The aim of the present study was to isolate, identify and characterise novel strains of lactic acid bacteria and bifidobacteria with probiotic properties from the faeces of exclusively breast-fed ...infants. Of the 4680 isolated colonies, 758 exhibited resistance to low pH and tolerance to high concentrations of bile salts; of these, only forty-two exhibited a strong ability to adhere to enterocytes in vitro. The identities of the isolates were confirmed by 16S ribosomal RNA (rRNA) sequencing, which permitted the grouping of the forty-two bacteria into three different strains that showed more than 99 % sequence identity with Lactobacillus paracasei, Lactobacillus rhamnosus and Bifidobacterium breve, respectively. The strain identification was confirmed by sequencing the 16S-23S rRNA intergenic spacer regions. Strains were assayed for enzymatic activity and carbohydrate utilisation, and they were deposited in the Collection Nationale de Cultures de Microorganismes (CNCM) of the Institute Pasteur and named L. paracasei CNCM I-4034, B. breve CNCM I-4035 and L. rhamnosus CNCM I-4036. The strains were susceptible to antibiotics and did not produce undesirable metabolites, and their safety was assessed by acute ingestion in immunocompetent and immunosuppressed BALB/c mouse models. The three novel strains inhibited in vitro the meningitis aetiological agent Listeria monocytogenes and human rotavirus infections. B. breve CNCM I-4035 led to a higher IgA concentration in faeces and plasma of mice. Overall, these results suggest that L. paracasei CNCM I-4034, B. breve CNCM I-4035 and L. rhamnosus CNCM I-4036 should be considered as probiotic strains, and their human health benefits should be further evaluated.
Infant cereals play an important role in the complementary feeding period. The aim of this study was to review existing research about the quantity, type, and degree of infant cereal processing, with ...a special focus on whole grain infant cereals. Accumulating evidence shows many benefits of whole grain consumption for human health. Likewise, consumers are frequently linking the term whole grains to healthiness and naturality, and sustainable food production becomes a more important aspect when choosing an infant cereal brand. Whole grain cereals should be consumed as early as possible, i.e., during infancy. However, there are several challenges that food manufacturers are facing that need to be addressed. Recommendations are needed for the intake of whole grain cereals for infants and young children, including product-labeling guidelines for whole grain foods targeting these age stages. Another challenge is minimizing the higher contaminant content in whole grains, as well as those formed during processing. Yet, the greatest challenge may be to drive consumers' acceptance, including taste. The complementary feeding period is absolutely key in shaping the infant's food preferences and habits; therefore, it is the appropriate stage in life at which to introduce whole grain cereals for the acceptance of whole grains across the entire lifespan.
Currently, the marketing of electronic cigarettes as a safe alternative to smoking has increased, which is associated with greater use of these devices, especially among young people and smokers ...interested in quitting tobacco cigarettes. Given the growing use of this type of product, there is a need to determine the consequences of electronic cigarettes on human health, especially since many of the compounds contained in the aerosol and liquid of these devices have a high potential to be carcinogenic and genotoxic. Additionally, many of these compounds' aerosol concentrations exceed the safe limits. We have evaluated the levels of genotoxicity and changes in DNA methylation patterns associated with vaping. We analyzed a total of 90 peripheral blood samples from a population of vapers (n = 32), smokers (n = 18), and controls (n = 32), in which the frequencies of genotoxicity were determined by the cytokinesis-blocking micronuclei (CBMN) assay and the patterns of methylation of the repetitive elements of LINE-1 through the Quantitative Methylation Specific PCR (qMSP) assay. Here we show an increase in genotoxicity levels associated with vaping habits. Additionally, the group of vapers showed changes at the epigenetic level specifically associated with the loss of methylation of the LINE-1 elements. These changes in LINE-1 methylation patterns were reflected in its representative RNA expression detected in vapers.
•Exposure to e-cigarette aerosols corresponds to a risk factor of elevated genotoxicity.•The use of e-cigarretes induces epigenetic alterations, in particular those associated with the loss of methylation of LINE-1 elements.•Epigenetic modifications may explain the increased transcription regulation process.
Aphanomyces root rot (ARR) is a devastating disease that affects the production of pea. The plants are prone to infection at any growth stage, and there are no chemical or cultural controls. Thus, ...the development of resistant pea cultivars is important. Phenomics technologies to support the selection of resistant cultivars through phenotyping can be valuable. One such approach is to couple imaging technologies with deep learning algorithms that are considered efficient for the assessment of disease resistance across a large number of plant genotypes. In this study, the resistance to ARR was evaluated through a CNN-based assessment of pea root images. The proposed model, DeepARRNet, was designed to classify the pea root images into three classes based on ARR severity scores, namely, resistant, intermediate, and susceptible classes. The dataset consisted of 1581 pea root images with a skewed distribution. Hence, three effective data-balancing techniques were identified to solve the prevalent problem of unbalanced datasets. Random oversampling with image transformations, generative adversarial network (GAN)-based image synthesis, and loss function with class-weighted ratio were implemented during the training process. The result indicated that the classification F1-score was 0.92 ± 0.03 when GAN-synthesized images were added, 0.91 ± 0.04 for random resampling, and 0.88 ± 0.05 when class-weighted loss function was implemented, which was higher than when an unbalanced dataset without these techniques were used (0.83 ± 0.03). The systematic approaches evaluated in this study can be applied to other image-based phenotyping datasets, which can aid the development of deep-learning models with improved performance.
Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell ...(CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV).
In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy.
CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months;
= 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months;
= 0.004). These significant correlations were not observed in CVC analyses.
CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.
Complementary feeding (CF) is an important determinant of early and later life nutrition with great implications for the health status and the development of an adequate growth. Parents can choose ...between homemade foods (HMFs) and/or commercial infant foods (CIFs). There is no consistent evidence as to whether HMFs provide a better nutritional profile and variety over CIFs. The aim of this study was to compare the nutritional profiles and food variety of HMFs versus CIFs in the Spanish market targeted for infants (6-11 months) and young children (12-18 months). Thirty mothers with their children aged 6 to 18 months were included in this cross-sectional study, following a 3-day weighed food diary of which HMFs were collected and chemically analyzed. HMFs meals for infant provided significantly lower energy, higher protein and higher fiber, for young children provided significantly higher protein and fiber than CIFs meals. HMFs fruit purees for infant shown significantly higher fiber and for young children provided higher energy than CIFs. HMFs meals contained a significantly greater number of different vegetables than CIFs meals (3.7 vs. 3.3), with carrot as the most frequently used in both. However, in CIFs fruit purees shown higher different fruits than HMFs, in both the banana was the fruit most frequently used. There was a predominance of meat and lack of oily fish and legumes in both HMFs and CIFs meals. HMFs and CIFs were equally characterized by a soft texture and yellow-orange colours. Importantly, our findings emphasize the need for clear guidelines for the preparation of HMFs as well as the promotion of food variety (taste and textures) in both HMFs and CIFs to suit infants' and young children's nutritional and developmental needs.
Parkinson's disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use ...Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson's disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson's disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson's disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson's disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson's disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson's disease drug development.
Rusts are among the most important foliar biotrophic fungal diseases in legumes.
crop can be severely damaged by
, to which partial resistance has been identified. Nevertheless, the underlying ...genetic basis and molecular mechanisms of this resistance are poorly understood in
. To prioritise the causative variants controlling partial resistance to rust in
, a recombinant inbred line (RIL) population, segregating for response to this pathogen, was used to combine the detection of related phenotypic- and expression-quantitative trait loci (pQTLs and eQTLs, respectively). RILs'
disease severity (DS) was recorded in three independent screenings at seedling (growth chamber) and in one season of exploratory screening at adult plant stage (semi-controlled field conditions). A continuous DS range was observed in both conditions and used for pQTL mapping. Different pQTLs were identified under the growth chamber and semi-controlled field conditions, indicating a distinct genetic basis depending on the plant developmental stage and/or the environment. Additionally, the expression of nine genes related to
resistance in
was quantified for each RIL individual and used for eQTL mapping. One
-eQTL and one trans-eQTL were identified controlling the expression variation of one gene related to rust resistance - a member of glycosyl hydrolase family 17. Integrating phenotyping, gene expression and linkage mapping allowed prioritising four candidate genes relevant for disease-resistance precision breeding involved in adaptation to biotic stress, cellular, and organelle homeostasis, and proteins directly involved in plant defence.
Dystonia is a neurological disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and postures, often occurring in absence of any structural brain ...abnormality. Psychiatric comorbidities, including anxiety, depression, obsessive-compulsive disorder and schizophrenia, are frequent in patients with dystonia. While mutations in a fast-growing number of genes have been linked to Mendelian forms of dystonia, the cellular, anatomical, and molecular basis remains unknown for most genetic forms of dystonia, as does its genetic and biological relationship to neuropsychiatric disorders. Here we applied an unbiased systems-biology approach to explore the cellular specificity of all currently known dystonia-associated genes, predict their functional relationships, and test whether dystonia and neuropsychiatric disorders share a genetic relationship. To determine the cellular specificity of dystonia-associated genes in the brain, single-nuclear transcriptomic data derived from mouse brain was used together with expression-weighted cell-type enrichment. To identify functional relationships among dystonia-associated genes, we determined the enrichment of these genes in co-expression networks constructed from 10 human brain regions. Stratified linkage-disequilibrium score regression was used to test whether co-expression modules enriched for dystonia-associated genes significantly contribute to the heritability of anxiety, major depressive disorder, obsessive-compulsive disorder, schizophrenia, and Parkinson's disease. Dystonia-associated genes were significantly enriched in adult nigral dopaminergic neurons and striatal medium spiny neurons. Furthermore, 4 of 220 gene co-expression modules tested were significantly enriched for the dystonia-associated genes. The identified modules were derived from the substantia nigra, putamen, frontal cortex, and white matter, and were all significantly enriched for genes associated with synaptic function. Finally, we demonstrate significant enrichments of the heritability of major depressive disorder, obsessive-compulsive disorder and schizophrenia within the putamen and white matter modules, and a significant enrichment of the heritability of Parkinson's disease within the substantia nigra module. In conclusion, multiple dystonia-associated genes interact and contribute to pathogenesis likely through dysregulation of synaptic signalling in striatal medium spiny neurons, adult nigral dopaminergic neurons and frontal cortical neurons. Furthermore, the enrichment of the heritability of psychiatric disorders in the co-expression modules enriched for dystonia-associated genes indicates that psychiatric symptoms associated with dystonia are likely to be intrinsic to its pathophysiology.
Histamine is a biogenic amine that can cause food poisoning in an increasing fraction of the population. Histamine detection and quantification are crucial for evaluating the freshness of food ...products and informing histamine-sensitive consumers regarding histamine concentration in fermented or processed food products. Several analytical methods exist for quantifying histamine from food samples, most based on chromatographic analysis. This review summarizes the current knowledge of analytical methodologies for detecting and quantifying histamine. We highlight the importance of using timely detection tools for biogenic amines to indicate the degree of freshness or deterioration of food. A multidisciplinary approach based on molecular and enzymatic methods for detecting and quantifying histamine and other biogenic amines is presented, where histamine dehydrogenase and histamine oxidase enzymes from microbial sources stand out as potential molecular tools for histamine detection, and with which rapid, scalable, and user-friendly assay platforms can be used. In addition to typical enzyme technology concerns, the enzymatic detection of histamine faces substrate specificity and substrate inhibition challenges that affect the specific identification of histamine and the detection limit of the enzymatic assay. These challenges can be overcome by enzyme engineering, immobilization, or their simultaneous integration to obtain biocatalysts with increased histamine detection, quantification, or performance.
•Detection and quantification of histamine in food is an essential aspect of public health.•Using a fast and straightforward method to detect biogenic amines is crucial for food safety.•A multidisciplinary approach is needed to find new histamine detection methods.•Biocatalytic engineering could improve enzymes for successful use of histamine detection.
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