3 ng/mL with a corresponding sensitivity of 97% and specificity of 81%. According to our findings ACAN is a reliable potential biomarker in plasma samples to detect ATAAD with high sensitivity and specificity.trans-Fatty acids (TFAs) are food-derived fatty acids associated with various diseases including cardiovascular diseases. However, the underlying etiology is poorly understood. Here, we show a pro-apoptotic mechanism of TFAs such as elaidic acid (EA), in response to DNA interstrand crosslinks (ICLs) induced by cisplatin (CDDP). We previously reported that TFAs promote apoptosis induced by doxorubicin (Dox), a double strand break (DSB)-inducing agent, via a non-canonical apoptotic pathway independent of tumor suppressor p53 and apoptosis signal-regulating kinase (ASK1), a reactive oxygen species (ROS)-responsive kinase. However, here we found that in the case of CDDP-induced apoptosis, EA-mediated pro-apoptotic action was reversed by knockout of either p53 or ASK1, despite no increase in p53 apoptotic activity. Upon CDDP treatment, EA predominantly enhanced ROS generation, ASK1-p38/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathway activation, and ultimately cell death, all of which were suppressed either by co-treatment of the NADPH oxidase (Nox) inhibitor Apocynin, or by knocking out its regulatory protein, receptor-interacting protein 1 (RIP1). These results demonstrate that in response to CDDP ICLs, TFAs promote p53-dependent apoptosis through the enhancement of the Nox-RIP1-ASK1-MAPK pathway activation, providing insight into the diverse pathogenetic mechanisms of TFAs according to the types of DNA damage.Niemann-Pick disease type C (NPC) is a treatable autosomal recessive neurodegenerative condition which leads to a variety of progressive manifestations. Despite most cases being diagnosed at a young age, disease prevalence may be underestimated, especially in adults, and interpretation of NPC1 and NPC2 variants can be difficult. This study aims to identify potential pathogenic variants in a large cohort of healthy individuals and classify their risk of pathogenicity to assist with future interpretation of variants. The CARTaGENE (CaG) cohort was used to identify possible variants of NPC1 and NPC2. Nine-hundred and eleven RNA samples and 198 exome sequencing were screened for genetic variants through a bio-informatic pipeline performing alignment and variant calling. The identified variants were analyzed using annotations for allelic frequency, pathogenicity and conservation scores. The ACMG guidelines were used to classify the variants. These were then compared to existing databases and previous studies of NPC prevalence, including the Tübingen NPC database. Thirty-two distinct variants were identified after running the samples in the RNA-sequencing pipeline, two of which were classified as pathogenic and 21 of which were not published previously. Furthermore, 46 variants were both identified in our population and with the Tübingen database, the majority of which were of uncertain significance. Ten additional variants were found in our exome-sequencing sample. This study of a sample from a population living in Quebec demonstrates a variety of rare variants, some of which were already described in the literature as well as some novel variants. Classifying these variants is arduous given the scarcity of available literature, even so in a population of healthy individuals. Yet using this data, we were able to identify two pathogenic variants within our population and several new variants not previously identified.MicroRNAs as cancer biomarkers in serum, plasma, and other body fluids are often used but analysis of miRNA in urine is limited. We investigated the expression of selected miRNAs in the paired urine, serum, cervical scrape, and tumor tissue specimens from the women with cervical precancer and cancer with a view to identify if urine miRNAs could be used as reliable non-invasive biomarkers for an early diagnosis and prognosis of cervical cancer. Expression of three oncomiRs (miR-21, miR-199a, and miR-155-5p) and three tumor suppressors (miR-34a, miR-145, and miR-218) as selected by database search in cervical pre-cancer, cancer, and normal controls including cervical cancer cell lines were analyzed using qRT-PCR. The expression of miRNAs was correlated with various clinicopathological parameters, including HPV infection and survival outcome. We observed a significant overexpression of the oncomiRs and the downregulation of tumor suppressor miRNAs. A combination of miR-145-5p, miR-218-5p, and miR-34a-5p in urine yielded 100% sensitivity and 92.8% specificity in distinguishing precancer and cancer patients from healthy controls and it well correlates with those of serum and tumor tissues. The expression of miR-34a-5p and miR-218-5p were found to be independent prognostic factors for the overall survival of cervical cancer patients. We conclude that the evaluation of the above specific miRNA expression in non-invasive urine samples may serve as a reliable biomarker for early detection and prognosis of cervical cancer.Arbitrary (65 RAPD, 25 ISSR, 23 DAMD), gene-targeted (22 SCoT, 33 CBDP) and co-dominant sequence specific (40 SSR) markers were used individually, or in combinations, to examine the genetic variability within and among 70 selected Indian mango genotypes based on geographic origin (East India, West India, North India, South India) and fruit status (Selection, Hybrid, Landrace). The highest genetic variability was demonstrated by the East Indian populations, followed by those from South India, West India, and North India, when measured in terms of Na, Ne, H, I, PB%, Ht and Hs. Interestingly, the local genotypes of Odisha, which forms a part of East Indian populations, showed the highest diversity compared to hybrid or selection groups, suggesting that the indigenous genotypes hold a greater potential for exploiting the unique and favourable alleles. The maximum genetic variability was detected in geographical/fruit status populations with SSRs (Na-1.76/1.88, Ne-1.48/1.51, H-0.28/0.30, I-0.41/0.45, PB%-76.1/86.9, Ht-0.31/0.32 and Hs-0.28/0.30), followed by CBDPs and SCoTs, reflecting their preeminence for examining the level of genetic polymorphism and diversity. Outcome of AMOVA based analyses as well as low-to-moderate coefficient of genetic differentiation (Gst) and high gene flow (Nm) indicated a greater amount of intra-population genetic variation compared to heterogeneity at inter-population level. Information generated through this investigation could facilitate conservation and further exploitation of mango germplasm including genetic improvement through breeding.This study investigated whether metal artifact reduction (MAR) applied computed tomography (CT) scans could be used to generate precise digital models and explored possible correlations between the amount of metal artifact and model accuracy. Thirty maxillofacial CT scans were randomly selected and a MAR algorithm was applied. By subtracting the original and MAR-applied CT images, the amount of metal artifact was quantified. Digital models were generated from the original and the MAR-applied CT data. Paired digital models were superimposed and shape deviation in planar surface was measured at 10 points in 4 planes. Statistical analyses were performed to compare deviations and to assess correlations between the amount of artifact and deviation. The MAR algorithm reduced metal artifact in all cases. The overall mean deviation of the MAR-applied models was 0.0868 mm, with no significant difference according to the reference plane. The amount of artifact did not significantly influence the accuracy of the digital models. MAR-applied CT is a convenient source for digital modeling with clinically acceptable accuracy. The MAR algorithm can be used regardless of the amount of metal artifact, which are generated by dental prostheses, for the quick and convenient manipulation of dental digital models.Flow conditions have been shown to be important in improving longevity and functionality of primary hepatocytes, but the impact of flow on HepaRG cells is largely unknown. We studied the expression of genes encoding CYP enzymes and transporter proteins and CYP1 and CYP3A4 activity during 8 weeks of culture in HepaRG cells cultured under static conditions (conventional 24-/96-well plate culture with common bicarbonate/CO2 buffering) and under flow conditions in an organ-on-chip (OOC) device. Since the OOC-device is a closed system, bicarbonate/CO2 buffering was not possible, requiring application of another buffering agent, such as HEPES. In order to disentangle the effects of HEPES from the effects of flow, we also applied HEPES-supplemented medium in static cultures and studied gene expression and CYP activity. We found that cells cultured under flow conditions in the OOC-device, as well as cells cultured under static conditions with HEPES-supplemented medium, showed more stable gene expression levels. Furthermore, only cells cultured in the OOC-device showed relatively high baseline CYP1 activity, and their gene expression levels of selected CYPs and transporters were most similar to gene expression levels in human primary hepatocytes. However, there was a decrease in baseline CYP3A4 activity under flow conditions compared to HepaRG cells cultured under static conditions. Altogether, the present study shows that HepaRG cells cultured in the OOC-device were more stable than in static cultures, being a promising in vitro model to study hepatoxicity of chemicals upon chronic exposure.Chorioamnionitis, inflammation of fetal membranes, is an important cause of preterm birth and a risk factor for the development of adverse neonatal outcomes including sepsis and intestinal pathologies. Intestinal bile acids (BAs) accumulation and hepatic cytokine production are involved in adverse intestinal outcomes. These findings triggered us to study the liver and enterohepatic circulation (EHC) following intra-amniotic (IA) lipopolysaccharide (LPS) exposure. An ovine chorioamnionitis model was used in which circulatory cytokines and outcomes of the liver and EHC of preterm lambs were longitudinally assessed following IA administration of 10 mg LPS at 5, 12 or 24h or 2, 4, 8 or 15d before preterm birth. Hepatic inflammation was observed, characterized by increased hepatic cytokine mRNA levels (5h – 2d post IA LPS exposure) and increased erythropoietic clusters (at 8 and 15 days post IA LPS exposure). Besides, 12h after IA LPS exposure, plasma BA levels were increased, whereas gene expression levels of several hepatic BA transporters were decreased. Initial EHC alterations normalized over time. Concluding, IA LPS exposure induces significant time-dependent changes in the fetal liver and EHC. These chorioamnionitis induced changes have potential postnatal consequences and the duration of IA LPS exposure might be essential herein.To evaluate the effect of aging, intra- and intersession repeatability and regional scotopic sensitivities in healthy and age-related macular degeneration (AMD) eyes. Intra- and intersession agreement and effect of age was measured in healthy individuals. The mean sensitivity (MS) and pointwise retinal sensitivities (PWS) within the central 24° with 505 nm (cyan) and 625 nm (red) stimuli were evaluated in 50 individuals (11 healthy and 39 AMD eyes). The overall intra- and intersession had excellent reliability (intraclass correlation coefficient, ICC > 0.90) and tests were highly correlated (Spearman rs = 0.75-0.86). Eyes with subretinal drusenoid deposit (SDD) had reduced PWS centrally, particularly at inferior and nasal retinal locations compared with controls and intermediate AMD (iAMD) without SDD. There was no difference in MS or PWS at any retinal location between iAMD without SDD and healthy individuals nor between iAMD with SDD and non-foveal atrophic AMD groups. Eyes with SDD have reduced rod function compared to iAMD without SDD and healthy eyes, but similar to eyes with non-foveal atrophy.