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PurposeUnderstanding the complex bidirectional interactions between neurons and glioma cells could help to identify new therapeutic targets. Herein, the techniques and application of novel neuroscience tools implemented to study the complex interactions between brain and malignant gliomas, their results, and the potential therapeutic opportunities were reviewed.MethodsLiterature search was performed on PubMed between 2001 and 2023 using the keywords "glioma", "glioblastoma", "circuit remodeling", "plasticity", "neuron networks" and "cortical networks". Studies including grade 2 to 4 gliomas, diffuse midline gliomas, and diffuse intrinsic pontine gliomas were considered.ResultsGlioma cells are connected through tumour microtubes and form a highly connected network within which pacemaker cells drive tumorigenesis. Unconnected cells have increased invasion capabilities. Glioma cells are also synaptically integrated within neural circuitry. Neurons promote tumour growth via paracrine and direct electrochemical mechanisms, including glutamatergic AMPA-receptors. Increased glutamate release in the tumor microenvironment and loss of peritumoral GABAergic inhibitory interneurons result in network hyperexcitability and secondary epilepsy. Functional imaging, local field potentials and subcortical mapping, performed in awake patients, have defined patterns of malignant circuit remodeling. Glioma-induced remodeling is frequent in language and even motor cortical networks, depending on tumour biological parameters, and influences functional outcomes.ConclusionThese data offer new insights into glioma tumorigenesis. Future work will be needed to understand how tumor intrinsic molecular drivers influence neuron-glioma interactions but also to integrate these results to design new therapeutic options for patients.

Background Lung ultrasound (LUS) has emerged as a useful tool in the acute phase of patients admitted for ST‐segment–elevation myocardial infarction. However, its long‐term significance remains uncertain, and risk scores do not include LUS findings as a predictor. This study aims to assess the 1‐year prognostic value of LUS and its ability to enhance existing risk scores. Methods and Results This is a multicenter prospective cohort study involving 373 patients with ST‐segment–elevation myocardial infarction. LUS was performed during the first 24 hours after angiography. LUS results were assessed both as a categorical (wet/dry lung) and continuous variable (LUS score). The primary end point comprised the following major adverse cardiovascular events: all‐cause mortality or hospitalization for heart failure, acute coronary syndrome, or stroke within 1 year. We also evaluated whether LUS could enhance the predictive value of the GRACE (Global Registry of Acute Coronary Events) score. Major adverse cardiovascular events occurred in 51 (13.7%) patients over a median follow‐up of 368 days. After multivariate analysis, the LUS score was an independent predictor (hazard ratio [HR], 1.06 [95% CI, 1.01–1.10]; P=0.009] for each additional B‐line), whereas the categorical classification was an independent predictor in patients with ST‐segment–elevation myocardial infarction Killip I (HR, 3.12 [95% CI, 1.34–7.31]; P=0.009). Incorporating LUS into GRACE resulted in a net reclassification index of 31.6% and a significant increase in the area under the curve; GRACE alone scored 0.705 compared with GRACE+LUS 0.791 (P=0.002). Conclusions Detecting B‐lines on LUS at the acute phase predicts major adverse cardiovascular events at 1 year in patients with ST‐segment–elevation myocardial infarction and enhances the predictive value of the GRACE score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04526535.

IMPORTANCE:. Timely intervention for clinically deteriorating ward patients requires that care teams accurately diagnose and treat their underlying medical conditions. However, the most common diagnoses leading to deterioration and the relevant therapies provided are poorly characterized. OBJECTIVES:. We aimed to determine the diagnoses responsible for clinical deterioration, the relevant diagnostic tests ordered, and the treatments administered among high-risk ward patients using manual chart review. DESIGN, SETTING, AND PARTICIPANTS:. This was a multicenter retrospective observational study in inpatient medical-surgical wards at four health systems from 2006 to 2020. Randomly selected patients (1000 from each health system) with clinical deterioration, defined by reaching the 95th percentile of a validated early warning score, electronic Cardiac Arrest Risk Triage, were included. MAIN OUTCOMES AND MEASURES:. Clinical deterioration was confirmed by a trained reviewer or marked as a false alarm if no deterioration occurred for each patient. For true deterioration events, the condition causing deterioration, relevant diagnostic tests ordered, and treatments provided were collected. RESULTS:. Of the 4000 included patients, 2484 (62%) had clinical deterioration confirmed by chart review. Sepsis was the most common cause of deterioration (41%; n = 1021), followed by arrhythmia (19%; n = 473), while liver failure had the highest in-hospital mortality (41%). The most common diagnostic tests ordered were complete blood counts (47% of events), followed by chest radiographs (42%) and cultures (40%), while the most common medication orders were antimicrobials (46%), followed by fluid boluses (34%) and antiarrhythmics (19%). CONCLUSIONS AND RELEVANCE:. We found that sepsis was the most common cause of deterioration, while liver failure had the highest mortality. Complete blood counts and chest radiographs were the most common diagnostic tests ordered, and antimicrobials and fluid boluses were the most common medication interventions. These results provide important insights for clinical decision-making at the bedside, training of rapid response teams, and the development of institutional treatment pathways for clinical deterioration.

La Muerte lagoon is an ephemeral endorheic water body located in the Monegros desert, Zaragoza, Spain. Amplicon sequencing of the 16S rRNA gene was performed to analyze the bacterial and archaeal communities in biofilm-sediment samples over three years, to understand the dynamic changes in the microbial community. PICRUSt and shotgun metagenomics were used to examine energy production and carbohydrate metabolism pathways. The dominant bacterial phyla were Actinobacteriota, Bacteroidota, Cyanobacteriota, and Pseudomonadota, while Halobacteriota was the predominant archaeal phylum. Despite seasonal environmental fluctuations, the biofilm community remained stable over time, suggesting resilience. The Calvin-Benson cycle was the main carbon fixation pathway, carried out by Cyanobacteria and purple non-sulfur bacteria. Nitrogen fixation by diazotrophs supplied an important nitrogen source. Organic carbon was derived primarily from autotrophs, with little use of allochthonous plant material. The comparison of biofilm-sediment and water column biotopes showed distinct but related prokaryote communities. Biofilm-sediments showed higher taxonomic diversity and different proportions of microbial phyla compared to the water column. This study provides initial insights into the complex microbial life in endorheic lagoons and underscores the importance of protecting these globally threatened habitats. The limited sample size in this study warrants further investigation with a more comprehensive sampling strategy to fully characterize the microbial communities and their functional roles in the different biotopes of La Muerte lagoon.

Introduction: The introduction of intraoperative fluorophores represented a significant advancement in neurosurgical practice. Nowadays they found different applications: in oncology to improve the visualization of tumoral tissue and optimize resection rates and in vascular neurosurgery to assess the exclusion of vascular malformations or the permeability of bypasses, with real-time intraoperative evaluations. Research question: A comprehensive knowledge of how fluorophores work is crucial to maximize their benefits and to incorporate them into daily neurosurgical practice. We would like to revise here their applications and clinical relevance. Material and methods: A focused literature review of relevant articles dealing with the versatile applications of fluorophores in neurosurgery was performed. Results: The fundamental mechanisms of action of intraoperative fluorophores are enlightened, examining their interactions with target tissues and the principles driving fluorescence-guided surgery. The clinical applications of the principal fluorophores, namely fluorescein sodium, 5-ALA and indocyanine green, are detailed, in regards to the management of vascular malformations, brain tumors and pathologies treated through endoscopic endonasal approaches. Discussion and conclusion: Future perspective dealing with the development of new technologies or of new molecules are discussed. By critically assessing the efficacy and applications of the different fluorophores, as well as charting their potential future uses, this paper seeks to guide clinicians in their practice and provide insights for driving innovation and progress in fluorescence-based surgery and research.

The review begins with an overview of the fundamental principles/physics underlying light, fluorescence, and other light-matter interactions in biological tissues. It then focuses on 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence spectroscopy methods used in neurosurgery (e.g., intensity, time-resolved) and in so doing, describe their specific features (e.g., hardware requirements, main processing methods) as well as their strengths and limitations. Finally, we review current clinical applications and future directions of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence spectroscopy in neurosurgery.

Abstract Background Plant defensins represent a major innate immune protein superfamily that displays strong inhibitory effects on filamentous fungi. The total number of plant defensins in a conifer species is unknown since there are no sequenced conifer genomes published, however the genomes of several angiosperm species provide an insight on the diversity of plant defensins. Here we report the identification of five new defensin-encoding genes from the Picea glauca genome and the characterization of two of their gene products, named PgD5 and endopiceasin. Results Screening of a P. glauca EST database with sequences of known plant defensins identified four genes with homology to the known P. glauca defensin PgD1, which were designated PgD2-5. Whereas in the mature PgD2-4 only 7–9 amino acids differed from PgD1, PgD5 had only 64% sequence identity. PgD5 was amplified from P. glauca genomic DNA by PCR. It codes for a precursor of 77-amino acid that is fully conserved within the Picea genus and has similarity to plant defensins. Recombinant PgD5, produced in Escherichia coli, had a molecular mass of 5.721 kDa, as determined by mass spectrometry. The PgD5 peptide exhibited strong antifungal activity against several phytopathogens without any effect on the morphology of the treated fungal hyphae, but strongly inhibited hyphal elongation. A SYTOX uptake assay suggested that the inhibitory activity of PgD5 could be associated with altering the permeability of the fungal membranes. Another completely unrelated defensin gene was identified in the EST library and named endopiceasin. Its gene codes for a 6-cysteine peptide that shares high similarity with the fungal defensin plectasin. Conclusions Screening of a P. glauca EST database resulted in the identification of five new defensin-encoding genes. PgD5 codes for a plant defensin that displays non-morphogenic antifungal activity against the phytopathogens tested, probably by altering membrane permeability. PgD5 has potential for application in the plant biotechnology sector. Endopiceasin appears to derive from an endo- or epiphytic fungal strain rather than from the plant itself.

MotivationNetwork diffusion and label propagation are fundamental tools in computational biology, with applications like gene-disease association, protein function prediction and module discovery. More recently, several publications have introduced a permutation analysis after the propagation process, due to concerns that network topology can bias diffusion scores. This opens the question of the statistical properties and the presence of bias of such diffusion processes in each of its applications. In this work, we characterized some common null models behind the permutation analysis and the statistical properties of the diffusion scores. We benchmarked seven diffusion scores on three case studies: synthetic signals on a yeast interactome, simulated differential gene expression on a protein-protein interaction network and prospective gene set prediction on another interaction network. For clarity, all the datasets were based on binary labels, but we also present theoretical results for quantitative labels.ResultsDiffusion scores starting from binary labels were affected by the label codification and exhibited a problem-dependent topological bias that could be removed by the statistical normalization. Parametric and non-parametric normalization addressed both points by being codification-independent and by equalizing the bias. We identified and quantified two sources of bias-mean value and variance-that yielded performance differences when normalizing the scores. We provided closed formulae for both and showed how the null covariance is related to the spectral properties of the graph. Despite none of the proposed scores systematically outperformed the others, normalization was preferred when the sought positive labels were not aligned with the bias. We conclude that the decision on bias removal should be problem and data-driven, i.e. based on a quantitative analysis of the bias and its relation to the positive entities.AvailabilityThe code is publicly available at https://github.com/b2slab/diffuBench and the data underlying this article are available at https://github.com/b2slab/retroData.Supplementary informationSupplementary data are available at Bioinformatics online.

The paper presents a two-color digital holographic interferometer. The set-up is devoted to the investigation of crack origin in hybrid industrial electronic components. Optical configuration and algorithms to recover the optical phase of two-color digitally encoded holograms are described. The method is based on a spatial-color-multiplexing scheme in which holographic reconstruction is performed using a spectral scanning algorithm. Experimental results exhibit in-plane and out-of-plane non uniform deformations that are the probable cause of the cracking of the component.

The paper presents a two-color digital holographic interferometer. The set-up is devoted to the study of the fundamental dynamic of unconsolidated materials. Optical configuration and algorithms to recover the optical phase of two-color digitally encoded holograms are described. The method is based on a spatial-color-multiplexing scheme in which holographic reconstruction is performed using adapted wavelength zero-padding and reconstructing distance. Experimental results are presented in the case of granular media excited in the frequency range 400Hz-3000Hz and exhibits the 3D movement.

The paper presents algorithms to recover the optical phase of digitally encoded holograms. Algorithms are based on the use of a numerical spherical reconstructing wave. Proof of the validity of the concept is performed through an experimental off axis digital holographic set-up. Two-color digital holographic reconstruction is also investigated. Application of the color set-up and algorithms concerns the simultaneous two-dimensional deformation measurement of an object submitted to a mechanical loading.

Optical full-field techniques have a great importance in modern experimental mechanics. Even if they are reasonably spread among the university laboratories, their diffusion in industrial companies remains very weak for several reasons, especially a lack of metrological performance assessment. A full-field measurement can be characterized by its resolution, bias, measuring range, and by a specific quantity, the spatial resolution. The present communication proposes an original procedure for the estimation in one single step of the resolution, bias and spatial resolution for a given operator (decoding algorithm, such as image correlation, low-pass filters, derivation tools, ...). This procedure is based on the construction of a particular multi-frequential field, and a Bode diagram representation of the results. This analysis is applied to various phase demodulating algorithms for the estimation of in-plane displacements.

The summer of 2022 was memorable and record-breaking, ranking as the second hottest summer in France since 1900, with a seasonal surface air temperature average of 22.7 ∘C. In particular, France experienced multiple record-breaking heatwaves during the meteorological summer. As the main heat reservoir of the Earth system, the oceans are at the forefront of events of this magnitude which enhance oceanic disturbances such as marine heatwaves (MHWs). In this study, we investigate the sea surface temperature (SST) of French maritime basins using remotely sensed measurements to track the response of surface waters to the atmospheric heatwaves and determine the intensity of such feedback. Beyond the direct relationship between SSTs and surface air temperatures, we explore the leading atmospheric parameters affecting the upper-layer ocean heat budget. Despite some gaps in data availability, the SSTs measured during the meteorological summer of 2022 were record-breaking, the mean SST was between 1.3 and 2.6 ∘C above the long-term average (1982–2011), and the studied areas experienced between 4 and 22 d where the basin-averaged SSTs exceeded the maximum recorded basin-averaged SSTs from 1982 to 2011. We found a significant SST response during heatwave periods with maximum temperatures measured locally at 30.8 ∘C in the north-western Mediterranean Sea. Our results show that in August 2022 (31 July to 13 August), France experienced above-average surface solar radiation correlated with below-average total cloud cover and negative wind speed anomalies. Our attribution analysis based on a simplified mixed-layer heat budget highlights the critical role of ocean–atmosphere fluxes in initiating abnormally warm SSTs, while ocean mixing plays a crucial role in the cessation of such periods. We find that the 2 m temperatures and specific humidity that are consistently linked to the advection of warm and moist air masses are key variables across all the studied regions. Our results reveal that the influence of wind on heatwaves is variable and of secondary importance. Moreover, we observe that the incident solar radiation has a significant effect only on the Bay of Biscay (BB) and the English Channel (EC) areas. Our study findings are consistent with previous research and demonstrate the vulnerability of the Mediterranean Sea to the increasing frequency of extreme weather events resulting from climate change. Furthermore, our investigation reveals that the recurring heatwave episodes during the summer of 2022 had an undeniable impact on all the surveyed maritime areas in France. Our study therefore provides valuable insights into the complex mechanisms underlying the ocean–atmosphere interaction and demonstrates the need for an efficient and sustainable operational system combining polar-orbiting and geostationary satellites to monitor the alterations that threaten the oceans in the context of climate change.

Abstract Commercial carotenoid production is dominated by chemical synthesis and plant extraction, both of which are unsustainable and can be detrimental to the environment. A promising alternative for the mass production of carotenoids from both an ecological and commercial perspective is microbial synthesis. To date, C30 carotenoid production in Bacillus subtilis has been achieved using plasmid systems for the overexpression of biosynthetic enzymes. In the present study, we employed a clustered regularly interspaced short palindromic repeat-Cas9 (CRISPR-Cas9) system to develop an efficient, safe, and stable C30 carotenoid-producing B. subtilis strain, devoid of plasmids and antibiotic selection markers. To this end, the expression levels of crtM (dehydrosqualene synthase) and crtN (dehydrosqualene desaturase) genes from Staphylococcus aureus were upregulated by the insertion of three gene copies into the chromosome of B. subtilis. Subsequently, the supply of the C30 carotenoid precursor farnesyl diphosphate (FPP), which is the substrate for CrtMN enzymes, was enhanced by expressing chromosomally integrated Bacillus megaterium-derived farnesyl diphosphate synthase (FPPS), a key enzyme in the FPP pathway, and abolishing the expression of farnesyl diphosphate phosphatase (YisP), an enzyme responsible for the undesired conversion of FPP to farnesol. The consecutive combination of these features resulted in a stepwise increased production of C30 carotenoids. For the first time, a B. subtilis strain that can endogenously produce C30 carotenoids has been constructed, which we anticipate will serve as a chassis for further metabolic engineering and fermentation optimization aimed at developing a commercial scale bioproduction process.

Abstract WHIM Syndrome is a rare immunodeficiency caused by gain-of-function CXCR4 mutations. Here we report a decrease in bone mineral density in 25% of WHIM patients and bone defects leading to osteoporosis in a WHIM mouse model. Imbalanced bone tissue is observed in mutant mice combining reduced osteoprogenitor cells and increased osteoclast numbers. Mechanistically, impaired CXCR4 desensitization disrupts cell cycle progression and osteogenic commitment of skeletal stromal/stem cells, while increasing their pro-osteoclastogenic capacities. Impaired osteogenic differentiation is evidenced in primary bone marrow stromal cells from WHIM patients. In mice, chronic treatment with the CXCR4 antagonist AMD3100 normalizes in vitro osteogenic fate of mutant skeletal stromal/stem cells and reverses in vivo the loss of skeletal cells, demonstrating that proper CXCR4 desensitization is required for the osteogenic specification of skeletal stromal/stem cells. Our study provides mechanistic insights into how CXCR4 signaling regulates the osteogenic fate of skeletal cells and the balance between bone formation and resorption.

The COVID-19 pandemic shed light on the prevailing inequality in the US, as traditionally marginalized groups were disproportionately affected by the disease. This paper seeks to understand how K-12 principals across a southern state in the United States, made decisions in light of these considerations. Specifically, we examined the major decisions principals were responsible for making, the underlying factors influencing these decisions, and the processes they used to make these decisions. We analyzed qualitative data from 173 surveys and 49 interviews using qualitative content analysis. Guided by Smith and Riley's crisis response framework, our findings revealed that principals made critical decisions relevant to addressing equity gaps for students, reopening schools, training teachers for virtual learning, and enforcing state and district mandates. These decisions were often informed by what was in the best interests of students, safety, and the general well-being of their teachers. This study is important because it highlights the factors informing principals' decisions, in addition to informing us about the decisions principals were forced to make throughout the pandemic. The limitations and implications are discussed.

The Central Valley is home to nearly 6.5 million people, and it is the most underserved patient population in California. The need for core services such as comprehensive healthcare is higher than ever, given that twenty-five percent live in poverty, and over fifty percent are Medicaid or uninsured. Currently, there are 133 active physicians per 100,000 people in the Central Valley in comparison with the California state rate of 222 active physicians per 100,000 people. Within the next ten years, California is expected to have a shortfall of up to 4,100 primary-care clinicians.There are approximately 2000 mobile clinics nationwide assisting 6,000,000 people annually. In addition, mobile clinics are viewed as serving those with a barrier to health care. Nationwide, fifty-three percent of low-income adults don’t trust the health care system, twenty-five percent lack transportation, twenty percent go without care due to inability to pay, and eleven percent are uninsured.

Abstract Digital image correlation, deflectometry and digital holography are some of the full-field optical measurement techniques that have matured in recent years. Their use in vibroacoustic applications is gaining attention and there is a need for cataloging their performance in order to provide, to a broad community of users and potential future users, quantitative and qualitative evaluations of these three approaches. This paper presents an experimental comparison of the three optical methods in the context of vibration measurements, along with classical reference measurements provided by an accelerometer and a laser Doppler vibrometer. The study is carried out on two mechanical structures exhibiting various vibration responses when submitted to an impact.

Abstract Background Despite recent advances in genetic engineering tools for effectively regulating and manipulating genes, efficient simultaneous multigene insertion methods have not been established in Bacillus subtilis. To date, multilocus integration systems in B. subtilis, which is one of the main industrial enzyme producers and a GRAS (generally regarded as safe) microbial host, rely on iterative rounds of plasmid construction for sequential insertions of genes into the B. subtilis chromosome, which is tedious and time consuming. Results In this study, we present development and proof-of-concept of a novel CRISPR-Cas9-based genome-editing strategy for the colorimetric detection of one-step multiple gene insertion in B. subtilis. First, up to three copies of the crtMN operon from Staphylococcus aureus, encoding a yellow pigment, were incorporated at three ectopic sites within the B. subtilis chromosome, rendering engineered strains able to form yellow colonies. Second, a single CRISPR-Cas9-based plasmid carrying a highly specific single guide RNA (sgRNA) targeting crtMN operon and a changeable editing template was constructed to facilitate simultaneous insertion of multiple gene-copies through homology-directed repair (HDR). Upon transformation of engineered strains with engineered plasmids, strains harboring up to three gene copies integrated into the chromosome formed white colonies because of the removal of the crtMN operon, clearly distinguishable from yellow colonies harboring undesired genetic modifications. As a result, construction of a plasmid-less, marker-free, high-expression stable producer B. subtilis strain can be completed in only seven days, demonstrating the potential that the implementation of this technology may bring for biotechnology purposes. Conclusions The novel technology expands the genome-editing toolset for B. subtilis and means a substantial improvement over current methodology, offering new application possibilities that we envision should significantly boost the development of B. subtilis as a chassis in the field of synthetic biology.

Deciphering the mechanism of secondary cell wall/SCW formation in plants is key to understanding their development and the molecular basis of biomass recalcitrance. Although transcriptional regulation is essential for SCW formation, little is known about the implication of post-transcriptional mechanisms in this process. Here we report that two bonafide RNA-binding proteins homologous to the animal translational regulator Musashi, MSIL2 and MSIL4, function redundantly to control SCW formation in Arabidopsis. MSIL2/4 interactomes are similar and enriched in proteins involved in mRNA binding and translational regulation. MSIL2/4 mutations alter SCW formation in the fibers, leading to a reduction in lignin deposition, and an increase of 4-O-glucuronoxylan methylation. In accordance, quantitative proteomics of stems reveal an overaccumulation of glucuronoxylan biosynthetic machinery, including GXM3, in the msil2/4 mutant stem. We showed that MSIL4 immunoprecipitates GXM mRNAs, suggesting a novel aspect of SCW regulation, linking post-transcriptional control to the regulation of SCW biosynthesis genes.

Complementary technique to preoperative fMRI and electrical brain stimulation (EBS) for glioma resection could improve dramatically the surgical procedure and patient care. Intraoperative RGB optical imaging is a technique for localizing functional areas of the human cerebral cortex that can be used during neurosurgical procedures. However, it still lacks robustness to be used with neurosurgical microscopes as a clinical standard. In particular, a robust quantification of biomarkers of brain functionality is needed to assist neurosurgeons. We propose a methodology to evaluate and optimize intraoperative identification of brain functional areas by RGB imaging. This consist in a numerical 3D brain model based on Monte Carlo simulations to evaluate intraoperative optical setups for identifying functional brain areas. We also adapted fMRI Statistical Parametric Mapping technique to identify functional brain areas in RGB videos acquired for 12 patients. Simulation and experimental results were consistent and showed that the intraoperative identification of functional brain areas is possible with RGB imaging using deoxygenated hemoglobin contrast. Optical functional identifications were consistent with those provided by EBS and preoperative fMRI. We also demonstrated that a halogen lighting may be particularity adapted for functional optical imaging. We showed that an RGB camera combined with a quantitative modeling of brain hemodynamics biomarkers can evaluate in a robust way the functional areas during neurosurgery and serve as a tool of choice to complement EBS and fMRI.

Introduction: Upon BMP-2 stimulation, the osteoblastic lineage commitment in C2C12 myoblasts is associated with a microenvironmental change that occurs over several days. How does BMP-2 operate a switch in adhesive machinery to adapt to the new microenvironment and to drive bone cell fate is not well understood. Here, we addressed this question for BMP-2 delivered either in solution or physically bound of a biomimetic film, to mimic its presentation to cells via the extracellular matrix (ECM).Methods: Biommetics films were prepared using a recently developed automated method that enable high content studies of cellular processes. Comparative gene expressions were done using RNA sequencing from the encyclopedia of the regulatory elements (ENCODE). Gene expressions of transcription factors, beta chain (1, 3, 5) integrins and cadherins (M, N, and Cad11) were studied using quantitative PCR. ECM proteins and adhesion receptor expressions were also quantified by Western blots and dot blots. Their spatial organization in and around cells was studied using immuno-stainings. The individual effect of each receptor on osteogenic transcription factors and alkaline phosphatase expression were studied using silencing RNA of each integrin and cadherin receptor. The organization of fibronectin was studied using immuno-staining and quantitative microscopic analysis.Results: Our findings highlight a switch of integrin and cadherin expression during muscle to bone transdifferentiation upon BMP-2 stimulation. This switch occurs no matter the presentation mode, for BMP-2 presented in solution or via the biomimetic film. While C2C12 muscle cells express M-cadherin and Laminin-specific integrins, the BMP-2-induced transdifferentiation into bone cells is associated with an increase in the expression of cadherin-11 and collagen-specific integrins. Biomimetic films presenting matrix-bound BMP-2 enable the revelation of specific roles of the adhesive receptors depending on the transcription factor.Discussion: While β3 integrin and cadherin-11 work in concert to control early pSMAD1,5,9 signaling, β1 integrin and Cadherin-11 control RunX2, ALP activity and fibronectin organization around the cells. In contrast, while β1 integrin is also important for osterix transcriptional activity, Cadherin-11 and β5 integrin act as negative osterix regulators. In addition, β5 integrin negatively regulates RunX2. Our results show that biomimetic films can be used to delinate the specific events associated with BMP-2-mediated muscle to bone transdifferentiation. Our study reveals how integrins and cadherins work together, while exerting distinct functions to drive osteogenic programming. Different sets of integrins and cadherins have complementary mechanical roles during the time window of this transdifferentiation.

Background Injuries to the proximal interphalangeal (PIP) joint are common and complex. However, the treatment of osteochondral defects of the head of the proximal phalanx has rarely been described. Herein, we propose a new technique for the management of unicondylar defects of the proximal phalanx that can restore joint amplitudes and provide PIP stability. Methods In this cadaveric feasibility study, unicondylar defects were generated using striking wedges and chisels. First, a transverse tunnel measuring 2 mm in diameter passing through the head of the proximal phalanx was made. A second tunnel at the base of the middle phalanx with the same diameter was then created. The hemitendon of the flexor carpi radialis graft was passed through each of these tunnels. The proximal end of the graft was interposed in the area with a loss of bone substance. The ligamentoplasty was then tensed and fixed by two anchors on the proximal phalanx. Joint amplitudes and frontal stability were measured preoperatively and postoperatively. Results There was no significant change in the joint’s range of motion: preoperatively, the mean mobility arcs were –2° to 113.80°, and they were –2° to 110° after the procedure (P=0.999). There was no significant difference in joint stability (P>0.05). Conclusions Ligamentoplasty with PIP interposition appears to be a possible solution for the management of unicondylar defects of the proximal phalanx. An evaluation of clinical results is planned in order to definitively confirm the validity of this procedure.