The selective 5-HT6 receptor antagonists SB-271046 and SB-399885 potentiate NCAM PSA immunolabeling of dentate granule cells, but not neurogenesis, in the hippocampal formation of mature Wistar rats

While there is now substantial evidence that 5-HT(6) antagonism leads to significantly improved cognitive ability, the mechanism(s) and/or pathway(s) involved are poorly understood. We have evaluated the consequence of chronic administration of the 5-HT(6) receptor antagonists SB-271046 and SB-399885 on neural cell adhesion molecule polysialylation state (NCAM PSA), a neuroplastic mechanism necessary for memory consolidation. Quantitative analysis of NCAM PSA immunopositive neurons in the dentate gyrus of drug-treated animals revealed a dose-dependent increase in polysialylated cell frequency following treatment with both SB-271046 and SB-399885. These effects could not be attributed to increased neurogenesis, as no difference in the rate of bromodeoxyuridine incorporation was apparent between the control and drug-treated groups. A substantial increase in the frequency of polysialylated cells in layer II of the entorhinal and perirhinal cortices was also observed, brain regions not previously associated with neurogenesis. Chronic treatment with SB-271046 or SB-399885 also significantly increased the activation of dentate polysialylation that is specific to learning. This effect does not occur with other cognition-enhancing drugs, such as tacrine, and this action potentially differentiates 5-HT(6) receptor antagonism as an unique neuroplastic mechanism for cognitive processes which may slow or reverse age/neurodegenerative related memory deficits.     

Bohle iridovirus as a vector for heterologous gene expression

The large double-stranded DNA (ds DNA) viruses were among the first to be used to construct recombinant viruses, but to date this has not been achieved with any members of the ds DNA virus family, Iridoviridae. We identified a non-essential gene, the viral homologue of eukaryotic initiation factor 2alpha (eIF-2alpha), in Bohle iridovirus (BIV, genus Ranavirus). A recombinant BIV was constructed with the neomycin resistance gene and the Bufo marinus (cane toad) adult globin gene inserted into the BIV eIF-2alpha region. Adult globin expressed by the virus was detected on western blot, demonstrating that foreign genes can be expressed by the recombinant BIV in vitro and suggesting the possibility of using a recombinant BIV in the biological control of cane toads.     

Dietary supplementation with fish oil modifies the ability of human monocytes to induce an inflammatory response

Monocytes/macrophages are key orchestrators of inflammation and are involved in the pathogenesis of chronic inflammatory disorders, including atherosclerosis. (n-3) Fatty acids, found in fish oil, have been shown to have protective effects in such disorders. To investigate possible modes of action, we used a monocyte:endothelial cell (EC) coculture model to investigate the pro-inflammatory potential of monocytes. Monocytes were isolated from the blood of donors with peripheral arterial disease (PAD) or control donors, before and after a 12-wk supplementation of their diet with fish oil. The monocytes were cultured with human umbilical vein EC (HUVEC) for 24 h, after which the ability of the HUVEC to recruit flowing neutrophils was tested. Monocytes from either group of donors stimulated the EC to support the adhesion and migration of neutrophils. Fish oil supplementation reduced the potency of monocytes from normal subjects, but not those from patients with PAD, to induce recruitment. Concurrent medication may have acted as a complicating factor. On subgroup analysis, only those free of medication showed a significant effect of fish oil. Responses before or after supplementation were not closely linked to patterns of secretion of cytokines by cultured monocytes, tested in parallel monocultures. These results suggest that fish oil can modulate the ability of monocytes to stimulate EC and that this might contribute to their protective effects against chronic inflammatory disorders. Benefits, however, may depend on existing medical status and on other treatments being received.     

IL-1β Drives Production of FGF-23 at the Onset of Chronic Kidney Disease in Mice

FGF-23 has arisen as an early biomarker of renal dysfunction, but at the onset of chronic kidney disease (CKD), data suggest that FGF-23 may be produced independently of the parathyroid hormone (PTH), 1,25(OH)₂-vitamin D₃ signaling axis. Iron status is inversely correlated to the level of circulating FGF-23, and improvement in iron bioavailability within patients correlates with a decrease in FGF-23. Alternately, recent evidence also supports a regulatory role of inflammatory cytokines in the modulation of FGF-23 expression. To determine the identity of the signal from the kidney-inducing upregulation of osteocytic FGF-23 at the onset of CKD, we utilized a mouse model of congenital CKD that fails to properly mature the glomerular capillary tuft. We profiled the sequential presentation of indicators of renal dysfunction, phosphate imbalance, and iron bioavailability and transport to identify the events that initiate osteocytic production of FGF-23 during the onset of CKD. We report here that elevations in circulating intact-FGF-23 coincide with the earliest indicators of renal dysfunction (P14), and precede changes in serum phosphate or iron homeostasis. Serum PTH was also not changed within the first month. Instead, production of the inflammatory protein IL-1β from the kidney and systemic elevation of it in the circulation matched the induction of FGF-23. IL-1β's ability to induce FGF-23 was confirmed on bone chips in culture and within mice in vivo. Furthermore, neutralizing antibody to IL-1β blocked FGF-23 expression in both our congenital model of CKD and a second nephrotoxic serum-mediated model. We conclude that early CKD resembles a situation of primary FGF-23 excess mediated by inflammation. These findings do not preclude that altered mineral availability or anemia can later modulate FGF-23 levels but find that in early CKD they are not the driving stimulus for the initial upregulation of FGF-23. © 2020 American Society for Bone and Mineral Research.     

Dietary and Physical Activity Patterns: Examining Fathers' Perspectives

PURPOSE.  Obesity adversely affects children, yet limited information is available on the familial environmental influence of fathers. The purpose of this study was to examine fathers' influences on their children's eating and activity patterns.
DESIGN AND METHODS. Participants for this mixed methods study was a convenience sample of 51 multi-ethnic fathers of children 8–12 years of age, who completed surveys addressing dietary and physical activity behaviors.
RESULTS.  An association was found between fathers' and children's weight status. Half the children snacked without parental guidance.
PRACTICE IMPLICATIONS.  Nurses need to assist children and their families to develop effective weight management strategies.