3D Analysis of the TCR/pMHCII Complex Formation in Monkeys Vaccinated with the First Peptide Inducing Sterilizing Immunity against Human Malaria

T-cell receptor gene rearrangements were studied in Aotus monkeys developing high antibody titers and sterilizing immunity against the Plasmodium falciparum malaria parasite upon vaccination with the modified synthetic peptide 24112, which was identified in the Merozoite Surface Protein 2 (MSP-2) and is known to bind to HLA-DR beta 1*0403 molecules with high capacity. Spectratyping analysis showed a preferential usage of V beta 12 and V beta 6 TCR gene families in 67% of HLA-DR beta 1*0403-like genotyped monkeys. Docking of peptide 24112 into the HLA-DR beta 1*0401-HA peptide-HA1.7TCR complex containing the VDJ rearrangements identified in fully protected monkeys showed a different structural signature compared to nonprotected monkeys. These striking results show the exquisite specificity of the TCR/pMHCII complex formation needed for inducing sterilizing immunity and provide important hints for a logical and rational methodology to develop multiepitopic, minimal subunit-based synthetic vaccines against infectious diseases, among them malaria.

Polimorfismos del gen Butirilcolinesterasa responsables de reacciones adversas en pacientes consumidores de “cocaína”

La butirilcolinesterasa humana (BChE; EC 3.1.1.8) es una enzima polimórfica sintetizada en el hígado y en el tejido adiposo, ampliamente distribuida en el organismo y encargada de hidrolizar algunos ésteres de colina como la procaína, ésteres alifáticos como el ácido acetilsalicílico, fármacos como la metilprednisolona, el mivacurium y la succinilcolina y drogas de uso y/o abuso como la heroína y la cocaína. Es codificada por el gen BCHE (OMIM 177400), habiéndose identificado más de 100 variantes, algunas no estudiadas plenamente, además de la forma más frecuente, llamada usual o silvestre. Diferentes polimorfismos del gen BCHE se han relacionado con la síntesis de enzimas con niveles variados de actividad catalítica. Las bases moleculares de algunas de esas variantes genéticas han sido reportadas, entre las que se encuentra las variantes Atípica (A), fluoruro-resistente del tipo 1 y 2 (F-1 y F-2), silente (S), Kalow (K), James (J) y Hammersmith (H). En este estudio, en un grupo de pacientes se aplicó el instrumento validado Lifetime Severity Index for Cocaine Use Disorder (LSI-C) para evaluar la gravedad del consumo de “cocaína” a lo largo de la vida. Además, se determinaron Polimorfismos de Nucleótido Simple (SNPs) en el gen BCHE conocidos como responsables de reacciones adversas en pacientes consumidores de “cocaína” mediante secuenciación del gen y se predijo el efecto delos SNPs sobre la función y la estructura de la proteína, mediante el uso de herramientas bio-informáticas. El instrumento LSI-C ofreció resultados en cuatro dimensiones: consumo a lo largo de la vida, consumo reciente, dependencia psicológica e intento de abandono del consumo. Los estudios de análisis molecular permitieron observar dos SNPs codificantes (cSNPs) no sinónimos en el 27.3% de la muestra, c.293A>G (p.Asp98Gly) y c.1699G>A (p.Ala567Thr), localizados en los exones 2 y 4, que corresponden, desde el punto de vista funcional, a la variante Atípica (A) [dbSNP: rs1799807] y a la variante Kalow (K) [dbSNP: rs1803274] de la enzima BChE, respectivamente. Los estudios de predicción In silico establecieron para el SNP p.Asp98Gly un carácter patogénico, mientras que para el SNP p.Ala567Thr, mostraron un comportamiento neutro. El análisis de los resultados permite proponer la existencia de una relación entre polimorfismos o variantes genéticas responsables de una baja actividad catalítica y/o baja concentración plasmática de la enzima BChE y algunas de las reacciones adversas ocurridas en pacientes consumidores de cocaína.

Do monkeys tweet?

Con texto sencillo acerca de las características de algunos animales y de sus sonidos, presenta una serie de preguntas y respuestas. La última pregunta, si los búhos ululan en medio de la noche, puede ser la única vez en que la respuesta fuera afirmativa.

Effects of the 5-HT(1A) agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on cocaine choice in cynomolgus monkeys

Drugs that alter brain serotonin (5-HT) function can modulate the behavioral effects of cocaine, but the underlying receptor mechanisms are poorly understood. The present study examined the effects of the selective 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.01-0.1 mg/kg, i.v.) on cocaine self-administration in the context of a choice procedure. Five adult male cynomolgus monkeys self-administered cocaine (saline, 0.003-0.03 mg/kg per injection) under a concurrent fixed-ratio 50 schedule of food (1-g banana-flavored pellets) and cocaine presentation. Allocation of responses to the cocaine-associated lever (cocaine choice) increased in a dose-related manner from < or =20% of total responses when saline or 0.003 mg/kg per injection cocaine was the alternative to food to > or =75% when 0.03 mg/kg per injection cocaine was available. In four of five monkeys, when choice was between a low cocaine dose and food, 0.01 mg/kg 8-OH-DPAT increased injection-lever responding. At cocaine doses which occasioned > or =75% cocaine choice, 8-OH-DPAT did not alter response allocation. In the fifth monkey, 8-OH-DPAT only decreased injection-lever responding. When choice was between saline and food, 8-OH-DPAT did not reliably shift responding to the injection lever, except at doses that disrupted operant performance. These results suggest that a 5-HT1A receptor agonist can increase the reinforcing strength of a low cocaine dose relative to a concurrently available non-drug reinforcer.

Assessment of the relative reinforcing strength of cocaine in socially housed monkeys using a choice procedure.

Position in the social hierarchy can influence brain dopamine function and cocaine reinforcement in nonhuman primates during early cocaine exposure. With prolonged exposure, however, initial differences in rates of cocaine self-administration between dominant and subordinate monkeys dissipate. The present studies used a choice procedure to assess the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys with extensive cocaine self-administration histories. Responding was maintained under a concurrent fixed-ratio 50 schedule of food and cocaine (0.003-0.1 mg/kg per injection) presentation. Responding on the cocaine-associated lever increased as a function of cocaine dose in all monkeys. Although response distribution was similar across social rank when saline or relatively low or high cocaine doses were the alternative to food, planned t tests indicated that cocaine choice was significantly greater in subordinate monkeys when choice was between an intermediate dose (0.01 mg/kg) and food. When a between-session progressive-ratio procedure was used to increase response requirements for the preferred reinforcer (either cocaine or food), choice of that reinforcer decreased in all monkeys. The average response requirement that produced a shift in response allocation from the cocaine-associated lever to the food-associated lever was higher in subordinates across cocaine doses, an effect that trended toward significance (p = 0.053). These data indicate that despite an extensive history of cocaine self-administration, most subordinate monkeys were more sensitive to the relative reinforcing strength of cocaine than dominant monkeys.

Natural Plasmodium infections in Brazilian wild monkeys: Reservoirs for human infections?

Four hundred and forty-eight samples of total blood from wild monkeys living in areas where human autochthonous malaria cases have been reported were screened for the presence of Plasmodium using microscopy and PCR analysis. Samples came from the following distinct ecological areas of Brazil: Atlantic forest (N = 140), semideciduous Atlantic forest (N = 257) and Cerrado (a savannah-like habitat) (N = 51). Thick and thin blood smears of each specimen were examined and Plasmodium infection was screened by multiplex polymerase chain reaction (multiplex PCR). The frequency of Plasmodium infections detected by PCR in Alouatta guariba clamitans in the Sao Paulo Atlantic forest was 11.3% or 8/71 (5.6% for Plasmodium malariae and 5.6% for Plasmodium vivax) and one specimen was positive for Plasmodium falciparum (1.4%); Callithrix sp. (N = 30) and Cebus apella (N = 39) specimens were negative by PCR tests. Microscopy analysis was negative for all specimens from the Atlantic forest. The positivity rate for Alouatta caraya from semideciduous Atlantic forest was 6.8% (16/235) in the PCR tests (5.5, 0.8 and 0.4% for P. malariae, P. falciparum and P. vivax, respectively), while C apella specimens were negative. Parasitological examination of I he samples using thick smears revealed Plasmodium sp. infections in only seven specimens, which had few parasites (3.0%). Monkeys from the Cerrado (a savannah-like habitat) (42 specimens of A. caraya, 5 of Callithrix jacchus and 4 of C. apella) were negative in both tests. The parasitological prevalence of P. vivax and P. malariae in wild monkeys from Atlantic forest and semideciduous Atlantic forest and the finding of a positive result for P.falciparum in Alouatta from both types of forest support the hypothesis that monkeys belonging to this genus could be a potential reservoir. Furthermore, these findings raise the question of the relationship between simian and autochthonous human malaria in extra-Amazonian regions. (C) 2008 Elsevier B.V. All rights reserved.

Skull Modularity in Neotropical Marsupials and Monkeys: Size Variation and Evolutionary Constraint and Flexibility

An organism is built through a series of contingent factors, yet it is determined by historical, physical, and developmental constraints. A constraint should not be understood as an absolute obstacle to evolution, as it may also generate new possibilities for evolutionary change. Modularity is, in this context, an important way of organizing biological information and has been recognized as a central concept in evolutionary biology bridging on developmental, genetics, morphological, biochemical, and physiological studies. In this article, we explore how modularity affects the evolution of a complex system in two mammalian lineages by analyzing correlation, variance/covariance, and residual matrices (without size variation). We use the multivariate response to selection equation to simulate the behavior of Eutheria and Metharia skulls in terms of their evolutionary flexibility and constraints. We relate these results to classical approaches based on morphological integration tests based on functional/developmental hypotheses. Eutherians (Neotropical primates) showed smaller magnitudes of integration compared with Metatheria (didelphids) and also skull modules more clearly delimited. Didelphids showed higher magnitudes of integration and their modularity is strongly influenced by within-groups size variation to a degree that evolutionary responses are basically aligned with size variation. Primates still have a good portion of the total variation based on size; however, their enhanced modularization allows a broader spectrum of responses, more similar to the selection gradients applied (enhanced flexibility). Without size variation, both groups become much more similar in terms of modularity patterns and magnitudes and, consequently, in their evolutionary flexibility. J. Exp. Zool. (Mol. Dev. Evol.) 314B:663-683, 2010. (C) 2010 Wiley-Liss, Inc.

Evaluation of dental pulp repair using low level laser therapy (688 nm and 785 nm) morphologic study in capuchin monkeys

The aim of this study was to evaluate the hypothesis that low-level laser therapy (LLLT) 688 nm and 785 nm accelerate dentin barrier formation and repair process after traumatic pulp exposure. The sample consisted of 45 premolars of capuchin monkeys (Cebus apella) with pulp exposure Class V cavities. All premolars were treated with calcium hydroxide (Ca(OH)(2)), divided in groups of 15 teeth each, and analyzed on 7(th), 25(th), and 60(th) day. Group GI - only Ca(OH)(2), GIF- laser 688 nm, and GIII - laser 785 nm. Laser beam was used in single and punctual dose with the parameters: continuous, 688 nm and 785 nm wavelength, tip`s area of 0.00785 cm(2), power 50 mW, application time 20 s, dose 255 J/cm(2), energy 2 J. Teeth were capped with Ca(OH)(2), Ca(OH)(2) cement and restored with amalgam. All groups presented pulp repair. On 25(th) day the thickness of the formed dentin barrier was different between the groups GI and GII (p < 0.05) and between groups GI and GIII (p < 0.01). On 60(th) day there was difference between GI and GIII (p < 0.01). It may be concluded that, LLLT 688 nm and 785 nm accelerated dentin barrier formation and consequently pulp repair process, with best results using infrared laser 785 nm. (c) 2009 by Astro Ltd. Published exclusively by WLLEY-VCH Verlag GmbH & Co. KGaA

Distribution of potential suitable hammers and transport of hammer tools and nuts by wild capuchin monkeys

Selection and transport of objects to use as tools at a distant site are considered to reflect planning. Ancestral humans transported tools and tool-making materials as well as food items. Wild chimpanzees also transport selected hammer tools and nuts to anvil sites. To date, we had no other examples of selection and transport of stone tools among wild nonhuman primates. Wild bearded capuchins (Cebus libidinosus) in Boa Vista (Piaui, Brazil) routinely crack open palm nuts and other physically well-protected foods on level surfaces (anvils) using stones (hammers) as percussive tools. Here we present indirect evidence, obtained by a transect census, that stones suitable for use as hammers are rare (study 1) and behavioral evidence of hammer transport by twelve capuchins (study 2). To crack palm nuts, adults transported heavier and harder stones than to crack other less resistant food items. These findings show that wild capuchin monkeys selectively transport stones of appropriate size and hardness to use as hammers, thus exhibiting, like chimpanzees and humans, planning in tool-use activities.

Five Little Monkeys Jumping on the Bed : En litteraturstudie om hur arbete med sång, rim och ramsor kan främja barns utveckling av engelska som främmande språk i grundskolans tidigare år.

Syftet med litteraturstudien är att undersöka hur arbete med sång, rim och ramsor kan främja yngre elevers språkutveckling i engelska som främmande språk. Detta görs genom att fokusera på främjandet av barns språkinlärning, hur lärare bör arbeta med sång, rim och ramsor inom engelska som främmande språk, samt lärares attityder till ett sådant arbetssätt. Arbetet genomfördes som en systematisk litteraturstudie innehållande en bakgrund med relevant teori, samt analys av fem vetenskapliga studier rörande ämnet. Dessa gav möjlighet till en bred bild av området, då länder och perspektiv varierade. Studierna valdes ut genom sökning i databaser efter relevans och tillförlitlighet. I studiernas resultat framgick att majoriteten av tillfrågade lärare och elever var positivt inställda till arbete med sång och ramsor i engelskundervisning, och den språkutveckling dessa metoder innebar. Genom arbete med läraren som förebild motiverades eleverna. Dock fanns en avsaknad av material och kunskap för att kunna genomföra och bedöma undervisning innehållande sång och ramsor. En avsaknad av rim i de studier som analyserats berörs även i studien, likaså en brist på svenska studier. Sammanfattningsvis verkar sång och ramsor enligt de granskade studierna ha ett värde i engelskundervisning. Dock finns det behov av mer forskning och kunskap för att få starkare underlag för användning av dessa metoder i undervisning.

Frequency of Toxoplasma gondii antibodies in tufted capuchin monkeys (Cebus apella nigritus) from an ecological station in the State of São Paulo, Brazil

A toxoplasmose é uma das zoonoses mais difundidas no mundo, causada pelo Toxoplasma gondii, um protozoário parasita intracelular obrigatório. Uma alta porcentagem de animais apresenta anticorpos específicos causados por exposição prévia, levando a uma infecção crônica. Os felídeos são os hospedeiros definitivos e outros animais homeotérmicos, incluindo os primatas, são os hospedeiros intermediários. Este estudo objetivou determinar a prevalência da infecção por T. gondii em macacos-prego (Cebus apella nigritus) de vida livre da Estação Ecológica localizada na Mata de Santa Teresa, Ribeirão Preto, SP, Brasil. Anticorpos anti-T. gondii foram pesquisados pelo método de aglutinação direta modificada (MAT) em amostras de soro de 36 macacos-prego, utilizando-se o título oito como de corte. Dos animais estudados, 3/36 (8,33%; IC95% 3,0-21,9%) apresentaram anticorpos anti-T. gondii, todos com título 32. Nenhuma diferença significativa (P>0,05) foi observada com relação ao sexo (1/3 machos e 2/3 fêmeas), e à idade (1/3 jovens e 2/3 adultos). Assim, estes resultados demonstram alta prevalência de anticorpos anti-T. gondii em primatas no estado de São Paulo.

Exposure to rabies virus in a population of free-ranging capuchin monkeys (Cebus apella nigritus) in a fragmented, environmentally protected area in southeastern Brazil

The aim of this study is to assess the frequency of rabies antibodies in free-ranging capuchin monkeys (Cebus apella nigritus) in a fragmented, environmentally protected, rural area of southeastern Brazil. Thirty-six free-ranging monkeys were tested by the rapid fluorescent focus inhibition test for detection of antibodies against rabies virus. Four individuals (11.11 %) had neutralizing antibody titers a parts per thousand yen0.25 IU/mL, demonstrating rabies virus exposure.

Early healing after elevation of the maxillary sinus floor applying a lateral access: a histological study in monkeys

AimTo describe the early healing within the void obtained after the elevation of the sinus mucosa and simultaneous implant installation without the use of any grafting material in monkeys.Material and methodsImplants were installed simultaneously with the elevation of the maxillary sinus using the lateral approach in eight monkeys without the use of grafting material. The healing after 4, 10, 20 and 30 days was evaluated in the area distal to the implants. Paraffin sections were prepared and analyzed using qualitative histological methods.ResultsThe healing process was initiated by the formation of a coagulum and followed by a provisional matrix and woven bone. Subsequently, a parallel-fiber bone replaced woven bone. The dimension of the elevated area shrank during the healing process. Sprouts of woven bone, present to a moderate extent after 4 days, were more numerous after 10 and 20 days. Newly formed bone originated from the sinus walls and septa, while there was no evidence of participation of the Schneiderian membrane in this process. After 30 days, the window access appeared to be closed by a layer of newly formed trabecular bone.ConclusionsThe coagulum that filled the void distal to the implant after simultaneous elevation of the sinus floor gave rise to newly formed bone. However, the void occupied by the coagulum shrank substantially. The Schneiderian membrane did not provide a basis for new bone formation in the early phase of healing.To cite this article:Scala A, Botticelli D, Rangel IG Jr, de Oliveira JA, Okamoto R, Lang NP. Early healing after elevation of the maxillary sinus floor applying a lateral access: a histological study in monkeys.Clin. Oral Impl. Res. 21, 2010; 1320-1326.doi: 10.1111/j.1600-0501.2009.01964.x.

Effects of cyclosporin, phenytoin, and nifedipine on the synthesis and degradation of gingival collagen in tufted capuchin monkeys (Cebus apella): Histochemical and MMP-1 and -2 and collagen I gene expression analyses

Background: The purpose of this experimental study was to evaluate the collagen fiber distribution histologically after phenytoin, cyclosporin, or nifedipine therapy and to correlate it with collagen I and matrix metalloproteinase (MMP)-1 and -2 gene expression levels.Methods: Gingival samples from the canine area were obtained from 12 male monkeys (Cebus apella). The mesial part of each sample was assessed by reverse transcription-polymerase chain reaction, whereas the distal part was processed histologically for picrosirius red and hematoxylin and eosin stainings, as well as for collagen IV immunostaining. One week after the first biopsy, the animals were assigned to three groups that received daily oral dosages of cyclosporin, phenytoin, or nifedipine for 120 days. Additional gingival samples were obtained on days 52 and 120 of treatment from two animals from each group on the opposite sides from the first biopsies.Results: Picrosirius red staining showed a predominance of mature collagen fibers in the control group. Conversely, there was an enlargement of areas occupied by immature collagen fibers in all groups at days 52 and 120, which was not uniform over each section. There was a general trend to lower levels of MMP-1 gene expression on day 52 and increased levels on day 120. Phenytoin led to increased levels of MMP-2 and collagen I gene expression on day 120, whereas the opposite was observed in the nifedipine group.Conclusion: Cyclosporin, phenytoin, and nifedipine led to phased and drug-related gene expression patterns, resulting in impaired collagen metabolism, despite the lack of prominent clinical signs.