active in distinct types of pericytes throughout the cerebrovascular network, but have different roles in pericyte tone depending on the pericyte location. This has important implications for how pericytes influence vasomotion and neurovascular coupling, which are central processes in CBF regulation. This work also provides the first evidence of TRPC3 channel activity in pericytes in vivo, furthering our understanding of the diverse signaling pathways within these brain mural cells.

neuroscience↗

bioRxiv2024

Pia-FLOW: Deciphering hemodynamic maps of the pial vascular connectome and its response to arterial occlusion

The pial vasculature is the sole source of blood supply to the neocortex. The brain is contained within the skull, a vascularized bone marrow with a unique anatomical connection to the brain. Recent developments in tissue clearing have enabled unprecedented mapping of the entire pial and calvarial vasculature. However, what are the absolute flow rates values of those vascular networks? This information cannot accurately be retrieved with the commonly used bioimaging methods. Here, we introduce Pia-FLOW, a new approach based on large-scale fluo-rescence localization microscopy, to attain hemodynamic imaging of the whole murine pial and calvarial vasculature at frame rates up to 1000 Hz and spatial resolution reaching 5.4 {micro}m. Using Pia-FLOW, we provide detailed maps of flow velocity, direction and vascular diameters which can serve as ground-truth data for further studies, advancing our understanding of brain fluid dynamics. Furthermore, Pia-FLOW revealed that the pial vascular network functions as one unit for robust allocation of blood after stroke.

neuroscience↗

bioRxiv2023

Biodiversity in mountain soils above the treeline

Despite the importance of healthy soils for human livelihood, wellbeing, and safety, current gaps in our knowledge and understanding of biodiversity in soil are numerous, undermining conservation efforts. These gaps are particularly wide in mountain regions where healthy soils are especially important for human safety and yet evidence is accumulating of ongoing degradation, posing significant threats to ecosystem functioning and human settlements. To analyse these gaps in detail, we synthesise current research on the global diversity of microorganisms, cryptogams, and invertebrates in mountain soils above the treeline. This synthesis is based on a semi-quantitative survey of the literature and an expert-based analysis. Our work reveals not only deficiencies in geographic cover but also significant gaps in taxonomic coverage, particularly among soil protists and invertebrates, and a lack of (functional and ecological) description of the uncultivated majority of prokaryotes, fungi, and protists. We subsequently build on this overview to highlight opportunities for research on mountain soils as systems of co-occurring species that interact in complex environmental matrices to fulfil critical functions and make essential contributions to life on land. Closing gaps in biodiversity research in mountain soil is crucial to enhance our understanding and to promote laws and guidelines advancing international soil biodiversity conservation targets in mountains. Addressing sparse and biased data, recognizing the impact of environmental changes on mountain ecosystems, and advocating dedicated policies are essential strategies to safeguard mountain soils and their biodiversity. GLOSSARY O_TBL View this table: org.highwire.dtl.DTLVardef@16682fdorg.highwire.dtl.DTLVardef@121b9feorg.highwire.dtl.DTLVardef@139eadeorg.highwire.dtl.DTLVardef@16abd74org.highwire.dtl.DTLVardef@bc3da9_HPS_FORMAT_FIGEXP M_TBL C_TBL

ecology↗

bioRxiv2023

Transcranial cortex-wide imaging of murine ischemic perfusion with large-field multifocal illumination fluorescence microscopy

Ischemic stroke is a common cause of death worldwide and a main cause of morbidity. Presently, computed tomography and magnetic resonance imaging are the mainstay for stroke diagnosis and therapeutic monitoring. These modalities are often limited in terms of accessibility as well as their ability to map brain perfusion with sufficient spatial and temporal resolution, particularly in the context of preclinical studies, thus calling for development of new brain perfusion techniques featuring rapid imaging speed, cost-effectiveness, and ease of use. Herein, we report on cortex-wide perfusion imaging in murine ischemic stroke with large-field multi-focal illumination fluorescence microscopy (LMI). We attained quantitative readings of hemodynamic and structural changes in cerebral vascular network and pial vessels at capillary level resolution and 80 Hz frame rate fully transcranially. The in vivo perfusion maps accurately delineated the ischemic core and penumbra, further exhibiting strong correlation with ex vivo triphenyl tetrazolium chloride staining. Interestingly, monitoring of therapeutic effects of thrombolysis in stroke has revealed that early recanalization could effectively save the penumbra whilst reducing the infarct area. Furthermore, cross-strain comparison of perfusion dynamics affirmed that C57BL/6 mice, benefiting from more extensive pial collateral recruitment, feature a larger penumbra and smaller infarct core as compared to BALB/c mice which have few or no collaterals. Finally, we apply LMI to show that sensory stimulation-based treatment enhances blood flow and abolish perfusion deficit in the ischemic core and penumbra regions. The simple, cost-effective and minimally invasive nature of the proposed approach offers new venues for brain perfusion research under various disease conditions such as stroke, neurodegeneration or epileptic seizures.

neuroscience↗

bioRxiv2023

Development of a genetically-encoded sensor for probing endogenous nociceptin opioid peptide release

Nociceptin/orphanin-FQ (N/OFQ) is a recently appreciated critical opioid peptide with key regulatory functions in several central behavioral processes including motivation, stress, feeding, and sleep. The functional relevance of N/OFQ action in the mammalian brain remains unclear due to a lack of high-resolution approaches to detect this neuropeptide with appropriate spatial and temporal resolution. Here we develop and characterize NOPLight, a genetically encoded sensor that sensitively reports changes in endogenous N/OFQ release. We characterized the affinity, pharmacological profile, spectral properties, kinetics, ligand selectivity, and potential interaction with intracellular signal transducers of NOPLight in vitro. Its functionality was established in acute brain slices by exogeneous N/OFQ application and chemogenetic induction of endogenous N/OFQ release from PNOC neurons. In vivo studies with fibre photometry enabled direct recording of NOPLight binding to exogenous N/OFQ receptor ligands, as well as detection of endogenous N/OFQ release within the paranigral ventral tegmental area (pnVTA) during natural behaviors and chemogenetic activation of PNOC neurons. In summary, we show here that NOPLight can be used to detect N/OFQ opioid peptide signal dynamics in tissue and freely behaving animals.

neuroscience↗

bioRxiv2023

CAF variants control the tumor-immune microenvironment and predict skin cancer malignancy

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression and treatment outcome. This study dissects the yet unresolved intra-tumoral variety of CAFs in three skin cancer types -- Basal Cell Carcinoma, Squamous Cell Carcinoma, and Melanoma -- at molecular and spatial single-cell resolution. By integral analysis of the fibroblasts with the tumor microenvironment, including epithelial, mesenchymal, and immune cells, we characterize three distinct CAF subtypes: myofibroblast-like RGS5+ CAFs, matrix CAFs (mCAFs), and immunomodulatory CAFs (iCAFs). Notably, large cohort tissue analysis reveals marked shifts in CAF subtype patterns with increasing malignancy. Two CAF types exhibit immunomodulatory capabilities via distinct mechanisms. mCAFs synthesize extracellular matrix and have the ability to ensheath tumor nests, potentially limiting T cell invasion in low-grade tumors. In contrast, iCAFs are enriched in late-stage tumors, especially infiltrative BCC and high-grade melanoma, and express unexpectedly high mRNA and protein levels of cytokines and chemokines, pointing to their integral role in immune cell recruitment and activation. This finding is further supported by our observation that in vitro exposure of primary healthy fibroblasts to skin cancer cell secretomes induces an iCAF-like phenotype with immunomodulatory functions. Thus, targeting CAF variants, particularly the immunomodulatory iCAF subtype, holds promise for improved efficacy of immunotherapy in skin cancers.

cancer biology↗

bioRxiv2023

Spatial Signatures of Biological Soil Crusts and Community Level Self-Organization in Drylands

In dryland landscapes, patches of vascular plants can respond to environmental stress by adjusting their spatial pattern to intercept runoff more effectively, i.e., spatially self-organize, and maintain productivity. However, vegetation patch dynamics in drylands often assumes interspaces of plant patches are composed only of bare soil. Biological soil crusts (BSCs) are complex communities, largely of cyanobacteria, algae, lichens, and bryophytes, living in the soil surface in drylands and often cover more area than vascular plants. BSCs often occur in patches of light cyanobacteria and dark-mixed aggregates and can significantly affect and respond to ecohydrological feedbacks in dryland ecosystems. However, little is known about their spatial patterns and dynamics. In this study, we investigate spatial attributes of BSC patches, their spatial interactions with vascular plants, and factors that drive variation in these attributes. We collected ultra-high-resolution (1-cm) data on spatial patterns of BSCs and vascular plants at 26 sites across three ecoregions of the Southwest of the United States of America. Our analysis shows that light cyanobacterial BSCs vary most in their patch shape complexity along the aridity gradient, while dark-mixed BSCs vary strongly in their abundance. The abundance of dark-mixed BSCs is significantly affected by the soil template, namely soil texture and calcareousness, as well as vascular plants to persist under stress. Furthermore, species associations also change with environmental stress. Light cyanobacteria BSCs, likely a significant source of runoff, may act as a buffer for woody plants against drying, as spatial interactions between these biota become more positive (i.e., spatially aggregated) with greater aridity. While dark-mixed BSCs rely significantly on soil conditions and reduce in abundance as a response to aridity stress, we find evidence that they may have some capacity to spatially adjust under conditions of constant aridity. The interaction of dark-mixed BSCs with light cyanobacteria patches becomes more positive with slope. We conclude that light cyanobacteria BSCs can likely change patch shape in response to water limitation, while dark-mixed BSCs have a reduced capacity to do so - providing further evidence that the abundance of dark-mixed BSCs will decline in the future under drying. BSCs and vascular plants coordinate in space in response to resource availability, suggesting the need to consider self-organization of multiple assemblages to fully understand dryland response to climatic change.

ecology↗