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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Advanced genomics identifies growth effectors for proteotoxic ER stress recovery in Arabidopsis thaliana

Abstract Adverse environmental and pathophysiological situations can overwhelm the biosynthetic capacity of the endoplasmic reticulum (ER), igniting a potentially lethal condition known as ER stress. ER stress hampers growth and triggers a conserved cytoprotective signaling cascade, the unfolded protein response (UPR) for ER homeostasis. As ER stress subsides, growth is resumed. Despite the pivotal role of the UPR in growth restoration, the underlying mechanisms for growth resumption are yet unknown. To discover these, we undertook a genomics approach in the model plant species Arabidopsis thaliana and mined the gene reprogramming roles of the UPR modulators, basic leucine zipper28 (bZIP28) and bZIP60, in ER stress resolution. Through a network modeling and experimental validation, we identified key genes downstream of the UPR bZIP-transcription factors (bZIP-TFs), and demonstrated their functional roles. Our analyses have set up a critical pipeline for functional gene discovery in ER stress resolution with broad applicability across multicellular eukaryotes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Spectroscopic analysis reveals that soil phosphorus availability and plant allocation strategies impact feedstock quality of nutrient-limited switchgrass

Abstract The perennial native switchgrass adapts better than other plant species do to marginal soils with low plant-available nutrients, including those with low phosphorus (P) content. Switchgrass roots and their associated microorganisms can alter the pools of available P throughout the whole soil profile making predictions of P availability in situ challenging. Plant P homeostasis makes monitoring of P limitation via measurements of plant P content alone difficult to interpret. To address these challenges, we developed a machine-learning model trained with high accuracy using the leaf tissue chemical profile, rather than P content. By applying this learned model in field trials across two sites with contrasting extractable soil P, we observed that actual plant available P in soil was more similar than expected, suggesting that adaptations occurred to alleviate the apparent P constraint. These adaptations come at a metabolic cost to the plant that have consequences for feedstock chemical components and quality. We observed that other biochemical signatures of P limitation, such as decreased cellulose-to-lignin ratios, were apparent, indicating re-allocation of carbon resources may have contributed to increased P acquisition. Plant P allocation strategies also differed across sites, and these differences were correlated with the subsequent year’s biomass yields.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Structural and mechanistic basis for redox sensing by the cyanobacterial transcription regulator RexT

Abstract Organisms have a myriad of strategies for sensing, responding to, and combating reactive oxygen species, which are unavoidable consequences of aerobic life. In the heterocystous cyanobacterium Nostoc sp. PCC 7120, one such strategy is the use of an ArsR-SmtB transcriptional regulator RexT that senses H 2 O 2 and upregulates expression of thioredoxin to maintain cellular redox homeostasis. Different from many other members of the ArsR-SmtB family which bind metal ions, RexT has been proposed to use disulfide bond formation as a trigger to bind and release DNA. Here, we present high-resolution crystal structures of RexT in the reduced and H 2 O 2 -treated states. These structures reveal that RexT showcases the ArsR-SmtB winged-helix-turn-helix fold and forms a vicinal disulfide bond to orchestrate a response to H 2 O 2 . The importance of the disulfide-forming Cys residues was corroborated using site-directed mutagenesis, mass spectrometry, and H 2 O 2 -consumption assays. Furthermore, an entrance channel for H 2 O 2 was identified and key residues implicated in H 2 O 2 activation were pinpointed. Finally, bioinformatics analysis of the ArsR-SmtB family indicates that the vicinal disulfide “redox switch” is a unique feature of cyanobacteria in the Nostocales order, presenting an interesting case where an ArsR-SmtB protein scaffold has been evolved to showcase peroxidatic activity and facilitate redox-based regulation.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2024

Non-invasive ventral cervical magnetoneurography as a proxy of in vivo lipopolysaccharide-induced inflammation

Maintenance of autonomic homeostasis is continuously calibrated by sensory fibers of the vagus nerve and sympathetic chain that convey compound action potentials (CAPs) to the central nervous system. Lipopolysaccharide (LPS) intravenous challenge reliably elicits a robust inflammatory response that can resemble systemic inflammation and acute endotoxemia. Here, we administered LPS intravenously in nine healthy subjects while recording ventral cervical magnetoneurography (vcMNG)-derived CAPs at the rostral Right Nodose Ganglion (RNG) and the caudal Right Carotid Artery (RCA) with optically pumped magnetometers (OPM). We observed vcMNG RNG and RCA neural firing rates that tracked changes in TNF-α levels in the systemic circulation. Further, endotype subgroups based on high and low IL-6 responders segregate RNG CAP frequency (at 30-120 min) and based on high and low IL-10 response discriminate RCA CAP frequency (at 0-30 min). These vcMNG tools may enhance understanding and management of the neuroimmune axis that can guide personalized treatment based on an individual’s distinct endophenotype.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Sexual dimorphism and the multi-omic response to exercise training in rat subcutaneous white adipose tissue

Subcutaneous white adipose tissue (scWAT) is a dynamic storage and secretory organ that regulates systemic homeostasis, yet the impact of endurance exercise training (ExT) and sex on its molecular landscape is not fully established. Utilizing an integrative multi-omics approach, and leveraging data generated by the Molecular Transducers of Physical Activity Consortium (MoTrPAC), we show profound sexual dimorphism in the scWAT of sedentary rats and in the dynamic response of this tissue to ExT. Specifically, the scWAT of sedentary females displays -omic signatures related to insulin signaling and adipogenesis, whereas the scWAT of sedentary males is enriched in terms related to aerobic metabolism. These sex-specific -omic signatures are preserved or amplified with ExT. Integration of multi-omic analyses with phenotypic measures identifies molecular hubs predicted to drive sexually distinct responses to training. Overall, this study underscores the powerful impact of sex on adipose tissue biology and provides a rich resource to investigate the scWAT response to ExT.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Sample preparation with sucrose cryoprotection dramatically alters Zn distribution in the rodent hippocampus, as revealed by elemental mapping

Transition metal ions (Fe, Mn, Cu, Zn) are essential for healthy brain function, but altered concentration, distribution, or chemical form of the metal ions has been implicated in numerous brain pathologies. Currently, it is not possible to image the cellular or sub-cellular distribution of metal ions in vivo and therefore, studying brain-metal homeostasis largely relies on ex vivo in situ elemental mapping. Sample preparation methods that accurately preserve the in vivo elemental distribution are essential if one wishes to translate the knowledge of elemental distributions measured ex vivo toward increased understanding of chemical and physiological pathways of brain disease. Furthermore, the choice of sample preparation is particularly important for metal ions that exist in a labile or mobile form, for which the in vivo distribution could be easily distorted by inappropriate sample preparation. One of the most widely studied brain structures, the hippocampus, contains a large pool of labile and mobile Zn. Herein, we describe how sucrose cryoprotection, the gold standard method of preparing tissues for immuno-histochemistry or immuno-fluorescence, which is also often used as a sample preparation method for elemental mapping studies, drastically alters hippocampal Zn distribution. Based on the results of this study, in combination with a comparison against the strong body of published literature that has used either rapid plunge freezing of brain tissue, or sucrose cryo-protection, we strongly urge investigators in the future to cease using sucrose cryoprotection as a method of sample preparation for elemental mapping, especially if Zn is an analyte of interest.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Plastic recognition and electrogenic uniport translocation of 1 st -, 2 nd -, and 3 rd -row transition and post-transition metals by primary-active transmembrane P 1B-2 -type ATPase pumps

Transmembrane P 1B -type ATPase pumps catalyze the extrusion of transition metal ions across cellular lipid membranes to maintain essential cellular metal homeostasis and detoxify toxic metals. Zn(II)-pumps of the P 1B-2 -type subclass, in addition to Zn 2+ , select diverse metals (Pb 2+ , Cd 2+ and Hg 2+ ) at their transmembrane binding site and feature promiscuous metal-dependent ATP hydrolysis in the presence of these metals. Yet, a comprehensive understanding of the transport of these metals, their relative translocation rates, and transport mechanism remain elusive. We developed a platform for the characterization of primary-active Zn(II)-pumps in proteoliposomes to study metal selectivity, translocation events and transport mechanism in real-time, employing a “multi-probe” approach with fluorescent sensors responsive to diverse stimuli (metals, pH and membrane potential). Together with atomic-resolution investigation of cargo selection by X-ray absorption spectroscopy (XAS), we demonstrate that Zn(II)-pumps are electrogenic uniporters that preserve the transport mechanism with 1 st -, 2 nd - and 3 rd -row transition metal substrates. Promiscuous coordination plasticity, guarantees diverse, yet defined, cargo selectivity coupled to their translocation.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

Mutation of active site glutamate in serine hydroxymethyltransferase allows trapping a reactive intermediate: a combined neutron and X-ray crystallography study

Serine hydroxymethyltransferase (SHMT) is a pyridoxal-5′-phosphate (PLP) dependent enzyme that catalyzes a chemical transformation essential for the one-carbon (1C) metabolism. SHMT reversibly converts L-Ser into Gly and transfers a 1C unit to tetrahydrofolate (THF) to give 5,10-methylene-THF (5,10-MTHF). 5,10-MTHF, a 1C-unit donor, plays a crucial role in the downstream biomolecular syntheses required for the cell homeostasis and proliferation. SHMT is a prominent target for the drug discovery to battle bacterial and parasitic infections, and to treat various types of cancer. SHMT-catalyzed chemistry is governed by the general acid-base catalysis. Knowledge of the catalytic mechanism can aid drug design but can only be achieved when the atomic details of each reaction step are mapped, including accurate determination of hydrogen atom positions. Here we utilized the inactive E53Q mutant of Thermus thermophilus ( Tth ) SHMT to directly determine protonation states with room-temperature neutron crystallography and to capture a reactive intermediate containing the PLP-L-Ser external aldimine and THF in the enzyme active site. We observed protonation of the Schiff base nitrogen (N SB ) in the PLP internal aldimine but no change in the protonation states of other ionizable PLP groups and active site residues compared to wild-type Tth SHMT. X-ray structural analysis of the ternary intermediate complex E53Q-Ser-THF that eluded previous structural characterization shows the strategic positioning of the E53Q side chain in close proximity to the external aldimine and THF and reinforces the proposed role for E53 as the driver of proton transfer events along the reaction pathway.

Drago, Victoria N. [Oak Ridge National Laboratory ↗
DOE OSTI2020

A structural framework for unidirectional transport by a bacterial ABC exporter

The ATP-binding cassette (ABC) transporter of mitochondria (Atm1) mediates iron homeostasis in eukaryotes, while the prokaryotic homolog from Novosphingobium aromaticivorans (NaAtm1) can export glutathione derivatives and confer protection against heavy-metal toxicity. To establish the structural framework underlying the NaAtm1 transport mechanism, we determined eight structures by X-ray crystallography and single-particle cryo-electron microscopy in distinct conformational states, stabilized by individual disulfide crosslinks and nucleotides. As NaAtm1 progresses through the transport cycle, conformational changes in transmembrane helix 6 (TM6) alter the glutathione-binding site and the associated substrate-binding cavity. Significantly, kinking of TM6 in the post-ATP hydrolysis state stabilized by MgADPVO4 eliminates this cavity, precluding uptake of glutathione derivatives. The presence of this cavity during the transition from the inward-facing to outward-facing conformational states, and its absence in the reverse direction, thereby provide an elegant and conceptually simple mechanism for enforcing the export directionality of transport by NaAtm1. One of the disulfide crosslinked NaAtm1 variants characterized in this work retains significant glutathione transport activity, suggesting that ATP hydrolysis and substrate transport by Atm1 may involve a limited set of conformational states with minimal separation of the nucleotide-binding domains in the inward-facing conformation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Single-cell visualization and quantification of trace metals in Chlamydomonas lysosome-related organelles

Significance Transition metals are of crucial importance for primary productivity; their scarcity limits crop yield in agriculture and carbon sequestration on a global scale. Copper (Cu), iron (Fe), and manganese (Mn) are among the most important trace elements that enable the redox chemistry in oxygenic photosynthesis. The single-celled, eukaryotic green alga Chlamydomonas reinhardtii is a choice experimental system for studying trace metal homeostasis in the context of phototrophy, offering all the advantages of a classical microbial system with a well-characterized photosystem and trace metal metabolism machinery of relevance to plants. This project identifies and differentiates different trace metal storage sites in Chlamydomonas and uncovers the dynamics of trace metal storage and mobilization in situations of fluctuating resources.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2022

Structure of the human cation–chloride cotransport KCC1 in an outward-open state

Cation–chloride cotransporters (CCCs) catalyze electroneutral symport of Cl - with Na + and/or K + across membranes. CCCs are fundamental in cell volume homeostasis, transepithelia ion movement, maintenance of intracellular Cl - concentration, and neuronal excitability. Here, we present a cryoelectron microscopy structure of human K + –Cl - cotransporter (KCC)1 bound with the VU0463271 inhibitor in an outward-open state. In contrast to many other amino acid–polyamine–organocation transporter cousins, our first outward-open CCC structure reveals that opening the KCC1 extracellular ion permeation path does not involve hinge-bending motions of the transmembrane (TM) 1 and TM6 half-helices. Instead, rocking of TM3 and TM8, together with displacements of TM4, TM9, and a conserved intracellular loop 1 helix, underlie alternate opening and closing of extracellular and cytoplasmic vestibules. We show that KCC1 intriguingly exists in one of two distinct dimeric states via different intersubunit interfaces. Our studies provide a blueprint for understanding the mechanisms of CCCs and their inhibition by small molecule compounds.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Root angle is controlled by EGT1 in cereal crops employing an antigravitropic mechanism

Root angle in crops represents a key trait for efficient capture of soil resources. Root angle is determined by competing gravitropic versus antigravitropic offset (AGO) mechanisms. Here we report a root angle regulatory gene termed ENHANCED GRAVITROPISM1 ( EGT1 ) that encodes a putative AGO component, whose loss-of-function enhances root gravitropism. Mutations in barley and wheat EGT1 genes confer a striking root phenotype, where every root class adopts a steeper growth angle. EGT1 encodes an F-box and Tubby domain-containing protein that is highly conserved across plant species. Haplotype analysis found that natural allelic variation at the barley EGT1 locus impacts root angle. Gravitropic assays indicated that Hvegt1 roots bend more rapidly than wild-type. Transcript profiling revealed Hvegt1 roots deregulate reactive oxygen species (ROS) homeostasis and cell wall-loosening enzymes and cofactors. ROS imaging shows that Hvegt1 root basal meristem and elongation zone tissues have reduced levels. Atomic force microscopy measurements detected elongating Hvegt1 root cortical cell walls are significantly less stiff than wild-type. In situ analysis identified HvEGT1 is expressed in elongating cortical and stele tissues, which are distinct from known root gravitropic perception and response tissues in the columella and epidermis, respectively. We propose that EGT1 controls root angle by regulating cell wall stiffness in elongating root cortical tissue, counteracting the gravitropic machinery’s known ability to bend the root via its outermost tissues. We conclude that root angle is controlled by EGT1 in cereal crops employing an antigravitropic mechanism.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Identification and characterization of a small-molecule metallophore involved in lanthanide metabolism

Many bacteria secrete metallophores, low-molecular-weight organic compounds that bind ions with high selectivity and affinity, in order to access essential metals from the environment. Previous work has elucidated the structures and biosynthetic machinery of metallophores specific for iron, zinc, nickel, molybdenum, and copper. No physiologically relevant lanthanide-binding metallophore has been discovered despite the knowledge that lanthanide metals (Ln) have been revealed to be essential cofactors for certain alcohol dehydrogenases across a diverse range of phyla. Here, we report the biosynthetic machinery, the structure, and the physiological relevance of a lanthanophore, methylolanthanin. The structure of methylolanthanin exhibits a unique 4-hydroxybenzoate moiety which has not previously been described in other metallophores. We find that production of methylolanthanin is required for normal levels of Ln accumulation in the methylotrophic bacterium Methylobacterium extorquens AM1, while overexpression of the molecule greatly increases bioaccumulation and adsorption. Our results provide a clearer understanding of how Ln-utilizing bacteria sense, scavenge, and store Ln; essential processes in the environment where Ln are poorly bioavailable. More broadly, the identification of this lanthanophore opens doors for study of how biosynthetic gene clusters are repurposed for additional functions and the complex relationship between metal homeostasis and fitness.

Science & Technology - Other Topics↗
DOE OSTI2022

Bacterial exometabolites influence Chlamydomonas cell cycle and double algal productivity

Algal-bacterial interactions provide clues to algal physiology, but mutualistic interactions are complicated by dynamic exchange. In this study, we characterized the response of Chlamydomonas reinhardtii to the presence of a putative alga-benefitting commensal bacterium ( Arthrobacter strain ‘P2b’). Co-cultivation promoted chlorophyll content, biomass, average cell size, and number of dividing cells, relative to axenic cultures. Addition of bacterial spent medium (whole, size-fractionated and heat-treated) had similar effects, indicating P2b does not require algal interaction to promote growth. Nutrients and pH were excluded as putative effectors, collectively indicating a commensal interaction mediated by Arthrobacter -released small exometabolite(s). Proteogenomic comparison revealed similar response to co-cultivation and spent media, including differential cell cycle regulation, extensive downregulation of flagellar genes and histones, carbonic anhydrase and RubisCO downregulation, upregulation of some chlorophyll, amino acid and carbohydrate biosynthesis genes, and changes to redox and Fe homeostasis. Further, Arthrobacter protein expression indicated some highly expressed putative secondary metabolites. Together, these results revealed that low molecular weight bacterial metabolites can elicit major physiological changes in algal cell cycle regulation, perhaps through a more productive G1 phase, that lead to substantial increases in photosynthetically-produced biomass. This work illustrates that model commensal interactions can be used to shed light on algal response to stimulating bacteria.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

The genetic architecture of leaf stable carbon isotope composition in Zea mays and the effect of transpiration efficiency on leaf elemental accumulation

With increased demand on freshwater resources for agriculture, it is imperative that more water-use efficient crops are developed. Leaf stable carbon isotope composition, δ 13 C, is a proxy for transpiration efficiency and a possible tool for breeders, but the underlying mechanisms effecting δ 13 C in C 4 plants are not known. It has been suggested that differences in specific leaf area (SLA), which potentially reflects variation in internal CO 2 diffusion, can impact leaf δ 13 C. Furthermore, although it is known that water movement is important for elemental uptake, it is not clear how manipulation of transpiration for increased water-use efficiency may impact nutrient accumulation. Here, we characterize the genetic architecture of leaf δ 13 C and test its relationship to SLA and the ionome in five populations of maize. Five significant QTL for leaf δ 13 C were identified, including novel QTL as well as some that were identified previously in maize kernels. One of the QTL regions contains an Erecta-like gene, the ortholog of which has been shown to regulate transpiration efficiency and leaf δ 13 C in Arabidopsis. QTL for δ 13 C were located in the same general chromosome region, but slightly shifted, when comparing data from two different years. Our data does not support a relationship between δ 13 C and SLA, and of the 19 elements analyzed, only a weak correlation between molybdenum and δ 13 C was detected. Together these data add to the genetic understanding of leaf δ 13 C in maize and suggest that improvements to plant water use may be possible without significantly influencing elemental homeostasis.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Identification of genetic interactions with priB links the PriA/PriB DNA replication restart pathway to double-strand DNA break repair in Escherichia coli

Collisions between DNA replication complexes (replisomes) and impediments such as damaged DNA or proteins tightly bound to the chromosome lead to premature dissociation of replisomes at least once per cell cycle in Escherichia coli. Left unrepaired, these events produce incompletely replicated chromosomes that cannot be properly partitioned into daughter cells. DNA replication restart, the process that reloads replisomes at prematurely terminated sites, is therefore essential in E. coli and other bacteria. Three replication restart pathways have been identified in E. coli: PriA/PriB, PriA/PriC, and PriC/Rep. A limited number of genetic interactions between replication restart and other genome maintenance pathways have been defined, but a systematic study placing replication restart reactions in a broader cellular context has not been performed. We have utilized transposon-insertion sequencing to identify new genetic interactions between DNA replication restart pathways and other cellular systems. Known genetic interactors with the priB replication restart gene (uniquely involved in the PriA/PriB pathway) were confirmed and several novel priB interactions were discovered. Targeted genetic and imaging-based experiments with priB and its genetic partners revealed significant double-strand DNA break accumulation in strains with mutations in dam, rep, rdgC, lexA, or polA. Modulating the activity of the RecA recombinase partially suppressed the detrimental effects of rdgC or lexA mutations in ΔpriB cells. Taken together, our results highlight roles for several genes in double-strand DNA break homeostasis and define a genetic network that facilitates DNA repair/processing upstream of PriA/PriB-mediated DNA replication restart in E. coli.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Grf10 regulates the response to copper, iron, and phosphate in Candida albicans

Abstract The pathogenic yeast, Candida albicans, and other microbes must be able to handle drastic changes in nutrient availability within the human host. Copper, iron, and phosphate are essential micronutrients for microbes that are sequestered by the human host as nutritional immunity; yet high copper levels are employed by macrophages to induce toxic oxidative stress. Grf10 is a transcription factor important for regulating genes involved in morphogenesis (filamentation, chlamydospore formation) and metabolism (adenylate biosynthesis, 1-carbon metabolism). The grf10Δ mutant exhibited resistance to excess copper in a gene dosage-dependent manner but grew the same as the wild type in response to other metals (calcium, cobalt, iron, manganese, and zinc). Point mutations in the conserved residues D302 and E305, within a protein interaction region, conferred resistance to high copper and induced hyphal formation similar to strains with the null allele. The grf10Δ mutant misregulated genes involved with copper, iron, and phosphate uptake in YPD medium and mounted a normal transcriptional response to high copper. The mutant accumulated lower levels of magnesium and phosphorus, suggesting that copper resistance is linked to phosphate metabolism. Our results highlight new roles for Grf10 in copper and phosphate homeostasis in C. albicans and underscore the fundamental role of Grf10 in connecting these with cell survival.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Synchrotron fluorescence imaging of individual mouse beta-cells reveals changes in zinc, calcium, and iron in a model of low-grade inflammation

Pancreatic beta-cells synthesize and secrete insulin maintaining an organism's energy homeostasis. In humans, beta-cell dysfunction and death contribute to the pathogenesis of type 2 diabetes (T2D). Although the causes of beta-cell dysfunction are complex, obesity-induced low-grade systemic inflammation plays a role. For example, obese individuals exhibiting increased levels of proinflammatory cytokines IL-6 and IL-1beta have a higher risk of beta-cell dysfunction and T2D. Interestingly, obesity-induced inflammation changes the expression of several cellular metal regulating genes, prompting this study to examine changes in the beta-cell metallome after exposure to proinflammatory-cytokines. Here, primary mouse beta-cells were exposed to a combination of IL-6 and IL-1beta for 48 hours, were chemically fixed and imaged by synchrotron X-ray fluorescent microscopy. Quantitative analysis showed a surprising 2.4-fold decrease in the mean total cellular content of zinc from 158 ± 57.7 femtograms (fg) to 65.7 ± 29.7 fg; calcium decreased from 216 ± 67.4 to 154.3 ± 68.7 fg (control vs. cytokines, respectively). The mean total cellular iron content slightly increased from 30.4 ± 12.2 to 47.2 ± 36.4 fg after cytokine treatment; a sub-population of cells (38%) exhibited larger increases of iron density. Changes in the subcellular distributions of zinc and calcium were observed after cytokine exposure. Beta-cells contained numerous iron puncta that accumulated still more iron after exposure to cytokines. These findings provide evidence that exposure to low levels of cytokines is sufficient to cause changes in the total cellular content and/or subcellular distribution of several metals known to be critical for normal beta-cell function.

59 BASIC BIOLOGICAL SCIENCES↗