The Flavonol-Anthocyanin Pathway in Blackberry and Arabidopsis: State of the Art

Flavonols and anthocyanins are plant secondary metabolites with an increasing interest due to their beneficial effects on human health. They are present in all plants, participating in plant protection against biotic and abiotic stresses. However, only some plant species accumulate them in relevant amounts, as is the case for berries. Among the health benefits reported is prevention of metabolic syndrome, s, including prevention of insulin resistance associated to type 2 diabetes. Therefore, there is a big interest to improve contents on plant foods to benefit health through the diet, as well as to obtain them for functional ingredients for food supplements. In fulfillment of this objective, a deep study about their biosynthetic pathway has been carried out in model plants, where the genome is available. However, not all species that accumulate them in high amounts have their genome sequenced, as is the case for blackberry. Transcriptomic approaches have been undertaken to gain knowledge of its specific biosynthetic pathway and regulatory elements, aiming to improve bioactive contents in the edible parts. Furthermore, determining the regulatory pathways will help to improve yields and in vitro production. For this purpose, a review on elicitors used to trigger this pathway is presented

Biotic elicitation as a tool to improve strawberry and raspberry extract potential on metabolic syndromeâ related enzymes in vitro

BackgroundRaspberry and strawberry are high valueâ added food products that can contribute to human health due to the abundance of polyphenols that they contain. Polyphenols are secondary metabolites and therefore devoted to improve plant adaptation, these polyphenol profile can be induced applying different stimuli, such as certain bacteria. The aim of this study was twofold: (i) to evaluate the ability of two bacterial strains to modulate secondary metabolisms in strawberry and raspberry, and (ii) to explore the ability of plant extracts to modify enzyme activities related to metabolic syndrome.ResultsTotal phenolic and anthocyanin content was higher in strawberries than in raspberries, despite similar antioxidant capacities. Strawberry extracts performed better on the tested enzymes, except on αâ glucosidase inhibition capacity. Bacillus amyloliquefaciens stabilized the effects of extracts at different points in time, and Pseudomonas fluorescens modified plant metabolism after more inoculations (spring) in both species, improving the effects of raspberry extracts on αâ glucosidase, COX1, and COX2, and of strawberry on αâ amylase and COX1.ConclusionIt is good to include these two fruits in the diet because they improve the activity of metabolic syndromeâ related enzymes. Applying either strain during plant growth modifies the bioactive profile of the plants, improving the effects of the fruit extracts on human health. © 2018 Society of Chemical IndustryPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148422/1/jsfa9507_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148422/2/jsfa9507.pd

Taphonomic and spatial analyses from the Early Pleistocene site of Venta Micena 4 (Orce, Guadix-Baza Basin, southern Spain)

Venta Micena is an area containing several palaeontological sites marking the beginning of the Calabrian stage (Early Pleistocene). The richness of the fossil accumulation including species of Asian, African and European origin, makes Venta Micena a key site for the the palaeoecological and palaeoenvironmental study of southern Europe during the Early Pleistocene. Thus, research has been focused on Venta Micena 3, which was originally interpreted as a single palaeosurface associated with a marshy context, in which most of the fauna was accumulated by Pachycrocuta brevirostris. Recent excavations have unearthed a new site, Venta Micena 4, located in the same stratigraphic unit (Unit C) and in close proximity to Venta Micena 3. Here we show the first analyses regarding the taphonomic and spatial nature of this new site, defining two stratigraphic boundaries corresponding to two different depositional events. Furthermore, the taphonomic analyses of fossil remains seem to indicate a different accumulative agent than Pachycrocuta, thus adding more complexity to the palaeobiological interpretation of the Venta Micena area. These results contribute to the discussion of traditional interpretations made from Venta Micena 3.Peer reviewe

To den or not to den. Contributions to the taphonomic history of the Early Pleistocene site of Venta Micena 4 (Orce, Guadix-Baza Basin)

Venta Micena (Orce, Guadix-Baza Basin, Spain) is an Early Pleistocene locality renowned for the richness and quality of its palaeontological record. VM is spread over an area of 2.5 km2, where several exposed fossil outcrops are visible amidst its gorges and ravines. The best known of these sites, VM3, has been interpreted as a hyaena den. In addition, a new site, named VM4, has recently been the focus of fieldwork and taphonomic studies. The publication by Luzón et al. (2021) pointed out that VM4 presents a more complex history than VM3. First, two different sub-levels were identified: VM4-I and VM4-II. Secondly, the preliminary taphonomic analysis showed conspicuous differences with regard to VM3. Nevertheless, such interpretation has been challenged by Palmqvist et al. (2022) who proposed that VM3 and VM4 are both the result of a single depositional process, entailing the selective transport of skeletal parts by the giant extinct hyaena Pachycrocuta brevirostris back to its den. Using well-preserved faunal elements whose depositional context and provenance are reliable, in this paper we show that: 1) there are two clearly defined sub-levels in VM4 with some shared taphonomic characteristics as well as some notable differences; 2) VM3 and VM4 exhibit enough divergence to support differences in site formation processes; 3) The interpretation of both VM4-I and VM4-II is more consistent with their characterisation as open-air sites in which multiple agents and depositional processes contributed to its formation, rather than with hyaena dens. Nevertheless, excavations are still in progress at VM4 and therefore any results and interpretations ought to be considered as provisional

Pliocene to Middle Pleistocene climate history in the Guadix-Baza Basin, and the environmental conditions of early Homo dispersal in Europe

The Guadix-Baza Basin (GBB) in Andalucia, Spain, comprises palaeontological and archaeological sites dating from the Early Pliocene to the Middle Pleistocene, including some of the earliest sites with evidence for the presence of early humans (Homo sp.) in Europe. Thus, the history of climate and environments in this basin contributes significantly to our understanding of the conditions under which early humans spread into Europe during the Early Pleistocene. Here we present estimates of precipitation and primary productivity in the GBB from the Pliocene to the Middle Pleistocene based on dental ecometrics in fossil communities of large herbivorous mammals, and perform an ecometrics-based distribution modelling to analyse the environmental conditions of Early and Middle Pleistocene human sites in Europe. Our results show that Early Pleistocene humans generally occupied on average relatively diverse habitats with ecotones, such as woodlands and savannas, but avoided very open and harsh (cool or dry) environments. During the Middle Pleistocene in Europe, humans occupied a comparatively much broader range of environments than during the Early Pleistocene, but were on average more concentrated in environments where the dental ecometric of mammals indicate wooded palaeoenvironments. In the earliest human occupation sites of the GBB, Barranco Leon and Fuente Nueva 3, the mean annual precipitation and net primary production estimates indicate climatic conditions close to modern Mediterranean sclerophyllous woodland environments, but with slightly higher primary productivity, indicating some similarity with East African woodlands. On the other hand, the environments did not resemble African grassland savannas. The browse-dominated diets of ungulates from Barranco Leon and Fuente Nueva 3 further suggest palaeoenvironments where grasses were a minor component of the vegetation. In the slightly older site of Venta Micena that has no evidence for the presence of hominins, dental ecometric estimates indicate climate and environments similar to Mediterranean "forest steppe" environments existing in the surroundings of Baza today. Grasses were prevalent in the diet of some taxa, especially equids, in Venta Micena, but most of the species show browse-dominated diets even there. (C) 2021 The Authors. Published by Elsevier Ltd.Peer reviewe

A multi-proxy approach to the palaecological reconstruction of the Orce Basin Archaeological Zone (Granada, Spain)

Comunicación oral presentada en XXI INQUA Congress. July 14th – 20th 2023, Rome (Italy)The Orce Basin Archaeological Zone (OZAB, Granada, Spain) extends over a surface area of some > 8.5 km2 and constitutes one of the richest Pleistocene vertebrate fossil records in western Europe including one of the oldest hominin presence in this part of Eurasia. Exceptionally rich collections of stone tools have been excavated from both of the Orce Oldowan sites: Barranco León (BL) (1.4 Ma) and Fuente Nueva 3 (FN3) (1.2 Ma), while BL has yielded a hominin deciduous lower molar. We present a multi-proxy approach to determine the palaeoeocological context of these first hominin settlements in Western Europe. By combining results from macrovertebrates, microvertebrates, as well as from pollen and stable isotopes from macrovertebrate tooth enamel, we determine whether the palaeo landscapes were dominated by savanna or open woodland. The results reveal the regional specificities of the OAZB, and also allow us to infer local features within the Orce sites. Overall, our data reveal the dominance of a typically Mediterranean climate and landscape since 1.8 Ma ago. The climatic conditions were generally more humid than at present, with warmer temperatures during the coldest months, indicating a higher net primary productivity (NPP). We find that precipitation and NPP appear to have been limiting factors for hominin presence in the OAZB. Thus, at the older palaeontological site of Venta Micena (1.6 Ma), climatic conditions appear to have been less compatible with hominin presence than during the BL and FN3 sequences, when early hominins inhabiting the OAZB were able to cope with changing climatic and environmental settings. Lastly, the comparison of the isotopic results of the Orce sites with those of the contemporaneous Shungura Formation (Ethiopia) reveals that the habitat in the westernmost part of Eurasia was distinctly unlike a typical African savanna

Not seen before. Unveiling depositional context and Mammuthus meridionalis exploitation at Fuente Nueva 3 (Orce, southern Iberia) through taphonomy and microstratigraphy

Meat consumption by early hominins is a hotly debated issue. A key question concerns their access to large mammal carcasses, including megafauna. Currently, the evidence of anthropic cut marks on proboscidean bones older than -or close to- 1.0 Ma are restricted to the archaeological sites of Dmanisi (Georgia), Olduvai (Tanzania), Gona (Ethiopia), Olorgesailie (Kenya) and La Boella (Spain). During an inspection of the almost complete carcass of Mammuthus meridionalis (FN3-5-MPS) from the Oldowan site of Fuente Nueva 3 (Orce, Spain, c. 1.2 Ma), a few traces compatible with human-made cut marks and carnivore tooth marks were found. From this finding and previous interpretations the following questions arise: When and under what conditions was FN3-5-MPS deposited? What is the nature of the marks found on the surface of the bones of this mammoth? To answer, we have conducted a high-resolution analysis of these remains, combining both taphonomic and microstratigraphic data. Our results, using microstratigraphic and micromorphological analyses of sediments based on thin-sections, show that this individual was deposited in a marshy environment. Subsequently, the carcass was exploited by hominins and large felids that left their marks on the surface of some of its bones. For this purpose, the identification and characterisation of both cut marks and tooth marks were performed using high-resolution 3D modelling, geometric morphometrics, and artificially intelligent algorithms. Based on the anatomical position of both the cut and tooth marks, we propose that both the hominins and the saber-toothed cats had early access to the animal. Finally, this paper shows how an interdisciplinary approach can shed detailed light on the particular story regarding the death and processing of the carcass of a female mammoth, deposited at Fuente Nueva 3.This research has been carried out thanks to projects PID 2021.125098NB.I00 funding by MCIN/AEI/10.13039/501100011033/FEDER Una manera de hacer Europa and ProyExcel_00274 funding by Dirección General de Planificación de la Investigación (Consejería de Universidad, Investigación e Innovación, Junta de Andalucía). In addition, this research has been supported by the following projects of the Spanish government: PID2021-122533NB-I00, PID2021-123092NB-C21, PID2022-136832NB-I00. We also acknowledge the support provided by the PALARQ Foundation through the project Ref: PR2004_19/01

Peripheral T-lymphocytes express WNT7A and its restoration in leukemia-derived lymphoblasts inhibits cell proliferation

<p>Abstract</p> <p>Background</p> <p>WNT7a, a member of the Wnt ligand family implicated in several developmental processes, has also been reported to be dysregulated in some types of tumors; however, its function and implication in oncogenesis is poorly understood. Moreover, the expression of this gene and the role that it plays in the biology of blood cells remains unclear. In addition to determining the expression of the <it>WNT7A </it>gene in blood cells, in leukemia-derived cell lines, and in samples of patients with leukemia, the aim of this study was to seek the effect of this gene in proliferation.</p> <p>Methods</p> <p>We analyzed peripheral blood mononuclear cells, sorted CD3 and CD19 cells, four leukemia-derived cell lines, and blood samples from 14 patients with Acute lymphoblastic leukemia (ALL), and 19 clinically healthy subjects. Reverse transcription followed by quantitative Real-time Polymerase chain reaction (qRT-PCR) analysis were performed to determine relative <it>WNT7A </it>expression. Restoration of WNT7a was done employing a lentiviral system and by using a recombinant human protein. Cell proliferation was measured by addition of WST-1 to cell cultures.</p> <p>Results</p> <p>WNT7a is mainly produced by CD3 T-lymphocytes, its expression decreases upon activation, and it is severely reduced in leukemia-derived cell lines, as well as in the blood samples of patients with ALL when compared with healthy controls (<it>p </it>≤0.001). By restoring <it>WNT7A </it>expression in leukemia-derived cells, we were able to demonstrate that WNT7a inhibits cell growth. A similar effect was observed when a recombinant human WNT7a protein was used. Interestingly, restoration of <it>WNT7A </it>expression in Jurkat cells did not activate the canonical Wnt/β-catenin pathway.</p> <p>Conclusions</p> <p>To our knowledge, this is the first report evidencing quantitatively decreased <it>WNT7A </it>levels in leukemia-derived cells and that <it>WNT7A </it>restoration in T-lymphocytes inhibits cell proliferation. In addition, our results also support the possible function of <it>WNT7A </it>as a tumor suppressor gene as well as a therapeutic tool.</p

Not seen before. Unveiling depositional context and Mammuthus meridionalis exploitation at Fuente Nueva 3 (Orce, southern Iberia) through taphonomy and microstratigraphy

Meat consumption by early hominins is a hotly debated issue. A key question concerns their access to large mammal carcasses, including megafauna. Currently, the evidence of anthropic cut marks on proboscidean bones older than -or close to- 1.0 Ma are restricted to the archaeological sites of Dmanisi (Georgia), Olduvai (Tanzania), Gona (Ethiopia), Olorgesailie (Kenya) and La Boella (Spain). During an inspection of the almost complete carcass of Mammuthus meridionalis (FN3-5-MPS) from the Oldowan site of Fuente Nueva 3 (Orce, Spain, c. 1.2 Ma), a few traces compatible with human-made cut marks and carnivore tooth marks were found. From this finding and previous interpretations the following questions arise: When and under what conditions was FN3-5-MPS deposited? What is the nature of the marks found on the surface of the bones of this mammoth? To answer, we have conducted a high-resolution analysis of these remains, combining both taphonomic and microstratigraphic data. Our results, using microstratigraphic and micromorphological analyses of sediments based on thin-sections, show that this individual was deposited in a marshy environment. Subsequently, the carcass was exploited by hominins and large felids that left their marks on the surface of some of its bones. For this purpose, the identification and characterisation of both cut marks and tooth marks were performed using high-resolution 3D modelling, geometric morphometrics, and artificially intelligent algorithms. Based on the anatomical position of both the cut and tooth marks, we propose that both the hominins and the saber-toothed cats had early access to the animal. Finally, this paper shows how an interdisciplinary approach can shed detailed light on the particular story regarding the death and processing of the carcass of a female mammoth, deposited at Fuente Nueva 3.Research at Fuente Nueva 3 is currently possible thanks to the support and approval of the Consejería de Turismo, Cultura y Deporte (Junta de Andalucía, Spain) through the General Research Project (2023–2026) Evolución humana y paleoecología a partir de los yacimientos pleistocenos de la Zona Arqueológica ‘Cuenca de Orce’. Retos y desafíos (Ref: SIDPH/DI/MCM). This research has been carried out thanks to projects PID 2021.125098NB.I00 funding by MCIN/AEI/10.13039/501100011033/ FEDER Una manera de hacer Europa and ProyExcel_00274 funding by Dirección General de Planificación de la Investigación (Consejería de Universidad, Investigación e Innovación, Junta de Andalucía). In addition, this research has been supported by the following projects of the Spanish government: PID2021-122533NB-I00, PID2021-123092NBC21, PID2022-136832NB-I00. We also acknowledge the support provided by the PALARQ Foundation through the project Ref: PR2004_19/01. The research of C.S-B., D.B., P-P., S.T., J.A., and H.-A.B. is funded by the CERCA Programme/Generalitat de Catalunya. A.F.M. was supported by an APOST postdoctoral grant (APOST/2021/110, Generalitat Valenciana) cofinanced by the European Social Fund, and is currently supported by a Margarita Salas contract from the Ayudas para la recualificación del sistema universitario español (MS21-048), Ministerio de Universidades del Gobierno de España, financed by the European Union-NextGenerationEU. S.T. is supported by a Margarita Salas employment contract for access to the Spanish System of Science, Technology, and Innovation at the Universitat Rovira i Virgili (2021URV-MS-03) funded by the European Union-NextGenerationEU, the Ministry of Universities and the Recovery, Transformation and Resilience Plan. P.P. is supported by a Juan de la Cierva - Incorporación contract (grant IJC2020-044108-I) funded by MCIN/AEI/10.13039/501100011033 and “European Union-NextGenerationEU/PRTR”. Similiarly, we also have to acknowledge the financial support provided by the PALARQ Foundation, funded through the project titled “Dilucidando la acción de los carnívoros en los yacimientos del Pleistoceno Inferior Ibérico del Pontón de la Oliva (Madrid) y de Fuente Nueva 3 y de Venta Micena 3 y 4 (Granada). Ref: PR2004_19/01”. The work of J.S. was funded by the Academy of Finland during this work (AoF. project nr. 340775/346292, NEPA - Non-analogue ecosystems in the past)

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks