| 1. |
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| 2. |
- Böhm, Julia K., et al.
(författare)
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Extended Coagulation Profiling in Isolated Traumatic Brain Injury : A CENTER-TBI Analysis
- 2022
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Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 36:3, s. 927-941
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Trauma-induced coagulopathy in traumatic brain injury (TBI) remains associated with high rates of complications, unfavorable outcomes, and mortality. The underlying mechanisms are largely unknown. Embedded in the prospective multinational Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, coagulation profiles beyond standard conventional coagulation assays were assessed in patients with isolated TBI within the very early hours of injury.METHODS: Results from blood samples (citrate/EDTA) obtained on hospital admission were matched with clinical and routine laboratory data of patients with TBI captured in the CENTER-TBI central database. To minimize confounding factors, patients with strictly isolated TBI (iTBI) (n = 88) were selected and stratified for coagulopathy by routine international normalized ratio (INR): (1) INR < 1.2 and (2) INR ≥ 1.2. An INR > 1.2 has been well adopted over time as a threshold to define trauma-related coagulopathy in general trauma populations. The following parameters were evaluated: quick's value, activated partial thromboplastin time, fibrinogen, thrombin time, antithrombin, coagulation factor activity of factors V, VIII, IX, and XIII, protein C and S, plasminogen, D-dimer, fibrinolysis-regulating parameters (thrombin activatable fibrinolysis inhibitor, plasminogen activator inhibitor 1, antiplasmin), thrombin generation, and fibrin monomers.RESULTS: Patients with iTBI with INR ≥ 1.2 (n = 16) had a high incidence of progressive intracranial hemorrhage associated with increased mortality and unfavorable outcome compared with patients with INR < 1.2 (n = 72). Activity of coagulation factors V, VIII, IX, and XIII dropped on average by 15-20% between the groups whereas protein C and S levels dropped by 20%. With an elevated INR, thrombin generation decreased, as reflected by lower peak height and endogenous thrombin potential (ETP), whereas the amount of fibrin monomers increased. Plasminogen activity significantly decreased from 89% in patients with INR < 1.2 to 76% in patients with INR ≥ 1.2. Moreover, D-dimer levels significantly increased from a mean of 943 mg/L in patients with INR < 1.2 to 1,301 mg/L in patients with INR ≥ 1.2.CONCLUSIONS: This more in-depth analysis beyond routine conventional coagulation assays suggests a counterbalanced regulation of coagulation and fibrinolysis in patients with iTBI with hemostatic abnormalities. We observed distinct patterns involving key pathways of the highly complex and dynamic coagulation system that offer windows of opportunity for further research. Whether the changes observed on factor levels may be relevant and explain the worse outcome or the more severe brain injuries by themselves remains speculative.
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| 3. |
- Böhm, Julia K., et al.
(författare)
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Global Characterisation of Coagulopathy in Isolated Traumatic Brain Injury (iTBI) : A CENTER-TBI Analysis
- 2020
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Ingår i: Neurocritical Care. - : Encyclopedia of Global Archaeology/Springer Verlag. - 1541-6933 .- 1556-0961. ; 35:1, s. 184-196
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Tidskriftsartikel (refereegranskat)abstract
- Background: Trauma-induced coagulopathy in patients with traumatic brain injury (TBI) is associated with high rates of complications, unfavourable outcomes and mortality. The mechanism of the development of TBI-associated coagulopathy is poorly understood.Methods: This analysis, embedded in the prospective, multi-centred, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, aimed to characterise the coagulopathy of TBI. Emphasis was placed on the acute phase following TBI, primary on subgroups of patients with abnormal coagulation profile within 4 h of admission, and the impact of pre-injury anticoagulant and/or antiplatelet therapy. In order to minimise confounding factors, patients with isolated TBI (iTBI) (n = 598) were selected for this analysis.Results: Haemostatic disorders were observed in approximately 20% of iTBI patients. In a subgroup analysis, patients with pre-injury anticoagulant and/or antiplatelet therapy had a twice exacerbated coagulation profile as likely as those without premedication. This was in turn associated with increased rates of mortality and unfavourable outcome post-injury. A multivariate analysis of iTBI patients without pre-injury anticoagulant therapy identified several independent risk factors for coagulopathy which were present at hospital admission. Glasgow Coma Scale (GCS) less than or equal to 8, base excess (BE) less than or equal to − 6, hypothermia and hypotension increased risk significantly.Conclusion: Consideration of these factors enables early prediction and risk stratification of acute coagulopathy after TBI, thus guiding clinical management.
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| 4. |
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| 5. |
- Berntman, Emma, et al.
(författare)
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The role of CD1d-restricted NK T lymphocytes in the immune response to oral infection with Salmonella typhimurium.
- 2005
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Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 35:7, s. 2100-2109
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Tidskriftsartikel (refereegranskat)abstract
- CD1d-restricted natural killer T (NKT) cells belong to the innate-like lymphocytes which respond rapidly to stress and infectious challenge. We have studied murine CD1d-restricted NKT cells in the early immune response to virulent Salmonella enterica serovar Typhimurium after oral infection. In the liver and spleen, neutrophil and macrophage numbers had increased several-fold by day 5 post-infection, while the frequency of B and T lymphocytes decreased. These cellular changes occurred independently of CD1d-restricted NKT cells, and further, CD1d-restricted T cells did not influence the bacterial load. However, in CD1d+ mice NK1.1+ T cells and invariant CD1d-restricted T cells were activated by the infection, as demonstrated by an increase in size, up-regulation of CD69 and production of IFN-. The NK1.1 antigen was down-modulated on these cells during the course of infection, while TCR levels were unaffected. While dendritic cells (DC) up-regulated CD1d-levels upon 24 h of in vitro exposure to the bacteria, increased CD1d expression was not evident on DC in vivo during infection. Furthermore, in vitro re-stimulation of CD1d-restricted T cells isolated from infected mice demonstrated a significant skewing of the cytokine profile, with suppressed IL-4 and increased IFN- production.
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| 6. |
- Blokland, G. A. M., et al.
(författare)
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Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders
- 2022
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
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| 7. |
- Borg, Julia, et al.
(författare)
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Oesophageal dysmotility, delayed gastric emptying and gastrointestinal symptoms in patients with diabetes mellitus.
- 2007
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Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 24:11, s. 1235-1239
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Tidskriftsartikel (refereegranskat)abstract
- Aims Gastroparesis is a common gastrointestinal complication in diabetes mellitus, whereas dysfunction in the other gastrointestinal organs has been less thoroughly investigated. Furthermore, it is not known whether there is any relationship between motility and dysmotility between these organs. The aim of this study was to examine whether diabetic patients with gastrointestinal symptoms also have motility disturbances in the oesophagus and stomach and, if so, whether there are any associations between these disturbances. Methods Thirty-one patients with diabetes mellitus who complained of gastrointestinal symptoms were asked to complete a questionnaire about their symptoms. They were further investigated with oesophageal manometry and gastric emptying scintigraphy. Results Fifty-eight per cent of the patients had abnormal oesophageal function, and 68% had delayed gastric emptying. Abdominal fullness was the only symptom that related to any dysfunction, and it was associated with delayed gastric emptying (P = 0.02). We did not find any relationship in motility or dysmotility between the oesophagus and the stomach. Conclusion Oesophageal dysmotility, as well as gastroparesis, are common in patients with diabetes who have gastrointestinal symptoms. It is important to investigate these patients further, to be able to reach an accurate diagnosis and instigate appropriate treatment. Our findings indicate that the oesophagus and the stomach function as separate organs and that pathology in one does not necessarily mean pathology in the other.
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| 8. |
- Carlson, Rolf, et al.
(författare)
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Cross-Cultural Perception of Discourse Phenomena
- 2009
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Ingår i: INTERSPEECH 2009. - BAIXAS : ISCA-INST SPEECH COMMUNICATION ASSOC. ; , s. 1723-1726
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Konferensbidrag (refereegranskat)abstract
- We discuss perception studies of two low level indicators of discourse phenomena by Swedish. Japanese, and Chinese native speakers. Subjects were asked to identify upcoming prosodic boundaries and disfluencies in Swedish spontaneous speech. We hypothesize that speakers of prosodically unrelated languages should be less able to predict upcoming phrase boundaries but potentially better able to identify disfluencies, since indicators of disfluency are more likely to depend upon lexical, as well as acoustic information. However, surprisingly, we found that both phenomena were fairly well recognized by native and non-native speakers, with, however, some possible interference from word tones for the Chinese subjects.
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| 9. |
- Carlson, Rolf, et al.
(författare)
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Prediction of upcoming Swedish prosodic boundaries by Swedish and American listeners
- 2004
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Ingår i: Proc of Intl Conference on Speech Prosody 2004. - Nara, Japan. ; , s. 329-332
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Konferensbidrag (refereegranskat)abstract
- We describe results of a study of perceptually based predictions of upcoming prosodic breaks in spontaneous Swedish speech materials by native speakers of Swedish and of standard American English. The question addressed here is the extent to which listeners are able, on the basis of acoustic and prosodic features, to predict the occurrence of upcoming boundaries, and if so, whether they are able to distinguish different degrees of boundary strength. An experiment was conducted in which spontaneous utterance fragments (both long and short versions) were presented to listeners, who were instructed to guess whether or not the fragments were followed by a prosodic break, and if so, what the strength of the break was, where boundary presence and strength had been independently labeled. Results revealed that both listening groups were indeed able to predict whether or not a boundary (of a particular strength) followed the fragment, suggesting that prosodic rather than lexico-grammatical information was being used as a primary cue.
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| 10. |
- Eichenlaub, Manuel, et al.
(författare)
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Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems
- 2024
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Ingår i: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593. ; 26:4, s. 263-275
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Tidskriftsartikel (refereegranskat)abstract
- Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC), that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels is suggested that enables the collection of comparator data with these characteristics. This work is an important step towards establishing a future standard for the performance evaluation of CGM systems.
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| 11. |
- Elmberg, Maria, et al.
(författare)
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Increased Risk of Arthropathies and Joint Replacement Surgery in Patients With Genetic Hemochromatosis: A Study of 3,531 Patients and Their 11,794 First-Degree Relatives
- 2013
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Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 65:5, s. 678-685
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Tidskriftsartikel (refereegranskat)abstract
- Objective Genetic hemochromatosis (GH) is an autosomal recessive disease in individuals of Northern and Western European descent. Heterozygosity for the C282Y mutation is common (620%). Arthropathy is one of the few complications of GH suggested not to be associated with iron body stores; synovial iron deposition remains in iron-depleted patients. Previous studies suggest an elevated prevalence of clinical and radiographic signs of arthropathy in patients with GH, and 2 smaller studies suggest a possibly elevated risk of joint replacement surgery, but more mixed results are shown regarding risks with HFE genotype. We therefore assessed the risks of arthropathy and joint replacement surgery in patients with GH and in their first-degree relatives (FDRs). Methods We performed a population-based cohort study of 3,531 patients with GH and of their 11,794 FDRs (assumed to be heterozygous for the C282Y mutation) using nationwide Swedish population-based health and census registers. Hazard ratios (HRs) of arthropathies and joint replacement surgeries among patients and their FDRs (versus the general population) were assessed using Cox regression. Results Between 1997 and 2005, 406 of 3,531 patients were reported/hospitalized with any noninfectious arthropathies, including osteoarthritis, corresponding to an HR of 2.38 (95% confidence interval [95% CI] 2.142.64). Patients were also at increased risk of hip replacement (HR 2.77, 95% CI 2.273.38) and knee replacement (HR 2.14, 95% CI 1.582.88) surgery. Among the 11,794 FDRs (patients excluded), we found no increased risk of any of the joint morbidities. Conclusion Patients with GH, but not their FDRs, are at increased risk of arthropathies, including the need for joint replacement surgery.
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| 12. |
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| 13. |
- Hansen, Wiebke, et al.
(författare)
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Invasive legume affects species and functional composition of mountain meadow plant communities
- 2021
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Ingår i: Biological Invasions. - : Springer. - 1387-3547 .- 1573-1464. ; 23:1, s. 281-296
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Tidskriftsartikel (refereegranskat)abstract
- Plant invasions are among the key drivers of global biodiversity and ecosystem change. They often cause reductions in native species richness and overall biodiversity. Nitrogen-fixing plants are problematic as they affect soil nutrient availability and outcompete species of nutrient-poor sites. Here we assessed the impacts of the legumeLupinus polyphylluson species and functional diversity of mountain meadow communities in the UNESCO Biosphere Reserve Rhon. We compared species diversity (richness, evenness and effective species number), functional diversity (functional richness, evenness, divergence and dispersion) and similarity of plots in three characteristic vegetation types (Nardusgrassland, mesic and wet mountain hay meadows) between different lupine cover classes. We calculated community weighted means (CWMs) of single plant traits and plotted them against lupine cover classes. The invasion ofL. polyphyllushomogenizes vegetation composition since the similarity among plots of the different vegetation types increased with increasing lupine cover. It significantly affected species diversity in terms of richness and effective species number and the functional divergence of the vegetation. The trait set of species occurring together with lupine was shifted towards more competitive trait values. We demonstrate strongly negative impacts ofL. polyphylluson different mountain meadow vegetation types sinceL. polyphyllus, fosters the growth of competitive species and leads to overall more productive plant communities.
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| 14. |
- Hess, Timo, et al.
(författare)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 15. |
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| 16. |
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| 17. |
- Julia Piovan, Maria, et al.
(författare)
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Germination Response to Osmotic Potential, Osmotic Agents, and Temperature of Five Halophytes Occurring along a Salinity Gradient
- 2019
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Ingår i: International journal of plant sciences. - : University of Chicago Press. - 1058-5893 .- 1537-5315. ; 180:4, s. 345-355
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Tidskriftsartikel (refereegranskat)abstract
- Premise of research. Halophyte species grow where salt concentrations are high. Still, their germination may be affected by salts, either by creating an osmotic potential that prevents water uptake or by dissociating in ions that can cause different grades of toxicity. With the increase of salinized areas, it becomes important to understand the behavior of these species. Methodology. We studied how the germination of five halophyte species that occur along a salinity gradient in the Bahia Blanca coastal zone, Atriplex undulata, Cyclolepis genistoides, Allenrolfea patagonica, Sarcocornia perennis, and Heterostachys ritteriana, responds to variations in osmotic agents, osmotic potential, and temperature. Seeds were exposed to different osmotic potentials using NaCl (neutral salt), Na2CO3 (alkaline salt), and mannitol solutions in a germination chamber experiment. Germination was recorded during 42 d. Germination percentage, mean germination time, and synchrony were calculated. Pivotal results. Our experimental results showed that for the five halophyte species under study, germination was mostly driven by osmotic potentials and osmotic agents. At high osmotic potential, the germination response did not differ significantly from controls, except for Allenrolfea and Cyclolepis, which showed lower germination when treated with Na2CO3. Low osmotic potentials and Na2CO3 were detrimental to germination, reflected by lower germination percentages, higher mean germination times, and lower synchrony. Conclusions. In general, the response to the alkaline salt was more negative than that to the neutral salt or mannitol, regardless of the species. Each species showed a different response to the salts under study, and this response matched well with the distribution of species along the salinity gradient observed in the field.
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| 18. |
- Kattge, Jens, et al.
(författare)
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TRY plant trait database - enhanced coverage and open access
- 2020
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Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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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.
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| 19. |
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| 20. |
- Knödlseder, Nastassia, et al.
(författare)
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Engineering selectivity of Cutibacterium acnes phages by epigenetic imprinting
- 2022
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- Cutibacterium acnes (C. acnes) is a gram-positive bacterium and a member of the human skin microbiome. Despite being the most abundant skin commensal, certain members have been associated with common inflammatory disorders such as acne vulgaris. The availability of the complete genome sequences from various C. acnes clades have enabled the identification of putative methyltransferases, some of them potentially belonging to restrictionmodification (R-M) systems which protect the host of invading DNA. However, little is known on whether these systems are functional in the different C. acnes strains. To investigate the activity of these putative R-M and their relevance in host protective mechanisms, we analyzed the methylome of six representative C. acnes strains by Oxford Nanopore Technologies (ONT) sequencing. We detected the presence of a 6-methyladenine modification at a defined DNA consensus sequence in strain KPA171202 and recombinant expression of this R-M system confirmed its methylation activity. Additionally, a R-M knockout mutant verified the loss of methylation properties of the strain. We studied the potential of one C. acnes bacteriophage (PAD20) in killing various C. acnes strains and linked an increase in its specificity to phage DNA methylation acquired upon infection of a methylation competent strain. We demonstrate a therapeutic application of this mechanism where phages propagated in R-M deficient strains selectively kill R-M deficient acne-prone clades while probiotic ones remain resistant to phage infection.
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| 21. |
- Naoumova, Julia, et al.
(författare)
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Soft tissue profile changes after vertical ramus osteotomy
- 2008
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Ingår i: European Journal of Orthodontics. - : Oxford University Press (OUP). - 0141-5387 .- 1460-2210. ; 30:4, s. 359-365
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Tidskriftsartikel (refereegranskat)abstract
- Patients with mandibular prognathism have, for a number of years, been treated by orthognathic surgery and post-surgical changes in the facial profile have been widely reported. However, little is known about the influence of gender and age on the soft tissues. The aim of this study was to investigate changes in the soft tissue profile following orthognathic surgery and to evaluate gender and age differences in the ratios of soft-to-hard tissue change. Forty-two Caucasian adults (18 males and 24 females) aged from 17 to 46 years with mandibular prognathism who underwent vertical ramus osteotomy were included. Lateral cephalograms were taken 2-8 months pre- (T1) and 12-19 months post- (T2) surgically. Five skeletal, two dental, and seven soft tissue parameters were hand traced. Paired and unpaired Student's t-tests, Pearson's correlation coefficients, and multiple regression analyses were used to evaluate the data. Due to the setback of the mandible, soft and hard tissues changed in a 1:1 ratio at the mentolabial fold and chin in females and 1:1,1 in males. Significant differences of soft-to-hard tissue ratios were found at points Pg (P < 0.05) and Gn (P < 0.01). Age effects on the ratios were not significant. Other effects of the mandibular setback on the soft tissue profile were a significant increase in facial convexity, a deepening of the mentolabial fold, an increase in lower lip thickness, and a decrease in upper lip thickness, which increased the nasolabial angle. These findings indicate that use of gender-specific ratios in treatment planning might improve the accuracy of predicting treatment results
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| 22. |
- Nilton, Anna, et al.
(författare)
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Zinc Finger Protein 148 Is Dispensable for Primitive and Definitive Hematopoiesis in Mice
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoiesis is regulated by transcription factors that induce cell fate and differentiation in hematopoietic stem cells into fully differentiated hematopoietic cell types. The transcription factor zinc finger protein 148 (Zfp148) interacts with the hematopoietic transcription factor Gata1 and has been implicated to play an important role in primitive and definitive hematopoiesis in zebra fish and mouse chimeras. We have recently created a gene-trap knockout mouse model deficient for Zfp148, opening up for analyses of hematopoiesis in a conventional loss-of-function model in vivo. Here, we show that Zfp148-deficient neonatal and adult mice have normal or slightly increased levels of hemoglobin, hematocrit, platelets and white blood cells, compared to wild type controls. Hematopoietic lineages in bone marrow, thymus and spleen from Zfp148(gt/gt) mice were further investigated by flow cytometry. There were no differences in T-cells (CD4 and CD8 single positive cells, CD4 and CD8 double negative/positive cells) in either organ. However, the fraction of CD69- and B220-positive cells among lymphocytes in spleen was slightly lower at postnatal day 14 in Zfp148(gt/gt) mice compared to wild type mice. Our results demonstrate that Zfp148-deficient mice generate normal mature hematopoietic populations thus challenging earlier studies indicating that Zfp148 plays a critical role during hematopoietic development.
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| 23. |
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| 24. |
- Reimann, Julia, et al.
(författare)
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Archaeal Signal Transduction : Impact of Protein Phosphatase Deletions on Cell Size, Motility, and Energy Metabolism in Sulfolobus acidocaldarius
- 2013
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Ingår i: Molecular & Cellular Proteomics. - : Elsevier BV. - 1535-9476 .- 1535-9484. ; 12:12, s. 3908-3923
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the in vitro and in vivo functions of the only two identified protein phosphatases, Saci-PTP and Saci-PP2A, in the crenarchaeal model organism Sulfolobus acidocaldarius were investigated. Biochemical characterization revealed that Saci-PTP is a dual-specific phosphatase (against pSer/pThr and pTyr), whereas Saci-PP2A exhibited specific pSer/pThr activity and inhibition by okadaic acid. Deletion of saci_pp2a resulted in pronounced alterations in growth, cell shape and cell size, which could be partially complemented. Transcriptome analysis of the three strains (Δsaci_ptp, Δsaci_pp2a and the MW001 parental strain) revealed 155 genes that were differentially expressed in the deletion mutants, and showed significant changes in expression of genes encoding the archaella (archaeal motility structure), components of the respiratory chain and transcriptional regulators. Phosphoproteome studies revealed 801 unique phosphoproteins in total, with an increase in identified phosphopeptides in the deletion mutants. Proteins from most functional categories were affected by phosphorylation, including components of the motility system, the respiratory chain, and regulatory proteins. In the saci_pp2a deletion mutant the up-regulation at the transcript level, as well as the observed phosphorylation pattern, resembled starvation stress responses. Hypermotility was also observed in the saci_pp2a deletion mutant. The results highlight the importance of protein phosphorylation in regulating essential cellular processes in the crenarchaeon S. acidocaldarius.
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| 25. |
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| 26. |
- Rohayem, Jacques, et al.
(författare)
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Antiviral strategies to control calicivirus infections
- 2010
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 87:2, s. 162-178
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Forskningsöversikt (refereegranskat)abstract
- Caliciviridae are human or non-human pathogenic viruses with a high diversity. Some members of the Caliciviridae, i.e. human pathogenic norovirus or rabbit hemorrhagic disease virus (RHDV), are worldwide emerging pathogens. The norovirus is the major cause of viral gastroenteritis worldwide, accounting for about 85% of the outbreaks in Europe between 1995 and 2000. In the United States, 25 million cases of infection are reported each year. Since its emergence in 1984 as an agent of fatal hemorrhagic diseases in rabbits, RHDV has killed millions of rabbits and has been dispersed to all of the inhabitable continents. In view of their successful and apparently increasing emergence, the development of antiviral strategies to control infections due to these viral pathogens has now become an important issue in medicine and veterinary medicine. Antiviral strategies have to be based on an understanding of the epidemiology, transmission, clinical symptoms, viral replication and immunity to infection resulting from infection by these viruses. Here, we provide an overview of the mechanisms underlying calicivirus infection, focusing on the molecular aspects of replication in the host cell. Recent experimental data generated through an international collaboration on structural biology, virology and drug design within the European consortium VIZIER is also presented. Based on this analysis, we propose antiviral strategies that may significantly impact on the epidemiological characteristics of these highly successful viral pathogens.
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| 27. |
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| 28. |
- Rolf, Julia, 1979
(författare)
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Genetics and functions of innate-like lymphocyte subsets
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The immune system contains three different branches: innate immunity, adaptive immunity and innate-like lymphocytes that share properties both with the innate and adaptive immune cells. The innate-like lymphocytes have the capacity to rapidly become activated by invading pathogens and also to modulate immune responses and thereby inhibit or promote inflammation. However, understanding of the innate-like lymphocyte properties and functions has remained incomplete. This thesis describes the properties, genetic regulation, gene-expression profile and functional response of innate-like lymphocyte populations in mice. To determine the role of the innate-like B lymphocyte subset called marginal zone (MZ) B cells in autoimmunity this population was studied in the nonobese diabetic (NOD) mouse model of autoimmune diabetes. The MZ B cell population size was expanded compared to the non-autoimmune C57Bl/6 mice. The increase in MZ B cell numbers occurred before autoimmunity was initiated and not as a secondary consequence of diabetes. The MZ B cell population in NOD mice was genetically most strongly associated with diabetes-susceptibility loci Idd9/11 on chromosome 4. In addition to MZ B cells, the innate-like lymphocyte population termed natural killer T (NKT) cells was studied. NKT cells possess potent immunomodulatory functions and are divided into two subsets based on the TCR usage. Microarray technology was utilized for analyzing the global gene expression profile of the two NKT cell subsets in comparison to conventional CD4+ T cells. The NKT cells over-expressed genes encoding NK cell receptors, pro-cytotoxic molecules and chemokine-receptors that promote homing to inflamed tissues. Expression of transcription factors associated with immune cell development, such as Hhex and Id2 was induced already during thymic development. The microarray analysis of the NKT cell subsets has provided profound new insights into their features, transcriptional regulation and potential functions. The functional role of NKT cells in infectious disease was studied during infection by the pathogenic bacteria Salmonella typhimurium. The NKT cells became strongly activated by the ongoing Salmonella infection and participated in fighting Salmonella during the early phase of the infection through production of IFN-gamma. Activation of NKT cells via infection caused by an intracellular pathogen strongly skewed the NKT cells towards IFN-gamma dominated immunity. This thesis explores the properties of innate-like lymphocyte populations, with emphasize on the underlying genetic regulation and global gene expression profile. In addition, the functional role of the NKT cells in the immune response against infection is described.
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| 29. |
- Rolf, Julia, 1979, et al.
(författare)
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Molecular profiling reveals distinct functional attributes of CD1d-restricted natural killer (NK) T cell subsets.
- 2008
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Ingår i: Molecular immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 45:9, s. 2607-20
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Tidskriftsartikel (refereegranskat)abstract
- CD1d-restricted natural killer T (NKT) cells can have multiple effects on an immune response, including the activation, regulation and attraction of innate immune cells, and modulation of adaptive immunity. Recent studies reveal that there are distinct subsets of NKT cells which selectively perform some of the functions attributed to CD1d-restricted cells, but the mechanisms underlying these functional differences have not been resolved. Our aim in this study was to identify novel NKT cell associated traits that would provide important insight into NKT cell activation and function. To this end, we have performed gene expression profiling of two separate subsets of NKT cells, analyzing genes differentially expressed in these cells compared to conventional CD4(+)NK1.1(-) T cells. We identify different sets of genes over expressed in each of the two NKT cell types, as well as genes that are common to the two CD1d-restricted NKT cell populations analyzed. A large number of these genes are highly relevant for NKT cell development, activation and function. Each NKT subtype displayed a unique set of chemokine receptors, integrins and molecules related to effector function, supporting the notion that distinct NKT cells can be selectively engaged and have diverse functions in different types of immune reactions.
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| 30. |
- Rolf, Julia, et al.
(författare)
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The enlarged population of marginal zone/CD1d(high) B lymphocytes in nonobese diabetic mice maps to diabetes susceptibility region Idd11.
- 2005
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Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 174:8, s. 4821-4827
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Tidskriftsartikel (refereegranskat)abstract
- The NOD mouse is an important experimental model for human type 1 diabetes. T cells are central to NOD pathogenesis, and their function in the autoimmune process of diabetes has been well studied. In contrast, although recognized as important players in disease induction, the role of B cells is not clearly understood. In this study we characterize different subpopulations of B cells and demonstrate that marginal zone (MZ) B cells are expanded 2- to 3-fold in NOD mice compared with nondiabetic C57BL/6 (B6) mice. The NOD MZ B cells displayed a normal surface marker profile and localized to the MZ region in the NOD spleen. Moreover, the MZ B cell population developed early during the ontogeny of NOD mice. By 3 wk of age, around the time when autoreactive T cells are first activated, a significant MZ B cell population of adult phenotype was found in NOD, but not B6, mice. Using an F2(B6 x NOD) cross in a genome-wide scan, we map the control of this trait to a region on chromosome 4 (logarithm of odds score, 4.4) which includes the Idd11 and Idd9 diabetes susceptibility loci, supporting the hypothesis that this B cell trait is related to the development of diabetes in the NOD mouse.
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| 31. |
- Schäfer, David, et al.
(författare)
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Multiscale Investigation of Sodium-Ion Battery Anodes: Analytical Techniques and Applications
- 2024
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Ingår i: Advanced Energy Materials. - 1614-6840 .- 1614-6832. ; 14:15
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Tidskriftsartikel (refereegranskat)abstract
- The anode/electrolyte interface behavior, and by extension, the overall cell performance of sodium-ion batteries is determined by a complex interaction of processes that occur at all components of the electrochemical cell across a wide range of size- and timescales. Single-scale studies may provide incomplete insights, as they cannot capture the full picture of this complex and intertwined behavior. Broad, multiscale studies are essential to elucidate these processes. Within this perspectives article, several analytical and theoretical techniques are introduced, and described how they can be combined to provide a more complete and comprehensive understanding of sodium-ion battery (SIB) performance throughout its lifetime, with a special focus on the interfaces of hard carbon anodes. These methods target various length- and time scales, ranging from micro to nano, from cell level to atomistic structures, and account for a broad spectrum of physical and (electro)chemical characteristics. Specifically, how mass spectrometric, microscopic, spectroscopic, electrochemical, thermodynamic, and physical methods can be employed to obtain the various types of information required to understand battery behavior will be explored. Ways are then discussed how these methods can be coupled together in order to elucidate the multiscale phenomena at the anode interface and develop a holistic understanding of their relationship to overall sodium-ion battery function.
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| 32. |
- Sjögren, Julia, et al.
(författare)
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Reduced Vestibulo-Ocular Reflex During Fast Head Rotation in Complete Darkness
- 2023
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Ingår i: Perceptual and Motor Skills. - 0031-5125.
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Tidskriftsartikel (refereegranskat)abstract
- The human vestibulo-ocular reflex (VOR) leads to maintenance of the acuity of an image on the retina and contributes to the perception of orientation during high acceleration head movements. Our objective was to determine whether vision affects the horizontal VOR by assessing and comparing the performance at the boundaries of contribution of: (a) unrestricted visual information and (b) no visual information. Understanding how the VOR performs under both lighted and unlighted conditions is of paramount importance to avoiding falls, perhaps particularly among the elderly. We tested 23 participants (M age = 35.3 years, standard error of mean (SEM) = 2.0 years). The participants were tested with the video Head Impulse Test (vHIT), EyeSeeCam from Interacoustics™, which assesses whether VOR is of the expected angular velocity compared to head movement angular velocity. The vHIT tests were performed under two conditions: (a) in a well-lit room and (b) in complete darkness. The VOR was analyzed by evaluating the gain (quotient between eye and head angular velocity) at 40, 60 and 80 ms time stamps after the start of head movement. Additionally, we calculated the approximate linear gain between 0-100 ms through regression. The gain decreased significantly faster across time stamps in complete darkness (p < .001), by 10% in darkness compared with a 2% decrease in light. In complete darkness, the VOR gain gradually declined, reaching a marked reduction at 80 ms by 10% (p < .001), at which the head velocities were 150°/second or faster. The approximate linear gain value was not significantly different in complete darkness and in light. These findings suggest that information from the visual system can modulate the high velocity VOR. Subsequently, fast head turns might cause postural imbalance and momentary disorientation in poor light in people with reduced sensory discrimination or motor control, like the elderly.
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| 33. |
- Song, J., et al.
(författare)
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Extracellular matrix of secondary lymphoid organs impacts on B-cell fate and survival
- 2013
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 110:31
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Tidskriftsartikel (refereegranskat)abstract
- We describe a unique extracellular matrix (ECM) niche in the spleen, the marginal zone (MZ), characterized by the basement membrane glycoproteins, laminin alpha 5 and agrin, that promotes formation of a specialized population of MZ B lymphocytes that respond rapidly to blood-borne antigens. Mice with reduced laminin alpha 5 expression show reduced MZ B cells and increased numbers of newly formed (NF) transitional B cells that migrate from the bone marrow, without changes in other immune or stromal cell compartments. Transient integrin alpha 6 beta 1-mediated interaction of NF B cells with laminin alpha 5 in the MZ supports the MZ B-cell population, their long-term survival, and antibody response. Data suggest that the unique 3D structure and biochemical composition of the ECM of lymphoid organs impacts on immune cell fate.
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| 34. |
- Steinmetz, Julia, et al.
(författare)
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Descriptive Proteome Analysis to Investigate Context-Dependent Treatment Responses to OXPHOS Inhibition in Colon Carcinoma Cells Grown as Monolayer and Multicellular Tumor Spheroids
- 2020
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 5:28, s. 17242-17254
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Tidskriftsartikel (refereegranskat)abstract
- We have previously identified selective upregulation of the mevalonate pathway genes upon inhibition of oxidative phosphorylation (OXPHOS) in quiescent cancer cells. Using mass spectrometry-based proteomics, we here investigated whether these responses are corroborated on the protein level and whether proteomics could yield unique insights into context-dependent biology. HCT116 colon carcinoma cells were cultured as monolayer cultures, proliferative multicellular tumor spheroids (P-MCTS), or quiescent (Q:MCTS) multicellular tumor spheroids and exposed to OXPHOS inhibitors: nitazoxanide, FCCP, oligomycin, and salinomycin or the HMG-CoA-reductase inhibitor simvastatin at two different doses for 6 and 24 h. Samples were processed using an in-depth bottom-up proteomics workflow resulting in a total of 9286 identified protein groups. Gene set enrichment analysis showed profound differences between the three cell systems and confirmed differential enrichment of hypoxia, OXPHOS, and cell cycle progression-related protein responses in P-MCTS and QMCTS. Treatment experiments showed that the observed drug-induced alterations in gene expression of metabolically challenged cells are not translated directly to the protein level, but the results reaffirmed OXPHOS as a selective vulnerability of quiescent cancer cells. This work provides rationale for the use of deep proteome profiling to identify context-dependent treatment responses and encourages further studies investigating metabolic processes that could be co-targeted together with OXPHOS to eradicate quiescent cancer cells.
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| 35. |
- Weitere, Markus, et al.
(författare)
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Disentangling multiple chemical and non-chemical stressors in a lotic ecosystem using a longitudinal approach
- 2021
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Ingår i: SCIENCE OF THE TOTAL ENVIRONMENT. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 769
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Tidskriftsartikel (refereegranskat)abstract
- Meeting ecological and water quality standards in lotic ecosystems is often failed due to multiple stressors. However, disentangling stressor effects and identifying relevant stressor-effect-relationships in complex environmental settings remain major challenges. By combining state-of-the-art methods from ecotoxicology and aquatic ecosystem analysis, we aimed here to disentangle the effects of multiple chemical and non-chemical stressors along a longitudinal land use gradient in a third-order river in Germany. We distinguished and evaluated four dominant stressor categories along this gradient: (1) Hydromorphological alterations: Flow diversity and substrate diversity correlated with the EU-Water Framework Directive based indicators for the quality element macroinvertebrates, which deteriorated at the transition from near-natural reference sites to urban sites. (2) Elevated nutrient levels and eutrophication: Low to moderate nutrient concentrations together with complete canopy cover at the reference sites correlated with low densities of benthic algae (biofilms). We found no more systematic relation of algal density with nutrient concentrations at the downstream sites, suggesting that limiting concentrations are exceeded already at moderate nutrient concentrations and reduced shading by riparian vegetation. (3) Elevated organic matter levels: Wastewater treatment plants (WWTP) and stormwater drainage systems were the primary sources of bioavailable dissolved organic carbon. Consequently, planktonic bacterial production and especially extracellular enzyme activity increased downstream of those effluents showing local peaks. (4) Micropollutants and toxicity-related stress: WWTPs were the predominant source of toxic stress, resulting in a rapid increase of the toxicity for invertebrates and algae with only one order of magnitude below the acute toxic levels. This toxicity correlates negatively with the contribution of invertebrate species being sensitive towards pesticides (SPEAR(pesticides) index), probably contributing to the loss of biodiversity recorded in response to WWTP effluents. Our longitudinal approach highlights the potential of coordinated community efforts in supplementing established monitoring methods to tackle the complex phenomenon of multiple stress.
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| 36. |
- Westerbacka, Jukka, et al.
(författare)
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Splanchnic balance of free fatty acids, endocannabinoids, and lipids in subjects with nonalcoholic fatty liver disease
- 2010
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Ingår i: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 139:6, s. 1961-1971.e1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Animal studies suggest that endocannabinoids could contribute to the development of nonalcoholic fatty liver disease (NAFLD). In addition, NAFLD has been shown to be associated with multiple changes in lipid concentrations in liver biopsies. There are no data on splanchnic free fatty acid (FFA), glycerol, ketone body, endocannabinoid, and lipid fluxes in vivo in subjects with NAFLD.METHODS: We performed hepatic venous catheterization studies in combination with [(2)H(2)]palmitate infusion in the fasting state and during a low-dose insulin infusion in 9 subjects with various degrees of hepatic steatosis as determined using liver biopsy. Splanchnic balance of endocannabinoids and individual lipids was determined using ultra performance liquid chromatography coupled to mass spectrometry.RESULTS: Concentrations of the endocannabinoid 2-arachidonoylglycerol were higher in arterialized (91 ± 33 μg/L basally) than in hepatic venous (51 ± 19 μg/L; P < .05) plasma. Fasting arterial (r = 0.72; P = .031) and hepatic venous (r = 0.70; P = .037) concentrations of 2-arachidonoylglycerol were related positively to liver fat content. Analysis of fluxes of 85 different triglycerides showed that the fatty liver overproduces saturated triglycerides. In the plasma FFA fraction in the basal state, the relative amounts of palmitoleate and linoleate were lower and those of stearate and oleate were higher in the hepatic vein than in the artery. Absolute concentrations of all nontriglyceride lipids were comparable in arterialized venous plasma and the hepatic vein both in the basal and insulin-stimulated states.CONCLUSIONS: The human fatty liver takes up 2-arachidonoylglycerol and overproduces triacylglycerols containing saturated fatty acids, which might reflect increased de novo lipogenesis.
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