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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 1,081 records · Page 60
All sourcesNASA NTRSDOE OSTI
DOE OSTI2017

Polybenzimidazole based random copolymers containing hexafluoroisopropylidene functional groups for gas separations at elevated temperatures

Polybenzimidazoles (PBIs) are attractive membrane materials for H 2 /CO 2 separation at hydrocarbon fuel derived synthesis gas operating conditions due to their exceptional physicochemical stability and promising permselectivity character. PBI molecular structure modification is a viable approach to disrupt chain packing altering the free-volume architecture which results in improved gas transport characteristics. This work is focused on the synthesis and characterization of novel PBI random copolymers for application as elevated temperature H 2 /CO 2 membranes. The co-polymerization route is expected to result in tailorable permeability and selectivity by combining the high H 2 permeability aspect of the highly disrupted loosely packed hexafluoroisopropylidene diphenyl group containing PBI segments (6F-PBI) with the highly selective tightly packed phenylene group containing PBI segments (m-PBI). 6F/m-PBI copolymers with varying 6F-PBI and m-PBI ratios having high inherent viscosity were synthesized. The structure and ratio of the 6F- and m-PBI fractions were confirmed using FTIR and NMR spectroscopic techniques. The measured gas transport properties of copolymer thin films cast in controlled environment were measured as a function of the operating conditions. Lastly, the H 2 permeability increased while H 2 /CO 2 selectivity decreased as the 6F-PBI copolymer fraction was increased.

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

Conserving asphalt resources: Rethinking rejuvenator performance evaluation through peptizing efficiency

Timely rejuvenation and restoration of asphalt are essential conservation practices that help preserve and extend the service life of roads, bridges, driveways, and parking lots. The performance of asphalt rejuvenators is often assessed based on their diffusion rates and softening power, yet these metrics alone fail to capture true rejuvenation potential. Here, this study integrates density functional theory (DFT) modeling with experimental analysis to show that rejuvenation effectiveness is primarily governed by molecular interactions with oxidized asphaltene nanoaggregates. DFT results revealed that amide- and unsaturated-chain compounds, such as hexadecanamide, oleic acid, and 9,17-octadecadienal, act cooperatively to disrupt π–π stacking and exfoliate asphaltene layers, reducing binding strength and enhancing dispersion. Unlike bulky, rigid molecules that remain trapped, these components remain mobile and repeatedly interact with multiple aggregation sites. Experimental validation using rheometry and FTIR confirmed that such molecularly compatible rejuvenators restore the binder flexibility and polydispersity, even when diffusion is relatively slow. Building on this mechanistic foundation, six rejuvenators (A2, A5, A7, A8, A9, and A10) were evaluated using a three-metric performance framework encompassing cracking resistance (Glover–Rowe parameter), UV stability, and surface hydrophobicity. Among the six rejuvenators evaluated, A9 exhibited the highest overall performance, reducing the Glover–Rowe cracking parameter by 85% (from 351 kPa to 53 kPa), demonstrating the greatest resistance to UV-induced aging with a stability index of 4.17 h·kPa⁻¹, and increasing surface hydrophobicity to a contact angle of 103.6°. Its superior performance is primarily attributed to its amide- and unsaturated-chain components, which act cooperatively to disrupt π–π stacking interactions and exfoliate asphaltene layers, thereby promoting molecular deagglomeration and enhancing long-term durability. These results shift the criteria for selecting rejuvenators: effective candidates must pair the electronic capability to unlock aged asphaltenes with sufficient structural stability to resist secondary aging and restore hydrophobicity. Restoring hydrophobicity is critical, as aging reduces the asphalt’s water repellency and increases water diffusion, which in turn accelerates moisture-related damage; consequently, a high-performing rejuvenator must effectively restore the binder’s hydrophobic characteristic. Collectively, these findings provide a framework for the rational design of next-generation of bio-based rejuvenators that enhance pavement longevity and promote long-term sustainability.

Aging↗
DOE OSTI2017

A model for simulating adaptive, dynamic flows on networks: Application to petroleum infrastructure

Simulation models can greatly improve decisions meant to control the consequences of disruptions to critical infrastructures. We describe a dynamic flow model on networks purposed to inform analyses by those concerned about consequences of disruptions to infrastructures and to help policy makers design robust mitigations. We conceptualize the adaptive responses of infrastructure networks to perturbations as market transactions and business decisions of operators. We approximate commodity flows in these networks by a diffusion equation, with nonlinearities introduced to model capacity limits. To illustrate the behavior and scalability of the model, we show its application first on two simple networks, then on petroleum infrastructure in the United States, where we analyze the effects of a hypothesized earthquake.

02 PETROLEUM↗
DOE OSTI2026

Uncertainty quantification and reliability assessment for intermodal freight transportation

Intermodal freight optimization models support cost-effective, low-emission, and timely goods movement by coordinating trucks, rail, and barges. These models determine optimal flows, routing, and modal switches while respecting infrastructure and operational constraints. However, their real-world utility is often undermined by pervasive uncertainties-such as fluctuating transportation costs and emissions, variable terminal capacities, and uncertain freight demand-that distort key performance outcomes, including total system cost, carbon footprint, and transit time reliability. This study presents a structured framework for quantifying uncertainty in intermodal freight transportation (IFT) optimization. The framework evaluates how input uncertainty affects system performance and reliability, a critical need for ensuring that model-based decisions remain robust under real-world variability, especially amid volatile fuel prices, shifting demand, and growing disruptions. It integrates three complementary methods: (1) Sobol-based global sensitivity analysis to identify influential parameters affecting cost, emissions, and transit time, (2) Monte Carlo-based capacity perturbation analysis to assess robustness under probabilistic facility disruptions, and (3) Monte Carlo filtering with Bayesian inference to detect threshold-based performance vulnerabilities. The results highlight diesel truck unit cost as the dominant driver of variability. To improve system resilience, planners should prioritize uncertainty in fuel-related parameters when designing intermodal strategies.

Intermodal freight transportation↗
DOE OSTI2022

Vulnerability and resilience of urban energy ecosystems to extreme climate events: A systematic review and perspectives

We reviewed the present studies on the vulnerability and resilience of the energy ecosystem (most parts of the energy ecosystem), considering extreme climate events. This study revealed that the increased interactions formed during the transformation of the energy landscape into an ecosystem could notably increase the vulnerability of the energy infrastructure. Such complex ecosystem cannot be assessed using the present state of the art models used by the energy system modelers. Therefore, this study introduces a novel analogy known as the COVID analogy to understand the propagation of disruption within and beyond the energy ecosystem and organized the present state of the art based on the COVID analogy. The analogy helps to categorize the vulnerability of the energy infrastructure into three stages. The study revealed that although there are many publications covering the vulnerability and resilience of the energy infrastructure, considering extreme climate events, the majority are focused on the direct impact of extreme climate on the energy ecosystem. In addition, most of the studies do not consider the impact of future climate variations during this assessment. The propagation of disruptions was assessed mainly for wildfires and hurricanes. Further, there is a clear research gap in considering vulnerability assessment for interconnected energy infrastructure. Here, the transformation of energy systems into a complex ecosystem notably increases the complexity, making it difficult to assess vulnerability and resilience. A shift from a centralized to decentralized modeling architecture could be beneficial when considering the complexities brought by that transformation. Hybrid models consisting of both physical and data-driven machine learning techniques could also be beneficial in this context.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Deoxynivalenol exposure induces autophagy/apoptosis and epigenetic modification changes during porcine oocyte maturation

Deoxynivalenol (DON) is a widespread trichothecene mycotoxin which contaminates agricultural staples and elicits a complex spectrum of toxic effects on humans and animals. It has been shown that DON impairs oocyte maturation, reproductive function and causes abnormal fetal development in mammals; however, the mechanisms remain unclear. In the present study, we investigate the possible reasons of the toxic effects of DON on porcine oocytes. Our results showed that DON significantly inhibited porcine oocyte maturation and disrupted meiotic spindle by reducing p-MAPK protein level, which caused retardation of cell cycle progression. In addition, up-regulated LC3 protein expression and aberrant Lamp2, LC3 and mTOR mRNA levels were observed with DON exposure, together with Annexin V-FITC staining assay analysis, these results indicated that DON treatment induced autophagy/apoptosis in porcine oocytes. We also showed that DON exposure increased DNA methylation level in porcine oocytes through altering DNMT3A mRNA levels. Histone methylation levels were also changed showing with increased H3K27me3 and H3K4me2 protein levels, and mRNA levels of their relative methyltransferase genes, indicating that epigenetic modifications were affected. Taken together, our results suggested that DON exposure reduced porcine oocytes maturation capability through affecting cytoskeletal dynamics, cell cycle, autophagy/apoptosis and epigenetic modifications. - Highlights: • DON exposure disrupted meiotic spindle by reducing p-MAPK expression. • DON exposure caused retardation of cell cycle progression in porcine oocytes. • DON triggered autophagy and early-apoptosis in porcine oocytes. • DON exposure led to aberrant epigenetic modifications in porcine oocytes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Crosstalk between liver antioxidant and the endocannabinoid systems after chronic administration of the FAAH inhibitor, URB597, to hypertensive rats

Hypertension is accompanied by perturbations to the endocannabinoid and antioxidant systems. Thus, potential pharmacological treatments for hypertension should be examined as modulators of these two metabolic systems. The aim of this study was to evaluate the effects of chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor [3-(3-carbamoylphenyl)phenyl]N-cyclohexylcarbamate (URB597) on the endocannabinoid system and on the redox balance in the livers of DOCA-salt hypertensive rats. Hypertension caused an increase in the levels of endocannabinoids [anandamide (AEA), 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-dopamine (NADA)] and CB{sub 1} receptor and the activities of FAAH and monoacylglycerol lipase (MAGL). These effects were accompanied by an increase in the level of reactive oxygen species (ROS), a decrease in antioxidant activity/level, enhanced expression of transcription factor Nrf2 and changes to Nrf2 activators and inhibitors. Moreover, significant increases in lipid, DNA and protein oxidative modifications, which led to enhanced levels of proapoptotic caspases, were also observed. URB597 administration to the hypertensive rats resulted in additional increases in the levels of AEA, NADA and the CB{sub 1} receptor, as well as decreases in vitamin E and C levels, glutathione peroxidase and glutathione reductase activities and Nrf2 expression. Thus, after URB597 administration, oxidative modifications of cellular components were increased, while the inflammatory response was reduced. This study revealed that chronic treatment of hypertensive rats with URB597 disrupts the endocannabinoid system, which causes an imbalance in redox status. This imbalance increases the levels of electrophilic lipid peroxidation products, which later participate in metabolic disturbances in liver homeostasis. - Highlights: • Chronic administration of URB597 to hypertensive rats reduces liver inflammation. • URB597 enhances the redox imbalance in the liver of hypertensive rats. • URB597 alters lipid metabolism, which results in enhanced lipid peroxidation. • URB597 disrupts crosstalk between antioxidants, including the Nrf2 pathway and endocannabinoid system.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice

Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18 ± 5 ng/ml vs 472 ± 58 ng/ml; P < 0.001) and disrupted the metabolic and anti-inflammatory glucocorticoid function. Adrenal removal did not exacerbate the cholestasis extent. In contrast, the cholestasis-associated liver injury was markedly lower in adrenalectomized mice as compared to controls as evidenced by a 84%–93% decrease in liver necrosis and plasma alanine aminotransferase and bile acid levels (P < 0.001 for all). Gene expression analysis on livers from adrenalectomized mice suggested the absence of bile acid toxicity-associated farnesoid X receptor signaling in the context of a 44% (P < 0.01) and 82% (P < 0.001) reduction in sodium/bile acid cotransporter member 1 transcript level as compared to respectively control and non-diseased mice. Adrenalectomy reduced the expression of the cholesterol synthesis gene HMG-CoA reductase by 70% (P < 0.05), which translated into a 73% lower plasma total cholesterol level (P < 0.05). Treatment of C57BL/6 mice with the glucocorticoid receptor antagonist RU-486 recapitulated the protective effect of adrenalectomy on indices of liver injury and hypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. - Highlights: • Cholestasis is associated with increased plasma glucocorticoid levels in mice. • Adrenalectomy lowers cholestasis-associated liver injury and hypercholesterolemia. • GR antagonist RU-486 similarly improves the cholestasis phenotype. • Endogenous glucocorticoids promote re-uptake of circulating bile acids into liver.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

TBECH, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane, alters androgen receptor regulation in response to mutations associated with prostate cancer

Point mutations in the AR ligand-binding domain (LBD) can result in altered AR structures leading to changes of ligand specificity and functions. AR mutations associated to prostate cancer (PCa) have been shown to result in receptor activation by non-androgenic substances and anti-androgenic drugs. Two AR mutations known to alter the function of anti-androgens are the AR{sub T877A} mutation, which is frequently detected mutation in PCa tumors and the AR{sub W741C} that is rare and has been derived in vitro following exposure of cells to the anti-androgen bicalutamide. AR activation by non-androgenic environmental substances has been suggested to affect PCa progression. In the present study we investigated the effect of AR mutations (AR{sub W741C} and AR{sub T877A}) on the transcriptional activation following exposure of cells to an androgenic brominated flame retardant, 1,2-dibromo-4-(1,2 dibromoethyl) cyclohexane (TBECH, also named DBE-DBCH). The AR mutations resulted in higher interaction energies and increased transcriptional activation in response to TBECH diastereomer exposures. The AR{sub T877A} mutation rendered AR highly responsive to low levels of DHT and TBECH and led to increased AR nuclear translocation. Gene expression analysis showed a stronger induction of AR target genes in LNCaP cells (AR{sub T877A}) compared to T-47D cells (AR{sub WT}) following TBECH exposure. Furthermore, AR knockdown experiments confirmed the AR dependency of these responses. The higher sensitivity of AR{sub T877A} and AR{sub W741C} to low levels of TBECH suggests that cells with these AR mutations are more susceptible to androgenic endocrine disrupters. - Highlights: • TBECH, is an endocrine disrupting compound that differ in activity depending on AR structure and sequence. • TBECH interaction with the human AR-LBD containing the mutations W741C and T877A is increased compared to the wild type receptor • The mutations, W741C and T877A, are more potent than the wild type receptor at inducing AR nuclear translocation and transcriptional activation following TBECH exposure. • TBECH mediates action on androgen response genes via AR signaling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Regulation of steroid hormones and energy status with cysteamine and its effect on spermatogenesis

Although it is well known that cysteamine is a potent chemical for treating many diseases including cystinosis and it has many adverse effects, the effect of cysteamine on spermatogenesis is as yet unknown. Therefore the objective of this investigation was to explore the effects of cysteamine on spermatogenesis and the underlying mechanisms. Sheep were treated with vehicle control, 10 mg/kg or 20 mg/kg cysteamine for six months. After that, the semen samples were collected to determine the spermatozoa motility by computer-assisted sperm assay method. Blood samples were collected to detect the levels of hormones and the activity of enzymes. Spermatozoa and testis samples were collected to study the mechanism of cysteamine's actions. It was found that the effects of cysteamine on spermatogenesis were dose dependent. A low dose (10 mg/kg) cysteamine treatment increased ovine spermatozoa motility; however, a higher dose (20 mg/kg) decreased both spermatozoa concentration and motility. This decrease might be due to a reduction in steroid hormone production by the testis, a reduction in energy in the testis and spermatozoa, a disruption in the blood-testis barrier, or a breakdown in the vital signaling pathways involved in spermatogenesis. The inhibitory effects of cysteamine on sheep spermatogenesis may be used to model its effects on young male patients with cystinosis or other diseases that are treated with this drug. Further studies on spermatogenesis that focus on patients treated with cysteamine during the peripubertal stage are warranted. - Highlights: • Dose dependent effects of cysteamine on spermatogenesis • A low dose (10 mg/kg) increased spermatozoa motility. • A higher dose (20 mg/kg) decreased both concentration and motility of spermatozoa. • Disruption in the blood-testis barrier caused reduction in concentration and motility.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Distribution, lipid-bilayer affinity and kinetics of the metabolic effects of dinoseb in the liver

Dinoseb is a highly toxic pesticide of the dinitrophenol group. Its use has been restricted, but it can still be found in soils and waters in addition to being a component of related pesticides that, after ingestion by humans or animals, can originate the compound by enzymatic hydrolysis. As most dinitrophenols, dinoseb uncouples oxidative phosphorylation. In this study, distribution, lipid bilayer affinity and kinetics of the metabolic effects of dinoseb were investigated, using mainly the isolated perfused rat liver, but also isolated mitochondria and molecular dynamics simulations. Dinoseb presented high affinity for the hydrophobic region of the lipid bilayers, with a partition coefficient of 3.75 × 10{sup 4} between the hydrophobic and hydrophilic phases. Due to this high affinity for the cellular membranes dinoseb underwent flow-limited distribution in the liver. Transformation was slow but uptake into the liver space was very pronounced. For an extracellular concentration of 10 μM, the equilibrium intracellular concentration was equal to 438.7 μM. In general dinoseb stimulated catabolism and inhibited anabolism. Half-maximal stimulation of oxygen uptake in the whole liver occurred at concentrations (2.8–5.8 μM) at least ten times above those in isolated mitochondria (0.28 μM). Gluconeogenesis and ureagenesis were half-maximally inhibited at concentrations between 3.04 and 5.97 μM. The ATP levels were diminished, but differently in livers from fed and fasted rats. Dinoseb disrupts metabolism in a complex way at concentrations well above its uncoupling action in isolated mitochondria, but still at concentrations that are low enough to be dangerous to animals and humans even at sub-lethal doses. - Highlights: • Dinoseb presents high affinity for the hydrophobic region of the lipid bilayers. • Its cellular concentration may exceed the extracellular one by a factor of 43.9. • One order of magnitude separates the active concentrations in mitochondria and liver. • Hepatic metabolism is disrupted in the concentration range up to 10 μM.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Low level exposure to inorganic mercury interferes with B cell receptor signaling in transitional type 1 B cells

Mercury (Hg) has been implicated as a factor contributing to autoimmune disease in animal models and humans. However the mechanism by which this occurs has remained elusive. Since the discovery of B cells it has been appreciated by immunologists that during the normal course of B cell development, some immature B cells must be generated that produce immunoglobulin reactive to self-antigens (auto-antibodies). However in the course of normal development, the vast majority of immature auto-reactive B cells are prevented from maturing by processes collectively known as tolerance. Autoimmune disease arises when these mechanisms of tolerance are disrupted. In the B cell compartment, it is firmly established that tolerance depends in part upon negative selection of self-reactive immature (transitional type 1) B cells. In these cells negative selection depends upon signals generated by the B Cell Receptor (BCR), in the sense that those T1 B cells who's BCRs most strongly bind to, and so generate the strongest signals to self-antigens are neutralized. In this report we have utilized multicolor phosphoflow cytometry to show that in immature T1 B cells Hg attenuates signal generation by the BCR through mechanisms that may involve Lyn, a key tyrosine kinase in the BCR signal transduction pathway. We suggest that exposure to low, environmentally relevant levels of Hg, disrupts tolerance by interfering with BCR signaling in immature B cells, potentially leading to the appearance of mature auto-reactive B cells which have the ability to contribute to auto-immune disease. - Highlights: • Hg{sup 2+} interferes with BCR-mediated activation of ERK in immature T1 B cells. • Hg{sup 2+} acts upstream of ERK. • BCR mediated activation of Syk and the CD79a ITAM are attenuated in immature T1 B cells by Hg{sup 2+}. • The mechanism whereby which Hg{sup 2+} affects Syk and CD7a activation involves the tyrosine phosphokinase Lyn.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Bombyx mori nucleopolyhedrovirus BM5 protein regulates progeny virus production and viral gene expression

Bombyx mori nucleopolyhedrovirus (BmNPV) orf5 (Bm5) is a core gene of lepidopteran baculoviruses and encodes the protein with the conserved amino acid residues (DUF3627) in its C-terminus. Here, we found that Bm5 disruption resulted in lower titers of budded viruses and fewer numbers of occlusion bodies (OBs) in B. mori cultured cells and larvae, although viral genome replication was not affected. Bm5 disruption also caused aberrant expression of various viral genes at the very late stage of infection. Immunocytochemical analysis revealed that BM5 localized to the nuclear membrane. We also found that DUF3627 is important for OB production, transcriptional regulation of viral genes, and subcellular localization of BM5. Compared with wild-type BmNPV infection, larval death was delayed when B. mori larvae were infected with Bm5 mutants. These results suggest that BM5 is involved in progeny virus production and regulation of viral gene expression at the very late stage of infection. -- Highlights: •The role of BmNPV BM5 protein was examined in B. mori cultured cells and larvae. •BM5 contributes to efficient production of budded viruses and occlusion bodies. •BM5 regulates viral gene expression at the very late stage of infection. •BM5 dominantly localizes to the nuclear membrane. •Bm5 mutant showed v-cath down-regulation and resulting delay of larval death.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Characterization of the disassembly and reassembly of the HBV glycoprotein surface antigen, a pliable nanoparticle vaccine platform

While nanoparticle vaccine technology is gaining interest due to the success of vaccines like those for the human papillomavirus that is based on viral capsid nanoparticles, little information is available on the disassembly and reassembly of viral surface glycoprotein-based nanoparticles. One such particle is the hepatitis B virus surface antigen (sAg) that exists as nanoparticles. Here we show, using biochemical analysis coupled with electron microscopy, that sAg nanoparticle disassembly requires both reducing agent to disrupt intermolecular disulfide bonds, and detergent to disrupt hydrophobic interactions that stabilize the nanoparticle. Particles were otherwise resistant to salt and urea, suggesting the driving mechanism of particle formation involves hydrophobic interactions. We reassembled isolated sAg protein into nanoparticles by detergent removal and reassembly resulted in a wider distribution of particle diameters. Knowledge of these driving forces of nanoparticle assembly and stability should facilitate construction of epitope-displaying nanoparticles that can be used as immunogens in vaccines.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Inhibition of TGF-β pathway reverts extracellular matrix remodeling in T. cruzi-infected cardiac spheroids

Highlights: • A model of cardiac spheroids to study fibrosis in pathological processes is proposed. • The study evaluates a TGF-β inhibitor in restoring extracellular matrix balance disrupted by T. cruzi infection. • Inhibition of TGF-β signaling reduces fibrosis and hypertrophy in infected-cardiac spheroids. • The extracellular matrix remodeling is achieved through regulation of MMP-2 activity and TIMP-1 expression. Chagasic cardiomyopathy (CC) is the main manifestation of Chagas Disease (CD). CC is a progressive dysfunctional illness, in which transforming growth factor beta (TGF-β) plays a central role in fibrogenesis and hypertrophy. In the present study, we tested in a three-dimensional (3D) model of cardiac cells culture (named cardiac spheroids), capable of mimicking the aspects of fibrosis and hypertrophy observed in CC, the role of TGF-β pathway inhibition in restoring extracellular matrix (ECM) balance disrupted by T. cruzi infection. Treatment of T. cruzi-infected cardiac spheroids with SB 431542, a selective inhibitor of TGF-β type I receptor, resulted in a reduction in the size of spheroids, which was accompanied by a decrease in parasite load and in fibronectin expression. The inhibition of TGF-β pathway also promoted an increase in the activity of matrix metalloproteinase (MMP)-2 and a decrease in tissue inhibitor of matrix metalloproteinase (TIMP)-1 expression, which may be one of the mechanisms regulating extracellular matrix remodeling. Therefore, our study provides new insights into the molecular mechanisms by which inhibition of TGF-β signaling reverts fibrosis and hypertrophy generated by T. cruzi during CC and also highlights the use of cardiac spheroids as a valuable tool for the study of fibrogenesis and anti-fibrotic compounds.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A high-sugar diet affects cellular and humoral immune responses in Drosophila

Highlights: • A high-sugar diet impairs the in vivo phagocytosis. • A high-sugar diet disrupts the F-actin extension and the sessile hemocyte structure. • A high-sugar diet activates JNK and Toll pathways in innate immune system. A high-sugar diet (HSD) induces Type 2 diabetes (T2D) and obesity, which severely threaten human health. The Drosophila T2D model has been constructed to study the mechanisms of insulin resistance, diet-induced cardiovascular diseases and other conditions. Innate immunity is the first line of defense against invading pathogens and parasites. However, few studies have focused on the relationship between a HSD and the innate immune response in Drosophila. In this study, we fed flies a high-sucrose diet and observed defects in the phagocytosis of latex beads and B. bassiana spores. The actin cytoskeleton was also disrupted in hemocytes from HSD-fed larvae. Furthermore, HSD induced the differentiation of lamellocytes in the lymph gland and circulating hemolymph, which rarely occurs in healthy bodies, via JNK signaling. In addition, the Toll and JNK pathways were excessively activated in the fat bodies of HSD-fed larvae, and a large number of dead cells were observed. Finally, HSD induced the aberrant activation of the innate immune system, including inflammation. Our results have established a connection between T2D and the innate immune response.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Onset of magnetic reconnection in a collisionless, high-β plasma

In a magnetized, collisionless plasma, the magnetic moment of the constituent particles is an adiabatic invariant. An increase in the magnetic-field strength in such a plasma hence leads to an increase in the thermal pressure perpendicular to the field lines. Above a $\unicode[STIX]{x1D6FD}$ -dependent threshold (where $\unicode[STIX]{x1D6FD}$ is the ratio of thermal to magnetic pressure), this pressure anisotropy drives the mirror instability, producing strong distortions in the field lines on ion-Larmor scales. The effect of this instability on magnetic reconnection is investigated using a simple analytical model for the formation of a current sheet (CS) and the associated production of pressure anisotropy. The difficulty in maintaining an isotropic, Maxwellian particle distribution during the formation and subsequent thinning of a CS in a collisionless plasma, coupled with the low threshold for the mirror instability in a high- $\unicode[STIX]{x1D6FD}$ plasma, imply that the geometry of reconnecting magnetic fields can differ radically from the standard Harris-sheet profile often used in simulations of collisionless reconnection. Because of this, depending on the rate of CS formation and the initial CS thickness, tearing modes whose growth rates and wavenumbers are boosted by this difference may disrupt the mirror-infested CS before standard tearing modes can develop. A quantitative theory is developed to illustrate this process, which may find application in the tearing-mediated disruption of kinetic magnetorotational ‘channel’ modes.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2018

Tuning Inner-Ear Tip-Link Affinity Through Alternatively Spliced Variants of Protocadherin-15

Human hearing relies upon the tip-to-tip interaction of two nonclassical cadherins, protocadherin-15 (PCDH15) and cadherin-23 (CDH23). Together, these proteins form a filament called the tip link that connects neighboring stereocilia of mechanosensitive hair cells. As sound waves enter the cochlea, the stereocilia deflect and tension is applied to the tip link, opening nearby transduction channels. Disruption of the tip link by loud sound or calcium chelators eliminates transduction currents and illustrates that tip-link integrity is critical for mechanosensing. Tip-link remodeling after disruption is a dynamic process, which can lead to the formation of atypical complexes that incorporate alternatively spliced variants of PCDH15. These variants are categorized into six groups (N1–N6) based upon differences in the first two extracellular cadherin (EC) repeats. Here, we characterized the two N-terminal EC repeats of all PCDH15 variants (pcdh15(N1) to pcdh15(N6)) and combined these variants to test complex formation. We solved the crystal structure of a new complex composed of CDH23 EC1-2 (cdh23) and pcdh15(N2) at 2.3 Å resolution and compared it to the canonical cdh23–pcdh15(N1) complex. While there were subtle structural differences, the binding affinity between cdh23 and pcdh15(N2) is ~6 times weaker than cdh23 and pcdh15(N1) as determined by surface plasmon resonance analysis. Steered molecular dynamics simulations predict that the unbinding force of the cdh23–pcdh15(N2) complex can be lower than the canonical tip link. Our results demonstrate that alternative heterophilic tip-link structures form stable protein–protein interactions in vitro and suggest that homophilic PCDH15–PCDH15 tip links form through the interaction of additional EC repeats.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗