| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Herrera-Rivero, Marisol, et al.
(författare)
-
Exploring the genetics of lithium response in bipolar disorders.
- 2023
-
Ingår i: Research square.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
|
|
| 5. |
- Gupta, Deepesh Kumar, 1990-, et al.
(författare)
-
Fate of bi-nucleated cells: the role of septin and Ras
- 2018
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Integrin-mediated adhesion is required to complete cytokinesis, and failure in the process can generate tetraploid cells, which are potentially oncogenic. The effect of cell detachment on the cytokinesis process and on the following cell cycle was analyzed in the non-transformed human fibroblast cell line BJ and in BJ cells expressing SV40 LT (BJ-LT) +/- an oncogenic Ras mutant. In non-adherent BJ and BJ-LT cells, ALIX could not be recruited to the midbody (MB) and cytokinetic abscission did not occur. Based on the results from several approaches, this block was concluded to be overcome in the detached BJ-LT-Ras cells. Non-adherent BJ and BJ-LT cells maintained the septin-associated intercellular bridge (ICB) formed by cleavage furrow ingression, for more than 24 hours. After re-adhesion to fibronectin most such cells divided by cytofission due to tension exerted on the narrow bridge, while a minor fraction of the cell population instead became bi-nucleated because of regression of the intercellular bridge. Adherent bi-nucleated BJ-LT cells progressed through the cell cycle and at mitosis they divided into two mono-nucleated (4N) cells, while adherent bi-nucleated BJ cells were arrested in the G1 phase and became senescent. Thus, p53-dependent mechanism(s) prevented the formation of tetraploid cells from non-transformed bi-nucleated cells. The two centrosomes in the adherent bi-nucleated cells rapidly fused, indicating that p53 was activated via the PIDDosome mechanism. The results show that several mechanisms contribute to prevent detached normal cells from generating tumor-causing tetraploid cells, and that expression of an activating Ras mutation can promote cytokinesis in detached tumor cells.
|
|
| 6. |
|
|
| 7. |
- Kumar, Bhaskar Pal, et al.
(författare)
-
Photoredox-Catalyzed Stereoselective Vinylation Reactions with Vinylbenziodoxol(on)es
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We have disclosed an efficient transition-metal-free radical-mediated C-C cross-coupling reaction of 4-alkyl-1,4-DHPs and VBXs through photo-redox catalysis to afford vinylated products in good yields with retention of configuration from parent VBXs. This mild photocatalysis system featured excellent functional group tolerance, a wide range of substrate scope and unique stereoselectivities. The utility of this new protocol has been demonstrated via the syntheses of diastereoselective C-vinyl glycosides. Preliminary mechanistic studies signify the involvement of radicals and the formation of ligand coupled TS in the reaction pathway.
|
|
| 8. |
- Mahmud, A. K. M. Firoj, et al.
(författare)
-
A core transcriptional response for biofilm formation by Y. pseudotuberculosis
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Previous transcriptional profiling of the enteropathogen Yersinia pseudotuberculosis during persistent stages of colonisation of mouse cecal lymphoid follicles indicated the possible involvement of biofilm in infection maintenance. Not much is known about the mechanisms responsible for biofilm formation by this pathogen, and most current knowledge is based on results of experiments conducted using the related Y. pestis pathogen that forms biofilm in the flea gut. In this study, we performed transcriptional profiling of Y. pseudotuberculosis in biofilms from different biofilm-inducing conditions, bile exposure, amino acid deprivation and in vivo mimicking conditions with and without oxygen. The comparison of differential expression of genes in biofilm versus planktonic bacteria showed a set of 54 core genes that were similarly regulated, independent of inducing condition. This set included many genes that were previously shown to be associated with biofilms, such as hutG, hsmF, hmsT and cpxP that were upregulated and other genes such as hmsP and rfaH that were downregulated. There were also novel biofilm-associated genes, including genes encoding hypothetical proteins. To identify the genes involved in inducing biofilm formation, the gene expression of bacteria during an early initial phase when biofilm starts to form after induction by bile or amino acid depletion was determined. Comparisons of the resulting gene expression profiles with the profiles of non-induced bacteria incubated for the same period of time showed a set of core genes associated with early biofilm formation. This set included genes involved in quorum sensing, pili biogenesis and genes indicative of a potential metabolic shift involving nitrogen utilisation. Genes encoding components of sugar phosphotransferase systems were also upregulated during biofilm induction. Assays of biofilm formation by bacteria deleted of some of these core genes showed that strains lacking hpr and luxS, which are known to be important for functional sugar phosphotransferase systems and quorum sensing, as well as glnL encoding a sensory histidine kinase were most negatively affected. Most of the deletion mutant strains tested were affected, but the effect was less severe, suggesting high levels of redundancy in the pathways involved in biofilm formation by this pathogen.
|
|
| 9. |
- Zhou Hagström, Nanna, 1993-, et al.
(författare)
-
Megahertz-rate Ultrafast X-ray Scattering and Holographic Imaging at the European XFEL
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The advent of X-ray free-electron lasers (XFELs) has revolutionized fundamental science, from atomic to condensed matter physics, from chemistry to biology, giving researchers access to X-rays with unprecedented brightness, coherence, and pulse duration. All XFEL facilities built until recently provided X-ray pulses at a relatively low repetition rate, with limited data statistics. Here, we present the results from the first megahertz repetition rate X-ray scattering experiments at the Spectroscopy and Coherent Scattering (SCS) instrument of the European XFEL. We illustrate the experimental capabilities that the SCS instrument offers, resulting from the operation at MHz repetition rates and the availability of the novel DSSC 2D imaging detector. Time-resolved magnetic X-ray scattering and holographic imaging experiments in solid state samples were chosen as representative examples, providing an ideal test-bed for operation at megahertz rates. Nevertheless, our results are relevant and applicable to any other non-destructive XFEL experiments in the soft X-ray range.
|
|
