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Mitochondria contain about 1,000–1,500 proteins that fulfil multiple functions. Mitochondrial proteins originate from two genomes: mitochondrial and nuclear. Hence, proper mitochondrial function requires synchronization of gene expression in the nucleus and in mitochondria and necessitates efficient import of mitochondrial proteins into the organelle from the cytosol. Furthermore, the mitochondrial proteome displays high plasticity to allow the adaptation of mitochondrial function to cellular requirements. Maintenance of this complex and adaptable mitochondrial proteome is challenging, but is of crucial importance to cell function. Defects in mitochondrial proteostasis lead to proteotoxic insults and eventually cell death. Different quality control systems monitor the mitochondrial proteome. The cytosolic ubiquitin–proteasome system controls protein transport across the mitochondrial outer membrane and removes damaged or mislocalized proteins. Concomitantly, a number of mitochondrial chaperones and proteases govern protein folding and degrade damaged proteins inside mitochondria. The quality control factors also regulate processing and turnover of native proteins to control protein import, mitochondrial metabolism, signalling cascades, mitochondrial dynamics and lipid biogenesis, further ensuring proper function of mitochondria. Thus, mitochondrial protein quality control mechanisms are of pivotal importance to integrate mitochondria into the cellular environment.The mitochondrial proteome comprises ~1,000–1,500 nuclear-encoded and mitochondrial-encoded proteins. To ensure proper mitochondrial function, cells use multiple mechanisms of quality control that survey mitochondrial protein biogenesis, import and folding, and allow mitochondria to adapt to the changing needs as well as to respond to stresses that compromise proteostasis.

Statistical control is widely used in correlational studies with the intent of providing more accurate estimates of relationships among variables, more conservative tests of hypotheses, or ruling out alternative explanations for empirical findings. However, the use of control variables can produce uninterpretable parameter estimates, erroneous inferences, irreplicable results, and other barriers to scientific progress. As a result, methodologists have provided a great deal of advice regarding the use of statistical control, to the point that researchers might have difficulties sifting through and prioritizing the available suggestions. We integrate and condense this literature into a set of 10 essential recommendations that are generally applicable and which, if followed, would substantially enhance the quality of published organizational research. We provide explanations, qualifications, and examples following each recommendation.

Spinal cord injury leads to a massive response of innate immune cells in non-regenerating mammals, but also in successfully regenerating zebrafish. However, the role of the immune response in successful regeneration is poorly defined. Here we show that inhibiting inflammation reduces and promoting it accelerates axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for repair. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Tnf-α and Il-1β. Inhibiting Tnf-α does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-α. In contrast, decreasing Il-1β levels or number of Il-1β + neutrophils rescue functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1β function impairs regeneration in irf8 and wildtype animals. Hence, inflammation is dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish. While proinflammatory signalling is preventive to axon regrowth, activated macrophages can be beneficial, for example by limiting the inflammation. This study uses mutant zebrafish lines that lack macrophages and/or microglia to show that peripheral macrophages are necessary in axon regrowth following complete transection of spinal cord.

Key Points The vast majority of mitochondrial and chloroplast proteins are cytosolically synthesized and have to be translocated into the organelle. Precursor proteins contain amino acid-based signals. These signals supply information allowing the proteins to target, and interact with, the cytosolic chaperones that provide guidance to organelles. Translocases at the outer membrane of mitochondria and chloroplasts form the general entry gate into both organelles. The translocases of both organelles consist of three receptors, which bind to the multitude of different precursor proteins and deliver them to a translocation pore formed by a protein with β-barrel structure. Despite similarities with respect to their composition, the translocons differ with respect to signal length requirement and their energizing of the translocation event. The mode of translocation is also distinct between the translocation machineries: mitochondrial import across the outer membrane is affinity-driven, whereas the passage of precursor proteins into chloroplasts is modulated by GTP binding and hydrolysis, and by phosphorylation events. Mitochondria and chloroplasts import the vast majority of their proteins across two membranes. Although the import and initial sorting of precursor proteins is mediated by translocases that are functionally similiar in the outer membrane of both organelles, they each have a unique mode of translocation. Mitochondria and chloroplasts import the vast majority of their proteins across two membranes, and use translocases of the outer membrane as an entry gate. These translocases interact with the incoming precursor protein and guiding chaperone factors. Within the translocon, precursor-protein receptors dock to a central component that mediates both transfer through a cation-selective channel and initial sorting towards internal subcompartments. Despite these similarities, the mode of translocation differs between the two organelles: in chloroplasts, GTP-binding and hydrolysis by the receptors is required for transport, whereas in mitochondria passage of the preprotein is driven by its increasing affinity for the translocase subunits.

Help-seeking is important to access appropriate care and improve mental health. However, individuals often delay or avoid seeking help for mental health problems. Interventions to improve help-seeking have been developed, but their effectiveness is unclear. A systematic review and meta-analysis were therefore conducted to examine the effectiveness of mental health related help-seeking interventions. Nine databases in English, German and Chinese were searched for randomised and non-randomised controlled trials. Effect sizes were calculated for attitudes, intentions and behaviours to seek formal, informal and self-help. Ninety-eight studies with 69 208 participants were included. Interventions yielded significant short-term benefits in terms of formal help-seeking, self-help, as well as mental health literacy and personal stigma. There were also positive long-term effects on formal help-seeking behaviours. The most common intervention types were strategies to increase mental health literacy, destigmatisation (both had positive short-term effects on formal help-seeking behaviours) as well as motivational enhancement (with positive long-term effects on formal help-seeking behaviours). Interventions improved formal help-seeking behaviours if delivered to people with or at risk of mental health problems, but not among children, adolescents or the general public. There was no evidence that interventions increased the use of informal help. Few studies were conducted in low- and middle-income countries (LMICs). This study provides evidence for the effectiveness of help-seeking interventions in terms of improving attitudes, intentions and behaviours to seek formal help for mental health problems among adults. Future research should develop effective interventions to improve informal help-seeking, for specific target groups and in LMICs settings.

The author examines statistical control in a random sample of 60 articles published in four top journals during 2000 to 2002. Authors’bases for including control variables, clarity regarding measures and methods, and reporting of results were recorded. Potential problems included a lack of explanations for inclusion, unclear descriptions of measures and methods, incomplete reporting, and other flaws. Implications for interpreting results, replication, future reviews, and effect sizes are discussed. Twelve recommendations for addressing these issues are offered.

Mitochondrial biogenesis and functions depend on the import of precursor proteins via the ‘translocase of the outer membrane’ (TOM complex). Defects in protein import lead to an accumulation of mitochondrial precursor proteins that induces a range of cellular stress responses. However, constitutive quality-control mechanisms that clear trapped precursor proteins from the TOM channel under non-stress conditions have remained unknown. Here we report that in Saccharomyces cerevisiae Ubx2, which functions in endoplasmic reticulum-associated degradation, is crucial for this quality-control process. A pool of Ubx2 binds to the TOM complex to recruit the AAA ATPase Cdc48 for removal of arrested precursor proteins from the TOM channel. This mitochondrial protein translocation-associated degradation (mitoTAD) pathway continuously monitors the TOM complex under non-stress conditions to prevent clogging of the TOM channel with precursor proteins. The mitoTAD pathway ensures that mitochondria maintain their full protein-import capacity, and protects cells against proteotoxic stress induced by impaired transport of proteins into mitochondria. In Saccharomyces cerevisiae , Ubx2 promotes clearing trapped precursor proteins from the channel of the translocase of the outer membrane, in a translocation-associated degradation pathway that maintains the protein import capacity of mitochondria.

The use of corrosion inhibitors is a cost-effective corrosion mitigation strategy for carbon steel. There is an increased focus on developing and using low-cost, biodegradable and environmentally friendly inhibitor formulations. Plant-based extracts have been evaluated in many studies using a multitude of electrochemical methods and characterisation techniques. Although plant extracts appear as promising alternatives for commercially synthesised inhibitor formulations, a significant amount of optimisation is required. The majority of the research on plant extracts does not elucidate the effect of other synergistic combinations in commercial inhibitor formulations. Therefore, further development of plant extracts as corrosion inhibitors is of significant interest.

Messenger RNA (mRNA) homeostasis represents an essential part of gene expression, in which the generation of mRNA by RNA polymerase is counter-balanced by its degradation by nucleases. The conserved 5′-to-3′ exoribonuclease Xrn1 has a crucial role in eukaryotic mRNA homeostasis by degrading decapped or cleaved mRNAs post-translationally and, more surprisingly, also co-translationally. Here we report that active Xrn1 can directly and specifically interact with the translation machinery. A cryo-electron microscopy structure of a programmed Saccharomyces cerevisiae 80S ribosome–Xrn1 nuclease complex reveals how the conserved core of Xrn1 enables binding at the mRNA exit site of the ribosome. This interface provides a conduit for channelling of the mRNA from the ribosomal decoding site directly into the active center of the nuclease, thus separating mRNA decoding from degradation by only 17 ± 1 nucleotides. These findings explain how rapid 5′-to-3′ mRNA degradation is coupled efficiently to its final round of mRNA translation.The cryo-EM structure of the Saccharomyces cerevisiae 80S ribosome–Xrn1 nuclease complex reveals how the conserved core of Xrn1 allows binding at the mRNA exit channel of the ribosome, ensuring efficient degradation of mRNA after the final round of translation.

Among the greatest challenges in soft sensor development for bioprocesses are variable process lengths, multiple process phases, and erroneous model inputs due to sensor faults. This review article describes these three challenges and critically discusses the corresponding solution approaches from a data scientist’s perspective. This main part of the article is preceded by an overview of the status quo in the development and application of soft sensors. The scope of this article is mainly the upstream part of bioprocesses, although the solution approaches are in most cases also applicable to the downstream part. Variable process lengths are accounted for by data synchronization techniques such as indicator variables, curve registration, and dynamic time warping. Multiple process phases are partitioned by trajectory or correlation-based phase detection, enabling phase-adaptive modeling. Sensor faults are detected by symptom signals, pattern recognition, or by changing contributions of the corresponding sensor to a process model. According to the current state of the literature, tolerance to sensor faults remains the greatest challenge in soft sensor development, especially in the presence of variable process lengths and multiple process phases.