The amino acid sequences of 47 P-type ATPases from several eukaryotic and bacterial kingdoms were divided into three structural segments based on individual hydropathy profiles. Each homologous segment was (1) multiply aligned and functionally evaluated, (2) statistically analyzed to determine the degrees of sequence similarity, and (3) used for the construction of parsimonious phylogenetic trees. The results show that all of the P-type ATPases analyzed comprise a single family with four major clusters correlating with their cation specificities and biological sources as follows: cluster 1: Ca(2+)-transporting ATPases; cluster 2: Na(+)- and gastric H(+)-ATPases; cluster 3: plasma membrane H(+)-translocating ATPases of plants, fungi, and lower eukaryotes; and cluster 4: all but one of the bacterial P-type ATPases (specific for K+, Cd2+, Cu2+ and an unknown cation). The one bacterial exception to this general pattern was the Mg(2+)-ATPase of Salmonella typhimurium, which clustered with the eukaryotic sequences. Although exceptions were noted, the similarities of the phylogenetic trees derived from the three segments analyzed led to the probability that the N-terminal segments 1 and the centrally localized segments 2 evolved from a single primordial ATPase which existed prior to the divergence of eukaryotes from prokaryotes. By contrast, the C-terminal segments 3 appear to be eukaryotic specific, are not found in similar form in any of the prokaryotic enzymes, and are not all demonstrably homologous among the eukaryotic enzymes. These C-terminal domains may therefore have either arisen after the divergence of eukaryotes from prokaryotes or exhibited more rapid sequence divergence than either segment 1 or 2, thus masking their common origin. The relative rates of evolutionary divergence for the three segments were determined to be segment 2 < segment 1 < segment 3. Correlative functional analyses of the most conserved regions of these ATPases, based on published site-specific mutagenesis data, provided preliminary evidence for their functional roles in the transport mechanism. Our studies define the structural and evolutionary relationships among the P-type ATPases. They should provide a guide for the design of future studies of structure-function relationships employing molecular genetic, biochemical, and biophysical techniques.
Background: In addition to its physical health benefits, physical activity is increasingly recognized as a means to support mental health. Regular moderate-to-vigorous physical activity (MVPA) is associated with improved mental well-being, reduced likelihood of developing mental illness, and improved symptom management. Despite these benefits, most people fail to achieve minimum recommended levels of MVPA. Population levels of physical activity have further declined since the onset of the COVID-19 pandemic and implementation of public health measures (e.g., shelter-in-place protocols). The potential impact of this decline on mental heath outcomes warrants ongoing investigation.Purpose: To investigate associations between changes in MVPA and mental health (depressive symptoms, anxiety symptoms, and life satisfaction) in adults impacted by the COVID-19 pandemic.Method: Research followed a cross-sectional design. English-speaking adults were invited to complete an online questionnaire. MVPA was assessed retrospectively (before COVID-19) and currently (during COVID-19) with the International Physical Activity Questionnaire. Mental health was assessed with the Patient Health Questionnaire, 9-Item (PHQ-9), the Generalized Anxiety Disorder, 7-Item (GAD-7), and the Satisfaction with Life Scale (SWLS). Regression was used to assess relationships between MVPA and mental health. ANOVA with follow-up tests examined whether participants who differed in mental health status (e.g., no symptoms vs. severe symptoms) differed in their change in MVPA. T-tests were used to examine differences in mental health symptomatology between participants who were sufficiently (i.e., achieving MVPA guidelines of ≥ 150 min/week) vs. insufficiently active.Results: Prior to COVID-19, 68.2% of participants were classified as being sufficiently active, vs. 60.6% during COVID-19. The majority of participants reported experiencing some level of depressive symptoms (62.0%) or anxiety symptoms (53.7%). After controlling for covariates, changes in MVPA accounted for significant variability in the PHQ-9 (7.7%), GAD-7 (2.5%), and SWLS (1.5 %). Participants with clinically significant mental health symptomatology reported greater declines in MVPA than those who reported no symptoms. Conversely, participants who were sufficiently active during COVID-19 reported significantly lower depression and anxiety, and higher life satisfaction.Conclusion: Participants who experienced the greatest declines in MVPA reported relatively greater psychological distress and lower life satisfaction. While preliminary, these findings suggest the importance of maintaining and promoting physical activity during a period of pandemic.
Interleukins and neurotrophins levels are altered in the periphery of patients with major depression and suicidal behavior, however it is not clear if similar abnormalities occur in the central nervous system. Our objective was to examine the association of IL-6, IL-1β, BDNF, and GDNF levels between postmortem plasma, cerebrospinal fluid (CSF), and brain tissue in a heterogeneous diagnostic subject groups including normal controls, mood disorders only, mood disorders with AUD/SUD (alcohol abuse disorder, substance abuse disorder), and AUD/SUD without mood disorders. To address these questions we collected postmortem plasma (n = 29), CSF (n = 28), and brain (BA10) (n = 57) samples from individuals with mood disorder, mood disorder with AUD/SUD, AUD/SUD and normal controls. These samples were analyzed using a multiplex based luminex assay with a customized 4-plex cytokine/interleukins- IL-6, IL-1β, BDNF, and GDNF human acute phase based on xMAP technology platform. Protein levels were determined using a Luminex 200 instrument equipped with Xponent-analyzing software. We observed IL-6 (p = 2.1e-07), and GDNF (p = 0.046) were significantly correlated between brain and CSF. In addition, IL-6 (p = 0.031), were significantly correlated between brain and plasma. Overall diagnostic group analysis showed a significant difference with brain GDNF, p = 0.0106. Pairwise comparisons showed that GDNF level is—39.9 ± 12 pg/ml, p = 0.0106, was significantly higher than in the brains derived from mood disorders compared to normal controls, —23.8 ± 5.5 pg/ml, p = 0.034. Brain BDNF was higher in suicide (p = 0.0023), males compared to females (p = 0.017), and psychiatric medication treated vs. non-treated (p = 0.005) individuals. Overall, we demonstrate that blood IL-6, GDNF and BDNF could be informative peripheral biomarkers of brain biology associated with mood disorders, substance disorders, and suicide.
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