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International Journal of Food... Jun 2024To study potential ramifications of antimicrobial resistance, we carried out adaptive laboratory evolution assays (ALE) to isolate three resistant variants (RVs) of...
To study potential ramifications of antimicrobial resistance, we carried out adaptive laboratory evolution assays (ALE) to isolate three resistant variants (RVs) of Salmonella enterica Typhimurium, employing three different types of food preservation methods: 1) an emergent technology, plasma-activated water (PAW), leading to variant RV-PAW; a traditional method, heat, leading to variant RV-HT, and a natural antimicrobial compound, carvacrol, leading to variant RV-CAR. The variant resistant to plasma-activated water, RV-PAW, had mutations in rpoA and rpoD; it showed increased tolerance to heat in orange juice but ultimately did not pose a significant threat, as it exhibited a fitness cost at refrigeration temperature (8 °C), whereas its virulence against Caenorhabditis elegans decreased. The variant resistant to heat, RV-HT, had mutations in flhC, dnaJ: it exhibited a fitness cost at high growth temperatures (43 °C) and induced morphofunctional alterations in C. elegans. The variant resistant to carvacrol, RV-CAR, had mutations in sseG, flhA, wbaV, lon; this variant not only exhibited significantly higher thermotolerance in both laboratory media and food models but also effectively increased its growth fitness at refrigeration temperatures while retaining its virulence, evidenced by the highest percentage of Smurf phenotype in C. elegans. To address these challenges, we applied a process combining thermal treatment with citral, with the aim of leveraging the sublethal damage caused in RVs by heat treatments in orange juice. This approach achieves enhanced microbial inactivation without having to escalate the intensity of the thermal treatment. The result was particularly encouraging in the case of RV-CAR, the most challenging strain, for which we improved lethality by up to 3 log inactivation cycles.
PubMed: 38945050
DOI: 10.1016/j.ijfoodmicro.2024.110810 -
Journal of Hazardous Materials Jun 2024Aluminum (Al) toxicity severely restricts the growth and productivity of elephant grass in acidic soils around the world. However, the molecular mechanisms of Al...
Aluminum (Al) toxicity severely restricts the growth and productivity of elephant grass in acidic soils around the world. However, the molecular mechanisms of Al response have not been investigated in elephant grass. In this study, we conducted phenotype, physiology, and transcriptome analysis of elephant grass roots in response to Al stress. Phenotypic analysis revealed that a low concentration of Al stress improved root growth while higher Al concentrations inhibit root growth. Al stress significantly increased the citrate (CA) content in roots, while the expression levels of genes related to citrate synthesis were substantially changed. The multidrug and toxic compound extrusion (MATE) family were identified as hub genes in the co-expression network of Al response in elephant grass roots. Phylogenetic analysis showed that hub genes CpMATE93 and CpMATE158 belonged to the same clade as other MATE genes reported to be involved in citrate transport. Additionally, overexpression of CpMATE93 conferred Al resistance in yeast cells. These results provide a theoretical basis for further studies of molecular mechanisms in the elephant grass response to Al stress and could help breeders develop elite cultivars with Al tolerance.
PubMed: 38944995
DOI: 10.1016/j.jhazmat.2024.135011 -
Computers in Biology and Medicine Jun 2024Extracting phenotype-representative flow patterns and their associated numerical metrics is a bottleneck in the clinical translation of advanced cardiac flow imaging...
BACKGROUND
Extracting phenotype-representative flow patterns and their associated numerical metrics is a bottleneck in the clinical translation of advanced cardiac flow imaging modalities. We hypothesized that reduced-order models (ROMs) are a suitable strategy for deriving simple and interpretable clinical metrics of intraventricular flow suitable for further assessments. Combined with machine learning (ML) flow-based ROMs could provide new insight to help diagnose and risk-stratify patients.
METHODS
We analyzed 2D color-Doppler echocardiograms of 81 non-ischemic dilated cardiomyopathy (DCM) patients, 51 hypertrophic cardiomyopathy (HCM) patients, and 77 normal volunteers (Control). We applied proper orthogonal decomposition (POD) to build patient-specific and cohort-specific ROMs of LV flow. Each ROM aggregates a low number of components representing a spatially dependent velocity map modulated along the cardiac cycle by a time-dependent coefficient. We tested three classifiers using deliberately simple ML analyses of these ROMs with varying supervision levels. In supervised models, hyperparameter grid search was used to derive the ROMs that maximize classification power. The classifiers were blinded to LV chamber geometry and function. We ran vector flow mapping on the color-Doppler sequences to help visualize flow patterns and interpret the ML results.
RESULTS
POD-based ROMs stably represented each cohort through 10-fold cross-validation. The principal POD mode captured >80 % of the flow kinetic energy (KE) in all cohorts and represented the LV filling/emptying jets. Mode 2 represented the diastolic vortex and its KE contribution ranged from <1 % (HCM) to 13 % (DCM). Semi-unsupervised classification using patient-specific ROMs revealed that the KE ratio of these two principal modes, the vortex-to-jet (V2J) energy ratio, is a simple, interpretable metric that discriminates DCM, HCM, and Control patients. Receiver operating characteristic curves using V2J as classifier had areas under the curve of 0.81, 0.91, and 0.95 for distinguishing HCM vs. Control, DCM vs. Control, and DCM vs. HCM, respectively.
CONCLUSIONS
Modal decomposition of cardiac flow can be used to create ROMs of normal and pathological flow patterns, uncovering simple interpretable flow metrics with power to discriminate disease states, and particularly suitable for further processing using ML.
PubMed: 38944903
DOI: 10.1016/j.compbiomed.2024.108760 -
Journal of Animal Science and... Jul 2024Biologically annotated neural networks (BANNs) are feedforward Bayesian neural network models that utilize partially connected architectures based on SNP-set...
BACKGROUND
Biologically annotated neural networks (BANNs) are feedforward Bayesian neural network models that utilize partially connected architectures based on SNP-set annotations. As an interpretable neural network, BANNs model SNP and SNP-set effects in their input and hidden layers, respectively. Furthermore, the weights and connections of the network are regarded as random variables with prior distributions reflecting the manifestation of genetic effects at various genomic scales. However, its application in genomic prediction has yet to be explored.
RESULTS
This study extended the BANNs framework to the area of genomic selection and explored the optimal SNP-set partitioning strategies by using dairy cattle datasets. The SNP-sets were partitioned based on two strategies-gene annotations and 100 kb windows, denoted as BANN_gene and BANN_100kb, respectively. The BANNs model was compared with GBLUP, random forest (RF), BayesB and BayesCπ through five replicates of five-fold cross-validation using genotypic and phenotypic data on milk production traits, type traits, and one health trait of 6,558, 6,210 and 5,962 Chinese Holsteins, respectively. Results showed that the BANNs framework achieves higher genomic prediction accuracy compared to GBLUP, RF and Bayesian methods. Specifically, the BANN_100kb demonstrated superior accuracy and the BANN_gene exhibited generally suboptimal accuracy compared to GBLUP, RF, BayesB and BayesCπ across all traits. The average accuracy improvements of BANN_100kb over GBLUP, RF, BayesB and BayesCπ were 4.86%, 3.95%, 3.84% and 1.92%, and the accuracy of BANN_gene was improved by 3.75%, 2.86%, 2.73% and 0.85% compared to GBLUP, RF, BayesB and BayesCπ, respectively across all seven traits. Meanwhile, both BANN_100kb and BANN_gene yielded lower overall mean square error values than GBLUP, RF and Bayesian methods.
CONCLUSION
Our findings demonstrated that the BANNs framework performed better than traditional genomic prediction methods in our tested scenarios, and might serve as a promising alternative approach for genomic prediction in dairy cattle.
PubMed: 38945998
DOI: 10.1186/s40104-024-01044-1 -
NeoReviews Jul 2024Bronchopulmonary dysplasia (BPD) is the heterogeneous chronic lung developmental disease of prematurity, which is often accompanied by multisystem comorbidities.... (Review)
Review
Bronchopulmonary dysplasia (BPD) is the heterogeneous chronic lung developmental disease of prematurity, which is often accompanied by multisystem comorbidities. Pulmonary vascular disease and pulmonary hypertension (PH) contribute significantly to the pathogenesis and pathophysiology of BPD and dramatically influence the outcomes of preterm infants with BPD. When caring for those patients, clinicians should consider the multitude of phenotypic presentations that fall under the "BPD-PH umbrella," reflecting the need for matching therapies to specific physiologies to improve short- and long-term outcomes. Individualized management based on the patient's prenatal and postnatal risk factors, clinical course, and cardiopulmonary phenotype needs to be identified and prioritized to provide optimal care for infants with BPD-PH.
Topics: Humans; Bronchopulmonary Dysplasia; Hypertension, Pulmonary; Infant, Newborn; Infant, Premature; Risk Factors
PubMed: 38945971
DOI: 10.1542/neo.25-7-e415 -
Experimental Animals Jun 2024The complement active product, C3a, and the receptor C3aR comprise an axis that exerts various biological functions, such as protection against infection. C3a is highly...
The complement active product, C3a, and the receptor C3aR comprise an axis that exerts various biological functions, such as protection against infection. C3a is highly expressed in the inflamed skin and blood from patients with psoriasiform dermatitis. However, the role of the C3a/C3aR axis in psoriasiform dermatitis remains unclear because conflicting results using C3 mice have been published. In this study, to elucidate the contribution of commensal microbiota in C3 and wild-type (WT) mice were subjected to imiquimod-induced psoriasiform dermatitis under different housing conditions. C3 mice showed increased epidermal thickness and keratinocyte proliferation markers in the inflamed ear compared to WT mice upon treatment with IMQ. These inflamed phenotypes were observed in both cohoused and separately housed conditions, and antibiotic treatment did not abolish the aggravation of IMQ-induced psoriasiform dermatitis in C3 mice. These results suggested that the difference of commensal microbiota is not important for the C3-involved psoriasiform dermatitis. Keratinocyte hyperproliferation is a major feature of the inflamed skin in patients with psoriasiform dermatitis. In vitro experiments showed that C3a and C3aR agonists inhibited keratinocyte proliferation, which was abolished by introduction of a C3aR antagonist. Collectively, these results suggest that the C3a/C3aR axis plays a critical role in psoriasiform dermatitis development by inhibiting keratinocyte proliferation, regardless of the regulation of the commensal microbiota.
PubMed: 38945882
DOI: 10.1538/expanim.24-0043 -
Revue Des Maladies Respiratoires Jun 2024COPD has become more prevalent among women, revealing a specific feminine phenotype. Women experience greater dyspnea and a more impaired quality of life. The main...
INTRODUCTION
COPD has become more prevalent among women, revealing a specific feminine phenotype. Women experience greater dyspnea and a more impaired quality of life. The main objective of this study was to assess the effect of gender on dyspnea during a pulmonary rehabilitation program (PRP).
METHODS
Retrospective study including COPD patients having participated in PRPs. The following data were analyzed according to gender before and after a PRP: dyspnea, quality of life, anxiety and depression, exercise capacity, muscle function (quadriceps and inspiratory muscles).
RESULTS
More than 500 patients (252 men and 252 women) were included. We did not find a significant effect of gender on the evolution of dyspnea, anxiety or depressive disorders, exercise capacity, inspiratory muscle strength, or overall quality of life score. That said, we found a possible effect on the sub-scores of the quality of life questionnaire, and regarding quadriceps strength. All criteria improved during the program in both groups.
CONCLUSIONS
During a PRP, gender does not impact the evolution of dyspnea. While women may nonetheless benefit to a greater extent in terms of quality of life sub-scores (impact, activities, symptoms) and quadriceps strength, these results still require confirmation.
PubMed: 38945799
DOI: 10.1016/j.rmr.2024.06.007 -
Digestive and Liver Disease : Official... Jun 2024VETC (vessel that encapsulate tumor cluster) is a peculiar vascular phenotype observed in hepatocellular carcinoma (HCC), associated with distant metastases and poor...
BACKGROUND AND AIM
VETC (vessel that encapsulate tumor cluster) is a peculiar vascular phenotype observed in hepatocellular carcinoma (HCC), associated with distant metastases and poor outcome. VETC has been linked to the Tie2/Ang2 axis and is characterized by lymphocytes poor (cold) tumor microenvironment (TME). In this setting the role of Tumor Associated Macrophages (TAMs) has never been explored. Aim of the study is to investigate the presence and features of TAMs in VETC HCC and the possible interplay between TAMs and endothelial cells (ECs).
METHODS
The series under study included 42 HCC. Once separated according to the VETC phenotype (21 VETC; 21 VETC) we stained consecutive slides with immunohistochemistry for CD68, CD163 and Tie2. Slides were then scanned and QuPath used to quantify morphological features.
RESULTS
VETC cases were significantly (p < 0.001) enriched with large, lipid rich CD163+ TAMs (M2 oriented) that were spatially close to ECs; HCC cells significantly (p: 0.002) overexpressed Tie2 with a polarization toward ECs.
CONCLUSIONS
The pro-metastatic attitude of VETC is sustained by a strict morphological relationship between immunosuppressive M2-TAMs, ECs and Tie2-expressing HCC cells.
PubMed: 38945759
DOI: 10.1016/j.dld.2024.06.016 -
Science Bulletin May 2024During the past 3000 years, cattle on the Qinghai-Xizang Plateau have developed adaptive phenotypes under the selective pressure of hypoxia, ultraviolet (UV) radiation,...
During the past 3000 years, cattle on the Qinghai-Xizang Plateau have developed adaptive phenotypes under the selective pressure of hypoxia, ultraviolet (UV) radiation, and extreme cold. The genetic mechanism underlying this rapid adaptation is not yet well understood. Here, we present whole-genome resequencing data for 258 cattle from 32 cattle breeds/populations, including 89 Tibetan cattle representing eight populations distributed at altitudes ranging from 3400 m to 4300 m. Our genomic analysis revealed that Tibetan cattle exhibited a continuous phylogeographic cline from the East Asian taurine to the South Asian indicine ancestries. We found that recently selected genes in Tibetan cattle were related to body size (HMGA2 and NCAPG) and energy expenditure (DUOXA2). We identified signals of sympatric introgression from yak into Tibetan cattle at different altitudes, covering 0.64%-3.26% of their genomes, which included introgressed genes responsible for hypoxia response (EGLN1), cold adaptation (LRP11), DNA damage repair (LATS1), and UV radiation resistance (GNPAT). We observed that introgressed yak alleles were associated with noncoding variants, including those in present EGLN1. In Tibetan cattle, three yak introgressed SNPs in the EGLN1 promoter region reduced the expression of EGLN1, suggesting that these genomic variants enhance hypoxia tolerance. Taken together, our results indicated complex adaptation processes in Tibetan cattle, where recently selected genes and introgressed yak alleles jointly facilitated rapid adaptation to high-altitude environments.
PubMed: 38945748
DOI: 10.1016/j.scib.2024.05.030 -
Journal of Gastrointestinal and Liver... Jun 2024Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral...
BACKGROUND AND AIMS
Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown.
MATERIALS
We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis.
RESULTS
The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC.
CONCLUSIONS
We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
Topics: Humans; Membrane Proteins; Polymorphism, Single Nucleotide; Lipase; Female; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Middle Aged; 17-Hydroxysteroid Dehydrogenases; Genetic Predisposition to Disease; Case-Control Studies; Hepatitis B, Chronic; Prognosis; Adult; Turkey; Risk Factors; Prospective Studies; Phenotype; Genetic Association Studies; Acyltransferases; Phospholipases A2, Calcium-Independent
PubMed: 38944871
DOI: 10.15403/jgld-5474