Biology subjects

Kennedy, C.

Publications and source records attributed to Kennedy, C..

11 recordsLinked to original sources

bioRxiv2026

Overlapping flower and pollen production in two imperiled pitcher plants raises conservation challenges

Balancing sexual reproduction with vegetative growth poses challenges for many plants. Additionally, reproductive effort, such as production of pollen or flowers, is not always correlated with numbers of viable and germinable seeds. Energetic tradeoffs like these can be particularly fraught for imperiled species and might be especially complicated in landscapes with a possibility of interspecific hybridization. In this multi-year study, we track the reproductive effort, flowering phenology, and reproductive output of two interfertile Sarracenia (pitcher plants). We show that reproductive effort varies among years and sites, and that production of pollen and flowers does not always result in higher seed output. We demonstrate that phenological overlap in the timing of flower production and pollen viability could enable hybridization, and that the more imperiled taxon produces fewer seeds per flower. Results have implications for conservation of these pitcher plants, management of hybridization in these and other systems, and general principles of reproductive allocation.

ecology↗

bioRxiv2025

TWEAK is increased in ulcerative colitis and contributes to fibroblast-mediated monocyte activation via heterologous non-canonical NF-kB/STAT3 signalling

Background and AimsInteractions between fibroblasts and monocytes have emerged as a contributing factor in IBD pathogenesis and therapy resistance, owing to the ability of both cell types to participate in tissue inflammation and repair. We have previously shown that the TNF superfamily factor TWEAK (TNFSF12) can induce a UC-like inflammatory profile in colonic fibroblasts in vitro, in turn promoting monocyte adhesion and activation. However, the mechanisms underlying fibroblast-monocyte communication and its dysregulation in colitis are incompletely understood. MethodsHere we use co-culture models, human biopsies from ulcerative colitis (UC) patients and healthy donors, and public single-cell transcriptomics to characterise the mechanisms underlying fibroblast-mediated monocyte activation. ResultsWe show that TWEAK-treated inflammatory fibroblasts induce a transcriptional programme that resembles early monocyte/macrophage intermediates in UC and is enriched for genes associated with resistance to anti-TNF (TREM1, OSM, IL1B) and susceptibility to IBD (NOD2, ATG16L1). We find that conditioned media from TWEAK-treated fibroblast causes a sustained activation of STAT3 phosphorylation in monocytes, and that inhibition of the NF-{kappa}B Inducing Kinase (NIK) impairs the ability of inflammatory fibroblasts to activate STAT3 phosphorylation in monocytes, resulting in reduced expression of inflammatory mediators. Using tissues from UC patients, we show that the expansion of CD90+/PDPN+ inflammatory fibroblasts in UC correlates with the accumulation of TWEAK+ myeloid cells in the colonic mucosa, and that these fibroblasts co-localise with infiltrating monocytes in sites of active inflammation. ConclusionTogether, our findings suggest that the TWEAK/NF-{kappa}B/STAT3 axis represents an attractive target to tune inflammatory stroma/monocyte crosstalk.

immunology↗

bioRxiv2025

Proteomic Signatures of Podocyte Injury Are Reflected in Urinary Extracellular Vesicles in Pediatric Nephrotic Syndrome.

Idiopathic nephrotic syndrome (NS) is a common glomerulopathy in children and presents with significant proteinuria. There are no reliable clinical or biochemical markers of disease relapse, or prognosis. Extracellular vesicles (EVs) are small, membrane-bound biological effectors released from stressed cells. We previously showed increases in podocyte-specific urinary EVs from children with disease relapse in NS, with numbers returning to near-zero in remission. Herein, we have expanded this work to evaluate puromycin aminonucleoside (PAN) injury by characterizing proteomic signatures of podocytes and their EVs in vitro. In addition, we performed data-independent proteomic analysis (DIA) to characterize changes in signatures of EVs from pediatric patients with active NS versus remission. Our key findings reveal PAN-injured podocytes increase large EV (LEV) secretion in vitro; moreover, DIA uncovered changes in cellular and LEV proteomes that were also observed in urinary LEVs from patients with active disease. Urinary LEV proteomes from children with active NS were significantly different than those in remission, highlighted by 645 and 240 unique proteins associated with disease or remission, respectively. This foundational work provides the impetus for a larger, prospective biomarker study aimed at identifying EV-specific proteins associated with relapse versus remission.

cell biology↗

bioRxiv2025

Chemical Inhibition of Splicing-Related Protein Kinases Reveals Phosphorylation-Driven Regulation of RNA Alternative Splicing in Arabidopsis Seedlings

Serine / arginine (SR) protein kinases (SRPKs) are capable of transmitting external signals to the spliceosome by phosphorylating SR proteins. In plants, few studies have looked at the regulation of RNA splicing by post-translational modification (PTMs), despite the spliceosome and splicing factor proteins exhibiting extensive phosphorylation. Many of these PTM events have the potential to dramatically change the expression of various genes, such as those involved in abiotic stress. Here, we sought to explore the regulatory function of Arabidopsis thaliana SRPKs in the context of RNA alternative splicing. To do so, we utilized four well-known and well-characterized chemical inhibitors specifically designed to target and inhibit SRPK enzymatic activity. Our data found that SRPK chemical inhibitors SPHINX31 and SRPIN340 induced shorter root development phenotypes and an abolishment of root hair formation. Using a multi-omics approach combining transcriptomics and phosphoproteomics, we find extensive changes in the splicing of genes involved in root development, RNA splicing, cytoskeletal organization, and cell differentiation. We also reveal splicing factors exhibiting differential alternative splicing as well as a down-regulated in their phosphorylation status. Overall, our data indicate that AtSRPKs phosphorylate diverse splicing factors and influence the alternative splicing of genes involved in root development and a wide-range of related pathways.

plant biology↗

bioRxiv2025

Global extent and change in human modification of terrestrial ecosystems from 1990 to 2022

Habitat loss and degradation associated with industrial development is the primary threat and dominant driver of biodiversity loss globally. Spatially-explicit datasets that estimate human pressures are essential to understand the extent and rate of anthropogenic impacts on ecosystems and are critical to inform conservation commitments and efforts under the Global Biodiversity Framework. We leveraged the human modification framework to generate comprehensive, consistent, detailed, robust, temporal, and contemporary datasets to map cumulative and individual threats associated with industrial human activities to terrestrial biodiversity and ecosystems from 1990 to 2022. In [~]2022, 43% of terrestrial lands had very low levels of modification, while 27%, 20%, and 10% had low, moderate, and high modification, respectively. Nearly [2/3] of biomes and [1/2] of ecoregions currently ([~]2022) are moderately-modified, and 24% of terrestrial ecosystems (31 M km2) experienced increased modification from 1990 to 2020. About 29% of countries and 31% of ecoregions might also be particularly vulnerable to biodiversity loss given their above-average increased modification and less than 30% protection.

ecology↗

bioRxiv2024

Shaping Kale Morphology and Physiology Using Different LED Light Recipes

Light serves as a fundamental factor in plant development, both as an energy source and as an environmental cue. With the advent of light-emitting diode (LED) technology, light can be precisely manipulated to influence key plant traits. Here, we assess effects of light intensity and spectral composition on the growth and physiology of Kale (Brassica oleracea). Kale is known for its phenotypic plasticity and nutritional composition, making it a crop well-suited for indoor cultivation either as microgreens or as large leafy plants. Here, we employ a combination of advanced phenotyping, computer vision, gas chromatography-mass spectrometry (GC-MS) metabolomics, and liquid chromatography-mass spectrometry (LC-MS)-based quantitative proteomics to characterize the molecular changes that underpin light-dictated differences in the growth and metabolism of two different commercially grown kale cultivars under different light intensities and spectral compositions. We identify time-of-day and cultivar-specific light intensity and spectral composition-induced changes related to growth, shade avoidance, photosynthesis and several aspects of nutritional composition, including amino acids, glucosinolates and carotenoids. Our results offer a key resource to the plant community and demonstrate the translational potential of light manipulation in tailoring kale growth and nutritional content for enhanced crop productivity and/or health benefits, while simultaneously offering a more cost-effective solution for contemporary agricultural challenges. Significance StatementThe effects of light intensity and spectral composition differentially affect the diel molecular responses of Kale (Brassica oleracea). Our results demonstrate the translational potential of light manipulation in tailoring plant growth and nutritional content for enhanced crop productivity.

plant biology↗

bioRxiv2023

Twilight length alters growth, flowering time, and clock function in Arabidopsis via LHY/CCA1

The plant circadian clock governs growth and development by syncing biological processes to periodic environmental changes. Decades of research has shown how the clock enables plants to respond to two environmental variables that change at different latitudes and over different seasons: photoperiod and temperature. However, a third variable, twilight length, has so far gone unstudied. The duration of twilight changes across the planet, lengthening with latitude and changing across seasons, and yet most circadian experiments are performed in lab environments with no twilight. Here, using controlled growth setups, we show that twilight length impacts plant growth and changes flowering time via the LHY/CCA1 morning module of the Arabidopsis circadian clock. Using a series of progressively truncated no-twilight photoperiods, we also found that plants are more sensitive to twilight length compared to equivalent changes in solely photoperiod. Further, transcriptome and proteome analyses indicated that twilight length alters the regulation of proteins involved in reactive oxygen species metabolism, photosynthesis, and carbon metabolism. Genetic analyses also implicated a twilight sensing pathway from phytochromes D and E, the morning elements of the circadian clock and modulating flowering time through the GI-FT pathway. Overall, our findings call for more nuanced models of daylength perception in plants and posit that twilight length is an important determinant of plant growth, development, and circadian function.

plant biology↗

bioRxiv2020

The Incubot: A 3D Printer-Based Microscope for Long-Term Live Cell Imaging within a Tissue Culture Incubator

Commercial live cell imaging systems represent a large financial burden to research groups, while current open source incubator microscopy systems lack adaptability and are sometimes inadequate for complex imaging experimentation. We present here a low-cost microscope designed for inclusion within a conventional tissue culture incubator. The build is constructed using an entry level 3D printer as the basis for the motion control system, with Raspberry Pi imaging and software integration, allowing for reflected, oblique, and fluorescence imaging of live cell monolayers. The open source nature of the design is aimed to facilitate adaptation by both the community at large and by individual researchers/groups. The development of an adaptable and easy-to-use graphic user interface (GUI) allows for the scientist to be at the core of experimental design. Simple modifications of the base GUI code, or generation of an entirely purpose-built script, will allow microscopists to place their experimental design as the priority, as opposed to designing experiments to fit their current equipment. The build can be constructed for a cost of roughly C1000 and thus serves as a low-cost and adaptable addition to the open source microscopy community. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=176 SRC="FIGDIR/small/121608v2_ufig1.gif" ALT="Figure 1"> View larger version (68K): org.highwire.dtl.DTLVardef@1aa58ceorg.highwire.dtl.DTLVardef@ac4678org.highwire.dtl.DTLVardef@467ae2org.highwire.dtl.DTLVardef@12da951_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2019

Iterative feature selection method to discover predictive variables and interactions for high-dimensional transplant genomic data

After allogeneic hematopoietic stem cell transplantation (allo-HCT), donor-derived immune cells can trigger devastating graft-versus-host disease (GVHD). The clinical effects of GVHD are well established; however, genetic mechanisms that contribute to the condition remain unclear. Candidate gene studies and genome-wide association studies have shown promising results, but they are limited to a few functionally derived genes and those with strong main effects. Transplant-related genomic studies examine two individuals simultaneously as a single case, which adds additional analytical challenges. In this study, we propose a hybrid feature selection algorithm, iterative Relief-based algorithm followed by a random forest (iRBA-RF), to reduce the SNPs from the original donor-recipient paired genotype data and select the most predictive SNP sets in association with the phenotypic outcome in question. The proposed method does not assume any main effect of the SNPs; instead, it takes into account the SNP interactions. We applied the iRBA-RF to a cohort (n=331) of acute myeloid leukemia (AML) patients and their fully 10 of 10 (HLA-A, -B, -C, -DRB1, and -DQB1) HLA-matched healthy unrelated donors and assessed two case-control scenarios: AML patients vs healthy donor as case vs control and acute GVHD group vs non-GVHD group as case vs control, respectively. The results show that iRBA-RF can efficiently reduce the size of SNPs set down to less than 0.05%. Moreover, the literature review showed that the selected SNPs appear functionally involved in the pathologic pathways of the phenotypic diseases in question, which may potentially explain the underlying mechanisms. This proposed method can effectively and efficiently analyze ultra-high dimensional genomic data and could help provide new insights into the development of transplant-related complications from a genomic perspective.

bioinformatics↗

bioRxiv2018

A novel method for comparison of arterial remodeling in hypertension: quantification of arterial trees and recognition of remodeling patterns on histological sections

Remodeling of spatially heterogeneous arterial trees is routinely quantified on tissue sections by averaging linear dimensions, with lack of comparison between different organs and models. The impact of experimental models or hypertension treatment modalities on organ-specific vascular remodeling remains undefined. A wide variety of arterial remodeling types has been demonstrated for hypertensive models, which include differences across organs. The purpose of this study was to reassess methods for measurement of arterial remodeling and to establish a morphometric algorithm for standard and comparable quantification of vascular remodeling in hypertension in different vascular beds. We performed a novel and comprehensive morphometric analysis of terminal arteries in the brain, heart, lung, liver, kidney, spleen, stomach, intestine, skin, skeletal muscle, and adrenal glands of control and Goldblatt hypertensive rats on routinely processed tissue sections. Mean dimensions were highly variable but grouping them into sequential 5 m intervals permitted creation of reliable linear regression equations and complex profiles. Averaged arterial dimensions demonstrated seven remodeling patterns that were distinct from conventional inward-outward and hypertrophic-eutrophic definitions. Numerical modeling predicted at least twenty variants of arterial spatial conformations. Recognition of remodeling variants was not possible using averaged dimensions, their ratios, or the remodeling and growth index. To distinguish remodeling patterns, a three-dimensional modeling was established and tested. The proposed algorithm permits quantitative analysis of arterial remodeling in different organs and may be applicable for comparative studies between animal hypertensive models and in human hypertension. Arterial wall tapering is the most important factor to consider in arterial morphometry, while perfusion fixation with vessel relaxation is not necessary. Terminal arteries in organs undergo the same remodeling pattern in Goldblatt rats, except for organs with hemodynamics affected by the arterial clip. The existing remodeling nomenclature should be replaced by a numerical classification applicable to any type of arterial remodeling.\n\nAuthor summaryArterial hypertension effects modern nations and is characterised by systemic hypertensive angiopathy that affects all organs. Arterial remodeling is a main factor to be analyzed in animal models and human. Despite abundant data, there is a significant lack of comparative analysis on arterial remodeling. The data from the present study have established a novel methodological approach to assess and compare arterial remodeling in hypertension. We have developed an effective algorithm for morphometry of intra-organ arteries to standardize remodeling assessment and allow comparisons between different hypertensive models, organs and species. Our study opens the possibility to assess remodeling using conventional widely used histological tissue sections with no need for special perfusion-fixation. The method will elucidate the improvement and development of animal models of hypertension, and enhance the assessment of experimental therapeutic modalities.

pathology↗

bioRxiv2017

Global and local excitation and inhibition shape the dynamics of the cortico-striatal-thalamo-cortical pathway

The cortico-striatal-thalamo-cortical (CSTC) pathway is a brain circuit that controls movement execution, habit formation and reward. Hyperactivity in the CSTC pathway is involved in obsessive compulsive disorder, a neuropsychiatric disorder characterized by the execution of repetitive involuntary movements. The striatum shapes the activity of the CSTC pathway through the coordinated activation of two classes of medium spiny neurons (MSNs) expressing D1 or D2 dopamine receptors. The exact mechanisms by which balanced excitation/inhibition of these cells controls the network dynamics of the CSTC pathway remain unclear. Here we use non-linear modeling of neuronal activity and bifurcation theory to investigate how global and local changes in excitation/inhibition of MSNs regulate the activity of the CSTC pathway. Our findings indicate that a global and proportionate increase in excitation/inhibition pushes the system to states of generalized hyper-activity throughout the entire CSTC pathway. Certain disproportionate changes in global excitation/inhibition trigger network oscillations. Local changes in the excitation/inhibition of MSNs generate specific oscillatory behaviors in MSNs and in the CSTC pathway. These findings indicate that subtle changes in the relative strength of excitation/inhibition of MSNs can powerfully control the network dynamics of the CSTC pathway in ways that are not easily predicted by its synaptic connections.

neuroscience↗