Aerosol <i>Mycobacterium tuberculosis</i> Infection Causes Rapid Loss of Diversity in Gut Microbiota

<div><p><i>Mycobacterium tuberculosis</i> is an important human pathogen, and yet diagnosis remains challenging. Little research has focused on the impact of <i>M. tuberculosis</i> on the gut microbiota, despite the significant immunological and homeostatic functions of the gastrointestinal tract. To determine the effect of <i>M. tuberculosis</i> infection on the gut microbiota, we followed mice from <i>M. tuberculosis</i> aerosol infection until death, using 16S rRNA sequencing. We saw a rapid change in the gut microbiota in response to infection, with all mice showing a loss and then recovery of microbial community diversity, and found that pre-infection samples clustered separately from post-infection samples, using ecological beta-diversity measures. The effect on the fecal microbiota was observed as rapidly as six days following lung infection. Analysis of additional mice infected by a different <i>M. tuberculosis</i> strain corroborated these results, together demonstrating that the mouse gut microbiota significantly changes with <i>M. tuberculosis</i> infection.</p></div

Phylogenetic profile of bacterial genera for uninfected and <i>M. tuberculosis</i> H37Rv infected mice.

<p>Stacked bar charts for uninfected and H37Rv-infected mice of the 16 main genera identified based on ≥1% abundance present in at least two samples. Unclassified sequences are not shown. The black colored bar along x-axis indicates the five uninfected mice, while the red colored bar indicates mice infected with H37Rv.</p

Differentially abundant OTUs identified between uninfected and <i>M. tuberculosis</i> H37Rv infected mice.

<p>OTUs are ordered by consensus taxonomic classification, with OTUs scaled by relative abundances for each row ranging from low relative abundance (blue) to high relative abundance (red).</p

Gut microbiota composition of <i>M. tuberculosis</i> H37Rv infected mice is significantly different from uninfected mice.

<p>(<b>A</b>) Unweighted and (<b>B</b>) weighted Unifrac measures of beta-diversity visualized using Principle Coordinate Analysis (PCoA) for the comparison of H37Rv-infected mice to uninfected mice at a single time point. Blue dots indicate samples collected pre-infection. Red dots indicate samples collected post-infection. Variance for first two component axes is shown as percent of total variance. In both unweighted and weighted Unifrac measures, there was a statistically significant difference (AMOVA p≤0.005). (<b>C</b>) Network analysis of OTUs partitioned among samples, using a five sequence cutoff, and colored by phylum.</p

Differentially abundant OTUs identified between pre-infection and post-infection.

<p>OTUs are ordered by consensus taxonomic classification, with OTUs scaled by relative abundances for each row ranging from low relative abundance (blue) to high relative abundance (red).</p

Community structure of individual <i>M. tuberculosis</i> CDC1551 infected mice over time.

<p>(<b>A</b>) Survival time in days post-infection for each mouse. (<b>B</b>) Phylogenetic profile of bacterial genera. Stacked bar charts in chronological order for each mouse of the 18 main genera identified based on ≥1% abundance present in at least two samples. Unclassified sequences are not shown. Black colored bars along x-axis indicate samples taken prior to infection, while red colored bars indicate post-infection. Each group represents an individual mouse, followed to death. The mice are represented sequentially, with mouse 1 on the left, and mouse 5 on the right. (<b>C</b>) Community diversity in each sample as measured by the Shannon diversity index, plotted against the percent survival time.</p

Composition of the gut microbiota significantly changes with <i>M. tuberculosis</i> CDC1551 infection.

<p>(<b>A</b>) Unweighted and (<b>B</b>) weighted Unifrac measures of beta-diversity visualized using Principle Coordinate Analysis (PCoA) following individual mice over time with <i>M. tuberculosis</i> CDC1551 infection. Blue dots indicate samples collected pre-infection. Red dots indicate samples collected post-infection. Variance for first two component axes is shown as percent of total variance. An analysis of molecular variance (AMOVA) was performed to test whether the separation of uninfected and TB-infected samples was statistically significant. In both unweighted and weighted Unifrac measures, there was a statistically significant difference (p<0.001). (<b>C</b>) Network analysis of OTUs partitioned among samples, using a five sequence cutoff, and colored by phylum.</p

Hierarchical Multicomponent Nanoheterostructures via Facet-to-Facet Attachment of Anisotropic Semiconductor Nanoparticles

As performance and functionality requirements for solution-processed nanomaterials become more stringent and demanding, there is an ever-growing need for hierarchical nanostructures with sophisticated architecture and complex composition. However, the production of structurally complex nanomaterials is often not possible by direct synthesis. In this work, we describe synthetic methodology to covalently link presynthesized anisotropic semiconductor nanoparticles of different composition in a stoichiometrically controlled manner via specific facet sites at room temperature. We demonstrate that CdSe nanorods can be cojoined with CdTe tetrapods via a competitive cation-exchange process with Ag⁺ that results in linking between the tips of the tetrapod arms with only one end of each nanorod via a Ag₂Se–Ag₂Te interface. This selective linking was engineered by having a large fraction of CdSe nanorods present in the reaction, which sterically hindered homolinking between Ag₂Se-tipped CdSe nanorods and Ag₂Te-tipped CdTe tetrapods with themselves. Cation back-exchange with Cd²⁺ and a size-selective purification to remove unlinked products yields samples enriched in heterolinked CdTe tetrapod–CdSe nanorod structures. High-resolution transmission electron microscopy and energy-dispersive X-ray spectroscopy confirmed the structure and composition of the nanorod-linked tetrapods, while time-resolved and pump-dependent photoluminescence data were consistent with a type II band offset at the CdTe–CdSe interface. The synthetic approach to colloidal nanoheterostructures described here is highly distinct from traditional methods involving a series of nucleation and growth steps at elevated temperature

IFN-α-secreting pDCs peak in the pancreatic islets of NOD mice at 8–9 weeks.

<p>(<b>A</b>) Infiltrating leukocytes (FVD⁻CD45⁺) from pancreatic islets were analyzed by flow cytometry for total number per mouse of T-cells (CD3⁺B220⁻CD19⁻), B-cells (CD3⁻B220⁺CD19⁺), pDCs (CD3⁻CD19⁻BST2⁺CD11c^intB220⁺), inflammatory DCs (CD3⁻CD19⁻BST2⁻CD11c^hiMHC-II⁺) and macrophages (CD3⁻CD19⁻F4/80⁺CD11b⁺MHC-II⁺) from 3 to >23 weeks of age in NOD and B6 mice (mean ± sem, <i>n</i> = 4–21 mice, 2–5 independent experiments). * p<0.05, ** p<0.005, *** p<0.0005 compared to 4-week-old B6. (<b>B</b>) Representative dot plots of FVD⁻CD45⁺CD3⁻CD19⁻ islet cells with the percentage of pDC and inflammatory DC subsets of total CD45⁺ cells indicated (mean ± sem, <i>n</i> = 4–21 mice, 2–5 independent experiments). (<b>C</b>) Expression of interferon response genes IRF7 and ISG15 is assessed by qPCR of RNA from handpicked islets of NOD (black bars) or B6 (open bars) mice at 3 and >8 weeks (<i>n</i> = 6–11 mice, 3 independent experiments). * p<0.05, ** p<0.005. (<b>D</b>) IFN-α levels in supernatants from cultured NOD islets at 4–17 weeks of age after 40h ± TLR9 ligand CpG₁₅₈₅ is assessed by ELISA (mean ± sem, <i>n</i> = 6–23 mice, 6–9 independent experiments). nd = not detected. *** p<0.0005 compared to “No” stimulation at same age.</p

Direct Bandgap Light Emission from Strained Germanium Nanowires Coupled with High‑Q Nanophotonic Cavities

A silicon-compatible light source is the final missing piece for completing high-speed, low-power on-chip optical interconnects. In this paper, we present a germanium nanowire light emitter that encompasses all the aspects of potential low-threshold lasers: highly strained germanium gain medium, strain-induced pseudoheterostructure, and high-Q nanophotonic cavity. Our nanowire structure presents greatly enhanced photoluminescence into cavity modes with measured quality factors of up to 2000. By varying the dimensions of the germanium nanowire, we tune the emission wavelength over more than 400 nm with a single lithography step. We find reduced optical loss in optical cavities formed with germanium under high (>2.3%) tensile strain. Our compact, high-strain cavities open up new possibilities for low-threshold germanium-based lasers for on-chip optical interconnects