Axonal growth arrests after an increased accumulation of Schwann cells expressing senescence markers and stromal cells in acellular nerve allografts

Acellular nerve allografts (ANAs) and other nerve constructs do not reliably facilitate axonal regeneration across long defects (>3 cm). Causes for this deficiency are poorly understood. In this study, we determined what cells are present within ANAs before axonal growth arrest in nerve constructs and if these cells express markers of cellular stress and senescence. Using the Thy1-GFP rat and serial imaging, we identified the time and location of axonal growth arrest in long (6 cm) ANAs. Axonal growth halted within long ANAs by 4 weeks, while axons successfully regenerated across short (3 cm) ANAs. Cellular populations and markers of senescence were determined using immunohistochemistry, histology, and senescence-associated β-galactosidase staining. Both short and long ANAs were robustly repopulated with Schwann cells (SCs) and stromal cells by 2 weeks. Schwann cells (S100β(+)) represented the majority of cells repopulating both ANAs. Overall, both ANAs demonstrated similar cellular populations with the exception of increased stromal cells (fibronectin(+)/S100β(−)/CD68(−) cells) in long ANAs. Characterization of ANAs for markers of cellular senescence revealed that long ANAs accumulated much greater levels of senescence markers and a greater percentage of Schwann cells expressing the senescence marker p16 compared to short ANAs. To establish the impact of the long ANA environment on axonal regeneration, short ANAs (2 cm) that would normally support axonal regeneration were generated from long ANAs near the time of axonal growth arrest (“stressed” ANAs). These stressed ANAs contained mainly S100β(+)/p16(+) cells and markedly reduced axonal regeneration. In additional experiments, removal of the distal portion (4 cm) of long ANAs near the time of axonal growth arrest and replacement with long isografts (4 cm) rescued axonal regeneration across the defect. Neuronal culture derived from nerve following axonal growth arrest in long ANAs revealed no deficits in axonal extension. Overall, this evidence demonstrates that long ANAs are repopulated with increased p16(+) Schwann cells and stromal cells compared to short ANAs, suggesting a role for these cells in poor axonal regeneration across nerve constructs

Vortices in Saturn's Northern Hemisphere (2008-2015) observed by Cassini ISS

We use observations from the Imaging Science Subsystem on Cassini to create maps of Saturn's Northern Hemisphere (NH) from 2008 to 2015, a time period including a seasonal transition (i.e., spring equinox in 2009) and the 2010 giant storm. The processed maps are used to investigate vortices in the NH during the period of 2008–2015. All recorded vortices have diameters (east‐west) smaller than 6000 km except for the largest vortex that developed from the 2010 giant storm. The largest vortex decreased its diameter from ~11,000 km in 2011 to ~5000 km in 2015, and its average diameter is ~6500 km during the period of 2011–2015. The largest vortex lasts at least 4 years, which is much longer than the lifetimes of most vortices (less than 1 year). The largest vortex drifts to north, which can be explained by the beta drift effect. The number of vortices displays varying behaviors in the meridional direction, in which the 2010 giant storm significantly affects the generation and development of vortices in the middle latitudes (25–45°N). In the higher latitudes (45–90°N), the number of vortices also displays strong temporal variations. The solar flux and the internal heat do not directly contribute to the vortex activities, leaving the temporal variations of vortices in the higher latitudes (45–90°N) unexplained

Millimeter-scale exfoliation of hBN with tunable flake thickness

As a two-dimensional (2D) dielectric material, hexagonal boron nitride (hBN) is in high demand for applications in photonics, nonlinear optics, and nanoelectronics. Unfortunately, the high-throughput preparation of macroscopic-scale, high-quality hBN flakes with controlled thickness is an ongoing challenge, limiting device fabrication and technological integration. Here, we present a metal thin-film exfoliation method to prepare hBN flakes with millimeter-scale dimension, near-unity yields, and tunable flake thickness distribution from 1-7 layers, a substantial improvement over scotch tape exfoliation. The single crystallinity and high quality of the exfoliated hBN are demonstrated with optical microscopy, atomic force microscopy, Raman spectroscopy, and second harmonic generation. We further explore a possible mechanism for the effectiveness and selectivity based on thin-film residual stress measurements, density functional theory calculations, and transmission electron microscopy imaging of the deposited metal films. We find that the magnitude of the residual tensile stress induced by thin film deposition plays a key role in determining exfoliated flake thickness in a manner which closely resembles 3D semiconductor spalling. Lastly, we demonstrate that our exfoliated, large-area hBN flakes can be readily incorporated as encapsulating layers for other 2D monolayers. Altogether, this method brings us one step closer to the high throughput, mass production of hBN-based 2D photonic, optoelectronic, and quantum devices.Comment: 21 pages, 5 figures, work completed at Stanford Universit

Allelic Variation on Murine Chromosome 11 Modifies Host Inflammatory Responses and Resistance to Bacillus anthracis

Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36–74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT

Forecasting ground-based sensitivity to the Rayleigh scattering of the CMB in the presence of astrophysical foregrounds

The Rayleigh scattering of cosmic microwave background (CMB) photons off the neutral hydrogen produced during recombination effectively creates an additional scattering surface after recombination that encodes new cosmological information, including the expansion and ionization history of the universe. A first detection of Rayleigh scattering is a tantalizing target for next-generation CMB experiments. We have developed a Rayleigh scattering forecasting pipeline that includes instrumental effects, atmospheric noise, and astrophysical foregrounds (e.g., Galactic dust, cosmic infrared background, or CIB, and the thermal Sunyaev-Zel'dovich effect). We forecast the Rayleigh scattering detection significance for several upcoming ground-based experiments, including SPT-3G+, Simons Observatory, CCAT-prime, and CMB-S4, and examine the limitations from atmospheric and astrophysical foregrounds as well as potential mitigation strategies. When combined with Planck data, we estimate that the ground-based experiments will detect Rayleigh scattering with a significance between 1.6 and 3.7, primarily limited by atmospheric noise and the CIB.Comment: 19 pages, 7 figures (v2 additional author added

Exceptional electronic transport and quantum oscillations in thin bismuth crystals grown inside van der Waals materials

Confining materials to two-dimensional forms changes the behavior of electrons and enables new devices. However, most materials are challenging to produce as uniform thin crystals. Here, we present a new synthesis approach where crystals are grown in a nanoscale mold defined by atomically-flat van der Waals (vdW) materials. By heating and compressing bismuth in a vdW mold made of hexagonal boron nitride (hBN), we grow ultraflat bismuth crystals less than 10 nanometers thick. Due to quantum confinement, the bismuth bulk states are gapped, isolating intrinsic Rashba surface states for transport studies. The vdW-molded bismuth shows exceptional electronic transport, enabling the observation of Shubnikov-de Haas quantum oscillations originating from the (111) surface state Landau levels, which have eluded previous studies. By measuring the gate-dependent magnetoresistance, we observe multi-carrier quantum oscillations and Landau level splitting, with features originating from both the top and bottom surfaces. Our vdW-mold growth technique establishes a platform for electronic studies and control of bismuth's Rashba surface states and topological boundary modes. Beyond bismuth, the vdW-molding approach provides a low-cost way to synthesize ultrathin crystals and directly integrate them into a vdW heterostructure

Phylogeography of Japanese encephalitis virus:genotype is associated with climate

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate