Biology subjects

Halder, T.

Publications and source records attributed to Halder, T..

4 recordsLinked to original sources

bioRxiv2026

Prime editing of an evolutionarily informed PEPC residue enhances photosynthesis and grain nutrition in C₃ rice

C4 photosynthesis evolved through adaptive changes in key metabolic enzymes that enhance carbon fixation efficiency, yet transferring such traits into C3 crops has met limited success. Using precision prime editing, we introduced an evolutionarily conserved single amino acid substitution (Arg[->]Gly) into phosphoenolpyruvate carboxylase (PEPC) in rice. Edited plants exhibited enhanced PEPC activity in the presence of the feedback inhibitor malate, increased chlorophyll content, elevated photosynthetic rates under ambient CO2, and increased seed size and weight. Remarkably, seeds from the edited lines showed simultaneous enrichment of zinc (Zn), iron (Fe), and protein, hereafter referred to as ZiP rice. This work demonstrates that a single, evolutionarily guided residue change can reprogram core carbon metabolism in a C3 crop, enabling concurrent improvements in photosynthesis and grain nutritional quality.

plant biology↗

bioRxiv2025

Development of a Stable Human iPSC Line from Peripheral Blood: A Control Resource for Disease Modeling

IntroductionTraditional disease modeling approaches have primarily utilized animal models and immortalized cell lines to investigate disease mechanisms and develop therapeutic strategies. However, previous research indicates that only about 5% of therapeutic interventions tested in animal models eventually receive regulatory approval for human use, highlighting limitations. The discovery of human-induced pluripotent stem cells (iPSCs) by Yamanakas team in 2007 has revolutionized the field with remarkable possibilities for modeling human diseases, drug testing, and regenerative medicine. Differentiated cells derived from iPSCs in two-dimensional (2D) monolayers offer a relatively straightforward system to study disease pathogenesis and underlying molecular mechanisms. ObjectiveThe present study aimed to generate and characterize an induced pluripotent stem cell (iPSC) line from peripheral blood mono-nuclear cells (PBMCs) of a healthy individual intending to serve as an age and gender-matched control for future disease modeling and regenerative medicine research. Materials and MethodsPBMCs were isolated from a healthy 31-year-old male volunteer. Somatic reprogramming was performed using episomal vectors expressing OCT3/4, SOX2, KLF4, and L-MYC. The resulting colonies were cultured and characterized for pluripotency markers by immunocytochemistry demonstrating the ability to differentiate into three germ layers. Karyotype analysis was performed to check the chromosomal abnormalities. InferencesThe resulting iPSC line exhibited pluripotency markers with the differentiation ability into three germ layers. Karyotyping analysis confirmed a normal chromosomal profile in both the donor and the reprogrammed iPSC line. This iPSC line could be a valuable resource as a healthy control for disease modeling and will contribute to advancing stem cell research with potential for regenerative medicine applications.

molecular biology↗

bioRxiv2023

High-throughput single-cell phenotypic profiling and backtracing exposes and predicts clinically relevant subpopulations in isogenic Staphylococcus aureus communities.

Isogenic bacterial cell populations are phenotypically heterogenous and may include subpopulations of antibiotic tolerant or heteroresistant cells. The reversible nature of these phenotypes and lack of biomarkers to differentiate functionally different, but morphologically identical cells is a challenge for research and clinical detection. To overcome this, we present Cellular Phenotypic Profiling and backTracing (CPPT), a flexible fluorescence-activated cell sorting platform, that uses optical probes to visualize and quantify cellular traits and connects the resulting phenotypic profile with a cells experimentally determined fate in single cell-derived growth and antibiotic susceptibility analysis. By applying CPPT on Staphylococcus aureus populations we recorded phenotypic signatures for dormant cells, exposed microanatomy-independent bimodal growth patterns in colony-derived cells, and revealed different culturability of single cells on solid compared to liquid media. We demonstrate that vancomycin-bodipyFL marks cellular subpopulations with increased likelihood to survive antibiotic exposure, showcasing the value of CPPT for discovery of clinically relevant biomarkers.

microbiology↗

bioRxiv2018

Performance evaluation of inverse methods for identification and characterization of oscillatory brain sources: Ground truth validation & empirical evidences

Oscillatory brain electromagnetic activity is an established tool to study neurophysiological mechanisms of human behavior using electro-encephalogram (EEG) and magneto-encephalogram (MEG) techniques. Often, to extract source level information in the cortex, researchers have to rely on inverse techniques that generate probabilistic estimation of the cortical activation underlying EEG/ MEG data from sensors located outside the body. State of the art source localization methods using current density estimates such as exact low resolution electromagnetic tomography (eLORETA) and minimum norm estimates (MNE) as well as beamformers such as Dynamic Imaging of Coherent Sources (DICS) and Linearly Constrained Minimum Variance (LCMV) have over the years been established as the prominent techniques of choice. However, these algorithms produce a distributed map of brain activity underlying sustained and transient responses during neuroimaging studies of behavior. Furthermore, the volume conduction effects, phase lags between sources and noise of the environment play a considerable role in adding uncertainty to source localization. There are very few comparative analyses that evaluates the \"ground truth detection\" capabilities of these methods and evaluates their efficacies based on sources in temporal cortex relevant for auditory processing as well as mesial temporal lobe epilepsies. In this Methods article, we compare the aforementioned techniques to estimate sources of spectral event generators in the cortex using a two-pronged approach. First, we simulated EEG data with point dipole (single and two-point), as well as, distributed dipole modelling techniques to validate the accuracy and sensitivity of each one of these methods of source localization. The abilities of the techniques were tested by comparing the localization error, focal width, false positive ratios while detecting already known location of neural activity generators under varying signal to noise ratios and depths of sources from cortical surface. Secondly, we performed source localization on empricial EEG data collected from human participants while they listened to rhythmic tone stimuli binaurally. Importantly, we found a less-distributed activation map is generated by LCMV and DICS when compared to eLORETA. However, control of false positives is much superior in eLORETA especially while using realistic distributed dipole scenarios. We also highlight the strengths and drawbacks of eLORETA, LCMV and DICS following a comprehensive analysis of simulated and empirical EEG data.

neuroscience↗