Transcription Factor Activity Inference in Systemic Lupus Erythematosus

Background: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease with diverse clinical manifestations. Although most of the SLE-associated loci are located in regulatory regions, there is a lack of global information about transcription factor (TFs) activities, the mode of regulation of the TFs, or the cell or sample-specific regulatory circuits. The aim of this work is to decipher TFs implicated in SLE. Methods: In order to decipher regulatory mechanisms in SLE, we have inferred TF activities from transcriptomic data for almost all human TFs, defined clusters of SLE patients based on the estimated TF activities and analyzed the differential activity patterns among SLE and healthy samples in two different cohorts. The Transcription Factor activity matrix was used to stratify SLE patients and define sets of TFs with statistically significant differential activity among the disease and control samples. Results: TF activities were able to identify two main subgroups of patients characterized by distinct neutrophil-to-lymphocyte ratio (NLR), with consistent patterns in two independent datasets—one from pediatric patients and other from adults. Furthermore, after contrasting all subgroups of patients and controls, we obtained a significant and robust list of 14 TFs implicated in the dysregulation of SLE by different mechanisms and pathways. Among them, well-known regulators of SLE, such as STAT or IRF, were found, but others suggest new pathways that might have important roles in SLE. Conclusions: These results provide a foundation to comprehend the regulatory mechanism underlying SLE and the established regulatory factors behind SLE heterogeneity that could be potential therapeutic targets.Innovative Medicines Initiative 2 Joint Undertaking (JU) - 831434 (3TR)European Union’s Horizon 2020 research and innovation program and EFPIANIH AR69572 and NIH RO-1 grant AR06957

Hepcidin Response to Exercise: A Review.

Given the multiple functions of iron in the body, any state of iron deficiency will induce a series of secondary effects that could compromise sports performance. Low serum iron levels are commonly observed in athletes during the course of a training period, especially in those performing aerobic exercises and resistance training. Sometimes, body iron levels will even fall below those detected in sedentary individuals, and we could go as far as to say that iron deficiency is the most frequently observed nutrition disorder among athletes of any sport. Hepcidin, a hormone secreted by hepatocytes whose principal mechanism of action is the degradation of ferroportin (the main iron exporter from macrophages and the basolateral membrane of duodenal enterocytes), has been proposed as the main regulator of the body’s iron reserves. Thus, elevated serum hepcidin levels lead to diminished iron absorption and recycling, while lower levels of the hormone will cause greater iron absorption. Among the factors that affect the hepcidin response produced, we should highlight an individual’s total iron levels, erythropoietic demands, state of hypoxia, dietary iron, inflammation and physical exercise. Given the important role played by iron regulatory mechanisms in physical performance, this report reviews our current understanding of the physiological response of hepcidin to different sports intensities and modalities.post-print98 K

Effects of Nutritional Supplements on Judo‐Related Performance: A Review.

The potential ergogenic effect of nutritional supplements depends on their dosage and the type of exercise executed. Aiming at reviewing the research literature regarding sport supplements utilized in judo in order to improve performance, a literature search was performed at the following databases: Dialnet, PubMed, Scielo, Scopus and SportDiscus. A total of 11 articles met the inclusion criteria and were selected. Evidence revised indicates that supplementation with caffeine, β-alanine, sodium bicarbonate, creatine, and β-hydroxy-β-methylbutyrate has a positive effect on judo-related performance. Moreover, there is evidence suggesting that combining some of these nutritional supplements may produce an additive effect.post-print412 K

Analysis of Sport Supplement Consumption and Body Composition in Spanish Elite Rowers.

The aim of this study was to analyze the anthropometric characteristics and sport supplement (SS) consumption patterns of heavyweight and lightweight international rowers. Methods: The 13 heavyweights (11 males) and seven lightweights (five males) of the Spanish National Rowing Team were recruited for the study. Body composition was measured by bio-impedance analysis, and the questionnaire used in this investigation was previously validated to assess SS consumption. According to anthropometrics parameters, it was reported that male heavyweight rowers were heavier (p < 0.001) and taller (p < 0.001), but no statistical di erences were reported for % body fat (p = 0.104) or % lean body mass (p = 0.161). All rowers reported consumption of at least one SS. Based on the Australian Institute of Sport’s classification, higher medical supplement consumption was observed when comparing heavyweight rowers to lightweight rowers (2.5 1.1 vs. 1.7 0.5, p = 0.040). There were no di erences in the totals of group A (strong scientific evidence for sports scenarios, p = 0.069), group B (emerging scientific support, deserving of further research, p = 0.776), or group C (scientific evidence not supportive of benefit and/or security amongst athletes, p = 0.484). The six most consumed SSs were iron (85%), ca eine (85%), -alanine (85%), energy bars (85%), vitamin supplements (80%), and isotonic drinks (80%), with no statistical di erences between heavyweight and lightweight rowers (p > 0.05). These results suggest that the absence of di erences in body composition (expressed as a percentage) do not represent anthropometric disadvantages for heavyweight rowers. In addition, SS consumption was similar between rowers, reporting only higher medical supplement consumption in heavyweight rowers.post-print931 K

Analysis of the consumption of sports supplements in elite fencers according to sex and competitive level

Background: The aim of this study was to analyze the consumption of sports supplements (SS) in competitive level fencers and compare differences based on sex and competitive level (international and national). Methods: A total of 49 fencers (18 men and 31 women) of national (n = 16) and international (n = 33) level completed a questionnaire with questions about SS consumption and the possible repercussions on health and / or sports performance. The results were analyzed based on the different categorizations established by the Australian Institute of Sport (AIS), as well as by sex and level of competence to which the participants belonged to. Results: 46.9% of fencers have consumed SS with the main motivation being performance improvement (34.2%). Medical doctors were the individuals who were more likely to advise men to consume SS (50.0% vs 5.6%; OR = 3.29 [1.50–7.20]). Friends were most likely to advise women (38.9% vs 8.3%; OR = 1.75 [1.05–2.93]). The most consumed SS were sport drinks (44.9%), vitamin C (43.4%), sport bars (38.8%), and caffeine (28.6%). In regards to the SS categories, it was observed differences in the interaction level·sex in medical supplements (p = 0.017). In addition, there was a higher prevalence of whey protein consumption in women (25.8% vs 0%; p = 0.020) and iron consumption in men (33% vs 6.5%; p = 0.039). Conclusions: The prevalence of SS use in fencers is within the values previously reported in athletes of the same competitive level. There were no differences by sex and competitive level in the total consumption of SS, nor in each of the groups of level of evidence, being sport drinks, bars and caffeine the most consumed SS

Electroantennographic Responses of Cerambyx welensii Küster to Host-Related Volatiles

Wood-boring insects, such as Cerambyx welensii Küster, are involved in oak decline in Mediterranean areas. To advance our understanding of the olfactory perception of C. welensii, we recorded electroantennographic (EAG) responses from male and female antennae to 32 tree volatile organic compounds typical of emissions from its main Quercus L. hosts, and also analysed the dose-dependent response. Cerambyx welensii antennae responded to 24 chemicals. Eight odorants elicited the highest EAG responses (normalized values of over 98%): 1,8-cineole, limonene-type blend, β-pinene, pinene-type blend, sabinene, α-pinene, turpentine and (E)-2-hexenal. Cerambyx welensii exhibits a broad sensitivity to common tree volatiles. The high EAG responses to both limoneneand pinene-type blends suggest the detection of specific blends of the main foliar monoterpenes emitted by Q. suber L. and Q. ilex L. (limonene, α- and β-pinene, sabinene and myrcene), which could influence the intraspecific host choice by C. welensii, and in particular, females may be able to detect oak trees with a limonene-type chemotype. In addition, C. welensii showed high antennal activity to some odorants that characterize emissions from non-host tree species (1,8-cineole, β-pinene, α-pinene, turpentine, δ 3 -carene and camphene). The results obtained may be applicable to optimize monitoring and mass-trapping programmes in an integrated pest management context: This research was funded primarily by the Andalusian Regional Council of Environment and Spatial Planning and conducted through a collaborative agreement between the University of Huelva and University of Córdoba (Ref.15-2003-UHU) We thank Peter Gordon and Julia G. Fenn for commenting on an earlier version of the manuscrip

Effects of an acute exercise bout on serum hepcidin levels

Iron deficiency is a frequent and multifactorial disorder in the career of athletes, particularly in females. Exercise-induced disturbances in iron homeostasis produce deleterious effects on performance and adaptation to training; thus, the identification of strategies that restore or maintain iron homeostasis in athletes is required. Hepcidin is a liver-derived hormone that degrades the ferroportin transport channel, thus reducing the ability of macrophages to recycle damaged iron, and decreasing iron availability. Although it has been suggested that the circulating fraction of hepcidin increases during early post-exercise recovery (~3 h), it remains unknown how an acute exercise bout may modify the circulating expression of hepcidin. Therefore, the current review aims to determine the post-exercise expression of serum hepcidin in response to a single session of exercise. The review was carried out in the Dialnet, Elsevier, Medline, Pubmed, Scielo and SPORTDiscus databases, using hepcidin (and “exercise” or “sport” or “physical activity”) as a strategy of search. A total of 19 articles were included in the review after the application of the inclusion/exclusion criteria. This search found that a single session of endurance exercise (intervallic or continuous) at moderate or vigorous intensity (60–90% VO2peak) stimulates an increase in the circulating levels of hepcidin between 0 h and 6 h after the end of the exercise bout, peaking at ~3 h post-exercise. The magnitude of the response of hepcidin to exercise seems to be dependent on the pre-exercise status of iron (ferritin) and inflammation (IL-6). Moreover, oxygen disturbances and the activation of a hypoxia-induced factor during or after exercise may stimulate a reduction of hepcidin expression. Meanwhile, cranberry flavonoids supplementation promotes an anti-oxidant effect that may facilitate the post-exercise expression of hepcidin. Further studies are required to explore the effect of resistance exercise on hepcidin expression

Evaluation of Physical Fitness, Body Composition, and Adherence to Mediterranean Diet in Adolescents from Estonia: The AdolesHealth Study

Unhealthy lifestyles, low levels of physical fitness, and adherence to the Mediterranean diet (MD) are associated with bad quality of life and the development of a wide range of non-communicable diseases (NCDs). The current study aimed to evaluate the level of adherence to the MD in physical fitness performance and body composition parameters in children and adolescents of Estonia. Therefore, 413 adolescents (56% boys) from the city of Tartu completed the Mediterranean Diet Questionnaire (KIDMED) for analyzing the adherence to MD and performed the Alpha Fitness Test for measuring physical fitness and body composition. A 41.67% of low, 44.05% of average, and 14.28% of high adherence to MD was detected, without difference between genders (p = 0.747). In the Alpha Fitness battery, a higher performance was observed in all tests for boys vs. girls (p < 0.05). In relation to body composition, higher height, weight, and waist values were observed in boys (p < 0.05) and a lower body fat percentage (p < 0.01) without differences in body mass index (BMI; p = 0.906). The adherence to the MD is classified as average/low. Gender significantly influences all variables of the Alpha Fitness battery and anthropometrics measures excepting BMI. According the levels of adherence to the MD, no statistically different prevalence was observed for Non-Overweight (N-Oweight), Non-Overfat (N-Ofat), or Non-Overwaist (N-Owaist). Still, a risk factor for Overweight (Oweight) in boys with low adherence was observed in comparison to those with a mid-level of adherence to the MD

Association between Adherence to the Mediterranean Diet and Physical Fitness with Body Composition Parameters in 1717 European Adolescents: The AdolesHealth Study

Obesity, low levels of physical fitness, and unhealthy eating patterns are responsible for part of the health problems of adolescents today. The current study aimed at examining the association between the adherence to the Mediterranean diet (MD), through each answer to the items of the Adherence to the MD Questionnaire (KIDMED), and physical fitness with body composition parameters (body mass index (BMI), percentage of body fat, and waist circumference) in 1717 Europeanadolescents(N=900boys,N=817girls). Dataofbodycomposition,physicalfitnessresults, and the answers to KIDMED were analyzed by the Student’s t-test. Additionally, the effect size (ES) was calculated and a Chi-square test analyzed the proportion of participants with and without over waistcircumference,overfat,andoverweightineachKIDMEDquestion. Therelativeriskofsuffering over waist circumference, overfat and overweight in relation to the responses was calculated by Odd-Ratio. AdherencetotheMDdidnotinfluencetheconditionofoverwaistcircumference,overfat and overweight, although certain dietary habits were identified as risk factors for their development. Over waist circumference, overfat, and overweight boys and girls presented higher levels of body mass, waist circumference, body fat percentage, and BMI (p < 0.001; ES = 1.73–3.38), as well as lower levels of all the parameters of the physical fitness analyzed (p < 0.001; ES = 0.45–1.08), except the handgrip test. A direct relationship between fitness and over waist circumference, overfat, and overweight was found

Extracellular Protease ADAMTS1 Is Required at Early Stages of Human Uveal Melanoma Development by Inducing Stemness and Endothelial-Like Features on Tumor Cells

We would like to thank members of JCRM’s laboratory and GENYO’s support units for helping with animal handling, technical assistance, and further discussion. The results published here are in part based upon data generated by the TCGA Research Network (www.cancer.gov/tcga). This manuscript will be part of CPT PhD Thesis belonging to the Doctorate Program on Biomedicine, UGR, Spain.Extracellular matrix remodeling within the tumor microenvironment has been recognized as a relevant dynamic framework during tumor growth. However, research on proteases that trigger this remodeling keeps revealing a wide range of actions including both pro- and anti-tumorigenic. The extracellular protease ADAMTS1 exemplifies this dual role. In this work, we first confirmed a positive correlation of ADAMTS1 with endothelial-like phenotype of human melanoma cells together with the finding of associated signatures, including key genes such as endothelial CDH5. Using a CRISPR-Cas9 approach, we observed that the inhibition of ADAMTS1 in an aggressive uveal melanoma model compromised its endothelial-like properties, and more importantly, caused a robust blockade on the progression of tumor xenografts. Although vasculature emerged affected in ADAMTS1-deficient tumors, the most relevant action implied the downregulation of endothelial CDH5 in tumor cells, in association with stemness markers. Indeed, melanoma sphere assays also revealed a deficient commitment to form spheres in the absence of ADAMTS1, directly correlating with stemness markers and, remarkably, also with CDH5. Finally, taking advantage of advanced bioinformatics tools and available public data of uveal melanomas, we disclosed new prognosis factors, including endothelial elements and ADAMTS proteases. Our findings support the key role of ADAMTS proteases for uveal melanoma development since earlier stages, modulating the complex crosstalk between extracellular matrix and the induction of stemness and endothelial-like features. To our knowledge, this is the first report that supports the development of therapeutic targets on the extracellular matrix to overcome uveal melanoma.This research was supported by Ministerio de Economía y Competitividad and Instituto de Salud Carlos III from Spain, co-financed by FEDER (PI16/00345 to JCRM) and from Consejería de Salud de la Junta de Andalucía (OH-0028-2018, PE-0225-2018)