Tumors from individuals with cancer are frequently genetically profiled for information about the driving forces behind the disease. We present the CancerMine resource, a text-mined and routinely ...updated database of drivers, oncogenes and tumor suppressors in different types of cancer. All data are available online ( http://bionlp.bcgsc.ca/cancermine ) and downloadable under a Creative Commons Zero license for ease of use.
This paper reviews clinical and asymptomatic
Toxoplasma gondii infection in humans and other animals in the USA. Seroprevalence of
T. gondii in humans and pigs is declining. Modes of transmission, ...epidemiology and environmental contamination with oocysts on land and sea are discussed.
First published in 1984, and reissued in a facsimile edition that preserves the formal ingenuity of the original text, Designing Designing contains a crucial and invigorating selection of J. C. ...Jones’ writings on design methodology.
Autism spectrum disorder is a construct used to describe individuals with a specific combination of impairments in social communication and repetitive behaviours, highly restricted interests and/or ...sensory behaviours beginning early in life. The worldwide prevalence of autism is just under 1%, but estimates are higher in high-income countries. Although gross brain pathology is not characteristic of autism, subtle anatomical and functional differences have been observed in post-mortem, neuroimaging and electrophysiological studies. Initially, it was hoped that accurate measurement of behavioural phenotypes would lead to specific genetic subtypes, but genetic findings have mainly applied to heterogeneous groups that are not specific to autism. Psychosocial interventions in children can improve specific behaviours, such as joint attention, language and social engagement, that may affect further development and could reduce symptom severity. However, further research is necessary to identify the long-term needs of people with autism, and treatments and the mechanisms behind them that could result in improved independence and quality of life over time. Families are often the major source of support for people with autism throughout much of life and need to be considered, along with the perspectives of autistic individuals, in both research and practice.
The biguanide metformin is widely prescribed for Type II diabetes and has anti-neoplastic activity in laboratory models. Despite evidence that inhibition of mitochondrial respiratory complex I by ...metformin is the primary cause of its cell-lineage-specific actions and therapeutic effects, the molecular interaction(s) between metformin and complex I remain uncharacterized. In the present paper, we describe the effects of five pharmacologically relevant biguanides on oxidative phosphorylation in mammalian mitochondria. We report that biguanides inhibit complex I by inhibiting ubiquinone reduction (but not competitively) and, independently, stimulate reactive oxygen species production by the complex I flavin. Biguanides also inhibit mitochondrial ATP synthase, and two of them inhibit only ATP hydrolysis, not synthesis. Thus we identify biguanides as a new class of complex I and ATP synthase inhibitor. By comparing biguanide effects on isolated complex I and cultured cells, we distinguish three anti-diabetic and potentially anti-neoplastic biguanides (metformin, buformin and phenformin) from two anti-malarial biguanides (cycloguanil and proguanil): the former are accumulated into mammalian mitochondria and affect oxidative phosphorylation, whereas the latter are excluded so act only on the parasite. Our mechanistic and pharmacokinetic insights are relevant to understanding and developing the role of biguanides in new and existing therapeutic applications, including cancer, diabetes and malaria.
Recently, researchers in clinical psychology have endeavored to create network models of the relationships between symptoms, both within and across mental disorders. Symptoms that connect two mental ...disorders are called "bridge symptoms." Unfortunately, no formal quantitative methods for identifying these bridge symptoms exist. Accordingly, we developed four network statistics to identify bridge symptoms: bridge strength, bridge betweenness, bridge closeness, and bridge expected influence. These statistics are nonspecific to the type of network estimated, making them potentially useful in individual-level psychometric networks, group-level psychometric networks, and networks outside the field of psychopathology such as social networks. We first tested the fidelity of our statistics in predicting bridge nodes in a series of simulations. Averaged across all conditions, the statistics achieved a sensitivity of 92.7% and a specificity of 84.9%. By simulating datasets of varying sample sizes, we tested the robustness of our statistics, confirming their suitability for network psychometrics. Furthermore, we simulated the contagion of one mental disorder to another, showing that deactivating bridge nodes prevents the spread of comorbidity (i.e., one disorder activating another). Eliminating nodes based on bridge statistics was more effective than eliminating nodes high on traditional centrality statistics in preventing comorbidity. Finally, we applied our algorithms to 18 group-level empirical comorbidity networks from published studies and discussed the implications of this analysis.
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•Modular co-culture engineering for chemical production.•Sensor-producer systems enable high-throughput applications.•Strategies for engineering stable microbial ...communities.•Strategies for stabilizing population dynamics.
The microbial production of chemicals has traditionally relied on a single engineered microbe to enable the complete bioconversion of substrate to final product. Recently, a growing fraction of research has transitioned towards employing a modular co-culture engineering strategy using multiple microbes growing together to facilitate a divide-and-conquer approach for chemical biosynthesis. Here, we review key success stories that leverage the unique advantages of co-culture engineering, while also addressing the critical concerns that will limit the wide-spread implementation of this technology. Future studies that address the need to monitor and control the population dynamics of each strain module, while maintaining robust flux routes towards a wide range of desired products will lead the efforts to realize the true potential of co-culture engineering.
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