Search Results (8)

Major depressive disorder (MDD) involves dysregulation of the hypothalamic–pituitary–adrenal axis, neuroinflammation, serotonergic dysfunction, and impaired neurotrophic signaling. Whether combining corticosterone (CORT) with chronic restraint stress (CRS) produces a more comprehensive depression-like phenotype than either model alone remains unexplored. Male C57BL/6N mice were assigned to four groups—Sham (n = 7), CORT (20 mg/kg s.c.; n = 7), CRS (3 h/day; n = 7), and CORT + CRS (C+C; n = 8)—and evaluated by behavioral tests, hippocampal qRT-PCR, Western blot, LC-MS/MS metabolomics, and immunohistochemistry. All experimental groups showed elevated immobility in tail suspension and forced swim tests without inter-group differences. Two-way ANOVA revealed a behavioral–molecular dissociation: FST immobility showed CORT and CRS main effects without a significant interaction, whereas hippocampal LC-MS/MS analytes exhibited strong CORT × CRS interactions. The C+C group showed the strongest 5-HT1A receptor (HTR1A) upregulation, the greatest reductions in Trk-b and DCX, and unique decreases in serum dopamine, glutamine, and adenosine. Representative Western blot densitometry indicated the largest p-ERK/ERK reduction in C+C (54%), while p-CREB/CREB was most suppressed in CRS (52%). BDNF and NeuN proteins were lowest in C+C (68% and 61% reductions). Combined CORT + CRS produces the most comprehensive depression-related molecular profile, integrating multiple pathological domains. Full article

Apicortin, a tubulin/microtubule-binding protein, was first described in 2009 as a protein characteristic of apicomplexans; it was found to be present in all Apicomplexa genomes already sequenced. Apart from these, it was found only in Trichoplax adhaerens, the only known representative of Placozoa at the time. Subsequent analyses revealed that it is present in both closely and distantly related taxa of Apicomplexa (Chrompodellids, Squirmids, Dinoflagellates, and Perkinsids, i.e., in Myzozoa). On the other hand, it turned out that it is also present in early-branching fungi that reproduce by zoospores. Now, we have shown that apicortin is found in many deep-branching opisthokonts. In addition to these fungi and T. adhaerens, it is also present in other simple animals, including further Placozoa and Ctenophora, and another opisthokont clade, choanoflagellates. However, apicortin-homologous sequences detected in the genomes/transcriptomes of bilaterian animals are the result of contamination. Full article

The decarbonization of the electricity grid is one of the actions that can help reduce fossil fuel emissions, and thus their impact on global warming in the future. This decarbonization will be achieved mainly through the integration and widespread diffusion of renewable power sources. This is also going to be supported by the shift from the paradigm of production–transmission–distribution, where electricity production oversees large-size power plants, to renewable-based distributed/diffused production, where electricity is generated very close or even by the same (group of) user(s) (or prosumers in the latter case). The number of mid-/small-size installations based on renewable energy technologies will therefore increase substantially, and the related renewable generation will be dominant against that from large-size power plants. Unfortunately, this will very likely reduce the reliability of the grid, unless appropriate countermeasures are taken/implemented, hopefully at the same time that the paradigm shift is being achieved. To this aim, it is important to identify the anomalies and main fault causes that might possibly affect some of the central renewable (wind, PV, hydrogen) and ancillary technologies that will be used to establish future renewable-based power systems. Accordingly, this paper presents a literature survey, also extending the focus to related datasets that can be used for deeper investigation. It is highlighted that the gaps mainly refer to a lack of a common taxonomy that prevents the establishment of structured knowledge in the scope of renewable-based power systems, a lack of contributions to anomalies/faults specific to wind turbines, and a lack of datasets related to electrolyzers, fuel cells, DC/x conversion, and monitoring and communication systems. Further, in the case of monitoring and communication systems, the scientific literature is both very dated, therefore not considering possible new aspects that would be currently worthy of investigation, and not oriented toward the particular domain addressed, thus considering peculiar aspects that are left out. Full article

TPPP (tubulin polymerization promoting protein)-like proteins contain one or more p25alpha (Pfam05517) domains. TPPP-like proteins occur in different types as determined by their length (e.g., long-, short-, truncated-, and fungal-type TPPP) and include the protein apicortin, which possesses another domain, doublecortin (DCX, Pfam 03607). These various TPPP-like proteins are found in various phylogenomic groups. In particular, short-type TPPPs and apicortin are well-represented in the Myzozoa, which include apicomplexans and related taxa, chrompodellids, dinoflagellates, and perkinsids. The long-, truncated-, and fungal-type TPPPs are not found in the myzozoans. Apicortins are found in all apicomplexans except one piroplasmid species, present in several other myzozoans, and seem to be correlated with the conoid and apical complex. Short-type TPPPs are predominantly found in myzozoans that have flagella, suggesting a role in flagellum assembly or structure. Full article

Doublecortin-like kinase 1 (DCLK1) is a functional serine/threonine (S/T)-kinase and a member of the doublecortin family of proteins which are characterized by their ability to bind to microtubules (MTs). DCLK1 is a proposed cancer driver gene, and its upregulation is associated with poor overall survival in several solid cancer types. However, how DCLK1 associates with MTs and how its kinase function contributes to pro-tumorigenic processes is poorly understood. This review builds on structural models to propose not only the specific functions of the domains but also attempts to predict the impact of individual somatic missense mutations on DCLK1 functions. Somatic missense mutations in DCLK1 are most frequently located within the N-terminal MT binding region and likely impact on the ability of DCLK1 to bind to αβ-tubulin and to polymerize and stabilize MTs. Moreover, the MT binding affinity of DCLK1 is negatively regulated by its auto-phosphorylation, and therefore mutations that affect kinase activity are predicted to indirectly alter MT dynamics. The emerging picture portrays DCLK1 as an MT-associated protein whose interactions with tubulin heterodimers and MTs are tightly controlled processes which, when disrupted, may confer pro-tumorigenic properties. Full article

Parental exposure to insults was initially considered safe if stopped before conception. In the present investigation, paternal or maternal preconception exposure to the neuroteratogen chlorpyrifos was investigated in a well-controlled avian model (Fayoumi) and compared to pre-hatch exposure focusing on molecular alterations. The investigation included the analysis of several neurogenesis, neurotransmission, epigenetic and microRNA genes. A significant decrease in the vesicular acetylcholine transporter (SLC18A3) expression was detected in the female offspring in the three investigated models: paternal (57.7%, p < 0.05), maternal (36%, p < 0.05) and pre-hatch (35.6%, p < 0.05). Paternal exposure to chlorpyrifos also led to a significant increase in brain-derived neurotrophic factor (BDNF) gene expression mainly in the female offspring (27.6%, p < 0.005), while its targeting microRNA, miR-10a, was similarly decreased in both female (50.5%, p < 0.05) and male (56%, p < 0.05) offspring. Doublecortin’s (DCX) targeting microRNA, miR-29a, was decreased in the offspring after maternal preconception exposure to chlorpyrifos (39.8%, p < 0.05). Finally, pre-hatch exposure to chlorpyrifos led to a significant increase in protein kinase C beta (PKCß; 44.1%, p < 0.05), methyl-CpG-binding domain protein 2 (MBD2; 44%, p < 0.01) and 3 (MBD3; 33%, p < 0.05) genes expression in the offspring. Although extensive studies are required to establish a mechanism–phenotype relationship, it should be noted that the current investigation does not include phenotype assessment in the offspring. Full article

In 2009, apicortin was identified in silico as a characteristic protein of apicomplexans that also occurs in the placozoa, Trichoplax adhaerens. Since then, it has been found that apicortin also occurs in free-living cousins of apicomplexans (chromerids) and in flagellated fungi. It contains a partial p25-α domain and a doublecortin (DCX) domain, both of which have tubulin/microtubule binding properties. Apicortin has been studied experimentally in two very important apicomplexan pathogens, Toxoplasma gondii and Plasmodium falciparum. It is localized in the apical complex in both parasites. In T. gondii, apicortin plays a key role in shaping the structure of a special tubulin polymer, conoid. In both parasites, its absence or downregulation has been shown to impair pathogen–host interactions. Based on these facts, it has been suggested as a therapeutic target for treatment of malaria and toxoplasmosis. Full article

We previously introduced the brain erythropoietin (EPO) circle as a model to explain the adaptive ‘brain hardware upgrade’ and enhanced performance. In this fundamental circle, brain cells, challenged by motor-cognitive tasks, experience functional hypoxia, triggering the expression of EPO among other genes. We attested hypoxic cells by a transgenic reporter approach under the ubiquitous CAG promoter, with Hif-1α oxygen-dependent degradation-domain (ODD) fused to CreERT2-recombinase. To specifically focus on the functional hypoxia of excitatory pyramidal neurons, here, we generated CaMKIIα-CreERT2-ODD::R26R-tdTomato mice. Behavioral challenges, light-sheet microscopy, immunohistochemistry, single-cell mRNA-seq, and neuronal cultures under normoxia or hypoxia served to portray these mice. Upon complex running wheel performance as the motor-cognitive task, a distinct increase in functional hypoxic neurons was assessed immunohistochemically and confirmed three-dimensionally. In contrast, fear conditioning as hippocampal stimulus was likely too short-lived to provoke neuronal hypoxia. Transcriptome data of hippocampus under normoxia versus inspiratory hypoxia revealed increases in CA1 CaMKIIα-neurons with an immature signature, characterized by the expression of Dcx, Tbr1, CaMKIIα, Tle4, and Zbtb20, and consistent with accelerated differentiation. The hypoxia reporter response was reproduced in vitro upon neuronal maturation. To conclude, task-associated activity triggers neuronal functional hypoxia as a local and brain-wide reaction mediating adaptive neuroplasticity. Hypoxia-induced genes such as EPO drive neuronal differentiation, brain maturation, and improved performance. Full article