Regulated bioluminescence as a tool for bioremediation process monitoring and control of bacterial cultures

An effective on-line monitoring technique for toxic waste bioremediation using bioluminescent microorganisms has shown great potential for the description and optimization of biological processes. The lux genes of the bacterium Vibrio fischeri are used by this species to produce visible light. The lux genes can be genetically fused to the control region of a catabolic gene, with the result that bioluminescence is produced whenever the catabolic gene is induced. Thus the detection of light from a sample indicates that genetic expression from a specific gene is occurring. This technique was used to monitor biodegradation of specific contaminants from waste sites. For these studies, fusions between the lux genes and the operons for naphthalene and toluene/xylene degradation were constructed. Strains carrying one of these fusions respond sensitively and specifically to target substrates. Bioluminescence from these cultures can be rapidly measured in a nondestructive and noninvasive manner. The potential for this technique in this and other biological systems is discussed

Hic-5, an adaptor-like nuclear receptor coactivator

In recent years, numerous nuclear receptor-interacting proteins have been identified that influence nuclear transcription through their direct modification of chromatin. Along with coactivators that possess histone acetyltransferase (HAT) or methyltransferase activity, other coactivators that lack recognizable chromatin-modifying activity have been discovered whose mechanism of action is largely unknown. The presence of multiple protein-protein interaction motifs within mechanistically undefined coactivators suggests that they function as adaptor molecules, either recruiting or stabilizing promoter-specific protein complexes. This perspective will focus on a family of nuclear receptor coactivators (i.e., group III LIM domain proteins related to paxillin) that appear to provide a scaffold to stabilize receptor interactions with chromatin-modifying coregulators

Academic performance of children with sickle cell disease in the United States: A meta-analysis

Background: Students with sickle cell disease are at risk for poor academic performance due to the combined and/or interactive effects of environmental, psychosocial, and disease-specific factors. Poor academic performance has significant social and health consequences. Objective: To study academic achievement and attainment in children with sickle cell disease in the United States. Design: Medline, Embase, SCOPUS, CINAHL, ERIC, and PsycINFO were searched for peer-reviewed articles. Studies of children (ages 5–18) diagnosed with sickle cell disease of any genotype reporting academic achievement (standardized tests of reading, math, and spelling) or attainment (grade retention or special education) outcomes were included. Outcomes were analyzed using a random effects model. Achievement scores were compared to within study controls or normative expectations. Prevalence of grade retention and special education services were compared to national (United States) estimates for Black students. Age at assessment and overall IQ were evaluated separately for association with reading and mathematics scores. Subgroup analyses of reading and math scores were analyzed by cerebral infarct status (no cerebrovascular accident, silent infarct, stroke). Results: There were 44 eligible studies. Students with sickle cell disease scored 0.70, 0.87, and 0.80 (p < 0.001) SD below normative expectations on measures of reading, mathematics, and spelling, respectively. Compared to unaffected sibling and/or healthy controls (k = 8, n = 508), reading and math scores were 0.40 (p = 0.017) and 0.36 (p = 0.033) SD below expectations. Grade retention was approximately 10 times higher in students with sickle cell disease than Black students nationally. Intellectual functioning explained 97.3 and 85.8% of the variance in reading and mathematics performance, respectively (p < 0.001). Subgroup analyses revealed significant differences in reading (p = 0.034) and mathematics (p < 0.001) based on infarct status, with lower performance associated with presence of a silent infarct or stroke. Conclusion: Students with sickle cell disease demonstrate notable academic difficulties and are at high risk for grade retainment. Development of academic interventions and increased access to school support services are needed for this vulnerable population. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020179062

Bioluminescent reporters for catabolic gene expression and pollutant bioavailability

The application of visualized catabolic nah-gene expression using a luxCDABE gene fusion provides a valuable method to measure quantitatively and specifically naphthalene and salicylate bioavailability. It has been demonstrated that the physiological state of the test culture together with the intrinsic regulation mechanisms of the naphthalene degradation pathway as well as the physiological aspects of the lux gene fusion have to be taken into account. The method presented provides a high potential for in situ bioprocess monitoring. In addition, the results obtained with immobilized cells provide a basis for the development of biosensors for environmental applications in specific pollutant monitoring in waste streams and soil slurry systems but, as a general method, also for more conventional biotechnological process control. 8 refs., 2 figs., 1 tab

Recommendations for a practical implementation of circulating tumor DNA mutation testing in metastatic non-small-cell lung cancer

BACKGROUND: Liquid biopsy (LB) is a rapidly evolving diagnostic tool for precision oncology that has recently found its way into routine practice as an adjunct to tissue biopsy (TB). The concept of LB refers to any tumor-derived material, such as circulating tumor DNA (ctDNA) or circulating tumor cells that are detectable in blood. An LB is not limited to the blood and may include other fluids such as cerebrospinal fluid, pleural effusion, and urine, among others. PATIENTS AND METHODS: The objective of this paper, devised by international experts from various disciplines, is to review current challenges as well as state-of-the-art applications of ctDNA mutation testing in metastatic non-small-cell lung cancer (NSCLC). We consider pragmatic scenarios for the use of ctDNA from blood plasma to identify actionable targets for therapy selection in NSCLCs. RESULTS: Clinical scenarios where ctDNA mutation testing may be implemented in clinical practice include complementary tissue and LB testing to provide the full picture of patients’ actual predictive profiles to identify resistance mechanism (i.e. secondary mutations), and ctDNA mutation testing to assist when a patient has a discordant clinical history and is suspected of showing intertumor or intratumor heterogeneity. ctDNA mutation testing may provide interesting insights into possible targets that may have been missed on the TB. Complementary ctDNA LB testing also provides an option if the tumor location is hard to biopsy or if an insufficient sample was taken. These clinical use cases highlight practical scenarios where ctDNA LB may be considered as a complementary tool to TB analysis. CONCLUSIONS: Proper implementation of ctDNA LB testing in routine clinical practice is envisioned in the near future. As the clinical evidence of utility expands, the use of LB alongside tissue sample analysis may occur in the patient cases detailed here