TRPA1 receptor modulation attenuates bladder overactivity induced by spinal cord injury

The ankyrin-repeat transient receptor potential 1 (TRPA1) has been implicated in pathological conditions of the bladder, but its role in overactive bladder (OAB) following spinal cord injury (SCI) remains unknown. In this study, using a rat SCI model, we assessed the relevance of TRPA1 in OAB induced by SCI. SCI resulted in tissue damage, inflammation, and changes in bladder contractility and in voiding behavior. Moreover, SCI caused upregulation of TRPA1 protein and mRNA levels, in bladder and in dorsal root ganglion (DRG; L6-S1), but not in corresponding segment of spinal cord. Alteration in bladder contractility following SCI was evidenced by enhancement in cinnamaldehyde-, capsaicin-, or carbachol-induced bladder contraction as well as in its spontaneous phasic activity. Of relevance to voiding behavior, SCI induced increase in the number of nonvoiding contractions (NVCs), an important parameter associated with the OAB etiology, besides alterations in other urodynamic parameters. HC-030031 (TRPA1 antagonist) treatment decreased the number and the amplitude of NVCs while the TRPA1 antisense oligodeoxynucleotide (AS-ODN) treatment normalized the spontaneous phasic activity, decreased the cinnamaldehyde-induced bladder contraction and the number of NVCs in SCI rats. In addition, the cinnamaldehyde-induced bladder contraction was reduced by exposure of the bladder preparations to HC-030031. The efficacy of TRPA1 AS-ODN treatment was confirmed by means of the reduction of TRPA1 expression in the DRG, in the corresponding segment of the spinal cord and in the bladder, specifically in detrusor muscle. The present data show that the TRPA1 activation and upregulation seem to exert an important role in OAB following SCI.     

Characterization of white zones produced on Pinus radiata wood chips by Ganoderma australe and Ceriporiopsis subvermispora

White zones produced on biodegraded Pinus radiata wood chips were characterized by micro-localized-FTIR (Fourier Transformed Infra Red) spectroscopy and scanning electron microscopy. Both techniques permitted assignment of the white zones to a selective lignin removal process. Although both fungi studied have degraded lignin selectively in these restricted superficial areas, chemical analysis of the wood chips indicated that Ganoderma australe removed 16% of the initial amount of glucan at the 20% weight loss level. Ceriporiopsis subvermispora did not remove glucan at weight loss values below 17%. Prolonged biodegradation resulted in reduction of white zones by G. australe, and increased white zones from C. subvermispora decayed samples. This revised version was published online in July 2006 with corrections to the Cover Date.     

The effect of agriculture on the seasonal dynamics and functional diversity of benthic biofilm in tropical headwater streams

Tropical streams are one of the most endangered ecosystems in the world due to the constant pressures from human activities. Among these activities, agriculture represents a land use that is crucial for human development but also a key driver of stream degradation and biodiversity decline in the tropics. Against this background, we investigated indirect effects of agriculture (alterations in stream flow and nutrient availability) and climate characteristics (water temperature) on benthic biofilm communities in tropical streams (São Paulo State, Brazil). Three first‐order streams draining catchments dominated by agricultural land use (sugarcane for bioenergy production, pasture) with some remaining riparian forest were studied for 1 year. We focused on the relationships of benthic biofilm biomass, algal biomass, diatom community, and functional structure with streamflow dynamics, nitrate concentrations, and water temperature. Our results indicate that these biological responses were mainly mediated by flow and water temperature and not by resource availability in the studied headwater streams. This result could be explained by the heavy rains and elevated runoff generation in these tropical catchments under agricultural influence, which might override the known effects of nutrient enrichment on benthic biofilm communities. Considering forecast climate and land‐use changes in tropical streams, our findings may suggest potential shifts in benthic biofilm communities, with functional consequences for aquatic food webs in these environments. Abstract in Brazilian Portuguese is available with online material.     

Peripheral effect of a kappa opioid receptor antagonist on nociception evoked by formalin injected in TMJ of pregnant rats

The effect of sex hormones on orofacial pain modulation is poorly understood. Therefore, this study aimed to investigate the effect of hormonal changes as a result of pregnancy, as well as that of the kappa (kappa) opioid receptor antagonist on female rats' sensitivity to the temporomandibular joint (TMJ) formalin test. Initially, female rats at estrus and pregnant females on day 19 of pregnancy received a 50 microl formalin (1.5%) injection in the right TMJ. The pregnant females showed a reduction in nociceptive responses to the TMJ formalin test when compared with those at estrus. Then, the selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), was co-administered with the formalin. Next, additional groups received the kappa (200 microg) receptor antagonist or 0.9% NaCl 24 hours prior to the periarticular injection of formalin. Co-administration of nor-BNI with formalin into the TMJ region had no significant effect. The pre-injection of selective kappa-opioid receptor antagonist, nor-BNI, significantly enhanced the nociceptive behavioral responses in pregnant females. When applied in the contralateral TMJ, nor-BNI did not affect the magnitude of the nociceptive response induced by formalin. It can be concluded that: 1) The increase of the sex hormone levels, as result of pregnancy, induces a reduction of nociceptive behavioral responses to the TMJ formalin test; 2) the peripheral kappa opioid receptor activation, by endogenous opioid agonists release, is involved in the antinociception to TMJ formalin test, induced by pregnancy.     

Metabolite Profiling of Pleurotus ostreatus Grown on Sisal Agro-Industrial Waste Supplemented with Cocoa Almond Tegument and Wheat Bran

Pleurotus ostreatus is an edible fungus with high nutritional value that uses industrial and agricultural lignocellulosic residues as substrates for growth and reproduction. Understanding their growth metabolic dynamics on agro-industrial wastes would help to develop economically viable and eco-friendly biotechnological strategies for food production. Thus, we used UHPLC/MS/MS and GNPS as an innovative approach to investigate the chemical composition of two strains of P. ostreatus, coded as BH (Black Hirataki) and WH (White Hirataki), grown on sisal waste mixture (SW) supplemented with 20 % cocoa almond tegument (CAT) or 20 % of wheat bran (WB). Metabolite dereplication allowed the identification of 53 metabolites, which included glycerophospholipids, fatty acids, monoacylglycerols, steroids, carbohydrates, amino acids, and flavonoids. This is the first report of the identification of these compounds in P. ostreatus, except for the steroid ergosterol. Most of the metabolites described in this work possess potential biological activities, which support the nutraceutical properties of P. ostreatus. Thus, the results of this study provide essential leads to the understanding of white-rot fungi chemical plasticity aiming at developing alternative biotechnologies strategies for waste recycling.     

Myrtenal-induced V-ATPase inhibition - A toxicity mechanism behind tumor cell death and suppressed migration and invasion in melanoma

Background

Metastatic tumor cells have acidic extracellular pH and differential electrochemical H⁺ gradients generated across their cell membranes by V-type H⁺-ATPases. This study shows that inhibition of the V-ATPases by the plant-derived monoterpene Myrtenal results in tumor cell death and decreased metastatic dissemination in mice.

Time–activity budget of greater rheas (Rhea americana, Aves) on a human-disturbed area: the role of habitat, time of the day, season and group size

The aim of this study was to evaluate activity–time budget, habitat use and how seasonality and group size influence the expression of greater rhea behaviours. Greater rheas are threatened South American birds; habitat loss, predation and hunting are the main factors responsible for population declines. The study was conducted in farmlands within a matrix of commercial Eucalyptus plantation and remnants of natural habitats of cerrado vegetation (savannah-like) in southeastern Brazil. Rhea groups were located visually in different habitats visited monthly from January 2004 to December 2005. Time spent searching greater rheas in each habitat was equally distributed. Data were collected using scan sampling with instantaneous recording of behaviours every minute. The time–activity budget of greater rheas was influenced by habitat structure, time of the day, season and group size. Rheas spent more time in open areas than in forested areas (p < 0.001). Vigilance behaviours were more displayed in forested areas, in the dry season and by solitary and small groups of birds. Resting behaviours occurred more often in open lands and within groups with more than three rheas. Food availability, good visibility and low human presence are the possible factors for the preference of greater rheas for pasturelands. The results support the resource availability hypothesis, where it is expected that habitats with a higher food availability will be more used by the animals, group size hypothesis, where the scarcity of resources will lead to smaller groups of animals and that forestry modifies greater rheas habitat use and behaviours.     

Enzymatic hydrolysis of chemithermomechanically pretreated sugarcane bagasse and samples with reduced initial lignin content

Chemithermomechanical (CTM) processing was used to pretreat sugarcane bagasse with the aim of increasing cell wall accessibility to hydrolytic enzymes. Yields of the pretreated samples were in the range of 75-94%. Disk refining and alkaline-CTM and alkaline/sulfite-CTM pretreatments yielded pretreated materials with 21.7, 17.8, and 15.3% of lignin, respectively. Hemicellulose content was also decreased to some extent. Fibers of the pretreated materials presented some external fibrillation, fiber curling, increased swelling, and high water retention capacity. Cellulose conversion of the alkaline-CTM- and alkaline/sulfite-CTM-pretreated samples reached 50 and 85%, respectively, after 96 h of enzymatic hydrolysis. Two samples with low initial lignin content were also evaluated after the mildest alkaline-CTM pretreatment. One sample was a partially delignified mill-processed bagasse. The other was a sugarcane hybrid selected in a breeding program. Samples with lower initial lignin content were hydrolyzed considerably faster in the first 24 h of enzymatic digestion. For example, enzymatic hydrolysis of the sample with the lowest initial lignin content (14.2%) reached 64% cellulose conversion after only 24 h of hydrolysis when compared with the 30% observed for the mill-processed bagasse containing an initial lignin content of 24.4%.     

IKZF1 deletions associate with CRLF2 overexpression leading to a poor prognosis in B-cell precursor acute lymphoblastic leukaemia

Cytokine Receptor-Like Factor 2 (CRLF2) overexpression occurs in 5-15% of B-cell precursor acute lymphoblastic leukaemia (B-ALL). In ∼50% of these cases, the mechanisms underlying this dysregulation are unknown. IKAROS Family Zinc Finger 1 (IKZF1) is a possible candidate to play a role in this dysregulation since it binds to the CRLF2 promoter region and suppresses its expression. We hypothesised that IKZF1 loss of function, caused by deletions or its short isoforms expression, could be associated with CRLF2 overexpression in B-ALL. A total of 131 paediatric and adult patients and 7 B-ALL cell lines were analysed to investigate the presence of IKZF1 deletions and its splicing isoforms expression levels, the presence of CRLF2 rearrangements or mutations, CRLF2 expression and JAK2 mutations. Overall survival analyses were performed according to the CRLF2 and IKZF1 subgroups. Our analyses showed that 25.2% of patients exhibited CRLF2 overexpression (CRLF2-high). CRLF2-high was associated with the presence of IKZF1 deletions (IKZF1del, p = 0.001), particularly with those resulting in dominant-negative isoforms (p = 0.006). Moreover, CRLF2 expression was higher in paediatric samples with high loads of the short isoform IK4 (p = 0.011). It was also associated with the occurrence of the IKZF1 plus subgroup (p = 0.004). Furthermore, patients with CRLF2-high/IKZF1del had a poorer prognosis in the RELLA05 protocol (p = 0.067, 36.1 months, 95%CI 0.0-85.9) and adult cohort (p = 0.094, 29.7 months, 95%CI 11.8–47.5). In this study, we show that IKZF1 status is associated with CRLF2-high and dismal outcomes in B-ALL patients regardless of age.