| 1. |
- Adori, Csaba, et al.
(author)
-
Exploring the role of neuropeptide S in the regulation of arousal : a functional anatomical study
- 2016
-
In: Brain Structure and Function. - : Springer. - 1863-2653 .- 1863-2661. ; 221:7, s. 3521-3546
-
Journal article (peer-reviewed)abstract
- Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep.
|
|
| 2. |
- Agaton, C., et al.
(author)
-
Affinity proteomics for systematic protein profiling of chromosome 21 gene products in human tissues
- 2003
-
In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 2, s. 405-
-
Journal article (peer-reviewed)abstract
- Here we show that an affinity proteomics strategy using affinity-purified antibodies raised against recombinant human protein fragments can be used for chromosome-wide protein profiling. The approach is based on affinity reagents raised toward bioinformatics-designed protein epitope signature tags corresponding to unique regions of individual gene loci. The genes of human chromosome 21 identified by the genome efforts were investigated, and the success rates for de novo cloning, protein production, and antibody generation were 85, 76, and 56%, respectively. Using human tissue arrays, a systematic profiling of protein expression and subcellular localization was undertaken for the putative gene products. The results suggest that this affinity proteomics strategy can be used to produce a proteome atlas, describing distribution and expression of proteins in normal tissues as well as in common cancers and other forms of diseased tissues.
|
|
| 3. |
- Aili, Katarina, 1980-, et al.
(author)
-
Sleep disturbances predict future sickness absence among individuals with lower back or neck-shoulder pain : A 5-year prospective study
- 2015
-
In: Scandinavian Journal of Public Health. - London : SAGE Publications. - 1403-4948 .- 1651-1905. ; 43:3, s. 315-323
-
Journal article (peer-reviewed)abstract
- Background: Musculoskeletal pain is one of the most common causes of sickness absence. Sleep disturbances are often co-occurring with pain, but the relationship between sleep and pain is complex. Little is known about the importance of self-reported sleep, when predicting sickness absence among persons with musculoskeletal pain. This study aims to study the association between self-reported sleep quality and sickness absence 5 years later, among individuals stratified by presence of lower back pain (LBP) and neck and shoulder pain (NSP). Methods: The cohort (n = 2286) in this 5-year prospective study (using data from the MUSIC-Norrtalje study) was stratified by self-reported pain into three groups: no LBP or NSP, solely LBP or NSP, and oncurrent LBP and NSP. Odds ratios (ORs) for the effect of self-reported sleep disturbances at baseline on sickness absence (> 14 consecutive days), 5 years later, were calculated. Results: Within all three pain strata, individuals reporting the most sleep problems showed a significantly higher OR for all-cause sickness absence, 5 years later. The group with the most pronounced sleep problems within the concurrent LBP and NSP stratum had a significantly higher OR (OR 2.00; CI 1.09-3.67) also for long-term sickness absence (> 90days) 5 years later, compared to the group with the best sleep. Conclusions: Sleep disturbances predict sickness absence among individuals regardless of co-existing features of LBP and/or NSP. The clinical evaluation of patients should take possible sleep disturbances into account in the planning of treatments.
|
|
| 4. |
- Ajalloueian, Fatemeh, et al.
(author)
-
One-Stage Tissue Engineering of Bladder Wall Patches for an Easy-To-Use Approach at the Surgical Table
- 2013
-
In: Tissue Engineering. Part C, Methods. - : Mary Ann Liebert Inc. - 1937-3384 .- 1937-3392. ; 19:9, s. 688-696
-
Journal article (peer-reviewed)abstract
- We present a method for producing a cell-scaffold hybrid construct at the bedside. The construct is composed of plastic-compressed collagen together with a poly(e-caprolactone) (PCL)-knitted mesh that yields an integrated, natural-synthetic scaffold. This construct was evaluated by seeding of minced bladder mucosa, followed by proliferation in vitro. High mechanical strength in combination with a biological environment suitable for tissue growth was achieved through the creation of a hybrid construct that showed an increased tensile strength (17.9 +/- 2.6 MPa) when compared to plastic-compressed collagen (0.6 +/- 0.12 MPa). Intimate contact between the collagen and the PCL fabric was required to ensure integrity without delamination of the construct. This contact was achieved by surface alkaline hydrolysis of the PCL, followed by adsorption of poly(vinyl) alcohol. The improvement in hydrophilicity of the PCL-knitted mesh was confirmed through water contact angle measurements, and penetration of the collagen into the mesh was evaluated by scanning electron microscopy (SEM). Particles of minced bladder mucosa tissue were seeded onto this scaffold, and the proliferation was followed for 6 weeks in vitro. Results obtained from phase contrast microscopy, SEM, and histological staining indicated that cells migrated from the minced tissue particles and reorganized on the scaffold. Cells were viable and proliferative, with morphological features characteristic of urothelial cells. Proliferation reached the point at which a multilayer with a resemblance to stratified urothelium was achieved. This successful method could potentially be used for in vivo applications in reconstructive urology as an engineered autologous tissue transplant without the requirement for in vitro culture before transplantation.
|
|
| 5. |
- Alneberg, Johannes, et al.
(author)
-
Genomes from uncultivated prokaryotes : a comparison of metagenome-assembled and single-amplified genomes
- 2018
-
In: Microbiome. - : BioMed Central. - 2049-2618. ; 6
-
Journal article (peer-reviewed)abstract
- Background: Prokaryotes dominate the biosphere and regulate biogeochemical processes essential to all life. Yet, our knowledge about their biology is for the most part limited to the minority that has been successfully cultured. Molecular techniques now allow for obtaining genome sequences of uncultivated prokaryotic taxa, facilitating in-depth analyses that may ultimately improve our understanding of these key organisms. Results: We compared results from two culture-independent strategies for recovering bacterial genomes: single-amplified genomes and metagenome-assembled genomes. Single-amplified genomes were obtained from samples collected at an offshore station in the Baltic Sea Proper and compared to previously obtained metagenome-assembled genomes from a time series at the same station. Among 16 single-amplified genomes analyzed, seven were found to match metagenome-assembled genomes, affiliated with a diverse set of taxa. Notably, genome pairs between the two approaches were nearly identical (average 99.51% sequence identity; range 98.77-99.84%) across overlapping regions (30-80% of each genome). Within matching pairs, the single-amplified genomes were consistently smaller and less complete, whereas the genetic functional profiles were maintained. For the metagenome-assembled genomes, only on average 3.6% of the bases were estimated to be missing from the genomes due to wrongly binned contigs. Conclusions: The strong agreement between the single-amplified and metagenome-assembled genomes emphasizes that both methods generate accurate genome information from uncultivated bacteria. Importantly, this implies that the research questions and the available resources are allowed to determine the selection of genomics approach for microbiome studies.
|
|
| 6. |
- Altai, Mohamed, et al.
(author)
-
Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with (188)Re.
- 2014
-
In: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 87, s. 519-28
-
Journal article (peer-reviewed)abstract
- Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all (188)Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The (188)Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of (188)Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental (188)Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of (188)Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
|
|
| 7. |
- Alvez, Maria Bueno, et al.
(author)
-
Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Journal article (peer-reviewed)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
|
|
| 8. |
- Ameur, Adam, et al.
(author)
-
SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
- 2017
-
In: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
-
Journal article (peer-reviewed)abstract
- Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
|
|
| 9. |
- Andersson, A. F., et al.
(author)
-
Comparative analysis of human gut microbiota by barcoded pyrosequencing
- 2008
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:7
-
Journal article (peer-reviewed)abstract
- Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.
|
|
| 10. |
- Andersson, Sandra, et al.
(author)
-
Insufficient antibody validation challenges oestrogen receptor beta research
- 2017
-
In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
-
Journal article (peer-reviewed)abstract
- The discovery of oestrogen receptor beta (ER beta/ESR2) was a landmark discovery. Its reported expression and homology with breast cancer pharmacological target ER alpha (ESR1) raised hopes for improved endocrine therapies. After 20 years of intense research, this has not materialized. We here perform a rigorous validation of 13 anti-ER beta antibodies, using well-characterized controls and a panel of validation methods. We conclude that only one antibody, the rarely used monoclonal PPZ0506, specifically targets ER beta in immunohistochemistry. Applying this antibody for protein expression profiling in 44 normal and 21 malignant human tissues, we detect ER beta protein in testis, ovary, lymphoid cells, granulosa cell tumours, and a subset of malignant melanoma and thyroid cancers. We do not find evidence of expression in normal or cancerous human breast. This expression pattern aligns well with RNA-seq data, but contradicts a multitude of studies. Our study highlights how inadequately validated antibodies can lead an exciting field astray.
|
|
