Bone resorption by osteoclasts involves fine tuning of RHOA activity by its microtubule-associated exchange factor GEF-H1.

Bone health is controlled by the balance between bone formation by osteoblasts and degradation by osteoclasts. A disequilibrium in favor of bone resorption leads to osteolytic diseases characterized by decreased bone density. Osteoclastic resorption is dependent on the assembly of an adhesion structure: the actin ring, also called podosome belt or sealing zone, which is composed of a unique patterning of podosomes stabilized by microtubules.

Detection of Brain Metastases by Contrast-Enhanced MRI: Comparison of Gadopiclenol and Gadobenate in a Mouse Model.

Objectives: The aim of this study was to evaluate the capacity of gadopiclenol, a high-relaxivity gadolinium-based contrast agent to detect brain metastases in mice as a function of dose (0.08 mmol/kg or 0.1 mmol/kg) compared with gadobenate at 0.

Gender inequality, women's empowerment, and adolescent birth rates in 363 Latin American cities.

Background: Gender inequality is high in Latin America (LA). Empowering girls and young women and reducing gender gaps has been proposed as a pathway to reduce adolescent pregnancy. We investigated the associations of urban measures of women's empowerment and gender inequality with adolescent birth rates (ABR) in 366 Latin American cities in nine countries.

The osteoclast cytoskeleton - current understanding and therapeutic perspectives for osteoporosis.

Osteoclasts are giant multinucleated myeloid cells specialized for bone resorption, which is essential for the preservation of bone health throughout life. The activity of osteoclasts relies on the typical organization of osteoclast cytoskeleton components into a highly complex structure comprising actin, microtubules and other cytoskeletal proteins that constitutes the backbone of the bone resorption apparatus. The development of methods to differentiate osteoclasts in culture and manipulate them genetically, as well as improvements in cell imaging technologies, has shed light onto the molecular mechanisms that control the structure and dynamics of the osteoclast cytoskeleton, and thus the mechanism of bone resorption.

Effect of Long-Term Retention of Gadolinium on Metabolism of Deep Cerebellar Nuclei After Repeated Injections of Gadodiamide in Rats.

Objectives: The aim of this study was to determine potential metabolism and histological modifications due to gadolinium retention within deep cerebellar nuclei (DCN) after linear gadolinium-based contrast agent injection (gadodiamide) in rats at 1 year after the last injection.

Materials And Methods: Twenty female rats received 20 doses of gadodiamide (0.6 mmol of gadolinium per kilogram each) over 5 weeks.

Contrast-to-Dose Relationship of Gadopiclenol, an MRI Macrocyclic Gadolinium-based Contrast Agent, Compared with Gadoterate, Gadobenate, and Gadobutrol in a Rat Brain Tumor Model.

Background Detection of cerebral lesions at MRI may benefit from a chemically stable and more sensitively detected gadolinium-based contrast agent (GBCA). Gadopiclenol, a macrocyclic GBCA with at least twofold higher relaxivity, is currently undergoing clinical trials in humans. Purpose To determine the relationship between MRI contrast enhancement and the injected dose of gadopiclenol in a glioma rat model compared with those of conventional GBCA at label dose.

Dock5 is a new regulator of microtubule dynamic instability in osteoclasts.

Background Information: Osteoclast resorption is dependent on a podosome-rich structure called sealing zone. It tightly attaches the osteoclast to the bone creating a favourable acidic microenvironment for bone degradation. This adhesion structure needs to be stabilised by microtubules whose acetylation is maintained by down-regulation of deacetylase HDAC6 and/or of microtubule destabilising kinase GSK3β activities.

Combined strategy of siRNA and osteoclast actin cytoskeleton automated imaging to identify novel regulators of bone resorption shows a non-mitotic function for anillin.

Osteoclasts are the main cells responsible for the resorption of mineralized extracellular matrices. They are the major targets for anti-resorptive therapies to manage osteoporosis, a major public health problem. Osteoclasts are giant multinucleated cells that can organize their a unique adhesion structure based on a belt of podosomes, which is the keystone of the bone resorption apparatus.

Methods to Investigate the Role of Rho GTPases in Osteoclast Function.

The actin cytoskeleton is essential for the biology of osteoclasts, in particular during bone resorption. As key regulators of actin dynamics, the small GTPases of the Rho family are very important in the control of osteoclast activity. The study of Rho GTPase signaling pathways is essential to uncover the mechanisms of bone resorption and can have interesting applications for the treatment of osteolytic diseases.

One-year Retention of Gadolinium in the Brain: Comparison of Gadodiamide and Gadoterate Meglumine in a Rodent Model.

Purpose To compare the long-term brain elimination kinetics and gadolinium species in healthy rats after repeated injections of the contrast agents gadodiamide (a linear contrast agent) or gadoterate (a macrocyclic contrast agent). Materials and Methods Nine-week-old rats received five doses of 2.4 mmol gadolinium per kilogram of body weight over 5 weeks and were followed for 12 months with T1-weighted MRI (n = 140 rats, corresponding to seven time points, two contrast agents, and 10 rats per group).

Moderate Renal Failure Accentuates T1 Signal Enhancement in the Deep Cerebellar Nuclei of Gadodiamide-Treated Rats.

Objectives: The purpose of this preclinical study was to investigate whether moderate chronic kidney disease is a factor in potentiating gadolinium (Gd) uptake in the brain.

Materials And Methods: A comparative study was performed on renally impaired (subtotal nephrectomy) rats versus rats with normal renal function. The animals received 4 daily injections of 0.

ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome.

Chromosomal abnormalities are implicated in a substantial number of human developmental syndromes, but for many such disorders little is known about the causative genes. The recently described 1q41q42 microdeletion syndrome is characterized by characteristic dysmorphic features, intellectual disability and brain morphological abnormalities, but the precise genetic basis for these abnormalities remains unknown. Here, our detailed analysis of the genetic abnormalities of 1q41q42 microdeletion cases identified TP53BP2, which encodes apoptosis-stimulating protein of p53 2 (ASPP2), as a candidate gene for brain abnormalities.

Abscisic Acid: a versatile phytohormone in plant signaling and beyond.

As sessile organisms, plants cannot escape from adverse conditions and, therefore, they have developed complex responses to the changing environment. Plant responses to abiotic cues involve changes in metabolism, photosynthesis, gene expression, ion levels, etc., and must be perfectly coordinated by phytohormones.

Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation.

Osteoporosis is caused by excessive activity of bone-degrading osteoclasts over bone-forming osteoblast. Standard antiosteolytic treatments inhibit bone resorption by inducing osteoclast loss, with the adverse effect of hindering also bone formation. Formation of the osteoclast sealing zone requires Dock5, a guanine nucleotide exchange factor for the small GTPase Rac, and C21, a chemical inhibitor of Dock5, decreases bone resorption by cultured osteoclasts.

The mineral dissolution function of osteoclasts is dispensable for hypertrophic cartilage degradation during long bone development and growth.

During long bone development and post-natal growth, the cartilaginous model of the skeleton is progressively replaced by bone, a process known as endochondral ossification. In the primary spongiosa, osteoclasts degrade the mineralized cartilage produced by hypertrophic chondrocytes to generate cartilage trabeculae that osteoblasts embed in bone matrix. This leads to the formation of the trabecular bone network of the secondary spongiosa that will undergo continuous remodeling.

Modulation of osteoclast differentiation and bone resorption by Rho GTPases.

Bone is a dynamic tissue constantly renewed through a regulated balance between bone formation and resorption. Excessive bone degradation by osteoclasts leads to pathological decreased bone density characteristic of osteolytic diseases such as post-menopausal osteoporosis or bone metastasis. Osteoclasts are multinucleated cells derived from hematopoietic stem cells via a complex differentiation process.

Biotechnological approaches to study plant responses to stress.

Multiple biotic and abiotic environmental stress factors affect negatively various aspects of plant growth, development, and crop productivity. Plants, as sessile organisms, have developed, in the course of their evolution, efficient strategies of response to avoid, tolerate, or adapt to different types of stress situations. The diverse stress factors that plants have to face often activate similar cell signaling pathways and cellular responses, such as the production of stress proteins, upregulation of the antioxidant machinery, and accumulation of compatible solutes.

The Rac1 exchange factor Dock5 is essential for bone resorption by osteoclasts.

Osteoporosis, which results from excessive bone resorption by osteoclasts, is the major cause of morbidity for elder people. Identification of clinically relevant regulators is needed to develop novel therapeutic strategies. Rho GTPases have essential functions in osteoclasts by regulating actin dynamics.

ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development.

Cell polarity plays a key role in the development of the central nervous system (CNS). Interestingly, disruption of cell polarity is seen in many cancers. ASPP2 is a haplo-insufficient tumor suppressor and an activator of the p53 family.

Rapid-clearance iron nanoparticles for inflammation imaging of atherosclerotic plaque: initial experience in animal model.

Purpose: To evaluate the use of a recently developed fast-clearing ultrasmall superparamagnetic iron oxide (USPIO) for detection of vascular inflammation in atherosclerotic plaque.

Materials And Methods: The study protocol was approved by the animal experimentation ethics committee. A recently introduced USPIO, P904, and a reference-standard USPIO, ferumoxtran-10, were tested in a rabbit model of induced aortic atherosclerosis.

The Rho GTPase Wrch1 regulates osteoclast precursor adhesion and migration.

An excess of osteoclastic bone resorption relative to osteoblastic bone formation results in progressive bone loss, characteristic of osteoporosis. Understanding the mechanisms of osteoclast differentiation is essential to develop novel therapeutic approaches to prevent and treat osteoporosis. We showed previously that Wrch1/RhoU is the only RhoGTPase whose expression is induced by RANKL during osteoclastogenesis.

ASPP2: a gene that controls life and death in vivo.

The fundamental role of apoptosis in tumor prevention and the important role of p53 in this process are now universally recognized. Recently, several families of p53-binding proteins have been shown to influence p53's decision to direct the cells either into the apoptotic pathway or in cell cycle arrest. Among them, the ASPP family specifically regulate p53-dependent apoptosis.

ASPP2 is a haploinsufficient tumor suppressor that cooperates with p53 to suppress tumor growth.

ASPP2 stimulates the apoptotic function of the p53 family in vivo. We show here that ASPP2-/- pups died before weaning. This postnatal lethality was significantly enhanced in p53+/- background and both deletions are synthetic lethal.

Magnetic susceptibility matching at the air-tissue interface in rat lung by using a superparamagnetic intravascular contrast agent: influence on transverse relaxation time of hyperpolarized helium-3.

Transverse relaxation of hyperpolarized helium-3 magnetization in respiratory airways highly depends on local magnetic field gradients induced by the magnetic susceptibility difference between gas and pulmonary tissue. Fast transverse relaxation is known to be an important feature that yields information about lung microstructure and function, but it is also an essential limitation in designing efficient strategies for lung imaging. Using intravascular injections of a superparamagnetic contrast agent in rats, it was possible to increase the overall susceptibility of the perfused lung tissues and hence to match it with the gas susceptibility.

Spatial and temporal expression of S100B in cells of oligodendrocyte lineage.

The analysis of oligodendrocyte (OL) lineage development has been facilitated by the immunocytochemical characterization of OL-specific antigens and definition of the phenotypes sequentially acquired by differentiating OLs. The purpose of the present study was to address an enduring discrepancy between several reported cases of S100B immunodetection in CNS myelin and myelinating OLs on the one hand, and the systematic use of the S100B protein as an alleged astrocytic marker in studies of the mammalian CNS on the other. To resolve this discrepancy, we have compared the developmental distribution of EGFP+ cells in the CNS of s100b-enhanced green fluorescent protein (EGFP) (Vives et al.