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1.	Carraminana, Albert, et al. (författare) Rationale and Study Design for an Individualized Perioperative Open Lung Ventilatory Strategy in Patients on One-Lung Ventilation (iPROVE-OLV) 2019 Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : W B SAUNDERS CO-ELSEVIER INC. - 1053-0770 .- 1532-8422. ; 33:9, s. 2492-2502 Tidskriftsartikel (refereegranskat)abstract Objective: The aim of this clinical trial is to examine whether it is possible to reduce postoperative complications using an individualized perioperative ventilatory strategy versus using a standard lung-protective ventilation strategy in patients scheduled for thoracic surgery requiring one-lung ventilation. Design: International, multicenter, prospective, randomized controlled clinical trial. Setting: A network of university hospitals. Participants: The study comprises 1,380 patients scheduled for thoracic surgery. Interventions: The individualized group will receive intraoperative recruitment maneuvers followed by individualized positive end-expiratory pressure (open lung approach) during the intraoperative period plus postoperative ventilatory support with high-flow nasal cannula, whereas the control group will be managed with conventional lung-protective ventilation. Measurements and Main Results: Individual and total number of postoperative complications, including atelectasis, pneumothorax, pleural effusion, pneumonia, acute lung injury; unplanned readmission and reintubation; length of stay and death in the critical care unit and in the hospital will be analyzed for both groups. The authors hypothesize that the intraoperative application of an open lung approach followed by an individual indication of high-flow nasal cannula in the postoperative period will reduce pulmonary complications and length of hospital stay in high-risk surgical patients. (C) 2019 Published by Elsevier Inc.
2.	Cruz, Raquel, et al. (författare) Novel genes and sex differences in COVID-19 severity 2022 Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 31:22, s. 3789-3806 Tidskriftsartikel (refereegranskat)abstract Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.
3.	Ferrando, Carlos, et al. (författare) Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy : a randomised controlled trial 2020 Ingår i: British Journal of Anaesthesia. - : ELSEVIER SCI LTD. - 0007-0912 .- 1471-6771. ; 124:1, s. 110-120 Tidskriftsartikel (refereegranskat)abstract Background: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. Methods: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. Results: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. Conclusions: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found.
4.	Martínez-Sánchez, Noelia, et al. (författare) Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance 2017 Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 26:1, s. 212-229.e12 Tidskriftsartikel (refereegranskat)abstract Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.
5.	Bernal, Ximena E., et al. (författare) Empowering Latina scientists 2019 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 363:6429, s. 825-826 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
6.	Kassebaum, Nicholas J., et al. (författare) Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658 Tidskriftsartikel (refereegranskat)abstract Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
7.	Kattge, Jens, et al. (författare) TRY plant trait database - enhanced coverage and open access 2020 Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188 Tidskriftsartikel (refereegranskat)abstract Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
8.	Martinez-Alvarez, Concepcion, et al. (författare) Injection and adhesion palatoplasty : a preliminary study in a canine model 2013 Ingår i: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 183:2, s. 654-662 Tidskriftsartikel (refereegranskat)abstract Background: Raising mucoperiosteal flaps in traditional palatoplasty impairs mid-facial growth. Hyaluronic acid-based hydrogels have been successfully tested for minimally invasive craniofacial bone generation in vivo as carriers of bone morphogenetic protein-2 (BMP-2). We aimed to develop a novel flapless technique for cleft palate repair by injecting a BMP-2 containing hydrogel. Material and methods: Dog pups with congenital cleft palate were either non-treated (n = 4) or treated with two-flap palatoplasty (n = 6) or with the proposed injection/adhesion technique (n = 5). The experimental approach was to inject a hyaluronic acid-based hydrogel containing hydroxyapatite and BMP-2 subperiosteally at the cleft palate margins of pups aged six weeks. At week ten, a thin strip of the medial edge mucosa was removed and the margins were closed directly. Occlusal photographs and computed tomography (CT) scans were obtained up to week 20. Results: Four weeks after the gel injection the cleft palate margins had reached the midline and engineered bone had enlarged the palatal bones. Removal of the medial edge mucosa and suturing allowed complete closure of the cleft. Compared to traditional palatoplasty, the injection/adhesion technique was easier, and the post-surgical recovery was faster. CT on week 20 revealed some overlapping or "bending" of palatal shelves in the two-flap repair group, which was not observed in the experimental nor control groups. Conclusion: A minimally invasive technique for cleft palate repair upon injectable scaffolds in a dog model of congenital cleft palate is feasible. Results suggest better growth of palatal bones. This represents an attractive clinical alternative to traditional palatoplasty for cleft palate patients.
9.	Lundy, Lian, et al. (författare) Making Waves : Collaboration in the time of SARS-CoV-2 - rapid development of an international co-operation and wastewater surveillance database to support public health decision-making 2021 Ingår i: Water Research. - : Elsevier. - 0043-1354 .- 1879-2448. ; 199 Tidskriftsartikel (refereegranskat)abstract The presence of SARS-CoV-2 RNA in wastewater was first reported in March 2020. Over the subsequent months, the potential for wastewater surveillance to contribute to COVID-19 mitigation programmes has been the focus of intense national and international research activities, gaining the attention of policy makers and the public. As a new application of an established methodology, focused collaboration between public health practitioners and wastewater researchers is essential to developing a common understanding on how, when and where the outputs of this non-invasive community-level approach can deliver actionable outcomes for public health authorities. Within this context, the NORMAN SCORE “SARS-CoV-2 in sewage” database provides a platform for rapid, open access data sharing, validated by the uploading of 276 data sets from nine countries to-date. Through offering direct access to underpinning meta-data sets (and describing its use in data interpretation), the NORMAN SCORE database is a resource for the development of recommendations on minimum data requirements for wastewater pathogen surveillance. It is also a tool to engage public health practitioners in discussions on use of the approach, providing an opportunity to build mutual understanding of the demand and supply for data and facilitate the translation of this promising research application into public health practice.
10.	Muscarella, Robert, et al. (författare) The global abundance of tree palms 2020 Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 29:9, s. 1495-1514 Tidskriftsartikel (refereegranskat)abstract AimPalms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change.LocationTropical and subtropical moist forests.Time periodCurrent.Major taxa studiedPalms (Arecaceae).MethodsWe assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure.ResultsOn average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work.ConclusionsTree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests.
11.	Neugart, Susanne, et al. (författare) A synchronized, large-scale field experiment using Arabidopsis thaliana reveals the significance of the UV-B photoreceptor UVR8 under natural conditions 2024 Ingår i: Plant, Cell and Environment. - : Blackwell Publishing. - 0140-7791 .- 1365-3040. Tidskriftsartikel (refereegranskat)abstract This study determines the functional role of the plant ultraviolet-B radiation (UV-B) photoreceptor, UV RESISTANCE LOCUS 8 (UVR8) under natural conditions using a large-scale 'synchronized-genetic-perturbation-field-experiment'. Laboratory experiments have demonstrated a role for UVR8 in UV-B responses but do not reflect the complexity of outdoor conditions where 'genotype × environment' interactions can mask laboratory-observed responses. Arabidopsis thaliana knockout mutant, uvr8-7, and the corresponding Wassilewskija wild type, were sown outdoors on the same date at 21 locations across Europe, ranging from 39°N to 67°N latitude. Growth and climatic data were monitored until bolting. At the onset of bolting, rosette size, dry weight, and phenolics and glucosinolates were quantified. The uvr8-7 mutant developed a larger rosette and contained less kaempferol glycosides, quercetin glycosides and hydroxycinnamic acid derivatives than the wild type across all locations, demonstrating a role for UVR8 under field conditions. UV effects on rosette size and kaempferol glycoside content were UVR8 dependent, but independent of latitude. In contrast, differences between wild type and uvr8-7 in total quercetin glycosides, and the quercetin-to-kaempferol ratio decreased with increasing latitude, that is, a more variable UV response. Thus, the large-scale synchronized approach applied demonstrates a location-dependent functional role of UVR8 under natural conditions.
12.	Teresita Martin-Marquez, Beatriz, et al. (författare) The DNA co-vaccination using Sm antigen and IL-10 as prophylactic experimental therapy ameliorates nephritis in a model of lupus induced by pristane 2021 Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:10 Tidskriftsartikel (refereegranskat)abstract Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies such as anti-Sm. Studies in patients with SLE and murine models of lupus reveal that the most critical anti-Sm autoantibodies are predominantly direct against D1((83-119),) D2, and B/B epitopes.Objectives: The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D1(83-119), D2, B/B, and B/B-COOH in co-vaccination with IFN-gamma or IL-10 in a murine model of lupus induced by pristane.Material and methods: To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D1(83-119), D2, B'/B, B'/B-COOH, IFN-gamma, or IL-10. Lupus was induced by 0.5 mL of pristane via intraperitoneal in BALB/c female mice. Immunoprecipitation with K562 cells was metabolically labeled with S-35 and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-gamma from splenocytes supernatants. Proteinuria was assessed monthly, and lupus nephritis was evaluated by immunofluorescence, and electron microscopy.Results: The prophylactic co-vaccination with D2/IL-10 reduced the expression of kidney damage observed by electron microscopy, direct immunofluorescence, and H & E, along with reduced level of anti-nRNP/Sm antibodies (P = 0.048).Conclusion: The prophylactic co-vaccination of IL-10 with D2 in pristane-induced lupus ameliorates the renal damage maybe by acting as prophylactic DNA tolerizing therapy.
13.	Wang, Haidong, et al. (författare) Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015. 2016 Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
14.	Wang, Haidong, et al. (författare) Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015 2016 Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
15.	Zamora, Juan Carlos, et al. (författare) Considerations and consequences of allowing DNA sequence data as types of fungal taxa 2018 Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185 Tidskriftsartikel (refereegranskat)abstract Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
16.	2019 Tidskriftsartikel (refereegranskat)
17.	Alvarez, Beatriz, et al. (författare) An Exopolysaccharide-Deficient Mutant of Lactobacillus rhamnosus GG Efficiently Displays a Protective Llama Antibody Fragment against Rotavirus on Its Surface 2015 Ingår i: Applied and Environmental Microbiology. - 0099-2240 .- 1098-5336. ; 81:17, s. 5784-5793 Tidskriftsartikel (refereegranskat)abstract Rotavirus is the leading cause of infantile diarrhea in developing countries, where it causes a high number of deaths among infants. Two vaccines are available, being highly effective in developed countries although markedly less efficient in developing countries. As a complementary treatment to the vaccines, a Lactobacillus strain producing an anti-rotavirus antibody fragment in the gastrointestinal tract could potentially be used. In order to develop such an alternative therapy, the effectiveness of Lactobacillus rhamnosus GG to produce and display a VHH antibody fragment (referred to as anti-rotavirus protein 1 [ARP1]) on the surface was investigated. L. rhamnosus GG is one of the best-characterized probiotic bacteria and has intrinsic antirotavirus activity. Among four L. rhamnosus GG strains [GG (CMC), GG (ATCC 53103), GG (NCC 3003), and GG (UT)] originating from different sources, only GG (UT) was able to display ARP1 on the bacterial surface. The genomic analysis of strain GG (UT) showed that the genes welE and welF of the EPS cluster are inactivated, which causes a defect in exopolysaccharide (EPS) production, allowing efficient display of ARP1 on its surface. Finally, GG (UT) seemed to confer a level of protection against rotavirus-induced diarrhea similar to that of wild-type GG (NCC 3003) in a mouse pup model, indicating that the EPS may not be involved in the intrinsic antirotavirus activity. Most important, GG (EM233), a derivative of GG (UT) producing ARP1, was significantly more protective than the control strain L. casei BL23.
18.	Amaia Beatriz, Ortega-Santos, 1995-, et al. (författare) Enzymatic biofuel cells embedded polymer-based soft actuators 2022 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Enzymatic biofuel cells are presented as an untethered alternative energy source that could power small implantable or wearable medical devices. However, most of these catalytic processes do not provide with enough energy to power common small electronic-mechanical devices. On the other hand, conducting polymer-based actuators are of great interest for their biocompatibility, flexibility, processability, possibility to be miniaturized and low power consumption. So far, these artificial muscles have been driven by external power sources that prevent them for being completely autonomous. There is a need for a novel power source to elaborate actuators that could use physiological processes as a driving force. These soft actuators’ low power consumption matches the electrical power generated by the biocatalysis of some enzymes, such as glucose oxidase and laccase in presence of glucose and oxygen in aqueous media. Here, we present the latest results in the development of polypyrrole-based soft actuators powered by enzymatic biofuel cells. The actuator consists of a tri-layer conductive substrate on which the polypyrrole is electrodeposited in both sides. The polypyrrole layers act as the active part, expanding and contracting upon a redox reaction, resulting in a bending movement. Tetrathiofulvlene-7,7,8,8-tetracyanoquinodimethane (TTF-TCNQ) and 2,2′-azino-di-(3-ethylbenzthiazoline sulfonic acid) (ABTS) electron transfer mediators are cast on the surface of the polypyrrole to help the electron transmission. The glucose oxidase and laccase enzymes are immobilized in the modified-conducting polymer surface, integrating the electrode to the actuator. The bio-catalysis of enzymes in presence of glucose and oxygen in aqueous solution provides the actuator with the electrons needed for the redox reaction, converting the chemical energy into mechanical energy, i.e., movement. The glucose-self-powered soft actuator may contribute to the development of more complex implantable, ingestible, or wearable biomedical devices such as cardio-stimulators, insulin pumps, or muscle implants.
19.	Amaia Beatriz, Ortega-Santos, 1995-, et al. (författare) The effect of enzyme immobilization methods in polypyrrole-based soft actuators driven by glucose and O2 2023 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
20.	Avallone, Genaro, et al. (författare) La llamada “crisis de refugiados”, las migraciones y sus consecuencias en Europa. Informe 1y 2 : Percepciones y discursos de las y los estudiantes universitarios 2017 Rapport (populärvet., debatt m.m.)
21.	Bernhardt, Paul V., et al. (författare) Tailoring mixed-valence Co-III/Fe-II complexes for their potential use as sensitizers in dye sensitized solar cells 2008 Ingår i: New Journal of Chemistry. - : Royal Society of Chemistry (RSC). - 1144-0546 .- 1369-9261. ; 32:4, s. 705-711 Tidskriftsartikel (refereegranskat)abstract Dinuclear class II Co-III/Fe-II mixed-valence complexes of type [LnCo (III)(mu-NC) Fe-II(CN)(3)L-2](m-) (where L-n represents a pentadentate macrocycle and L-2 a bpy ligand or two cyanides) have electronic properties that make them possible sensitizers in DSSC ( dye sensitized solar cells). For this purpose the new complex Na-2[{trans-L14COOCo III( m-NC)} Fe II( CN) 5] has been prepared and characterized by the usual methods and its sensitizer properties compared with those of the already known [{trans-L14COOCo (III)(mu-NC)}Fe-II(CN)(5)](2-)(CN)(3)(bipy)(eq,ax)](ClO4). The complex [{trans-L14COOCo (III)(mu-NC)}Fe-II(CN)(5)](2-) has been designed for the actuation of an electron injection from the cobalt centre on MMCT, while the [{trans-L14COOCo (III)(mu-NC)}Fe-II(CN)(3)(bipy)](+) structure can produce a tuned injection from the iron centre via an MLCT electronic state, as described for similar systems. The characterization on solid oxide semiconductor supports has been carried out for these two complexes and the results have been compared with the behaviour observed in aqueous solution and in solvents of varying polarities. Their use in DSSC has been checked and, while a sensitizer response is observed for [{trans-L14COOCo (III)(mu-NC)}Fe-II(CN)(5)](2-), complex [{trans-L14COOCoIII(mu-NC)}Fe-II(CN)(3)(bipy)(eq,ax)](+) does not produce any electrical current on illumination. The low efficiency of the built DSSC can be easily related both with the very low value of the extinction coefficient of the MMCT band responsible for the electron injection, and with the small driving force for the reduction of the complex with the standard I-2/I-3 (-) system used after electron injection.
22.	Bugaytsova, Jeanna, et al. (författare) Acid Responsive Helicobacter pylori Adherence : Implications for Chronic Infection and Disease Annan publikation (övrigt vetenskapligt/konstnärligt)
23.	Cancemi, Annalisa, et al. (författare) Longitudinal change in cerebro-placental ratio (CPR) between 37 and 40 weeks of pregnancy is associated with non-reassuring fetal status and increased risk of cesarean section 2023 Ingår i: Journal of Maternal-Fetal and Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 36:1 Tidskriftsartikel (refereegranskat)abstract Objective: To evaluate in low-risk pregnancies if longitudinal change in cerebro-placental ratio (CPR) between 37 and 40 weeks of pregnancy is associated with cesarean section (CS) for non-reassuring fetal status (NRFS) during labor. Methods: This is a prospective observational study of women with singleton low-risk pregnancies who underwent an ultrasound scan at 36 + 0 to 37 + 6 and 39 + 0 to 41 + 6 weeks of pregnancy, when the CPR was calculated from the middle cerebral artery (MCA) and umbilical artery (UA) pulsatility indices. Managing professionals were kept blinded to the Doppler results. The association of the longitudinal change between both CPR (z-velocity) to CS for NRFS was evaluated by logistic regression. Results: A total of 401 pregnancies were included. The mean time interval between both CPR evaluations was 21 days (SD 7). A CS for fetal distress was performed in 7% of pregnancies. Independent of the CPR at 37 weeks, the likelihood of CS for fetal distress was significantly decreased by the longitudinal changes from 37 to 40 weeks (OR 0.61, 95%CI 0.4–0.92; p=.018). This association remained significant after further adjustment for potential confounders (nulliparity, maternal weight at booking and estimated fetal weight at 37): (OR 0.64, 95%CI 0.41–0.98; p=.044). Conclusions: The longitudinal change of CPR between 37 and 40 weeks is associated with the need for CS for NRFS during labor.
24.	Cervin, Matti, et al. (författare) The centrality of doubting and checking in the network structure of obsessive-compulsive symptom dimensions in youth 2020 Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 59:7, s. 880-889 Tidskriftsartikel (refereegranskat)abstract Objective. Obsessive-compulsive disorder (OCD) is a heterogeneous condition with well-established symptom dimensions across the lifespan. The objective of the present study was to use network analysis to investigate the internal structure and central features of these dimensions in unselected schoolchildren and in youth with OCD.Method. We estimated the network structure of OCD symptom dimensions in 6,991 schoolchildren and 704 youth diagnosed with OCD from 18 sites across six countries. All participants completed the Obsessive Compulsive Inventory - Child Version.Results. In both the school-based and clinic-based samples, the OCD dimensions formed an interconnected network with doubting/checking emerging as a highly central node, i.e. exerting strong influence over other symptom dimensions in the network. The centrality of the doubting/checking dimension was consistent across countries, genders, age groups, clinical status, and tic disorder comorbidity. Network differences were observed for age and gender in the school-based but not the clinic-based samples.Conclusion. The centrality of doubting/checking in the network structure of childhood OCD adds to classic and recent conceptualizations of the disorder in which the important role of doubt in disorder severity and maintenance is highlighted. The present results suggest that doubting/checking is a potentially important target for further research into the etiology and treatment of childhood OCD.
25.	Concepcion Gil-Rodriguez, Maria, et al. (författare) De Novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia de Lange Syndrome-Overlapping Phenotypes 2015 Ingår i: Human Mutation. - : Wiley: 12 months. - 1059-7794 .- 1098-1004. ; 36:4, s. 454-462 Tidskriftsartikel (refereegranskat)abstract Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS-like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS-like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3-associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for approximate to 1%-2% of CdLS-like phenotypes.
26.	Dolan, Brendan, et al. (författare) Clearance of small intestinal crypts involves goblet cell mucus secretion by intracellular granule rupture and enterocyte ion transport 2022 Ingår i: Science Signaling. - : American Association for the Advancement of Science (AAAS). - 1945-0877 .- 1937-9145. ; 15:752 Tidskriftsartikel (refereegranskat)abstract Goblet cells in the small intestinal crypts contain large numbers of mucin granules that are rapidly discharged to clean bacteria from the crypt. Because acetylcholine released by neuronal and nonneuronal cells controls many aspects of intestinal epithelial function, we used tissue explants and organoids to investigate the response of the small intestinal crypt to cholinergic stimulation. The activation of muscarinic acetylcholine receptors initiated a coordinated and rapid emptying of crypt goblet cells that flushed the crypt contents into the intestinal lumen. Cholinergic stimulation induced an expansion of the granule contents followed by intracellular rupture of the mucin granules. The mucus expanded intracellularly before the rupture of the goblet cell apical membrane and continued to expand after its release into the crypt lumen. The goblet cells recovered from membrane rupture and replenished their stores of mucin granules. Mucus secretion from the goblet cells depended on Ca2+ signaling and the expansion of the mucus in the crypt depended on gap junctions and on ion and water transport by enterocytes adjacent to the goblet cells. This distinctive mode of mucus secretion, which we refer to as “expanding secretion,” efficiently cleans the small intestine crypt through coordinated mucus, ion, and fluid secretion by goblet cells and enterocytes.
27.	Fakih, Dalia, et al. (författare) Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs 2018 Ingår i: Jci Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 3:17 Tidskriftsartikel (refereegranskat)abstract The respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), bacteria and mucus accumulates instead. To address the mechanisms behind the mucus accumulation, the proteome of bronchoalveolar lavages from COPD patients and mucus collected in an elastase-induced mouse model of COPD was analyzed, revealing similarities with each other and with the protein content in colonic mucus. Moreover, stratified laminated sheets of mucus were observed in airways from patients with CF and COPD and in elastase-exposed mice. On the other hand, the mucus accumulation in the elastase model was reduced in Muc5b-KO mice. While mucus plugs were removed from airways by washing with hypertonic saline in the elastase model, mucus remained adherent to epithelial cells. Bacteria were trapped on this mucus, whereas, in non-elastase-treated mice, bacteria were found on the epithelial cells. We propose that the adherence of mucus to epithelial cells observed in CF, COPD, and the elastase-induced mouse model of COPD separates bacteria from the surface cells and, thus, protects the respiratory epithelium.
28.	Fernández-Gago, Rocío, et al. (författare) Thawing boar semen in the presence of seminal plasma improves motility, modifies subpopulation patterns and reduces chromatin alterations. 2017 Ingår i: Reproduction, fertility, and development. - : CSIRO PUBLISHING. - 1031-3613. ; 29:8, s. 1576-1584 Tidskriftsartikel (refereegranskat)abstract Seminal plasma could have positive effects on boar semen after thawing. In the present study we investigated changes in the motility and chromatin structure in spermatozoa over 4h incubation (37°C) of boar semen thawed in the presence of 0%, 10% or 50% seminal plasma from good-fertility boars. Cryopreserved doses were used from seven males, three of which were identified as susceptible to post-thawing chromatin alterations. Motility was analysed by computer-aided sperm analysis every hour, and data were used in a two-step clustering, yielding three subpopulations of spermatozoa (slow non-linear, fast non-linear, fast linear). Chromatin structure was analysed using a sperm chromatin structure assay and flow cytometry to determine the DNA fragmentation index (%DFI) as a percentage, the standard deviation of the DFI (SD-DFI) and the percentage of high DNA stainability (%HDS), indicating chromatin compaction. Thawing without seminal plasma resulted in a rapid loss of motility, whereas seminal plasma helped maintain motility throughout the incubation period and preserved the subpopulation comprising fast and linear spermatozoa. The incidence of chromatin alterations was very low in samples from non-susceptible males, whereas samples from males susceptible to post-thawing chromatin alterations exhibited marked alterations in%DFI and%HDS. Seminal plasma partly prevented these alterations in samples from susceptible males. Overall, 50% seminal plasma was the most efficient concentration to protect motility and chromatin. Some changes were concomitant with physiological events reported previously (e.g., semen thawed with 50% seminal plasma increased the production of reactive oxygen species and yielded higher fertility after AI). Thawing in the presence of seminal plasma could be particularly useful in the case of samples susceptible to post-thawing chromatin damage.
29.	Fullman, Nancy, et al. (författare) Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: A systematic analysis from the Global Burden of Disease Study 2016 2018 Ingår i: The Lancet. - : Lancet Publishing Group. - 1474-547X .- 0140-6736. ; 391:10136, s. 2236-2271 Tidskriftsartikel (refereegranskat)
30.	Macías García, Beatriz, et al. (författare) The mitochondria of stallion spermatozoa are more sensitive than the plasmalemma to osmotic induced stress: role of c-Jun N-terminal Kinase (JNKs) pathway 2012 Ingår i: Journal of Andrology. - Schaumburg, IL, United States : American Society of Andrology. - 0196-3635 .- 1939-4640. ; 33:1, s. 105-113 Tidskriftsartikel (refereegranskat)abstract Cryopreservation introduces extreme temperature and osmolality changes that impart lethal and sublethal effects on spermatozoa. Additionally, there is evidence that the osmotic stress induced by cryopreservation causes oxidative stress to spermatozoa. The main sources of reactive oxygen species in mammalian sperm are the mitochondria. In view of this, the aim of our study was to test whether or not osmotic stress was able to induce mitochondrial damage and to explore the osmotic tolerance of the mitochondria of stallion spermatozoa. Ejaculates from 7 stallions were subjected to osmolalities ranging from 75 to 1500 mOsm/kg, and the effect on sperm membrane integrity and mitochondrial membrane potential was studied. Additionally, the effects of changes in osmolality from hyposmotic to isosmotic and from hyperosmotic to isosmotic solutions were studied (osmotic excursions). The cellular volume of stallion spermatozoa under isosmotic conditions was 20.4 ± 0.33 μm3. When exposed to low osmolality, the stallion spermatozoa behaved like a linear osmometer, whereas exposure to high osmolalities up to 900 mOsm/kg resulted in decreased sperm volume. Although sperm membranes were relatively resistant to changes in osmolality, mitochondrial membrane potential decreased when osmolalities were low or very high (10.7 ± 1.74 and 16.5 ± 1.70 at 75 and 150 mOsm/kg, respectively, and 13.1 ± 1.83 at 1500 mOsm/kg), whereas in isosmolar controls the percentage of stallion sperm mitochondria with a high membrane potential was 41.1 ± 1.69 (P < .01). Osmotic excursions induced greater damage than exposure of spermatozoa to a given nonphysiologic osmolality, and again the mitochondria were more prone to damage induced by osmotic excursions than was the sperm plasma membrane. In search of intracellular components that could mediate these changes, we have detected for the first time the c-Jun N-terminal kinase 1/2 in stallion spermatozoa, which are apparently involved in the regulation of the viability of these cells.
31.	Martínez, Beatriz, et al. (författare) Evaluation of the LSA-SAF Gross Primary Production product derived from SEVIRI/MSG data (MGPP) 2020 Ingår i: ISPRS Journal of Photogrammetry and Remote Sensing. - : Elsevier BV. - 0924-2716. ; 159, s. 220-236 Tidskriftsartikel (refereegranskat)abstract The objective of this study is to describe a completely new 10-day gross primary production (GPP) product(MGPP LSA-411) based on data from the geostationary SEVIRI/MSG satellite within the LSA SAF (Land SurfaceAnalysis SAF) as part of the SAF (Satellite Application Facility) network of EUMETSAT.The methodology relies on the Monteith approach. It considers that GPP is proportional to the absorbedphotosynthetically active radiation APAR and the proportionality factor is known as the light use efficiency ε. Aparameterization of this factor is proposed as the product of a εmax, corresponding to the canopy functioningunder optimal conditions, and a coefficient quantifying the reduction of photosynthesis as a consequence ofwater stress. A three years data record (2015–2017) was used in an assessment against site-level eddy covariance(EC) tower GPP estimates and against other Earth Observation (EO) based GPP products. The site-level comparisonindicated that the MGPP product performed better than the other EO based GPP products with 48% ofthe observations being below the optimal accuracy (absolute error < 1.0 g m−2 day−1) and 75% of these databeing below the user requirement threshold (absolute error < 3.0 g m−2 day−1). The largest discrepanciesbetween the MGPP product and the other GPP products were found for forests whereas small differences wereobserved for the other land cover types. The integration of this GPP product with the ensemble of LSA-SAF MSG
32.	Martinez-Romera, Beatriz, et al. (författare) Nordic Action for a Transformation to Low-carbon Shipping. 2017 Rapport (övrigt vetenskapligt/konstnärligt)abstract The Paris Agreement aims to hold the increase in average global temperatures to well below 2°C above pre-industrial levels, and to pursue efforts to limit it to 1.5°C,1 but it does not refer specifically to emissions of greenhouse gases by the international maritime transport sector. This Report presents the findings of a project commissioned by the Nordic Council of Ministers through the Nordic Working Group for Global Climate Negotiations (NOAK) focusing on opportunities for Nordic countries to achieve a transition to low-carbon shipping globally, nationally and regionally. The Report is informed by a discussion paper released in November 2016 and a workshop convened in Malmö in December 2016, in which representatives of governments, businesses and the research community participated. The key findings of this Workshop Report are as follows.(1) Technology and finance.Promising technical and financial options are available to Nordic countries to support or lead a transition to low-carbon shipping. The Report presents these options in the form of a low-carbon road map for the sector (see Figure 1), which includes illustrative actions and outcomes concerning technological and operational measures, partnerships between the public and private sectors, and supporting policies and finance.(2) Public policy.Opportunities exist for Nordic countries to support and lead development of the public policies needed for transitions to low-carbon shipping. Internationally, Nordic countries are well positioned to lead efforts by the International Maritime Organization and others to define global targets for the sector and to build global ambition through partnerships with developing countries and flag registries.Outside the IMO, Nordic countries can catalyze transitions to low-carbon shipping through actions including market-based measures in Nordic countries, support for private-sector standards, low-carbon targets for Nordic fleets, arranging dialogue between stakeholders, including financiers and charterers, showcasing innovative Nordic practices, and building Nordic-led global partnerships such as “climate clubs”.(3) Collaboration.The actions described above are interdependent and interconnected. The success of a Nordic agenda for low-carbon shipping depends on the inclusion of all relevant stakeholders, the coordination of policies, and a holistic view of shipping and the important roles of Nordic governments, businesses and civil society within the sector.
33.	Matabuena, Marcos, et al. (författare) Identification of Asthma Phenotypes in the Spanish MEGA Cohort Study Using Cluster Analysis 2023 Ingår i: Archivos de Bronconeumologia. - : Elsevier BV. - 0300-2896. ; 59:4, s. 223-231 Tidskriftsartikel (refereegranskat)abstract Introduction: The definition of asthma phenotypes has not been fully established, neither there are cluster studies showing homogeneous results to solidly establish clear phenotypes. The purpose of this study was to develop a classification algorithm based on unsupervised cluster analysis, identifying clusters that represent clinically relevant asthma phenotypes that may share asthma-related outcomes. Methods: We performed a multicentre prospective cohort study, including adult patients with asthma (N = 512) from the MEGA study (Mechanisms underlying the Genesis and evolution of Asthma). A standardised clinical history was completed for each patient. Cluster analysis was performed using the kernel k-groups algorithm. Results: Four clusters were identified. Cluster 1 (31.5% of subjects) includes adult-onset atopic patients with better lung function, lower BMI, good asthma control, low ICS dose, and few exacerbations. Cluster 2 (23.6%) is made of adolescent-onset atopic asthma patients with normal lung function, but low adherence to treatment (59% well-controlled) and smokers (48%). Cluster 3 (17.1%) includes adult-onset patients, mostly severe non-atopic, with overweight, the worse lung function and asthma control, and receiving combination of treatments. Cluster 4 (26.7%) consists of the elderly-onset patients, mostly female, atopic (64%), with high BMI and normal lung function, prevalence of smokers and comorbidities. Conclusion: We defined four phenotypes of asthma using unsupervised cluster analysis. These clusters are clinically relevant and differ from each other as regards FEV1, age of onset, age, BMI, atopy, asthma severity, exacerbations, control, social class, smoking and nasal polyps.
34.	Miravitlles, Marc, et al. (författare) Characteristics of individuals with alpha-1 antitrypsin deficiency from Northern and Southern European countries : EARCO international registry 2023 Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 61:3 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
35.	Miravitlles, Marc, et al. (författare) Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency : EARCO international registry 2022 Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 23:1 Tidskriftsartikel (refereegranskat)abstract Background: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PIZZ, PISZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. Results: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PIZZ (60.2%), followed by PISZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). Conclusions: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registrationwww.clinicaltrials.gov
36.	Moreno-Amador, Beatriz, et al. (författare) Measuring symptoms of obsessive-compulsive and related disorders using a single dimensional self-report scale 2023 Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 14 Tidskriftsartikel (refereegranskat)abstract Background: Obsessions and compulsions are heterogenous but can be classified into obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), hoarding disorder (HD), hair-pulling disorder (HPD), and skin-picking disorder (SPD). OCD is in itself heterogenous, with symptoms clustering around four major symptom dimensions: contamination/cleaning, symmetry/ordering, taboo obsessions, and harm/checking. No single self-report scale captures the full heterogeneity of OCD and related disorders, limiting assessment in clinical practice and research on nosological relations among the disorders.Methods: To provide a single self-report scale of OCD and related disorders that respects the heterogeneity of OCD, we expanded the DSM-5-based Obsessive-Compulsive and Related Disorders-Dimensional Scales (OCRD-D) so that is also includes the four major symptom dimensions of OCD. A psychometric evaluation and an exploration of the overarching relations among the dimensions were conducted using an online survey which was completed by 1,454 Spanish adolescents and adults (age span = 15–74 years). Approximately 8 months after the initial survey, 416 participants completed the scale again.Results: The expanded scale showed excellent internal psychometric properties, adequate test-retest correlations, known groups validity, and correlations in the expected directions with well-being, depression/anxiety symptoms, and satisfaction with life. The higher-order structure of the measure indicated that harm/checking and taboo obsessions formed a common disturbing thoughts factor and that HPD and SPD formed a common body-focused repetitive behaviors factor.Conclusion: The expanded OCRD-D (OCRD-D-E) shows promise as a unified way to assess symptoms across the major symptom dimensions of OCD and related disorders. The measure may be useful in clinical practice (e.g., screening) and research, but more research on construct validity, incremental validity, and clinical utility is needed.
37.	Moreno-Amador, Beatriz, et al. (författare) Sensory Overresponsivity and Symptoms Across the Obsessive-Compulsive Spectrum: Web-Based Longitudinal Observational Study 2023 Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 25, s. 1-12 Tidskriftsartikel (refereegranskat)abstract Background:Sensory overresponsivity (SOR) has emerged as a potential endophenotype in obsessive-compulsive disorder (OCD), but few studies have examined SOR in relation to the major symptom dimensions of OCD and to symptoms across the full obsessive-compulsive (OC) symptom spectrum.Objective:This study had 2 main objectives. First, we examined the psychometric properties of the SOR Scales in a community-based sample of Spanish adolescents and adults. Second, we identified how SOR difficulties are related to symptoms across the full OC spectrum (eg, OC, body dysmorphic, hoarding, skin-picking, and hair-pulling symptoms), including the heterogeneity of OC symptoms.Methods:We translated the SOR Scales into Spanish—a measure that assesses SOR across the 5 sensory modalities—and created a web-based version of the measure. A sample of 1454 adolescents and adults (mean age 23.84, SD 8.46 years) participated in the study, and 388 (26.69%) participants completed the survey twice (approximately 8 months apart). The survey also contained a web-based measure that assesses symptoms across the full OC spectrum: harm and checking, taboo obsessions, contamination or cleaning, symmetry and ordering, body dysmorphic, hoarding, hair-pulling, and skin-picking symptoms.Results:The psychometric properties of the SOR Scales were excellent, and the test-retest reliability was adequate. All types of SOR were related to all major symptom dimensions of OCD and to all OC spectrum symptoms.Conclusions:SOR across the sensory modalities can be validly assessed using a web-based measure. SOR emerged as a pure transdiagnostic phenomenon in relation to symptoms across the OC spectrum, with no specific sensory modality being more strongly related to OC symptoms. SOR can shed much needed light on basic mechanisms that are important for the onset and maintenance of OC spectrum symptoms, and this study shows that large-scale web-based studies can aid in this endeavor. Future studies should examine whether SOR precedes or emerges alongside OC symptoms.
38.	Nakanishi, Tomoko, et al. (författare) Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality 2021 Ingår i: Journal of Clinical Investigation. - : American Society For Clinical Investigation. - 0021-9738 .- 1558-8238. ; 131:23 Tidskriftsartikel (refereegranskat)abstract BACKGROUND. There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition. METHODS. We combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank. RESULTS. We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors. CONCLUSIONS. The major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.
39.	Nyström, Elisabeth E. L., et al. (författare) An intercrypt subpopulation of goblet cells is essential for colonic mucus barrier function 2021 Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 372:6539 Tidskriftsartikel (refereegranskat)abstract The intestinal mucus layer, an important element of epithelial protection, is produced by goblet cells. Intestinal goblet cells are assumed to be a homogeneous cell type. In this study, however, we delineated their specific gene and protein expression profiles and identified several distinct goblet cell populations that form two differentiation trajectories. One distinct subtype, the intercrypt goblet cells (icGCs), located at the colonic luminal surface, produced mucus with properties that differed from the mucus secreted by crypt-residing goblet cells. Mice with defective icGCs had increased sensitivity to chemically induced colitis and manifested spontaneous colitis with age. Furthermore, alterations in mucus and reduced numbers of icGCs were observed in patients with both active and remissive ulcerative colitis, which highlights the importance of icGCs in maintaining functional protection of the epithelium.
40.	Palomo-Carrion, Rocio, et al. (författare) Mini-symposium: Powered mobility : Facilitating participation in children with Spinal Muscular Atrophy (SMA) type 1. Ready for the Race? 2023 Ingår i: ; , s. 86-86 Konferensbidrag (refereegranskat)abstract OBJECTIVESThe symposium will provide the know-how about powered mobility use in children with Spinal Muscular Atrophy Type I. Define what are the barriers of their mobility and how powered mobility can facilitate participation and social interaction. Disseminate the importance of family involvement in early powered mobility through the use of adapted motorized devices supporting development of functional strategies that improve the child's access to their natural environment. SUMMARYChildren diagnosed with spinal muscular atrophy (SMA) have motor disorders that affect their mobility, restricting activities of daily living and participation. Powered mobility when used within their natural environment, involving the family, can encourage their motivation to be mobile and facilitate participation. Experiences of self-produced mobility gives opportunities for learning and interaction and facilitates autonomy. The child’s exploratory activity with an adapted powered device causes continuous changes of position in relation to the physical and social environment, giving new perspectives and opportunities for interaction and participation.OUTLINE OF the Symposium- Introduction 5’. Bea de Andrés..- What are the barriers in the participation of SMA type I in the natural environment? What do the families think? 15’. Maribel Ródenas y Rocío Palomo.- What can powered mobility offer in SMA type I? Ready for the race? 25’ Ródenas M, De Andrés B, Palomo R.- Why is Driving to Learn a powerful developing experience? How to apply the two parts of the process-based Assessment of Learning Powered mobility use (ALP)? Lisbeth Nilsson 30’’- Discussion. 15’
41.	Pañeda Murcia, Beatriz, et al. (författare) Divine Onomastic Attributs in the Greco-Roman World : A New Proposal of Taxonomy 2022 Ingår i: Calling upon Gods, Offering Bodies : Strategies of Human-Divine Communication in the Roman Empire from Individual Experience to Social Reproduction - Strategies of Human-Divine Communication in the Roman Empire from Individual Experience to Social Reproduction. Konferensbidrag (refereegranskat)
42.	Pañeda Murcia, Beatriz, et al. (författare) Women’s Choice : Divine Epithets in the Female Epigraphic Record of Hispania 2022. - Peter Lang Ingår i: Calling upon Gods, Offering Bodies : Strategies of Human-Divine Communication in the Roman Empire from Individual Experience to Social Reproduction - Strategies of Human-Divine Communication in the Roman Empire from Individual Experience to Social Reproduction. Konferensbidrag (refereegranskat)
43.	Pardo-Camacho, Cristina, et al. (författare) Mucosal Plasma Cell Activation and Proximity to Nerve Fibres Are Associated with Glycocalyx Reduction in Diarrhoea-Predominant Irritable Bowel Syndrome : Jejunal Barrier Alterations Underlying Clinical Manifestations 2022 Ingår i: Cells. - Basel : MDPI. - 2073-4409. ; 11:13 Tidskriftsartikel (refereegranskat)abstract Irritable bowel syndrome (IBS) is a disorder of brain-gut interaction characterised by abdominal pain and changes in bowel habits. In the diarrhoea subtype (IBS-D), altered epithelial barrier and mucosal immune activation are associated with clinical manifestations. We aimed to further evaluate plasma cells and epithelial integrity to gain understanding of IBS-D pathophysiology. One mucosal jejunal biopsy and one stool sample were obtained from healthy controls and IBS-D patients. Gastrointestinal symptoms, stress, and depression scores were recorded. In the jejunal mucosa, RNAseq and gene set enrichment analyses were performed. A morphometric analysis by electron microscopy quantified plasma cell activation and proximity to enteric nerves and glycocalyx thickness. Immunoglobulins concentration was assessed in the stool. IBS-D patients showed differential expression of humoral pathways compared to controls. Activation and proximity of plasma cells to nerves and IgG concentration were also higher in IBS-D. Glycocalyx thickness was lower in IBS-D compared to controls, and this reduction correlated with plasma cell activation, proximity to nerves, and clinical symptoms. These results support humoral activity and loss of epithelial integrity as important contributors to gut dysfunction and clinical manifestations in IBS-D. Additional studies are needed to identify the triggers of these alterations to better define IBS-D pathophysiology.
44.	Robinson, Sam, et al. (författare) The globalization of science diplomacy in the early 1970s : a historical exploration 2023 Ingår i: Science and Public Policy. - : Oxford University Press. - 0302-3427 .- 1471-5430. ; 50:4, s. 749-758 Tidskriftsartikel (refereegranskat)abstract The early 1970s brought fundamental transitions in international scientific collaboration that significantly affected the international relations in global patterns that are still relevant today. This article uses a multi-perspective approach to argue that the underlying condition for the globalization of science diplomacy was the increasing participation of recently independent countries in international technoscientific affairs, examining critical research areas, including space exploration, oceanography, nuclear technoscience, the environmental sciences, and health and population studies. Themes emerged at that time that continue to characterize what we term 'Global Science Diplomacy': multipolarity, resistance and agency, lack of global consensus, regional alliances and interests, and the centrality of the United Nations system to the conduct of transnational science. This survey is a first step in historical reflection on this phenomenon and shows that it was the emergence of the Global South in Science Diplomacy affairs that made Science Diplomacy global at the beginning of the 1970s.
45.	Sánchez-Cano, Beatriz, et al. (författare) Solar Energetic Particle Events Detected in the Housekeeping Data of the European Space Agency's Spacecraft Flotilla in the Solar System 2023 Ingår i: Space Weather. - : American Geophysical Union (AGU). - 1542-7390. ; 21:8 Tidskriftsartikel (refereegranskat)abstract Despite the growing importance of planetary Space Weather forecasting and radiation protection for science and robotic exploration and the need for accurate Space Weather monitoring and predictions, only a limited number of spacecraft have dedicated instrumentation for this purpose. However, every spacecraft (planetary or astronomical) has hundreds of housekeeping sensors distributed across the spacecraft, some of which can be useful to detect radiation hazards produced by solar particle events. In particular, energetic particles that impact detectors and subsystems on a spacecraft can be identified by certain housekeeping sensors, such as the Error Detection and Correction (EDAC) memory counters, and their effects can be assessed. These counters typically have a sudden large increase in a short time in their error counts that generally match the arrival of energetic particles to the spacecraft. We investigate these engineering datasets for scientific purposes and perform a feasibility study of solar energetic particle event detections using EDAC counters from seven European Space Agency Solar System missions: Venus Express, Mars Express, ExoMars-Trace Gas Orbiter, Rosetta, BepiColombo, Solar Orbiter, and Gaia. Six cases studies, in which the same event was observed by different missions at different locations in the inner Solar System are analyzed. The results of this study show how engineering sensors, for example, EDAC counters, can be used to infer information about the solar particle environment at each spacecraft location. Therefore, we demonstrate the potential of the various EDAC to provide a network of solar particle detections at locations where no scientific observations of this kind are available.
46.	Schneider, Hannah, et al. (författare) The human transmembrane mucin MUC17 responds to TNF alpha by increased presentation at the plasma membrane 2019 Ingår i: Biochemical Journal. - : Portland Press Ltd.. - 0264-6021 .- 1470-8728. ; 476, s. 2281-2295 Tidskriftsartikel (refereegranskat)abstract Transmembrane mucin MUC17 is an integral part of the glycocalyx as it covers the brush border membrane of small intestinal enterocytes and presents an extended O-glycosylated mucin domain to the intestinal lumen. Here, we identified two unknown phosphorylated serine residues, S4428 and S4492, in the cytoplasmic tail of human MUC17. We have previously demonstrated that MUC17 is anchored to the apical membrane domain via an interaction with the scaffolding protein PDZK1. S4492, localized in the C-terminal PDZ binding motif of MUC17, was mutated to generate phosphomimetic and phosphodeficient variants of MUC17. Using Caco-2 cells as a model system, we found that induction of an inflammatory state by long-term stimulation with the proinflammatory cytokine TNF alpha resulted in an increase of MUC17 protein levels and enhanced insertion of MUC17 and its two phospho-variants into apical membranes. Up-regulation and apical insertion of MUC17 was followed by shedding of MUC17-containing vesicles. Transmembrane mucins have previously been shown to play a role in the prevention of bacterial colonization by acting as sheddable decoys for encroaching bacteria. Overexpression and increased presentation at the plasma membrane of wild-type MUC17 and its phosphodeficient variant MUC17 S-4492A protected Caco-2 cells against adhesion of enteropathogenic Escherichia coli, indicating that C-terminal phosphorylation of MUC17 may play a functional role in epithelial cell protection. We propose a new function for MUC17 in inflammation, where MUC17 acts as a second line of defense by preventing attachment of bacteria to the epithelial cell glycocalyx in the small intestine.
47.	Sharpen, Jack D. A., et al. (författare) Transglutaminase 3 crosslinks the secreted gel-forming mucus component Mucin-2 and stabilizes the colonic mucus layer 2022 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1 Tidskriftsartikel (refereegranskat)abstract The colonic mucus layer is organized as a two-layered system providing a physical barrier against pathogens and simultaneously harboring the commensal flora. The factorscontributing to the organization of this gel network are not well understood. In this study, the impact of transglutaminase activity on this architecture was analyzed. Here, we show that transglutaminase TGM3 is the major transglutaminase-isoform expressed and synthesized in the colon. Furthermore, intrinsic extracellular transglutaminase activity in the secreted mucus was demonstrated in vitro and ex vivo. Absence of this acyl-transferase activity resulted in faster degradation of the major mucus component the MUC2 mucin and changed the biochemical properties of mucus. Finally, TGM3-deficient mice showed an early increased susceptibility to Dextran Sodium Sulfate-induced colitis. Here, we report that natural isopeptide cross-linking by TGM3 is important for mucus homeostasis and protection of the colon from inflammation, reducing the risk of colitis. © 2022, The Author(s).
48.	Tavares, Julia, et al. (författare) Basin-wide variation in tree hydraulic safety margins predicts the carbon balance of Amazon forests 2023 Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 617:7959, s. 111-117 Tidskriftsartikel (refereegranskat)abstract Tropical forests face increasing climate risk(1,2), yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, ?(50)) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk(3-5), little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters ?(50) and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both ?(50) and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM(50 )forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon(6,7), with strong implications for the Amazon carbon sink.
49.	Thorell, Kaisa, 1983, et al. (författare) The Helicobacter pylori Genome Project: insights into H. pylori population structure from analysis of a worldwide collection of complete genomes 2023 Ingår i: Nature Communications. - 2041-1723. ; 14:1 Tidskriftsartikel (refereegranskat)abstract Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.
50.	Tumpara, Srinu, et al. (författare) A novel mouse monoclonal antibody c42 against c-terminal peptide of alpha-1-antitrypsin 2021 Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:4 Tidskriftsartikel (refereegranskat)abstract The C-terminal-fragments of alpha1-antitrypsin (AAT) have been identified and their diverse biological roles have been reported in vitro and in vivo. These findings prompted us to develop a monoclonal antibody that specifically recognizes C-36 peptide (corresponding to residues 359–394) resulting from the protease-associated cleavage of AAT. The C-36-targeting mouse mono-clonal Immunoglobulin M (IgM) antibody (containing κ light chains, clone C42) was generated and enzyme-linked immunosorbent assay (ELISA)-tested by Davids Biotechnologie GmbH, Germany. Here, we addressed the effectiveness of the novel C42 antibody in different immunoassay formats, such as dot-and Western blotting, confocal laser microscopy, and flow cytometry. According to the dot-blot results, our novel C42 antibody detects the C-36 peptide at a range of 0.1–0.05 µg and shows no cross-reactivity with native, polymerized, or oxidized forms of full-length AAT, the AAT-elastase complex mixture, as well as with shorter C-terminal fragments of AAT. However, the C42 antibody does not detect denatured peptide in SDS-PAGE/Western blotting assays. On the other hand, our C42 antibody, unconjugated as well as conjugated to DyLight488 fluorophore, when applied for immunofluorescence microscopy and flow cytometry assays, specifically detected the C-36 peptide in human blood cells. Altogether, we demonstrate that our novel C42 antibody successfully recognizes the C-36 peptide of AAT in a number of immunoassays and has potential to become an important tool in AAT-related studies.

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