Biology subjects

Majumdar, R.

Publications and source records attributed to Majumdar, R..

7 recordsLinked to original sources

bioRxiv2026

Chromosome-arm-specific telomere length governs dual modes of structural genome evolution in IDH-mutant astrocytoma

IDH-mutant astrocytomas maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, producing extreme inter-arm telomere length heterogeneity, yet how this heterogeneity shapes structural genome evolution remains unknown. Using Oxford Nanopore long-read sequencing of 20 IDH-mutant astrocytomas, we profiled structural variants (SVs), copy number variants, extrachromosomal DNA (ecDNA) and measured allele-specific telomere lengths from individual long reads. We identified pervasive complex rearrangements, including chromothripsis and foldback events consistent with breakage-fusion-bridge cycles, and widespread ecDNAs. SV breakpoints were enriched at telomeric and centromeric regions regardless of local telomere length, revealing constitutive structural fragility. Arm-level telomere length analysis uncovered a dual-mode model: arms with short telomeres preferentially harbored breakage-associated events, while arms with long ALT-maintained telomeres were enriched for ecDNA and amplification-associated events. These findings identify chromosome-arm-specific telomere length as a determinant of structural genome evolution in ALT-driven tumors.

cancer biology↗

bioRxiv2026

Evolutionary and Deep Learning Models Highlight Deleterious Mutations Behind the History of Sugar Beet Breeding

Sugar beet (Beta vulgaris ssp. vulgaris) is a major global source of sucrose. Domestication and a history of breeding have shaped the distribution of deleterious mutations across the genome. Accurately resolving these variants offers a compelling avenue to accelerate crop improvement through breeding or genetic engineering. We combine three scales of evolutionary time: protein conservation defined by conservation across all living organisms (SIFT), angiosperm-wide DNA language deep learning model (PlantCaduceus), and fine-scale evolutionary rates from Amaranthaceae plant family sequence alignments to define a high-confidence set of deleterious variants enriched for alleles under negative selection. We then evaluate these deleterious mutations across a multi-study panel of more than 1,900 whole-genome sequenced wild and cultivated beet accessions. We found that domesticated beet accessions exhibit higher deleterious load relative to wild maritima, yet sugar beet carries significantly fewer deleterious variants than other cultivated beet crops. Historical trends show a decline in genetic load across more than a century of sugar beet entries in the U.S. NPGS, reflecting sustained purging during modern breeding. This combinatorial method of leveraging evolutionary conservation reveals how deleterious mutations have shaped sugar beet breeding history and provides potential targets for future selection, causal-variant discovery, and precision genome engineering.

genomics↗

bioRxiv2023

A facile green synthesis approach to silver nanoparticles using calyx from Abelmoschus esculentus and its anthelmintic activity

In recent years, technology pertaining to nanobiomaterials has taken rapid strides, with the development of novel materials having unique properties. Silver nanoparticles (AgNPs) have gained attention among these materials due to their high chemical stability, surface-to-volume ratio, and strong antimicrobial activity. The traditional method for synthesizing AgNPs involves toxic chemicals, which can have negative environmental impacts and pose health risks. Hence, there is a growing need for green synthesis methods for AgNPs that are environmentally friendly and safe for animal and human health. In this study, we explore the green synthesis of AgNPs using calyx from Abelmoschus esculentus, also known as okra, as an anthelmintic. Raillietina spp. is a common poultry parasite causing significant economic losses to the livestock industry. It is a major cause of ailment and mortality in livestock, deterring the host health. While chemical-based anthelmintic drugs are available, the increasing prevalence of drug-resistant parasite strains has made searching for new and effective treatments imperative. Although ethnomedicine has been promising for treating various diseases, including parasitic infections, nanoparticles have emerged as a viable alternative to traditional anthelmintic curative development. Our study aims at investigating the recent advances in nanomedicine, particularly AgNPs, as anthelmintic agents, which has shown remarkable alterations in the levels of tegumental enzymes, eventually leading to their paralysis and death. We discuss the mechanisms of action of AgNPs against Raillietina spp. and highlight the potential benefits of using biosynthesized curatives that interfere with the host-parasite interface to treat parasite-related disorders.

zoology↗

bioRxiv2023

Biosynthesis, Characterization and Anthelmintic Activity of Silver Nanoparticles of Clerodendrum infortunatum Isolate

Over the past few decades, the green synthesis of nanoparticles has gained importance for their therapeutic efficacy and eco-friendly nature. Integrating green chemistry principles into multidisciplinary nanoscience research has paved the way for developing environmentally benign and sustainable methods for synthesizing gold and silver nanoparticles. In the present study, the flowers obtained from Clerodendrum infortunatum (L.), belonging to the family Verbenaceae, have been used for biosynthesizing silver nanoparticles (AgNPs) to evaluate the anthelmintic potential. UV-Vis spectroscopy, XRD, FTIR and TEM analyses were performed to ascertain the formation of AgNPs. Clerodendrum-derived AgNP (CLE-AgNP) has significantly affected the normal physiological functions of the poultry parasite Raillietina spp, a menace to the livestock industry. Our study manifests that CLE-AgNPs cause considerable distortion of the surface tegument of this cestode parasite leading to changes in the host-parasite interface. The histochemical localization studies of the tegument-associated enzymes viz. AcPase, AlkPase, ATPase and 5-Nu, exposed to the drug, showed a substantial activity decline, thus establishing the anthelmintic potential of the CLE-AgNPs.

zoology↗

bioRxiv2023

Anthelmintic efficacy of Holarrhena pubescens against Raillietina spp. in domestic fowl through ultrastructural, histochemical, biochemical and GLCM analysis

Holarrhena pubescens is a well-known medicinal plant used in ethno-traditional medicine and tribal folklore medicine in West Bengal, India. This article focuses on depicting the anthelmintic efficacy of ethanolic extract and Ethyl acetate fraction of the stem bark of Holarrhena pubescens against the cestode Raillietina spp. through efficacy testing, ultra-structural observations, histochemical and biochemical studies on some tegumental enzymes i.e., Acid Phosphatase (AcPase), Alkaline Phosphatase (AlkPase), Adenosine Triphosphatase (ATPase) and 5-Nucleotidase (5-Nu) along with Gray Level Co-occurrence Matrix (GLCM) analysis of histochemistry images. Praziquantel was used as the reference drug. Investigations revealed 10mg/ml of crude extract was determined as the most efficacious dose and the Ethyl acetate fraction showed the most anthelmintic property. Ultrastructural studies through Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) clearly showed the damage in head, sucker, proglottids, proximal and distal cytoplasm (DC), microtriches (MT), basal lamina (BL), nuclear membrane (NM), and, nucleolus (NL) in the treated worms. Histochemical studies revealed decrease in staining intensity for all the tegumental enzymes in the treated worms compared to control. The GLCM analysis strongly supported the result of histochemical studies. Biochemical studies revealed marked reduction in enzyme activity in the treated worms with maximum reduction in the activity of 5-Nu (77.8%) followed by ATPase (63.17%).

zoology↗

bioRxiv2022

Photoacoustic imaging reveals mechanisms of rapid-acting insulin formulations dynamics at the injection site

ObjectiveUltra-rapid insulin formulations control postprandial hyperglycemia; however, inadequate understanding of injection site absorption mechanisms is limiting further advancement. We used photoacoustic imaging to investigate the injection site dynamics of dye-labeled insulin lispro in the Humalog(R) and Lyumjev(R) formulations using the murine ear cutaneous model and correlated it with results from unlabeled insulin lispro in pig subcutaneous injection model. MethodsWe employed dual-wavelength optical-resolution photoacoustic microscopy to study the absorption and diffusion of the near-infrared dye-labeled insulin lispro in the Humalog and Lyumjev formulations in mouse ears. We mathematically modeled the experimental data to calculate the absorption rate constants and diffusion coefficients. We studied the pharmacokinetics of the unlabeled insulin lispro in both the Humalog and Lyumjev formulations as well as a formulation lacking both the zinc and phenolic preservative in pigs. The association state of insulin lispro in each of the formulations was characterized using SV-AUC and NMR spectroscopy. ResultsThrough experiments using murine and swine models, we show that the hexamer dissociation rate of insulin lispro is not the absorption rate-limiting step. We demonstrated that the excipients in the Lyumjev formulation produce local tissue expansion and speed both insulin diffusion and microvascular absorption. We also show that the diffusion of insulin lispro at the injection site drives its initial absorption; however, the rate at which the insulin lispro crosses the blood vessels is its overall absorption rate-limiting step. ConclusionsThis study provides insights into injection site dynamics of insulin lispro and the impact of formulation excipients. It also demonstrates photoacoustic microscopy as a promising tool for studying protein therapeutics. The results from this study address critical questions around the subcutaneous behavior of insulin lispro and the formulation excipients, which could be useful to make faster and better controlled insulin formulations in the future. HighlightsO_LIHexamer dissociation is not the absorption rate-limiting step for insulin lispro C_LIO_LILyumjev excipients enhance insulin microvascular absorption and diffusion C_LIO_LIVascular endothelial transit determines the overall absorption for insulin lispr C_LIO_LIInsulin diffusion studied for the first time at the injection site of live animals C_LIO_LIIn vivo imaging is a powerful tool to study injection site dynamics C_LI

systems biology↗

bioRxiv2019

A role for keratins in supporting mitochondrial organization and function in skin keratinocytes

Mitochondria fulfill essential roles in ATP production, metabolic regulation, calcium signaling, generation of reactive oxygen species (ROS) and additional determinants of cellular health. Recent studies have highlighted a role for mitochondria during cell differentiation, including in skin epidermis. The observation of oxidative stress in keratinocytes from Krt16 null mouse skin, a model for pachyonychia congenita (PC)-associated palmoplantar keratoderma, prompted us to examine the role of Keratin (K) 16 protein and its partner K6 in regulating the structure and function of mitochondria. Electron microscopy revealed major anomalies in mitochondrial ultrastructure in late stage, E18.5, Krt6a/Krt6b null embryonic mouse skin. Follow-up studies utilizing biochemical, metabolic, and live imaging readouts showed that, relative to controls, skin keratinocytes null for Krt6a/Krt6b or Krt16 exhibit elevated ROS, reduced mitochondrial respiration, intracellular distribution differences and altered movement of mitochondria within the cell. These findings highlight a novel role for K6 and K16 in regulating mitochondrial morphology, dynamics and function and shed new light on the causes of oxidative stress observed in PC and related keratin-based skin disorders.

cell biology↗