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Rivera, C.

Publications and source records attributed to Rivera, C..

At least 19 recordsLinked to original sources

Milpa polyculture enhances productivity through crop complementarity and potential carry over effects

Polycultures have long been practiced in traditional agriculture, yet their ecology-based benefits have remained underexplored. Here, under realistic conditions, we experimentally evaluated the productivity and ecological interactions in cultivated milpa, a traditional Mesoamerican polyculture of maize, squash and beans, using a substitutive design in which total plant density was held constant while varying species composition. Specifically, we asked whether productivity gains arose through complementary or selection effects, and whether these gains were associated with changes in arthropod communities and herbivory. We additionally evaluated whether prior cultivation influenced maize performance in the following season. Milpa plots produced significantly higher total yields, more than 2.6 times those of monocultures, despite poor bean performance. In particular, squash and maize equivalent yields increased approximately threefold. We found that these improvements were mainly explained by complementary effects rather than selection effects. Arthropod communities responded in species-specific ways to crop diversity, with predator abundance tracking herbivore presence. However, no consistent patterns emerged between herbivore load, predator abundance and plant damage, suggesting that belowground plant interactions may play a more important role than top-down herbivore control in explaining complementarity effects. In the following season, maize yield increased by [~]30% in plots previously planted with squash or beans, with milpa plots showing intermediate responses. These findings demonstrate that milpa can substantially enhance productivity while generating benefits that extend into the advantages and soil into the following growing season. Overall, our results suggest that complementarity among crops is the primary driver of productivity in milpa under low-input conditions.

ecology↗

Reversible peptide self-assembly enables sustained drug delivery with tuneable pharmacokinetics

Therapeutic peptides combine high target specificity with potent biological activity.1 However, treatment success is often limited by rapid clearance and the need for frequent injections.2, 3 This challenge is particularly acute for therapeutic peptides used in obesity, where clinical benefit must be balanced against dose-dependent adverse effects. In nature, these constraints are overcome by storing hormones as reversible fibrils,4 but pharmacokinetic control is essential for widespread adoption of bio-inspired self-assembled depots for therapeutic peptides. Here, we show that tuneable pharmacokinetics can be achieved and modelled by mapping the fundamental chemical parameters of reversibly self-assembly in vitro. We demonstrate this approach for the amylin analogue pramlintide. Amylin analogues are under development for the next generation of diabetes and obesity treatments, with improved mechanism of action e.g. preserving lean body mass.5-8 Pramlintide is an approved drug with a well-established safety profile, however, it has a comparable half-life to native amylin.8-12 In a pilot study, we achieve in vitro-in vivo correlation, increasing the half-life of pramlintide 20-82-fold in rats, while controlling burst release. These findings demonstrate that the optimisation of pharmacokinetics can be decoupled from peptide engineering, establishing a generalisable framework for generating long-acting peptide formulations by emulating native storage mechanisms.

biophysics↗

Ganglioside GM1-enriched rafts regulate the neuronal chloride co-transporter 1 KCC2.

During brain development, dynamic remodeling of membrane lipid composition accompanies the maturation of inhibitory neurotransmission and the progressive establishment of low intracellular chloride levels. Central to this developmental transition is the neuronal K-Cl- cotransporter KCC2, whose stabilization at the plasma membrane enables the emergence of hyperpolarizing GABAergic signaling. Although KCC2 regulation by protein partners has been extensively characterized, whether lipid remodeling actively contributes to its membrane organization and chloride transport remains unclear. Here we identify the ganglioside GM1, a complex lipid abundant in plasma membrane of neurons, as a developmentally regulated lipid determinant of KCC2 membrane localization and function. We show that KCC2 interacts with GM1 within plasma membrane lipid rafts and that this interaction increases during postnatal brain maturation. Molecular modeling identified a conserved ganglioside-binding domain (GBD) in KCC2 centered on tryptophan 318 (W318). Biophysical analyses revealed a specific and saturable interaction between this domain and GM1 that is abolished by the epilepsy-associated W318S mutation. Disruption of KCC2-GM1 interactions, either by W318S mutation or by pharmacological depletion of GM1, excludes KCC2 from lipid rafts, alters its membrane diffusion and clustering, and reduces its surface stability. Functionally, these perturbations impair KCC2-mediated chloride extrusion and disrupt the somato-dendritic chloride gradient in hippocampal neurons. Consistent with these cellular effects, GM1-deficient (St3gal5-/-) mice exhibit selective reduced hippocampal KCC2 expression. Together, these findings reveal a lipid-protein mechanism that links developmental membrane remodeling to KCC2 stabilization and chloride homeostasis, highlighting membrane lipids as active regulators of transporter maturation and inhibitory circuit development.

neuroscience↗

Early emergence for thermal processing in the neonatal somatosensory cortex and its perturbation in ASD

Thermal perception is essential for neonatal adaptation and survival, yet the cortical processing during early development remains unknown. Here we show that non-painful cool, but not warm, orofacial stimulation evokes robust and lateralized activation in the whisker-related somatosensory cortex (wS1) of neonatal mice during the first postnatal week. These responses, revealed by mesoscopic in vivo imaging and electrophysiological recordings, partly overlap with tactile representations from the same region, indicating early regionalization of thermotactile maps. In a mouse model of autism spectrum disorder deficient for Magel2, we found altered spatial encoding of cool stimuli accompanied by increased local field potential activity, suggestive of cortical hyperexcitability. Our findings establish that the cortical processing of cool sensory information emerges from the first week of life and is disrupted in a genetic model of autism, highlighting early vulnerability of thermosensory circuits and their potential contributions to neurodevelopmental disorders.

neuroscience↗

Ionic modulation of interpenetrating network formation, structure and recovery in low-polymeric, supramolecular hyaluronic acid based-hydrogel

The formation of interpenetrating polymer networks (IPNs) in polysaccharide-based hydrogels is influenced by ion valency and coordination chemistry. In this work, hyaluronic acid (HA) and kappa-carrageenan ({kappa}-CG) were combined at low polymer concentrations suitable for injectable hydrogel applications and enriched with monovalent (K+), divalent (Ca2+), and trivalent (Al3+) ions to investigate ion-specific contributions to network formation, structure and recovery. FTIR spectroscopy showed that K+ did not produce detectable sulfate or carboxylate shifts, consistent with a predominantly physical mixture and the absence of IPN formation. Ca2+ induced concentration-dependent shifts in both the amide/carboxylate region and the sulfate band (1232 [->] 1236 cm-1), absent at a low concentration but reemerging at higher concentrations, consistent with local chain compaction, complexation of HA carboxylates and bridging between{kappa} -CG helices, indicating promotion of a semi-interpenetrated network structure above a thresh-old concentration. Al3+ induced a distinct shoulder in the HA carboxylate region, confirming HA coordination and co-crosslinking with{kappa} -CG, yielding a semi-IPN. Microrheology showed progressively stronger local confinement with increasing ion valency corroborating insights from spectroscopy, while recovery tests showed Ca2+ attained the highest recovery potential possibly due to more robust network formation, Al3+ systems displayed moderate recovery but overscreening at high concentrations resulted in network collapse, and K+ systems displayed poor recovery.Importantly, these ion-specific outcomes must be interpreted in the context of combined electrostatic screening effects, which contribute to charge neutralization and polymer chain association independent of coordination chemistry. Collectively, these findings highlight ion charge as critical design levers which may be leveraged in tailoring mechanical properties of interpenetrating network hydrogels for injectable applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=124 SRC="FIGDIR/small/675661v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@1924ee2org.highwire.dtl.DTLVardef@7916cforg.highwire.dtl.DTLVardef@1c89221org.highwire.dtl.DTLVardef@f1c2c7_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIIncorporation of{kappa} -carrageenan ({kappa}CG) into a chemically unmodified hyaluronic-acid (HA) based hydrogel even at low concentrations is a potentially viable route for more efficient structuring. C_LIO_LIInterpenetrating network formation, structure and recovery of HA-{kappa} CG networks can be tuned by charge density and coordination behavior of the crosslinking ion. C_LIO_LICa2+ reinforces{kappa} CG junction zones, yielding the highest elastic moduli and recovery capacity, with evidence of semi-IPN formation pointing to more robust network formation relative to Al3+ and K+. C_LI

biochemistry↗

Cleavage region organizes the structural architecture of the B2 SINE ribozyme

The SINE-encoded B2 retrotransposon is an RNA Polymerase III transcript that gets upregulated during various cellular stress responses. The B2 noncoding RNA can directly inhibit RNA Polymerase II, leading to a significant downregulation of transcripts during stress. Our recent findings have shown that B2 is a self-cleaving epigenetic ribozyme and that cleavage can be induced by interactions with epigenetic factors, co-regulating its function across distinct chromatin-binding target loci. Here, by integrating RNA chemical probing, small angle X-ray scattering, and 3D motif modeling, we determine structural ensemble-to-function relations for the B2 SINE ribozyme RNA. Perturbations of the RNA suggest that the B2 SINE ribozyme has a well-defined secondary structure and dynamic tertiary structure that both critically depend on the presence of the active site of cleavage. In an RNA engineering approach, we examine the effect of point mutations, deletions of the main cleavage site and deletions of the cleavage domain on the structural ensemble of the RNA. By combining this with functional data, we obtain relations of structural ensembles to various functional states. This perturbative approach serves as a template to unravel the relation of structural ensembles to functional states for other ncRNA and mRNA systems.

biophysics↗

Elevated prevalence of the global panzootic chytrid strain in 1 Ecuadorian anurans of the Amazonian lowlands

Considerable attention has been directed to studying the infection dynamics of the fungal pathogen, Batrachochytrium dendrobatidis (Bd), affecting amphibians in the high elevations of the Neotropics. Lowland forests of the same realm, on the other hand, remain relatively understudied in this context. Herein, an attempt to bridge this gap was made by investigating the occurrence of Bd in several anuran taxa inhabiting the Amazonian lowlands in the northeast of Ecuador. To this end, 207 anurans belonging to 10 different families, 25 different genera, and 55 distinct host species were sampled for Bd DNA in 2008. Data on the taxonomy, morphology (i.e., weight and snout-vent length), and life-long aquatic dependency of hosts (i.e., aquatic index) were also collated to serve as potential predictors of infection prevalence. Genotyping via quantitative PCR revealed the presence of the global panzootic lineage of Bd (Bd-GPL) in the Ecuadorian Amazon. The overall infection prevalence of Bd was determined to be 58%, which is a relatively high prevalence rate of Bd reported for any amphibian population from the lowlands of the Neotropics to date. A total of 88% of sampled anuran families tested positive for the infection at varying proportions. A logistic regression analysis showed a significant negative relationship between host weight and the proportion of Bd infections (p < 0.05). However, no significant associations were observed between host taxonomy, aquatic dependency, or snout-vent length and Bd prevalence. Our findings contribute to the understanding of Bd dynamics in the Neotropical lowlands and emphasize the need for future research on the ecological factors influencing Bd in the Amazon and their implications for amphibian conservation.

evolutionary biology↗

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging

Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic (ATA) compared to distal segments of the aorta and that tissues in both the medial and adventitial compartments of the ATA stiffen during aging. Single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T-lymphocytes accumulate in the adventitia and likely promote fibrosis, while activation of mechanosensitive piezo-1 enhances medial vasoconstriction. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

bioengineering↗

Bumetanide increases microglia-interneuron contact following traumatic brain injury

ObjectiveThe Na-K-Cl cotransporter (NKCC1) inhibitor bumetanide has prominent positive effects on the pathophysiology of many neurological disorders. Here we studied whether bumetanide could influence post-traumatic cognitive decline and inflammatory processes by regulating astrocyte and microglia activation. MethodControlled cortical impacted (CCI) animals were treated with bumetanide during the first post-CCI week. Immunochemistry, flow cytometry, immunoassay, and in vivo imaging were used to study astrocytic and microglial morphology and phenotype as well as adult neurogenesis. Telemetric electroencephalograms and cognitive behavioral test were performed at one-month post CCI. ResultsBumetanide prevented CCI-induced decrease in hippocampal neurogenesis and parvalbumin positive interneuron loss. Deletion of NKCC1 in astrocytes neither rescued interneurons nor promote neurogenesis. Interestingly, bumetanide had a strong effect on microglial activation by inducing polarization towards the M1-like phenotype 3 days post-CCI and the M2-like phenotype 7 days post-CCI. Bumetanide increased microglial Brain-derived neurotrophic factor (BDNF) expression and interaction with parvalbumin interneurons. The early treatment with bumetanide resulted in improvements in working and episodic memory, one-month post-CCI, as well as the normalization of theta band oscillations. InterpretationHere, we disclose a novel mechanism for the neuroprotective action of bumetanide mediated by an acceleration of microglial activation dynamics that leads to an increase of parvalbumin interneuron survival following CCI, possibly resulting from increased microglial BDNF expression and contact with interneurons. Salvage of interneurons may normalize ambient gamma-aminobutyric acid (GABA) resulting in the preservation of adult neurogenesis processes as well as contributing to bumetanide-mediated improvement of cognitive performance.

neuroscience↗

Biophysical and functional characterization of K+-Cl- co-transporters from Drosophila melanogaster and Hydra vulgaris

The cation-chloride co-transporter (CCC) superfamily includes ion symporters, which co-transport monovalent cations and Cl-. CCCs have crucial roles in shaping signalling and neuronal connectivity in the vertebrate brain. K+-Cl- co-transporters (KCCs) are a subfamily of CCCs and carry out the symport of K+ and Cl- ions across the plasma membrane. The KCC proteins are involved in various physiological processes, such as cell volume regulation, transepithelial ion transport, synapse formation and signal transmission, and blood pressure regulation. Among KCCs, KCC2 has gained attention because of its unique and crucial functions in the central nervous system neuronal network. Loss of activity of this transporter has been associated with several neurological disorders including schizophrenia, epilepsy, and chronic pain. On the other hand, only a limited number of studies of KCCs have been published for invertebrates. Among invertebrate proteins, the Drosophila melanogaster KCC (DmKCC) has been studied most and suggested critical for neuronal transmission. Also Cnidarian Hydra vulgaris has been shown to have a functional KCC (HvKCC). Comparative analyses of these transporters with vertebrate ones and understanding functional and biophysical aspects of them as a model system can help understand the KCC mechanism of ion transport and its regulation and evolution broadly. In this study, we chose DmKCC and HvKCC as model systems and purified DmKCC and HvKCC from Sf9 insect cells and characterized their biophysical properties with differential scanning fluorimetry and light scattering techniques. We tested their functionality using a fluorescence assay and developed a method to measure recombinant KCC ion transport activity with flame photometry.

biochemistry↗

Wiring multiple microenvironment proteomes uncovers the biology in head and neck cancer

The poor prognosis of head and neck cancer (HNC) is associated with the presence of metastasis within the lymph nodes (LNs). Herein, the proteome of 140 multisite samples from a 59-HNC patient cohort, including primary and matched LN-negative or -positive tissues, saliva, and blood cells, reveals insights into the biology and potential metastasis biomarkers that may assist in clinical decision making. Protein profiles are strictly associated with immune modulation across datasets, and this provides the basis for investigating immune markers associated with metastasis. The proteome of LN metastatic cells recapitulates the proteome of the primary tumor sites. Conversely, the LN microenvironment proteome highlights the candidate prognostic markers. By integrating prioritized peptide, protein, and transcript levels with machine learning models, we identified a nodal metastasis signature in the blood and saliva. In summary, we present the deepest proteome characterization wiring multiple sampling sites in HNC, thus providing a promising basis for understanding tumoral biology and identifying metastasis-associated signatures.

cancer biology↗

Protomer alignment modulates specificity of RNA substrate recognition by Ire1

The unfolded protein response (UPR) maintains protein folding homeostasis in the endoplasmic reticulum (ER). In metazoan cells, the Ire1 branch of the UPR initiates two functional outputs-- non-conventional mRNA splicing and selective mRNA decay (RIDD). By contrast, Ire1 orthologs from Saccharomyces cerevisiae and Schizosaccharomyces pombe are specialized for only splicing or RIDD, respectively. The functional specialization lies in Ire1s RNase activity, which is either stringently splice-site specific (as in S. cerevisiae) or promiscuous (as in S. pombe). Here, we developed an assay that reports on Ire1s RNase promiscuity. We found that conversion of two amino acids within the RNase domain of S. cerevisiae Ire1 to their S. pombe counterparts rendered it promiscuous. Using biochemical assays and computational modeling, we show that the mutations rewired a pair of salt bridges at Ire1 RNase domains dimer interface, changing its protomer alignment. Thus, Ire1 protomer alignment affects its substrates specificity.

biochemistry↗

Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the unfolded protein response (UPR) in models of neurodegeneration

Alteration to endoplasmic reticulum (ER) proteostasis is observed on a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteostasis and cell function. The UPR is initiated by specialized stress sensors that engage gene expression programs through the concerted action of the transcription factors ATF4, ATF6f, and XBP1s. Although UPR signaling is generally studied as unique linear signaling branches, correlative evidence suggests that ATF6f and XBP1s may physically interact to regulate a subset of UPR-target genes. Here, we designed an ATF6f-XBP1s fusion protein termed UPRplus that behaves as a heterodimer in terms of its selective transcriptional activity. Cell-based studies demonstrated that UPRplus has stronger an effect in reducing the abnormal aggregation of mutant huntingtin and alpha-synuclein when compared to XBP1s or ATF6 alone. We developed a gene transfer approach to deliver UPRplus into the brain using adeno-associated viruses (AAVs) and demonstrated potent neuroprotection in vivo in preclinical models of Parkinsons and Huntingtons disease. These results support the concept where directing UPR-mediated gene expression toward specific adaptive programs may serve as a possible strategy to optimize the beneficial effects of the pathway in different disease conditions.

neuroscience↗

βPix sequesters IDOL and prevents LDL receptor degradation through a β2AR-regulated signaling pathway in Alport Syndrome

Alport syndrome (AS) is a rare disease of the glomerular basement membrane type IV collagen causing progressive renal failure. We reported increased accumulation of low-density lipoprotein (LDL) receptor (LDLR) and subsequent LDL cholesterol (LDL-C) uptake in renal tubular epithelial cells (TEC) in Alport mice, but the mechanisms regulating LDLR stability and function remain unknown. Here, we show that a selective {beta}2-Adrenoceptor ({beta}2AR) agonist, salbutamol, decreased LDLR levels and LDL-C uptake in Alport kidneys accompanied with reduced albuminuria and improved cardiac systolic and diastolic function. Similarly, salbutamol decreased LDL-C uptake in HK2 and HEK293 human renal epithelial cell lines, in smooth muscle cells from an X-linked hereditary nephropathy dog model (a large animal model of AS), and in TECs differentiated from AS patient-derived iPSCs. We show that the Rac1/Cdc42 guanine nucleotide exchange factor {beta}1Pix blocked {beta}2AR-induced LDLR degradation and, hence, increased LDL-C uptake. {beta}1Pix also abrogated ubiquitination and degradation of LDLR induced by the inducible degrader of the LDLR (IDOL), an E3 ubiquitin ligase that promotes lysosomal LDLR ubiquitination and degradation. We identify a multimolecular complex comprised of {beta}Pix, IDOL, and LDLR and demonstrate that {beta}Pix counteracts {beta}2AR-mediated LDLR degradation by sequestering IDOL. Our findings show {beta}Pix acts as a significant post-transcriptional regulator of IDOL-mediated LDLR degradation and identify {beta}2AR activation as a potential treatment for Alport pathology.

molecular biology↗

Patient iPSC-astrocytes show transcriptional and functional dysregulation in schizophrenia

Human astrocytes are multifunctional brain cells and may contribute to the pathophysiology of schizophrenia (SCZ). We differentiated astrocytes from induced pluripotent stem cells of monozygotic twins discordant for SCZ, and found sex-specific gene expression and signaling pathway alterations related particularly to inflammation and synaptic functions. While Ingenuity Pathway Analysis identified SCZ disease and synaptic transmission pathway changes in SCZ astrocytes, the most consistent findings were related to collagen and cell adhesion associated pathways. Neuronal responses to glutamate and GABA differed between astrocytes from control persons, affected twins, and their unaffected co-twins, and were normalized by clozapine treatment. SCZ astrocyte cell transplantation to the mouse forebrain caused gene expression changes in demyelination, synaptic dysfunction and inflammation pathways of mouse brain cells and resulted in behavioral changes in cognitive and olfactory functions. Altogether, our results show that astrocytes contribute to both familial risk and clinical manifestation of SCZ in a sex-specific manner.

neuroscience↗

A framework for studying behavioral evolution by reconstructing ancestral repertoires

Although extensive behavioral changes often exist between closely related animal species, our understanding of the genetic basis underlying the evolution of behavior has remained limited. Here, we propose a new framework to study behavioral evolution by computational estimation of ancestral behavioral repertoires. We measured the behaviors of individuals from six species of fruit flies using unsupervised techniques and identified suites of stereotyped movements exhibited by each species. We then fit a Generalized Linear Mixed Model to estimate the suites of behaviors exhibited by ancestral species, as well as the intra- and inter-species behavioral covariances. We found that much of intraspecific behavioral variation is explained by differences between individuals in the status of their behavioral hidden states, what might be called their "mood." Lastly, we propose a method to identify groups of behaviors that appear to have evolved together, illustrating how sets of behaviors, rather than individual behaviors, likely evolved. Our approach provides a new framework for identifying co-evolving behaviors and may provide new opportunities to study the genetic basis of behavioral evolution.

animal behavior and cognition↗

TrkB activation in Parvalbumin interneurons orchestrates cortical plasticity

Activation state of Parvalbumin (PV) interneurons regulates neuronal plasticity, driving the closure of developmental critical periods and alternating between high and low plasticity states in response to experience in adulthood. We now show that PV plasticity states are regulated through the activation of TrkB neurotrophin receptors. Activation of an optically activatable TrkB (optoTrkB) specifically in PV interneurons switches adult cortical networks into a state of elevated plasticity within minutes by decreasing excitability of PV neurons. OptoTrkB activation induces changes in gene expression related to neuronal plasticity and excitability, and increases the phosphorylation of Kv3.1 channels. OptoTrkB activation shifted cortical networks towards a low PV configuration, promoting oscillatory synchrony and ocular dominance plasticity. Visual plasticity induced by fluoxetine was lost in mice lacking TrkB in PV neurons. Our data suggest a novel mechanism that dynamically regulates PV interneurons configuration state and orchestrates cortical networks during adulthood. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/063503v2_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@4c521corg.highwire.dtl.DTLVardef@a2ec04org.highwire.dtl.DTLVardef@353775org.highwire.dtl.DTLVardef@1cc0448_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Toward A Reproducible, Scalable Framework for Processing Large Neuroimaging Datasets

Emerging neuroimaging datasets (collected through modalities such as Electron Microscopy, Calcium Imaging, or X-ray Microtomography) describe the location and properties of neurons and their connections at unprecedented scale, promising new ways of understanding the brain. These modern imaging techniques used to interrogate the brain can quickly accumulate gigabytes to petabytes of structural brain imaging data. Unfortunately, many neuroscience laboratories lack the computational expertise or resources to work with datasets of this size: computer vision tools are often not portable or scalable, and there is considerable difficulty in reproducing results or extending methods. We developed an ecosystem of neuroimaging data analysis pipelines that utilize open source algorithms to create standardized modules and end-to-end optimized approaches. As exemplars we apply our tools to estimate synapse-level connectomes from electron microscopy data and cell distributions from X-ray microtomography data. To facilitate scientific discovery, we propose a generalized processing framework, that connects and extends existing open-source projects to provide large-scale data storage, reproducible algorithms, and workflow execution engines. Our accessible methods and pipelines demonstrate that approaches across multiple neuroimaging experiments can be standardized and applied to diverse datasets. The techniques developed are demonstrated on neuroimaging datasets, but may be applied to similar problems in other domains.

neuroscience↗