The IgA1 immune complex-mediated activation of the MAPK/ERK kinase pathway in mesangial cells is associated with glomerular damage in IgA nephropathy

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, has significant morbidity and mortality as 20-40% of patients progress to end-stage renal disease within 20 years of onset. In order to gain insight into the molecular mechanisms involved in the progression of IgAN, we systematically evaluated renal biopsies from such patients. This showed that the MAPK/ERK signaling pathway was activated in the mesangium of patients presenting with over 1 g/day proteinuria and elevated blood pressure, but absent in biopsy specimens of patients with IgAN and modest proteinuria (<1 g/day). ERK activation was not associated with elevated galactose-deficient IgA1 or IgG specific for galactose-deficient IgA1 in the serum. In human mesangial cells in vitro, ERK activation through mesangial IgA1 receptor (CD71) controlled pro-inflammatory cytokine secretion and was induced by large-molecular-mass IgA1-containing circulating immune complexes purified from patient sera. Moreover, IgA1-dependent ERK activation required renin-angiotensin system as its blockade was efficient in reducing proteinuria in those patients exhibiting substantial mesangial activation of ERK. Thus, ERK activation alters mesangial cell-podocyte crosstalk, leading to renal dysfunction in IgAN. Assessment of MAPK/ERK activation in diagnostic renal biopsies may predict the therapeutic efficacy of renin-angiotensin system blockers in IgAN. Kidney International (2012) 82, 1284-1296; doi:10.1038/ki.2012.192; published online 5 September 2012

Population size of threatened and endemic birds of the Cerrado in Estacao Ecologica de Itirapina, a fragmented area in the State of Sao Paulo, Brazil

The pressures for land use change have led to an increasing isolation of habitat remnants throughout the world. The goal of this study was to estimate the population size and density of some endemic and threatened species in a nature reserve in the Cerrado biome. One hundred and thirty four point transects were undertaken at the Estacao Ecologica de Itirapina (EEI), one of the last natural grassland savannah remnants in Sao Paulo state, in the south-east of Brazil between September and December 2006 and densities estimated for seven species (four endemic to the Cerrado, one near-endemic and two grassland specialists). Neither species reached the minimum viable population size of 500-5000 individuals. Four species, White-banded Tanager, White-rumped Tanager, Black-throated Saltator and Sharp-tailed Tyrant have populations ranging from 112 to 248 individuals, while the other species have a low population (< 60 individuals). The mean densities of Sharp-tailed Tyrant and Cock-tailed Tyrant in the EEI grassland showed similar values to those observed in larger areas of the Cerrado, which may indicate that the EEL grassland area is well conserved. In spite of the restricted size of the EEI, small areas can maintain some endemic and threatened bird populations, thus contributing to local biodiversity and the ecological processes in the region. The capacity of fragments of Cerrado (similar to 2,000 ha) to maintain populations of endemic and threatened bird species is unlikely to be effective in the long term.

Prevalence of oral habits in children with cleft lip and palate

This study investigated the prevalence of oral habits in children with clefts aged three to six years, compared to a control group of children without clefts in the same age range, and compared the oral habits between children with clefts with and without palatal fistulae. The sample was composed of 110 children aged 3 to 6 years with complete unilateral cleft lip and palate and 110 children without alterations. The prevalence of oral habits and the correlation between habits and presence of fistulae (for children with clefts) were analyzed by questionnaires applied to the children caretakers. The cleft influenced the prevalence of oral habits, with lower prevalence of pacifier sucking for children with cleft lip and palate and higher prevalence for all other habits, with significant association (P < 0.05). There was no significant association between oral habits and presence of fistulae (P > 0.05). The lower prevalence of pacifier sucking and higher prevalence of other oral habits agreed with the postoperative counseling to remove the pacifier sucking habit when the child is submitted to palatoplasty, possibly representing a substitution of habits. There was no causal relationship between habits and presence of palatal fistulae

Role of M2 muscarinic receptor in the airway response to methacholine of mice selected for minimal or maximal acute inflammatory response

Airway smooth muscle constriction induced by cholinergic agonists such as methacholine (MCh), which is typically increased in asthmatic patients, is regulated mainly by muscle muscarinic M3 receptors and negatively by vagal muscarinic M2 receptors. Here we evaluated basal (intrinsic) and allergen-induced (extrinsic) airway responses to MCh. We used two mouse lines selected to respond maximally (AIRmax) or minimally (AIRmin) to innate inflammatory stimuli. We found that in basal condition AIRmin mice responded more vigorously to MCh than AIRmax. Treatment with a specific M2 antagonist increased airway response of AIRmax but not of AIRmin mice. The expression of M2 receptors in the lung was significantly lower in AIRmin compared to AIRmax animals. AIRmax mice developed a more intense allergic inflammation than AIRmin, and both allergic mouse lines increased airway responses to MCh. However, gallamine treatment of allergic groups did not affect the responses to MCh. Our results confirm that low or dysfunctional M2 receptor activity is associated with increased airway responsiveness to MCh and that this trait was inherited during the selective breeding of AIRmin mice and was acquired by AIRmax mice during allergic lung inflammation

Leptin modulates norepinephrine-mediated melatonin synthesis in cultured rat pineal gland

Pineal melatonin synthesis can be modulated by many peptides, including insulin. Because melatonin appears to alter leptin synthesis, in this work we aimed to investigate whether leptin would have a role on norepinephrine- (NE-)mediated melatonin synthesis in cultured rat pineal glands. According to our data, cultured rat pineal glands express leptin receptor isoform b (Ob-Rb). Pineal expression of Ob-Rb mRNA was also observed in vivo. Administration of leptin (1 nM) associated with NE ( 1 µM) reduced melatonin content as well as arylalkylamine-N-acetyl transferase (AANAT) activity and expression in cultured pineal glands. Leptin treatment per se induced the expression of STAT3 in cultured pineal glands, but STAT3 does not participate in the leptin modulation of NE-mediated pineal melatonin synthesis. In addition, the expression of inducible cAMP early repressor (ICER) was further induced by leptin challenge when associated with NE. In conclusion, leptin inhibition of pineal melatonin synthesis appears to be mediated by a reduction in AANAT activity and expression as well as by increased expression of Icer mRNA. Peptidergic signaling within the pineal gland appears to be one of the most important signals which modulates melatonin synthesis; leptin, as a member of this system, is not an exception