Defect-Seeded Atomic Layer Deposition of Metal Oxides on the Basal Plane of 2D Layered Materials

Atomic layer deposition (ALD) on mechanically exfoliated 2D layered materials spontaneously produces network patterns of metal oxide nanoparticles in triangular and linear deposits on the basal surface. The network patterns formed under a range of ALD conditions and were independent of the orientation of the substrate in the ALD reactor. The patterns were produced on MoS2 or HOPG when either tetrakis(dimethylamido)titanium or bis(ethylcyclopentadienyl)manganese were used as precursors, suggesting that the phenomenon is general for 2D materials. Transmission electron microscopy revealed the presence, prior to deposition, of dislocation networks along the basal plane of mechanically exfoliated 2D flakes, indicating that periodical basal plane defects related to disruptions in the van der Waals stacking of layers, such as perfect line dislocations and triangular extended stacking faults networks, introduce a surface reactivity landscape that leads to the emergence of patterned deposition

A putative ariadne-like E3 ubiquitin ligase (PAUL) that interacts with the muscle-specific kinase (MuSK).

Formation of the postsynaptic membrane at the skeletal neuromuscular junction (NMJ) requires activation of the muscle-specific receptor tyrosine kinase (MuSK). Few intracellular mediators or modulators of MuSK actions are known. E3 ubiquitin ligases may serve this role, because activities of several receptor tyrosine kinases, G-protein-coupled receptors and channels are modulated by ubiquitination. Here, we report identification of a putative Ariadne-like ubiquitin ligase (PAUL) that binds to the cytoplasmic domain of MuSK. PAUL is expressed in numerous tissues of developing and adult mice, and is present at NMJs in muscle fibers but is not confined to them.Peer reviewe

Trauma-informed care in the UK:where are we? A qualitative study of health policies and professional perspectives

BACKGROUND: Trauma-informed (TI) approach is a framework for a system change intervention that transforms the organizational culture and practices to address the high prevalence and impact of trauma on patients and healthcare professionals, and prevents re-traumatization in healthcare services. Review of TI approaches in primary and community mental healthcare identified limited evidence for its effectiveness in the UK, however it is endorsed in various policies. This study aimed to investigate the UK-specific context through exploring how TI approaches are represented in health policies, and how they are understood and implemented by policy makers and healthcare professionals. METHODS: A qualitative study comprising of a document analysis of UK health policies followed by semi-structured interviews with key informants with direct experience of developing and implementing TI approaches. We used the Ready Extract Analyse Distil (READ) approach to guide policy document review, and the framework method to analyse data. RESULTS: We analysed 24 documents and interviewed 11 professionals from healthcare organizations and local authorities. TI approach was included in national, regional and local policies, however, there was no UK- or NHS-wide strategy or legislation, nor funding commitment. Although documents and interviews provided differing interpretations of TI care, they were aligned in describing the integration of TI principles at the system level, contextual tailoring to each organization, and addressing varied challenges within health systems. TI care in the UK has had piecemeal implementation, with a nation-wide strategy and leadership visible in Scotland and Wales and more disjointed implementation in England. Professionals wanted enhanced coordination between organizations and regions. We identified factors affecting implementation of TI approaches at the level of organization (leadership, service user involvement, organizational culture, resource allocation, competing priorities) and wider context (government support, funding). Professionals had conflicting views on the future of TI approaches, however all agreed that government backing is essential for implementing policies into practice. CONCLUSIONS: A coordinated, more centralized strategy and provision for TI healthcare, increased funding for evaluation, and education through professional networks about evidence-based TI health systems can contribute towards evidence-informed policies and implementation of TI approaches in the UK. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12913-022-08461-w

Palmitoylation of Desmoglein 2 Is a Regulator of Assembly Dynamics and Protein Turnover.

Desmosomes are prominent adhesive junctions present between many epithelial cells as well as cardiomyocytes. The mechanisms controlling desmosome assembly and remodeling in epithelial and cardiac tissue are poorly understood. We recently identified protein palmitoylation as a mechanism regulating desmosome dynamics. In this study, we have focused on the palmitoylation of the desmosomal cadherin desmoglein-2 (Dsg2) and characterized the role that palmitoylation of Dsg2 plays in its localization and stability in cultured cells. We identified two cysteine residues in the juxtamembrane (intracellular anchor) domain of Dsg2 that, when mutated, eliminate its palmitoylation. These cysteine residues are conserved in all four desmoglein family members. Although mutant Dsg2 localizes to endogenous desmosomes, there is a significant delay in its incorporation into junctions, and the mutant is also present in a cytoplasmic pool. Triton X-100 solubility assays demonstrate that mutant Dsg2 is more soluble than wild-type protein. Interestingly, trafficking of the mutant Dsg2 to the cell surface was delayed, and a pool of the non-palmitoylated Dsg2 co-localized with lysosomal markers. Taken together, these data suggest that palmitoylation of Dsg2 regulates protein transport to the plasma membrane. Modulation of the palmitoylation status of desmosomal cadherins can affect desmosome dynamics

Si microwire-array solar cells

Si microwire-array solar cells with Air Mass 1.5 Global conversion efficiencies of up to 7.9% have been fabricated using an active volume of Si equivalent to a 4 μm thick Si wafer. These solar cells exhibited open-circuit voltages of 500 mV, short-circuit current densities (J_(sc)) of up to 24 mA cm^(-2), and fill factors >65% and employed Al_2O_3 dielectric particles that scattered light incident in the space between the wires, a Ag back reflector that prevented the escape of incident illumination from the back surface of the solar cell, and an a-SiN_x:H passivation/anti-reflection layer. Wire-array solar cells without some or all of these design features were also fabricated to demonstrate the importance of the light-trapping elements in achieving a high J_(sc). Scanning photocurrent microscopy images of the microwire-array solar cells revealed that the higher J_(sc) of the most advanced cell design resulted from an increased absorption of light incident in the space between the wires. Spectral response measurements further revealed that solar cells with light-trapping elements exhibited improved red and infrared response, as compared to solar cells without light-trapping elements

Intestinal epithelial replacement by transplantation of cultured murine and human cells into the small intestine.

Adult intestinal epithelial stem cells are a promising resource for treatment of intestinal epithelial disorders that cause intestinal failure and for intestinal tissue engineering. We developed two different animal models to study the implantation of cultured murine and human intestinal epithelial cells in the less differentiated "spheroid" state and the more differentiated "enteroid" state into the denuded small intestine of mice. Engraftment of donor cells could not be achieved while the recipient intestine remained in continuity. However, we were able to demonstrate successful implantation of murine and human epithelial cells when the graft segment was in a bypassed loop of jejunum. Implantation of donor cells occurred in a random fashion in villus and crypt areas. Engraftment was observed in 75% of recipients for murine and 36% of recipients for human cells. Engrafted spheroid cells differentiated into the full complement of intestinal epithelial cells. These findings demonstrate for the first time successful engraftment into the small bowel which is optimized in a bypassed loop surgical model

Development of Functional Microfold (M) Cells from Intestinal Stem Cells in Primary Human Enteroids.

Background & aimsIntestinal microfold (M) cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer's patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs), and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting.MethodsHuman intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium.ResultsFunctional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2) in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells.ConclusionsHuman intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium preferentially infect these cells in an in vitro setting. We anticipate that this model can be used to generate large numbers of M cells for further functional studies of these key cells of intestinal immune induction and their impact on controlling enteric pathogens and the intestinal microbiome

Music Information Technology and Professional Stakeholder Audiences: Mind the Adoption Gap

The academic discipline focusing on the processing and organization of digital music information, commonly known as Music Information Retrieval (MIR), has multidisciplinary roots and interests. Thus, MIR technologies have the potential to have impact across disciplinary boundaries and to enhance the handling of music information in many different user communities. However, in practice, many MIR research agenda items appear to have a hard time leaving the lab in order to be widely adopted by their intended audiences. On one hand, this is because the MIR field still is relatively young, and technologies therefore need to mature. On the other hand, there may be deeper, more fundamental challenges with regard to the user audience. In this contribution, we discuss MIR technology adoption issues that were experienced with professional music stakeholders in audio mixing, performance, musicology and sales industry. Many of these stakeholders have mindsets and priorities that differ considerably from those of most MIR academics, influencing their reception of new MIR technology. We mention the major observed differences and their backgrounds, and argue that these are essential to be taken into account to allow for truly successful cross-disciplinary collaboration and technology adoption in MIR

The central image of a gravitationally lensed quasar

A galaxy can act as a gravitational lens, producing multiple images of a background object. Theory predicts there should be an odd number of images but, paradoxically, almost all observed lenses have 2 or 4 images. The missing image should be faint and appear near the galaxy's center. These ``central images'' have long been sought as probes of galactic cores too distant to resolve with ordinary observations. There are five candidates, but in one case the third image is not necessarily a central image, and in the others, the central component might be a foreground source rather than a lensed image. Here we report the most secure identification of a central image, based on radio observations of PMN J1632-0033, one of the latter candidates. Lens models incorporating the central image show that the mass of the lens galaxy's central black hole is less than 2 x 10^8 M_sun, and the galaxy's surface density at the location of the central image is more than 20,000 M_sun per square parsec, in agreement with expectations based on observations of galaxies hundreds of times closer to the Earth.Comment: Nature, in press [7 pp, 2 figs]. Standard media embargo applies before publicatio