Biology subjects

Aluru, N.

Publications and source records attributed to Aluru, N..

7 recordsLinked to original sources

bioRxiv2026

The effects of elevated seawater pH and total alkalinity following dosing of sodium hydroxide in Calanus finmarchicus

Ocean Alkalinity Enhancement (OAE) is a marine carbon dioxide removal (mCDR) strategy that involves adding alkaline substances to surface waters to enhance CO2 uptake and storage. The dispersal of alkaline materials such as sodium hydroxide (NaOH) into seawater can cause rapid increases in pH and total alkalinity (TA) that substantially exceeds natural variability in marine environments. Such fluctuations may negatively affect marine life, especially small animals like copepods who cannot avoid OAE plumes and whose physiological processes could be disrupted by large and rapid shifts in seawater pH. To address knowledge gaps regarding potential biological impacts of OAE, we studied these effects in Calanus finmarchicus, a keystone copepod species in the Northwest Atlantic Ocean. We exposed C. finmarchicus from the late juvenile copepodite stages and adult females to NaOH-dosed seawater at pH 10.5 ([~]5,000 {micro}mol kg-1 TA) and pH 9.0 ([~]3,150 {micro}mol kg-1 TA) for durations that reflect expected short-term exposure times during field OAE deployments (pH 10.5: 1, 5, 10 minutes; pH 9.0: 1, 15, 30 minutes). None of the treatment combinations resulted in mortality immediately after the initial exposure. Individuals were monitored for survival for 72 hours post-exposure (hpe), and only one treatment group (juveniles exposed to pH 10.5 for 10 minutes) showed a significant reduction in final survival; no other pH-duration combination showed increased mortality. Effects on the ability to initiate an escape response were more substantial. Adult females treated with pH 10.5 for 5 or 10 minutes showed a significant reduction in escape response immediately after exposure. In contrast, juveniles showed no immediate change in escape response following exposure to pH 10.5 or pH 9.0, although juveniles exposed to pH 10.5 for 10 minutes exhibited reduced escape response at 24 hpe. Using microrespirometry, we measured oxygen consumption following a 10-minute exposure to pH 10.5 and detected no effect on routine metabolic rate immediately post-exposure or at 12 hpe. Overall, our results suggest that C. finmarchicus is relatively tolerant to short-term exposures to very high pH and alkalinity. Future work should prioritize longer-term exposure under more moderate ocean OAE conditions.

ecology↗

bioRxiv2024

Gene expression and DNA methylation changes in response to hypoxia in toxicant-adapted Atlantic killifish (Fundulus heteroclitus)

Coastal fish populations are threatened by multiple anthropogenic impacts, including the accumulation of industrial contaminants and the increasing frequency of hypoxia. Some populations of the Atlantic killifish (Fundulus heteroclitus), like those in New Bedford Harbor (NBH), Massachusetts, have evolved a resistance to dioxin-like polychlorinated biphenyls (PCBs) that may influence their ability to cope with secondary stressors. To address this question, we compared hepatic gene expression and DNA methylation patterns in response to mild or severe hypoxia in killifish from NBH and Scorton Creek (SC), a reference population from a relatively pristine environment. We hypothesized that NBH fish would show altered responses to hypoxia due to trade-offs linked to toxicant resistance. Our results revealed substantial differences between populations. SC fish demonstrated a dose-dependent changes in gene expression in response to hypoxia, while NBH fish exhibited a muted transcriptional response to severe hypoxia. Interestingly, NBH fish showed significant DNA methylation changes in response to hypoxia, while SC fish did not exhibit notable epigenetic alterations. These findings suggest that toxicant-adapted killifish may face trade-offs in their molecular response to environmental stress, potentially impacting their ability to survive severe hypoxia in coastal habitats. Further research is needed to elucidate the functional implications of these epigenetic modifications and their role in adaptive stress responses. Summary StatementThis study reveals how evolved resistance to toxicants in killifish may compromise their ability to respond to hypoxia, highlighting trade-offs that impact survival in stressed coastal environments.

physiology↗

bioRxiv2024

Cross-generational plasticity in Atlantic silversides (Menidia menidia) under the combined effects of hypoxia and acidification

We investigated the potential for cross-generational plasticity to influence how offspring respond to hypoxia and ocean acidification (hereafter HypOA) in the coastal forage fish Atlantic silverside (Menidia menidia). Mature wild silversides were treated with a control [dissolved oxygen (DO):100% air saturation (a.s.) / pCO2: 650 {micro}atm] or HypOA conditions [DO: 40% a.s. / pCO2: 2300 {micro}atm] for 10 days prior to spawning. Their offspring were reared under both treatments in factorial experimental design. Parental acclimation to HypOA altered several offspring traits, including increased embryo survival under HypOA and an overall reduction in post-hatch growth rate. Offspring from HypOA-treated parents that were reared under control conditions had larger eyes across the developmental period. When compared against the overall control group, larvae directly exposed to HypOA exhibited 2,416 differentially expressed transcripts (DETs). Although most of these DETs were specific to individual parental treatments, the most enriched Gene Ontology terms were conserved across parental treatments, including terms related to neurotransmitter secretion, nervous system development, axon pathfinding, calcium channel activity, proteolysis, and extracellular matrix organization. Larvae from HypOA-treated parents that were reared under control conditions exhibited a shift in constitutive gene expression similar to that seen in larvae directly exposed to HypOA. This highly consistent finding indicates that parental acclimation before fertilization promotes the transcriptional frontloading of genes in offspring. This effect may have primed regulatory functions in offspring that sense and respond to low DO and elevated pCO2 conditions. Though, our results suggest that this altered developmental phenotype may have some negative fitness consequences for offspring.

ecology↗

bioRxiv2022

Developmental exposure to domoic acid targets reticulospinal neurons and leads to aberrant myelination in the spinal cord

Harmful algal blooms (HABs) produce neurotoxins that affect human health. Developmental exposure of zebrafish embryos to the HAB toxin domoic acid (DomA) causes myelin defects, loss of reticulospinal neurons, and behavioral deficits. However, it is unclear whether DomA primarily targets myelin sheaths, leading to the loss of reticulospinal neurons, or reticulospinal neurons, causing myelin defects. Here, we show that while exposure to DomA at 2 dpf did not reduce the number of oligodendrocyte precursors prior to myelination, it led to fewer myelinating oligodendrocytes that produced shorter myelin sheaths and aberrantly wrapped neuron cell bodies. DomA-exposed larvae lacked Mauthner neurons prior to the onset of myelination, suggesting that axonal loss is not secondary to myelin defects. The loss of the axonal targets may have led oligodendrocytes to inappropriately myelinate neuronal cell bodies. Consistent with this, GANT61, which reduces oligodendrocyte number, caused a reduction in aberrantly myelinated neuron cell bodies in DomA-exposed fish. Together, these results suggest that DomA initially alters reticulospinal neurons and the loss of axons causes aberrant myelination of nearby cell bodies. The identification of initial targets and perturbed cellular processes provides a mechanistic understanding of how DomA alters neurodevelopment, leading to structural and behavioral phenotypes.

pharmacology and toxicology↗

bioRxiv2020

PCB126 exposure revealed alterations in m6A RNA modifications in transcripts associated with AHR activation

Chemical modifications of proteins, DNA and RNA moieties play critical roles in regulating gene expression. Emerging evidence suggests these RNA modifications (epitranscriptomics) have substantive roles in basic biological processes. One of the most common modifications in mRNA and noncoding RNAs is N6-methyladenosine (m6A). In a subset of mRNAs, m6A sites are preferentially enriched near stop codons, in 3 UTRs, and within exons, suggesting an important role in the regulation of mRNA processing and function including alternative splicing and gene expression. Very little is known about the effect of environmental chemical exposure on m6A modifications. As many of the commonly occurring environmental contaminants alter gene expression profiles and have detrimental effects on physiological processes, it is important to understand the effects of exposure on this important layer of gene regulation. Hence, the objective of this study was to characterize the acute effects of developmental exposure to PCB126, an environmentally relevant dioxin-like PCB, on m6A methylation patterns. We exposed zebrafish embryos to PCB126 for 6 hours starting from 72 hours post-fertilization and profiled m6A RNA using methylated RNA immunoprecipitation followed by sequencing (MeRIP-seq). Our analysis revealed 117 and 217 m6A peaks in the DMSO and PCB126 samples (FDR 5%), respectively. The majority of the peaks were preferentially located around the 3UTR and stop codons. Statistical analysis revealed 15 m6A marked transcripts to be differentially methylated by PCB126 exposure. These include transcripts that are known to be activated by AHR agonists (e.g., ahrra, tiparp, nfe2l2b) as well as others that are important for normal development (vgf, cebpd, foxi1). These results suggest that environmental chemicals such as dioxin-like PCBs could affect developmental gene expression patterns by altering m6A levels. Further studies are necessary to understand the functional consequences of exposure-associated alterations in m6A levels.

pharmacology and toxicology↗

bioRxiv2020

Computational Recipe for Designing Antibodies against the Ebola Virus

A conceptual basis for antiviral therapy is to deliver a synthetic antibody that binds to a viral surface protein, and thus prevents the virus from deploying its cell-entry mechanism. The fast and untraceable virus mutations take lives of thousands of people before the immune system can produce the inhibitory antibody. In this paper, we devised a computational recipe to predict both the viral escape mutations and the possible inhibitory synthetic antibodies. We combined bioinformatics, structural biology, and molecular dynamics (MD) simulations to explore the most likely viral mutations and the candidate antibodies that can inhibit those escape mutations. Specifically, using the crystal structures of the Sudan and Zaire Ebola viral GPs in complex to their respective antibodies (ABs), we have performed an extensive set of MD simulations, both on the wild-type structures and on a large array of additional complexes designed and generated through combinatorial mutations. We discovered that our methods enabled the successful redesign of antibody sequences to essentially all likely glycoprotein mutations. Our findings and the computational methodology developed here for general antibody design can facilitate therapy of current and possibly next generations of viruses. Significance of the ManuscriptThis manuscript has high significance both methodologically and in potential biomedical application. In methodology, the manuscript combines molecular dynamics, Monte Carlo calculations, and bioinformatics in a novel way to simulate the evolutionary arms race between an evolving viral coat protein and a counter-evolving antibody against the virus. This simulation is shown to provide a method for designing a synthetic antibody against the newly emerging viral strains. This work is done in the context of ongoing work in other laboratories in which cells can be induced to produce synthetic antibodies and those synthetic antibodies can be edited (via, for example, CRISPR) to have an arbitrary sequence in the region that binds the viral coat protein. Putting those experimental methods together with the computational methods we present in this paper has the potential to provide a important approach to produce antibodies-on-demand against evolving viruses.

immunology↗

bioRxiv2019

Domoic acid disruption of neurodevelopment and behaviorinvolves altered myelination in the spinal cord

Harmful algal blooms (HABs) produce potent neurotoxins that threaten human health. Early life exposure to low levels of the HAB toxin domoic acid (DomA) produces long-lasting behavioral deficits, but the mechanisms involved are unknown. Using zebrafish, we investigated the developmental window of susceptibility to low doses of DomA and examined cellular and molecular targets. Larvae exposed to DomA at 2 days post-fertilization (dpf), but not at 1 or 4 dpf, showed consistent deficits in startle behavior including reduced responsiveness and altered kinematics. Similarly, myelination in the spinal cord was disorganized after exposure only at 2 dpf. Time-lapse imaging revealed disruption of the initial stages of myelination. DomA down-regulated genes required for maintaining myelin structure and the axonal cytoskeleton. These results identify a developmental window of susceptibility to DomA-induced behavioral deficits involving altered gene expression and disrupted myelin structure, and establish a zebrafish model for investigating the underlying mechanisms. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=34 SRC="FIGDIR/small/842294v1_ufig1.gif" ALT="Figure 1"> View larger version (8K): org.highwire.dtl.DTLVardef@198491org.highwire.dtl.DTLVardef@14e6e84org.highwire.dtl.DTLVardef@39d118org.highwire.dtl.DTLVardef@1cea6c7_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗