Biology subjects

Mandal, P. K.

Publications and source records attributed to Mandal, P. K..

9 recordsLinked to original sources

bioRxiv2026

Oligella otitidis sp. nov., isolated from middle ear discharge of children with chronic suppurative otitis media

Oligella otitidis MSHR-50489EDL strain (ATCC: TSD-462-; DSMZ: DSM 118617) is a new species of the genus Oligella that was isolated from a middle ear discharge swab from a child with chronic suppurative otitis media (CSOM). This Gram-negative coccobacillus produces small, circular, smooth, whitish-opaque and occasionally mucoid colonies. It grows in aerobic conditions at a temperature range from 25-42{degrees}C. Phylogenetic analysis demonstrates a relationship to other species of the genera Oligella and average nucleotide identity and digital DNA-DNA hybridization values indicate a distinct species in comparison to other Oligella species. Thus far, the majority of isolates exhibit resistance to ciprofloxacin, the first line treatment for CSOM.

microbiology↗

bioRxiv2025

Nutritional iron deficiency elicits profound rewiring of red pulp macrophage functions via high FPN and SYK-mediated signaling

Iron deficiency is the most common nutritional disorder worldwide, yet how individual cell types adjust to iron scarcity remains unclear. Splenic red pulp macrophages (RPMs) are essential for systemic iron homeostasis. They manage exceptionally high iron flux by recycling aged red blood cells through erythrophagocytosis, a specialized form of efferocytosis. However, how RPMs adapt their clearance and metabolic programs to iron deficiency remains unexplored. Here, we show that RPMs from mildly anemic, iron-deficient mice exhibit enhanced erythrophagocytic capacity. Proteomic profiling and flow cytometry revealed expansion and activation of lysosomal and mitochondrial networks, accompanied by elevated mitochondrial respiration. This metabolic rewiring and the increase in erythrophagocytosis depended on branched-chain amino acid (BCAA) catabolism. These responses were distinct from alternative macrophage activation states and absent in liver and peritoneal macrophages. Mechanistically, the low hepcidin-high ferroportin axis and SYK kinase activity emerged as drivers of this functional rewiring. Pharmacological inhibition of SYK or BCAA catabolism blunted iron-deficiency-induced erythrophagocytic and mitochondrial adaptations of RPMs. Together, these findings reveal a non-canonical metabolic reprogramming of RPMs that enhances their specialized clearance functions during systemic iron scarcity, raising possiblity that similar signaling circuits may operate in other efferocytic macrophage subsets under altered ferroportin-SYK axis activity.

cell biology↗

bioRxiv2023

Characterization and Expression Analysis of Nitrate Reductase 6-1ABD Gene in Hexaploid Bread Wheat Under Different Nitrogen Regime

Nitrate reductase (NR) is the key rate-limiting enzyme of the nitrogen (N) assimilation process in plants, which has not been characterized in bread wheat under nitrogen stress, especially with respect to their homeologues. Total 9 NRs were identified and classified into 3 groups, which showed a close relationship with different wheat ancestors. The occurrence of N-responsive cis-acting regulatory elements like MYB, MYC, G-Box and GATA-motif confirmed their N-responsiveness. Expression of all the three groups of NR under N-stress revealed NR 6-1ABD group to be the most N-responsive, which was characterized further in detail. The study was carried out in two genotypes contrasting for their N-responsiveness (HD 2967: Highly responsive to applied N, and Choti Lerma: Less responsive to applied N) selected on the basis of field evaluation. Homeologous differences within a genotype were found much more than the genotypic differences of a specific homeologue coding sequence. Among the three homeologues, though NR 6-1D homeologue was found most responsive to N-stress, the contribution was maximum for this homeologue followed by NR 6-1A and least by NR 6-1B. We found that the expression of homeologues was linked to the presence of N-responsive cis- elements. All the homeologues of NR 6-1 in Choti Lerma were found less responsive to N-stress, in comparison to HD 2967, which might also be linked to N-use efficiency. Homeologous expression of NR 6-1ABD revealed negligible contribution of B-homeologue to N-stress. Homeologous differences of NR 6-1ABD was found much more than the genotypic differences. Hence, our study on wheat NR will be helpful in manipulating the specific homeologue of the NR gene in the future.

plant biology↗

bioRxiv2023

Unraveling the Interplay of Different Traits and Parameters Related to Nitrogen Use Efficiency in Wheat: Insights for Grain Yield Influence

Enhancing Nitrogen Use Efficiency (NUE) in wheat to optimize grain yield is a significant challenge. To address this challenge, a comprehensive study was conducted to investigate various morphological, biochemical, molecular parameters, and agronomic traits related to NUE. By examining various traits under both optimum-N (ON) and stressed-N (SN) conditions, the study explores the interrelationships among these traits, providing novel insights not previously reported. A set of 278 diverse wheat genotypes were assessed, encompassing eight NUE-related traits: Grain Yield, Biomass, Grain nitrogen, N at head, N at harvest, N-uptake, Nitrogen Uptake Efficiency, Nitrogen Utilization Efficiency, and NUE under both ON and SN conditions in the field. The findings demonstrated a significant positive correlation between grain yield and all NUE-related traits, highlighting their significance in comprehending the biological NUE of wheat plants. Notably, the study identified N-uptake and N-uptake related traits as key factors influencing the impact of soil nitrogen status on yield and associated parameters. These traits hold particular importance for selecting wheat genotypes with optimal yield and NUE in wheat cultivation. To complement the field data, representative genotypes were further subjected to a hydroponics experiment under absolute nitrogen control. This experiment provided insights into the effects of nitrogen stress on morphological parameters and the performance of eight essential nitrogen and carbon metabolizing enzymes. Correlation analysis highlighted the substantial influence of four key N-metabolizing enzymes, namely Nitrate Reductase, Glutamine Synthetase, Glutamate Oxo-Glutarate Amino Transferase, and Glutamate Dehydrogenase, on grain yield. Additionally, this study underscored the direct and indirect associations between seedling parameters and field traits, emphasizing the significance of shoot and root length parameters in nitrogen acquisition under nitrogen stress. In conclusion, these findings offer valuable insights into the intricate network of traits and parameters that influence wheat grain yield under varying nitrogen regimes. This knowledge can aid in the selection of wheat genotypes with enhanced NUE and grain yield, particularly in scenarios of reduced nitrogen application. Key PointsO_LIA comprehensive study in field and hydroponics conditions revealed differential responses of various morphological, biochemical, molecular parameters, and agronomic traits to different nitrogen levels. C_LIO_LIN-uptake related traits in field condition and chlorophyll content and morphological parameters in hydroponics condition were found as essential factors contributing to variations under both optimum and stressed N conditions. C_LIO_LIAmong the parameters observed in the seedling stage, SL and RL, along with the enzymes NR, GS, GOGAT, and GDH, demonstrated their influence on GY. C_LI

plant biology↗

bioRxiv2022

Impaired iron recycling from erythrocytes is an early iron-dependent hallmark of aging

Aging affects iron homeostasis, as evidenced by tissue iron loading and toxicity and common anemia in the elderly. Iron needs in mammals are met primarily by iron-recycling from senescent red blood cells (RBCs), a task chiefly accomplished by splenic red pulp macrophages (RPMs) via erythrophagocytosis. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a condition that has been largely unexplored to date. Here, we found that 10-11-months-old female mice exhibit iron loading, diminished lysosomal activity, and decreased erythrophagocytosis rate in RPMs. These impairments lead to the retention of senescent hemolytic RBCs in the spleen, and the formation of undegradable iron- and heme-rich extracellular protein aggregates, likely derived from ferroptotic RPMs. We further found that feeding mice an iron-reduced diet alleviates iron accumulation in RPMs, enhances their ability to clear erythrocytes, and limits ferroptosis. Consequently, this diet ameliorates hemolysis of splenic RBCs and the formation of iron-rich aggregates, increasing serum iron availability in aging mice. Using RPM-like cells, we show that the diminished iron-recycling capacity of RPMs is underlain by iron accumulation and reduced expression of heme-catabolizing enzyme heme oxygenase 1 (HO-1). Taken together, we identified RPM collapse as an early hallmark of aging and demonstrated that dietary iron reduction improves iron turnover efficacy.

physiology↗

bioRxiv2021

Comparison of seven modelling algorithms for GABA-edited 1H-MRS

Edited MRS sequences are widely used for studying GABA in the human brain. Several algorithms are available for modelling these data, deriving metabolite concentration estimates through peak fitting or a linear combination of basis spectra. The present study compares seven such algorithms, using data obtained in a large multi-site study. GABA-edited (GABA+, TE = 68 ms MEGA-PRESS) data from 222 subjects at 20 sites were processed via a standardised pipeline, before modelling with FSL-MRS, Gannet, AMARES, QUEST, LCModel, Osprey and Tarquin, using standardised vendor-specific basis sets (for GE, Philips and Siemens) where appropriate. After referencing metabolite estimates (to water or creatine), systematic differences in scale were observed between datasets acquired on different vendors hardware, presenting across algorithms. Scale differences across algorithms were also observed. Using the correlation between metabolite estimates and voxel tissue fraction as a benchmark, most algorithms were found to be similarly effective in detecting differences in GABA+. An inter-class correlation across all algorithms showed single-rater consistency for GABA+ estimates of around 0.38, indicating moderate agreement. Upon inclusion of a basis set component explicitly modelling the macromolecule signal underlying the observed 3.0 ppm GABA peaks, single-rater consistency improved to 0.44. Correlation between discrete pairs of algorithms varied, and was concerningly weak in some cases. Our findings highlight the need for consensus on appropriate modelling parameters across different algorithms, and for detailed reporting of the parameters adopted in individual studies to ensure reproducibility and meaningful comparison of outcomes between different studies. HighlightsO_LIGABA-edited MRS data from 222 healthy adults across 20 research sites were analyzed C_LIO_LIData were modelled using seven different algorithms, yielding GABA+ and Glx estimates C_LIO_LIModerate agreement was seen across all the tested algorithms C_LIO_LIAdding a component to represent co-edited macromolecule signals improved concordance C_LIO_LIBaseline modelling emerged as major factor differentiating outcomes C_LI

neuroscience↗

bioRxiv2020

Bacteriophage infection produces membrane vesicles in Escherichia coli via both explosive cell lysis and membrane blebbing

Membrane Vesicles (MVs) are membrane-bound spherical nanostructures that prevail in all three domains of life. In Gram-negative bacteria, MVs are thought to be produced through blebbing of the outer membrane and are often referred to as outer membrane vesicles (OMVs). We have recently described another mechanism of MV biogenesis in Pseudomonas aeruginosa that involves explosive cell lysis events which shatters cellular membranes into fragments that rapidly anneal into MVs. Interestingly, MVs are often observed within preparations of lytic bacteriophage, however the source of these MVs and their association with bacteriophage infection has not been explored. In this study we aimed to determine if MV biogenesis is associated with lytic bacteriophage infection. Live super-resolution microscopy demonstrated that explosive cell lysis of E. coli cells infected with either bacteriophage T4 or T7, produced MVs derived from shattered membrane fragments. Infection by either bacteriophage was also associated with the formation of membrane blebs on intact bacteria. TEM revealed multiple classes of MVs within phage lysates, consistent with multiple mechanisms of MV biogenesis. These findings suggest that bacteriophage infection may be a major contributor to the abundance of bacterial MVs in nature.

microbiology↗

bioRxiv2020

Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma

Retrotransposons are sequences which transpose within genomes using RNA as an intermediate. Long INterpersed Element-1 (LINE1 or L1) is the only active retrotransposon occupying around 17% of the human genome with an estimated 500,000 copies. An active L1 encodes two proteins (L1ORF1p and L1ORF2p); both of which are critical in the process of retrotransposition. In-order to propagate to the nextgeneration, L1s remain active in germ tissues and at an early stage of development. Surprisingly, by some unknown mechanism, L1 also shows activity in certain parts of the normal brain and many cancers. L1 activity is generally determined by assaying L1ORF1p because of its high expression and availability of the antibody. However, due to its lowerexpression and the unavailability of a robust antibody, detection of L1ORF2p has been limited. L1ORF2p is the crucial protein in the process of retrotransposition as it provides endonuclease and reverse transcriptase (RT) activity. Here, we report a novel human L1ORF2p antibody generated using an 80-amino-acid stretch from the RT domain, which is highly conserved among different species. The antibody detects significant L1ORF2p expression in murine germ tissues and human oral squamous cell carcinoma (OSCC) samples. This particular cancer is prevalent in India due to excessive use of tobacco. Here, using our in-house antibodies against L1 proteins, we show that more than fifty percent of samples are positive for L1 proteins. Overall, we reported a novel L1ORF2p antibody that detects L1 activity in germ tissues and OSCC

cancer biology↗

bioRxiv2018

HSCs contribute actively to native multilineage hematopoiesis but with reduced differentiation capacity upon aging

A hallmark of adult hematopoiesis is the continuous replacement of blood cells with limited lifespans. It is well established that adult hematopoietic stem cells (HSCs) are active contributors to these processes after transplantation, yet their role in native hematopoiesis has recently been called into question. Here, we use inducible lineage tracing from genetically marked adult HSCs to explore their roles in the steady state. We show that adult HSCs contribute robustly to all lineages via intermediate progenitor cells, but with neglible production of hematopoietic cells with a known fetal origin. We further reveal that the timing for regeneration of distinct blood lineages varies substantially. Finally, HSC contribution to multilineage hematopoiesis in aged animals declines with increasing age. Therefore, while HSCs are active contributors to native adult hematopoiesis, it appears that the numerical increase of HSCs is a physiologically relevant compensatory mechanism to account for a reduced differentiation capacity with age.

developmental biology↗