Cafeteria Diet-Induced Obesity Worsens Experimental CKD.

Obesity is a significant risk factor for chronic kidney disease (CKD). This study aimed to evaluate the impact of obesity on the development of kidney fibrosis in a model of cafeteria diet rats undergoing 5/6th nephrectomy (SNx). Collagen 1, 3, and 4 expression, adipocyte size, macrophage number, and the expression of 30 adipokines were determined.

Cardiac remodeling associated with chronic kidney disease is enhanced in a rat model of metabolic syndrome: Preparation of mesenchymal transition.

Cardiac alteration due to chronic kidney disease is described by tissue fibrosis. This remodeling involves myofibroblasts of various origins, including epithelial or endothelial to mesenchymal transitions. In addition, obesity and insulin resistance together or separately seem to exacerbate cardiovascular risk in chronic kidney disease (CKD).

The Shank3 knock in mouse enables isoform-specific functional studies of Shank3a.

Background: Shank3 is a scaffolding protein essential for the organization and function of the glutamatergic postsynapse. Monogenic mutations in gene are among the leading genetic causes of Autism Spectrum Disorders (ASD). The multiplicity of Shank3 isoforms seems to generate as much functional diversity and yet, there are no tools to study endogenous Shank3 proteins in an isoform-specific manner.

Impact of Highly Saturated versus Unsaturated Fat Intake on Carbohydrate Metabolism and Vascular Reactivity in Rat.

Palm olein (PO) and lard are considered harmful to health because of their highly saturated fatty acid content. On the contrary, olive oil (OO) with its high level of polyunsaturated fatty acids is considered healthier. This study aims to evaluate the effects of high consumption of these oils on carbohydrate metabolism and vascular function.

Skeletal Muscle Phenotype in Patients Undergoing Long-Term Hemodialysis Awaiting Kidney Transplantation.

Background And Objectives: Age and comorbidity-related sarcopenia represent a main cause of muscle dysfunction in patients on long-term hemodialysis. However, recent findings suggest muscle abnormalities that are not associated with sarcopenia. The aim of this study was to isolate functional and cellular muscle abnormalities independently of other major confounding factors, including malnutrition, age, comorbidity, or sedentary lifestyle, which are common in patients on maintenance hemodialysis.

Effects of high-fat diets on inflammation and antioxidant status in rats : comparison between palm olein and olive oil.

Palm olein (PO) and olive oil (OO) are widely consumed in the world. PO is considered harmful to health, whereas OO is considered healthy. The aim of the study was to compare the effects of consumption of these oils on antioxidant status and inflammation in rats.

Restoring glutamate receptosome dynamics at synapses rescues autism-like deficits in Shank3-deficient mice.

Shank3 monogenic mutations lead to autism spectrum disorders (ASD). Shank3 is part of the glutamate receptosome that physically links ionotropic NMDA receptors to metabotropic mGlu5 receptors through interactions with scaffolding proteins PSD95-GKAP-Shank3-Homer. A main physiological function of the glutamate receptosome is to control NMDA synaptic function that is required for plasticity induction.

Shear Wave Elastography, a New Tool for Diaphragmatic Qualitative Assessment: A Translational Study.

Prolonged mechanical ventilation is often associated with either a decrease (known atrophy) or an increase (supposed injury) in diaphragmatic thickness. Shear wave elastography is a noninvasive technique that measures shear modulus, a surrogate of tissue stiffness and mechanical properties. To describe changes in shear modulus (SM) during the ICU stay and the relationship with alterations in muscle thickness.

Dynapaenia and sarcopaenia in chronic haemodialysis patients: do muscle weakness and atrophy similarly influence poor outcome?

Background: Sarcopaenia, defined as a decline in both muscle mass and function, has been recognized as a major determinant of poor outcome in haemodialysis (HD) patients. It is generally assumed that sarcopaenia is driven by muscle atrophy related to protein-energy wasting. However, dynapaenia, defined as weakness without atrophy, has been characterized by a different disease phenotype from sarcopaenia.

Impact of diets rich in olive oil, palm oil or lard on myokine expression in rats.

It has recently emerged that myokines may be an important skeletal muscle adaptive response to obesogenic diets in sedentary subjects (who do not exercise). This study aimed to assess the influence of various high fat (HF) diets rich in either crude palm oil (cPO), refined palm oil (rPO), olive oil (OO) or lard on the modulation of myokine gene expression in the gastrocnemius. Five groups of 8 rats were each fed HF or control diet for 12 weeks.

High dietary intake of palm oils compromises glucose tolerance whereas high dietary intake of olive oil compromises liver lipid metabolism and integrity.

Purpose: Palm (PO) and olive oils (OO) are the two most consumed and/or used oils in the world for food elaboration. These oils should not be confused with the solid palm stearin which is widely used in pastry making. Large number of studies was reported dealing with adverse/beneficial cardiovascular effects of PO and OO, whereas few studies were conducted to compare their potential effects on hepatic steatosis and liver lipid metabolism.

SNAP23-Kif5 complex controls mGlu1 receptor trafficking.

Metabotropic glutamate receptors are expressed at excitatory synapses and control synaptic transmission in mammalian brain. These receptors are involved in numerous patho-physiological functions. However, little is known about the molecular determinants responsible for their intracellular transport and membrane targeting.

The RhoGEF DOCK10 is essential for dendritic spine morphogenesis.

By regulating actin cytoskeleton dynamics, Rho GTPases and their activators RhoGEFs are implicated in various aspects of neuronal differentiation, including dendritogenesis and synaptogenesis. Purkinje cells (PCs) of the cerebellum, by developing spectacular dendrites covered with spines, represent an attractive model system in which to decipher the molecular signaling underlying these processes. To identify novel regulators of dendritic spine morphogenesis among members of the poorly characterized DOCK family of RhoGEFs, we performed gene expression profiling of fluorescence-activated cell sorting (FACS)-purified murine PCs at various stages of their postnatal differentiation.

Distinct subsynaptic localization of type 1 metabotropic glutamate receptors at glutamatergic and GABAergic synapses in the rodent cerebellar cortex.

Type 1 metabotropic glutamate (mGlu1) receptors play a pivotal role in different forms of synaptic plasticity in the cerebellar cortex, e.g. long-term depression at glutamatergic synapses and rebound potentiation at GABAergic synapses.

The stoichiometry of scaffold complexes in living neurons - DLC2 functions as a dimerization engine for GKAP.

Quantitative spatio-temporal characterization of protein interactions in living cells remains a major challenge facing modern biology. We have investigated in living neurons the spatial dependence of the stoichiometry of interactions between two core proteins of the N-methyl-D-aspartate (NMDA)-receptor-associated scaffolding complex, GKAP (also known as DLGAP1) and DLC2 (also known as DYNLL2), using a novel variation of fluorescence fluctuation microscopy called two-photon scanning number and brightness (sN&B). We found that dimerization of DLC2 was required for its interaction with GKAP, which, in turn, potentiated GKAP self-association.

Cdk5 induces constitutive activation of 5-HT6 receptors to promote neurite growth.

The serotonin6 receptor (5-HT6R) is a promising target for treating cognitive deficits of schizophrenia often linked to alterations of neuronal development. This receptor controls neurodevelopmental processes, but the signaling mechanisms involved remain poorly understood. Using a proteomic strategy, we show that 5-HT6Rs constitutively interact with cyclin-dependent kinase 5 (Cdk5).

Rho-GTPase-activating protein interacting with Cdc-42-interacting protein 4 homolog 2 (Rich2): a new Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase-activating protein that controls dendritic spine morphogenesis.

Development of dendritic spines is important for synaptic function, and alteration in spine morphogenesis is often associated with mental disorders. Rich2 was an uncharacterized Rho-GAP protein. Here we searched for a role of this protein in spine morphogenesis.

Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation.

Synaptic long-term potentiation (LTP) is a key mechanism involved in learning and memory, and its alteration is associated with mental disorders. Shank3 is a major postsynaptic scaffolding protein that orchestrates dendritic spine morphogenesis, and mutations of this protein lead to mental retardation and autism spectrum disorders. In the present study we investigated the role of a new Shank3-associated protein in LTP.

Dynamic remodeling of scaffold interactions in dendritic spines controls synaptic excitability.

Scaffolding proteins interact with membrane receptors to control signaling pathways and cellular functions. However, the dynamics and specific roles of interactions between different components of scaffold complexes are poorly understood because of the dearth of methods available to monitor binding interactions. Using a unique combination of single-cell bioluminescence resonance energy transfer imaging in living neurons and electrophysiological recordings, in this paper, we depict the role of glutamate receptor scaffold complex remodeling in space and time to control synaptic transmission.

GKAP-DLC2 interaction organizes the postsynaptic scaffold complex to enhance synaptic NMDA receptor activity.

At glutamatergic brain synapses, scaffolding proteins regulate receptor location and function. The targeting and organization of scaffolding proteins in the postsynaptic density (PSD) is poorly understood, but it is known that a core protein of the glutamatergic receptor postsynaptic scaffold complex, guanylate-kinase-associated protein (GKAP) interacts with dynein light chain 2 (DLC2, also known as DYNLL2), a protein associated with molecular motors. In the present study, we combined BRET imaging, immunostaining and electrophysiological recording to assess the role of the GKAP-DLC2 interaction in the functional organization of the glutamatergic synapse.

Calpain 2 is required for sister chromatid cohesion.

Calpains form a family of Ca(2+)-dependent cysteine proteases involved in diverse cellular processes. However, the specific functions of each calpain isoform remain unknown. Recent reports have shown that calpain 2 (Capn2) is essential for cell viability.

Calpain 1 binding capacities of the N1-line region of titin are significantly enhanced by physiological concentrations of calcium.

Calpain 1, an ubiquitous well-known calcium-dependent intracellular protease, was recently shown to bind tightly to the proximal end of the I-band titin segment in a calcium-dependent manner [Raynaud et al. (2005) FEBS J. 272, 2578-2590].

Calpain 2 expression pattern and sub-cellular localization during mouse embryogenesis.

Regulation of migration and proliferation by calpain has been shown in various cell types; however, no data are available concerning calpain 2 (capn2) localization in embryonic tissues. Here, we report the expression pattern of capn2 during mouse embryonic development. Expression of the capn2 gene is observed throughout embryonic development.

Direct interaction enables cross-talk between ionotropic and group I metabotropic glutamate receptors.

Functional interplay between ionotropic and metabotropic receptors frequently involves complex intracellular signaling cascades. The group I metabotropic glutamate receptor mGlu5a co-clusters with the ionotropic N-methyl-d-aspartate (NMDA) receptor in hippocampal neurons. In this study, we report that a more direct cross-talk can exist between these types of receptors.

NF-kappaB-dependent expression of the antiapoptotic factor c-FLIP is regulated by calpain 3, the protein involved in limb-girdle muscular dystrophy type 2A.

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in the cysteine protease calpain 3 (CAPN3) that leads to selective muscle wasting. We previously showed that CAPN3 deficiency is associated with a profound perturbation of the NF-kappaB/IkappaB alpha survival pathway. In this study, the consequences of altered NF-kappaB/IkappaB alpha pathway were investigated using biological materials from LGMD2A patients.