Functional characterization of two enhancers located downstream FOXP2

Background: Mutations in the coding region of FOXP2 are known to cause speech and language impairment. However, it is not clear how dysregulation of the gene contributes to language deficit. Interestingly, microdeletions of the region downstream the gene have been associated with cognitive deficits. Methods: Here, we investigate changes in FOXP2 expression in the SK-N-MC neuroblastoma human cell line after deletion by CRISPR-Cas9 of two enhancers located downstream of the gene. Results: Deletion of any of these two functional enhancers downregulates FOXP2, but also upregulates the closest 3′ gene MDFIC. Because this effect is not statistically significant in a HEK 293 cell line, derived from the human kidney, both enhancers might confer a tissue specific regulation to both genes. We have also found that the deletion of any of these enhancers downregulates six well-known FOXP2 target genes in the SK-N-MC cell line. Conclusions: We expect these findings contribute to a deeper understanding of how FOXP2 and MDFIC are regulated to pace neuronal development supporting cognition, speech and language.Spanish National Research and Development Plan PI14/01884Instituto de Salud Carlos III PI14/01884FEDER PI14/0188

Development of Microsatellite Markers in the Razor Clam Solen Marginatus (Bivalvia: Solenidae)

[Abstract] Four microsatellite loci in the razor clam Solen marginatus are described. Loci were isolated from the sequences of intersimple sequence repeat (ISSR) markers and an enriched library. Detailed analysis of these sequences led to the design of eight primer pairs. Allelic variation was assessed in 20 individuals from Redondela, Spain. The genetic variation observed in the markers presented here will be useful for future studies on the population structure of Solen marginatus in the wild and for aquaculture of this species.Xunta de Galicia; PGIDT03MA10301PR

Isolation and characterization of polymorphic microsatellite loci in the razor clam "Ensis siliqua"

[Abstract] Five polymorphic microsatellite loci in the razor clam Ensis siliqua are described. A collection consisting of 34 individuals from Finisterre, Spain, was analysed. Loci were isolated from the sequences of intersimple sequence repeat (ISSR) markers. Detailed analysis of 42 ISSR markers led to the design of 16 primer pairs. Five of these yielded consistent and polymorphic products. The number of alleles ranged from five to 23 per locus with the observed heterozygosity ranging from 0.46 to 0.94. Linkage equilibrium was observed in all loci and three of them showed significant deviations from Hardy–Weinberg equilibrium

The natural frequencies of the resting human brain: an MEG-based atlas

Brain oscillations are considered to play a pivotal role in neural communication. However, detailed information regarding the typical oscillatory patterns of individual brain regions is surprisingly scarce. In this study we applied a multivariate data-driven approach to create an atlas of the natural frequencies of the resting human brain on a voxel-by-voxel basis. We analysed resting-state magnetoencephalography (MEG) data from 128 healthy adult volunteers obtained from the Open MEG Archive (OMEGA). Spectral power was computed in source space in 500 ms steps for 82 frequency bins logarithmically spaced from 1.7 to 99.5 Hz. We then applied k-means clustering to detect characteristic spectral profiles and to eventually identify the natural frequency of each voxel. Our results provided empirical confirmation of the canonical frequency bands and revealed a region-specific organisation of intrinsic oscillatory activity, following both a medial-to-lateral and a posterior-to-anterior gradient of increasing frequency. In particular, medial fronto-temporal regions were characterised by slow rhythms (delta/theta). Posterior regions presented natural frequencies in the alpha band, although with differentiated generators in the precuneus and in sensory-specific cortices (i.e., visual and auditory). Somatomotor regions were distinguished by the mu rhythm, while the lateral prefrontal cortex was characterised by oscillations in the high beta range (>20 Hz). Importantly, the brain map of natural frequencies was highly replicable in two independent subsamples of individuals. To the best of our knowledge, this is the most comprehensive atlas of ongoing oscillatory activity performed to date. Critically, the identification of natural frequencies is a fundamental step towards a better understanding of the functional architecture of the human brainThis work was supported by FEDER/Ministerio de Ciencia, Innovación y Universidades – Agencia Estatal de Investigación, Spain (grant PGC2018-100682-B-I00 to AC and PC) and the Comunidad de Madrid POEJ/FSE (grant PEJD-2017-PRE/SOC-3859 to AC). MM was supported by the Universidad Autónoma de Madrid (FPI-UAM-2017 fellowship). JG was supported by Deutsche Forschungsgemeinschaft (GR 2024/5-1 and GR 2024/8-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Thermochemical characterization of eight seaweed species and evaluation of their potential use as an alternative for biofuel production and source of bioactive compounds

Algae are underexplored resources in Western countries and novel approaches are needed to boost their industrial exploitation. In this work, eight edible seaweeds were subjected to their valorization in terms of nutritional characterization, thermochemical properties, and bioactive profile. Our results suggest that seaweeds present a rich nutritional profile, in which carbohydrates are present in high proportions, followed by a moderate protein composition and a valuable content of !-3 polyunsaturated fatty acids. The thermochemical characterization of seaweeds showed that some macroalgae present a low ash content and high volatile matter and carbon fixation rates, being promising sources for alternative biofuel production. The bioactive profile of seaweeds was obtained from their phenolic and carotenoid content, together with the evaluation of their associated bioactivities. Among all the species analyzed, Porphyra purpurea presented a balanced composition in terms of carbohydrates and proteins and the best thermochemical profile. This species also showed moderate anti-inflammatory activity. Additionally, Himanthalia elongata extracts showed the highest contents of total phenolics and a moderate carotenoid content, which led to the highest rates of antioxidant activity. Overall, these results suggest that seaweeds can be used as food or functional ingredient to increase the nutritional quality of food formulations.The research leading to these results was supported by MICINN supporting the Ramón y Cajal grant for M.A. Prieto (RYC-2017-22891); by Xunta de Galicia for supporting the program EXCELENCIA-ED431F (1 December 2020), the post-doctoral grant of L. Cassani (ED481B- 2021/152), and the program Grupos de Referencia Competitiva (GRUPO AA1-GRC 2018) that supports the work of M. Barral-Martínez. The authors thank the program BENEFICIOS DO CONSUMO DAS ESPECIES TINTORERA-(CO-0019-2021) that supports the work of F. Chamorro. The research leading to these results was supported by the European Union through the “NextGenerationEU” program supporting the “Margarita Salas” grant awarded to P. Garcia-Perez. The authors are grateful to AlgaMar enterprise (www.algamar.com, accessed 30 December 2021) for the collaboration and algae material provision. The project SYSTEMIC Knowledge hub on Nutrition and Food Security has received funding from national research funding parties in Belgium (FWO), France (INRA), Germany (BLE), Italy (MIPAAF), Latvia (IZM), Norway (RCN), Portugal (FCT), and Spain (AEI) in a joint action of JPI HDHL, JPI-OCEANS and FACCE-JPI launched in 2019 under the ERA-NET ERA-HDHL (nº 696295).info:eu-repo/semantics/publishedVersio

Characterization of in vitro antioxidant, antitumor and anti-inflammatory properties of plant species from Rosaceae family

Since ancient times, humans have employed different plant species to prepare traditional remedies and treat diseases, due to the health-promoting effects associated with these plants. Among them, several species belonging to the Rosaceae family, namely Agrimonia eupatoria L., Filipendula ulmaria (L.) Maxim. and Rosa canina L., which have been used in different preparations, like infusions, decoctions or tinctures, to treat diverse illnesses and diseases [1]. Nowadays, the search for natural derived ingredients has prompted the study of these traditional plants. The present work aimed to evaluate the biological properties of the above-mentioned Rosaceae species, in order to promote their applications in different sectors. Antioxidant activity was evaluated by different in vitro assays: 2,2-diphenylpycrilhydrazyl (DPPH) radical scavenging assay, thiobarbituric acid reactive substances (TBARS) assay for inhibition of lipid peroxidation, OxHLIA assay for inhibition of oxidative hemolysis, and reducing power determination. Antitumor activity was tested against four tumor cell lines: MCF-7, CaCo, AGS and NCI-H460. Finally, anti-inflammatory activity was assessed by the inhibition of inflammation on lipopolysaccharide-induced RAW264.7 murine macrophages. Considering the results, all plant extracts showed antioxidant effects in the tested assays, especially F. ulmaria. All tested extracts also displayed relevant antitumor effects against the four tested tumor cell lines, mostly F. ulmaria, which exhibited the lowest growth inhibition 50 values (GI50) ranging from 34 to 86 μg/mL of extract, presenting a noteworthy cytotoxic effect. Finally, R. canina showed significant anti-inflammatory effects, with effective concentration 50 values (EC50) of 20 μg/mL of extract. Therefore, the studied plants may be considered as promising natural sources of bioactive compounds with multifunctional biological properties for the development of several biobased applications.The research leading to these results was supported by MICINN supporting the Ramón y Cajal grant for M.A. Prieto (RYC-2017-22891) and the Juan de la Cierva Formación grant for T. Oludemi (FJC2019-042549-I), by Xunta de Galicia for supporting the program EXCELENCIA-ED431F 2020/12, the pre-doctoral grant of P. Garcia-Oliveira (ED481A-2019/295) and the program Grupos de Referencia Competitiva (GRUPO AA1-GRC 2018) that supports the work of M. Barral-Martinez. Authors are grateful to Ibero-American Program on Science and Technology (CYTED—AQUA-CIBUS, P317RT0003), to the Bio Based Industries Joint Undertaking (JU) under grant agreement No 888003 UP4HEALTH Project (H2020-BBI-JTI-2019) that supports the work of P. Garcia-Perez. The JU receives support from the European Union‘s Horizon 2020 research and innovation program and the Bio Based Industries Consortium. The project SYSTEMIC Knowledge hub on Nutrition and Food Security, has received funding from national research funding parties in Belgium (FWO), France (INRA), Germany (BLE), Italy (MIPAAF), Latvia (IZM), Norway (RCN), Portugal (FCT), and Spain (AEI) in a joint action of JPI HDHL, JPI-OCEANS and FACCE-JPI launched in 2019 under the ERA-NET ERA-HDHL (n° 696295). Authors are also grateful to Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to the CIMO (UIDB/00690/2020).info:eu-repo/semantics/publishedVersio

Sleep time estimated by an actigraphy watch correlates with CSF tau in cognitively unimpaired elders: the modulatory role of APOE

There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer’s Disease core biomarkers (amyloid-β-42 and –40, phosphorylated-tau-181, and total-tau) in elderly individuals, considering possible confounders and effect modifiers, particularly the APOE ε4 allele. One hundred and twenty-seven cognitively unimpaired volunteers enrolled in the Valdecilla Study for Memory and Brain Aging participated in this study. Seventy percent of the participants were women with a mean age of 65.5 years. After adjustment for covariates, reduced sleep time significantly predicted higher t-tau and p-tau. This association was mainly due to the APOE ε4 carriers. Our findings suggest that total sleep time, estimated by an actigraphy watch, is an early biomarker of tau pathology and that APOE modulates this relationship. The main limitation of this study is the limited validation of the actigraphy technology used. Sleep monitoring with wearables may be a useful and inexpensive screening test to detect early neurodegenerative changes.This work was supported by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitario, PI08/0139, PI12/02288, PI16/01652, and PI20/01011), the JPND (DEMTEST PI11/03028), the CIBERNED, and the Siemens Healthineer

Plasma miR-486-5p Expression Is Upregulated in Atrial Fibrillation Patients with Broader Low-Voltage Areas

Atrial fibrillation (AF) is the most common arrhythmia worldwide, affecting 1% of the population over 60 years old. The incidence and prevalence of AF are increasing globally, representing a relevant health problem, suggesting that more advanced strategies for predicting risk stage are highly needed. miRNAs mediate several processes involved in AF. Our aim was to identify miRNAs with a prognostic value as biomarkers in patients referred for AF ablation and its association with LVA extent, based on low-voltage area (LVA) maps. In this study, we recruited 44 AF patients referred for catheter ablation. We measured the expression of 84 miRNAs in plasma from peripheral blood in 3 different groups based on LVA extent. Expression analysis showed that miR-486-5p was significantly increased in patients with broader LVA (4-fold, p = 0.0002; 5-fold, p = 0.0001). Receiver operating characteristic curve analysis showed that miR-486-5p expression could predict atrium LVA (AUC, 0.8958; p = 0.0015). Also, miR-486-5p plasma levels were associated with AF-type (AUC, 0.7137; p = 0.0453). In addition, miR-486-5p expression was positively correlated with LVA percentage, left atrial (LA) area, and LA volume (r = 0.322, p = 0.037; r = 0.372, p = 0.015; r = 0.319, p = 0.045, respectively). These findings suggest that miR-486-5p expression might have prognostic significance in LVA extent in patients with AFThis research was funded by Xunta de Galicia: Programa de Consolidación de Unidades de Investigación Competitivas do SUG (GRC 2019/02), the Centro Singular de Investigación de Galicia acreditación 2019–2022 (ED431G 2019/02), the European Union European Regional Development Fund (ERDF), and National Institute of Health Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (ISCIII) Madrid, Spain (PI18/00821, CIBERCV CB16/11/00226 and FAISCA Intramural Project 2019)S

Oculomotor dysfunction in idiopathic and LRRK2-parkinson's disease and at-risk individuals

Background: Video-oculography constitutes a highly-sensitive method of characterizing ocular movements, which could detect subtle premotor changes and contribute to the early diagnosis of Parkinson's disease (PD). Objective: To investigate potential oculomotor differences between idiopathic PD (iPD) and PD associated with the G2019S variant of LRRK2 (L2PD), as well as to evaluate oculomotor function in asymptomatic carriers of the G2019S variant of LRRK2. Methods: The study enrolled 129 subjects: 30 PD (16 iPD, 14 L2PD), 23 asymptomatic carriers, 13 non-carrier relatives of L2PD patients, and 63 unrelated HCs. The video-oculographic evaluation included fixation, prosaccade, antisaccade, and memory saccade tests. Results: We did not find significant differences between iPD and L2PD. Compared to controls, PD patients displayed widespread oculomotor deficits including larger microsaccades, hypometric vertical prosaccades, increased latencies in all tests, and lower percentages of successful antisaccades and memory saccades. Non-carrier relatives showed oculomotor changes with parkinsonian features, such as fixation instability and hypometric vertical saccades. Asymptomatic carriers shared multiple similarities with PD, including signs of unstable fixation and hypometric vertical prosaccades; however, they were able to reach percentages of successful antisaccade and memory saccades similar to controls, although at the expense of longer latencies. Classification accuracy of significant oculomotor parameters to differentiate asymptomatic carriers from HCs ranged from 0.68 to 0.74, with BCEA, a marker of global fixation instability, being the parameter with the greatest classification accuracy. Conclusions: iPD and LRRK2-G2019S PD patients do not seem to display a differential oculomotor profile. Several oculomotor changes in asymptomatic carriers of LRRK2 mutations could be considered premotor biomarkers

Influence of physiological variables and comorbidities on plasma Aβ40, Aβ42, and p-tau181 levels in cognitively unimpaired individuals

Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aβ40, Aβ42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aβ40 and Aβ42 levels but not on the Aβ42/Aβ40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aβ40 and Aβ42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.Funding: This research received no external funding. Acknowledgments: This study was made possible thanks to donations from Germán González, Unidos por un Reto, Trail Nocturno de Cicero, La Trasmerana, and Primer Memorial Ángel Negrete. We would like to thank the participants of the Valdecilla Cohort for their selfless help and collaboration with research on neurodegenerative diseases. We would like to particularly acknowledge the patients and the Biobank Valdecilla (PT20/00067) in the Spanish Biobank Network for their collaboration