ABSTRACT
Quinoa (Chenopodium quinoa Willd.) leafy greens (QLGs) are plant-based foods of high nutritional value that have been scarcely studied. In this work, the nutritional and functional composition of three QLGs varieties was evaluated. A protein content higher than 35 g 100 g-1 dw with a well-balanced essential amino acid composition was found making them a good source of vegetable protein. In addition, elevated contents of dietary fibre and minerals, higher than those detected in quinoa seeds and other leafy vegetables, were found. The lipid profile showed higher contents of linoleic (C18:2, ω6) (20.2 %) and linolenic acids (C18:3, ω3) (52.8 %) with low ω6/ ω3 ratios (â¼0.4/1). A total sugar content <1 g 100 g-1 dw was found for all varieties tested, lower than that obtained in seeds. The saponin content varied between 0.76 and 0.87 %. Also, high values of total phenolic compounds (969.8-1195.4 mg gallic acid 100 g-1), mainly hydroxycinnamic acids and flavonoids, and great antioxidant activities (7.64-8.90 g Trolox kg-1) were found. Multivariate analysis here used allowed us to classify the samples according to the quinoa variety evaluated, and the sequential stepwise multiple regression applied revealed that the PUFA and sucrose contents negatively influenced the protein content while the palmitic acid content affected positively this parameter. Overall, this study shows that QLGs are promising nutritious and functional plant-based foods supporting the necessity of promoting their cultivation, commercialization, and consumption.
Subject(s)
Chenopodium quinoa , Chenopodium quinoa/chemistry , Phenols/analysis , Seeds/chemistry , Dietary Carbohydrates/analysis , Antioxidants/analysisABSTRACT
Univariate (Analysis of Variance_ANOVA) and multivariate (Principal Component Analysis (PCA) and Canonical Discriminant Analysis (CDA)) analyses were performed in order to classify and authenticate the seeds from different varieties of quinoa (Chenopodium quinoa Will.), and amaranth (Amaranthus cruentus L.). The univariate analysis showed differences between species for sucrose, K, Ca, unsaturated fatty acids, and the ω6/ω3 ratio. Nevertheless, to strengthen this classification, a PCA was applied separating the samples in 2 groups; group 1, formed by quinoa seeds, presented higher contents of margaroleic, eicosadienoic, behenic, erucic, linolenic, linoleic, and gadoleic acids, proteins, sucrose, and total sugars. Group 2, formed by amaranth seeds, showed positive values for Mn, Mg, Fe, P, Zn, Ca, fiber, glucose, and ω6/ω3 ratio. Furthermore, the CDA models developed resulted in a probability of event of 100% when classifying the samples in the groups quinoa or amaranth, highlighting the good sensitivity of the models used.
Subject(s)
Amaranthus , Chenopodium quinoa , Carbohydrates , Fatty Acids, Unsaturated , SucroseABSTRACT
We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden. In some regions, a drop in current levels of external ancestry suggests that ancient immigrants contributed proportionately less to the modern Scandinavian gene pool than indicated by the ancestry of genomes from the Viking and Medieval periods. Finally, we show that a north-south genetic cline that characterizes modern Scandinavians is mainly due to the differential levels of Uralic ancestry and that this cline existed in the Viking Age and possibly earlier.
Subject(s)
Genome, Human , Humans , Europe , Genetic Variation , Scandinavian and Nordic Countries , United Kingdom , White People/genetics , White People/history , Human MigrationABSTRACT
The impact of human mobility on the northern European urban populations during the Viking and Early Middle Ages and its repercussions in Scandinavia itself are still largely unexplored. Our study of the demographics in the final phase of the Viking era is the first comprehensive multidisciplinary investigation that includes genetics, isotopes, archaeology, and osteology on a larger scale. This early Christian dataset is particularly important as the earlier common pagan burial tradition during the Iron Age was cremation, hindering large-scale DNA analyses. We present genome-wide sequence data from 23 individuals from the 10th to 12th century Swedish town of Sigtuna. The data revealed high genetic diversity among the early urban residents. The observed variation exceeds the genetic diversity in distinct modern-day and Iron Age groups of central and northern Europe. Strontium isotope data suggest mixed local and non-local origin of the townspeople. Our results uncover the social system underlying the urbanization process of the Viking World of which mobility was an intricate part and was comparable between males and females. The inhabitants of Sigtuna were heterogeneous in their genetic affinities, probably reflecting both close and distant connections through an established network, confirming that early urbanization processes in northern Europe were driven by migration.
Subject(s)
DNA/genetics , Emigration and Immigration , Genome-Wide Association Study , Strontium/chemistry , Bone and Bones/chemistry , Cities , Emigration and Immigration/history , Female , Genomics , History, Ancient , Humans , Male , Strontium Isotopes , SwedenABSTRACT
OBJECTIVES: The objective of this study has been to confirm the sex and the affinity of an individual buried in a well-furnished warrior grave (Bj 581) in the Viking Age town of Birka, Sweden. Previously, based on the material and historical records, the male sex has been associated with the gender of the warrior and such was the case with Bj 581. An earlier osteological classification of the individual as female was considered controversial in a historical and archaeological context. A genomic confirmation of the biological sex of the individual was considered necessary to solve the issue. MATERIALS AND METHODS: Genome-wide sequence data was generated in order to confirm the biological sex, to support skeletal integrity, and to investigate the genetic relationship of the individual to ancient individuals as well as modern-day groups. Additionally, a strontium isotope analysis was conducted to highlight the mobility of the individual. RESULTS: The genomic results revealed the lack of a Y-chromosome and thus a female biological sex, and the mtDNA analyses support a single-individual origin of sampled elements. The genetic affinity is close to present-day North Europeans, and within Sweden to the southern and south-central region. Nevertheless, the Sr values are not conclusive as to whether she was of local or nonlocal origin. DISCUSSION: The identification of a female Viking warrior provides a unique insight into the Viking society, social constructions, and exceptions to the norm in the Viking time-period. The results call for caution against generalizations regarding social orders in past societies.
Subject(s)
Burial/history , Military Personnel/history , Adult , Anthropology, Physical , DNA/analysis , DNA/genetics , Female , Genomics , History, Medieval , Humans , Sweden/ethnologyABSTRACT
Neuroblastoma is an aggressive, relapse-prone childhood tumor of the sympathetic nervous system. Current treatment modalities do not fully exploit the genetic basis between the different molecular subtypes and little is known about the targets discovered in recent mutational and genetic studies. Neuroblastomas with poor prognosis are often characterized by 1p36 deletion, containing the kinesin gene KIF1B. Its beta isoform, KIF1Bß, is required for NGF withdrawal-dependent apoptosis, mediated by the induction of XIAP-associated Factor 1 (XAF1). Here, we showed that XAF1 low expression correlates with poor survival and disease status. KIF1Bß deletion results in loss of XAF1 expression, suggesting that XAF1 is indeed a downstream target of KIF1Bß. XAF1 silencing protects from NGF withdrawal and from KIF1Bß-mediated apoptosis. Overexpression of XAF1 impairs tumor progression whereas knockdown of XAF1 promotes tumor growth, suggesting that XAF1 may be a candidate tumor suppressor in neuroblastoma and its associated pathway may be important for developing future interventions.
Subject(s)
Intracellular Signaling Peptides and Proteins/metabolism , Kinesins/metabolism , Neoplasm Proteins/metabolism , Neuroblastoma/pathology , Adaptor Proteins, Signal Transducing , Animals , Apoptosis/physiology , Apoptosis Regulatory Proteins , Biomarkers, Tumor/analysis , Cell Line, Tumor , F-Box Proteins/metabolism , Gene Expression Regulation, Neoplastic/physiology , Heterografts , Humans , Kaplan-Meier Estimate , Mice , Mice, Knockout , Neuroblastoma/metabolism , Neuroblastoma/mortality , Prognosis , Tumor Suppressor Proteins/metabolismABSTRACT
UNLABELLED: Inherited KIF1B loss-of-function mutations in neuroblastomas and pheochromocytomas implicate the kinesin KIF1B as a 1p36.2 tumor suppressor. However, the mechanism of tumor suppression is unknown. We found that KIF1B isoform ß (KIF1Bß) interacts with RNA helicase A (DHX9), causing nuclear accumulation of DHX9, followed by subsequent induction of the proapoptotic XIAP-associated factor 1 (XAF1) and, consequently, apoptosis. Pheochromocytoma and neuroblastoma arise from neural crest progenitors that compete for growth factors such as nerve growth factor (NGF) during development. KIF1Bß is required for developmental apoptosis induced by competition for NGF. We show that DHX9 is induced by and required for apoptosis stimulated by NGF deprivation. Moreover, neuroblastomas with chromosomal deletion of 1p36 exhibit loss of KIF1Bß expression and impaired DHX9 nuclear localization, implicating the loss of DHX9 nuclear activity in neuroblastoma pathogenesis. SIGNIFICANCE: KIF1Bß has neuroblastoma tumor-suppressor properties and promotes and requires nuclear-localized DHX9 for its apoptotic function by activating XAF1 expression. Loss of KIF1Bß alters subcellular localization of DHX9 and diminishes NGF dependence of sympathetic neurons, leading to reduced culling of neural progenitors, and, therefore, might predispose to tumor formation.
Subject(s)
DEAD-box RNA Helicases/metabolism , Kinesins/metabolism , Neoplasm Proteins/metabolism , Nerve Growth Factor/genetics , Neuroblastoma/genetics , Animals , Apoptosis , Cell Nucleus/metabolism , Chromosomes, Human, Pair 1 , DEAD-box RNA Helicases/genetics , Humans , Karyopherins/metabolism , Kinesins/genetics , Mice , Mice, Inbred C57BL , Neoplasm Proteins/genetics , PC12 Cells , Rats , Sequence Deletion , Sympathetic Nervous System/metabolism , Tumor Cells, CulturedABSTRACT
Accumulating evidence points to reactive oxygen species (ROS) as important signaling molecules for cardiomyocyte differentiation in embryonic stem (ES) cells. Given that ES cells are normally maintained and differentiated in medium containing supraphysiological levels of glucose (25 mM), a condition which is known to result in enhanced cellular ROS formation, we questioned whether this high glucose concentration was necessary for cardiomyocyte lineage potential. We show here that ES cells cultured in physiological glucose (5 mM), maintained their general stemness qualities but displayed an altered mitochondrial metabolism, which resulted in decreased ROS production. Furthermore, ES and induced pluripotent stem (iPS) cells differentiated in lower glucose concentrations failed to generate cardiomyocyte structures; an effect mimicked with antioxidant treatments using catalase, N-acetyl cysteine and mitoubiquinone, under high glucose conditions in ES cells. Molecular analysis revealed that ES cells differentiated in 5 mM glucose had reduced expression of the pro-cardiac NOX4 gene and diminished phosphorylation of p38 mitogen-activated protein kinase (MAPK), together with specific changes in the cardiac transcriptional network. These outcomes could be reversed by supplementation of low glucose cultures with ascorbic acid, paradoxically acting as a pro-oxidant. Furthermore, forced expression of an upstream p38 MAPK kinase (MKK6) could bypass the requirement for ROS during differentiation to cardiomyocytes under low glucose conditions, illustrating a key role for p38 in the cardiac differentiation program. Together these data demonstrate that endogenous ROS control is important for cardiomyocyte formation from ES cells, and furthermore that supraphysiological glucose, by supplying ROS, is absolutely required.
Subject(s)
Cell Differentiation/drug effects , Embryonic Stem Cells/metabolism , Glucose/pharmacology , Mitochondria/metabolism , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Reactive Oxygen Species/metabolism , Animals , Cell Culture Techniques , Embryonic Stem Cells/cytology , Embryonic Stem Cells/drug effects , Gene Expression Regulation , Mice , Myocytes, Cardiac/drug effects , NADPH Oxidase 4 , NADPH Oxidases/genetics , NADPH Oxidases/metabolism , Phosphorylation , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Functional loss of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration during embryonic development and tumour invasion. In most carcinomas, transcriptional repression has emerged as the main mechanism responsible for E-cadherin downregulation. Here, we report the identification of class I bHLH factor E2-2 (TCF4/ITF2) as a new EMT regulator. Both isoforms of E2-2 (E2-2A and E2-2B) induce a full EMT when overexpressed in MDCK cells but without affecting the tumorigenic properties of parental cells, in contrast to other EMT inducers, such as Snail1 or class I bHLH E47. E-cadherin repression mediated by E2-2 is indirect and independent of proximal E-boxes of the promoter. Knockdown studies indicate that E2-2 expression is dispensable for maintenance of the EMT driven by Snail1 and E47. Comparative gene-profiling analysis reveals that E2-2 factors induce similar, yet distinct, genetic programs to that induced by E47 in MDCK cells. These results, together with the embryonic expression pattern of Tcf4 and E2A (which encodes E12/E47), support a distinct role for E2-2 and suggest an interesting interplay between E-cadherin repressors in the regulation of physiological and pathological EMT processes.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Epithelium/metabolism , Mesoderm/metabolism , TCF Transcription Factors/metabolism , Animals , Cadherins/genetics , Cadherins/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Movement , Dogs , Embryo, Mammalian/metabolism , Epithelial Cells/cytology , Epithelial Cells/metabolism , Gene Expression Profiling , Humans , Mesoderm/embryology , Mice , Neoplasm Invasiveness , Promoter Regions, Genetic/genetics , RNA, Small Interfering/metabolism , Snail Family Transcription Factors , TCF Transcription Factors/genetics , Transcription Factor 7-Like 1 Protein , Transcription Factor 7-Like 2 Protein , Transcription Factors/metabolism , Transcription, Genetic , Up-RegulationABSTRACT
Rat liver and Trypanosoma cruzi tyrosine aminotransferases (TATs) share over 40% sequence identity, but differ in their substrate specificities. To explore the molecular features related to these differences, comparative mutagenesis studies were conducted on full length T. cruzi TAT and N-terminally truncated rat TAT recombinant enzymes. The functionality of Arg315 and Arg417 in rat TAT was investigated for comparison with the conserved Arg292 and Arg386 in aspartate and bacterial aromatic aminotransferases (ASATs and ARATs). The rat TAT Arg315Lys variant remained fully active indicating that, as in T. cruzi TAT and contrary to subfamily Ialpha aminotransferases, this residue is not critical for activity. In contrast, the Arg417Gln variant was inactive. The catalytic relevance of the putative rat TAT active site residues Asn54 and Arg57, which are strictly conserved in TATs (Asn17 and Arg20 in T. cruzi TAT) but differ in ASATs and ARATs, was also explored. The substitutions Arg57Ala and Arg57Gln abolished enzymatic activity of these mutants. In both variants, spectral studies demonstrated that aromatic but not dicarboxylic substrates could efficiently bind in the active site. Thus, Arg57 appears to be functionally equivalent to Arg292 of ASATs and ARATs. Asn54 also appears to be involved in the catalytic mechanism of rat TAT since its exchange for Ser lowered the k(cat)/K(m) ratios towards its substrates. Mutation of the analogous residues in T. cruzi TAT also lowered the catalytic efficiencies (k(cat)/K(m)) of the variants substantially. The results imply that the mamalian TAT is more closely related to the T. cruzi TAT than to ASATs and ARATs.