The Role of Cannabinoids in CNS Development: Focus on Proliferation and Cell Death.

The active principles of Cannabis sativa are potential treatments for several diseases, such as pain, seizures and anorexia. With the increase in the use of cannabis for medicinal purposes, a more careful assessment of the possible impacts on embryonic development becomes necessary. Surveys indicate that approximately 3.9% of pregnant women use cannabis in a recreational and/or medicinal manner. However, although the literature has already described the presence of endocannabinoid system components since the early stages of CNS development, many of their physiological effects during this stage have not yet been established. Moreover, it is still uncertain how the endocannabinoid system can be altered in terms of cell proliferation and cell fate, neural migration, neural differentiation, synaptogenesis and particularly cell death. In relation to cell death in the CNS, knowledge about the effects of cannabinoids is scarce. Thus, the present work aims to review the role of the endocannabinoid system in different aspects of CNS development and discuss possible side effects or even opportunities for treating some conditions in the development of this tissue.

Microbacterium plantarum sp. nov. and Microbacterium thalli sp. nov., two endophytic metal-resistant bacteria isolated from Sphaeralcea angustifolia (Cav.) G. Don and Prosopis laevigata (Humb. et Bonpl. ex Willd) M.C. Johnston.

Four Gram-positive, aerobic, catalase- and oxidase-negative, rod-shaped, motile endophytic bacterial strains, designated NM3R9T, NE1TT3, NE2TL11 and NE2HP2T, were isolated from the inner tissues (leaf and stem) of Sphaeralcea angustifolia and roots of Prosopis laevigata. They were characterized using a polyphasic approach, which revealed that they represent two novel Microbacterium species. Phylogenetic analysis based on 16S rRNA gene sequencing showed that the species closest to NE2HP2T was Microbacterium arborescens DSM 20754T (99.6 %) and that closest to NM3R9T, NE2TL11 and NE2TT3 was Microbacterium oleivorans NBRC 103075T (97.4 %). The whole-genome average nucleotide identity value between strain NM3R9T and Microbacterium imperiale DSM 20530T was 90.91 %, and that between strain NE2HP2T and M. arborecens DSM 20754T was 91.03 %. Digital DNA-DNA hybridization showed values of less than 70 % with the type strains of related species. The polar lipids present in both strains included diphosphatidylglycerol, phosphatidylglycerol, glycolipids and unidentified lipids, whereas the major fatty acids included anteiso-C15 : 0, anteiso-C17 : 0, iso-C16 : 0 and C16 : 0. Whole-cell sugars included mannose, rhamnose and galactose. Strains NM3R9T and NE2HP2T showed physiological characteristics different from those present in closely related Microbacterium species. According to the taxonomic analysis, both strains belong to two novel species. The name Microbacterium plantarum sp. nov. is proposed for strain NE2HP2T (=LMG 30875T=CCBAU 101117T) and Microbacterium thalli sp. nov. for strains NM3R9T (=LMG 30873T=CCBAU 101116T), NE1TT3 (=CCBAU 101114) and NE2TL11 (=CCBAU 101115).

Retinal Toxicity Induced by Chemical Agents.

Vision is an important sense for humans, and visual impairment/blindness has a huge impact in daily life. The retina is a nervous tissue that is essential for visual processing since it possesses light sensors (photoreceptors) and performs a pre-processing of visual information. Thus, retinal cell dysfunction or degeneration affects visual ability and several general aspects of the day-to-day of a person's lives. The retina has a blood-retinal barrier, which protects the tissue from a wide range of molecules or microorganisms. However, several agents, coming from systemic pathways, reach the retina and influence its function and survival. Pesticides are still used worldwide for agriculture, contaminating food with substances that could reach the retina. Natural products have also been used for therapeutic purposes and are another group of substances that can get to the retina. Finally, a wide number of medicines administered for different diseases can also affect the retina. The present review aimed to gather recent information about the hazard of these products to the retina, which could be used to encourage the search for more healthy, suitable, or less risky agents.

The Production and Evaluation of an Electrochemical Sensors for Strychnine and Its Main Metabolite Strychnine N-Oxide for Their Use in Biological Samples.

Strychnine (STN) and its major metabolite Strychnine N-Oxide (SNO) were examined electrochemically. Both parent compounds and its major metabolite showed electroactivity on glassy carbon electrodes using CV and DPV techniques. One oxidation peak at 1008 mV was observed for STN with the optimum peak intensity at pH 7. SNO produced two oxidation peaks, at 617 mV and 797 mV, at pH 5. The peaks demonstrated irreversible behaviour and the irreversibility of the system was confirmed at different scan rates. A calibration curve was produced for both CV and DPV measurements and the sensitivity of the proposed EC method was good compared with previous electrochemical and non-electrochemical methods. The precision of oxidation peak of STN using the STN-MIP method produced a maximum value of 11.5% and 2.32% for inter-day and intraday %RSD, respectively. The average% recovery was around 92%. The electrochemical method has been successfully applied to the determination of STN in spiked plasma and urine samples. For SNO, both anodic peaks of SNO demonstrated irreversible behaviour. A different sweep rate was used for calculating the number of 'transfer electrons' in the system; based on this, the mechanism of oxidation reaction was proposed. Calibration curves for both oxidative peaks were produced using DPV measurements. The second anodic peak demonstrated high linearity and precision with %RSD < 1.96%.

Functional genomics of a Spiroplasma associated with the carmine cochineals Dactylopius coccus and Dactylopius opuntiae.

BACKGROUND: Spiroplasma is a widely distributed endosymbiont of insects, arthropods, and plants. In insects, Spiroplasma colonizes the gut, hemolymph, and reproductive organs of the host. Previous metagenomic surveys of the domesticated carmine cochineal Dactylopius coccus and the wild cochineal D. opuntiae reported sequences of Spiroplasma associated with these insects. However, there is no analysis of the genomic capabilities and the interaction of this Spiroplasma with Dactylopius. RESULTS: Here we present three Spiroplasma genomes independently recovered from metagenomes of adult males and females of D. coccus, from two different populations, as well as from adult females of D. opuntiae. Single-copy gene analysis showed that these genomes were > 92% complete. Phylogenomic analyses classified these genomes as new members of Spiroplasma ixodetis. Comparative genome analysis indicated that they exhibit fewer genes involved in amino acid and carbon catabolism compared to other spiroplasmas. Moreover, virulence factor-encoding genes (i.e., glpO, spaid and rip2) were found incomplete in these S. ixodetis genomes. We also detected an enrichment of genes encoding the type IV secretion system (T4SS) in S. ixodetis genomes of Dactylopius. A metratranscriptomic analysis of D. coccus showed that some of these T4SS genes (i.e., traG, virB4 and virD4) in addition to the superoxide dismutase sodA of S. ixodetis were overexpressed in the ovaries. CONCLUSION: The symbiont S. ixodetis is a new member of the bacterial community of D. coccus and D. opuntiae. The recovery of incomplete virulence factor-encoding genes in S. ixodetis of Dactylopius suggests that this bacterium is a non-pathogenic symbiont. A high number of genes encoding the T4SS, in the S. ixodetis genomes and the overexpression of these genes in the ovary and hemolymph of the host suggest that S. ixodetis use the T4SS to interact with the Dactylopius cells. Moreover, the transcriptional differences of S. ixodetis among the gut, hemolymph and ovary tissues of D. coccus indicate that this bacterium can respond and adapt to the different conditions (e.g., oxidative stress) present within the host. All this evidence proposes that there is a strong interaction and molecular signaling in the symbiosis between S. ixodetis and the carmine cochineal Dactylopius.

Functional characterization of culturable fungi from microbiomes of the "conical cobs" Mexican maize (Zea mays L.) landrace.

Mexican maize landraces, produced for local consumption, are adapted to different environmental conditions, and their yield is affected by abiotic and biotic factors, including the use of agrochemicals. The search for sustainable alternatives to agrochemicals includes the study of the culturable microbial communities. In this study, the fungal communities associated with 2 Mexican maize landraces reddish and bluish "conical cobs" were found to be comprised of Ascomycota fungi, represented by 89 strains within 6 orders (Pleosporales, Hypocreales, Onygenales, Capnodiales, Helotiales, and Eurotiales) and 16 genera. Cellulases and metallophores production were the primary enzymatic products and plant growth-promoting activities were detected among the isolates. Penicillium, Didymella, and Fusarium strains had the most active enzymatic and plant growth promoting activities, however, Aspergillus sp. HES2-2.2, Talaromyces sp. RS1-7, and Penicillium sp. HFS3-3 showed antagonistic activity against the four phytopathogenic Fusarium strains Fusarium oxysporum, Fusarium sambucinum, Fusarium fujikuroi and Fusarium incarnatum-equiseti and also a high and diverse production of enzymatic and plant growth promoting activities; here we identified fungal strains as candidates to promote maize growth.

Caffeine exposure alters adenosine system and neurochemical markers during retinal development.

Evidence points to beneficial properties of caffeine in the adult central nervous system, but teratogenic effects have also been reported. Caffeine exerts most of its effects by antagonizing adenosine receptors, especially A1 and A2A subtypes. In this study, we evaluated the role of caffeine on the expression of components of the adenosinergic system in the developing avian retina and the impact of caffeine exposure upon specific markers for classical neurotransmitter systems. Caffeine exposure (5-30 mg/kg by in ovo injection) to 14-day-old chick embryos increased the expression of A1 receptors and concomitantly decreased A2A adenosine receptors expression after 48 h. Accordingly, caffeine (30 mg/kg) increased [(3) H]-8-cyclopentyl-1,3-dipropylxanthine (A1 antagonist) binding and reduced [(3) H]-ZM241385 (A2A antagonist) binding. The caffeine time-response curve demonstrated a reduction in A1 receptors 6 h after injection, but an increase after 18 and 24 h. In contrast, caffeine exposure increased the expression of A2A receptors from 18 and 24 h. Kinetic assays of [(3) H]-S-(4-nitrobenzyl)-6-thioinosine binding to the equilibrative adenosine transporter ENT1 revealed an increase in Bmax with no changes in Kd , an effect accompanied by an increase in adenosine uptake. Immunohistochemical analysis showed a decrease in retinal content of tyrosine hydroxylase, calbindin and choline acetyltransferase, but not Brn3a, after 48 h of caffeine injection. Furthermore, retinas exposed to caffeine had increased levels of phosphorylated extracellular signal-regulated kinase and cAMP-response element binding protein. Overall, we show an in vivo regulation of the adenosine system, extracellular signal-regulated kinase and cAMP-response element binding protein function and protein expression of specific neurotransmitter systems by caffeine in the developing retina. The beneficial or maleficent effects of caffeine have been demonstrated by the work of different studies. It is known that during animal development, caffeine can exert harmful effects, impairing the correct formation of CNS structures. In this study, we demonstrated cellular and tissue effects of caffeine's administration on developing chick embryo retinas. Those effects include modulation of adenosine receptors (A1 , A2 ) content, increasing in cAMP response element-binding protein (pCREB) and extracellular signal-regulated kinase phosphorylation (pERK), augment of adenosine equilibrative transporter content/activity, and a reduction of some specific cell subpopulations. ENT1, Equilibrative nucleoside transporter 1.

Isolation and characterization of yeasts associated with plants growing in heavy-metal- and arsenic-contaminated soils.

Yeasts were quantified and isolated from the rhizospheres of 5 plant species grown at 2 sites of a Mexican region contaminated with arsenic, lead, and other heavy metals. Yeast abundance was about 10(2) CFU/g of soil and 31 isolates were obtained. On the basis of the phylogenetic analysis of 26S rRNA and internal transcribed spacer fragment, 6 species were identified within the following 5 genera: Cryptococcus (80.64%), Rhodotorula (6.45%), Exophiala (6.45%), Trichosporon (3.22%), and Cystobasidium (3.22%). Cryptococcus spp. was the predominant group. Pectinases (51.6%), proteases (51.6%), and xylanases (41.9%) were the enzymes most common, while poor production of siderophores (16.1%) and indole acetic acid (9.67%) was detected. Isolates of Rhodotorula mucilaginosa and Cystobasidium sloffiae could promote plant growth and seed germination in a bioassay using Brassica juncea. Resistance of isolates by arsenic and heavy metals was as follows: As(3+) ≥ 100 mmol/L, As(5+) ≥ 30 mmol/L, Zn(2+) ≥ 2 mmol/L, Pb(2+) ≥ 1.2 mmol/L, and Cu(2+) ≥ 0.5 mmol/L. Strains of Cryptococcus albidus were able to reduce arsenate (As(5+)) into arsenite (As(3+)), but no isolate was capable of oxidizing As(3+). This is the first study on the abundance and identification of rhizosphere yeasts in a heavy-metal- and arsenic-contaminated soil, and of the reduction of arsenate by the species C. albidus.

Pancreatic mucinous cystadenoma with serum CA 19-9 over 1,000,000 U/mL: a case report and review of the literature.

BACKGROUND: The diagnosis of pancreatic cystic neoplasms has become more accurate recently. In some cases, however, doubt remains regarding the lesion's malignant potential. CA 19-9 has long been identified as a reliable biomarker in differentiating pancreatic benign and malignant lesions, especially in non-jaundiced patients. CASE REPORT AND DISCUSSION: We report a case of a young female who presented with a mucinous lesion in the tail of the pancreas and a serum CA 19-9 over 1,000,000 U/mL. She was taken to surgery and had a distal pancreatectomy and splenectomy. Pathology reports showed only a mucinous cystadenoma. After 1 year of follow-up, her serum CA 19-9 was normal. Following that, the work-up in these lesions, the role of the biomarker in pancreatic adenocarcinoma and in the differentiation between benign and malignant lesions is discussed.

Adenosine receptors: expression, function and regulation.

Adenosine receptors (ARs) comprise a group of G protein-coupled receptors (GPCR) which mediate the physiological actions of adenosine. To date, four AR subtypes have been cloned and identified in different tissues. These receptors have distinct localization, signal transduction pathways and different means of regulation upon exposure to agonists. This review will describe the biochemical characteristics and signaling cascade associated with each receptor and provide insight into how these receptors are regulated in response to agonists. A key property of some of these receptors is their ability to serve as sensors of cellular oxidative stress, which is transmitted by transcription factors, such as nuclear factor (NF)-κB, to regulate the expression of ARs. Recent observations of oligomerization of these receptors into homo- and heterodimers will be discussed. In addition, the importance of these receptors in the regulation of normal and pathological processes such as sleep, the development of cancers and in protection against hearing loss will be examined.

New Insights on Dietary Polyphenols for the Management of Oxidative Stress and Neuroinflammation in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a neurodegenerative and vascular pathology that is considered one of the leading causes of blindness worldwide, resulting from complications of advanced diabetes mellitus (DM). Current therapies consist of protocols aiming to alleviate the existing clinical signs associated with microvascular alterations limited to the advanced disease stages. In response to the low resolution and limitations of the DR treatment, there is an urgent need to develop more effective alternative therapies to optimize glycemic, vascular, and neuronal parameters, including the reduction in the cellular damage promoted by inflammation and oxidative stress. Recent evidence has shown that dietary polyphenols reduce oxidative and inflammatory parameters of various diseases by modulating multiple cell signaling pathways and gene expression, contributing to the improvement of several chronic diseases, including metabolic and neurodegenerative diseases. However, despite the growing evidence for the bioactivities of phenolic compounds, there is still a lack of data, especially from human studies, on the therapeutic potential of these substances. This review aims to comprehensively describe and clarify the effects of dietary phenolic compounds on the pathophysiological mechanisms involved in DR, especially those of oxidative and inflammatory nature, through evidence from experimental studies. Finally, the review highlights the potential of dietary phenolic compounds as a prophylactic and therapeutic strategy and the need for further clinical studies approaching the efficacy of these substances in DR management.

Mycobiota of Mexican Maize Landraces with Auxin-Producing Yeasts That Improve Plant Growth and Root Development.

Compared to agrochemicals, bioinoculants based on plant microbiomes are a sustainable option for increasing crop yields and soil fertility. From the Mexican maize landrace "Raza cónico" (red and blue varieties), we identified yeasts and evaluated in vitro their ability to promote plant growth. Auxin production was detected from yeast isolates and confirmed using Arabidopsis thaliana plants. Inoculation tests were performed on maize, and morphological parameters were measured. Eighty-seven yeast strains were obtained (50 from blue corn and 37 from red corn). These were associated with three families of Ascomycota (Dothideaceae, Debaryomycetaceae, and Metschnikowiaceae) and five families of Basidiomycota (Sporidiobolaceae, Filobasidiaceae, Piskurozymaceae, Tremellaceae, and Rhynchogastremataceae), and, in turn, distributed in 10 genera (Clavispora, Rhodotorula, Papiliotrema, Candida, Suhomyces, Soliccocozyma, Saitozyma Holtermaniella, Naganishia, and Aeurobasidium). We identified strains that solubilized phosphate and produced siderophores, proteases, pectinases, and cellulases but did not produce amylases. Solicoccozyma sp. RY31, C. lusitaniae Y11, R. glutinis Y23, and Naganishia sp. Y52 produced auxins from L-Trp (11.9-52 µg/mL) and root exudates (1.3-22.5 µg/mL). Furthermore, they stimulated the root development of A. thaliana. Inoculation of auxin-producing yeasts caused a 1.5-fold increase in maize plant height, fresh weight, and root length compared to uninoculated controls. Overall, maize landraces harbor plant growth-promoting yeasts and have the potential for use as agricultural biofertilizers.

Expression of A1 adenosine receptors in the developing avian retina: in vivo modulation by A(2A) receptors and endogenous adenosine.

Little is known about the mechanisms that regulate the expression of adenosine receptors during CNS development. We demonstrate here that retinas from chick embryos injected in ovo with selective adenosine receptor ligands show changes in A1 receptor expression after 48 h. Exposure to A1 agonist N6-cyclohexyladenosine (CHA) or antagonist 8-Cyclopentyl-1, 3-dipropylxanthine (DPCPX) reduced or increased, respectively, A1 receptor protein and [³H]DPCPX binding, but together, CHA+DPCPX had no effect. Interestingly, treatment with A(2A) agonist 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino] ethyl]phenyl] propanoic acid (CGS21680) increased A1 receptor protein and [³H]DPCPX binding, and reduced A(2A) receptors. The A(2A) antagonists 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-trizolo[1,5-c] pyrimidine (SCH58261) and 4-(2-[7-amino-2-[2-furyl][1,2,4]triazolo[2,3-a][1,3,5]triazo-5-yl-amino]ethyl)phenol (ZM241385) had opposite effects on A1 receptor expression. Exposure to CGS21680 + CHA did not change A1 receptor levels, whereas CHA + ZM241385 or CGS21680 + DPCPX had no synergic effect. The blockade of adenosine transporter with S-(4-nitrobenzyl)-6-thioinosine (NBMPR) also reduced [³H]DPCPX binding, an effect blocked by DPCPX, but not enhanced by ZM241385. [³H]DPCPX binding kinetics showed that treatment with CHA reduced and CGS21680 increased the Bmax, but did not affect Kd values. CHA, DPCPX, CGS21680, and ZM241385 had no effect on A1 receptor mRNA. These data demonstrated an in vivo regulation of A1 receptor expression by endogenous adenosine or long-term treatment with A1 and A(2A) receptors modulators.

Evaluation of the prematurity retinopathy and other eye changes in the newborn.

OBJECTIVE: To assess the prevalence of ophthalmologic manifestations in newborns in a maternity hospital in the city of São Paulo, SP, and the main risk factors related with the development of retinopathy of prematurity. METHODS: A retrospective, longitudinal study with patients born from 2015 to 2017 who required ophthalmological evaluation. The research variables were obtained by analysis of the newborn medical charts. RESULTS: A total of 773 patients were studied. The sample consisted of 288 examinations performed by indication of gestational age ≤32 weeks: 118 (42.4%) in 2015, 105 (42.2%) in 2016, 65 (26.4%) cases in 2017. There were 329 evaluations indicated due to birth weight: 113 (40.6%) in 2015, 108 (43.4%) in 2016, and 108 (43.9%) in 2017. The prevalence of associated risk factors was 97 (34.9%) cases in 2015, 96 (38.6%) in 2016, and 54 (22%) in 2017, followed by mechanical ventilation with 82 (29.5%) cases in 2015, 64 (25.7%) in 2016 and 41 (16.7%) in 2017, and continuous positive airway pressure with 59 (21.2%) cases in 2015, 72 (28.9%) in 2016, and 46 (18.7%) in 2017. For the other indications, the evaluations performed due to congenital syphilis were the majority in the 3-year period of the study, with 55 (19.8%) newborns in 2015, 54 (21.7%) in 2016, and 59 (24.0%) in 2017. The most prevalent ophthalmologic diagnosis was retinopathy of prematurity, with 79 (35.3%) cases in 2015, 64 (32.2%) in 2016, and 41 (24.1%) in 2017. CONCLUSION: Most neonates born in the organization do not present risk factors for ophthalmological manifestations. Retinopathy of prematurity was the disease with greater strength of association found in our study. For the other indications, the evaluations performed due to congenital syphilis prevail in the 3- year period of the study.

Lack of professional recognition: main reason for stress in military police.

Introduction: Military police officers play a crucial role in contemporary society, which is marked by the increase in criminality. Therefore, these professionals are constantly under pressure, both socially and professionally, so occupational stress is something present in their routine. Objectives: To investigate the stress levels of military police officers in the municipality of Fortaleza and its metropolitan region. Methods: This was a cross-sectional, quantitative study, conducted with 325 military police officers (53.1% men; 20> 51 years old) who belonged to military police battalions. The Police Stress Questionnaire was used to identify the stress level, following the Likert scale from 1 to 7; the higher the score, the higher the stress level. Results: The results indicated that the lack of professional recognition is the main stress factor among military police officers (Median = 7.00). Other items were relevant to the quality of life of these professionals, which are: "risks of injuries or wounds resulting from the profession", "working on days off", "lack of human resources", "excessive bureaucracy in the police service", " having the perception that we are pressured to give up free time "," lawsuits resulting from police service," "going to court, relationship with the judicial actors, " and "use of inadequate equipment for the service," respectively (Median = 6. 00). Conclusions: The stress of these professionals is organizational in nature and comes from factors that transcend the violence with which they deal.

Introdução: O policial militar desempenha uma função de suma relevância na sociedade contemporânea, a qual é marcada pelo avanço da criminalidade. Desse modo, esse profissional se encontra constantemente sob pressão, tanto social quanto trabalhista, de maneira que o estresse ocupacional é algo presente em sua rotina. Objetivos: Investigar os níveis de estresse em policiais militares da cidade de Fortaleza e região metropolitana. Métodos: Trata-se de um estudo transversal, de natureza quantitativa, realizado com 325 policiais militares, sendo (53,1% do sexo masculino; 20 > 51 anos de idade) pertencentes aos batalhões de policiamento militar. O questionário Police Stress Questionnaire foi utilizado para identificar o nível de estresse, seguindo a escala Likert de 1 a 7 - quanto maior a pontuação, maior o nível de estresse. Resultados: Os resultados indicaram que a falta de reconhecimento profissional é o principal fator de estresse entre os policiais militares (mediana = 7,00). Outros itens foram relevantes na qualidade de vida desses profissionais, são eles: "riscos de lesões ou ferimentos resultantes da profissão", "trabalhar em dias de folga", "falta de recursos humanos", "excesso de burocracia no serviço policial", "ter a percepção que somos pressionados a abdicar o tempo livre", "processos de justiça decorrentes do serviço policial", "idas ao tribunal, relação com os intervenientes judiciais" e "uso de equipamentos inadequado para o serviço" respectivamente (mediana = 6,00). Conclusões: O estresse desses profissionais é de cunho organizacional e provém de fatores que transcendem à violência com a qual lidam.

Developmental regulation of neuronal survival by adenosine in the in vitro and in vivo avian retina depends on a shift of signaling pathways leading to CREB phosphorylation or dephosphorylation.

Previous studies have shown a cAMP/protein kinase A-dependent neuroprotective effect of adenosine on glutamate or re-feeding-induced apoptosis in chick retina neuronal cultures. In the present work, we have studied the effect of adenosine on the survival of retinal progenitor cells. Cultures obtained from 6-day-old (E6) or from 8-day-old (E8) chick embryos were challenged 2 h (C0) or 1 day (C1) after seeding and analyzed after 3-4 days in vitro. Surprisingly, treatment with the selective A2a adenosine receptor agonists N(6) -[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) or 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid (CGS21680) promoted cell death when added at E6C0 but not at E6C1 or E8C0. DPMA-induced cell death involved activation of A2a receptors and the phospholipase C/protein kinase C but not the cAMP/protein kinase A pathway, and was not correlated with early modulation of precursor cells proliferation. Regarding cyclic nucleotide responsive element binding protein (CREB) phosphorylation, cultures from E6 embryos behave in an opposite manner from that from E8 embryos, both in vitro and in vivo. While the phospho-CREB level was high at E6C0 cultures and could be diminished by DPMA, it was lower at E8C0 and could be increased by DPMA. Similar to what was observed in cell survival studies, CREB dephosphorylation induced by DPMA in E6C0 cultures was dependent on the Phospholipase C/protein kinase C pathway. Accordingly, cell death induced by DPMA was inhibited by okadaic acid, a phosphatase blocker. Moreover, DPMA as well as the adenosine uptake blocker nitrobenzyl mercaptopurine riboside (NBMPR) modulate cell survival and CREB phosphorylation in a population of cells in the ganglion cell layer in vivo. These data suggest that A2a adenosine receptors as well as CREB may display a novel and important function by controlling the repertoire of developing retinal neurons.

Edible Fruit Plant Species in the Amazon Forest Rely Mostly on Bees and Beetles as Pollinators.

Edible fruit plants of tropical forests are important for the subsistence of traditional communities. Understanding the most important pollinators related to fruit and seed production of these plants is a necessary step to protect their pollination service and assure the food security of these communities. However, there are many important knowledge gaps related to floral biology and pollination in megadiverse tropical rainforests, such as the Amazon Forest, due mainly to the high number of plant species. Our study aims to indicate the main pollinators of edible plants (mainly fruits) of the Amazon forest. For this, we adopted a threefold strategy: we built a list of edible plant species, determined the pollination syndrome of each species, and performed a review on the scientific literature searching for their pollinator/visitors. The list of plant species was determined from two specialized publications on Amazon fruit plants, totaling 188 species. The pollination syndrome was determined for 161 species. The syndromes most frequently found among the analyzed species were melittophily (bee pollination), which was found in 101 of the analyzed plant species (54%) and cantharophily (beetle pollination; 26 species; 14%). We also found 238 pollinator/visitor taxa quoted for 52 (28%) plant species in previous publications, with 124 taxa belonging to Apidae family (bees; 52%), mainly from Meliponini tribe (58 taxa; 47%). Knowledge about pollinators is an important step to help on preserving their ecosystem services and maintaining the productivity of fruit trees in the Amazon.

Detection of Common Deletional of α-Thalassemia 3.7 Kb from Metropolitan Region of Manaus, Amazonas, Brazil.

BACKGROUND: Alpha Thalassemia (α-thal) is a heterogeneous group of hereditary alterations caused by deletions that affect alpha regulatory genes, and the 3.7Kb deletion is the most frequent worldwide. The prevalence ranges from 20% and 35% in Brazil, depending mainly on race, predominant in Afro-descendants. PURPOSE: The aim was to determine α-thal -α3.7Kb and -α4.2Kb deletions, estimating their frequency in individuals from six regions of Amazonas State. METHODS: Volunteers age between 18-59 years old of both genders participated in the study. Blood was collected from March 2014 to September 2017 at the health centers of each participant city. α-thal3.7Kb was performed by GAP-PCR, while α-thal4.2Kb by Multiplex-PCR. The total samples collected from each city were: Manaus (capital), 356 (19.7%); Iranduba 232 (12.8%); Manacapuru, 287 (15.9%); Presidente Figueiredo, 370 (20.5%); Itacoatiara, 301 (16.6%); and Coari, 263 (14.5%). RESULTS: The average age among males was 35.3±14.8, while for females, it was 36.7±14.9 years old. Microcytosis (MCV <80fL) was found in 158 individuals (8,46%) and α-thal diagnosed in 143 individuals (7.9%), and all of these individuals carried the 3.7Kb deletion 5.95% in heterozygous and 1.95% in homozygous. α-thal4.2kb was not found in any volunteer. The association analyses to the α-thal3.7kb genotypes were statistically significant for all hematological parameters (p<.001), except serum iron and serum ferritin analyses. CONCLUSION: This study highlights α-thal 3.7kb deletion as an important public health problem, especially in a population not yet characterized about this disease. Thus, epidemiological studies using molecular tools become relevant in regions where the disease is underestimated, contributing to a better understanding of thalassemia incidence and iron deficiency anemias incidence of the participating cities. We reinforce that future molecular studies in North Region from Brazil can be utilized to describe other genetic anemias as structural hemoglobinopathies that have already proven to be highly prevalent in Brazil.

We and herbivores eat endophytes.

Health depends on the diet and a vegetal diet promotes health by providing fibres, vitamins and diverse metabolites. Remarkably, plants may also provide microbes. Fungi and bacteria that reside inside plant tissues (endophytes) seem better protected to survive digestion; thus, we investigated the reported evidence on the endophytic origin of some members of the gut microbiota in animals such as panda, koala, rabbits and tortoises and several herbivore insects. Data examined here showed that some members of the herbivore gut microbiota are common plant microbes, which derived to become stable microbiota in some cases. Endophytes may contribute to plant fibre or antimetabolite degradation and synthesis of metabolites with the plethora of enzymatic activities that they display; some may have practical applications, for example, Lactobacillus plantarum found in the intestinal tract, plants and in fermented food is used as a probiotic that may defend animals against bacterial and viral infections as other endophytic-enteric bacteria do. Clostridium that is an endophyte and a gut bacterium has remarkable capabilities to degrade cellulose by having cellulosomes that may be considered the most efficient nanomachines. Cellulose degradation is a challenge in animal digestion and for biofuel production. Other endophytic-enteric bacteria may have cellulases, pectinases, xylanases, tannases, proteases, nitrogenases and other enzymatic capabilities that may be attractive for biotechnological developments, indeed many endophytes are used to promote plant growth. Here, a cycle of endophytic-enteric-soil-endophytic microbes is proposed which has relevance for health and comprises the fate of animal faeces as natural microbial inoculants for plants that constitute bacterial sources for animal guts.

Size and isolation of naturally isolated habitats do not affect plant-bee interactions: A case study of ferruginous outcrops within the eastern Amazon forest.

Pollination may be severely affected by the decreasing size and increasing isolation of habitat patches. However, most studies that have considered the effects of these two variables on plant-pollinator interactions have been carried out in areas that have undergone anthropogenic fragmentation, and little is known about their effects in natural habitats. The Carajás National Forest and Campos Ferruginosos National Park are two protected areas in the eastern Amazon where one can find isolated ferruginous outcrops characterized by iron-rich soil and herbaceous-shrub vegetation surrounded by Amazon forest. These patches of canga provide an opportunity to analyze plant-pollinator interactions in naturally fragmented areas. Our objective was to test whether the size and isolation of naturally isolated outcrops located in Carajás affect plant-pollinator interactions by using pollination syndromes and interaction networks. We determined the pollination syndromes of 771 plant species that occurred in eleven canga patches and performed field work to analyze plant-pollinator networks in nine canga patches. The structure of the plant-pollinator networks was not affected by the size or isolation of the canga patches. Generalist species were present in all canga areas, indicating that they are important in maintaining the plant communities in isolated canga patches. The lack of significance related to the distance between canga patches suggests that the forest does not prevent pollinator movement between canga patches.