We have a mutually beneficial relationship with the trillions of microorganisms inhabiting our gastrointestinal tract. However, maintaining this relationship requires recognizing these organisms as affable and restraining inflammatory responses to these organisms when encountered in hostile settings. How and when the immune system develops tolerance to our gut microbial members is not well understood. Here we identify a specific pre-weaning interval in which gut microbial antigens are encountered by the immune system to induce antigen specific tolerance to gut bacteria. Intriguingly for some bacterial taxa, physiologic encounters with the immune system are restricted to this interval, despite abundance of these taxa in the gut lumen at later times outside this interval. Antigen specific tolerance to gut bacteria induced during this pre-weaning interval is stable and maintained even if these taxa are encountered later in life in an inflammatory setting. However, inhibiting microbial antigen encounter during this interval or extending these encounters beyond the normal interval, results in a failure to induce tolerance and robust antigen specific effector responses to gut bacteria upon reencounter in an inflammatory setting. Thus, we have identified a defined pre-weaning interval critical for developing tolerance to gut bacteria and maintaining the mutually beneficial relationship with our gut microbiota.

No abstract

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu.

The proto-oncogene c-Myc has a pivotal function in growth control, differentiation, and apoptosis and is frequently affected in human cancer, including breast cancer. Ubiquitin-specific protease 22 (USP22), a member of the USP family of deubiquitinating enzymes (DUBs), mediates deubiquitination of target proteins, including histone H2B and H2A, telomeric repeat binding factor 1, and cyclin B1. USP22 is also a component of the mammalian SAGA transcriptional co-activating complex. In this study, we explored the functional role of USP22 in modulating c-Myc stability and its physiological relevance in breast cancer progression. We found that USP22 promotes deubiquitination of c-Myc in several breast cancer cell lines, resulting in increased levels of c-Myc. Consistent with this, USP22 knockdown reduces c-Myc levels. Furthermore, overexpression of USP22 stimulates breast cancer cell growth and colony formation, and increases c-Myc tumorigenic activity. In conclusion, the present study reveals that USP22 in breast cancer cell lines increases c-Myc stability through c-Myc deubiquitination, which is closely correlated with breast cancer progression.

No abstract

Protonic ceramic electrochemical cells (PCECs) have attracted considerable attention owing to their ability to reversibly convert chemical fuels into electricity at low temperatures below 600 °C. However, extreme sintering conditions during conventional convectionbased heating induce critical problems for PCECs such as nonstoichiometric electrolytes and microstructural coarsening of the electrodes, leading to performance deterioration. Therefore, we fabricated PCECs via a microwave-assisted sintering process (MW-PCEC). Owing to the ultrafast ramping rate (∼50 °C/min) with bipolar rotation and the resistive heating nature of microwave-assisted sintering, undesirable cation diffusion and grain growth were effectively suppressed, thus producing PCECs with stoichiometric electrolytes and nanostructured fuel electrodes. The MW-PCEC achieved electrochemical performance in both in fuel cell (0.85 W cm −2 ) and in electrolysis cell (1.88 A cm −2 ) modes at 600 °C (70% and 254% higher than the conventionally sintered PCEC, respectively) demonstrating the effectiveness of using an ultrafast sintering technique to fabricate high-performance PCECs.

Holography is a promising approach to implement the three-dimensional (3D) projection beyond the present two-dimensional technology. True 3D holography requires abilities of arbitrary 3D volume projection with high-axial resolution and independent control of all 3D voxels. However, it has been challenging to implement the true 3D holography with high-reconstruction quality due to the speckle. Here, we propose the practical solution to realize speckle-free, high-contrast, true 3D holography by combining random-phase, temporal multiplexing, binary holography, and binary optimization. We adopt the random phase for the true 3D implementation to achieve the maximum axial resolution with fully independent control of the 3D voxels. We develop the high-performance binary hologram optimization framework to minimize the binary quantization noise, which provides accurate and high-contrast reconstructions for 2D as well as 3D cases. Utilizing the fast operation of binary modulation, the full-color high-framerate holographic video projection is realized while the speckle noise of random phase is overcome by temporal multiplexing. Our high-quality true 3D holography is experimentally verified by projecting multiple arbitrary dense images simultaneously. The proposed method can be adopted in various applications of holography, where we show additional demonstration that realistic true 3D hologram in VR and AR near-eye displays. The realization will open a new path towards the next generation of holography.

No abstract