Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Programmable Porous Polymers Via Direct Bubble Writing With Surfactan-Free Inks

Fabrication of macroporous polymers with functionally graded architecture or chemistry bears transformative potential in acoustic damping, energy storage materials, flexible electronics, and filtration, but is hardly reachable with current processes. Here, we introduce thiol-ene chemistries in direct bubble writing, a recent technique for additive manufacturing of foams with locally controlled cell size, density and macroscopic shape. Surfactant-free and solvent-free graded 3D foams without drying-induced shrinkage were fabricated by direct bubble writing at an unparalleled ink viscosity of 410 cP (40 times higher than previous formulations). Functionalities including shape memory, high glass transition temperatures ( \u3e25 °C), and chemical gradients were demonstrated. These results extend direct bubble writing from aqueous inks to non-aqueous formulations, while the liquid flow rate (3 mL min-1) exceeds chip microfluidic techniques. Altogether, direct bubble writing with thiol-ene inks promises rapid one-step fabrication of functional materials with locally controlled gradients in the chemical, mechanical, and architectural domains

Programmable Porous Polymers via Direct Bubble Writing with Surfactant-Free Inks

Fabrication of macroporous polymers with functionally graded architecture or chemistry bears transformative potential in acoustic damping, energy storage materials, flexible electronics, and filtration, but is hardly reachable with current processes. Here, we introduce thiol-ene chemistries in direct bubble writing, a recent technique for additive manufacturing of foams with locally controlled cell size, density and macroscopic shape. Surfactant-free and solvent-free graded 3D foams without drying-induced shrinkage were fabricated by direct bubble writing at an unparalleled ink viscosity of 410 cP (40 times higher than previous formulations). Functionalities including shape memory, high glass transition temperatures ( \u3e25 °C), and chemical gradients were demonstrated. These results extend direct bubble writing from aqueous inks to non-aqueous formulations, while the liquid flow rate (3 mL min-1) exceeds chip microfluidic techniques. Altogether, direct bubble writing with thiol-ene inks promises rapid one-step fabrication of functional materials with locally controlled gradients in the chemical, mechanical, and architectural domains

CDK7 and MITF repress a transcription program involved in survival and drug tolerance in melanoma

International audienceMelanoma cell phenotype switching between differentiated melanocytic and undifferentiated mesenchymal-like states drives metastasis and drug resistance. CDK7 is the serine/threonine kinase of the basal transcription factor TFIIH. We show that dedifferentiation of melanocytic-type melanoma cells into mesenchymal-like cells and acquisition of tolerance to targeted therapies is achieved through chronic inhibition of CDK7. In addition to emergence of a mesenchymal-type signature, we identify a GATA6-dependent gene expression program comprising genes such as AMIGO2 or ABCG2 involved in melanoma survival or targeted drug tolerance, respectively. Mechanistically, we show that CDK7 drives expression of the melanocyte lineage transcription factor MITF that in turn binds to an intronic region of GATA6 to repress its expression in melanocytic-type cells. We show that GATA6 expression is activated in MITF-low melanoma cells of patient-derived xenografts. Taken together, our data show how the poorly characterized repressive function of MITF in melanoma participates in a molecular cascade regulating activation of a transcriptional program involved in survival and drug resistance in melanoma

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Expanding the Diversity of Mycobacteriophages: Insights into Genome Architecture and Evolution

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists