Shifts in the Fecal Microbiota Associated with Adenomatous Polyps

BACKGROUND: Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. METHODS: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547). RESULTS: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. CONCLUSIONS: These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer. IMPACT: This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota

Protein Expression Redirects Vesicular Stomatitis Virus RNA Synthesis to Cytoplasmic Inclusions

Positive-strand and double-strand RNA viruses typically compartmentalize their replication machinery in infected cells. This is thought to shield viral RNA from detection by innate immune sensors and favor RNA synthesis. The picture for the non-segmented negative-strand (NNS) RNA viruses, however, is less clear. Working with vesicular stomatitis virus (VSV), a prototype of the NNS RNA viruses, we examined the location of the viral replication machinery and RNA synthesis in cells. By short-term labeling of viral RNA with 5′-bromouridine 5′-triphosphate (BrUTP), we demonstrate that primary mRNA synthesis occurs throughout the host cell cytoplasm. Protein synthesis results in the formation of inclusions that contain the viral RNA synthesis machinery and become the predominant sites of mRNA synthesis in the cell. Disruption of the microtubule network by treatment of cells with nocodazole leads to the accumulation of viral mRNA in discrete structures that decorate the surface of the inclusions. By pulse-chase analysis of the mRNA, we find that viral transcripts synthesized at the inclusions are transported away from the inclusions in a microtubule-dependent manner. Metabolic labeling of viral proteins revealed that inhibiting this transport step diminished the rate of translation. Collectively those data suggest that microtubule-dependent transport of viral mRNAs from inclusions facilitates their translation. Our experiments also show that during a VSV infection, protein synthesis is required to redirect viral RNA synthesis to intracytoplasmic inclusions. As viral RNA synthesis is initially unrestricted, we speculate that its subsequent confinement to inclusions might reflect a cellular response to infection

Architecture Gets it Wrong

Sean Ahlquist Associate Professor of Architecture, Taubman College of Architecture and Urban Planning, University of Michigan ARCHITECTURE GETS IT WRONG: BUT THAT’S OKAY IF IT’S READY FOR THE AUTHORSHIP OF AN OTHERNESS We’re at a moment in time where a history of architecture shaped by a narrow set of viewpoints is being more heavily scrutinized for its ramifications in exacerbating social inequities. Personally, I see the prejudice of architectures that compete against my daughter and her worldview constructed through autism spectrum disorder. That architecture fails, at times, its okay but only if it has the capacity to be reshaped. If it can be indeterminately reshaped by otherly actions and social motivations to form a common ground that not just welcomes but is of my daughter’s “neuro-atypicality”. Diversity implies unknowing-ness. This talk will discuss whether architecture can transcend its own authorship and dismiss its desire to narrate from a set of inevitably constrained viewpoints, and unfurl the means that are necessary for architecture to be party to crafting a social and material language of diversity

Numerical Simulation of the Mechanical Behavior of a Weft-Knitted Carbon Fiber Composite under Tensile Loading

Knitted textiles are a popular reinforcement in polymer composites for their high drape properties and superior impact energy absorption, making them suitable for specific composite components. Nevertheless, limited attention has been paid to modeling the mechanical behavior of knitted fabric composites since knitted textiles generally offer lower stiffness and strength. This study presents a 3D finite element (FE) modeling of a precise geometrical model of weft-knitted carbon fiber thermoplastic composite to better understand its nonlinear mechanical behavior and interface damage mechanisms under tension. Toward this end, a representative volume element (RVE) of the weft-knitted fabric composite with periodic boundary conditions (PBCs) is generated based on actual dimensions. The validity of the textile RVE to represent the macroscopic behavior was evaluated prior to analyzing the composite. The effect of fiber tow/matrix debonding during tension on the mechanical behavior of the composite is investigated using the cohesive zone model (CZM). Finally, the predicted results of the mechanical behavior of the composite with and without considering the interface failure are compared with the experimental measurements. It is found that the fiber tow/matrix interfacial strength has a significant effect on the tensile performance of the knitted fabric composites, particularly when they are subjected to a large strain. According to the simulation results, the highest tensile performance of the composite is achieved when the interfacial debonding is prevented. However, considering the fiber/matrix debonding in the modeling is essential to achieve a good agreement with the experimental results. In addition, it is concluded that stretching the fabric before composite manufacturing can substantially increase the tensile stiffness of the knitted composite

5-year milestone reached in collaborative partnership between CF Unit and UK fitness provider

Ledger, SJ ORCiD: 0000-0001-7364-8535Exercise is recommended for all children with CF, howeveradherence and levels of participation in unsupervised exerciseprogrammes are variable. This collaboration, which started in 2011, aimsto improve levels of participation by providing free gym membershipto all children with CF receiving care from GOSH and one parent/carer.Complimentary Personal Training (PT) sessions are available for thoseaged 5–17 years. Swimming is encouraged for babies and pre-schoolers

5-year milestone reached in collaborative partnership between CF Unit and UK fitness provider

Exercise is recommended for all children with CF, howeveradherence and levels of participation in unsupervised exerciseprogrammes are variable. This collaboration, which started in 2011, aimsto improve levels of participation by providing free gym membershipto all children with CF receiving care from GOSH and one parent/carer.Complimentary Personal Training (PT) sessions are available for thoseaged 5–17 years. Swimming is encouraged for babies and pre-schoolers

A heterogeneous single-atom palladium catalyst surpassing homogeneous systems for Suzuki coupling

Palladium-catalysed cross-coupling reactions, central tools in fine-chemical synthesis, predominantly employ soluble metal complexes despite recognized challenges with product purification and catalyst reusability1,2,3. Attempts to tether these homogeneous catalysts on insoluble carriers have been thwarted by suboptimal stability, which leads to a progressively worsening performance due to metal leaching or clustering4. The alternative application of supported Pd nanoparticles has faced limitations because of insufficient activity under the mild conditions required to avoid thermal degradation of the substrates or products. Single-atom heterogeneous catalysts lie at the frontier 5,6,7,8,9,10,11,12,13,14,15,16,17,18. Here, we show that the Pd atoms anchored on exfoliated graphitic carbon nitride (Pd-ECN) capture the advantages of both worlds, as they comprise a solid catalyst that matches the high chemoselectivity and broad functional group tolerance of state-of-the-art homogeneous catalysts for Suzuki couplings, and also demonstrate a robust stability in flow. The adaptive coordination environment within the macroheterocycles of ECN facilitates each catalytic step. The findings illustrate the exciting opportunities presented by nanostructuring single atoms in solid hosts for catalytic processes that remain difficult to heterogenize