Objective
To characterize the peptidome of the Behçet's disease–associated HLA–B*51:01 allotype as well as the differential features of major peptide subsets and their distinct endoplasmic reticulum ...aminopeptidase 1 (ERAP‐1)–mediated processing.
Methods
The endogenous B*51:01‐bound peptidome was characterized from 721.221 transfectant cells, after affinity chromatography and acid extraction, by tandem mass spectrometry. Recombinant ERAP‐1 variants were used to digest synthetic B*51:01 ligands. HLA and transporter associated with antigen processing (TAP) binding affinities of peptide ligands were calculated with well‐established algorithms. ERAP‐1 and ERAP‐2 from 721.221 cells were characterized by genomic sequencing and Western blotting.
Results
The B*51:01 peptidome consisted of 29.5% octamers, 61.7% nonamers, 4.8% decamers, and 4.0% longer peptides. The major peptide motif consisted of Pro and Ala at position 2, aliphatic/aromatic position 3 residues, and Val and Ile at the C‐terminal position. The ligands with Pro or Ala at position 2 constituted 2 distinct subpeptidomes. Peptides with Pro at position 2 showed higher affinity for B*51:01 and lower affinity for TAP than those with Ala at position 2. Most important, both peptide subsets differed drastically in the susceptibility of their position 1 residues to ERAP‐1, revealing a distinct influence of this enzyme on both subpeptidomes, which may alter their balance, affecting the global affinity of B*51:01–peptide complexes.
Conclusion
ERAP‐1 has a significant influence on the B*51:01 peptidome and its affinity. This influence is based on very distinct effects on the 2 subpeptidomes, whereby only peptides in the subpeptidome with Ala at position 2 are extensively destroyed, except when their position 1 residues are ERAP‐1 resistant. This pattern provides a mechanism for the epistatic association of ERAP‐1 and B*51:01 in Behçet's disease.
This paper presents an hourly management method for energy generated in grid-connected wind farms using battery storage (Wind–Batteries systems). The method proposed is analysed technically and ...economically.
Electricity generation in wind farms does not usually coincide with the electrical demand curve. If the wind-power penetration becomes high in the Spanish electrical grid, energy management will become necessary for some wind farms. A method is proposed in this paper to adjust the generation curve to the demand curve by storing electrical energy in batteries during off-peak hours (low demand) and selling stored energy to the grid during peak hours (high demand).
With the results obtained and reported in this paper, for a Wind–Batteries system to be economically as profitable as a Wind-Only system, the selling price of the energy provided by the batteries during peak hours should be between 22 and 66
c€/kWh, depending on the technology and cost of the batteries. Comparison with flexible thermal generation has been performed.
Additionally, the results are compared with those obtained if using hydrogen (Wind–Hydrogen system, which uses an electrolyser, hydrogen tank, and fuel cell instead of batteries), concluding that the Wind–Batteries system is both economically and energetically far more suitable.
According to several studies, inflammatory factors could be related to the pathogenesis of idiopathic restless legs syndrome (RLS). In addition, RLS and Parkinson's disease (PD) have shown a possible ...relationship, and recent studies have shown an association between
rs1922452 and
rs951818 single nucleotide variants (SNVs) and the risk for PD. For these reasons, we investigated the possible association between common variants in the
genes (which encoded proteins involved in inflammatory and autoimmune responses) and the risk for RLS in a Caucasian Spanish population. We assessed the frequencies of
rs1922452,
rs951818, and
rs870849 genotypes and allelic variants in 285 patients with idiopathic RLS and 350 healthy controls using a specific
-based qPCR assay. We also analyzed the possible influence of the genotypes' frequencies on several variables, including age at onset of RLS, gender, family history of RLS, and response to drugs commonly used in the treatment of RLS. We found a lack of association between the frequencies of genotypes and allelic variants of the 3 SNVs studied and the risk of RLS, and a weak though significant association between the
rs1922452 GG genotype and an older age at onset of RLS. With the exception of this association, our findings suggest that common SNVs in the
genes are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people.
Over the last century, marine mammals have been dramatically reduced in the world's oceans. We examined evidence that this change caused dietary and foraging pattern shifts of the Andean condor ...(Vultur gryphus) in Patagonia. We hypothesized that, after the decrease in marine mammals and the increase in human use of coastlines, condor diet changed to a more terrestrial diet, which in turn influenced their foraging patterns. We evaluated the diet by means of stable isotope analysis (δ13C, δ15N and δ34S) of current (last decade) and historical (1841–1933) feathers. We further evaluated the movement patterns of 23 condors using satellite tracking of individuals. Condors reduced their use of marine-derived prey in recent compared with historical times from 33 ± 13% to less than 8 ± 3% respectively; however, they still breed close to the coast. The average distance between the coast and nests was 62.5 km, but some nests were located close to the sea (less than 5 km). Therefore, some birds must travel up to 86 km from nesting sites, crossing over the mountain range to find food. The worldwide reduction in marine mammal carcasses, especially whales, may have major consequences on the foraging ecology of scavengers, as well as on the flux of marine inputs within terrestrial ecosystems.
Plant glutamate receptor-like (GLR) genes encode ion channels with demonstrated roles in electrical and calcium (Ca
2+
) signaling. The expansion of the GLR family along the lineage of land plants, ...culminating in the appearance of a multiclade system among flowering plants, has been a topic of interest since their discovery nearly 25 years ago. GLRs are involved in many physiological processes, from wound signaling to transcriptional regulation to sexual reproduction. Emerging evidence supports the notion that their fundamental functions are conserved among different groups of plants as well. In this review, we update the physiological and genetic evidence for GLRs, establishing their role in signaling and cell-cell communication. Special emphasis is given to the recent discussion of GLRs' atomic structures. Along with functional assays, a structural view of GLRs' molecular organization presents a window for novel hypotheses regarding the molecular mechanisms underpinning signaling associated with the ionic fluxes that GLRs regulate. Newly uncovered transcriptional regulations associated with GLRs-which propose the involvement of genes from all clades of
Arabidopsis thaliana
in ways not previously observed-are discussed in the context of the broader impacts of GLR activity. We posit that the functions of GLRs in plant biology are probably much broader than anticipated, but describing their widespread involvement will only be possible with (
a
) a comprehensive understanding of the channel's properties at the molecular and structural levels, including protein-protein interactions, and (
b
) the design of new genetic approaches to explore stress and pathogen responses where precise transcriptional control may result in more precise testable hypotheses to overcome their apparent functional redundancies.
Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, ...parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. The most prevalent form of NBIA is pantothenate kinase-associated neurodegeneration (PKAN) associated with mutations in the gene of pantothenate kinase 2 (PANK2), which is essential for coenzyme A (CoA) synthesis. There is no cure for NBIA nor is there a standard course of treatment. In the current work, we describe that fibroblasts derived from patients harbouring PANK2 mutations can reproduce many of the cellular pathological alterations found in the disease, such as intracellular iron and lipofuscin accumulation, increased oxidative stress, and mitochondrial dysfunction. Furthermore, mutant fibroblasts showed a characteristic senescent morphology. Treatment with pantothenate, the PANK2 enzyme substrate, was able to correct all pathological alterations in responder mutant fibroblasts with residual PANK2 enzyme expression. However, pantothenate had no effect on mutant fibroblasts with truncated/incomplete protein expression. The positive effect of pantothenate in particular mutations was also confirmed in induced neurons obtained by direct reprograming of mutant fibroblasts. Our results suggest that pantothenate treatment can stabilize the expression levels of PANK2 in selected mutations. These results encourage us to propose our screening model as a quick and easy way to detect pantothenate-responder patients with PANK2 mutations. The existence of residual enzyme expression in some affected individuals raises the possibility of treatment using high dose of pantothenate.
We have investigated if the heterologous expression of a functional green alga plastocyanin in the diatom Phaeodactylum tricornutum can improve photosynthetic activity and cell growth. Previous in ...vitro assays showed that a single‐mutant of the plastocyanin from the green algae Chlamydomonas reinhardtii is effective in reducing P. tricornutum photosystem I. In this study, in vivo assays with P. tricornutum strains expressing this plastocyanin indicate that even the relatively low intracellular concentrations of holo‐plastocyanin detected (≈4 μM) are enough to promote an increased growth (up to 60%) under iron‐deficient conditions as compared with the WT strain, measured as higher cell densities, content in pigments and active photosystem I, global photosynthetic rates per cell, and even cell volume. In addition, the presence of plastocyanin as an additional photosynthetic electron carrier seems to decrease the over‐reduction of the plastoquinone pool. Consequently, it promotes an improvement in the maximum quantum yield of both photosystem II and I, together with a decrease in the acceptor side photoinhibition of photosystem II—also associated to a reduced oxidative stress—a decrease in the peroxidation of membrane lipids in the choroplast, and a lower degree of limitation on the donor side of photosystem I. Thus the heterologous plastocyanin appears to act as a functional electron carrier, alternative to the native cytochrome c6, under iron‐limiting conditions.
Craniosynostosis must often be corrected using surgery, by which the affected bone tissue is remodeled. Nowadays, surgical reconstruction relies mostly on the subjective judgement of the surgeon to ...best restore normal skull shape, since remodeled bone is manually placed and fixed. Slight variations can compromise the cosmetic outcome. The objective of this study was to describe and evaluate a novel workflow for patient-specific correction of craniosynostosis based on intraoperative navigation and 3D printing. The workflow was followed in five patients with craniosynostosis. Virtual surgical planning was performed, and patient-specific cutting guides and templates were designed and manufactured. These guides and templates were used to control osteotomies and bone remodeling. An intraoperative navigation system based on optical tracking made it possible to follow preoperative virtual planning in the operating room through real-time positioning and 3D visualization. Navigation accuracy was estimated using intraoperative surface scanning as the gold-standard. An average error of 0.62 mm and 0.64 mm was obtained in the remodeled frontal region and supraorbital bar, respectively. Intraoperative navigation is an accurate and reproducible technique for correction of craniosynostosis that enables optimal translation of the preoperative plan to the operating room.
Oxidative Stress Markers in Multiple Sclerosis Jiménez-Jiménez, Félix Javier; Alonso-Navarro, Hortensia; Salgado-Cámara, Paula ...
International journal of molecular sciences,
06/2024, Letnik:
25, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The pathogenesis of multiple sclerosis (MS) is not completely understood, but genetic factors, autoimmunity, inflammation, demyelination, and neurodegeneration seem to play a significant role. Data ...from analyses of central nervous system autopsy material from patients diagnosed with multiple sclerosis, as well as from studies in the main experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), suggest the possibility of a role of oxidative stress as well. In this narrative review, we summarize the main data from studies reported on oxidative stress markers in patients diagnosed with MS and in experimental models of MS (mainly EAE), and case–control association studies on the possible association of candidate genes related to oxidative stress with risk for MS. Most studies have shown an increase in markers of oxidative stress, a decrease in antioxidant substances, or both, with cerebrospinal fluid and serum/plasma malonyl-dialdehyde being the most reliable markers. This topic requires further prospective, multicenter studies with a long-term follow-up period involving a large number of patients with MS and controls.
Photoperiod regulates many different developmental processes, including floral induction in several species and tuber formation in potato. Research in Arabidopsis led to the identification of ...FLOWERING LOCUS T (FT) as a main component of the florigen or mobile flowering promoting signal produced in the leaves. A similar mobile signal or tuberigen has been reported to induce tuber formation in potato, recent evidence obtained in our laboratory indicates that a potato homolog of FT encodes this signal. Flowering regulators, like CONSTANS and miR172 , also play a role in tuberization, although it remains unclear whether these regulators function in identical pathways. Here, we highlight differential regulation of these genes in flowering and tuberization control and discuss on their possible tuberization-related function.
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