Chemical characterization of oligosaccharides in the milk of six species of New and Old World monkeys.

Human and great ape milks contain a diverse array of milk oligosaccharides, but little is known about the milk oligosaccharides of other primates, and how they differ among taxa. Neutral and acidic oligosaccharides were isolated from the milk of three species of Old World or catarrhine monkeys (Cercopithecidae: rhesus macaque (Macaca mulatta), toque macaque (Macaca sinica) and Hamadryas baboon (Papio hamadryas)) and three of New World or platyrrhine monkeys (Cebidae: tufted capuchin (Cebus apella) and Bolivian squirrel monkey (Saimiri boliviensis); Atelidae: mantled howler (Alouatta palliata)). The milks of these species contained 6-8% total sugar, most of which was lactose: the estimated ratio of oligosaccharides to lactose in Old World monkeys (1:4 to 1:6) was greater than in New World monkeys (1:12 to 1:23). The chemical structures of the oligosaccharides were determined mainly by (1)H-NMR spectroscopy. Oligosaccharides containing the type II unit (Gal(β1-4)GlcNAc) were found in the milk of the rhesus macaque, toque macaque, Hamadryas baboon and tufted capuchin, but oligosaccharides containing the type I unit (Gal(β1-3)GlcNAc), which have been found in human and many great ape milks, were absent from the milk of all species studied. Oligosaccharides containing Lewis x (Gal(β1-4)[Fuc(α1-3)]GlcNAc) and 3-fucosyl lactose (3-FL, Gal(β1-4)[Fuc(α1-3)]Glc) were found in the milk of the three cercopithecid monkey species, while 2-fucosyl lactose (5'-FL, Fuc(α1-2)Gal(β1-4)Glc) was absent from all species studied. All of these milks contained acidic oligosaccharides that had N-acetylneuraminic acid as part of their structures, but did not contain oligosaccharides that had N-glycolylneuraminic acid, in contrast to the milk or colostrum of great apes which contain both types of acidic oligosaccharides. Two GalNAc-containing oligosaccharides, lactose 3'-O-sulfate and lacto-N-novopentaose I (Gal(β1-3)[Gal(β1-4)GlcNAc(β1-6)]Gal(β1-4)Glc) were found only in the milk of rhesus macaque, hamadryas baboon and tufted capuchin, respectively. Further research is needed to determine the extent to which the milk oligosaccharide patterns observed among these taxa represent wider phylogenetic trends among primates and how much variation occurs among individuals or species.

Stable isotope ratios indicate diet and habitat use in New World monkeys.

This paper demonstrates the use of stable isotope ratios of carbon and nitrogen in animal tissue for indicating aspects of species behavioral strategy. We analyzed hair from individuals representing four species of New World monkeys (Alouatta palliata, the mantled howler; Ateles geoffroyi, the spider monkey; Cebus capucinus, the capuchin; and Brachyteles arachnoides, the woolly-spider monkey or muriqui) for delta 13C and delta 15N using previously developed methods. There are no significant differences in either carbon or nitrogen ratios between sexes, sampling year, or year of analysis. Seasonal differences in delta 13C reached a low level of significance but do not affect general patterns. Variation within species was similar to that recorded previously within single individuals. The omega 13C data show a bimodal distribution with significant difference between the means. The two monkey populations living in an evergreen forest were similar to each other and different from the other two monkey populations that inhabited dry, deciduous forests. This bimodal distribution is independent of any particular species' diet and reflects the level of leaf cover in the two types of forest. The delta 15N data display three significantly different modes. The omnivorous capuchins were most positive reflecting a trophic level offset. The spider monkeys and the muriquis were similar to one another and significantly more positive than the howlers. This distribution among totally herbivorous species correlates with the ingestion of legumes by the howler monkey population. In combination, these data indicate that museum-curated primate material can be analyzed to yield information on forest cover and diet in populations and species lacking behavioral data.

The role of B cells in solid organ transplantation.

The role of antibodies in chronic injury to organ transplants has been suggested for many years, but recently emphasized by new data. We have observed that when immunosuppressive potency decreases either by intentional weaning of maintenance agents or due to homeostatic repopulation after immune cell depletion, the threshold of B cell activation may be lowered. In human transplant recipients the result may be donor-specific antibody, C4d+ injury, and chronic rejection. This scenario has precise parallels in a rhesus monkey renal allograft model in which T cells are depleted with CD3 immunotoxin, or in a CD52-T cell transgenic mouse model using alemtuzumab to deplete T cells. Such animal models may be useful for the testing of therapeutic strategies to prevent DSA. We agree with others who suggest that weaning of immunosuppression may place transplant recipients at risk of chronic antibody-mediated rejection, and that strategies to prevent this scenario are needed if we are to improve long-term graft and patient outcomes in transplantation. We believe that animal models will play a crucial role in defining the pathophysiology of antibody-mediated rejection and in developing effective therapies to prevent graft injury. Two such animal models are described herein.

Metacognition in monkeys during an oculomotor task.

This study investigated whether rhesus monkeys show evidence of metacognition in a reduced, visual oculomotor task that is particularly suitable for use in fMRI and electrophysiology. The 2-stage task involved punctate visual stimulation and saccadic eye movement responses. In each trial, monkeys made a decision and then made a bet. To earn maximum reward, they had to monitor their decision and use that information to bet advantageously. Two monkeys learned to base their bets on their decisions within a few weeks. We implemented an operational definition of metacognitive behavior that relied on trial-by-trial analyses and signal detection theory. Both monkeys exhibited metacognition according to these quantitative criteria. Neither external visual cues nor potential reaction time cues explained the betting behavior; the animals seemed to rely exclusively on internal traces of their decisions. We documented the learning process of one monkey. During a 10-session transition phase, betting switched from random to a decision-based strategy. The results reinforce previous findings of metacognitive ability in monkeys and may facilitate the neurophysiological investigation of metacognitive functions.

Reversible inactivation of macaque frontal eye field.

The macaque frontal eye field (FEF) is involved in the generation of saccadic eye movements and fixations. To better understand the role of the FEF, we reversibly inactivated a portion of it while a monkey made saccades and fixations in response to visual stimuli. Lidocaine was infused into a FEF and neural inactivation was monitored with a nearby microelectrode. We used two saccadic tasks. In the delay task, a target was presented and then extinguished, but the monkey was not allowed to make a saccade to its location until a cue to move was given. In the step task, the monkey was allowed to look at a target as soon as it appeared. During FEF inactivation, monkeys were severely impaired at making saccades to locations of extinguished contralateral targets in the delay task. They were similarly impaired at making saccades to locations of contralateral targets in the step task if the target was flashed for < or =100 ms, such that it was gone before the saccade was initiated. Deficits included increases in saccadic latency, increases in saccadic error, and increases in the frequency of trials in which a saccade was not made. We varied the initial fixation location and found that the impairment specifically affected contraversive saccades rather than affecting all saccades made into head-centered contralateral space. Monkeys were impaired only slightly at making saccades to contralateral targets in the step task if the target duration was 1000 ms, such that the target was present during the saccade: latency increased, but increases in saccadic error were mild and increases in the frequency of trials in which a saccade was not made were insignificant. During FEF inactivation there usually was a direct correlation between the latency and the error of saccades made in response to contralateral targets. In the delay task, FEF inactivation increased the frequency of making premature saccades to ipsilateral targets. FEF inactivation had inconsistent and mild effects on saccadic peak velocity. FEF inactivation caused impairments in the ability to fixate lights steadily in contralateral space. FEF inactivation always caused an ipsiversive deviation of the eyes in darkness. In summary, our results suggest that the FEF plays major roles in (1) generating contraversive saccades to locations of extinguished or flashed targets, (2) maintaining contralateral fixations, and (3) suppressing inappropriate ipsiversive saccades.

Activity against Mycobacterium smegmatis and M. tuberculosis by extract of South African medicinal plants

Seven ethnobotanically selected medicinal plants were screened for their antimycobacterial activity. The mininium inhibitory concentration (MIC) of four plants namely Artemisia afra, Dodonea angustifolia, Drosera capensis and Galenia africana ranged from 0.781 to 6.25 mg/mL against Mycobacterium smegmatis. G. africana showed the best activity exhibiting an MIC of 0.78 mg/mL and a minimum bactericidal concentration (MBC) of 1.56 mg/mL. The MICs of ethanol extracts of A angustifolia and G. africana against M. tuberculosis were found to be 5.0 and 1.2 mg/mL respectively. The mammalian cytotoxicity IC50 value of the most active antimycobacterial extract, from G. africana, was found to be 101.3 mu g/mL against monkey kidney Vero cells. Since the ethanol G. africana displayed the best antimycobacterial activity, it was subjected to fractionation which led to the isolation of a flavone, 5,7,2'-trihydroxyflavone. The MIC of this compound was found to be 0.031 mg/mL against M. smegmatis and 0.10 mg/mL against M. tuberculosis. This study gives some scientific basis to the 14 traditional use of these plants for TB-related symptoms. Copyright (C) 2008 John Wiley & Sons, Ltd.

Phylloseptin-1 (PSN-1) from Phyllomedusa sauvagei skin secretion: a novel broad-spectrum antimicrobial peptide with antibiofilm activity

Amphibian skin secretions have proven to be rich sources of antimicrobial peptides that are proposed to be fundamental components of the innate immune system. As amphibian skin is a multi-functional organ playing, among other things, a crucial role in respiration, it has been deemed that a core biological role for such peptides is control of microbial flora on this surface. To date, however, antimicrobial efficacy has been universally determined by means of establishing minimum inhibitory concentrations (MICs) using planktonic organisms rather than those within a biofilm such as would occur on this exposed surface. Here we describe the identification and structural characterisation of a novel 19 amino acid residue antimicrobial peptide of the phylloseptin family, named PSN-1, from the skin secretion of the waxy monkey frog, Phyllomedusa sauvagei. PSN-1 displayed broad-spectrum activity against a range of planktonic organisms with a high potency (MIC 5 µM) against Staphylococcus aureus. In a specific bioassay with the same organism grown as a biofilm, the minimal biofilm eradication concentration (MBEC) was found to be of the same high potency (5 µM). The present data would suggest that evaluation of actions and potency of amphibian skin secretion antimicrobial peptides might best be achieved by evaluating MBEC rather than MIC using planktonic organisms and that data arising from such studies may have more biological relevance in reflecting the purpose for which they have evolved through natural selection.

Olfactory discrimination in the western lowland gorilla, Gorilla gorilla gorilla

The olfactory abilities of great apes have been subject to little empirical investigation, save for a few observational reports. This study, using an habituation/dishabituation task, provides experimental evidence for a core olfactory ability, namely, olfactory discrimination, in the gorilla. In Experiment 1, six zoo-housed western lowland gorillas were individually presented with the same odour on four trials, and with a novel odour on the fifth trial. Odours (almond and vanilla) were presented on plastic balls, and behavioural responses of sniffing and chewing/licking the balls were recorded. A second experiment presented the same odour on four trials and no odour on the fifth to examine whether any dishabituation was due to the presence of a new odour or the absence of the familiar odour. Gorillas habituated their behaviour with repeated presentation of the same odour, but dishabituated, i. e. increased sniffing and chewing/licking, when presented with the novel odour. No dishabituation was noted when using water as the stimulus across all trials or when used as the novel odour. Overall, results show that gorillas are able to discriminate between odours. © 2012 Japan Monkey Centre and Springer.

Sequence divergence of measles virus haemagglutinin during natural evolution and adaptation to cell culture

Phylogenetic analysis of the sequence of the H gene of 75 measles virus (MV) strains (32 published and 43 new sequences) was carried out. The lineage groups described from comparison of the nucleotide sequences encoding the C-terminal regions of the N protein of MV were the same as those derived from the H gene sequences in almost all cases. The databases document a number of distinct genotype switches that have occurred in Madrid (Spain). Well-documented is the complete replacement of lineage group C2, the common European genotype at that time, with that of group D3 around the autumn of 1993. No further isolations of group C2 took place in Madrid after this time. The rate of mutation of the H gene sequences of MV genotype D3 circulating in Madrid from 1993 to 1996 was very low (5 x 10(-4) per annum for a given nucleotide position). This is an order of magnitude lower than the rates of mutation observed in the HN genes of human influenza A viruses. The ratio of expressed over silent mutations indicated that the divergence was not driven by immune selection in this gene. Variations in amino acid 117 of the H protein (F or L) may be related to the ability of some strains to haemagglutinate only in the presence of salt. Adaptation of MV to different primate cell types was associated with very small numbers of mutations in the H gene. The changes could not be predicted when virus previously grown in human B cell lines was adapted to monkey Vero cells. In contrast, rodent brain-adapted viruses displayed a lot of amino acid sequence variation from normal MV strains. There was no convincing evidence for recombination between MV genotypes.

Electron microscopic features of experimental choroidal neovascularization

We produced choroidal neovascularization in the rhesus monkey by diminishing the blood supply to the inner retina and producing defects in Bruch's membrane by photocoagulation. The neovascular fronds which developed either infiltrated the subretinal space or proliferated through necrotic and gliotic retina into the vitreous cavity. Sequential electron microscopic sections of neovascular fronds in the subretinal space demonstrated that the advancing capillary sprouts were composed of primitive endothelial tubes surrounded by pericytes and enmeshed in a loose basement-membrane-like substance. More mature capillaris and displayed endothelial fenestrations and endothelial-pericyte membranous contacts. Large neovascular fronds developed major feeding vessels that closely resembled normal small choroidal arteries and veins. Retinal pigment epithelial cells in various guises were in constant association with proliferating neovascular networks.

Morphologic fluorescein angiographic, and light microscopic features of experimental choroidal neovascularization

We induced choroidal neovascularization in the rhesus monkey by impoverishing the blood supply to the inner retina and producing defects in Bruch's membrane by photocoagulation. Fourteen of 46 eyes undergoing photocoagulation developed neovascular fronds which were identified and categorized by histopathologic examination and fluorescein angiography. All new vessels gained access to the retina through defects in Bruch's membrane at the site of photocoagulation marks. In eight eyes the new vessels remained localized to the immediate vicinity of photocoagulation marks. In four eyes neovascular fronds infiltrated the subretinal space for distances up to 6 disk diameters from the point of entry into the retina. In the two eyes choroidovitreal neovascular complexes developed but rapidly regressed shortly after gaining the vitreous cavity. Fluorescein angiography demonstrated that all neovascular fronds were grossly incompetent to dye but that formed feeding channels had some degree of integrity. Light microscopic studies showed the proliferating networks to be composed of capillaries with well-formed basement membranes and more mature vessels with the basic structure of choroidal arteries and veins.

Survey of challenges and best practice strategies for participant recruitment to research projects in northern ireland

Participant recruitment is understood to be one of the most difficult aspects of the research process. Researchers are now devoting increasing amounts of time and resources to understand how participants decide to take part in research and what researchers can do to make their work appeal to potential participants. The purpose of the study is to assess the problems experienced by researchers in Northern Ireland when recruiting human participants into trials and studies and to gain insight into how researchers handle and overcome these issues. The main research question being addressed by this research is to develop an understanding of the problems experienced by staff when recruiting human participants to research projects. Methods used to increase study recruitment were also examined. The participants in this research are investigators and other associated staff on research studies based in Northern Ireland. Potential participants were identified through contacts with research active organizations such as the academic researchers in Queen’s University Belfast and research physicians and clinical trialists employed by the Belfast Health and Social Care Trust. Each organization forwarded on the survey request via email or newsletters. Researchers willing to take part accessed the questionnaire through the Survey Monkey website. This study utilised a cross-sectional questionnaire design.

Use of SLAM and PVRL4 and Identification of Pro-HB-EGF as Cell Entry Receptors for Wild Type Phocine Distemper Virus

Signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for the morbilliviruses, measles (MV), canine distemper (CDV), rinderpest and peste des petits ruminants (PPRV) viruses, while CD46 is a receptor for vaccine strains of MV. More recently poliovirus like receptor 4 (PVRL4), also known as nectin 4, has been identified as a receptor for MV, CDV and PPRV on the basolateral surface of polarised epithelial cells. PVRL4 is also up-regulated by MV in human brain endothelial cells. Utilisation of PVRL4 as a receptor by phocine distemper virus (PDV) remains to be demonstrated as well as confirmation of use of SLAM. We have observed that unlike wild type (wt) MV or wtCDV, wtPDV strains replicate in African green monkey kidney Vero cells without prior adaptation, suggesting the use of a further receptor. We therefore examined candidate molecules, glycosaminoglycans (GAG) and the tetraspan proteins, integrin β and the membrane bound form of heparin binding epithelial growth factor (proHB-EGF),for receptor usage by wtPDV in Vero cells. We show that wtPDV replicates in Chinese hamster ovary (CHO) cells expressing SLAM and PVRL4. Similar wtPDV titres are produced in Vero and VeroSLAM cells but more limited fusion occurs in the latter. Infection of Vero cells was not inhibited by anti-CD46 antibody. Removal/disruption of GAG decreased fusion but not the titre of virus. Treatment with anti-integrin β antibody increased rather than decreased infection of Vero cells by wtPDV. However, infection was inhibited by antibody to HB-EGF and the virus replicated in CHO-proHB-EGF cells, indicating use of this molecule as a receptor. Common use of SLAM and PVRL4 by morbilliviruses increases the possibility of cross-species infection. Lack of a requirement for wtPDV adaptation to Vero cells raises the possibility of usage of proHB-EGF as a receptor in vivo but requires further investigation.

Tools and Environments for Networked Electronic Performance

A collection of software and hardware tools and environments that facilitate collective networked performance between electronic musicians. Tools include 'Chat Monkey', a live chat tool for performance, 'DMA Sequencing', a step sequencer using open sound control messaging and multi nodal control, 'tutti, duet, trio, solo, quartet', an ensemble management environment, and 'Por Larrañaga', a cigar box based electro-acoustic instrument with embedded sensors and controllers. Notable performances: w/BLISS, NCAD, Dublin, 1 March 2015; w/BLISS, NI Science Festival, Belfast, 21 Feb 2015

Avaliação da satisfação do utente na comunicação com os profissionais de saúde construção e validação de um instrumento

A satisfação do utente na comunicação com profissionais de saúde é um indicador de qualidade dos serviços ou instituições. Na literatura não encontramos instrumentos padronizados e validados, que avaliem a satisfação do utente na comunicação com os profissionais de saúde. O presente estudo tem como objetivo construir e validar um instrumento para avaliar a satisfação do utente na comunicação com os profissionais de saúde. Desenvolvemos este estudo em três ciclos. Um primeiro, revisão da literatura, para identificar dimensões e itens da comunicação interpessoal na saúde. No segundo ciclo, conduzimos um método de Delphi modificado em três rondas, com recurso à plataforma informática de questionários Survey Monkey, no qual participou um painel de 25 peritos; estabelecemos como critério mínimo de retenção para a ronda seguinte os itens que recebessem 70% do consenso por parte do painel. Após as três rondas, obtivemos um instrumento com seis dimensões comunicacionais (comunicação verbal, comunicação não verbal, empatia, respeito, resolução de problemas e material de apoio), vinte e cinco itens específicos, e mais seis dimensões genéricas, que avaliam cada uma das dimensões. No terceiro ciclo avaliamos as características psicométricas, em termos de sensibilidade, validade do construto e fidelidade, numa amostra de 348 participantes. Os resultados mostram que todas as categorias de resposta estavam representadas em todos os itens. Validade do construto- a análise fatorial identificou uma solução de seis componentes que explicam 71% da variância total. Fiabilidade - os valores da correlação item-total variam entre 0,387 e 0,722, existindo uma correlação positiva moderada a forte. O valor de alfa de Cronbach (α=0,928) indica que a consistência interna é excelente. O instrumento construído apresenta boas propriedades psicométricas. Fica assim disponível uma nova ferramenta para auxiliar na gestão e no processo de planeamento necessários ao incremento da qualidade nos serviços e instituições de saúde.