Robust circuitry-based scores of structural importance of human brain areas.

We consider the 1015-vertex human consensus connectome computed from the diffusion MRI data of 1064 subjects. We define seven different orders on these 1015 graph vertices, where the orders depend on parameters derived from the brain circuitry, that is, from the properties of the edges (or connections) incident to the vertices ordered. We order the vertices according to their degree, the sum, the maximum, and the average of the fiber counts on the incident edges, and the sum, the maximum and the average length of the fibers in the incident edges. We analyze the similarities of these seven orders by the Spearman correlation coefficient and by their inversion numbers and have found that all of these seven orders have great similarities. In other words, if we interpret the orders as scoring of the importance of the vertices in the consensus connectome, then the scores of the vertices will be similar in all seven orderings. That is, important vertices of the human connectome typically have many neighbors connected with long and thick axonal fibers (where thickness is measured by fiber numbers), and their incident edges have high maximum and average values of length and fiber-number parameters, too. Therefore, these parameters may yield robust ways of deciding which vertices are more important in the anatomy of our brain circuitry than the others.

Implementation of a circular supply chain model using reusable components in multiple product generations.

The paper deals with a version of Economic Order Quantity (EOQ) and Economic Production Quantity (EPQ) models that considers the reusability of raw materials and components in multiple product generations. With the scarcity of available raw materials and disruptions in supply chains, production companies need to find novel solutions to meet demand. Additionally, waste management of used products is becoming an increasing problem for the environment. Our study presents available solutions for managing end-of-life products and aims to present a cost minimization EOQ/EPQ model. The model considers the use of components extracted from the previous product generation and new components during the production of the new product generation. The study aims to answer the following research questions (i) what is the optimal strategy for the company for the number of cycles of extracted and new components during the production? (ii) Which variables affects the optimal strategy of the company? The presented model allows companies to use the value created for a longer period, and reduces the amount of raw material extracted and waste generated.

Peptidergic neurons of the Edinger-Westphal nucleus express TRPA1 ion channel that is downregulated both upon chronic variable mild stress in male mice and in humans who died by suicide.

BACKGROUND: Transient receptor potential ankyrin 1 (TRPA1), a cation channel, is expressed predominantly in primary sensory neurons, but its central distribution and role in mood control are not well understood. We investigated whether TRPA1 is expressed in the urocortin 1 (UCN1)-immunoreactive centrally projecting Edinger-Westphal nucleus (EWcp), and we hypothesized that chronic variable mild stress (CVMS) would reduce its expression in mice. We anticipated that TRPA1 mRNA would be present in the human EWcp, and that it would be downregulated in people who died by suicide. METHODS: We exposed Trpa1 knockout and wild-type mice to CVMS or no-stress control conditions. We then performed behavioural tests for depression and anxiety, and we evaluated physical and endocrinological parameters of stress. We assessed EWcp Trpa1 and Ucn1 mRNA expression, as well as UCN1 peptide content, using RNA-scope in situ hybridization and immunofluorescence. We tested human EWcp samples for TRPA1 using reverse transcription polymerase chain reaction. RESULTS: Trpa1 mRNA was colocalized with EWcp/UCN1 neurons. Non-stressed Trpa1 knockout mice expressed higher levels of Ucn1 mRNA, had less body weight gain and showed greater immobility in the forced swim test than wild-type mice. CVMS downregulated EWcp/Trpa1 expression and increased immobility in the forced swim test only in wild-type mice. We confirmed that TRPA1 mRNA expression was downregulated in the human EWcp in people who died by suicide. LIMITATIONS: Developmental compensations and the global lack of TRPA1 may have influenced our findings. Because experimental data came from male brains only, we have no evidence for whether findings would be similar in female brains. Because a TRPA1-specific antibody is lacking, we have provided mRNA data only. Limited access to high-quality human tissues restricted sample size. CONCLUSION: TRPA1 in EWcp/UCN1 neurons might contribute to the regulation of depression-like behaviour and stress adaptation response in mice. In humans, TRPA1 might contribute to mood control via EWcp/UCN1 neurons.

Human Somatostatin SST4 Receptor Transgenic Mice: Construction and Brain Expression Pattern Characterization.

Somatostatin receptor subtype 4 (SST4) has been shown to mediate analgesic, antidepressant and anti-inflammatory functions without endocrine actions; therefore, it is proposed to be a novel target for drug development. To overcome the species differences of SST4 receptor expression and function between humans and mice, we generated an SST4 humanized mouse line to serve as a translational animal model for preclinical research. A transposon vector containing the hSSTR4 and reporter gene construct driven by the hSSTR4 regulatory elements were created. The vector was randomly inserted in Sstr4-deficient mice. hSSTR4 expression was detected by bioluminescent in vivo imaging of the luciferase reporter predominantly in the brain. RT-qPCR confirmed the expression of the human gene in the brain and various peripheral tissues consistent with the in vivo imaging. RNAscope in situ hybridization revealed the presence of hSSTR4 transcripts in glutamatergic excitatory neurons in the CA1 and CA2 regions of the hippocampus; in the GABAergic interneurons in the granular layer of the olfactory bulb and in both types of neurons in the primary somatosensory cortex, piriform cortex, prelimbic cortex and amygdala. This novel SST4 humanized mouse line might enable us to investigate the differences of human and mouse SST4 receptor expression and function and assess the effects of SST4 receptor agonist drug candidates.