Deleting Rac1 improves vertebral bone quality and resistance to fracture in a murine ovariectomy model.

Summary: The roles of Rac1 and Rac2 in regulating osteoclast-mediated bone quality in postmenopausal osteoporosis were evaluated using an ovariectomized murine model. Animals' bone composition and architecture were evaluated. Our results demonstrate that the deletion of Rac1 increases vertebral bone quality compared to wild-type bones in an ovariectomized model.

Acute exercise protects against calcium-induced cardiac mitochondrial permeability transition pore opening in doxorubicin-treated rats.

The use of DOX (doxorubicin), an antibiotic used in oncological treatments, is limited by a dose-related cardiotoxicity against which acute exercise is protective. However, the mitochondrial-related mechanisms of this protection remain unknown. Therefore the present study aimed to determine the effects of an acute endurance exercise bout performed 24 h before DOX treatment on heart and liver mitochondrial function.

Endurance training reverts heart mitochondrial dysfunction, permeability transition and apoptotic signaling in long-term severe hyperglycemia.

The present study analyzed the effects of endurance training against cardiac mitochondrial dysfunction, particularly on the susceptibility to mitochondrial permeability transition pore (MPTP) induction in streptozotocin (STZ)-induced hyperglycemia. Twenty-four young male Wistar rats were randomly assigned into sedentary citrate (SED+CIT), sedentary type I diabetes (SED+STZ; 50mg/kg), T+CIT (14-week treadmill running, 60min/day) and T+STZ (injected 4weeks before training). After 18weeks, isolated heart mitochondria were used for in vitro oxygen consumption and transmembrane potential (∆Ψ) assessment.

NLRC5 limits the activation of inflammatory pathways.

Nod-like receptors (NLRs) are intracellular sentinel proteins that are implicated in the detection of microbes and danger signals, thereby controlling several key innate immune pathways. The human genome encodes 22 NLR proteins, the function of many of which remains unknown. In this study, we present the identification and characterization of NLRC5, a NLR protein whose expression is found predominantly in cells of the myeloid and lymphoid lineages.

Morphological tegument alterations of adult Schistosoma mansoni, harbored in non anti-helminthic treated, high-immune-tolerogenic and low-inflammatory mice.

The present study exhibits original results of S. mansoni tegumental alterations due to contact with the immune system of non anti-helminthic treated mice. We compared, by SEM, the tegument of adult worms recovered from strains of mice genetically selected to extreme phenotypes of resistance (TR strain) and susceptibility (TS strain) to egg-albumin oral tolerance (OT).

Age-related gene-specific changes of A-to-I mRNA editing in the human brain.

A-to-I editing is an adenosine-to-inosine modification of mRNA particularly widespread in the human brain, where it affects thousands of genes. A growing body of evidence suggests that A-to-I RNA editing is necessary for normal development and maintenance in mammals and that its deficiencies contribute to a number of pathological states. In this study, we examined whether mRNA editing levels of two mRNA species, CYFIP2 and GABRA3, change with aging.

How a microbial drug transporter became essential for crop cultivation on acid soils: aluminium tolerance conferred by the multidrug and toxic compound extrusion (MATE) family.

Background: Aluminium (Al) toxicity is a major agricultural constraint for crop cultivation on acid soils, which comprise a large portion of the world's arable land. One of the most widely accepted mechanisms of Al tolerance in plants is based on Al-activated organic acid release into the rhizosphere, with organic acids forming stable, non-toxic complexes with Al. This mechanism has recently been validated by the isolation of bona-fide Al-tolerance genes in crop species, which encode membrane transporters that mediate Al-activated organic acid release leading to Al exclusion from root apices.

A dose-escalation phase I trial of nimotuzumab, an antibody against the epidermal growth factor receptor, in patients with advanced solid malignancies.

Purpose: Nimotuzumab is a humanized monoclonal antibody which inhibits the ligand-dependent activation of epidermal growth factor receptor (EGFR). We conducted a phase I trial to assess the pharmacodynamic (PD) effects of escalating doses of nimotuzumab administered alone in patients with advanced solid cancers patients.

Experimental Design: Patients were treated with escalating doses of weekly intravenous nimotuzumab at doses ranging between 100 and 800 mg.

Cell resilience in species life spans: a link to inflammation?

Species differences in life span have been attributed to cellular survival during various stressors, designated here as 'cell resilience'. In primary fibroblast cultures, cell resilience during exposure to free radicals, hypoglycemia, hyperthermia, and various toxins has shown generally consistent correlations with the species characteristic life spans of birds and mammals. However, the mechanistic links of cell resilience in fibroblast cultures to different species life spans are poorly understood.

Systems biology and longevity: an emerging approach to identify innovative anti-aging targets and strategies.

Human aging and longevity are complex and multi-factorial traits that result from a combination of environmental, genetic, epigenetic and stochastic factors, each contributing to the overall phenotype. The multi-factorial process of aging acts at different levels of complexity, from molecule to cell, from organ to organ systems and finally to organism, giving rise to the dynamic "aging mosaic". At present, an increasing amount of experimental data on genetics, genomics, proteomics and other -omics are available thanks to new high-throughput technologies but a comprehensive model for the study of human aging and longevity is still lacking.

Nitric oxide mediates the hormonal control of Crassulacean acid metabolism expression in young pineapple plants.

Genotypic, developmental, and environmental factors converge to determine the degree of Crassulacean acid metabolism (CAM) expression. To characterize the signaling events controlling CAM expression in young pineapple (Ananas comosus) plants, this photosynthetic pathway was modulated through manipulations in water availability. Rapid, intense, and completely reversible up-regulation in CAM expression was triggered by water deficit, as indicated by the rise in nocturnal malate accumulation and in the expression and activity of important CAM enzymes.

Tei index to assess fetal cardiac performance in fetuses at risk for fetal inflammatory response syndrome.

Objectives: To examine, in patients with premature rupture of the amniotic membranes (PROM) at < 34 weeks of gestation, the relationship between fetal myocardial performance measured by the Tei index and fetal inflammatory response syndrome (FIRS).

Methods: A case-control study was conducted including 15 preterm PROM patients with gestational age between 24 and 33 weeks admitted to Hospital de Clínicas de Porto Alegre, and 15 controls with the same gestational age range. Fetal echocardiography with Doppler was performed at admission for the preterm PROM group, with serial examinations every 7-10 days thereafter until delivery, and at the time of inclusion in the control group.

Th17 cells are the dominant T cell subtype primed by Shigella flexneri mediating protective immunity.

The T cell response to Shigella, the causative agent of bacillary dysentery, remains poorly understood. Using a murine model of infection, we report that Shigella flexneri primes predominately IL-17A- and IL-22-producing Th17 cells. Shigella-specific Th1 cells are only significantly induced on secondary infection, whereas specific Th2 and CD8(+) T cells are undetectable.

Two functionally distinct members of the MATE (multi-drug and toxic compound extrusion) family of transporters potentially underlie two major aluminum tolerance QTLs in maize.

Crop yields are significantly reduced by aluminum (Al) toxicity on acidic soils, which comprise up to 50% of the world's arable land. Al-activated release of ligands (such as organic acids) from the roots is a major Al tolerance mechanism in plants. In maize, Al-activated root citrate exudation plays an important role in tolerance.

Filamin A regulates monocyte migration through Rho small GTPases during osteoclastogenesis.

Osteoclastogenesis (OCG) results from the fusion of monocytes after stimulation with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB ligand (RANKL). Migration of monocytes into close proximity precedes critical fusion events that are required for osteoclast formation. Cellular migration requires leading-edge actin cytoskeleton assembly that drives cellular locomotion.

Next-generation sequencing in aging research: emerging applications, problems, pitfalls and possible solutions.

Recent technological advances that allow faster and cheaper DNA sequencing are now driving biological and medical research. In this review, we provide an overview of state-of-the-art next-generation sequencing (NGS) platforms and their applications, including in genome sequencing and resequencing, transcriptional profiling (RNA-Seq) and high-throughput survey of DNA-protein interactions (ChIP-Seq) and of the epigenome. Particularly, we focus on how new methods made possible by NGS can help unravel the biological and genetic mechanisms of aging, longevity and age-related diseases.

Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry.

Autophagy is emerging as a crucial defense mechanism against bacteria, but the host intracellular sensors responsible for inducing autophagy in response to bacterial infection remain unknown. Here we demonstrated that the intracellular sensors Nod1 and Nod2 are critical for the autophagic response to invasive bacteria. By a mechanism independent of the adaptor RIP2 and transcription factor NF-kappaB, Nod1 and Nod2 recruited the autophagy protein ATG16L1 to the plasma membrane at the bacterial entry site.

Impact of Loughborough Intermittent Shuttle Test versus soccer match on physiological, biochemical and neuromuscular parameters.

The aim of the present study was to analyze the impact of Loughborough Intermittent Shuttle Test (LIST) versus soccer match on heart rate (HR), muscle damage, redox status, blood leukocytes and neuromuscular function throughout 72 h recovery. Sixteen male soccer players (21.3 +/- 1.

Endurance training improves gastrocnemius mitochondrial function despite increased susceptibility to permeability transition.

The aim of the present work was to test the hypothesis that moderate endurance treadmill training ameliorates gastrocnemius mitochondrial bioenergetics and increases the tolerance to the calcium-induced mitochondrial permeability transition pore (MPTP) opening. Twelve adult (6-8 week old) male Wistar rats were randomly divided into two groups (n=6per group): sedentary and trained (14 week of endurance treadmill running, 60min/day). Several end-points for invitro gastrocnemius mitochondrial function including oxygen consumption, transmembrane electric potential and susceptibility to calcium-induced MPTP opening were evaluated.

Role of Nod1 in mucosal dendritic cells during Salmonella pathogenicity island 1-independent Salmonella enterica serovar Typhimurium infection.

Recent advances in immunology have highlighted the critical function of pattern-recognition molecules (PRMs) in generating the innate immune response to effectively target pathogens. Nod1 and Nod2 are intracellular PRMs that detect peptidoglycan motifs from the cell walls of bacteria once they gain access to the cytosol. Salmonella enterica serovar Typhimurium is an enteric intracellular pathogen that causes a severe disease in the mouse model.