| 1. |
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| 2. |
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| 3. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Aye, Cho-Cho, et al.
(författare)
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CBL/CAP Is Essential for Mitochondria Respiration Complex I Assembly and Bioenergetics Efficiency in Muscle Cells
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:4
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Tidskriftsartikel (refereegranskat)abstract
- CBL is rapidly phosphorylated upon insulin receptor activation. Mice whole body CBL depletion improved insulin sensitivity and glucose clearance; however, the precise mechanisms remain unknown. We depleted either CBL or its associated protein SORBS1/CAP independently in myocytes and assessed mitochondrial function and metabolism compared to control cells. CBL- and CAP-depleted cells showed increased mitochondrial mass with greater proton leak. Mitochondrial respiratory complex I activity and assembly into respirasomes were reduced. Proteome profiling revealed alterations in proteins involved in glycolysis and fatty acid degradation. Our findings demonstrate CBL/CAP pathway couples insulin signaling to efficient mitochondrial respiratory function and metabolism in muscle.
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| 6. |
- Malbet, F., et al.
(författare)
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Faint objects in motion: the new frontier of high precision astrometry
- 2021
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 51:3, s. 845-886
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Tidskriftsartikel (refereegranskat)abstract
- Sky survey telescopes and powerful targeted telescopes play complementary roles in astronomy. In order to investigate the nature and characteristics of the motions of very faint objects, a flexibly-pointed instrument capable of high astrometric accuracy is an ideal complement to current astrometric surveys and a unique tool for precision astrophysics. Such a space-based mission will push the frontier of precision astrometry from evidence of Earth-mass habitable worlds around the nearest stars, to distant Milky Way objects, and out to the Local Group of galaxies. As we enter the era of the James Webb Space Telescope and the new ground-based, adaptive-optics-enabled giant telescopes, by obtaining these high precision measurements on key objects that Gaia could not reach, a mission that focuses on high precision astrometry science can consolidate our theoretical understanding of the local Universe, enable extrapolation of physical processes to remote redshifts, and derive a much more consistent picture of cosmological evolution and the likely fate of our cosmos. Already several missions have been proposed to address the science case of faint objects in motion using high precision astrometry missions: NEAT proposed for the ESA M3 opportunity, micro-NEAT for the S1 opportunity, and Theia for the M4 and M5 opportunities. Additional new mission configurations adapted with technological innovations could be envisioned to pursue accurate measurements of these extremely small motions. The goal of this White Paper is to address the fundamental science questions that are at stake when we focus on the motions of faint sky objects and to briefly review instrumentation and mission profiles.
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| 7. |
- Rodriguez-Cuenca, Sergio, et al.
(författare)
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Allostatic hypermetabolic response in PGC1α/β heterozygote mouse despite mitochondrial defects
- 2021
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Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:9
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Tidskriftsartikel (refereegranskat)abstract
- Aging, obesity, and insulin resistance are associated with low levels of PGC1α and PGC1β coactivators and defective mitochondrial function. We studied mice deficient for PGC1α and PGC1β [double heterozygous (DH)] to investigate their combined pathogenic contribution. Contrary to our hypothesis, DH mice were leaner, had increased energy dissipation, a pro-thermogenic profile in BAT and WAT, and improved carbohydrate metabolism compared to wild types. WAT showed upregulation of mitochondriogenesis/oxphos machinery upon allelic compensation of PGC1α4 from the remaining allele. However, DH mice had decreased mitochondrial OXPHOS and biogenesis transcriptomes in mitochondria-rich organs. Despite being metabolically healthy, mitochondrial defects in DH mice impaired muscle fiber remodeling and caused qualitative changes in the hepatic lipidome. Our data evidence first the existence of organ-specific compensatory allostatic mechanisms are robust enough to drive an unexpected phenotype. Second, optimization of adipose tissue bioenergetics is sufficient to maintain a healthy metabolic phenotype despite a broad severe mitochondrial dysfunction in other relevant metabolic organs. Third, the decrease in PGC1s in adipose tissue of obese and diabetic patients is in contrast with the robustness of the compensatory upregulation in the adipose of the DH mice.
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| 8. |
- van Leeuwen, F., et al.
(författare)
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Gaia Data Release 1 : Open cluster astrometry: Performance, limitations, and future prospects
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601
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Tidskriftsartikel (refereegranskat)abstract
- Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs.
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| 9. |
- Vialas, Vital, et al.
(författare)
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A multicentric study to evaluate the use of relative retention times in targeted proteomics
- 2017
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Ingår i: Journal of Proteomics. - : Elsevier BV. - 1874-3919. ; 152, s. 138-149
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Tidskriftsartikel (refereegranskat)abstract
- Despite the maturity reached by targeted proteomic strategies, reliable and standardized protocols are urgently needed to enhance reproducibility among different laboratories and analytical platforms, facilitating a more widespread use in biomedical research. To achieve this goal, the use of dimensionless relative retention times (iRT), defined on the basis of peptide standard retention times (RT), has lately emerged as a powerful tool. The robustness, reproducibility and utility of this strategy were examined for the first time in a multicentric setting, involving 28 laboratories that included 24 of the Spanish network of proteomics laboratories (ProteoRed-ISCIII). According to the results obtained in this study, dimensionless retention time values (iRTs) demonstrated to be a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups both intra- and inter-laboratories. iRT values also showed very low variability over long time periods. Furthermore, parallel quantitative analyses showed a high reproducibility despite the variety of experimental strategies used, either MRM (multiple reaction monitoring) or pseudoMRM, and the diversity of analytical platforms employed. Biological significance From the very beginning of proteomics as an analytical science there has been a growing interest in developing standardized methods and experimental procedures in order to ensure the highest quality and reproducibility of the results. In this regard, the recent (2012) introduction of the dimensionless retention time concept has been a significant advance. In our multicentric (28 laboratories) study we explore the usefulness of this concept in the context of a targeted proteomics experiment, demonstrating that dimensionless retention time values is a useful tool for transferring and sharing peptide retention times across different chromatographic set-ups.
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| 10. |
- Alerstam, Erik, et al.
(författare)
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Single-fiber diffuse optical time-of-flight spectroscopy
- 2012
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Ingår i: Optics Letters. - 0146-9592. ; 37:14, s. 2877-2879
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate interstitial diffuse optical time-of-fight spectroscopy based on a single fiber for both light delivery and detection. Detector saturation due to the massive short-time reflection is avoided by ultrafast gating of a single photon avalanche diode. We show that the effects of scattering and absorption are separable and that absorption can be assessed independently of scattering. Measurements on calibrated liquid phantoms and subsequent Monte Carlo-based evaluation illustrate that absorption coefficients can be accurately assessed over a wide range of medically relevant optical properties. Our findings pave the way to simplified and less invasive interstitial in vivo spectroscopy. (C) 2012 Optical Society of America
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| 11. |
- Benatar, Michael, et al.
(författare)
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Safety and efficacy of arimoclomol in patients with early amyotrophic lateral sclerosis (ORARIALS-01) : a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial
- 2024
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Ingår i: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 23:7, s. 687-699
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Tidskriftsartikel (refereegranskat)abstract
- Background: Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder leading to muscle weakness and respiratory failure. Arimoclomol, a heat-shock protein-70 (HSP70) co-inducer, is neuroprotective in animal models of amyotrophic lateral sclerosis, with multiple mechanisms of action, including clearance of protein aggregates, a pathological hallmark of sporadic and familial amyotrophic lateral sclerosis. We aimed to evaluate the safety and efficacy of arimoclomol in patients with amyotrophic lateral sclerosis.Methods: ORARIALS-01 was a multinational, randomised, double-blind, placebo-controlled, parallel-group trial done at 29 centres in 12 countries in Europe and North America. Patients were eligible if they were aged 18 years or older and met El Escorial criteria for clinically possible, probable, probable laboratory-supported, definite, or familial amyotrophic lateral sclerosis; had an ALS Functional Rating Scale-Revised score of 35 or more; and had slow vital capacity at 70% or more of the value predicted on the basis of the participant's age, height, and sex. Patients were randomly assigned (2:1) in blocks of 6, stratified by use of a stable dose of riluzole or no riluzole use, to receive oral arimoclomol citrate 1200 mg/day (400 mg three times per day) or placebo. The Randomisation sequence was computer generated centrally. Investigators, study personnel, and study participants were masked to treatment allocation. The primary outcome was the Combined Assessment of Function and Survival (CAFS) rank score over 76 weeks of treatment. The primary outcome and safety were analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03491462, and is completed.Findings: Between July 31, 2018, and July 17, 2019, 287 patients were screened, 245 of whom were enrolled in the trial and randomly assigned. The modified intention-to-treat population comprised 239 patients (160 in the arimoclomol group and 79 in the placebo group): 151 (63%) were male and 88 (37%) were female; mean age was 57·6 years (SD 10·9). CAFS score over 76 weeks did not differ between groups (mean 0·51 [SD 0·29] in the arimoclomol group vs 0·49 [0·28] in the placebo group; p=0·62). Cliff's delta comparing the two groups was 0·039 (95% CI –0·116 to 0·194). Proportions of participants who died were similar between the treatment groups: 29 (18%) of 160 patients in the arimoclomol group and 18 (23%) of 79 patients in the placebo group. Most deaths were due to disease progression. The most common adverse events were gastrointestinal. Adverse events were more often deemed treatment-related in the arimoclomol group (104 [65%]) than in the placebo group (41 [52%]) and more often led to treatment discontinuation in the arimoclomol group (26 [16%]) than in the placebo group (four [5%]).Interpretation: Arimoclomol did not improve efficacy outcomes compared with placebo. Although available biomarker data are insufficient to preclude future strategies that target the HSP response, safety data suggest that a higher dose of arimoclomol would not have been tolerated.Funding: Orphazyme.
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| 12. |
- Bousquet, Jean, et al.
(författare)
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Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018) : Change management in allergic rhinitis and asthma multimorbidity using mobile technology
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 143:3, s. 864-879
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Tidskriftsartikel (refereegranskat)abstract
- Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
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| 13. |
- Braga, Antonio, et al.
(författare)
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Panchromatic sensitized solar cells based on metal sulfide quantum dots grown directly on nanostructured TiO2 electrodes
- 2011
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Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 2:5, s. 454-460
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Tidskriftsartikel (refereegranskat)abstract
- The use of narrow band gap semiconductors such as PbS may expand the light absorption range to the near-infrared region in quantum-dot-sensitized solar cells (QDSCs), increasing the generated photocurrent. However, the application of PbS as a sensitizer in QDSCs causes some problems of stability and high recombination. Here, we show that the direct growth of a CdS coating layer on previously deposited PbS by the simple method of successive ionic layer adsorption and reaction (SILAR) minimizes these problems. A remarkable short-circuit current density for PbS/CdS QDSCs is demonstrated, ∼11 mA/cm2, compared to that of PbS QDSCs, with photocurrents lower than 4 mA/cm2, using polysulfide electrolyte in both cells. The cell efficiency reached a promising 2.21% under 1 sun of simulated irradiation (AM1.5G, 100 mW/cm2). Enhancement of the solar cell performance beyond the arithmetic addition of the efficiencies of the single constituents (PbS and CdS) is demonstrated for the nanocomposite PbS/CdS configuration. PbS dramatically increases the obtained photocurrents, and the CdS coating stabilizes the solar cell behavior. © 2011 American Chemical Society.
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| 14. |
- Canosa, Antonio, et al.
(författare)
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A novel p.Ser108LeufsTer15 SOD1 mutation leading to the formation of a premature stop codon in an apparently sporadic ALS patient : insights into the underlying pathomechanisms
- 2018
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 72
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Tidskriftsartikel (refereegranskat)abstract
- We report an apparently sporadic amyotrophic lateral sclerosis patient carrying a heterozygous novel frameshift SOD1 mutation (p.Ser108LeufsTer15), predicted to cause a premature protein truncation. RTPCR analysis of SOD1 mRNA and SDS-PAGE/Western blot analysis of PBMC demonstrated that mRNA from the mutant allele is expressed at levels similar to those of the wild-type allele, but the truncated protein is undetectable also in the insoluble fraction and after proteasome inhibition. Accordingly, the dismutation activity in erythrocytes is halved. Thus, the pathogenic mechanism associated with this mutation might be based on an insufficient activity of SOD1 that would make motor neurons more vulnerable to oxidative injury. However, it cannot be excluded that p.Ser108LeufsTer15 SOD1 is present in the nervous tissue and, being less charged and hence having less repulsive forces than the wild-type protein, may trigger toxic mechanisms as a consequence of its propensity to aggregate.
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| 15. |
- Conroy-Beam, Daniel, et al.
(författare)
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Assortative mating and the evolution of desirability covariation
- 2019
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Ingår i: Evolution and human behavior. - : Elsevier. - 1090-5138 .- 1879-0607. ; 40:5, s. 479-491
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Tidskriftsartikel (refereegranskat)abstract
- Mate choice lies dose to differential reproduction, the engine of evolution. Patterns of mate choice consequently have power to direct the course of evolution. Here we provide evidence suggesting one pattern of human mate choice-the tendency for mates to be similar in overall desirability-caused the evolution of a structure of correlations that we call the d factor. We use agent-based models to demonstrate that assortative mating causes the evolution of a positive manifold of desirability, d, such that an individual who is desirable as a mate along any one dimension tends to be desirable across all other dimensions. Further, we use a large cross-cultural sample with n = 14,478 from 45 countries around the world to show that this d-factor emerges in human samples, is a cross-cultural universal, and is patterned in a way consistent with an evolutionary history of assortative mating. Our results suggest that assortative mating can explain the evolution of a broad structure of human trait covariation.
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| 16. |
- Conroy-Beam, Daniel, et al.
(författare)
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Contrasting Computational Models of Mate Preference Integration Across 45 Countries
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Humans express a wide array of ideal mate preferences. Around the world, people desire romantic partners who are intelligent, healthy, kind, physically attractive, wealthy, and more. In order for these ideal preferences to guide the choice of actual romantic partners, human mating psychology must possess a means to integrate information across these many preference dimensions into summaries of the overall mate value of their potential mates. Here we explore the computational design of this mate preference integration process using a large sample of n = 14,487 people from 45 countries around the world. We combine this large cross-cultural sample with agent-based models to compare eight hypothesized models of human mating markets. Across cultures, people higher in mate value appear to experience greater power of choice on the mating market in that they set higher ideal standards, better fulfill their preferences in choice, and pair with higher mate value partners. Furthermore, we find that this cross-culturally universal pattern of mate choice is most consistent with a Euclidean model of mate preference integration.
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| 17. |
- Corrales Vargas, Andrea, et al.
(författare)
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Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 810
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pesticides and metals may disrupt thyroid function, which is key to fetal brain development. Objectives: To evaluate if current-use pesticide exposures, lead and excess manganese alter free thyroxine (FT4), free triiodothyronine (FT3), and thyroid stimulating hormone (TSH) concentrations in pregnant women from the Infants' Environmental Health Study (ISA). Methods: At enrollment, we determined women's (n = 400) specific-gravity corrected urinary pesticide (μg/L) metabolite concentrations of mancozeb (ethylene thiourea (ETU)), pyrimethanil, thiabendazole, chlorpyrifos, synthetic pyrethroids, and 2,4-D. We also measured manganese hair (MnH) (μg/g) and blood (MnB) (μg/L), and blood lead (PbB) (μg/L) concentrations. To detect an immediate and late effect on thyroid homeostasis, we determined TSH, FT4 and FT3 in serum obtained at the same visit (n = 400), and about ten weeks afterwards (n = 245). We assessed associations between exposures and outcomes with linear regression and general additive models, Bayesian multivariate linear regression, and Bayesian kernel machine regression. Results: About 80%, 94%, and 100% of the women had TSH, FT4, and FT3 within clinical reference ranges, respectively. Women with higher urinary ETU, and pyrimethanil-metabolites, had lower FT4: β = −0.79 (95%CI = −1.51, −0.08) and β = −0.29 (95%CI = −0.62, −0.03), respectively, for each tenfold increase in exposure. MnB was positively associated with FT4 (β = 0.04 (95%CI = 0.00, 0.07 per 1 μg/L increase), and women with high urinary pyrethroid-metabolite concentrations had decreased TSH (non-linear effects). For the late-effect analysis, metabolites of pyrethroids and chlorpyrifos, as well as MnH, and PbB were associated decreased TSH, or increased FT4 and/or FT3. Discussion: Mancozeb (ETU) and pyrimethanil may inhibit FT4 secretion (hypothyroidism-like effect), while chlorpyrifos, pyrethroids, MnB, MnH, PbB and Mn showed hyperthyroidism-like effects. Some effects on thyroid homeostasis seemed to be immediate (mancozeb (ETU), pyrimethanil, MnB), others delayed (chlorpyrifos, MnH, PbB), or both (pyrethroids), possibly reflecting different mechanisms of action.
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| 18. |
- Domínguez-Rodrigo, Manuel, et al.
(författare)
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Early Pleistocene faunivorous hominins were not kleptoparasitic, and this impacted the evolution of human anatomy and socio-ecology
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Humans are unique in their diet, physiology and socio-reproductive behavior compared to other primates. They are also unique in the ubiquitous adaptation to all biomes and habitats. From an evolutionary perspective, these trends seem to have started about two million years ago, coinciding with the emergence of encephalization, the reduction of the dental apparatus, the adoption of a fully terrestrial lifestyle, resulting in the emergence of the modern anatomical bauplan, the focalization of certain activities in the landscape, the use of stone tools, and the exit from Africa. It is in this period that clear taphonomic evidence of a switch in diet with respect to Pliocene hominins occurred, with the adoption of carnivory. Until now, the degree of carnivorism in early humans remained controversial. A persistent hypothesis is that hominins acquired meat irregularly (potentially as fallback food) and opportunistically through klepto-foraging. Here, we test this hypothesis and show, in contrast, that the butchery practices of early Pleistocene hominins (unveiled through systematic study of the patterning and intensity of cut marks on their prey) could not have resulted from having frequent secondary access to carcasses. We provide evidence of hominin primary access to animal resources and emphasize the role that meat played in their diets, their ecology and their anatomical evolution, ultimately resulting in the ecologically unrestricted terrestrial adaptation of our species. This has major implications to the evolution of human physiology and potentially for the evolution of the human brain.
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| 19. |
- Esteban-Cornejo, Irene, et al.
(författare)
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Fitness, cortical thickness and surface area in overweight/obese children: The mediating role of body composition and relationship with intelligence
- 2019
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Ingår i: NeuroImage. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 1053-8119 .- 1095-9572. ; 186, s. 771-781
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Tidskriftsartikel (refereegranskat)abstract
- Cortical thickness and surface area are thought to be genetically unrelated and shaped by independent neurobiological events suggesting that they should be considered separately in morphometric analyses. Although the developmental trajectories of cortical thickness and surface area may differ across brain regions and ages, there is no consensus regarding the relationships of physical fitness with cortical thickness and surface area as well as for its subsequent influence on intelligence. Thus, this study examines: (i) the associations of physical fitness components (i.e., cardiorespiratory fitness, speed-agility and muscular fitness) with overall and regional cortical thickness and surface area; (ii) whether body composition indicators (i.e., body mass index, fat-free mass index and fat mass index) mediate these associations; and (iii) the association of physical fitness and cortical thickness with intelligence in overweight/obese children. A total of 101 overweight/obese children aged 8-11 years were recruited in Granada, Spain. The physical fitness components were assessed following the ALPHA health-related fitness test battery. T1-weighted images were acquired with a 3.0 Tesla Siemens Magnetom Tim Trio system. We used FreeSurfer software version 5.3.0 to assess cortical thickness (mm) and surface area (mm(2)). The main results showed that cardiorespiratory fitness and speed-agility were related to overall cortical thickness (beta = 0.321 and beta = 0.302, respectively; both P amp;lt; 0.05), and in turn, cortical thickness was associated with higher intelligence (beta = 0.198, P amp;lt; 0.05). Muscular fitness was not related to overall cortical thickness. None of the three physical fitness components were related to surface area (p amp;gt; 0.05). The associations of cardiorespiratory fitness and speed-agility with overall cortical thickness were mediated by fat mass index (56.86% amp; 62.28%, respectively). In conclusion, cardiorespiratory fitness and speed-agility, but not muscular fitness, are associated with overall cortical thickness, and in turn, thicker brain cortex is associated with higher intelligence in overweight/obese children. Yet, none of the three physical fitness components were related to surface area. Importantly, adiposity may hinder the benefits of cardiorespiratory fitness and speed-agility on cortical thickness. Understanding individual differences in brain morphology may have important implications for educators and policy makers who aim to determine policies and interventions to maximize academic learning and occupational success later in life.
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| 20. |
- García-Sanchez, Marta, et al.
(författare)
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Differential Responses of Bovine Monocyte-Derived Macrophages to Infection by Neospora caninum Isolates of High and Low Virulence
- 2019
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Neospora caninum, a protozoan parasite closely related to Toxoplasma gondii, represents one of the main causes of abortion in cattle. Macrophages (Mempty sets) are mediators of the innate immune response against infection and likely one of the first cells encountered by the parasite during the host infection process. In this study, we investigated in vitro how high or low virulent isolates of N. caninum (Nc-Spain7 and Nc-Spain1H, respectively) interact with bovine monocyte-derived Mempty sets and the influence of the isolate virulence on the subsequent cellular response. Both isolates actively invaded, survived and replicated in the Mempty sets. However, Nc-Spain7 showed a higher invasion rate and a replication significantly faster, following an exponential growth model, whereas Nc-Spain1H presented a delayed replication and a lower growth rate without an exponential pattern. N. caninum infection induced a hypermigratory phenotype in bovine Mempty sets that was characterized by enhanced motility and transmigration in vitro and was accompanied by morphological changes and abrogated extracellular matrix degradation. A significantly higher hypermotility was observed with the highly virulent isolate Nc-Spain7. Nc-Spain1H-infected Mempty sets showed elevated reactive oxygen species (ROS) production and IL12p40 expression, which also resulted in increased IFN-gamma release by lymphocytes, compared to cells infected with Nc-Spain7. Furthermore, IL-10 was upregulated in Mempty sets infected with both isolates. Infected Mempty sets exhibited lower expression of MHC Class II, CD86, and CD1b molecules than uninfected Mempty sets, with non-significant differences between isolates. This work characterizes for the first time N. caninum replication in bovine monocyte-derived Mempty sets and details isolate-dependent differences in host cell responses to the parasite.
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| 21. |
- Gõmez-Elvira, Javier, et al.
(författare)
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Curiosity's rover environmental monitoring station : Overview of the first 100 sols
- 2014
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:7, s. 1680-1688
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Tidskriftsartikel (refereegranskat)abstract
- In the first 100 Martian solar days (sols) of the Mars Science Laboratory mission, the Rover Environmental Monitoring Station (REMS) measured the seasonally evolving diurnal cycles of ultraviolet radiation, atmospheric pressure, air temperature, ground temperature, relative humidity, and wind within Gale Crater on Mars. As an introduction to several REMS-based articles in this issue, we provide an overview of the design and performance of the REMS sensors and discuss our approach to mitigating some of the difficulties we encountered following landing, including the loss of one of the two wind sensors. We discuss the REMS data set in the context of other Mars Science Laboratory instruments and observations and describe how an enhanced observing strategy greatly increased the amount of REMS data returned in the first 100 sols, providing complete coverage of the diurnal cycle every 4 to 6 sols. Finally, we provide a brief overview of key science results from the first 100 sols. We found Gale to be very dry, never reaching saturation relative humidities, subject to larger diurnal surface pressure variations than seen by any previous lander on Mars, air temperatures consistent with model predictions and abundant short timescale variability, and surface temperatures responsive to changes in surface properties and suggestive of subsurface layering. Key Points Introduction to the REMS results on MSL mission Overiview of the sensor information Overview of operational constraints
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| 22. |
- Hop, Paul J., et al.
(författare)
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Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS
- 2022
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science. - 1946-6234 .- 1946-6242. ; 14:633
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.
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| 23. |
- Lee, Chunsik, et al.
(författare)
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VEGF-B prevents excessive angiogenesis by inhibiting FGF2/FGFR1 pathway
- 2023
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Ingår i: SIGNAL TRANSDUCTION AND TARGETED THERAPY. - : SPRINGERNATURE. - 2095-9907 .- 2059-3635. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.
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| 24. |
- Madrigal, Irene, et al.
(författare)
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Efficient application of next-generation sequencing for the diagnosis of rare genetic syndromes
- 2014
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Ingår i: Journal of Clinical Pathology. - : BMJ. - 0021-9746 .- 1472-4146. ; 67:12, s. 1099-1103
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Tidskriftsartikel (refereegranskat)abstract
- Aims The causes of intellectual disability, which affects 1%-3% of the general population, are highly heterogeneous and the genetic defect remains unknown in around 40% of patients. The application of next-generation sequencing is changing the nature of biomedical diagnosis. This technology has quickly become the method of choice for searching for pathogenic mutations in rare uncharacterised genetic diseases. Methods Whole-exome sequencing was applied to a series of families affected with intellectual disability in order to identify variants underlying disease phenotypes. Results We present data of three families in which we identified the disease-causing mutations and which benefited from receiving a clinical diagnosis: Cornelia de Lange, Cohen syndrome and Dent-2 disease. The genetic heterogeneity and the variability in clinical presentation of these disorders could explain why these patients are difficult to diagnose. Conclusions The accessibility to next-generation sequencing allows clinicians to save much time and cost in identifying the aetiology of rare diseases. The presented cases are excellent examples that demonstrate the efficacy of next-generation sequencing in rare disease diagnosis.
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| 25. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 26. |
- Sorokowska, Agnieszka, et al.
(författare)
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Affective Interpersonal Touch in Close Relationships : A Cross-Cultural Perspective
- 2021
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Ingår i: Personality and Social Psychology Bulletin. - : Sage Publications. - 0146-1672 .- 1552-7433. ; 47:12, s. 1705-1721
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Tidskriftsartikel (refereegranskat)abstract
- Interpersonal touch behavior differs across cultures, yet no study to date has systematically tested for cultural variation in affective touch, nor examined the factors that might account for this variability. Here, over 14,000 individuals from 45 countries were asked whether they embraced, stroked, kissed, or hugged their partner, friends, and youngest child during the week preceding the study. We then examined a range of hypothesized individual-level factors (sex, age, parasitic history, conservatism, religiosity, and preferred interpersonal distance) and cultural-level factors (regional temperature, parasite stress, regional conservatism, collectivism, and religiosity) in predicting these affective-touching behaviors. Our results indicate that affective touch was most prevalent in relationships with partners and children, and its diversity was relatively higher in warmer, less conservative, and religious countries, and among younger, female, and liberal people. This research allows for a broad and integrated view of the bases of cross-cultural variability in affective touch.
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| 27. |
- Tazelaar, Gijs H.P., et al.
(författare)
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Whole genome sequencing analysis reveals post-zygotic mutation variability in monozygotic twins discordant for amyotrophic lateral sclerosis
- 2023
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 122, s. 76-87
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis is a heterogeneous, fatal neurodegenerative disease, characterized by motor neuron loss and in 50% of cases also by cognitive and/or behavioral changes. Mendelian forms of ALS comprise approximately 10-15% of cases. The majority is however considered sporadic, but also with a high contribution of genetic risk factors. To explore the contribution of somatic mutations and/or epigenetic changes to disease risk, we performed whole genome sequencing and methylation analyses using samples from multiple tissues on a cohort of 26 monozygotic twins discordant for ALS, followed by in-depth validation and replication experiments. The results of these analyses implicate several mechanisms in ALS pathophysiology, which include a role for de novo mutations, defects in DNA damage repair and accelerated aging.
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| 28. |
- Walter, Kathryn, et al.
(författare)
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Sex Differences in Mate Preferences Across 45 Countries : A Large-Scale Replication
- 2020
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Ingår i: Psychological Science. - : SAGE Publications. - 0956-7976 .- 1467-9280. ; 31:4, s. 408-423
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Tidskriftsartikel (refereegranskat)abstract
- Considerable research has examined human mate preferences across cultures, finding universal sex differences in preferences for attractiveness and resources as well as sources of systematic cultural variation. Two competing perspectives-an evolutionary psychological perspective and a biosocial role perspective-offer alternative explanations for these findings. However, the original data on which each perspective relies are decades old, and the literature is fraught with conflicting methods, analyses, results, and conclusions. Using a new 45-country sample (N = 14,399), we attempted to replicate classic studies and test both the evolutionary and biosocial role perspectives. Support for universal sex differences in preferences remains robust: Men, more than women, prefer attractive, young mates, and women, more than men, prefer older mates with financial prospects. Cross-culturally, both sexes have mates closer to their own ages as gender equality increases. Beyond age of partner, neither pathogen prevalence nor gender equality robustly predicted sex differences or preferences across countries.
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