Three Dimensional Reconfigurable Optical Singularities in Bilayer Photonic Crystals

Metasurfaces and photonic crystals have revolutionized classical and quantum manipulation of light, and opened the door to studying various optical singularities related to phases and polarization states. However, traditional nanophotonic devices lack reconfigurability, hindering the dynamic switching and optimization of optical singularities. This paper delves into the underexplored concept of tunable bilayer photonic crystals (BPhCs), which offer rich interlayer coupling effects. Utilizing silicon nitride-based BPhCs, we demonstrate tunable bidirectional and unidirectional polarization singularities, along with spatiotemporal phase singularities. Leveraging these tunable singularities, we achieve dynamic modulation of bound-state-in-continuum states, unidirectional guided resonances, and both longitudinal and transverse orbital angular momentum. Our work paves the way for multidimensional control over polarization and phase, inspiring new directions in ultrafast optics, optoelectronics, and quantum optics

Photo-activatable Cre recombinase regulates gene expression in vivo

Techniques allowing precise spatial and temporal control of gene expression in the brain are needed. Herein we describe optogenetic approaches using a photo-activatable Cre recombinase (PA-Cre) to stably modify gene expression in the mouse brain. Blue light illumination for 12 hours via optical fibers activated PA-Cre in the hippocampus, a deep brain structure. Two-photon illumination through a thinned skull window for 100 minutes activated PA-Cre within a sub-millimeter region of cortex. Light activation of PA-Cre may allow permanent gene modification with improved spatiotemporal precision compared to standard methods

A Multi-Scale Approach to Study Biochemical and Biophysical Aspects of Resveratrol on Diesel Exhaust Particle-Human Primary Lung Cell Interaction

Diesel exhaust particles (DEPs) are major air pollutants that lead to numerous human disorders, especially pulmonary diseases, partly through the induction of oxidative stress. Resveratrol is a polyphenol that ameliorates the production of reactive oxygen species (ROS) and delays aging-related processes. Herein we studied the cytoprotective effect of resveratrol on DEP-exposed human lung cells in a factorial experimental design. This work investigates biophysical features including cellular compositions and biomechanical properties, which were measured at the single-cell level using confocal Raman microspectroscopy (RM) and atomic force microscopy (AFM), respectively. Principal component analysis (PCA), hierarchical cluster analysis (HCA) and partial least square regression (PLS) analysis were applied to analyze Raman spectra with and without resveratrol protection. The health status of individual cells could be effectively predicted using an index derived from characteristic Raman spectral peak (e.g., 1006 cm−1) based on PLS model. AFM measurements indicated that cellular adhesion force was greatly reduced, while Young’s modulus was highly elevated in resveratrol treated DEP-exposed cells. Anti-oxidant resveratrol reduced DEP-induced ROS production and suppressed releases of several cytokines and chemokines. These findings suggest resveratrol may enhance resistance of human lung cells (e.g., SAEC) to air pollutants (e.g. DEPs)

High‐Performance Doped Silver Films: Overcoming Fundamental Material Limits for Nanophotonic Applications

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137336/1/adma201605177-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137336/2/adma201605177_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137336/3/adma201605177.pd

Controllable Formation of the Crystalline Phases in Ge-Ga-S Chalcogenide Glass-Ceramics

We prepared chemically stoichiometric, S-poor and S-rich Ge–Ga–S glasses and annealed them at a temperature that was 20°C higher than its respective glass transition temperature. We aimed at tuning the formation of the different crystals in chalcogenide glass-ceramics. Through systematic characterization of the structure using X-ray diffraction and Raman scattering spectra, we found that, GeS2 and GeS crystals only can be created in S-rich and S-poor glass-ceramics, respectively, while all GeS, Ga2S3, and GeS2 crystals exist in chemically stoichiometric glass-ceramics. Moreover, we demonstrated the homogeneous distribution of the crystals can be formed in the S-rich glass-ceramics from the surface to the interior via composition designing. The present approach blazes a new path to control the growth of the different crystals in chalcogenide glass-ceramicsThis research was supported by the Zhejiang Administration of foreign experts affairs project of China (Z20150650), and the Australian Research Council (ARC) Centre of Excellence for Ultrahigh bandwidth Device for Optical System (CE110001018), ARC Discovery programs (DP110102753

Renal defects associated with improper polarization of the CRB and DLG polarity complexes in MALS-3 knockout mice

Kidney development and physiology require polarization of epithelia that line renal tubules. Genetic studies show that polarization of invertebrate epithelia requires the crumbs, partition-defective-3, and discs large complexes. These evolutionarily conserved protein complexes occur in mammalian kidney; however, their role in renal development remains poorly defined. Here, we find that mice lacking the small PDZ protein mammalian LIN-7c (MALS-3) have hypomorphic, cystic, and fibrotic kidneys. Proteomic analysis defines MALS-3 as the only known core component of both the crumbs and discs large cell polarity complexes. MALS-3 mediates stable assembly of the crumbs tight junction complex and the discs large basolateral complex, and these complexes are disrupted in renal epithelia from MALS-3 knockout mice. Interestingly, MALS-3 controls apico-basal polarity preferentially in epithelia derived from metanephric mesenchyme, and defects in kidney architecture owe solely to MALS expression in these epithelia. These studies demonstrate that defects in epithelial cell polarization can cause cystic and fibrotic renal disease

Overlapping effector interfaces define the multiple functions of the HIV-1 Nef polyproline helix

Background: HIV-1 Nef is a multifunctional protein required for full pathogenicity of the virus. As Nef has no known enzymatic activity, it necessarily functions through protein-protein interaction interfaces. A critical Nef protein interaction interface is centered on its polyproline segment (P69VRPQVPLRP78) which contains the helical SH3 domain binding protein motif, PXXPXR. We hypothesized that any Nef-SH3 domain interactions would be lost upon mutation of the prolines or arginine of PXXPXR. Further, mutation of the non-motif “X” residues, (Q73, V74, and L75) would give altered patterns of inhibition for different Nef/SH3 domain protein interactions. Results: We found that mutations of either of the prolines or the arginine of PXXPXR are defective for Nef-Hck binding, Nef/activated PAK2 complex formation and enhancement of virion infectivity (EVI). Mutation of the non-motif “X” residues (Q, V and L) gave similar patterns of inhibition for Nef/activated PAK2 complex formation and EVI which were distinct from the pattern for Hck binding. These results implicate an SH3 domain containing protein other than Hck for Nef/activated PAK2 complex formation and EVI. We have also mutated Nef residues at the N-and C-terminal ends of the polyproline segment to explore interactions outside of PXXPXR. We discovered a new locus GFP/F (G67, F68, P69 and F90) that is required for Nef/activated PAK2 complex formation and EVI. MHC Class I (MHCI) downregulation was only partially inhibited by mutating the PXXPXR motif residues, but was fully inhibited by mutating the C-terminal P78. Further, we observed that MHCI downregulation strictly requires G67 and F68. Our mutational analysis confirms the recently reported structure of the complex between Nef, AP-1 μ1 and the cytoplasmic tail of MHCI, but does not support involvement of an SH3 domain protein in MHCI downregulation. Conclusion: Nef has evolved to be dependent on interactions with multiple SH3 domain proteins. To the N- and C- terminal sides of the polyproline helix are multifunctional protein interaction sites. The polyproline segment is also adapted to downregulate MHCI with a non-canonical binding surface. Our results demonstrate that Nef polyproline helix is highly adapted to directly interact with multiple host cell proteins

The emerging landscape of single-molecule protein sequencing technologies

Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell profiling. These technologies will in turn facilitate biological discovery and open new avenues for ultrasensitive disease diagnostics.This Perspective describes new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry that will eventually enable broad sequence coverage in single-cell proteomics.</p

AMD, an Automated Motif Discovery Tool Using Stepwise Refinement of Gapped Consensuses

Motif discovery is essential for deciphering regulatory codes from high throughput genomic data, such as those from ChIP-chip/seq experiments. However, there remains a lack of effective and efficient methods for the identification of long and gapped motifs in many relevant tools reported to date. We describe here an automated tool that allows for de novo discovery of transcription factor binding sites, regardless of whether the motifs are long or short, gapped or contiguous