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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 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Integration of SARS-CoV-2 testing and genomic sequencing into influenza sentinel surveillance in Uganda, January to December 2022

The Uganda Virus Research Institute, National Influenza Center laboratory integrated SARS-CoV-2 polymerase chain reaction testing and genomic sequencing into the influenza surveillance program that was established in 2007. A total of 7,698 nasopharyngeal/oropharyngeal (NP/OP) swab samples were collected and analyzed from ILI/SARI sentinel sites across the country from January to December 2022. All samples were tested for influenza and SARS-CoV-2. Of these, 252 (3.3%), 162 (2.1%), and 589 (7.7%) were positive for influenza A, influenza B, and SARS-CoV-2, respectively. Out of 414 influenza-positive samples, 122 (29.5%) were AH1pdm09, 130 (31.4%) were AH3, and 162 (39.1%) were B-Victoria. All SARS-CoV-2 sequenced samples were of the Omicron variant, with subvariants of concern known to evade the immune system being detected, such as BQ.1 and XBB.2. Other SARS-CoV-2 positive samples collected from other health centers in the community outside the surveillance sites were included into SARS-CoV-2 genomic sequencing with similar patterns with respect to variants. In all, the ILI/SARI surveillance system has shown to be an efficient, cost-effective, and sustainable program, providing a ready platform to monitor the circulation of SARS-CoV-2 in communities at the national level while remaining vigilant for the persistent threat of influenza. The integration of SARS-CoV-2 detection and genomic surveillance into the influenza surveillance program will strengthen the laboratory response capacity, as well as facilitate the timely release of SARS-CoV-2 genomic information to be used to complement the multiple response strategies for COVID-19 pandemic mitigation.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Modeling Cell Survival Fraction and Other Dose-Response Relationships for Immunodeficient C.B-17 SCID Mice Exposed to 320-kV X Rays

US homeland security concerns related to potential misuse of γ-ray-emitting radiation sources employed in radiobiological research (eg, shielded cesium-137 irradiators) led to recommendations by the National Research Council to conduct studies into possibly replacing γ-ray irradiators used in research involving small rodent and other models with X-ray instruments. A limiting factor is suitability of the X-ray photon energy spectra. The objective of our research was to demonstrate the suitability of the radiation energy spectrum of 320-kV X rays after filtration (HVL = 4 mm Cu) for in-vivo cytotoxicity studies in immunodeficient C.B-17 SCID mice. By using a previously-published Hazard Function (HF) model to characterize dose-response relationships for in vivo bone marrow and spleen cell survival fractions and also to characterize the acute lethality risk (hematopoietic syndrome mode) we demonstrate that the filtered 320-kV X-ray beam appears suitable for such studies. A key finding for C.B-17 SCID mice when compared to results previously obtained for immunocompetent C.B-17 mice is that the immunodeficient mice appear to be more radioresistant, implicating a possible role of the immune system capacity in radiosensitivity of mammals.

Scott, Bobby R.↗
DOE OSTI2025

Plasma proteomic biomarkers of physical frailty in heart failure: a propensity score matched discovery-based pilot study

Background: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomics evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF. We aimed to identify plasma proteomic biomarkers that are differentially expressed between physically frail and non physically frail adults with HF. Methods: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was used to match pairs of physically frail (n = 20) vs. non-physically frail (n = 20) patients on clinical characteristics. Plasma samples were processed using a sensitive liquid chromatography mass spectrometry platform, utilizing a multiplexed tandem mass tag-labeled quantitative proteomics approach. Differentially expressed proteins were quantified individually using paired t tests with associated log fold change of 0.3 and Fisher’s combined p values. Results: The sample (n = 40) was 62.8±16.9 years old, 58% female, and 55% NYHA Class III/IV. Proteomics analysis revealed 7 proteins differentially expressed using full differential criteria: matrix metalloproteinase-14 was downregulated in frailty, and copine-1, low affinity immunoglobulin gamma Fc region receptor III-A and III-B, probable non-functional immunoglobulin kappa variable 2D-24, glutathione S-transferase Mu 1, and argininosuccinate lyase were upregulated in frailty. Conclusions: Proteomic biomarkers related to the immune system, stress response, and detoxification were differentially expressed between physically frail and non-physically frail adults with HF.

Biomarkers↗
DOE OSTI2021

Metagenomic insights into the taxonomy, function, and dysbiosis of prokaryotic communities in octocorals

Background. In octocorals (Cnidaria Octocorallia), the functional relationship between host health and its symbiotic consortium has yet to be determined. Here, we employed comparative metagenomics to uncover the distinct functional and phylogenetic features of the microbiomes of healthy Eunicella gazella, Eunicella verrucosa, and Leptogorgia sarmentosa tissues, in contrast with the microbiomes found in seawater and sediments. We further explored how the octocoral microbiome shifts to a pathobiome state in E. gazella. Results. Multivariate analyses based on 16S rRNA genes, Clusters of Orthologous Groups of proteins (COGs), Protein families (Pfams), and secondary metabolite-biosynthetic gene clusters annotated from 20 Illumina-sequenced metagenomes each revealed separate clustering of the prokaryotic communities of healthy tissue samples of the three octocoral species from those of necrotic E. gazella tissue and surrounding environments. While the healthy octocoral microbiome was distinguished by so-far uncultivated Endozoicomonadaceae, Oceanospirillales, and Alteromonadales phylotypes in all host species, a pronounced increase of Flavobacteriaceae and Alphaproteobacteria, originating from seawater, was observed in necrotic E. gazella tissue. Increased abundances of eukaryotic-like proteins, exonucleases, restriction endonucleases, CRISPR/Cas proteins, and genes encoding for heat-shock proteins, inorganic ion transport, and iron storage distinguished the prokaryotic communities of healthy octocoral tissue regardless of the host species. An increase of arginase and nitric oxide reductase genes, observed in necrotic E. gazella tissues, suggests the existence of a mechanism for suppression of nitrite oxide production by which octocoral pathogens may overcome the host’s immune system. Conclusions. This is the first study to employ primer-less, shotgun metagenome sequencing to unveil the taxonomic, functional, and secondary metabolism features of prokaryotic communities in octocorals. Our analyses reveal that the octocoral microbiome is distinct from those of the environmental surroundings, is host genus (but not species) specific, and undergoes large, complex structural changes in the transition to the dysbiotic state. Host-symbiont recognition, abiotic-stress response, micronutrient acquisition, and an antiviral defense arsenal comprising multiple restriction endonucleases, CRISPR/Cas systems, and phage lysogenization regulators are signatures of prokaryotic communities in octocorals. We argue that these features collectively contribute to the stabilization of symbiosis in the octocoral holobiont and constitute beneficial traits that can guide future studies on coral reef conservation and microbiome therapy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Multiscale affinity maturation simulations to elicit broadly neutralizing antibodies against HIV

The design of vaccines against highly mutable pathogens, such as HIV and influenza, requires a detailed understanding of how the adaptive immune system responds to encountering multiple variant antigens (Ags). Here, we describe a multiscale model of B cell receptor (BCR) affinity maturation that employs actual BCR nucleotide sequences and treats BCR/Ag interactions in atomistic detail. We apply the model to simulate the maturation of a broadly neutralizing Ab (bnAb) against HIV. Starting from a germline precursor sequence of the VRC01 anti-HIV Ab, we simulate BCR evolution in response to different vaccination protocols and different Ags, which were previously designed by us. The simulation results provide qualitative guidelines for future vaccine design and reveal unique insights into bnAb evolution against the CD4 binding site of HIV. Our model makes possible direct comparisons of simulated BCR populations with results of deep sequencing data, which will be explored in future applications.

Conti, Simone (ORCID:000000017986567X)↗
DOE OSTI2021

Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates

A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Genomic Dissection of Anthracnose ( Colletotrichum sublineolum ) Resistance Response in Sorghum Differential Line SC112-14

Sorghum production is expanding to warmer and more humid regions where its production is being limited by multiple fungal pathogens. Anthracnose, caused by Colletotrichum sublineolum , is one of the major diseases in these regions, where it can cause yield losses of both grain and biomass. In this study, 114 recombinant inbred lines (RILs) derived from resistant sorghum line SC112-14 were evaluated at four distinct geographic locations in the United States for response to anthracnose. A genome scan using a high-density linkage map of 3,838 single nucleotide polymorphisms (SNPs) detected two loci at 5.25 and 1.18 Mb on chromosomes 5 and 6, respectively, that explain up to 59% and 44% of the observed phenotypic variation. A bin-mapping approach using a subset of 31 highly informative RILs was employed to determine the disease response to inoculation with ten anthracnose pathotypes in the greenhouse. A genome scan showed that the 5.25 Mb region on chromosome 5 is associated with a resistance response to nine pathotypes. Five SNP markers were developed and used to fine map the locus on chromosome 5 by evaluating 1,500 segregating F 2:3 progenies. Based on the genotypic and phenotypic analyses of 11 recombinants, the locus was narrowed down to a 470-kb genomic region. Following a genome-wide association study based on 574 accessions previously phenotyped and genotyped, the resistance locus was delimited to a 34-kb genomic interval with five candidate genes. All five candidate genes encode proteins associated with plant immune systems, suggesting they may act in synergy in the resistance response.

Genetics & Heredity↗
DOE OSTI2023

Leveraging microfluidic dielectrophoresis to distinguish compositional variations of lipopolysaccharide in E. coli

Lipopolysaccharide (LPS) is the unique feature that composes the outer leaflet of the Gram-negative bacterial cell envelope. Variations in LPS structures affect a number of physiological processes, including outer membrane permeability, antimicrobial resistance, recognition by the host immune system, biofilm formation, and interbacterial competition. Rapid characterization of LPS properties is crucial for studying the relationship between these LPS structural changes and bacterial physiology. However, current assessments of LPS structures require LPS extraction and purification followed by cumbersome proteomic analysis. This paper demonstrates one of the first high-throughput and non-invasive strategies to directly distinguish Escherichia coli with different LPS structures. Using a combination of three-dimensional insulator-based dielectrophoresis (3DiDEP) and cell tracking in a linear electrokinetics assay, we elucidate the effect of structural changes in E. coli LPS oligosaccharides on electrokinetic mobility and polarizability. We show that our platform is sufficiently sensitive to detect LPS structural variations at the molecular level. To correlate electrokinetic properties of LPS with the outer membrane permeability, we further examined effects of LPS structural variations on bacterial susceptibility to colistin, an antibiotic known to disrupt the outer membrane by targeting LPS. Our results suggest that microfluidic electrokinetic platforms employing 3DiDEP can be a useful tool for isolating and selecting bacteria based on their LPS glycoforms. Future iterations of these platforms could be leveraged for rapid profiling of pathogens based on their surface LPS structural identity.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Shotgun Immunoproteomic Approach for the Discovery of Linear B-Cell Epitopes in Biothreat Agents Francisella tularensis and Burkholderia pseudomallei

Peptide-based subunit vaccines are coming to the forefront of current vaccine approaches, with safety and cost-effective production among their top advantages. Peptide vaccine formulations consist of multiple synthetic linear epitopes that together trigger desired immune responses that can result in robust immune memory. The advantages of linear compared to conformational epitopes are their simple structure, ease of synthesis, and ability to stimulate immune responses by means that do not require complex 3D conformation. Prediction of linear epitopes through use of computational tools is fast and cost-effective, but typically of low accuracy, necessitating extensive experimentation to verify results. On the other hand, identification of linear epitopes through experimental screening has been an inefficient process that requires thorough characterization of previously identified full-length protein antigens, or laborious techniques involving genetic manipulation of organisms. In this study, we apply a newly developed generalizable screening method that enables efficient identification of B-cell epitopes in the proteomes of pathogenic bacteria. As a test case, we used this method to identify epitopes in the proteome of Francisella tularensis (Ft), a Select Agent with a well-characterized immunoproteome. Our screen identified many peptides that map to known antigens, including verified and predicted outer membrane proteins and extracellular proteins, validating the utility of this approach. We then used the method to identify seroreactive peptides in the less characterized immunoproteome of Select Agent Burkholderia pseudomallei (Bp). This screen revealed known Bp antigens as well as proteins that have not been previously identified as antigens. Although B-cell epitope prediction tools Bepipred 2.0 and iBCE-EL classified many of our seroreactive peptides as epitopes, they did not score them significantly higher than the non-reactive tryptic peptides in our study, nor did they assign higher scores to seroreactive peptides from known Ft or Bp antigens, highlighting the need for experimental data instead of relying on computational epitope predictions alone. The present workflow is easily adaptable to detecting peptide targets relevant to the immune systems of other mammalian species, including humans (depending upon the availability of convalescent sera from patients), and could aid in accelerating the discovery of B-cell epitopes and development of vaccines to counter emerging biological threats.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Antimicrobial Peptide Mimics for Clinical Use: Does Size Matter?

The search for efficient antimicrobial therapies that can alleviate suffering caused by infections from resistant bacteria is more urgent than ever before. Infections caused by multi-resistant pathogens represent a significant and increasing burden to healthcare and society and researcher are investigating new classes of bioactive compounds to slow down this development. Antimicrobial peptides from the innate immune system represent one promising class that offers a potential solution to the antibiotic resistance problem due to their mode of action on the microbial membranes. However, challenges associated with pharmacokinetics, bioavailability and off-target toxicity are slowing down the advancement and use of innate defensive peptides. Improving the therapeutic properties of these peptides is a strategy for reducing the clinical limitations and synthetic mimics of antimicrobial peptides are emerging as a promising class of molecules for a variety of antimicrobial applications. These compounds can be made significantly shorter while maintaining, or even improving antimicrobial properties, and several downsized synthetic mimics are now in clinical development for a range of infectious diseases. A variety of strategies can be employed to prepare these small compounds and this review describes the different compounds developed to date by adhering to a minimum pharmacophore based on an amphiphilic balance between cationic charge and hydrophobicity. These compounds can be made as small as dipeptides, circumventing the need for large compounds with elaborate three-dimensional structures to generate simplified and potent antimicrobial mimics for a range of medical applications. This review highlights key and recent development in the field of small antimicrobial peptide mimics as a promising class of antimicrobials, illustrating just how small you can go.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Sex- and age-specific aspects of human peripheral T-cell dynamics

Background: The diversity of the antigenic T cell receptor (TCR) repertoire clonally expressed on T lymphocytes is a key element of the adaptive immune system protective functions. A decline in diversity in the older adults is associated with health deterioration. This diversity is generated by the rearrangement of TRB genes coding for TCR chains during lymphocyte differentiation in the thymus, but is essentially maintained by peripheral T lymphocytes proliferation for most of life. Deep sequencing of rearranged TRB genes from blood cells allows the monitoring of peripheral T cell repertoire dynamics. We analysed two aspects of rearranged TRB diversity, related to T lymphocyte proliferation and to the distribution of the T cell clone size, in a collection of repertoires obtained from 1 to 74 years-old donors. Results: Our results show that peripheral T lymphocytes expansion differs according to the recombination status of their TRB loci. Their proliferation rate changes with age, with different patterns in men and women. T cell clone size becomes more heterogeneous with time, and, in adults, is always more even in women. Importantly, a longitudinal analysis of TRB repertoires obtained at ten years intervals from individual men and women confirms the findings of this cross-sectional study. Conclusions: Peripheral T lymphocyte proliferation partially depends on their thymic developmental history. The rate of proliferation of T cells differing in their TRB rearrangement status is different in men and women before the age of 18 years old, but similar thereafter.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Diverse ATPase Proteins in Mobilomes Constitute a Large Potential Sink for Prokaryotic Host ATP

Prokaryote mobilome genomes rely on host machineries for survival and replication. Given that mobile genetic elements (MGEs) derive their energy from host cells, we investigated the diversity of ATP-utilizing proteins in MGE genomes to determine whether they might be associated with proteins that could suppress related host proteins that consume energy. A comprehensive search of 353 huge phage genomes revealed that up to 9% of the proteins have ATPase domains. For example, ATPase proteins constitute ~3% of the genomes of Lak phages with ~550 kbp genomes that occur in the microbiomes of humans and other animals. Statistical analysis shows the number of ATPase proteins increases linearly with genome length, consistent with a large sink for host ATP during replication of megaphages. Using metagenomic data from diverse environments, we found 505 mobilome proteins with ATPase domains fused to diverse functional domains. Among these composite ATPase proteins, 61.6% have known functional domains that could contribute to host energy diversion during the mobilome infection cycle. As many have domains that are known to interact with nucleic acids and proteins, we infer that numerous ATPase proteins are used during replication and for protection from host immune systems. We found a set of uncharacterized ATPase proteins with nuclease and protease activities, displaying unique domain architectures that are energy intensive based on the presence of multiple ATPase domains. In many cases, these composite ATPase proteins genomically co-localize with small proteins in genomic contexts that are reminiscent of toxin-antitoxin systems and phage helicase-antibacterial helicase systems. Small proteins that function as inhibitors may be a common strategy for control of cellular processes, thus could inspire future biochemical experiments for the development of new nucleic acid and protein manipulation tools, with diverse biotechnological applications.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Prophylactic treatment with PEGylated bovine IFNλ3 effectively bridges the gap in vaccine-induced immunity against FMD in cattle

Foot-and-mouth disease (FMD) is a vesicular disease of cloven-hoofed animals with devastating economic implications. The current FMD vaccine, routinely used in enzootic countries, requires at least 7 days to induce protection. However, FMD vaccination is typically not recommended for use in non-enzootic areas, underscoring the need to develop new fast-acting therapies for FMD control during outbreaks. Interferons (IFNs) are among the immune system’s first line of defense against viral infections. Bovine type III IFN delivered by a replication defective adenovirus (Ad) vector has effectively blocked FMD in cattle. However, the limited duration of protection—usually only 1–3 days post-treatment (dpt)—diminishes its utility as a field therapeutic. Here, we test whether polyethylene glycosylation (PEGylation) of recombinant bovine IFNλ3 (PEGboIFNλ3) can extend the duration of IFN-induced prevention of FMDV infection in both vaccinated and unvaccinated cattle. We treated groups of heifers with PEGboIFNλ3 alone or in combination with an adenovirus-based FMD O1Manisa vaccine (Adt-O1M) at either 3 or 5 days prior to challenge with homologous wild type FMDV. We found that pre-treatment with PEGboIFNλ3 was highly effective at preventing clinical FMD when administered at either time point, with or without co-administration of Adt-O1M vaccine. PEGboIFNλ3 protein was detectable systemically for >10 days and antiviral activity for 4 days following administration. Furthermore, in combination with Adt-O1M vaccine, we observed a strong induction of FMDV-specific IFNγ+ T cell response, demonstrating its adjuvanticity when co-administered with a vaccine. Our results demonstrate the promise of this modified IFN as a pre-exposure prophylactic therapy for use in emergency outbreak scenarios.

biotherapeutics↗
DOE OSTI2022

Mechanism of Peptide Agonist Binding in CXCR4 Chemokine Receptor

Chemokine receptors are key G-protein-coupled receptors (GPCRs) that control cell migration in immune system responses, development of cardiovascular and central nervous systems, and numerous diseases. In particular, the CXCR4 chemokine receptor promotes metastasis, tumor growth and angiogenesis in cancers. CXCR4 is also used as one of the two co-receptors for T-tropic HIV-1 entry into host cells. Therefore, CXCR4 serves as an important therapeutic target for treating cancers and HIV infection. Apart from the CXCL12 endogenous peptide agonist, previous studies suggested that the first 17 amino acids of CXCL12 are sufficient to activate CXCR4. Two 17-residue peptides with positions 1–4 mutated to RSVM and ASLW functioned as super and partial agonists of CXCR4, respectively. However, the mechanism of peptide agonist binding in CXCR4 remains unclear. Here, we have investigated this mechanism through all-atom simulations using a novel Peptide Gaussian accelerated molecular dynamics (Pep-GaMD) method. The Pep-GaMD simulations have allowed us to explore representative binding conformations of each peptide and identify critical low-energy states of CXCR4 activated by the super versus partial peptide agonists. Our simulations have provided important mechanistic insights into peptide agonist binding in CXCR4, which are expected to facilitate rational design of new peptide modulators of CXCR4 and other chemokine receptors.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

In-vivo neuronal dysfunction by Aβ and tau overlaps with brain-wide inflammatory mechanisms in Alzheimer’s disease

The molecular mechanisms underlying neuronal dysfunction in Alzheimer’s disease (AD) remain uncharacterized. Here, we identify genes, molecular pathways and cellular components associated with whole-brain dysregulation caused by amyloid-beta (Aβ) and tau deposits in the living human brain. We obtained in-vivo resting-state functional MRI (rs-fMRI), Aβ- and tau-PET for 47 cognitively unimpaired and 16 AD participants from the Translational Biomarkers in Aging and Dementia cohort. Adverse neuronal activity impacts by Aβ and tau were quantified with personalized dynamical models by fitting pathology-mediated computational signals to the participant’s real rs-fMRIs. Then, we detected robust brain-wide associations between the spatial profiles of Aβ-tau impacts and gene expression in the neurotypical transcriptome (Allen Human Brain Atlas). Within the obtained distinctive signature of in-vivo neuronal dysfunction, several genes have prominent roles in microglial activation and in interactions with Aβ and tau. Moreover, cellular vulnerability estimations revealed strong association of microglial expression patterns with Aβ and tau’s synergistic impact on neuronal activity (q < 0.001). These results further support the central role of the immune system and neuroinflammatory pathways in AD pathogenesis. Neuronal dysregulation by AD pathologies also associated with neurotypical synaptic and developmental processes. In addition, we identified drug candidates from the vast LINCS library to halt or reduce the observed Aβ-tau effects on neuronal activity. Top-ranked pharmacological interventions target inflammatory, cancer and cardiovascular pathways, including specific medications undergoing clinical evaluation in AD. Our findings, based on the examination of molecular-pathological-functional interactions in humans, may accelerate the process of bringing effective therapies into clinical practice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Factors affecting the production of sugarcane yield and sucrose accumulation: suggested potential biological solutions

Environmental stresses are the main constraints on agricultural productivity and food security worldwide. This issue is worsened by abrupt and severe changes in global climate. The formation of sugarcane yield and the accumulation of sucrose are significantly influenced by biotic and abiotic stresses. Understanding the biochemical, physiological, and environmental phenomena associated with these stresses is essential to increase crop production. This review explores the effect of environmental factors on sucrose content and sugarcane yield and highlights the negative effects of insufficient water supply, temperature fluctuations, insect pests, and diseases. This article also explains the mechanism of reactive oxygen species (ROS), the role of different metabolites under environmental stresses, and highlights the function of environmental stress-related resistance genes in sugarcane. This review further discusses sugarcane crop improvement approaches, with a focus on endophytic mechanism and consortium endophyte application in sugarcane plants. Endophytes are vital in plant defense; they produce bioactive molecules that act as biocontrol agents to enhance plant immune systems and modify environmental responses through interaction with plants. This review provides an overview of internal mechanisms to enhance sugarcane plant growth and environmental resistance and offers new ideas for improving sugarcane plant fitness and crop productivity.

Mehdi, Faisal↗
DOE OSTI2024

Tetranuclear Polypyridylruthenium(II) Complexes as Selective Nucleic Acid Stains for Flow Cytometric Analysis of Monocytic and Epithelial Lung Carcinoma Large Extracellular Vesicles

Selective staining of extracellular vesicles (EVs) is a major challenge for diagnostic and therapeutic applications. Herein, the EV labeling properties of a new class of tetranuclear polypyridylruthenium(II) complexes, Rubb7-TNL and Rubb7-TL, as phosphorescent stains are described. These new stains have many advantages over standard stains to detect and characterize EVs, including: high specificity for EV staining versus cell staining; high phosphorescence yields; photostability; and a lack of leaching from EVs until incorporation with target cells. As an example of their utility, large EVs released from control (basal) or lipopolysaccharide (LPS)-stimulated THP-1 monocytic leukemia cells were studied as a model of immune system EVs released during bacterial infection. Key findings from EV staining combined with flow cytometry were as follows: (i) LPS-stimulated THP-1 cells generated significantly larger and more numerous large EVs, as compared with those from unstimulated cells; (ii) EVs retained native EV physical properties after staining; and (iii) the new stains selectively differentiated intact large EVs from artificial liposomes, which are models of cell membrane fragments or other lipid-containing debris, as well as distinguished two distinct subpopulations of monocytic EVs within the same experiment, as a result of biochemical differences between unstimulated and LPS-stimulated monocytes. Comparatively, the staining patterns of A549 epithelial lung carcinoma-derived EVs closely resembled those of THP-1 cell line-derived EVs, which highlighted similarities in their selective staining despite their distinct cellular origins. This is consistent with the hypothesis that these new phosphorescent stains target RNA within the EVs.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗