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Luz, S.

Publications and source records attributed to Luz, S..

3 recordsLinked to original sources

BioNE: Integration of network embeddings for supervised learning

A network embedding approach reduces the analysis complexity of large biological networks by converting them to lowdimensional vector representations (features/embeddings). These lower-dimensional vectors can then be used in machine learning prediction tasks with a wide range of applications in computational biology and bioinformatics. Several network embedding approaches have been proposed with different methods of generating vector representations. These network embedding approaches can be quite diverse in terms of data representation and implementation. Moreover, most were not originally developed for biological networks. Therefore comparing and assessing the performance of these diverse models in practice, in biological contexts, can be challenging. To facilitate such comparisons, we have developed the BioNE framework for integration of different embedding methods in prediction tasks. Using this framework one can easily assess, for instance, whether combined vector representations from multiple embedding methods offer complementary information with regards to the network features and thus better performance on prediction tasks. In this paper, we present the BioNE software suite for embedding integration, which applies network embedding methods following standardised network preparation steps, and integrates the vector representations achieved by these methods using three different techniques. BioNE enables selection of prediction models, oversampling methods, feature selection methods, cross-validation type and cross-validation parameters. Availability and implementationBioNE pipeline and detailed explanation of implementation is freely available on GitHub, at https://github.com/pooryaparvizi/BioNE

bioinformatics↗

Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)-mediated plasticity in the paraventricular thalamic nucleus promotes a fundamental adaptation to stress

BACKGROUNDHabituation is defined as a progressive decline in response to repeated exposure to a familiar and predictable stimulus and is highly conserved across species. Disrupted habituation is a signature of post-traumatic stress disorder (PTSD). In rodents, habituation is observed in neural, neuroendocrine and behavioral responses to repeated exposure to the predictable and moderately intense stress or restraint. We previously demonstrated that lesions to the posterior division of the paraventricular thalamic nucleus (pPVT) impairs habituation. However, the underlying molecular mechanisms and specific neural connections among the pPVT and other brain regions that underlie habituation are unknown. METHODSBehavioral and neuroendocrine habituation was assessed in adult male Sprague-Dawley restraints using the repeated restraint paradigm. Pan neuronal and Cre-dependent Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) were used to chemogenetically inhibit the pPVT and the subpopulation of pPVT neurons that project to the medial prefrontal cortex (mPFC), respectively. Activity-regulated cytoskeleton-associated protein (Arc) expression was knocked down in the pPVT using siRNA directed towards Arc. Golgi staining was used to assess structural plasticity of pPVT neurons. Local field potential recordings were used to assess coherent neural activity between the pPVT and mPFC. The attentional set-shifting task was used to assess mPFC-dependent behavior. RESULTSHere, we show that Arc promotes habituation by increasing stress-induced spinogenesis in the pPVT, increasing coherent neural activity with the mPFC, and improving mPFC-mediated cognitive flexibility. CONCLUSIONOur results demonstrate that Arc induction in the pPVT regulates habituation to repeated restraint and mPFC function. One Sentence SummaryWe demonstrate that Arc in the posterior division of the paraventricular thalamic nucleus promotes habituation to repeated stress by increasing dendritic spines.

neuroscience↗

FTY720 (Fingolimod), a modulator of sphingosine-1-phosphate receptors, increases baseline hypothalamic-pituitary adrenal axis activity and alters behaviors relevant to affect and anxiety

FTY720 (fingolimod) is an analog of sphingosine, a ubiquitous sphingolipid. Phosphorylated FTY720 (FTY720-P) non-selectively binds to sphingosine-1-phosphate receptors (S1PRs) and regulates multiple cellular processes including cell proliferation, inflammation, and angiogenesis. We recently demonstrated that S1PR3 expression in the medial prefrontal cortex (mPFC) of rats promotes stress resilience and that S1PR3 expression in blood may serve as a biomarker for PTSD. Here we investigate the effects of FTY720 in regulating the stress response. We found that single and repeated intraperitoneal injections of FTY720 increased baseline plasma adrenocorticotropic hormone (ACTH) and corticosterone concentrations. FTY720 also mitigated restraint-induced increases in ACTH and corticosterone. FTY720 reduced social anxiety- and despair-like behavior as assessed by increased social interaction time and reduced time spent immobile in the Porsolt forced swim test. In blood, FTY720 administration reduced lymphocyte and reticulocyte counts, but raised erythrocyte counts. FTY720 also reduced mRNA of angiopoietin 1, endothelin 1, plasminogen 1, Vegf-B, and Mmp2 in the medial prefrontal cortex, suggesting that FTY720 reduced angiogenesis. The antidepressant-like and anxiolytic-like effects of FTY720 may be attributed to reduced angiogenesis as increased stress-induced blood vessel density in the brain contributes to depression- and anxiety-like behavior in rats. Together, these results suggest that S1PRs regulate baseline HPA axis activity but reduces social anxiety and despair providing further evidence that S1PRs are important and novel regulators of stress-related functions.

neuroscience↗