Biology subjects

Naik, S.

Publications and source records attributed to Naik, S..

At least 19 recordsLinked to original sources

bioRxiv2026

A role for CIZ1, a Nuclear Matrix Protein Overexpressed in Cancer Cells, in Controlling the Initiation of DNA Replication

DNA replication licensing is tightly coordinated with cell-cycle progression to ensure genome stability. Here we demonstrate that CIZ1, a nuclear matrix scaffold protein in human cells, coordinates DNA replication licensing through direct interactions with the Origin Recognition Complex (ORC), CDC6, and Cyclins E/A-CDK2. The C-terminal zinc finger region of CIZ1 mediates binding to the cyclin-binding motifs of ORC1 and CDC6, and Cyclin -CDK-dependent phosphorylation regulates these interactions. Cell cycle analyses demonstrated a dynamic association of CIZ1 with ORC1 and CDC6. Functional studies showed that CIZ1 depletion impaired MCM loading, reduced DNA synthesis, delayed S-phase progression and inhibited cell proliferation. Cancer cells overexpressing CIZ1 exhibited an enhanced dependency on its expression, and CRISPR tiling screens identified the C-terminal regulatory region containing cyclin-binding motifs and CDK phosphorylation sites as essential for cell proliferation. Acute degradation of CIZ1 further revealed an unexpected role in maintaining CCCTC-binding factor (CTCF) occupancy at specific genomic loci and regulating transcriptional programs associated with cell adhesion and migration, indicating that CIZ1 links DNA replication with higher-order genome organization. Finally, depletion of CIZ1 significantly suppressed colorectal tumor growth in xenograft models. Together, these findings establish CIZ1 as a multifunctional scaffold that integrates DNA replication licensing, Cyclin -CDK signaling, and chromatin architecture.

molecular biology↗

bioRxiv2026

Provisional extracellular matrix signaling network regulates tumor lymphoneogenesis and response to immunotherapy

Tertiary lymphoid structures (TLS) predict response to checkpoint inhibition, and conventional dendritic cells (cDC) are required to build and maintain them. What renders a niche permissive for their assembly is unknown: chemokines recruit the cellular constituents but do not specify how they organize. Here we show that the organizing signal is a matrix fragment. Proteolysis of the proteoglycan versican (VCAN) releases the matrikine versikine, constitutively in germinal center light zones and inducibly in tumor stroma. Versikine activates CD11b+ cDC and expands cDC1 to assemble TLS-archetypal triads, apposed DC: CD4+ T: CD8+ T units. Versikine-conditioned DC engage progenitor-exhausted CD8+ T cells (Tpex) and Th1-polarized follicular helper CD4+ T cells. Excess unproteolyzed VCAN inverts this toward DC-Treg crosstalk and Tpex loss. Versikine supplied as mRNA or recombinant protein sensitizes refractory tumors to PD-L1 blockade. VCAN proteolysis prospectively predicted outcomes after PD-1 blockade in metastatic colorectal cancer. Matrikines organize chemokine-recruited cells into functional immune niches.

immunology↗

bioRxiv2026

Longitudinal single-cell and spatial transcriptomics reveals intratumor heterogeneity, therapeutic response, and comparative value of canine marginal zone lymphoma

Diffuse B-cell lymphomas are the most prevalent canine hematologic malignancies, and their clinical presentation resembles that of human B-cell non-Hodgkin lymphomas (NHLs). However, a lack of a clear subtyping framework perpetuates imprecise treatment approaches that fail to address mechanisms of therapy resistance. Here, we employed deep phenotyping via serial sampling and longitudinal transcriptomics to evaluate intratumoral composition and therapy response in a 6-year-old neutered male goldendoodle with stage 5A marginal zone lymphoma (MZL). Following sequential treatment consisting of a single IV dose of oncolytic vesicular stomatitis virotherapy (VSV) and standard CHOP chemotherapy 30 days later, we performed scRNAseq on seven serial lymph node biopsies and spatial sequencing on a resection taken 10 days post-VSV treatment. B cells (>90%) comprised three transcriptionally distinct and temporally stable subpopulations, with specific copy number profiles and robust spatial organization despite disrupted lymph node architecture. Analysis across subpopulations revealed downregulation of the quiescence program including KLF2, suggesting similarity to KLF2-deficient human MZL. While VSV successfully reached target B cells, downstream transcriptional responses were predominantly localized to the T-cell compartment. T cells ([≤]6%) showed increased proliferation and upregulation of cytotoxicity markers post-VSV administration, enriching for leukocyte-mediated cytotoxicity pathways consistent with an anti-viral immune response. Ultimately, these results provide an in vivo proof-of-concept for the treatment paradigm in canine lymphoma, while emphasizing the need for improved subtyping frameworks and multidimensional treatment strategies targeting intratumoral heterogeneity.

cancer biology↗

bioRxiv2026

Comparison of HDO production from Glucose as a marker of Glucose metabolism

PURPOSEGlycolytic production of HDO from the metabolism of perdeuterated glucose provides a means for metabolic imaging with 2H MRI. The present study compared HDO production from a cost-efficient [2,3,4,6,6-2H5]glucose with [2H7]glucose in vitro and in vivo. METHODS2H NMR spectroscopy was performed to measure glucose consumption, lactate, and HDO production in the SFxL glioblastoma cell line. In vivo studies in healthy mice using 2H magnetic resonance spectroscopy were performed at 11.1 T after administering a bolus of either metabolic contrast agent. In vivo metabolite levels were quantified using unlocalized and slice-selective localized spectra. RESULTSOur in vitro results demonstrated similar glucose consumption and HDO production kinetics, although significant differences in lactate labeling were observed. The in vivo study showed comparable glucose consumption and HDO production kinetics following tail-vein bolus administration of either metabolic contrast agent, while lactate was not detected in the brain. CONCLUSION[2,3,4,6,6-2H5]glucose shows comparable HDO production to [2H7]glucose, while offering lower cost and reduced spectral complexity. These findings place [2,3,4,6,6-2H5]glucose as an alternative to [2H7]glucose for HDO-based DMI studies.

neuroscience↗

bioRxiv2025

ATRX Deficiency Drives Aberrant Type I Interferon Signalling Through cGAS-Dependent Transcriptional Dysregulation

The X-linked -thalassaemia intellectual disability syndrome (ATRX) protein is a chromatin remodeller involved in transcriptional regulation and genome stability. While the importance of ATRX in development and malignancy is well recognised, its role in innate immunity is less well defined. In two unrelated patients demonstrating cerebral white matter disease, learning difficulties and a persistent upregulation of interferon stimulated gene expression in whole blood, we identified the same Y1758C missense substitution in ATRX. Using patient-derived cells, engineered fibroblasts and neuronal models, we show that this substitution, and other loss of function mutations in ATRX, result in enhanced type I interferon signalling through a cGAS-dependent mechanism uncoupled from the DNA sensing activity of cGAS. Loss of ATRX function leads to alterations in the chromatin distribution of DAXX and H3.3, with cGAS essential for the changes in nucleosome composition and gene expression mediated by ATRX deficiency. Thus, our study highlights a previously unrecognized link between ATRX dysfunction and inflammation involving a non-canonical role of cGAS.

immunology↗

bioRxiv2025

Distinct mechanisms decommission redundant enhancers to facilitate phenotypic evolution

The evolutionary loss of morphological traits is often driven by changes in gene regulation. Many developmental genes are controlled by multiple, redundant enhancers, raising the question of how robust regulatory systems can be dismantled to permit phenotypic transitions. We show that the loss of larval trichomes in Drosophila sechellia resulted from the independent inactivation of four embryonic enhancers of the shavenbaby gene. Each enhancer was extinguished by a distinct mechanism: (1) a large deletion that removed essential sequences, (2) the loss of activator sites and gain of repressor sites, (3) the acquisition of a long-range silencer, and (4) the unmasking of pre-existing repression. Notably, three of these mechanisms relied on repression, pointing to repression as a rapid route for the evolutionary loss of robust regulatory elements. These results show that robustness in gene regulation does not prevent morphological change but instead provides multiple opportunities for mutations to reduce enhancer activity, giving selection many paths to reshape form.

evolutionary biology↗

bioRxiv2025

From proteins to species ranges: a framework for understanding thermal adaptation during range expansions

Species distributions are governed by both ecological and evolutionary processes. Traditionally, ecological factors have been the primary focus of species distribution studies, but recent work emphasizes the importance of rapid evolution through local adaptation. Here, we focus on adaptation to changing temperatures, which is one of the central challenges populations face today. Importantly, thermal adaptation may be affected by the underlying thermodynamics. Despite many existing models in the fields of thermal biology and spatial evolutionary ecology, there is little integrative theory. However, understanding and modelling the thermodynamic constraints on thermal adaptation is likely essential for more nuanced predictions of the impacts of climate change. By integrating molecular mechanisms and population dynamics in a unified modelling framework, we here study how temperature-dependent processes at the protein level influence the macroecological patterns of range expansions. Our results highlight the importance of the microscopic processes underlying thermal adaptation for capturing the evolutionary ecology of range expansions. Specifically, the molecular bases of thermal adaptation define how and how fast thermal performance can evolve, which determines range expansion speeds. In general, our framework predicts that adaptation to warmer temperatures will be easier than adaptation to cold. Our study underscores the necessity for more interdisciplinary work, combining molecular mechanisms with population dynamics in space in order to improve climate change modeling, enhance prediction accuracy and provide better information for management and conservation of natural populations. Significance StatementAs global temperatures shift, species must adapt to new climates, but how molecular changes scale up to influence population- and ecosystem-level patterns is poorly understood. Here, we link mutations affecting protein stability and enzyme activity to species abilities to expand along temperature gradients. Our models show that adaptation is faster at warmer temperatures and more constrained in the cold, reflecting how mutations shape protein function. Thermodynamic effects amplify the impact of beneficial mutations at higher temperatures, potentially accelerating evolutionary responses. By connecting molecular biophysics to population dynamics and range expansion, this work provides a cross-scale framework for predicting how organisms respond to warming environments.

evolutionary biology↗

bioRxiv2025

Effective imaging and treatment of Acute Myeloid Leukemia with radiotheranostics targeting the activated conformation of integrin-Beta2

There remains an unmet clinical need for improved treatment strategies in Acute Myeloid Leukemia (AML). Although radiopharmaceutical therapies targeting non-cancer-selective antigens have shown promise in AML, their clinical utility is often limited by prolonged bone marrow suppression. Using a unique proteomics-based strategy, we recently identified the active conformation of integrin-{beta}2 (aITGB2) as a novel, tumor-selective target for AML. Importantly, this conformational epitope is expressed widely on AML cells but minimally on normal marrow progenitors/healthy tissues. Here we first confirmed widespread aITGB2 expression on AML tumors that was largely independent of tumor genotype or prior therapeutic regimen. We developed diagnostic and therapeutic radiopharmaceuticals targeting aITGB2 utilizing a conformation-specific antibody (clone 7065). PET/CT imaging with 89Zr and 134Ce-labeled 7065 in AML models revealed high target-mediated uptake, greater than that compared to standard of care [18F]-FDG. PET/CT imaging with [89Zr]DFO*-7065 showed reduced binding to normal bone marrow and immune cells in humanized immune system mice compared to [89Zr]DFO*-anti-CD33. For therapy, we developed [225Ac]Macropa-PEG4-7065 using an optimized chelator-linker combination. Treatment with [225Ac]Macropa-PEG4-7065 in Nomo-1 and PDX AML disseminated models delayed tumor growth and improved overall survival compared to controls, including [225Ac]DOTA-anti-CD33, a clinical stage-radioimmunotherapy under evaluation in AML. Relapsed tumors demonstrated persistent aITGB2 expression, supporting continued development of fractionated dosing schemes, and proteomics analysis indicated activation of TCA cycle and carbon metabolism pathways, consistent with therapy-induced stress responses. These findings highlight [89Zr]DFO*-7065 and [225Ac]Macropa-7065 as a promising aITGB2-targeted theranostic pair with potential for imaging and treatment in future clinical translation. One Sentence SummaryThis study demonstrates promising preclinical efficacy of aITGB2-targeted radiotheranostics for selective imaging and therapy in AML.

cancer biology↗

bioRxiv2025

The hidden predictors of human haematopoietic clonal fate

Human haematopoietic stem and progenitor cells (HSPCs) exhibit heterogeneous lineage output, but the molecular programs underlying clonal fate remain poorly defined. To address this, we developed a human haematopoietic organoid supporting differentiation into 15 lineages and used it to track barcoded HSPC clones over time. By integrating single-cell transcriptomes, surface phenotypes, and clonal fate, we applied machine learning to identify clonal fate modules - gene and marker signatures predictive of lineage commitment. This approach uncovered hidden transcriptional and surface correlates of multipotency, including CD200, which marked a subset of HSCs with broad output capacity, which we leveraged to increase manufactured type 1 dendritic cell purity for immunotherapy applications. Our study provides a framework for decoding clonal fate decisions in human HSPCs and identifies molecular features that distinguish truly multipotent clones, advancing strategies for stem cell purification and therapeutic engineering.

cell biology↗

bioRxiv2025

Identifying the Minimal Number of Protein Markers for Cell Type Annotation Using MiniMarS

Over the past decade, there has been an explosion in the characterisation and discovery of cell populations using single-cell technologies. Single-cell multi-omics data, particularly those incorporating gene and protein expression, are increasingly commonplace and can lead to more refined characterisation of cell types. A common challenge for biologists is to isolate cells of interest using a minimal number of markers for cytometry experiments. Although several methods exist for marker selection, there is limited guidance on the relative performance of these methods, and a wrapper package that combines multiple methods is lacking. The method that performs best can vary depending on the dataset and it can be challenging for researchers to test multiple methods for a given dataset. To address these issues, we present MiniMarS (Minimal Marker Selection), an R package that serves as a wrapper for 10 different algorithms. It allows users to determine the best-performing algorithm for identifying the optimal number of markers that will delineate cell populations in their dataset. MiniMarS uses pre-annotated cells with protein features from CyTOF or sequencing-based assays such as CITE-seq and Abseq as input. Outputs include 1) the minimum number of protein markers required to identify the annotated cell populations using a range of marker selection algorithms, and 2) a range of metrics to evaluate the performance of each algorithm. MiniMarS effectively differentiated populations across various datasets, including those from human blood, bone marrow, thymus, mouse spleen, and lymph nodes, even after subsampling over 41,000 cells to 2,500 cells. MiniMarS also identified 15 markers from CITE-seq data, which were then used to successfully identify the same 11 cell subsets in a CyTOF dataset (F1 score>0.9). Additionally, we showed that by appropriately combining clusters, MiniMarS improves the F1 score of a rare population identification (<1% of total cells) by 28.7%. Together, these findings highlight the broad applicability of MiniMarS in identifying appropriate markers for distinguishing cell populations.

bioinformatics↗

bioRxiv2025

Genetic barcoding uncovers the clonal makeup of solid and liquid biopsies

Intra-tumoral heterogeneity (ITH) is fueling tumor progression in breast cancer, as specific clones present within a tumor may have a selective advantage to colonize distant organs and escape therapy. Accurate sampling of ITH is therefore a pressing challenge in clinical oncology, to adequately predict recurrence and inform rational and personalized therapies. Here we used cellular barcoding to track the spatio-temporal composition of human breast cancer clones in six preclinical models - across two cell lines and four patient derived xenografts (PDXs). This allowed direct side-by-side quantitative comparison not only of intra-tumor clonal composition, but also of how that composition was reflected in needle biopsies and cell-free DNA (cfDNA). These analyses highlighted several clinically relevant findings. First, the use of orthogonal genetic and optical barcoding revealed that clonal diversity in the center of non-necrotic primary tumors was significantly higher compared to their periphery. Second, cfDNA barcode analysis suggested that DNA shedding in the vasculature varied largely, not only depending on necrosis and tumor burden, but also between models. Third, combining information captured in both solid and liquid biopsies can provide a more robust assessment of tumor clonal composition. Taken together, these results showcases the utility of these barcoded models to optimize the use of solid and liquid biopsies as surrogate markers of ITH.

cancer biology↗

bioRxiv2025

A Transcriptomic Atlas of Healthy Human Skin Links Regional Identity to Inflammatory Disease.

Human skin is not a uniform organ but a mosaic of anatomically distinct niches, with each site finely tuned to unique environmental demands and immune pressures. Yet, the molecular determinants that define these regional identities and their relationship to site-specific vulnerability to inflammatory disease remain poorly understood. Here, we generate a high-resolution single-cell atlas of human skin, profiling 274,834 cells from 96 healthy samples across 7 anatomically distinct sites (acral, arm, axilla, back, face, leg and scalp). Our analysis reveals striking region-specific transcriptional and cellular networks, uncovering how local immune-stromal crosstalk governs tissue homeostasis and underpins anatomical susceptibility to distinct inflammatory diseases such as such as systemic lupus erythematosus (SLE), atopic dermatitis (AD), and psoriasis. These findings illuminate the tissue-intrinsic foundations of regional immune identity and provide a blueprint/resource for the development of precision therapies tailored to the distinct immunological microenvironments of specific anatomical skin sites.

systems biology↗

bioRxiv2025

Gastrointestinal colonization as a source of Staphylococcus aureus in atopic dermatitis

Atopic dermatitis (AD) is a prevalent inflammatory skin disease with complex pathogenesis. Both skin and gut microbiota influence AD, with Staphylococcus aureus, in particular, exacerbating the disease. However, the relationship between S. aureus colonization in the gut and skin, and whether it affects AD, remains unclear. Using a combination of culture-based methods, microbiome analysis, and genome sequencing of S. aureus from multiple body sites of children with and without AD, we found that the gut represents a major reservoir of genetically diverse S. aureus that is transmitted to the skin, including mutants associated with worse disease. We validated this association between S. aureus gastrointestinal colonization and AD in an independent human cohort and demonstrated its direct effect on disease in an infantile AD mouse model, wherein S. aureus gastrointestinal colonization worsened skin inflammation. Overall, this study identifies a previously unrecognized S. aureus reservoir, with implications for microbiota-targeting therapies in AD.

microbiology↗

bioRxiv2025

Keratins coordinate tissue spreading by balancing spreading forces with tissue material properties

For tissues to spread, they must be deformable while maintaining their structural integrity. How these opposing requirements are balanced within spreading tissues is not yet well understood. Here, we show that keratin intermediate filaments function in epithelial spreading by adapting tissue mechanical resilience to the stresses arising in the tissue during the spreading process. By analysing the expansion of the enveloping cell layer (EVL) over the large yolk cell in early zebrafish embryos in vivo, we found that keratin network maturation in EVL cells is promoted by stresses building up within the spreading tissue. Through genetic interference and tissue rheology experiments, complemented by a vertex model with mechanochemical feedback, we demonstrate that stress-induced keratin network maturation in the EVL increases tissue viscosity, which is essential for preventing tissue rupture. Interestingly, keratins are also required in the yolk cell for mechanosensitive actomyosin network contraction and flow, the force-generating processes pulling the EVL. These dual mechanosensitive functions of keratins enable a balance between pulling force production in the yolk cell and the mechanical resilience of the EVL against stresses generated by these pulling forces, thereby ensuring uniform and robust tissue spreading.

developmental biology↗

bioRxiv2024

Interferon-sensitized hematopoietic progenitors dynamically alter organismal immunity

Inflammation has enduring impacts on organismal immunity. However, the precise mechanisms by which tissue-restricted inflammation conditions systemic responses are poorly understood. Here, we leveraged a highly compartmentalized model of skin inflammation and identified a surprising type I interferon (IFN)- mediated activation of hematopoietic stem/progenitor cells (HSPCs) that results in profound changes to systemic host responses. Post-inflamed mice were protected from atherosclerosis and had worse outcomes following influenza virus infection. This IFN-mediated HSPC modulation was dependent on IFNAR signaling and could be recapitulated with the administration of recombinant IFN. Importantly, the transfer of post-inflamed HSPCs was sufficient to transmit the immune suppression phenotype. IFN modulation of HSPCs was rooted both in long-term changes in chromatin accessibility and the emergence of an IFN- responsive functional state from multiple progenitor populations. Collectively, our data reveal the profound and enduring effect of transient inflammation and more specifically type I IFN signaling and set the stage for a more nuanced understanding of HSPC functional modulation by peripheral immune signals.

immunology↗

bioRxiv2024

A multi-track landscape of haematopoiesis informed by cellular barcoding and agent-based modelling

In classic ball-and-stick models of haematopoiesis the implicit assumption is that all cells within each defined stem or progenitor cell population are equivalent in their fate. Instead, more recent models suggest a haematopoietic stem and progenitor cell (HSPC) continuum of lineage bias and commitment, which is largely inferred through snapshot analysis of single cell gene expression or clonal fate. However, the dynamic assessment of lineage commitment of specific HSPC populations and their clonal output over time in vivo is still lacking but is essential to fully inform accurate models of haematopoiesis. Here, using cellular barcoding we compare the single cell output of long-term haematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs), multipotent progenitors (LMPPs), common myeloid progenitors (CMPs), common lymphoid progenitors (CLPs), and macrophage/dendritic cell progenitors (MDPs). Each population was assessed for their output to multiple haematopoietic cell types spanning a subset of time points from 9 to 112 days of haematopoiesis after transplantation. These analyses revealed a wide range of clonal fate patterns that were inconsistent with their eponymous labels, i.e. stem and multipotent progenitors were rarely multi- or equipotent, and common progenitors were often highly restricted in their fate. To better describe how these clonal patterns integrate into a revised landscape, a novel agent-based mathematical modelling approach that explicitly accounts for haematopoiesis at a clonal level was developed to allow the simulation of growth, timing and branching of clonal trajectories that underlie the process. Rather than a continuum, the proposed model is suggestive of multiple tracks down which clonal trajectories progress, and where fate can branch to a track of lower potency at multiple points down the entire cascade of haematopoiesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/587126v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@b09137org.highwire.dtl.DTLVardef@de064org.highwire.dtl.DTLVardef@10705e3org.highwire.dtl.DTLVardef@139b6f_HPS_FORMAT_FIGEXP M_FIG C_FIG In a multi-track model, while some HSPCs are multipotent and branch into daughters with committed fate (left trajectory), other HSPCs may already committed or biased to a certain lineage such that their daughters inherit and maintain it in subsequent divisions during haematopoiesis. However, this commitment/fate bias is not evident through current phenotypic definitions of HSPC subsets (background colour) but occurs through putative expression of transcription factors, epigenetic programming or other factor that is currently unresolved (as indicated by the coloured fate potential triangles inside cells).

immunology↗

bioRxiv2024

Clonal analysis of fetal hematopoietic stem/progenitor cell subsets reveals how post-transplantation capabilities are distributed

It has been proposed that adult haematopoiesis is sustained by multipotent progenitor (MPP) clones that are specified during development. From an immunophenotypic perspective, it is known that hematopoietic stem cell (HSC) and MPPs are present in the fetal liver yet our understanding of how fetal MPPs functionally compare to those in the adult bone marrow is incomplete. Using acute-term transplantations, we found that at a population-level fetal immunophenotypic MPP classes exhibited similar lineage biases as adult cells, albeit with some difference in lymphoid output. Clonal assessment of fetal MPPs engraftment revealed that lineage biases largely resulted from differences in the pattern of single-or bi-lineage differentiation. Immunophenotypic long-term (LT)-and short-term (ST)-HSCs in the fetal liver were distinguished from MPPs according to propensity for clonal multi-lineage differentiation. We also discovered that a large cohort of long-term repopulating units (LT-RU) were within the immunophenotypic ST-HSC population, a significant portion of these were labelled using Flt3-cre. This finding has two implications: (1) use of the CD150+ LT-HSC immunophenotype alone will systematically underestimate the size and diversity of the fetal LT-RU pool; and, (2), given fetal LT-RUs with a ST-HSC immunophenotype have the functional attributes required to persist into adulthood.

developmental biology↗

bioRxiv2023

Cardiac function and ECM morphology are altered with high fat diets in Drosophila

Cardiovascular disease is characterized by aberrant and excessive extracellular matrix (ECM) remodelling, termed fibrosis. Fibrotic remodelling is typically triggered by inflammation, which occurs systemically in obesity. Despite the contribution of fibrosis to adverse clinical outcomes and disease progression, there are no available treatments for this condition. Developing therapeutics for chronic conditions requires an understanding of in vivo ECM regulation, and how the ECM responds to a systemic challenge. We have therefore developed a Drosophila model for obesity via chronic high fat diet feeding and evaluated the response of the cardiac ECM to this metabolic challenge. We found that this model displays a striking disorganization of the cardiac ECM, with corresponding deficits in heart function. Our study shows that different genotypes tolerate varying levels of high fat diets, and that some genotypes may require a different percentage of fat supplementation for achieving an optimal obesity phenotype.

molecular biology↗