Biology subjects

Singh, A.

Publications and source records attributed to Singh, A..

At least 307 records · Page 17Linked to original sources

bioRxiv2024

Chemoproteomic profiling of substrate specificity in gut microbiota-associated bile salt hydrolases

The gut microbiome possesses numerous biochemical enzymes that biosynthesize metabolites that impact human health. Bile acids comprise a diverse collection of metabolites that have important roles in metabolism and immunity. The gut microbiota-associated enzyme that is responsible for the gateway reaction in bile acid metabolism is bile salt hydrolase (BSH), which controls the hosts overall bile acid pool. Despite the critical role of these enzymes, the ability to profile their activities and substrate preferences remains challenging due to the complexity of the gut microbiota, whose metaproteome includes an immense diversity of protein classes. Using a systems biochemistry approach employing activity-based probes, we have identified gut microbiota-associated BSHs that exhibit distinct substrate preferences, revealing that different microbes contribute to the diversity of the host bile acid pool. We envision that this chemoproteomic approach will reveal how secondary bile acid metabolism controlled by BSHs contributes to the etiology of various inflammatory diseases.

microbiology↗

bioRxiv2024

Daily Rhythms in Metabolic and Locomotor Behaviour of Prematurely Ageing PolgA Mice

Ageing is an inherent and intricate biological process that takes place in living organisms as time progresses. It involves the decline of multiple physiological functions, leading to body structure and overall performance modifications. The ageing process differs among individuals and is influenced by various factors, including lifestyle, environment, and genetic makeup. Metabolic changes and reduced locomotor activity are common hallmarks of ageing. Our study focuses on exploring these phenomena in prematurely ageing PolgA(D257A/D257A) mice (also known as PolgA) aged 41-42 weeks, as they closely mimic human ageing. We assess parameters such as oxygen consumption (VO2), carbon dioxide production (VCO2), respiratory exchange ratio (RER), and locomotor activity using a metabolic cage for four days and comparing them with age-matched wild-type littermates (WT). Our findings revealed that VO2, VCO2, RER, locomotor activities, water intake, and feeding behaviour show a daily rhythm, aligning with roughly a 24-hour cycle. We observed that the RER was significantly increased in PolgA mice compared to WT mice during the night-time of the light-dark cycle, suggesting a shift towards a higher reliance on carbohydrate metabolism due to more food intake during the active phase. Additionally, female PolgA mice displayed a distinct phenotype with reduced walking speed, walking distance, body weight, and grip strength in comparison to male PolgA and WT mice, indicating an early sign of ageing. Taken together, our research highlights the impact of sex-specific patterns on ageing traits in PolgA mice aged 41-42 weeks, which may be attributable to human ageing phenotypes. The unique genetic composition and accelerated ageing characteristics of PolgA mice make them invaluable in ageing studies, facilitating the investigation of underlying biological mechanisms and the identification of potential therapeutic targets for age-related diseases.

physiology↗

bioRxiv2024

Feedback and Feedforward Regulation of Interneuronal Communication

We formulate a mechanistic model capturing the dynamics of neurotransmitter release in a chemical synapse. The proposed modeling framework captures key aspects such as the random arrival of action potentials (AP) in the presynaptic (input) neuron, probabilistic docking and release of neurotransmitter-filled vesicles, and clearance of the released neurotransmitter from the synaptic cleft. Feedback regulation is implemented by having the released neurotransmitter impact the vesicle docking rate that occurs biologically through "autoreceptors" on the presynaptic membrane. Our analytical results show that these feedbacks can amplify or buffer fluctuations in neurotransmitter levels depending on the relative interplay of neurotransmitter clearance rate with the AP arrival rate and the vesicle replenishment rate, with faster clearance rates leading to noise amplification. We next consider a postsynaptic (output) neuron that fires an AP based on integrating upstream neurotransmitter activity. Investigating the postsynaptic AP firing times, we identify scenarios that lead to band-pass filtering, i.e., the output neuron frequency is maximized at intermediate input neuron frequencies. We extend these results to consider feedforward regulation where in addition to a direct excitatory synapse, the input neuron also impacts the output indirectly via an inhibitory interneuron, and we identify parameter regimes where feedforward neuronal networks result in band-pass filtering.

neuroscience↗

bioRxiv2024

Mitochondria drive microglial NRLP3 inflammasome activation via TSPO

Uncontrolled microglial response is core to neuroinflammatory brain diseases. The correlation between the mitochondrial protein TSPO and inflammation has so far failed to explain whether TSPO positively or negatively regulates microglial function. The recent evidence on the species specificity of TSPO in microglia demands a deeper understanding of the protein biology in these brain-resident macrophages. To this end, we have here enrolled a murine model of microglial cells showing that TSPO is required for the priming of mitochondria to inflammation and a conduit for its escalation. Namely, in response to inflammatory cues TSPO is stabilised on the mitochondria where it binds and sequesters NOD-like receptor (NLR) protein (i), represses the PARK2-mediated mitophagy (ii) and engages the retrograde communication with the nucleus via the accumulation of the Nf-kB to promote the expression of pro-inflammatory genes (iii). Notably, the TSPO sustained inflammatory response drives cellular demise and ultimately leads to excitotoxicity (iv). Our findings advance the current knowledge of TSPO widening the understanding of mitochondria in inflammation and indicating a target for their regulation.

cell biology↗

bioRxiv2024

The transcription factor ATML1 maintains giant cell identity by inducing synthesis of its own (very) long-chain fatty acid-containing ligands

During development, cells not only adopt specialized identities but also maintain those identities. Endoreduplication is thought to maintain cell identity. High concentrations of ARABIDOPSIS THALIANA MERISTEM LAYER1 (ATML1) specify giant cell identity and induce endoreduplication in sepals. How different concentrations of ATML1 can specify different identities remains unclear. Here, we show that high concentrations of ATML1 induce the biosynthesis of both long-chain and very long-chain fatty acids (LCFAs/VLCFAs), and these fatty acids are required for the maintenance of giant cell identity. Inhibition of VLCFA biosynthesis causes endoreduplicated giant cells to resume division and lose their identity, indicating that endoreduplication is not sufficient to maintain cell identity. Structural predictions suggest that LCFA-containing lipids bind to the START domain 2 of ATML1, causing ATML1 dimerization and its auto-activation. Our data and modeling imply that ATML1 induces biosynthesis of its own lipid ligands in a positive feedback loop, shedding light on the intricate network dynamics that specify and maintain giant cell identity. Teaser: Endoreduplicated cells in Arabidopsis thaliana sepals divide and de-differentiate in the absence of VLCFA biosynthesis.

plant biology↗

bioRxiv2024

Unveiling shared genetic regulators for plant architectural and biomass yield traits in sorghum

Sorghum is emerging as an ideal genetic model for designing high-biomass bioenergy crops. Biomass yield, a complex trait influenced by various plant architectural features, is typically regulated by numerous genes. This study aims to dissect the genetic mechanisms underlying fourteen plant architectural and ten biomass yield traits in a sorghum association panel (SAP) across two growing seasons. We identified 321 associated loci via genome-wide association studies involving 234,264 single nucleotide polymorphisms (SNPs). These loci encompass both genes with a priori links to biomass traits, such as maturity, dwarfing (Dw), leafbladeless1, cryptochrome, and several loci not previously linked to roles in determining these traits. We identified 22 pleiotropic loci associated with variation in multiple phenotypes. Three of these loci, located on chromosomes 3 (S03_15463061), 6 (S06_42790178; Dw2), and 9 (S09_57005346; Dw1), exert significant and consistent effects on multiple traits. Additionally, we identified three genomic hotspots on chromosomes 6, 7, and 9, containing multiple SNPs associated with variation in plant architecture and biomass yield traits. Positive correlations were observed among linked SNPs close to or within the same genomic regions. Thirteen haplotypes were identified from these positively correlated SNPs on chr 6, with haplotypes 8 and 11 emerging as optimal combinations, exhibiting pronounced effects on the traits. Lastly, network analysis revealed that loci associated with flowering, plant heights, leaf characteristics, plant number, and tiller number per plant were highly interconnected with other genetic loci linked to plant architecture and biomass yield traits. The pyramiding of favorable alleles related to these traits holds promise for enhancing the future development of bioenergy sorghum crops.

plant biology↗

bioRxiv2024

Bridging fungal resistance and plant growth through constitutive overexpression of Thchit42 gene in Pelargonium graveolens

Pelargonium graveolens essential oil possesses significant attributes, known for perfumery and aromatherapy. However, optimal yield and propagation are predominantly hindered by biotic stress. All biotechnological approaches have yet to prove effective in addressing fungal resistance. The current study developed transgenic geranium bridging molecular mechanism of fungal resistance and plant growth by introducing cassette 35S::Thchit42. Furthermore, 120 independently putative transformed explants were regenerated on kanamycin fortified medium. Primarily transgenic lines were demonstrated peak pathogenicity and antifungal activity against formidable Colletotrichum gloeosporioides and Fusarium oxysporum. Additionally, phenotypic analysis revealed [~]2fold increase in leaf size and [~]2.1fold enhanced oil content. To elucidate the molecular mechanisms for genotypic cause, De novo transcriptional profiles were analyzed to indicate that the auxin-regulated longifolia gene is accountable for augmentation in leaf size, and ZF RICESLEEPER attributes growth upregulation. Collectively, data provides valuable insights into unravelling the mechanism of Thchit42-mediated crosstalk between morphological and chemical alteration in transgenic plants. This knowledge might create novel opportunities to cultivate fungal-resistant geranium throughout all seasons to fulfil demand.

plant biology↗

bioRxiv2024

The binding of Mint/X11 PDZ domains to CaV2 calcium channels predates bilaterian animals

PDZ domain mediated interactions with voltage-gated calcium (CaV) channel C-termini play important roles in localizing membrane Ca2+ signaling. The first such interaction was described between the scaffolding protein Mint-1 and CaV2.2 in mammals. In this study, we show through various in silico analyses that Mint is an animal-specific gene with a highly divergent N-terminus but a strongly conserved C-terminus comprised of a phosphotyrosine binding domain, two tandem PDZ domains (PDZ-1 and PDZ-2), and a C-terminal auto-inhibitory element that binds and inhibits PDZ-1. In addition to CaV2 channels, most genes that interact with Mint are also deeply conserved including amyloid precursor proteins, presenilins, neurexin, and CASK and Veli which form a tripartite complex with Mint in bilaterians. Through yeast and bacterial 2-hybrid experiments, we show that Mint and CaV2 channels from cnidarians and placozoans interact in vitro, and in situ hybridization revealed co-expression in dissociated neurons from the cnidarian Nematostella vectensis. Unexpectedly, the Mint orthologue from the ctenophore Hormiphora californiensis strongly binds the divergent C-terminal ligands of cnidarian and placozoan CaV2 channels, despite neither the ctenophore Mint, nor the placozoan and cnidarian orthologues, binding the ctenophore CaV2 channel C-terminus. Altogether, our analyses suggest that the capacity of Mint to bind CaV2 channels predates pre-bilaterian animals, and that evolutionary changes in CaV2 channel C-terminal sequences resulted in altered binding modalities with Mint.

evolutionary biology↗

bioRxiv2024

Delayed cerebrovascular dysfunction and social deficits after traumatic brain injury

Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. Acute TBI modifies neurovascular physiology and behavior but a gap in our understanding are the chronic physiological implications of altered brain perfusion on behavioral activities, particularly social interactions. We investigated longitudinal functional vascular networks across the brain for 2-months post- TBI and its impact on social behavior. Adult C57/BL6 male mice received a moderate cortical TBI. Behavior (foot-fault, open-field, 3-chamber social preference) was assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi) followed by magnetic resonance imaging (MRI, 9.4T). Anatomical MRI (T2-weighted), dynamic susceptibility contrast (DSC) perfusion weighted MRI (PWI) were acquired at each temporal epoch. After the final 60dpi MRI, animals underwent transcardial perfusion fixation to map angioarchitecture. MRI data were analyzed using standardized protocols followed by cross-correlations between social behavior, cerebral perfusion, and vascular metrics. Social behavior deficits at 60dpi emerged as reduced interaction with a familiar cage-mate (partner). We observed multiphasic decrements in cerebral blood flow (CBF) encompassing lesion and perilesional cortex where acute reductions at 3-14dpi partially recovered by 30dpi, followed by significant reductions in perfusion at 60dpi. The CBF perturbations extended antero-posteriorly from the ipsilateral TBI impact site but also adulterated contralateral brain regions. CBF reductions impacted regions known to regulate social behavior including hippocampus, hypothalamus, and rhinal cortex. Alongside perfusion deficits at 60dpi, social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interaction. Thus, the novel temporal neurovascular loss, and subsequent recovery followed by chronic decrements are broadly reflected by social interaction perturbations. Our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions, where early evaluation can potentially predict long-term outcomes. Thus, our study provides a clinically relevant timeline of alterations in functional vascular recovery that can guide research for future therapeutics.

neuroscience↗

bioRxiv2024

Unveiling Frailty: Comprehensive and Sex-Specific Characterization in Prematurely Aging PolgA Mice

Frailty, a geriatric syndrome, is assessed using the frailty phenotype (FP) and frailty index (FI). While these approaches have been applied to aging mice, their effectiveness in prematurely aging mouse models such as PolgAD257A/D257A (PolgA) has not been completely explored. We demonstrated that frailty became evident in PolgA mice around 40 weeks, validated through body weight loss, reduced walking speed, decreased physical activity, and weaker grip strength. Moreover, we also identified sex differences in these mice with females exhibiting higher frailty compared to males. Frailty prevalence in PolgA mice at 40 weeks parallels that observed in naturally aging mice at 27 months and aging humans at 65-70 years. These findings contribute to understanding frailty onset and sex-specific patterns, emphasizing the significance of the PolgA mouse model in investigating aging and related disorders.

physiology↗

bioRxiv2024

Experimental evolution for improved post-infection survival selects for increased disease resistance in Drosophila melanogaster

Disease resistance (defined as the host capacity to limit systemic infection intensity) and disease tolerance (defined as the host capacity to limit infection-induced damage) are two complementary defense strategies that help the hosts maximize their survival and fitness when infected with pathogens and parasites. In addition to the underlying physiological mechanisms, existing theory postulates that these two strategies differ in terms of the conditions under which each strategy evolves in host populations, their evolutionary dynamics, and the ecological and epidemiological consequences of their evolution. Here we explored if one or both of these strategies evolve when host populations are subjected to selection for increased post-infection survival. We experimentally evolved Drosophila melanogaster populations, selecting for the flies that survived an infection with the entomopathogen Enterococcus faecalis, and found that the host populations evolved increased disease resistance in response. This was despite the physiological costs associated with increased resistance. We did not find evidence of any change in disease tolerance in the host populations. We have therefore demonstrated that in an experimental evolution set-up, where insect hosts must survive an infection with a pathogenic bacterium, the hosts evolve improved disease resistance but not disease tolerance.

evolutionary biology↗

bioRxiv2024

Microenvironment Shapes Cell State, Plasticity, and Heterogeneity of Small Cell Lung Cancer

Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intra-tumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the tumor microenvironment (TME) exhibits substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAF) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Together, our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLCs adaptable nature, opening possibilities for re-programming the intercellular communications that shape SCLC tumor states.

cancer biology↗

bioRxiv2024

Unique growth and morphology properties of Clade 5 Clostridioides difficile strains revealed by single-cell time-lapse microscopy

Clostridioides difficile is a gastrointestinal pathogen of both humans and agricultural animals and thus a major One Health threat. The C. difficile species consists of five main clades, with Clade 5 currently undergoing speciation from Clades 1-4. Clade 5 strains are highly prevalent in agricultural animals and can cause zoonotic infections, suggesting that these strains have evolved phenotypes that distinguish them from Clade 1-4 strains. Here, we compare the growth properties of Clade 5 strains to those of Clade 1-4 strains using anaerobic time-lapse microscopy coupled with automated image analysis. Our analyses indicate that Clade 5 strains grow faster and are more likely to form long chains of cells than Clade 1-4 strains. Using comparative genomic and CRISPRi analyses, we show that the chaining phenotype of Clade 5 strains is driven by the orientation of the invertible cmr switch sequence, with chaining strains exhibiting a bias to the cmr-ON state. Interestingly, Clade 5 strains with a bias towards the cmr-ON state shifted to a largely cmr-OFF state during murine infection, suggesting that the cmr-OFF state is under positive selection during infection. Collectively, our data reveal that Clade 5 strains have distinct growth properties, which may allow them to inhabit diverse ecological niches. Author SummaryThe Clade 5 strains of the Clostridioides difficile species are so phylogenetically divergent that they almost meet the threshold of being a distinct species. Although these strains are ubiquitously isolated from agricultural and environmental settings and an important source of zoonotic and community-acquired infections, it is unclear whether they have distinct phenotypic properties that allow them to colonize diverse hosts or persist in the environment. By combining a novel anaerobic time-lapse microscopy method with automated image analysis, we discovered that Clade 5 strains grow faster than strains from other C. difficile clades and that they frequently form long chains. These chaining properties are driven by the environmentally responsive expression of a non-canonical signal transduction system, which our analyses suggest is selected against during murine infection. Collectively, our analyses reveal that Clade 5 strains have distinct growth properties that may promote their persistence in the environment.

microbiology↗

bioRxiv2024

Comparison of six methods for stabilizing metapopulation dynamics and for their robustness against census noise

Natural populations face growing extinction risks due to mismatches between traits and ecological conditions, exacerbated by habitat degradation and climate change. While several population control methods have been proposed to protect vulnerable populations, their effectiveness in spatially structured populations (metapopulations) and resilience to census inaccuracies remain unexplored. This study uses simulations to evaluate six control methods, originally designed to stabilize isolated populations, in metapopulations. We compared these methods across twelve ecological conditions based on three stability metrices and implementation costs. Without interventions, the twelve metapopulation scenarios exhibited distinct dynamics and extinction susceptibilities. Comparing the control methods against these baseline dynamics, we found that Adaptive Limiter Control consistently reduced extinction probabilities, while Lower Limiter Control effectively minimized population fluctuations in most settings, followed by Adaptive and Both Limiter Controls. These performance rankings remained robust despite simulated census errors. Our findings provide actionable insights for conservation policies aimed at stabilizing vulnerable metapopulations and offer a general framework for studying metapopulation dynamics using external interventions.

ecology↗

bioRxiv2024

Machine Learning-Based Identification of B4GALNT1 as a Key Player in Hepatocellular Carcinoma: A Comprehensive Bioinformatics and Structural Analysis

Liver hepatocellular carcinoma (LIHC) is one of the most frequent types of malignant cancer in the globe. The identification of new biomarkers for the LIHC is critical. We used TCGA-LIHC gene expression datasets for this study. Several feature selection methods were used to find the top gene signatures that distinguish LIHC cancer from normal samples. Eleven machine learning algorithms were used on these selected characteristics, and model performance evaluation revealed that Naive Bayes Classifiers (AUC = 0.965) performs the best for a selection of 55 protein coding genes. Among 55 protein coding genes we found B4GALNT1 (Beta-1,4-N-acetyl-galactosaminyltransferase 1) which is differentially regulated in LIHC. With several evidence B4GALNT1 plays crucial role in tumorigenesis in many cancers, therefore we conducted systematic bioinformatics approach with mutational and structural analysis of B4GALNT1 in LIHC. Moreover, survival analysis, immune cell infiltration, most significant associated methylated CpG probe and access the accuracy of B4GALNT1 conducted to find the potential role of B4GALNT1. The results suggested that B4GALNT1 was significantly expressed in most cancers including LIHC. Finally, 16 missense mutations identified through cBioportal, Cosmic Database, and Human Variant Database, among which 6 mutations (P64Q, S131F, A311S, R340Q, D478H, and P507Q) found to be deleterious when analysed by in-silico prediction algorithms such as SIFT, PolyPhen2, I Mutent2 and CADD in LIHC. Molecular Dynamics simulation analysis was performed to understand the atomic details of the structure and functional changes. Results from this study suggest the impact of these missense variants on the structure of the B4GALNT1 protein and its pathogenic relevance. Our study demonstrated that B4GALNT1 may be evaluated as a novel target for liver cancer therapy because it has been found to be overexpressed in Liver and correlates with a poor prognosis.

bioinformatics↗

bioRxiv2024

Evolution of a bistable genetic system in fluctuating and non- fluctuating environments

Epigenetic mechanisms can generate bacterial lineages capable of spontaneously switching between distinct phenotypes. Currently, mathematical models and simulations propose epigenetic switches as a mechanism of adaptation to deal with fluctuating environments. However, bacterial evolution experiments for testing these predictions are lacking. Here, we exploit an epigenetic switch in Salmonella enterica, the opvAB operon, to show clear evidence that OpvAB bistability persists in changing environments but not in stable conditions. Epigenetic control of transcription in the opvAB operon produces OpvABOFF (phage-sensitive) and OpvABON (phage-resistant) cells in a reversible manner and may be interpreted as an example of bet-hedging to preadapt Salmonella populations to the encounter with phages. Our experimental observations and computational simulations illustrate the adaptive value of epigenetic variation as evolutionary strategy for mutation avoidance in fluctuating environments. In addition, our study provides experimental support to game theory models predicting that phenotypic heterogeneity is advantageous in changing and unpredictable environments.

microbiology↗

bioRxiv2024

Two paralogous PHD finger proteins participate inParamecium tetraurelia's natural genome editing

The unicellular eukaryote Paramecium tetraurelia contains functionally distinct nuclei: germline micronuclei (MICs) and a somatic macronucleus (MAC). During sexual reproduction, the MIC genome is reorganized into a new MAC genome and the old MAC is lost. Almost 45,000 unique Internal Eliminated Sequences (IESs) distributed throughout the genome require precise excision to guarantee a functional new MAC genome. Here, we characterize a pair of paralogous PHD finger proteins involved in DNA elimination. DevPF1, the early-expressed paralog, is present in only some of the gametic and post-zygotic nuclei during meiosis. Both DevPF1 and DevPF2 localize in the new developing MACs, where IESs excision occurs. In DevPF2 knockdown (KD) long IESs are preferentially retained and late-expressed small RNAs decrease; no length preference for retained IESs was observed in DevPF1-KD and development-specific small RNAs were abolished. The expression of at least two genes from the new MAC with roles in genome reorganization seems to be influenced by DevPF1- and DevPF2-KD. Thus, both PHD fingers are crucial for new MAC genome development, with distinct functions, potentially via regulation of non-coding and coding transcription in the MICs and new MACs.

molecular biology↗

bioRxiv2024

Stimulation of NCAM1-14.3.3.ζδ-derived Peptide Interaction Fuels Angiogenesis and Osteogenesis in Ageing

The skeletal structure and bone marrow endothelium collectively form a critical functional unit essential for bone development, health, and aging. At the core of osteogenesis and bone formation lies the dynamic process of angiogenesis. In this study, we reveal a potent new endogenous anabolic NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction, which stimulates bone angiogenesis and osteogenesis during homeostasis, aging, and age-related bone diseases. Employing high-resolution imaging and inducible cell-specific mouse genetics, our results elucidate the pivotal role of the NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction in driving the expansion of Clec14a+ angiogenic endothelial cells. Notably, Clec14a+ endothelial cells express key osteogenic factors. The NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction in osteoblasts drives osteoblast differentiation, ultimately contributing to the genesis of new bone. Moreover, the NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction leads to a reduction in bone resorption. In age-associated vascular and bone loss diseases, stimulating the NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction not only promotes angiogenesis but also reverses bone loss. Consequently, harnessing the endogenous anabolic potential of the NCAM1-14.3.3.{zeta}{delta}-derived-Peptide interaction emerges as a promising therapeutic modality for managing age-related bone diseases.

cell biology↗