Biology subjects

Nadig, N.

Publications and source records attributed to Nadig, N..

5 recordsLinked to original sources

bioRxiv2025

Unmasking Early Microglial Remodeling in an Alzheimer's Disease Mouse Model

Early neuroimmune remodeling is a critical yet understudied component of Alzheimers disease (AD) pathogenesis. To investigate microglial contributions to AD development prior to overt plaque deposition, we developed an open-source morphometric pipeline to systematically quantify hippocampal microglial structure and activation states in pre-plaque 5xFAD mice. Across [~]11,000 cells, we extracted multidimensional parameters including area, circularity, convex hull, branch points, nearest-neighbor distance, and nuclear features, alongside Iba1 and CD68 intensity measurements. While no significant overt gliosis was observed at this early stage, microglia from 5xFAD mice exhibited subtle trends toward increased structural complexity compared to wild-type controls. Importantly, significant sex-specific differences were detected within the CA1 subregion: male 5xFAD microglia displayed hyper-ramified morphologies consistent with enhanced surveillance states, whereas female microglia demonstrated greater density and a more reactive phenotype. Correlation analyses revealed a conserved association between microglial complexity and Iba1/CD68 expression, independent of sex or genotype, underscoring a fundamental link between cytoskeletal remodeling and phagolysosomal activity. These findings highlight the capacity of morphometric profiling to sensitively detect early, region-specific, and sex-dependent shifts in microglial phenotype before amyloid deposition. By integrating quantitative morphology with canonical molecular markers, this framework provides a robust and unbiased approach for characterizing microglial activation trajectories. Such early readouts may inform biomarker discovery and therapeutic strategies aimed at modulating microglial responses to delay or prevent AD progression.

neuroscience↗

bioRxiv2024

Secretome analysis of cancer-associated fibroblasts from prostate cancer to identify potential therapeutic targets

Tumor microenvironment (TME) is a complex entity comprising of several cell types secreted factors as well as an extracellular matrix. A dynamic interaction between tumor cells and their environment profoundly influences tumor survival, aggressiveness, and progression. Cancer- associated fibroblasts (CAFs) are one of the major cellular components of TME and serve as a major source of various secreted factors. These factors are known to modulate tumor survival and progression, as well as their response to therapy. Despite the importance of the TME factors on various aspects of tumor cell behavior, to date factors unique to CAFs that could be potential therapeutic targets are not identified in most systems. This study was aimed at identifying such factors from CAFs which may impact tumor behavior such as the ability to metastasize, response to therapy, relapse, etc. This would aid in identifying therapeutic targets originating from the TME. Furthermore, targeting those factors along with conventional chemotherapeutic drugs is likely to enhance the overall efficacy of the therapy. This study has used fibroblasts derived from Benign Prostatic Hyperplasia (BPH) and prostate cancer for comparing the secretome using a quantitative proteomics approach. 66 proteins unique to CAFs and 24 unique to control (BPH) fibroblasts have been identified. Besides 236 proteins are differentially expressed between control and cancer- associated fibroblasts. Using in-silico approaches the potential processes that may be influenced by the differentially expressed proteins have also been identified. This study has identified both qualitative and quantitative differences between the secretomes of normal and cancer-associated fibroblasts with further validation, this paves the way for identifying therapeutic targets.

cancer biology↗

bioRxiv2024

Modular, inducible, and titratable expression systems for Escherichia coli and Acinetobacter baumannii

Gene expression systems that transcend species barriers are needed for cross-species analysis of gene function. In particular, expression systems that can be utilized in both model and pathogenic bacteria underpin comparative functional approaches that inform conserved and variable features of bacterial physiology. Here, we develop replicative and integrative vectors alongside a novel, IPTG-inducible promoter that can be used in the model bacterium Escherichia coli K-12 as well as strains of the antibiotic-resistant pathogen, Acinetobacter baumannii. We generate modular vectors that transfer by conjugation at high efficiency and either replicate or integrate into the genome, depending on design. Embedded in these vectors, we also developed a synthetic, IPTG-inducible promoter, PabstBR, that induces to a high level, but is less leaky than the commonly used trc promoter. We show that PabstBR is titratable at both the population and single cell level, regardless of species, highlighting the utility of our expression systems for cross-species functional studies. Finally, as a proof of principle, we use our integrating vector to develop a reporter for the E. coli envelope stress {sigma} factor, RpoE, and deploy the reporter in E. coli and A. baumannii, finding that A. baumannii does not recognize RpoE-dependent promoters unless RpoE is heterologously expressed. We envision that these vector and promoter tools will be valuable for the community of researchers that study fundamental biology of E. coli and A. baumannii. ImportanceAcinetobacter baumannii is a multidrug-resistant, hospital-acquired pathogen with the ability to cause severe infections. Understanding the unique biology of this non-model bacterium may lead to the discovery of new weaknesses that can be targeted to treat antibiotic-resistant infections. Here, we provide expression tools that can be used to study gene function in A. baumannii, including in drug-resistant clinical isolates. These tools are also compatible with the model bacterium, Escherichia coli, enabling cross-species comparisons of gene function. We anticipate that the use of these tools by the scientific community will accelerate our understanding of Acinetobacter biology.

microbiology↗

bioRxiv2024

Comparative transcriptome of normal and cancer- associated fibroblasts

The characteristics of a tumor are largely determined by its interaction with the surrounding micro-environment (TME). TME consists of both cellular and non-cellular components. Cancer associated fibroblasts (CAFs) are a major component of the TME. They are a source of many secreted factors that influence the survival and progression of tumors as well as their response to drugs. Identification of markers either overexpressed in CAFs or unique to CAFs would pave the way for novel therapeutic strategies that would combine conventional chemotherapy and TME-targeted therapy for a better outcome. We have used fibroblast derived from Benign Prostatic Hyperplasia (BPH) and prostate cancer to perform a transcriptome analysis in order to get a comparative profile of normal and cancer-associated fibroblasts. This has identified 818 differentially expressed mRNAs and 17 lincRNAs between normal and cancer-associated fibroblasts.

cancer biology↗

bioRxiv2022

Gene expression signature of castrate resistant prostate cancer

Prostate gland is a highly androgen dependent gland and hence the first line of treatment for metastatic prostate cancer happens to be androgen ablation. This is achieved by multiple non-surgical methods. However, most of these cancers although respond well initially, become resistant to androgen ablation sooner or later. These cancers then become extremely aggressive and difficult to treat, thereby drastically affect the patient prognosis. The purpose of this project was to identify a gene expression signature for castrate resistant prostate cancer which may aid in identification of mechanisms responsible for castrate resistance. For this purpose, we have collected patient samples belonging to a. Control group; b. Castrate Sensitive group and c. Castrate resistant group. Gene expression profiling has been done on these samples using RNA-seq and several differentially expressed genes identified between the castrate sensitive and resistant groups. We have also identified some genes which are expressed in the castrate resistant group alone, which is of interest since these may have an implication in evolution of castrate resistance and also prognosis. We have compared this with data from The Cancer Genome Atlas (TCGA). Using criteria such as overall survival, disease free survival, progression free survival and biochemical recurrence, we have identified genes which may have relevance in progression to castrate resistance and in prognosis. Functional annotation of these genes may give an insight into the mechanism of development of castrate resistance.

cancer biology↗