Influence of migration on the thought process of individuals at ultra-high risk for psychosis

Objective: To assess the influence of migration on the psychopathological presentation of individuals at ultra-high risk for psychosis (UHR) in São Paulo, Brazil. Methods: This study is part of the Subclinical Symptoms and Prodromal Psychosis (SSAPP) project, a cohort study in São Paulo, Brazil, designed to follow individuals at UHR. After screening with the Prodromal Questionnaire (PQ) and a clinical interview, the Global Assessment of Functioning (GAF) was administered, a neuropsychological assessment was performed, sociodemographic and migration data were obtained. We then analyzed UHR individuals who had migration data to see if migration had any effect on their cognition and psychopathology. Chi-square tests were used for categorical variables, and Student's t test or analysis of variance (ANOVA) were used for nonparametric and parametric distributions, respectively. Results: The sample was composed of 42 at-risk subjects, of whom 5 had a migration history in the past two generations. Those with migration history showed significantly more formal thought disturbances (p = 0.012) and sleeping problems (p = 0.033) compared to those without. Conclusions: Our data reinforce migration as a risk factor for psychosis in developing countries as well, and highlights the importance of studying the specific effect of this factor in UHR psychopathology.

A green metal-free "one-pot" microwave assisted synthesis of 1,4-dihydrochromene triazoles.

The synthesis of several 4-aryl-1,4-dihydrochromene-triazoles was achieved via a metal-free "one-pot" procedure using PEG400 as the sole solvent in an eco-friendly process. Using microwave irradiation, the triazole derivatives were obtained in good yields and short reaction times starting from readily accessible building blocks.

Influence of migration on the thought process of individuals at ultra-high risk for psychosis.

OBJECTIVE: To assess the influence of migration on the psychopathological presentation of individuals at ultra-high risk for psychosis (UHR) in São Paulo, Brazil. METHODS: This study is part of the Subclinical Symptoms and Prodromal Psychosis (SSAPP) project, a cohort study in São Paulo, Brazil, designed to follow individuals at UHR. After screening with the Prodromal Questionnaire (PQ) and a clinical interview, the Global Assessment of Functioning (GAF) was administered, a neuropsychological assessment was performed, sociodemographic and migration data were obtained. We then analyzed UHR individuals who had migration data to see if migration had any effect on their cognition and psychopathology. Chi-square tests were used for categorical variables, and Student's t test or analysis of variance (ANOVA) were used for nonparametric and parametric distributions, respectively. RESULTS: The sample was composed of 42 at-risk subjects, of whom 5 had a migration history in the past two generations. Those with migration history showed significantly more formal thought disturbances (p = 0.012) and sleeping problems (p = 0.033) compared to those without. CONCLUSIONS: Our data reinforce migration as a risk factor for psychosis in developing countries as well, and highlights the importance of studying the specific effect of this factor in UHR psychopathology.

Diversity, ecology, and bioprospecting of culturable fungi in lakes impacted by anthropogenic activities in Maritime Antarctica.

In this study, we accessed culturable fungal assemblages present in the sediments of three lakes potentially impacted anthropogenically in the Fildes Peninsula, King George Island, Antarctica and identified 63 taxa. Cladosporium sp. 2, Pseudeurotium hygrophilum, and Pseudogymnoascus verrucosus were recovered from the sampled sediments of all lakes. High concentrations of metals and the lowest fungal diversity indices were detected in the sediments of the Central Lake, which can be influenced by human activities due to their proximity to research stations to those of the other two lakes, which were far from the Antarctic stations. At least one type of biological activity was demonstrated by 40 fungal extracts. Among these, P. hygrophilum, P. verrucosus, Penicillium glabrum, and Penicillium solitum demonstrated strong trypanocidal, herbicidal, and antifungal activities. Our results suggest that an increase of the anthropogenic activities in the region might have affected the microbial diversity and composition. In addition, the fungal diversity in these lakes may be a useful model to study the effect of anthropogenic activities in Antarctica. We isolated a diverse group of fungal taxa from Antarctic lake sediments, which have the potential to produce novel compounds for the both the medical and agriculture sectors.

Diversity and bioprospecting of cultivable fungal assemblages in sediments of lakes in the Antarctic Peninsula.

We recovered 195 fungal isolates from the sediments of different lakes in the Antarctic Peninsula, which were screened to detect bioactive compounds. Forty-two taxa belonging to the phyla Ascomycota, Basidiomycota, and Mortierellomycota were identified. Thelebolus globosus, Antarctomyces psychrotrophicus, Pseudogymnoascus verrucosus, Vishniacozyma victoriae, and Phenoliferia sp. were found to be the most prevalent. The fungal assemblages showed high diversity and richness, but low dominance values. However, the diversity indices and fungal distribution ranged according to the different lake sediments. Sixty fungal extracts displayed at least one biological activity against the evaluated targets. Among them, Pseudogymnoascus destructans showed selective trypanocidal activity, Cladosporium sp. 1 and Trichoderma polysporum showed antifungal activity, and Pseudogymnoascus appendiculatus and Helotiales sp. showed high herbicidal activity. We detected a rich and diverse fungal community composed of cold cosmopolitan and psychrophilic endemic taxa recognized as decomposers, symbiotics, pathogens, and potential new species, in the sediments of Antarctic lakes. The dynamics and balance of this fungal community represents an interesting aquatic web model for further ecological and evolutionary studies under extreme conditions and potential climate changes in the regions. In addition, we detected fungal taxa and isolates able to produce bioactive compounds that may represent the source of prototype molecules for applications in medicine and agriculture.

Cultivable fungi present in deep-sea sediments of Antarctica: taxonomy, diversity, and bioprospecting of bioactive compounds.

We accessed the culturable mycobiota present in marine sediments at different depths in Antarctica Ocean. Acremonium fusidioides, Penicillium allii-sativi, Penicillium chrysogenum, Penicillium palitans, Penicillium solitum, and Pseudogymnoascus verrucosus were identified. Penicillium allii-sativi was the dominant species. At least one isolate of each species was capable to present antifungal, trypanocidal, leishmanicidal, antimalarial, nematocidal, or herbicidal activities. Penicillium produced extracts with strong trypanocidal and antimalarial activities, and the extracts of P. solitum and P. chrysogenum demonstrated strong antimalarial activities. Acremonium fusidioides and P. verrucosus displayed strong selective herbicidal properties. The 1H NMR signals for extracts of A. fusidioides, P. chrysogenum, and P. solitum indicated the presence of highly functionalized secondary metabolites, which may be responsible for the biological activities detected. In the deep marine Antarctic sediments, we detected fungal assemblages in which the Penicillium species were found to be dominant and demonstrated capabilities to survive and/or colonise that poly-extreme habitat. Penicillium being a polyextremophile Antarctic species, exhibited strong biological activities and the presence of aromatic compounds in its extracts may indicate that they are wild ancient strains with high genetic and biochemical potentials that enable them to produce bioactive compounds which can be researched in further studies and used in the chemotherapy of neglected tropical diseases as well as in agriculture.

Potent stimulation of eosinopoiesis in murine bone-marrow by myriadenolide is mediated by cysteinyl-leukotriene signaling.

We describe the potent effect of myriadenolide (Myr), a naturally occurring labdane diterpene, in promoting the production of eosinophils in cultured bone-marrow from several inbred mouse strains. This enhancing effect is lineage-selective and requires the eosinophil growth factors, Interleukin(IL)-5 or GM-CSF. Myr acts over a very low concentration range (10-10-10-14 M), if added at the beginning of the cell cultivation. Its enhancing effect increases between 24 h and 10 days of culture. We used both pharmacological and genetical tools to analyze its mechanism of action. Several lines of evidence show that the enhancing effect of Myr requires functional integrity of the 5-lipoxygenase (5-LO) pathway, and of CysLT1 receptors, which transduce the effects of cysteinyl-leukotrienes generated through this pathway. Myr also protects developing eosinophils from apoptosis induced by exogenous prostaglandin E2 (PGE2), but not by NO, indicating that it acts upstream of NO in the PGE2-initiated proapoptotic pathway which requires iNOS and CD95. Exposure to NO concentrations insufficient to induce apoptosis abolished the ability of eosinophils to respond to Myr, suggesting the involvement of a NO-sensitive cellular target. Myr has potential as a chemically defined research tool, which can be used to generate large numbers of eosinophils, thereby overcoming current limitations in the biochemical and molecular biological study of murine eosinophils, which has so far depended on complex, labor-intensive and long-term culture protocols for in vitro expansion. SUMMARY: Potent enhancing effects of Myr on eosinophil production in bone marrow stimulated by GM-CSF and IL-5 are mediated by the 5-LO pathway.

Two new usnic acid derivatives from the endophytic fungus Mycosphaerella sp.

The endophytic fungus Mycosphaerella sp. (UFMGCB2032) was isolated from the healthy leaves of Eugenia bimarginata, a plant from the Brazilian savanna. Two novel usnic acid derivatives, mycousfuranine (1) and mycousnicdiol (2), were isolated from the ethyl acetate extract, and their structure was elucidated by NMR and MS analyses. Compounds 1 and 2 exhibited moderate antifungal activities against Cryptococcus neoformans and Cryptococcus gattii, each with minimum inhibitory concentration values of 50.0 µg/mL and 250.0 µg/mL, respectively.

Cobalt-Catalyzed Stereoselective Synthesis of 2,5- trans-THF Nitrile Derivatives as a Platform for Diversification: Development and Mechanistic Studies.

A straightforward protocol integrating a sustainable approach for the synthesis of new 2,5- trans-THF nitrile derivatives enabling an easy diversification of its side chain scaffolds is described. The reaction tolerated different aromatic and alkyl substituents, affording the corresponding 2,5- trans-THFs in high diastereoselectivity. A detailed mechanistic study using DFT calculation reveals details of the ligand-exchange step, suggesting an inner-sphere syn attack to form the 2,5- trans stereochemistry as the most likely pathway, excluding the previous cation radical intermediate. The formation of a Co-C intermediate is suggested on the basis of the homolytic cleavage to give the previously proposed free carbon radical intermediate.

Cultivable fungi present in Antarctic soils: taxonomy, phylogeny, diversity, and bioprospecting of antiparasitic and herbicidal metabolites.

Molecular biology techniques were used to identify 218 fungi from soil samples collected from four islands of Antarctica. These consisted of 22 taxa of 15 different genera belonging to the Zygomycota, Ascomycota, and Basidiomycota. Mortierella, Antarctomyces, Pseudogymnoascus, and Penicillium were the most frequently isolated genera and Penicillium tardochrysogenum, Penicillium verrucosus, Goffeauzyma gilvescens, and Mortierella sp. 2 the most abundant taxa. All fungal isolates were cultivated using solid-state fermentation to obtain their crude extracts. Pseudogymnoascus destructans, Mortierella parvispora, and Penicillium chrysogenum displayed antiparasitic activities, whilst extracts of P. destructans, Mortierella amoeboidea, Mortierella sp. 3, and P. tardochrysogenum showed herbicidal activities. Reported as pathogenic for bats, different isolates of P. destructans exhibited trypanocidal activities and herbicidal activity, and may be a source of bioactive molecules to be considered for chemotherapy against neglected tropical diseases. The abundant presence of P. destructans in soils of the four islands gives evidence supporting that soils in the Antarctic Peninsula constitute a natural source of strains of this genus, including some P. destructans strains that are phylogenetically close to those that infect bats in North America and Europe/Palearctic Asia.

In vitro leishmanicidal, antibacterial and antitumour potential of anhydrocochlioquinone A obtained from the fungus Cochliobolus sp.

The bioassay-guided fractionation of the ethyl acetate extract of the fungus Cochliobolus sp. highlighted leishmanicidal activity and allowed for anhydrocochlioquinone A (ANDC-A) isolation. MS, 1D and 2D NMR spectra of this compound were in agreement with those published in the literature. ANDC-A exhibited leishmanicidal activity with EC 50 value of 22.4 microgram/mL (44 mu M) and, when submitted to the microdilution assay against Gram-ositive and Gram-negative bacteria, showed a minimal inhibitory concentration against Staphylococcus aureus ATCC 25295 of 128 microgram/mL (248.7 mu M). It was also active against five human cancer cell lines, showing IC50 values from 5.4 to 20.3 mu M. ANDC-A demonstrated a differential selectivity for HL-60 (SI 5.5) and THP-1 (SI 4.3) cell lines in comparison with Vero cells and was more selective than cisplatin and doxorubicin against MCF-7 cell line in comparison with human peripheral blood mononuclear cells. ANDC-A was able to eradicate clonogenic tumour cells at concentrations of 20 and 50 mu M and induced apoptosis in all tumour cell lines at 20 mu M. These results suggest that ANDC-A might be used as a biochemical tool in the study of tumour cells biochemistry as well as an anticancer agent with durable effects on tumours.

Cognition and impulsivity in adults with attention deficit hyperactivity disorder with and without cocaine and/or crack dependence.

BACKGROUND: Substance use disorder (SUD) is a common comorbidity in adults with attention deficit-hyperactivity disorder (ADHD). However,there have been few studies on cognitive profiles of these patients. Impulsivity is also commonly increased in both disorders. The central aim of this study was to compare cognition and impulsivity in subjects who had ADHD and cocaine dependence (ADHD+COC group) to those with ADHD only (ADHD-noSUD group). We hypothesized that the ADHD+COC group would show more marked cognitive dysfunction and greater impulsivity than their counterparts with ADHD only. METHODS: A total of 70 adult patients diagnosed with ADHD according to (DSM-IV-TR) criteria were enrolled; 36 with ADHD+COC and 34 with ADHD-noSUD. All study participants were evaluated with a sociodemographic questionnaire; the Mini International Neuropsychiatric Interview; the Adult ADHD Self-Report Scale; the Addiction Severity Index; the Alcohol, Smoking and Substance Involvement Screening Test; the Barratt Impulsiveness Scale; and a comprehensive neurocognitive battery. RESULTS: Compared to individuals with ADHD-noSUD, ADHD+COC individuals had significantly lower mean IQ and higher motor impulsivity. On average, the ADHD+COC group also performed more poorly on tasks assessing verbal skills, vigilance, implicit learning during decision making, and ADHD-noSUD performed more poorly on selective attention, information processing, and visual search. CONCLUSIONS: Our results support the integrative theory of ADHD based on the cognitive and affective neuroscience model, and suggests that ADHD-noSUD patients have impairments in cognitive regulation, while ADHD+COC patients have impairments in both cognitive and affective regulation.

Biological activities of ophiobolin K and 6-epi-ophiobolin K produced by the endophytic fungus Aspergillus calidoustus.

Endophytic fungi represent ubiquitous microbial organisms able to live in the tissues of different plants around the world and represent a prolific source of bioactive metabolites. In the present study, the endophytic fungus Aspergillus calidoustus was isolated from the medicinal plant Acanthospermum australe (Asteraceae), and identified using molecular, physiological and morphological methods. A methylene chloride crude extract of A. calidoustus has been produced and subjected to antifungal bioassay-directed fractionation which resulted in the isolation of the two bioactive compounds: ophiobolin K and 6-epi-ophiobolin K. These pure compounds displayed antifungal activity against fungal plant pathogens, protozoal activity against Trypanosoma cruzi, and cytotoxic activity against human tumoral cell lines. The results show that A. calidoustus was able to produce the antifungal and cytotoxic metabolites ophiobolin K and 6-epi-ophiobolin K, which may help the fungus to colonise and occupy the substratum as well as survive in natural environments.

Fungi associated with rocks of the Atacama Desert: taxonomy, distribution, diversity, ecology and bioprospection for bioactive compounds.

This study assessed the diversity of cultivable rock-associated fungi from Atacama Desert. A total of 81 fungal isolates obtained were identified as 29 Ascomycota taxa by sequencing different regions of DNA. Cladosporium halotolerans, Penicillium chrysogenum and Penicillium cf. citrinum were the most frequent species, which occur at least in four different altitudes. The diversity and similarity indices ranged in the fungal communities across the latitudinal gradient. The Fisher-α index displayed the higher values for the fungal communities obtained from the siltstone and fine matrix of pyroclastic rocks with finer grain size, which are more degraded. A total of 23 fungal extracts displayed activity against the different targets screened. The extract of P. chrysogenum afforded the compounds α-linolenic acid and ergosterol endoperoxide, which were active against Cryptococcus neoformans and methicillin-resistance Staphylococcus aureus respectively. Our study represents the first report of a new habitat of fungi associated with rocks of the Atacama Desert and indicated the presence of interesting fungal community, including species related with saprobes, parasite/pathogen and mycotoxigenic taxa. The geological characteristics of the rocks, associated with the presence of rich resident/resilient fungal communities suggests that the rocks may provide a favourable microenvironment fungal colonization, survival and dispersal in extreme conditions.

Diversity and bioprospection of fungal community present in oligotrophic soil of continental Antarctica.

We surveyed the diversity and capability of producing bioactive compounds from a cultivable fungal community isolated from oligotrophic soil of continental Antarctica. A total of 115 fungal isolates were obtained and identified in 11 taxa of Aspergillus, Debaryomyces, Cladosporium, Pseudogymnoascus, Penicillium and Hypocreales. The fungal community showed low diversity and richness, and high dominance indices. The extracts of Aspergillus sydowii, Penicillium allii-sativi, Penicillium brevicompactum, Penicillium chrysogenum and Penicillium rubens possess antiviral, antibacterial, antifungal, antitumoral, herbicidal and antiprotozoal activities. Bioactive extracts were examined using (1)H NMR spectroscopy and detected the presence of secondary metabolites with chemical shifts. Our results show that the fungi present in cold-oligotrophic soil from Antarctica included few dominant species, which may have important implications for understanding eukaryotic survival in cold-arid oligotrophic soils. We hypothesize that detailed further investigations may provide a greater understanding of the evolution of Antarctic fungi and their relationships with other organisms described in that region. Additionally, different wild pristine bioactive fungal isolates found in continental Antarctic soil may represent a unique source to discover prototype molecules for use in drug and biopesticide discovery studies.

Bioactive endophytic fungi isolated from Caesalpinia echinata Lam. (Brazilwood) and identification of beauvericin as a trypanocidal metabolite from Fusarium sp.

Aiming to identify new sources of bioactive secondary metabolites, we isolated 82 endophytic fungi from stems and barks of the native Brazilian tree Caesalpinia echinata Lam. (Fabaceae). We tested their ethyl acetate extracts in several in vitro assays. The organic extracts from three isolates showed antibacterial activity against Staphylococcus aureus and Escherichia coli [minimal inhibitory concentration (MIC) 32-64 µg/mL]. One isolate inhibited the growth of Salmonella typhimurium (MIC 64 µg/mL) and two isolates inhibited the growth of Klebsiella oxytoca (MIC 64 µg/mL), Candida albicans and Candida tropicalis (MIC 64-128 µg/mL). Fourteen extracts at a concentration of 20 µg/mL showed antitumour activities against human breast cancer and human renal cancer cells, while two isolates showed anti-tumour activities against human melanoma cancer cells. Six extracts were able to reduce the proliferation of human peripheral blood mononuclear cells, indicating some degree of selective toxicity. Four isolates were able to inhibit Leishmania (Leishmania) amazonensis and one isolate inhibited Trypanosoma cruzi by at least 40% at 20 µg/mL. The trypanocidal extract obtained from Fusarium sp. [KF611679] culture was subjected to bioguided fractionation, which revealed beauvericin as the compound responsible for the observed toxicity of Fusarium sp. to T. cruzi. This depsipeptide showed a half maximal inhibitory concentration of 1.9 µg/mL (2.43 µM) in a T. cruzi cellular culture assay.

Diversity patterns, ecology and biological activities of fungal communities associated with the endemic macroalgae across the Antarctic peninsula.

We surveyed diversity patterns and engaged in bioprospecting for bioactive compounds of fungi associated with the endemic macroalgae, Monostroma hariotii and Pyropia endiviifolia, in Antarctica. A total of 239 fungal isolates were obtained, which were identified to represent 48 taxa and 18 genera using molecular methods. The fungal communities consisted of endemic, indigenous and cold-adapted cosmopolitan taxa, which displayed high diversity and richness, but low dominance indices. The extracts of endemic and cold-adapted fungi displayed biological activities and may represent sources of promising prototype molecules to develop drugs. Our results suggest that macroalgae along the marine Antarctic Peninsula provide additional niches where fungal taxa can survive and coexist with their host in the extreme conditions. We hypothesise that the dynamics of richness and dominance among endemic, indigenous and cold-adapted cosmopolitan fungal taxa might be used to understand and model the influence of climate change on the maritime Antarctic mycota.