CK2—An Emerging Target for Neurological and Psychiatric Disorders

Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses. Full and conditional CK2 knockout mice have further elucidated the importance of CK2 in brain development, neuronal activity, and behavior. This review will discuss recent advances in the field that point to CK2 as a regulator of neuronal functions and as a potential novel target to treat neurological and psychiatric disorders

The Replication Database:Documenting the Replicability of Psychological Science

In psychological science, replicability—repeating a study with a new sample achieving consistent results (Parsons et al., 2022)—is critical for affirming the validity of scientific findings. Despite its importance, replication efforts are few and far between in psychological science with many attempts failing to corroborate past findings. This scarcity, compounded by the difficulty in accessing replication data, jeopardizes the efficient allocation of research resources and impedes scientific advancement. Addressing this crucial gap, we present the Replication Database (https://forrt-replications.shinyapps.io/fred_explorer), a novel platform hosting 1,239 original findings paired with replication findings. The infrastructure of this database allows researchers to submit, access, and engage with replication findings. The database makes replications visible, easily findable via a graphical user interface, and tracks replication rates across various factors, such as publication year or journal. This will facilitate future efforts to evaluate the robustness of psychological research

Selectivity Enhancement by Using Double-Layer MOX-Based Gas Sensors Prepared by Flame Spray Pyrolysis (FSP)

Here we present a novel concept for the selective recognition of different target gases with a multilayer semiconducting metal oxide (SMOX)-based sensor device. Direct current (DC) electrical resistance measurements were performed during exposure to CO and ethanol as single gases and mixtures of highly porous metal oxide double- and single-layer sensors obtained by flame spray pyrolysis. The results show that the calculated resistance ratios of the single- and double-layer sensors are a good indicator for the presence of specific gases in the atmosphere, and can constitute some building blocks for the development of chemical logic devices. Due to the inherent lack of selectivity of SMOX-based gas sensors, such devices could be especially relevant for domestic applications

Alterations of Expression of the Serotonin 5-HT4 Receptor in Brain Disorders

The serotonin 4 receptor, 5-HT4R, represents one of seven different serotonin receptor families and is implicated in a variety of physiological functions and their pathophysiological variants, such as mood and depression or anxiety, food intake and obesity or anorexia, or memory and memory loss in Alzheimer’s disease. Its central nervous system expression pattern in the forebrain, in particular in caudate putamen, the hippocampus and to lesser extent in the cortex, predispose it for a role in executive function and reward-related actions. In rodents, regional overexpression or knockdown in the prefrontal cortex or the nucleus accumbens of 5-HT4R was shown to impact mood and depression-like phenotypes, food intake and hypophagia; however, whether expression changes are causally involved in the etiology of such disorders is not clear. In this context, more data are emerging, especially based on PET technology and the use of ligand tracers that demonstrate altered 5-HT4R expression in brain disorders in humans, confirming data stemming from post-mortem tissue and preclinical animal models. In this review, we would like to present the current knowledge of 5-HT4R expression in brain regions relevant to mood/depression, reward and executive function with a focus on 5-HT4R expression changes in brain disorders or caused by drug treatment, at both the transcript and protein levels

CK2—An Emerging Target for Neurological and Psychiatric Disorders

Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses. Full and conditional CK2 knockout mice have further elucidated the importance of CK2 in brain development, neuronal activity, and behavior. This review will discuss recent advances in the field that point to CK2 as a regulator of neuronal functions and as a potential novel target to treat neurological and psychiatric disorders

Enhancing nonlinear solvers for the Navier–Stokes equations with continuous (noisy) data assimilation

We consider nonlinear solvers for the incompressible, steady (or at a fixed time step for unsteady) Navier–Stokes equations in the setting where partial measurement data of the solution is available. The measurement data is incorporated/assimilated into the solution through a nudging term addition to the Picard iteration that penalized the difference between the coarse mesh interpolants of the true solution and solver solution, analogous to how continuous data assimilation (CDA) is implemented for time dependent PDEs. This was considered in the paper (Li et al. 2023), and we extend the methodology by improving the analysis to be in the norm instead of a weighted norm where the weight depended on the coarse mesh width, and to the case of noisy measurement data. For noisy measurement data, we prove that the CDA-Picard method is stable and convergent, up to the size of the noise. Numerical tests illustrate the results, and show that a very good strategy when using noisy data is to use CDA-Picard to generate an initial guess for the classical Newton iteration

The Dopamine D5 receptor contributes to activation of cholinergic interneurons during L-DOPA induced dyskinesia

International audienceThe dopamine D5 receptor (D5R) is a Gαs-coupled dopamine receptor belonging to the dopamine D1-like receptor family. Together with the dopamine D2 receptor it is highly expressed in striatal cholinergic interneurons and therefore is poised to be a positive regulator of cholinergic activity in response to L-DOPA in the dopamine-depleted parkinsonian brain. Tonically active cholinergic interneurons become dysregulated during chronic L-DOPA administration and participate in the expression of L-DOPA induced dyskinesia. The molecular mechanisms involved in this process have not been elucidated, however a correlation between dyskinesia severity and pERK expression in cholinergic cells has been described. To better understand the function of the D5 receptor and how it affects cholinergic interneurons in L-DOPA induced dyskinesia, we used D5R knockout mice that were rendered parkinsonian by unilateral 6-OHDA injection. In the KO mice, expression of pERK was strongly reduced indicating that activation of these cells is at least in part driven by the D5 receptor. Similarly, pS6, another marker for the activity status of cholinergic interneurons was also reduced. However, mice lacking D5R exhibited slightly worsened locomotor performance in response to L-DOPA and enhanced LID scores. Our findings suggest that D5R can modulate L-DOPA induced dyskinesia and is a critical activator of CINs via pERK and pS6