Team Approach: Diagnosis, Management, and Prevention of Sudden Cardiac Arrest in the Athlete.

¼ Sudden cardiac events during sports competition are rare but tragic occurrences that require a timely, comprehensive response by well-prepared athletic trainers and medical providers. This sequence should prioritize prompt emergency medical system activation, immediate initiation of cardiopulmonary resuscitation (CPR), automated early defibrillation (AED), and comprehensive advanced life support efforts.¼ Exercise-induced cardiac remodeling, referred to as the "athlete's heart," refers to a host of adaptive changes that increase cardiac chamber size and wall thickness to allow for greater pressures and volumes during exercise. This remodeling phenotype may overlap with other inherited cardiomyopathies and cardiac abnormalities, which can complicate clinical care. The long-term implications of this electrical and structural remodeling on cardiac function are unknown.¼ Although the best screening strategies to optimize primary prevention of sudden cardiac arrest is an evolving topic, the effectiveness of CPR and early defibrillation use in treating out-of-hospital sudden cardiac arrest has been well-established, despite their reported underuse.

Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC. We next undertake an interventional, double-blind, dual-centre, prospective clinical trial, in which CRC patients take either placebo or EcN for two weeks prior to resection of neoplastic and adjacent normal colorectal tissue (ACTRN12619000210178). We detect enrichment of EcN in tumor samples over normal tissue from probiotic-treated patients (primary outcome of the trial). Next, we develop early CRC intervention strategies. To detect lesions, we engineer EcN to produce a small molecule, salicylate. Oral delivery of this strain results in increased levels of salicylate in the urine of adenoma-bearing mice, in comparison to healthy controls. To assess therapeutic potential, we engineer EcN to locally release a cytokine, GM-CSF, and blocking nanobodies against PD-L1 and CTLA-4 at the neoplastic site, and demonstrate that oral delivery of this strain reduces adenoma burden by ~50%. Together, these results support the use of EcN as an orally-deliverable platform to detect disease and treat CRC through the production of screening and therapeutic molecules.

High Rate of Clinically Meaningful Achievement in Outcomes After Subacromial Balloon Spacer Implantation for Massive Irreparable Rotator Cuff Tears: A Systematic Review and Meta-analysis.

BACKGROUND: Subacromial balloon spacers have been introduced as a potential treatment option for patients with massive irreparable rotator cuff tears. However, it is important to comprehensively assess the clinical efficacy of this procedure in the context of an increasing amount of contemporary literature. PURPOSE: To perform a systematic review of the contemporary literature to understand the propensity for clinically meaningful improvements after subacromial balloon spacer implantation for massive irreparable rotator cuff tears. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: The PubMed, Ovid/MEDLINE, and Cochrane databases were queried in July 2022 for data pertaining to studies reporting clinically significant outcomes after subacromial balloon spacer implantation. Freeman-Tukey double arcsine transformation was used to quantify the pooled rate of clinically meaningful improvements in outcomes as evaluated using the minimal clinically important difference (MCID), Patient Acceptable Symptom State (PASS), and substantial clinical benefit (SCB). Qualitative analysis was performed when data were variably presented to avoid misleading reporting. RESULTS: There were 10 studies included, all of which reported MCID achievement. The overall pooled rate of MCID achievement for the Constant-Murley score was 83% (95% CI, 71%-93%; range, 40%-98%), with 6 of 8 studies reporting rates equal to or exceeding 85%. One study reported a 98% rate of PASS achievement for the Constant-Murley score at 3-year follow-up. The rate of MCID achievement for the American Shoulder and Elbow Surgeons (ASES) score ranged between 83% and 87.5%. The rate of PASS achievement for the ASES score was 56% at 2-year follow-up, while the rate of SCB achievement for the ASES score was 83% and 82% at 1- and 2-year follow-up, respectively. At 1-year follow-up, 74% and 78% of patients achieved the MCID for the Numeric Rating Scale and Oxford Shoulder Score, respectively. At 3 years, 69% of patients achieved the MCID for the Numeric Rating Scale and 87% achieved it for the Oxford Shoulder Score. CONCLUSION: Patients who underwent isolated subacromial balloon spacer implantation for massive irreparable rotator cuff tears demonstrated a high rate of clinically significant improvement in outcomes at short- to mid-term follow-up. A paucity of literature exists to appropriately define and evaluate the rates of achieving the PASS and SCB after subacromial balloon spacer implantation, necessitating further study.

Kinetic modeling identifies targets for engineering improved photosynthetic efficiency in potato (Solanum tuberosum cv. Solara).

Potato (Solanum tuberosum) is a significant non-grain food crop in terms of global production. However, its yield potential might be raised by identifying means to release bottlenecks within photosynthetic metabolism, from the capture of solar energy to the synthesis of carbohydrates. Recently, engineered increases in photosynthetic rates in other crops have been directly related to increased yield - how might such increases be achieved in potato? To answer this question, we derived the photosynthetic parameters Vcmax and Jmax to calibrate a kinetic model of leaf metabolism (e-Photosynthesis) for potato. This model was then used to simulate the impact of manipulating the expression of genes and their protein products on carbon assimilation rates in silico through optimizing resource investment among 23 photosynthetic enzymes, predicting increases in photosynthetic CO2 uptake of up to 67%. However, this number of manipulations would not be practical with current technologies. Given a limited practical number of manipulations, the optimization indicated that an increase in amounts of three enzymes - Rubisco, FBP aldolase, and SBPase - would increase net assimilation. Increasing these alone to the levels predicted necessary for optimization increased photosynthetic rate by 28% in potato.

Outcomes after débridement, antibiotics, and implant retention for prosthetic joint infection in shoulder arthroplasty.

BACKGROUND: Patients who undergo total shoulder arthroplasty usually have excellent long-term outcomes. However, a subset of patients is diagnosed with a prosthetic joint infection (PJI) requiring revision procedures and prolonged recovery. The purpose of this study was to evaluate rates of recurrent shoulder PJI in patients undergoing débridement, antibiotics, and implant retention (DAIR), single-stage revision, and 2-stage revision. We also sought to compare outcomes and complications across procedures. METHODS: Retrospective chart review was conducted for patients diagnosed with PJI after primary shoulder arthroplasty between January 2010 and August 2021. Patients were included if they underwent treatment with DAIR, single-stage revision, or 2-stage revision. Demographic information, surgical details, complications, laboratory data, postoperative antibiotic regimen, and infectious pathogen were collected. Postoperative patient-reported outcomes were collected: American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation, Shoulder Activity Scale, and PROMIS Upper Extremity. Chi-square, t test, and 1-way analysis of variance were used as appropriate to evaluate each factor. RESULTS: Sixty-five patients were included in the study, 26% treated with DAIR, 9% treated with single-stage revision, and 65% treated with 2-stage revision. There were no significant differences in patient comorbidities. Patients undergoing DAIR were diagnosed significantly earlier than those undergoing single- and 2-stage revision procedures (12.6 ± 22.9 months vs. 49.6 ± 48.4 vs. 25.0 ± 26.6, P = .010). Recurrent PJI was noted in 23.1% of patients: 29.4% of DAIR patients, no single-stage patients, and 23.8% of 2-stage patients (P = .330). Patients undergoing 2-stage revision with treatment failure had a significantly higher Elixhauser Comorbidity Index (0.2 ± 3.7 vs. 3.7 ± 3.9, P = .027). There was no significant difference in patient-reported outcomes across groups. CONCLUSION: Patients undergoing treatment of shoulder PJI with DAIR did not have an increased rate of reinfection compared with single-stage and 2-stage revision procedures. Patients treated with DAIR were diagnosed with PJI significantly earlier than those undergoing single-stage and 2-stage revision procedures. There was no difference in complication rates between groups. This information adds to the body of work detailing outcomes after DAIR for shoulder PJI and provides encouraging data for use in this patient population. Future studies with a larger sample size may be conducted to further investigate specific pathogens, infection timelines, and antibiotic regimens that reduce the risk of treatment failure.

Transdiagnostic failure to adapt interoceptive precision estimates across affective, substance use, and eating disorders: A replication study.

Recent computational theories of interoception suggest that perception of bodily states rests upon an expected reliability- or precision-weighted integration of afferent signals and prior beliefs. The computational psychiatry framework further suggests that aberrant precision-weighting may lead to misestimation of bodily states, potentially hindering effective visceral regulation and promoting psychopathology. In a previous study, we fit a Bayesian computational model of perception to behavior on a heartbeat tapping task to test whether aberrant precision-weighting was associated with misestimation of bodily states. We found that, during an interoceptive perturbation designed to amplify afferent signal precision (inspiratory breath-holding), healthy individuals increased the precision-weighting assigned to ascending cardiac signals (relative to resting conditions), while individuals with symptoms of anxiety, depression, substance use disorders, and/or eating disorders did not. A second study also replicated the pattern observed in healthy participants. In this pre-registered study, we aimed to replicate our prior findings in a new transdiagnostic patient sample (N=285) similar to the one in the original study. These new results successfully replicated those found in our previous study, indicating that, transdiagnostically, patients were unable to adjust beliefs about the reliability of interoceptive signals - preventing the ability to accurately perceive changes in their bodily state. Follow-up analyses combining samples from the previous and current study (N=719) also afforded the power to identify group differences within narrower diagnostic groups and to examine predictive accuracy when logistic regression models were trained on one sample and tested on the other. Given the increased confidence in the generalizability of these effects, future studies should examine the utility of interceptive precision measures in predicting treatment outcomes or identify whether these computational mechanisms might represent novel therapeutic targets for improving visceral regulation.

The proteasome regulates body weight and systemic nutrient metabolism during fasting.

The ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway are the primary means of degradation in mammalian tissues. We sought to determine the individual contribution of the UPS and autophagy to tissue catabolism during fasting. Mice were overnight fasted for 15 h before regaining food access ("Fed" group, n = 6) or continuing to fast ("Fast" group, n = 7) for 3 h. In addition, to investigate the effects of autophagy on systemic metabolism and tissue degradation, one group of mice was fasted for 18 h and treated with chloroquine ("Fast + CLQ" group, n = 7) and a fourth group of mice was treated with bortezomib ("Fast + Bort" group, n = 7) to assess the contribution of the UPS. Body weight, tissue weight, circulating hormones and metabolites, intracellular signaling pathways, and protein synthesis were investigated. Fasting induced the loss of body weight, liver mass, and white adipose tissue in the Fast and the Fast + CLQ group, whereas the Fast + Bort group maintained tissue and body weight. Fasting reduced glucose and increased ß hydroxybutyrate in the circulation of all mice. Both changes were most profound in the Fast + Bort group compared with the other fasting conditions. Molecular signaling indicated a successful inhibition of hepatic UPS with bortezomib and an upregulation of the PI3K/AKT/mTOR pathway. The latter was further supported by an increase in hepatic protein synthesis with bortezomib. Inhibition of the UPS through bortezomib blocks body weight loss and tissue catabolism during an acute overnight fast in mice. The effects were likely mediated through a combined effect of the drug on biomolecule degradation and synthesis.NEW & NOTEWORTHY Bortezomib treatment prevents tissue and body weight loss during fasting. The loss of proteasome activity with bortezomib exacerbates fasting-induced ketogenesis. During fasting, bortezomib increases AMPK and PI3K/AKT signaling in the liver, which promotes protein synthesis.

Active learning impairments in substance use disorders when resolving the explore-exploit dilemma: A replication and extension of previous computational modeling results.

BACKGROUND: Substance use disorders (SUDs) represent a major public health risk. Yet, our understanding of the mechanisms that maintain these disorders remains incomplete. In a recent computational modeling study, we found initial evidence that SUDs are associated with slower learning rates from negative outcomes and less value-sensitive choice (low "action precision"), which could help explain continued substance use despite harmful consequences. METHODS: Here we aimed to replicate and extend these results in a pre-registered study with a new sample of 168 individuals with SUDs and 99 healthy comparisons (HCs). We performed the same computational modeling and group comparisons as in our prior report (doi: 10.1016/j.drugalcdep.2020.108208) to confirm previously observed effects. After completing all pre-registered replication analyses, we then combined the previous and current datasets (N = 468) to assess whether differences were transdiagnostic or driven by specific disorders. RESULTS: Replicating prior results, SUDs showed slower learning rates for negative outcomes in both Bayesian and frequentist analyses (partial η2=.02). Previously observed differences in action precision were not confirmed. Learning rates for positive outcomes were also similar between groups. Logistic regressions including all computational parameters as predictors in the combined datasets could differentiate several specific disorders from HCs, but could not differentiate most disorders from each other. CONCLUSIONS: These results provide robust evidence that individuals with SUDs adjust behavior more slowly in the face of negative outcomes than HCs. They also suggest this effect is common across several different SUDs. Future research should examine its neural basis and whether learning rates could represent a new treatment target or moderator of treatment outcome.

The green and sustainable radiology department.

As manmade climate change threatens the health of the planet, it is important that we understand and address the contribution of healthcare to global emissions. Medical imaging is a significant contributor to overall emissions. This article aims to highlight key issues and examples of sustainable practices, in order to empower radiologists to make a change within their department.

Clinical Evaluation of the Sleepy and Sleepless Patient.

OBJECTIVE: This article addresses the approach to the evaluation of patients who present to a neurologist with excessive daytime sleepiness or difficulty sleeping. LATEST DEVELOPMENTS: Greater emphasis on the importance of sleep reflects the growing scientific understanding that sleep is critical to overall health and well-being. Consumer sleep technologies, which measure parameters related to sleep, may provide insight into an individual's sleep-related symptoms and tendencies and have a role in patient-centered sleep evaluation when used within an appropriate clinical context. ESSENTIAL POINTS: A thorough review of a patient's history and physical examination findings are important components of the assessment and management of their sleep-related symptoms. An understanding of how the clinical context relates to the categorization of sleep disorders can impact a patient's symptoms, comorbid neurologic disorders, and overall well-being. Many neurologic conditions are strongly associated with sleep disturbance, risk factors for the development of a sleep disorder, or both. Therefore, it is critical for neurologists to be familiar and comfortable with taking a focused sleep history. Modalities such as in-laboratory polysomnography, home sleep apnea testing, multiple sleep latency testing, and actigraphy, as well as contextualized and prudent use of data obtained from consumer sleep technologies, can be helpful in appropriately selected patients. Mindful integration of these objective data facilitates the diagnosis and management of sleep disorders.

The Ratio of Key Metabolic Transcripts Is a Predictive Biomarker of Breast Cancer Metastasis to the Lung.

Understanding the rewired metabolism underlying organ-specific metastasis in breast cancer could help identify strategies to improve the treatment and prevention of metastatic disease. Here, we used a systems biology approach to compare metabolic fluxes used by parental breast cancer cells and their brain- and lung-homing derivatives. Divergent lineages had distinct, heritable metabolic fluxes. Lung-homing cells maintained high glycolytic flux despite low levels of glycolytic intermediates, constitutively activating a pathway sink into lactate. This strong Warburg effect was associated with a high ratio of lactate dehydrogenase (LDH) to pyruvate dehydrogenase (PDH) expression, which correlated with lung metastasis in patients with breast cancer. Although feature classification models trained on clinical characteristics alone were unable to predict tropism, the LDH/PDH ratio was a significant predictor of metastasis to the lung but not to other organs, independent of other transcriptomic signatures. High lactate efflux was also a trait in lung-homing metastatic pancreatic cancer cells, suggesting that lactate production may be a convergent phenotype in lung metastasis. Together, these analyses highlight the essential role that metabolism plays in organ-specific cancer metastasis and identify a putative biomarker for predicting lung metastasis in patients with breast cancer. SIGNIFICANCE: Lung-homing metastatic breast cancer cells express an elevated ratio of lactate dehydrogenase to pyruvate dehydrogenase, indicating that ratios of specific metabolic gene transcripts have potential as metabolic biomarkers for predicting organ-specific metastasis.

DNA selection by the master transcription factor PU.1.

The master transcriptional regulator PU.1/Spi-1 engages DNA sites with affinities spanning multiple orders of magnitude. To elucidate this remarkable plasticity, we have characterized 22 high-resolution co-crystallographic PU.1/DNA complexes across the addressable affinity range in myeloid gene transactivation. Over a purine-rich core (such as 5'-GGAA-3') flanked by variable sequences, affinity is negotiated by direct readout on the 5' flank via a critical glutamine (Q226) sidechain and by indirect readout on the 3' flank by sequence-dependent helical flexibility. Direct readout by Q226 dynamically specifies PU.1's characteristic preference for purines and explains the pathogenic mutation Q226E in Waldenström macroglobulinemia. The structures also reveal how disruption of Q226 mediates strand-specific inhibition by DNA methylation and the recognition of non-canonical sites, including the authentic binding sequence at the CD11b promoter. A re-synthesis of phylogenetic and structural data on the ETS family, considering the centrality of Q226 in PU.1, unifies the model of DNA selection by ETS proteins.

Elevated decision uncertainty and reduced avoidance drives in depression, anxiety and substance use disorders during approach-avoidance conflict: a replication study.

BACKGROUND: Decision-making under approach-avoidance conflict (AAC; e.g., sacrificing quality of life to avoid feared outcomes) may be affected in multiple psychiatric disorders. Recently, we used a computational (active inference) model to characterize information processing differences during AAC in individuals with depression, anxiety and/or substance use disorders. Individuals with psychiatric disorders exhibited increased decision uncertainty (DU) and reduced sensitivity to unpleasant stimuli. This preregistered study aimed to determine the replicability of this processing dysfunction. METHODS: A new sample of participants completed the AAC task. Individual-level computational parameter estimates, reflecting decision uncertainty and sensitivity to unpleasant stimuli ("emotion conflict"; EC), were obtained and compared between groups. Subsequent analyses combining the prior and current samples allowed assessment of narrower disorder categories. RESULTS: The sample in the present study included 480 participants: 97 healthy controls, 175 individuals with substance use disorders and 208 individuals with depression and/or anxiety disorders. Individuals with substance use disorders showed higher DU and lower EC values than healthy controls. The EC values were lower in females, but not males, with depression and/or anxiety disorders than in healthy controls. However, the previously observed difference in DU between participants with depression and/or anxiety disorders and healthy controls did not replicate. Analyses of specific disorders in the combined samples indicated that effects were common across different substance use disorders and affective disorders. LIMITATIONS: There were differences, although with small effect size, in age and baseline intellectual functioning between the previous and current sample, which may have affected replication of DU differences in participants with depression and/or anxiety disorders. CONCLUSION: The now robust evidence base for these clinical group differences motivates specific questions that should be addressed in future research: can DU and EC become behavioural treatment targets, and can we identify neural substrates of DU and EC that could be used to measure severity of dysfunction or as neuromodulatory treatment targets?

Rice-Body Synovitis, Foreign Body Reaction, and Rotator Cuff Failure After Subacromial Balloon Spacer Augmentation of a Rotator Cuff Repair: A Case Report.

CASE: A 66-year-old woman presented with shoulder pain and weakness 4 months after augmentation of a rotator cuff repair with a Stryker InSpace subacromial balloon spacer. A magnetic resonance imaging (MRI) demonstrated a failed rotator cuff repair, large effusion with rice bodies, synovitis, axillary lymphadenopathy, loose anchors, and erosive changes to the greater tuberosity. Arthroscopy revealed balloon fragmentation surrounded by diffusely hyperemic synovium without repairable cuff tissue. Final cultures proved negative for infection. Histologic evaluation revealed ulcerated synovium with diffuse chronic and focal acute inflammation. CONCLUSION: Despite promising early results, augmentation of a rotator cuff repair with a subacromial balloon spacer introduces a risk of inflammatory reaction that may mimic a deep infection and compromise rotator cuff healing.

Artificial intelligence for automated identification of total shoulder arthroplasty implants.

BACKGROUND: Accurate and rapid identification of implant manufacturer and model is critical in the evaluation and management of patients requiring revision total shoulder arthroplasty (TSA). Failure to correctly identify implant designs in these circumstances may lead to delay in care, unexpected intraoperative challenges, increased morbidity, and excess health care costs. Deep learning (DL) permits automated image processing and holds the potential to mitigate such challenges while improving the value of care rendered. The purpose of this study was to develop an automated DL algorithm to identify shoulder arthroplasty implants from plain radiographs. METHODS: A total of 3060 postoperative images from patients who underwent TSA between 2011 and 2021 performed by 26 fellowship-trained surgeons at 2 independent tertiary academic hospitals in the Pacific Northwest and Mid-Atlantic Northeast were included. A DL algorithm was trained using transfer learning and data augmentation to classify 22 different reverse TSA and anatomic TSA prostheses from 8 implant manufacturers. Images were split into training and testing cohorts (2448 training and 612 testing images). Optimized model performance was assessed using standardized metrics including the multiclass area under the receiver operating characteristic curve (AUROC) and compared with a reference standard of implant data from operative reports. RESULTS: The algorithm classified implants at a mean speed of 0.079 seconds (±0.002 seconds) per image. The optimized model discriminated between 8 manufacturers (22 unique implants) with AUROCs of 0.994-1.000, accuracy of 97.1%, and sensitivities between 0.80 and 1.00 on the independent testing set. In the subset of single-institution implant predictions, a DL model identified 6 specific implants with AUROCs of 0.999-1.000, accuracy of 99.4%, and sensitivity >0.97 for all implants. Saliency maps revealed key differentiating features across implant manufacturers and designs recognized by the algorithm for classification. CONCLUSION: A DL model demonstrated excellent accuracy in identifying 22 unique TSA implants from 8 manufacturers. This algorithm may provide a clinically meaningful adjunct in assisting with preoperative planning for the failed TSA and allows for scalable expansion with additional radiographic data and validation efforts.

Complete Restoration of Native Glenoid Width Improves Glenohumeral Biomechanics After Simulated Latarjet.

BACKGROUND: The amount of glenoid width that must be restored with a Latarjet procedure in order to reestablish glenohumeral stability has not been determined. PURPOSE/HYPOTHESIS: The purpose of this article was to determine the percentage of glenoid width restoration necessary for glenohumeral stability after Latarjet by measuring anterior humeral head translation and force distribution on the coracoid graft. The hypothesis was that at least 100% of glenoid width restoration with Latarjet would be required to maintain glenohumeral stability. STUDY DESIGN: Controlled laboratory study. METHODS: Nine cadaveric shoulders were prepared and mounted on an established shoulder simulator. A lesser tuberosity osteotomy (LTO) was performed to allow accurate removal of glenoid bone. Coracoid osteotomy was performed, and the coracoid graft was sized to a depth of 10 mm. Glenoid bone was sequentially removed, and Latarjet was performed using 2 screws to reestablish 110%, 100%, 90%, and 80% of native glenoid width. The graft was passed through a subscapularis muscle split, and the LTO was repaired. A motion tracking system recorded glenohumeral translations, and force distribution was recorded using a TekScan pressure sensor secured to the glenoid face and coracoid graft. Testing conditions included native; LTO; Bankart tear; and 110%, 100%, 90%, and 80% of glenoid width restoration with Latarjet. Glenohumeral translations were recorded while applying an anteroinferior load of 44 N at 90° of humerothoracic abduction and 0° or 45° of glenohumeral external rotation. Force distribution was recorded without an anteroinferior load. RESULTS: Anterior humeral head translation progressively increased as the proportion of glenoid width restored decreased. A marked increase in anterior humeral head translation was found with 90% versus 100% glenoid width restoration (10.8 ± 3.0 vs 4.1 ± 2.6 mm, respectively; P < .001). Greater glenoid bone loss also led to increased force on the coracoid graft relative to the native glenoid bone after Latarjet. A pronounced increase in force on the coracoid graft was seen with 90% versus 100% glenoid width restoration (P < .001). CONCLUSION: Anterior humeral head translation and force distribution on the coracoid graft dramatically increased when <100% of the native glenoid width was restored with a Latarjet procedure. CLINICAL RELEVANCE: If a Latarjet is unable to fully restore the native glenoid width, surgeons should consider alternative graft sources to minimize the risk of recurrent instability or coracoid overload.

BUB-1 and CENP-C recruit PLK-1 to control chromosome alignment and segregation during meiosis I in C. elegans oocytes.

Phosphorylation is a key post-translational modification that is utilised in many biological processes for the rapid and reversible regulation of protein localisation and activity. Polo-like kinase 1 (PLK-1) is essential for both mitotic and meiotic cell divisions, with key functions being conserved in eukaryotes. The roles and regulation of PLK-1 during mitosis have been well characterised. However, the discrete roles and regulation of PLK-1 during meiosis have remained obscure. Here, we used Caenorhabditis elegans oocytes to show that PLK-1 plays distinct roles in meiotic spindle assembly and/or stability, chromosome alignment and segregation, and polar body extrusion during meiosis I. Furthermore, by a combination of live imaging and biochemical analysis we identified the chromosomal recruitment mechanisms of PLK-1 during C. elegans oocyte meiosis. The spindle assembly checkpoint kinase BUB-1 directly recruits PLK-1 to the kinetochore and midbivalent while the chromosome arm population of PLK-1 depends on a direct interaction with the centromeric-associated protein CENP-CHCP-4. We found that perturbing both BUB-1 and CENP-CHCP-4 recruitment of PLK-1 leads to severe meiotic defects, resulting in highly aneuploid oocytes. Overall, our results shed light on the roles played by PLK-1 during oocyte meiosis and provide a mechanistic understanding of PLK-1 targeting to meiotic chromosomes.

Improving crop yield potential: Underlying biological processes and future prospects.

The growing world population and global increases in the standard of living both result in an increasing demand for food, feed and other plant-derived products. In the coming years, plant-based research will be among the major drivers ensuring food security and the expansion of the bio-based economy. Crop productivity is determined by several factors, including the available physical and agricultural resources, crop management, and the resource use efficiency, quality and intrinsic yield potential of the chosen crop. This review focuses on intrinsic yield potential, since understanding its determinants and their biological basis will allow to maximize the plant's potential in food and energy production. Yield potential is determined by a variety of complex traits that integrate strictly regulated processes and their underlying gene regulatory networks. Due to this inherent complexity, numerous potential targets have been identified that could be exploited to increase crop yield. These encompass diverse metabolic and physical processes at the cellular, organ and canopy level. We present an overview of some of the distinct biological processes considered to be crucial for yield determination that could further be exploited to improve future crop productivity.