Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis

Heart rate variability (HRV) is an objective, non-invasive tool to assessing autonomic dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). People with CFS/ME tend to have lower HRV; however, in the literature there are only a few previous studies (most of them inconclusive) on their association with illness-related complaints. To address this issue, we assessed the value of different diurnal HRV parameters as potential biomarker in CFS/ME and also investigated the relationship between these HRV indices and self-reported symptoms in individuals with CFS/ME.Peer ReviewedPostprint (published version

Site-specific immobilization of DNA on silicon surfaces by using the thiol-yne reaction

[EN] Covalent immobilization of ssDNA fragments onto silicon-based materials was performed using the thiol-yne reaction. Chemical functionalization provided alkyne groups on the surface where the thiol-modified oligonucleotide probes can be easily photoattached as microarrays, reaching an immobilization density around 30 pmol cm(-2). The developed method presents the advantages of spatially controlled probe anchoring (by using a photomask), direct attachment without using cross-linkers, and short irradiation times (20 min). Hybridization efficiencies up to 70%, with full complementary strands, were reached. The approach was evaluated by scoring single nucleotide polymorphisms with a discrimination ratio around 15. Moreover, the potential applicability of the proposed methodology is demonstrated through the specific detection of 20 nM of a genomic target of bacterial Escherichia coli.This research was supported by Ministerio de Ciencia e Innovacion (CTQ2013-45875-R) and Generalitat Valenciana (PROMETEO/2010/008).Escorihuela Fuentes, J.; Bañuls Polo, M.; Puchades, R.; Maquieira Catala, Á. (2014). Site-specific immobilization of DNA on silicon surfaces by using the thiol-yne reaction. Journal of Materials Chemistry B. 2(48):8510-8517. https://doi.org/10.1039/c4tb01108bS8510851724

Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis

Heart rate variability (HRV) is an objective, non-invasive tool to assessing autonomic dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). People with CFS/ME tend to have lower HRV; however, in the literature there are only a few previous studies (most of them inconclusive) on their association with illness-related complaints. To address this issue, we assessed the value of different diurnal HRV parameters as potential biomarker in CFS/ME and also investigated the relationship between these HRV indices and self-reported symptoms in individuals with CFS/ME. In this case-control study, 45 female patients who met the 1994 CDC/Fukuda definition for CFS/ME and 25 age- and gender-matched healthy controls underwent HRV recording-resting state tests. The intervals between consecutive heartbeats (RR) were continuously recorded over three 5-min periods. Time- and frequency-domain analyses were applied to estimate HRV variables. Demographic and clinical features, and self-reported symptom measures were also recorded. CFS/ME patients showed significantly higher scores in all symptom questionnaires (p < 0.001), decreased RR intervals (p < 0.01), and decreased HRV time- and frequency-domain parameters (p < 0.005), except for the LF/HF ratio than in the healthy controls. Overall, the correlation analysis reached significant associations between the questionnaires scores and HRV time- and frequency-domain measurements (p < 0.05). Furthermore, separate linear regression analyses showed significant relationships between self-reported fatigue symptoms and mean RR (p = 0.005), RMSSD (p = 0.0268) and HFnu indices (p = 0.0067) in CFS/ME patients, but not in healthy controls. Our findings suggest that ANS dysfunction presenting as increased sympathetic hyperactivity may contribute to fatigue severity in individuals with ME/CFS. Further studies comparing short- and long-term HRV recording and self-reported outcome measures with previous studies in larger CFS/ME cohorts are urgently warranted

Improved Performance of DNA Microarray Multiplex Hybridization Using Probes Anchored at Several Points by Thiol-Ene or Thiol-Yne Coupling Chemistry

[EN] Nucleic acid microarray-based assay technology has shown lacks in reproducibility, reliability, and analytical sensitivity. Here, a new strategy of probe attachment modes for silicon-based materials is built up. Thus, hybridization ability is enhanced by combining thiol-ene or thiol-yne click chemistry reactions with a multipoint attachment of polythiolated probes. The viability and performance of this approach was demonstrated by specifically determining Salmonella PCR products up to a 20 pM sensitivity level.The authors thank Dr. Elena Pinilla for her helpful discussion about AFM results. This work was funded by EU’s program Horizon 2020 ICT-26-2014-644242, Spanish Ministry MINECO CTQ/2013/45875-R FEDER, and local administration GVA PROMETEO II 2014/40. The authors acknowledge Luis Tortajada-Genaro and Regina Niñoles Rodenes for kindly providing the Salmonella and Campylobacter PCR products. F.M. is member of Inserm.Bañuls Polo, M.; Jimenez-Meneses, P.; Meyer, A.; Vasseur, J.; Morvan, F.; Escorihuela Fuentes, J.; Puchades, R.... (2017). Improved Performance of DNA Microarray Multiplex Hybridization Using Probes Anchored at Several Points by Thiol-Ene or Thiol-Yne Coupling Chemistry. Bioconjugate Chemistry. 28(2):496-506. https://doi.org/10.1021/acs.bioconjchem.6b00624S49650628

Epigenetic alterations in hippocampus of SAMP8 senescent mice and modulation by voluntary physical exercise

The senescence-accelerated SAMP8 mouse model displays features of cognitive decline and Alzheimer's disease. With the purpose of identifying potential epigenetic markers involved in aging and neurodegeneration, here we analyzed the expression of 84 mature miRNAs, the expression of histone-acetylation regulatory genes and the global histone acetylation in the hippocampus of 8-month-old SAMP8 mice, using SAMR1 mice as control. We also examined the modulation of these parameters by 8 weeks of voluntary exercise. Twenty-one miRNAs were differentially expressed between sedentary SAMP8 and SAMR1 mice and seven miRNAs were responsive to exercise in both strains. SAMP8 mice showed alterations in genes involved in protein acetylation homeostasis such as Sirt1 and Hdac6 and modulation of Hdac3 and Hdac5 gene exprssion by exercise. Global histone H3 acetylation levels were reduced in SAMP8 compared with SAMR1 mice and reached control levels in response to exercise. In sum, data presented here provide new candidate epigenetic markers for aging and neurodegeneration and suggest that exercise training may prevent or delay some epigenetic alterations associated with accelerated aging

Direct and label-free monitoring oligonucleotide immobilization, non-specific binding and DNA biorecognition

NOTICE: this is the author’s version of a work that was accepted for publication in Sensors and Actuators B: Chemical. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Sensors and Actuators B: Chemical, [VOL 192, (1 March 2014)] DOI 10.1016/j.snb.2013.10.110DNA binding chemistry on silicon surface has been investigated. Aminated oligonucleotide probes were immobilized on the chip surface by chemical silanization and further covalent attachment. The chemistries employed were the classical 3-aminopropyltriethoxysilane/glutaraldehyde and, for comparison purposes, the novel 3-isocyanatepropyltriethoxysilane, that allows the direct attachment of the aminated probe. Alternatively, a thiolated oligonucleotide was also photochemically immobilized by means of a thioether linkage. The experiments were followed label-free by Dual Polarization Interferometry. All chemical and photochemical methods gave rise to a probe density immobilization in the order of 1.0-2.5 x 10(10) molecules/mm(2), similar to the values reported for other chemistries. The obtained data suggest that DNA strands are anchored in a different conformation depending on the immobilization method employed. In order to avoid non-specific binding of target molecules, ethanolamine and inert proteins were assayed, and successful results were obtained when using small size proteins such as gelatine. Hybridization efficiency was around 20% for aminosilane-based immobilized probes, and more than 4-fold this value when the other immobilization methods were employed. The ability for recognition complementary DNA strands discriminating non-complementary ones was applied for species identification in mixtures. (C) 2013 Elsevier B.V. All rights reserved.Research projects MASCREEN CTQ2010-15943 from the Spanish Ministerio de Ciencia e Innovacion, and PROMETEO 2010/008 from the Generalitat Valenciana are gratefully acknowledged for financial support.López Paz, JL.; González Martínez, MÁ.; Escorihuela Fuentes, J.; Bañuls Polo, MJ.; Puchades Pla, R.; Maquieira Catala, Á. (2014). Direct and label-free monitoring oligonucleotide immobilization, non-specific binding and DNA biorecognition. Sensors and Actuators B: Chemical. 192:221-228. https://doi.org/10.1016/j.snb.2013.10.110S22122819

Long-term exercise modulates hippocampal gene expression in sencescent females mice

Altres ajuts: FI-DGR 2011 de la Generalitat de CatalunyaThe senescence-accelerated SAMP8 mouse is considered a useful non-transgenic model for studying aspects of progressive cognitive decline and Alzheimer's disease (AD). Using SAMR1 mice as controls, here we explored the effects of 6 months of voluntary wheel running in 10-month-old female SAMP8 mice. Exercise in SAMP8 mice improved phenotypic features associated with premature aging (i.e., skin color and body tremor) and enhanced vascularization and BDNF gene expression in the hippocampus compared with controls. With the aim of identifying genes involved in brain aging responsive to long-term exercise, we performed whole genome microarray studies in hippocampus from sedentary SAMP8 (P8sed), SAMR1 (R1sed), and exercised SAMP8 (P8run) mice. The genes differentially expressed in P8sed versus R1sed were considered as putative aging markers (i) and those differentially expressed in P8run versus P8sed were considered as genes modulated by exercise (ii). Genes differentially expressed in both comparisons (i and ii) were considered as putative aging genes responsive to physical exercise. We identified 34 genes which met both criteria. Gene ontology analysis revealed that they are mainly involved in functions related to extracellular matrix maintenance. Selected genes were validated by real-time quantitative PCR assays, i.e., collagen type 1 alpha 1 (col1a1), collagen type 1 alpha 2 (col1a2), fibromodulin (fmod), prostaglandin D(2) synthase (ptgds), and aldehyde dehydrogenase (Aldh1a2). As a whole, our study suggests that exercise training during adulthood may prevent or delay gene expression alterations and processes associated with hippocampal aging in at-risk subjects

Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis

Heart rate variability (HRV) is an objective, non-invasive tool to assessing autonomic dysfunction in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). People with CFS/ME tend to have lower HRV; however, in the literature there are only a few previous studies (most of them inconclusive) on their association with illness-related complaints. To address this issue, we assessed the value of different diurnal HRV parameters as potential biomarker in CFS/ME and also investigated the relationship between these HRV indices and self-reported symptoms in individuals with CFS/ME.Peer Reviewe

High-fat diet induced adiposity and insulin resistance in mice lacking the myotonic dystrophy protein kinase

AbstractMyotonic dystrophy 1 (MD1) is caused by a CTG expansion in the 3′-unstranslated region of the myotonic dystrophy protein kinase (DMPK) gene. MD1 patients frequently present insulin resistance and increased visceral adiposity. We examined whether DMPK deficiency is a genetic risk factor for high-fat diet-induced adiposity and insulin resistance using the DMPK knockout mouse model. We found that high-fat fed DMPK knockout mice had significantly increased body weights, hypertrophic adipocytes and whole-body insulin resistance compared with wild-type mice. This nutrient–genome interaction should be considered by physicians given the cardiometabolic risks and sedentary lifestyle associated with MD1 patients

Rcor2 underexpression in senescent mice: A target for inflammaging?

[Background] Aging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program.[Methods] To assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.[Results] P8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes.[Conclusions] Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging. © 2014 Alvarez-López et al.; licensee BioMed Central Ltd.Peer Reviewe