Systems Biology
Causal influences of osteoarthritis on COVID-19: a Mendelian randomization study
Front Med (Lausanne). 2023 Oct 31;10:1287043. doi: 10.3389/fmed.2023.1287043. eCollection 2023.
ABSTRACT
OBJECTIVE: Although observational and genetic studies have indicated a correlation between OA and COVID-19, it remains uncertain whether osteoarthritis (OA) contributes to the severity of COVID-19. Here, we aimed to investigate the potential causal links between the two.
METHODS: In this study, we conducted Mendelian randomization (MR) analysis to investigate whether there is a potential causal connection between OA and COVID-19 outcomes. The analysis utilized publicly available GWAS summary datasets, incorporating data on OA (N = 455,221), SARS-CoV-2 infection (N = 2,597,856), hospitalized COVID-19 (N = 2,095,324), and critical COVID-19 (N = 1,086,211). Additionally, we performed a literature analysis to establish a molecular network connecting OA and COVID-19.
RESULTS: The MR analysis showed causal effects of OA on hospitalized COVID-19 (OR: 1.21, 95% CI: 1.02-1.43, p = 0.026) and critical COVID-19 (OR: 1.35, 95% CI: 1.09-1.68, p = 0.006) but not on SARS-CoV-2 infection as such (OR: 1.00, 95% CI: 0.92-1.08, p = 0.969). Moreover, the literature-based pathway analysis uncovered a set of specific genes, such as CALCA, ACE, SIRT1, TNF, IL6, CCL2, and others, that were found to mediate the association between OA and COVID-19.
CONCLUSION: Our findings indicate that OA elevates the risk of severe COVID-19. Therefore, larger efforts should be made in the prevention of COVID-19 in OA patients.
PMID:38020136 | PMC:PMC10644031 | DOI:10.3389/fmed.2023.1287043
Synthetic genetic circuits to uncover the OCT4 trajectories of successful reprogramming of human fibroblasts
Sci Adv. 2023 Dec;9(48):eadg8495. doi: 10.1126/sciadv.adg8495. Epub 2023 Nov 29.
ABSTRACT
Reprogramming human fibroblasts to induced pluripotent stem cells (iPSCs) is inefficient, with heterogeneity among transcription factor (TF) trajectories driving divergent cell states. Nevertheless, the impact of TF dynamics on reprogramming efficiency remains uncharted. We develop a system that accurately reports OCT4 protein levels in live cells and use it to reveal the trajectories of OCT4 in successful reprogramming. Our system comprises a synthetic genetic circuit that leverages noise to generate a wide range of OCT4 trajectories and a microRNA targeting endogenous OCT4 to set total cellular OCT4 protein levels. By fusing OCT4 to a fluorescent protein, we are able to track OCT4 trajectories with clonal resolution via live-cell imaging. We discover that a supraphysiological, stable OCT4 level is required, but not sufficient, for efficient iPSC colony formation. Our synthetic genetic circuit design and high-throughput live-imaging pipeline are generalizable for investigating TF dynamics for other cell fate programming applications.
PMID:38019912 | DOI:10.1126/sciadv.adg8495
Dynamic changes to the plant cuticle include the production of volatile cuticular wax-derived compounds
Proc Natl Acad Sci U S A. 2023 Dec 5;120(49):e2307012120. doi: 10.1073/pnas.2307012120. Epub 2023 Nov 29.
ABSTRACT
The cuticle is a hydrophobic structure that seals plant aerial surfaces from the surrounding environment. To better understand how cuticular wax composition changes over development, we conducted an untargeted screen of leaf surface lipids from black cottonwood (Populus trichocarpa). We observed major shifts to the lipid profile across development, from a phenolic and terpene-dominated profile in young leaves to an aliphatic wax-dominated profile in mature leaves. Contrary to the general pattern, levels of aliphatic cis-9-alkenes decreased in older leaves following their accumulation. A thorough examination revealed that the decrease in cis-9-alkenes was accompanied by a concomitant increase in aldehydes, one of them being the volatile compound nonanal. By applying exogenous alkenes to P. trichocarpa leaves, we show that unsaturated waxes in the cuticle undergo spontaneous oxidative cleavage to generate aldehydes and that this process occurs similarly in other alkene-accumulating systems such as balsam poplar (Populus balsamifera) leaves and corn (Zea mays) silk. Moreover, we show that the production of cuticular wax-derived compounds can be extended to other wax components. In bread wheat (Triticum aestivum), 9-hydroxy-14,16-hentriacontanedione likely decomposes to generate 2-heptadecanone and 7-octyloxepan-2-one (a caprolactone). These findings highlight an unusual route to the production of plant volatiles that are structurally encoded within cuticular wax precursors. These processes could play a role in modulating ecological interactions and open the possibility for engineering bioactive volatile compounds into plant waxes.
PMID:38019866 | DOI:10.1073/pnas.2307012120
TimiGP: An R package to depict the tumor microenvironment from bulk transcriptomics
STAR Protoc. 2023 Nov 27;4(4):102742. doi: 10.1016/j.xpro.2023.102742. Online ahead of print.
ABSTRACT
Exploring the clinical relevance of diverse immune cell types within the tumor microenvironment is pivotal for unraveling cancer intricacies and developing treatments. Here, we present a protocol for using tumor immune microenvironment illustration based on gene pairs, an R package to deduce cell-cell interactions, unveiling the association between immune cell relative abundance and patient prognoses from bulk gene expression and survival data. We describe steps for harnessing cell-type markers derived from single-cell RNA sequencing data to map the tumor immune microenvironment across a spectrum of cancer types. For complete details on the use and execution of this protocol, please refer to Li et al. (2023).1.
PMID:38019649 | DOI:10.1016/j.xpro.2023.102742
IL-17A Orchestrates Reactive Oxygen Species/HIF1α-Mediated Metabolic Reprogramming in Psoriasis
J Immunol. 2023 Nov 29:ji2300319. doi: 10.4049/jimmunol.2300319. Online ahead of print.
ABSTRACT
Immune cell-derived IL-17A is one of the key pathogenic cytokines in psoriasis, an immunometabolic disorder. Although IL-17A is an established regulator of cutaneous immune cell biology, its functional and metabolic effects on nonimmune cells of the skin, particularly keratinocytes, have not been comprehensively explored. Using multiomics profiling and systems biology-based approaches, we systematically uncover significant roles for IL-17A in the metabolic reprogramming of human primary keratinocytes (HPKs). High-throughput liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy revealed IL-17A-dependent regulation of multiple HPK proteins and metabolites of carbohydrate and lipid metabolism. Systems-level MitoCore modeling using flux-balance analysis identified IL-17A-mediated increases in HPK glycolysis, glutaminolysis, and lipid uptake, which were validated using biochemical cell-based assays and stable isotope-resolved metabolomics. IL-17A treatment triggered downstream mitochondrial reactive oxygen species and HIF1α expression and resultant HPK proliferation, consistent with the observed elevation of these downstream effectors in the epidermis of patients with psoriasis. Pharmacological inhibition of HIF1α or reactive oxygen species reversed IL-17A-mediated glycolysis, glutaminolysis, lipid uptake, and HPK hyperproliferation. These results identify keratinocytes as important target cells of IL-17A and reveal its involvement in multiple downstream metabolic reprogramming pathways in human skin.
PMID:38019129 | DOI:10.4049/jimmunol.2300319
A transcriptomic atlas of acute stress response to low pH in multiple <em>Issatchenkia orientalis</em> strains
Microbiol Spectr. 2023 Nov 29:e0253623. doi: 10.1128/spectrum.02536-23. Online ahead of print.
ABSTRACT
Issatchenkia orientalis is a promising industrial chassis to produce biofuels and bioproducts due to its high tolerance to multiple environmental stresses such as low pH, heat, and other chemicals otherwise toxic for the most widely used microbes. Yet, little is known about specific mechanisms of such tolerance in this organism, hindering our ability to engineer this species to produce valuable biochemicals. Here, we report a comprehensive study of the mechanisms of acidic tolerance in this species via transcriptome profiling across variable pH for 12 different strains with different phenotypes. We found multiple regulatory mechanisms involved in tolerance to low pH in different strains of I. orientalis, marking potential targets for future gene editing and perturbation experiments.
PMID:38018981 | DOI:10.1128/spectrum.02536-23
Natural product biosynthetic potential reflects macroevolutionary diversification within a widely distributed bacterial taxon
mSystems. 2023 Nov 29:e0064323. doi: 10.1128/msystems.00643-23. Online ahead of print.
ABSTRACT
This is the most comprehensive study performed thus far on the biosynthetic potential within the Flavobacteriaceae family. Our findings reveal intertwined taxonomic and natural product biosynthesis diversification within the family. We posit that the carbohydrate, peptide, and secondary metabolism triad synergistically shaped the evolution of this keystone bacterial taxon, acting as major forces underpinning the broad host range and opportunistic-to-pathogenic behavior encompassed by species in the family. This study further breaks new ground for future research on select Flavobacteriaceae spp. as reservoirs of novel drug leads.
PMID:38018967 | DOI:10.1128/msystems.00643-23
Beta-cell intrinsic dynamics rather than gap junction structure dictates subpopulations in the islet functional network
Elife. 2023 Nov 29;12:e83147. doi: 10.7554/eLife.83147. Online ahead of print.
ABSTRACT
Diabetes is caused by the inability of electrically coupled, functionally heterogeneous -cells within the pancreatic islet to provide adequate insulin secretion. Functional networks have been used to represent synchronized oscillatory [Ca2+] dynamics and to study -cell subpopulations, which play an important role in driving islet function. The mechanism by which highly synchronized -cell subpopulations drive islet function is unclear. We used experimental and computational techniques to investigate the relationship between functional networks, structural (gap-junction) networks, and intrinsic -cell dynamics in slow and fast oscillating islets. Highly synchronized subpopulations in the functional network were differentiated by intrinsic dynamics, including metabolic activity and KATP channel conductance, more than structural coupling. Consistent with this, intrinsic dynamics were more predictive of high synchronization in the islet functional network as compared to high levels of structural coupling. Finally, dysfunction of gap junctions, which can occur in diabetes, caused decreases in the efficiency and clustering of the functional network. These results indicate that intrinsic dynamics rather than structure drive connections in the functional network and highly synchronized subpopulations, but gap junctions are still essential for overall network efficiency. These findings deepen our interpretation of functional networks and the formation of functional sub-populations in dynamic tissues such as the islet.
PMID:38018905 | DOI:10.7554/eLife.83147
CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy
Autophagy. 2023 Nov 29. doi: 10.1080/15548627.2023.2288528. Online ahead of print.
ABSTRACT
CARM1 (coactivator associated arginine methyltransferase 1) has recently emerged as a powerful regulator of skeletal muscle biology. However, the molecular mechanisms by which the methyltransferase remodels muscle remain to be fully understood. In this study, carm1 skeletal muscle-specific knockout (mKO) mice exhibited lower muscle mass with dysregulated macroautophagic/autophagic and atrophic signaling, including depressed AMP-activated protein kinase (AMPK) site-specific phosphorylation of ULK1 (unc-51 like autophagy activating kinase 1; Ser555) and FOXO3 (forkhead box O3; Ser588), as well as MTOR (mechanistic target of rapamycin kinase)-induced inhibition of ULK1 (Ser757), along with AKT/protein kinase B site-specific suppression of FOXO1 (Ser256) and FOXO3 (Ser253). In addition to lower mitophagy and autophagy flux in skeletal muscle, carm1 mKO led to increased mitochondrial PRKN/parkin accumulation, which suggests that CARM1 is required for basal mitochondrial turnover and autophagic clearance. carm1 deletion also elicited PPARGC1A (PPARG coactivator 1 alpha) activity and a slower, more oxidative muscle phenotype. As such, these carm1 mKO-evoked adaptations disrupted mitophagy and autophagy induction during food deprivation and collectively served to mitigate fasting-induced muscle atrophy. Furthermore, at the threshold of muscle atrophy during food deprivation experiments in humans, skeletal muscle CARM1 activity decreased similarly to our observations in mice, and was accompanied by site-specific activation of ULK1 (Ser757), highlighting the translational impact of the methyltransferase in human skeletal muscle. Taken together, our results indicate that CARM1 governs mitophagic, autophagic, and atrophic processes fundamental to the maintenance and remodeling of muscle mass. Targeting the enzyme may provide new therapeutic approaches for mitigating skeletal muscle atrophy.
PMID:38018843 | DOI:10.1080/15548627.2023.2288528
Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: A systematic review
Immun Inflamm Dis. 2023 Nov;11(11):e1090. doi: 10.1002/iid3.1090.
ABSTRACT
AIM: Respiratory disease (RD) is one of the most common diseases characterized by lung dysfunction. Many diagnostic mechanisms have been used to identify the pathogenic agents of responsible for RD. Among these, proteomics emerges as a valuable diagnostic method for pinpointing the specific proteins involved in RD pathogenesis. Therefore, in this study, for the first time, we examined the protein markers involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), asthma, bronchiolitis obliterans (BO), and chemical warfare victims exposed to mustard gas, using the proteomics method as a systematic study.
MATERIALS AND METHODS: A systematic search was performed up to September 2023 on several databases, including PubMed, Scopus, ISI Web of Science, and Cochrane. In total, selected 4246 articles were for evaluation according to the criteria. Finally, 119 studies were selected for this systematic review.
RESULTS: A total of 13,806 proteins were identified, 6471 in COPD, 1603 in Asthma, 5638 in IPF, three in BO, and 91 in mustard gas exposed victims. Alterations in the expression of these proteins were observed in the respective diseases. After evaluation, the results showed that 31 proteins were found to be shared among all five diseases.
CONCLUSION: Although these 31 proteins regulate different factors and molecular pathways in all five diseases, they ultimately lead to the regulation of inflammatory pathways. In other words, the expression of some proteins in COPD and mustard-exposed patients increases inflammatory reactions, while in IPF, they cause lung fibrosis. Asthma, causes allergic reactions due to T-cell differentiation toward Th2.
PMID:38018577 | DOI:10.1002/iid3.1090
2,5-Dihydroxyterephthalic Acid: A Matrix for Improved Detection and Imaging of Amino Acids
Anal Chem. 2023 Nov 28. doi: 10.1021/acs.analchem.3c01731. Online ahead of print.
ABSTRACT
Amino acids (AAs), which are low-molecular-weight (low-MW) metabolites, serve as essential building blocks not only for protein synthesis but also for maintaining the nitrogen balance in living systems. In situ detection and imaging of AAs are crucial for understanding more complex biological processes. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a label-free mass spectrometric imaging technique that enables the simultaneous detection and imaging of the spatial distribution and relative abundance of different endogenous/exogenous compounds in biological samples. The excellent efficiency of MALDI-MSI is attributed to the choice of the MALDI matrix. However, to the best of our knowledge, no matrix has been specifically developed for AAs. Herein, we report a MALDI matrix, 2,5-dihydroxyterephthalic acid (DHT), which can improve the detection and imaging of AAs in biological samples by MALDI-MS. Our results indicated that DHT exhibited strong ultraviolet-visible (UV-vis) absorption, uniform matrix deposition, and high vacuum stability. Moreover, the matrix-related ion signals produced from DHT were reduced by 50 and 71.8% at m/z < 500 compared to the commonly used matrices of 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA), respectively, in their respective organic solvents. In terms of quantitative performance, arginine, glutamic acid, glutamine, and proline can be detected with limits of detection of 6, 4, 6, and 4 ng/mL, respectively, using the DHT as the matrix. Using DHT as the matrix, all 20 protein AAs were successfully detected in human serum by MALDI-MS, whereas only 7 and 10 AAs were detected when DHB and CHCA matrices were used, respectively. Furthermore, 20 protein AAs and taurine were successfully detected and imaged in a section of edible Crassostrea gigas (oyster) tissue for the first time. Our study demonstrates that using DHT as a matrix can improve the detection and imaging of AAs in biological samples by MALDI-MS.
PMID:38018128 | DOI:10.1021/acs.analchem.3c01731
Preventive effect of culture supernatant of epithelial-like peritoneal mesothelial cells on peritoneal fibrosis
Perit Dial Int. 2023 Nov 28:8968608231213577. doi: 10.1177/08968608231213577. Online ahead of print.
ABSTRACT
Peritoneal fibrosis (PF) is a primary reason for discontinuing peritoneal dialysis, which involves characteristic changes of peritoneal mesothelial cells (PMCs). We previously reported preventive effects of implanting human epithelial-like PMCs (P-Epi) for mouse PF caused by mechanical peritoneum scrapings. In the present study, we analysed the preventive effects of culture supernatant of P-Epi in PF. Concentrated culture supernatant of P-Epi or human fibroblast-like PMCs (P-Fibro) or vehicles was injected into nude mice that had undergone mechanical scraping of the parietal and visceral peritoneum, and thickness and amount of adhesions were analysed. Although increased peritoneal adhesions and peritoneum thickening were observed in the vehicle-injected positive control group compared to the sham operation group, fewer number of adhesions and less thickness were observed in the mice treated with culture supernatant of P-Epi, but not P-Fibro, compared to the vehicle-injected positive controls. Immunofluorescent analysis revealed that the expression of extracellular matrix, type I collagen and fibronectin, was lower in the mice treated with culture supernatant of P-Epi than in the vehicle-injected positive controls. In addition, exosomes from P-Epi significantly reduced transforming growth factor-β (TGF-β)-induced expressions of type I collagen and fibronectin in 3T3 fibroblast cells. Collectively, culture supernatant of P-Epi has preventive effects on PF, thus cell therapy is not necessarily required. Further exploration of substances secreted by P-Epi and their protective mechanisms could lead to the development of therapeutic strategies to limit PF.
PMID:38017611 | DOI:10.1177/08968608231213577
How is Big Data reshaping preclinical aging research?
Lab Anim (NY). 2023 Nov 28. doi: 10.1038/s41684-023-01286-y. Online ahead of print.
ABSTRACT
The exponential scientific and technological progress during the past 30 years has favored the comprehensive characterization of aging processes with their multivariate nature, leading to the advent of Big Data in preclinical aging research. Spanning from molecular omics to organism-level deep phenotyping, Big Data demands large computational resources for storage and analysis, as well as new analytical tools and conceptual frameworks to gain novel insights leading to discovery. Systems biology has emerged as a paradigm that utilizes Big Data to gain insightful information enabling a better understanding of living organisms, visualized as multilayered networks of interacting molecules, cells, tissues and organs at different spatiotemporal scales. In this framework, where aging, health and disease represent emergent states from an evolving dynamic complex system, context given by, for example, strain, sex and feeding times, becomes paramount for defining the biological trajectory of an organism. Using bioinformatics and artificial intelligence, the systems biology approach is leading to remarkable advances in our understanding of the underlying mechanism of aging biology and assisting in creative experimental study designs in animal models. Future in-depth knowledge acquisition will depend on the ability to fully integrate information from different spatiotemporal scales in organisms, which will probably require the adoption of theories and methods from the field of complex systems. Here we review state-of-the-art approaches in preclinical research, with a focus on rodent models, that are leading to conceptual and/or technical advances in leveraging Big Data to understand basic aging biology and its full translational potential.
PMID:38017182 | DOI:10.1038/s41684-023-01286-y
The foraging ecology of yellow-billed and red- billed choughs changed between two climatically different years
Sci Rep. 2023 Nov 27;13(1):20908. doi: 10.1038/s41598-023-46336-0.
ABSTRACT
Climate change is affecting the alpine ecosystem at an unprecedented rate, with marked changes in spring phenology and the elevation distribution of birds. Changes in the European Alps are happening rapidly, and it is possible behaviours stand to change from one year to the next. The year 2022 was characterised by climatic extremes: Italy experienced its hottest year ever, and it was the driest since 1800. Here, we assessed whether the foraging ecology of two coexisting upland bird species, the yellow-billed and the red-billed chough, changed from 2021 to 2022. We assessed foraging stay times, flock size, propensity to mixed flocking, foraging home ranges and altitudinal distribution. Stay times of both species when foraging in monospecific flocks significantly shortened in 2022, especially in the case of the red-billed chough. The two corvids are known to influence each other when foraging together. In 2021, as expected, the stay times of the red-billed chough decreased when in the presence of the congener, but this did not occur in 2022. Instead, the yellow-billed chough increased its altitudinal foraging distribution in 2022. The results are in line with the hypothesis that large climate variations may disrupt the foraging ecology of mountain birds. However, as it is not possible to draw solid conclusions from just two years of observations, further field research will have to be planned in the future.
PMID:38016972 | DOI:10.1038/s41598-023-46336-0
mb-PHENIX: Diffusion and Supervised Uniform Manifold Approximation for denoising microbiota data
Bioinformatics. 2023 Nov 28:btad706. doi: 10.1093/bioinformatics/btad706. Online ahead of print.
ABSTRACT
MOTIVATION: Microbiota data encounters challenges arising from technical noise and the curse of dimensionality, which affect the reliability of scientific findings. Furthermore, abundance matrices exhibit a zero-inflated distribution due to biological and technical influences. Consequently, there is a growing demand for advanced algorithms that can effectively recover missing taxa while also considering the preservation of data structure.
RESULTS: We present mb-PHENIX, an open-source algorithm developed in Python that recovers taxa abundances from the noisy and sparse microbiota data. Our method infers the missing information of count matrix (in 16S microbiota and shotgun studies) by applying imputation via diffusion with supervised Uniform Manifold Approximation Projection (sUMAP) space as initialization. Our hybrid machine learning approach allows to denoise microbiota data, revealing differential abundance microbes among study groups where traditional abundance analysis fails.
AVAILABILITY: The mb-PHENIX algorithm is available at https://github.com/resendislab/mb-PHENIX. An easy-to-use implementation is available on Google Colab (see GitHub).
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
PMID:38015858 | DOI:10.1093/bioinformatics/btad706
Evaluation of Diagnostic Significance of Salivary miRNA-184 and miRNA-21 in Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders
Head Neck Pathol. 2023 Nov 28. doi: 10.1007/s12105-023-01600-7. Online ahead of print.
ABSTRACT
BACKGROUND: Altered levels of miRNAs might affect the pathogenesis of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD). This study evaluated the diagnostic potential of salivary miRNA-21 and miRNA-184 in OSCC and OPMD.
METHODS: We recruited a total of 90 subjects including OSCC, OPMD, and healthy controls. RNA was isolated from the saliva samples of the study subjects. Expression of miRNA-21 and miRNA-184 was analyzed using qRT-PCR. Their levels were compared and the diagnostic cut-off was determined using the ROC curve.
RESULTS: There was a significant increase in miRNA-21 and a decrease in miRNA-184 in OSCC and OPMD as compared to healthy controls (p < 0.001). Levels of salivary miRNA-21 and miRNA-184 can differentiate OSCC and OPMD from controls and premalignant conditions from malignant conditions.
CONCLUSION: Salivary miRNA-21 and miRNA-184 may be beneficial for the early detection of OSCC and OPMD. Also, saliva can be used for detecting neoplastic transformation of oral mucosa since it is non-invasive and easily accessible.
PMID:38015343 | DOI:10.1007/s12105-023-01600-7
Analysis of B7-H4 Expression Across Salivary Gland Carcinomas Reveals Adenoid Cystic Carcinoma-Specific Prognostic Relevance
Mod Pathol. 2023 Oct 28;37(1):100371. doi: 10.1016/j.modpat.2023.100371. Online ahead of print.
ABSTRACT
B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed.
PMID:38015043 | DOI:10.1016/j.modpat.2023.100371
Comparative biodegradation analysis of three compostable polyesters by a marine microbial community
Appl Environ Microbiol. 2023 Nov 28:e0106023. doi: 10.1128/aem.01060-23. Online ahead of print.
ABSTRACT
Biodegradable plastics can be used in applications where the end product cannot be efficiently recycled due to high levels of contaminations, e.g., food or soil. Some of these plastics have a dedicated end of life, such as composting, but their degradation in the marine environment is poorly understood. In this study we showed that marine microbial communities can degrade a range of biodegradable polymers with different physical and chemical properties and use these as a sole carbon source for growth. We have also provided insights into the degradation mechanisms using a combined metagenomic and metaproteomic approach. In addition, we have identified three new enzymes that are capable of degrading both aliphatic polymers and aliphatic-aromatic copolymers, which can be used for biotechnological applications.
PMID:38014952 | DOI:10.1128/aem.01060-23
Complete genome sequence of <em>Solobacterium moorei</em> JCM 10645<sup>T</sup> isolated from a human stool sample
Microbiol Resour Announc. 2023 Nov 29:e0096523. doi: 10.1128/MRA.00965-23. Online ahead of print.
ABSTRACT
Solobacterium moorei JCM 10645T is an obligately anaerobic Gram-positive bacterium that was isolated from a human stool sample, generally known as a bacterium associated with sepsis, bacteremia, halitosis, and periodontal disease. In this study, we report the complete genome sequence of this strain, which is 2.615 Mbp with a 37.2% GC content.
PMID:38014937 | DOI:10.1128/MRA.00965-23
Selection and characterization of ssDNA aptamer targeting Macrobrachium rosenbergii nodavirus capsid protein: A potential capture agent in gold-nanoparticle-based aptasensor for viral protein detection
J Fish Dis. 2023 Nov 28. doi: 10.1111/jfd.13892. Online ahead of print.
ABSTRACT
The giant freshwater prawn holds a significant position as a valuable crustacean species cultivated in the aquaculture industry, particularly well-known and demanded among the Southeast Asian countries. Aquaculture production of this species has been impacted by Macrobrachium rosenbergii nodavirus (MrNV) infection, which particularly affects the larvae and post-larvae stages of the prawn. The infection has been recorded to cause mortality rates of up to 100% among the affected prawns. A simple, fast, and easy to deploy on-site detection or diagnostic method is crucial for early detection of MrNV to control the disease outbreak. In the present study, novel single-stranded DNA aptamers targeting the MrNV capsid protein were identified using the systematic evolution of ligands by exponential enrichment (SELEX) approach. The aptamer was then conjugated with the citrate-capped gold nanoparticles (AuNPs), and the sensitivity of this AuNP-based aptasensor for the detection of MrNV capsid protein was evaluated. Findings revealed that the aptamer candidate, APT-MrNV-CP-1 was enriched throughout the SELEX cycle 4, 9, and 12 with the sequence percentage of 1.76%, 9.09%, and 12.42%, respectively. The conjugation of APT-MrNV-CP-1 with citrate-capped AuNPs exhibited the highest sensitivity in detecting the MrNV capsid protein, where the presence of 62.5 nM of the viral capsid protein led to a significant agglomeration of the AuNPs. This study demonstrated the practicality of an AuNP-based aptasensor for disease diagnosis, particularly for detecting MrNV infection in giant freshwater prawns.
PMID:38014615 | DOI:10.1111/jfd.13892