Investigating the regulation of the unc-33 promoter by environmental stressors.

Environmental factors such as prenatal stress are hypothesized to contribute to the development of schizophrenia. Lee and colleagues determined rats exposed to prenatal stress exhibited decreased levels of only one protein, DPYSL2, in their prefrontal cortex and hippocampus. DYPSL2, a protein seen to be inactivated in schizophrenic patients, is important for neuronal development. The C. elegans homolog of DPYSL2, UNC-33, is also found to be critical for axonal outgrowth and synapse formation. Herein, we study the effects of environmental stressors such as increasing temperatures and pathogens on the expression of GFP driven by the unc-33 promoter. Results indicate that neuronal GFP expression was lower in C. elegans exposed to these prenatal stressors, making this the first report denoting an environmental regulation of the unc -33 promoter. This study provides insight into unc-33 and the regulation of its expression in relation to temperature and infection.

Burnout and Self-Perceived Stress in Workers in Essential Services after the Impact of Hurricanes Irma and Maria.

OBJECTIVE: To examine the levels of burnout and self-perceived stress in workers at the Puerto Rico Electric Power Authority, who experienced major disasters: Hurricanes Irma and Maria. METHODS: A quantitative descriptive cross-sectional study with a non-probabilistic convenience sample was conducted in workers at the Puerto Rico Electric Power Authority. A structured questionnaire was administered to a sample of 163 eligible participants, aged 21 years and older, who participated voluntarily. Using employees of the electric company, the study examined the relationships between burnout and several characteristics (years of employment, existing health conditions, and coping strategies) both before and after Hurricanes Irma and Maria. Burnout was assessed with Gil-Monte's Spanish Burnout Inventory, and self-perceived stress was assessed with the 14-item Perceived Stress Scale. RESULTS: Before the hurricanes, 16.6% of the workers reported high levels of burnout syndrome, while, after the hurricanes, the proportion increased to one-fifth (20.9%). Prior to the 2 hurricanes, more than one-fourth (23.4%) of the sample reported being extremely stressed; after the hurricanes, that proportion increased to 55%. Factors such as years of employment, counseling, and self-perceived stress showed significant statistical associations (P < .05) with burnout. CONCLUSION: From a public health standpoint, priority should be given to this population, thereby preventing burnout and any other negative effects of the aftermath (i.e., the lengthy response, recovery, and reconstruction) of these kinds of major disaster.

Joint effects of climate, tree size, and year on annual tree growth derived from tree-ring records of ten globally distributed forests.

Tree rings provide an invaluable long-term record for understanding how climate and other drivers shape tree growth and forest productivity. However, conventional tree-ring analysis methods were not designed to simultaneously test effects of climate, tree size, and other drivers on individual growth. This has limited the potential to test ecologically relevant hypotheses on tree growth sensitivity to environmental drivers and their interactions with tree size. Here, we develop and apply a new method to simultaneously model nonlinear effects of primary climate drivers, reconstructed tree diameter at breast height (DBH), and calendar year in generalized least squares models that account for the temporal autocorrelation inherent to each individual tree's growth. We analyze data from 3811 trees representing 40 species at 10 globally distributed sites, showing that precipitation, temperature, DBH, and calendar year have additively, and often interactively, influenced annual growth over the past 120 years. Growth responses were predominantly positive to precipitation (usually over ≥3-month seasonal windows) and negative to temperature (usually maximum temperature, over ≤3-month seasonal windows), with concave-down responses in 63% of relationships. Climate sensitivity commonly varied with DBH (45% of cases tested), with larger trees usually more sensitive. Trends in ring width at small DBH were linked to the light environment under which trees established, but basal area or biomass increments consistently reached maxima at intermediate DBH. Accounting for climate and DBH, growth rate declined over time for 92% of species in secondary or disturbed stands, whereas growth trends were mixed in older forests. These trends were largely attributable to stand dynamics as cohorts and stands age, which remain challenging to disentangle from global change drivers. By providing a parsimonious approach for characterizing multiple interacting drivers of tree growth, our method reveals a more complete picture of the factors influencing growth than has previously been possible.

Apolipoprotein E/Amyloid-ß Complex Accumulates in Alzheimer Disease Cortical Synapses via Apolipoprotein E Receptors and Is Enhanced by APOE4.

Apolipoprotein E (apoE) colocalizes with amyloid-ß (Aß) in Alzheimer disease (AD) plaques and in synapses, and evidence suggests that direct interactions between apoE and Aß are important for apoE's effects in AD. The present work examines the hypothesis that apoE receptors mediate uptake of apoE/Aß complex into synaptic terminals. Western blot analysis shows multiple SDS-stable assemblies in synaptosomes from human AD cortex; apoE/Aß complex was markedly increased in AD compared with aged control samples. Complex formation between apoE and Aß was confirmed by coimmunoprecipitation experiments. The apoE receptors low-density lipoprotein receptor (LDLR) and LDLR-related protein 1 (LRP1) were quantified in synaptosomes using flow cytometry, revealing up-regulation of LRP1 in early- and late-stage AD. Dual-labeling flow cytometry analysis of LRP1- and LDLR positives indicate most (approximately 65%) of LDLR and LRP1 is associated with postsynaptic density-95 (PSD-95)-positive synaptosomes, indicating that remaining LRP1 and LDLR receptors are exclusively presynaptic. Flow cytometry analysis of Nile red labeling revealed a reduction in cholesterol esters in AD synaptosomes. Dual-labeling experiments showed apoE and Aß concentration into LDLR and LRP1-positive synaptosomes, along with free and esterified cholesterol. Synaptic Aß was increased by apoE4 in control and AD samples. These results are consistent with uptake of apoE/Aß complex and associated lipids into synaptic terminals, with subsequent Aß clearance in control synapses and accumulation in AD synapses.

Tau Spread, Apolipoprotein E, Inflammation, and More: Rapidly Evolving Basic Science in Alzheimer Disease.

To date, Alzheimer disease drug candidates have produced negative results in human trials, and progress in moving new targets out of the laboratory and into trials has been slow. However, based on 3 decades of previous work, there is reason to hope that amyloid-based and other novel therapies will move at a faster pace toward successful clinical trials. This article highlights selected preclinical research topics that are rapidly advancing in the laboratory.

Pre-synaptic C-terminal truncated tau is released from cortical synapses in Alzheimer's disease.

The microtubule-associated protein tau has primarily been associated with axonal location and function; however, recent work shows tau release from neurons and suggests an important role for tau in synaptic plasticity. In our study, we measured synaptic levels of total tau using synaptosomes prepared from cryopreserved human postmortem Alzheimer's disease (AD) and control samples. Flow cytometry data show that a majority of synaptic terminals are highly immunolabeled with the total tau antibody (HT7) in both AD and control samples. Immunoblots of synaptosomal fractions reveal increases in a 20 kDa tau fragment and in tau dimers in AD synapses, and terminal-specific antibodies show that in many synaptosome samples tau lacks a C-terminus. Flow cytometry experiments to quantify the extent of C-terminal truncation reveal that only 15-25% of synaptosomes are positive for intact C-terminal tau. Potassium-induced depolarization demonstrates release of tau and tau fragments from pre-synaptic terminals, with increased release from AD compared to control samples. This study indicates that tau is normally highly localized to synaptic terminals in cortex where it is well-positioned to affect synaptic plasticity. Tau cleavage may facilitate tau aggregation as well as tau secretion and propagation of tau pathology from the pre-synaptic compartment in AD. Results demonstrate the abundance of tau, mainly C-terminal truncated tau, in synaptic terminals in aged control and in Alzheimer's disease (AD) samples. Tau fragments and dimers/oligomers are prominent in AD synapses. Following depolarization, tau release is potentiated in AD nerve terminals compared to aged controls. We hypothesize (i) endosomal release of the different tau peptides from AD synapses, and (ii) together with phosphorylation, fragmentation of synaptic tau exacerbates tau aggregation, synaptic dysfunction, and the spread of tau pathology in AD. Aß = amyloid-beta.