Biology subjects

Mohan, D.

Publications and source records attributed to Mohan, D..

12 recordsLinked to original sources

bioRxiv2025

Punarnavayolepa Choornam in Iron Deficiency Anaemia management: Pharmaceutic insights and biological activity.

Background and AimIndigenous medical systems employ unique pharmaceutical techniques to meet the therapeutic needs. In the Indian System of Medicine, Ayurveda, a unique method called "Ayolepam" is described that facilitates efficient iron absorption from its source to the formulation. Punarnavayolepa Choornam (PC), prepared from Boerhavia diffusa L., is one such novel Ayolepam formulation developed by a traditional Ayurveda school of South India, widely used in the clinical management of iron deficiency anaemia. This study aims at scientifically evaluating the Ayolepam technique by assessing the iron binding and bioavailability properties of PC, prepared from the leaves, root and whole plant of B. diffusa, using in-vitro model systems.. Experimental ProcedureThe iron content in both raw and processed samples of PC was quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). A simulated in-vitro digestion model employed to assess the release of bioavailable iron from the formulation. Subsequently, iron bioavailability was evaluated using the Caco-2 cell model of human intestinal epithelium following the ferrozine method. Results and ConclusionPC preparation from leaves, whole plant and roots of B. diffusa, showed significant increase in iron content compared to the raw material. In-vitro digestion studies confirmed the efficient release of bioavailable iron from these formulations, and subsequent Caco-2 cell assays confirmed their iron bioavailability properties. In conclusion, these findings provide a preliminary scientific basis for this novel and unique pharmaceutical design from a traditional school of Ayurveda, supporting its clinical application.

pharmacology and toxicology↗

bioRxiv2024

Non-canonical Wnt signaling triggered by WNT2B drives adrenal aldosterone production

The steroid hormone aldosterone, produced by the zona glomerulosa (zG) of the adrenal gland, is a master regulator of plasma electrolytes and blood pressure. While aldosterone control by the renin-angiotensin system is well understood, other key regulatory factors have remained elusive. Here, we replicated a prior association between a non-coding variant in WNT2B and an increased risk of primary aldosteronism, a prevalent and debilitating disease caused by excessive aldosterone production. We further show that in both mice and humans, WNT2B is expressed in the mesenchymal capsule surrounding the adrenal cortex, in close proximity to the zG. Global loss of Wnt2b in the mouse results in a dysmorphic and hypocellular zG, with impaired aldosterone production. Similarly, humans harboring WNT2B loss-of-function mutations develop a novel form of Familial Hyperreninemic Hypoaldosteronism, designated here as Type 4. Additionally, we demonstrate that WNT2B signals by activating the non-canonical Wnt/planar cell polarity pathway. Our findings identify WNT2B as a key regulator of zG function and aldosterone production with important clinical implications. HighlightsO_LIWNT2B variant is associated with increased risk for primary aldosteronism C_LIO_LIWnt2b knock-out mice show defects in adrenal morphology C_LIO_LIWnt2b knock-out mice have hyperreninemic hypoaldosteronism C_LIO_LIWNT2B activates non-canonical Wnt/planar cell polarity signaling C_LIO_LIWNT2B deficiency causes a new form of familial hyperreninemic hypoaldosteronism C_LI

genetics↗

bioRxiv2023

Functional connectivity in northern swamp deer (Rucervus duvaucelii duvaucelii) population across a fragmented, human-dominated landscape along Gangetic Plains of north India: Implications for conservation in non-protected areas

The Indian subcontinent has witnessed disproportionate declines in large mammalian herbivore communities. The northern swamp deer (Rucervus duvaucelii duvaucelii) exemplifies the conservation challenges of typical non-protected area species, where apart from distribution status other ecological information is limited for the upper Gangetic basin population. We combined elements of radio-telemetry and conservation genetics to evaluate dispersal patterns, population connectivity and assess genetic variation and inbreeding status of this population living across a highly human-dominated area. We genetically identified 266 unique swamp deer and further analyses revealed presence of two spatially-admixed genetic lineages with moderate heterozygosity (Ho=0.51, SD= 0.10) and low inbreeding (FIS=0.133) status. Multi- disciplinary evidence suggests that the small, isolated grassland patches between Jhilmil Jheel Conservation Reserve (JJCR) and Hastinapur Wildlife Sanctuary (HWLS) are highly preferred by swamp deer during migrations and are genetically connected. The southern part of the area in HWLS showed early signatures of genetic discontinuity that require immediate conservation attention. We hypothesized that the human settlement history of this landscape, river dynamics and species ability to negotiate various pressures and disperse has helped to maintain such connectivity. While these signatures are encouraging for this small, isolated cervid population, careful management interventions are required to ensure the integrity and functionality of this landscape. We recommend a scientifically robust population estimation approach across this landscape and a multi-stakeholder-driven strategies to augment population and habitat recovery, plantation and riverscape management to ensure long-term survival of this species.

ecology↗

bioRxiv2022

Broadly neutralizing antibodies target the coronavirus fusion peptide

The potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2 cleavage site. Two antibodies, COV44-62 and COV44-79, broadly neutralize a range of alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.1 and BA.2, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2 cleavage site. Importantly, COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings identify the fusion peptide as the target of the broadest neutralizing antibodies in an epitope-agnostic screen, highlighting this site as a candidate for next-generation coronavirus vaccine development. One-Sentence SummaryRare monoclonal antibodies from COVID-19 convalescent individuals broadly neutralize coronaviruses by targeting the fusion peptide.

immunology↗

bioRxiv2021

Waning grasslands: a quantitative temporal evaluation of the grassland habitats across human-dominated upper Gangetic Plains, north India

Grassland habitats currently face severe anthropogenic exploitations leading to cascading effects on the survival of grassland-dependent biodiversity globally, particularly in non-protected areas. Significant amount of such biodiversity-rich grasslands in India are found outside protected areas but lack quantitative information on their status. We evaluated the current and historical (30 years) status of the grasslands using a combination of intensive field surveys and GIS tools across one of the most fertile, human-dominated region: the upper Gangetic Plains of north India. On-ground mapping and visual classifications revealed 57% decline in grassland habitats between 1985 (418 km2) and 2015 (178km2), mostly driven by conversion to croplands (74% contribution). Radio-telemetry data from the largest endemic cervid swamp deer (n=2) showed grassland-dominated average home range (50% BBMM) size of 1.02 km2. The animals highly preferred these patches (average Ivlevs index- 0.85) and showed highest temporal continuity (88%) compared to other LULC classes. Camera trapping within the core habitats suggests critical use of these patches as fawning/breeding grounds. Habitat suitability analysis indicates only [~]18% of the entire area along Ganges is suitable for swamp deer. Accurate mapping (86% accuracy) and characterization of four major grass species revealed a total 144.04 km{superscript 2} vegetation area, dominted by Saccharum sp. (35%). We recommend protection and recovery of these critical grassland patches to maintain dynamic corridors and other appropriate management strategies involving multiple stakeholders to ensure survival of this critical ecosystem. Such evaluations, if spatially expanded, would be critical to restore this rapidly vanishing ecosystem worldwide.

ecology↗

bioRxiv2021

Avian haemosporidians (Plasmodium and Haemoproteus) in selected bird groups (Old world Flycatchers, Warblers, Babblers, and Thrushes) of India and their phylogenetic relationships with other lineages of the world

The avian haemosporidians (Plasmodium and Haemoproteus) are widely distributed and may affect the host populations from body damage at individual level to the extinction of a population. The knowledge about their status may help in future avifauna conservation plans. Hence, we examined the avian haemosporidians status, in selected bird groups (Old world Flycatchers, Warblers, Babblers, and Thrushes) of India, and their phylogenetic relationships with other known lineages of the world. We used the common genetic marker (Cytochrome b gene fragment of 479 bp) with information on the geographic distribution of parasite and host species available at MalAvi database. The prevalence of avian haemosporidians, from northern, eastern, and southern parts of India and phylogenetic genetic analysis of lineages was carried out to know the genetic relatedness among them at local and world level. The MCC tree revealed six Haemosporidian lineages in which one was common (H_MSP01) and five were unique (H_CYOPOL01, H_CHD01, H_CYORUB01, H_EUMTHA01, and P_GEOCIT01). The avian host richness Index was 2.0852. 9.9%, prevalence of Haemosporidian infection was found in 111 DNA samples belonging to 6 host species. The Haemoproteus prevalence was found to be 9.0 % across five host species (Phylloscopus trochiloides, Cyornis poliogenys, C. hainanus dialilaemus, C. rubeculoides, Eumiyas thalassinus) and Plasmodium prevalence was 0.9% in Geokichla citrina. Spatial phylogeny at global level showed H_MSP01 lineage, found in different host species in India, was genetically related to H. pallidus lineages (COLL2 and PFC1) in parts of Africa, Europe, North America, Malaysia, and Philippines. The Plasmodium lineage (P_GEOCIT01) was related to PADOM16 in Egypt with poor sequence similarity (93.89%). The statistical analysis suggested that the haemosporidians host species distribution range was directly and significantly associated with the altitude, minimum temperature, and relative humidity. H_MSP01 distribution was in accordance with H. pallidus having a wide geographic and host range.

genetics↗

bioRxiv2021

An innovative approach for determining composite wheat quality index to identify quality enriched genotypes - insights and implications

Ranking test entries or test sites on a quality basis is very difficult in wheat as value addition is perceived by several grain properties and end-products. Here, a novel approach has been developed and tested by deriving wheat quality index based on principal component analysis of 13 physico-chemical grain parameters and 3 end products of 45 wheat varieties. Depending upon the observed index range (0.15 to 0.71), the cultivars were assorted into 3 distinct classes i.e. elite, moderate and poor. The top group ascertained high quality standards of grain suited for bread and chapati whereas bottom group assured better cookies quality. This technique was also tested to differentiate quality enriched test sites within a zone or demarcate the most suited production environments to harness good quality wheat. The index will have an implication on farmers (premium price for varietal segregation), industry (product specific quality cultivars), and consumers (superior quality products).

biochemistry↗

bioRxiv2021

Disentangling the effects of past logging and ongoing cryptic anthropogenic disturbance on vegetation structure and composition in Himalayan Foothills, India

Most tropical forests have undergone commercial logging. Even where logging has ceased, subsistence harvest of forest resources often persists especially in South-East Asia. Understanding of impacts of frequent forest resources extraction in areas recovering from past selective logging would be essential for designing the appropriate management interventions. We studied the impacts of current chronic anthropogenic disturbances (hereafter CAD) and past selective logging on vegetation structure, diversity, and regeneration, and the invasion of a non-native shrub, Lantana camara, in three major forest types in the Himalayan foothills, India. We analyzed field data on intensity of CAD and vegetation variables, collected from 269 stratified random plots, using ordination and generalized linear (mixed) modeling approaches. Our results, based on 2758 adult trees of 54 species, showed that forest types differed in disturbance regimes depending on protection level and availability of fodder tree species. Intensity of CAD depended on proximity to settlements (for livestock related disturbances). Whereas selective logging, including firewood collection, was associated with land protection status. Selective logging reduced the extent of mature forest but facilitated regeneration, thereby promoting secondary forest features such as tree density and canopy cover. In contrast, the interaction between lopping and selective logging was negatively associated with regeneration. Past logging facilitated L. camara invasion in Dry and Hill forests but not in Moist forest. Finally, while selective logging marginally enhanced tree diversity, CAD reduced native shrub diversity. Our study demonstrates that selective logging followed by CAD arrest forest recovery, as evident from the suppression of mature forest elements, loss of shrub biomass, reduced regeneration rate, and facilitation of invasive species. To abate these impacts, alternative livelihood/subsistence options that sustain forests and local communities should be explored. Additionally, CAD management should be site-specific as local ecological contexts modify their impacts on forests.

ecology↗

bioRxiv2020

Can crop phenology and plant height be channelized to improvise wheat productivity in diverse production environments?

Non-grain parameters like height, flowering and maturity should also be tried to break yield plateau in wheat. This study explores such possibilities by analysing performance of released and pre-released varieties evaluated in ten diverse production environments of India during the period 2000-2020. Regression analysis supports relevance of such non-grain determinants in grain yield under every environment but magnitude of impact can vary. Collective contribution of non-grain parameters can be high in a production environment where growth condition is most favourable for wheat growth and every factor is important in such situations. They contribute less in the environments engrossed with abiotic stress and merely one or two factors can be earmarked for selection. Besides yield, this selection strategy can also enhance grain weight in certain environments. At a time when selection for grain attributes is not providing further push; it would be worth trying to explore these non-grain field indicators as selection strategy for further advancement in productivity and grain weight of bread wheat.

developmental biology↗

bioRxiv2020

Circulating adiponectin mediates the association between omentin gene polymorphism and cardiometabolic health in Asian Indians

BackgroundPlasma omentin levels have been shown to be associated with circulating adiponectin concentrations and cardiometabolic disease-related outcomes. However, the findings have been inconsistent due to high level of confounding. In this study, we aim to examine the association of omentin gene polymorphism with plasma adiponectin levels and cardiometabolic health status using a genetic approach, which is less prone to confounding, and investigate whether these associations are modified by lifestyle factors such as diet and physical activity. MethodsThe study included 945 normal glucose tolerant and 941 unrelated individuals with type 2 diabetes randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Study participants were further classified into cardiometabolically healthy and unhealthy, where cardiometabolically healthy were those without hypertension, diabetes, and dyslipidemia. Fasting serum adiponectin levels were measured by radioimmunoassay. The A326T (rs2274907) single nucleotide polymorphism (SNP) in the exon 4 of the omentin gene was screened by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. ResultsThe A allele of the omentin SNP was significantly associated with lower adiponectin concentrations after adjusting for age, sex, body mass index (BMI), waist circumference (WC) and cardiometabolic health status (p=1.90 x 10-47). There was also a significant association between circulating adiponectin concentrations and cardiometabolic health status after adjusting for age, sex, BMI, WC and Omentin SNP (p=7.47x10-10). However, after adjusting for age, sex, BMI, WC and adiponectin levels, the association of A allele with cardiometabolic health status disappeared (p=0.79) suggesting that adiponectin serves as a mediator of the association between omentin SNP and cardiometabolic health status. There were no significant interactions between the SNP and dietary factors on adiponectin levels and cardiometabolic health status (p>0.25, for all comparisons). ConclusionsOur findings show that adiponectin might function as a mechanistic link between omentin SNP and increased risk of cardiometabolic diseases independent of common and central obesity in this Asian Indian population. Further studies are required to confirm the molecular mechanisms involved in this triangular relationship between omentin gene, adiponectin and cardiometabolic diseases.

genetics↗

bioRxiv2020

The aggregate effect of implementation strength of family planning programs on modern contraceptive use at the health systems level in rural Malawi

Background To explore the association between the strength of implementation of family planning (FP) programs on the use of modern contraceptives. Specifically, how strongly these programs are being implemented across a health facility’s catchment area in Malawi and the odds of a woman in that catchment area is using modern contraceptives. This information can be used to assess whether the combined impact of multiple large-scale FP programs is leading to change in the health outcomes they aim to improve.Methods and findings We used data from the 2017 Implementation Strength Assessment (ISA) that quantified how much of family planning programs at the health facility and community health worker levels were being implemented across every district of Malawi. We used a summary measure developed in a previous study that employs quantitative methods to combine data across FP domains and health system levels. We tested the association of this summary measure for implementation strength with household data from the 2015 Malawi Demographic Health Survey (DHS). We found that areas with stronger implementation of FP programs had higher odds of women using modern contraceptives compared with areas with weaker implementation. The association of ISA with use of modern contraception was different by education, marital status, and geography. After controlling for these factors, we found that the adjusted odds of using a modern contraceptive was three times higher in catchment areas with high implementation strength compared to those with lower strength.Conclusion Metrics that summarize how strongly FP programs are being implemented were used to show a statistically significantly positive relationship between increasing implementation strength and higher rates of modern contraceptive use. Decisionmakers at the various levels of health authority can use this type of summary measure to better understand the combined impact of their diverse FP programming and inform future programmatic and policy decisions. The findings also reinforce the idea that having a well-supported and supplied cadre of community health workers supplementing FP provision at the health facility can be an important health systems mechanism, especially in rural settings and to target youth populations.View Full Text

scientific communication and education↗

bioRxiv2018

Improved Analysis of Phage ImmunoPrecipitation Sequencing (PhIP-Seq) Data Using a Z-score Algorithm

Phage ImmunoPrecipitation Sequencing (PhIP-Seq) is a massively multiplexed, phage-display based methodology for analyzing antibody binding specificities, with several advantages over existing techniques, including the uniformity and completeness of proteomic libraries, as well as high sample throughput and low cost. Data generated by the PhIP-Seq assay are unique in many ways. The only published analytical approach for these data suffers from important limitations. Here, we propose a new statistical framework with several improvements. Using a set of replicate mock immunoprecipitations (negative controls lacking antibody input) to generate background binding distributions, we establish a statistical model to quantify antibody-dependent changes in phage clone abundance. Our approach incorporates robust regression of experimental samples against the mock IPs as a means to calculate the expected phage clone abundance, and provides a generalized model for calculating each clones expected abundance-associated standard deviation. In terms of bias removal and detection sensitivity, we demonstrate that this z-score algorithm outperforms the previous approach. Further, in a large cohort of autoantibody-defined Sjogrens Syndrome (SS) patient sera, PhIP-Seq robustly identified Ro52, Ro60, and SSB/La as known autoantigens associated with SS. In an effort to identify novel SS-specific binding specificities, SS z-scores were compared with z-scores obtained by screening Ropositive sera from patients with systemic lupus erythematosus (SLE). This analysis did not yield any commonly targeted SS-specific autoantigens, suggesting that if they exist at all, their epitopes are likely to be discontinuous or post-translationally modified. In summary, we have developed an improved algorithm for PhIP-Seq data analysis, which was validated using a large set of sera with clinically characterized autoantibodies. This z-score approach will substantially improve the ability of PhIP-Seq to detect and interpret antibody binding specificities. The associated Python code is freely available for download here: https://github.com/LarmanLab/PhIP-Seq-Analyzer.

bioinformatics↗