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Objectives: Activation, a construct including energy and activity, is a central feature of Bipolar Spectrum Disorders (BSDs). Prior research found motor activity is associated with affect, and this relationship may be stronger for individuals with BSDs. The aims of this study were to investigate bidirectional relationships between physical activity and mood and evaluate whether bipolar risk status moderated potential associations., Methods: Young adults at low-risk, high-risk, and diagnosed with BSD participated in a 20-day EMA study in which they wore an actiwatch to measure physical activity and sleep/wake cycles. They also reported depressive and hypo/manic symptoms three times daily. Multilevel linear models were estimated to examine how bipolar risk group moderated bidirectional relationships between physical activity and mood symptoms at within-day and between-day timescales., Results: Physical activity was significantly associated with subsequent mood symptoms at the within-day level. The relationship between physical activity and depressive symptoms was moderated by BSD risk group. An increase in physical activity resulted in a greater reduction of depressive symptoms for the BSD group compared to the low-risk and high-risk groups., Conclusions: Interventions targeting activity like behavioral activation may improve residual inter-episode mood symptoms., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Activated extracellular signal-regulated kinase (ERK) signaling mediated plasticity-related gene transcription has been proposed for one possible mechanism by which 17β-estradiol (E2) enhances synaptic plasticity and memory. Because activated ERK also enhances plasticity-related mRNA translation in the dendrites of neurons, we sought to determine the effects of E2 on activation of ERK, phosphorylation of translation initiation factors, and dendritic mRNA translation in hippocampal neurons. Acute E2 application resulted in a rapid, transient increase in phosphorylation of translation initiation factors, ribosomal protein (S6) and eIF4E binding protein1 (4EBP1), in an activated ERK-dependent manner. Since phosphorylation of these translation factors enhance mRNA translation, we tested E2's effect on dendritic mRNA translation. Using a green fluorescent protein (GFP)-based dendritic mRNA translation reporter (reporter plasmid construct consisted of a GFP gene fused to the 3' untranslated region (UTR) from CAMKIIα, which contains dendritic resident mRNA targeting and mRNA translational regulatory elements) we showed that E2 treatment resulted in increased somatic and dendritic GFP mRNA translation in GFP-reporter transfected hippocampal neurons. Translation inhibitor anisomycin and ERK inhibitor U0126 blocked E2 effects. Taken together, our results provide a novel mechanism by which E2 may trigger local protein synthesis of α-CaMKII in the dendrites, which is necessary for modulation of synaptic plasticity., (Published by Elsevier Ltd.)

Bacteria inhabit natural and artificial environments with diverse and fluctuating osmolalities, salinities and temperatures. Many maintain cytoplasmic hydration, growth and survival most effectively by accumulating kosmotropic organic solutes (compatible solutes) when medium osmolality is high or temperature is low (above freezing). They release these solutes into their environment when the medium osmolality drops. Solutes accumulate either by synthesis or by transport from the extracellular medium. Responses to growth in high osmolality medium, including biosynthetic accumulation of trehalose, also protect Salmonella typhimurium from heat shock. Osmotically regulated transporters and mechanosensitive channels modulate cytoplasmic solute levels in Bacillus subtilis, Corynebacterium glutamicum, Escherichia coli, Lactobacillus plantarum, Lactococcus lactis, Listeria monocytogenes and Salmonella typhimurium. Each organism harbours multiple osmoregulatory transporters with overlapping substrate specificities. Membrane proteins that can act as both osmosensors and osmoregulatory transporters have been identified (secondary transporters ProP of E. coli and BetP of C. glutamicum as well as ABC transporter OpuA of L. lactis). The molecular bases for the modulation of gene expression and transport activity by temperature and medium osmolality are under intensive investigation with emphasis on the role of the membrane as an antenna for osmo- and/or thermosensors.

This study had three aims: 1) to cross-validate previously reported findings that sober alcoholics compared to nonalcoholic peers have reduced ERP P300 amplitudes to visual target stimuli at the Pz electrode; 2) to test the hypothesis that alcoholics from VA Hospital treatment programs will manifest more ERP indications of brain dysfunction than peer alcoholics from community treatment programs (paralleling our neuropsychological findings in these samples); and 3) to explore differences among the groups in ERP responses to the little-studied nontarget stimuli. Nineteen VA alcoholics, 32 community alcoholics, and 24 peer community controls were given a visual "oddball" stimulus task. The total group of alcoholics had significantly lower P300 amplitudes than controls for target stimuli at the Pz electrode but VA and community alcoholic subgroups did not differ. There were no latency differences between or among the groups. On the nontarget stimuli, alcoholics had significantly higher P100 and lower N100 amplitudes than the controls at all three scored electrodes (Fz, Cz, and Pz). We conclude that cross-validation of reduced P300 amplitudes at Pz in sober alcoholics was obtained but that differences in severity of brain dysfunction, at least as measured by neuropsychological test performance, cannot account for alcoholics' ERP changes relative to controls. Finally, our data suggest that ERP changes to nontarget visual stimuli should be investigated in addition to the more traditional ERP measures to target stimuli.

The effects of alcohol and sleep deprivation on choice reaction time (RT) as a function of stimulus intensity, stimulus quality, and response compatibility were investigated. Fifty-four male subjects were assigned to one of three levels of alcohol (0.00, 0.07, or 0.10 BAC), and one of two levels of sleep deprivation (0 or 24 h). Stimulus intensity, stimulus quality, and response compatibility were varied (high or low), with RTs identified according to time on task. Significant main effects of each of the stimulus variables were present in baseline analysis, with low-level conditions producing longer RTs. Alcohol produced an overall slowing of RT. The combination of both treatments led to larger increases in RT for low stimulus quality. Sleep deprivation increased RT for high stimulus intensity. Alcohol increased RT for low stimulus intensity, but only when subjects were not sleep deprived. These results imply higher risk with degraded stimulus conditions, e.g., driving in settings of low visibility or at night.

In a dual-modality paradigm, visual and auditory event-related potentials were elicited in 40 alcoholic men and 30 controls, equated with the alcoholics on age and education. Half of each group had first-degree relatives who were alcoholic (family history positive). The amplitude of the visual N1 component was reduced among the alcoholics, but their auditory N1 amplitudes were normal. Average N1 amplitudes were also smaller in the family history positive subjects but this effect was significant only for auditory stimuli. Alcoholics showed reduced average P3 amplitudes to both visual and auditory signals, particularly in the family history positive group. Clearly, stratification by family history is useful for ascertainment of ERP variation among alcoholics. There were no effects on P3 latency. Among several possible explanations of P3 deficits in alcoholics, two are particularly interesting: (1) alcoholics cannot mobilize sufficient processing resources in the service of effortful cognitive functions; (2) alcoholics, being poorly motivated, apply insufficient effort to cognitive tasks. An experiment designed to test these hypotheses is described.