Adesmia pinifolia, a Native High-Andean Species, as a Potential Candidate for Phytoremediation of Cd and Hg.

This study highlights Adesmia pinifolia, a native high-Andean species, as a potential candidate for the phytoremediation of soils contaminated with Cd and Hg. In this work, a semi-hydronic assay with different doses of Cd (3, 4.5, and 6 mg L-1) and Hg (0.8, 1.2, and 1.6 mg L-1) was analysed to evaluate the establishment of plants, antioxidant defence systems, oxidative stress, and the ability to accumulate heavy metals. The results indicate high survival rates (>80%); however, Cd significantly reduced shoot and root biomass, while Hg increased root biomass with the 1.6 mg L-1 treatment. Cd and Hg tend to accumulate more in roots (2534.24 µg/g and 596.4 µg g-1, respectively) compared to shoots (398.53 µg g-1 and 140.8 µg g-1, respectively). A significant decrease in the bioconcentration factor of Cd and Hg in roots was observed as metal levels increased, reaching the maximum value at 3 mg L-1 (805.59 ± 54.38) and 0.8 mg L-1 (804.54 ± 38.09). The translocation factor, <1 for both metals, suggests that translocation from roots to shoots is limited. An overproduction of reactive oxygen species (ROS) was observed, causing lipid peroxidation and oxidative damage to plant membranes. Tolerance strategies against subsequent toxicity indicate that enhanced glutathione reductase (GR) activity and glutathione (GSH) accumulation modulate Cd and Hg accumulation, toxicity, and tolerance.

Surface Plasmon Resonance as a Tool to Elucidate the Molecular Determinants of Key Transcriptional Regulators Controlling Rhizobial Lifestyles.

Bacteria must be provided with a battery of tools integrated into regulatory networks, in order to respond and, consequently, adapt their physiology to changing environments. Within these networks, transcription factors finely orchestrate the expression of genes in response to a variety of signals, by recognizing specific DNA sequences at their promoter regions. Rhizobia are host-interacting soil bacteria that face severe changes to adapt their physiology from free-living conditions to the nitrogen-fixing endosymbiotic state inside root nodules associated with leguminous plants. One of these cues is the low partial pressure of oxygen within root nodules.Surface plasmon resonance (SPR) constitutes a technique that allows to measure molecular interactions dynamics at real time by detecting changes in the refractive index of a surface. Here, we implemented the SPR methodology to analyze the discriminatory determinants of transcription factors for specific interaction with their target genes. We focused on FixK2, a CRP/FNR-type protein with a central role in the complex oxygen-responsive regulatory network in the soybean endosymbiont Bradyrhizobium diazoefficiens. Our study unveiled relevant residues for protein-DNA interaction as well as allowed us to monitor kinetics and stability protein-DNA complex. We believe that this approach can be employed for the characterization of other relevant transcription factors which can assist to the better understanding of the adaptation of bacteria with agronomic or human interest to their different modes of life.

Volatile organic compounds measured by proton transfer reaction mass spectrometry over the complex terrain of Quintero Bay, Central Chile.

This research provides new evidence regarding the different kinds of air quality episodes, and their underlying mechanisms, that frequently impact the urban area of Quintero Bay in Central Chile, which is located along complex coastal terrain and is surrounded by industries. The monitoring campaign was carried out in January 2022 and encompassed two distinctive meteorological regimes. The first part of the month was dominated by a coastal low centered to the south of Quintero, which resulted in prevailing northerly flow (or weak southerlies) and a deep cloud-topped marine boundary layer. After a 2-3-day transition, the latter collapsed, and a clear-sky regime ensued, which was characterized by a shallow boundary layer and strong southerly winds during the daytime that lasted until the end of the campaign. By using proton transfer reaction time of flight mass spectrometry (PTR-TOF-MS) at a high temporal resolution (1 s), we measured high levels of volatile organic compounds (VOCs) during air quality episodes in real time. The episodes detected were associated with different prevailing meteorological regimes, suggesting that different point sources were involved. In the first episode, propene/cyclopropane, butenes, benzene, toluene and ethylbenzene/xylenes were associated with north and northwesterly weak winds. Complaints associated with hydrocarbon odor were reported. The pollution originated from industrial and petrochemical units located to the north of Quintero, which transport and store natural gas, liquified petroleum gas and oil. The second episode was linked to an oil refinery located south of our measurement site. In this case, high levels of phenol, furan and cresols occurred under strong southwesterly winds. During this event, headaches and dizziness were reported. By contrast, the levels of other aromatic compounds (benzene, toluene, ethylbenzene/xylenes) were lower than in the first air pollution episode.

Advances in Simulating the Global Spatial Heterogeneity of Air Quality and Source Sector Contributions: Insights into the Global South.

High-resolution simulations are essential to resolve fine-scale air pollution patterns due to localized emissions, nonlinear chemical feedbacks, and complex meteorology. However, high-resolution global simulations of air quality remain rare, especially of the Global South. Here, we exploit recent developments to the GEOS-Chem model in its high-performance implementation to conduct 1-year simulations in 2015 at cubed-sphere C360 (∼25 km) and C48 (∼200 km) resolutions. We investigate the resolution dependence of population exposure and sectoral contributions to surface fine particulate matter (PM2.5) and nitrogen dioxide (NO2), focusing on understudied regions. Our results indicate pronounced spatial heterogeneity at high resolution (C360) with large global population-weighted normalized root-mean-square difference (PW-NRMSD) across resolutions for primary (62-126%) and secondary (26-35%) PM2.5 species. Developing regions are more sensitive to spatial resolution resulting from sparse pollution hotspots, with PW-NRMSD for PM2.5 in the Global South (33%), 1.3 times higher than globally. The PW-NRMSD for PM2.5 for discrete southern cities (49%) is substantially higher than for more clustered northern cities (28%). We find that the relative order of sectoral contributions to population exposure depends on simulation resolution, with implications for location-specific air pollution control strategies.

Effects of Pubertal Timing and Pubertal Tempo on Social Physique Anxiety, Self-determined Motivation, and Exercise in Early Adolescent Girls.

PURPOSE: Research has shown that there is a decrease in physical activity levels during early adolescence, especially for girls. Previous studies have shown that the social physique anxiety (SPA) may be a controlling factor influencing exercise motivation and engagement in this behavior; however, the potential role that puberty plays in this decrease has not been considered until now. The objective of the present study was to examine the impact of pubertal timing and pubertal tempo on SPA and exercise motivation and behavior. METHODS: Data from 328 early adolescent girls, aged between 9 and 12 at the time of joining the study, were collected in 3 waves over a 2-year period. Using structural equation modeling techniques, different 3-time-point growth models were estimated to examine if earlier maturing and compressed maturing in girls had differential effects on SPA and exercise motivation and behavior. RESULTS: The results from growth analyses suggest that early maturing (according to all the pubertal indicators considered, except menstruation) tends to translate into (1) an increase in SPA levels and (2) a decrease in exercise - in the latter case, by reducing self-determined motivation. However, no differential effects from any of the pubertal indicators were found for compressed maturing in girls. DISCUSSION: These results highlight the need for increased efforts toward developing programs aimed at helping early maturing girls to cope with the challenges of puberty with a particular focus on SPA experiences and exercise motivation and behavior.

Is There Any Relationship between Physical Activity Levels and Academic Achievement? A Cross-Cultural Study among Spanish and Chilean Adolescents.

The current scientific literature has shown significant disparity in results when physical activity is linked to academic achievement among adolescents. Thus, the main objectives of this study were (1) to analyze the relationship among students' academic achievement, intention to be physically active, and physical activity levels depending on the country (Spain or Chile), as well as to analyze these relationships based on students' socio-economic status, type of school, school year, gender, and body mass index; and (2) to analyze the differences between all these variables depending on the students' country and gender. In total, 3052 adolescents participated in the research (14.58 ± 1.39 years): 734 Chilean students (336 males and 398 females) and 2318 Spanish students (1180 males and 1138 females). Various questionnaires were used to measure the study variables. The results revealed significant relationships between academic achievement and the rest of the variables in Spanish adolescents, but in the Chilean population, academic achievement was significantly related only to socio-economic status and the type of school. Moreover, Spanish students obtained higher scores, especially the males, except for academic achievement, which was higher in females. There were also significant differences in academic achievement, intention to be physically active, physical activity levels, and socio-economic status depending on the country, with all scores being higher in Spain. Given the results, the country seems to be an important factor when comparing academic achievement and physical activity levels, besides other demographic variables.

COVID-19 in School Teachers: Job Satisfaction and Burnout through the Job Demands Control Model.

The recent pandemic has influenced teachers' mental health and well-being. The present work follows the Job-Demands-Control model, analyzing changes in the demands, control, and social support during COVID-19, and how they influence job satisfaction, emotional exhaustion, depersonalization, and personal accomplishment among school teachers. The sample comprised 172 school teachers. The instruments applied were The Maslach Burnout Inventory (MBI), The Job Satisfaction Teacher Index (Organization for Economic Cooperation and Development (OECD), 2014), and The Demand Control Support Questionnaire (DCSQ). Job satisfaction was predicted exclusively by social support, revealing the importance of social interactions at work. Emotional exhaustion and depersonalization were predicted by job demands, showing that an increase in job demands (i.e., COVID) affects individuals' feelings of burnout. The results show that it would be interesting to design strategies that guarantee job control in the teaching context. This would open multiple pathways to implement healthier methodological processes for teachers and the consequent research to support these processes.

Weight-Teasing and Eating Disorders-A Comparative Study in Adolescent and Adult Samples.

Disordered eating, unhealthy weight-control behaviours and body dissatisfaction are associated with diminished mental health. A key aspect that has been identified for the development of disordered eating behaviours and body dissatisfaction is to be teased. Additionally, the literature suggests that weight may affect the relationship between weight-teasing and disordered eating and body dissatisfaction, although this pattern is unclear. This study presents two cross-sectional studies with an adult and an adolescent sample. The adolescent sample comprised 15,224 participants, and the adult sample comprised 321 participants, all from Spain. Hierarchical regression analyses were conducted. Aims: to assess the relations among disordered eating, body dissatisfaction, weight, and weight-teasing among adolescents and adults; and to examine whether weight-teasing, weight, age, and gender predict disordered eating and body dissatisfaction in adults and adolescents. The results showed that adolescent girls presented greater effects, and all interactions were significant between weight-teasing and eating disorders. Adults also showed greater effects for women, and only eating disorder interactions were significant. Weight-control behaviours did not show any relationship with weight-teasing. Conclusion: Different approaches may be used in the prevention of eating disorders. Our results show that weight-teasing affects adults differently from adolescents.

Fine-Tuning Modulation of Oxidation-Mediated Posttranslational Control of Bradyrhizobium diazoefficiens FixK2 Transcription Factor.

FixK2 is a CRP/FNR-type transcription factor that plays a central role in a sophisticated regulatory network for the anoxic, microoxic and symbiotic lifestyles of the soybean endosymbiont Bradyrhizobium diazoefficiens. Aside from the balanced expression of the fixK2 gene under microoxic conditions (induced by the two-component regulatory system FixLJ and negatively auto-repressed), FixK2 activity is posttranslationally controlled by proteolysis, and by the oxidation of a singular cysteine residue (C183) near its DNA-binding domain. To simulate the permanent oxidation of FixK2, we replaced C183 for aspartic acid. Purified C183D FixK2 protein showed both low DNA binding and in vitro transcriptional activation from the promoter of the fixNOQP operon, required for respiration under symbiosis. However, in a B. diazoefficiens strain coding for C183D FixK2, expression of a fixNOQP'-'lacZ fusion was similar to that in the wild type, when both strains were grown microoxically. The C183D FixK2 encoding strain also showed a wild-type phenotype in symbiosis with soybeans, and increased fixK2 gene expression levels and FixK2 protein abundance in cells. These two latter observations, together with the global transcriptional profile of the microoxically cultured C183D FixK2 encoding strain, suggest the existence of a finely tuned regulatory strategy to counterbalance the oxidation-mediated inactivation of FixK2 in vivo.

Optimized CRISPR-RfxCas13d system for RNA targeting in zebrafish embryos.

CRISPR-Cas systems have been used to induce DNA mutagenesis for gene function discovery. However, the development of tools to eliminate RNAs provides complementary and unique approaches to disrupt gene expression. Here, we present a workflow to perform specific, efficient, and cost-effective mRNA knockdown in zebrafish embryos using our in vivo optimized CRISPR-RfxCas13d (CasRx) system. Although the described protocol focuses on mRNA knockdown in zebrafish embryos, it can also be applied to other vertebrates. For complete details on the use and execution of this protocol, please refer to Kushawah et al. (2020).

Dissection of FixK2 protein-DNA interaction unveils new insights into Bradyrhizobium diazoefficiens lifestyles control.

The FixK2 protein plays a pivotal role in a complex regulatory network, which controls genes for microoxic, denitrifying, and symbiotic nitrogen-fixing lifestyles in Bradyrhizobium diazoefficiens. Among the microoxic-responsive FixK2 -activated genes are the fixNOQP operon, indispensable for respiration in symbiosis, and the nnrR regulatory gene needed for the nitric-oxide dependent induction of the norCBQD genes encoding the denitrifying nitric oxide reductase. FixK2 is a CRP/FNR-type transcription factor, which recognizes a 14 bp-palindrome (FixK2 box) at the regulated promoters through three residues (L195, E196, and R200) within a C-terminal helix-turn-helix motif. Here, we mapped the determinants for discriminatory FixK2 -mediated regulation. While R200 was essential for DNA binding and activity of FixK2 , L195 was involved in protein-DNA complex stability. Mutation at positions 1, 3, or 11 in the genuine FixK2 box at the fixNOQP promoter impaired transcription activation by FixK2 , which was residual when a second mutation affecting the box palindromy was introduced. The substitution of nucleotide 11 within the NnrR box at the norCBQD promoter allowed FixK2 -mediated activation in response to microoxia. Thus, position 11 within the FixK2 /NnrR boxes constitutes a key element that changes FixK2 targets specificity, and consequently, it might modulate B. diazoefficiens lifestyle as nitrogen fixer or as denitrifier.

The state of science on severe air pollution episodes: Quantitative and qualitative analysis.

Severe episodic air pollution blankets entire cities and regions and have a profound impact on humans and their activities. We compiled daily fine particle (PM2.5) data from 100 cities in five continents, investigated the trends of number, frequency, and duration of pollution episodes, and compared these with the baseline trend in air pollution. We showed that the factors contributing to these events are complex; however, long-term measures to abate emissions from all anthropogenic sources at all times is also the most efficient way to reduce the occurrence of severe air pollution events. In the short term, accurate forecasting systems of such events based on the meteorological conditions favouring their occurrence, together with effective emergency mitigation of anthropogenic sources, may lessen their magnitude and/or duration. However, there is no clear way of preventing events caused by natural sources affected by climate change, such as wildfires and desert dust outbreaks.

Air pollution and COVID-19 lockdown in a large South American city: Santiago Metropolitan Area, Chile.

The implementation of confinement and physical distancing measures to restrict people's activities and transit in the midst of the COVID-19 pandemic allowed us to study how these measures affect the air quality in urban areas with high pollution rates, such as Santiago, Chile. A comparative study between the concentrations of PM10, PM2.5, NOx, CO, and O3 during the months of March to May 2020 and the corresponding concentrations during the same period in 2017-2019 is presented. A combination of surface measurements from the air quality monitoring network of the city, remote satellite measurements, and simulations of traffic activity and road transport emissions allowed us to quantify the change in the average concentrations of each pollutant. Average relative changes of traffic emissions (between 61% and 68%) implied statistically significant concentrations reductions of 54%, 13%, and 11% for NOx, CO, and PM2.5, respectively, during the pandemic period compared to historical period. In contrast, the average concentration of O3 increased by 63% during 2020 compared to 2017-2019. The nonlinear response observed in the pollution levels can be attributed to the changes in the vehicular emission patterns during the pandemic and to the role of other sources such as residential emissions or secondary PM.

Expectancy-Value Model Related to Physical Activity Behaviors in Chilean and Spanish Adolescents.

The purpose of the study is to comparatively test the expectancy-value model in Chilean and Spanish samples. The model proposes: a social world (composed of social support, physical activity teasing, and weight teasing), expectancy (composed of perceived competence and appearance), task values (composed of enjoyment and stress) to predict physical activity and intention to be physically active. Participants were 497 (Chilean) and 1365 (Spanish) adolescents. Structural equation models and multi-group modelling were used. All the models presented adequate fit to the data. The results show that physical activity teasing is a contextual and essential variable; perceived competence and enjoyment influenced physical activity and intentions to be physically active; some differences appeared in the prediction of physical activity and intentions to be physically active when the multi-group model was run. Culturally tailored interventions are key to improving physical activity (PA) behaviors.

CRISPR-Cas13d Induces Efficient mRNA Knockdown in Animal Embryos.

Early embryonic development is driven exclusively by maternal gene products deposited into the oocyte. Although critical in establishing early developmental programs, maternal gene functions have remained elusive due to a paucity of techniques for their systematic disruption and assessment. CRISPR-Cas13 systems have recently been employed to degrade RNA in yeast, plants, and mammalian cell lines. However, no systematic study of the potential of Cas13 has been carried out in an animal system. Here, we show that CRISPR-RfxCas13d (CasRx) is an effective and precise system to deplete specific mRNA transcripts in zebrafish embryos. We demonstrate that zygotically expressed and maternally provided transcripts are efficiently targeted, resulting in a 76% average decrease in transcript levels and recapitulation of well-known embryonic phenotypes. Moreover, we show that this system can be used in medaka, killifish, and mouse embryos. Altogether, our results demonstrate that CRISPR-RfxCas13d is an efficient knockdown platform to interrogate gene function in animal embryos.

Multidecadal environmental pollution in a mega-industrial area in central Chile registered by tree rings.

One of the most polluted areas in Chile is the Ventanas Industrial Area (VIA; 32.74°S / 71.48°W), which started in 1958 and today comprises around 16 industries in an area of ca. 4 km2. A lack of consistent long-term instrumental records precludes assessing the history of contamination in the area and also limits the evaluation of mitigation actions taken since the late 1980s. Here, we use dendrochemistry as an environmental proxy to analyze environmental changes over several decades at the VIA. We present chemical measurements of tree rings from planted, exotic Cupressus macrocarpa growing near the VIA with 4-year resolution over a period of 52 years (1960-2011). These data provide unprecedented information on regional anthropogenic pollution and are compared with a tree-ring elemental record of 48 years (1964-2011) from the Isla Negra (INE) control site not exposed to VIA emissions. For the 48 years of overlap between both sites, higher concentrations of Zn, V, Co, Cd, Ag, Fe, Cr, and Al were especially registered after the year 2000 at VIA compared to INE for the periods under study. Concentrations of Pb, Cu, As, Fe, Mo, Cr, and Zn increased through time, particularly over the period 1980-1990. Decontamination plans activated in 1992 appear to have had a positive effect on the amount of some elements, but the chemical concentration in the tree rings suggest continued accumulation of pollutants in the environment. Only after several years of implementation of the mitigation measures have some elements tended to decrease in concentration, especially at the end of the evaluated period. Dendrochemistry is a useful tool to provide a long-term perspective of the dynamics of trace metal pollution and represents a powerful approach to monitor air quality variability to extend the instrumental records back in time.

Factores asociados a la falta de adherencia al tratamiento en pacientes con diabetes mellitus tipo 2

RESUMEN Introducción: la diabetes mellitus es una enfermedad prevalente y con un alto costo para la salud pública. No obstante, la falta de cumplimiento terapéutico se relaciona con un aumento de la morbimortalidad. Objetivo: determinar los factores asociados a la falta de adherencia al tratamiento en pacientes con diabetes mellitus tipo 2 que acuden al Hospital Nacional de Itauguá en 2018. Material y métodos: estudio observacional, descriptivo, prospectivo, de corte longitudinal, con componente analítico, realizado en hombres y mujeres mayores de 18 años con diagnóstico de diabetes mellitus tipo 2 que acudieron en forma ambulatoria a los consultorios del programa de diabetes del Hospital Nacional de Itauguá en 2018. La adherencia al tratamiento fue determinada con dos escalas validadas que midieron la adherencia farmacológica (Morisky-Green) y no farmacológica (IMEVID). Resultados: se estudiaron 338 pacientes, siendo 66% de sexo femenino. La edad media fue 56±7 años. La frecuencia de falta de adherencia al tratamiento fue 70% y los factores que se asociaron significativamente fueron la presencia de complicaciones crónicas (53%), la monoterapia farmacológica (35%), la presencia de efectos adversos medicamentosos (17%), el tiempo de evolución mayor a diez años (16%) y la mala relación médico-paciente (16%). Conclusiones: existe una alta frecuencia de falta de adherencia al tratamiento en pacientes con diabetes mellitus (70%). La presencia de complicaciones crónicas y la monoterapia farmacológica fueron los factores más frecuentemente asociados. Esta información permitirá la toma de decisiones para ayudar a los pacientes a mejorar su cumplimiento terapéutico.

ABSTRACT Introduction: Diabetes mellitus is a prevalent disease with a high cost for public health. However, the lack of therapeutic compliance prevents that the morbidity and mortality associated with this pathology can be avoided. Objective: To determine the factors associated with the lack of adherence to treatment in patients with type 2 diabetes mellitus who attend the National Hospital of Itauguá in 2018. Material and methods: Observational, descriptive, prospective, longitudinal study, with analytical component, carried out in men and women older than 18 years with diagnosis of type 2 diabetes mellitus who attended the outpatient clinics of the National Hospital diabetes program in Itauguá in 2018. Adherence to treatment was determined with two validated scales that measured pharmacological (Morisky-Green) and non-pharmacological (IMEVID) adherence. Results: Three hundred and thirty eight patients were studied, 66% being female. The average age was 56 ± 7 years. The frequency of lack of adherence to treatment was 70% and the factors that were significantly associated were the presence of chronic complications (53%), pharmacological monotherapy (35%), presence of adverse drug effects (17%), time of evolution greater than ten years (16%) and poor doctor-patient relationship (16%). Conclusions: There is a high frequency of lack of adherence to treatment in patients with diabetes mellitus (70%). The presence of chronic complications and pharmacological monotherapy were the most frequently associated factors. This information will allow decision-making to help patients improve their therapeutic compliance.

The CbrB Regulon: Promoter dissection reveals novel insights into the CbrAB expression network in Pseudomonas putida.

CbrAB is a high ranked global regulatory system exclusive of the Pseudomonads that responds to carbon limiting conditions. It has become necessary to define the particular regulon of CbrB and discriminate it from the downstream cascades through other regulatory components. We have performed in vivo binding analysis of CbrB in P. putida and determined that it directly controls the expression of at least 61 genes; 20% involved in regulatory functions, including the previously identified CrcZ and CrcY small regulatory RNAs. The remaining are porines or transporters (20%), metabolic enzymes (16%), activities related to protein translation (5%) and orfs of uncharacterised function (38%). Amongst the later, we have selected the operon PP2810-13 to make an exhaustive analysis of the CbrB binding sequences, together with those of crcZ and crcY. We describe the implication of three independent non-palindromic subsites with a variable spacing in three different targets; CrcZ, CrcY and operon PP2810-13 in the CbrAB activation. CbrB is a quite peculiar σN-dependent activator since it is barely dependent on phosphorylation for transcriptional activation. With the depiction of the precise contacts of CbrB with the DNA, the analysis of the multimerisation status and its dependence on other factors such as RpoN o IHF, we propose a model of transcriptional activation.

Searching for a Cell-Based Therapeutic Tool for Haemophilia A within the Embryonic/Foetal Liver and the Aorta-Gonads-Mesonephros Region.

The development of new strategies based on cell therapy approaches to correct haemophilia A (HA) requires further insights into new cell populations capable of producing coagulation factor VIII (FVIII) and presenting stable engraftment potential. The major producers of FVIII in the adult are liver sinusoidal endothelial cells (LSECs) and in a lesser degree bone marrow-derived cells, both of which have been shown to ameliorate the bleeding phenotype in adult HA mice after transplantation. We have previously shown that cells from the foetal liver (FL) and the aorta-gonads-mesonephros (AGM) haematopoietic locations possess higher LSEC engraftment potential in newborn mice compared with adult-derived LSECs, constituting likely therapeutic targets for the treatment of HA in neonates. However, less is known about the production of FVIII in embryonic locations. Quantitative polymerase chain reaction and Western blot analysis were performed to assess the relative level of FVIII production in different embryonic tissues and at various developmental stages, identifying the FL and AGM region from day 12 (E12) as prominent sources of FVIII. Furthermore, FL-derived VE-cad+CD45-Lyve1+/- endothelial/endothelial progenitor cells, presenting vascular engraftment potential, produced high levels of F8 ribonucleic acid compared with CD45+ blood progenitors or Dlk1+ hepatoblasts. In addition, we show that the E11 AGM explant cultures expanded cells with LSEC repopulation activity, instrumental to further understand signals for in vitro generation of LSECs. Taking into account the capacity for FVIII expression, culture expansion and newborn engraftment potential, these results support the use of cells with foetal characteristics for correction of FVIII deficiency in young individuals.

What Leads to Loneliness? An Integrative Model of Social, Motivational, and Emotional Approaches in Adolescents.

Loneliness has been linked to many physical and mental health problems, especially during adolescence. From evolutionary, social needs, and cognitive approaches, this study examined whether emotional repair, relatedness need, and peer-rated indicators of relations behave in predicting loneliness, considering all approaches together. The sample consisted of 373 adolescents measured longitudinally at three time points. Results of a cross-lagged panel design found that, considering all the influences together, relatedness need showed the highest strength to predict loneliness. Furthermore, adolescents who were accepted by their peers and whose relatedness need was satisfied activated emotional regulation which additionally produced a decrease in prospective feelings of loneliness. In addition, loneliness has been shown to be a consequence of these variables.