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2. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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3. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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4. |
- Pashako, Frida, et al.
(author)
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Europe
- 2017
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In: Time Frames: Conservation Policies for Twentieth-Century Architectural Heritage. - New York: Routledge, 2017. : Routledge. - 9781351980357 ; , s. 197-350
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Book chapter (other academic/artistic)
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5. |
- Block, Keith I., et al.
(author)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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In: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
-
Research review (peer-reviewed)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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6. |
- Nguyen, Thanh N, et al.
(author)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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In: Neurology. - 1526-632X. ; 100:4
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Journal article (peer-reviewed)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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9. |
- Casillo, Angela, et al.
(author)
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Structural characterization of an all-aminosugar-containing capsular polysaccharide from Colwellia psychrerythraea 34H
- 2017
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In: Antonie van Leeuwenhoek. International Journal of General and Molecular Microbiology. - : Springer Science and Business Media LLC. - 0003-6072 .- 1572-9699. ; 110:11, s. 1377-1387
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Journal article (peer-reviewed)abstract
- Colwellia psychrerythraea strain 34H, a Gram-negative bacterium isolated from Arctic marine sediments, is considered a model to study the adaptation to cold environments. Recently, we demonstrated that C. psychrerythraea 34H produces two different extracellular polysaccharides, a capsular polysaccharide and a medium released polysaccharide, which confer cryoprotection to the bacterium. In this study, we report the structure of an additional capsular polysaccharide produced by Colwellia grown at a different temperature. The structure was determined using chemical methods, and one- and two-dimensional NMR spectroscopy. The results showed a trisaccharide repeating unit made up of only amino-sugar residues: N-acetyl-galactosamine, 2,4-diacetamido-2,4,6-trideoxy-glucose (bacillosamine), and 2-acetamido-2-deoxyglucuronic acid with the following structure: -> 4)-beta-d-GlcpNAcA-(1 -> 3)-beta-d-QuipNAc4NAc-(1 -> 3)-beta-d-GalpNAc-(1 ->. The 3D model, generated in accordance with H-1,H-1-NOE NMR correlations and consisting of ten repeating units, shows a helical structure. In contrast with the other extracellular polysaccharides produced from Colwellia at 4 A degrees C, this molecule displays only a low ice recrystallization inhibition activity.
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10. |
- Hess, Timo, et al.
(author)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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In: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
-
Journal article (peer-reviewed)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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11. |
- Küller, Rikard, et al.
(author)
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Brain and Environment: The Use of Brain Wave Analysis in Environmental Psychology
- 2008
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In: IAPS 20 Conference Proceedings on CD-Rom.
-
Conference paper (peer-reviewed)abstract
- In neuroscience a number of new techniques have been developed by means of which it has become possible to study the activity of the living human brain. By means of these techniques we are beginning to understand the neurophysiology behind environmental attitudes and preferences. In addition to an introduction to cognitive neuroscience, this invited symposium contains a number of presentations, where brain wave analysis has been employed in Environmental Psychology.
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12. |
- Lazzaroni, Francesca, et al.
(author)
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Circulating biomarkers in familial cerebral cavernous malformation
- 2024
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In: EBioMedicine. - : Elsevier. - 2352-3964. ; 99
-
Journal article (peer-reviewed)abstract
- Background Cerebral Cavernous Malformation (CCM) is a rare cerebrovascular disease, characterized by the presence of multiple vascular malformations that may result in intracerebral hemorrhages (ICHs), seizure(s), or focal neurological deficits (FND). Familial CCM (fCCM) is due to loss of function mutations in one of the three independent genes KRIT1 (CCM1), Malcavernin (CCM2), or Programmed Cell death 10 (PDCD10/CCM3). The aim of this study was to identify plasma protein biomarkers of fCCM to assess the severity of the disease and predict its progression.Methods Here, we have investigated plasma samples derived from n = 71 symptomatic fCCM patients (40 female/31 male) and n =17 healthy donors (HD) (9 female/8 male) of the Phase 1/2 Treat_CCM trial, using multiplexed protein profiling approaches.Findings Biomarkers as sCD14 (p = 0.00409), LBP (p = 0.02911), CXCL4 (p = 0.038), ICAM-1 (p = 0.02013), ANG2 (p = 0.026), CCL5 (p = 0.00403), THBS1 (p = 0.0043), CRP (p = 0.0092), and HDL (p = 0.027), were significantly different in fCCM compared to HDs. Of note, sENG (p = 0.011), THBS1 (p = 0.011) and CXCL4 (p = 0.011), were correlated to CCM genotype. sROBO4 (p = 0.014), TM (p = 0.026) and CRP (p = 0.040) were able to predict incident adverse clinical events, such as ICH, FND or seizure. GDF-15, FLT3L, CXCL9, FGF-21 and CDCP1, were identified as predictors of the formation of new MRI-detectable lesions over 2-year follow-up. Furthermore, the functional relevance of ang2, thbs1, robo4 and cdcp1 markers was validated by zebrafish pre-clinical model of fCCM.Interpretation Overall, our study identifies a set of biochemical parameters to predict CCM progression, suggesting biological interpretations and potential therapeutic approaches to CCM disease.
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14. |
- Rahm, Johan, et al.
(author)
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The Psychological Factors Underlying Participation in Nature Conservation Projects: Wetland restoration and forest preservation examined through the framework of the Value-Belief-Norm theory
- 2008
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In: IAPS 20 Conference Proceedings on CD-Rom.
-
Conference paper (peer-reviewed)abstract
- The conservation of biological diversity is a matter of uttermost importance and its significance is stressed in the environmental goals of the Swedish government. Among the environmental goals there are several distinctly defined goals related to biological diversity which are to be accomplished within a set amount of time. In order to succeed with these goals it is important to understand what influences people to participate in conservation projects. The present study casts light on the psychological factors behind the participation in nature conservation projects aiming to promote biodiversity. Two projects, wetland restoration and forest preservation, are examined through the framework of the VBN (Value-Belief-Norm) theory. A survey was conducted among 120 farmland owners and 160 forest owners in southern Sweden. Results point to the importance of knowledge and commitment for the awareness of threats to biodiversity, ascription of a personal responsibility and the activation of personal norms. The importance of the interplay between psychological and contextual factors for explaining the participation is also highlighted.
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15. |
- Bramsen, Jesper B., et al.
(author)
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A large-scale chemical modification screen identifies design rules to generate siRNAs with high activity, high stability and low toxicity
- 2009
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In: Nucleic Acids Research. - : Oxford University Press. - 0305-1048 .- 1362-4962. ; 37:9, s. 2867-2881
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Journal article (peer-reviewed)abstract
- The use of chemically synthesized short interfering RNAs (siRNAs) is currently the method of choice to manipulate gene expression in mammalian cell culture, yet improvements of siRNA design is expectably required for successful application in vivo. Several studies have aimed at improving siRNA performance through the introduction of chemical modifications but a direct comparison of these results is difficult. We have directly compared the effect of 21 types of chemical modifications on siRNA activity and toxicity in a total of 2160 siRNA duplexes. We demonstrate that siRNA activity is primarily enhanced by favouring the incorporation of the intended antisense strand during RNA-induced silencing complex (RISC) loading by modulation of siRNA thermodynamic asymmetry and engineering of siRNA 3'-overhangs. Collectively, our results provide unique insights into the tolerance for chemical modifications and provide a simple guide to successful chemical modification of siRNAs with improved activity, stability and low toxicity.
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16. |
- Bruno, Roberto, et al.
(author)
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Comparative Study of the Kinetic Properties of Proton and Alpha Beams in the Alfvénic Wind Observed by SWA-PAS On Board Solar Orbiter
- 2024
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 969:2
-
Journal article (peer-reviewed)abstract
- The problems of heating and acceleration of solar wind particles are of significant and enduring interest in astrophysics. The interactions between waves and particles are crucial in determining the distributions of proton and alpha particles, resulting in non-Maxwellian characteristics, including temperature anisotropies and particle beams. These processes can be better understood as long as the beam can be separated from the core for the two major components of the solar wind. We utilized an alternative numerical approach that leverages the clustering technique employed in machine learning to differentiate the primary populations within the velocity distribution rather than employing the conventional bi-Maxwellian fitting method. Separation of the core and beam revealed new features for protons and alphas. We estimated that the total temperature of the two beams was slightly higher than that of their respective cores, and the temperature anisotropy for the cores and beams was larger than 1. We concluded that the temperature ratio between alphas and protons largely over 4 is due to the presence of a massive alpha beam, which is approximately 50% of the alpha core. We provided evidence that the alpha core and beam populations are sensitive to Alfvénic fluctuations and the surfing effect found in the literature can be recovered only when considering the core and beam as a single population. Several similarities between proton and alpha beams would suggest a common and local generation mechanism not shared with the alpha core, which may not have necessarily been accelerated and heated locally.
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17. |
- Cardoso Pereira, Cássio, et al.
(author)
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Subtle structures with not-so-subtle functions : A data set of arthropod constructs and their host plants
- 2022
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In: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 103:4
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Journal article (peer-reviewed)abstract
- The construction of shelters on plants by arthropods might influence other organisms via changes in colonization, community richness, species composition, and functionality. Arthropods, including beetles, caterpillars, sawflies, spiders, and wasps often interact with host plants via the construction of shelters, building a variety of structures such as leaf ties, tents, rolls, and bags; leaf and stem galls, and hollowed out stems. Such constructs might have both an adaptive value in terms of protection (i.e., serve as shelters) but may also exert a strong influence on terrestrial community diversity in the engineered and neighboring hosts via colonization by secondary occupants. Although different traits of the host plant (e.g., physical, chemical, and architectural features) may affect the potential for ecosystem engineering by insects, such effects have been, to a certain degree, overlooked. Further analyses of how plant traits affect the occurrence of shelters may therefore enrich our understanding of the organizing principles of plant-based communities. This data set includes more than 1000 unique records of ecosystem engineering by arthropods, in the form of structures built on plants. All records have been published in the literature, and span both natural structures (91% of the records) and structures artificially created by researchers (9% of the records). The data were gathered between 1932 and 2021, across more than 50 countries and several ecosystems, ranging from polar to tropical zones. In addition to data on host plants and engineers, we aggregated data on the type of constructs and the identity of inquilines using these structures. This data set highlights the importance of these subtle structures for the organization of terrestrial arthropod communities, enabling hypotheses testing in ecological studies addressing ecosystem engineering and facilitation mediated by constructs. There are no copyright restrictions and please cite this paper when using the data in publications.
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18. |
- Costa, Filipa A., et al.
(author)
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Provision of pharmaceutical care by community pharmacists across Europe : Is it developing and spreading?
- 2017
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In: Journal of Evaluation In Clinical Practice. - : John Wiley & Sons. - 1356-1294 .- 1365-2753. ; 23:6, s. 1336-1347
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Journal article (peer-reviewed)abstract
- Rationale, Aims, and Objectives: Pharmaceutical care involves patient-centred pharmacist activity to improve medicines management by patients. The implementation of this service in a comprehensive manner, however, requires considerable organisation and effort, and indeed, it is often not fully implemented in care settings. The main objective was to assess how pharmaceutical care provision within community pharmacy has evolved over time in Europe. Method: A cross-sectional questionnaire-based survey of community pharmacies, using a modified version of the Behavioural Pharmaceutical Care Scale (BPCS) was conducted in late 2012/early 2013 within 16 European countries and compared with an earlier assessment conducted in 2006. Results: The provision of comprehensive pharmaceutical care has slightly improved in all European countries that participated in both editions of this survey (n=8) with progress being made particularly in Denmark and Switzerland. Moreover, there was a wider country uptake, indicating spread of the concept. However, due to a number of limitations, the results should be interpreted with caution. Using combined data from participating countries, the provision of pharmaceutical care was positively correlated with the participation of the community pharmacists in patient-centred activities, routine use of pharmacy software with access to clinical data, participation in multidisciplinary team meetings, and having specialized education. Conclusions: The present study demonstrated a slight evolution in self-reported provision of pharmaceutical care by community pharmacists across Europe, as measured by the BPCS. The slow progress suggests a range of barriers, which are preventing pharmacists moving beyond traditional roles. Support from professional bodies and more patient-centred community pharmacy contracts, including remuneration for pharmaceutical care services, are likely to be required if quicker progress is to be made in the future.
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19. |
- Freud, Lindsay R., et al.
(author)
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Prenatal vs postnatal diagnosis of 22q11.2 deletion syndrome: cardiac and noncardiac outcomes through 1 year of age
- 2024
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In: American Journal of Obstetrics and Gynecology. - 0002-9378 .- 1097-6868. ; 230:3
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Journal article (peer-reviewed)abstract
- Background: The 22q11.2 deletion syndrome is the most common microdeletion syndrome and is frequently associated with congenital heart disease. Prenatal diagnosis of 22q11.2 deletion syndrome is increasingly offered. It is unknown whether there is a clinical benefit to prenatal detection as compared with postnatal diagnosis. Objective: This study aimed to determine differences in perinatal and infant outcomes between patients with prenatal and postnatal diagnosis of 22q11.2 deletion syndrome. Study Design: This was a retrospective cohort study across multiple international centers (30 sites, 4 continents) from 2006 to 2019. Participants were fetuses, neonates, or infants with a genetic diagnosis of 22q11.2 deletion syndrome by 1 year of age with or without congenital heart disease; those with prenatal diagnosis or suspicion (suggestive ultrasound findings and/or high-risk cell-free fetal DNA screen for 22q11.2 deletion syndrome with postnatal confirmation) were compared with those with postnatal diagnosis. Perinatal management, cardiac and noncardiac morbidity, and mortality by 1 year were assessed. Outcomes were adjusted for presence of critical congenital heart disease, gestational age at birth, and site. Results: A total of 625 fetuses, neonates, or infants with 22q11.2 deletion syndrome (53.4% male) were included: 259 fetuses were prenatally diagnosed (156 [60.2%] were live-born) and 122 neonates were prenatally suspected with postnatal confirmation, whereas 244 infants were postnatally diagnosed. In the live-born cohort (n=522), 1-year mortality was 5.9%, which did not differ between groups but differed by the presence of critical congenital heart disease (hazard ratio, 4.18; 95% confidence interval, 1.56–11.18; P<.001) and gestational age at birth (hazard ratio, 0.78 per week; 95% confidence interval, 0.69–0.89; P<.001). Adjusting for critical congenital heart disease and gestational age at birth, the prenatal cohort was less likely to deliver at a local community hospital (5.1% vs 38.2%; odds ratio, 0.11; 95% confidence interval, 0.06–0.23; P<.001), experience neonatal cardiac decompensation (1.3% vs 5.0%; odds ratio, 0.11; 95% confidence interval, 0.03–0.49; P=.004), or have failure to thrive by 1 year (43.4% vs 50.3%; odds ratio, 0.58; 95% confidence interval, 0.36–0.91; P=.019). Conclusion: Prenatal detection of 22q11.2 deletion syndrome was associated with improved delivery management and less cardiac and noncardiac morbidity, but not mortality, compared with postnatal detection.
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20. |
- Hudson, Lawrence N., et al.
(author)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Journal article (peer-reviewed)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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22. |
- Jin, Yuesheng, et al.
(author)
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Fusion of the AHRR and NCOA2 genes through a recurrent translocation t(5;8)(p15;q13) in soft tissue angiofibroma results in upregulation of aryl hydrocarbon receptor target genes.
- 2012
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In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 51:5, s. 510-520
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Journal article (peer-reviewed)abstract
- Soft tissue angiofibroma is a recently delineated tumor type of unknown cellular origin. Cytogenetic analysis of four cases showed that they shared a t(5;8)(p15;q13). In three of them it was the sole change, underlining its pathogenetic significance. FISH mapping suggested the involvement of the aryl hydrocarbon receptor repressor (AHRR) and nuclear receptor coactivator 2 (NCOA2) genes in 5p15 and 8q13, respectively. RT-PCR revealed in-frame AHRR/NCOA2 and NCOA2/AHHR transcripts in all four cases. Interphase FISH on paraffin-embedded tissue from 10 further cases without cytogenetic data showed that three were positive for fusion of AHRR and NCOA2. While AHRR has never been implicated in gene fusions before, NCOA2 is the 3'-partner in fusions with MYST3 and ETV6 in leukemias and with PAX3 and HEY1 in sarcomas. As in the previously described fusion proteins, NCOA2 contributes with its two activation domains to the AHRR/NCOA2 chimera, substituting for the repressor domain of AHRR. Because the amino terminal part of the transcription factor AHRR, responsible for the recognition of xenobiotic response elements in target genes and for heterodimerization, shows extensive homology with the aryl hydrocarbon receptor (AHR), the fusion is predicted to upregulate the AHR/ARNT signaling pathway. Indeed, global gene expression analysis showed upregulation of CYP1A1 as well as other typical target genes of this pathway, such as those encoding toll-like receptors. Apart from providing a diagnostic marker for soft tissue angiofibroma, the results also suggest that this tumor constitutes an interesting model for evaluating the cellular effects of AHR signaling. © 2012 Wiley Periodicals, Inc.
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24. |
- Johansson, Patrik, et al.
(author)
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A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma
- 2020
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:2
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Journal article (peer-reviewed)abstract
- Glioblastoma (GBM) is a malignant brain tumor with few therapeutic options. The disease presents with a complex spectrum of genomic aberrations, but the pharmacological consequences of these aberrations are partly unknown. Here, we report an integrated pharmacogenomic analysis of 100 patient-derived GBM cell cultures from the human glioma cell culture (HGCC) cohort. Exploring 1,544 drugs, we find that GBM has two main pharmacological subgroups, marked by differential response to proteasome inhibitors and mutually exclusive aberrations in TP53 and CDKN2A/B. We confirm this trend in cell and in xenotransplantation models, and identify both Bcl-2 family inhibitors and p53 activators as potentiators of proteasome inhibitors in GBM cells, We can further predict the responses of individual cell cultures to several existing drug classes, presenting opportunities for drug repurposing and design of stratified trials. Our functionally profiled biobank provides a valuable resource for the discovery of new treatments for GBM.
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25. |
- Küller, Rikard, et al.
(author)
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Cognitive neuroscience – A brief introduction
- 2008
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In: URBAN DIVERSITIES, BIOSPHERE AND WELL-BEING: DESIGNING AND MANAGING OUR COMMON ENVIRONMENT (IAPS 20 Conference Proceedings on CD-Rom).
-
Conference paper (peer-reviewed)abstract
- Abstract in UndeterminedIn neuroscience a number of new techniques have been developed by means of which it has become possible to study the activity of the living human brain. By means of these techniques we are beginning to understand the neurophysiology behind environmental attitudes and preferences. The mechanisms involve links between the sensory and control parts of the cortex and specific nuclei for reward and aversion, amongst others located in the limbic system of the brain. Such links are highly resistant to extinction and have a lasting effect on the individual’s behaviour later in life. However, the highly flexible human brain is constantly prepared for revisions and additions even later in life.
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26. |
- Küller, Rikard, et al.
(author)
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How does the brain respond to everyday objects?
- 2008
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In: URBAN DIVERSITIES, BIOSPHERE AND WELL-BEING: DESIGNING AND MANAGING OUR COMMON ENVIRONMENT (IAPS 20 Conference Proceedings on CD-Rom).
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Conference paper (peer-reviewed)abstract
- Abstract in UndeterminedAn experiment is described where the participants were presented with pictures of four different objects and were also allowed to handle the objects while their brain activity was recorded by means of EEG. The objects were also evaluated by means of semantic scales. When the objects were visually displayed significant effects appeared in the posterior part of the brain, but when the participants were allowed to handle the objects pronounced effects appeared both in the anterior and posterior cortex. The most important conclusion from the study is that the aesthetic properties of common objects will influence the general activity of the brain in a systematic way similar from one person to another.
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27. |
- Lazar, Tamas, et al.
(author)
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PED in 2021 : A major update of the protein ensemble database for intrinsically disordered proteins
- 2021
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 49:D1, s. 404-411
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Journal article (peer-reviewed)abstract
- The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.0, has been completely redesigned and reimplemented with cutting-edge technology and now holds about six times more data (162 versus 24 entries and 242 versus 60 structural ensembles) and a broader representation of state of the art ensemble generation methods than the previous version. The database has a completely renewed graphical interface with an interactive feature viewer for region-based annotations, and provides a series of descriptors of the qualitative and quantitative properties of the ensembles. High quality of the data is guaranteed by a new submission process, which combines both automatic and manual evaluation steps. A team of biocurators integrate structured metadata describing the ensemble generation methodology, experimental constraints and conditions. A new search engine allows the user to build advanced queries and search all entry fields including cross-references to IDP-related resources such as DisProt, MobiDB, BMRB and SASBDB. We expect that the renewed PED will be useful for researchers interested in the atomic-level understanding of IDP function, and promote the rational, structure-based design of IDP-targeting drugs.
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28. |
- Marino, Ana-Maria
(author)
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Experimental combination therapy of brain cancer cell models
- 2012
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Licentiate thesis (other academic/artistic)abstract
- Epigenetic alterations and aberrant expression of genes controlling epigenetic mechanisms have been identified in several cancers, including medulloblastoma and glioma, the most common primary brain tumors in children and adults, respectively. We have been investigating if combination therapy using histone deacetylase inhibitors (HDACi) and receptor tyrosine kinase inhibitors (RTKi) will enhance glioblastoma and medulloblastoma cell killing. In medulloblastoma studies we combined a DNA methylation inhibitor, an HDAC inhibitor together with tyrosine kinase inhibitors. In the first study (Paper I) we have shown that combining HDACi with the RTKi gefitinib and vandetanib resulted in enhanced cell killing and reduced clonogenic survival. Mono-therapy using HDACi sodium 4-PB induced minor cell killing effects in neither of the analyzed cell lines. Similar results were observed after mono-therapy using gefitinib or vandetanib. However the combination of 4-PB with gefitinib resulted in significantly increased cell death compared to mono treatment in both cell lines. Furthermore, the double therapy resulted in a significant decrease in colony formation. The second study (Manuscript) showed that combination of drugs that inhibit two of the most important epigenetic factors (gene methylation and post-translational modifications of protein histone-associated DNA with small molecule inhibitors of receptor tyrosine kinase) enhances cell killing in two medulloblastoma cell lines. The HDACi, 4-phenylbutyrate (4-PB) and the demethylation agent, 5-Aza-2’deoxycytidine (5-Aza-dC) had minor effects on medulloblastoma cell cytotoxity when used as single agents. A significant enhancement in cell cytotoxity was seen when these drugs were combined with imatinib or sorafenib. Triple combinations resulted in accumulation of cells with subG1 DNA content and were associated with a decrease in the expression of histone deacetylase genes and reduced global methylation. This occurred together with an increase in apoptosis. Taken together these results suggest that combinations of these drugs may be beneficial in the treatment of medulloblastoma.
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29. |
- Marino Miguelez, Maria Henar, et al.
(author)
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Microfluidic Detection of < 400 CFU/ML E. COLI in Whole Blood Within One Hour
- 2023
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In: 2023 22nd International Conference on Solid-State Sensors, Actuators and Microsystems, Transducers 2023. - : Institute of Electrical and Electronics Engineers Inc.. ; , s. 1009-1011
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Conference paper (peer-reviewed)abstract
- We report a novel workflow for the isolation of bacteria from whole blood samples. We detected E. coli from 50 μL of whole blood in concentrations as low as 400 CFU/mL in less than 1 h using a microfluidic device. The method presented consists of reducing the number of blood cells found in whole blood by selectively lysing the blood cells with a solution of saponin and sodium cholate. We demonstrate that the bacteria grow during the time of loading in the microchip and can continue to be grown afterwards on the chip. Additionally, we show our approach is compatible with some of the most common sepsis-causing bacteria. The method can half the bacterial culture time needed for antibiotic susceptibility testing (AST) of bloodstream infections.
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30. |
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31. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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32. |
- Mohandasan, Anjana, et al.
(author)
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Photometric binaries in 14 Magellanic Cloud star clusters
- 2024
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 681
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Journal article (peer-reviewed)abstract
- Binary stars play a major role in determining the dynamic evolution of star clusters. We used images collected with the Hubble Space Telescope to study fourteen star clusters of the Magellanic Clouds that span an age interval between ∼0.6 and 2.1 Gyr and masses of 104 − 105 M⊙. We estimated the fraction of binary systems composed of two main-sequence stars and the fraction of candidate blue-straggler stars (BSSs). Moreover, we derived the structural parameters of the cluster, including the core radius, central density, mass function, and total mass. We find that the fraction of binaries with a mass ratio larger than 0.7 ranges from ∼7% in NGC 1846 to ∼20% in NGC 2108. The radial and luminosity distribution can change from one cluster to another. However, when we combine the results from all the clusters, we find that binaries follow a flat radial trend and no significant correlation with the mass of the primary star. We find no evidence for a relation between the fractions of binaries and BSSs. We combined the results on binaries in the studied Magellanic Cloud clusters with those obtained for 67 Galactic globular clusters and 78 open clusters. We detect a significant anti-correlation between the binary fraction in the core and the mass of the host cluster. However, star clusters with similar masses exhibit a wide range of binary fractions. Conversely, there is no evidence of a correlation between the fraction of binaries and the cluster age or the dynamic age.
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33. |
- Niklison-Chirou, Maria Victoria, et al.
(author)
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TAp73 is a marker of glutamine addiction in medulloblastoma
- 2017
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In: Genes & Development. - : COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. - 0890-9369 .- 1549-5477. ; 31:17, s. 1738-1753
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Journal article (peer-reviewed)abstract
- Medulloblastoma is the most common solid primary brain tumor in children. Remarkable advancements in the understanding of the genetic and epigenetic basis of these tumors have informed their recent molecular classification. However, the genotype/phenotype correlation of the subgroups remains largely uncharacterized. In particular, the metabolic phenotype is of great interest because of its druggability, which could lead to the development of novel and more tailored therapies for a subset of medulloblastoma. p73 plays a critical role in a range of cellular metabolic processes. We show overexpression of p73 in a proportion of non-WNT medulloblastoma. In these tumors, p73 sustains cell growth and proliferation via regulation of glutamine metabolism. We validated our results in a xenograft model in which we observed an increase in survival time in mice on a glutamine restriction diet. Notably, glutamine starvation has a synergistic effect with cisplatin, a component of the current medulloblastoma chemotherapy. These findings raise the possibility that glutamine depletion can be used as an adjuvant treatment for p73-expressing medulloblastoma.
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34. |
- Oleszkiewicz, A., et al.
(author)
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Hedonic perception of odors in children aged 5–8 years is similar across 18 countries : Preliminary data
- 2022
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In: International Journal of Pediatric Otorhinolaryngology. - : Elsevier BV. - 0165-5876 .- 1872-8464. ; 157
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Journal article (peer-reviewed)abstract
- Objective: Olfactory preference emerges very early in life, and the sense of smell in children rapidly develops until the second decade of life. It is still unclear whether hedonic perception of odors is shared in children inhabiting different regions of the globe.Methods: Five-hundred ten healthy children (N = 510; ngirls = 256; nboys = 254) aged from 5 to 8 years from 18 countries rated the pleasantness of 17 odors.Results: The hedonic perception of odors in children aged between 5 and 8 years was rather consistent across 18 countries and mainly driven by the qualities of an odor and the overall ability of children to label odorants.Conclusion: Conclusions from this study, being a secondary analysis, are limited to the presented set of odors that were initially selected for the development of U-Sniff test and present null findings for the cross-cultural variability in hedonic perception of odors across 18 countries. These two major issues should be addressed in the future to either contradict or replicate the results presented herewith. This research lays fundament for posing further research questions about the developmental aspects of hedonic perception of odors and opens a new door for investigating cross-cultural differences in chemosensory perception of children.
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35. |
- Osoegawa, Kazutoyo, et al.
(author)
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Quality control project of NGS HLA genotyping for the 17th International HLA and Immunogenetics Workshop
- 2019
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In: Human Immunology. - : ELSEVIER SCIENCE INC. - 0198-8859 .- 1879-1166. ; 80:4, s. 228-236
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Journal article (peer-reviewed)abstract
- The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups, scored the 15 independently generated sets of NGS HLA genotyping data, and generated "consensus" HLA genotypes for each of the 50 cell lines. Proficiency Testing (PT) was subsequently organized using four sets of 24 cell lines, selected from 48 of 50 PS cell lines, to validate the quality of NGS HLA typing data from the 34 participating IHIW laboratories. Completion of the PT program with a minimum score of 95% concordance at the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci satisfied the requirements to submit NGS HLA typing data for the 17th IHIW projects. Together, these PS and PT efforts constituted the 17th IHIW Quality Control project. Overall PT concordance rates for HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1, HLA-DRB3, HLA-DRB4 and HLA-DRB5 were 98.1%, 97.0% and 98.1%, 99.0%, 98.6%, 98.8%, 97.6%, 96.0%, 99.1%, 90.0% and 91.7%, respectively. Across all loci, the majority of the discordance was due to allele dropout. The high cost of NGS HLA genotyping per experiment likely prevented the retyping of initially failed HLA loci. Despite the high HLA genotype concordance rates of the software, there remains room for improvement in the assembly of more accurate consensus DNA sequences by NGS HLA genotyping software.
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36. |
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37. |
- Quaglia, Federica, et al.
(author)
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DisProt in 2022 : improved quality and accessibility of protein intrinsic disorder annotation
- 2022
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 50:D1, s. D480-D487
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Journal article (peer-reviewed)abstract
- The Database of Intrinsically Disordered Proteins (DisProt, URL: https://disprot.org) is the major repository of manually curated annotations of intrinsically disordered proteins and regions from the literature. We report here recent updates of DisProt version 9, including a restyled web interface, refactored Intrinsically Disordered Proteins Ontology (IDPO), improvements in the curation process and significant content growth of around 30%. Higher quality and consistency of annotations is provided by a newly implemented reviewing process and training of curators. The increased curation capacity is fostered by the integration of DisProt with APICURON, a dedicated resource for the proper attribution and recognition of biocuration efforts. Better interoperability is provided through the adoption of the Minimum Information About Disorder (MIADE) standard, an active collaboration with the Gene Ontology (GO) and Evidence and Conclusion Ontology (ECO) consortia and the support of the ELIXIR infrastructure.
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38. |
- Romero, Gustavo Q., et al.
(author)
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Climate variability and aridity modulate the role of leaf shelters for arthropods : A global experiment
- 2022
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:11, s. 3694-3710
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Journal article (peer-reviewed)abstract
- Current climate change is disrupting biotic interactions and eroding biodiversity worldwide. However, species sensitive to aridity, high temperatures, and climate variability might find shelter in microclimatic refuges, such as leaf rolls built by arthropods. To explore how the importance of leaf shelters for terrestrial arthropods changes with latitude, elevation, and climate, we conducted a distributed experiment comparing arthropods in leaf rolls versus control leaves across 52 sites along an 11,790 km latitudinal gradient. We then probed the impact of short- versus long-term climatic impacts on roll use, by comparing the relative impact of conditions during the experiment versus average, baseline conditions at the site. Leaf shelters supported larger organisms and higher arthropod biomass and species diversity than non-rolled control leaves. However, the magnitude of the leaf rolls' effect differed between long- and short-term climate conditions, metrics (species richness, biomass, and body size), and trophic groups (predators vs. herbivores). The effect of leaf rolls on predator richness was influenced only by baseline climate, increasing in magnitude in regions experiencing increased long-term aridity, regardless of latitude, elevation, and weather during the experiment. This suggests that shelter use by predators may be innate, and thus, driven by natural selection. In contrast, the effect of leaf rolls on predator biomass and predator body size decreased with increasing temperature, and increased with increasing precipitation, respectively, during the experiment. The magnitude of shelter usage by herbivores increased with the abundance of predators and decreased with increasing temperature during the experiment. Taken together, these results highlight that leaf roll use may have both proximal and ultimate causes. Projected increases in climate variability and aridity are, therefore, likely to increase the importance of biotic refugia in mitigating the effects of climate change on species persistence.
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39. |
- Schriever, Valentin A., et al.
(author)
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Development of an International Odor Identification Test for Children : The Universal Sniff Test
- 2018
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In: The Journal of Pediatrics. - : Elsevier BV. - 0022-3476 .- 1097-6833. ; 198, s. 265-272
-
Journal article (peer-reviewed)abstract
- ObjectiveTo assess olfactory function in children and to create and validate an odor identification test to diagnose olfactory dysfunction in children, which we called the Universal Sniff (U-Sniff) test.Study designThis is a multicenter study involving 19 countries. The U-Sniff test was developed in 3 phases including 1760 children age 5-7 years. Phase 1: identification of potentially recognizable odors; phase 2: selection of odorants for the odor identification test; and phase 3: evaluation of the test and acquisition of normative data. Test-retest reliability was evaluated in a subgroup of children (n = 27), and the test was validated using children with congenital anosmia (n = 14). Results Twelve odors were familiar to children and, therefore, included in the U-Sniff test. Children scored a mean +/- SD of 9.88 +/- 1.80 points out of 12. Normative data was obtained and reported for each country. The U-Sniff test demonstrated a high test-retest reliability (r(27) = 0.83, P < .001) and enabled discrimination between normosmia and children with congenital anosmia with a sensitivity of 100% and specificity of 86%.ConclusionsThe U-Sniff is a valid and reliable method of testing olfaction in children and can be used internationally.
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40. |
- Telloni, Daniele, et al.
(author)
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Linking Small-scale Solar Wind Properties with Large-scale Coronal Source Regions through Joint Parker Solar Probe-Metis/Solar Orbiter Observations
- 2022
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In: Astrophysical Journal. - : IOP Publishing Ltd. - 0004-637X .- 1538-4357. ; 935:2
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Journal article (peer-reviewed)abstract
- The solar wind measured in situ by Parker Solar Probe in the very inner heliosphere is studied in combination with the remote-sensing observation of the coronal source region provided by the METIS coronagraph aboard Solar Orbiter. The coronal outflows observed near the ecliptic by Metis on 2021 January 17 at 16:30 UT, between 3.5 and 6.3 R (circle dot) above the eastern solar limb, can be associated with the streams sampled by PSP at 0.11 and 0.26 au from the Sun, in two time intervals almost 5 days apart. The two plasma flows come from two distinct source regions, characterized by different magnetic field polarity and intensity at the coronal base. It follows that both the global and local properties of the two streams are different. Specifically, the solar wind emanating from the stronger magnetic field region has a lower bulk flux density, as expected, and is in a state of well-developed Alfvenic turbulence, with low intermittency. This is interpreted in terms of slab turbulence in the context of nearly incompressible magnetohydrodynamics. Conversely, the highly intermittent and poorly developed turbulent behavior of the solar wind from the weaker magnetic field region is presumably due to large magnetic deflections most likely attributed to the presence of switchbacks of interchange reconnection origin.
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41. |
- van Nuijs, Alexander L. N., et al.
(author)
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Multi-year inter-laboratory exercises for the analysis of illicit drugs and metabolites in wastewater : development of a quality control system
- 2018
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In: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 103, s. 34-43
-
Research review (peer-reviewed)abstract
- Thirty-seven laboratories from 25 countries present the development of an inter-laboratory testing scheme for the analysis of seven illicit drug residues in standard solutions, tap- and wastewater. Almost 10 000 concentration values were evaluated: triplicates of up to five samples and 26 laboratories per year. The setup was substantially improved with experiences gained across the six repetitions (e.g. matrix type, sample conditions, spiking levels). From this, (pre-)analytical issues (e.g. pH adjustment, filtration) were revealed for specific analytes which resulted in formulation of best-practice protocols for inter-laboratory setup and analytical procedures. The results illustrate the effectiveness of the interlaboratory setup to assess laboratory performance in the framework of wastewater-based epidemiology. The exercise proved that measurements of laboratories were of high quality (>80% satisfactory results for six out of seven analytes) and that analytical follow-up is important to assist laboratories in improving robustness of wastewater-based epidemiology results.
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