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Biology subjects

Rajkumar, R.

Publications and source records attributed to Rajkumar, R..

5 recordsLinked to original sources

Molecular profiling implicates immune-driven adaptive homeostasis in maintaining intraocular pressure with age

Aging and ocular hypertension are primary risk factors for glaucoma - a major cause of blindness worldwide. Ocular hypertension results from dysfunction in the outflow tissues - the trabecular meshwork (TM) and Schlemm's canal (SC), which are key regulators of intraocular pressure (IOP) homeostasis. Despite lifelong multifaceted stress to the outflow pathway, ocular hypertension sufficient to develop glaucoma occurs in only a minority of individuals. The mechanisms that preserve physiological IOP with aging in most individuals remain poorly understood. Using single-cell RNA sequencing and protein validation in mouse outflow tissues, we found that aging is accompanied by subtype-specific changes in TM cells, including altered extracellular matrix maintenance, reduced trophic signaling to SC, and increased profibrotic signaling. Coincident with these changes, we observed age-dependent immune remodeling, marked by increased macrophage abundance in outflow tissues. Our model predicts that macrophages maintain SC homeostasis via VEGFA signaling - normally supplied by the TM and required for normal SC function, but impaired with age. This pattern supports a paradigm in which adaptive immune remodeling contributes to preserving IOP homeostasis despite progressive aging-associated cellular dysfunction. More broadly, we identify the TM/SC outflow pathway as a model for understanding how aging tissues preserve physiological function through coordinated structural, trophic, and adaptive immune remodeling.

cell biology↗

Environmental correlates of tree reproductive phenology in a tropical state of India - insights from a citizen science project

Tropical tree reproductive phenology is sensitive to changing climate, but inter-individual and interannual variability at the regional scale is poorly understood. While large-scale and long-term datasets of environmental variables are available, reproductive phenology needs to be measured in-site, limiting the spatiotemporal scales of the data. We leveraged a unique dataset assembled by SeasonWatch, a citizen-science phenology monitoring programme in India to assess the environmental correlates of flowering in three ubiquitous and economically important tree species - jackfruit, mango and tamarind - in the south-western Indian state of Kerala. We explored (i) seasonal patterns in the flowering status of trees (ii) environmental correlates of flowering onset considering only trees with consecutive observations and (iii) spatiotemporal patterns in these environmental correlates to aid future hypotheses for changing phenology patterns. We used 165006 phenology observations spread over 19591 individual trees over 9 years. We first used bootstrapped circular statistics that accounts for observation biases in time to examine consistency in seasonality of flowering status over the whole season, and flowering onset across years and trees. Similar to results from cohort-based tree monitoring, we demonstrate seasonality in flowering status and onset across species, but also report large interannual and inter-individual variability. We then used used generalized linear mixed models with remotely sensed observations (ERA5-LAND) to show that some of the interannual variation in flowering onset across individuals was associated with environmental variables. Soil moisture, minimum temperature and solar radiation had significant associations with the onset of flowering but these effects were heterogeneous across species and habitats across Kerala. Our results become increasingly important in the face of large spatiotemporal change in the climate of this landscape and other tropical regions. We demonstrate the potential and limitations of citizen- science observations in making and testing predictions at scale for predictive climate science in tropical landscapes. Open Research StatementData are not yet provided. Environmental data used in this manuscript are from publicly available sources. All SeasonWatch data, the phenology data used in the manuscript, is licensed under the open-access creative commons license CC BY 4.0: https://creativecommons.org/licenses/by/4.0/ and is available upon request. Processed data and code used in this manuscript will be made publicly accessible through Zenodo upon acceptance of the manuscript. This manuscript does not use any novel code.

ecology↗

Modulation of the spontaneous brain activity and functional connectivity in the triple resting-state networks following the visual oddball paradigm

The default mode network (DMN), the salience network (SN), and the central executive network (CEN) could be considered as the core resting-state brain networks (RSN) due to their involvement in a wide range of cognitive tasks. Despite the large body of knowledge relating to their regional spontaneous activity (RSA) and functional connectivity (FC) of these networks, less is known about the influence of task-associated activity on these parameters and on the interaction between these three networks. We have investigated the effects of the visual-oddball paradigm on three fMRI measures (amplitude of low-frequency fluctuations for RSA, regional homogeneity for local FC, and degree centrality for global FC) in these three core RSN networks. A rest-task-rest paradigm was used and the RSNs were identified using independent component analysis (ICA) on the resting-state data. We found that the task-related brain activity induced different patterns of significant changes within the three RS networks. Most changes were strongly associated with the task performance. Furthermore, the task-activity significantly increased the inter-network correlations between the SN and CEN as well as between the DMN and CEN, but not between the DMN and SN. A significant dynamical change in RSA, alongside local and global FC within the three core resting-state networks following a simple cognitive activity may be an expression of the distinct involvement of these networks in the performance of the task and their various outcomes.

neuroscience↗

Excitatory-Inhibitory Balance within EEG Microstates and Resting-state fMRI Networks: Assessed via Simultaneous PET-MR-EEG Imaging

The symbiosis of neuronal activities and glucose energy metabolism is reflected in the generation of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) signals. However, their association with the balance between neuronal excitation and inhibition (E/I-B), which is closely related to the activities of glutamate and GABA ({gamma} -aminobutyric acid) and the receptor availability (RA) of GABAA and mGluR5, remains unexplored. This study investigates these associations during the resting state (RS) condition using simultaneously recorded PET/MR/EEG (trimodal) data. Glucose metabolism and neuroreceptor binding availability (non-displaceable binding potential (BPND)) of GABAA and mGluR5 were found to be significantly higher and closely linked within core resting-state networks (RSNs). The neuronal generators of EEG microstates and the fMRI measures were most tightly associated with the BPND of GABAA relative to mGluR5 BPND and the glucose metabolism, emphasising a predominance of inhibitory processes within in the core RSNs at rest.

neuroscience↗

Estrogen accelerates heart regeneration by promoting inflammatory responses in zebrafish

Sexual differences are observed in the onset and prognosis of human cardiovascular diseases, but the underlying mechanisms are not clear. Here, we report that zebrafish heart regeneration is faster in females, can be accelerated by estrogen and suppressed by estrogen-antagonist tamoxifen. Injuries to the heart, but not other tissues, increased plasma estrogen level and expression of estrogen receptors, especially esr2a, in zebrafish hearts. The resulting endocrine disruption induces the expression of female-specific protein vitellogenin in male zebrafish. Transcriptomic analyses suggested heart injuries triggered more pronounced immune and inflammatory responses in females. These responses, previously shown to enhance heart regeneration, could be enhanced by estrogen treatment in males and reduced by tamoxifen in female. Furthermore, a brief exposure to estrogen could precondition zebrafish for an accelerated heart regeneration. Altogether, this study reveals that heart regeneration is modulated by an estrogen-inducible inflammatory response to heart injury. These findings elucidate a previously unknown layer of control in zebrafish heart regeneration and provides a new model system for the study of sexual differences in human cardiac repair.

developmental biology↗