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In plants, thousands of nucleus‐encoded proteins translated in the cytosol are sorted to chloroplasts and mitochondria by binding to specific receptors of the TOC (translocon on the outer chloroplast membrane) and the TOM (translocon on the outer mitochondrial membrane) complexes for import into those organelles. The degradation pathways for these receptors are unclear. Here, we discovered a converged ubiquitin‐proteasome pathway for the degradation of Arabidopsis thaliana TOC and TOM tail‐anchored receptors. The receptors are ubiquitinated by E3 ligase(s) and pulled from the outer membranes by the AAA+ adenosine triphosphatase CDC48, after which a previously uncharacterized cytosolic protein, transmembrane domain (TMD)‐binding protein for tail‐anchored outer membrane proteins (TTOP), binds to the exposed TMDs at the C termini of the receptors and CDC48, and delivers these complexes to the 26S proteasome. [ABSTRACT FROM AUTHOR]

The present longitudinal study aims at investigating the interplay between child temperament, mother–child interaction quality and child Theory of Mind (ToM) at preschool age with regard to the development of child problem behavior at school age in 115 participants. Maternal sensitivity and child temperament were assessed when children were 4 years old. At 5 years of age, child ToM was assessed. At 8 years of age, child problem behavior was assessed. Results showed that child problem behavior was independently predicted by child temperamental negative affectivity and maternal sensitivity. The current study underlines the important role of both endogenous as well as exogenous factors for healthy child development. [ABSTRACT FROM AUTHOR]

The majority of proteins localised to mitochondria are encoded by the nuclear genome, with approximately 1500 proteins imported into mammalian mitochondria. Dysfunction in this fundamental cellular process is linked to a variety of pathologies including neuropathies, cardiovascular disorders, myopathies, neurodegenerative diseases and cancer, demonstrating the importance of mitochondrial protein import machinery for cellular function. Correct import of proteins into mitochondria requires the co‐ordinated activity of multimeric protein translocation and sorting machineries located in both the outer and inner mitochondrial membranes, directing the imported proteins to the destined mitochondrial compartment. This dynamic process maintains cellular homeostasis, and its dysregulation significantly affects cellular signalling pathways and metabolism. This review summarises current knowledge of the mammalian mitochondrial import machinery and the pathological consequences of mutation of its components. In addition, we will discuss the role of mitochondrial import in cancer, and our current understanding of the role of mitochondrial import in neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease. [ABSTRACT FROM AUTHOR]

The right temporoparietal junction (rTPJ) has been associated with the ability to reorient attention to unexpected stimuli and the capacity to understand others' mental states (theory of mind [ToM]/false belief). Using activation likelihood estimation meta-analysis we previously unraveled that the anterior rTPJ is involved in both, reorienting of attention and ToM, possibly indicating a more general role in attention shifting. Here, we used neuronavigated transcranial magnetic stimulation to directly probe the role of the rTPJ across attentional reorienting and false belief. Task performance in a visual cueing paradigm and false belief cartoon task was investigated after application of continuous theta burst stimulation (cTBS) over anterior rTPJ (versus vertex, for control). We found that attentional reorienting was significantly impaired after rTPJ cTBS compared with control. For the false belief task, error rates in trials demanding a shift in mental state significantly increased. Of note, a significant positive correlation indicated a close relation between the stimulation effect on attentional reorienting and false belief trials. Our findings extend previous neuroimaging evidence by indicating an essential overarching role of the anterior rTPJ for both cognitive functions, reorienting of attention and ToM. Hum Brain Mapp 37:796-807, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Organellar proteins synthesized in the cytosol are usually selective for only one destination in a cell but some proteins are localized in more than one compartment, for example in both mitochondria and chloroplasts. The mechanism of dual targeting of proteins to mitochondria and chloroplasts is yet poorly understood. Previously, we observed that the dual targeting peptide of threonyl-tRNA synthetase in Arabidopsis thaliana ( At ThrRS-dTP) interacts with the mitochondrial receptor At Tom20 mainly through its N-terminal part. Here we report on the interaction of At ThrRS-dTP with the chloroplastic receptor At Toc34, presenting for the first time the mode of interactions of a dual targeting peptide with both Tom20 and Toc34. By NMR spectroscopy we investigated changes in 15 N HSQC spectra of At ThrRS-dTP as a function of At Toc34 concentration. Line broadening shows that the interaction with At Toc34 involves residues along the entire sequence, which is not the case for At Tom20. The N-terminal φχχφφ motif, which plays an important role in At Tom20 recognition, shows no specificity for At Toc34. These results are supported by import competition studies into both mitochondria and chloroplasts, in which the effect of peptides corresponding to different segments of At ThrRS-dTP on in vitro import of organelle specific proteins was examined. This demonstrates that the N-terminal A2-Y29 segment of At ThrRS-dTP is essential for import into both organelles, while the C-terminal L30-P60 part is important for chloroplastic import efficiency. In conclusion, we have demonstrated that the recognition of the dual targeting peptide of At Thr-tRNA synthetase is different for the mitochondrial and chloroplastic receptors. [ABSTRACT FROM AUTHOR]

Abstract: The role of the mitochondrial protein receptor Tom22p in the interaction of pro-apoptotic protein Bax with yeast mitochondria was investigated. Co-immunoprecipitation assays showed that human Bax interacted with different TOM subunits, including Tom22p. Expression of the cytosolic receptor domain of human Tom22 increased Bax mitochondrial localization, but decreased the proportion of active Bax. BN–PAGE showed that the cytosolic domain of Tom22 interfered with the oligomerization of Bax. These data suggest that the interaction with the cytosolic domain of Tom22 helps Bax to acquire a conformation able to interact with the outer mitochondrial membrane. Structured summary of protein interactions: BAX and BAX physically interact with TOM22 by anti bait coimmunoprecipitation (View interaction) BAX physically interacts with TOM70 by anti bait coimmunoprecipitation (View interaction) BAX physically interacts with TOM22 , TOM70 and TOM40 by anti bait coimmunoprecipitation (View interaction) BAX physically interacts with TOM22 by anti bait coimmunoprecipitation (View interaction) BAX and BAX bind by blue native page (View interaction) BAX physically interacts with TOM40 by anti bait coimmunoprecipitation (View interaction) [Copyright &y& Elsevier]

Abstract: Bax insertion into the mitochondrial outer membrane is essential for the implementation of apoptosis. However, little is known about the first stage of Bax integration into the mitochondrial outer membrane. We have recently shown that TOM22, a mitochondrial outer membrane receptor, is important for insertion, although other reports have suggested that only mitochondrial lipids are involved in this process. Here, we show that monomers, but not dimers, of Bax require the presence of TOM22 and TOM40 to integrate into mitochondria. In addition we show that once inserted into the membrane, Bax can act as a receptor for cytosolic Bax. [Copyright &y& Elsevier]

The translocase of the outer mitochondrial membrane (TOM) is composed of receptors, a channel protein, and its modulators that function together to import proteins into mitochondria. Although the import pathway of proteins directed to the mitochondrial matrix has been well characterized, recent studies into the import pathway taken by proteins into the other submitochondrial compartments have broadened our understanding into the way the TOM machinery recognizes, interacts, and translocates proteins. [ABSTRACT FROM AUTHOR]

Recent changes in the commercial and military aerospace industries have caused us to question the traditional ways of measuring, predicting and assuring product reliability. These industries have been unique in that both quality and reliability have been almost completely controlled by government standards, a condition that will not survive the current upheaval in these markets. Traditional reliability prediction methods for military and commercial aerospace products use a probabilistic approach, such as that of MIL-HDBK-217, and Reliability Assurance relies on fixed quality levels in design and manufacture. These approaches almost uniformly assume that predicted equipment reliability is the sum of the predicted reliabilities of the electronic and electromechanical parts in the equipment and that once designed, reliability is a fixed attribute of the hardware. This paper describes a comprehensive approach to avionics reliability assurance which addresses all potential causes of unreliability. It is applicable to both commercial and military products. The approaches described here may be viewed as the next logical step beyond the traditional approach to quality and reliability found in current Military Standards. This paper is a call to change the way we think about reliability assurance in the military and aerospace markets. Six new approaches are suggested: (1) Adopt a continuous improvement, zero- defects mentality in the design of military and aerospace products; (2) develop a design-to-world-class cost and schedule mentality; (3) adapt world-class process control methods to low-volume, high- reliability manufacturing; (4) accept ownership for quality and reliability of all components and materials; (5) adapt world-class design practices to military and aerospace products; and (6) recognize that quality and reliability of parts, materials, and systems are the responsibility of those who manufacture them. [ABSTRACT FROM AUTHOR]