| 1. |
- Sheils, T. K., et al.
(författare)
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TCRD and Pharos 2021: mining the human proteome for disease biology
- 2021
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 49:D1
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Tidskriftsartikel (refereegranskat)abstract
- In 2014, the National Institutes of Health (NIH) initiated the Illuminating the Druggable Genome (IDG) program to identify and improve our understanding of poorly characterized proteins that can potentially be modulated using small molecules or biologics. Two resources produced from these efforts are: The Target Central Resource Database (TCRD) (http://juniper.health.unm.edu/tcrd/) and Pharos (https://pharos.nih.gov/), a web interface to browse the TCRD. The ultimate goal of these resources is to highlight and facilitate research into currently understudied proteins, by aggregating a multitude of data sources, and ranking targets based on the amount of data available, and presenting data in machine learning ready format. Since the 2017 release, both TCRD and Pharos have produced two major releases, which have incorporated or expanded an additional 25 data sources. Recently incorporated data types include human and viral-human protein-protein interactions, protein-disease and protein-phenotype associations, and drug-induced gene signatures, among others. These aggregated data have enabled us to generate new visualizations and content sections in Pharos, in order to empower users to find new areas of study in the druggable genome.
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| 2. |
- Aghajanian, G. K., et al.
(författare)
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Torgny Svensson, M.D., Ph.D. (1945-2020)
- 2020
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Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 1740-634X. ; 45:11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Ardalan, Maryam, 1979, et al.
(författare)
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Rapid effects of S-ketamine on the morphology of hippocampal astrocytes and BDNF serum levels in a sex-dependent manner
- 2020
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 32, s. 94-103
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of major depressive disorder (MDD) is higher in women than men. Importantly, a differential behavioral response by sex to the antidepressant response to ketamine in rodents has been reported. Mechanistically, male depressed-like animals showed an increased spine density after ketamine treatment via restoration of synaptic protein levels while those proteins were not altered in female rats. In addition, preclinical studies indicate that the impairment of astrocytic plasticity is one of the contributing mechanisms in the pathophysiology of MDD. Accordingly, in this study, we determined the effect of sex on the rapid morphological alteration of hippocampal astrocytes and the serum level of BDNF one hour after S-ketamine injection. A single intraperitoneal dose of S-ketamine (15 mg/kg) or saline was injected to the male and female Flinders Sensitive Line (FSL) rats, a genetic animal model of depression and their brains were perfused one hour after treatment. The size of the GFAP positive astrocytes in the hippocampal subregions was measured. The volume of different hippocampal subregions was assessed using the Cavalieri estimator. Moreover, serum levels of BDNF were measured with enzyme-linked immunosorbent assay (ELISA) kits. The volume of hippocampal subregions significantly increased one hour after S-ketamine in both male and female FSL animals. However, a substantial alteration in the morphology of the hippocampal astrocytes was observed only in the female rats. Additionally, significantly increased serum BDNF levels in the female depressed rats were observed one hour after S-ketamine treatment. Our results indicate that the rapid effects of S-ketamine on the morphology of the hippocampal astrocytes and the serum level of BDNF are sex-dependent.
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| 4. |
- Zahoranszky-Kohalmi, G., et al.
(författare)
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Workflow of Integrated Resources to Catalyze Network Driven COVID-19 Research
- 2022
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X. ; 62:3, s. 718-729
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Tidskriftsartikel (refereegranskat)abstract
- In the event of an outbreak due to an emerging pathogen, time is of the essence to contain or to mitigate the spread of the disease. Drug repositioning is one of the strategies that has the potential to deliver therapeutics relatively quickly. The SARS-CoV-2 pandemic has shown that integrating critical data resources to drive drug-repositioning studies, involving host-host, host-pathogen, and drug-target interactions, remains a time-consuming effort that translates to a delay in the development and delivery of a life-saving therapy. Here, we describe a workflow we designed for a semiautomated integration of rapidly emerging data sets that can be generally adopted in a broad network pharmacology research setting. The workflow was used to construct a COVID-19 focused multimodal network that integrates 487 host-pathogen, 63 278 host- host protein, and 1221 drug-target interactions. The resultant Neo4j graph database named "Neo4COVID19" is made publicly accessible via a web interface and via API calls based on the Bolt protocol. Details for accessing the database are provided on a landing page (https://neo4covid19.ncats.io/). We believe that our Neo4COVID19 database will be a valuable asset to the research community and will catalyze the discovery of therapeutics to fight COVID-19.
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| 5. |
- Sandberg, Johan V, et al.
(författare)
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Low neuropeptide Y in cerebrospinal fluid in bipolar patients is associated with previous and prospective suicide attempts.
- 2014
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Ingår i: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. - : Elsevier BV. - 1873-7862. ; 24:12, s. 1907-15
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Tidskriftsartikel (refereegranskat)abstract
- The attempted and accomplished suicide rates in patients with bipolar disorder are 40-50% and 15-20%, respectively. No biological markers that help predict suicide been identified. Human and experimental animal data indicate that dysregulation of the neuropeptide Y (NPY) system plays a role in depression, anxiety, and posttraumatic stress disorder (PTSD). The aim of this study was to explore if low cerebrospinal fluid (CSF) NPY is associated with (1) past suicide attempts, (2) future suicide attempts, and (3) trait anxiety. Lumbar puncture was performed on 120 clinically stable patients with bipolar disorder enrolled in the St Göran Bipolar Project, where the number of previous suicide attempts was documented. NPY-like immunoreactivity (NPY-LI) was determined in cerebrospinal fluid (CSF). Patients were reexamined one year after the lumbar puncture and suicide attempts were recorded. NPY-LI was significantly lower in patients with a history of suicide attempt than in patients who had not attempted suicide prior to lumbar puncture. Importantly, NPY-LI was markedly lower in patients who made a suicide attempt during the follow-up period compared to patients who did not. Patients who attempted suicide during the follow-up also had markedly lower NPY-LI than those with previous suicide attempts who did not reattempt. Our results suggest that low CSF NPY-LI predicts future suicide attempts. The data are in line with the hypothesis that NPY signaling is altered in affective disorders and states of emotional dysregulation.
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| 6. |
- Strenn, Nina, 1984, et al.
(författare)
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Expression of inflammatory markers in a genetic rodent model of depression
- 2015
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 281, s. 348-357
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Tidskriftsartikel (refereegranskat)abstract
- The complex bidirectional communication between the central nervous system and the peripheral immune system is of possible relevance for both normal brain functions and the development of psychiatric disorders. The aim of this investigation was to study central expression of inflammatory markers in a genetic rat model of depression (the Flinders Sensitive line (FSL) and its control, the Flinders Resistant line (FRL)). A peripheral immune activation was induced by lipopolysaccharide (LPS) in order to investigate possible differences in immune reactions between the two rat lines. To confirm behavioural differences between the rat lines the forced swim test was performed, a test to assess depressive-like behaviour. Expression of candidate inflammatory genes was measured in amygdala, hippocampus, hypothalamus, prefrontal cortex and striatum using quantitative real time PCR. Our results show, for the first time, significantly lower central expression of the glial-specific protein S100B and complement factor C3 in several brain regions of the FSL rats compared to controls, both at baseline and after peripheral immune stimulation. No significant differences in immune responses to LPS were observed between the rats lines. Both S100B and C3 have been suggested to be of relevance for brain development and plasticity as well as brain disorders. These proteins may be of importance for the behavioural differences between the FSL and FRL rats, and this model may be useful in studies exploring the influence of the immune system on brain functions.
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