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Copper is an essential nutrient whose redox properties make it both beneficial and toxic to the cell. Recent progress in studying transition metal signalling has forged new links between researchers of different disciplines that can help translate basic research in the chemistry and biology of copper into clinical therapies and diagnostics to exploit copper-dependent disease vulnerabilities. This concept is particularly relevant in cancer, as tumour growth and metastasis have a heightened requirement for this metal nutrient. Indeed, the traditional view of copper as solely an active site metabolic cofactor has been challenged by emerging evidence that copper is also a dynamic signalling metal and metalloallosteric regulator, such as for copper-dependent phosphodiesterase 3B (PDE3B) in lipolysis, mitogen-activated protein kinase kinase 1 (MEK1) and MEK2 in cell growth and proliferation and the kinases ULK1 and ULK2 in autophagy. In this Perspective, we summarize our current understanding of the connection between copper and cancer and explore how challenges in the field could be addressed by using the framework of cuproplasia, which is defined as regulated copper-dependent cell proliferation and is a representative example of a broad range of metalloplasias. Cuproplasia is linked to a diverse array of cellular processes, including mitochondrial respiration, antioxidant defence, redox signalling, kinase signalling, autophagy and protein quality control. Identifying and characterizing new modes of copper-dependent signalling offers translational opportunities that leverage disease vulnerabilities to this metal nutrient.

Science and Engineering (S&E) fairs are a valuable educational activity and are believed to increase students' engagement and learning in science and engineering. However, due to differences in resources, many schools do not implement fairs to achieve these benefits for their students. This study reports the findings of a program intended to increase the participation of students from low-achieving and under-resourced schools in a regional fair program that feeds into the international fair competition. We found that the number of schools and projects participating in our regional fair increased dramatically since the start of the program. Teachers had mostly positive expectations for the project and expressed buy-in for the effort the project would take. They recruited a diverse pool of students to participate in the school fairs. Quasi-experimental methods allowed us to explore the impact of completing S&E fairs on student gains on science self-efficacy, interest and value perceptions. Controlling for pre-existing differences in these attitudes, we found that students not completing projects showed declines in their science attitudes during the year. Students who completed projects maintained similar attitudes, while those whose projects advanced to the regional fair had substantial gains on all three variables. It is unknown whether this gain can be attributed to the experience of engaging with a quality project, from being the kind of student who completes a quality project, or some other factor. Future research with greater experimental control could address these questions.

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.

Xylella fastidiosa, an etiological agent of emerging crop diseases around the world, is naturally competent for the uptake of DNA from the environment that is incorporated into its genome by homologous recombination. Homologous recombination between subspecies of X. fastidiosa was inferred by in silico studies and was hypothesized to cause disease emergence. However, no experimental data are available on the degree to which X. fastidiosa strains are capable of competence and whether recombination can be experimentally demonstrated between subspecies. Here, using X. fastidiosa strains from different subspecies, natural competence in 11 of 13 strains was confirmed with plasmids containing antibiotic markers flanked by homologous regions and, in three of five strains, with dead bacterial cells used as source of donor DNA. Recombination frequency differed among strains and was correlated to growth rate and twitching motility. Moreover, intersubspecific recombination occurred readily between strains of subsp. fastidiosa and multiplex, as demonstrated by movement of antibiotic resistance and green fluorescent protein from donor to recipient cells and confirmed by DNA sequencing of the flanking arms of recombinant strains. Results demonstrate that natural competence is widespread among X. fastidiosa strains and could have an impact in pathogen adaptation and disease development.

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by a-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that a-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative phosphorylation. Collectively, our data argue that a-fetoprotein may be secreted by bioenergetically stressed tissue to suppress the immune system, an effect that may explain the recurrent or chronic infections that are observed in a subset of mitochondrial diseases or in other disorders with secondary mitochondrial dysfunction., Introduction To maintain homeostasis, tissue and organ systems must adapt in unison to varying metabolic challenges (1). These responses involve a cell autonomous component that acts locally at the affected [...]

A group of aggressive pathogens have evolved to colonize the plant xylem. In this vascular tissue, where water and nutrients are transported from the roots to the rest of the plant, pathogens must be able to thrive under acropetal xylem sap flow and scarcity of nutrients while having direct contact only with predominantly dead cells. Nevertheless, a few bacteria have adapted to exclusively live in the xylem, and various pathogens may colonize other plant niches without causing symptoms unless they reach the xylem. Once established, the pathogens modulate its physicochemical conditions to enhance their growth and virulence. Adaptation to the restrictive lifestyle of the xylem leads to genome reduction in xylem-restricted bacteria, as they have a higher proportion of pseudogenes in their genome. The basis of xylem adaptation is not completely understood; therefore, a need still exists for model systems to advance the knowledge on this topic. [ABSTRACT FROM AUTHOR]