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- 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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| 20. |
- Gonzalez-Mendoza, V. M., et al.
(författare)
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Phospholipases C and D and Their Role in Biotic and Abiotic Stresses
- 2021
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Ingår i: Plants-Basel. - : MDPI AG. - 2223-7747. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Plants, as sessile organisms, have adapted a fine sensing system to monitor environmental changes, therefore allowing the regulation of their responses. As the interaction between plants and environmental changes begins at the surface, these changes are detected by components in the plasma membrane, where a molecule receptor generates a lipid signaling cascade via enzymes, such as phospholipases (PLs). Phospholipids are the key structural components of plasma membranes and signaling cascades. They exist in a wide range of species and in different proportions, with conversion processes that involve hydrophilic enzymes, such as phospholipase-C (PLC), phospholipase-D (PLD), and phospholipase-A (PLA). Hence, it is suggested that PLC and PLD are highly conserved, compared to their homologous genes, and have formed clusters during their adaptive history. Additionally, they generate responses to different functions in accordance with their protein structure, which should be reflected in specific signal transduction responses to environmental stress conditions, including innate immune responses. This review summarizes the phospholipid systems associated with signaling pathways and the innate immune response.
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| 21. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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- Schlebusch, Carina M., et al.
(författare)
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Possible positive selection for an arsenic-protective haplotype in humans
- 2013
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 121:1, s. 53-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite.Objectives: We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups. Methods: Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American populations from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian populations (n = 97). The last two groups have presumably lower historical exposure to arsenic.Results: We found a significantly higher frequency of the protective AS3MT haplotype in the SAC population (68.7%) compared with the HGDP (14.3%, p < 0.001, Fisher exact test) and Peruvian (50.5%, p < 0.001) populations. Genome-wide microsatellite (n = 671) analysis showed no detectable level of population structure between SAC and Peruvian populations (measure of population differentiation FST = 0.006) and low levels of structure between SAC and HGDP populations (FST < 0.055 for all pairs of populations compared). Conclusions: Because population stratification seems unlikely to explain the differences in AS3MT haplotype frequencies, our data raise the possibility that, during a few thousand years, natural selection for tolerance to the environmental stressor arsenic may have increased the frequency of protective variants of AS3MT. Further studies are needed to investigate this hypothesis.
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| 26. |
- Spalding, KL, et al.
(författare)
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Dynamics of fat cell turnover in humans
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 453:7196, s. 783-787
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Tidskriftsartikel (refereegranskat)
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| 27. |
- Wilkie, F. L., et al.
(författare)
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Cognitive functioning in younger and older HIV-1 - Infected adults
- 2003
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - : Wolters Kluwer. - 1525-4135 .- 1944-7884. ; 33, s. S93-S105
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Tidskriftsartikel (refereegranskat)abstract
- In young adults, a major neurologic complication of HIV-1 infection is cognitive motor impairment. Epidemiologic findings suggest that increasing age is a significant risk factor for HIV-1-associated dementia as the AIDS-defining illness. Findings from the few studies that have directly measured cognition in younger and older HIV-1-infected adults, however, have been mixed, in pan, because of small sample sizes and other methodologic differences between studies. The authors present preliminary findings on cognitive functioning in symptomatic HIV-1-infected younger (aged 20-39 years) and older (aged 50 years or older) adults. Independent of age, HIV-1 infection was accompanied by learning and memory retrieval deficits, which were significantly associated with high plasma viral loads in the young adults. Relative to the younger and older HIV-1-negative (HIV-1-) groups, only the younger HIV-1-positive (HIV-1(+))group had significantly longer reaction times (RTs). Within the older HIV-1(+) group, however, longer simple and choice RTs were significantly correlated with higher viral loads and lower CD4 cell counts. Although HIV-1 infection affects cognition independent of age, longitudinal studies involving large numbers of older individuals are needed to determine whether there are age differences in the prevalence, nature, and severity of HIV-1-associated cognitive dysfunction.
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| 28. |
- Wilkie, F. L., et al.
(författare)
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HUMANS : An English and Spanish neuropsychological test battery for assessing HIV-1-infected individuals - Initial report
- 2004
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Ingår i: Applied neuropsychology. - : Taylor & Francis. - 0908-4282 .- 1532-4826. ; 11:3, s. 121-133
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Tidskriftsartikel (refereegranskat)abstract
- A neuropsychological battery for testing HIV-1-infected individuals in Spanish was developed. We refer to this battery as the HIV/University of Miami Annotated Neuropsychological test battery in Spanish (HUMANS). The HUMANS battery includes recommendations of the National Institute of Mental Health Neuropsychology Workgroup on HIV-1 infection and measures processes in the following 7 cognitive domains: attention, verbal and visual memory, information processing speed, abstraction and executive functioning, language, visuospatial and visuo-constructive, and motor Administration requires approximately 3 to 4 hr The English version of the battery is sensitive to HIV-1 serostatus and Centers for Disease Control clinical disease stage. We report on the test selection, translation, and adaptation of this parallel English battery into Spanish using methods to eliminate linguistically and culturally biased items in some tests. The importance of standardized neuropsychological instruments equivalent in different languages to test HIV-1-positive individuals for impairment is emphasized. Validation and reliability studies are in progress.
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| 29. |
- Ameer, S. S., et al.
(författare)
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Exposure to inorganic arsenic and mitochondrial DNA copy number and telomere length in peripheral blood
- 2016
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Ingår i: Arsenic Research and Global Sustainability - Proceedings of the 6th International Congress on Arsenic in the Environment, AS 2016. - 9781138029415 ; , s. 450-452
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Konferensbidrag (refereegranskat)abstract
- Exposure to inorganic arsenic (iAs) is a risk factor for cancer. Alterations in mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) have been associated with cancer risk. Two Argentinean groups were studied: A) Puna area of Andes and B) Chaco. Arsenic exposure was assessed as the sum of arsenic metabolites (iAs, MMA, and DMA) in urine (U-As) using HPLC-HG-ICPMS. MtDNAcn, TL, and genotype of the arsenic-methylating gene AS3MT were determined in blood by real-timePCR. The Chaco participants had less-efficient metabolism, with higher%iAs and%MMA in urine, and lower frequency of the efficient-metabolizing AS3MT haplotype. U-As was associated with increased mtDNAcn in Chaco but not in Andes. U-As was associated with longer TL in Chaco, but less so in Andes. Individuals with%iAs>median showed significantly higher mtDNAcn and TL in both groups. Arsenic was associated with increased mtDNAcn and TL, particularly in individuals with less-efficient arsenic metabolism, who might have increased risk for arsenic-related cancer.
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| 31. |
- Ardila-Ardila, A., et al.
(författare)
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HUMANS: una batería neuropsicologica para la evaluación de pacientes infectados con VIH-1 : [Humans: a neuropsychological battery for evaluating HIV-1 infected patients]
- 2003
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Ingår i: Revista de Neurocirugía. - 1514-3716. ; 36:8, s. 756-762
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Forskningsöversikt (refereegranskat)abstract
- Objective. To develop a neuropsychological test battery in Spanish for the cognitive evaluation of HIV-1 infected patients. Development. Departing from the suggestions presented by the work group of the National Institute of Mental Health (USA), a neuropsychological assessment battery was developed. It was named HUMANS (HIV/University of Miami Annotated Neuropsychological test battery in Spanish). This battery includes the following domains: 1) attention and speed of processing information, 2) memory, 3) executive function, 4) language, 5) visuospacial/visuoconstructive abilities, and 6) motor abilities. Administration takes about 3-4 hours. The English parallel version of this battery has been successfully used in English for over a decade with HIV-1 infected patients. In the paper the development and adaptation to Spanish language of the HUMANS neuropsychology section is presented Conclusions. HUMANS neuropsychological test battery fulfill the recommendations presented by the workgroup of the National Institute of Mental Health for evaluating HIV-1 infected patients. Studies regarding validity and reliability are still required.
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| 34. |
- Broberg, K., et al.
(författare)
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Exposure to inorganic arsenic and gene expression in peripheral blood
- 2016
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Ingår i: Arsenic Research and Global Sustainability - Proceedings of the 6th International Congress on Arsenic in the Environment, AS 2016. - 9781138029415 ; , s. 448-449
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Konferensbidrag (refereegranskat)abstract
- Arsenic is an established carcinogen and a risk factor for several non-malignant diseases. Mechanisms of arsenic toxicity may include interference with gene expression. The impact of arsenic exposure on gene expression was evaluated in women (n = 80) living in the Puna of the northern Argentinian Andes with varying concentrations (10–1251 μg/L) of arsenic in drinking water. DirectHyb HumanHT-12 v4.0 was used for genome wide gene expression analysis. Robust linear regression model was used to each array to evaluate the relations between arsenic exposure, gene expression and with the influence of arsenic metabolism efficiency. Also, Ingenuity Pathway Analysis (IPA) was performed to look for relevant pathways, diseases, networks etc. associated with the genes. In the association between arsenic and gene expression, most of the genes were downregu-lated. Pathway analyses revealed different expression pattern associated with arsenic exposure between women with high and low urinary %MMA, indicating variation in arsenic susceptibility by arsenic-methylation.
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- de Haan, J. E. S., et al.
(författare)
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Stabilising system frequency using HVDC between the Continental European, Nordic, and Great Britain systems
- 2016
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Ingår i: Sustainable Energy, Grids and Networks. - : Elsevier. - 2352-4677. ; 5, s. 125-134
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Tidskriftsartikel (refereegranskat)abstract
- For future efficiency improvement of the frequency containment process (primary control) within European power systems, cooperation between (multiple) synchronous areas using their controllable HVDC interconnections is optioned. However, the differences in system size, HVDC interconnection capacity, and the balancing performance per individual system will have its specific system frequency effect for each different balancing cooperation concept. Consequently, without alignment on cooperation, HVDC balancing might lead to disproportional support between systems, to frequency oscillations, reserve unreliability and non-compliancy, and to network constraints. Therefore, this work assesses frequency quality and associated DC power flows for several balancing arrangements, using a developed load-frequency control model with frequency interdependency for coupled power system. For a trilateral balancing cooperation case study, it is found that certain cooperation concepts result in undesired frequency oscillation and poor frequency quality. However, cooperation where especially fast-response services are shared, such as virtual inertia, show improved system frequency performance. For the case where power imbalances are proportionately distributed among the systems, it is concluded that power transfers over HVDC interconnections are limited and additional control optimisation can be performed. Those concepts with aligned central or coordinated control show best results for a future cooperation for balancing between synchronous areas.
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| 44. |
- Fernandes Gomes, Bárbara, et al.
(författare)
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α-Synuclein seed amplification assay as a diagnostic tool for parkinsonian disorders.
- 2023
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Ingår i: Parkinsonism & related disorders. - 1873-5126. ; 117
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Tidskriftsartikel (refereegranskat)abstract
- Synucleinopathies such as Parkinson's disease (PD) and multiple system atrophy (MSA) can be challenging to diagnose due to the symptom overlap with, for example, atypical parkinsonisms like progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Seed amplification assays (SAA), developed for the detection of α-synuclein (αSyn) aggregates in CSF, have been successful when used as a biomarker evaluation for synucleinopathies. In this study, we investigated the potential of this assay to not only detect αSyn seeds in CSF, but also discriminate between movement disorders.The αSyn-SAA was tested in a Scandinavian cohort composed of 129 CSF samples from patients with PD (n=55), MSA (n=27), CBD (n=7), and PSP (n=16), as well as healthy controls (HC, n=24).The αSyn seed amplification assay (αSyn-SAA) was able to correctly identify all PD samples as positive (sensitivity of 100%) while also discriminating the PD group from HC (70.8% specificity, p<0.0001) and tauopathies [CBD (71% specificity) and PSP (75% specificity), p<0.0001)]. The αSyn-SAA was also able to identify almost all MSA samples as positive for αSyn aggregation (sensitivity of 92.6%). In general, this assay is able to discriminate between the synucleinopathies and tauopathies analyzed herein (p<0.0001) despite the overlapping symptoms in these diseases.These findings suggest the αSyn-SAA is a useful diagnostic tool for differentiating between different parkinsonian disorders, although further optimization may be needed.
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| 47. |
- Li, Chen, et al.
(författare)
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Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length
- 2020
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Ingår i: American Journal of Human Genetics. - : CELL PRESS. - 0002-9297 .- 1537-6605. ; 106:3, s. 389-404
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
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