| 1. |
-
- 2019
-
Tidskriftsartikel (refereegranskat)
|
|
| 2. |
- Nilsson, Emma, et al.
(författare)
-
Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome
- 2018
-
Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 103:12, s. 4465-4477
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown. Objective: To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate them to phenotypic variations. Design/Participants: In a case-control study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-, and body mass index. matched controls (n = 14) were analyzed by array-based DNA methylation and mRNA expression profiling. Results: Eighty-five unique transcripts were differentially expressed in muscle from women with PCOS vs controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS had reduced expression of genes involved in immune system pathways. Two CpG sites showed differential DNA methylation after correction for multiple testing. However, an mRNA expression of similar to 30% of the differentially expressed genes correlated with DNA methylation levels of CpG sites in or near the gene. Functional follow-up studies demonstrated that KLF10 is under transcriptional control of insulin, where insulin promotes glycogen accumulation in myotubes of human muscle cells. Testosterone downregulates the expression levels of COL1A1 and MAP2K6. Conclusion: PCOS is associated with aberrant skeletal muscle gene expression with dysregulated pathways. Furthermore, we identified specific changes in muscle DNA methylation that may affect gene expression. This study showed that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, can explain the metabolic abnormalities seen in these women.
|
|
| 3. |
- Vanzella, E., et al.
(författare)
-
An extremely metal-poor star complex in the reionization era : Approaching Population III stars with JWST
- 2023
-
Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 678
-
Tidskriftsartikel (refereegranskat)abstract
- We present JWST/Near Infrared Spectrograph (NIRSpec) integral field spectroscopy (IFS) of a lensed Population III candidate stellar complex (dubbed Lensed And Pristine 1, LAP1), with a lensing-corrected stellar mass of ≲104 M⊙ and an absolute luminosity of MUV > −11.2 (mUV > 35.6), confirmed at redshift 6.639 ± 0.004. The system is strongly amplified (μ ≳ 100) by straddling a critical line of the Hubble Frontier Field galaxy cluster MACS J0416. Although the stellar continuum is currently not detected in the Hubble and JWST/Near Infrared Camera (NIRCam) and Near Infrared Imager and Slitless Spectrograph (NIRISS) imaging, arclet-like shapes of Lyman and Balmer lines, Lyα, Hγ, Hβ and Hα are detected with NIRSpec IFS with signal-to-noise ratios (S/N) of approximately 5 − 13 and large equivalent widths (> 300 − 2000 Å), along with a remarkably weak [O III]λλ4959, 5007 at S/N ≃ 4. LAP1 shows a large ionizing photon production efficiency, log(ξion[erg Hz−1]) > 26. From the metallicity indexes R23 = ([O III] + [O II])/Hβ ≲ 0.74 and R3 = ([O III]/Hβ) = 0.55 ± 0.14, we derive an oxygen abundance of 12 + log(O/H)≲6.3. Intriguingly, the Hα emission is also measured in mirrored subcomponents where no [O III] is detected, providing even more stringent upper limits on the metallicity if in situ star formation is ongoing in this region (12 + log(O/H) < 6). The formal stellar mass limit of the subcomponents would correspond to ∼103 M⊙ or MUV fainter than −10. Alternatively, this metal-free, pure line-emitting region could be the first case of a fluorescing H I gas region induced by transverse escaping ionizing radiation from a nearby star complex. The presence of large equivalent-width hydrogen lines and the deficiency of metal lines in such a small region make LAP1 the most metal-poor star-forming region currently known in the reionization era and a promising site that may host isolated, pristine stars.
|
|
| 4. |
- Bentow, C., et al.
(författare)
-
International multi-center evaluation of a novel chemiluminescence assay for the detection of anti-dsDNA antibodies
- 2016
-
Ingår i: Lupus. - : SAGE PUBLICATIONS LTD. - 0961-2033 .- 1477-0962. ; 25:8, s. 864-872
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Anti-double stranded desoxyribonucleic acid (anti-dsDNA) antibodies are considered fairly specific for systemic lupus erythematosus (SLE) and their quantification is useful for the clinical management of SLE patients. We assessed the diagnostic performance of the QUANTA Flash dsDNA chemiluminescent immunoassay (CIA) in comparison to an ELISA, using patients from five participating countries. The main focus was to evaluate the correlation between anti-dsDNA antibody results from the CIA and global SLE disease activity, as measured by the SLE Disease Activity Index 2000 (SLEDAI-2K). Patients and methods: A total of 1431 samples (SLE, n=843; disease controls, n=588) from five countries (Canada, USA, Portugal, Sweden and Spain) were tested with QUANTA Flash dsDNA (Inova Diagnostics, San Diego, CA, USA). Data obtained with the QUANTA Lite dsDNA SC ELISA (Inova Diagnostics) were available for samples from three sites (Canada, USA and Sweden, n=566). The SLEDAI-2K scores were available for 805 SLE patients and a cut-off ofamp;gt;4 was used to define active disease. Results: QUANTA Flash dsDNA had a sensitivity of 54.3% for the diagnosis of SLE, combined with 89.8% specificity. Anti-dsDNA antibody levels were significantly higher (pamp;lt;0.0001) in active SLE (SLEDAI-2Kamp;gt;4; n=232; median value 83.0IU/mL) versus the inactive patients (n=573; median value 22.3IU/mL), and the SLEDAI-2K scoring correlated with their dsDNA antibody levels (Spearmans rho=0.44, pamp;lt;0.0001). Similar but less pronounced findings were also found for the ELISA, in relation to disease activity. Conclusions: The QUANTA Flash dsDNA assay showed good clinical performance in a large international multi-center study. Additionally, the strong correlation between anti-dsDNA antibody results and SLEDAI-2K scores supported the potential utility of QUANTA Flash dsDNA for monitoring disease activity.
|
|
| 5. |
- Czeh, B., et al.
(författare)
-
Long-Term Stress Disrupts the Structural and Functional Integrity of GABAergic Neuronal Networks in the Medial Prefrontal Cortex of Rats
- 2018
-
Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical and experimental data suggest that fronto-cortical GABAergic deficits contribute to the pathophysiology of major depressive disorder (MDD). To further test this hypothesis, we used a well characterized rat model for depression and examined the effect of stress on GABAergic neuron numbers and GABA-mediated synaptic transmission in the medial prefrontal cortex (mPFC) of rats. Adult male Wistar rats were subjected to 9-weeks of chronic mild stress (CMS) and based on their hedonic-anhedonic behavior they were behaviorally phenotyped as being stress-susceptible (anhedonic) or stress-resilient. Post mortem quantitative histopathology was used to examine the effect of stress on parvalbumin (PV)-, calretinin- (CR), calbindin- (CB), cholecystokinin- (CCK), somatostatin-(SST) and neuropeptide Y-positive (NPY+) GABAergic neuron numbers in all cortical subareas of the mPFC (anterior cingulate (Cg1), prelimbic (PrL) and infralimbic (IL) cortexes). In vitro, whole-cell patch-clamp recordings from layer II-III pyramidal neurons of the ventral mPFC was used to examine GABAergic neurotransmission. The cognitive performance of the animals was assessed in a hippocampal-prefrontal-cortical circuit dependent learning task. Stress exposure reduced the number of CCK-, CR- and PV-positive GABAergic neurons in the mPFC, most prominently in the IL cortex. Interestingly, in the stress-resilient animals, we found higher number of neuropeptide Y-positive neurons in the entire mPFC. The electrophysiological analysis revealed reduced frequencies of spontaneous and miniature IPSCs in the anhedonic rats and decreased release probability of perisomatic-targeting GABAergic synapses and alterations in GABA(B) receptor mediated signaling. In turn, pyramidal neurons showed higher excitability. Anhedonic rats were also significantly impaired in the object-place paired-associate learning task. These data demonstrate that long-term stress results in functional and structural deficits of prefrontal GABAergic networks. Our findings support the concept that fronto-limbic GABAergic dysfunctions may contribute to emotional and cognitive symptoms of MDD.
|
|
| 6. |
|
|
