Microbiol Resour Announc. 2024 Apr 23:e0007524. doi: 10.1128/mra.00075-24. Online ahead of print.

ABSTRACT

We report four Chitinophaga sp. strains isolated from wastewater collected onboard the International Space Station. Here, we present three finished and one draft genome. Taxonomic ranks established by genome-based analysis indicate that these Chitinophaga sp. strains represent candidates for a new species.

PMID:38651911 | DOI:10.1128/mra.00075-24

Int J Neonatal Screen. 2024 Apr 16;10(2):33. doi: 10.3390/ijns10020033.

ABSTRACT

Screening newborns using genome sequencing is being explored due to its potential to expand the list of conditions that can be screened. Previously, we proposed the need for large-scale pilot studies to assess the feasibility of screening highly penetrant genetic neurodevelopmental disorders. Here, we discuss the initial experience from the GUARDIAN study and the systemic gaps in clinical services that were identified in the early stages of the pilot study.

PMID:38651398 | DOI:10.3390/ijns10020033

Front Microbiol. 2024 Apr 4;15:1393362. doi: 10.3389/fmicb.2024.1393362. eCollection 2024.

ABSTRACT

[This corrects the article DOI: 10.3389/fmicb.2022.872708.].

PMID:38650886 | PMC:PMC11034363 | DOI:10.3389/fmicb.2024.1393362

Front Plant Sci. 2024 Apr 8;15:1365951. doi: 10.3389/fpls.2024.1365951. eCollection 2024.

ABSTRACT

Chestnut blight (caused by Cryphonectria parasitica), together with Phytophthora root rot (caused by Phytophthora cinnamomi), has nearly extirpated American chestnut (Castanea dentata) from its native range. In contrast to the susceptibility of American chestnut, many Chinese chestnut (C. mollissima) genotypes are resistant to blight. In this research, we performed a series of genome-wide association studies for blight resistance originating from three unrelated Chinese chestnut trees (Mahogany, Nanking and M16) and a Quantitative Trait Locus (QTL) study on a Mahogany-derived inter-species F2 family. We evaluated trees for resistance to blight after artificial inoculation with two fungal strains and scored nine morpho-phenological traits that are the hallmarks of species differentiation between American and Chinese chestnuts. Results support a moderately complex genetic architecture for blight resistance, as 31 QTLs were found on 12 chromosomes across all studies. Additionally, although most morpho-phenological trait QTLs overlap or are adjacent to blight resistance QTLs, they tend to aggregate in a few genomic regions. Finally, comparison between QTL intervals for blight resistance and those previously published for Phytophthora root rot resistance, revealed five common disease resistance regions on chromosomes 1, 5, and 11. Our results suggest that it will be difficult, but still possible to eliminate Chinese chestnut alleles for the morpho-phenological traits while achieving relatively high blight resistance in a backcross hybrid tree. We see potential for a breeding scheme that utilizes marker-assisted selection early for relatively large effect QTLs followed by genome selection in later generations for smaller effect genomic regions.

PMID:38650705 | PMC:PMC11033410 | DOI:10.3389/fpls.2024.1365951

Comput Struct Biotechnol J. 2024 Apr 2;23:1562-1571. doi: 10.1016/j.csbj.2024.03.030. eCollection 2024 Dec.

ABSTRACT

Human leukocyte antigen (HLA) genes play pivotal roles in numerous immunological applications. Given the immense number of polymorphisms, achieving accurate high-throughput HLA typing remains challenging. This study aimed to harness the human pan-genome reference consortium (HPRC) resources as a potential benchmark for HLA reference materials. We meticulously annotated specific four field-resolution alleles for 11 HLA genes (HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1, -DRB3, -DRB4 and -DRB5) from 44 high-quality HPRC personal genome assemblies. For sequencing, we crafted HLA-specific probes and conducted capture-based targeted sequencing of the genomic DNA of the HPRC cohort, ensuring focused and comprehensive coverage of the HLA region of interest. We used publicly available short-read whole-genome sequencing (WGS) data from identical samples to offer a comparative perspective. To decipher the vast amount of sequencing data, we employed seven distinct software tools: OptiType, HLA-VBseq, HISAT genotype, SpecHLA, T1K, QzType, and DRAGEN. Each tool offers unique capabilities and algorithms for HLA genotyping, allowing comprehensive analysis and validation of the results. We then compared these results with benchmarks derived from personal genome assemblies. Our findings present a comprehensive four-field-resolution HLA allele annotation for 44 HPRC samples. Significantly, our innovative targeted next-generation sequencing (NGS) approach for HLA genes showed superior accuracy compared with conventional short-read WGS. An integrated analysis involving QzType, T1K, and DRAGEN was developed, achieving 100% accuracy for all 11 HLA genes. In conclusion, our study highlighted the combination of targeted short-read sequencing and astute computational analysis as a robust approach for HLA genotyping. Furthermore, the HPRC cohort has emerged as a valuable assembly-based reference in this realm.

PMID:38650588 | PMC:PMC11035020 | DOI:10.1016/j.csbj.2024.03.030

Bioresour Bioprocess. 2021 Dec 14;8(1):125. doi: 10.1186/s40643-021-00485-0.

ABSTRACT

Vibrio natriegens is a promising industrial chassis with a super-fast growth rate and high substrate uptake rates. V. natriegens was previously engineered to produce 1,3-propanediol (1,3-PDO) from glycerol by overexpressing the corresponding genes in a plasmid. However, antibiotic selection pressure for plasmid stability was not satisfactory and plasmid loss resulted in reduced productivity of the bioprocess. In this study, we developed an antibiotic-free plasmid stabilization system for V. natriegens. The system was achieved by shifting the glpD gene, one of the essential genes for glycerol degradation, from the chromosome to plasmid. With this system, engineered V. natriegens can stably maintain a large expression plasmid during the whole fed-batch fermentation and accumulated 69.5 g/L 1,3-PDO in 24 h, which was 23% higher than that based on antibiotic selection system. This system was also applied to engineering V. natriegens for the production of 3-hydroxypropionate (3-HP), enabling the engineered strain to accumulate 64.5 g/L 3-HP in 24 h, which was 30% higher than that based on antibiotic system. Overall, the developed strategy could be useful for engineering V. natriegens as a platform for the production of value-added chemicals from glycerol.

PMID:38650249 | DOI:10.1186/s40643-021-00485-0

Bioresour Bioprocess. 2021 Dec 16;8(1):128. doi: 10.1186/s40643-021-00483-2.

ABSTRACT

Zymomonas mobilis is a well-recognized ethanologenic bacterium with outstanding characteristics which make it a promising platform for the biotechnological production of relevant building blocks and fine chemicals compounds. In the last years, research has been focused on the physiological, genetic, and metabolic engineering strategies aiming at expanding Z. mobilis ability to metabolize lignocellulosic substrates toward biofuel production. With the expansion of the Z. mobilis molecular and computational modeling toolbox, the potential of this bacterium as a cell factory has been thoroughly explored. The number of genomic, transcriptomic, proteomic, and fluxomic data that is becoming available for this bacterium has increased. For this reason, in the forthcoming years, systems biology is expected to continue driving the improvement of Z. mobilis for current and emergent biotechnological applications. While the existing molecular toolbox allowed the creation of stable Z. mobilis strains with improved traits for pinpointed biotechnological applications, the development of new and more flexible tools is crucial to boost the engineering capabilities of this bacterium. Novel genetic toolkits based on the CRISPR-Cas9 system and recombineering have been recently used for the metabolic engineering of Z. mobilis. However, they are mostly at the proof-of-concept stage and need to be further improved.

PMID:38650193 | DOI:10.1186/s40643-021-00483-2

Med Sci Sports Exerc. 2024 Apr 23. doi: 10.1249/MSS.0000000000003457. Online ahead of print.

ABSTRACT

PURPOSE: Exercise training during the National Aeronautics and Space Administration (NASA) 70-day bed rest study effectively counteracted the decline in aerobic capacity, muscle mass, strength, and endurance. We aimed to characterize the genomic response of the participants' vastus lateralis (VL) on day 64 of bed rest with and without exercise countermeasures.

METHODS: Twenty-two healthy young males were randomized into three groups: 1) bed rest only (n = 7), 2) bed rest + aerobic (6 d/wk) and resistance training (3 d/wk) on standard equipment (n = 7), and 3) bed rest + aerobic and resistance training using a flywheel device (n = 8). The VL gene and microRNA microarrays were analyzed using GeneSpring GX 14.9.1.

RESULTS: Bed rest significantly altered the expression of 2113 annotated genes in at least one out of the three study groups (fold change (FC) > 1.2; P < 0.05). Interaction analysis revealed that exercise attenuated the bed rest effect of 511 annotated genes (FC 1.2, P < 0.05). In the bed rest only group, a predominant downregulation of genes was observed while in the two exercise groups there was a notable attenuation or reversal of this effect, with no significant differences between the two exercise modalities. Enrichment analysis identified functional categories and gene pathways, many of them related to the mitochondria. Additionally, bed rest significantly altered the expression of 35 microRNAs (FC > 1.2, P < 0.05) with no difference between the three groups. Twelve are known to regulate some of the mitochondrial-related genes that were altered following bed rest.

CONCLUSIONS: Mitochondrial gene expression was a significant component of the molecular response to long-term bed rest. While exercise attenuated the FC in the downregulation of many genes, it did not completely counteract all the molecular consequences.

PMID:38650118 | DOI:10.1249/MSS.0000000000003457

Microb Pathog. 2024 Apr 20:106657. doi: 10.1016/j.micpath.2024.106657. Online ahead of print.

ABSTRACT

Staphylococcus aureus is a major human pathogen that can cause infections that range from superficial skin and mucosal infections to life threatening disseminated infections. S. aureus can attach to medical devices and host tissues and form biofilms that allow the bacteria to evade the host immune system and provide protection from antimicrobial agents. To counter host-generated oxidative and nitrosative stress mechanisms that are part of the normal host responses to invading pathogens, S. aureus utilizes low molecular weight (LMW) thiols, such as bacillithiol (BSH). Additionally, S. aureus synthesizes its own nitric oxide (NO), which combined with its downstream metabolites may also protect the bacteria against specific host responses. We have previously shown that LMW thiols are required for biofilm formation in Mycobacterium smegmatis and Pseudomonas aeruginosa. Here, we show that the S. aureus bshC mutant strain, which is defective in the last step of the BSH pathway and lacks BSH, is impaired in biofilm formation. We also identify a possible S-nitrosobacillithiol reductase (BSNOR), similar in sequence to an S-nitrosomycothiol reductase found in M. smegmatis and show that the putative S. aureus bsnoR mutant strain has reduced levels of BSH and decreased biofilm formation. Our studies also show that NO plays an important role in biofilm formation and that acidified sodium nitrite severely reduces biofilm thickness. These studies provide insight into the roles of oxidative and nitrosative stress mechanisms on biofilm formation and indicate that BSH and NO are key players in normal biofilm formation in S. aureus.

PMID:38649100 | DOI:10.1016/j.micpath.2024.106657

J Neural Eng. 2024 Apr 22. doi: 10.1088/1741-2552/ad417c. Online ahead of print.

ABSTRACT

Traditional quantification of fluorescence signals, such as&#xD;∆F/F, relies on ratiometric measures that necessitate a baseline for compar-&#xD;ison, limiting their applicability in dynamic analyses. Our goal here is to&#xD;develop a baseline-independent method for analyzing fluorescence data that&#xD;fully exploits temporal dynamics to introduce a novel approach for dynami-&#xD;cal super-resolution analysis, including in subcellular resolution.&#xD;Approach: We introduce ARES (Autoregressive RESiduals), a novel method&#xD;that leverages the temporal aspect of fluorescence signals. By focusing on&#xD;the quantification of residuals following linear autoregression, ARES obviates&#xD;the need for a predefined baseline, enabling a more nuanced analysis of signal&#xD;dynamics.&#xD;Main Result: We delineate the foundational attributes of ARES, illustrat-&#xD;ing its capability to enhance both spatial and temporal resolution of calcium&#xD;fluorescence activity beyond the conventional ratiometric measure (∆F/F).&#xD;Additionally, we demonstrate ARES's utility in elucidating intracellular cal-&#xD;cium dynamics through the detailed observation of calcium wave propagation&#xD;within a dendrite.&#xD;Significance: ARES stands out as a robust and precise tool for the quan-&#xD;tification of fluorescence signals, adept at analyzing both spontaneous and&#xD;evoked calcium dynamics. Its ability to facilitate the subcellular localiza-&#xD;tion of calcium signals and the spatiotemporal tracking of calcium dynam-&#xD;ics-where traditional ratiometric measures falter-underscores its potential&#xD;to revolutionize baseline-independent analyses in the field.

PMID:38648784 | DOI:10.1088/1741-2552/ad417c

Int Arch Allergy Immunol. 2024 Apr 22:1-6. doi: 10.1159/000538500. Online ahead of print.

ABSTRACT

INTRODUCTION: The association between food protein-induced enterocolitis syndrome (FPIES) and wheat ingestion in children with celiac disease is unknown at this time.

METHODS: We present seven cases of children with celiac disease who presented with symptoms of wheat-triggered acute FPIES (a-FPIES). An oral food challenge (OFC) with wheat allergen followed by 4 h of observation was performed. Activation of innate system cells was measured at baseline (T0), during symptoms (Ts), and 4 h after symptom onset (Ts + 4). A panel of human inflammatory cytokines was also performed.

RESULTS: All patients reacted to the first allergen dose. Three patients experienced a decrease of 30 mm Hg in systolic blood pressure and tachycardia and required hemodynamic resuscitation. Neutrophilia and a decrease in eosinophil count were evident at 4 h after symptom onset. At 4 h after symptom onset, cytokines (IL-6 and IL-8, and to a lesser degree, IL-10) were elevated.

CONCLUSION: In a small sample of celiac patients with wheat exposure in an OFC, symptoms and acute immunological changes in serum inflammatory cytokine profile were consistent with a-FPIES.

PMID:38648739 | DOI:10.1159/000538500

J Agric Food Chem. 2024 Apr 22. doi: 10.1021/acs.jafc.3c07698. Online ahead of print.

ABSTRACT

For healthier human nutrition, it is desirable to provide food with a high content of nutraceuticals such as polyphenolics, vitamins, and carotenoids. We investigated to what extent high growth irradiance influences the content of phenolics, α-tocopherol and carotenoids, in wild rocket (Diplotaxis tenuifolia), which is increasingly used as a salad green. Potted plants were grown in a climate chamber with a 16 h day length at photosynthetic photon flux densities varying from 20 to 1250 μmol m-2 s-1. Measurements of the maximal quantum yield of photosystem II, FV/FM, and of the epoxidation state of the violaxanthin cycle (V-cycle) showed that the plants did not suffer from excessive light for photosynthesis. Contents of carotenoids belonging to the V-cycle, α-tocopherol and several quercetin derivatives, increased nearly linearly with irradiance. Nonintrusive measurements of chlorophyll fluorescence induced by UV-A and blue light relative to that induced by red light, indicating flavonoid and carotenoid content, allowed not only a semiquantitative measurement of both compounds but also allowed to follow their dynamic changes during reciprocal transfers between low and high growth irradiance. The results show that growth irradiance has a strong influence on the content of three different types of compounds with antioxidative properties and that it is possible to determine the contents of flavonoids and specific carotenoids in intact leaves using chlorophyll fluorescence. The results may be used for breeding to enhance healthy compounds in wild rocket leaves and to monitor their content for selection of appropriate genotypes.

PMID:38648561 | DOI:10.1021/acs.jafc.3c07698

PLoS One. 2024 Apr 22;19(4):e0300441. doi: 10.1371/journal.pone.0300441. eCollection 2024.

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal agent of coronavirus disease 2019 (COVID-19), has infected millions of individuals worldwide, which poses a severe threat to human health. COVID-19 is a systemic ailment affecting various tissues and organs, including the lungs and liver. Intrahepatic cholangiocarcinoma (ICC) is one of the most common liver cancer, and cancer patients are particularly at high risk of SARS-CoV-2 infection. Nonetheless, few studies have investigated the impact of COVID-19 on ICC patients.

METHODS: With the methods of systems biology and bioinformatics, this study explored the link between COVID-19 and ICC, and searched for potential therapeutic drugs.

RESULTS: This study identified a total of 70 common differentially expressed genes (DEGs) shared by both diseases, shedding light on their shared functionalities. Enrichment analysis pinpointed metabolism and immunity as the primary areas influenced by these common genes. Subsequently, through protein-protein interaction (PPI) network analysis, we identified SCD, ACSL5, ACAT2, HSD17B4, ALDOA, ACSS1, ACADSB, CYP51A1, PSAT1, and HKDC1 as hub genes. Additionally, 44 transcription factors (TFs) and 112 microRNAs (miRNAs) were forecasted to regulate the hub genes. Most importantly, several drug candidates (Periodate-oxidized adenosine, Desipramine, Quercetin, Perfluoroheptanoic acid, Tetrandrine, Pentadecafluorooctanoic acid, Benzo[a]pyrene, SARIN, Dorzolamide, 8-Bromo-cAMP) may prove effective in treating ICC and COVID-19.

CONCLUSION: This study is expected to provide valuable references and potential drugs for future research and treatment of COVID-19 and ICC.

PMID:38648205 | DOI:10.1371/journal.pone.0300441

Bioresour Bioprocess. 2024 Jan 18;11(1):12. doi: 10.1186/s40643-023-00726-4.

ABSTRACT

The evaluation of plant-based feedstocks is an important aspect of biorefining. Nicotiana glauca is a solanaceous, non-food crop that produces large amounts of biomass and is well adapted to grow in suboptimal conditions. In the present article, compatible sequential solvent extractions were applied to N. glauca leaves to enable the generation of enriched extracts containing higher metabolite content comparing to direct leaf extracts. Typically, between 60 to 100 metabolite components were identified within the fractions. The occurrence of plant fatty acids, fatty acid alcohols, alkanes, sterols and terpenoids was detected by gas liquid chromatography-mass spectrometry (GC-MS) and metabolite identification was confirmed by comparison of physico-chemical properties displayed by available authentic standards. Collectively, co-products such waxes, oils, fermentable sugars, and terpenoids were all identified and quantified. The enriched fractions of N. glauca revealed a high level of readily extractable hydrocarbons, oils and high value co-products. In addition, the saccharification yield and cell wall composition analyses in the stems revealed the potential of the residue material as a promising lignocellulosic substrate for the production of fermentable sugars. In conclusion a multifractional cascade for valuable compounds/commodities has been development, that uses N. glauca biomass. These data have enabled the evaluation of N. glauca material as a potential feedstock for biorefining.

PMID:38647836 | PMC:PMC10991672 | DOI:10.1186/s40643-023-00726-4

Diabetologia. 2024 Apr 22. doi: 10.1007/s00125-024-06149-w. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Non-adherence to medication is a frequent barrier in the treatment of patients with type 2 diabetes mellitus, potentially limiting the effectiveness of evidence-based treatments. Previous studies have mostly relied on indirect adherence measures to analyse outcomes based on adherence. The aim of this study was to use LC-MS/MS in urine-a non-invasive, direct and objective measure-to assess non-adherence to cardiometabolic drugs and analyse its association with kidney and cardiovascular outcomes.

METHODS: This cohort study includes 1125 participants from the PROVALID study, which follows patients with type 2 diabetes mellitus at the primary care level. Baseline urine samples were tested for 79 cardiometabolic drugs and metabolites thereof via LC-MS/MS. An individual was classified as totally adherent if markers for all drugs were detected, partially non-adherent when at least one marker for one drug was detected, and totally non-adherent if no markers for any drugs were detected. Non-adherence was then analysed in the context of cardiovascular (composite of myocardial infarction, stroke and cardiovascular death) and kidney (composite of sustained 40% decline in eGFR, sustained progression of albuminuria, kidney replacement therapy and death from kidney failure) outcomes.

RESULTS: Of the participants, 56.3% were totally adherent, 42.0% were partially non-adherent, and 1.7% were totally non-adherent to screened cardiometabolic drugs. Adherence was highest to antiplatelet and glucose-lowering agents and lowest to lipid-lowering agents. Over a median (IQR) follow-up time of 5.10 (4.12-6.12) years, worse cardiovascular outcomes were observed with non-adherence to antiplatelet drugs (HR 10.13 [95% CI 3.06, 33.56]) and worse kidney outcomes were observed with non-adherence to antihypertensive drugs (HR 1.98 [95% CI 1.37, 2.86]).

CONCLUSIONS/INTERPRETATION: This analysis shows that non-adherence to cardiometabolic drug regimens is common in type 2 diabetes mellitus and negatively affects kidney and cardiovascular outcomes.

PMID:38647650 | DOI:10.1007/s00125-024-06149-w

Bioresour Bioprocess. 2023 Apr 30;10(1):30. doi: 10.1186/s40643-023-00647-2.

ABSTRACT

Currently, microbial manufacturing is widely used in various fields, such as food, medicine and energy, for its advantages of greenness and sustainable development. Process optimization is the committed step enabling the commercialization of microbial manufacturing products. However, the present optimization processes mainly rely on experience or trial-and-error method ignoring the intrinsic connection between cellular physiological requirement and production performance, so in many cases the productivity of microbial manufacturing could not been fully exploited at economically feasible cost. Recently, the rapid development of omics technologies facilitates the comprehensive analysis of microbial metabolism and fermentation performance from multi-levels of molecules, cells and microenvironment. The use of omics technologies makes the process optimization more explicit, boosting microbial manufacturing performance and bringing significant economic benefits and social value. In this paper, the traditional and omics technologies-guided process optimization of microbial manufacturing are systematically reviewed, and the future trend of process optimization is prospected.

PMID:38647562 | PMC:PMC10992112 | DOI:10.1186/s40643-023-00647-2

Brief Bioinform. 2024 Mar 27;25(3):bbae174. doi: 10.1093/bib/bbae174.

ABSTRACT

Molecular generative models have exhibited promising capabilities in designing molecules from scratch with high binding affinities in a predetermined protein pocket, offering potential synergies with traditional structural-based drug design strategy. However, the generative processes of such models are random and the atomic interaction information between ligand and protein are ignored. On the other hand, the ligand has high propensity to bind with residues called hotspots. Hotspot residues contribute to the majority of the binding free energies and have been recognized as appealing targets for designed molecules. In this work, we develop an interaction prompt guided diffusion model, InterDiff to deal with the challenges. Four kinds of atomic interactions are involved in our model and represented as learnable vector embeddings. These embeddings serve as conditions for individual residue to guide the molecular generative process. Comprehensive in silico experiments evince that our model could generate molecules with desired ligand-protein interactions in a guidable way. Furthermore, we validate InterDiff on two realistic protein-based therapeutic agents. Results show that InterDiff could generate molecules with better or similar binding mode compared to known targeted drugs.

PMID:38647154 | PMC:PMC11033848 | DOI:10.1093/bib/bbae174

Essays Biochem. 2024 Apr 22:EBC20230093. doi: 10.1042/EBC20230093. Online ahead of print.

ABSTRACT

Heparan sulfate (HS) is a glycosaminoglycan, polysaccharides that are considered to have arisen in the last common unicellular ancestor of multicellular animals. In this light, the large interactome of HS and its myriad functions in relation to the regulation of cell communication are not surprising. The binding of proteins to HS determines their localisation and diffusion, essential for embryonic development and homeostasis. Following the biosynthesis of the initial heparosan polymer, the subsequent modifications comprise an established canonical pathway and a minor pathway. The more frequent former starts with N-deacetylation and N-sulfation of GlcNAc residues, the latter with C-5 epimerisation of a GlcA residue adjacent to a GlcNAc. The binding of proteins to HS is driven by ionic interactions. The multivalent effect arising from the many individual ionic bonds between a single protein and a polysaccharide chain results in a far stronger interaction than would be expected from an ion-exchange process. In many instances, upon binding, both parties undergo substantial conformational change, the resulting hydrogen and van der Waal bonds contributing significant free energy to the binding reaction. Nevertheless, ionic bonds dominate the protein-polysaccharide interaction kinetically. Together with the multivalent effect, this provides an explanation for the observed trapping of HS-binding proteins in extracellular matrix. Importantly, individual ionic bonds have been observed to be dynamic; breaking and reforming, while the protein remains bound to the polysaccharide. These considerations lead to a model for 1D diffusion of proteins in extracellular matrix on HS, involving mechanisms such as sliding, chain switching and rolling.

PMID:38646914 | DOI:10.1042/EBC20230093

Front Immunol. 2024 Apr 5;15:1294020. doi: 10.3389/fimmu.2024.1294020. eCollection 2024.

ABSTRACT

Endogenous retroviruses (ERVs) derived from the long terminal repeat (LTR) family of transposons constitute a significant portion of the mammalian genome, with origins tracing back to ancient viral infections. Despite comprising approximately 8% of the human genome, the specific role of ERVs in the pathogenesis of COVID-19 remains unclear. In this study, we conducted a genome-wide identification of ERVs in human peripheral blood mononuclear cells (hPBMCs) and primary lung epithelial cells from monkeys and mice, both infected and uninfected with SARS-CoV-2. We identified 405, 283, and 206 significantly up-regulated transposable elements (TEs) in hPBMCs, monkeys, and mice, respectively. This included 254, 119, 68, and 28 ERVs found in hPBMCs from severe and mild COVID-19 patients, monkeys, and transgenic mice expressing the human ACE2 receptor (hACE2) and infected with SARS-CoV-2. Furthermore, analysis using the Genomic Regions Enrichment of Annotations Tool (GREAT) revealed certain parental genomic sequences of these up-regulated ERVs in COVID-19 patients may be involved in various biological processes, including histone modification and viral replication. Of particular interest, we identified 210 ERVs specifically up-regulated in the severe COVID-19 group. The genes associated with these differentially expressed ERVs were enriched in processes such as immune response activation and histone modification. HERV1_I-int: ERV1:LTR and LTR7Y: ERV1:LTR were highlighted as potential biomarkers for evaluating the severity of COVID-19. Additionally, validation of our findings using RT-qPCR in Bone Marrow-Derived Macrophages (BMDMs) from mice infected by HSV-1 and VSV provided further support to our results. This study offers insights into the expression patterns and potential roles of ERVs following viral infection, providing a valuable resource for future studies on ERVs and their interaction with SARS-CoV-2.

PMID:38646531 | PMC:PMC11026653 | DOI:10.3389/fimmu.2024.1294020

Front Oncol. 2024 Apr 4;14:1377373. doi: 10.3389/fonc.2024.1377373. eCollection 2024.

ABSTRACT

INTRODUCTION: The progression of solid cancers is manifested at the systemic level as molecular changes in the metabolome of body fluids, an emerging source of cancer biomarkers.

METHODS: We analyzed quantitatively the serum metabolite profile using high-resolution mass spectrometry. Metabolic profiles were compared between breast cancer patients (n=112) and two groups of healthy women (from Poland and Norway; n=95 and n=112, respectively) with similar age distributions.

RESULTS: Despite differences between both cohorts of controls, a set of 43 metabolites and lipids uniformly discriminated against breast cancer patients and healthy women. Moreover, smaller groups of female patients with other types of solid cancers (colorectal, head and neck, and lung cancers) were analyzed, which revealed a set of 42 metabolites and lipids that uniformly differentiated all three cancer types from both cohorts of healthy women. A common part of both sets, which could be called a multi-cancer signature, contained 23 compounds, which included reduced levels of a few amino acids (alanine, aspartate, glutamine, histidine, phenylalanine, and leucine/isoleucine), lysophosphatidylcholines (exemplified by LPC(18:0)), and diglycerides. Interestingly, a reduced concentration of the most abundant cholesteryl ester (CE(18:2)) typical for other cancers was the least significant in the serum of breast cancer patients. Components present in a multi-cancer signature enabled the establishment of a well-performing breast cancer classifier, which predicted cancer with a very high precision in independent groups of women (AUC>0.95).

DISCUSSION: In conclusion, metabolites critical for discriminating breast cancer patients from controls included components of hypothetical multi-cancer signature, which indicated wider potential applicability of a general serum metabolome cancer biomarker.

PMID:38646441 | PMC:PMC11027565 | DOI:10.3389/fonc.2024.1377373