| 1. |
- Faux, Pierre, et al.
(författare)
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Neanderthal introgression in SCN9A impacts mechanical pain sensitivity
- 2023
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Ingår i: Communications Biology. - 2399-3642. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of similar to 123kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function. Neanderthal-derived variants in the SCN9A gene (encoding the voltage gated sodium channel, Nav1.7) are associated with enhanced experimental mechanical pain sensitivity in modern humans.
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| 2. |
- Mendoza-Revilla, Javier, et al.
(författare)
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Disentangling Signatures of Selection Before and After European Colonization in Latin Americans
- 2022
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 39:4
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Tidskriftsartikel (refereegranskat)abstract
- Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.
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| 3. |
- Navarro-Pardo, F., et al.
(författare)
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Nanofiber-supported CuS nanoplatelets as high efficiency counter electrodes for quantum dot-based photoelectrochemical hydrogen production
- 2017
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Ingår i: Materials Chemistry Frontiers. - : Royal Society of Chemistry. - 2052-1537. ; 1:1, s. 65-72
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Tidskriftsartikel (refereegranskat)abstract
- We developed a hierarchically assembled hybrid counter electrode (CE) based on copper sulfide (CuS) nanoplatelets grown on polymer nanofibers. The resulting CE was used in a quantum dot (QD)-based photoelectrochemical (PEC) system for H2 generation in the presence of sacrificial agents (S2−/SO32−). The concept is to increase the specific surface area of the CE, aiming at maximizing charge exchange at the electrode, which boosts efficient generation of H2 and to obtain a stable structure for long-term operation of the device. Structural and morphological characterization indicated the presence of a covellite crystalline phase (CuS). PEC tests showed that the CuS nanoplatelets grown in the CEs could replace Pt CEs in either visible-active or near infrared (NIR)-active QD-based PEC systems. Specifically, saturation of the photocurrent density (∼7.5 mA cm−2) occurred at ∼0.6 V versus the RHE, when using a NIR QD-based TiO2 photoanode and a nanofiber-supported CuS as the CE. Stability tests of the nanofiber-supported CuS CE showed that 85% of the initial photocurrent density was maintained after ∼1 h, which is similar to that obtained with the Pt foil CE (86%). In contrast, CuS nanostructures directly deposited on FTO glass without nanofibers (CuS/FTO CE) exhibited poor stability. CuS/FTO CE degraded quickly, showing a 90% drop in the initial photocurrent within 200 s testing whereas a 14% drop in the initial photocurrent was observed for the CuxS on brass within 10 min of testing. Our new nanofiber supported-CuS CE stands out due to its higher performance compared to brass and its similar stability compared to Pt during long term PEC operation. Additionally, our hybrid CE showed a better catalytic performance than the Pt CE and good stability in cyclic voltammetry tests. These results demonstrate that the nanofiber-supported CuS is a promising cost effective alternative to Pt as a highly efficient CE for PEC H2 generation
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| 4. |
- Tong, Xin, et al.
(författare)
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Heavy Metal-free, Near-infrared Colloidal Quantum Dots for Efficient Photoelectrochemical Hydrogen Generation
- 2017
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Ingår i: Nano Energy. - : Elsevier. - 2211-2855. ; 31, s. 441-449
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Tidskriftsartikel (refereegranskat)abstract
- Photoelectrochemical (PEC) hydrogen generation based on colloidal quantum dots (QDs) is very promising because of its high solar energy to fuel conversion efficiency and low fabrication costs. However, its commercial development is hindered by various challenges, including the widespread use of toxic heavy metal–based QDs as sensitizers. We report an environmentally friendly, high efficiency PEC device in which the photoanode consists of a mesoporous TiO2 film sensitized with heavy metal-free, near-infrared (NIR) colloidal CuInSexS2-x (CISeS) QDs. To reduce surface-related traps, we grew an ultrathin ZnS shell on the CISeS core QDs by cation exchange. The PEC cell based on this core/shell CISeS/ZnS QDs exhibits suppressed charge recombination and a saturated photocurrent density of ~5.3 mA/cm2 under one sun illumination (AM 1.5 G, 100 mW/cm2). In addition, the as-prepared PEC device shows an outstanding stability, exhibiting a drop of only 23% after 9 h illumination. The success in using such core/shell CISeS/ZnS QDs paves the way to realize environment-friendly, high efficiency and cost-effective PEC devices for hydrogen production.
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| 5. |
- Trendafilova, Teodora, et al.
(författare)
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Sodium-calcium exchanger-3 regulates pain “wind-up” : From human psychophysics to spinal mechanisms
- 2022
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273 .- 1097-4199. ; 110:16, s. 2571-2587.e13
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Tidskriftsartikel (refereegranskat)abstract
- Repeated application of noxious stimuli leads to a progressively increased pain perception; this temporal summation is enhanced in and predictive of clinical pain disorders. Its electrophysiological correlate is “wind-up,” in which dorsal horn spinal neurons increase their response to repeated nociceptor stimulation. To understand the genetic basis of temporal summation, we undertook a GWAS of wind-up in healthy human volunteers and found significant association with SLC8A3 encoding sodium-calcium exchanger type 3 (NCX3). NCX3 was expressed in mouse dorsal horn neurons, and mice lacking NCX3 showed normal, acute pain but hypersensitivity to the second phase of the formalin test and chronic constriction injury. Dorsal horn neurons lacking NCX3 showed increased intracellular calcium following repetitive stimulation, slowed calcium clearance, and increased wind-up. Moreover, virally mediated enhanced spinal expression of NCX3 reduced central sensitization. Our study highlights Ca2+ efflux as a pathway underlying temporal summation and persistent pain, which may be amenable to therapeutic targeting.
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