| 1. |
- Klinth, Mårten, 1990, et al.
(author)
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Investigating the Clitellata (Annelida) of Icelandic springs with alternative barcodes
- 2019
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In: Fauna Norvegica. - 1502-4873 .- 1891-5396. ; 39, s. 119-132
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Journal article (peer-reviewed)abstract
- DNA barcoding is an invaluable tool to identify clitellates, regardless of life stage or cryptic morphology. However, as COI (the standard barcode for animals) is relatively long (658 bp), sequencing it requires DNA of high quality. When DNA is fragmented due to degradation, alternative barcodes of shorter length present an option to obtain genetic material. We attempted to sequence 187 clitellates sampled from springs in Iceland. However, the material had been stored at room temperature for two years, and DNA of the worms had degraded, and only three COI sequences were produced (i.e., <2% success rate). Using two alternative barcodes of 16S (one ca. 320 bp, the other ca. 70 bp long) we increased the number of sequenced specimens to 51. Comparisons of the 16S sequences showed that even the short 70 bp fragment contained enough genetic variation to separate all clitellate species in the material. Combined with morphological examinations we recognized a total of 23 species, where at least 8 are new records for Iceland, some belonging to genera new for Iceland: Cernosvitoviella and Pristina. All the new taxa are included in an updated species list of Icelandic Clitellata. The material revealed some stygophilic species previously known to inhabit springs, but true stygobionts, which are restricted to groundwater habitats, were not found. Our study shows that short 16S fragments can be obtained from DNA too degraded to be used in traditional COI barcoding, and contain enough genetic variation to separate closely related clitellate species.
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| 2. |
- Heyman Lindén, Lovisa, et al.
(author)
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Lingonberries alter the gut microbiota and prevent low-grade inflammation in high-fat diet fed mice
- 2016
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In: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 60
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Journal article (peer-reviewed)abstract
- Background: The gut microbiota plays an important role in the development of obesity and obesity-associated impairments such as low-grade inflammation. Lingonberries have been shown to prevent diet-induced obesity and low-grade inflammation. However, it is not known whether the effect of lingonberry supplementation is related to modifications of the gut microbiota. The aim of the present study was to describe whether consumption of different batches of lingonberries alters the composition of the gut microbiota, which could be relevant for the protective effect against high fat (HF)-induced metabolic alterations. Methods: Three groups of C57BL/6J mice were fed HF diet with or without a supplement of 20% lingonberries from two different batches (Lingon1 and Lingon2) during 11 weeks. The composition and functionality of the cecal microbiota were assessed by 16S rRNA sequencing and PICRUSt. In addition, parameters related to obesity, insulin sensitivity, hepatic steatosis, inflammation and gut barrier function were examined. Results: HF-induced obesity was only prevented by the Lingon1 diet, whereas both batches of lingonberries reduced plasma levels of markers of inflammation and endotoxemia (SAA and LBP) as well as modified the composition and functionality of the gut microbiota, compared to the HF control group. The relative abundance of Akkermansia and Faecalibacterium, genera associated with healthy gut mucosa and antiinflammation, was found to increase in response to lingonberry intake. Conclusions: Our results show that supplementation with lingonberries to an HF diet prevents low-grade inflammation and is associated with significant changes of the microbiota composition. Notably, the antiinflammatory properties of lingonberries seem to be independent of effects on body weight gain.
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| 3. |
- Lawaczeck Körner, Kajsa
(author)
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Walking Along, Wandering Off and Going Astray A Critical Normativity Approach to Walking as a Situated Architectural Experience
- 2016
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Doctoral thesis (other academic/artistic)abstract
- There is a lack of attention toward the diversity in experiences of architecture that are expressed through walking. Through the application of autoethnography and critical perspectives of queer and feminist theory, this dissertation develops a method for investigating experiences of architecture in regard to the activity of walking. In addition, this thesis addresses the influence of form, materiality, and social aspects on walk conditions, thus providing architectural perspectives on design and planning that aim to address a heterogeneity among people who walk or are involved in walk matters in their everyday life. The result is an investigatory framework—critical normativity—that consists of three components: observations through a walk diary, the walk technique going astray, and the theoretical application of a critical terminology. These components work to address and situate experiences of spatiality and materiality and their impact on our walk experiences. The walk diary is a data collecting technique that stresses subjectivity of experiences, going astray is an approach that should encourage associations and openness in attitude in the investigatory phase, and the critical terminology is a theoretical framework addressing normativity and thereby positioning the interpretations of the empirical material. The applied main concepts of the critical terminology are: dis-/orientation, background/foreground, performativity, differences, situated knowledges and partial perspective, all of which are derived from queer and feminist theory. The dissertation shows that the researchers, eventually also designers and planners, will benefit from actively engaging themselves in the world of walking by reflecting and incorporating their own walk experiences into their methods and work, in order to develop empathy with the research topic, as well as critically situating their own knowledge perspectives. This way—i.e. by applying a critical normativity—the formation of walk related identities will inevitably activate: questions of e.g. desires; power to act; identity formation; subjectivity and temporality in regard to the experiences of space and materiality. In the application of the investigatory framework—critical normativity—the impact and dynamics of time, in regard to variation in action possibilities, are also addressed. This points to the fact that, in order to include a range of walk needs and behaviors, perception of difference—in particular difference that has not been pre-defined—in itself should be addressed, along with further development of performativity perspectives and identity formation as important constituents of walk conditions.
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| 4. |
- Sasaki, Yutaka, et al.
(author)
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The anti-tumour effect of cisplatin and ifosfamide on xenografted squamous cell carcinoma of the head and neck is schedule-dependent.
- 2012
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In: Oral Oncology. - : Elsevier BV. - 1879-0593 .- 1368-8375. ; 48, s. 61-66
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Journal article (peer-reviewed)abstract
- The role of chemotherapy (CHX) in squamous cell carcinoma of the head and neck (SCCHN) has been expanding. Although combination chemotherapy regimens regularly produce significantly high response rates, meta-analyses show little benefit regarding final outcome. One way to improve induction CHX is to improve drug combinations and schedules for CHX. Cisplatin (CDDP) is one of the most active drugs in the treatment of patients with SCCHN, and it is used in most combinations. Ifosfamide (IFO) is another agent that has shown activity in the treatment of patients with SCCHN. A poorly differentiated squamous cell carcinoma xenografted to nude mice was used. CDDP (2.5mg/kg) and IFO (100mg/kg) as single bolus doses induced significant retardation of tumour growth. Single drug administration was compared with CDDP given before IFO and IFO given before CDDP. Mean specific growth delay (SGD) for untreated controls was 0. For CDDP as single drug it was 1.50, for IFO as single drug it was 0.79, for CDDP given 4h before IFO it was 1.79, and for IFO given 4h before CDDP it was 2.90. Maximum toxicity, calculated as change in median weight at day 7, was less than 10%. The efficacy and toxicity of CDDP and IFO is schedule-dependent, with IFO given before CDDP being more effective than CDDP given before IFO. This is in contrast to most schedules used clinically. The toxicities were comparable. The number of combinations of drugs with respect to order and time interval is of a magnitude that would not be possible to test clinically. In the pursuit of more efficient combinations, the importance of order and schedule of drugs and also the potential of xenografted SSCHN are underestimated.
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| 5. |
- Müller, Thomas R., et al.
(author)
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Additive effects of booster mRNA vaccination and SARS-CoV-2 Omicron infection on T cell immunity across immunocompromised states
- 2023
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In: Science Translational Medicine. - 1946-6234 .- 1946-6242. ; 15:704, s. eadg9452-
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Journal article (peer-reviewed)abstract
- Suboptimal immunity to SARS-CoV-2 mRNA vaccination has frequently been observed in individuals with various immunodeficiencies. Given the increased antibody evasion properties of emerging SARS-CoV-2 subvariants, it is necessary to assess whether other components of adaptive immunity generate resilient and protective responses against infection. We assessed T cell responses in 279 individuals, covering five different immunodeficiencies and healthy controls, before and after booster mRNA vaccination, as well as after Omicron infection in a subset of patients. We observed robust and persistent Omicron-reactive T cell responses that increased markedly upon booster vaccination and correlated directly with antibody titers across all patient groups. Poor vaccination responsiveness in immunocompromised or elderly individuals was effectively counteracted by the administration of additional vaccine doses. Functionally, Omicron-reactive T cell responses exhibited a pronounced cytotoxic profile and signs of longevity, characterized by CD45RA+ effector memory subpopulations with stem cell-like properties and increased proliferative capacity. Regardless of underlying immunodeficiency, booster-vaccinated and Omicron-infected individuals appeared protected against severe disease and exhibited enhanced and diversified T cell responses against conserved and Omicron-specific epitopes. Our findings indicate that T cells retain the ability to generate highly functional responses against newly emerging variants, even after repeated antigen exposure and a robust immunological imprint from ancestral SARS-CoV-2 mRNA vaccination.
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| 6. |
- Sepulveda-Falla, Diego, et al.
(author)
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A multifactorial model of pathology for age of onset heterogeneity in familial Alzheimer's disease.
- 2021
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In: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 141, s. 217-233
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Journal article (peer-reviewed)abstract
- Presenilin-1 (PSEN1) mutations cause familial Alzheimer's disease (FAD) characterized by early age of onset (AoO). Examination of a large kindred harboring the PSEN1-E280A mutation reveals a range of AoO spanning 30years. The pathophysiological drivers and clinical impact of AoO variation in this population are unknown. We examined brains of 23 patients focusing on generation and deposition of beta-amyloid (Aβ) and Tau pathology profile. In 14 patients distributed at the extremes of AoO, we performed whole-exome capture to identify genotype-phenotype correlations. We also studied kinome activity, proteasome activity, and protein polyubiquitination in brain tissue, associating it with Tau phosphorylation profiles. PSEN1-E280A patients showed a bimodal distribution for AoO. Besides AoO, there were no clinical differences between analyzed groups. Despite the effect of mutant PSEN1 on production of Aβ, there were no relevant differences between groups in generation and deposition of Aβ. However, differences were found in hyperphosphorylated Tau (pTau) pathology, where early onset patients showed severe pathology with diffuse aggregation pattern associated with increased activation of stress kinases. In contrast, late-onset patients showed lesser pTau pathology and a distinctive kinase activity. Furthermore, we identified new protective genetic variants affecting ubiquitin-proteasome function in early onset patients, resulting in higher ubiquitin-dependent degradation of differentially phosphorylated Tau. In PSEN1-E280A carriers, altered γ-secretase activity and resulting Aβ accumulation are prerequisites for early AoO. However, Tau hyperphosphorylation pattern, and its degradation by the proteasome, drastically influences disease onset in individuals with otherwise similar Aβ pathology, hinting toward a multifactorial model of disease for FAD. In sporadic AD (SAD), a wide range of heterogeneity, also influenced by Tau pathology, has been identified. Thus, Tau-induced heterogeneity is a common feature in both AD variants, suggesting that a multi-target therapeutic approach should be used to treat AD.
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| 7. |
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| 8. |
- Dobrydnjov, Igor, et al.
(author)
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Intrathecal and oral clonidine as prophylaxis for postoperative alcohol withdrawal syndrome : a randomized double-blinded study
- 2004
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In: Anesthesia and Analgesia. - 0003-2999 .- 1526-7598. ; 98:3, s. 738-744
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Journal article (peer-reviewed)abstract
- In this study, we evaluated the effect of intrathecal and oral clonidine as supplements to spinal anesthesia with lidocaine in patients at risk of postoperative alcohol withdrawal syndrome (AWS). We hypothesized that clonidine would have a prophylactic effect on postoperative AWS. Forty-five alcohol-dependent patients (daily ethanol intake >60 g) scheduled for transurethral resection of the prostate were double-blindly randomized into three groups. All patients received hyperbaric lidocaine 100 mg intrathecally. The diazepam group (DiazG) was premedicated with diazepam 10 mg orally; the intrathecal clonidine group (Cloni/tG) received a placebo (saline) tablet and clonidine 150 μg intrathecally; and the oral clonidine group (Clonp/oG) received clonidine 150 μg orally. For patients diagnosed with AWS, the Clinical Institute Withdrawal Assessment for Alcohol, revised scale, was used. Twelve patients in the DiazG had symptoms of AWS, compared with two in the Cloni/tG and one in the Clonp/oG. The median Clinical Institute Withdrawal Assessment for Alcohol, revised scale, score was 12 in the DiazG versus 1 in the clonidine-treated groups. Two patients in the DiazG had severe delirium. Patients receiving oral clonidine had a slightly decreased mean arterial blood pressure 6–12 h after spinal anesthesia (P < 0.05); patients in the DiazG had a hyperdynamic circulatory reaction 24–72 h after surgery. In conclusion, preoperative clonidine 150 μg, intrathecally or orally, prevented significant postoperative AWS in ethanol-dependent patients.
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| 9. |
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| 10. |
- Aharrouche, M., et al.
(author)
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Time resolution of the ATLAS barrel liquid argon electromagnetic calorimeter
- 2008
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 597:2-3, s. 178-188
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Journal article (peer-reviewed)abstract
- The time reconstruction performance of the ATLAS electromagnetic calorimeter readout is studied. The contribution of the electronics to the time resolution is estimated to be about 20 ps, thus demonstrating the possibility of achieving a small constant term in the time resolution for particles. The resolution to electromagnetic showers produced by an electron beam is also measured. After correction for the effects due to the calorimeter geometry, a 100 ps constant term is found for a typical cell.
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