OMA1 mediates local and global stress responses against protein misfolding in CHCHD10 mitochondrial myopathy

Mitochondrial stress triggers a response in the cell's mitochondria and nucleus, but how these stress responses are coordinated in vivo is poorly understood. Here, we characterize a family with myopathy caused by a dominant p.G58R mutation in the mitochondrial protein CHCHD10. To understand the disease etiology, we developed a novel knock-in mouse model and found that mutant CHCHD10 aggregates in affected tissues, applying a toxic protein stress to the inner mitochondrial membrane. Unexpectedly, survival of CHCHD10 knock-in mice depended on a protective stress response mediated by OMA1. The OMA1 stress response acted both locally within mitochondria, inhibiting mitochondrial fusion, and signaled outside the mitochondria, activating the integrated stress response. We additionally identified an isoform switch in the terminal complex of the electron transport chain as a novel component of this response. Our results demonstrate that OMA1 is essential for neonatal survival conditionally in the setting of inner mitochondrial membrane stress, coordinating local and global stress responses to reshape the mitochondrial network and proteome.

Topological Design of Multi-Material Compliant Mechanisms with Global Stress Constraints

This paper presents an approach for the topological design of multi-material compliant mechanisms with global stress constraints. The element stacking method and the separable stress interpolation scheme are applied to calculate the element stiffness and element stress of multi-material structures. The output displacement of multi-material compliant mechanisms is maximized under the constraints of the maximum stress and the structural volume of each material. The modified P-norm method is applied to aggregate the local von Mises stress constraints for all the finite elements to a global stress constraint. The sensitivities are calculated by the adjoint method, and the method of moving asymptotes is utilized to update the optimization problem. Several numerical examples are presented to demonstrate the effectiveness of the proposed method. The appearance of the de facto hinges in the optimal mechanisms can be suppressed effectively by using the topology optimization model with global stress constraints, and the stress constraints for each material can be met.

Restoring Global Gene Regulation through Experimental Evolution Uncovers a NAP (Nucleoid-Associated Protein)-Like Behavior of Crp/Cap

Here we report that mutations in the topA gene compensate for loss of cAMP, showing that the interplay between Crp and the supercoiling status of promoters is key to global stress response. Furthermore, we observed an effect of apoCrp on gene expression in the absence of its effector cAMP. This provides support for the proposed NAP-like role for Crp, suggesting that it represents an intermediate point in the evolution of a ligand-controlled TF from a NAP.

Structural Equation Modeling of a Global Stress Index in Healthy Soldiers

Accumulation of stress is a prognostic trigger for cardiovascular disease. Classical scores for cardiovascular risk estimation typically do not consider psychosocial stress. The aim of this study was to develop a global stress index (GSI) from healthy participants by combining individual measures of acute and chronic stress from childhood to adult life. One-hundred and ninety-two female and male soldiers completed the Perceived Stress Scale (PSS4), Trier Inventory for Chronic Stress (TICS), Hospital Anxiety and Depression Scale (HADS), Childhood Trauma Questionnaire (CTQ), Posttraumatic Diagnostic Scale Checklist (PDS), and the Deployment Risk and Resilience Inventory (DRRI-2). The underlying structure for the GSI was examined through structural equation modeling. The final hierarchical multilevel model revealed fair fit by taking modification indices into account. The highest order had a g-factor called the GSI. On a second level the latent variables stress, HADS and CTQ were directly loading on the GSI. A third level with the six CTQ subscales was implemented. On the lowest hierarchical level all manifest variables and the DRRI-2/PDS sum scores were located. The presented GSI serves as a valuable and individual stress profile for soldiers and could potentially complement classical cardiovascular risk factors.

The effect of psychological distress on IVF outcomes: Reality or speculations?

Introduction Infertility is a problem that affects millions of people worldwide. The aim of this study was to assess the effect of stress, depression and anxiety on the IVF outcomes in Kazakhstan. Methods The prospective cohort study was performed using questionnaires to assess psychological distress in 304 infertile female in three different cities in Kazakhstan. Results The average age of participants was 33.7 years with infertility duration of 5.9 years. Regarding stress, depression and anxiety we found that more than 80% of all respondents had CES-D score higher than 16, indicating that they are at risk of developing clinical depression. On average, FPI subscales’ scores, global stress score and anxiety scale (STAI-S and STAI-T) scores were statistically significantly higher among not pregnant women than pregnant women. Similarly, in simple logistic regression analysis all FPI subscales scores, global stress scale score and anxiety scales’ scores were negatively associated with clinical pregnancy. Conclusion Rates of stress, anxiety and depression among IVF patients are higher than in general population. If the level of infertility-related stress is higher, IVF success rate is lower. Findings of our study indicate the need for the specific psychological interventions for all infertility women, to improve IVF success rate.

Evaluating Daily Versus Global Stress Appraisals’ Sensitivity to Mild Cognitive Impairment

Stress is an important correlate of cognitive aging that manifests in everyday life. Infrequent trait-based stress measures may not be as sensitive to mild cognitive impairment (MCI) as ecological momentary assessments (EMA). We compared EMA to global trait-based stress measures in discriminating MCI. A sample of 248 adults from the Einstein Aging Study (Mage=77.33 years, SD=5.04; 68 with MCI) were prompted to report whether a stressor occurred and to rate the severity up to four times daily for 14 days. Global perceived stress and neuroticism were assessed at baseline. Although MCI status was unrelated to stressor frequency (p>.05), individuals with MCI appraised their daily stressors as more severe than cognitively intact participants (p=.03). No MCI-related differences emerged on global stress or neuroticism assessments (ps>.05). Results suggest everyday stress markers may be more sensitive to differentiating MCI than global assessments and point toward their utility for early identification of pathological declines.