Activated microglia mediate synapse loss and short-term memory deficits in a mouse model of transthyretin-related oculoleptomeningeal amyloidosis

Oculoleptomeningeal amyloidosis (OA) is a fatal and untreatable hereditary disease characterized by the accumulation of transthyretin (TTR) amyloid within the central nervous system. The mechanisms underlying the pathogenesis of OA, and in particular how amyloid triggers neuronal damage, are still unknown. Here, we show that amyloid fibrils formed by a mutant form of TTR, A25T, activate microglia, leading to the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and nitric oxide. Further, we found that A25T amyloid fibrils induce the activation of Akt, culminating in the translocation of NFκB to the nucleus of microglia. While A25T fibrils were not directly toxic to neurons, the exposure of neuronal cultures to media conditioned by fibril-activated microglia caused synapse loss that culminated in extensive neuronal death via apoptosis. Finally, intracerebroventricular (i.c.v.) injection of A25T fibrils caused microgliosis, increased brain TNF-α and IL-6 levels and cognitive deficits in mice, which could be prevented by minocycline treatment. These results indicate that A25T fibrils act as pro-inflammatory agents in OA, activating microglia and causing neuronal damage.     

Nature and Age of Neighbours Matter: Interspecific Associations among Tree Species Exist and Vary across Life Stages in Tropical Forests

Detailed information about interspecific spatial associations among tropical tree species is scarce, and hence the ecological importance of those associations may have been underestimated. However, they can play a role in community assembly and species diversity maintenance. This study investigated the spatial dependence between pairs of species. First, the spatial associations (spatial attraction and spatial repulsion) that arose between species were examined. Second, different sizes of trees were considered in order to evaluate whether the spatial relationships between species are constant or vary during the lifetime of individuals. Third, the consistency of those spatial associations with the species-habitat associations found in previous studies was assessed. Two different tropical ecosystems were investigated: a montane cloud forest and a lowland moist forest. The results showed that spatial associations among species exist, and these vary among life stages and species. The rarity of negative spatial interactions suggested that exclusive competition was not common in the studied forests. On the other hand, positive interactions were common, and the results of this study strongly suggested that habitat associations were not the only cause of spatial attraction among species. If this is true, habitat associations and density dependence are not the only mechanisms that explain species distribution and diversity; other ecological interactions, such as facilitation among species, may also play a role. These spatial associations could be important in the assembly of tropical tree communities and forest succession, and should be taken into account in future studies.     

Changes in soil organic carbon under perennial crops

This study evaluates the dynamics of soil organic carbon (SOC) under perennial crops across the globe. It quantifies the effect of change from annual to perennial crops and the subsequent temporal changes in SOC stocks during the perennial crop cycle. It also presents an empirical model to estimate changes in the SOC content under crops as a function of time, land use, and site characteristics. We used a harmonized global dataset containing paired‐comparison empirical values of SOC and different types of perennial crops (perennial grasses, palms, and woody plants) with different end uses: bioenergy, food, other bio‐products, and short rotation coppice. Salient outcomes include: a 20‐year period encompassing a change from annual to perennial crops led to an average 20% increase in SOC at 0–30 cm (6.0 ± 4.6 Mg/ha gain) and a total 10% increase over the 0–100 cm soil profile (5.7 ± 10.9 Mg/ha). A change from natural pasture to perennial crop decreased SOC stocks by 1% over 0–30 cm (?2.5 ± 4.2 Mg/ha) and 10% over 0–100 cm (?13.6 ± 8.9 Mg/ha). The effect of a land use change from forest to perennial crops did not show significant impacts, probably due to the limited number of plots; but the data indicated that while a 2% increase in SOC was observed at 0–30 cm (16.81 ± 55.1 Mg/ha), a decrease in 24% was observed at 30–100 cm (?40.1 ± 16.8 Mg/ha). Perennial crops generally accumulate SOC through time, especially woody crops; and temperature was the main driver explaining differences in SOC dynamics, followed by crop age, soil bulk density, clay content, and depth. We present empirical evidence showing that the FAO perennialization strategy is reasonable, underscoring the role of perennial crops as a useful component of climate change mitigation strategies.     

Practice models and challenges in teledermatology: a study of collective experiences from teledermatologists

Background

Despite increasing practice of teledermatology in the U.S., teledermatology practice models and real-world challenges are rarely studied.

Methods

The primary objective was to examine teledermatology practice models and shared challenges among teledermatologists in California, focusing on practice operations, reimbursement considerations, barriers to sustainability, and incentives. We conducted in-depth interviews with teledermatologists that practiced store-and-forward or live-interactive teledermatology from January 1, 2007 through March 30, 2011 in California.

Results

Seventeen teledermatologists from academia, private practice, health maintenance organizations, and county settings participated in the study. Among them, 76% practiced store-and-forward only, 6% practiced live-interactive only, and 18% practiced both modalities. Only 29% received structured training in teledermatology. The average number of years practicing teledermatology was 4.29 years (SD±2.81). Approximately 47% of teledermatologists served at least one Federally Qualified Health Center. Over 75% of patients seen via teledermatology were at or below 200% federal poverty level and usually lived in rural regions without dermatologist access. Practice challenges were identified in the following areas. Teledermatologists faced delays in reimbursements and non-reimbursement of teledermatology services. The primary reason for operational inefficiency was poor image quality and/or inadequate history. Costly and inefficient software platforms and lack of communication with referring providers also presented barriers.

Conclusion

Teledermatology enables underserved populations to access specialty care. Improvements in reimbursement mechanisms, efficient technology platforms, communication with referring providers, and teledermatology training are necessary to support sustainable practices.     

The phylogenetic position of Haasiella (Basidiomycota, Agaricomycetes) and the relationships between H. venustissima and H. splendidissima

Based on a combined ITS-LSU rDNA analysis, the omphalinoid genus Haasiella is shown to be part of the Hygrophoroid clade and sister to Hygrophorus. H. venustissima and H. splendidissima are conspecific; H. splendidissima is the tetrasporic/clamped and heterothallic form of H. venustissima.     

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

We sought to examine interactions of the prion protein (PrP^C) with monoaminergic systems due to: the role of PrP^C in both Prion and Alzheimer diseases, which include clinical depression among their symptoms, the implication of monoamines in depression, and the hypothesis that PrP^C serves as a scaffold for signaling systems. To that effect we compared both behavior and monoaminergic markers in wild type (WT) and PrP^C-null (PrP^−/−) mice. PrP^−/− mice performed poorly when compared with WT in forced swimming, tail suspension, and novelty suppressed feeding tests, typical of depressive-like behavior, but not in the control open field nor rotarod motor tests; cyclic AMP responses to stimulation of D1 receptors by dopamine was selectively impaired in PrP^−/− mice, and responses to serotonin, but not to norepinephrine, also differed between genotypes. Contents of dopamine, tyrosine hydroxylase, and the 5-HT5A serotonin receptor were increased in the cerebral cortex of PrP^−/−, as compared with WT mice. Microscopic colocalization, as well as binding in overlay assays were found of PrP^C with both the 5HT5A and D1, but not D4 receptors. The data are consistent with the scaffolding of monoaminergic signaling modules by PrP^C, and may help understand the pathogenesis of clinical depression and neurodegenerative disorders.