Dynamics of centipede locomotion revealed by large-scale traction force microscopy.

We present a novel approach to traction force microscopy (TFM) for studying the locomotion of 10 cm long walking centipedes on soft substrates. Leveraging the remarkable elasticity and ductility of kudzu starch gels, we use them as a deformable gel substrate, providing resilience against the centipedes' sharp leg tips. By optimizing fiducial marker size and density and fine-tuning imaging conditions, we enhance measurement accuracy. Our TFM investigation reveals traction forces along the centipede's longitudinal axis that effectively counterbalance inertial forces within the 0-10 mN range, providing the first report of non-vanishing inertia forces in TFM studies. Interestingly, we observe waves of forces propagating from the head to the tail of the centipede, corresponding to its locomotion speed. Furthermore, we discover a characteristic cycle of leg clusters engaging with the substrate: forward force (friction) upon leg tip contact, backward force (traction) as the leg pulls the substrate while stationary, and subsequent forward force as the leg tip detaches to reposition itself in the anterior direction. This work opens perspectives for TFM applications in ethology, tribology and robotics.

Safety of Inulin and Sinistrin: Combining Several Sources for Pharmacovigilance Purposes.

Introduction: Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome. Objective: To assess the safety of inulin and sinistrin use in France. Methods: We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin: first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin. Results: From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign. Conclusion: Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches.

Migrating Epithelial Monolayer Flows Like a Maxwell Viscoelastic Liquid.

We perform a bidimensional Stokes experiment in an active cellular material: an autonomously migrating monolayer of Madin-Darby canine kidney epithelial cells flows around a circular obstacle within a long and narrow channel, involving an interplay between cell shape changes and neighbor rearrangements. Based on image analysis of tissue flow and coarse-grained cell anisotropy, we determine the tissue strain rate, cell deformation, and rearrangement rate fields, which are spatially heterogeneous. We find that the cell deformation and rearrangement rate fields correlate strongly, which is compatible with a Maxwell viscoelastic liquid behavior (and not with a Kelvin-Voigt viscoelastic solid behavior). The value of the associated relaxation time is measured as τ=70±15 min, is observed to be independent of obstacle size and division rate, and is increased by inhibiting myosin activity. In this experiment, the monolayer behaves as a flowing material with a Weissenberg number close to one which shows that both elastic and viscous effects can have comparable contributions in the process of collective cell migration.

A new agarose-based microsystem to investigate cell response to prolonged confinement.

Emerging evidence suggests the importance of mechanical stimuli in normal and pathological situations for the control of many critical cellular functions. While the effect of matrix stiffness has been and is still extensively studied, few studies have focused on the role of mechanical stresses. The main limitation of such analyses is the lack of standard in vitro assays enabling extended mechanical stimulation compatible with dynamic biological and biophysical cell characterization. We have developed an agarose-based microsystem, the soft cell confiner, which enables the precise control of confinement for single or mixed cell populations. The rigidity of the confiner matches physiological conditions and its porosity enables passive medium renewal. It is compatible with time-lapse microscopy, in situ immunostaining, and standard molecular analyses, and can be used with both adherent and non-adherent cell lines. Cell proliferation of various cell lines (hematopoietic cells, MCF10A epithelial breast cells and HS27A stromal cells) was followed for several days up to confluence using video-microscopy and further documented by Western blot and immunostaining. Interestingly, even though the nuclear projected area was much larger upon confinement, with many highly deformed nuclei (non-circular shape), cell viability, assessed by live and dead cell staining, was unaffected for up to 8 days in the confiner. However, there was a decrease in cell proliferation upon confinement for all cell lines tested. The soft cell confiner is thus a valuable tool to decipher the effects of long-term confinement and deformation on the biology of cell populations. This tool will be instrumental in deciphering the impact of nuclear and cytoskeletal mechanosensitivity in normal and pathological conditions involving highly confined situations, such as those reported upon aging with fibrosis or during cancer.

Fast determination of coarse-grained cell anisotropy and size in epithelial tissue images using Fourier transform.

Mechanical strain and stress play a major role in biological processes such as wound healing or morphogenesis. To assess this role quantitatively, fixed or live images of tissues are acquired at a cellular precision in large fields of views. To exploit these data, large numbers of cells have to be analyzed to extract cell shape anisotropy and cell size. Most frequently, this is performed through detailed individual cell contour determination, using so-called segmentation computer programs, complemented if necessary by manual detection and error corrections. However, a coarse-grained and faster technique can be recommended in at least three situations: first, when detailed information on individual cell contours is not required; for instance, in studies which require only coarse-grained average information on cell anisotropy. Second, as an exploratory step to determine whether full segmentation can be potentially useful. Third, when segmentation is too difficult, for instance due to poor image quality or too large a cell number. We developed a user-friendly, Fourier-transform-based image analysis pipeline. It is fast (typically 10^{4} cells per minute with a current laptop computer) and suitable for time, space, or ensemble averages. We validate it on one set of artificial images and on two sets of fully segmented images, one from a Drosophila pupa and the other from a chicken embryo; the pipeline results are robust. Perspectives include in vitro tissues, nonbiological cellular patterns such as foams and xyz stacks.

[Tubular renal acidosis]. / Les acidoses tubulaires rénales.

Renal tubular acidosis (RTAs) are a group of metabolic disorders characterized by metabolic acidosis with normal plasma anion gap. There are three main forms of RTA: a proximal RTA called type II and a distal RTA (type I and IV). The RTA type II is a consequence of the inability of the proximal tubule to reabsorb bicarbonate. The distal RTA is associated with the inability to excrete the daily acid load and may be associated with hyperkalaemia (type IV) or hypokalemia (type I). The most common etiology of RTA type IV is the hypoaldosteronism. The RTAs can be complicated by nephrocalcinosis and obstructive nephrolithiasis. Alkalinization is the cornerstone of treatment.

[Contribution of imaging in the diagnosis of epiploic appendagitis]. / Apport de l'imagerie dans le diagnostic des appendagites épiploïques.

INTRODUCTION: Primary epiploic appendagitis is known to be a rare finding among causes of acute abdomen. Depending on location, it may mimic several disorders such as colonic diverticulitis and acute appendicitis. Diagnosis is sometimes performed during surgery. METHODS: This is a retrospective descriptive study. The authors report the contribution of imaging for the diagnosis of appendagitis in seven patients investigated between July 2010 and April 2013 by abdominal and pelvic ultrasound or computed tomography (CT). RESULTS: CT scan confirmed the diagnosis in six patients avoiding unnecessary surgery and hospitalization. The seventh patient was a pregnant woman in whom the diagnosis of appendagitis was made during surgery for appendicitis. CONCLUSION: Appendagitis is a rare cause of acute abdominal pain. Outcome is favorable with medical treatment only. Abdominal ultrasound and CT are helpful diagnostic tests avoiding useless surgical procedure.

[Colonic amoebiasis simulating a cecal tumor: case report]. / Amœbome colique simulant une tumeur cæcale : à propos d'un cas.

Colonic ameboma is a rare inflammatory pseudo-tumor of the colon that can mimic cancer development. This case was located in the cecum and appeared malignant from a macroscopic view. Accordingly a right hemicolectomy was performed, followed by an end-to-side ileocolic anastomosis. The pathology study enabled us to correct the diagnosis and affirm its amebic origin.

[Recurrence of hydatid cyst of liver: predictive factors: Tunisian experience]. / Les facteurs prédictifs de récidive du kyste hydatique du foie : l'expérience tunisienne.

Cystic echinococcosis is a public health problem. Surgery represents the basic treatment and the surgeon is regularly faced with the choice of the appropriate surgical procedure (radical versus conservative surgical approach). The conservative procedure is safe and easy but can lead to a recurrence in the site of residual cavity. The aim of this study was to evaluate the predictive factors of the recurrence of hepatic hydatid cysts, to optimize surgical management and to implement preventive measures. The current retrospective study included 391 patients with hepatic hydatid cysts operated at our institution from 1996 to 2006. The diagnosis of recurrence was suspected by radiological survey and confirmed at laparotomy. The univariate study of predictive factors of recurrence was based on the Fisher test and the multivariate one on the logistic regression model. The recurrence rate reached 12% in our study with an average period of 50 months. Univariate analysis showed that the predictive factors of recurrence were: the rural origin of patients, the voluminous cysts larger than 7 cm, and unilocular hydatid cyst. Multivariate analysis showed that only voluminous cysts and unilocular ones were the predictive factors of recurrence. The unilocular and voluminous hydatid cysts represent the cysts that relapse frequently because of their immunogenic character and the presence of exocysts in the pericysts. This is very important for the therapeutic strategy the main aim of which is to prevent the recurrence.

Microarray analysis reveals overexpression of IBSP in human carotid plaques.

PURPOSE: Vascular calcification was considered to be a passive, degenerative, and end-stage process of vascular disease. However, bone associated proteins such as bone morphogenetic proteins, osteopontin, osteonectin, osteocalcin, and matrix Gla protein (MGP) have been found in the calcified atherosclerotic lesions. We studied by microarray analysis whether intact tissue and carotid plaque from the same patient differ in transcriptional profiling in response to arterial calcification. MATERIAL AND METHODS: mRNA gene expression was measured by an Affymetrix GeneChip Human Gene 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 68 specimens of endarterectomy from 34 patients. RESULTS: Integrin-binding sialoprotein (IBSP) was found to be differentially expressed. IBSP mRNA is over expressed in atheroma plaque (3.74 fold, p = 1.41E-09) in an intraindividual comparison. Besides, Carbonic anhydrase II (CA2) which known to be a putative calcification inhibitory molecule is over expressed more than 1.7 fold in carotid plaque (p = 1.26E-06). CONCLUSION: Although further evidence is needed, our results support previously available data. To our knowledge, this is the first report comparing gene expression between intact arterial tissue and carotid plaque using microarray analysis in order to identify calcification related genes. We suggest that plaques show a more pronounced induction of IBSP that may cause arterial calcification.

4D traction force microscopy reveals asymmetric cortical forces in migrating Dictyostelium cells.

We present a 4D (x; y; z; t) force map of Dictyostelium cells crawling on a soft gel substrate. Vertical forces are of the same order as the tangential ones. The cells pull the substratum upward along the cell, medium, or substratum contact line and push it downward under the cell except for the pseudopods. We demonstrate quantitatively that the variations in the asymmetry in cortical forces correlates with the variations of the direction and speed of cell displacement.

Epidemiological study, immunohistochemistry and in situ hybridization studies of nasopharyngeal carcinomas: a Tunisian report.

Nasopharyngeal carcinomas (NPC) are a significant problem of public health in Tunisia. They are particular because of their characteristic geographic distribution. The aims of this study were, first, to appreciate the presence of Epstein-Barr virus (EBV) genome by immunohistochemistry (IHC) and in situ hybridization (ISH) and to compare their benefits to NPC diagnosis and, secondly, to verify the relation between NPC and factors bound to the food and environment conditions. Biopsies, recruited at the department of pathology of EPS Charles Nicolle at Tunis, were analyzed for EBV genome presence by ISH of EBV-encoded small RNA1 (EBER1). IHC was done with encoded nuclear antigen (EBNA1), latent membrane proteins (LMP1), and antigen BZ1 anti-Z EBV-replication activator (ZEBRA). An epidemiological study based upon the analysis of a detailed questionnaire submitted to patients (all from the north of Tunisia) and 60 witnesses was done. The statistic analysis was realised by SPSS Windows 11.5 Advanced Statistics. All samples were classified as Undifferentiated Carcinoma of Nasopharyngeal type (UCNT). We found a sex ratio of 2 with a bimodal repartition. ISH showed 96.6% positive samples. IHC revealed the EBV in 90% of cases and 66.7%, respectively, with EBNA1 and LMP1. The statistic analysis showed a meaningful relation (P<0.05, OR>3) between NPC and dietary factors (spices and piquant condiment), alcohol and the water quality.

[Primary hydatid cyst of the psoas muscle: description of 9 cases in Tunisia and review of the literature]. / Kyste hydatique primitif du psoas: 9 cas tunisiens et revue de la littérature.

The psoas muscle is an uncommon location for hydatid cyst accounting for only 1 to 3% of cases. The purpose of this report is to describe the epidemiologic, clinical, paraclinical, and therapeutic features of primary hydatid cyst of the psoas muscle. A retrospective study conducted in Surgery Department A at the Rabta Hospital in Tunisia compiled a total of 9 cases of primary hydatid cyst of the psoas muscle treated between 1980 and 2006. There were 6 men and 3 women with a mean age of 42.8 years. Symptomatology was nonspecific with pain in 6 cases. Discovery was coincidental in two cases. Clinical examination detected a mass in the presents of an abdominal mass in 7 cases. Radiologic findings (ultrasound and/or CT scan) confirmed diagnosis in 8 cases. In one case a mistaken diagnosis of psoas muscle abscess was made in a patient with an infected hydatid cyst. Serological tests were performed in 4 cases and were positive in 3. All patients underwent surgical treatment. The extraperitoneal approach (Leriche) was used in 7 cases and the transperitoneal approach via median laparotomy in 2. In all cases the surgical procedure consisted of partial cystectomy leaving a part of the pericystic against neurovascular structures. There was no operative mortality. The only postoperative complication was urinary infection in one patient. Mean follow-up was 2.5 years. One local recurrence was observed 4 years after surgical treatment and required reoperation.

Changes in the magnitude and distribution of forces at different Dictyostelium developmental stages.

The distribution of forces exerted by migrating Dictyostelium amebae at different developmental stages was measured using traction force microscopy. By using very soft polyacrylamide substrates with a high fluorescent bead density, we could measure stresses as small as 30 Pa. Remarkable differences exist both in term of the magnitude and distribution of forces in the course of development. In the vegetative state, cells present cyclic changes in term of speed and shape between an elongated form and a more rounded one. The forces are larger in this first state, especially when they are symmetrically distributed at the front and rear edge of the cell. Elongated vegetative cells can also present a front-rear asymmetric force distribution with the largest forces in the crescent-shaped rear of the cell (uropod). Pre-aggregating cells, once polarized, only present this last kind of asymmetric distribution with the largest forces in the uropod. Except for speed, no cycle is observed. Neither the force distribution of pre-aggregating cells nor their overall magnitude are modified during chemotaxis, the later being similar to the one of vegetative cells (F(0) approximately 6 nN). On the contrary, both the force distribution and overall magnitude is modified for the fast moving aggregating cells. In particular, these highly elongated cells exert lower forces (F(0) approximately 3 nN). The location of the largest forces in the various stages of the development is consistent with the myosin II localization described in the literature for Dictyostelium (Yumura et al.,1984. J Cell Biol 99:894-899) and is confirmed by preliminary experiments using a GFP-myosin Dictyostelium strain.

Kyste hydatique primitif du psoas : 9 cas tunisiens et revue de la litterature

Le muscle psoas est une localisation exceptionnelle du kyste hydatique ne representant que 1 a 3des cas. Le but de ce travail est d'etudier les caracteristiques epidemio- logiques; cliniques; paracliniques et therapeutiques de cette entite. Notre etude est retrospective consecutive portant sur 9 cas de kystes hydatiques primitifs du psoas colliges entre 1980 et 2006 dans le service de chirurgie A de l'Hopital La Rabta. Il s'agissait de 6 hommes et 3 femmes dont l'age moyen etait de 42;8 ans. La symptomatologie etait atypique dominee par les douleurs retrouvees dans 6 cas. La decouverte etait fortuite dans deux cas. L'examen physique retrouvait une masse du flanc dans 7 cas. Le diagnostic etait confirme par la radiologie (echographie et/ou tomodensitometrie) dans 8 cas. Dans 1 cas; le diagnostic d'abces du psoas etait pose a tort chez un patient porteur d'un kyste hydatique infecte. La serologie hydatique pratiquee dans 4 cas etait positive dans 3 cas. Tous les patients etaient operes. La voie d'abord etait extra peritoneale (Leriche) dans 7 cas et transperitoneale a travers une laparotomie mediane dans 2 cas. Le geste a consiste dans tous les cas en une kystectomie partielle laissant une calotte de perikyste contre les elements vasculo-nerveux. La mortalite etait nulle. Un seul patient s'est complique en postoperatoire d'une infection urinaire. Le suivi moyen etait de 2;5 ans. Au cours de la surveillance postoperatoire; une seule recidive locale etait diagnostiquee a 4 ans postoperatoire ayant necessite une nouvelle intervention

Periodic adhesive fingers between contacting cells.

We study in detail the properties of fingers, a particular type of cell-cell adhesive structures appearing in adherens junctions. These periodic patterns break the symmetry of cell-cell contacts. We show that finger formation is driven by cadherin interactions and actin growth. A theoretical model is introduced in which the growth of fingers is limited by membrane tension. The steady shape and formation kinetics of fingers are experimentally measured and compared with the theoretical predictions.

Membrane and acto-myosin tension promote clustering of adhesion proteins.

Physicists have studied the aggregation of adhesive proteins, giving a central role to the elastic properties of membranes, whereas cell biologists have put the emphasis on the cytoskeleton. However, there is a dramatic lack of experimental studies probing both contributions on cellular systems. Here, we tested both mechanisms on living cells. We compared, for the same cell line, the growth of cadherin-GFP patterns on recombinant cadherin-coated surfaces, with the growth of vinculin-GFP patterns on extracellular matrix protein-coated surfaces by using evanescent wave microscopy. In our setup, cadherins are not linked to actin, whereas vinculins are. This property allows us to compare formation of clusters with proteins linked or not to the cytoskeleton and thus study the role of membrane versus cytoskeleton in protein aggregation. Strikingly, the motifs we obtained on both surfaces share common features: they are both elongated and located at the cell edges. We showed that a local force application can impose this symmetry breaking in both cases. However, the origin of the force is different as demonstrated by drug treatment (butanedione monoxime) and hypotonic swelling. Cadherins aggregate when membrane tension is increased, whereas vinculins (cytoplasmic proteins of focal contacts) aggregate when acto-myosin stress fibers are pulling. We propose a mechanism by which membrane tension is localized at cell edges, imposing flattening of membrane and enabling aggregation of cadherins by diffusion. In contrast, cytoplasmic proteins of focal contacts aggregate by opening cryptic sites in focal contacts under acto-myosin contractility.