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Directionality of auxin transport is determined by polar localization of PIN-FORMED (PIN) proteins. Here the authors show that Arabidopsis WAV3 E3 ubiquitin ligases contribute to PIN polarity by selectively antagonizing ectopic deposition of de novo synthesized PIN proteins following cell division.

The Quantum Instrumentation Control Kit (QICK) is a standalone open-source qubit controller that was first introduced in 2022. In this follow-up work, we present recent upgrades to the QICK and the experimental use cases they uniquely enabled for superconducting qubit systems. These include multiplexed signal generation and readout, mixer-free readout, predistorted fast flux pulses, and phase-coherent pulses for parametric operations, including high-fidelity parametric entangling gates. We explain in detail how the QICK was used to enable these experiments.

Masticatory muscle myositis (MMM) is the second most common inflammatory myopathy diagnosed in dogs, but it is rarely described in puppies. The disease is characterized by the production of autoantibodies against 2M myofibers contained in masticatory muscle, although the cause of this production is still unclear. The aim of the present case report was to describe the clinical presentation, diagnostic findings, treatment, and follow-up of an atypical case of chronic masticatory muscle myositis in a very young dog. A 5-month old Cavalier king Charles Spaniel (CKCS) was presented to the AniCura Istituto Veterinario Novara with a two weeks, progressive history of lethargy and difficulty in food prehension. Neurological examination revealed bilateral masticatory muscle atrophy, mandibular ptosis with the jaw kept open, inability to close the mouth without manual assistance, jaw pain, and bilateral reduction of palpebral reflex and menace reaction; vision was maintained. A myopathy was suspected. Computed tomography (CT), magnetic resonance imaging (MRI), enzyme-linked immunosorbent assay test for 2M antibodies, and histopathological examination of masticatory muscle biopsy confirmed the diagnosis of MMM. Glucocorticoids treatment was started and clinical signs promptly improved. To the authors' knowledge, this is the first case describing mandibular ptosis in a dog affected by chronic MMM, successfully managed with medical treatment and the first report describing the CT and MRI findings in a young CKCS affected by MMM.

Summary: The widely used non-steroidal anti-inflammatory drugs (NSAIDs) are derivatives of the phytohormone salicylic acid (SA). SA is well known to regulate plant immunity and development, whereas there have been few reports focusing on the effects of NSAIDs in plants. Our studies here reveal that NSAIDs exhibit largely overlapping physiological activities to SA in the model plant Arabidopsis. NSAID treatments lead to shorter and agravitropic primary roots and inhibited lateral root organogenesis. Notably, in addition to the SA-like action, which in roots involves binding to the protein phosphatase 2A (PP2A), NSAIDs also exhibit PP2A-independent effects. Cell biological and biochemical analyses reveal that many NSAIDs bind directly to and inhibit the chaperone activity of TWISTED DWARF1, thereby regulating actin cytoskeleton dynamics and subsequent endosomal trafficking. Our findings uncover an unexpected bioactivity of human pharmaceuticals in plants and provide insights into the molecular mechanism underlying the cellular action of this class of anti-inflammatory compounds.

Characterizing plant membrane transporters via genetic methods is complicated by functional redundancy among multi-gene transporter families. Here Zhang et al. use an artificial microRNA-based screen to overcome this issue and show that ABCB6 and ABCB20 act redundantly to regulate auxin transport.

Plant ATP binding cassette (ABC) transporters are membrane proteins that are important for transporting a wide range of compounds, including secondary metabolites and phytohormones. In Arabidopsis, some members of the ABCB subfamily of ABC transporter, also known as Multi-Drug Resistance proteins (MDRs), have been implicated in auxin transport. However, reports on the roles of the auxin-mediated ABCBs in fleshy fruit development are rare. Here, we present that SlABCB4, a member of the tomato ABCB subfamily, transports auxin in the developing fruit of tomato. Transient expression of SlABCB4-GFP fusion proteins in tobacco cells showed plasma membrane localization. The transport activity of SlABCB4, expressed in Nicotiana benthamiana protoplasts, revealed substrate specificity for indole-3-acetic acid export. Gene expression analysis of SlABCB4 revealed high expression levels at the early stages of fruit development. Therefore, SlABCB4 is considered to facilitate auxin distribution in tomato fruit, which is important for tomato fruit development.

Viruses are obligatory parasites that depend on host cellular factors for their replication as well as for their local and systemic movement to establish infection. Although myosin motors are thought to contribute to plant virus infection, their exact roles in the specific infection steps have not been addressed. Here we investigated the replication, cell-to-cell and systemic spread of Tobacco mosaic virus (TMV) using dominant negative inhibition of myosin activity. We found that interference with the functions of three class VIII myosins and two class XI myosins significantly reduced the local and long-distance transport of the virus. We further determined that the inactivation of myosins XI-2 and XI-K affected the structure and dynamic behavior of the ER leading to aggregation of the viral movement protein (MP) and to a delay in the MP accumulation in plasmodesmata (PD). The inactivation of myosin XI-2 but not of myosin XI-K affected the localization pattern of the 126k replicase subunit and the level of TMV accumulation. The inhibition of myosins VIII-1, VIII-2 and VIII-B abolished MP localization to PD and caused its retention at the plasma membrane. These results suggest that class XI myosins contribute to the viral propagation and intracellular trafficking, whereas myosins VIII are specifically required for the MP targeting to and virus movement through the PD. Thus, TMV appears to recruit distinct myosins for different steps in the cell-to-cell spread of the infection.

Abstract Circulating cytokines orchestrate immune reactions and are promising drug targets for immune-mediated and inflammatory diseases. Exploring the genetic architecture of circulating cytokine levels could yield key insights into causal mediators of human disease. Here, we performed genome-wide association studies (GWAS) for 40 circulating cytokines in meta-analyses of 74,783 individuals. We detected 359 significant associations between cytokine levels and variants in 169 independent loci, including 150 trans- and 19 cis-acting loci. Integration with transcriptomic data point to key regulatory mechanisms, such as the buffering function of the Atypical Chemokine Receptor 1 (ACKR1) acting as scavenger for multiple chemokines and the role of tumor necrosis factor receptor-associated factor 1 (TRAFD1) in modulating the cytokine storm triggered by TNF signaling. Applying Mendelian randomization (MR), we detected a network of complex cytokine interconnections with TNF-b, VEGF, and IL-1ra exhibiting pleiotropic downstream effects on multiple cytokines. Drug target cis-MR using 2 independent proteomics datasets paired with colocalization revealed G-CSF/CSF-3 and CXCL9/MIG as potential causal mediators of asthma and Crohn’s disease, respectively, but also a potentially protective role of TNF-b in multiple sclerosis. Our results provide an overview of the genetic architecture of circulating cytokines and could guide the development of targeted immunotherapies.

The genus Cecropia (Urticaceae) comprises 61 tree species primarily found in tropical rainforests from Mexico to South America, including Argentina, Brazil, Paraguay, and Panama. These species are under-researched, with most studies focusing on phenolic derivatives from leaf extracts. Traditionally, Cecropia species are used to treat ailments such as asthma, bronchitis, and diabetes. This study focuses on the underexplored species C. longipes from Panama, aiming to analyze triterpene derivatives in its leaves. Through a series of chromatographic separations and purifications, three pentacyclic triterpenoids were isolated. Using 1D and 2D NMR experiments and HRESI-MS analysis, the following compounds were identified: 19α hydroxyasiatic acid, 1α,3β,23-trihydroxyolean-12-en-28-oic acid, and rosamultic acid. These compounds were isolated for the first time from C. longipes and the genus Cecropia. Genotoxicity tests using S. cerevisiae revealed that two compounds exhibited genotoxic activity at all concentrations. For 19α hydroxyasiatic acid, genotoxic potential was observed at higher concentrations, unrelated to oxidative stress, suggesting other mechanisms.

Abstract The introduction of mammography screening programs has significantly reduced breast cancer mortality rates. Nevertheless, some lesions remain undetected, especially in dense breast tissue. Studies have shown that phase-contrast imaging can improve breast cancer diagnosis by increasing soft tissue contrast. Furthermore, grating-based phase-contrast imaging enables the simultaneous acquisition of absorption, phase-contrast, and scattering, so-called dark-field images. The latter allows the classification of microcalcifications. In addition, breast computed tomography (BCT) systems can identify and discriminate overlapping but clinically relevant structures. This study investigates the benefit of combining grating-based phase-contrast with BCT. We explore the potential of grating-based phase-contrast breast computed tomography (gbpc-BCT) with a breast phantom and a freshly dissected fibroadenoma. Improved image contrast could be achieved with radiation doses comparable to those used in clinical BCT.

Triple-negative breast cancer (TNBC) is an aggressive heterogeneous form of breast cancer that accounts for 15 %-20 % of all breast cancers. Characterized by an absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, TNBCs are often treated with surgery, chemotherapy, radiation, and, most recently, with immunotherapy; however, patients with treatment-resistant TNBC often relapse and have an extremely poor prognosis. Here we present a case of recurrent metastatic TNBC responsive to the TRK inhibitor larotrectinib.

The formation of fibre breaks governs the longitudinal tensile failure of a unidirectional ply. It is widely believed that matrix plasticity, matrix cracking, and fibre-matrix debonding created near these fibre breaks help reduce the resulting stress concentrations. Therefore, to determine if matrix cracking and fibre-matrix debonding surrounding fibre breaks occur in a glass fibre-epoxy composite, we performed in-situ tensile tests combined with holotomography at a resolution of 150 nm. Despite their presence in single-fibre composites manufactured with the same constituents, they were absent in regular composites. This suggests that single-fibre composites are not representative of regular composites. The study provides fresh insight into the damage mechanisms in these materials.

Abstract Background Distal femoral fractures account for less than 1% of all fractures. The therapy of choice is usually surgical stabilization. Despite advances in implant development over the past few years, complication rate remains comparatively high. The aim of this study is to analyze our results with plate fixation of distal femoral fractures with a focus on complication and fracture healing rates. Methods In this retrospective cohort study, patients (> 18 years) with distal femoral fractures treated at an urban level I trauma center between 2015 and 2022 were analyzed. Results In total, 206 patients (167 female, 39 male) with an average age of 75 (SD 16) years were diagnosed with a fracture of the distal femur. One hundred fourteen of these patients were treated surgically by means of plate osteosynthesis. In 13 cases (11.41%), a revision procedure had to be performed. The indication for surgical revision was mechanical failure in eight cases (7.02%) and septic complication in five cases (4.39%). Periprosthetic fractures were more likely to cause complications overall (19.6% versus 4.76%) and further included all documented septic complications. The analysis of modifiable surgical factors in the context of plate osteosynthesis showed higher complication rates for cerclage in the fracture area compared with plate-only stabilizations (44.44% versus 22.22%). Conclusions The data show an increased amount of revisions and a significantly higher number of septic complications in the treatment of periprosthetic fractures of the distal femur compared with non-periprosthetic fractures. The detected combination of plates together with cerclage was associated with higher complication rates. Level of evidence Level III retrospective comparative study.

Abstract Spatially resolved transcriptomics has revolutionized RNA studies by aligning RNA abundance with tissue structure, enabling direct comparisons between histology and gene expression. Traditional approaches to identifying signature genes often involve preliminary data grouping, which can overlook subtle expression patterns in complex tissues. We present Spatial Gradient Screening, an algorithm which facilitates the supervised detection of histology-associated gene expression patterns without prior data grouping. Utilizing spatial transcriptomic data along with single-cell deconvolution from injured mouse cortex, and TCR-seq data from brain tumors, we compare our methodology to standard differential gene expression analysis. Our findings illustrate both the advantages and limitations of cluster-free detection of gene expression, offering more profound insights into the spatial architecture of transcriptomes. The algorithm is embedded in SPATA2, an open-source framework written in R, which provides a comprehensive set of tools for investigating gene expression within tissue.

Mucosal immunity and trained innate immunity of the gut play a pivotal role in maintaining intestinal homeostasis and defending against microbial pathogens. This review provides an overview of the mechanisms underlying mucosal immunity and the concept of trained innate immunity in the gut. We discuss the interaction between gut microbiota and the host immune system, highlighting the role of epithelial cells, dendritic cells, and innate lymphoid cells, as well as the novel concept of trained innate immunity and its role in perpetuating or attenuating gut inflammation. We also comment on the current models for investigating mucosal immunity, their limitations, and how they can be overcome. Additionally, we explore the potential therapeutic implications of modulating mucosal immunity and trained innate immunity in gastrointestinal diseases. Only by elucidating the mechanisms underlying mucosal immunity and the concept of trained innate immunity, innovative approaches to modulate immune responses and restore intestinal homeostasis in the context of gastrointestinal disorders could be implemented.

Abstract Loss-of-function mutations in the homotrimeric serine protease HTRA1 cause cerebral vasculopathy. Here, we establish independent approaches to achieve the functional correction of trimer assembly defects. Focusing on the prototypical R274Q mutation, we identify an HTRA1 variant that promotes trimer formation thus restoring enzymatic activity in vitro. Genetic experiments in Htra1 R274Q mice further demonstrate that expression of this protein-based corrector in trans is sufficient to stabilize HtrA1-R274Q and restore the proteomic signature of the brain vasculature. An alternative approach employs supramolecular chemical ligands that shift the monomer-trimer equilibrium towards proteolytically active trimers. Moreover, we identify a peptidic ligand that activates HTRA1 monomers. Our findings open perspectives for tailored protein repair strategies.

Abstract Neuroglia critically shape the brain´s response to ischemic stroke. However, their phenotypic heterogeneity impedes a holistic understanding of the cellular composition of the early ischemic lesion. Here we present a single cell resolution transcriptomics dataset of the brain´s acute response to infarction. Oligodendrocyte lineage cells and astrocytes range among the most transcriptionally perturbed populations and exhibit infarction- and subtype-specific molecular signatures. Specifically, we find infarction restricted proliferating oligodendrocyte precursor cells (OPCs), mature oligodendrocytes and reactive astrocytes, exhibiting transcriptional commonalities in response to ischemic injury. OPCs and reactive astrocytes are involved in a shared immuno-glial cross talk with stroke-specific myeloid cells. Within the perilesional zone, osteopontin positive myeloid cells accumulate in close proximity to CD44+ proliferating OPCs and reactive astrocytes. In vitro, osteopontin increases the migratory capacity of OPCs. Collectively, our study highlights molecular cross talk events which might govern the cellular composition of acutely infarcted brain tissue.

Objetivo: Determinar si existen cambios epidemiológicos en los pacientes hospitalizados en un servicio de medicina interna del Hospital Nacional Edgardo Rebagliati Martins comparando la información de los periodos 2008 y 2018. Materiales y métodos: Estudio observacional, retrospectivo y transversal, con un nivel analítico-descriptivo y un diseño no experimental. Se usó la información de los registros de enfermería de 1640 pacientes mayores de 18 años hospitalizados en el Servicio de Medicina Interna N.º 5 (piso 7C) del Hospital Edgardo Rebagliati Martins (Jesús María-Lima, Perú) durante los años 2008 y 2018. Se analizaron variables sociodemográficas (sexo y edad) y clínicas (servicio de procedencia, diagnóstico, estancia hospitalaria y condición de egreso). Se utilizó el programa Excel para el registro y la creación de la base de datos; para el procesamiento de datos se empleó el lenguaje de programación R, versión 4.0.2, y como plataforma de análisis se usó Stata, versión 17. Para el análisis descriptivo, las variables se organizaron en tablas como frecuencias absolutas y relativas; para determinar las diferencias en las características clínicas, se aplicó la prueba de McNemar, y para determinar los factores asociados a la mortalidad, se usaron los modelos de regresión logística. Todos los análisis se realizaron considerando un valor de p < 0,05, que fueron estadísticamente significativos. Resultados: Al comparar ambos periodos, se determinaron diferencias en las variables sexo (OR = 0,60; IC 95 %: 0,50-0,74; p < 0,01), estancia hospitalaria (OR = 1,9; IC 95 %: 1,50-2,40; p < 0,01),servicio de procedencia (OR = 0,65; IC 95 %: 0,50-0,85; p < 0,01), defunción (OR = 1,90; IC 95 %: 1,40-2,60; p < 0,01) y tipo de enfermedad (OR = 0,76; IC 95 %:0,59-0,97; p= 0,03). No se determinaron diferencias según grupo etario entre ambos periodos. Conclusiones: Existen diferencias estadísticamente significativas que evidencian la transición epidemiológica al comparar la información de ambos periodos, por tanto, resulta necesario establecer un enfoque integral, multidisciplinario e innovador para la atención de los pacientes con enfermedades crónicas.

Este artículo evalúa el estado actual de la ciberseguridad en Colombia. Para ello, se analiza la política pública en tres momentos clave. En primer lugar, se revisan los CONPES 3701 de 2011 y 3854 de 2016 para comprender las acciones iniciales del país en este tema. En segundo lugar, se estudian el CONPES 3995 de 2020 y la Estrategia Nacional de Ciberdefensa y Ciberseguridad, como evolución de la política pública en materia de ciberseguridad. Posteriormente, se examinan las amenazas digitales surgidas entre 2019 y 2021, en el contexto de la pandemia, y la reacción del Estado frente a ellas. Los resultados evidencian que, aunque las capacidades técnicas han mejorado, las capacidades organizacionales no han avanzado al mismo ritmo, lo que indica que la estrategia debe fortalecerse para que sea exitosa. Finalmente, se revisan las propuestas del gobierno actual en materia de ciberseguridad.

By offering the opportunity to make longer trips at a lower level of physical activity, the e-bike provides a promising alternative to car use. Despite all advantages (e-)cycling brings to urban accessibility, the environment, physical and mental health, not all car commuters regard the e-bike as a suitable alternative yet in their daily activity patterns. This study reports on changes in behavioral intention and actual e-cycling brought about by an e-cycling incentive program in the province of Noord-Brabant, the Netherlands. The impact of the program on behavioral intention and the actual change to e-cycling were analyzed based on a longitudinal three-wave survey design on past, intended, and actual commuting behavior. To explore the changes in behavioral intentional, the differences between intention and actual behavior and the factors influencing them, descriptive and ordinal logistic regression analyses were conducted. To explore the dynamics between e-cycling intentions and behavior a longitudinal structural equation model was developed. In general, this study shows that the incentive program has a positive impact on participants’ behavioral change to e-cycling during the incentive program. Results show that two-third of the participants actually use the e-bike as much as they intended at the start of the program. People who were used to taking the conventional bicycle to work before the stimulation program, are more consistent between their intention and behavior. Results also show that personal beliefs, habits, and goal-related variables do not influence the intention–behavior consistency.

ABSTRACT BACKGROUND: Chile presents one of the lowest organ donation rates, resulting in pediatric liver waitlist mortality rates up to 38.1%. Live donor liver transplantation is one of the main alternatives to decrease waitlist mortality, mostly utilized in our country for small children up to 20 kg. AIMS: The aim of this study was to report a three-case series of adult-to-pediatric living donor liver transplantation using a full left lobe graft. METHODS: We report three cases of children with more than 20 kg who received complete left hemi-grafts in different clinical scenarios. The indications and techniques adopted are discussed. RESULTS: Three children, two girls and one boy, aged 11, 7, and 3 years, were transplanted. The indications for transplant were fulminant hepatitis of autoimmune etiology, hepatoblastoma, and chronic liver failure due to autoimmune hepatitis, respectively. The evolution was satisfactory in all three children, and to date, all are well, approximately 12–24 months after the transplant. CONCLUSIONS: The use of a living donor left lateral segment (segments 2 and 3) has been successfully employed in pediatric liver transplantation. However, it is only suitable for infants and low-weight children. This approach using the whole left hemi-liver graft contributes to the reduction of small-for-size syndrome, mortality rate, and waiting times associated with deceased donors.

Abstract Background Geographical environments influence people's active mobility behaviors, contributing to their physical and mental health. The use of Virtual Reality (VR) in experimental research can unveil new insights into the relationship between exposure to geographic environments and active mobility behaviors. This systematic review aims to (1) identify environmental attributes investigated in relation with walking and cycling, using VR, (2) assess their impacts on active mobility behaviors and attitudes, and (3) identify research gaps, strengths and limitations in VR-based experimental research. Methods Articles published between January 2010 and February 2022 within five databases (PubMed, Scopus, EBSCO, IEEE Xplore, and Cochrane Library) were explored using three keywords and their synonyms: Virtual Reality, Active mobility behavior, and Geographical environments. Studies focusing on indoor environments, driving simulation, disease-specific groups, non-relevant disciplines (e.g. military, emergency evacuation), VR methodology/software optimization, and those with static participants' involvement were excluded. The full protocol is available from PROSPERO (ID = CRD42022308366). Results Out of 3255 articles, 18 peer-reviewed papers met the selection criteria, mostly focusing on walking (83%). Most studies used head-mounted displays (94%) and relied on convenience sampling (72% below 100 participants). Both static (33%) and dynamic (45%) environmental attributes have been investigated, with only 22% of them simultaneously in the same virtual environment. Greenness and crowd density were the most frequent attributes, rather consistently associated with emotional states and movement behaviors. Few studies have taken into account participant’s previous VR experience (33%) and cybersickness (39%) while both are likely to affect an individual’s perception and behavior. Conclusions Future research should explore a broader range of environmental attributes, including static and dynamic ones, as well as a more complex integration of these attributes within a single experiment to mimic the effect of realistic environments on people's active mobility behaviors and attitudes. Larger and more diverse population samples are deemed required to improve result generalizability. Despite methodological challenges, VR emerges as a promising tool to disentangle the effect of complex environments on active mobility behaviors.

Abstract Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours.

Abstract Background Greenness exposure has been associated with many health benefits, for example through the pathway of providing opportunities for physical activity (PA). Beside the limited body of longitudinal research, most studies overlook to what extent different types of greenness exposures may be associated with varying levels of PA and sedentary behavior (SB). In this study, we investigated associations of greenness characterized by density, diversity and vegetation type with self-reported PA and SB over a 9-year period, using data from the ORISCAV-LUX study (2007–2017, n = 628). Methods The International Physical Activity Questionnaire (IPAQ) short form was used to collect PA and SB outcomes. PA was expressed as MET-minutes/week and log-transformed, and SB was expressed as sitting time in minutes/day. Geographic Information Systems (ArcGIS Pro, ArcMap) were used to collect the following exposure variables: Tree Cover Density (TCD), Soil-adjusted Vegetation Index (SAVI), and Green Land Use Mix (GLUM). The exposure variables were derived from publicly available sources using remote sensing and cartographic resources. Greenness exposure was calculated within 1000m street network buffers around participants’ exact residential address. Results Using Random Effects Within-Between (REWB) models, we found evidence of negative within-individual associations of TCD with PA (β = − 2.60, 95% CI − 4.75; − 0.44), and negative between-individual associations of GLUM and PA (β = − 2.02, 95% CI − 3.73; − 0.32). There was no evidence for significant associations between greenness exposure and SB. Significant interaction effects by sex were present for the associations between TCD and both PA and SB. Neighborhood socioeconomic status (NSES) did not modify the effect of greenness exposure on PA and SB in the 1000 m buffer. Discussion Our results showed that the relationship between greenness exposure and PA depended on the type of greenness measure used, which stresses the need for the use of more diverse and complementary greenness measures in future research. Tree vegetation and greenness diversity, and changes therein, appeared to relate to PA, with distinct effects among men and women. Replication studies are needed to confirm the relevance of using different greenness measures to understand its’ different associations with PA and SB.

Pleural mesothelioma (PM) is characterized by rapid growth, local invasion, and limited therapeutic options. The multifunctional oncoprotein Y‐box‐binding protein‐1 (YB‐1) is frequently overexpressed in cancer and its inhibition reduces aggressive behavior in multiple tumor types. Here, we investigated the effects of YB‐1 on target gene regulation and PM cell behavior. Whereas siRNA‐mediated YB‐1 knockdown reduced cell motility, YB‐1 overexpression resulted in scattering, increased migration, and intravasation in vitro. Furthermore, YB‐1 stimulated PM cell spreading in zebrafish. Combined knockdown and inducible overexpression of YB‐1 allowed bidirectional control and rescue of cell migration, the pattern of which was closely followed by the mRNA and protein levels of EGFR and the protein level of snail, whereas the mRNA levels of MMP1, EPHA5, and PARK2 showed partial regulation by YB‐1. Finally, we identified snail as a critical regulator of YB‐1‐mediated cell motility in PM. This study provides insights into the mechanism underlying the aggressive nature of PM and highlights the important role of YB‐1 in this cancer. In this context, we found that YB‐1 closely regulates EGFR and snail, and, moreover, that YB‐1‐induced cell migration depends on snail.

Abstract Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the mechanisms controlling the responses of specific cell types and their crosstalk is required to develop an efficient strategy for better regeneration. Here, we combine spatial and single-cell transcriptomics to chart the transcriptomic signature of the injured male murine cerebral cortex, and identify specific states of different glial cells contributing to this signature. Interestingly, distinct glial cells share a large fraction of injury-regulated genes, including inflammatory programs downstream of the innate immune-associated pathways Cxcr3 and Tlr1/2. Systemic manipulation of these pathways decreases the reactivity state of glial cells associated with poor regeneration. The functional relevance of the discovered shared signature of glial cells highlights the importance of our resource enabling comprehensive analysis of early events after brain injury.

Abstract Solution‐based atomic layer deposition (sALD) is an emerging technique that transfers the principle of traditional atomic layer deposition (ALD) from the gas phase into a wet chemical environment. This new preparation technique has new and unique properties and requirements. A large number of new surfaces and reactants are available to produce active 2D materials. In this work a reproducible procedure to coat silicon wafers with a densely packed monolayer of (3‐Mercaptopropyl)trimethoxysilane (MPTMS) molecules is presented. These highly functionalized surfaces can be used to seed the nucleation of SnS2 in a solution‐based ALD procedure. A coating routine for the production of SnS2 is adapted from ALD to sALD and insight into the nucleation behavior of the reactands is given. X‐ray reflectometry (XRR) is used to resolve the nucleation process of SnS2 on an MPTMS self assembled monolayer (SAM) during the first three cycles of an sALD procedure. The comparison of ex situ XRR, in situ XRR, grazing incidence wide‐angle X‐ray scattering (GIWAXS), atomic force microscopy (AFM), energy dispersive X‐ray spectroscopy (EDX) measurements, and density functional theory (DFT) calculations find that SnS2 first forms a closed layer and then continues to grow in islands on thiol functionalized silane SAMs. Subsequent coating cycles will continue the growth of the islands laterally and in height.

Abstract A recent study outlines the phenotypes of brain border region macrophages in developing, normal and glioblastoma‐affected brains. For the first time, the authors show in‐vivo turnover of human brain border macrophages. The findings have implications for the understanding of brain border immunity and potential macrophage targeting therapies. keypoints Human border region macrophages are distinct from microglia. These distinct phenotypes are established early during embryonal development ‐ Brain border macrophages are partially replaced by bone marrow‐derived myeloid cells. The transcriptional phenotypes of glioblastoma‐associated macrophage are determined by the anatomical region.

Idiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS.

Abstract Spatially isolated plant populations in agricultural landscapes exhibit genetic responses not only to habitat fragmentation per se but also to the composition of the landscape matrix between habitat patches. These responses can only be understood by examining how the landscape matrix influences among‐habitat movements of pollinators and seed vectors, which act as genetic linkers among populations. We studied the forest herb Polygonatum multiflorum and its associated pollinator and genetic linker, the bumblebee Bombus pascuorum, in three European agricultural landscapes. We aimed to identify which landscape features affect the movement activity of B. pascuorum between forest patches and to assess the relative importance of these features in explaining the forest herb's population genetic structure. We applied microsatellite markers to estimate the movement activity of the bumblebee as well as the population genetic structure of the forest herb. We modelled the movement activity as a function of various landscape metrics. Those metrics found to explain the movement activity best were then used to explain the population genetic structure of the forest herb. The bumblebee movement activity was affected by the cover of maize fields and semi‐natural grasslands on a larger spatial scale and by landscape heterogeneity on a smaller spatial scale. For some measures of the forest herb's population genetic structure, that is, allelic richness, observed heterozygosity and the F‐value, the combinations of landscape metrics, which explained the linker movement activity best, yielded lower AICc values than 95% of the models including all possible combinations of landscape metrics. Synthesis: The genetic linker, B. pascuorum, mediates landscape effects on the population genetic structure of the forest herb P. multiflorum. Our study indicates, that the movement of the genetic linker among forest patches, and thus the pollen driven gene flow of the herb, depends on the relative value of floral resources in the specific landscape setting. Noteworthy, the population genetic structure of the long‐lived, clonal forest herb species correlated with recent land‐use types such as maize, which have been existing for not more than a few decades within these landscapes. This underscores the short time in which land‐use changes can influence the evolutionary potential of long‐lived wild plants.