Biology subjects

Dwivedi, A.

Publications and source records attributed to Dwivedi, A..

At least 19 recordsLinked to original sources

bioRxiv2026

The Landscape of Stop Codon-Free Regions in Primates: A Reservoir of Proto-Genes

Gene duplication has long been viewed as the primary source of new genes, yet growing evidence suggests that de novo emergence from non-coding DNA may be more common than previously assumed, requiring unbiased genome-wide strategies to identify its structural precursors. New protein-coding genes can arise from non-coding DNA, but the sequence features enabling this transition remain unclear. Here, we systematically identify and characterise stop-codon-free regions (SCFRs) across telomere-to-telomere assemblies of human and six other primates. Short SCFRs are abundant and widely distributed, whereas long SCFRs are rare and increasingly associated with coding overlap, moderate GC enrichment, and structured exon-intron contexts. We define exon shadows as in-frame SCFR extensions beyond annotated exon boundaries that lack stop codons, revealing latent coding-compatible sequence adjacent to established exons. We also detect introns fully spanned by single SCFRs, consistent with exitron-like architectures. Repeat composition, codon usage, and Fourier spectral analyses show that length filtering enriches for gene-like features and identifies a subset of long SCFRs with codon-scale periodicity. Together, these findings provide a framework for identifying extended ORF-like regions that may serve as substrates for de novo gene emergence in primates.

genomics↗

bioRxiv2026

Ancient human genomes from Ladakh reveal Tibetan, South Asian, and Central Asian admixture over the last three millennia

The trans-Himalayan region of Ladakh occupies a strategic position at the crossroads of South Asia, the Tibetan Plateau, and Central Asia, with archaeological evidence pointing to long-term cultural exchanges across these regions. However, the human genetic history of Ladakh remains largely unexplored. We generated paleogenomic data from seven individuals recovered from two sites in Western Ladakh - the Old Lady Spider Cave and Hanu - of which six are dated to 531-585 CE and one to the 19th century CE. The older individuals share substantial genetic ancestry with Tibetan groups but also harbor major contributions from two additional sources: one corresponding to the currently-oldest observation of the Ancestral North Indian genetic component that characterizes several present-day populations in North India and Pakistan, and another related to ancient Central Asian groups, with admixture events occurring between [~]2,100-2,500 years ago. In contrast, the later individual falls within a previously described ancient northern Himalayan genetic cline based on [~]1,100-1,300-year-old individuals from Himachal Pradesh, with ancestries related to ancient Tibetan and Steppe-related sources. Stable isotope analysis suggests that these individuals were local to Ladakh in late life and practiced an agro-pastoralist subsistence. Our study establishes that Ladakhs central role in Eurasian economic and socio-cultural networks was shaped by dynamic and sustained gene flow linking high-altitude Himalayan groups with both lowland South Asia and Inner Asia.

genetics↗

bioRxiv2026

Distinct trajectories of urbanization shape the human gut microbiome across South Asia

Human gut microbiomes respond to lifestyle transitions, yet the extent to which these responses are conserved across spatio-cultural contexts remains undercharacterized. We present the South Asian MicroBiome ARray (SAMBAR), a population-scale 16S gut microbiome study of 575 adults from ten geographically and socio-culturally diverse South Asian communities. Each community was sampled in ancestral villages and urban centers, enabling controlled comparisons of geography and lifestyle. Relative to global cohorts, SAMBAR microbiomes occupy a distinct compositional space with stronger correlation to geography and community membership than lifestyle. Although urbanization is consistently associated with increased abundance of disease-linked taxa, microbiome responses to lifestyle transitions are largely community-driven, including the acquisition of wheat- and dairying-associated microbial modules in some communities that may facilitate non-genetic adaptation to lactase non-persistence. Microbiome responses to urbanization are heterogeneous even at regional scales, reflecting local culture and geography and underscoring the need for community-specific investigations of health impacts.

microbiology↗

bioRxiv2025

A cytokinin-auxin antagonistic module regulates nitrogen-triggered tiller outgrowth in rice

Tillering is a key trait that shapes aboveground architecture and directly contributes to rice yield. However, integration of environmental cues to genetic regulators for controlling tiller outgrowth remains poorly understood. We investigated the effects of nitrogen, one of the critical environmental factors, on the early stages of tiller bud outgrowth. Comprehensive temporal transcriptomic analyses in response to two nitrogen forms, nitrate (NO -) and ammonium (NH +), identified gene-regulatory networks for nitrogen-triggered tiller outgrowth, with phytohormone signaling as the central interface. Pharmacological, molecular, and genetic experiments established cytokinin-auxin antagonism as a central regulator of the nitrogen-mediated tillering. Cytokinin promoted bud outgrowth by repressing the TCP transcription factor OsTB1, the key inhibitor of tillering, via Cytokinin Response Factors OsERF53/54. OsERF53/54 further reduced polar auxin transport by repressing OsPIN1a to promote bud activation. Conversely, auxin promoted bud dormancy by inducing OsTB1 and OsPIN1a via OsARF11/16. Both NO - and NH + triggered tiller outgrowth and induced largely overlapping transcriptional responses, with a temporal delay for NO -. Adequate nitrogen supplies induced cytokinin signaling while inhibiting auxin signaling and transport in tiller buds, thereby triggering bud outgrowth. Together, we identify a key regulatory role of auxin-cytokinin antagonistic module for integrating nitrogen signals to determine tiller bud fate.

plant biology↗

bioRxiv2025

Transcriptomic profiles from stereo-EEGs reveal the local cell microenvironment in human epilepsy

Objectives: Our understanding of the pathomechanisms of epilepsy has improved through techniques that access the living human brain. We recently reported that explanted stereo-electroencephalography (SEEG) electrodes from patients with epilepsy carry residual biomolecules and cells which may be utilised for transcriptome and DNA methylation profiling. Methods: Here, we applied bioinformatic and other analyses to explore the transcriptomes (RNA sequencing-based) of those SEEG cases to better understand the types of recovered transcripts in terms of representation of genes expressed by different cell types, brain structures, and the extent to which the signal may reflect local epileptiform activity. Results: Electrodes from all clinical cases retained protein-coding transcripts which reflected the local molecular microenvironment as well as epileptiform activity. Expression of genes involved in housekeeping functions as well as markers of neuronal activity were consistent between patients and between the electrode locations within the brain. We detected transcripts representing various cell types and subtypes including excitatory and inhibitory neurons, all major classes of glia, and endothelial cells, as well as transcripts enriched in specific brain regions. Several genes showed a gradient of expression depending on the electrode position within the brain. We found examples of gene expression that correlated with epileptiform activity as recorded by SEEG. Interpretation: These findings extend the evidence that SEEG electrodes reflect the molecular microenvironments of brain activity in patients with epilepsy, both at sites of seizure onset and within the wider seizure network. The approach has potential applications in intraoperative surgical decision-making as well as to identify molecular biomarkers or therapeutic targets for the drug-resistant epilepsies.

neuroscience↗

bioRxiv2025

PIF4-mediated regulation of H2O2 homeostasis controls Arabidopsis seedling thermomorphogenesis

Thermomorphogenesis under high ambient temperature involves extensive developmental changes, including hypocotyl elongation at the seedling stage, in Arabidopsis. Reactive Oxygen Species (ROS), particularly hydrogen peroxide (H2O2), are important signaling molecules, playing crucial roles in plant development and stress responses. While ROS-homeostasis is shown to be crucial for maintaining cellular functions and mediating various developmental responses, the involvement of ROS-homeostasis in the regulation of thermomorphogenic responses and the underlying genetic basis remains poorly understood. In this study, comprehensive transcriptomic analyses revealed strong induction of ROS homeostasis and signaling genes in Arabidopsis seedlings under high ambient temperature. Pharmacological and genetic experiments showed that maintaining H2O2 homeostasis is crucial for seedling thermomorphogenesis. We identified PHYTOCHROME INTERACTING FACTOR 4 (PIF4) as a key regulator of H2O2 homeostasis via direct transcriptional activation of CAT2 and CAT3 genes, which are involved in the regulation of H2O2 levels, to modulate hypocotyl elongation under high temperature. Genetic and biochemical experiments confirmed that CATs act downstream to PIF4 in the same signaling pathway to regulate high-temperature-responsive hypocotyl elongation. Interestingly, elevated H2O2 levels reduced PIF4 protein abundance under high temperature. Together, our findings establish a PIF4-CAT-H2O2 regulatory module, functioning alongside the canonical PIF4-Auxin module, that integrates to auxin signaling to fine-tune hypocotyl elongation under high temperature by maintaining H2O2 homeostasis. HighlightsO_LIHigh ambient temperature significantly affects ROS homeostasis and signaling genes in Arabidopsis seedlings. C_LIO_LIH2O2 homeostasis is crucial for high-temperature-mediated hypocotyl elongation, a signature feature of Arabidopsis thermomorphogenesis. C_LIO_LIPHYTOCHROME INTERACTING FACTOR 4 (PIF4) regulates the expression of CATALASE genes in a temperature-dependent manner to maintain H2O2 levels for seedling thermomorphogenesis. C_LIO_LIElevated H2O2 level reduces PIF4 protein abundance, thus forming a PIF4-CAT-H2O2 regulatory module that integrates with auxin to fine-tune hypocotyl elongation under high temperature. C_LI

plant biology↗

bioRxiv2025

Integrative comparative transcriptomics using cultivated and wild rice reveals key regulators of developmental and photosynthetic progression along the rice leaf developmental gradient

A comprehensive understanding of gene regulatory networks and the key regulators underlying developmental and physiological progression along the leaf developmental gradient is crucial for optimizing photosynthetic competence. Comparisons of developmental and photosynthetic features across successive leaf developmental stages revealed pronounced differences between wild rice (Oryza australiensis) and three cultivated rice accessions. Global gene expression profiling identified three major transcriptional phases across leaf stages: a predominance of developmental genes at SAM+Pi (initiating primordia) and P3; genes for photosynthetic transition at P3 and P4; and enriched core photosynthetic genes at P4 and P5. O. australiensis showed a more prominent expression of developmental and photosynthetic genes than cultivated accessions across leaf stages. Multivariate analysis further supported a distinct transcriptional landscape in O. australiensis compared with cultivated accessions. Integration of gene expression with species-specific variations in regulatory sequences, derived from synteny-anchored orthology analysis, generated stage-resolved gene regulatory networks and identified key transcription factors (TFs) mediating the developmental and physiological progression. A cross-species comparison of TF-target regulatory networks revealed extensive stage- and accession-dependent rewiring of the regulatory networks of key TFs, with strong regulatory divergence in O. australiensis. Gene silencing of two candidate TFs, OsDOF8 and OsARID2, altered the rice photosynthetic competence with accession-specific effects. Taken together, the study highlights promoter-driven regulatory divergence as a potential mechanism underlying developmental and photosynthetic differences among the rice accessions. The resource is available through an interactive public database, Rice DEV-LEAF (https://nipgr.ac.in/DEV-LEAF/), enabling exploration of gene expression dynamics and regulatory networks across the rice leaf developmental gradient.

plant biology↗

bioRxiv2025

The 1000+ mouse project: large-scale spatiotemporal parametrization and modeling of preclinical cancer immunotherapies

Preclinical studies of chimeric antigen receptor (CAR)-T cell immunotherapies are often based on monitoring bioluminescent tumors implanted in mice to assess anti-tumor cytotoxicity. Here, we introduce maRQup (murine automatic Radiance Quantification and parametrization), an easy-to-use method that automatically processes bioluminescent tumor images for quantitative analysis. We demonstrate the ability of maRQup to analyze CAR-T cell treatments over >1,000 tumor-bearing mice. We compare CD19-targeting CAR-T cells comprising either a CD28 or a 4-1BB costimulatory domain, and found the former controlled the tumor burden better initially, while the latter reduced the frequency of tumor relapse. We also applied maRQup to demonstrate faster tumor growth during the initial growth phase as compared to the relapse phase and to spatiotemporally analyze the high variability in immunotherapeutic control of tumors, based on their anatomical location. maRQup provides quantitative and statistically-robust insights on preclinical experiments that will contribute to the optimization of immunotherapies.

immunology↗

bioRxiv2025

LCLNCRdb: A Comprehensive Resource for Investigating long non-coding RNAs in Lung Cancer

Lung cancer is a primary cause of death worldwide, accounting for a substantial number of mortalities. It involves several molecular mechanisms that are influenced by long non-coding RNAs (lncRNAs), a specific types of RNA molecules that do not code for proteins. Several research have revealed the importance of long non-coding RNAs (lncRNAs) in the initiation, progression, and development of resistance to lung cancer therapy. However, there are no centralized web resources or databases that collect and integrate information regarding lung cancer associated lncRNAs. This led to the development of the LCLNCRdb, a manually curated database that includes data from various sources, such as published research articles, and The Cancer Genome Atlas (TCGA) data portal. This database contains detailed information on 1102 lncRNAs that have differential expression patterns in lung cancer patients, such as lncRNA name, entrez ID, Ensemble ID, HGNC ID, NONCODE ID, lung cancer type, source, lncRNA expression pattern, experimental techniques, network analysis, and survival analysis details. The database offers a user-friendly platform for browsing, retrieving, and downloading data, and it features a dedicated submission page for researchers to share newly identified lncRNAs related to lung cancer. LCLNCRdb aims to enhance our knowledge of lncRNA deregulation in lung cancer and provides a valuable and timely resource for lncRNA research. The database is freely accessible at (https://dbtcmi.in/tools/lclncrdb/main.html).

bioinformatics↗

bioRxiv2024

Regular Plasmodium falciparum importation onto Bioko Island, Equatorial Guinea, hampers malaria elimination from the island

The Bioko Island Malaria Elimination Project (BIMEP) has made significant progress in reducing the prevalence of Plasmodium falciparum on Bioko Island, Equatorial Guinea. However, like other malaria endemic islands like Sao Tome and Principe and Zanzibar, Tanzania, elimination efforts are hampered by imported infections. In an effort to understand the local transmission dynamics and the influence of importation on Bioko Islands P. falciparum population, whole-genome sequences were generated from field samples collected during the BIMEPs 2019 Malaria Indicator Survey (MIS). Within the sub-Saharan African context, we observed Bioko Island parasites did not significantly differentiate from nearby continental neighbors. Among Bioko infections, within-host diversity and the quantity of polyclonal infections appear similar to an area of moderate malaria transmission. However, we observed higher than expected genetic diversity among Bioko parasites, similar to high transmission areas, suggesting imported strains are contributing to transmission on the island. Among Biokos closest geographical neighbors, the flow of parasites with Bioko appeared more pronounced with the Gabonese parasite population, implying more importation may be coming from this region than others. Overall, despite significant investment in malaria control, results illustrate the challenges of eliminating malaria without both interrupting local transmission and accounting for importation from higher transmission areas, likely due to human migration. For there to be sustained progress towards elimination, the BIMEP needs, if feasible, to conduct targeted interventions of outgoing/incoming travelers, and ideally expand malaria control interventions to the continental region of Equatorial Guinea. ImportancePlasmodium falciparum accounts for the majority of malaria deaths globally, with over 500,000 estimated deaths in 2023, predominantly in sub-Saharan Africa, despite strong investment in control and elimination interventions. Incorporating sequencing technologies into malaria surveillance is viewed as a powerful tool to improve control strategies, including identifying parasite transmission pathways. Here, we provide the first genomic characterization of P. falciparum on Bioko Island and Equatorial Guinea since malaria control began in 2004, and use these data to better understand the contribution of neighboring regions to Biokos P. falciparum population. Results highlight the need to account for offisland contributors to transmission and to understand how unmitigated transmission in neighboring regions can hamper progress. This study furthers our understanding of how the flow of parasites between regions impacts infectious disease control and provides foundational genomic data in a previously undescribed region that can be used to inform malaria elimination efforts.

genomics↗

bioRxiv2024

Prioritization of Lung Cancer Candidate Genes using Moment of Inertia Tensor Analysis

A variety of factors contribute to the complexity of lung cancer progression. To comprehend the disease, candidate genes must be investigated. Present study aimed to employ an alignment-free method to prioritize candidate genes based on the physicochemical properties of the amino acids. It uses the moment of inertia tensor that measures the mass distribution around an axis of rotation, to compute the rotational energy and angular momentum of amino acids in protein sequences. The computed features were compared to those of established lung cancer genes, leading to the identification of 26 candidate genes with a high degree of similarity. These genes participate in critical biological processes that regulate the mitotic cell cycle and cell development. The prognostic significance of these genes was also assessed and four genes (IL1A, CDC25C, IL4R, and TGFBR1) were found to be associated with poor survival. Additionally, the role of prioritized genes and potential drugs that target these genes in other cancer types was also examined. Our method will help to discover new biomarkers and intervention strategies for lung cancer.

bioinformatics↗

bioRxiv2024

High-Resolution Multimodal Profiling of Human Epileptic Brain Activity via Explanted Depth Electrodes

Understanding neurological disorders necessitates systems-level approaches that integrate multimodal data, but progress has been hindered by limited sample availability, and the absence of combined electrophysiological and molecular data from live patients. Here, we demonstrate that intracranial stereoelectroencephalography (SEEG) electrodes used for identifying the seizure focus in epilepsy patients enable the integration of RNA sequencing, genomic variants and epigenome maps with in vivo recordings and brain imaging. Specifically, we report a method, MoPEDE (Multimodal Profiling of Epileptic Brain Activity via Explanted Depth Electrodes) that recovers extensive protein-coding transcripts, DNA methylation and mutation profiles from explanted SEEG electrodes matched with electrophysiological and radiological data allowing for high-resolution reconstructions of brain structure and function in human patients. Our study shows that epilepsies of different aetiologies have distinct molecular landscapes and identify transcripts correlating with neurophysiological signals, including immediate early genes, inflammation markers, and axon guidance molecules. Additionally, we identify DNA methylation profiles indicative of transcriptionally permissive or restrictive chromatin states. While gene expression gradients corresponded with the assigned epileptogenicity index, we found outlier molecular fingerprints in some electrodes, potentially indicating seizure generation or propagation zones not detected during electroclinical assessments. These findings validate that RNA profiles, genetic variation and genome-wide epigenetic data from explanted SEEG electrodes offer high-resolution surrogate molecular landscapes of brain activity. Our transformative MoPEDE approach has the potential to enhance diagnostic decisions and deepen our understanding of epileptogenic network processes in the human brain.

genomics↗

bioRxiv2024

The genetic landscape, gene flow and adaptation in Ladakh highlanders of trans-Himalayas

Trans-Himalayan Ladakh has witnessed complex cultural movements and demographic changes since the Neolithic period, which is still continue despite the harsh, inhospitable and cold climate. Although geographically isolated from mainland South Asia, Ladakh has historic trade routes and is well connected and accessible to travelers from Tibet and Central Asia. Despite its rich cultural heritage, a detailed description of the genetic landscape of the Ladakh region is completely lacking, particularly with regard to genome-wide analysis and larger sample sizes. Therefore, in the current study, we genotyped 80 individuals from Kargil and Leh districts of the Union Territory of Ladakh, India. Here, we performed a comprehensive genetic analysis based on allele frequency and haplotype sharing. Our analysis revealed the presence of two distinct genetic lineages in the region with quite distinct genetic composition. The population of Leh Region is more similar to East Asian and Southeast Asian populations. In contrast, the population of the Kargil Region (LDKLA) is more similar to Indo-European populations. Demographic modeling suggests that the Leh group shares a genetic history with Tibetans, while the Kargil group showed great affinities with Kashmiri Muslims, Gujjars and Nepalese Brahmins, and both showed recent admixture. Both groups have experienced a founder event around during 11th to 22nd generations ago, the duration of which coincided with the Mughal invasion. The genome-wide scan for a signal of positive selection revealed genetic signatures of high-altitude adaptation (EPAS1 and ELMO2) in the Leh population, while in the Kargil population the key gene signatures were associated with immunity and female fertility.

genetics↗

bioRxiv2023

Intranasal CRMP2-Ubc9 Inhibitor Regulates NaV1.7 to Alleviate Trigeminal Neuropathic Pain

Dysregulation of voltage-gated sodium NaV1.7 channels in sensory neurons contributes to chronic pain conditions, including trigeminal neuropathic pain. We previously reported that chronic pain results in part from increased SUMOylation of collapsin response mediator protein 2 (CRMP2), leading to an increased CRMP2/NaV1.7 interaction and increased functional activity of NaV1.7. Targeting this feed-forward regulation, we developed compound 194, which inhibits CRMP2 SUMOylation mediated by the SUMO-conjugating enzyme Ubc9. We further demonstrated that 194 effectively reduces the functional activity of NaV1.7 channels in dorsal root ganglia neurons and alleviated inflammatory and neuropathic pain. Here, we employed a comprehensive array of investigative approaches, encompassing biochemical, pharmacological, genetic, electrophysiological, and behavioral analyses, to assess the functional implications of NaV1.7 regulation by CRMP2 in trigeminal ganglia (TG) neurons. We confirmed the expression of Scn9a, Dpysl2, and UBE2I within TG neurons. Furthermore, we found an interaction between CRMP2 and NaV1.7, with CRMP2 being SUMOylated in these sensory ganglia. Disrupting CRMP2 SUMOylation with compound 194 uncoupled the CRMP2/NaV1.7 interaction, impeded NaV1.7 diffusion on the plasma membrane, and subsequently diminished NaV1.7 activity. Compound 194 also led to a reduction in TG neuron excitability. Finally, when intranasally administered to rats with chronic constriction injury of the infraorbital nerve (CCI-ION), 194 significantly decreased nociceptive behaviors. Collectively, our findings underscore the critical role of CRMP2 in regulating NaV1.7 within TG neurons, emphasizing the importance of this indirect modulation in trigeminal neuropathic pain.

neuroscience↗

bioRxiv2023

Parallelized Acquisition of Orbitrap and Astral Analyzers Enables High-Throughput Quantitative Analysis.

The growing trend towards high-throughput proteomics demands rapid liquid chromatography-mass spectrometry (LC-MS) cycles that limit the available time to gather the large numbers of MS/MS fragmentation spectra required for identification. Orbitrap analyzers scale performance with acquisition time, and necessarily sacrifice sensitivity and resolving power to deliver higher acquisition rates. We developed a new mass spectrometer that combines a mass resolving quadrupole, the Orbitrap and the novel Asymmetric Track Lossless (Astral) analyzer. The new hybrid instrument enables faster acquisition of high-resolution accurate mass (HRAM) MS/MS spectra compared to state-of-the-art mass spectrometers. Accordingly, new proteomics methods were developed that leverage the strengths of each HRAM analyzer, whereby the Orbitrap analyzer performs full scans with high dynamic range and resolution, synchronized with Astral analyzers acquisition of fast and sensitive HRAM MS/MS scans. Substantial improvements are demonstrated over previous methods using current state-of-the-art mass spectrometers. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=100 SRC="FIGDIR/small/543408v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1eedfdeorg.highwire.dtl.DTLVardef@1ab7939org.highwire.dtl.DTLVardef@a3b2f8org.highwire.dtl.DTLVardef@13ac46b_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2022

Transcriptome analysis reveals robust transcriptional reprogramming during early stages of Cicer-Ascochyta interaction

Ascochyta blight (AB) caused by a filamentous fungus Ascochyta rabiei is a major threat to global chickpea production. The mechanisms underlying chickpea response to A. rabiei remain elusive. Here, we investigated the comparative transcriptional dynamics of AB-resistant and susceptible chickpea genotypes upon A. rabiei infection to understand the early host defence response. Our findings revealed that AB-resistant plants underwent rapid and extensive transcriptional reprogramming compared to susceptible host. At early stage (24-hpi), mainly cell wall remodeling and secondary metabolite pathways were highly activated, while DEGs related with signaling components viz. protein kinases, transcription factors, and hormonal pathways show remarkable upsurge at 72-hpi, especially in resistant genotype. Notably, our data suggests imperative role of JA, ET, and ABA signaling in providing immunity against A. rabiei. Furthermore, gene co-expression networks and modules corroborated the importance of cell wall remodeling, signal transduction and phytohormone pathways. The hub genes such as MYB14, PRE6 and MADS-SOC1 discovered in these modules might be the master regulators governing chickpea immunity. Overall, we not only provide novel insights for comprehensive understanding of immune signaling components mediating AB resistance/susceptibility at early Cicer-Ascochyta interactions, but also offer a valuable resource for developing AB-resistant chickpea. HighlightsComparative transcriptomic and co-expression analysis of AB-resistant and susceptible chickpea genotypes reveals high-amplitude transcriptional dynamics in resistant plants, and also identifies TFs, PKs and phytohormone-crosstalk as core regulators for AB-resistance.

plant biology↗

bioRxiv2022

High temperature limits leaf size via direct control of cell cycle by coordinated functions of PIF4 and TCP4

High ambient temperature suppresses Arabidopsis rosette leaf area, in contrast to elongation of stem and petiole. While the mechanism underlying temperature-induced elongation response is extensively studied, the genetic basis of temperature-regulation of leaf size is largely unknown. Here we show that warm temperature inhibits cell proliferation in the Arabidopsis leaves resulting in fewer cells compared to the control condition. Cellular phenotyping, genetic, and biochemical analyses established the key roles of PIF4 and TCP4 transcription factors in the suppression of Arabidopsis leaf area under high temperature by a reduction in cell number. We show that temperature-mediated suppression of cell proliferation requires PHYTOCHROME INTERACTING FACTOR 4 (PIF4). PIF4 interacts with TEOSINTE BRANCHED1/CYCLOIDEA/PCF4 (TCP4) and regulates the expression of cell cycle inhibitor, KIP-RELATED PROTEIN 1 (KRP1), to control the leaf size under high temperature. Warm temperature induces binding of both PIF4 and TCP4 to the KRP1 promoter. PIF4 binding to KRP1 under high temperature is TCP4 dependent as TCP4 regulates PIF4 levels under high temperature. We propose a model where a warm temperature-mediated accumulation of PIF4 in the leaf cells promotes its binding to the KRP1 promoter in a TCP4-dependent way to regulate cell production and leaf size. Our finding of high temperature-mediated transcriptional upregulation of KRP1 integrates a developmental signal with an environmental signal that converges on a basal cell regulatory process. One sentence summaryHigh ambient temperature suppresses Arabidopsis leaf area by reducing cell proliferation via PIF4- and TCP4-dependent transcription control of KRP1.

plant biology↗

bioRxiv2020

Blood clot fracture properties are dependent on red blood cell and fibrin content

Thrombus fragmentation during endovascular stroke treatment, such as mechanical thrombectomy, leads to downstream emboli, resulting in poor clinical outcomes. Clinical studies suggest that fragmentation risk is dependent on clot composition. This current study presents the first experimental characterization of the fracture properties of blood clots, in addition to the development of a predictive model for blood clot fragmentation. A bespoke experimental test-rig and compact tension specimen fabrication has been developed to measure fracture toughness of thrombus material. Fracture tests are performed on three physiologically relevant clot compositions: a high fibrin 5% H clot, a medium fibrin 20% H clot, a low-fibrin 40% H clot. Fracture toughness is observed to significantly increase with increasing fibrin content, i.e. red blood cell-rich clots are more prone to tear during loading compared to the fibrin-rich clots. Results also reveal that the mechanical behaviour of clot analogues is significantly different in compression and tension. Finite element cohesive zone modelling of clot fracture experiments show that fibrin fibres become highly aligned in the direction perpendicular to crack propagation, providing a significant toughening mechanism. The results presented in this study provide the first characterization of the fracture behaviour of blood clots and are of key importance for development of next-generation thrombectomy devices and clinical strategies.

bioengineering↗