Biology subjects

Erturk, A.

Publications and source records attributed to Erturk, A..

At least 19 recordsLinked to original sources

bioRxiv2026

BaSiCPy: Scalable and Robust Shading Correction for Optical Microscopy Images

Quantitative fluorescence microscopy is frequently confounded by spatially varying illumination and temporal intensity drift. Although BaSiC is a widely adopted retrospective correction method, it can fail when foreground content is strongly correlated across images--a common regime in time-lapse, tiled and volumetric acquisitions--and its application often requires manual parameter tuning that limits reproducibility and scalability. We introduce BaSiCPy, a foreground-aware implementation of BaSiC that improves illumination profile estimation under correlated foreground structures, provides automatic hyperparameter selection and accelerates large-scale processing through GPU support. BaSiCPy is distributed as an open-source Python package with graphical and programmatic interfaces, facilitating integration into contemporary bioimage analysis workflows.

bioengineering↗

bioRxiv2025

De novo H3.3K27M-altered Diffuse Midline Glioma in human brainstem organoids to dissect GD2 CAR T cell function

Diffuse midline glioma (DMG) is a rare yet highly aggressive paediatric cancer primarily arising in the pontine region of the brainstem, necessitating the development of scalable patient-representative models for treatment advance1,2. Here, we developed an FGF4-driven human brainstem organoid model, with high representation of pontine glial lineages. By genetically engineering de novo H3.3K27M-altered DMG, we show that this brainstem glial specification is essential for driving DMG tumorigenesis, resulting in tumours that recapitulate the infiltrative nature and molecular heterogeneity of patient samples. By performing prolonged GD2 CAR T cell treatment in this model, we could mirror variable treatment outcomes as observed in the clinic3,4 and demonstrate a high level of CAR T cell transcriptional heterogeneity. From these CAR T cell functional states, we could identify the most potent effector population and validated NCAM1 as a selection marker for their enrichment. In contrast, NCAM1- cells were linked to a cellular stress response, previously associated to immunotherapy resistance5. Furthermore, incorporating the brain-resident myeloid compartment resulted in DMG-specific, largely immunosuppressive microglia subtypes6. These disease-representative microglia reduced GD2 CAR T cell treatment efficacy and we identified the functional profiles most susceptible to this microglia-dependent immune modulation. Thus, we present a scalable human DMG model with critical applications towards understanding CAR T cell functionality to aid therapy development for this detrimental disease.

cancer biology↗

bioRxiv2025

DISCO-seq: 3D single-cell transcriptomics of intact biological systems

Single-cell transcriptomics has transformed tissue analysis, yet current methods struggle to integrate whole-tissue 3D architecture. Conventional techniques restrict molecular profiling to pre-selected 2D sections, losing systemic context and introducing anatomical bias by sampling less than 0.001% of a whole organism. To overcome these challenges, we developed DISCO-seq, a tissue-clearing chemistry that enables superior RNA accessibility compared to fresh or fixed tissues. DISCO-seq integrates whole-organ or organism 3D imaging with both untargeted and targeted transcriptomics, yielding high-quality RNA from cleared tissues comparable to standard samples. We demonstrate its versatility by investigating tumor heterogeneity in a syngeneic glioblastoma mouse model, using 3D imaging to identify spatially distinct microenvironments and characterize their unique transcriptomic signatures. Moreover, DISCO-seq enabled unbiased, whole-body mapping of SARS-CoV-2 S1 protein deposition in mice, followed by transcriptomic profiling of spatially defined niches. By bridgingmesoscale 3D imaging with single-cell transcriptomics, DISCO-seq establishes a paradigm for anatomically contextualized, hypothesis-free tissue interrogation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=111 SRC="FIGDIR/small/693352v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@758ee5org.highwire.dtl.DTLVardef@1f862c6org.highwire.dtl.DTLVardef@1cf3b9org.highwire.dtl.DTLVardef@c5082e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDISCO-seq integrates RNA-preserving tissue-clearing chemistry with whole-organ or organism 3D imaging, enabling anatomically unbiased single-cell transcriptomics. C_LIO_LIDISCO-seq yields RNA quality and transcriptome profiles equivalent to those obtained from matched fresh or fixed tissues. C_LIO_LIDISCO-seq identifies discrete glioblastoma microenvironments and defines their transcriptomic states within the intact brain. C_LIO_LIDISCO-seq enables whole-body mapping of SARS-CoV-2 S1 and uncovers region-specific immune and metabolic responses across anatomical niches. C_LI Supplementary movies can be seen at: http://discotechnologies.org/DISCO-seq/

systems biology↗

bioRxiv2025

Leonardo: a toolset to correct sample-induced artifacts in light sheet microscopy images

Selective plane illumination microscopy (SPIM, also known as light sheet fluorescence microscopy) is the method of choice for studying morphogenesis and function in biological specimens over extended periods, as it permits gentle and rapid volumetric imaging. In inhomogeneous samples, however, sample-induced artifacts, including light absorption, scattering, and refraction, can impact the image quality, particularly as the focal plane gets deeper into the sample. Here, we present Leonardo, the first toolbox designed to address the major sample-induced artifacts by using two modules: (1) DeStripe removes stripe artifacts in SPIM caused by light absorption while preserving fine sample structures; (2) Fuse reconstructs a single high-quality image from dualsided illumination and/or dual-sided detection, while eliminating blur and optical distortions caused by light scattering and refraction. The efficacy of Leonardo is validated on a wide range of biological samples, from minimally invasive experiments on sensitive specimens (translucent embryonic and optically opaque larval zebrafish) to cleared mouse samples up to two centimeters in size. We provide model code and a Napari-based graphical user interface, enabling the SPIM community to easily apply Leonardo to advance light sheet imaging of inhomogeneous and complex specimens.

bioinformatics↗

bioRxiv2025

LipiGo: A Versatile DNA-Lipid Nanoparticle Hybrid for Precision Drug Delivery

Lipid nanoparticles (LNPs) are established carriers for nucleic acid delivery, however, achieving efficient delivery to non-hepatic tissues remains a major challenge. Here, we present LipiGo, a nanocarrier platform engineered by integrating short single stranded DNA molecules into the lipid nanoparticle structure. Using whole body tissue clearing, advanced imaging and AI-based analysis, we show that LipiGo redirects functional mRNA delivery to lymphoid organs, particularly the spleen. Immune cell profiling further reveals enhanced uptake within key immune populations, including antigen-presenting cells, compared to standard LNPs. Beyond passive redistribution, LipiGo leverages DNA hybridization to enable modular attachment of targeting ligands for active targeting as demonstrated by cell-specific delivery to white adipocytes. Overall, the dual-purpose design principle of LipiGo demonstrates high modularity and efficiency, enabling tissue and cell specific delivery beyond hepatic applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/676334v2_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@9b69eorg.highwire.dtl.DTLVardef@1b45bd0org.highwire.dtl.DTLVardef@1f7b79dorg.highwire.dtl.DTLVardef@37a673_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2025

A look at the ground: time lapse camera trapping to determine the composition and abundance of small sized wildlife communities

Micromammals are critical species in the context of ecosystem functioning, assuming a significant role as prey species and environmental engineers. Nevertheless, they present a challenge when developing monitoring programs. As a proof of concept, a time-lapse based camera-trapping non-invasive protocol was tested with the application of the Space to Event Model (STE) was determined. The objective of this study was to estimate the density of micromammals in Donana National Park (DNP, Southwest Spain) by comparing estimates against independent ones obtained from capture-mark-recapture (CRM) methodology with a standardized protocol using Sherman traps. The micromammal species richness in the area exhibited a strong correlation with the capture methodology employed. Regarding the estimation of abundance, the densities of micromammals determined by STE were found to be within the range of the estimations of minimum population size determined by CRM. The STE, which was found to be promising, also allowed the determination of the abundance of other small-sized terrestrial wildlife, such as reptiles. Our findings indicate its potential for camera trap multi-species monitoring. In terms of practicability, field and data processing efforts for STE are both viable and will continue to improve as new automatic identification tools are incorporated. It is imperative that the STE protocols are examined in a series of study areas exhibiting varying micromammal densities and species compositions, in addition to other small-sized terrestrial wildlife.

ecology↗

bioRxiv2024

Deep Learning and 3D Imaging Reveal Whole-Body Alterations in Obesity

Many diseases, such as obesity, have systemic effects that impact multiple organ systems throughout the body. However, tools for comprehensive, high-resolution analysis of disease-associated changes at the whole-body scale have been lacking. Here, we developed a suite of deep learning-based image analysis algorithms (MouseMapper) and integrated it with tissue clearing and light-sheet microscopy to enable a comprehensive analysis of diseases impacting diverse systems across the mouse body. This approach enables the quantitative analysis of cellular and structural changes across the entire mouse body at unprecedented resolution and scale, including tracking nerves over several centimeters in whole animal bodies. To demonstrate its power, we applied MouseMapper to study nervous and immune systems in high-fat diet induced obesity. We uncovered widespread changes in both immune cell distribution and nerve structures, including alterations in the trigeminal nerve characterized by a reduced number of nerve endings in obese mice. These structural abnormalities were associated with functional deficits of whisker sensing and proteomic changes in the trigeminal ganglion, primarily affecting pathways related to axon growth and the complement system. Additionally, we found heterogeneity in obesity-induced whole-body inflammation across different tissues and organs. Our study demonstrates MouseMappers capability to discover and quantify pathological alterations at the whole-body level, offering a powerful approach for investigating the systemic impacts of various diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/608300v1_ufig1.gif" ALT="Figure 1"> View larger version (74K): org.highwire.dtl.DTLVardef@17d2601org.highwire.dtl.DTLVardef@14a2d3dorg.highwire.dtl.DTLVardef@e04114org.highwire.dtl.DTLVardef@d0b8b5_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWe developed MouseMapper: AI-driven pipeline for whole-body structural analysis in mice C_LIO_LIMouseMapper revealed obesity-induced changes in nerves and immune cells across multiple organs C_LIO_LIMouseMapper identified facial nerve alterations in obesity linked to impaired whisker sensitivity C_LIO_LIMouseMapper has the potential for holistic 3D analysis of systemic diseases C_LI Supplementary Videos can be seen at: http://discotechnologies.org/MouseMapper/

systems biology↗

bioRxiv2024

Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution compared to standard antibodies

The blood-brain barrier (BBB) poses a significant challenge drug delivery to the brain. BBB-crossing molecules are emerging as a new class of therapeutics with significant potential for central nervous system (CNS) indications. In particular, transferrin receptor (TfR)- and CD98 heavy chain (CD98hc)-targeting molecules have been demonstrated to cross the BBB for enhanced brain delivery. Previously, we reported TfR and CD98hc antibody transport vehicles (ATVTfR and ATVCD98hc) that utilize these BBB receptors to improve CNS drug delivery1,2. Here, we provide a comprehensive and unbiased biodistribution characterization of ATVTfR and ATVCD98hc compared to a standard IgG at a multiscale level, ranging from whole-body to brain region- and cell type-targeting specificity. Mouse whole-body tissue clearing revealed distinct organ localization for each molecule. In the CNS, ATVTfR and ATVCD98hc not only achieves enhanced brain delivery but importantly, much broader parenchymal distribution in contrast to the severely limited distribution observed with a standard antibody that was not able to be improved even at very high dose levels. Using cell sorting and single-cell RNA sequencing of mouse brain, we revealed that standard IgG predominantly localizes to perivascular and leptomeningeal cells and reaches the CNS by entering the CSF, rather than crossing the BBB. In contrast, ATVTfR and ATVCD98hc enables broad parenchymal cell-specific distribution via transcytosis through brain endothelial cells (BECs) along the neurovasculature. Finally, we extended the translational relevance of our findings by revealing enhanced and broad brain and spinal cord biodistribution of ATVTfR compared to standard IgG in cynomolgus monkey. Taken together, this multiscale analysis reveals in-depth biodistribution differences between ATVTfR, ATVCD98hc, and standard IgG. These results may better inform platform selection for specific therapeutic targets of interest, optimally matching platforms to desired CNS target engagement, peripheral organ exposures, and predict or potentially reduce off-target effects.

neuroscience↗

bioRxiv2024

Cortex Folding by Combined Progenitor Expansion and Adhesion-Controlled Neuronal Migration

Folding of the mammalian cerebral cortex into sulcal fissures and gyral peaks is the result of complex processes that are incompletely understood. Previously we showed that genetic deletion of Flrt1/3 adhesion molecules causes folding of the smooth mouse cortex into sulci resulting from increased lateral dispersion and faster neuron migration, without progenitor expansion. Here, we find that combining the Flrt1/3 double knockout with an additional genetic deletion that causes progenitor expansion, greatly enhances cortex folding. Expansion of intermediate progenitors by deletion of Cep83 results in enhanced formation of sulci. Expansion of apical progenitors by deletion of Fgf10 results in enhanced formation of gyri. Single cell transcriptomics and simulations suggest that changes in adhesive properties of cortical neurons, their proportions and densities in the cortical plate, combined with lateral dispersion during their radial migration are important folding parameters. These results identify key developmental mechanisms that cooperate to promote cortical gyrification. HIGHLIGHTSO_LICortex folding is enhanced by combining progenitor expansion and divergent migration. C_LIO_LIConcomitant expansion of intermediate progenitors results in the formation of sulci C_LIO_LIConcomitant expansion of apical progenitors results in the formation of gyri C_LIO_LIProgenitors differentially affect cortical neurons with distinct adhesive properties C_LI

neuroscience↗

bioRxiv2023

Single-cell precision nanotechnology in vivo

Targeting nanoparticle therapeutics with cellular accuracy in whole organisms could open breakthrough opportunities in precision medicine. However, evaluating and fine-tuning the biodistribution of such systems in the whole organism at the cellular level remains a major obstacle. Here, we constructed targetable DNA origami, and analyzed biodistribution in transparent mice, in addition to studying tolerability, clearance kinetics, and immune response parameters. Untargeted DNA origami primarily accumulated in the spleen and the liver, while an immune cell-targeting variant successfully attached to immune cells throughout the body. A cancer cell-targeting mimetic co-localized on solid-tumor metastasis in the liver and the lung. These findings indicate that DNA origami can be directed in vivo, providing an important proof-of-concept and highlights the potential of high-resolution tissue-clearing imaging technologies in their development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/550304v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@ce216borg.highwire.dtl.DTLVardef@f40bb4org.highwire.dtl.DTLVardef@2c6a66org.highwire.dtl.DTLVardef@1fd7fde_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIThis study demonstrates the potential of DNA origami-based drug delivery systems as versatile tool for for targeted delivery, which could be used to treat a range of diseases with applications. C_LIO_LIThe immune compatibility, half-life, targeting efficiency, and the biodistribution evaluation of DNA origami indicate its potential for systemic drug delivery. C_LIO_LIOur approach enables the assessment of biodistribution of nanoparticles in the intact body with a sensitivity to the single-cell level, highlighting the high-resolution tissue clearing technoloies in revealing DNA origamis feasibility for drug targeting. C_LI

bioengineering↗

bioRxiv2023

Virtual reality empowered deep learning analysis of brain activity

Tissue clearing and fluorescent microscopy are powerful tools for unbiased organ-scale protein expression studies. Critical for interpreting expression patterns of large imaged volumes are reliable quantification methods. Here, we present DELiVR a deep learning pipeline that uses virtual reality (VR)-generated training data to train deep neural networks, and quantify c-Fos as marker for neuronal activity in cleared mouse brains and map its expression at cellular resolution. VR annotation significantly accelerated the speed of generating training data compared to conventional 2D slice based annotation. DELiVR detects cells with much higher precision than current threshold-based pipelines, and provides an extensive toolbox for data visualization, inspection and comparison. We applied DELiVR to profile cancer-related mouse brain activity, and discovered a novel activation pattern that distinguishes between weight-stable cancer and cancer-associated weight loss. Thus, DELiVR provides a robust mouse brain analysis pipeline at cellular scale that can be used to study brain activity patterns in health and disease. The DELiVR software, Fiji plugin and documentation can be found at https://www.DISCOtechnologies.org/DELiVR/. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=169 SRC="FIGDIR/small/540970v1_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@172d5bforg.highwire.dtl.DTLVardef@2f1d80org.highwire.dtl.DTLVardef@139e7a0org.highwire.dtl.DTLVardef@95dce1_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDELiVR detects labelled cells in cleared brains with deep learning C_LIO_LIDELiVR is trained by annotating ground-truth data in virtual reality (VR) C_LIO_LIDELiVR is launched via a FIJI plugin anywhere from PCs to clusters C_LIO_LIUsing DELiVR, we found new brain activity patterns in weight-stable vs. cachectic cancer C_LI Supplementary Videos can be seen at: https://www.DISCOtechnologies.org/DELiVR/

bioinformatics↗

bioRxiv2023

SARS-CoV-2 Spike Protein Accumulation in the Skull-Meninges-Brain Axis: Potential Implications for Long-Term Neurological Complications in post-COVID-19

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the viruss acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis. Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spikes persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway. Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities. Graphical Summary O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/535604v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@b223eforg.highwire.dtl.DTLVardef@15539e9org.highwire.dtl.DTLVardef@4d17a9org.highwire.dtl.DTLVardef@14c63af_HPS_FORMAT_FIGEXP M_FIG C_FIG Short SummaryThe accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis presents potential molecular mechanisms and therapeutic targets for neurological complications in long-COVID-19 patients.

neuroscience↗

bioRxiv2023

Whole mouse body histology using standard IgG antibodies

Most diseases involve multiple interconnected physiological systems, but histological evaluation of their pathology is currently limited to small tissue samples. Here, we present wildDISCO, a technology that uses cholesterol extraction to enable deep tissue penetration of standard 150 kDa IgG antibodies in chemically fixed whole mice. Combining wildDISCO with whole mouse clearing, we generate whole-body maps of the nervous, immune, and lymphatic systems and show their close interactions throughout the mouse body. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=158 SRC="FIGDIR/small/528921v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@f0de23org.highwire.dtl.DTLVardef@187fe94org.highwire.dtl.DTLVardef@15ac0faorg.highwire.dtl.DTLVardef@133703e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIWildDISCO uses new tissue chemistry based on {beta}-cyclodextrin to enable histology in whole mouse bodies using full-size antibodies C_LIO_LIWildDISCO generates the first whole mouse body atlases for neurons, immune cells, blood and lymph vessels C_LIO_LIThe whole mouse atlases are available online to study the biological systems in health and disease C_LIO_LIVirtual Reality (VR) exploration of these atlases disentangles complex anatomical structures between organs and biological systems C_LI Supplementary Videos can be seen athttp://discotechnologies.org/wildDISCO/

biochemistry↗

bioRxiv2022

Probe set selection for targeted spatial transcriptomics

Targeted spatial transcriptomics methods capture the topology of cell types and states in tissues at single cell- and subcellular resolution by measuring the expression of a predefined set of genes. The selection of an optimal set of probed genes is crucial for capturing and interpreting the spatial signals present in a tissue. However, current selections often rely on marker genes, precluding them from detecting continuous spatial signals or novel states. We present Spapros, an end-to-end probe set selection pipeline that optimizes both probe set specificity for cell type identification and within-cell-type expression variation to resolve spatially distinct populations while taking into account prior knowledge, as well as probe design and expression constraints. To facilitate data analysis and interpretation, Spapros also provides rules for cell type identification. We evaluated Spapros by selecting probes on 6 different data sets and built an evaluation pipeline with 12 quality metrics to find that Spapros outperforms other selection approaches in both cell type recovery and recovering expression variation beyond cell types. Furthermore, we used Spapros to design a SCRINSHOT experiment of adult lung tissue to demonstrate how probes selected with Spapros identify cell types of interest and detect spatial variation even within cell types. Spapros enables optimal probe set selection, probe set evaluation, and probe design, as a freely available Python package.

bioinformatics↗

bioRxiv2021

Proteomics of spatially identified tissues in whole organs

Spatial molecular profiling of complex tissues is essential to investigate cellular function in physiological and pathological states. However, methods for molecular analysis of biological specimens imaged in 3D as a whole are lacking. Here, we present DISCO-MS, a technology combining whole-organ imaging, deep learning-based image analysis, and ultra-high sensitivity mass spectrometry. DISCO-MS yielded qualitative and quantitative proteomics data indistinguishable from uncleared samples in both rodent and human tissues. Using DISCO-MS, we investigated microglia activation locally along axonal tracts after brain injury and revealed known and novel biomarkers. Furthermore, we identified initial individual amyloid-beta plaques in the brains of a young familial Alzheimers disease mouse model, characterized the core proteome of these aggregates, and highlighted their compositional heterogeneity. Thus, DISCO-MS enables quantitative, unbiased proteome analysis of target tissues following unbiased imaging of entire organs, providing new diagnostic and therapeutic opportunities for complex diseases, including neurodegeneration. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/466753v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1e37035org.highwire.dtl.DTLVardef@dbaa98org.highwire.dtl.DTLVardef@19cece1org.highwire.dtl.DTLVardef@183c032_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIDISCO-MS combines tissue clearing, whole-organ imaging, deep learning-based image analysis, and ultra-high sensitivity mass spectrometry C_LIO_LIDISCO-MS yielded qualitative and quantitative proteomics data indistinguishable from fresh tissues C_LIO_LIDISCO-MS enables identification of rare pathological regions & their subsequent molecular analysis C_LIO_LIDISCO-MS revealed core proteome of plaques in 6 weeks old Alzheimer s disease mouse model Supplementary Video can be seen at: http://discotechnologies.org/DISCO-MS/ C_LI

bioengineering↗

bioRxiv2019

The Ocular Glymphatic Clearance System

Despite high metabolic activity, the retina and optic nerve head lack traditional lymphatic drainage. We here identified a novel ocular glymphatic clearance route for fluid and wastes via the proximal optic nerve. Amyloid-{beta} (A{beta}) was cleared from the vitreous via a pathway driven by the ocular-cranial pressure difference. After traversing the lamina barrier, intra-axonal A{beta} was cleared via the perivenous space and subsequently drained to lymphatic vessels. Light-induced pupil constriction enhanced, while atropine or raising intracranial pressure blocked efflux. In two distinct murine models of glaucoma, A{beta} leaked from the eye via defects in the lamina barrier instead of directional axonal efflux. The discovery of a novel pathway for removal of fluid and metabolites from the intraocular space prompts a reevaluation of the core principles governing eye physiology and provides a framework for new therapeutic approaches to treat common eye diseases, including glaucoma. One Sentence SummaryGlymphatic pathway clears ocular amyloid-{beta} via optic nerve and fails in glaucoma.

physiology↗

bioRxiv2019

A 3D High Resolution Generative Deep-learning Network for Fluorescence Microscopy Image

Deep learning technology enables us acquire high resolution image from low resolution image in biological imaging free from sophisticated optical hardware. However, current methods require a huge number of the precisely registered low-resolution (LR) and high-resolution (HR) volume image pairs. This requirement is challengeable for biological volume imaging. Here, we proposed 3D deep learning network based on dual generative adversarial network (dual-GAN) framework for recovering HR volume images from LR volume images. Our network avoids learning the direct mappings from the LR and HR volume image pairs, which need precisely image registration process. And the cycle consistent network makes the predicted HR volume image faithful to its corresponding LR volume image. The proposed method achieves the recovery of 20x/1.0 NA volume images from 5x/0.16 NA volume images collected by light-sheet microscopy. In essence our method is suitable for the other imaging modalities.

neuroscience↗

bioRxiv2019

Cellular and Molecular Probing of Intact Transparent Human Organs

Optical tissue transparency permits cellular and molecular investigation of complex tissues in 3D, a fundamental need in biomedical sciences. Adult human organs are particularly challenging for this approach, owing to the accumulation of dense and sturdy molecules in decades-aged human tissues. Here, we introduce SHANEL method utilizing a new tissue permeabilization approach to clear and label stiff human organs. We used SHANEL to generate the first intact transparent adult human brain and kidney, and perform 3D histology using antibodies and dyes in centimeters depth. Thereby, we revealed structural details of sclera, iris and suspensory ligament in the human eye, and the vessels and glomeruli in the human kidney. We also applied SHANEL on transgenic pig organs to map complex structures of EGFP expressing beta cells in >10 cm size pancreas. Overall, SHANEL is a robust and unbiased technology to chart the cellular and molecular architecture of intact large mammalian organs.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=170 SRC=\"FIGDIR/small/643908v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (89K):\norg.highwire.dtl.DTLVardef@14fea50org.highwire.dtl.DTLVardef@1a04274org.highwire.dtl.DTLVardef@6ae1fforg.highwire.dtl.DTLVardef@11b31b0_HPS_FORMAT_FIGEXP M_FIG C_FIG Supplementary Movies of SHANEL are available at http://discotechnologies.org/SHANEL/

cell biology↗