Tissue Rigidity Research Articles

Interleukin-1β Modulation of the Mechanobiology of Primary Human Pulmonary Fibroblasts: Potential Implications in Lung Repair.

Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1β and used Atomic Force Microscopy to unveil that IL-1β significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1β stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1β may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1β-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1β provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.

Short De-Etiolation Increases the Rooting of VC801 Avocado Rootstock.

Dark-grown (etiolated) branches of many recalcitrant plant species root better than their green counterparts. Here it was hypothesized that changes in cell-wall properties and hormones occurring during etiolation contribute to rooting efficiency. Measurements of chlorophyll, carbohydrate and auxin contents, as well as tissue compression, histological analysis and gene-expression profiles were determined in etiolated and de-etiolated branches of the avocado rootstock VC801. Differences in chlorophyll content and tissue rigidity, and changes in xyloglucan and pectin in cambium and parenchyma cells were found. Interestingly, lignin and sugar contents were similar, suggesting that de-etiolated branches resemble the etiolated ones in this respect. Surprisingly, the branches that underwent short de-etiolation rooted better than the etiolated ones, and only a slight difference in IAA content between the two was observed. Gene-expression profiles revealed an increase in ethylene-responsive transcripts in the etiolated branches, which correlated with enrichment in xyloglucan hydrolases. In contrast, transcripts encoding pectin methylesterase and pectolyases were enriched in the de-etiolated branches. Taken together, it seems that the short de-etiolation period led to fine tuning of the conditions favoring adventitious root formation in terms of auxin–ethylene balance and cell-wall properties.

Показники еластичності клубово-поперекового м`язу у пацієнтів з болем в нижній частині спини в залежності від наявності синдрому доброякісної гіпермобільності суглобів

Pain in the lower back is a highly urgent problem that leads to a decrease in the quality of life of a large number of patients in the modern world. At the same time, the causes of pain in the lower back are different and their combination has not been sufficiently studied to date. It is known that the presence of benign joint hypermobility syndrome in a patient significantly worsens the course and manifestations of pain in the lower back. One of the components of pain in the lower back is changes in the iliopsoas muscle. This is psoas syndrome. At the same time, the diagnosis of psoas syndrome in practical medicine is complicated by the lack of specific laboratory tests and imaging techniques. The purpose of this work was to study the possibilities of determining the tension of the iliopsoas muscle using shear wave elastometry in patients with pain syndrome in the lower back and the difference between their tensions depending on the presence of benign hypermobility syndrome in patients. Material and methods. We examined 83 patients with lower back pain aged 42.31±1.54 years, 41 were female and 42 were male. To participate in the study, all patients underwent X-ray and ultrasound examination of the hip joints. Patients were excluded from the study in the presence of signs of osteoarthritis. To determine the presence of signs of hypermobility of the joints, we used the criteria of Baiton; the diagnosis was made on condition of obtaining more than 5 points. Among the patients examined by the Bayton criteria, 18 patients were diagnosed with benign joint hypermobility syndrome, among them 13 women and 5 men. As a control group, we selected 15 patients aged 45.6±1.74 years without complaints of pain in the lumbar region of the back and hips and without signs of benign joint hypermobility syndrome. We used shear wave elastometry to determine the stiffness of the distal parts of the lumbosacral muscle. A visual analog scale of pain (from 1 to 10) was used to determine the severity of the pain syndrome. Conclusion. We found that all patients with complaints of pain in the lower back had a significantly higher tension of the iliopsoas muscle in comparison with the group of conditionally healthy patients. The increase in tension had a strong correlation with the severity of pain syndrome according to the data of the visual analogue scale. Indicators of muscle tissue rigidity did not depend on the presence and severity of benign joint hypermobility syndrome

Soft Substrate Promotes Osteosarcoma Cell Self-Renewal, Differentiation, and Drug Resistance Through miR-29b and Its Target Protein Spin 1

Stiffening of the extracellular matrix (ECM) is considered a typical remolding of the microenvironment in multistep tumor progression. However, the molecular mechanisms by which the tumor cell responds to the ECM mechanical cues remain elusive. Here, we demonstrated that microRNA-29b (miR-29b) and its downstream signaling play critical regulatory roles that osteosarcoma cells sense the ECM stiffness to maintain the cancer stem cell-like ability. Polyacrylamide gels with a stiffness of 7, 20, and 55 kPa were used to mimic the rigidity of connective tissue, muscle tissue, and bone tissue. It was found that the stemness properties including self-renewal ability, differentiation potential, and drug resistance of osteosarcoma cells were strongly enhanced with reducing substrate stiffness, whereas spreading area, proliferation, and migration were inhibited. Moreover, miR-29 was obviously downregulated in soft substrate-cultured osteosarcoma cells, and the expression of stemness-related transcription factors (Sox2, Nanog, and Oct4) and the sphere formation ability were significantly inhibited by ectopic expression of miR-29b-5p. The soft substrate-induced miR-29 downregulation could increase Spin 1 expression and activate phosphatidylinositol 3-kinase (PI3K)/Akt and Stat3 signaling, which were suppressed by the increase in miR-29b-5p. Taken together, our results elucidated that miR-29 could be a novel mechanical sensor which manipulates osteosarcoma cell stemness. This finding uncovers the fact that the mechanical cue of the cancer niche could take part in the regulation of cancer progression through operating microRNAs and their downstream signaling.

Differential fibrotic phenotypes of hepatic stellate cells within 3D liver organoids.

Liver fibrosis occurs in most cases of chronic liver disease, which are somewhat common, but also a potentially deadly group of diseases. In vitro modeling of liver fibrosis relies primarily on the isolation of in vivo activated hepatic stellate cells (aHSCs) and studying them in standard tissue culture dishes (two-dimensional [2D]). In contrast, modeling of fibrosis in a biofabricated three-dimensional (3D) construct allows us to study changes to the environment, such as extracellular matrix (ECM) composition and structure, and tissue rigidity. In the current study, we used aHSCs produced through subcultures in 2D and encapsulated them in a 3D collagen gel to form spherical constructs. In parallel, and as a comparison, we used an established HSC line, LX-2, representing early and less severe fibrosis. Compared with LX-2 cells, the aHSCs created a stiffer environment and expressed higher levels of TIMP1 and LOXL2, all of which are indicative of advanced liver fibrosis. Collectively, this study presents a fibrosis model that could be incorporated with multi-cellular models to more accurately reflect the effects of a severe fibrotic environment on liver function.

Development of Scaffolds with Adjusted Stiffness for Mimicking Disease-Related Alterations of Liver Rigidity.

Drug-induced liver toxicity is one of the most common reasons for the failure of drugs in clinical trials and frequent withdrawal from the market. Reasons for such failures include the low predictive power of in vivo studies, that is mainly caused by metabolic differences between humans and animals, and intraspecific variances. In addition to factors such as age and genetic background, changes in drug metabolism can also be caused by disease-related changes in the liver. Such metabolic changes have also been observed in clinical settings, for example, in association with a change in liver stiffness, a major characteristic of an altered fibrotic liver. For mimicking these changes in an in vitro model, this study aimed to develop scaffolds that represent the rigidity of healthy and fibrotic liver tissue. We observed that liver cells plated on scaffolds representing the stiffness of healthy livers showed a higher metabolic activity compared to cells plated on stiffer scaffolds. Additionally, we detected a positive effect of a scaffold pre-coated with fetal calf serum (FCS)-containing media. This pre-incubation resulted in increased cell adherence during cell seeding onto the scaffolds. In summary, we developed a scaffold-based 3D model that mimics liver stiffness-dependent changes in drug metabolism that may more easily predict drug interaction in diseased livers.

Mechanical stimulation in Brachypodium distachyon: Implications for fitness, productivity, and cell wall properties.

Mechanical stimulation, including exposure to wind, is a common environmental variable for plants. However, knowledge about the morphogenetic response of the grasses (Poaceae) to mechanical stimulation and impact on relevant agronomic traits is very limited. Two natural accessions of Brachypodium distachyon were exposed to wind and mechanical treatments. We surveyed a wide range of stem‐related traits to determine the effect of the two treatments on plant growth, development, and stem biomass properties. Both treatments induced significant quantitative changes across multiple scales, from the whole plant down to cellular level. The two treatments resulted in shorter stems, reduced biomass, increased tissue rigidity, delayed flowering, and reduced seed yield in both accessions. Among changes in cell wall‐related features, a substantial increase in lignin content and pectin methylesterase activity was most notable. Mechanical stimulation also reduced the enzymatic sugar release from the cell wall, thus increasing biomass recalcitrance. Notably, treatments had a distinct and opposite effect on vascular bundle area in the two accessions, suggesting genetic variation in modulating these responses to mechanical stimulation. Our findings highlight that exposure of grasses to mechanical stimulation is a relevant environmental factor affecting multiple traits important for their utilization in food, feed, and bioenergy applications.

Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts.

SummaryThe link between integrin activity regulation and cellular mechanosensing of tissue rigidity, especially on different extracellular matrix ligands, remains poorly understood. Here, we find that primary mouse mammary gland stromal fibroblasts (MSFs) are able to spread efficiently, generate high forces, and display nuclear YAP on soft collagen-coated substrates, resembling the soft mammary gland tissue. We describe that loss of the integrin inhibitor, SHARPIN, impedes MSF spreading specifically on soft type I collagen but not on fibronectin. Through quantitative experiments and computational modeling, we find that SHARPIN-deficient MSFs display faster force-induced unbinding of adhesions from collagen-coated beads. Faster unbinding, in turn, impairs force transmission in these cells, particularly, at the stiffness optimum observed for wild-type cells. Mechanistically, we link the impaired mechanotransduction of SHARPIN-deficient cells on collagen to reduced levels of collagen-binding integrin α11β1. Thus integrin activity regulation and α11β1 play a role in collagen-specific mechanosensing in MSFs.

Investigation of PRDM7 and PRDM12 expression pattern during mouse embryonic development by using a modified passive clearing technique

Recent developments in tissue clearing methods such as CLARITY (Clear Lipid-exchanged Acrylamide-hybridized Rigid Imaging/Immunostaining/In situ hybridization-compatible Tissue hYdrogel) have allowed for the three-dimensional analysis of biological structures in whole, intact tissue, providing greater understanding of spatial relationships and biological circuits. Nonetheless, studies have reported issues with maintaining structural integrity and preventing tissue disintegration, preventing the wide application of these techniques to fragile tissues such as developing embryos. Here, we present optimized passive clearing techniques, mPACT-A, that improve tissue rigidity without the expense of optical transparency. We also present a further modified mPACT-A protocol that is specifically optimized for handling mouse embryos, which are small and fragile, such that they easily dismantle when processed via established tissue clearing methods. We demonstrate proof-of-concept by investigating the expression of two relatively understudied PRDM proteins, PRDM7 and PRDM12, in intact cleared mouse embryos at various stages of development. We observed strong PRDM7 and PRDM12 expression in the developing mouse nervous system, suggestive of potential roles in neural development that will be tested in future functional studies.

Magnetic resonance elastography quantification of the solid-to-fluid transition of liver tissue due to decellularization

Maintenance of tissue extracellular matrix (ECM) and its biomechanical properties for tissue engineering is one of the substantial challenges in the field of decellularization and recellularization. Preservation of the organ-specific biomatrix is crucial for successful recellularization to support cell survival, proliferation, and functionality. However, understanding ECM properties with and without its inhabiting cells as well as the transition between the two states lacks appropriate test methods capable of quantifying bulk viscoelastic parameters in soft tissues.We used compact magnetic resonance elastography (MRE) with 400, 500, and 600 Hz driving frequency to investigate rat liver specimens for quantification of viscoelastic property changes resulting from decellularization. Tissue structures in native and decellularized livers were characterized by collagen and elastin quantification, histological analysis, and scanning electron microscopy.Decellularization did not affect the integrity of microanatomy and structural composition of liver ECM but was found to be associated with increases in the relative amounts of collagen by 83-fold (37.4 ± 17.5 vs. 0.5 ± 0.01 μg/mg, p = 0.0002) and elastin by approx. 3-fold (404.1 ± 139.6 vs. 151.0 ± 132.3 μg/mg, p = 0.0046). Decellularization reduced storage modulus by approx. 9-fold (from 4.9 ± 0.8 kPa to 0.5 ± 0.5 kPa, p < 0.0001) and loss modulus by approx. 7-fold (3.6 kPa to 0.5 kPa, p < 0.0001), indicating a marked loss of global tissue rigidity as well as a property shift from solid towards more fluid tissue behavior (p = 0.0097).Our results suggest that the rigidity of liver tissue is largely determined by cellular components, which are replaced by fluid-filled spaces when cells are removed. This leads to an overall increase in tissue fluidity and a viscous drag within the relatively sparse remaining ECM. Compact MRE is an excellent tool for quantifying the mechanical properties of decellularized biological tissue and a promising candidate for useful applications in tissue engineering.

Midline raphe scroti artery flap for penile shaft reconstruction

Aim: To investigate a novel method for penile shaft reconstruction. Methods: Penile tissue loss is caused by injury, infections, obesity or cancer resection. Reconstructive techniques comprise skin grafts with the risk of scarring and tissue rigidity. To develop an alternative reconstructive procedure, the pertinent vascular anatomy was studied on fresh cadavers instilled with red latex, which permitted the design of the midline raphe scrotal artery flap (MiRA). After anatomical proof-of-feasibility, penile reconstruction was performed in adult patients with classic buried penis or after cancer resection. Results: Anatomical studies revealed a novel finding of two scrotal septa, each with the terminal branch of the internal pudendal artery. Pedicled on both arteries, a neurovascular island flap could be harvested. In the presence of excess scrotal tissue, the entire circumference of the penile shaft could be covered by this flap. Patients with penile skin defects and excess scrotal tissue were eligible for flap harvest. The flap was raised either as an extended island flap pedicled on both septal arteries for complete penile shaft coverage, or as a VY-flap for partial reconstruction; the donor site was closed primarily. Post-operative complications included swelling or partial wound dehiscence. There were no flap losses or perfusion problems. Patients reported full sensitivity to the penile shaft skin and sufficient skin elasticity for erection. Conclusion: The MiRA flap is a technically safe neurovascular flap suitable for the reconstruction of partial or full defects of the penile shaft, such as after type III buried penis surgery, and provides sufficiently elastic and sensitive skin for functional penile reconstruction.

Changes in spinal cord stiffness in the course of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis

Experimental autoimmune encephalomyelitis (EAE) is a commonly used mouse model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS) characterized by demyelination leading to brain and spinal cord malfunctions. We postulate that not only biological but also biomechanical properties play an important role in impairements of CNS function. Atomic force microscopy (AFM) was applied to investigate mechanical properties of spinal cords collected from EAE mice in preonset, onset, peak, and chronic disease phases. Biomechanical changes were compared with histopathological alterations observed in the successive phases. The deformability of gray matter did not change, while rigidity of white matter increased during the onset phase, remained at the same level in the peak phase and decreased in the chronic phase. Inflammatory infiltration and laminin content accompanied the tissue rigidity increase, whereas demyelination and axonal damage showed an opposite effect. The increase in white matter rigidity can be regarded as an early signature of EAE.

Usefulness of real-time elastography for diagnosing lymph node metastasis of skin cancer: does elastography potentially eliminate the need for sentinel lymph node biopsy in squamous cell carcinoma?

The metastatic involvement of regional lymph nodes is the most important prognostic factor for overall survival of skin cancer patients. The sonographic technique of freehand real-time tissue elastography (RTE), which displays tissue rigidity as a colour overlay of the tissue image, was developed. Our purpose was to evaluate the benefit of RTE for detecting lymph node metastases of skin cancer non-invasively before operation. We first selected lymph nodes of skin cancer patients which had already been diagnosed by biopsy as being reactive or metastatic, and then retrospectively collected images of RTE and B-mode and colour Doppler ultrasound on those lymph nodes performed preoperatively. Twenty-one lymph nodes from 12 patients with squamous cell carcinoma (SCC), 23 lymph nodes from 14 patients with malignant melanoma (MM) and 14 lymph nodes from six patients with extramammary Paget disease (Paget) were investigated. Elastographic images were assessed on a scale of one to four according to the percentage of high elasticity (hard) area (HEA) in the lymph node. In all three skin cancers, lymph nodes evaluated as grade 3 or 4 by RTE were metastatic. All lymph nodes evaluated as grade 1 or 2 by RTE were reactive in SCC, whereas some lymph nodes evaluated as grade 1 or 2 were metastatic in MM and Paget. Real-time tissue elastography may aid in distinguishing reactive lymph nodes from metastatic ones especially in SCC.

The optimization of the length of the lower limbs after hip arthroplasty.

The purpose of this research was to evaluate the effectiveness of hip joint arthroplasty in patients with different correction of the length of the legs and identifying factors that influence the outcome. We analyzed 93 patientsoperated upon with an initial shortening of the limb length by more than 3cm. The difference in the length of the limbs ranged from 3 to 12cm, which averaged 5cm. Immediately after surgery and after three to12months, a control examination was performed with measurement of the length of the lower extremities and the function of the joint, using the Harris scale. The study revealed three versions of the result of the correction of the length of the limb after hip joint arthroplasty: saving limb shortening (n= 16 (17%) with HHS 80 (95% CI, 78.4 to 83.4%); full restoration of limb length (n= 70 (75,5%) with HHS 78 (95% CI, 74.6 to 80.2%); excess limb lengthening (n= 7 (7.5%) with HHS 68 (95% CI, 63.5 to 73.5%). So that, incorrect lengthening of the lower limb during arthroplasty leads to lameness, discomfort, muscle tension, which ultimately leads to pain. Optimal result of hip arthroplasty and ensure the necessary amplitude of movements, it is advisable to use prediction criteria of the leveling of the limb length, which are: the duration of the disease, presence of consequences of previous operations, gender, age, degree of tissue rigidity, severity of hip-spine syndrome, and scoliotic deformity.

Mechanical Heterogeneity in Tissues Promotes Rigidity and Controls Cellular Invasion

We study the influence of cell-level mechanical heterogeneity in epithelial tissues using a vertex-based model. Heterogeneity is introduced into the cell shape index (p_{0}) that tunes the stiffness at a single-cell level. The addition of heterogeneity can always enhance the mechanical rigidity of the epithelial layer by increasing its shear modulus, hence making it more rigid. There is an excellent scaling collapse of our data as a function of a single scaling variable f_{r}, which accounts for the overall fraction of rigid cells. We identify a universal threshold f_{r}^{*} that demarcates fluid versus solid tissues. Furthermore, this rigidity onset is far below the contact percolation threshold of rigid cells. These results give rise to a separation of rigidity and contact percolation processes that leads to distinct types of solid states. We also investigate the influence of heterogeneity on tumor invasion dynamics. There is an overall impedance of invasion as the tissue becomes more rigid. Invasion can also occur in an intermediate heterogeneous solid state that is characterized by significant spatial-temporal intermittency.

Effectiveness of achillotomy in children with arthrogryposis

Introduction. Ponseti method is a widespread treatment for clubfoot in children with arthrogryposis. Closed subcutaneous achillotomy in these patients could not completely rectify the equinus deformity due to tissue rigidity which often leads to reconsideration of the tenotomy principles.&#x0D; Aim. This study aimed to formulate the anticipating criteria to assess the effectiveness of achillotomy in order to develop a different achillotomy approach for children with arthrogryposis.&#x0D; Materials and methods. This study retrospectively analyzed closed subcutaneous achillotomy in 28 patients (56 feet) with arthrogryposis. The mean age of the patients was 5.4 months (range 2–8 months). The children were subdivided into two groups according to the residual equinus deformity after the completion of Ponseti serial casting. All patients were physically and radiographically examined.&#x0D; Results and discussion. The first group included 12 patients (24 feet), which achieved foot neutral position or dorsiflexion ≥5° after achillotomy. The second group consisted of 16 patients (32 feet) with residual equinus after achillotomy who required surgery. X-ray images showed that the patients in the second group had significantly wider tibiocalcaneal angle and smaller talocalcaneal angle in lateral view (р &lt; 0.01). The correction values of the equinus deformity after achillotomy in the children with arthrogryposis were greatly limited: 27° (20°–30°) and 19° (10°–30°) in the first and second groups, respectively.&#x0D; Conclusion. Closed subcutaneous achillotomy for effective equinus elimination during clubfoot treatment by Ponseti method should be performed only after complete correction at the level of tarsal joints. X-ray examination of the feet is recommended for the children with arthrogryposis in order to evaluate the talocalcaneal divergence and heel position more comprehensively. Furthermore, the values of tibiocalcaneal and talocalcaneal angles in lateral view prior to achillotomy are essential prognostic factors of its effectiveness. Moreover, the severity of equinus contracture should be considered prior to achillotomy. Achilles tenotomy is inappropriate if equinus deformity exceeds 30°. In such cases, open surgery should be considered.

A Novel Technique Enables Quantifying the Molecular Interaction of Solvents with Biological Tissues

The pharmaceutical industry uses various solvents to increase drug penetrability to tissues. The solvent’s choice affects the efficacy of a drug. In this paper, we provide an unprecedented means of relating a solvent to a tissue quantitatively. We show that the solvents induce reorientation of the tissue surface molecules in a way that favors interaction and, therefore, penetrability of a solvent to a tissue. We provide, for the first time, a number for this tendency through a new physical property termed Interfacial Modulus (Gs). Gs, which so far was only predicted theoretically, is inversely proportional to such interactions. As model systems, we use HeLa and HaCaT tissue cultures with water and with an aqueous DMSO solution. The measurements are done using Centrifugal Adhesion Balance (CAB) when set to effective zero gravity. As expected, the addition of DMSO to water reduces Gs. This reduction in Gs is usually higher for HaCaT than for HeLa cells, which agrees with the common usage of DMSO in dermal medicine. We also varied the rigidities of the tissues. The tissue rigidity is not expected to relate to Gs, and indeed our results didn’t show a correlation between these two physical properties.

Assessing Tumor Mechanics by MR Elastography at Different Strain Levels.

Malignant tumors are associated with increased tissue rigidity, which can be an indicator of tumor progression. MR elastography (MRE) has the potential to study the variations of tumor mechanical properties. ex vivo studies have shown the ability of MRE to assess increase of mechanical properties; nevertheless, it has not yet been observed in vivo. To propose a method to assess the increase in mechanical properties of tumors in vivo under static external compression using MRE. Prospective, experimental study. Forty-six SCID mice with subcutaneous tumor implantation (patient-derived hepatocellular carcinoma xenografts, Model 1, n = 13, and Model 2, n = 33). 7.0T; a spin echo sequence was used for anatomical images and a modified spin echo sequence for elastography acquisitions with a vibration frequency of 600 Hz. An inflatable balloon was placed on the abdomen to apply a load to the tumor. MRE acquisitions were performed at the basal state and at increasing compression levels. Anatomical images were used to calculate the octahedral shear strain between the tumor at the basal strain state and each strain level. For six mice (Model 2), each static preloading scan was acquired twice consecutively without moving the mouse to evaluate repeatability. Statistical Tests: The Bland-Altman method was used to assess repeatability. Correlations between tumor stiffness and deformation were evaluated with Pearson correlation coefficients. For stiffness (G*), a good repeatability was obtained between the acquisitions; the limits of agreement of the Bland-Altman test were [-10.17%; 11.49%] with an absolute bias of 0.66%. A significant correlation between tumor stiffness and deformation was observed for both models (Model 1: r = 0.57, P < 0.0001 and Model 2: r = 0.31, P < 0.0001). We establish that tumor mechanical properties can increase under mechanical compression. This increase can effectively be monitored using a proposed MRE setup. 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1982-1989.

Oscillatory cortical forces promote three dimensional cell intercalations that shape the murine mandibular arch

Multiple vertebrate embryonic structures such as organ primordia are composed of confluent cells. Although mechanisms that shape tissue sheets are increasingly understood, those which shape a volume of cells remain obscure. Here we show that 3D mesenchymal cell intercalations are essential to shape the mandibular arch of the mouse embryo. Using a genetically encoded vinculin tension sensor that we knock-in to the mouse genome, we show that cortical force oscillations promote these intercalations. Genetic loss- and gain-of-function approaches show that Wnt5a functions as a spatial cue to coordinate cell polarity and cytoskeletal oscillation. These processes diminish tissue rigidity and help cells to overcome the energy barrier to intercalation. YAP/TAZ and PIEZO1 serve as downstream effectors of Wnt5a-mediated actomyosin polarity and cytosolic calcium transients that orient and drive mesenchymal cell intercalations. These findings advance our understanding of how developmental pathways regulate biophysical properties and forces to shape a solid organ primordium.

Ultrasound imaging of abdominal sarcoidosis: State of the art.

Since it has been recognized that sarcoidosis (SA) is not an exclusive disorder of the lungs but can also affect other organs such as the liver and spleen, efforts have been made to define specific imaging criteria for the diagnosis of the single organ involvement, and the concept has been reinforced that the exclusion of alternative causes is important to achieve the correct diagnosis. Ultrasound (US) is a useful tool to evaluate patients with suspected abdominal SA, such as of the liver, spleen, kidney, pancreas and other organs, showing findings such as organomegaly, focal lesions and lymphadenopathy. While the diagnosis of abdominal SA is more predictable in the case of involvement of other organs (e.g., lungs), the problem is more complex in the case of isolated abdominal SA. The recent use of contrast-enhanced ultrasound and endoscopic ultrasound elastography has provided additional information about the enhancement patterns and tissue rigidity in abdominal SA. Here we critically review the role of US in abdominal SA, reporting typical findings and limitations of current evidence and by discussing future perspectives of study.