Computer simulation of genomic data has become increasingly popular for assessing and validating biological models or for gaining an understanding of specific data sets. Several computational tools ...for the simulation of next-generation sequencing (NGS) data have been developed in recent years, which could be used to compare existing and new NGS analytical pipelines. Here we review 23 of these tools, highlighting their distinct functionality, requirements and potential applications. We also provide a decision tree for the informed selection of an appropriate NGS simulation tool for the specific question at hand.
Rheumatoid arthritis (RA) is an autoimmune/inflammatory disease affecting 0.5 to 1% of adults worldwide and frequently leads to joint destruction and disability. Early diagnosis and early and ...effective therapy may prevent joint damage and lead to better long-term results. Therefore, reliable biomarkers and outcome measures are needed. Refinement of the understanding of molecular pathways involved in disease pathogenesis have been achieved by combining knowledge on RA-associated genes, environmental factors and the presence of serological elements. The presence of autoantibodies is a distinctive feature of RA. Rheumatoid Factor and Anti-Citrullinated Protein Antibodies are the two most remarkable autoantibodies in RA and provide different clinical and pathophysiological information. They precede the onset of disease symptoms and predict a more severe disease course, indicating a pathogenetic role in RA. Therefore, they promote a more accurate prognosis and contribute for a better disease management. Several RA-associated autoantibody systems have been identified: Anti-Carbamylated Antibodies, Anti-BRAF, Anti-Acetylated, Anti-PAD4 antibodies and others. Hopefully, the characterization of a comprehensive array of novel autoantibody systems in RA will provide unique pathogenic insights of relevance for the development of diagnostic and prognostic approaches compatible with an effective personalized medicine.
This research addresses the importance of pine wood sawdust granulometry on the processing of medium-density polyethylene (MDPE)/wood composites by rotational molding and its effects on the ...morphological, mechanical and aesthetical properties of parts, aiming to contribute for the development of sustainable wood polymer composites (WPC) for rotational molding applications. Pine wood sawdust was sieved (<150, 150, 300, 500, 710, >1000 µm) and analyzed for its physical, morphological and thermal characteristics. Rotational molded parts were produced with matrix/wood ratios from 90/10 to 70/30 wt% considering different wood granulometries. As a natural material, wood changed its color during processing. Granulometries below 500 µm presented better sintering, homogeneity and less part defects. Furthermore, 300-500 µm favored the impact resistance (1316 N), as irregular brick-shaped wood was able to anchor to PE despite the weak interfacial adhesion observed. The increase of wood content from 10 to 30% reduced the impact properties by 40%, as a result of a highly porous structure formed, revealing sintering difficulties during processing. WPC parts of differentiated aesthetics and functionalities were achieved by rotational molding. A clear relationship between wood granulometry and WPC processing, structure and properties was identified.
Blood phenylalanine (Phe) is used as the primary marker to evaluate metabolic control. Our study aimed to describe the metabolic control of patients with phenylketonuria (PKU) comparing three ...different treatment recommendations (European guidelines/US guidelines/Portuguese consensus). This was a retrospective, observational, single centre study in patients with PKU collecting data on blood Phe levels from 2017. Nutritional intake data and sapropterin (BH4) prescription were collected at the last appointment of 2017. The final sample studied included 87 patients (48% females) 13 hyperphenylalaninemia; 47 mild PKU; 27 classical PKU with a median age of 18 y (range: 1-36 y). The median number of blood Phe measurements for patients was 21 (range: 6-89). In patients aged < 12 y, the median blood Phe level was 300 μmol/L (range 168-480) and 474 μmol/L (range 156-1194) for patients ≥ 12 y. Overall, a median of 83% of blood Phe levels were within the European PKU guidelines target range. In patients aged ≥ 12 years, there was a higher median % of blood Phe levels within the European PKU guidelines target range (≥12 y: 84% vs. <12 y: 56%). In children < 12 y with classical PKU (
2), only 34% of blood Phe levels were within target range for all 3 guidelines and 49% with mild PKU (
11). Girls had better control than boys (89% vs. 66% median Phe levels within European Guidelines). Although it is clear that 50% or more patients were unable to achieve acceptable metabolic control on current treatment options, a globally agreed upper Phe target associated with optimal outcomes for age groups is necessary. More studies need to examine how clinics with dissimilar resources, different therapeutic Phe targets and frequency of monitoring relate to metabolic control.
Transfer RNA fragments (tRFs) have gene silencing effects similarly to miRNAs, can be sorted into extracellular vesicles (EVs) and are emerging as potential circulating biomarkers for cancer ...diagnoses. We aimed at analyzing the expression of tRFs in gastric cancer (GC) and understanding their potential as biomarkers. We explored miRNA datasets from gastric tumors and normal adjacent tissues (NATs) from TCGA repository, as well as proprietary 3D-cultured GC cell lines and corresponding EVs, in order to identify differentially represented tRFs using MINTmap and R/Bioconductor packages. Selected tRFs were validated in patient-derived EVs. We found 613 Differentially Expressed (DE)-tRFs in the TCGA dataset, of which 19 were concomitantly upregulated in TCGA gastric tumors and present in 3D cells and EVs, but barely expressed in NATs. Moreover, 20 tRFs were expressed in 3D cells and EVs and downregulated in TCGA gastric tumors. Of these 39 DE-tRFs, 9 tRFs were also detected in patient-derived EVs. Interestingly, the targets of these 9 tRFs affect neutrophil activation and degranulation, cadherin binding, focal adhesion and the cell-substrate junction, highlighting these pathways as major targets of EV-mediated crosstalk with the tumor microenvironment. Furthermore, as they are present in four distinct GC datasets and can be detected even in low quality patient-derived EV samples, they hold promise as GC biomarkers. By repurposing already available NGS data, we could identify and cross-validate a set of tRFs holding potential as GC diagnosis biomarkers.
Extracellular vesicles (EVs) secreted by tumor cells modulate recipient cells' behavior, but their effects in normal cells from the tumor microenvironment remain poorly known. In this study, we ...dissected the functional impact of gastric cancer cell-derived EVs (GC-EVs), representative of distinct GC histotypes, on the behavior of normal isogenic epithelial and mesenchymal cells. GC-EVs were isolated by differential centrifugation and characterized by transmission electron microscopy, nanoparticle tracking analysis, and imaging flow-cytometry. Epithelial and mesenchymal cells were challenged with GC-EVs and submitted to proliferation, migration, and invasion assays. Expression of epithelial and mesenchymal markers was followed by immunofluorescence and flow-cytometry. Our results indicated that GC-EVs secreted by diffuse-type cancer cells decrease the migration of recipient cells. This effect was more prominent and persistent for mesenchymal recipient cells, which also increased Fibronectin expression in response to EVs. GC-EVs secreted by cancer cells derived from tumors with an intestinal component increased invasion of recipient epithelial cells, without changes in EMT markers. In summary, this study demonstrated that GC-EVs modulate the migration and invasion of epithelial and mesenchymal cells from the tumor microenvironment, in a histotype-dependent manner, highlighting new features of intestinal and diffuse-type GC cells, which may help explaining differential metastasis patterns and aggressiveness of GC histotypes.
Invasive species disrupt relations between endemics and their ecosystem and are an increasing biodiversity conservation problem. The
genus comprises the most successful invasive reptile species, ...including the worldwide-distributed
. In this study, we used 12S and ND2 sequences to taxonomically identify and tentatively determine the diversity and origin of these invaders in Cabo Verde while also clarifying this for several Western Indian Ocean (WIO) populations. By comparing our sequences to recently published ones, we showed, for the first time, that Cabo Verde individuals belong to the
lineage and that both of its sublineages (a and b) occur there. Both haplotypes are also in Madeira, which indicates a connection between these archipelagos, possibly related to the past Portuguese trading routes. Across the WIO, results clarified the identity of many island and coastal populations, showing that this likely invasive
lineage is widespread in the region, including northern Madagascar, with important conservation implications. Colonisation origins were difficult to access due to the wide geographical spread of these haplotypes; thus, several possible scenarios were outlined. The introduction of this species throughout western and eastern Africa may threaten endemic taxa and needs to be closely monitored.
We aimed to report the implementation of a phenylketonuria (PKU) transition program and study the effects of follow-up with an adult team on metabolic control, adherence, and loss of follow-up. ...Fifty-five PKU patients were analysed in the study periods (SP): 2 years before (SP1) and after the beginning of adult care (SP2). Retrospective data on metabolic control and number of clinic appointments were collected for each SP, and protein intakes were analysed. In SP2, three patients (6%) were lost to follow-up. There was a small but statistically significant increase in median number of annual blood spots from SP1 to SP2: 11 (7-15) vs. 14 (7-20);
= 0.002. Mean ± SD of median blood Phe remained stable (525 ± 248 µmol/L vs. 552 ± 225 µmol/L;
= 0.100); median % of blood Phe < 480 µmol/L decreased (51 (4-96)% vs. 37 (5-85)%;
= 0.041) and median number of clinic appointments increased from SP1 to SP2: (5 (4-6) vs. 11 (8-13);
< 0.001). No significant differences were found regarding any parameter of protein intake. Our results suggest that the implementation of an adult service was successful as impact on metabolic control was limited and attendance remained high. Continuous dietetic care likely contributed to these results by keeping patients in follow-up and committed to treatment.
In phenylketonuria (PKU), modified casein glycomacropeptide supplements (CGMP-AA) are used as an alternative to the traditional phenylalanine (Phe)-free L-amino acid supplements (L-AA). However, ...studies focusing on the long-term nutritional status of CGMP-AA are lacking. This retrospective study evaluated the long-term impact of CGMP-AA over a mean of 29 months in 11 patients with a mean age at CGMP-AA onset of 28 years (range 15-43) 8 females; 2 hyperphenylalaninaemia (HPA), 3 mild PKU, 3 classical PKU and 3 late-diagnosed. Outcome measures included metabolic control, anthropometry, body composition and biochemical parameters.
CGMP-AA, providing 66% of protein equivalent intake from protein substitute, was associated with no significant change in blood Phe with CGMP-AA compared with baseline (562 ± 289 µmol/L vs 628 ± 317 µmol/L; p = 0.065). In contrast, blood tyrosine significantly increased on CGMP-AA (52.0 ± 19.2 μmol/L vs 61.4 ± 23.8 μmol/L; p = 0.027).
Biochemical nutritional markers remained unchanged which is an encouraging finding in adults with PKU, many of whom are unable to maintain full adherence with nutritionally fortified protein substitutes. Longitudinal, prospective studies with larger sample sizes are necessary to fully understand the metabolic impact of using CGMP-AA in PKU.
During the 20th century processed and ready-to-eat foods became routinely consumed resulting in a sharp rise of fat, salt, and sugar intake in people's diets. Currently, the global incidence of ...obesity, raised blood lipids, hypertension, and diabetes in an increasingly aged population contributes to the rise of atherothrombotic events and cardiovascular diseases (CVD) mortality. Drug-based therapies are valuable strategies to tackle and help manage the socio-economic impact of atherothrombotic disorders though not without adverse side effects. The inclusion of fresh fruits and vegetables rich in flavonoids to human diets, as recommended by WHO offers a valuable nutritional strategy, alternative to drug-based therapies, to be explored in the prevention and management of atherothrombotic diseases at early stages. Though polyphenols are mostly associated to color and taste in foods, food flavonoids are emerging as modulators of cholesterol biosynthesis, appetite and food intake, blood pressure, platelet function, clot formation, and anti-inflammatory signaling, supporting the health-promoting effects of polyphenol-rich diets in mitigating the impact of risk factors in atherothrombotic disorders and CVD events. Here we overview the current knowledge on the effect of polyphenols particularly of flavonoid intake on the atherothrombotic risk factors and discuss the caveats and challenges involved with current experimental cell-based designs.
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