DnaJs are enriched in tau regulators.

The aberrant accumulation of tau protein is implicated as a pathogenic factor in many neurodegenerative diseases. Tau seeding may underlie its predictable spread in these diseases. Molecular chaperones can modulate tau pathology, but their effects have mainly been studied in isolation. This study employed a semi-high throughput assay to identify molecular chaperones influencing tau seeding using Tau RD P301S FRET Biosensor cells, which express a portion of tau containing the frontotemporal dementia-related P301S tau mutation fused to a FRET biosensor. Approximately fifty chaperones from five major families were screened using live cell imaging to monitor FRET-positive tau seeding. Among the tested chaperones, five exhibited significant effects on tau in the primary screen. Notably, three of these were from the DnaJ family. In subsequent studies, overexpression of DnaJA2, DnaJB1, and DnaJB6b resulted in significant reductions in tau levels. Knockdown experiments by shRNA revealed an inverse correlation between DnaJB1 and DnaJB6b with tau levels. DnaJB6b overexpression, specifically, reduced total tau levels in a cellular model with a pre-existing pool of tau, partially through enhanced proteasomal degradation. Further, DnaJB6b interacted with tau complexes. These findings highlight the potent chaperone activity within the DnaJ family, particularly DnaJB6b, towards tau.

Assessing Curcumin Uptake and Clearance and Their Influence on Superoxide Dismutase Activity in Drosophila melanogaster.

While normal levels of reactive oxygen and nitrogen species (RONS) are required for proper organismal function, increased levels result in oxidative stress. Oxidative stress may be managed via the scavenging activities of antioxidants (e.g., curcumin) and the action of enzymes, including superoxide dismutase (SOD). In this work, the uptake and clearance of dietary curcuminoids (consisting of curcumin, demethoxycurcumin, and bisdemethoxycurcumin) was assessed in Drosophila melanogaster larvae following chronic or acute exposure. High levels of curcuminoid uptake and loss were observed within a few hours and leveled off within eight hours post treatment onset. The addition or removal of curcuminoids from media resulted in corresponding changes in SOD activity, and the involvement of each of the three SOD genes was assessed for their contribution to total SOD activity. Taken together, these data provide insight into the uptake and clearance dynamics of curcuminoids and indicate that, while SOD activity generally increases following curcuminoid treatment, the individual SOD genes appear to contribute differently to this response.

Chaperoning activity of the cyclophilin family prevents tau aggregation.

Tauopathies, such as Alzheimer's disease, are characterized by the misfolding and progressive accumulation of the microtubule associated protein tau. Chaperones, tasked with maintaining protein homeostasis, can become imbalanced with age and contribute to the progression of neurodegenerative disease. Cyclophilins are a promising pool of underinvestigated chaperones with peptidyl-prolyl isomerase activity that may play protective roles in regulating tau aggregation. Using a Thioflavin T fluorescence-based assay to monitor in vitro tau aggregation, all eight cyclophilins, which include PPIA to PPIH prevent tau aggregation, with PPIB, PPIC, PPID, and PPIH showing the greatest inhibition. The low thermal stability of PPID and the strong heparin binding of PPIB undermines the simplistic interpretation of reduced tau aggregation. In a cellular model of tau accumulation, all cyclophilins, except PPID and PPIH, reduce insoluble tau. PPIB, PPIC, PPIE, and PPIF also reduce soluble tau levels with PPIC exclusively protecting cells from tau seeding. Overall, this study demonstrates cyclophilins prevent tau fibril formation and many reduce cellular insoluble tau accumulation with PPIC having the greatest potential as a molecular tool to mitigate tau seeding and accumulation.

Assessing the influence of curcumin in sex-specific oxidative stress, survival and behavior in Drosophila melanogaster.

Oxidative stress, which occurs from an imbalance of reactive oxygen and nitrogen species (RONS) and both endogenous and exogenous antioxidants, promotes aging and underlies sex-specific differences in longevity and susceptibility to age-related neurodegeneration. Recent evidence suggests that curcumin, a yellow pigment derived from turmeric and shown to exhibit antioxidant properties as a RONS scavenger, influences the regulation of genetic elements in endogenous antioxidant pathways. To investigate the role of curcumin in sex-specific in vivo responses to oxidative stress, Drosophila were reared on media supplemented with 0.25, 2.5 or 25 mmol l-1 curcuminoids (consisting of curcumin, demethoxycurcumin and bisdemethoxycurcumin) and resistance to oxidative stress and neural parameters were assessed. High levels of curcuminoids exhibited two sex-specific effects: protection from hydrogen peroxide as an oxidative stressor and alterations in turning rate in an open field. Taken together, these results suggest that the influence of curcuminoids as antioxidants probably relies on changes in gene expression and that sexual dimorphism exists in the in vivo response to curcuminoids.

Draft Genome Sequence of Vibrio sp. Strain OCN044, Isolated from Palmyra Atoll, Northern Line Islands.

Vibrio sp. strain OCN044 is a Gram-negative gammaproteobacterium found in marine environments. Presented here is the whole-draft genome sequence of nonpathogenic Vibrio sp. strain OCN044, isolated from a healthy Acropora cytherea colony off the western reef terrace of Palmyra Atoll.