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1.	Ahmad, Shafqat, et al. (author) Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. : combined analysis of 111,421 individuals of European ancestry 2013 In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 9:7, s. 1003607-1003607 Journal article (peer-reviewed)abstract Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
2.	Ahmad, Shafqat, et al. (author) Gene x physical activity interactions in obesity : combined analysis of 111,421 individuals of European ancestry 2013 In: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 9:7, s. e1003607- Journal article (peer-reviewed)abstract Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
3.	Alexandersson, Erik, et al. (author) Plant secretome proteomics 2013 In: Frontiers in Plant Science. - : Frontiers Media SA. - 1664-462X. ; 4 Research review (peer-reviewed)abstract The plant secretome refers to the set of proteins secreted out of the plant cell into the surrounding extracellular space commonly referred to as the apoplast. Secreted proteins maintain cell structure and acts in signaling and are crucial for stress responses where they can interact with pathogen effectors and control the extracellular environment. Typically, secreted proteins contain an N-terminal signal peptide and are directed through the endoplasmic reticulum/Golgi pathway. However, in plants many proteins found in the secretome lack such a signature and might follow alternative ways of secretion. This review covers techniques to isolate plant secretomes and how to identify and quantify their constituent proteins. Furthermore, bioinformatical tools to predict secretion signals and define the putative secretome are presented. Findings from proteomic studies and important protein families of plant secretomes, such as proteases and hydrolases, are highlighted.
4.	Ali, Amjad, et al. (author) A potential electrolyte (Ce1-x CaxO2-delta) for fuel cells:Theoretical andexperimental study 2018 In: Ceramics International. - : ELSEVIER SCI LTD. - 0272-8842 .- 1873-3956. ; 44:11, s. 12676-12683 Journal article (peer-reviewed)abstract First-principles calculations are performed using density function theory to explore the effects of dopant Ca in ceria (Ce1-x CaxO2-delta). The impact of oxygen vacancy on band gap and density of states is examined in doped ceria using generalized gradient approximations. Vacancy association and vacancy formation energies of the doped ceria are calculated to reveal the effect of dopant on ion conduction. The experimental study of the sample Ce0.875Ca0.125O2-delta) was performed to compare with the theoretical results. The obtained results from theoretical calculation and experimental techniques show that oxygen vacancy increases the volume, lattice constant (5.47315 angstrom) but decrease the band gap (1.72 eV) and bulk modulus. The dopant radius (1.173 angstrom) and lattice constant (5.4718 angstrom) are also calculated by equations which is close to the DFT lattice parameter. The result shows that oxygen vacancy shifts the density of states to lower energy region. Band gap is decreased due to shifting of valence states to conduction band. Vacancy formation shows a significance increase in density of states near the Fermi level. Density of states at Fermi level is proportional to the conductivity, so an increase in density of states near the Fermi level increases the conductivity. The experimental measured ionic conductivity is found to 0.095 S cm(-1) at 600 degrees C. The microstructural studies is also reported in this work.
5.	Ali, Ashfaq (author) Defence and signalling in Potato-Phytophthora infestans interactions 2012 Doctoral thesis (other academic/artistic)abstract Potato is one of the major food crops and its yield is severely affected by late blight disease caused by Phytophthora infestans. P. infestans has the ability to manipulate plant defence signalling by secreting effector molecules causing so called effector triggered susceptibility. Some plants can recognize these effectors via resistance proteins that reactivate plant defence and lead to effector triggered immunity. This thesis discusses identification and analysis of field-pathological relevant potato material for resistance against P. infestans. The two selected potato clones were shown to be resistant, in fields with diverse P.infestans populations, and in growth chambers with a highly virulent Swedish P.infestans strain. They have slightly different resistance reaction at phenotypic and molecular level. One of the two resistant potato clones (SW93-1015) showed an unusual reduction in hypersensitive reaction expansion and part of the induced defence system was constitutively expressed in this potato clone. These two resistant potato clones and the susceptible cultivar Desiree were studied by a combination of quantitative proteomics assisted with newly generated sequence data, and genome wide transcriptomics. A number of putative effector-targets in the potato secretome, often single members of large gene families were identified. These studies have also provided us with insight to components involved in successful plant defence amid hypersensitive response. By analysing crossing populations, a remarkably simple genetic resistance in the potato clone SW93-1015 was identified. We also present a primary global phosphoproteomics analysis that led to identification of novel phosphosites and phosphorylation of several P. infestans effectors. These findings lead us to a better understanding of plant pathogen interactions in field relevant systems and hopefully will allow us to create more tools to overcome this devastating crop disease.
6.	Ali, Ashfaq, et al. (author) Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? : Findings From the GLACIER and the MDC Studies 2016 In: Circulation. - 1942-325X .- 1942-3268. ; 9:2, s. 162-171 Journal article (peer-reviewed)abstract Background Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability.Methods and Results We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk [GLACIER Study; N=4312] and the Malmo Diet and Cancer Study [N=5352]). The genetic loci were amalgamated into a weighted genetic risk score (WGRS(TG)) by summing the triglyceride-elevating alleles (weighted by their established marginal effects) for all loci. Both BMI and the WGRS(TG) were strongly associated with triglyceride concentrations in GLACIER, with each additional BMI unit (kg/m(2)) associated with 2.8% (P=8.4x10(-84)) higher triglyceride concentration and each additional WGRS(TG) unit with 2% (P=7.6x10(-48)) higher triglyceride concentration. Each unit of the WGRS(TG) was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (P-interaction=0.056). Meta-analyses of results from the Swedish cohorts yielded a statistically significant WGRS(TG)xBMI interaction effect (P-interaction=6.0x10(-4)), which was strengthened by including data from the Danish cohorts (P-interaction=6.5x10(-7)). In the meta-analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRS(TG)xBMIxsex) was observed (P-interaction=0.03), where the WGRS(TG)xBMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci.Conclusions Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females.
7.	Ali, Ashfaq, et al. (author) Paranoid potato : phytophthora-resistant genotype shows constitutively activated defense 2012 In: Plant Signaling and Behavior. - : Informa UK Limited. - 1559-2316 .- 1559-2324. ; 7:3, s. 400-408 Journal article (peer-reviewed)abstract Phytophthora is the most devastating pathogen of dicot plants. There is a need for resistance sources with different modes of action to counteract the fast evolution of this pathogen. In order to better understand mechanisms of defense against P. infestans, we analyzed several clones of potato. Two of the genotypes tested, Sarpo Mira and SW93-1015, exhibited strong resistance against P. infestans in field trials, whole plant assays and detached leaf assays. The resistant genotypes developed different sizes of hypersensitive response (HR)-related lesions. HR lesions in SW93-1015 were restricted to very small areas, whereas those in Sarpo Mira were similar to those in Solanum demissum, the main source of classical resistance genes. SW93-1015 can be characterized as a cpr (constitutive expressor of PR genes) genotype without spontaneous microscopic or macroscopic HR lesions. This is indicated by constitutive hydrogen peroxide (H₂O₂) production and PR1 (pathogenesis-related protein 1) secretion. SW93-1015 is one of the first plants identified as having classical protein-based induced defense expressed constitutively without any obvious metabolic costs or spontaneous cell death lesions.
8.	Ali, Ashfaq, et al. (author) Quantitative proteomics and transcriptomics of potato in response to Phytophthora infestans in compatible and incompatible interactions 2014 In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 15 Journal article (peer-reviewed)abstract Background: In order to get global molecular understanding of one of the most important crop diseases worldwide, we investigated compatible and incompatible interactions between Phytophthora infestans and potato (Solanum tuberosum). We used the two most field-resistant potato clones under Swedish growing conditions, which have the greatest known local diversity of P. infestans populations, and a reference compatible cultivar. Results: Quantitative label-free proteomics of 51 apoplastic secretome samples (PXD000435) in combination with genome-wide transcript analysis by 42 microarrays (E-MTAB-1515) were used to capture changes in protein abundance and gene expression at 6, 24 and 72 hours after inoculation with P. infestans. To aid mass spectrometry analysis we generated cultivar-specific RNA-seq data (E-MTAB-1712), which increased peptide identifications by 17%. Components induced only during incompatible interactions, which are candidates for hypersensitive response initiation, include a Kunitz-like protease inhibitor, transcription factors and an RCR3-like protein. More secreted proteins had lower abundance in the compatible interaction compared to the incompatible interactions. Based on this observation and because the well-characterized effector-target C14 protease follows this pattern, we suggest 40 putative effector targets. Conclusions: In summary, over 17000 transcripts and 1000 secreted proteins changed in abundance in at least one time point, illustrating the dynamics of plant responses to a hemibiotroph. Half of the differentially abundant proteins showed a corresponding change at the transcript level. Many putative hypersensitive and effector-target proteins were single representatives of large gene families.
9.	Ali Ahmad, Syed Ossama, et al. (author) Application of two-dimensional materials in perovskite solar cells: recent progress, challenges, and prospective solutions 2021 In: Journal of Materials Chemistry C. - : ROYAL SOC CHEMISTRY. - 2050-7526 .- 2050-7534. ; 9:40, s. 14065-14092 Research review (peer-reviewed)abstract Perovskite solar cells (per-SCs) with high performance and cost-effective solution processing have been the center of interest for researchers in the past decade. Power conversion efficiencies (PCEs) have been gradually improved up to 25.2% with relatively improved stability, which is an unparalleled progress in all generations of solar cell (SC) technology. However, there are still some prevailing challenges regarding the stability and upscaling of these promising devices. Recently, 2D layered materials (LMs) have been extensively explored to overcome the prevailing challenges of poor stability (under moisture, light soaking and high temperature), halide segregation, hysteresis, involvement of toxic materials (i.e., lead), and upscaling of devices. A critical review addressing the recent developments in the use of 2D materials, especially transition metal dichalcogenides (TMDCs), is hence necessary. The development of novel synthesis and deposition techniques including liquid-metal synthesis and ultrasonic assisted spray pyrolysis has offered more efficient fabrication of 2D-LMs with controlled thickness and morphology. Effective functionalization approaches to increase the dispersability of 2D-LMs in non-polar solvents has boosted their potential application in solar cell technology as well. Moreover, compositing 2D TMDCs with suitable organic/inorganic compounds has enabled superior charge kinetics in all functional parts of per-SCs. In addition, newly developed materials such as graphyne and graphdyine along with 2D metal organic frameworks (MOFs) and covalent organic frameworks (COFs) have been employed in per-SCs to achieve PCEs up to 20%. This review summarizes the recent progress and challenges in the application of 2D-LMs in per-SCs and outlines the future pathways to further extend the PCE of per-SCs beyond 25%. This review particularly focuses on 2D-LMs as electrode materials and additives, the underlying charge (electron-hole) transport phenomenon in the functional layers, and their chemical and structural stability.
10.	Ali, Myzoon, et al. (author) Prevalence, Trajectory, and Predictors of Poststroke Pain: Retrospective Analysis of Pooled Clinical Trial Data Set 2023 In: Stroke. - 1524-4628. ; 54:12, s. 3107-3116 Journal article (peer-reviewed)abstract BACKGROUND: Poststroke pain remains underdiagnosed and inadequately managed. To inform the optimum time to initiate interventions, we examined prevalence, trajectory, and participant factors associated with poststroke pain. METHODS: Eligible studies from the VISTA (Virtual International Stroke Trials Archives) included an assessment of pain. Analyses of individual participant data examined demography, pain, mobility, independence, language, anxiety/depression, and vitality. Pain assessments were standardized to the European Quality of Life Scale (European Quality of Life 5 Dimensions 3 Level) pain domain, describing no, moderate, or extreme pain. We described pain prevalence, associations between participant characteristics, and pain using multivariable models. RESULTS: From 94 studies (n>48 000 individual participant data) in VISTA, 10 (n=10 002 individual participant data) included a pain assessment. Median age was 70.0 years (interquartile range [59.0-77.1]), 5560 (55.6%) were male, baseline stroke severity was National Institutes of Health Stroke Scale score 10 (interquartile range [7-15]). Reports of extreme pain ranged between 3% and 9.5% and were highest beyond 2 years poststroke (31/328 [9.5%]); pain trajectory varied by study. Poorer independence was significantly associated with presence of moderate or extreme pain (5 weeks-3 months odds ratio [OR], 1.5 [95% CI, 1.4-1.6]; 4-6 months OR, 1.7 [95% CI, 1.3-2.1]; >6 months OR, 1.5 [95% CI, 1.2-2.0]), and increased severity of pain (5 weeks-3 months: OR, 1.2 [95% CI, 1.1-1.2]; 4-6 months OR, 1.1 [95% CI, 1.1-1.2]; >6 months, OR, 1.2 [95% CI, 1.1-1.2]), after adjusting for covariates. Anxiety/depression and lower vitality were each associated with pain severity. CONCLUSIONS: Between 3% and 9.5% of participants reported extreme poststroke pain; the presence and severity of pain were independently associated with dependence at each time point. Future studies could determine whether and when interventions may reduce the prevalence and severity of poststroke pain.
11.	Ali, Myzoon, et al. (author) Validation of general pain scores from multidomain assessment tools in stroke 2024 In: FRONTIERS IN NEUROLOGY. - 1664-2295. ; 15 Journal article (peer-reviewed)abstract Purpose We describe how well general pain reported in multidomain assessment tools correlated with pain-specific assessment tools; associations between general pain, activities of daily living and independence after stroke.Materials and methods Analyses of individual participant data (IPD) from the Virtual International Stroke Trials Archive (VISTA) described correlation coefficients examining (i) direct comparisons of assessments from pain-specific and multidomain assessment tools that included pain, (ii) indirect comparisons of pain assessments with the Barthel Index (BI) and modified Rankin Scale (mRS), and (iii) whether pain identification could be enhanced by accounting for reported usual activities, self-care, mobility and anxiety/depression; factors associated with pain.Results European Quality of Life 3- and 5-Level (EQ-5D-3L and EQ-5D-5L), RAND 36 Item Health Survey 1.0 (SF-36) or the 0-10 Numeric Pain Rating Scale (NPRS) were available from 10/94 studies (IPD = 10,002). The 0-10 NPRS was the only available pain-specific assessment tool and was a reference for comparison with other tools. Pearson correlation coefficients between the 0-10 NPRS and (A) the EQ-5D-3L and (B) EQ5D-5 L were r = 0.572 (n = 436) and r = 0.305 (n = 1,134), respectively. mRS was better aligned with pain by EQ-5D-3L (n = 8,966; r = 0.340) than by SF-36 (n = 623; r = 0.318). BI aligned better with pain by SF-36 (n = 623; r = -0.320). Creating a composite score using the EQ-5D 3 L and 5 L comprising pain, mobility, usual-activities, self-care and anxiety/depression did not improve correlation with the 0-10 NPRS.Discussion The EQ-5D-3L pain domain aligned better than the EQ-5D-5L with the 0-10 NPRS and may inform general pain description where resources and assessment burden hinder use of additional, pain-specific assessments.
12.	Atabaki-Pasdar, Naeimeh, et al. (author) Statistical power considerations in genotype-based recall randomized controlled trials 2016 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6 Journal article (peer-reviewed)abstract Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for gene-metformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design.
13.	Broholm, Christa, et al. (author) Human adipogenesis is associated with genome-wide DNA methylation and gene-expression changes 2016 In: Epigenomics. - : Future Medicine Ltd. - 1750-1911 .- 1750-192X. ; 8:12, s. 1601-1617 Journal article (peer-reviewed)abstract Aim: To define the genomic distribution and function of DNA methylation changes during human adipogenesis. Methods: We isolated adipocyte-derived stem cells from 13 individuals and analyzed genome-wide DNA methylation and gene expression in cultured adipocyte-derived stem cells and mature adipocytes. Results: We observed altered DNA methylation of 11,947 CpG sites and altered expression of 11,830 transcripts after differentiation. De novo methylation was observed across all genomic elements. Co-existence of genes with both altered expression and DNA methylation was found in genes important for cell cycle and adipokine signaling. Conclusion: Human adipogenesis is associated with significant DNA methylation changes across the entire genome and may impact regulation of cell cycle and adipokine signaling.
14.	Clausen, Anders Ranegaard, et al. (author) Two thymidine kinases and one multisubstrate deoxyribonucleoside kinase salvage DNA precursors in Arabidopsis thaliana. 2012 In: The FEBS Journal. - : Wiley. - 1742-464X. ; 279:20, s. 3889-3897 Journal article (peer-reviewed)abstract Deoxyribonucleotides are the building blocks of DNA and can be synthesized via de novo and salvage pathways. Deoxyribonucleoside kinases (dNKs) salvage deoxyribonucleosides by transfer of a phosphate group to the 5' of a deoxyribonucleoside. This salvage pathway is well characterized in mammals but in contrast little is known about how plants salvage deoxyribonucleosides. We show that during salvage, deoxyribonucleosides can be phosphorylated by extracts of Arabidopsis thaliana into corresponding mono-phosphate compounds with a surprising preference for purines over pyrimidines. Deoxyribonucleoside kinase activities were present in all tissues during all growth stages. In the A. thaliana genome we identified two types of genes that could encode enzymes which are involved in the salvage of deoxyribonucleosides. Thymidine kinase activity was encoded by two thymidine kinase 1-like genes (AtTK1a and AtTK1b) and deoxyadenosine, deoxyguanosine and deoxycytidine kinase activities were encoded by a single AtdNK gene. T-DNA insertion lines of AtTK1a and AtTK1b mutant genes had normal growth, but AtTK1a AtTK1b double mutants died at an early stage, which indicates that AtTK1a and AtTK1b catalyze redundant reactions. Our results point out a crucial role for salvage of thymidine during early plant development. © 2012 The Authors Journal compilation © 2012 FEBS.
15.	Dawed, Adem Y., et al. (author) Evidence-based prioritisation and enrichment of genes interacting with metformin in type 2 diabetes 2017 In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 60:11, s. 2231-2239 Journal article (peer-reviewed)abstract Aims/hypothesis: There is an extensive body of literature suggesting the involvement of multiple loci in regulating the action of metformin; most findings lack replication, without which distinguishing true-positive from false-positive findings is difficult. To address this, we undertook evidence-based, multiple data integration to determine the validity of published evidence. Methods: We (1) built a database of published data on gene-metformin interactions using an automated text-mining approach (n = 5963 publications), (2) generated evidence scores for each reported locus, (3) from which a rank-ordered gene set was generated, and (4) determined the extent to which this gene set was enriched for glycaemic response through replication analyses in a well-powered independent genome-wide association study (GWAS) dataset from the Genetics of Diabetes and Audit Research Tayside Study (GoDARTS). Results: From the literature search, seven genes were identified that are related to the clinical outcomes of metformin. Fifteen genes were linked with either metformin pharmacokinetics or pharmacodynamics, and the expression profiles of a further 51 genes were found to be responsive to metformin. Gene-set enrichment analysis consisting of the three sets and two more composite sets derived from the above three showed no significant enrichment in four of the gene sets. However, we detected significant enrichment of genes in the least prioritised category (a gene set in which their expression is affected by metformin) with glycaemic response to metformin (p = 0.03). This gene set includes novel candidate genes such as SLC2A4 (p = 3.24 x 10(-04)) and G6PC (p = 4.77 x 10(-04)). Conclusions/interpretation: We have described a semi-automated text-mining and evidence-scoring algorithm that facilitates the organisation and extraction of useful information about gene-drug interactions. We further validated the output of this algorithm in a drug-response GWAS dataset, providing novel candidate loci for gene-metformin interactions.
16.	Gomez Jimenez, David, et al. (author) Single-cell analysis of myeloid cells in HPV+ tonsillar cancer 2022 Other publication (other academic/artistic)abstract The incidence of Human Papillomavirus positive (HPV+) tonsillar cancer has been sharply rising during the last two decades. Myeloid cells represent an appropriate therapeutic target due to their ability to orchestrate antigen-specific immunity within the tonsil, the availability of viral antigens, and the proximity of the tumor and the underlying lymphoid tissue. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV+ tonsillar cancer. Our analysis unveiled the existence of four dendritic cell lineages, two macrophage polarization processes, and their sequential maturation profiles. We observed an expansion of the myeloid compartment in HPV+ tonsillar cancer, accompanied by interferon-induced cellular responses both in DCs and monocyte-macrophages. Within the DC lineages, we describe a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s, in HPV+ lesions. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC profile. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which gave raise to inflammatory-activated, and chemokine-producing macrophages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1, activated DCs and macrophages in patient survival using signature scoring. The current study contributes towards the understanding of myeloid ontogeny and dynamics in human papilloma driven tonsillar cancer, and details myeloid biomarkers that can be used to predict therapy effects and assess patient prognosis.
17.	Hussain, Fida, et al. (author) A modeling approach for low-temperature SOFC-based micro-combined heat and power systems 2019 In: International Journal of Modern Physics B. - : WORLD SCIENTIFIC PUBL CO PTE LTD. - 0217-9792. ; 33:4 Journal article (peer-reviewed)abstract The world's challenge is to determine a more efficient, economical and environmental-friendly energy source to compete and replace the ongoing conventional energy resources. Solid oxide fuel cells (SOFCs) provide a highly efficient system to use divergent energy resources and have proved to provide the cleanest energy, least energy use, and lowest emissions. A techno-economic study is required to investigate the model design for SOFC-based micro-combined heat and power (m-CHP) systems for applications in terms of educational and commercial buildings. This work models and explores the optimized application of hydrogen gas-fueled SOFC-based m-CHP systems in educational buildings. Two educational departments' loads are presented and model of SOFC-based m-CHP system against the different electric power demands is performed, in order to provide a techno-economic assessment of the technology. For successful development of the technology, results are related to system rightsizing, operating strategies, thermal to electric ratios, and match between end-use, with an aim towards classifying the overall feasibility and essential application requirements.
18.	Hussain, Fida, et al. (author) Comparative electrochemical investigation of zinc based nano-composite anode materials for solid oxide fuel cell 2019 In: Ceramics International. - : Elsevier. - 0272-8842 .- 1873-3956. ; 45:1, s. 1077-1083 Journal article (peer-reviewed)abstract The structural and electrochemical properties of zinc based nano-composites anode materials with a composition of X0.25Ti0.5Zn0.70 (where X = Cu, Mn, Ag) have been investigated in this present study. The proposed Xo.zsTiousZno.70 oxide materials have been synthesized through sol-gel method. The doping effect of Cu, Mn, and Ag on TiZn oxides were analyzed in terms of electronic conduction and power density in hydrogen atmosphere at comparatively low temperature in the range of 650 degrees C. The crystal structure and surface morphology were examined by X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis techniques. The XRD patterns of composites depict that the average crystalline sizes lie in the range of 20-100 nm. Four -probe DC conductivity technique was used to measure the conductivity of the materials and maximum electrical conductivity of Ag0.25Ti0.05Zn0.70 oxide was found to be 7.81 S/cm at 650 degrees C. The band gap and absorption spectra were determined by ultra-violet visible (UV-Vis) and Fourier Transform Infrared spectroscopy (FTIR) techniques respectively. The maximum power density was achieved to be 354 mW/cm(2) at 650 degrees C by Ag0.25Ti0.05Zn0.70 oxide anode with SDC (electrolyte) and BSCF (conventional cathode) materials.
19.	Jimenez, David Gomez, et al. (author) Single-cell analysis of myeloid cells in HPV+ tonsillar cancer 2023 In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13 Journal article (peer-reviewed)abstract The incidence of human papillomavirus-positive (HPV+) tonsillar cancer has been sharply rising during the last decades. Myeloid cells represent an appropriate therapeutic target due to their proximity to virus-infected tumor cells, and their ability to orchestrate antigen-specific immunity, within the tonsil. However, the interrelationship of steady-state and inflammatory myeloid cell subsets, and their impact on patient survival remains unexplored. Here, we used single-cell RNA-sequencing to map the myeloid compartment in HPV+ tonsillar cancer. We observed an expansion of the myeloid compartment in HPV+ tonsillar cancer, accompanied by interferon-induced cellular responses both in dendritic cells (DCs) and monocyte-macrophages. Our analysis unveiled the existence of four DC lineages, two macrophage polarization processes, and their sequential maturation profiles. Within the DC lineages, we described a balance shift in the frequency of progenitor and mature cDC favoring the cDC1 lineage in detriment of cDC2s. Furthermore, we observed that all DC lineages apart from DC5s matured into a common activated DC transcriptional program involving upregulation of interferon-inducible genes. In turn, the monocyte-macrophage lineage was subjected to early monocyte polarization events, which give rise to either interferon-activated or CXCL-producing macrophages, the latter enriched in advanced tumor stages. We validated the existence of most of the single-cell RNA-seq clusters using 26-plex flow cytometry, and described a positive impact of cDC1 and interferon-activated DCs and macrophages on patient survival using gene signature scoring. The current study contributes to the understanding of myeloid ontogeny and dynamics in HPV-driven tonsillar cancer, and highlights myeloid biomarkers that can be used to assess patient prognosis.
20.	Kim, Min, et al. (author) Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort 2019 In: Alzheimer's & Dementia. - : Elsevier. - 1552-5260 .- 1552-5279. ; 15:6, s. 817-827 Journal article (peer-reviewed)abstract INTRODUCTION: A critical and as-yet unmet need in Alzheimer's disease (AD) is the discovery of peripheral small molecule biomarkers. Given that brain pathology precedes clinical symptom onset, we set out to test whether metabolites in blood associated with pathology as indexed by cerebrospinal fluid (CSF) AD biomarkers.METHODS: This study analyzed 593 plasma samples selected from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery study, of individuals who were cognitively healthy (n = 242), had mild cognitive impairment (n = 236), or had AD-type dementia (n = 115). Logistic regressions were carried out between plasma metabolites (n = 883) and CSF markers, magnetic resonance imaging, cognition, and clinical diagnosis.RESULTS: Eight metabolites were associated with amyloid β and one with t-tau in CSF, these were primary fatty acid amides (PFAMs), lipokines, and amino acids. From these, PFAMs, glutamate, and aspartate also associated with hippocampal volume and memory.DISCUSSION: PFAMs have been found increased and associated with amyloid β burden in CSF and clinical measures.
21.	Lankinen, Åsa, et al. (author) Plant immunity in natural populations and agricultural fields: Low presence of pathogenesis-related proteins in Solanum leaves 2018 In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13 Journal article (peer-reviewed)abstract Plant immunity has mainly been studied under controlled conditions, limiting our knowledge regarding the regulation of immunity under natural conditions where plants grow in association with multiple microorganisms. Plant pathology theory, based on laboratory data, predicts complex biochemical plant-pathogen interactions leading to coevolution of pathogen infectivity vs. plant recognition of microbes in multiple layers over time. However, plant immunity is currently not evaluated in relation to ecological time-scales and field conditions. Here we report status of immunity in plants without visible disease symptoms in wild populations of nightshades, Solanum dulcamara and Solanum nigrum, and in agricultural fields of potato, Solanum tuberosum. We analysed presence of pathogenesis-related proteins in over 500 asymptomatic leaf samples collected in the field in June, July and August over three years. Pathogenesis-related proteins were present in only one-third of the collected samples, suggesting low activity of the immune system. We could also detect an increase in pathogenesis-related proteins later in the growing season, particularly in S. tuberosum. Our findings, based on pathogenesis-related protein markers, indicate major gaps in our knowledge regarding the status and regulation of plant immunity under field conditions.
22.	Lenman, Marit, et al. (author) Effector-driven marker development and cloning of resistance genes against Phytophthora infestans in potato breeding clone SW93-1015 2016 In: TAG Theoretical and Applied Genetics. - : Springer Science and Business Media LLC. - 0040-5752 .- 1432-2242. ; 129, s. 105-115 Journal article (peer-reviewed)abstract Phytophthora infestans is one of the most devastating plant pathogens worldwide. We have earlier found that the SW93-1015 potato breeding clone has an efficient resistance against P. infestans under field conditions in Sweden, which has an unusually high local diversity of the pathogen. This potato clone has characteristics that are different from classical R-gene-mediated resistance such as elevated levels of hydrogen peroxide (H2O2) under controlled conditions. Analysis of 76 F1 potato progenies from two individual crosses resulted in nearly 50 % resistant clones, from both crosses. This result suggests that the SW93-1015 clone has a simplex genotype for this trait. Screening with over 50 different P. infestans effectors, containing the conserved motif RXLR (for Arg, any amino acid, Leu, Arg), revealed a specific response to Avr2, which suggests that SW93-1015 might contain a functional homolog of the R2 resistance gene. We cloned eight R2 gene homologs from SW93-1015, whereof seven have not been described before and one gene encoded a protein identical to Rpi-ABPT. Expression of this gene in potato cultivar D,sir,e provided R2-specific resistance, whereas other homologues did not. Using RNAseq analyses we designed a new DNA marker for the R2 resistance in SW93-1015. In summary, we have demonstrated the use of effector screening in practical breeding material and revealed the key resistance mechanism for SW93-1015.
23.	Lileikyte, Gabriele, et al. (author) Serum proteome profiles in patients treated with targeted temperature management after out-of-hospital cardiac arrest 2023 In: Intensive Care Medicine Experimental. - 2197-425X. ; 11:1 Journal article (peer-reviewed)abstract BACKGROUND: Definition of temporal serum proteome profiles after out-of-hospital cardiac arrest may identify biological processes associated with severe hypoxia-ischaemia and reperfusion. It may further explore intervention effects for new mechanistic insights, identify candidate prognostic protein biomarkers and potential therapeutic targets. This pilot study aimed to investigate serum proteome profiles from unconscious patients admitted to hospital after out-of-hospital cardiac arrest according to temperature treatment and neurological outcome.METHODS: Serum samples at 24, 48, and 72 h after cardiac arrest at three centres included in the Target Temperature Management after out-of-hospital cardiac arrest trial underwent data-independent acquisition mass spectrometry analysis (DIA-MS) to find changes in serum protein concentrations associated with neurological outcome at 6-month follow-up and targeted temperature management (TTM) at 33 °C as compared to 36 °C. Neurological outcome was defined according to Cerebral Performance Category (CPC) scale as "good" (CPC 1-2, good cerebral performance or moderate disability) or "poor" (CPC 3-5, severe disability, unresponsive wakefulness syndrome, or death).RESULTS: Of 78 included patients [mean age 66 ± 12 years, 62 (80.0%) male], 37 (47.4%) were randomised to TTM at 36 °C. Six-month outcome was poor in 47 (60.3%) patients. The DIA-MS analysis identified and quantified 403 unique human proteins. Differential protein abundance testing comparing poor to good outcome showed 19 elevated proteins in patients with poor outcome (log 2-fold change (FC) range 0.28-1.17) and 16 reduced proteins (log 2(FC) between - 0.22 and - 0.68), involved in inflammatory/immune responses and apoptotic signalling pathways for poor outcome and proteolysis for good outcome. Analysis according to level of TTM showed a significant protein abundance difference for six proteins [five elevated proteins in TTM 36 °C (log 2(FC) between 0.33 and 0.88), one reduced protein (log 2(FC) - 0.6)] mainly involved in inflammatory/immune responses only at 48 h after cardiac arrest. CONCLUSIONS: Serum proteome profiling revealed an increase in inflammatory/immune responses and apoptosis in patients with poor outcome. In patients with good outcome, an increase in proteolysis was observed, whereas TTM-level only had a modest effect on the proteome profiles. Further validation of the differentially abundant proteins in response to neurological outcome is necessary to validate novel biomarker candidates that may predict prognosis after cardiac arrest.
24.	Luukkonen, Panu K., et al. (author) Impaired hepatic lipid synthesis from polyunsaturated fatty acids in TM6SF2 E167K variant carriers with NAFLD 2017 In: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 67:1, s. 128-136 Journal article (peer-reviewed)abstract Background: Carriers of the transmembrane 6 superfamily member 2 E167K gene variant (TM6SF2(EK/KK)) have decreased expression of the TM6SF2 gene and increased risk of NAFLD and NASH. Unlike common 'obese/metabolic' NAFLD, these subjects lack hypertriglyceridemia and have lower risk of cardiovascular disease. In animals, phosphatidylcholine (PC) deficiency results in a similar phenotype. PCs surround the core of VLDL consisting of triglycerides (TGs) and cholesteryl-esters (CEs). We determined the effect of the TM6SF2 E167K on these lipids in the human liver and serum and on hepatic gene expression and studied the effect of TM6SF2 knockdown on hepatocyte handling of these lipids.Methods: Liver biopsies were taken from subjects characterized with respect to the TM6SF2 genotype, serum and liver lipidome, gene expression and histology. In vitro, after TM6SF2 knockdown in HuH-7 cells, we compared incorporation of different fatty acids into TGs, CEs, and PCs.Results: The TM6SF2(EK/KK) and TM6SF2EE groups had similar age, gender, BMI and HOMA-IR. Liver TGs and CEs were higher and liver PCs lower in the TM6SF2(EK/KK) than the TM6SF2EE group (p<0.05). Polyunsaturated fatty acids (PUFA) were deficient in liver and serum TGs and liver PCs but hepatic free fatty acids were relatively enriched in PUFA (p<0.05). Incorporation of PUFA into TGs and PCs in TM6SF2 knockdown hepatocytes was decreased (p< 0.05). Hepatic expression of TM6SF2 was decreased in variant carriers, and was co-expressed with genes regulated by PUFAs.Conclusions: Hepatic lipid synthesis from PUFAs is impaired and could contribute to deficiency in PCs and increased intrahepatic TG in TM6SF2 E167K variant carriers. (C) 2017 European Association for the Study of the Liver.
25.	Luukkonen, Panu K., et al. (author) Saturated fat is more metabolically harmful for the human liver than unsaturated fat or simple sugars 2018 In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:8, s. 1732-1739 Journal article (peer-reviewed)abstract OBJECTIVE: Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG. RESEARCH DESIGN AND METHODS: We overfed 38 overweight subjects (age 48 ± 2 years, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia), insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks. RESULTS: Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P < 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression. CONCLUSIONS: Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced the greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes. © 2018 by the American Diabetes Association.
26.	Mahmood, Rashid, et al. (author) Assessment of antidiabetic potential and phytochemical profiling of Rhazya stricta root extracts 2020 In: BMC Complementary Medicine and Therapies. - : Springer Nature. - 2662-7671. ; 20:1 Journal article (peer-reviewed)abstract Background: Diabetes mellitus is a chronic disease characterized by hyperglycemia that may occur due to genetic, environmental or lifestyle factors. Natural remedies have been used to treat diabetes since long and many antidiabetic compounds of varied efficacies have been isolated from medicinal plants. Rhazya stricta has been used for decades for the treatment of diabetes mellitus and associated ailments. Considering the folkloric use of R. stricta against diabetes, it was aimed to investigate the effectiveness of its root extracts against diabetes through in vitro assays and in vivo studies using animal model along with phytochemical profiling through GCMS. Methods: Various fractions of Rhazya stricta obtained through column chromatography were evaluated for a variety of assays including a-glucosidase, Dipeptidyl peptidase-IV (DPP-IV), beta-secretase and Glucagon-like peptide-1 (GLP-1) secretion studies. For the in vivo studies the alloxan-induced diabetic mice were treated with root extracts and blood glucose levels, HbA1C, and other biochemical markers along with the histological study of the liver were done. The phytochemical identification was performed using an Agilent 7890B GC coupled to a 7010 Triple Quadrupole (MS/MS) system. GraphPad Prism software version 5.01 was used for statistical analysis. Results: Majority of the extract fractions showed excellent results against diabetes by inhibiting enzymes DPP-IV (Up to 61%) and beta-secretase (Up to 83%) with IC50s 979 pg/ml and 169 mu g/ml respectively with increase in the GLP1 secretion. The results of in vivo studies indicated a marked reduction in blood glucose and HbA1c levels along with positive effects on other parameters like lipid profile, liver functions and renal functions of extract-treated mice as compared to control. The histological examination of the liver demonstrated hepatoprotective effects against diabetes led changes and various classes of phytochemicals were also identified through GCMS in different fractions. Conclusion: The results revealed strong antidiabetic activity of R. stricta root with the potential to protect body organs against diabetic changes. Moreover, a variety of phytochemicals has also been identified through GCMS that might be responsible for the antidiabetic potential of Rhazya stricta root.
27.	Merino, Irene, et al. (author) Metabolomic and transcriptomic analyses identify external conditions and key genes underlying high levels of toxic glycoalkaloids in tubers of stress-sensitive potato cultivars 2023 In: Frontiers in Plant Science. - 1664-462X. ; 14 Journal article (peer-reviewed)abstract Introduction: High levels of toxic steroidal glycoalkaloids (SGAs) in potato tubers constitute a recognized food quality problem. Tuber SGA levels vary between potato cultivars and can increase after post-harvest stresses such as wounding and light exposure. A few cultivars, e.g., ‘Magnum Bonum’ and ‘Lenape,’ have been withdrawn from commercial sales due to excessive SGA levels during some cultivation years. However, these sudden SGA increases are diffucult to predict, and their causes are not understood. To identify external and genetic factors that underlie sudden SGA increases in certain potato cultivars, we have here in a 2-year study investigated ‘Magnum Bonum’ and five additional table potato cultivars for their SGA levels after wounding and light exposure. Results and methods: Results showed that ‘Magnum Bonum’ has an unusual strong SGA response to light exposure, but not to wounding, whereas ‘Bintje’ displayed an opposite regulation. Levels of calystegine alkaloids were not significantly altered by treatments, implicating independent metabolic regulation of SGA and calystegine levels also under conditions of high SGA accumulation. Metabolomic and transcriptomic analyses identified a small number of key genes whose expression correlated with SGA differences between cultivars. Overexpression of two key genes in transgenic low-SGA potato cultivars increased their leaf SGA levels significantly. Discussion: The results show that a strong response to light can underlie the SGA peaks that occasionally occur in certain potato cultivars and indicate that a between-cultivar variation in the expression of single SGA key genes can account for cultivar SGA differerences. We propose that current attempts to mitigate the SGA hazard will benefit from an increased consideration of cultivar-dependent SGA responses to post-harvest conditions, particularly light exposure. The identified key SGA genes can now be used as a molecular tool in this work.
28.	Rafique, Asia, et al. (author) An efficient carbon resistant composite Ni0.6Zn0.4O2-delta-GDC anode for biogas fuelled solid oxide fuel cell 2019 In: Journal of Power Sources. - : ELSEVIER. - 0378-7753 .- 1873-2755. ; 438 Journal article (peer-reviewed)abstract This paper describes the fabrication of Ni0.6Zn0.4-Gd0.2Ce0.8O2-delta (NiZn-GDC) via a two-step wet chemical synthesis technique. This composite was found to be more thermally stable and carbon resistive under the intense reducing environment of biogas. This was confirmed by different characterization techniques. The maximum power density P-max, was achieved at 600 degrees C as 820 mW/cm(2) and 548 mW/cm(2) with hydrogen and biogas, respectively. Different characterization techniques have been performed, such as X-ray diffractometry (XRD), scanning electron microscopy (SEM/EDX), UV visible spectroscopy, and Raman spectroscopy. The XRD pattern by Rietveld refinement showed two-phase structures of the anode composite with an average crystallite size of 25 35 nm before and after reduction with methane. The optical band gap (E-g(opt)) of NiZn-GDC was calculated to be 2.24eV from the Tauc plot using absorbance data. The Nyquist plot was also drawn to study the AC electrochemical impedance spectra (EIS) of the nanocomposite anode from 450 degrees C to 600 degrees C in air. The maximum DC conductivity of 1.37 S/cm was observed at a temperature of 600 degrees C using the four-probe DC technique.
29.	Rafique, Asia, et al. (author) Multioxide phase-based nanocomposite electrolyte (M@SDC where M = Zn2+ / Ba2+/ La2+/Zr-2/Al3+) materials 2020 In: Ceramics International. - : ELSEVIER SCI LTD. - 0272-8842 .- 1873-3956. ; 46:52, s. 6882-6888 Journal article (peer-reviewed)abstract This paper deals with the development of a highly dense and stable electrolyte on the base of nanoionics oxide interface theory. This gives a comparative study of two-phase nanocomposite electrolytes that are developed for low temperature solid oxide fuel cells (LT-SOFCs). These nanocomposites are synthesised with different oxides, which are coated on the doped ceria that showed high oxide ion mobility for LT-SOFCs. These novel two-phase nanocomposite oxide ionic conductors (MCe0.8Sm0.2O2-MO2, where M = Zn2+/Ba2+/La3+/Zr2+/Al3+) were synthesised by a co-precipitation method. The interface study between these two phases was analysed by electrochemical impedance spectroscopy (EIS), while ionic conductivities were measured with DC conductivity (four probe method). The nanocomposite electrolytes exhibited higher conductivities with the increase of concentration of coated oxides but decreased at a certain level. The structural or morphological properties of the nanocomposite electrolytes were examined by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The thermal stability was investigated using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The maximum performance of 590 mW/cm(2) at 550 degrees C was obtained for the Zn@SDC based cell, and the rest of the coated samples Ba@SDC, La@SDC, Zr@SDC and Al@SDC based cells showed values of 550 mW/cm(2), 540 mW/cm(2), 450 mW/cm(2), 340 mW/cm(2), respectively, with hydrogen as a fuel. Therefore, the coated-SDC based nanocomposite materials are a good approach for lowering the operating temperature to achieve the challenges of the solid oxide fuel cells (SOFC). These two-phase nanocomposite electrolytes satisfy the all requirements which one electrolyte should have, like high ionic conduction, thermodynamic stability and negligible electronic conduction.
30.	Raza, Rizwan, et al. (author) Nanocomposite BaZr0.7Sm0.1Y0.2O3-delta-La0.8Sr0.2Co0.2Fe0.8O3-delta materials for single layer fuel cell 2017 In: International journal of hydrogen energy. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0360-3199 .- 1879-3487. ; 42:34, s. 22280-22287 Journal article (peer-reviewed)abstract Single layer fuel cell (SLFC) is a novel breakthrough in energy conversion technology. This study is to realize the physical-electrochemical co-driving mechanism of a single component device composed of mixed ionic and semiconductor material. This paper is focused on investigating the mechanism and characterization of synthesized nanocomposite BaZr0.7Sm0.1Y0.2O3-delta (BZSY) La0.8Sr0.2Co0.2Fe0.8O3-delta (LSCF) in proportion 1:1 and 3:7 for SLFC. The crystallographic structure and morphology is studied with X-ray diffraction (XRD) and scanning electron microscopy (SEM). The nano-particles lie in the range of 100 210 nm. Ultraviolet (UV) and electrochemical impedance spectroscopy (EIS) is used to analyze the semiconducting nature of nanocomposite (BZSY LSCF). The performance of SLFC was carried out at different temperatures ranging between 400 and 650 degrees C. The mixed conductivity of the synthesized material was about 2.3 S cm(-1). The synergic effect of junction and energy band gap towards charge separation as well as the promotion of ion transport by junction built in field contributes to the working principle and high power output in the SLFC. (C) 2017 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved.
31.	Resjö, Svante, et al. (author) Proteomic analysis of phytophthora infestans reveals the importance of cell wall proteins in pathogenicity 2017 In: Molecular and Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 16:11, s. 1958-1971 Journal article (peer-reviewed)abstract The oomycete Phytophthora infestans is the most harmful pathogen of potato. It causes the disease late blight, which generates increased yearly costs of up to one billion euro in the EU alone and is difficult to control. We have performed a large-scale quantitative proteomics study of six P. infestans life stages with the aim to identify proteins that change in abundance during development, with a focus on preinfectious life stages. Over 10 000 peptides from 2061 proteins were analyzed. We identified several abundance profiles of proteins that were up- or downregulated in different combinations of life stages. One of these profiles contained 59 proteins that were more abundant in germinated cysts and appressoria. A large majority of these proteins were not previously recognized as being appressorial proteins or involved in the infection process. Among those are proteins with putative roles in transport, amino acid metabolism, pathogenicity (including one RXLR effector) and cell wall structure modification. We analyzed the expression of the genes encoding nine of these proteins using RT-qPCR and found an increase in transcript levels during disease progression, in agreement with the hypothesis that these proteins are important in early infection. Among the nine proteins was a group involved in cell wall structure modification and adhesion, including three closely related, uncharacterized proteins encoded by PITG-01131, PITG-01132, and PITG-16135, here denoted Piacwp1-3. Transient silencing of these genes resulted in reduced severity of infection, indicating that these proteins are important for pathogenicity. Our results contribute to further insight into P. infestans biology, and indicate processes that might be relevant for the pathogen while preparing for host cell penetration and during infection. The mass spectrometry data have been deposited to ProteomeXchange via the PRIDE partner repository with the data set identifier PXD002446.
32.	Resjö, Svante, et al. (author) Quantitative Label-Free Phosphoproteomics of Six Different Life Stages of the Late Blight Pathogen Phytophthora infestans Reveals Abundant Phosphorylation of Members of the CRN Effector Family 2014 In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:4, s. 1848-1859 Journal article (peer-reviewed)abstract The oomycete Phytophthora infestans is the causal agent of late blight in potato and tomato. Since the underlying processes that govern pathogenicity and development in P. infestans are largely unknown, we have performed a large-scale phosphoproteomics study of six different P. infestans life stages. We have obtained quantitative data for 2922 phosphopeptides and compared their abundance. Life-stages-pecific phosphopeptides include ATP-binding cassette transporters and a kinase that only occurs in appressoria. In an extended data set, we identified 2179 phosphorylation sites and deduced 22 phosphomotifs. Several of the phosphomotifs matched consensus sequences of kinases that occur in P. infestans but not Arabidopsis. In addition, we detected tyrosine phosphopeptides that are potential targets of kinases resembling mammalian tyrosine kinases. Among the phosphorylated proteins are members of the RXLR and Crinkler effector families. The latter are phosphorylated in several life stages and at multiple positions, in sites that are conserved between different members of the Crinkler family. This indicates that proteins in the Crinkler family have functions beyond their putative role as (necrosis-inducing) effectors. This phosphoproteomics data will be instrumental for studies on oomycetes and host oomycete interactions. The data sets have been deposited to ProteomeXchange (identifier PXD000433).
33.	Salman, Muhammad, et al. (author) Trajectory of COVID-19 vaccine hesitancy post-vaccination and public's intention to take booster vaccines : A cross-sectional analysis 2023 In: Human Vaccines & Immunotherapeutics. - : Taylor & Francis. - 2164-5515 .- 2164-554X. ; 19:2 Journal article (peer-reviewed)abstract Vaccine hesitancy (VH) is not a new phenomenon in Pakistan and is regarded as one of the primary causes of unsatisfactory vaccination campaigns. This study determined post-vaccination COVID-19 VH, factors influencing COVID-19 vaccine uptake, and public's intent to receive booster vaccinations. A cross-sectional study was conducted among adult population of Lahore, Pakistan. Participants were recruited via convenience sampling between March and May 2022. SPSS version 22 was used for the data analysis. A total of 650 participants were included in the study (age = 28.1 & PLUSMN; 9.7 years; male-to-female ratio nearly 1: 1). The majority of participants received Sinopharm followed by Sinovac vaccine. The top three reasons of vaccine uptake were "only vaccinated individuals are allowed at the workplace, and educational institutes" (Relative importance index (RII) = 0.749), "only vaccinated people are allowed to go to markets, malls and other public places" (RII = 0.746), and "protect myself from the infection" (RII = 0.742). The mean COVID-19 VH score was 24.5 & PLUSMN; 6.2 (95% CI 23.9-24.9), with not being pro-vaccines and poor economic status were the significant predictors of COVID-19 vaccine hesitancy among immunized individuals (p < .05). Acceptance of booster vaccines was negatively associated with younger age and a lower level of education. Furthermore, being pro-vaccine was associated with a greater likelihood of accepting booster vaccines (p = .001). The Pakistani public continues to express VH toward COVID-19 vaccines. Therefore, aggressive measures must be taken to combat the community factors that contribute to it.
34.	Sandin, Marianne, et al. (author) An adaptive alignment algorithm for quality-controlled label-free LC-MS. 2013 In: Molecular & Cellular Proteomics. - 1535-9484 .- 1535-9476. ; 12:5, s. 1407-1420 Journal article (peer-reviewed)abstract Label-free quantification using precursor-based intensities is a versatile workflow for large-scale proteomics studies. The method requires extensive computational analysis and is therefore in need of robust quality control during the data mining stage. We present a new label-free data analysis workflow integrated into a multi-user software platform. A novel adaptive alignment algorithm has been developed to minimize the possible systematic bias introduced into the analysis. Parameters are estimated on the fly from the data at hand, producing a user-friendly analysis suite. Quality metrics are output in every step of the analysis as well as actively incorporated into the parameter estimation. We furthermore show the improvement of this system by comprehensive comparison to classical label-free analysis methodology as well as current state-of-the-art software.
35.	Sarfraz, Amina, et al. (author) Catalytic Effect of Silicon Carbide on the Composite Anode of Fuel Cells 2021 In: ACS Applied Energy Materials. - : AMER CHEMICAL SOC. - 2574-0962. ; 4:7, s. 6436-6444 Journal article (peer-reviewed)abstract High efficiency, fuel flexibility, and sustainable energy conversion make fuel cells attractive compared to conventional energy systems. The direct ethanol fuel cells have attracted much attention because of the direct utilization of ethanol fuel. Anode materials are required to enhance the catalytic activity of the liquid fuel, which oxidize the fuel at lower operating temperature. Therefore, the catalytic effect using silicon carbide has been investigated in the LiNiO2-delta anode. The material has been characterized, and it is found that SiC shows a cubic structure and LiNiO2-delta exhibits a hexagonal structure, while the LiNiO2-delta-SiC composite exhibits a mixed cubic and hexagonal phase. Scanning electron microscopy depicts that the material is porous. The Fourier transform infrared spectroscopy analysis shows the presence of Si-O-Si, Si-C, C=O, and Si-OH bonding. The LiNiO2-delta-SiC composite (1:0.3) exhibited a maximum electrical conductivity of 1.34 S cm(-1) at 650 degrees C with an electrical band gap of 0.84 eV. The fabricated cell with the LiNiO2-delta-SiC anode exhibits a power density of 0.20 W cm(-2) at 650 degrees C with liquid ethanol fuel. The results show that there is a promising catalytic activity of SiC in the fuel cell anode.
36.	Seidel, Laura (author) The Baltic Sea from the present to future : microbial carbon & nutrient cycling in a changing climate 2022 Doctoral thesis (other academic/artistic)abstract Climate Change is caused by the accelerated increase of anthropogenic greenhousegas emissions to the atmosphere and affects all ecosystems on our planet. A resultof higher CO2 uptake by the oceans as well as an increase of heat trapped in theatmosphere leads to, for example acidification, stratification, sea-level rise, oxygenloss, and temperature increase of the earth’s waterbodies. The IntergovernmentalPanel on Climate Change (IPCC) predicts the earth’s surface temperature to risebetween 1.0-5.7°C by the year 2100 and ocean temperatures are predicted to rise byup to 2.0°C.This thesis focuses on the effects of environmental changes on microbes and theirfunctions in coastal Baltic Sea sediments and overlying bottom-waters. The studiesexamine potential effects of ongoing climate change in combination with coastaleutrophication, as well as long-term warming due to e.g. climate change within anatural fluctuating system and a laboratory based incubation experiment.Investigation of coastal sediment and overlying bottom-waters showed thatpotential future changes on bacterial communities due to eutrophication incombination with climate change relies on the water depth and oxygen supply. Inaddition, the study of a natural seasonal fluctuating and long-term artificially heatedcoastal bay (compared to an unaffected control bay) gave insights into how theecosystem might react to future climate change. On one hand, bottom waters in theheated bay showed decreased bacterial diversity, suspended seasonal patterns pluselevated and prolonged cyanobacterial blooming. On the other hand, surfacesediment communities in the heated bay had an altered microbial community withdecreased seasonal variation and higher diversity likely due to a shallowing ofgeochemical layers. Furthermore, increased energy production occurred althoughhigher stress RNA transcripts suggested that the microbial community’stemperature optima were below that of the water. Nevertheless, incubationexperiments showed that exposure to short-term elevated temperatures shifted thecontrol bay microbial community closer to that of the heated bay with a similarresponse on RNA level at higher temperatures (28 °C).In summary, this thesis provides new insights into ongoing and likely future climatechange effects on coastal microbial communities, which are key players for nutrientandenergy cycling of the marine ecosystem.
37.	Seidel, Laura, et al. (author) Weakened resilience of benthic microbial communities in the face of climate change 2022 In: ISME Communications. - : Springer Nature. - 2730-6151. ; 2:1 Journal article (peer-reviewed)abstract Increased ocean temperature associated with climate change is especially intensified in coastal areas and its influence on microbialcommunities and biogeochemical cycling is poorly understood. In this study, we sampled a Baltic Sea bay that has undergone 50years of warmer temperatures similar to RCP5-8.5 predictions due to cooling water release from a nuclear power plant. The systemdemonstrated reduced oxygen concentrations, decreased anaerobic electron acceptors, and higher rates of sulfate reduction.Chemical analyses, 16S rRNA gene amplicons, and RNA transcripts all supported sediment anaerobic reactions occurring closer tothe sediment-water interface. This resulted in higher microbial diversities and raised sulfate reduction and methanogenesistranscripts, also supporting increased production of toxic sulfide and the greenhouse gas methane closer to the sediment surface,with possible release to oxygen deficient waters. RNA transcripts supported prolonged periods of cyanobacterial bloom that mayresult in increased climate change related coastal anoxia. Finally, while metatranscriptomics suggested increased energyproduction in the heated bay, a large number of stress transcripts indicated the communities had not adapted to the increasedtemperature and had weakened resilience. The results point to a potential feedback loop, whereby increased temperatures mayamplify negative effects at the base of coastal biochemical cycling.
38.	Siino, Valentina, et al. (author) Plasma proteome profiling of healthy individuals across the life span in a Sicilian cohort with long-lived individuals 2022 In: Aging Cell. - : Wiley. - 1474-9718 .- 1474-9726. ; 21:9 Journal article (peer-reviewed)abstract The study of healthy human aging is important for shedding light on the molecular mechanisms behind aging to promote well-being and to possibly predict and/or avoid the development of age-related disorders such as atherosclerosis and diabetes. Herein, we have employed an untargeted mass spectrometry-based approach to study age-related protein changes in a healthy Sicilian plasma cohort including long-lived individuals. This approach confirmed some of the previously known proteins correlated with age including fibulin-1, dystroglycan, and gamma-glutamyl hydrolase. Furthermore, our findings include novel proteins that correlate with age and/or with location and uric acid, which could represent a unique signature for healthy aging.
39.	Slieker, Roderick C, et al. (author) Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes : an IMIRHAPSODY Study 2021 In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:11, s. 2683-2693 Journal article (peer-reviewed)abstract Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease.
40.	Slieker, Roderick C, et al. (author) Identification of biomarkers for glycaemic deterioration in type 2 diabetes 2023 In: Nature Communications. - 2041-1723. ; 14, s. 1-18 Journal article (peer-reviewed)abstract We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.
41.	Slieker, Roderick C, et al. (author) Replication and cross-validation of type 2 diabetes subtypes based on clinical variables : an IMI-RHAPSODY study 2021 In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64:9, s. 1982-1989 Journal article (peer-reviewed)abstract Aims/hypothesis: Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes. In the current study we replicate and cross-validate these type 2 diabetes clusters in three large cohorts using variables readily measured in the clinic. Methods: In three independent cohorts, in total 15,940 individuals were clustered based on age, BMI, HbA1c, random or fasting C-peptide, and HDL-cholesterol. Clusters were cross-validated against the original clusters based on HOMA measures. In addition, between cohorts, clusters were cross-validated by re-assigning people based on each cohort’s cluster centres. Finally, we compared the time to insulin requirement for each cluster. Results: Five distinct type 2 diabetes clusters were identified and mapped back to the original four All New Diabetics in Scania (ANDIS) clusters. Using C-peptide and HDL-cholesterol instead of HOMA2-B and HOMA2-IR, three of the clusters mapped with high sensitivity (80.6–90.7%) to the previously identified severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) clusters. The previously described ANDIS mild age-related diabetes (MARD) cluster could be mapped to the two milder groups in our study: one characterised by high HDL-cholesterol (mild diabetes with high HDL-cholesterol [MDH] cluster), and the other not having any extreme characteristic (mild diabetes [MD]). When these two milder groups were combined, they mapped well to the previously labelled MARD cluster (sensitivity 79.1%). In the cross-validation between cohorts, particularly the SIDD and MDH clusters cross-validated well, with sensitivities ranging from 73.3% to 97.1%. SIRD and MD showed a lower sensitivity, ranging from 36.1% to 92.3%, where individuals shifted from SIRD to MD and vice versa. People belonging to the SIDD cluster showed the fastest progression towards insulin requirement, while the MDH cluster showed the slowest progression. Conclusions/interpretation: Clusters based on C-peptide instead of HOMA2 measures resemble those based on HOMA2 measures, especially for SIDD, SIRD and MOD. By adding HDL-cholesterol, the MARD cluster based upon HOMA2 measures resulted in the current clustering into two clusters, with one cluster having high HDL levels. Cross-validation between cohorts showed generally a good resemblance between cohorts. Together, our results show that the clustering based on clinical variables readily measured in the clinic (age, HbA1c, HDL-cholesterol, BMI and C-peptide) results in informative clusters that are representative of the original ANDIS clusters and stable across cohorts. Adding HDL-cholesterol to the clustering resulted in the identification of a cluster with very slow glycaemic deterioration. Graphical abstract: [Figure not available: see fulltext.]
42.	Ullah, Muhammad Kaleem, et al. (author) Tri-doped ceria (M0.2Ce0.8O2-δ, M= Sm0.1 Ca0.05 Gd0.05) electrolyte for hydrogen and ethanol-based fuel cells 2019 In: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388. ; 773, s. 548-554 Journal article (peer-reviewed)abstract In recent scientific research, an interest has been gained significantly by rare earth metals such as cerium (Ce), samarium (Sm) and gadolinium (Gd) due to their use in fuel cells as electrolyte and catalysts. When used in an electrolyte, these materials lower the fuel cell's operating temperature compared to a conventional electrolyte, for example, yittria-stabilized zirconia (YSZ) which operates at a high temperature (≥800 °C). In this paper, the tri-doped ceria, M0.2Ce0.8O2-δ(M = Sm0.1Ca0.05Gd0.05) electrolyte powders was synthesized using the co-precipitation method at 80 °C. These dopants were used for CeO2with a total molar ratio of 1 M. Dry-pressed powder technique was used to make fuel cell pellets from the powder and placed them in the furnace to sinter at 700 °C for 60 min. Electrical conductivity of such a pellet in air was 1.2 × 10−2S cm−1at 700 °C measured by the ProboStat-NorECs setup. The crystal structure was determined with the help of X-ray diffraction (XRD), which showed that all the dopants were successfully doped in CeO2. Raman spectroscopy and UV-VIS spectroscopy were also carried out to analyse the molecular vibrations and absorbance, respectively. The maximum open-circuit voltages (OCVs) for hydrogen and ethanol fuelled at 550 °C were observed to be 0.89 V and 0.71 V with power densities 314 mW cm−2and 52.8 mW cm−2, respectively.
43.	Varga, Tibor V, et al. (author) Lipidomic profiles, lipid trajectories and clinical biomarkers in female elite endurance athletes 2020 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10, s. 1-9 Journal article (peer-reviewed)abstract We assessed whether blood lipid metabolites and their changes associate with various cardiometabolic, endocrine, bone- and energy-related comorbidities of Relative Energy Deficiency in Sport (RED-S) in female elite endurance athletes. Thirty-eight Scandinavian female elite athletes underwent a day-long exercise test. Five blood samples were obtained during the day - at fasting state and before and after two standardized exercise tests. Clinical biomarkers were assessed at fasting state, while untargeted lipidomics was undertaken using all blood samples. Linear and logistic regression was used to assess associations between lipidomic features and clinical biomarkers. Overrepresentations of findings with P < 0.05 from these association tests were assessed using Fisher's exact tests. Self-organizing maps and a trajectory clustering algorithm were utilized to identify informative clusters in the population. Twenty associations PFDR < 0.05 were detected between lipidomic features and clinical biomarkers. Notably, cortisol demonstrated an overrepresentation of associations with P < 0.05 compared to other traits (PFisher = 1.9×10-14). Mean lipid trajectories were created for 201 named features for the cohort and subsequently by stratifying participants by their energy availability and menstrual dysfunction status. This exploratory analysis of lipid trajectories indicates that participants with menstrual dysfunction might have decreased adaptive response to exercise interventions.
44.	Varga, Tibor V., et al. (author) Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults 2017 In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:4, s. 1211-1222 Journal article (peer-reviewed)abstract Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.Methods: Participants from the GLACIER Study (N-max = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms;replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (Delta TC) and triglycerides (Delta TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; N-max = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N similar to 190 000) and functional annotation for the top ranking variants.Results: In total, 956 variants were associated (P < 0.01) with either Delta TC or Delta TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with Delta TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 x 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 x 10(-6)). The rs7412 variant at APOE was associated with DTC in GLACIER (P < 1.7 x 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with Delta TC and for Delta TG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 x 10(-4)), multiple variants at HPR (P-min = 1.5 x 10(-6)) and a variant at SIX5 (P = 1.9 x 10(-4)) showed evidence for association with CAD.Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.
45.	Wiechec, Emilia, et al. (author) Hypoxia induces radioresistance, epithelial?mesenchymal transition, cancer stem cell?like phenotype and changes in genes possessing multiple biological functions in head and neck squamous cell carcinoma 2022 In: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 47:3 Journal article (peer-reviewed)abstract Hypoxia has been linked with increased resistance to treatment in various solid tumors, including head and neck squamous cell carcinoma (HNSCC). The aim of the present study was to identify genes involved in hypoxia?mediated responses to radiotherapy in HNSCC. A total of three HNSCC cell lines with an epithelial phenotype were selected for this study and cultured under normoxic (21% O2) or hypoxic (1% O2) conditions. The sensitivity of the HNSCC cells to radiotherapy was assessed by a crystal violet assay. Western blotting (for protein expression), cDNA microarrays and reverse transcription?quantitative PCR (for gene expression) were also applied. Small interfering RNA silencing was used to knock down target genes. The results revealed that hypoxia negatively affected the response of HNSCC cells to radiotherapy. Of note, increased levels of N?cadherin, vimentin and fibronectin, as well as stem cell?associated transcription factors, were observed under hypoxia. The microarray analysis revealed a number of hypoxia?regulated genes that were involved in multiple biological functions. However, downregulation of hypoxia?regulated genes did not affect sensitivity to radiotherapy of the investigated cell lines. Taken together, the present findings indicated several important pathways and genes that were involved in hypoxia and radiotherapy resistance. It is hypothesized that panels of reported hypoxia?regulated genes may be useful for the prediction of radiotherapy responses in patients with HNSCC.
46.	Wilkinson, John L., et al. (author) Pharmaceutical pollution of the world's rivers 2022 In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:8 Journal article (peer-reviewed)abstract Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.

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