High-resolution Transcript Profiling Of The Atypical Biotrophic Interaction Between Theobroma Cacao And The Fungal Pathogen Moniliophthora Perniciosa.

Witches' broom disease (WBD), caused by the hemibiotrophic fungus Moniliophthora perniciosa, is one of the most devastating diseases of Theobroma cacao, the chocolate tree. In contrast to other hemibiotrophic interactions, the WBD biotrophic stage lasts for months and is responsible for the most distinctive symptoms of the disease, which comprise drastic morphological changes in the infected shoots. Here, we used the dual RNA-seq approach to simultaneously assess the transcriptomes of cacao and M. perniciosa during their peculiar biotrophic interaction. Infection with M. perniciosa triggers massive metabolic reprogramming in the diseased tissues. Although apparently vigorous, the infected shoots are energetically expensive structures characterized by the induction of ineffective defense responses and by a clear carbon deprivation signature. Remarkably, the infection culminates in the establishment of a senescence process in the host, which signals the end of the WBD biotrophic stage. We analyzed the pathogen's transcriptome in unprecedented detail and thereby characterized the fungal nutritional and infection strategies during WBD and identified putative virulence effectors. Interestingly, M. perniciosa biotrophic mycelia develop as long-term parasites that orchestrate changes in plant metabolism to increase the availability of soluble nutrients before plant death. Collectively, our results provide unique insight into an intriguing tropical disease and advance our understanding of the development of (hemi)biotrophic plant-pathogen interactions.

Atypical antipsychotics in the treatment of pathological aggression in children and adolescents: literature review and clinical recommendations

Objective: To review the literature about the use of atypical antipsychotics in the treatment of pathological aggression in children and adolescents. Method: The databases MEDLINE, SciELO, and LILACS were searched for publications in Portuguese or English from 1992 to August 2011 using the following keywords: mental disease, child, adolescent, treatment, atypical antipsychotic, aggressive behavior, aggression, and violent behavior. Results: Sixty-seven studies of good methodological quality and clinical interest and relevance were identified. Studies including children and adolescents were relatively limited, because few atypical antipsychotics have been approved by the Food and Drug Administration (FDA). All the medications included in this review (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole and clozapine) have some effectiveness in treating aggression in children and adolescents, and choices should be based on clinical indications and side effects. Conclusions: There are few studies about the effectiveness and safety of atypical antipsychotics for the pediatric population, and further randomized controlled studies with larger groups of patients and more diagnostic categories, such as severe conduct disorder and oppositional defiant disorder, should be conducted to confirm the results reported up to date and to evaluate the impact of long-term use.

Clonal relationship among atypical enteropathogenic Escherichia coli strains isolated from different animal species and humans

Forty-nine typical and atypical enteropathogenic Escherichia coli (EPEC) strains belonging to different serotypes and isolated from humans, pets (cats and dogs), farm animals (bovines, sheep, and rabbits), and wild animals (monkeys) were investigated for virulence markers and clonal similarity by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). The virulence markers analyzed revealed that atypical EPEC strains isolated from animals have the potential to cause diarrhea in humans. A close clonal relationship between human and animal isolates was found by MLST and PFGE. These results indicate that these animals act as atypical EPEC reservoirs and may represent sources of infection for humans. Since humans also act as a reservoir of atypical EPEC strains, the cycle of mutual infection of atypical EPEC between animals and humans, mainly pets and their owners, cannot be ruled out since the transmission dynamics between the reservoirs are not yet clearly understood.

Virulence features of atypical enteropathogenic Escherichia coli identified by the eae(+) EAF-negative stx(-) genetic profile

This study characterized 76 atypical enteropathogenic Escherichia coli (aEPEC) strains, previously classified by the eae(+) EAF-negative stx(-) genotype, isolated from children with diarrhea in Brazil. Presence of bfpA and bfpA/perA was detected in 2 and 6 strains, respectively. The expression of bundle-forming pilus (BFP), however, was observed by immunofluorescence in 1 bfpA and 3 bfpA/perA strains, classifying them as typical EPEC (tEPEC). The remaining 72 aEPEC strains were characterized by serotyping, intimin typing, adherence patterns to HEp-2 cells, capacity to induce actin aggregation (fluorescent actin staining test), and antimicrobial resistance. Our results show that aEPEC comprise a very heterogeneous group that does not present any prevalence or association regarding the studied characteristics. It also suggest that tEPEC and aEPEC must not be classified only by the reactivity with the EAF probe, and that the search of other markers present in pEAF, as well as the BFP expression, must be considered for this matter. (C) 2009 Elsevier Inc. All rights reserved.

The contribution of classical (beta(1/2)-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta(3)-adrenoceptor agonists of differing selectivities

The role of beta(3)- and other putative atypical beta-adrenaceptors in human white adipocytes and right atrial appendage has been investigated using CGP 12177 and novel phenylethanolamine and aryloxypropanolamine beta(3)-adrenoceptor (beta(3)AR) agonists with varying intrinsic activities and selectivities for human cloned PAR subtypes. The ability to demonstrate beta(1/2)AR antagonist-insensitive (beta(3) or other atypical beta AR-mediated) responses to CGP 12177 was critically dependent on the albumin batch used to prepare and incubate the adipocytes. Four aryloxypropanolamine selective beta(3)AR agonists (SB-226552, SB-229432, SB-236923, SB-246982) consistently elicited beta(1/2)AR antagonist-insensitive lipolysis. However, a phenylethanolamine (SB-220646) that was a selective full beta(3)AR agonist elicited full lipolytic and inotropic responses that were sensitive to beta(1/2)AR antagonism, despite it having very low efficacies at cloned beta(1)- and beta(2)ARs. A component of the response to another phenylethanolamine selective beta(3)AR agonist (SB-215691) was insensitive to beta(1/2)AR antagonism in some experiments. Because novel aryloxypropanolamine had a beta(1/2)AR antagonist-insensitive inotropic effect, these results establish more firmly that beta(3)ARs mediate lipolysis in human white adipocytes, and suggest that putative 'beta(4)ARs' mediate inotropic responses to CGP 12177. The results also illustrate the difficulty of predicting from studies on cloned beta ARs which beta ARs will mediate responses to agonists in tissues that have a high number of beta(1)- and beta(2)ARs or a low number of beta(3)ARs.

Impact of Atypical Retardation Patterns on Detection of Glaucoma Progression using the GDx with Variable Corneal Compensation

PURPOSE: To evaluate the impact of atypical retardation patterns (ARP) on detection of progressive retinal nerve fiber layer (RNFL) loss using scanning laser polarimetry with variable corneal compensation (VCC). DESIGN: Observational cohort study. METHODS: The study included 377 eyes of 221 patients with a median follow-up of 4.0 years. Images were obtained annually with the GDx VCC (Carl Zeiss Med, itec Inc, Dublin, California, USA), along with optic disc stereophotographs and standard automated perimetry (SAP) visual fields. Progression was determined by the Guided Progression Analysis software for SAP and by masked assessment of stereophotographs by expert graders. The typical scan score (TSS) was used to quantify the presence of ARPs on GDx VCC images. Random coefficients models were used to evaluate the relationship between ARP and RNFL thickness measurements over time. RESULTS: Thirty-eight eyes (10%) showed progression over time on visual fields, stereophotographs, or both. Changes in TSS scores from baseline were significantly associated with changes in RNFL thickness measurements in both progressing and nonprogressing eyes. Each I unit increase in TSS score was associated with a 0.19-mu m decrease in RNFL thickness measurement (P < .001) over time. CONCLUSIONS: ARPs had a significant effect on detection of progressive RNFL loss with the GDx VCC. Eyes with large amounts of atypical patterns, great fluctuations on these patterns over time, or both may show changes in measurements that can appear falsely as glaucomatous progression or can mask true changes in the RNFL. (Am J Ophthalmol 2009;148:155-163. (C) 2009 by Elsevier Inc. All rights reserved.)

Atypical enteropathogenic Escherichia coli genomic background allows the acquisition of non-EPEC virulence factors

Atypical enteropathogenic Escherichia coli (aEPEC) has been associated with infantile diarrhea in many countries. The clonal structure of aEPEC is the object of active investigation but few works have dealt with its genetic relationship with other diarrheagenic E. coli (DEC). This study aimed to evaluate the genetic relationship of aEPEC with other DEC pathotypes. The phylogenetic relationships of DEC strains were evaluated by multilocus sequence typing. Genetic diversity was assessed by pulsed-field gel electrophoresis (PFGE). The phylogram showed that aEPEC strains were distributed in four major phylogenetic groups (A, B1, B2 and D). Cluster I ( group B1) contains the majority of the strains and other pathotypes [enteroaggregative, enterotoxigenic and enterohemorrhagic E. coli ( EHEC)]; cluster II ( group A) also contains enteroaggregative and diffusely adherent E. coli; cluster III ( group B2) has atypical and typical EPEC possessing H6 or H34 antigen; and cluster IV ( group D) contains aEPEC O55:H7 strains and EHEC O157:H7 strains. PFGE analysis confirmed that these strains encompass a great genetic diversity. These results indicate that aEPEC clonal groups have a particular genomic background - especially the strains of phylogenetic group B1 that probably made possible the acquisition and expression of virulence factors derived from non-EPEC pathotypes.

Polymerase chain reaction compared to other laboratory findings and to clinical evaluation in the diagnosis of cutaneous tuberculosis and atypical mycobacteria skin infection

Cutaneous tuberculosis has re-emerged in the last 15 years together with the higher incidence of pulmonary tuberculosis and multidrug resistance. The choice for a single diagnostic tool among the many available today is a challenge. Our objective was to compare polymerase chain reaction (PCR) with other exams in the diagnosis of cutaneous tuberculosis and atypical mycobacteria skin infection. PCR and a set of five different exams were performed in 32 patients (34 samples of paraffin-embedded tissue) evaluated for 3 years in a university hospital, considering the response to mycobacterial infection treatment as a positive case. PCR was the most sensitive (88%) and specific (83%) exam. Culture, immunohistochemistry and acid-fast bacilli were not in agreement with clinical response to treatment. Although PCR is a useful tool, careful clinical exam is still the gold standard for the evaluation and treatment of cutaneous tuberculosis and mycobacteria skin infection.

Childhood radiation-associated atypical meningioma with novel complex rearrangements involving chromosomes 1 and 12

Meningiomas are recognized as the most common late complication following radiotherapy. However, cytogenetic studies in childhood atypical radiation-induced meningioma are sporadic, mainly because this condition generally occurs after a long latent period. In the present study we show the results of conventional and molecular cytogenetics in a 14-year-old boy with a secondary atypical meningioma. Apart from numerical changes, we found complex aberrations with the participation of chromosomes 1, 6 and 12. The invariable presence of loss of 1p was demonstrated by fluorescent in situ hybridization (FISH) analysis with probes directed to telomeric regions and by comparative genome hybridization (CGH). Previous cytogenetic studies on adult spontaneous and radiation-associated meningiomas showed loss of chromosome 22 as the most frequent change, followed by loss of the short arm of chromosome 1. To the best of our knowledge this is the first report of highly complex chromosome aberrations in the pediatric setting of meningioma.

Polyploidy in atypical grade II choroid plexus papilloma of the posterior fossa

Cytogenetic studies of choroid plexus tumors, particularly for atypical choroid plexus papillomas, have been rarely described. In the present report, the cytogenetic investigation of an atypical choroid plexus papilloma occurring at the posterior fossa of a 16-year-old male is described. Comparative genome hybridization analysis demonstrated gains of genetic material from almost all chromosomes. Chromosome losses involved 19p, regional losses at chromosome X and loss of chromosome Y. The presence of polyploid cells was confirmed by fluorescence in situ hybridization analysis with probes directed to centromeric regions. Furthermore, the microscopic analysis of cultures showed nuclear buds, nucleoplasmic bridges, and micronuclei in 23% of tumor cells suggesting the presence of complex chromosomal abnormalities. Previous cytogenetic studies on choroid plexus papillomas showed either normal, hypodiploid or hyperdiploid karyotypes. To the best of our knowledge, this is the first report of polyploidy in choroid plexus papilloma of intermediate malignancy grade. Although the mechanisms beneath such genome duplication remain to be elucidated, the observed abnormal nuclear shapes indicate constant restructuring of the tumor`s genome and deserves further investigation.

Anti-aversive effects of the atypical antipsychotic, aripiprazole, in animal models of anxiety

Aripiprazole is a unique antipsychotic that seems to act as a partial agonist at dopamine D2-receptors, contrasting with other drugs in this class, which are silent antagonists. Aripiprazole may also bind to serotonin receptors. Both neurotransmitters may play major roles in aversion-, anxiety-and panic-related behaviours. Thus, the present work tested the hypothesis that this antipsychotic could also have anti-aversive properties. Male Wistar rats received injections of aripiprazole (0.1-10 mg/kg) and were tested in the open field, in the elevated plus and T mazes (EPM and ETM, respectively) and in a contextual fear conditioning paradigm. Aripiprazole (1mg/kg) increased the percentage of entries onto the open arms of the EPM and attenuated escape responses in the ETM. In the latter model, the dose of 0.1 mg/kg also decreased the latency to leave the enclosed arm, suggesting anxiolytic- and panicolytic-like properties. This dose also decreased the time spent in freezing in a contextual fear conditioning. No significant motor effects were observed at these doses. The present data support the hypothesis that aripiprazole could inhibit anxiety-related responses. Acting as a partial agonist at dopamine receptors, this drug could effectively treat schizophrenia and, in contrast with most antipsychotic drugs, alleviate aversive states.

Aripiprazole, an atypical antipsychotic prevents the motor hyperactivity induced by psychotomimetics, and psyphostimulants in mice

Aripiprazole is an atypical antipsychotic that acts as a partial agonist at the dopamine D-2 receptor. It has been mainly investigated in dopamine-based models of schizophrenia, while its effects on glutamate-based paradigms have remained to be further characterized. Due to its unique mechanism of action, aripiprazole has also been considered as a replacement medication for psychostimulant abuse. Thus, in the present study we tested the hypothesis that aripiprazole would prevent the motor hyperactivity induced by psychostimulant and psychotomimetic drugs that act either by dopaminergic or glutamatergic mechanisms. Male Swiss mice received injections of aripiprazole (0.1-1 mg/kg) followed by drugs that enhance the dopamine-mediated neurotransmission, amphetamine (3 mg/kg) or cocaine (5 mg/kg), or by glutamate NMDA-receptor antagonists, ketamine (60 mg/kg) or MK-801 (0.4 mg/kg). Independent groups also received aripiprazole (0.1-1 mg/kg) or haloperidol (0.5 mg/kg) and were tested for catalepsy. All doses of aripiprazole were effective in preventing the motor stimulant effects of amphetamine and cocaine. Moreover, the higher dose also prevented the effects of ketamine and MK-801. The present study reports the effects of aripiprazole in dopaminergic and glutamatergic models predictive of antipsychotic activity, suggesting that both may be useful for screening novel partial agonists with antipsychotic activity. It also shows that aripiprazole may prevent the acute effects of psychostimulant drugs without significant motor impairment. C) 2007 Elsevier B.V. All rights reserved.

Expression of cell adhesion proteins and proteins related to angiogenesis and fatty acid metabolism in benign, atypical, and anaplastic meningiomas

Most meningiomas are benign tumours of arachnoidal origin, although a small number have high proliferative rates and invasive properties which complicate complete surgical resection and are associated with increased recurrence rates. Few prognostic indicators exist for meningiomas and further research is necessary to identify factors that influence tumour invasion, oedema and recurrence. Paraffin sections from 25 intracranial meningiomas were analysed for expression of the proteins vascular endothelial growth factor (VEGF), VEGF receptors Flt1 and Flk1, E-cadherin, metalloproteinases 2 and 9 (MMP2, MMP9), CD44, receptor for hyaluronic acid-mediated motility (RHAMM), hyaluronic acid (HA), CD45, cyclooxygenase 2 (COX2), brain fatty acid binding protein (BFABP), Ki67, and proliferating cell nuclear antigen (PCNA). Correlations among protein expression were found for several markers of proliferation (Ki67, PCNA, MI) and microvessel density (MVD). COX2 expression increased with increasing with tumour grade and correlated with Ki67, PCNA, MI, MVD, and BFABP. BFABP expression also correlated with Ki67 and PCNA expression. Relationships were also identified among angiogenic factors (VEGF, Flt1, Flk1) and proliferation markers. Oedema was found to correlate with MMP9 expression and MMP9 also correlated with proliferation markers. No correlations were found for MMP2, E-cadherin, or CD44 in meningiomas. In conclusion Ki67, PCNA, MI, MVD, BFABP, and COX2 were significantly correlated with meningioma tumour grade and with each other. These findings, by correlating both intracellular fatty acid transport and eicosanoid metabolism with tumour proliferation, as determined by Ki67 labelling and mitotic index, suggest fatty acids are involved in the progression of meningiomas.