Cortical projection of the inferior choroidal point as a reliable landmark to place the corticectomy and reach the temporal horn through a middle temporal gyrus approach

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Thomas Frigeri

2014-10-01

Full Text Available Objective To establish preoperatively the localization of the cortical projection of the inferior choroidal point (ICP and use it as a reliable landmark when approaching the temporal horn through a middle temporal gyrus access. To review relevant anatomical features regarding selective amigdalohippocampectomy (AH for treatment of mesial temporal lobe epilepsy (MTLE. Method The cortical projection of the inferior choroidal point was used in more than 300 surgeries by one authors as a reliable landmark to reach the temporal horn. In the laboratory, forty cerebral hemispheres were examined. Conclusion The cortical projection of the ICP is a reliable landmark for reaching the temporal horn.

Middle Temporal Gyrus Versus Inferior Temporal Gyrus Transcortical Approaches to High-Grade Astrocytomas in the Mediobasal Temporal Lobe: A Comparison of Outcomes, Functional Restoration, and Surgical Considerations.

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Quinones-Hinojosa, Alfredo; Raza, Shaan M; Ahmed, Ishrat; Rincon-Torroella, Jordina; Chaichana, Kaisorn; Olivi, Alessandro

2017-01-01

High-grade astrocytomas of the mesial temporal lobe may pose surgical challenges. Several approaches (trans-sylvian, subtemporal, and transcortical) have been designed to circumnavigate the critical neurovascular structures and white fiber tracts that surround this area. Considering the paucity of literature on the transcortical approach for these lesions, we describe our institutional experience with transcortical approaches to Grade III/IV astrocytomas in the mesial temporal lobe. Between 1999 and 2009, 23 patients underwent surgery at the Johns Hopkins Medical Institutions for Grade III/IV astrocytomas involving the mesial temporal lobe (without involvement of the temporal neocortex). Clinical notes, operative records, and imaging were reviewed. Thirteen patients had tumors in the dominant hemisphere. All patients underwent surgery via a transcortical approach (14 via the inferior temporal gyrus and 9 via the middle temporal gyrus). Gross total resection was obtained in 92 % of the cohort. Neurological outcomes were: clinically significant stroke (2 patients), new visual deficits (2 patients), new speech deficit (1 patient); seizure control (53 %). In comparison to reported results in the literature for the transylvian and subtemporal approaches, the transcortical approach may provide the access necessary for a gross total resection with minimal neurological consequences. In our series of patients, there was no statistically significant difference in outcomes between the middle temporal gyrus versus the inferior temporal gyrus trajectories.

Short-Term and Procedural Memory for Colours and Inferior Temporal Cortex Activity

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E. Castro-Sierra

1997-01-01

Full Text Available Two children (male, 10 years, and female, 13 years one month with tumours of the inferior temporal (IT cortex of the brain were studied post-surgically for their abilities to carry out a short-term memory test. This involved: differences in colour, number and shape of small plastic objects; differences in receptacles where these objects should be placed and in ways in which this placement should be done; a procedural task involving differences either in colour or in size of wooden rings employed in the task. Their performances in these tests, and those of patients with tumours of other encephalic areas, were compared with the performances of normal controls. The subjects with IT tumours spent a significantly greater amount of time than normal subjects of their age in carrying out the procedural task involving differences in colour. One of the IT subjects also spent a significantly greater amount of time in the procedural task involving size differences. Other differences in the performances of patients with encephalic tumours and the performances of normal controls were not significant. Results are discussed in relation to findings of colour and size perception and memory localized to the inferior temporal and middle temporal cortices.

A follow-up MRI study of the fusiform gyrus and middle and inferior temporal gyri in schizophrenia spectrum.

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Takahashi, Tsutomu; Zhou, Shi-Yu; Nakamura, Kazue; Tanino, Ryoichiro; Furuichi, Atsushi; Kido, Mikio; Kawasaki, Yasuhiro; Noguchi, Kyo; Seto, Hikaru; Kurachi, Masayoshi; Suzuki, Michio

2011-12-01

While longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive gray matter reduction of the superior temporal gyrus (STG) during the early phases of schizophrenia, it remains largely unknown whether other temporal lobe structures also exhibit similar progressive changes and whether these changes, if present, are specific to schizophrenia among the spectrum disorders. In this longitudinal MRI study, the gray matter volumes of the fusiform, middle temporal, and inferior temporal gyri were measured at baseline and follow-up scans (mean inter-scan interval=2.7 years) in 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. Both schizophrenia and schizotypal patients had a smaller fusiform gyrus than controls bilaterally at both time points, whereas no group difference was found in the middle and inferior temporal gyri. In the longitudinal comparison, the schizophrenia patients showed significant fusiform gyrus reduction (left, -2.6%/year; right, -2.3%/year) compared with schizotypal patients (left: -0.4%/year; right: -0.2%/year) and controls (left: 0.1%/year; right: 0.0%/year). However, the middle and inferior temporal gyri did not exhibit significant progressive gray matter change in all diagnostic groups. In the schizophrenia patients, a higher cumulative dose of antipsychotics during follow-up was significantly correlated with less severe gray matter reduction in the left fusiform gyrus. The annual gray matter loss of the fusiform gyrus did not correlate with that of the STG previously reported in the same subjects. Our findings suggest regional specificity of the progressive gray matter reduction in the temporal lobe structures, which might be specific to overt schizophrenia within the schizophrenia spectrum. Copyright © 2011 Elsevier Inc. All rights reserved.

Functional MRI of the vocalization-processing network in the macaque brain

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Michael eOrtiz-Rios

2015-04-01

Full Text Available Using functional magnetic resonance imaging in awake behaving monkeys we investigated how species-specific vocalizations are represented in auditory and auditory-related regions of the macaque brain. We found clusters of active voxels along the ascending auditory pathway that responded to various types of complex sounds: inferior colliculus (IC, medial geniculate nucleus (MGN, auditory core, belt, and parabelt cortex, and other parts of the superior temporal gyrus (STG and sulcus (STS. Regions sensitive to monkey calls were most prevalent in the anterior STG, but some clusters were also found in frontal and parietal cortex on the basis of comparisons between responses to calls and environmental sounds. Surprisingly, we found that spectrotemporal control sounds derived from the monkey calls (scrambled calls also activated the parietal and frontal regions. Taken together, our results demonstrate that species-specific vocalizations in rhesus monkeys activate preferentially the auditory ventral stream, and in particular areas of the antero-lateral belt and parabelt.

Amygdala lesions disrupt modulation of functional MRI activity evoked by facial expression in the monkey inferior temporal cortex

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Hadj-Bouziane, Fadila; Liu, Ning; Bell, Andrew H.; Gothard, Katalin M.; Luh, Wen-Ming; Tootell, Roger B. H.; Murray, Elisabeth A.; Ungerleider, Leslie G.

2012-01-01

We previously showed that facial expressions modulate functional MRI activity in the face-processing regions of the macaque monkey’s amygdala and inferior temporal (IT) cortex. Specifically, we showed that faces expressing emotion yield greater activation than neutral faces; we term this difference the “valence effect.” We hypothesized that amygdala lesions would disrupt the valence effect by eliminating the modulatory feedback from the amygdala to the IT cortex. We compared the valence effects within the IT cortex in monkeys with excitotoxic amygdala lesions (n = 3) with those in intact control animals (n = 3) using contrast agent-based functional MRI at 3 T. Images of four distinct monkey facial expressions—neutral, aggressive (open mouth threat), fearful (fear grin), and appeasing (lip smack)—were presented to the subjects in a blocked design. Our results showed that in monkeys with amygdala lesions the valence effects were strongly disrupted within the IT cortex, whereas face responsivity (neutral faces > scrambled faces) and face selectivity (neutral faces > non-face objects) were unaffected. Furthermore, sparing of the anterior amygdala led to intact valence effects in the anterior IT cortex (which included the anterior face-selective regions), whereas sparing of the posterior amygdala led to intact valence effects in the posterior IT cortex (which included the posterior face-selective regions). Overall, our data demonstrate that the feedback projections from the amygdala to the IT cortex mediate the valence effect found there. Moreover, these modulatory effects are consistent with an anterior-to-posterior gradient of projections, as suggested by classical tracer studies. PMID:23184972

The inferior, anterior temporal lobes and semantic memory clarified: novel evidence from distortion-corrected fMRI.

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Visser, M; Embleton, K V; Jefferies, E; Parker, G J; Ralph, M A Lambon

2010-05-01

The neural basis of semantic memory generates considerable debate. Semantic dementia results from bilateral anterior temporal lobe (ATL) atrophy and gives rise to a highly specific impairment of semantic memory, suggesting that this region is a critical neural substrate for semantic processing. Recent rTMS experiments with neurologically-intact participants also indicate that the ATL are a necessary substrate for semantic memory. Exactly which regions within the ATL are important for semantic memory are difficult to detect from these methods (because the damage in SD covers a large part of the ATL). Functional neuroimaging might provide important clues about which specific areas exhibit activation that correlates with normal semantic performance. Neuroimaging studies, however, have not consistently found anterior temporal lobe activation in semantic tasks. A recent meta-analysis indicates that this inconsistency may be due to a collection of technical limitations associated with previous studies, including a reduced field-of-view and magnetic susceptibility artefacts associated with standard gradient echo fMRI. We conducted an fMRI study of semantic memory using a combination of techniques which improve sensitivity to ATL activations whilst preserving whole-brain coverage. As expected from SD patients and ATL rTMS experiments, this method revealed bilateral temporal activation extending from the inferior temporal lobe along the fusiform gyrus to the anterior temporal regions, bilaterally. We suggest that the inferior, anterior temporal lobe region makes a crucial contribution to semantic cognition and utilising this version of fMRI will enable further research on the semantic role of the ATL. 2010 Elsevier Ltd. All rights reserved.

Transcranial Magnetic Stimulation over Left Inferior Frontal and Posterior Temporal Cortex Disrupts Gesture-Speech Integration.

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Zhao, Wanying; Riggs, Kevin; Schindler, Igor; Holle, Henning

2018-02-21

Language and action naturally occur together in the form of cospeech gestures, and there is now convincing evidence that listeners display a strong tendency to integrate semantic information from both domains during comprehension. A contentious question, however, has been which brain areas are causally involved in this integration process. In previous neuroimaging studies, left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG) have emerged as candidate areas; however, it is currently not clear whether these areas are causally or merely epiphenomenally involved in gesture-speech integration. In the present series of experiments, we directly tested for a potential critical role of IFG and pMTG by observing the effect of disrupting activity in these areas using transcranial magnetic stimulation in a mixed gender sample of healthy human volunteers. The outcome measure was performance on a Stroop-like gesture task (Kelly et al., 2010a), which provides a behavioral index of gesture-speech integration. Our results provide clear evidence that disrupting activity in IFG and pMTG selectively impairs gesture-speech integration, suggesting that both areas are causally involved in the process. These findings are consistent with the idea that these areas play a joint role in gesture-speech integration, with IFG regulating strategic semantic access via top-down signals acting upon temporal storage areas. SIGNIFICANCE STATEMENT Previous neuroimaging studies suggest an involvement of inferior frontal gyrus and posterior middle temporal gyrus in gesture-speech integration, but findings have been mixed and due to methodological constraints did not allow inferences of causality. By adopting a virtual lesion approach involving transcranial magnetic stimulation, the present study provides clear evidence that both areas are causally involved in combining semantic information arising from gesture and speech. These findings support the view that, rather than being

P1-27: Localizing Regions Activated by Surface Gloss in Macaque Visual Cortex by fMRI

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Gouki Okazawa

2012-10-01

Full Text Available Surface properties of objects such as gloss provide important information about the states or materials of objects in our visual experiences. Previous studies have shown that there are cortical regions responding to shapes, colors, faces etc. in the macaque visual cortex. However, we still lack the information about where the surface properties are processed in the macaque visual cortex. In this study, we examined whether there are regions activated by surface gloss, an important surface property, in the macaque visual cortex by using functional magnetic resonance imaging (fMRI. We trained two monkeys to fixate on a small spot on the screen in MRI scanner, while the images of glossy and matte objects were presented. As a control condition for low-level image features, such as spatial frequency or luminance contrast, we generated scrambled images by locally randomizing the luminance phases of images using wavelet filters. By contrasting the responses to glossy images to those to matte and scrambled images, we found the activation in wide regions along the ventral visual pathway including V1, V2, V3, V4, and the posterior part of the inferior temporal (IT cortex. In one monkey, we also found the activations in the central part of IT cortex. In another control experiment, we manipulated the image contrasts and found that the responses in these regions cannot be explained simply by the image contrasts. These results suggest that surface gloss is processed along the ventral pathway and, in the IT cortex there are distinct regions processing surface gloss.

Encoding of complexity, shape and curvature by macaque infero-temporal neurons

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Greet eKayaert

2011-07-01

Full Text Available We recorded responses of macaque infero-temporal (IT neurons to a stimulus set of Fourier Boundary Descriptor shapes wherein complexity, general shape and curvature were systematically varied. We analyzed the response patterns of the neurons to the different stimuli using multi-dimensional scaling. The resulting neural shape space differed in important ways from the physical, image-based shape space. We found a particular sensitivity for the presence of curved versus straight contours that existed only for the simple but not for the medium and highly complex shapes. Also, IT neurons could linearly separate the simple and the complex shapes within a low-dimensional neural shape space, but no distinction was found between the medium and high levels of complexity. None of these effects could be derived from physical image metrics, either directly or by comparing the neural data with similarities yielded by two models of low-level visual processing (one using wavelet-based filters and one that models position and size invariant object selectivity through four hierarchically organized neural layers. This study highlights the relevance of complexity to IT neural encoding, both as a neurally independently represented shape property and through its influence on curvature detection.

The nucleus pararaphales in the human, chimpanzee, and macaque monkey.

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Baizer, Joan S; Weinstock, Nadav; Witelson, Sandra F; Sherwood, Chet C; Hof, Patrick R

2013-03-01

The human cerebral cortex and cerebellum are greatly expanded compared to those of other mammals, including the great apes. This expansion is reflected in differences in the size and organization of precerebellar brainstem structures, such as the inferior olive. In addition, there are cell groups unique to the human brainstem. One such group may be the nucleus pararaphales (PRa); however, there is disagreement among authors about the size and location of this nucleus in the human brainstem. The name "pararaphales" has also been used for neurons in the medulla shown to project to the flocculus in the macaque monkey. We have re-examined the existence and status of the PRa in eight humans, three chimpanzees, and four macaque monkeys using Nissl-stained sections as well as immunohistochemistry. In the human we found a cell group along the midline of the medulla in all cases; it had the form of interrupted cell columns and was variable among cases in rostrocaudal and dorsoventral extent. Cells and processes were highly immunoreactive for non-phosphorylated neurofilament protein (NPNFP); somata were immunoreactive to the synthetic enzyme for nitric oxide, nitric oxide synthase, and for calretinin. In macaque monkey, there was a much smaller oval cell group with NPNFP immunoreactivity. In the chimpanzee, we found a region of NPNFP-immunoreactive cells and fibers similar to what was observed in macaques. These results suggest that the "PRa" in the human may not be the same structure as the flocculus-projecting cell group described in the macaque. The PRa, like the arcuate nucleus, therefore may be unique to humans.

Functional differentiation of macaque visual temporal cortical neurons using a parametric action space.

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Vangeneugden, Joris; Pollick, Frank; Vogels, Rufin

2009-03-01

Neurons in the rostral superior temporal sulcus (STS) are responsive to displays of body movements. We employed a parametric action space to determine how similarities among actions are represented by visual temporal neurons and how form and motion information contributes to their responses. The stimulus space consisted of a stick-plus-point-light figure performing arm actions and their blends. Multidimensional scaling showed that the responses of temporal neurons represented the ordinal similarity between these actions. Further tests distinguished neurons responding equally strongly to static presentations and to actions ("snapshot" neurons), from those responding much less strongly to static presentations, but responding well when motion was present ("motion" neurons). The "motion" neurons were predominantly found in the upper bank/fundus of the STS, and "snapshot" neurons in the lower bank of the STS and inferior temporal convexity. Most "motion" neurons showed strong response modulation during the course of an action, thus responding to action kinematics. "Motion" neurons displayed a greater average selectivity for these simple arm actions than did "snapshot" neurons. We suggest that the "motion" neurons code for visual kinematics, whereas the "snapshot" neurons code for form/posture, and that both can contribute to action recognition, in agreement with computation models of action recognition.

P1-5: Effect of Luminance Contrast on the Color Selective Responses in the Inferior Temporal Cortex Neurons of the Macaque Monkey

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Tomoyuki Namima

2012-10-01

Full Text Available Although the relationship between color signal and luminance signal is an important problem in visual perception, relatively little is known about how the luminance contrast affects the responses of color selective neurons in the visual cortex. In this study, we examined this problem in the inferior temporal (IT of the awake monkey performing a visual fixation task. Single neuron activities were recorded from the anterior and posterior color selective regions in IT cortex (AITC and PITC identified in previous studies where color selective neurons are accumulated. Color stimuli consisted of 28 stimuli that evenly distribute across the gamut of the CRT display defined on the CIE- xychromaticity diagram at two different luminance levels (5 cd/m 2or 20 cd/m 2 and 2 stimuli at white points. The background was maintained at 10 cd/m 2gray. We found that the effect of luminance contrast on the color selectivity was markedly different between AITC and PITC. When we examined the correlation between the responses to the bright stimuli and those to the dark stimuli with the same chromaticity coordinates, most AITC neurons exhibited high correlation whereas many PITC neurons showed no correlation or only weak correlation. In PITC, the effect was specifically large for neutral colors (white, gray, black and for colors with low saturation. These results indicate that the effect of luminance contrast on the color selective responses differs across different areas and suggest that the separation between color signal and luminance signal involves a higher stage of the cortical color processing.

Neuropsychology Outcomes Following Trephine Epilepsy Surgery: The Inferior Temporal Gyrus Approach for Amygdalohippocampectomy in Medically Refractory Mesial Temporal Lobe Epilepsy.

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Schoenberg, Mike R; Clifton, William E; Sever, Ryan W; Vale, Fernando L

2017-06-08

Surgery is indicated in cases of mesial temporal lobe epilepsy(MTLE) that are refractory to medical management. The inferior temporal gyrus (ITG) approach provides access to the mesial temporal lobe (MTL) structures with minimal tissue disruption. Reported neuropsychology outcomes following this approach are limited. To report neuropsychological outcomes using an ITG approach to amygdalohippocampectomy (AH) in patients with medically refractory MTLE based on a prospective design. Fifty-four participants had Engel class I/II outcome following resection of MTL using the ITG approach. All participants had localization-related epilepsy confirmed by long-term surface video-electroencephalography and completed pre/postsurgical evaluations that included magnetic resonance imaging (MRI), Wada test or functional MRI, and neuropsychology assessment. Clinical semiology/video-electroencephalography indicated that of the 54 patients, 28 (52%) had left MTLE and 26 (48%) had right MTLE. Dominant hemisphere resections were performed on 23 patients (43%), nondominant on 31(57%). Twenty-nine (29) had pathology-confirmed mesial temporal sclerosis (MTS). Group level analyses found declines in verbal memory for patients with language-dominant resections ( P .05). Neuropsychology outcomes of an ITG approach for selective mesial temporal resection are comparable to other selective AH techniques showing minimal adverse cognitive effects. These data lend support to the ITG approach for selective AH as an option for MTLE. © Congress of Neurological Surgeons 2017.

Stimulating the Brain's Language Network: Syntactic Ambiguity Resolution after TMS to the Inferior Frontal Gyrus and Middle Temporal Gyrus

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Acheson, D.J.; Hagoort, P.

2013-01-01

The posterior middle temporal gyrus (MTG) and inferior frontal gyrus (IFG) are two critical nodes of the brain's language network. Previous neuroimaging evidence has supported a dissociation in language comprehension in which parts of the MTG are involved in the retrieval of lexical syntactic

The Medial Temporal Lobe and the Left Inferior Prefrontal Cortex Jointly Support Interference Resolution in Verbal Working Memory

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Oztekin, Ilke; Curtis, Clayton E.; McElree, Brian

2009-01-01

During working memory retrieval, proactive interference (PI) can be induced by semantic similarity and episodic familiarity. Here, we used fMRI to test hypotheses about the role of the left inferior frontal gyrus (LIFG) and the medial temporal lobe (MTL) regions in successful resolution of PI. Participants studied six-word lists and responded to a…

Conceptual control across modalities: graded specialisation for pictures and words in inferior frontal and posterior temporal cortex

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Krieger-Redwood, Katya; Teige, Catarina; Davey, James; Hymers, Mark; Jefferies, Elizabeth

2015-01-01

Controlled semantic retrieval to words elicits co-activation of inferior frontal (IFG) and left posterior temporal cortex (pMTG), but research has not yet established (i) the distinct contributions of these regions or (ii) whether the same processes are recruited for non-verbal stimuli. Words have relatively flexible meanings – as a consequence, identifying the context that links two specific words is relatively demanding. In contrast, pictures are richer stimuli and their precise meaning is ...

Role of inferior temporal neurons in visual memory. II. Multiplying temporal waveforms related to vision and memory.

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Eskandar, E N; Optican, L M; Richmond, B J

1992-10-01

1. In the companion paper we reported on the activity of neurons in the inferior temporal (IT) cortex during a sequential pattern matching task. In this task a sample stimulus was followed by a test stimulus that was either a match or a nonmatch. Many of the neurons encoded information about the patterns of both current and previous stimuli in the temporal modulation of their responses. 2. A simple information processing model of visual memory can be formed with just four steps: 1) encode the current stimulus; 2) recall the code of a remembered stimulus; 3) compare the two codes; 4) and decide whether they are similar or different. The analysis presented in the first paper suggested that some IT neurons were performing the comparison step of visual memory. 3. We propose that IT neurons participate in the comparison of temporal waveforms related to vision and memory by multiplying them together. This product could form the basis of a crosscorrelation-based comparison. 4. We tested our hypothesis by fitting a simple multiplicative model to data from IT neurons. The model generated waveforms in separate memory and visual channels. The waveforms arising from the two channels were then multiplied on a point by point basis to yield the output waveform. The model was fitted to the actual neuronal data by a gradient descent method to find the best fit waveforms that also had the lowest total energy. 5. The multiplicative model fit the neuronal responses quite well. The multiplicative model made consistently better predictions of the actual response waveforms than did an additive model. Furthermore, the fit was better when the actual relationship between the responses and the sample and test stimuli were preserved than when that relationship was randomized. 6. We infer from the superior fit of the multiplicative model that IT neurons are multiplying temporally modulated waveforms arising from separate visual and memory systems in the comparison step of visual memory.

Effects of neonatal inferior prefrontal and medial temporal lesions on learning the rule for delayed nonmatching-to-sample.

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Málková, L; Bachevalier, J; Webster, M; Mishkin, M

2000-01-01

The ability of rhesus monkeys to master the rule for delayed nonmatching-to-sample (DNMS) has a protracted ontogenetic development, reaching adult levels of proficiency around 4 to 5 years of age (Bachevalier, 1990). To test the possibility that this slow development could be due, at least in part, to immaturity of the prefrontal component of a temporo-prefrontal circuit important for DNMS rule learning (Kowalska, Bachevalier, & Mishkin, 1991; Weinstein, Saunders, & Mishkin, 1988), monkeys with neonatal lesions of the inferior prefrontal convexity were compared on DNMS with both normal controls and animals given neonatal lesions of the medial temporal lobe. Consistent with our previous results (Bachevalier & Mishkin, 1994; Málková, Mishkin, & Bachevalier, 1995), the neonatal medial temporal lesions led to marked impairment in rule learning (as well as in recognition memory with long delays and list lengths) at both 3 months and 2 years of age. By contrast, the neonatal inferior convexity lesions yielded no impairment in rule-learning at 3 months and only a mild impairment at 2 years, a finding that also contrasts sharply with the marked effects of the same lesion made in adulthood. This pattern of sparing closely resembles the one found earlier after neonatal lesions to the cortical visual area TE (Bachevalier & Mishkin, 1994; Málková et al., 1995). The functional sparing at 3 months probably reflects the fact that the temporo-prefrontal circuit is nonfunctional at this early age, resulting in a total dependency on medial temporal contributions to rule learning. With further development, however, this circuit begins to provide a supplementary route for learning.

High baseline activity in inferior temporal cortex improves neural and behavioral discriminability during visual categorization

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Emadi, Nazli; Rajimehr, Reza; Esteky, Hossein

2014-01-01

Spontaneous firing is a ubiquitous property of neural activity in the brain. Recent literature suggests that this baseline activity plays a key role in perception. However, it is not known how the baseline activity contributes to neural coding and behavior. Here, by recording from the single neurons in the inferior temporal cortex of monkeys performing a visual categorization task, we thoroughly explored the relationship between baseline activity, the evoked response, and behavior. Specifically we found that a low-frequency (baseline activity. This enhancement of the baseline activity was then followed by an increase in the neural selectivity and the response reliability and eventually a higher behavioral performance. PMID:25404900

Distribution of glutamatergic, GABAergic, and glycinergic neurons in the auditory pathways of macaque monkeys.

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Ito, T; Inoue, K; Takada, M

2015-12-03

Macaque monkeys use complex communication calls and are regarded as a model for studying the coding and decoding of complex sound in the auditory system. However, little is known about the distribution of excitatory and inhibitory neurons in the auditory system of macaque monkeys. In this study, we examined the overall distribution of cell bodies that expressed mRNAs for VGLUT1, and VGLUT2 (markers for glutamatergic neurons), GAD67 (a marker for GABAergic neurons), and GLYT2 (a marker for glycinergic neurons) in the auditory system of the Japanese macaque. In addition, we performed immunohistochemistry for VGLUT1, VGLUT2, and GAD67 in order to compare the distribution of proteins and mRNAs. We found that most of the excitatory neurons in the auditory brainstem expressed VGLUT2. In contrast, the expression of VGLUT1 mRNA was restricted to the auditory cortex (AC), periolivary nuclei, and cochlear nuclei (CN). The co-expression of GAD67 and GLYT2 mRNAs was common in the ventral nucleus of the lateral lemniscus (VNLL), CN, and superior olivary complex except for the medial nucleus of the trapezoid body, which expressed GLYT2 alone. In contrast, the dorsal nucleus of the lateral lemniscus, inferior colliculus, thalamus, and AC expressed GAD67 alone. The absence of co-expression of VGLUT1 and VGLUT2 in the medial geniculate, medial superior olive, and VNLL suggests that synaptic responses in the target neurons of these nuclei may be different between rodents and macaque monkeys. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Study on CT scanning technique of inferior horn of lateral ventricle

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Kakoi, Iwao; Okubo, Mitsuo; Nakamura, Sumio; Yoshinaga, Toshihiko; Shimono, Tetsuo

1984-01-01

It is said that temporal lobe epilepsy (TLE), one of the incurable epilepsies, results from the lesions of various structrues located in the medial and deep portion of the temporal lobe such as the hippocampus and amygdaloid nucleus. Routine CT scanning techniques cannot adequately delineate these structures in the assessment of TLE. The anatomical relationship between these medial temporal structures and the inferior horn of lateral ventricle which is lateral to them and easily identified by CT lead us to believe that the sections through the longitudinal plane of the inferior horn may clearly delineate them. The present experimental study was undertaken to develop the CT scan technique of the inferior horn of lateral ventricle, which results in the clear delineation of the region of the hippocampus and amygdaloid nucleus. As a result, A total of the 3-4 reversed axial 5 mm-thick section centered at 2.5 cm cephalad to the roof of the external auditory canal at a reversed 25 0 angle to ABL are adequate to delineate the inferior horn and the medial temporal structures. This scan technique is considered to be useful in the assessment of TLE. (author)

One-way traffic: The inferior frontal gyrus controls brain activation in the middle temporal gyrus and inferior parietal lobule during divergent thinking.

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Vartanian, Oshin; Beatty, Erin L; Smith, Ingrid; Blackler, Kristen; Lam, Quan; Forbes, Sarah

2018-02-23

Contrary to earlier approaches that focused on the contributions of isolated brain regions to the emergence of creativity, there is now growing consensus that creative thought emerges from the interaction of multiple brain regions, often embedded within larger brain networks. Specifically, recent evidence from studies of divergent thinking suggests that kernel ideas emerge in posterior brain regions residing within the semantic system and/or the default mode network (DMN), and that the prefrontal cortex (PFC) regions within the executive control network (ECN) constrain those ideas for generating outputs that meet task demands. However, despite knowing that regions within these networks exhibit interaction, to date the direction of the relationship has not been tested directly. By applying Dynamic Causal Modeling (DCM) to fMRI data collected during a divergent thinking task, we tested the hypothesis that the PFC exerts unidirectional control over the middle temporal gyrus (MTG) and the inferior parietal lobule (IPL), vs. the hypothesis that these two sets of regions exert bidirectional control over each other (in the form of feedback loops). The data were consistent with the former model by demonstrating that the right inferior frontal gyrus (IFG) exerts unidirectional control over MTG and IPL, although the evidence was somewhat stronger in the case of the MTG than the IPL. Our findings highlight potential causal pathways that could underlie the neural bases of divergent thinking. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

Distributed acoustic cues for caller identity in macaque vocalization.

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Fukushima, Makoto; Doyle, Alex M; Mullarkey, Matthew P; Mishkin, Mortimer; Averbeck, Bruno B

2015-12-01

Individual primates can be identified by the sound of their voice. Macaques have demonstrated an ability to discern conspecific identity from a harmonically structured 'coo' call. Voice recognition presumably requires the integrated perception of multiple acoustic features. However, it is unclear how this is achieved, given considerable variability across utterances. Specifically, the extent to which information about caller identity is distributed across multiple features remains elusive. We examined these issues by recording and analysing a large sample of calls from eight macaques. Single acoustic features, including fundamental frequency, duration and Weiner entropy, were informative but unreliable for the statistical classification of caller identity. A combination of multiple features, however, allowed for highly accurate caller identification. A regularized classifier that learned to identify callers from the modulation power spectrum of calls found that specific regions of spectral-temporal modulation were informative for caller identification. These ranges are related to acoustic features such as the call's fundamental frequency and FM sweep direction. We further found that the low-frequency spectrotemporal modulation component contained an indexical cue of the caller body size. Thus, cues for caller identity are distributed across identifiable spectrotemporal components corresponding to laryngeal and supralaryngeal components of vocalizations, and the integration of those cues can enable highly reliable caller identification. Our results demonstrate a clear acoustic basis by which individual macaque vocalizations can be recognized.

Orientation-Cue Invariant Population Responses to Contrast-Modulated and Phase-Reversed Contour Stimuli in Macaque V1 and V2

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An, Xu; Gong, Hongliang; Yin, Jiapeng; Wang, Xiaochun; Pan, Yanxia; Zhang, Xian; Lu, Yiliang; Yang, Yupeng; Toth, Zoltan; Schiessl, Ingo; McLoughlin, Niall; Wang, Wei

2014-01-01

Visual scenes can be readily decomposed into a variety of oriented components, the processing of which is vital for object segregation and recognition. In primate V1 and V2, most neurons have small spatio-temporal receptive fields responding selectively to oriented luminance contours (first order), while only a subgroup of neurons signal non-luminance defined contours (second order). So how is the orientation of second-order contours represented at the population level in macaque V1 and V2? Here we compared the population responses in macaque V1 and V2 to two types of second-order contour stimuli generated either by modulation of contrast or phase reversal with those to first-order contour stimuli. Using intrinsic signal optical imaging, we found that the orientation of second-order contour stimuli was represented invariantly in the orientation columns of both macaque V1 and V2. A physiologically constrained spatio-temporal energy model of V1 and V2 neuronal populations could reproduce all the recorded population responses. These findings suggest that, at the population level, the primate early visual system processes the orientation of second-order contours initially through a linear spatio-temporal filter mechanism. Our results of population responses to different second-order contour stimuli support the idea that the orientation maps in primate V1 and V2 can be described as a spatial-temporal energy map. PMID:25188576

Noninvasive scalp recording of cortical auditory evoked potentials in the alert macaque monkey.

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Itoh, Kosuke; Nejime, Masafumi; Konoike, Naho; Nakada, Tsutomu; Nakamura, Katsuki

2015-09-01

Scalp-recorded evoked potentials (EP) provide researchers and clinicians with irreplaceable means for recording stimulus-related neural activities in the human brain, due to its high temporal resolution, handiness, and, perhaps more importantly, non-invasiveness. This work recorded the scalp cortical auditory EP (CAEP) in unanesthetized monkeys by using methods that are essentially identical to those applied to humans. Young adult rhesus monkeys (Macaca mulatta, 5-7 years old) were seated in a monkey chair, and their head movements were partially restricted by polystyrene blocks and tension poles placed around their head. Individual electrodes were fixated on their scalp using collodion according to the 10-20 system. Pure tone stimuli were presented while electroencephalograms were recorded from up to nineteen channels, including an electrooculogram channel. In all monkeys (n = 3), the recorded CAEP comprised a series of positive and negative deflections, labeled here as macaque P1 (mP1), macaque N1 (mN1), macaque P2 (mP2), and macaque N2 (mN2), and these transient responses to sound onset were followed by a sustained potential that continued for the duration of the sound, labeled the macaque sustained potential (mSP). mP1, mN2 and mSP were the prominent responses, and they had maximal amplitudes over frontal/central midline electrode sites, consistent with generators in auditory cortices. The study represents the first noninvasive scalp recording of CAEP in alert rhesus monkeys, to our knowledge. Copyright © 2015 Elsevier B.V. All rights reserved.

Does a single session of theta-burst transcranial magnetic stimulation of inferior temporal cortex affect tinnitus perception?

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Moser Tobias

2009-05-01

Full Text Available Abstract Background Cortical excitability changes as well as imbalances in excitatory and inhibitory circuits play a distinct pathophysiological role in chronic tinnitus. Repetitive transcranial magnetic stimulation (rTMS over the temporoparietal cortex was recently introduced to modulate tinnitus perception. In the current study, the effect of theta-burst stimulation (TBS, a novel rTMS paradigm was investigated in chronic tinnitus. Twenty patients with chronic tinnitus completed the study. Tinnitus severity and loudness were monitored using a tinnitus questionnaire (TQ and a visual analogue scale (VAS before each session. Patients received 600 pulses of continuous TBS (cTBS, intermittent TBS (iTBS and intermediate TBS (imTBS over left inferior temporal cortex with an intensity of 80% of the individual active or resting motor threshold. Changes in subjective tinnitus perception were measured with a numerical rating scale (NRS. Results TBS applied to inferior temporal cortex appeared to be safe. Although half of the patients reported a slight attenuation of tinnitus perception, group analysis resulted in no significant difference when comparing the three specific types of TBS. Converting the NRS into the VAS allowed us to compare the time-course of aftereffects. Only cTBS resulted in a significant short-lasting improvement of the symptoms. In addition there was no significant difference when comparing the responder and non-responder groups regarding their anamnestic and audiological data. The TQ score correlated significantly with the VAS, lower loudness indicating less tinnitus distress. Conclusion TBS does not offer a promising outcome for patients with tinnitus in the presented study.

High baseline activity in inferior temporal cortex improves neural and behavioral discriminability during visual categorization

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Nazli eEmadi

2014-11-01

Full Text Available Spontaneous firing is a ubiquitous property of neural activity in the brain. Recent literature suggests that this baseline activity plays a key role in perception. However, it is not known how the baseline activity contributes to neural coding and behavior. Here, by recording from the single neurons in the inferior temporal cortex of monkeys performing a visual categorization task, we thoroughly explored the relationship between baseline activity, the evoked response, and behavior. Specifically we found that a low-frequency (< 8 Hz oscillation in the spike train, prior and phase-locked to the stimulus onset, was correlated with increased gamma power and neuronal baseline activity. This enhancement of the baseline activity was then followed by an increase in the neural selectivity and the response reliability and eventually a higher behavioral performance.

Ancestry, Plasmodium cynomolgi prevalence and rhesus macaque admixture in cynomolgus macaques (Macaca fascicularis) bred for export in Chinese breeding farms.

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Zhang, Xinjun; Meng, Yuhuan; Houghton, Paul; Liu, Mingyu; Kanthaswamy, Sreetharan; Oldt, Robert; Ng, Jillian; Trask, Jessica Satkoski; Huang, Ren; Singh, Balbir; Du, Hongli; Smith, David Glenn

2017-04-01

Most cynomolgus macaques (Macaca fascicularis) used in the United States as animal models are imported from Chinese breeding farms without documented ancestry. Cynomolgus macaques with varying rhesus macaque ancestry proportions may exhibit differences, such as susceptibility to malaria, that affect their suitability as a research model. DNA of 400 cynomolgus macaques from 10 Chinese breeding farms was genotyped to characterize their regional origin and rhesus ancestry proportion. A nested PCR assay was used to detect Plasmodium cynomolgi infection in sampled individuals. All populations exhibited high levels of genetic heterogeneity and low levels of inbreeding and genetic subdivision. Almost all individuals exhibited an Indochinese origin and a rhesus ancestry proportion of 5%-48%. The incidence of P. cynomolgi infection in cynomolgus macaques is strongly associated with proportion of rhesus ancestry. The varying amount of rhesus ancestry in cynomolgus macaques underscores the importance of monitoring their genetic similarity in malaria research. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multiple pathways carry signals from short-wavelength-sensitive ('blue') cones to the middle temporal area of the macaque.

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Jayakumar, Jaikishan; Roy, Sujata; Dreher, Bogdan; Martin, Paul R; Vidyasagar, Trichur R

2013-01-01

We recorded spike activity of single neurones in the middle temporal visual cortical area (MT or V5) of anaesthetised macaque monkeys. We used flashing, stationary spatially circumscribed, cone-isolating and luminance-modulated stimuli of uniform fields to assess the effects of signals originating from the long-, medium- or short- (S) wavelength-sensitive cone classes. Nearly half (41/86) of the tested MT neurones responded reliably to S-cone-isolating stimuli. Response amplitude in the majority of the neurones tested further (19/28) was significantly reduced, though not always completely abolished, during reversible inactivation of visuotopically corresponding regions of the ipsilateral primary visual cortex (striate cortex, area V1). Thus, the present data indicate that signals originating in S-cones reach area MT, either via V1 or via a pathway that does not go through area V1. We did not find a significant difference between the mean latencies of spike responses of MT neurones to signals that bypass V1 and those that do not; the considerable overlap we observed precludes the use of spike-response latency as a criterion to define the routes through which the signals reach MT.

Monkey business : the illegal trade in Barbary macaques

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van Uhm, D.P.|info:eu-repo/dai/nl/380477025

2016-01-01

This article focuses on the organization, modus operandi and trade route of the illegal trade in Barbary macaques. The Barbary macaque is the most seized CITES mammal in the EU, accounting for almost 25% of live mammalrelated seizures. It is estimated that as few as 5,000-6,000 Barbary macaques

Mechanisms of spectral and temporal integration in the mustached bat inferior colliculus

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Wenstrup, Jeffrey James; Nataraj, Kiran; Sanchez, Jason Tait

2012-01-01

This review describes mechanisms and circuitry underlying combination-sensitive response properties in the auditory brainstem and midbrain. Combination-sensitive neurons, performing a type of auditory spectro-temporal integration, respond to specific, properly timed combinations of spectral elements in vocal signals and other acoustic stimuli. While these neurons are known to occur in the auditory forebrain of many vertebrate species, the work described here establishes their origin in the auditory brainstem and midbrain. Focusing on the mustached bat, we review several major findings: (1) Combination-sensitive responses involve facilitatory interactions, inhibitory interactions, or both when activated by distinct spectral elements in complex sounds. (2) Combination-sensitive responses are created in distinct stages: inhibition arises mainly in lateral lemniscal nuclei of the auditory brainstem, while facilitation arises in the inferior colliculus (IC) of the midbrain. (3) Spectral integration underlying combination-sensitive responses requires a low-frequency input tuned well below a neuron's characteristic frequency (ChF). Low-ChF neurons in the auditory brainstem project to high-ChF regions in brainstem or IC to create combination sensitivity. (4) At their sites of origin, both facilitatory and inhibitory combination-sensitive interactions depend on glycinergic inputs and are eliminated by glycine receptor blockade. Surprisingly, facilitatory interactions in IC depend almost exclusively on glycinergic inputs and are largely independent of glutamatergic and GABAergic inputs. (5) The medial nucleus of the trapezoid body (MNTB), the lateral lemniscal nuclei, and the IC play critical roles in creating combination-sensitive responses. We propose that these mechanisms, based on work in the mustached bat, apply to a broad range of mammals and other vertebrates that depend on temporally sensitive integration of information across the audible spectrum. PMID:23109917

Human exposure to herpesvirus B-seropositive macaques, Bali, Indonesia.

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Engel, Gregory A; Jones-Engel, Lisa; Schillaci, Michael A; Suaryana, Komang Gde; Putra, Artha; Fuentes, Agustin; Henkel, Richard

2002-08-01

Herpesvirus B (Cercopithecine herpesvirus 1) has been implicated as the cause of approximately 40 cases of meningoencephalitis affecting persons in direct or indirect contact with laboratory macaques. However, the threat of herpesvirus B in nonlaboratory settings worldwide remains to be addressed. We investigated the potential for exposure to herpesvirus B in workers at a "monkey forest" (a temple that has become a tourist attraction because of its monkeys) in Bali, Indonesia. In July 2000, 105 workers at the Sangeh Monkey Forest in Central Bali were surveyed about contact with macaques (Macaca fascicularis). Nearly half of those interviewed had either been bitten or scratched by a macaque. Prevalence of injury was higher in those who fed macaques. Serum from 31 of 38 Sangeh macaques contained antibodies to herpesvirus B. We conclude that workers coming into contact with macaques at the Sangeh Monkey Forest are at risk for exposure to herpesvirus B.

Genetic characterization of rhesus macaques (Macaca mulatta) in Nepal.

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Kyes, Randall C; Jones-Engel, Lisa; Chalise, Mukesh K; Engel, Gregory; Heidrich, John; Grant, Richard; Bajimaya, Shyam S; McDonough, John; Smith, David Glenn; Ferguson, Betsy

2006-05-01

Indian-origin rhesus macaques (Macaca mulatta) have long served as an animal model for the study of human disease and behavior. Given the current shortage of Indian-origin rhesus, many researchers have turned to rhesus macaques from China as a substitute. However, a number of studies have identified marked genetic differences between the Chinese and Indian animals. We investigated the genetic characteristics of a third rhesus population, the rhesus macaques of Nepal. Twenty-one rhesus macaques at the Swoyambhu Temple in Kathmandu, Nepal, were compared with more than 300 Indian- and Chinese-origin rhesus macaques. The sequence analyses of two mitochondrial DNA (mtDNA) loci, from the HVS I and 12 S rRNA regions, showed that the Nepali animals were more similar to Indian-origin than to Chinese-origin animals. The distribution of alleles at 24 short tandem repeat (STR) loci distributed across 17 chromosomes also showed greater similarity between the Nepali and Indian-origin animals. Finally, an analysis of seven major histocompatibility complex (MHC) alleles showed that the Nepali animals expressed Class I alleles that are common to Indian-origin animals, including Mamu-A*01. All of these analyses also revealed a low level of genetic diversity within this Nepali rhesus sample. We conclude that the rhesus macaques of Nepal more closely resemble rhesus macaques of Indian origin than those of Chinese origin. As such, the Nepali rhesus may offer an additional resource option for researchers who wish to maintain research protocols with animals that possess key genetic features characteristic of Indian-origin rhesus macaques. 2005 Wiley-Liss, Inc.

Mimetic Muscles in a Despotic Macaque (Macaca mulatta) Differ from Those in a Closely Related Tolerant Macaque (M. nigra).

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Burrows, Anne M; Waller, Bridget M; Micheletta, Jérôme

2016-10-01

Facial displays (or expressions) are a primary means of visual communication among conspecifics in many mammalian orders. Macaques are an ideal model among primates for investigating the co-evolution of facial musculature, facial displays, and social group size/behavior under the umbrella of "ecomorphology". While all macaque species share some social behaviors, dietary, and ecological parameters, they display a range of social dominance styles from despotic to tolerant. A previous study found a larger repertoire of facial displays in tolerant macaque species relative to despotic species. The present study was designed to further explore this finding by comparing the gross morphological features of mimetic muscles between the Sulawesi macaque (Macaca nigra), a tolerant species, and the rhesus macaque (M. mulatta), a despotic species. Five adult M. nigra heads were dissected and mimetic musculature was compared to those from M. mulatta. Results showed that there was general similarity in muscle presence/absence between the species as well as muscle form except for musculature around the external ear. M. mulatta had more musculature around the external ear than M. nigra. In addition, M. nigra lacked a zygomaticus minor while M. mulatta is reported to have one. These morphological differences match behavioral observations documenting a limited range of ear movements used by M. nigra during facial displays. Future studies focusing on a wider phylogenetic range of macaques with varying dominance styles may further elucidate the roles of phylogeny, ecology, and social variables in the evolution of mimetic muscles within Macaca Anat Rec, 299:1317-1324, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Combined ERP/fMRI evidence for early word recognition effects in the posterior inferior temporal gyrus.

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Dien, Joseph; Brian, Eric S; Molfese, Dennis L; Gold, Brian T

2013-10-01

Two brain regions with established roles in reading are the posterior middle temporal gyrus and the posterior fusiform gyrus (FG). Lesion studies have also suggested that the region located between them, the posterior inferior temporal gyrus (pITG), plays a central role in word recognition. However, these lesion results could reflect disconnection effects since neuroimaging studies have not reported consistent lexicality effects in pITG. Here we tested whether these reported pITG lesion effects are due to disconnection effects or not using parallel Event-related Potentials (ERP)/functional magnetic resonance imaging (fMRI) studies. We predicted that the Recognition Potential (RP), a left-lateralized ERP negativity that peaks at about 200-250 msec, might be the electrophysiological correlate of pITG activity and that conditions that evoke the RP (perceptual degradation) might therefore also evoke pITG activity. In Experiment 1, twenty-three participants performed a lexical decision task (temporally flanked by supraliminal masks) while having high-density 129-channel ERP data collected. In Experiment 2, a separate group of fifteen participants underwent the same task while having fMRI data collected in a 3T scanner. Examination of the ERP data suggested that a canonical RP effect was produced. The strongest corresponding effect in the fMRI data was in the vicinity of the pITG. In addition, results indicated stimulus-dependent functional connectivity between pITG and a region of the posterior FG near the Visual Word Form Area (VWFA) during word compared to nonword processing. These results provide convergent spatiotemporal evidence that the pITG contributes to early lexical access through interaction with the VWFA. Copyright © 2013 Elsevier Ltd. All rights reserved.

I scan, therefore I decline: The time course of difficulty monitoring in humans (homo sapiens) and macaques (macaca mulatta).

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Smith, J David; Boomer, Joseph; Church, Barbara A; Zakrzewski, Alexandria C; Beran, Michael J; Baum, Michael L

2018-05-01

The study of nonhumans' metacognitive judgments about trial difficulty has grown into an important comparative literature. However, the potential for associative-learning confounds in this area has left room for behaviorist interpretations that are strongly asserted and hotly debated. This article considers how researchers may be able to observe animals' strategic cognitive processes more clearly by creating temporally extended problems within which associative cues are not always immediately available. We asked humans and rhesus macaques to commit to completing spatially extended mazes or to decline completing them through a trial-decline response. The mazes could sometimes be completed successfully, but other times had a constriction that blocked completion. A deliberate, systematic scanning process could preevaluate a maze and determine the appropriate response. Latency analyses charted the time course of the evaluative process. Both humans and macaques appeared, from the pattern of their latencies, to scan the mazes through before committing to completing them. Thus monkeys, too, can base trial-decline responses on temporally extended evaluation processes, confirming that those responses have strategic cognitive-processing bases in addition to behavioral-reactive bases. The results also show the value of temporally and spatially extended problems to let researchers study the trajectory of animals' online cognitive processes. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A novel supra-temporal approach to retrobulbar anaesthesia in dogs: Preliminary study in cadavers.

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Chiavaccini, Ludovica; Micieli, Fabiana; Meomartino, Leonardo; Duffee, Lauren R; Vesce, Giancarlo

2017-05-01

A novel supra-temporal technique for retrobulbar anaesthesia in dogs is described and compared to the inferior temporal palpebral approach. Supra-temporal and inferior temporal palpebral retrobulbar injections were performed in 20 orbits of canine cadavers. Distribution of injected contrast medium within the intraconal space and around the optic nerve was analysed using computed tomography. There was adequate distribution of contrast medium within the intraconal space with both techniques. Concurrent intraconal and extraconal distribution was observed using the inferior temporal palpebral approach in 3/10 orbits and using the supra-temporal approach in 5/10 orbits. In 3/10 supra-temporal injections, the injected vehicle was distributed preferentially in the caudal aspect of the retrobulbar cone, closer to the orbital fissure. Accidental intraocular injection was never observed. The supra-temporal approach appears to be a valid alternative to the inferior temporal palpebral approach for retrobulbar anaesthesia in dogs, being less technically challenging. Further studies are required to confirm the clinical efficacy of this approach in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of 47 MHC class I sequences in Filipino cynomolgus macaques

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Campbell, Kevin J.; Detmer, Ann M.; Karl, Julie A.; Wiseman, Roger W.; Blasky, Alex J.; Hughes, Austin L.; Bimber, Benjamin N.; O’Connor, Shelby L.; O’Connor, David H.

2009-01-01

Cynomolgus macaques (Macaca fascicularis) provide increasingly common models for infectious disease research. Several geographically distinct populations of these macaques from Southeast Asia and the Indian Ocean island of Mauritius are available for pathogenesis studies. Though host genetics may profoundly impact results of such studies, similarities and differences between populations are often overlooked. In this study we identified 47 full-length MHC class I nucleotide sequences in 16 cynomolgus macaques of Filipino origin. The majority of MHC class I sequences characterized (39 of 47) were unique to this regional population. However, we discovered eight sequences with perfect identity and six sequences with close similarity to previously defined MHC class I sequences from other macaque populations. We identified two ancestral MHC haplotypes that appear to be shared between Filipino and Mauritian cynomolgus macaques, notably a Mafa-B haplotype that has previously been shown to protect Mauritian cynomolgus macaques against challenge with a simian/human immunodeficiency virus, SHIV89.6P. We also identified a Filipino cynomolgus macaque MHC class I sequence for which the predicted protein sequence differs from Mamu-B*17 by a single amino acid. This is important because Mamu-B*17 is strongly associated with protection against simian immunodeficiency virus (SIV) challenge in Indian rhesus macaques. These findings have implications for the evolutionary history of Filipino cynomolgus macaques as well as for the use of this model in SIV/SHIV research protocols. PMID:19107381

Anterior Temporal Lobe Morphometry Predicts Categorization Ability.

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Garcin, Béatrice; Urbanski, Marika; Thiebaut de Schotten, Michel; Levy, Richard; Volle, Emmanuelle

2018-01-01

Categorization is the mental operation by which the brain classifies objects and events. It is classically assessed using semantic and non-semantic matching or sorting tasks. These tasks show a high variability in performance across healthy controls and the cerebral bases supporting this variability remain unknown. In this study we performed a voxel-based morphometry study to explore the relationships between semantic and shape categorization tasks and brain morphometric differences in 50 controls. We found significant correlation between categorization performance and the volume of the gray matter in the right anterior middle and inferior temporal gyri. Semantic categorization tasks were associated with more rostral temporal regions than shape categorization tasks. A significant relationship was also shown between white matter volume in the right temporal lobe and performance in the semantic tasks. Tractography revealed that this white matter region involved several projection and association fibers, including the arcuate fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, and inferior longitudinal fasciculus. These results suggest that categorization abilities are supported by the anterior portion of the right temporal lobe and its interaction with other areas.

Effective Connectivity between Ventral Occipito-Temporal and Ventral Inferior Frontal Cortex during Lexico-Semantic Processing. A Dynamic Causal Modeling Study

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Marcela Perrone-Bertolotti

2017-06-01

Full Text Available It has been suggested that dorsal and ventral pathways support distinct aspects of language processing. Yet, the full extent of their involvement and their inter-regional connectivity in visual word recognition is still unknown. Studies suggest that they might reflect the dual-route model of reading, with the dorsal pathway more involved in grapho-phonological conversion during phonological tasks, and the ventral pathway performing lexico-semantic access during semantic tasks. Furthermore, this subdivision is also suggested at the level of the inferior frontal cortex, involving ventral and dorsal parts for lexico-semantic and phonological processing, respectively. In the present study, we assessed inter-regional brain connectivity and task-induced modulations of brain activity during a phoneme detection and semantic categorization tasks, using fMRI in healthy subject. We used a dynamic causal modeling approach to assess inter-regional connectivity and task demand modulation within the dorsal and ventral pathways, including the following network components: the ventral occipito-temporal cortex (vOTC; dorsal and ventral, the superior temporal gyrus (STG; dorsal, the dorsal inferior frontal gyrus (dIFG; dorsal, and the ventral IFG (vIFG; ventral. We report three distinct inter-regional interactions supporting orthographic information transfer from vOTC to other language regions (vOTC -> STG, vOTC -> vIFG and vOTC -> dIFG regardless of task demands. Moreover, we found that (a during semantic processing (direct ventral pathway the vOTC -> vIFG connection strength specifically increased and (b a lack of modulation of the vOTC -> dIFG connection strength by the task that could suggest a more general involvement of the dorsal pathway during visual word recognition. Results are discussed in terms of anatomo-functional connectivity of visual word recognition network.

Rhesus macaques (Macaca mulatta are natural hosts of specific Staphylococcus aureus lineages.

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Sanne van den Berg

Full Text Available Currently, there is no animal model known that mimics natural nasal colonization by Staphylococcus aureus in humans. We investigated whether rhesus macaques are natural nasal carriers of S. aureus. Nasal swabs were taken from 731 macaques. S. aureus isolates were typed by pulsed-field gel electrophoresis (PFGE, spa repeat sequencing and multi-locus sequence typing (MLST, and compared with human strains. Furthermore, the isolates were characterized by several PCRs. Thirty-nine percent of 731 macaques were positive for S. aureus. In general, the macaque S. aureus isolates differed from human strains as they formed separate PFGE clusters, 50% of the isolates were untypeable by agr genotyping, 17 new spa types were identified, which all belonged to new sequence types (STs. Furthermore, 66% of macaque isolates were negative for all superantigen genes. To determine S. aureus nasal colonization, three nasal swabs from 48 duo-housed macaques were taken during a 5 month period. In addition, sera were analyzed for immunoglobulin G and A levels directed against 40 staphylococcal proteins using a bead-based flow cytometry technique. Nineteen percent of the animals were negative for S. aureus, and 17% were three times positive. S. aureus strains were easily exchanged between macaques. The antibody response was less pronounced in macaques compared to humans, and nasal carrier status was not associated with differences in serum anti-staphylococcal antibody levels. In conclusion, rhesus macaques are natural hosts of S. aureus, carrying host-specific lineages. Our data indicate that rhesus macaques are useful as an autologous model for studying S. aureus nasal colonization and infection prevention.

Temporal order processing of syllables in the left parietal lobe.

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Moser, Dana; Baker, Julie M; Sanchez, Carmen E; Rorden, Chris; Fridriksson, Julius

2009-10-07

Speech processing requires the temporal parsing of syllable order. Individuals suffering from posterior left hemisphere brain injury often exhibit temporal processing deficits as well as language deficits. Although the right posterior inferior parietal lobe has been implicated in temporal order judgments (TOJs) of visual information, there is limited evidence to support the role of the left inferior parietal lobe (IPL) in processing syllable order. The purpose of this study was to examine whether the left inferior parietal lobe is recruited during temporal order judgments of speech stimuli. Functional magnetic resonance imaging data were collected on 14 normal participants while they completed the following forced-choice tasks: (1) syllable order of multisyllabic pseudowords, (2) syllable identification of single syllables, and (3) gender identification of both multisyllabic and monosyllabic speech stimuli. Results revealed increased neural recruitment in the left inferior parietal lobe when participants made judgments about syllable order compared with both syllable identification and gender identification. These findings suggest that the left inferior parietal lobe plays an important role in processing syllable order and support the hypothesized role of this region as an interface between auditory speech and the articulatory code. Furthermore, a breakdown in this interface may explain some components of the speech deficits observed after posterior damage to the left hemisphere.

Temporal lobe and inferior frontal gyrus dysfunction in patients with schizophrenia during face-to-face conversation: a near-infrared spectroscopy study.

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Takei, Yuichi; Suda, Masashi; Aoyama, Yoshiyuki; Yamaguchi, Miho; Sakurai, Noriko; Narita, Kosuke; Fukuda, Masato; Mikuni, Masahiko

2013-11-01

Schizophrenia (SC) is marked by poor social-role performance and social-skill deficits that are well reflected in daily conversation. Although the mechanism underlying these impairments has been investigated by functional neuroimaging, technical limitations have prevented the investigation of brain activation during conversation in typical clinical situations. To fill this research gap, this study investigated and compared frontal and temporal lobe activation in patients with SC during face-to-face conversation. Frontal and temporal lobe activation in 29 patients and 31 normal controls (NC) (n = 60) were measured during 180-s conversation periods by using near-infrared spectroscopy (NIRS). The grand average values of oxyhemoglobin concentration ([oxy-Hb]) changes during task performance were analyzed to determine their correlation with clinical variables and Positive and Negative Syndrome Scale (PANSS) subscores. Compared to NCs, patients with SC exhibited decreased performance in the conversation task and decreased activation in both the temporal lobes and the right inferior frontal gyrus (IFG) during task performance, as indicated by the grand average of [oxy-Hb] changes. The decreased activation in the left temporal lobe was negatively correlated with the PANSS disorganization and negative symptoms subscores and that in the right IFG was negatively correlated with illness duration, PANSS disorganization, and negative symptom subscores. These findings indicate that brain dysfunction in SC during conversation is related to functional deficits in both the temporal lobes and the right IFG and manifests primarily in the form of disorganized thinking and negative symptomatology. Copyright © 2013 Elsevier Ltd. All rights reserved.

Method of segmenting inferior horns of lateral ventricles using active contour models

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Hattori, Masumi; Koyama, Shuji; Kodera, Yoshie

2007-01-01

Recent research has suggested that the measurement of regional atrophy in the structure of the medial temporal lobe is a promising way to discriminate Alzheimer-type dementia patients from healthy control subjects. There are some reports that the inferior horns of the lateral ventricles are expanded by atrophying the structure of the medial temporal lobe. We developed a technique to automatically detect the region of the inferior horns of the lateral ventricles by gray-level thresholding and morphological processing. However, there were some incorrect regions in this method. Accordingly, we proposed a technique for which active contour models (ACM) were used. Our ACM incorporates the improved edge-based image and the external constraint to improve convergence and to reduce its dependence on initial estimation. In this study, we present the details of an algorithm that traces the contours of the inferior horns of the lateral ventricles and its performance relative to manual methods. The average degree of correspondence between the extract region and manual trace was measured in 30 inferior horns of 15 subjects. The average degree of correspondence of the proposed method was about 4% higher than that of the conventional method. These results suggest that the proposed method is more accurate than the conventional method. (author)

Gene targeting in adult rhesus macaque fibroblasts

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Wolf Don P

2008-03-01

Full Text Available Abstract Background Gene targeting in nonhuman primates has the potential to produce critical animal models for translational studies related to human diseases. Successful gene targeting in fibroblasts followed by somatic cell nuclear transfer (SCNT has been achieved in several species of large mammals but not yet in primates. Our goal was to establish the protocols necessary to achieve gene targeting in primary culture of adult rhesus macaque fibroblasts as a first step in creating nonhuman primate models of genetic disease using nuclear transfer technology. Results A primary culture of adult male fibroblasts was transfected with hTERT to overcome senescence and allow long term in vitro manipulations. Successful gene targeting of the HPRT locus in rhesus macaques was achieved by electroporating S-phase synchronized cells with a construct containing a SV40 enhancer. Conclusion The cell lines reported here could be used for the production of null mutant rhesus macaque models of human genetic disease using SCNT technology. In addition, given the close evolutionary relationship and biological similarity between rhesus macaques and humans, the protocols described here may prove useful in the genetic engineering of human somatic cells.

Out of sight but not out of mind: the neurophysiology of iconic memory in the superior temporal sulcus.

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Keysers, C; Xiao, D-K; Foldiak, P; Perrett, D I

2005-05-01

Iconic memory, the short-lasting visual memory of a briefly flashed stimulus, is an important component of most models of visual perception. Here we investigate what physiological mechanisms underlie this capacity by showing rapid serial visual presentation (RSVP) sequences with and without interstimulus gaps to human observers and macaque monkeys. For gaps of up to 93 ms between consecutive images, human observers and neurones in the temporal cortex of macaque monkeys were found to continue processing a stimulus as if it was still present on the screen. The continued firing of neurones in temporal cortex may therefore underlie iconic memory. Based on these findings, a neurophysiological vision of iconic memory is presented.

Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

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Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott; Brown, Scott A.; Boucher, Joseph F.; Yuan, Yang; Civil, Jacqueline R.; Gillhouse, Kimberly A.; Stubbs, Makeida N.; Hoggatt, Amber F.; Halliday, Lisa C.; Fortman, Jeffrey D.

2011-05-01

Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

Rotational displacement skills in rhesus macaques (Macaca mulatta).

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Hughes, Kelly D; Santos, Laurie R

2012-11-01

Rotational displacement tasks, in which participants must track an object at a hiding location within an array while the array rotates, exhibit a puzzling developmental pattern in humans. Human children take an unusually long time to master this task and tend to solve rotational problems through the use of nongeometric features or landmarks as opposed to other kinds of spatial cues. We investigated whether these developmental characteristics are unique to humans by testing rotational displacement skills in a monkey species, the rhesus macaque (Macaca mulatta), using a looking-time method. Monkeys first saw food hidden in two differently colored boxes within an array. The array was then rotated 180° and the boxes reopened to reveal the food in an expected or unexpected location. Our first two experiments explored the developmental time-course of performance on this rotational displacement task. We found that adult macaques looked longer at the unexpected event, but such performance was not mirrored in younger-aged macaques. In a third study, we systematically varied featural information and visible access to the array to investigate which strategies adult macaques used in solving rotational displacements. Our results show that adult macaques need both sets of information to solve the task. Taken together, these results suggest both similarities and differences in mechanisms by which human and nonhuman primates develop this spatial skill.

Estimation of Shear Wave Speed in the Rhesus Macaques Uterine Cervix

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Huang, Bin; Drehfal, Lindsey C.; Rosado-Mendez, Ivan M.; Guerrero, Quinton W.; Palmeri, Mark L.; Simmons, Heather A.; Feltovich, Helen; Hall, Timothy J.

2016-01-01

Cervical softness is a critical parameter in pregnancy. Clinically, preterm birth is associated with premature cervical softening and post-dates birth is associated with delayed cervical softening. In practice, the assessment of softness is subjective, based on digital examination. Fortunately, objective, quantitative techniques to assess softness and other parameters associated with microstructural cervical change are emerging. One of these is shear wave speed (SWS) estimation. In principle, this allows objective characterization of stiffness because waves travel more slowly in softer tissue. We are studying SWS in humans and rhesus macaques, the latter in order to accelerate translation from bench to bedside. For the current study, we estimated SWS in ex vivo cervices of rhesus macaques, n=24 nulliparous (never given birth) and n=9 multiparous (delivered at least 1 baby). Misoprostol (a prostaglandin used to soften human cervices prior to gynecological procedures) was administered to 13 macaques prior to necropsy (nulliparous: 7, multiparous: 6). SWS measurements were made at predetermined locations from the distal to proximal end of the cervix on both the anterior and posterior cervix, with 5 repeat measures at each location. The intent was to explore macaque cervical microstructure, including biological and spatial variability, to elucidate the similarities and differences between the macaque and the human cervix in order to facilitate future in vivo studies. We found that SWS is dependent on location in the normal nonpregnant macaque cervix, as in the human cervix. Unlike the human cervix, we detected no difference between ripened and unripened rhesus macaque cervix samples, nor nulliparous versus multiparous samples, although we observed a trend toward stiffer tissue in nulliparous samples. We found rhesus macaque cervix to be much stiffer than human, which is important for technique refinement. These findings are useful for guiding study of cervical

Manual lateralization in macaques: handedness, target laterality and task complexity.

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Regaiolli, Barbara; Spiezio, Caterina; Vallortigara, Giorgio

2016-01-01

Non-human primates represent models to understand the evolution of handedness in humans. Despite several researches have been investigating non-human primates handedness, few studies examined the relationship between target position, hand preference and task complexity. This study aimed at investigating macaque handedness in relation to target laterality and tastiness, as well as task complexity. Seven pig-tailed macaques (Macaca nemestrina) were involved in three different "two alternative choice" tests: one low-level task and two high-level tasks (HLTs). During the first and the third tests macaques could select a preferred food and a non-preferred food, whereas by modifying the design of the second test, macaques were presented with no-difference alternative per trial. Furthermore, a simple-reaching test was administered to assess hand preference in a social context. Macaques showed hand preference at individual level both in simple and complex tasks, but not in the simple-reaching test. Moreover, target position seemed to affect hand preference in retrieving an object in the low-level task, but not in the HLT. Additionally, individual hand preference seemed to be affected from the tastiness of the item to be retrieved. The results suggest that both target laterality and individual motivation might influence hand preference of macaques, especially in simple tasks.

Combined Transcriptomics and Metabolomics in a Rhesus Macaque Drug Administration Study

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Kevin J. Lee

2014-10-01

Full Text Available We describe a multi-omic approach to understanding the effects that the anti-malarial drug pyrimethamine has on immune physiology in rhesus macaques (Macaca mulatta. Whole blood and bone marrow RNA-Seq and plasma metabolome profiles (each with over 15,000 features have been generated for five naïve individuals at up to seven time-points before, during and after three rounds of drug administration. Linear modelling and Bayesian network analyses are both considered, alongside investigations of the impact of statistical modeling strategies on biological inference. Individual macaques were found to be a major source of variance for both omic data types, and factoring individuals into subsequent modelling increases power to detect temporal effects. A major component of the whole blood transcriptome follows the bone marrow with a time-delay, while other components of variation are unique to each compartment. We demonstrate that pyrimethamine administration does impact both compartments throughout the experiment, but very limited perturbation of transcript or metabolite abundance following each round of drug exposure is observed. New insights into the mode of action of the drug are presented in the context of pyrimethamine’s predicted effect on suppression of cell division and metabolism in the immune system.

Anterior Temporal Lobe Morphometry Predicts Categorization Ability

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Béatrice Garcin

2018-02-01

Full Text Available Categorization is the mental operation by which the brain classifies objects and events. It is classically assessed using semantic and non-semantic matching or sorting tasks. These tasks show a high variability in performance across healthy controls and the cerebral bases supporting this variability remain unknown. In this study we performed a voxel-based morphometry study to explore the relationships between semantic and shape categorization tasks and brain morphometric differences in 50 controls. We found significant correlation between categorization performance and the volume of the gray matter in the right anterior middle and inferior temporal gyri. Semantic categorization tasks were associated with more rostral temporal regions than shape categorization tasks. A significant relationship was also shown between white matter volume in the right temporal lobe and performance in the semantic tasks. Tractography revealed that this white matter region involved several projection and association fibers, including the arcuate fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, and inferior longitudinal fasciculus. These results suggest that categorization abilities are supported by the anterior portion of the right temporal lobe and its interaction with other areas.

Increased functional connectivity strength of right inferior temporal gyrus in first-episode, drug-naive somatization disorder.

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Su, Qinji; Yao, Dapeng; Jiang, Muliang; Liu, Feng; Jiang, Jiajing; Xu, Chunxing; Dai, Yi; Yu, Miaoyu; Long, Liling; Li, Hongzheng; Liu, Jianrong; Zhang, Zhikun; Zhang, Jian; Xiao, Changqing; Guo, Wenbin

2015-01-01

Evidence of brain structural and functional alterations have been implicated in patients with somatization disorder (SD). However, little is known about brain functional connectivity in SD. In the present study, resting-state functional magnetic resonance imaging (fMRI) and graph theory were used to obtain a comprehensive view of whole-brain functional connectivity and to investigate the changes of voxel-wise functional networks in patients with SD. Twenty-five first-episode, medication-naive patients with SD and 28 age-, sex- and education-matched healthy controls (HCs) underwent resting-state fMRI. The graph theory approach was employed to analyze the data. Compared to the HCs, patients with SD showed significantly increased functional connectivity strength in the right inferior temporal gyrus (ITG). There is a significant positive correlation between the z-values of the cluster in the right ITG and Hamilton Anxiety Scale scores. Our findings indicate that there is a disruption of the functional connectivity pattern in the right ITG in first-episode, treatment-naive patients with SD, which bears clinical significance. © The Royal Australian and New Zealand College of Psychiatrists 2014.

Human-wildlife conflict: proximate predictors of aggression between humans and rhesus macaques in India.

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Beisner, Brianne A; Heagerty, Allison; Seil, Shannon K; Balasubramaniam, Krishna N; Atwill, Edward R; Gupta, Brij K; Tyagi, Praveen C; Chauhan, Netrapal P S; Bonal, B S; Sinha, P R; McCowan, Brenda

2015-02-01

Macaques live in close contact with humans across South and Southeast Asia, and direct interaction is frequent. Aggressive contact is a concern in many locations, particularly among populations of rhesus and longtail macaques that co-inhabit urbanized cities and towns with humans. We investigated the proximate factors influencing the occurrence of macaque aggression toward humans as well as human aggression toward macaques to determine the extent to which human behavior elicits macaque aggression and vice versa. We conducted a 3-month study of four free-ranging populations of rhesus macaques in Dehradun, India from October-December 2012, using event sampling to record all instances of human-macaque interaction (N = 3120). Our results show that while human aggression was predicted by the potential for economic losses or damage, macaque aggression was influenced by aggressive or intimidating behavior by humans as well as recent rates of conspecific aggression. Further, adult female macaques participated in aggression more frequently than expected, whereas adult and subadult males participated as frequently as expected. Our analyses demonstrate that neither human nor macaque aggression is unprovoked. Rather, both humans and macaques are responding to one another's behavior. Mitigation of human-primate conflict, and indeed other types of human-wildlife conflict in such coupled systems, will require a holistic investigation of the ways in which each participant is responding to, and consequently altering, the behavior of the other. © 2015 Wiley Periodicals, Inc.

A novel trivalent HPV 16/18/58 vaccine with anti-HPV 16 and 18 neutralizing antibody responses comparable to those induced by the Gardasil quadrivalent vaccine in rhesus macaque model

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Fei Yin

2017-06-01

Full Text Available Persistent infection with human papillomavirus (HPV is a key factor in the development of precancerous lesions and invasive cervical cancer. Prophylactic vaccines to immunize against HPV are an effective approach to reducing HPV related disease burden. In this study, we investigated the immunogenicity and dosage effect of a trivalent HPV 16/18/58 vaccine (3vHPV produced in Escherichia coli (E.coli, with Gardasil quadrivalent vaccine (4vHPV, Merck & Co. as a positive control. Sera collected from rhesus macaques vaccinated with three dosage formulations of 3vHPV (termed low-, mid-, and high-dosage formulations, respectively, and the 4vHPV vaccine were analyzed by both Pseudovirus-Based Neutralization Assay (PBNA and Enzyme-Linked Immunosorbent Assay (ELISA. Strong immune responses against HPV 16/18/58 were successfully elicited, and dosage-dependence was observed, with likely occurrence of immune interference between different L1-VLP antigens. HPV 16/18 specific neutralizing antibody (nAb and total immunoglobulin G (IgG antibody responses in rhesus macaques receiving 3vHPV at the three dosages tested were generally non-inferior to those observed in rhesus macaques receiving 4vHPV throughout the study period. Particularly, HPV 18 nAb titers induced by the mid-dosage formulation that contained the same amounts of HPV 16/18 L1-VLPs as Gardasil 4vHPV were between 7.3 to 12.7-fold higher compared to the positive control arm from weeks 24–64. The durability of antibody responses specific to HPV 16/18 elicited by 3vHPV vaccines was also shown to be non-inferior to that associated with Gardasil 4vHPV. Keywords: Human papillomavirus, HPV 16/18/58, GMTs, Trivalent, Immunogenicity

Isolated inferior mesenteric portal hypertension with giant inferior mesenteric vein and anomalous inferior mesenteric vein insertion

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G Raghavendra Prasad

2013-01-01

Full Text Available Extrahepatic portal hypertension is not an uncommon disease in childhood, but isolated inferior mesenteric portal varices and lower gastrointestinal (GI bleed have not been reported till date. A 4-year-old girl presented with lower GI bleed. Surgical exploration revealed extrahepatic portal vein obstruction with giant inferior mesenteric vein and colonic varices. Inferior mesenteric vein was joining the superior mesenteric vein. The child was treated successfully with inferior mesenteric - inferior vena caval anastomosis. The child was relieved of GI bleed during the follow-up.

Early visual experience and the recognition of basic facial expressions: involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind.

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Kitada, Ryo; Okamoto, Yuko; Sasaki, Akihiro T; Kochiyama, Takanori; Miyahara, Motohide; Lederman, Susan J; Sadato, Norihiro

2013-01-01

Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience.

Glial cell morphological and density changes through the lifespan of rhesus macaques.

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Robillard, Katelyn N; Lee, Kim M; Chiu, Kevin B; MacLean, Andrew G

2016-07-01

How aging impacts the central nervous system (CNS) is an area of intense interest. Glial morphology is known to affect neuronal and immune function as well as metabolic and homeostatic balance. Activation of glia, both astrocytes and microglia, occurs at several stages during development and aging. The present study analyzed changes in glial morphology and density through the entire lifespan of rhesus macaques, which are physiologically and anatomically similar to humans. We observed apparent increases in gray matter astrocytic process length and process complexity as rhesus macaques matured from juveniles through adulthood. These changes were not attributed to cell enlargement because they were not accompanied by proportional changes in soma or process volume. There was a decrease in white matter microglial process length as rhesus macaques aged. Aging was shown to have a significant effect on gray matter microglial density, with a significant increase in aged macaques compared with adults. Overall, we observed significant changes in glial morphology as macaques age indicative of astrocytic activation with subsequent increase in microglial density in aged macaques. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque

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Davis, T. S.; Parker, R. A.; House, P. A.; Bagley, E.; Wendelken, S.; Normann, R. A.; Greger, B.

2012-12-01

Objective. It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation. Approach. An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task. Main results. The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0° ± 0.2° in visual space. Significance. These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.

Personality structure and social style in macaques.

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Adams, Mark James; Majolo, Bonaventura; Ostner, Julia; Schülke, Oliver; De Marco, Arianna; Thierry, Bernard; Engelhardt, Antje; Widdig, Anja; Gerald, Melissa S; Weiss, Alexander

2015-08-01

Why regularities in personality can be described with particular dimensions is a basic question in differential psychology. Nonhuman primates can also be characterized in terms of personality structure. Comparative approaches can help reveal phylogenetic constraints and social and ecological patterns associated with the presence or absence of specific personality dimensions. We sought to determine how different personality structures are related to interspecific variation in social style. Specifically, we examined this question in 6 different species of macaques, because macaque social style is well characterized and can be categorized on a spectrum of despotic (Grade 1) versus tolerant (Grade 4) social styles. We derived personality structures from adjectival ratings of Japanese (Macaca fuscata; Grade 1), Assamese (M. assamensis; Grade 2), Barbary (M. sylvanus; Grade 3), Tonkean (M. tonkeana; Grade 4), and crested (M. nigra; Grade 4) macaques and compared these species with rhesus macaques (M. mulatta; Grade 1) whose personality was previously characterized. Using a nonparametric method, fuzzy set analysis, to identify commonalities in personality dimensions across species, we found that all but 1 species exhibited consistently defined Friendliness and Openness dimensions, but that similarities in personality dimensions capturing aggression and social competence reflect similarities in social styles. These findings suggest that social and phylogenetic relationships contribute to the origin, maintenance, and diversification of personality. (c) 2015 APA, all rights reserved.

Correction of refractive errors in rhesus macaques (Macaca mulatta) involved in visual research.

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Mitchell, Jude F; Boisvert, Chantal J; Reuter, Jon D; Reynolds, John H; Leblanc, Mathias

2014-08-01

Macaques are the most common animal model for studies in vision research, and due to their high value as research subjects, often continue to participate in studies well into old age. As is true in humans, visual acuity in macaques is susceptible to refractive errors. Here we report a case study in which an aged macaque demonstrated clear impairment in visual acuity according to performance on a demanding behavioral task. Refraction demonstrated bilateral myopia that significantly affected behavioral and visual tasks. Using corrective lenses, we were able to restore visual acuity. After correction of myopia, the macaque's performance on behavioral tasks was comparable to that of a healthy control. We screened 20 other male macaques to assess the incidence of refractive errors and ocular pathologies in a larger population. Hyperopia was the most frequent ametropia but was mild in all cases. A second macaque had mild myopia and astigmatism in one eye. There were no other pathologies observed on ocular examination. We developed a simple behavioral task that visual research laboratories could use to test visual acuity in macaques. The test was reliable and easily learned by the animals in 1 d. This case study stresses the importance of screening macaques involved in visual science for refractive errors and ocular pathologies to ensure the quality of research; we also provide simple methodology for screening visual acuity in these animals.

Information processing architecture of functionally defined clusters in the macaque cortex.

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Shen, Kelly; Bezgin, Gleb; Hutchison, R Matthew; Gati, Joseph S; Menon, Ravi S; Everling, Stefan; McIntosh, Anthony R

2012-11-28

Computational and empirical neuroimaging studies have suggested that the anatomical connections between brain regions primarily constrain their functional interactions. Given that the large-scale organization of functional networks is determined by the temporal relationships between brain regions, the structural limitations may extend to the global characteristics of functional networks. Here, we explored the extent to which the functional network community structure is determined by the underlying anatomical architecture. We directly compared macaque (Macaca fascicularis) functional connectivity (FC) assessed using spontaneous blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) to directed anatomical connectivity derived from macaque axonal tract tracing studies. Consistent with previous reports, FC increased with increasing strength of anatomical connection, and FC was also present between regions that had no direct anatomical connection. We observed moderate similarity between the FC of each region and its anatomical connectivity. Notably, anatomical connectivity patterns, as described by structural motifs, were different within and across functional modules: partitioning of the functional network was supported by dense bidirectional anatomical connections within clusters and unidirectional connections between clusters. Together, our data directly demonstrate that the FC patterns observed in resting-state BOLD-fMRI are dictated by the underlying neuroanatomical architecture. Importantly, we show how this architecture contributes to the global organizational principles of both functional specialization and integration.

Molecular characterization and polymorphisms of butyrylcholinesterase in cynomolgus macaques.

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Uno, Yasuhiro; Uehara, Shotaro; Mahadhi, Hassan M D; Ohura, Kayoko; Hosokawa, Masakiyo; Imai, Teruko

2018-06-01

Butyrylcholinesterase (BChE), an enzyme essential for drug metabolism, has been investigated as antidotes against organophosphorus nerve agents, and the efficacy and safety have been studied in cynomolgus macaques. BChE polymorphisms partly account for variable BChE activities among individuals in humans, but have not been investigated in cynomolgus macaques. Molecular characterization was carried out by analyzing primary sequence, gene, tissue expression, and genetic variants. In cynomolgus and human BChE, phylogenetically closely related, amino acid residues important for enzyme function were conserved, and gene and genomic structure were similar. Cynomolgus BChE mRNA was most abundantly expressed in liver among the 10 tissue types analyzed. Re-sequencing found 26 non-synonymous genetic variants in 121 cynomolgus and 23 rhesus macaques, indicating that macaque BChE is polymorphic, although none of these variants corresponded to the null or defective alleles of human BChE. These results suggest molecular similarities of cynomolgus and human BChE. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Early visual experience and the recognition of basic facial expressions: involvement of the middle temporal and inferior frontal gyri during haptic identification by the early blind

Science.gov (United States)

Kitada, Ryo; Okamoto, Yuko; Sasaki, Akihiro T.; Kochiyama, Takanori; Miyahara, Motohide; Lederman, Susan J.; Sadato, Norihiro

2012-01-01

Face perception is critical for social communication. Given its fundamental importance in the course of evolution, the innate neural mechanisms can anticipate the computations necessary for representing faces. However, the effect of visual deprivation on the formation of neural mechanisms that underlie face perception is largely unknown. We previously showed that sighted individuals can recognize basic facial expressions by haptics surprisingly well. Moreover, the inferior frontal gyrus (IFG) and posterior superior temporal sulcus (pSTS) in the sighted subjects are involved in haptic and visual recognition of facial expressions. Here, we conducted both psychophysical and functional magnetic-resonance imaging (fMRI) experiments to determine the nature of the neural representation that subserves the recognition of basic facial expressions in early blind individuals. In a psychophysical experiment, both early blind and sighted subjects haptically identified basic facial expressions at levels well above chance. In the subsequent fMRI experiment, both groups haptically identified facial expressions and shoe types (control). The sighted subjects then completed the same task visually. Within brain regions activated by the visual and haptic identification of facial expressions (relative to that of shoes) in the sighted group, corresponding haptic identification in the early blind activated regions in the inferior frontal and middle temporal gyri. These results suggest that the neural system that underlies the recognition of basic facial expressions develops supramodally even in the absence of early visual experience. PMID:23372547

Hair loss and hair-pulling in rhesus macaques (Macaca mulatta).

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Lutz, Corrine K; Coleman, Kristine; Worlein, Julie; Novak, Melinda A

2013-07-01

Alopecia is a common problem in rhesus macaque colonies. A possible cause of this condition is hair-pulling; however the true relationship between hair-pulling and alopecia is unknown. The purpose of this study was to examine the relationship between hair loss and hair-pulling in 1258 rhesus macaques housed in 4 primate colonies across the United States. Alopecia levels ranged from 34.3% to 86.5% (mean, 49.3%) at the primate facilities. At facilities reporting a sex-associated difference, more female macaques were reported to exhibit alopecia than were males. In contrast, more males were reported to hair-pull. Animals reported to hair-pull were significantly more likely to have some amount of alopecia, but rates of hair-pulling were substantially lower than rates of alopecia, ranging from 0.6% to 20.5% (mean, 7.7%) of the populations. These results further demonstrate that hair-pulling plays only a small role in alopecia in rhesus macaques.

Memory of music: roles of right hippocampus and left inferior frontal gyrus.

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Watanabe, Takamitsu; Yagishita, Sho; Kikyo, Hideyuki

2008-01-01

We investigated neural correlates of retrieval success for music memory using event-related functional magnetic resonance imaging. To minimize the interference from MRI scan noise, we used sparse temporal sampling technique. Newly composed music materials were employed as stimuli, which enabled us to detect regions in absence of effects of experience with the music stimuli in this study. Whole brain analyses demonstrated significant retrieval success activities in the right hippocampus, bilateral lateral temporal regions, left inferior frontal gyrus and left precuneus. Anatomically defined region-of-interests analyses showed that the activity of the right hippocampus was stronger than that of the left, while the activities of the inferior frontal gyri showed the reverse pattern. Furthermore, performance-based analyses demonstrated that the retrieval success activity of the right hippocampus was positively correlated with the corrected recognition rate, suggesting that the right hippocampus contributes to the accuracy of music retrieval outcome.

Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophrenia.

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Jeong, Bumseok; Wible, Cynthia G; Hashimoto, Ryu-ichiro; Kubicki, Marek

2009-12-01

Functional studies in schizophrenia demonstrate prominent abnormalities within the left inferior frontal gyrus (IFG) and also suggest the functional connectivity abnormalities in language network including left IFG and superior temporal gyrus during semantic processing. White matter connections between regions involved in the semantic network have also been indicated in schizophrenia. However, an association between functional and anatomical connectivity disruptions within the semantic network in schizophrenia has not been established. Functional (using levels of processing paradigm) as well as diffusion tensor imaging data from 10 controls and 10 chronic schizophrenics were acquired and analyzed. First, semantic encoding specific activation was estimated, showing decreased activation within the left IFG in schizophrenia. Second, functional time series were extracted from this area, and left IFG specific functional connectivity maps were produced for each subject. In an independent analysis, tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) values between groups, and to correlate these values with functional connectivity maps. Schizophrenia patients showed weaker functional connectivity within the language network that includes left IFG and left superior temporal sulcus/middle temporal gyrus. FA was reduced in several white matter regions including left inferior frontal and left internal capsule. Finally, left inferior frontal white matter FA was positively correlated with connectivity measures of the semantic network in schizophrenics, but not in controls. Our results indicate an association between anatomical and functional connectivity abnormalities within the semantic network in schizophrenia, suggesting further that the functional abnormalities observed in this disorder might be directly related to white matter disruptions. 2009 Wiley-Liss, Inc.

Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.

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Laura M J Ylinen

2010-08-01

Full Text Available TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.

Navigation-assisted trans-inferotemporal cortex selective amygdalohippocampectomy for mesial temporal lobe epilepsy; preserving the temporal stem.

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Kishima, Haruhiko; Kato, Amami; Oshino, Satoru; Tani, Naoki; Maruo, Tomoyuki; Khoo, Hui Ming; Yanagisawa, Takufumi; Edakawa, Kotaro; Kobayashi, Maki; Tanaka, Masataka; Hosomi, Koichi; Hirata, Masayuki; Yoshimine, Toshiki

2017-03-01

Selective amygdalohippocampectomy (SAH) can be used to obtain satisfactory seizure control in patients with mesial temporal lobe epilepsy (MTLE). Several SAH procedures have been reported to achieve satisfactory outcomes for seizure control, but none yield fully satisfactory outcomes for memory function. We hypothesized that preserving the temporal stem might play an important role. To preserve the temporal stem, we developed a minimally invasive surgical procedure, 'neuronavigation-assisted trans-inferotemporal cortex SAH' (TITC-SAH). TITC-SAH was performed in 23 patients with MTLE (MTLE on the language-non-dominant hemisphere, n = 11). The inferior horn of the lateral ventricle was approached via the inferior or middle temporal gyrus along the inferior temporal sulcus under neuronavigation guidance. The hippocampus was dissected in a subpial manner and resected en bloc together with the parahippocampal gyrus. Seizure control at one year and memory function at 6 months postoperatively were evaluated. One year after TITC-SAH, 20 of the 23 patients were seizure-free (ILAE class 1), 2 were class 2, and 1 was class 3. Verbal memory improved significantly in 13 patients with a diagnosis of hippocampal sclerosis, for whom WMS-R scores were available both pre- and post-operatively. Improvements were seen regardless of whether the SAH was on the language-dominant or non-dominant hemisphere. No major complication was observed. Navigation-assisted TITC-SAH performed for MTLE offers a simple, minimally invasive procedure that appears to yield excellent outcomes in terms of seizure control and preservation of memory function, because this procedure does not damage the temporal stem. TITC-SAH should be one of the feasible surgical procedures for MTLE. SAH: Amygdalohippocampectomy; MTLE: Mesial temporal lobe epilepsy (MTLE); TITC-SAH: Ttrans-inferotemporal cortex SAH; ILAE: International League Against Epilepsy (ILAE); MRI: Magnetic resonance imaging; EEG

Cyto- and receptor architecture of area 32 in human and macaque brains.

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Palomero-Gallagher, Nicola; Zilles, Karl; Schleicher, Axel; Vogt, Brent A

2013-10-01

Human area 32 plays crucial roles in emotion and memory consolidation. It has subgenual (s32), pregenual (p32), dorsal, and midcingulate components. We seek to determine whether macaque area 32 has subgenual and pregenual subdivisions and the extent to which they are comparable to those in humans by means of NeuN immunohistochemistry and multireceptor analysis of laminar profiles. The macaque has areas s32 and p32. In s32, layer IIIa/b neurons are larger than those of layer IIIc. This relationship is reversed in p32. Layer Va is thicker and Vb thinner in s32. Area p32 contains higher kainate, benzodiazepine (BZ), and serotonin (5-HT)1A but lower N-methyl-D-aspartate (NMDA) and α2 receptor densities. Most differences were found in layers I, II, and VI. Together, these differences support the dual nature of macaque area 32. Comparative analysis of human and macaque s32 and p32 supports equivalences in cyto- and receptor architecture. Although there are differences in mean areal receptor densities, there are considerable similarities at the layer level. Laminar receptor distribution patterns in each area are comparable in the two species in layers III-Va for kainate, NMDA, γ-aminobutyric acid (GABA)B , BZ, and 5-HT1A receptors. Multivariate statistical analysis of laminar receptor densities revealed that human s32 is more similar to macaque s32 and p32 than to human p32. Thus, macaque 32 is more complex than hitherto known. Our data suggest a homologous neural architecture in anterior cingulate s32 and p32 in human and macaque brains. © 2013 Wiley Periodicals, Inc.

Development of sexual behavior in free-ranging female Japanese macaques.

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Leca, Jean-Baptiste; Gunst, Noëlle; Vasey, Paul L

2014-09-01

We studied the development of sexual behaviors in female Japanese macaques (Macaca fuscata) living at Arashiyama, Japan, in a group where adult females routinely exhibit sexual interactions with both males and females. Our cross-sectional data on juvenile, adolescent, and adult females supported most of our predictions related to the learning hypothesis, which holds that adolescence serves to provide females with a period in which to practice adult female-like sexual behavioral patterns, including sexual solicitations, sexual mounts, and spatio-temporal coordination during consortships. We found evidence for a gradual acquisition of adult-like behavioral patterns (e.g., more frequent solicitations with body contact, more frequent complete mounts, more diverse solicitation patterns and complete mounting postures, and longer consortships involving prolonged inter-mount grasping behavior between partners), and a gradual disappearance of less effective immature behavioral patterns (e.g., less frequent non-contact solicitations, ambiguous mounting initiations, and incomplete mounts). We distinguished between three major categories of sexual behavioral patterns based on their speed of development, ranging from fast (e.g., diversity in mounting postures and genital stimulation during mounting) to slow (e.g., contact solicitations and grasping behavior between consortship partners), with some being intermediate (e.g., range of solicitation patterns and expression of complete mounts). This study showed that the emergence of both conceptive and non-conceptive adult sexual behaviors can be traced back to immature behavioral patterns in adolescent female Japanese macaques, with a major threshold occurring at the age of 4 years. © 2014 Wiley Periodicals, Inc.

Activation in the Right Inferior Parietal Lobule Reflects the Representation of Musical Structure beyond Simple Pitch Discrimination

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Royal, Isabelle; Vuvan, Dominique T.; Zendel, Benjamin Rich; Robitaille, Nicolas; Schönwiesner, Marc; Peretz, Isabelle

2016-01-01

Pitch discrimination tasks typically engage the superior temporal gyrus and the right inferior frontal gyrus. It is currently unclear whether these regions are equally involved in the processing of incongruous notes in melodies, which requires the representation of musical structure (tonality) in addition to pitch discrimination. To this aim, 14 participants completed two tasks while undergoing functional magnetic resonance imaging, one in which they had to identify a pitch change in a series of non-melodic repeating tones and a second in which they had to identify an incongruous note in a tonal melody. In both tasks, the deviants activated the right superior temporal gyrus. A contrast between deviants in the melodic task and deviants in the non-melodic task (melodic > non-melodic) revealed additional activity in the right inferior parietal lobule. Activation in the inferior parietal lobule likely represents processes related to the maintenance of tonal pitch structure in working memory during pitch discrimination. PMID:27195523

Ex-vivo α-galactosylceramide activation of NKT cells in humans and macaques.

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Fernandez, Caroline S; Cameron, Garth; Godfrey, Dale I; Kent, Stephen J

2012-08-31

NKT cells are key mediators of antiviral and anticancer immunity. Experiments in mice have demonstrated that activation of NKT cells in vivo induces the expression of multiple effector molecules critical to successful immunity. Human clinical trials have shown similar responses, although in vivo activation of NKT cells in humans or primate models are far more limited in number and scope. Measuring ex vivo activation of NKT cells by the CD1d-restricted glycolipid ligand α-Galactosylceramide (α-GalCer) through cytokine expression profiles is a useful marker of NKT cell function, but for reasons that are unclear, this approach does not appear to work as well in humans and non-human primate macaque models in comparison to mice. We performed a series of experiments on human and macaque (Macaca nemestrina) fresh whole blood samples to define optimal conditions to detect NKT cell cytokine (TNF, IFNγ, IL-2) and degranulation marker (CD107a) expression by flow cytometry. We found that conditions previously described for mouse splenocyte NKT cell activation were suboptimal on human or macaque blood NKT cells. In contrast, a 6h incubation with brefeldin A added for the last 4h, in a 96-well plate based assay, and using an α-GalCer concentration of 1 μg/ml were optimal methods to stimulate NKT cells in fresh blood from both humans and macaques. Unexpectedly, we noted that blood NKT cells from macaques infected with SIV were more readily activated by α-GalCer than NKT cells from uninfected macaques, suggesting that SIV infection may have primed the NKT cells. In conclusion, we describe optimized methods for the ex vivo antigen-specific activation of human and macaque blood NKT cells. These assays should be useful in monitoring NKT cells in disease and in immunotherapy studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Risk and Resilience: Early Manipulation of Macaque Social Experience and Persistent Behavioral and Neurophysiological Outcomes

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Stevens, Hanna E.; Leckman, James F.; Coplan, Jeremy D.; Suomi, Stephen J.

2009-01-01

A literature review on macaque monkeys finds that peer rearing of young macaques and rearing of young macaques by mothers that are undergoing variable foraging conditions result in emotional and neurophysiological disturbance. Certain genotypes contribute to resilience to this disturbance. The findings have implications to child mental health and…

A long-acting integrase inhibitor protects female macaques from repeated high-dose intravaginal SHIV challenge.

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Andrews, Chasity D; Yueh, Yun Lan; Spreen, William R; St Bernard, Leslie; Boente-Carrera, Mar; Rodriguez, Kristina; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Ford, Susan; Mohri, Hiroshi; Cheng-Mayer, Cecilia; Hong, Zhi; Ho, David D; Markowitz, Martin

2015-01-14

Long-acting GSK1265744 (GSK744 LA) is a strand transfer inhibitor of the HIV/SIV (simian immunodeficiency virus) integrase and was shown to be an effective preexposure prophylaxis (PrEP) agent in a low-dose intrarectal SHIV (simian-human immunodeficiency virus) rhesus macaque challenge model. We examined the pharmacokinetics and efficacy of GSK744 LA as PrEP against repeat high-dose intravaginal SHIV challenge in female rhesus macaques treated with Depo-Provera (depot medroxyprogesterone acetate), which promotes viral transmission vaginally. When Depo-Provera-treated female rhesus macaques were dosed with GSK744 LA (50 mg/kg) monthly, systemic and tissue drug concentrations were lower than previously observed in male rhesus macaques. GSK744 concentrations were fivefold lower on average in cervical tissues than in rectal tissues. Eight female rhesus macaques were treated with GSK744 LA at week 0, and four female rhesus macaques served as controls. All animals received a high-dose challenge of SHIV162P3 at week 1. No infection was detected in GSK744 LA-treated rhesus macaques, whereas viremia was detected 1 to 2 weeks after SHIV challenge in all control animals. The GSK744 LA-treated rhesus macaques were given a second administration of drug at week 4 and further challenged at weeks 5 and 7. GSK744 LA treatment protected six of eight female rhesus macaques against three high-dose SHIV challenges, whereas all control animals became infected after the first challenge (P = 0.0003, log-rank test). These results support further clinical development of GSK744 LA for PrEP. Copyright © 2015, American Association for the Advancement of Science.

Identification and characterization of short tandem repeats in the Tibetan macaque genome based on resequencing data.

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Liu, San-Xu; Hou, Wei; Zhang, Xue-Yan; Peng, Chang-Jun; Yue, Bi-Song; Fan, Zhen-Xin; Li, Jing

2018-07-18

The Tibetan macaque, which is endemic to China, is currently listed as a Near Endangered primate species by the International Union for Conservation of Nature (IUCN). Short tandem repeats (STRs) refer to repetitive elements of genome sequence that range in length from 1-6 bp. They are found in many organisms and are widely applied in population genetic studies. To clarify the distribution characteristics of genome-wide STRs and understand their variation among Tibetan macaques, we conducted a genome-wide survey of STRs with next-generation sequencing of five macaque samples. A total of 1 077 790 perfect STRs were mined from our assembly, with an N50 of 4 966 bp. Mono-nucleotide repeats were the most abundant, followed by tetra- and di-nucleotide repeats. Analysis of GC content and repeats showed consistent results with other macaques. Furthermore, using STR analysis software (lobSTR), we found that the proportion of base pair deletions in the STRs was greater than that of insertions in the five Tibetan macaque individuals (Pgenome showed good amplification efficiency and could be used to study population genetics in Tibetan macaques. The neighbor-joining tree classified the five macaques into two different branches according to their geographical origin, indicating high genetic differentiation between the Huangshan and Sichuan populations. We elucidated the distribution characteristics of STRs in the Tibetan macaque genome and provided an effective method for screening polymorphic STRs. Our results also lay a foundation for future genetic variation studies of macaques.

Stepping toward a Macaque Model of HIV-1 Induced AIDS

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Jason T. Kimata

2014-09-01

Full Text Available HIV-1 exhibits a narrow host range, hindering the development of a robust animal model of pathogenesis. Past studies have demonstrated that the restricted host range of HIV-1 may be largely due to the inability of the virus to antagonize and evade effector molecules of the interferon response in other species. They have also guided the engineering of HIV-1 clones that can replicate in CD4 T-cells of Asian macaque species. However, while replication of these viruses in macaque hosts is persistent, it has been limited and without progression to AIDS. In a new study, Hatziioannou et al., demonstrate for the first time that adapted macaque-tropic HIV-1 can persistently replicate at high levels in pigtailed macaques (Macaca nemestrina, but only if CD8 T-cells are depleted at the time of inoculation. The infection causes rapid disease and recapitulates several aspects of AIDS in humans. Additionally, the virus undergoes genetic changes to further escape innate immunity in association with disease progression. Here, the importance of these findings is discussed, as they relate to pathogenesis and model development.

Representation of dynamic interaural phase difference in auditory cortex of awake rhesus macaques.

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Scott, Brian H; Malone, Brian J; Semple, Malcolm N

2009-04-01

Neurons in auditory cortex of awake primates are selective for the spatial location of a sound source, yet the neural representation of the binaural cues that underlie this tuning remains undefined. We examined this representation in 283 single neurons across the low-frequency auditory core in alert macaques, trained to discriminate binaural cues for sound azimuth. In response to binaural beat stimuli, which mimic acoustic motion by modulating the relative phase of a tone at the two ears, these neurons robustly modulate their discharge rate in response to this directional cue. In accordance with prior studies, the preferred interaural phase difference (IPD) of these neurons typically corresponds to azimuthal locations contralateral to the recorded hemisphere. Whereas binaural beats evoke only transient discharges in anesthetized cortex, neurons in awake cortex respond throughout the IPD cycle. In this regard, responses are consistent with observations at earlier stations of the auditory pathway. Discharge rate is a band-pass function of the frequency of IPD modulation in most neurons (73%), but both discharge rate and temporal synchrony are independent of the direction of phase modulation. When subjected to a receiver operator characteristic analysis, the responses of individual neurons are insufficient to account for the perceptual acuity of these macaques in an IPD discrimination task, suggesting the need for neural pooling at the cortical level.

Serotonin transporter genotype modulates social reward and punishment in rhesus macaques.

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Karli K Watson

Full Text Available Serotonin signaling influences social behavior in both human and nonhuman primates. In humans, variation upstream of the promoter region of the serotonin transporter gene (5-HTTLPR has recently been shown to influence both behavioral measures of social anxiety and amygdala response to social threats. Here we show that length polymorphisms in 5-HTTLPR predict social reward and punishment in rhesus macaques, a species in which 5-HTTLPR variation is analogous to that of humans.In contrast to monkeys with two copies of the long allele (L/L, monkeys with one copy of the short allele of this gene (S/L spent less time gazing at face than non-face images, less time looking in the eye region of faces, and had larger pupil diameters when gazing at photos of a high versus low status male macaques. Moreover, in a novel primed gambling task, presentation of photos of high status male macaques promoted risk-aversion in S/L monkeys but promoted risk-seeking in L/L monkeys. Finally, as measured by a "pay-per-view" task, S/L monkeys required juice payment to view photos of high status males, whereas L/L monkeys sacrificed fluid to see the same photos.These data indicate that genetic variation in serotonin function contributes to social reward and punishment in rhesus macaques, and thus shapes social behavior in humans and rhesus macaques alike.

Abstract Representations of Object-Directed Action in the Left Inferior Parietal Lobule.

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Chen, Quanjing; Garcea, Frank E; Jacobs, Robert A; Mahon, Bradford Z

2018-06-01

Prior neuroimaging and neuropsychological research indicates that the left inferior parietal lobule in the human brain is a critical substrate for representing object manipulation knowledge. In the present functional MRI study we used multivoxel pattern analyses to test whether action similarity among objects can be decoded in the inferior parietal lobule independent of the task applied to objects (identification or pantomime) and stimulus format in which stimuli are presented (pictures or printed words). Participants pantomimed the use of objects, cued by printed words, or identified pictures of objects. Classifiers were trained and tested across task (e.g., training data: pantomime; testing data: identification), stimulus format (e.g., training data: word format; testing format: picture) and specific objects (e.g., training data: scissors vs. corkscrew; testing data: pliers vs. screwdriver). The only brain region in which action relations among objects could be decoded across task, stimulus format and objects was the inferior parietal lobule. By contrast, medial aspects of the ventral surface of the left temporal lobe represented object function, albeit not at the same level of abstractness as actions in the inferior parietal lobule. These results suggest compulsory access to abstract action information in the inferior parietal lobe even when simply identifying objects.

Temporal dynamics of 2D motion integration for ocular following in macaque monkeys.

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Barthélemy, Fréderic V; Fleuriet, Jérome; Masson, Guillaume S

2010-03-01

Several recent studies have shown that extracting pattern motion direction is a dynamical process where edge motion is first extracted and pattern-related information is encoded with a small time lag by MT neurons. A similar dynamics was found for human reflexive or voluntary tracking. Here, we bring an essential, but still missing, piece of information by documenting macaque ocular following responses to gratings, unikinetic plaids, and barber-poles. We found that ocular tracking was always initiated first in the grating motion direction with ultra-short latencies (approximately 55 ms). A second component was driven only 10-15 ms later, rotating tracking toward pattern motion direction. At the end the open-loop period, tracking direction was aligned with pattern motion direction (plaids) or the average of the line-ending motion directions (barber-poles). We characterized the dependency on contrast of each component. Both timing and direction of ocular following were quantitatively very consistent with the dynamics of neuronal responses reported by others. Overall, we found a remarkable consistency between neuronal dynamics and monkey behavior, advocating for a direct link between the neuronal solution of the aperture problem and primate perception and action.

Analysis of carboxylesterase 2 transcript variants in cynomolgus macaque liver.

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Uno, Yasuhiro; Igawa, Yoshiyuki; Tanaka, Maori; Ohura, Kayoko; Hosokawa, Masakiyo; Imai, Teruko

2018-04-27

Carboxylesterase (CES) is important for the detoxification of a wide range of drugs and xenobiotics. In this study, the hepatic level of CES2 mRNA was examined in cynomolgus macaques used widely in preclinical studies for drug metabolism. Three CES2 mRNAs were present in cynomolgus macaque liver. The mRNA level was highest for cynomolgus CES2A (formerly CES2v3), much lower for cynomolgus CES2B (formerly CES2v1) and extremely low for cynomolgus CES2C (formerly CES2v2). Most various transcript variants produced from cynomolgus CES2B gene did not contain a complete coding region. Thus, CES2A is the major CES2 enzyme in cynomolgus liver. A new transcript variant of CES2A, CES2Av2, was identified. CES2Av2 contained exon 3 region different from wild-type (CES2Av1). In cynomolgus macaques expressing only CES2Av2 transcript, CES2A contained the sequence of CES2B in exon 3 and vicinity, probably due to gene conversion. On genotyping, this CES2Av2 allele was prevalent in Indochinese cynomolgus macaques, but not in Indonesian cynomolgus or rhesus macaques. CES2Av2 recombinant protein showed similar activity to CES2Av1 protein for several substrates. It is concluded that CES2A is the major cynomolgus hepatic CES2, and new transcript variant, CES2Av2, has similar functions to CES2Av1.

Heterologous Protection against Asian Zika Virus Challenge in Rhesus Macaques.

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Matthew T Aliota

2016-12-01

Full Text Available Zika virus (ZIKV; Flaviviridae, Flavivirus was declared a public health emergency of international concern by the World Health Organization (WHO in February 2016, because of the evidence linking infection with ZIKV to neurological complications, such as Guillain-Barre Syndrome in adults and congenital birth defects including microcephaly in the developing fetus. Because development of a ZIKV vaccine is a top research priority and because the genetic and antigenic variability of many RNA viruses limits the effectiveness of vaccines, assessing whether immunity elicited against one ZIKV strain is sufficient to confer broad protection against all ZIKV strains is critical. Recently, in vitro studies demonstrated that ZIKV likely circulates as a single serotype. Here, we demonstrate that immunity elicited by African lineage ZIKV protects rhesus macaques against subsequent infection with Asian lineage ZIKV.Using our recently developed rhesus macaque model of ZIKV infection, we report that the prototypical ZIKV strain MR766 productively infects macaques, and that immunity elicited by MR766 protects macaques against heterologous Asian ZIKV. Furthermore, using next generation deep sequencing, we found in vivo restoration of a putative N-linked glycosylation site upon replication in macaques that is absent in numerous MR766 strains that are widely being used by the research community. This reversion highlights the importance of carefully examining the sequence composition of all viral stocks as well as understanding how passage history may alter a virus from its original form.An effective ZIKV vaccine is needed to prevent infection-associated fetal abnormalities. Macaques whose immune responses were primed by infection with East African ZIKV were completely protected from detectable viremia when subsequently rechallenged with heterologous Asian ZIKV. Therefore, these data suggest that immunogen selection is unlikely to adversely affect the breadth of

Strength of Temporal White Matter Pathways Predicts Semantic Learning.

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Ripollés, Pablo; Biel, Davina; Peñaloza, Claudia; Kaufmann, Jörn; Marco-Pallarés, Josep; Noesselt, Toemme; Rodríguez-Fornells, Antoni

2017-11-15

Learning the associations between words and meanings is a fundamental human ability. Although the language network is cortically well defined, the role of the white matter pathways supporting novel word-to-meaning mappings remains unclear. Here, by using contextual and cross-situational word learning, we tested whether learning the meaning of a new word is related to the integrity of the language-related white matter pathways in 40 adults (18 women). The arcuate, uncinate, inferior-fronto-occipital and inferior-longitudinal fasciculi were virtually dissected using manual and automatic deterministic fiber tracking. Critically, the automatic method allowed assessing the white matter microstructure along the tract. Results demonstrate that the microstructural properties of the left inferior-longitudinal fasciculus predict contextual learning, whereas the left uncinate was associated with cross-situational learning. In addition, we identified regions of special importance within these pathways: the posterior middle temporal gyrus, thought to serve as a lexical interface and specifically related to contextual learning; the anterior temporal lobe, known to be an amodal hub for semantic processing and related to cross-situational learning; and the white matter near the hippocampus, a structure fundamental for the initial stages of new-word learning and, remarkably, related to both types of word learning. No significant associations were found for the inferior-fronto-occipital fasciculus or the arcuate. While previous results suggest that learning new phonological word forms is mediated by the arcuate fasciculus, these findings show that the temporal pathways are the crucial neural substrate supporting one of the most striking human abilities: our capacity to identify correct associations between words and meanings under referential indeterminacy. SIGNIFICANCE STATEMENT The language-processing network is cortically (i.e., gray matter) well defined. However, the role of the

Expression of Kv3.1b potassium channel is widespread in macaque motor cortex pyramidal cells: A histological comparison between rat and macaque.

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Soares, David; Goldrick, Isabelle; Lemon, Roger N; Kraskov, Alexander; Greensmith, Linda; Kalmar, Bernadett

2017-06-15

There are substantial differences across species in the organization and function of the motor pathways. These differences extend to basic electrophysiological properties. Thus, in rat motor cortex, pyramidal cells have long duration action potentials, while in the macaque, some pyramidal neurons exhibit short duration "thin" spikes. These differences may be related to the expression of the fast potassium channel Kv3.1b, which in rat interneurons is associated with generation of thin spikes. Rat pyramidal cells typically lack these channels, while there are reports that they are present in macaque pyramids. Here we made a systematic, quantitative comparison of the Kv3.1b expression in sections from macaque and rat motor cortex, using two different antibodies (NeuroMab, Millipore). As our standard reference, we examined, in the same sections, Kv3.1b staining in parvalbumin-positive interneurons, which show strong Kv3.1b immunoreactivity. In macaque motor cortex, a large sample of pyramidal neurons were nearly all found to express Kv3.1b in their soma membranes. These labeled neurons were identified as pyramidal based either by expression of SMI32 (a pyramidal marker), or by their shape and size, and lack of expression of parvalbumin (a marker for some classes of interneuron). Large (Betz cells), medium, and small pyramidal neurons all expressed Kv3.1b. In rat motor cortex, SMI32-postive pyramidal neurons expressing Kv3.1b were very rare and weakly stained. Thus, there is a marked species difference in the immunoreactivity of Kv3.1b in pyramidal neurons, and this may be one of the factors explaining the pronounced electrophysiological differences between rat and macaque pyramidal neurons. © 2017 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Expression of cytochrome P450 regulators in cynomolgus macaque.

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Uno, Yasuhiro; Yamazaki, Hiroshi

2017-09-11

1. Cytochrome P450 (P450) regulators including nuclear receptors and transcription factors have not been fully investigated in cynomolgus macaques, an important species used in drug metabolism studies. In this study, we analyzed 17 P450 regulators by sequence and phylogenetic analysis, and tissue expression. 2. Gene and genome structures of 17 P450 regulators were similar to the human orthologs, and the deduced amino acid sequences showed high sequence identities (92-95%) and more closely clustered in a phylogenetic tree, with the human orthologs. 3. Many of the P450 regulator mRNAs were preferentially expressed in the liver, kidney, and/or jejunum. Among the P450 regulator mRNAs, PXR was most abundant in the liver and jejunum, and HNF4α in the kidney. In the liver, the expression of most P450 regulator mRNAs did not show significant differential expression (>2.5-fold) between cynomolgus macaques bred in Cambodia, China, and Indonesia, or rhesus macaques. 4. By correlation analysis, most of the P450 regulators were significantly (p < 0.05) correlated to other P450 regulators, and many of them were also significantly (p < 0.05) correlated with P450s. 5. These results suggest that 17 P450 regulators of cynomolgus macaques had similar molecular characteristics to the human orthologs.

ABO blood group phenotype frequency estimation using molecular phenotyping in rhesus and cynomolgus macaques.

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Kanthaswamy, S; Ng, J; Oldt, R F; Valdivia, L; Houghton, P; Smith, D G

2017-11-01

A much larger sample (N = 2369) was used to evaluate a previously reported distribution of the A, AB and B blood group phenotypes in rhesus and cynomolgus macaques from six different regional populations. These samples, acquired from 15 different breeding and research facilities in the United States, were analyzed using a real-time quantitative polymerase chain reaction (qPCR) assay that targets single nucleotide polymorphisms (SNPs) responsible for the macaque A, B and AB phenotypes. The frequency distributions of blood group phenotypes of the two species differ significantly from each other and significant regional differentiation within the geographic ranges of each species was also observed. The B blood group phenotype was prevalent in rhesus macaques, especially those from India, while the frequencies of the A, B and AB phenotypes varied significantly among cynomolgus macaques from different geographic regions. The Mauritian cynomolgus macaques, despite having originated in Indonesia, showed significant (P ≪ .01) divergence from the Indonesian animals at the ABO blood group locus. Most Mauritian animals belonged to the B blood group while the Indonesian animals were mostly A. The close similarity in blood group frequency distributions between the Chinese rhesus and Indochinese cynomolgus macaques demonstrates that the introgression between these two species extends beyond the zone of intergradation in Indochina. This study underscores the importance of ABO blood group phenotyping of the domestic supply of macaques and their biospecimens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Task-based and resting-state fMRI reveal compensatory network changes following damage to left inferior frontal gyrus.

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Hallam, Glyn P; Thompson, Hannah E; Hymers, Mark; Millman, Rebecca E; Rodd, Jennifer M; Lambon Ralph, Matthew A; Smallwood, Jonathan; Jefferies, Elizabeth

2018-02-01

Damage to left inferior prefrontal cortex in stroke aphasia is associated with semantic deficits reflecting poor control over conceptual retrieval, as opposed to loss of knowledge. However, little is known about how functional recruitment within the semantic network changes in patients with executive-semantic deficits. The current study acquired functional magnetic resonance imaging (fMRI) data from 14 patients with semantic aphasia, who had difficulty with flexible semantic retrieval following left prefrontal damage, and 16 healthy age-matched controls, allowing us to examine activation and connectivity in the semantic network. We examined neural activity while participants listened to spoken sentences that varied in their levels of lexical ambiguity and during rest. We found group differences in two regions thought to be good candidates for functional compensation: ventral anterior temporal lobe (vATL), which is strongly implicated in comprehension, and posterior middle temporal gyrus (pMTG), which is hypothesized to work together with left inferior prefrontal cortex to support controlled aspects of semantic retrieval. The patients recruited both of these sites more than controls in response to meaningful sentences. Subsequent analysis identified that, in control participants, the recruitment of pMTG to ambiguous sentences was inversely related to functional coupling between pMTG and anterior superior temporal gyrus (aSTG) at rest, while the patients showed the opposite pattern. Moreover, stronger connectivity between pMTG and aSTG in patients was associated with better performance on a test of verbal semantic association, suggesting that this temporal lobe connection supports comprehension in the face of damage to left inferior prefrontal cortex. These results characterize network changes in patients with executive-semantic deficits and converge with studies of healthy participants in providing evidence for a distributed system underpinning semantic control that

Laboratory rhesus macaque social housing and social changes: Implications for research.

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Hannibal, Darcy L; Bliss-Moreau, Eliza; Vandeleest, Jessica; McCowan, Brenda; Capitanio, John

2017-01-01

Macaque species, specifically rhesus (Macaca mulatta), are the most common nonhuman primates (NHPs) used in biomedical research due to their suitability as a model of high priority diseases (e.g., HIV, obesity, cognitive aging), cost effective breeding and housing compared to most other NHPs, and close evolutionary relationship to humans. With this close evolutionary relationship, however, is a shared adaptation for a socially stimulating environment, without which both their welfare and suitability as a research model are compromised. While outdoor social group housing provides the best approximation of a social environment that matches the macaque behavioral biology in the wild, this is not always possible at all facilities, where animals may be housed indoors in small groups, in pairs, or alone. Further, animals may experience many housing changes in their lifetime depending on project needs, changes in social status, management needs, or health concerns. Here, we review the evidence for the physiological and health effects of social housing changes and the potential impacts on research outcomes for studies using macaques, particularly rhesus. We situate our review in the context of increasing regulatory pressure for research facilities to both house NHPs socially and mitigate trauma from social aggression. To meet these regulatory requirements and further refine the macaque model for research, significant advances must be made in our understanding and management of rhesus macaque social housing, particularly pair-housing since it is the most common social housing configuration for macaques while on research projects. Because most NHPs are adapted for sociality, a social context is likely important for improving repeatability, reproducibility, and external validity of primate biomedical research. Am. J. Primatol. 79:e22528, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An SIV/macaque model targeted to study HIV-associated neurocognitive disorders.

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Beck, Sarah E; Queen, Suzanne E; Metcalf Pate, Kelly A; Mangus, Lisa M; Abreu, Celina M; Gama, Lucio; Witwer, Kenneth W; Adams, Robert J; Zink, M Christine; Clements, Janice E; Mankowski, Joseph L

2018-04-01

Simian immunodeficiency virus (SIV) infection of pigtailed macaques is a highly representative and well-characterized animal model for HIV neuropathogenesis studies that provides an excellent opportunity to study and develop prognostic markers of HIV-associated neurocognitive disorders (HAND) for HIV-infected individuals. SIV studies can be performed in a controlled setting that enhances reproducibility and offers high-translational value. Similar to observations in HIV-infected patients receiving antiretroviral therapy (ART), ongoing neurodegeneration and inflammation are present in SIV-infected pigtailed macaques treated with suppressive ART. By developing quantitative viral outgrowth assays that measure both CD4+ T cells and macrophages harboring replication competent SIV as well as a highly sensitive mouse-based viral outgrowth assay, we have positioned the SIV/pigtailed macaque model to advance our understanding of latent cellular reservoirs, including potential CNS reservoirs, to promote HIV cure. In addition to contributing to our understanding of the pathogenesis of HAND, the SIV/pigtailed macaque model also provides an excellent opportunity to test innovative approaches to eliminate the latent HIV reservoir in the brain.

The genetic composition of populations of cynomolgus macaques (Macaca fascicularis) used in biomedical research.

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Kanthaswamy, S; Ng, J; Satkoski Trask, J; George, D A; Kou, A J; Hoffman, L N; Doherty, T B; Houghton, P; Smith, D G

2013-06-01

The genetic composition of cynomolgus macaques used in biomedical research is not as well-characterized as that of rhesus macaques. Populations of cynomolgus macaques from Sumatra, Corregidor, Mauritius, Singapore, Cambodia, and Zamboanga were analyzed using 24 STRs. The Sumatran and Cambodian populations exhibited the highest allelic diversity, while the Mauritian population exhibited the lowest. Sumatran cynomolgus macaques were the most genetically similar to all others, consistent with an Indonesian origin of the species. The high diversity among Cambodian animals may result from interbreeding with rhesus macaques. The Philippine and Mauritian samples were the most divergent from other populations, the former due to separation from the Sunda Shelf by deepwater and the latter due to anthropogenic translocation and extreme founder effects. Investigators should verify their research subjects' origin, ancestry, and pedigree to minimize risks to biomedical experimentation from genetic variance stemming from close kinship and mixed ancestry as these can obscure treatment effects. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus

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Nalca, Aysegul; Rossi, Franco D.; Miller, Lynn J.; Wiley, Michael R.; Perez-Sautu, Unai; Washington, Samuel C.; Norris, Sarah L.; Wollen-Roberts, Suzanne E.; Shamblin, Joshua D.; Kimmel, Adrienne E.; Bloomfield, Holly A.; Valdez, Stephanie M.; Sprague, Thomas R.; Principe, Lucia M.; Bellanca, Stephanie A.; Cinkovich, Stephanie S.; Lugo-Roman, Luis; Cazares, Lisa H.; Pratt, William D.; Palacios, Gustavo F.; Bavari, Sina; Pitt, M. Louise; Nasar, Farooq

2017-01-01

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present. PMID:28548637

High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus.

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Haddow, Andrew D; Nalca, Aysegul; Rossi, Franco D; Miller, Lynn J; Wiley, Michael R; Perez-Sautu, Unai; Washington, Samuel C; Norris, Sarah L; Wollen-Roberts, Suzanne E; Shamblin, Joshua D; Kimmel, Adrienne E; Bloomfield, Holly A; Valdez, Stephanie M; Sprague, Thomas R; Principe, Lucia M; Bellanca, Stephanie A; Cinkovich, Stephanie S; Lugo-Roman, Luis; Cazares, Lisa H; Pratt, William D; Palacios, Gustavo F; Bavari, Sina; Pitt, M Louise; Nasar, Farooq

2017-08-01

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present.

Processing of natural temporal stimuli by macaque retinal ganglion cells

NARCIS (Netherlands)

Hateren, J.H. van; Rüttiger, L.; Lee, B.B.

2002-01-01

This study quantifies the performance of primate retinal ganglion cells in response to natural stimuli. Stimuli were confined to the temporal and chromatic domains and were derived from two contrasting environments, one typically northern European and the other a flower show. The performance of the

Discovery of a secular trend in Cayo Santiago macaque reproduction.

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Hernández-Pacheco, Raisa; Rawlins, Richard G; Kessler, Matthew J; Delgado, Diana L; Ruiz-Lambides, Angelina V; Sabat, Alberto M

2016-02-01

Reproductive synchrony and the consequent clustering of births are hypothesized to be regulated by seasonal changes in rainfall and food availability. Such climate-related seasonality is, however, questionable in tropical populations occupying temporally invariant habitats year round. Using the long-term data of the Cayo Santiago rhesus macaques from 1973 to 2013, this study distinguishes synchrony (a greater than chance clustering of births) from seasonality (a cluster of births during a period of the year when abiotic conditions are favorable) and shows that females are highly synchronized (>72% of births in a 3-month period) but the effects of environmental zeitgebers on reproduction are overridden by biological factors. Specifically, biotic and abiotic factors including (i) loss of immature offspring; (ii) population density; (iii) age at delivery; (iv) rainfall; and (v) changes in colony management were modeled in relation to the annual onset of births and the median birth date. Females experiencing loss of immature offspring had an interbirth interval of trend in both the onset of births and the median date of birth is documented and the model predicts that the median birth date will advance across all calendar-based seasons by 2050. The secular trend in reproduction appears to be triggered by changes in the age at delivery of females, the absence of physiological constraints from maternal investment due to offspring loss, shorter interbirth interval, and a higher degree of coordination due to increasing population density. This study challenges the reproductive phenology previously described for rhesus macaques highlighting the importance of long-term studies in addressing the ultimate causes of reproductive synchrony. © 2015 Wiley Periodicals, Inc.

Mycobacterium kansasii Isolated from Tuberculinpositive Rhesus Macaques (Macaca mulatta) in the Absence of Disease.

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Shipley, Steven T; Johnson, David K; Roodgar, Morteza; Smith, David Glenn; Montgomery, Charles A; Lloyd, Steven M; Higgins, James A; Kriel, Edwin H; Klein, Hilton J; Porter, William P; Nazareno, Jerome B; Houghton, Paul W; Panda, Aruna; DeTolla, Louis J

2017-08-01

Mycobacterial infections are of primary health concern in NHP colonies in biomedical research. NHP are constantly monitored and screened for Mycobacterium spp. We report 6 Chinese-origin rhesus macaques infected with Mycobacterium kansasii that exhibited positive tuberculin skin tests in the absence of disease. Two of these macaques were being used for research purposes; the remaining 4 macaques were residing at the contract quarantine company. Histopathology and acid-fast staining of fixed tissues from all macaques showed that all were free of disease. Thoracic radiographs were negative for any signs of disease or infection. Samples from bronchial lavage and tissues including lung, spleen, hilar and mesenteric lymph nodes tested negative by PCR assay for Mycobacterium spp. One of the research macaques tested culture-positive for M. kansasii and a poorly characterized M. avium complex organism. One macaque from the contract quarantine facility tested culture positive for M. kansasii. Genomic testing and target gene RNA expression analysis of the 2 M. kansasii isolates were performed to evaluate possible kinship and affected genes that might contribute to susceptibility to mycobacterial infection. Genotyping of the 2 isolates revealed 2 genetically distinct strains (strains 1 and 4). The presence of positive tuberculin skin tests in the absence of disease raises serious concerns regarding diagnostic methods used for infected NHP.

A Characterization of Aerosolized Sudan Virus Infection in African Green Monkeys, Cynomolgus Macaques, and Rhesus Macaques

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Donald K. Nichols

2012-10-01

Full Text Available Filoviruses are members of the genera Ebolavirus, Marburgvirus, and “Cuevavirus”. Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV Boniface in non-human primates (NHP belonging to three different species. Groups of cynomolgus macaques (cyno, rhesus macaques (rhesus, and African green monkeys (AGM were challenged with target doses of 50 or 500 plaque-forming units (pfu of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4–5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT and aspartate transaminase (AST concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP.

Population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space.

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Feng, Lei; Jeon, Tina; Yu, Qiaowen; Ouyang, Minhui; Peng, Qinmu; Mishra, Virendra; Pletikos, Mihovil; Sestan, Nenad; Miller, Michael I; Mori, Susumu; Hsiao, Steven; Liu, Shuwei; Huang, Hao

2017-12-01

Animal models of the rhesus macaque (Macaca mulatta), the most widely used nonhuman primate, have been irreplaceable in neurobiological studies. However, a population-averaged macaque brain diffusion tensor imaging (DTI) atlas, including comprehensive gray and white matter labeling as well as bony and facial landmarks guiding invasive experimental procedures, is not available. The macaque white matter tract pathways and microstructures have been rarely recorded. Here, we established a population-averaged macaque brain atlas with high-resolution ex vivo DTI integrated into in vivo space incorporating bony and facial landmarks, and delineated microstructures and three-dimensional pathways of major white matter tracts in vivo MRI/DTI and ex vivo (postmortem) DTI of ten rhesus macaque brains were acquired. Single-subject macaque brain DTI template was obtained by transforming the postmortem high-resolution DTI data into in vivo space. Ex vivo DTI of ten macaque brains was then averaged in the in vivo single-subject template space to generate population-averaged macaque brain DTI atlas. The white matter tracts were traced with DTI-based tractography. One hundred and eighteen neural structures including all cortical gyri, white matter tracts and subcortical nuclei, were labeled manually on population-averaged DTI-derived maps. The in vivo microstructural metrics of fractional anisotropy, axial, radial and mean diffusivity of the traced white matter tracts were measured. Population-averaged digital atlas integrated into in vivo space can be used to label the experimental macaque brain automatically. Bony and facial landmarks will be available for guiding invasive procedures. The DTI metric measurements offer unique insights into heterogeneous microstructural profiles of different white matter tracts.

Illegal trade in Barbary macaques

NARCIS (Netherlands)

van Uhm, Daan|info:eu-repo/dai/nl/380477025

2014-01-01

While Morocco is well known as the main port between Africa and the EU for the illegal drugs trade and migration, the illegal trade in wildlife is flourishing as well. Next to the illegal large-scale trafficking of tortoises and birds, it is estimated that as few as 5,000 Barbary macaques remain in

Distortion of time interval reproduction in an epileptic patient with a focal lesion in the right anterior insular/inferior frontal cortices.

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Monfort, Vincent; Pfeuty, Micha; Klein, Madelyne; Collé, Steffie; Brissart, Hélène; Jonas, Jacques; Maillard, Louis

2014-11-01

This case report on an epileptic patient suffering from a focal lesion at the junction of the right anterior insular cortex (AIC) and the adjacent inferior frontal cortex (IFC) provides the first evidence that damage to this brain region impairs temporal performance in a visual time reproduction task in which participants had to reproduce the presentation duration (3, 5 and 7s) of emotionally-neutral and -negative pictures. Strikingly, as compared to a group of healthy subjects, the AIC/IFC case considerably overestimated reproduction times despite normal variability. The effect was obtained in all duration and emotion conditions. Such a distortion in time reproduction was not observed in four other epileptic patients without insular or inferior frontal damage. Importantly, the absolute extent of temporal over-reproduction increased in proportion to the magnitude of the target durations, which concurs with the scalar property of interval timing, and points to an impairment of time-specific rather than of non temporal (such as motor) mechanisms. Our data suggest that the disability in temporal reproduction of the AIC/IFC case would result from a distorted memory representation of the encoded duration, occurring during the process of storage and/or of recovery from memory and leading to a deviation of the temporal judgment during the reproduction task. These findings support the recent proposal that the anterior insular/inferior frontal cortices would be involved in time interval representation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Human behavior and opportunities for parasite transmission in communities surrounding long-tailed macaque populations in Bali, Indonesia.

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Lane-DeGraaf, Kelly E; Putra, I G A Arta; Wandia, I Nengah; Rompis, Aida; Hollocher, Hope; Fuentes, Agustin

2014-02-01

Spatial overlap and shared resources between humans and wildlife can exacerbate parasite transmission dynamics. In Bali, Indonesia, an agricultural-religious temple system provides sanctuaries for long-tailed macaques (Macaca fascicularis), concentrating them in areas in close proximity to humans. In this study, we interviewed individuals in communities surrounding 13 macaque populations about their willingness to participate in behaviors that would put them at risk of exposure to gastrointestinal parasites to understand if age, education level, or occupation are significant determinants of exposure behaviors. These exposure risk behaviors and attitudes include fear of macaques, direct contact with macaques, owning pet macaques, hunting and eating macaques, and overlapping water uses. We find that willingness to participate in exposure risk behaviors are correlated with an individual's occupation, age, and/or education level. We also found that because the actual risk of infection varies across populations, activities such as direct macaque contact and pet ownership, could be putting individuals at real risk in certain contexts. Thus, we show that human demographics and social structure can influence willingness to participate in behaviors putting them at increased risk for exposure to parasites. © 2013 Wiley Periodicals, Inc.

Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

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Kevin R McCarthy

Full Text Available In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm. Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac and pig-tailed macaques (SIVmne have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

Phylogeny and History of the Lost SIV from Crab-Eating Macaques: SIVmfa.

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McCarthy, Kevin R; Johnson, Welkin E; Kirmaier, Andrea

2016-01-01

In the 20th century, thirteen distinct human immunodeficiency viruses emerged following independent cross-species transmission events involving simian immunodeficiency viruses (SIV) from African primates. In the late 1900s, pathogenic SIV strains also emerged in the United Sates among captive Asian macaque species following their unintentional infection with SIV from African sooty mangabeys (SIVsmm). Since their discovery in the 1980s, SIVs from rhesus macaques (SIVmac) and pig-tailed macaques (SIVmne) have become invaluable models for studying HIV pathogenesis, vaccine design and the emergence of viruses. SIV isolates from captive crab-eating macaques (SIVmfa) were initially described but lost prior to any detailed molecular and genetic characterization. In order to infer the origins of the lost SIVmfa lineage, we located archived material and colony records, recovered its genomic sequence by PCR, and assessed its phylogenetic relationship to other SIV strains. We conclude that SIVmfa is the product of two cross-species transmission events. The first was the established transmission of SIVsmm to rhesus macaques, which occurred at the California National Primate Research Center in the late 1960s and the virus later emerged as SIVmac. In a second event, SIVmac was transmitted to crab-eating macaques, likely at the Laboratory for Experimental Medicine and Surgery in Primates in the early 1970s, and it was later spread to the New England Primate Research Center colony in 1973 and eventually isolated in 1986. Our analysis suggests that SIVmac had already emerged by the early 1970s and had begun to diverge into distinct lineages. Furthermore, our findings suggest that pathogenic SIV strains may have been more widely distributed than previously appreciated, raising the possibility that additional isolates may await discovery.

A single gp120 residue can affect HIV-1 tropism in macaques.

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Gregory Q Del Prete

2017-09-01

Full Text Available Species-dependent variation in proteins that aid or limit virus replication determines the ability of lentiviruses to jump between host species. Identifying and overcoming these differences facilitates the development of animal models for HIV-1, including models based on chimeric SIVs that express HIV-1 envelope (Env glycoproteins, (SHIVs and simian-tropic HIV-1 (stHIV strains. Here, we demonstrate that the inherently poor ability of most HIV-1 Env proteins to use macaque CD4 as a receptor is improved during adaptation by virus passage in macaques. We identify a single amino acid, A281, in HIV-1 Env that consistently changes during adaptation in macaques and affects the ability of HIV-1 Env to use macaque CD4. Importantly, mutations at A281 do not markedly affect HIV-1 Env neutralization properties. Our findings should facilitate the design of HIV-1 Env proteins for use in non-human primate models and thus expedite the development of clinically relevant reagents for testing interventions against HIV-1.

No costly prosociality among related long-tailed macaques (Macaca fascicularis).

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Sterck, Elisabeth H M; Olesen, Caroline U; Massen, Jorg J M

2015-08-01

Altruism, benefiting another at a cost to the donor, may be achieved through prosocial behavior. Studies of nonhuman animals typically investigate prosocial behavior with paradigms in which the donor can choose to give a recipient a food item, and the choice does not affect the donor's reward (which is either present or absent). In such tasks, long-tailed macaques (Macaca fascicularis) show prosocial behavior, especially toward kin. Here, we tested captive long-tailed macaques with related recipients in an alternative task, in which the donor had to give up a preferred reward to benefit the recipient; that is, they had to choose a lower valued reward for themselves to provide food to their kin. Overall, the macaques did not provide their kin with food. The task forced the donor to balance its prosocial behavior with its selfish choice for a higher value reward, a balance that turned out to favor selfish motives. Consequently, our study shows that a prosocial tendency is not sufficient to elicit costly prosocial behavior in long-tailed macaques. Subsequently, we feel that tasks in which the donor must choose a lower value reward to benefit another individual may allow the titration of the strength of prosocial behavior, and thus provides interesting possibilities for future comparative studies. (c) 2015 APA, all rights reserved).

A preference for mathematical processing outweighs the selectivity for Arabic numbers in the inferior temporal gyrus.

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Grotheer, Mareike; Jeska, Brianna; Grill-Spector, Kalanit

2018-03-28

A region in the posterior inferior temporal gyrus (ITG), referred to as the number form area (NFA, here ITG-numbers) has been implicated in the visual processing of Arabic numbers. However, it is unknown if this region is specifically involved in the visual encoding of Arabic numbers per se or in mathematical processing more broadly. Using functional magnetic resonance imaging (fMRI) during experiments that systematically vary tasks and stimuli, we find that mathematical processing, not preference to Arabic numbers, consistently drives both mean and distributed responses in the posterior ITG. While we replicated findings of higher responses in ITG-numbers to numbers than other visual stimuli during a 1-back task, this preference to numbers was abolished when participants engaged in mathematical processing. In contrast, an ITG region (ITG-math) that showed higher responses during an adding task vs. other tasks maintained this preference for mathematical processing across a wide range of stimuli including numbers, number/letter morphs, hands, and dice. Analysis of distributed responses across an anatomically-defined posterior ITG expanse further revealed that mathematical task but not Arabic number form can be successfully and consistently decoded from these distributed responses. Together, our findings suggest that the function of neuronal regions in the posterior ITG goes beyond the specific visual processing of Arabic numbers. We hypothesize that they ascribe numerical content to the visual input, irrespective of the format of the stimulus. Copyright © 2018 Elsevier Inc. All rights reserved.

Diversity and molecular phylogeny of mitochondrial DNA of rhesus macaques (Macaca mulatta) in Bangladesh.

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Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Kanthaswamy, Sree; Smith, David Glenn

2014-11-01

While studies of rhesus macaques (Macaca mulatta) in the eastern (e.g., China) and western (e.g., India) parts of their geographic range have revealed major genetic differences that warrant the recognition of two different subspecies, little is known about genetic characteristics of rhesus macaques in the transitional zone extending from eastern India and Bangladesh through the northern part of Indo-China, the probable original homeland of the species. We analyzed genetic variation of 762 base pairs of mitochondrial DNA from 86 fecal swab samples and 19 blood samples from 25 local populations of rhesus macaque in Bangladesh collected from January 2010 to August 2012. These sequences were compared with those of rhesus macaques from India, China, and Myanmar. Forty-six haplotypes defined by 200 (26%) polymorphic nucleotide sites were detected. Estimates of gene diversity, expected heterozygosity, and nucleotide diversity for the total population were 0.9599 ± 0.0097, 0.0193 ± 0.0582, and 0.0196 ± 0.0098, respectively. A mismatch distribution of paired nucleotide differences yielded a statistically significantly negative value of Tajima's D, reflecting a population that rapidly expanded after the terminal Pleistocene. Most haplotypes throughout regions of Bangladesh, including an isolated region in the southwestern area (Sundarbans), clustered with haplotypes assigned to the minor haplogroup Ind-2 from India reflecting an east to west dispersal of rhesus macaques to India. Haplotypes from the southeast region of Bangladesh formed a cluster with those from Myanmar, and represent the oldest rhesus macaque haplotypes of Bangladesh. These results are consistent with the hypothesis that rhesus macaques first entered Bangladesh from the southeast, probably from Indo-China, then dispersed westward throughout eastern and central India. © 2014 Wiley Periodicals, Inc.

Activation of the left inferior frontal gyrus in the first 200 ms of reading: evidence from magnetoencephalography (MEG).

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Cornelissen, Piers L; Kringelbach, Morten L; Ellis, Andrew W; Whitney, Carol; Holliday, Ian E; Hansen, Peter C

2009-01-01

It is well established that the left inferior frontal gyrus plays a key role in the cerebral cortical network that supports reading and visual word recognition. Less clear is when in time this contribution begins. We used magnetoencephalography (MEG), which has both good spatial and excellent temporal resolution, to address this question. MEG data were recorded during a passive viewing paradigm, chosen to emphasize the stimulus-driven component of the cortical response, in which right-handed participants were presented words, consonant strings, and unfamiliar faces to central vision. Time-frequency analyses showed a left-lateralized inferior frontal gyrus (pars opercularis) response to words between 100-250 ms in the beta frequency band that was significantly stronger than the response to consonant strings or faces. The left inferior frontal gyrus response to words peaked at approximately 130 ms. This response was significantly later in time than the left middle occipital gyrus, which peaked at approximately 115 ms, but not significantly different from the peak response in the left mid fusiform gyrus, which peaked at approximately 140 ms, at a location coincident with the fMRI-defined visual word form area (VWFA). Significant responses were also detected to words in other parts of the reading network, including the anterior middle temporal gyrus, the left posterior middle temporal gyrus, the angular and supramarginal gyri, and the left superior temporal gyrus. These findings suggest very early interactions between the vision and language domains during visual word recognition, with speech motor areas being activated at the same time as the orthographic word-form is being resolved within the fusiform gyrus. This challenges the conventional view of a temporally serial processing sequence for visual word recognition in which letter forms are initially decoded, interact with their phonological and semantic representations, and only then gain access to a speech code.

Polymorphisms of cytochrome P450 2B6 (CYP2B6) in cynomolgus and rhesus macaques.

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Uno, Yasuhiro; Uehara, Shotaro; Yamazaki, Hiroshi

2018-02-22

Cytochrome P450 2B6 (CYP2B6) is an important drug-metabolizing enzyme and is expressed in liver. Although human CYP2B6 variants account for variable enzyme properties among individuals and populations, CYP2B6 genetic variants have not been investigated in cynomolgus macaques, widely used in drug metabolism studies. CYP2B6 was resequenced in 120 cynomolgus macaques and 23 rhesus macaques by direct sequencing. Twenty-three non-synonymous variants were found, of which 12 and 3 were unique to cynomolgus macaques and rhesus macaques, respectively. By functional characterization using the 14 variant proteins, 8 variants (V114I, R253C, M435I, V459M, L465P, C475S, R487C, and R487H) showed different rate (>1.5-fold) of testosterone 16β-hydroxylation to wild type. However, the four variants (M435I, L465P, C475S, and R487H) were analyzed in liver microsomes, and the catalytic rates were not substantially different from wild type. Macaque CYP2B6 was polymorphic, and the genotype could partly account for variable enzyme activities of macaque CYP2B6. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Local anesthetic-induced myotoxicity as a cause of severe trismus after inferior alveolar nerve block.

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Smolka, Wenko; Knoesel, Thomas; Mueller-Lisse, Ullrich

2018-01-01

A case of a 60-year-old man with severe trismus after inferior alveolar nerve block is presented. MRI scans as well as histologic examination revealed muscle fibrosis and degeneration of the medial part of the left temporal muscle due to myotoxicity of a local anesthetic agent.

Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.

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Perigard, Christopher J; Parrula, M Cecilia M; Larkin, Matthew H; Gleason, Carol R

2016-06-01

In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss. © 2016 American Society for Veterinary Clinical Pathology.

Mixed-complexity artificial grammar learning in humans and macaque monkeys: evaluating learning strategies.

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Wilson, Benjamin; Smith, Kenny; Petkov, Christopher I

2015-03-01

Artificial grammars (AG) can be used to generate rule-based sequences of stimuli. Some of these can be used to investigate sequence-processing computations in non-human animals that might be related to, but not unique to, human language. Previous AG learning studies in non-human animals have used different AGs to separately test for specific sequence-processing abilities. However, given that natural language and certain animal communication systems (in particular, song) have multiple levels of complexity, mixed-complexity AGs are needed to simultaneously evaluate sensitivity to the different features of the AG. Here, we tested humans and Rhesus macaques using a mixed-complexity auditory AG, containing both adjacent (local) and non-adjacent (longer-distance) relationships. Following exposure to exemplary sequences generated by the AG, humans and macaques were individually tested with sequences that were either consistent with the AG or violated specific adjacent or non-adjacent relationships. We observed a considerable level of cross-species correspondence in the sensitivity of both humans and macaques to the adjacent AG relationships and to the statistical properties of the sequences. We found no significant sensitivity to the non-adjacent AG relationships in the macaques. A subset of humans was sensitive to this non-adjacent relationship, revealing interesting between- and within-species differences in AG learning strategies. The results suggest that humans and macaques are largely comparably sensitive to the adjacent AG relationships and their statistical properties. However, in the presence of multiple cues to grammaticality, the non-adjacent relationships are less salient to the macaques and many of the humans. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

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J Gerardo García-Lerma

2008-02-01

Full Text Available In the absence of an effective vaccine, HIV continues to spread globally, emphasizing the need for novel strategies to limit its transmission. Pre-exposure prophylaxis (PrEP with antiretroviral drugs could prove to be an effective intervention strategy if highly efficacious and cost-effective PrEP modalities are identified. We evaluated daily and intermittent PrEP regimens of increasing antiviral activity in a macaque model that closely resembles human transmission.We used a repeat-exposure macaque model with 14 weekly rectal virus challenges. Three drug treatments were given once daily, each to a different group of six rhesus macaques. Group 1 was treated subcutaneously with a human-equivalent dose of emtricitabine (FTC, group 2 received orally the human-equivalent dosing of both FTC and tenofovir-disoproxil fumarate (TDF, and group 3 received subcutaneously a similar dosing of FTC and a higher dose of tenofovir. A fourth group of six rhesus macaques (group 4 received intermittently a PrEP regimen similar to group 3 only 2 h before and 24 h after each weekly virus challenge. Results were compared to 18 control macaques that did not receive any drug treatment. The risk of infection in macaques treated in groups 1 and 2 was 3.8- and 7.8-fold lower than in untreated macaques (p = 0.02 and p = 0.008, respectively. All six macaques in group 3 were protected. Breakthrough infections had blunted acute viremias; drug resistance was seen in two of six animals. All six animals in group 4 that received intermittent PrEP were protected.This model suggests that single drugs for daily PrEP can be protective but a combination of antiretroviral drugs may be required to increase the level of protection. Short but potent intermittent PrEP can provide protection comparable to that of daily PrEP in this SHIV/macaque model. These findings support PrEP trials for HIV prevention in humans and identify promising PrEP modalities.

Diffusion tensor imaging study of the temporal stem in Alzheimer's disease

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Yue WANG

2014-03-01

Full Text Available Objective To study the changes of fractional anisotropy (FA value of white matter of brain and temporal stem in Alzheimer's disease (AD and amnestic mild cognitive impairment (aMCI patients as well as normal cognitive (NC aged people with diffusion tensor imaging (DTI, and explore the damage mechanism of temporal stem and its diagnostic value on AD and aMCI. Methods Ten patients with AD, 10 patients with aMCI and 10 NC volunteers as control group were scanned by routine MRI and DTI. FA values were calculated by post-processing software (DTIstudio in temporal stem (including anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus, and white matter in anterior frontal, temperal, parietal and occipital lobes. The data were analyzed by SPSS 13.0. If bilateral differences of FA values were not statistically significant (P > 0.05, the average values of bilateral FA were selected and compared among 3 groups. If bilateral differences of FA values were statistically significant (P < 0.05, the measurement values were directly compared. Results 1 There was no significantdifference of FA values in bilateral symmetric white matter and temporal stem among AD, aMCI and NC groups (P > 0.05, for all. 2 There was significant difference of FA values in anterior commissure, uncinate fasciculus and inferior occipitofrontal fasciculus between AD and aMCI groups (P < 0.05, for all. 3 There was significant difference of FA values in anterior commissure, uncinate fasciculus, inferior occipitofrontal fasciculus, anterior frontal and parietal lobes between AD and NC groups (P < 0.05, for all. 4 There was no significant difference of FA values in anterior commissure, uncinate fasciculus, inferior occipitofrontal fasciculus, anterior frontal lobe between aMCI and NC groups (P > 0.05, for all. Conclusions The significant difference of FA values in temporal stem among AD, aMCI and NC groups suggests that temporal stem fiber bundles are of great

New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

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Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

2015-08-01

A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

Nontraumatic temporal subcortical hemorrhage

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Weisberg, L.A.; Stazio, A.; Shamsnia, M.; Elliott, D.; Charity Hospital, New Orleans, LA

1990-01-01

Thirty patients with temporal hematomas were analyzed. Four with frontal extension survived. Of 6 with ganglionic extension, three had residual deficit. Of 8 with parietal extension, 4 had delayed deterioration and died, two patients recovered, and two with peritumoral hemorrhage due to glioblastoma multiforme died. Five patients with posterior temporal hematomas recovered. In 7 patients with basal-inferior temporal hematomas, angiography showed aneurysms in 3 cases, angiomas in 2 cases and no vascular lesion in 2 cases. Of 23 cases with negative angiography and no systemic cause for temporal hematoma, 12 patients were hypertensive and 11 were normotensive. Ten hypertensive patients without evidence of chronic vascular disease had the largest hematomas, extending into the parietal or ganglionic regions. Seven of these patients died; 3 had residual deficit. Eleven normotensive and two hypertensive patients with evidence of chronic vascular change had smaller hematomas. They survived with good functional recovery. (orig.)

Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells.

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Meng, Weixu; Li, Leike; Xiong, Wei; Fan, Xuejun; Deng, Hui; Bett, Andrew J; Chen, Zhifeng; Tang, Aimin; Cox, Kara S; Joyce, Joseph G; Freed, Daniel C; Thoryk, Elizabeth; Fu, Tong-Ming; Casimiro, Danilo R; Zhang, Ningyan; A Vora, Kalpit; An, Zhiqiang

2015-01-01

Nonhuman primates (NHPs) are used as a preclinical model for vaccine development, and the antibody profiles to experimental vaccines in NHPs can provide critical information for both vaccine design and translation to clinical efficacy. However, an efficient protocol for generating monoclonal antibodies from single antibody secreting cells of NHPs is currently lacking. In this study we established a robust protocol for cloning immunoglobulin (IG) variable domain genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A sorting strategy was developed using a panel of molecular markers (CD3, CD19, CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the kinetics of B cell response after vaccination. Specific primers for the rhesus macaque IG genes were designed and validated using cDNA isolated from macaque peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335) were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the cloned antibodies. The protocol was tested in a study using an experimental dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from the vaccinated rhesus macaques react with the dengue vaccine antigens. These results validate the protocol for cloning monoclonal antibodies in response to vaccination from single macaque antibody secreting cells, which have general applicability for determining monoclonal antibody profiles in response to other immunogens or vaccine studies of interest in NHPs.

Project Lifescape - The Macaques of India

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 6; Issue 9. Project Lifescape - The Macaques of India. Anindya Sinha. Classroom Volume 6 Issue 9 September 2001 pp 94-105. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/006/09/0094-0105 ...

Effects of Transportation on Antioxidant Status in Cynomolgus Macaques (Macaca fascicularis).

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Pan, Xueying; Lu, Liang; Zeng, Xiancheng; Chang, Yan; Hua, Xiuguo

2016-01-01

To evaluate the effects of transportation on oxidative stress in cynomolgus monkeys, we measured serum levels of reduced glutathione (GSH), malondialdehyde, and protein carbonyl (PC) and the activities of total antioxidant capacity (TAOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase in cynomolgus macaques before transportation (day 0), on the day of arrival (day 1), and on days 7, 14, and 21 after transportation. Compared with that on day 0, TAOC and catalase activities on days 1, 7, and 14 after transportation were significantly decreased, reached their nadirs on day 7, and increased thereafter to reach their pretransportation levels by day 21 after transportation. Compared with day 0 levels, mean SOD activity and GSH concentration were decreased significantly on day 1; they thereafter increased to reach their pretransportation measures by day 7 after transportation. In contrast, PC and malondialdehyde concentrations in serum and the activity of GSH-Px were increased on day 1 compared with day 0 and thereafter decreased to reach their pretransportation levels by day 14 after transportation. In summary, GSH, TAOC, catalase, and SOD levels decreased and malondialdehyde, PC, and GSH-Px concentrations increased in cynomolgus macaques after transportation. These results suggest that transportation might imbalance oxidant and antioxidant levels to create excess oxidative stress in cynomolgus macaques. Therefore, cynomolgus macaques should have at least 21 d to recover after transportation and regain their healthy status.

X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

International Nuclear Information System (INIS)

Feng, Youjun; Qi, Jianxun; Zhang, Huimin; Wang, Jinzi; Liu, Jinhua; Jiang, Fan; Gao, Feng

2005-01-01

X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β 2 m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides

X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide

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Feng, Youjun [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Graduate School, Chinese Academy of Sciences, Beijing (China); Qi, Jianxun [Graduate School, Chinese Academy of Sciences, Beijing (China); Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Zhang, Huimin; Wang, Jinzi [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); Liu, Jinhua [College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China); Jiang, Fan [Institute of Physics, Chinese Academy of Sciences, Beijing 100080 (China); Gao, Feng, E-mail: gaofeng@im.ac.cn [Laboratory of Molecular Immunology and Molecular Virology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080 (China); College of Veterinary Medicine, China Agricultural University, Beijing 100094 (China)

2006-01-01

X-ray crystallographic characterization of rhesus macaque MHC Mamu-A*02 complexed with an immunodominant SIV-Gag nonapeptide. Simian immunodeficiency virus (SIV) in the rhesus macaque is regarded as a classic animal model, playing a crucial role in HIV vaccine strategies and therapeutics by characterizing various cytotoxic T-lymphocyte (CTL) responses in macaque monkeys. However, the availability of well documented structural reports focusing on rhesus macaque major histocompatibility complex class I (MHC I) molecules remains extremely limited. Here, a complex of the rhesus macaque MHC I molecule (Mamu-A*02) with human β{sub 2}m and an immunodominant SIV-Gag nonapeptide, GESNLKSLY (GY9), has been crystallized. The crystal diffracts X-rays to 2.7 Å resolution and belongs to space group C2, with unit-cell parameters a = 124.11, b = 110.45, c = 100.06 Å, and contains two molecules in the asymmetric unit. The availability of the structure, which is being solved by molecular replacement, will provide new insights into rhesus macaque MHC I (Mamu-A*02) presenting pathogenic SIV peptides.

Social interactions through the eyes of macaques and humans.

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Richard McFarland

Full Text Available Group-living primates frequently interact with each other to maintain social bonds as well as to compete for valuable resources. Observing such social interactions between group members provides individuals with essential information (e.g. on the fighting ability or altruistic attitude of group companions to guide their social tactics and choice of social partners. This process requires individuals to selectively attend to the most informative content within a social scene. It is unclear how non-human primates allocate attention to social interactions in different contexts, and whether they share similar patterns of social attention to humans. Here we compared the gaze behaviour of rhesus macaques and humans when free-viewing the same set of naturalistic images. The images contained positive or negative social interactions between two conspecifics of different phylogenetic distance from the observer; i.e. affiliation or aggression exchanged by two humans, rhesus macaques, Barbary macaques, baboons or lions. Monkeys directed a variable amount of gaze at the two conspecific individuals in the images according to their roles in the interaction (i.e. giver or receiver of affiliation/aggression. Their gaze distribution to non-conspecific individuals was systematically varied according to the viewed species and the nature of interactions, suggesting a contribution of both prior experience and innate bias in guiding social attention. Furthermore, the monkeys' gaze behavior was qualitatively similar to that of humans, especially when viewing negative interactions. Detailed analysis revealed that both species directed more gaze at the face than the body region when inspecting individuals, and attended more to the body region in negative than in positive social interactions. Our study suggests that monkeys and humans share a similar pattern of role-sensitive, species- and context-dependent social attention, implying a homologous cognitive mechanism of

Cabotegravir long acting injection protects macaques against intravenous challenge with SIVmac251.

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Andrews, Chasity D; Bernard, Leslie St; Poon, Amanda Yee; Mohri, Hiroshi; Gettie, Natanya; Spreen, William R; Gettie, Agegnehu; Russell-Lodrigue, Kasi; Blanchard, James; Hong, Zhi; Ho, David D; Markowitz, Martin

2017-02-20

We evaluated the effectiveness of cabotegravir (CAB; GSK1265744 or GSK744) long acting as preexposure prophylaxis (PrEP) against intravenous simian immunodeficiency virus (SIV) challenge in a model that mimics blood transfusions based on the per-act probability of infection. CAB long acting is an integrase strand transfer inhibitor formulated as a 200 mg/ml injectable nanoparticle suspension that is an effective PrEP agent against rectal and vaginal simian/human immunodeficiency virus transmission in macaques. Three groups of rhesus macaques (n = 8 per group) were injected intramuscularly with CAB long acting and challenged intravenously with 17 animal infectious dose 50% SIVmac251 on week 2. Group 1 was injected with 50 mg/kg on week 0 and 4 to evaluate the protective efficacy of the CAB long-acting dose used in macaque studies mimicking sexual transmission. Group 2 was injected with 50 mg/kg on week 0 to evaluate the necessity of the second injection of CAB long acting for protection against intravenous challenge. Group 3 was injected with 25 mg/kg on week 0 and 50 mg/kg on week 4 to correlate CAB plasma concentrations at the time of challenge with protection. Five additional macaques remained untreated as controls. CAB long acting was highly protective with 21 of the 24 CAB long-acting-treated macaques remaining aviremic, resulting in 88% protection. The plasma CAB concentration at the time of virus challenge appeared to be more important for protection than sustaining therapeutic plasma concentrations with the second CAB long acting injection. These results support the clinical investigation of CAB long acting as PrEP in people who inject drugs.

Delineating the Macroscale Areal Organization of the Macaque Cortex In Vivo

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Ting Xu

2018-04-01

Full Text Available Summary: Complementing long-standing traditions centered on histology, fMRI approaches are rapidly maturing in delineating brain areal organization at the macroscale. The non-human primate (NHP provides the opportunity to overcome critical barriers in translational research. Here, we establish the data requirements for achieving reproducible and internally valid parcellations in individuals. We demonstrate that functional boundaries serve as a functional fingerprint of the individual animals and can be achieved under anesthesia or awake conditions (rest, naturalistic viewing, though differences between awake and anesthetized states precluded the detection of individual differences across states. Comparison of awake and anesthetized states suggested a more nuanced picture of changes in connectivity for higher-order association areas, as well as visual and motor cortex. These results establish feasibility and data requirements for the generation of reproducible individual-specific parcellations in NHPs, provide insights into the impact of scan state, and motivate efforts toward harmonizing protocols. : Noninvasive fMRI in macaques is an essential tool in translation research. Xu et al. establish the individual functional parcellation of the macaque cortex and demonstrate that brain organization is unique, reproducible, and valid, serving as a fingerprint for an individual macaque. Keywords: macaque, parcellation, cortical areas, gradient, functional connectivity

Interindividual Differences in Neonatal Imitation and the Development of Action Chains in Rhesus Macaques

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Ferrari, Pier Francesco; Paukner, Annika; Ruggiero, Angela; Darcey, Lisa; Unbehagen, Sarah; Suomi, Stephen J.

2009-01-01

The capacity to imitate facial gestures is highly variable in rhesus macaques and this variability may be related to differences in specific neurobehavioral patterns of development. This study evaluated the differential neonatal imitative response of 41 macaques in relation to the development of sensory, motor, and cognitive skills throughout the…

Social management of laboratory rhesus macaques housed in large groups using a network approach: A review.

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McCowan, Brenda; Beisner, Brianne; Hannibal, Darcy

2017-12-07

Biomedical facilities across the nation and worldwide aim to develop cost-effective methods for the reproductive management of macaque breeding groups, typically by housing macaques in large, multi-male multi-female social groups that provide monkey subjects for research as well as appropriate socialization for their psychological well-being. One of the most difficult problems in managing socially housed macaques is their propensity for deleterious aggression. From a management perspective, deleterious aggression (as opposed to less intense aggression that serves to regulate social relationships) is undoubtedly the most problematic behavior observed in group-housed macaques, which can readily escalate to the degree that it causes social instability, increases serious physical trauma leading to group dissolution, and reduces psychological well-being. Thus for both welfare and other management reasons, aggression among rhesus macaques at primate centers and facilities needs to be addressed with a more proactive approach.Management strategies need to be instituted that maximize social housing while also reducing problematic social aggression due to instability using efficacious methods for detection and prevention in the most cost effective manner. Herein we review a new proactive approach using social network analysis to assess and predict deleterious aggression in macaque groups. We discovered three major pathways leading to instability, such as unusually high rates and severity of trauma and social relocations.These pathways are linked either directly or indirectly to network structure in rhesus macaque societies. We define these pathways according to the key intrinsic and extrinsic variables (e.g., demographic, genetic or social factors) that influence network and behavioral measures of stability (see Fig. 1). They are: (1) presence of natal males, (2) matrilineal genetic fragmentation, and (3) the power structure and conflict policing behavior supported by this

Temporal and occipital lobe features in children with hypochondroplasia/FGFR3 gene mutation.

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Philpott, Cristina M; Widjaja, Elysa; Raybaud, Charles; Branson, Helen M; Kannu, Peter; Blaser, Susan

2013-09-01

Thanatophoric dysplasia (TD) and hypochondroplasia are both caused by FGFR3 (fibroblast growth factor receptor 3) gene mutations. Temporal lobe dysplasia has been well described in thanatophoric dysplasia; however, only a couple of anecdotal cases of temporal lobe dysplasia in hypochondroplasia have been described. To define temporal lobe abnormalities in patients with hypochondroplasia, given that they share the same genetic mutation. We identified brain imaging studies of nine children with hypochondroplasia. The temporal lobes were assessed on CT and MRI for size and configuration of the temporal horn and aberrant sulcation of the inferior surface of the temporal lobe. All children had a triangular-shape temporal horn and deep transverse fissures of the inferior temporal lobe surface. Neuroimaging in our cohort revealed enlarged temporal lobes and oversulcation of the mesial temporal and occipital lobes, with abnormal inferomedial orientation of these redundant gyri. Hippocampal dysplasia was also universal. We confirmed frequent inferomesial temporal and occipital lobe abnormalities in our cohort of children with hypochondroplasia. Murine models with mutant fgfr3 display increased neuroprogenitor proliferation, cortical thickness and surface area in the temporo-occipital cortex. This is thought to result in excessive convolution and likely explains the imaging findings in this patient cohort. (Note that fgfr3 is the same genetic mutation in mice as FGFR3 is in humans.).

The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human

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Yuan Qiaoping

2012-06-01

Full Text Available Abstract Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. Results We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs per individual in macaques than in humans, the ratio of dN/dS is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen-2 prediction in the macaque is more

Topical tenofovir protects against vaginal simian HIV infection in macaques coinfected with Chlamydia trachomatis and Trichomonas vaginalis.

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Makarova, Natalia; Henning, Tara; Taylor, Andrew; Dinh, Chuong; Lipscomb, Jonathan; Aubert, Rachael; Hanson, Debra; Phillips, Christi; Papp, John; Mitchell, James; McNicholl, Janet; Garcia-Lerma, Gerardo J; Heneine, Walid; Kersh, Ellen; Dobard, Charles

2017-03-27

Chlamydia trachomatis and Trichomonas vaginalis, two prevalent sexually transmitted infections, are known to increase HIV risk in women and could potentially diminish preexposure prophylaxis efficacy, particularly for topical interventions that rely on local protection. We investigated in macaques whether coinfection with Chlamydia trachomatis/Trichomonas vaginalis reduces protection by vaginal tenofovir (TFV) gel. Vaginal TFV gel dosing previously shown to provide 100 or 74% protection when applied either 30 min or 3 days before simian HIV(SHIV) challenge was assessed in pigtailed macaques coinfected with Chlamydia trachomatis/Trichomonas vaginalis and challenged twice weekly with SHIV162p3 for up to 10 weeks (two menstrual cycles). Three groups of six macaques received either placebo or 1% TFV gel 30 min or 3 days before each SHIV challenge. We additionally assessed TFV and TFV diphosphate concentrations in plasma and vaginal tissues in Chlamydia trachomatis/Trichomonas vaginalis coinfected (n = 4) and uninfected (n = 4) macaques. Chlamydia trachomatis/Trichomonas vaginalis coinfections were maintained during the SHIV challenge period. All macaques that received placebo gel were SHIV infected after a median of seven challenges (one menstrual cycle). In contrast, no infections were observed in macaques treated with TFV gel 30 min before SHIV challenge (P vaginal lymphocytes were significantly higher in Chlamydia trachomatis/Trichomonas vaginalis coinfected compared with Chlamydia trachomatis/Trichomonas vaginalis uninfected macaques. Our findings in this model suggest that Chlamydia trachomatis/Trichomonas vaginalis coinfection may have little or no impact on the efficacy of highly effective topical TFV modalities and highlight a significant modulation of TFV pharmacokinetics.

Complications after mesial temporal lobe surgery via inferiortemporal gyrus approach.

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Vale, Fernando L; Reintjes, Stephen; Garcia, Hermes G

2013-06-01

The purpose of this study was to identify the complications associated with the inferior temporal gyrus approach to anterior mesial temporal lobe resection for temporal lobe epilepsy. This retrospective study examined complications experienced by 483 patients during the 3 months after surgery. All surgeries were performed during 1998-2012 by the senior author (F.L.V.). A total of 13 complications (2.7%) were reported. Complications were 8 delayed subdural hematomas (1.6%), 2 superficial wound infections (0.4%), 1 delayed intracranial hemorrhage (0.2%), 1 small lacunar stroke (0.2%), and 1 transient frontalis nerve palsy (0.2%). Three patients with subdural hematoma (0.6%) required readmission and surgical intervention. One patient (0.2%) with delayed intracranial hemorrhage required readmission to the neuroscience intensive care unit for observation. No deaths or severe neurological impairments were reported. Among the 8 patients with subdural hematoma, 7 were older than 40 years (87.5%); however, this finding was not statistically significant (p = 0.198). The inferior temporal gyrus approach to mesial temporal lobe resection is a safe and effective method for treating temporal lobe epilepsy. Morbidity and mortality rates associated with this procedure are lower than those associated with other neurosurgical procedures. The finding that surgical complications seem to be more common among older patients emphasizes the need for early surgical referral of patients with medically refractory epilepsy.

Diet of the Assamese macaque Macaca assamensis in lime-stone habitats of Nonggang, China

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Qihai ZHOU, Hua WEI, Zhonghao HUANG, Chengming HUANG

2011-02-01

Full Text Available To enhance our understanding of dietary adaptations in macaques we studied the diet of the Assamese macaque Macaca assamensis in limestone seasonal rain forests at Nonggang Nature Reserve, China from September 2005 to August 2006. Our results show that although macaques fed on many plant species, 85.2% of the diet came from only 12 species, of which a bamboo species, Indocalamus calcicolus contributed to 62% of the diet. Young leaves were staple food items (74.1% of the diet for Assamese macaques at Nonggang, and constituted the bulk of monthly diets almost year-round, ranging from 44.9% (July to 92.9% (May. Young parts of Indocalamus calcicolus unexpanded leaves contributed to a large proportion of the young leaf diet in most months. Fruit accounted for only 17.4% of the diet, with a peak of consumption in July. We suggest that this highly folivorous diet may be related to the long lean season of fruit availability in limestone habitats as well as the utilization of cliffs of low fruit availability [Current Zoology 57 (1: 18–25, 2011].

Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques

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Kai-tao Hu

2015-04-01

Conclusions: Rhesus macaques can be used as animal models of bacterial vaginosis to develop drugs and test treatment efficacy. Furthermore, the topical application of sucrose gel induced the shifting of vaginal flora of rhesus macaques from a BV kind of flora to a lactobacilli-dominating flora.

Behavioral and anatomical consequences of early versus late symbol training in macaques.

Science.gov (United States)

Srihasam, Krishna; Mandeville, Joseph B; Morocz, Istvan A; Sullivan, Kevin J; Livingstone, Margaret S

2012-02-09

Distinct brain regions, reproducible from one person to the next, are specialized for processing different kinds of human expertise, such as face recognition and reading. Here, we explore the relationship between age of learning, learning ability, and specialized brain structures. Specifically, we ask whether the existence of reproducible cortical domains necessarily means that certain abilities are innate, or innately easily learned, or whether reproducible domains can be formed, or refined, by interactions between genetic programs and common early experience. Functional MRI showed that intensive early, but not late, experience caused the formation of category-selective regions in macaque temporal lobe for stimuli never naturally encountered by monkeys. And behaviorally, early training produced more fluent processing of these stimuli than the same training in adults. One explanation for these results is that in higher cortical areas, as in early sensory areas, experience drives functional clustering and functional clustering determines how that information is processed. Copyright © 2012 Elsevier Inc. All rights reserved.

Crisis del lóbulo temporal registrada mediante magnetoencefalografía: caso clínico Temporal lobe seizure recorded by magnetoencephalography: case report

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Carlos Amo

2004-09-01

Full Text Available La localización del inicio de las crisis es un factor importante para la evaluación prequirúrgica de la epilepsia. En este trabajo se describe la localización del inicio de una crisis registrada mediante magnetoencefalografía (MEG en un niño de 12 años que presenta crisis parciales complejas farmacorresistentes. La RM muestra una lesión de 20mm de diámetro en el hipocampo izquierdo. EEG de superficie con ondas theta temporales izquierdas. Registro MEG interictal con punta-onda aislada posterior e inferior a la lesión de la RM. Registro MEG ictal con punta-onda (2 Hz. La localización de los dipolos indica el inicio de la crisis en la circunvolución temporal inferior en la misma localización que la actividad interictal MEG. Esta actividad ictal se propaga bilateralmente a áreas frontales. El registro corticográfico intraquirúrgico confirma los resultados de la localización interictal mediante MEG.Ictal onset localization is a important factor in presurgical evaluation of epilepsy. This paper describes the localization of a seizure onset recorded by magnetoencephalography (MEG from a 12-year-old male patient who suffered from complex partial drug-resistant seizures. MRI revealed a 20mm diameter lesion located in left hippocampus. Scalp EEG showed left temporal theta waves. Interictal MEG registrations detected isolated spike-wave activity posterior and inferior to the MRI lesion. Ictal MEG showed continuous spike-wave activity (2 Hz. Dipole localization sited seizure onset in the inferior left temporal gyrus, the same localization of the interictal MEG activity. This ictal activity spreads bilaterally to frontal areas. Intrasurgical electrocorticography recording confirmed interictal MEG results.

Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques.

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Hu, Kai-tao; Zheng, Jin-xin; Yu, Zhi-jian; Chen, Zhong; Cheng, Hang; Pan, Wei-guang; Yang, Wei-zhi; Wang, Hong-yan; Deng, Qi-wen; Zeng, Zhong-ming

2015-04-01

Sucrose gel was used to treat bacterial vaginosis in a phase III clinical trial. However, the changes of vaginal flora after treatment were only examined by Nugent score in that clinical trial, While the vaginal microbiota of rhesus macaques is characterized by anaerobic, Gram-negative bacteria, few lactobacilli, and pH levels above 4.6, similar to the microbiota of patients with bacterial vaginosis. This study is aimed to investigate the change of the vaginal microbiota of rehsus macaques after topical use of sucrose gel to reveal more precisely the bacterial population shift after the topical application of sucrose gel. Sixteen rhesus macaques were treated with 0.5 g sucrose gel vaginally and three with 0.5 g of placebo gel. Vaginal swabs were collected daily following treatment. Vaginal pH levels and Nugent scores were recorded. The composition of the vaginal micotbiota was tested by V3∼V4 16S rDNA metagenomic sequencing. Dynamic changes in the Lactobacillus genus were analyzed by qPCR. The vaginal microbiota of rhesus macaques are dominated by anaerobic Gram-negative bacteria, with few lactobacilli and high pH levels above 4.6. After five days' treatment with topical sucrose gel, the component percentage of Lactobacillus in vaginal microbiota increased from 1.31% to 81.59%, while the component percentage of Porphyromonas decreased from 18.60% to 0.43%, Sneathia decreased from 15.09% to 0.89%, Mobiluncus decreased from 8.23% to 0.12%, etc.. The average vaginal pH values of 16 rhesus macaques of the sucrose gel group decreased from 5.4 to 3.89. There were no significant changes in microbiota and vaginal pH observed in the placebo group. Rhesus macaques can be used as animal models of bacterial vaginosis to develop drugs and test treatment efficacy. Furthermore, the topical application of sucrose gel induced the shifting of vaginal flora of rhesus macaques from a BV kind of flora to a lactobacilli-dominating flora. Copyright © 2015 The Authors. Published by

Molecular and functional aspects of menstruation in the macaque.

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Brenner, Robert M; Slayden, Ov D

2012-12-01

Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

Ranking network of a captive rhesus macaque society: a sophisticated corporative kingdom.

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Fushing, Hsieh; McAssey, Michael P; Beisner, Brianne; McCowan, Brenda

2011-03-15

We develop a three-step computing approach to explore a hierarchical ranking network for a society of captive rhesus macaques. The computed network is sufficiently informative to address the question: Is the ranking network for a rhesus macaque society more like a kingdom or a corporation? Our computations are based on a three-step approach. These steps are devised to deal with the tremendous challenges stemming from the transitivity of dominance as a necessary constraint on the ranking relations among all individual macaques, and the very high sampling heterogeneity in the behavioral conflict data. The first step simultaneously infers the ranking potentials among all network members, which requires accommodation of heterogeneous measurement error inherent in behavioral data. Our second step estimates the social rank for all individuals by minimizing the network-wide errors in the ranking potentials. The third step provides a way to compute confidence bounds for selected empirical features in the social ranking. We apply this approach to two sets of conflict data pertaining to two captive societies of adult rhesus macaques. The resultant ranking network for each society is found to be a sophisticated mixture of both a kingdom and a corporation. Also, for validation purposes, we reanalyze conflict data from twenty longhorn sheep and demonstrate that our three-step approach is capable of correctly computing a ranking network by eliminating all ranking error.

Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

Science.gov (United States)

Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

2016-01-01

Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

Ranking network of a captive rhesus macaque society: a sophisticated corporative kingdom.

Directory of Open Access Journals (Sweden)

Hsieh Fushing

2011-03-01

Full Text Available We develop a three-step computing approach to explore a hierarchical ranking network for a society of captive rhesus macaques. The computed network is sufficiently informative to address the question: Is the ranking network for a rhesus macaque society more like a kingdom or a corporation? Our computations are based on a three-step approach. These steps are devised to deal with the tremendous challenges stemming from the transitivity of dominance as a necessary constraint on the ranking relations among all individual macaques, and the very high sampling heterogeneity in the behavioral conflict data. The first step simultaneously infers the ranking potentials among all network members, which requires accommodation of heterogeneous measurement error inherent in behavioral data. Our second step estimates the social rank for all individuals by minimizing the network-wide errors in the ranking potentials. The third step provides a way to compute confidence bounds for selected empirical features in the social ranking. We apply this approach to two sets of conflict data pertaining to two captive societies of adult rhesus macaques. The resultant ranking network for each society is found to be a sophisticated mixture of both a kingdom and a corporation. Also, for validation purposes, we reanalyze conflict data from twenty longhorn sheep and demonstrate that our three-step approach is capable of correctly computing a ranking network by eliminating all ranking error.

Survey of prevalence of overweight body condition in laboratory-housed cynomolgus macaques (Macaca fascicularis).

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Bauer, Sharon A; Leslie, Ken E; Pearl, David L; Fournier, Jocelyn; Turner, Patricia V

2010-07-01

Excessive weight gain has been reported to occur in captive cynomolgus macaques with little to no change in diet. Overweight body condition can result in development of hyperglycemia and type 2 diabetes and should be avoided. The purpose of this survey was to assess the prevalence of overweight cynomolgus macaques in North American research facilities, including breeding colonies and short-term and long-term facilities, and to describe current methods used to assess body condition. The survey consisted of 51 questions covering animal population demographics, body weight and body condition scoring, feeding, and behavior. Voluntary participants included veterinarians and animal care managers. Respondents from 13 facilities completed the survey, and information was collected on 17,500 cynomolgus macaques. The majority of surveyed facilities housed juvenile and young adult macaques. The reported prevalence of overweight (greater than 10% of ideal body weight) animals ranged between 0% and 20% and reportedly was more frequent in animals younger than 10 y. Most facilities had weight reduction strategies in place. Despite these programs, a significant proportion of animals were reported as being overweight. The results of this survey demonstrate that most North American facilities housing cynomolgus macaques recognize the importance of tracking body condition regularly. However, implementing effective weight reduction programs may be difficult in captive housing environments. Because of the potential for adverse health effects, facilities should have a means of regularly tracking body weight as well as an action plan for managing overweight animals.

Use-Wear Patterns on Wild Macaque Stone Tools Reveal Their Behavioural History

OpenAIRE

Haslam, Michael; Gumert, Michael D.; Biro, Dora; Carvalho, Susana; Malaivijitnond, Suchinda

2013-01-01

Burmese long-tailed macaques (Macaca fascicularis aurea) are one of a limited number of wild animal species to use stone tools, with their tool use focused on pounding shelled marine invertebrates foraged from intertidal habitats. These monkeys exhibit two main styles of tool use: axe hammering of oysters, and pound hammering of unattached encased foods. In this study, we examined macroscopic use-wear patterns on a sample of 60 wild macaque stone tools from Piak Nam Yai Island, Thailand, that...

Effect of feature-selective attention on neuronal responses in macaque area MT

Science.gov (United States)

Chen, X.; Hoffmann, K.-P.; Albright, T. D.

2012-01-01

Attention influences visual processing in striate and extrastriate cortex, which has been extensively studied for spatial-, object-, and feature-based attention. Most studies exploring neural signatures of feature-based attention have trained animals to attend to an object identified by a certain feature and ignore objects/displays identified by a different feature. Little is known about the effects of feature-selective attention, where subjects attend to one stimulus feature domain (e.g., color) of an object while features from different domains (e.g., direction of motion) of the same object are ignored. To study this type of feature-selective attention in area MT in the middle temporal sulcus, we trained macaque monkeys to either attend to and report the direction of motion of a moving sine wave grating (a feature for which MT neurons display strong selectivity) or attend to and report its color (a feature for which MT neurons have very limited selectivity). We hypothesized that neurons would upregulate their firing rate during attend-direction conditions compared with attend-color conditions. We found that feature-selective attention significantly affected 22% of MT neurons. Contrary to our hypothesis, these neurons did not necessarily increase firing rate when animals attended to direction of motion but fell into one of two classes. In one class, attention to color increased the gain of stimulus-induced responses compared with attend-direction conditions. The other class displayed the opposite effects. Feature-selective activity modulations occurred earlier in neurons modulated by attention to color compared with neurons modulated by attention to motion direction. Thus feature-selective attention influences neuronal processing in macaque area MT but often exhibited a mismatch between the preferred stimulus dimension (direction of motion) and the preferred attention dimension (attention to color). PMID:22170961

Comparable cortical activation with inferior performance in women during a novel cognitive inhibition task.

Science.gov (United States)

Halari, R; Kumari, V

2005-03-07

Men are hypothesised to perform better than women at tasks requiring cognitive inhibition. The present study applied whole-brain functional magnetic resonance imaging to investigate the neural correlates of cognitive inhibition using a novel task, requiring detection of numbers decreasing in numerical order, in relation to sex. The study involved 19 young healthy subjects (9 men, 10 women). Behavioural sex differences favouring men were found on the inhibition, but not on the automatization (i.e. detection of numbers increasing in numerical order), condition of the task. Significant areas of activation associated with cognitive inhibition included the right inferior prefrontal and bilateral dorsolateral prefrontal cortices, left inferior and superior parietal lobes, and bilateral temporal regions across men and women. No brain region was significantly differently activated in men and women. Our findings demonstrate that (a) cognitive inhibition is dependent on intact processes within frontal and parietal regions, and (b) women show inferior cognitive inhibition despite of comparable activation to men in relevant regions. Equated behavioural performance may elicit sex differences in brain activation.

Plasmid-Mediated Quinolone Resistance in Shigella flexneri Isolated From Macaques

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Anthony J. Mannion

2018-03-01

Full Text Available Non-human primates (NHPs for biomedical research are commonly infected with Shigella spp. that can cause acute dysentery or chronic episodic diarrhea. These animals are often prophylactically and clinically treated with quinolone antibiotics to eradicate these possible infections. However, chromosomally- and plasmid-mediated antibiotic resistance has become an emerging concern for species in the family Enterobacteriaceae. In this study, five individual isolates of multi-drug resistant Shigella flexneri were isolated from the feces of three macaques. Antibiotic susceptibility testing confirmed resistance or decreased susceptibility to ampicillin, amoxicillin-clavulanic acid, cephalosporins, gentamicin, tetracycline, ciprofloxacin, enrofloxacin, levofloxacin, and nalidixic acid. S. flexneri isolates were susceptible to trimethoprim-sulfamethoxazole, and this drug was used to eradicate infection in two of the macaques. Plasmid DNA from all isolates was positive for the plasmid-encoded quinolone resistance gene qnrS, but not qnrA and qnrB. Conjugation and transformation of plasmid DNA from several S. flexneri isolates into antibiotic-susceptible Escherichia coli strains conferred the recipients with resistance or decreased susceptibility to quinolones and beta-lactams. Genome sequencing of two representative S. flexneri isolates identified the qnrS gene on a plasmid-like contig. These contigs showed >99% homology to plasmid sequences previously characterized from quinolone-resistant Shigella flexneri 2a and Salmonella enterica strains. Other antibiotic resistance genes and virulence factor genes were also identified in chromosome and plasmid sequences in these genomes. The findings from this study indicate macaques harbor pathogenic S. flexneri strains with chromosomally- and plasmid-encoded antibiotic resistance genes. To our knowledge, this is the first report of plasmid-mediated quinolone resistance in S. flexneri isolated from NHPs and warrants

Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques

DEFF Research Database (Denmark)

Yan, Guangmei; Zhang, Guojie; Fang, Xiaodong

2011-01-01

The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus...

Multineuronal vectorization is more efficient than time-segmental vectorization for information extraction from neuronal activities in the inferior temporal cortex.

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Kaneko, Hidekazu; Tamura, Hiroshi; Tate, Shunta; Kawashima, Takahiro; Suzuki, Shinya S; Fujita, Ichiro

2010-08-01

In order for patients with disabilities to control assistive devices with their own neural activity, multineuronal spike trains must be efficiently decoded because only limited computational resources can be used to generate prosthetic control signals in portable real-time applications. In this study, we compare the abilities of two vectorizing procedures (multineuronal and time-segmental) to extract information from spike trains during the same total neuron-seconds. In the multineuronal vectorizing procedure, we defined a response vector whose components represented the spike counts of one to five neurons. In the time-segmental vectorizing procedure, a response vector consisted of components representing a neuron's spike counts for one to five time-segment(s) of a response period of 1 s. Spike trains were recorded from neurons in the inferior temporal cortex of monkeys presented with visual stimuli. We examined whether the amount of information of the visual stimuli carried by these neurons differed between the two vectorizing procedures. The amount of information calculated with the multineuronal vectorizing procedure, but not the time-segmental vectorizing procedure, significantly increased with the dimensions of the response vector. We conclude that the multineuronal vectorizing procedure is superior to the time-segmental vectorizing procedure in efficiently extracting information from neuronal signals. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Topographical gradients of semantics and phonology revealed by temporal lobe stimulation.

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Miozzo, Michele; Williams, Alicia C; McKhann, Guy M; Hamberger, Marla J

2017-02-01

Word retrieval is a fundamental component of oral communication, and it is well established that this function is supported by left temporal cortex. Nevertheless, the specific temporal areas mediating word retrieval and the particular linguistic processes these regions support have not been well delineated. Toward this end, we analyzed over 1000 naming errors induced by left temporal cortical stimulation in epilepsy surgery patients. Errors were primarily semantic (lemon → "pear"), phonological (horn → "corn"), non-responses, and delayed responses (correct responses after a delay), and each error type appeared predominantly in a specific region: semantic errors in mid-middle temporal gyrus (TG), phonological errors and delayed responses in middle and posterior superior TG, and non-responses in anterior inferior TG. To the extent that semantic errors, phonological errors and delayed responses reflect disruptions in different processes, our results imply topographical specialization of semantic and phonological processing. Specifically, results revealed an inferior-to-superior gradient, with more superior regions associated with phonological processing. Further, errors were increasingly semantically related to targets toward posterior temporal cortex. We speculate that detailed semantic input is needed to support phonological retrieval, and thus, the specificity of semantic input increases progressively toward posterior temporal regions implicated in phonological processing. Hum Brain Mapp 38:688-703, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Longitudinal analysis reveals characteristically high proportions of bacterial vaginosis-associated bacteria and temporal variability of vaginal microbiota in northern pig-tailed macaques (Macaca leonina)

OpenAIRE

ZHU, Lin; LEI, Ai-Hua; ZHENG, Hong-Yi; LYU, Long-Bao; ZHANG, Zhi-Gang; ZHENG, Yong-Tang

2015-01-01

The complex and dynamic vaginal microbial ecosystem is critical to both health and disease of the host. Studies focusing on how vaginal microbiota influences HIV-1 infection may face limitations in selecting proper animal models. Given that northern pig-tailed macaques (Macaca leonina) are susceptible to HIV-1 infection, they may be an optimal animal model for elucidating the mechanisms by which vaginal microbiota contributes to resistance and susceptibility to HIV-1 infection. However, littl...

Evolutionary and biomedical insights from the rhesus macaque genome.

Science.gov (United States)

Gibbs, Richard A; Rogers, Jeffrey; Katze, Michael G; Bumgarner, Roger; Weinstock, George M; Mardis, Elaine R; Remington, Karin A; Strausberg, Robert L; Venter, J Craig; Wilson, Richard K; Batzer, Mark A; Bustamante, Carlos D; Eichler, Evan E; Hahn, Matthew W; Hardison, Ross C; Makova, Kateryna D; Miller, Webb; Milosavljevic, Aleksandar; Palermo, Robert E; Siepel, Adam; Sikela, James M; Attaway, Tony; Bell, Stephanie; Bernard, Kelly E; Buhay, Christian J; Chandrabose, Mimi N; Dao, Marvin; Davis, Clay; Delehaunty, Kimberly D; Ding, Yan; Dinh, Huyen H; Dugan-Rocha, Shannon; Fulton, Lucinda A; Gabisi, Ramatu Ayiesha; Garner, Toni T; Godfrey, Jennifer; Hawes, Alicia C; Hernandez, Judith; Hines, Sandra; Holder, Michael; Hume, Jennifer; Jhangiani, Shalini N; Joshi, Vandita; Khan, Ziad Mohid; Kirkness, Ewen F; Cree, Andrew; Fowler, R Gerald; Lee, Sandra; Lewis, Lora R; Li, Zhangwan; Liu, Yih-Shin; Moore, Stephanie M; Muzny, Donna; Nazareth, Lynne V; Ngo, Dinh Ngoc; Okwuonu, Geoffrey O; Pai, Grace; Parker, David; Paul, Heidie A; Pfannkoch, Cynthia; Pohl, Craig S; Rogers, Yu-Hui; Ruiz, San Juana; Sabo, Aniko; Santibanez, Jireh; Schneider, Brian W; Smith, Scott M; Sodergren, Erica; Svatek, Amanda F; Utterback, Teresa R; Vattathil, Selina; Warren, Wesley; White, Courtney Sherell; Chinwalla, Asif T; Feng, Yucheng; Halpern, Aaron L; Hillier, Ladeana W; Huang, Xiaoqiu; Minx, Pat; Nelson, Joanne O; Pepin, Kymberlie H; Qin, Xiang; Sutton, Granger G; Venter, Eli; Walenz, Brian P; Wallis, John W; Worley, Kim C; Yang, Shiaw-Pyng; Jones, Steven M; Marra, Marco A; Rocchi, Mariano; Schein, Jacqueline E; Baertsch, Robert; Clarke, Laura; Csürös, Miklós; Glasscock, Jarret; Harris, R Alan; Havlak, Paul; Jackson, Andrew R; Jiang, Huaiyang; Liu, Yue; Messina, David N; Shen, Yufeng; Song, Henry Xing-Zhi; Wylie, Todd; Zhang, Lan; Birney, Ewan; Han, Kyudong; Konkel, Miriam K; Lee, Jungnam; Smit, Arian F A; Ullmer, Brygg; Wang, Hui; Xing, Jinchuan; Burhans, Richard; Cheng, Ze; Karro, John E; Ma, Jian; Raney, Brian; She, Xinwei; Cox, Michael J; Demuth, Jeffery P; Dumas, Laura J; Han, Sang-Gook; Hopkins, Janet; Karimpour-Fard, Anis; Kim, Young H; Pollack, Jonathan R; Vinar, Tomas; Addo-Quaye, Charles; Degenhardt, Jeremiah; Denby, Alexandra; Hubisz, Melissa J; Indap, Amit; Kosiol, Carolin; Lahn, Bruce T; Lawson, Heather A; Marklein, Alison; Nielsen, Rasmus; Vallender, Eric J; Clark, Andrew G; Ferguson, Betsy; Hernandez, Ryan D; Hirani, Kashif; Kehrer-Sawatzki, Hildegard; Kolb, Jessica; Patil, Shobha; Pu, Ling-Ling; Ren, Yanru; Smith, David Glenn; Wheeler, David A; Schenck, Ian; Ball, Edward V; Chen, Rui; Cooper, David N; Giardine, Belinda; Hsu, Fan; Kent, W James; Lesk, Arthur; Nelson, David L; O'brien, William E; Prüfer, Kay; Stenson, Peter D; Wallace, James C; Ke, Hui; Liu, Xiao-Ming; Wang, Peng; Xiang, Andy Peng; Yang, Fan; Barber, Galt P; Haussler, David; Karolchik, Donna; Kern, Andy D; Kuhn, Robert M; Smith, Kayla E; Zwieg, Ann S

2007-04-13

The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

High resolution karyotype of Thai crab-eating macaque (Macaca fascicularis

Directory of Open Access Journals (Sweden)

Fan Xiaobo

2014-01-01

Full Text Available Comparative chromosome banding analysis and/or fluorescence in situ hybridization (FISH studies are established approaches to compare human and ape chromosomes. FISH banding is a relatively new and not routinely applied method very well suited to provide to a better understanding of the evolutionary history of primate and human phylogeny. Here multicolor banding (MCB-applying probes derived from Homo sapiens were used to analyze the chromosomes of Thai crab-eating macaque (Macaca fascicularis. The results agree with those of previous studies in other macaques, e.g. Macaca sylvanus or Macaca nemestrina. This result highlights that morphological differences within the Cercopithecoidea must be found rather in subchromosomal changes or even in epigenetics than in gross structural alterations.

Evidence of direct reciprocity, but not of indirect and generalized reciprocity, in the grooming exchanges of wild Barbary macaques (Macaca sylvanus).

Science.gov (United States)

Molesti, Sandra; Majolo, Bonaventura

2017-09-01

Reciprocity is one of the mechanisms that have been proposed to explain the exchange of social behaviors, such as grooming, in animals. Reciprocity assumes that individuals act as the donor and recipient of grooming and switch roles over time to balance the benefits and costs of this behavior. Three main patterns of reciprocity may follow a grooming given: (i) direct reciprocity, where the former recipient returns the grooming to the former donor; (ii) indirect reciprocity, where another individual returns the grooming to the former donor; and (iii) generalized reciprocity, where the former recipient returns the grooming to another individual. While there is evidence that direct reciprocity plays an important role in various species of animals, the role of indirect and generalized reciprocity is less clear and has been rarely analyzed. We tested the role of direct, indirect, and generalized reciprocity in explaining grooming exchanges of wild Barbary macaques, by analyzing the temporal contingency between giving and receiving grooming. We collected the occurrence and latency of the three types of grooming reciprocation during 1 hr long focal sessions run simultaneously on two partners who just stopped grooming (post-grooming session) or who were in proximity (i.e., within 1.5 m) without grooming each other (control session). We ran the analyses on 284 post-grooming and 63 control sessions. The results revealed a temporal contingency of grooming interactions exchanged according to direct reciprocity but not according to indirect or generalized reciprocity. Our results indicate that grooming distribution in Barbary macaques is partner-specific. We discuss the possible role of cognition and emotions in explaining direct reciprocity in animals. © 2017 Wiley Periodicals, Inc.

Adaptive evolution of simian immunodeficiency viruses isolated from two conventional progressor macaques with neuroaids

Energy Technology Data Exchange (ETDEWEB)

Foley, Brian T [Los Alamos National Laboratory; Korber, Bette T [Los Alamos National Laboratory

2008-01-01

Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicate better in peripheral blood mononuclear cells than virus from CNS. We speculate that these viruses were under different selective pressures in their separate compartments. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets. Analysis of the number of potential N-linked glycosylation sites (PNGS) in gp160 showed that there was a statistically significant loss of PNGS in viruses isolated from CNS in both macaques compared to SIVsmE543-3. Moreover, virus isolated from the brain in H631, had statistically significant loss of PNGS compared to virus isolated from CSF and plasma of the same animal. It is possible that the brain isolate may have adapted to decrease the number of PNGS given that humoral immune selection pressure is less likely to be encountered in the brain. These viruses provide a relevant model to study the adaptations required for SIV to induce encephalitis.

A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.

Science.gov (United States)

Barnable, Patrick; Calenda, Giulia; Ouattara, Louise; Gettie, Agegnehu; Blanchard, James; Jean-Pierre, Ninochka; Kizima, Larisa; Rodríguez, Aixa; Abraham, Ciby; Menon, Radhika; Seidor, Samantha; Cooney, Michael L; Roberts, Kevin D; Sperling, Rhoda; Piatak, Michael; Lifson, Jeffrey D; Fernandez-Romero, Jose A; Zydowsky, Thomas M; Robbiani, Melissa; Teleshova, Natalia

2014-01-01

To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M) and zinc acetate dihydrate (ZA) in carrageenan (CG) (MZC) inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV)-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100) and MC (1∶30, the only dilution tested), but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines) of vaginal (but not cervical) mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74%) did not significantly differ from CG (32-45%), it was within the range of protection (∼75%) against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

A MIV-150/zinc acetate gel inhibits SHIV-RT infection in macaque vaginal explants.

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Patrick Barnable

Full Text Available To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M and zinc acetate dihydrate (ZA in carrageenan (CG (MZC inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100 and MC (1∶30, the only dilution tested, but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines of vaginal (but not cervical mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74% did not significantly differ from CG (32-45%, it was within the range of protection (∼75% against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

Expression, purification, crystallization and preliminary X-ray diffraction analysis of rhesus macaque CD8αα homodimer

International Nuclear Information System (INIS)

Zong, Lili; Chen, Yong; Yan, Jinghua; Zhang, Jianhua

2010-01-01

CD8α exodomain protein, a crucial immune-system factor in rhesus macaque (M. mulatta), one of the best animal models for vaccine design, was assembled and crystallized. The full structure data will contribute to future studies of immune responses in rhesus macaques. As a T-cell co-receptor, CD8 binds to MHC class I molecules and plays a pivotal role in the activation of cytotoxic T lymphocytes. To date, structures of CD8 have been solved for two different mammals: human and mouse. The infection of rhesus macaques (Macaca mulatta) by simian immunodeficiency virus (SIV) is the best animal model for studying HIV. In this study, the rhesus macaque CD8 (rCD8) αα homodimer was obtained and rCD8α exodomain protein crystals were successfully obtained for further structural analysis. Diffraction data were collected to a resolution of 2.4 Å. The crystal belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 46.52, b = 56.28, c = 82.40 Å. These data will facilitate further studies on the structural differences between these CD8 structures and the cellular immune responses of rhesus macaque

Long-term immunogenicity studies of formalin-inactivated enterovirus 71 whole-virion vaccine in macaques.

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Chia-Chyi Liu

Full Text Available Enterovirus 71 (EV71 has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-γ and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.

Segregation of Brain Structural Networks Supports Spatio-Temporal Predictive Processing

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Valentina Ciullo

2018-05-01

Full Text Available The ability to generate probabilistic expectancies regarding when and where sensory stimuli will occur, is critical to derive timely and accurate inferences about updating contexts. However, the existence of specialized neural networks for inferring predictive relationships between events is still debated. Using graph theoretical analysis applied to structural connectivity data, we tested the extent of brain connectivity properties associated with spatio-temporal predictive performance across 29 healthy subjects. Participants detected visual targets appearing at one out of three locations after one out of three intervals; expectations about stimulus location (spatial condition or onset (temporal condition were induced by valid or invalid symbolic cues. Connectivity matrices and centrality/segregation measures, expressing the relative importance of, and the local interactions among specific cerebral areas respect to the behavior under investigation, were calculated from whole-brain tractography and cortico-subcortical parcellation.Results: Response preparedness to cued stimuli relied on different structural connectivity networks for the temporal and spatial domains. Significant covariance was observed between centrality measures of regions within a subcortical-fronto-parietal-occipital network -comprising the left putamen, the right caudate nucleus, the left frontal operculum, the right inferior parietal cortex, the right paracentral lobule and the right superior occipital cortex-, and the ability to respond after a short cue-target delay suggesting that the local connectedness of such nodes plays a central role when the source of temporal expectation is explicit. When the potential for functional segregation was tested, we found highly clustered structural connectivity across the right superior, the left middle inferior frontal gyrus and the left caudate nucleus as related to explicit temporal orienting. Conversely, when the interaction between

Segregation of Brain Structural Networks Supports Spatio-Temporal Predictive Processing.

Science.gov (United States)

Ciullo, Valentina; Vecchio, Daniela; Gili, Tommaso; Spalletta, Gianfranco; Piras, Federica

2018-01-01

The ability to generate probabilistic expectancies regarding when and where sensory stimuli will occur, is critical to derive timely and accurate inferences about updating contexts. However, the existence of specialized neural networks for inferring predictive relationships between events is still debated. Using graph theoretical analysis applied to structural connectivity data, we tested the extent of brain connectivity properties associated with spatio-temporal predictive performance across 29 healthy subjects. Participants detected visual targets appearing at one out of three locations after one out of three intervals; expectations about stimulus location (spatial condition) or onset (temporal condition) were induced by valid or invalid symbolic cues. Connectivity matrices and centrality/segregation measures, expressing the relative importance of, and the local interactions among specific cerebral areas respect to the behavior under investigation, were calculated from whole-brain tractography and cortico-subcortical parcellation. Results: Response preparedness to cued stimuli relied on different structural connectivity networks for the temporal and spatial domains. Significant covariance was observed between centrality measures of regions within a subcortical-fronto-parietal-occipital network -comprising the left putamen, the right caudate nucleus, the left frontal operculum, the right inferior parietal cortex, the right paracentral lobule and the right superior occipital cortex-, and the ability to respond after a short cue-target delay suggesting that the local connectedness of such nodes plays a central role when the source of temporal expectation is explicit. When the potential for functional segregation was tested, we found highly clustered structural connectivity across the right superior, the left middle inferior frontal gyrus and the left caudate nucleus as related to explicit temporal orienting. Conversely, when the interaction between explicit and

Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir.

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Avalos, Claudia R; Abreu, Celina M; Queen, Suzanne E; Li, Ming; Price, Sarah; Shirk, Erin N; Engle, Elizabeth L; Forsyth, Ellen; Bullock, Brandon T; Mac Gabhann, Feilim; Wietgrefe, Stephen W; Haase, Ashley T; Zink, M Christine; Mankowski, Joseph L; Clements, Janice E; Gama, Lucio

2017-08-15

A human immunodeficiency virus (HIV) infection cure requires an understanding of the cellular and anatomical sites harboring virus that contribute to viral rebound upon treatment interruption. Despite antiretroviral therapy (ART), HIV-associated neurocognitive disorders (HAND) are reported in HIV-infected individuals on ART. Biomarkers for macrophage activation and neuronal damage in cerebrospinal fluid (CSF) of HIV-infected individuals demonstrate continued effects of HIV in brain and suggest that the central nervous system (CNS) may serve as a viral reservoir. Using a simian immunodeficiency virus (SIV)/macaque model for HIV encephalitis and AIDS, we evaluated whether infected cells persist in brain despite ART. Eight SIV-infected pig-tailed macaques were virally suppressed with ART, and plasma and CSF viremia levels were analyzed longitudinally. To assess whether virus persisted in brain macrophages (BrMΦ) in these macaques, we used a macrophage quantitative viral outgrowth assay (MΦ-QVOA), PCR, and in situ hybridization (ISH) to measure the frequency of infected cells and the levels of viral RNA and DNA in brain. Viral RNA in brain tissue of suppressed macaques was undetectable, although viral DNA was detected in all animals. The MΦ-QVOA demonstrated that the majority of suppressed animals contained latently infected BrMΦ. We also showed that virus produced in the MΦ-QVOAs was replication competent, suggesting that latently infected BrMΦ are capable of reestablishing productive infection upon treatment interruption. This report provides the first confirmation of the presence of replication-competent SIV in BrMΦ of ART-suppressed macaques and suggests that the highly debated issue of viral latency in macrophages, at least in brain, has been addressed in SIV-infected macaques treated with ART. IMPORTANCE Resting CD4 + T cells are currently the only cells that fit the definition of a latent reservoir. However, recent evidence suggests that HIV

Acute-phase responses in healthy and diseased rhesus macaques (Macaca mulatta)

DEFF Research Database (Denmark)

Krogh, Anne Kirstine Havnsøe; Lundsgaard, Jo F. H.; Bakker, Jaco

2014-01-01

Five acute-phase reactants—serum amyloid A (SAA), C-reactive protein (CRP), haptoglobin, albumin, and iron—were measured using commercially available assays in 110 healthy rhesus macaques (Macaca mulatta), and reference intervals were established for future use in health monitoring of this species....... Reference intervals established were as follows: SAA, 29.5–87.7 mg/L; CRP, 0–17.5 mg/L; haptoglobin, 354.3–2,414.7 mg/L; albumin, 36.1–53.0 g/L; and iron, 13.3–40.2 lmol/L. Furthermore, changes in the acute-phase reactants were studied in two additional groups of animals: eight rhesus macaques suffering...... from acute traumatic injuries and nine rhesus macaques experimentally infected with Mycobacterium tuberculosis reflecting a chronic active inflammation. In animals with inflammation, SAA and haptoglobin concentrations were moderately increased, while CRP increased more than 200-fold. In addition, marked...

Pair housing for female longtailed and rhesus macaques in the laboratory: behavior in protected contact versus full contact.

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Baker, Kate C; Crockett, Carolyn M; Lee, Grace H; Oettinger, Brooke C; Schoof, Valérie; Thom, Jinhee P

2012-01-01

Pair housing for caged macaques in the laboratory generally allows unrestricted tactile contact but, less commonly, may involve limited contact via grooming-contact bars or perforated panels. The purpose of using this protected contact housing, which prevents entry into pair-mates' cages, typically is to accommodate research and management requirements. The study used behavioral data collected on 12 pairs of female longtailed macaques (Macaca fascicularis) at the Washington National Primate Research Center and 7 pairs of female rhesus macaques (Macaca mulatta) housed at the Tulane National Primate Research Center to assess the relative benefits of protected versus full protected contact. The study collected data in stable pairs housed first in protected contact followed by full contact. Species combined, the study found the presence of the panel was associated with lower levels of social grooming and higher levels of self-grooming, abnormal behavior, and tension-related behavior. Within species, only the protected- versus full-contact contrasts for abnormal and tension were statistically significant-and only for rhesus macaques. Results suggest that for female rhesus macaques, potential disadvantages or inconveniences of full contact should be balanced against the improved behavioral profile in comparison to protected contact. The use of protected contact among female longtailed macaques does not appear to require the same cost-benefit analysis. Copyright © Taylor & Francis Group, LLC

Design of Phase II Non-inferiority Trials.

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Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

Beneficial effect of hot spring bathing on stress levels in Japanese macaques.

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Takeshita, Rafaela S C; Bercovitch, Fred B; Kinoshita, Kodzue; Huffman, Michael A

2018-05-01

The ability of animals to survive dramatic climates depends on their physiology, morphology and behaviour, but is often influenced by the configuration of their habitat. Along with autonomic responses, thermoregulatory behaviours, including postural adjustments, social aggregation, and use of trees for shelter, help individuals maintain homeostasis across climate variations. Japanese macaques (Macaca fuscata) are the world's most northerly species of nonhuman primates and have adapted to extremely cold environments. Given that thermoregulatory stress can increase glucocorticoid concentrations in primates, we hypothesized that by using an available hot spring, Japanese macaques could gain protection against weather-induced cold stress during winter. We studied 12 adult female Japanese macaques living in Jigokudani Monkey Park, Japan, during the spring birth season (April to June) and winter mating season (October to December). We collected faecal samples for determination of faecal glucocorticoid (fGC) metabolite concentrations by enzyme immunoassay, as well as behavioural data to determine time spent in the hot springs, dominance rank, aggression rates, and affiliative behaviours. We used nonparametric statistics to examine seasonal changes in hot spring bathing, and the relationship between rank and air temperature on hot spring bathing. We used general linear mixed-effect models to examine factors impacting hormone concentrations. We found that Japanese macaques use hot spring bathing for thermoregulation during the winter. In the studied troop, the single hot spring is a restricted resource favoured by dominant females. High social rank had both costs and benefits: dominant females sustained high fGC levels, which were associated with high aggression rates in winter, but benefited by priority of access to the hot spring, which was associated with low fGC concentrations and therefore might help reduce energy expenditure and subsequent body heat loss. This unique

Radiographic changes in rhesus macaques affected by scurvy

International Nuclear Information System (INIS)

Morgan, J.P.; Eisele, P.H.

1992-01-01

Spontaneous vitamin C deficiency, or scurvy, was recognized in juvenile rhesus monkeys maintained in a research center as a result of being fed a commercial diet for 2 to 3 months with low levels of vitamin C. Most severely affected animals (13) were radiographed repeatedly up to day 300 following detection of the disease. Early radiographic changes consisted of widened, lucent metaphyses with lateral flaring and radiopaque metaphyseal lines at the junction of the metaphyses and physes. Physeal slippage was noted commonly. Following institution of vitamin C therapy, calcification of subperiosteal hemorrhage occurred in the metaphyseal regions. Metaphyses and physes returned to normal radiographic appearance within 15 to 30 days. Initially, the subperiosteal hemorrhage progressed and a longer time was required for solution of the calcified hematomas. The macaques improved clinically and were released from the hospital when fractures were stable at 4-5 weeks after admission. Of the 13 macaques studied, all but one returned as normal members of the colony

Context-dependent lexical ambiguity resolution: MEG evidence for the time-course of activity in left inferior frontal gyrus and posterior middle temporal gyrus.

Science.gov (United States)

Mollo, Giovanna; Jefferies, Elizabeth; Cornelissen, Piers; Gennari, Silvia P

An MEG study investigated the role of context in semantic interpretation by examining the comprehension of ambiguous words in contexts leading to different interpretations. We compared high-ambiguity words in minimally different contexts (to bowl, the bowl) to low-ambiguity counterparts (the tray, to flog). Whole brain beamforming revealed the engagement of left inferior frontal gyrus (LIFG) and posterior middle temporal gyrus (LPMTG). Points of interest analyses showed that both these sites showed a stronger response to verb-contexts by 200 ms post-stimulus and displayed overlapping ambiguity effects that were sustained from 300 ms onwards. The effect of context was stronger for high-ambiguity words than for low-ambiguity words at several different time points, including within the first 100 ms post-stimulus. Unlike LIFG, LPMTG also showed stronger responses to verb than noun contexts in low-ambiguity trials. We argue that different functional roles previously attributed to LIFG and LPMTG are in fact played out at different periods during processing. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Toxicity and efficacy of 2',3'-dideoxycytidine in clinical trials of pigtailed macaques infected with simian retrovirus type 2.

OpenAIRE

Tsai, C C; Follis, K E; Yarnall, M; Blakley, G A

1989-01-01

Four dosing regimens of 2',3'-dideoxycytidine (ddC) were administered intravenously for 10 to 28 days to 18 pigtailed macaques with simian acquired immunodeficiency syndrome. Ten macaques naturally infected with simian acquired immunodeficiency syndrome retrovirus serotype 2 (SRV-2), the etiologic agent of simian acquired immunodeficiency syndrome, received ddC by continuous intravenous infusion or by a daily bolus injection for 10 to 12 days. Another eight macaques that were negative for SRV...

Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques.

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Magnani, Diogo M; Rogers, Thomas F; Maness, Nicholas J; Grubaugh, Nathan D; Beutler, Nathan; Bailey, Varian K; Gonzalez-Nieto, Lucas; Gutman, Martin J; Pedreño-Lopez, Núria; Kwal, Jaclyn M; Ricciardi, Michael J; Myers, Tereance A; Julander, Justin G; Bohm, Rudolf P; Gilbert, Margaret H; Schiro, Faith; Aye, Pyone P; Blair, Robert V; Martins, Mauricio A; Falkenstein, Kathrine P; Kaur, Amitinder; Curry, Christine L; Kallas, Esper G; Desrosiers, Ronald C; Goldschmidt-Clermont, Pascal J; Whitehead, Stephen S; Andersen, Kristian G; Bonaldo, Myrna C; Lackner, Andrew A; Panganiban, Antonito T; Burton, Dennis R; Watkins, David I

2018-04-24

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.

PET CT Identifies Reactivation Risk in Cynomolgus Macaques with Latent M. tuberculosis.

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Philana Ling Lin

2016-07-01

Full Text Available Mycobacterium tuberculosis infection presents across a spectrum in humans, from latent infection to active tuberculosis. Among those with latent tuberculosis, it is now recognized that there is also a spectrum of infection and this likely contributes to the variable risk of reactivation tuberculosis. Here, functional imaging with 18F-fluorodeoxygluose positron emission tomography and computed tomography (PET CT of cynomolgus macaques with latent M. tuberculosis infection was used to characterize the features of reactivation after tumor necrosis factor (TNF neutralization and determine which imaging characteristics before TNF neutralization distinguish reactivation risk. PET CT was performed on latently infected macaques (n = 26 before and during the course of TNF neutralization and a separate set of latently infected controls (n = 25. Reactivation occurred in 50% of the latently infected animals receiving TNF neutralizing antibody defined as development of at least one new granuloma in adjacent or distant locations including extrapulmonary sites. Increased lung inflammation measured by PET and the presence of extrapulmonary involvement before TNF neutralization predicted reactivation with 92% sensitivity and specificity. To define the biologic features associated with risk of reactivation, we used these PET CT parameters to identify latently infected animals at high risk for reactivation. High risk animals had higher cumulative lung bacterial burden and higher maximum lesional bacterial burdens, and more T cells producing IL-2, IL-10 and IL-17 in lung granulomas as compared to low risk macaques. In total, these data support that risk of reactivation is associated with lung inflammation and higher bacterial burden in macaques with latent Mtb infection.

Somatostatin-immunoreactive senile plaque-like structures in the frontal cortex and nucleus accumbens of aged tree shrews and Japanese macaques.

Science.gov (United States)

Yamashita, Akiko; Fuchs, Eberhard; Taira, Masato; Yamamoto, Takamitsu; Hayashi, Motoharu

2012-06-01

Previously, we demonstrated decreased expression of somatostatin mRNA in aged macaque brain, particularly in the prefrontal cortex. To investigate whether or not this age-dependent decrease in mRNA is related to morphological changes, we analyzed somatostatin cells in the cerebra of aged Japanese macaques and compared them with those in rats and tree shrews, the latter of which are closely related to primates. Brains of aged macaques, tree shrews, and rats were investigated by immunohistochemistry with special emphasis on somatostatin. We observed degenerating somatostatin-immunoreactive cells in the cortices of aged macaques and tree shrews. Somatostatin-immunoreactive senile plaque-like structures were found in areas 6 and 8 and in the nucleus accumbens of macaques, as well as in the nucleus accumbens and the cortex of aged tree shrews, where amyloid accumulations were observed. Somatostatin degenerations may be related to amyloid accumulations and may play roles in impairments of cognitive functions during aging. © 2012 John Wiley & Sons A/S.

Variation in hair δ13C and δ15N values in long-tailed macaques (Macaca fascicularis) from Singapore

Science.gov (United States)

Schillaci, Michael A.; Castellini, J. Margaret; Stricker, Craig A.; Jones-Engel, Lisa; Lee, Benjamin P.Y.-H.

2014-01-01

Much of the primatology literature on stable isotope ratios of carbon (δ13C) and nitrogen (δ15N) has focused on African and New World species, with comparatively little research published on Asian primates. Here we present hair δ13C and δ15N isotope values for a sample of 33 long-tailed macaques from Singapore. We evaluate the suggestion by a previous researcher that forest degradation and biodiversity loss in Singapore have led to a decline in macaque trophic level. The results of our analysis indicated significant spatial variability in δ13C but not δ15N. The range of variation in δ13C was consistent with a diet based on C3 resources, with one group exhibiting low values consistent with a closed canopy environment. Relative to other macaque species from Europe and Asia, the macaques from Singapore exhibited a low mean δ13C value but mid-range mean δ15N value. Previous research suggesting a decline in macaque trophic level is not supported by the results of our study.

Resource use of Japanese macaques in heavy snowfall areas: implications for habitat management.

Science.gov (United States)

Enari, Hiroto; Sakamaki-Enari, Haruka

2013-07-01

Populations of Japanese macaque (Macaca fuscata) that inhabit the northernmost distribution of any nonhuman primates have been listed as endangered in Japan; however, macaques are widely known for being pests that cause agricultural damage. This study identified priority areas for the conservation and management of macaque habitats, by comparing the resource use of troops occupying remote mountains (montane troops) against troops inhabiting disturbed forests adjacent to settlements (rural troops). We collected species presence data across 2 years by radio-tracking two montane troops and two rural troops in the Shirakami Mountains. We developed seasonal utilization distributions by using the kernel method, and identified habitat characteristics by using ecological-niche factor analysis (ENFA). Our results indicate that environmental factors influencing the potential habitat varied widely with season in montane troops as compared with that in rural troops. ENFA results demonstrated that rural troops exhibited more biased resource use and narrower niche breadths than montane troops. Based on our findings, we propose that (1) primary broadleaf forests are the spring habitat conservation priority of montane troops; (2) the habitat unit--the product of habitat suitability index and its surface area--for montane troops is enhanced by removing old conifer plantations from the forest edge at low elevations; (3) such removal around settlements may also contribute toward removing a frontline refuge for rural troops intruding farmlands; and (4) intensive prevention measures against macaque intrusions into settlements during the bottleneck snowy season contribute toward reducing the habitat unit of rural troops.

Modeling vocalization with ECoG cortical activity recorded during vocal production in the macaque monkey.

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Fukushima, Makoto; Saunders, Richard C; Fujii, Naotaka; Averbeck, Bruno B; Mishkin, Mortimer

2014-01-01

Vocal production is an example of controlled motor behavior with high temporal precision. Previous studies have decoded auditory evoked cortical activity while monkeys listened to vocalization sounds. On the other hand, there have been few attempts at decoding motor cortical activity during vocal production. Here we recorded cortical activity during vocal production in the macaque with a chronically implanted electrocorticographic (ECoG) electrode array. The array detected robust activity in motor cortex during vocal production. We used a nonlinear dynamical model of the vocal organ to reduce the dimensionality of `Coo' calls produced by the monkey. We then used linear regression to evaluate the information in motor cortical activity for this reduced representation of calls. This simple linear model accounted for circa 65% of the variance in the reduced sound representations, supporting the feasibility of using the dynamical model of the vocal organ for decoding motor cortical activity during vocal production.

Reversal of interlaminar signal between sensory and memory processing in monkey temporal cortex.

Science.gov (United States)

Takeuchi, Daigo; Hirabayashi, Toshiyuki; Tamura, Keita; Miyashita, Yasushi

2011-03-18

The primate temporal cortex implements visual long-term memory. However, how its interlaminar circuitry executes cognitive computations is poorly understood. Using linear-array multicontact electrodes, we simultaneously recorded unit activities across cortical layers in the perirhinal cortex of macaques performing a pair-association memory task. Cortical layers were estimated on the basis of current source density profiles with histological verifications, and the interlaminar signal flow was determined with cross-correlation analysis between spike trains. During the cue period, canonical "feed-forward" signals flowed from granular to supragranular layers and from supragranular to infragranular layers. During the delay period, however, the signal flow reversed to the "feed-back" direction: from infragranular to supragranular layers. This reversal of signal flow highlights how the temporal cortex differentially recruits its laminar circuits for sensory and mnemonic processing.

A comparative study of middle cerebral pressure in dogs and macaques

Science.gov (United States)

Symon, Lindsay

1967-01-01

1. A comparison has been made of the pressures recorded from pial branches of the middle cerebral artery in dogs and macaques. This pressure has been shown to be between 88 and 95% of femoral arterial pressure in dogs under chloralose anaesthesia, and between 80 and 90% of femoral arterial pressure in macaques similarly anaesthetized. 2. The effect of occlusion of the main vessels in the neck is shown to differ considerably in the two species. Blood pressure within the forebrain of the dog is shown to be largely dependent upon the integrity of the external carotid artery, whereas in the monkey the external carotid artery is without effect in the maintenance of forebrain blood pressure. Occlusion of the four major arteries in the neck is shown to produce a greater effect in the macaque and to be accompanied by signs of medullary ischaemia in this species. 3. After occlusion of the main middle cerebral artery, arterial pressure measured distal to the occlusion depends upon the integrity of collateral vessels from the other cerebral arteries. When only a branch of the middle cerebral artery is occluded, the greater part of the residual blood pressure depends upon anastomoses from other branches of the middle cerebral artery itself. ImagesFig. 1 PMID:4963869

Natural and cross-inducible anti-SIV antibodies in Mauritian cynomolgus macaques.

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Hongzhao Li

Full Text Available Cynomolgus macaques are an increasingly important nonhuman primate model for HIV vaccine research. SIV-free animals without pre-existing anti-SIV immune responses are generally needed to evaluate the effect of vaccine-induced immune responses against the vaccine epitopes. Here, in order to select such animals for vaccine studies, we screened 108 naïve female Mauritian cynomolgus macaques for natural (baseline antibodies to SIV antigens using a Bio-Plex multiplex system. The antigens included twelve 20mer peptides overlapping the twelve SIV protease cleavage sites (-10/+10, respectively (PCS peptides, and three non-PCS Gag or Env peptides. Natural antibodies to SIV antigens were detected in subsets of monkeys. The antibody reactivity to SIV was further confirmed by Western blot using purified recombinant SIV Gag and Env proteins. As expected, the immunization of monkeys with PCS antigens elicited anti-PCS antibodies. However, unexpectedly, antibodies to non-PCS peptides were also induced, as shown by both Bio-Plex and Western blot analyses, while the non-PCS peptides do not share sequence homology with PCS peptides. The presence of natural and vaccine cross-inducible SIV antibodies in Mauritian cynomolgus macaques should be considered in animal selection, experimental design and result interpretation, for their best use in HIV vaccine research.

Pathways of seizure propagation from the temporal to the occipital lobe.

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Jacobs, Julia; Dubeau, François; Olivier, André; Andermann, Frederick

2008-12-01

Propagation of ictal epileptic discharges influences the clinical appearance of seizures. Fast propagation from the occipital to temporal lobe has been well described, but until now the reverse direction of spread has not been emphasized. We describe two patients who experienced ictal propagation from temporal to occipital regions. One case presented with amaurosis during a seizure with temporal onset and temporal-occipital spread. In the second, temporal-occipital spread was documented during a seizure, which continued in the occipital lobe for six minutes. Depth electrode studies suggested the temporal ictal onset of seizures in both patients. Propagation from temporal to occipital lobe structures must be considered in the assessment of patients who have seizures with both temporal and occipital features. The propagation may have predictive value for their surgical outcome. The underlying anatomical structure might be the inferior longitudinal fasciculus.

Evolutionary and biomedical insights from the rhesus macaque genome

DEFF Research Database (Denmark)

Gibbs, Richard A; Rogers, Jeffrey; Katze, Michael G

2007-01-01

The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied...

Reconciliation and relationship quality in Assamese macaques (Macaca assamensis)

NARCIS (Netherlands)

Cooper, M.A.; Bernstein, I.S.; Hemelrijk, C.K.

A consistent conclusion in reconciliation research is that animals that reconcile are likely to have strong social bonds. This has led to the hypothesis that reconciliation occurs most often between valuable social partners. We tested this hypothesis in a group of Assamese macaques (Macaca

Middle longitudinal fasciculus delineation within language pathways: A diffusion tensor imaging study in human

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Menjot de Champfleur, Nicolas, E-mail: nicolasdechampfleur@orange.fr [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Team “Plasticity of Central Nervous System, Stem Cells and Glial Tumors,” Institut National de la Santé et de la Recherche Médicale Unité 1051, Institut of Neurosciences of Montpellier, Saint Eloi Hospital, Montpellier (France); Lima Maldonado, Igor [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Team “Plasticity of Central Nervous System, Stem Cells and Glial Tumors,” Institut National de la Santé et de la Recherche Médicale Unité 1051, Institut of Neurosciences of Montpellier, Saint Eloi Hospital, Montpellier (France); Divisão de Neurologia e Epidemiologia (CPPHO), Complexo Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador-Bahia (Brazil); Moritz-Gasser, Sylvie [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Department of Neurology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); Machi, Paolo [Department of Neuroradiology, University Hospital Center, Gui de Chauliac Hospital, Montpellier (France); and others

2013-01-15

Introduction: The existence in the human brain of the middle longitudinal fasciculus (MdLF), initially described in the macaque monkey, is supported by diffusion tensor imaging studies. In the present work, we aim (1) to confirm that this fascicle is found constantly in control subjects with the use of DTI techniques and (2) to delineate the MdLF from the other fiber bundles that constitute the language pathways. Materials and methods: Tractography was realized in four right-handed healthy volunteers for the arcuate fascicle, uncinate fascicle, inferior fronto-occipital fascicle, inferior longitudinal fascicle and the middle longitudinal fascicle. The fiber tracts were characterized for their size, mean fractional anisotropy (FA), for their length, number of streamlines, and lateralization indices were calculated. Results: The MdLF is found constantly and it is clearly delineated from the other fascicles that constitute the language pathways, especially the ventral pathway. It runs within the superior temporal gyrus white matter from the temporal pole, then it extends caudally in the upper part of the sagittal stratum and the posterior part of the corona radiata, to reach the inferior parietal lobule (angular gyrus). We found a leftward asymmetry for all fiber tracts when considering the mean FA. Discussion: Using DTI methods, we confirm that the MdLF connects the angular gyrus and the superior temporal gyrus. On the basis of these findings, the role of the MdLF is discussed. Conclusion: The middle longitudinal fasciculus, connects the angular gyrus and the superior temporal gyrus and its course can be systematically differenciated from those of other fascicles composing both ventral and dorsal routes (IFOF, IFL, AF and UF)

Middle longitudinal fasciculus delineation within language pathways: A diffusion tensor imaging study in human

International Nuclear Information System (INIS)

Menjot de Champfleur, Nicolas; Lima Maldonado, Igor; Moritz-Gasser, Sylvie; Machi, Paolo

2013-01-01

Introduction: The existence in the human brain of the middle longitudinal fasciculus (MdLF), initially described in the macaque monkey, is supported by diffusion tensor imaging studies. In the present work, we aim (1) to confirm that this fascicle is found constantly in control subjects with the use of DTI techniques and (2) to delineate the MdLF from the other fiber bundles that constitute the language pathways. Materials and methods: Tractography was realized in four right-handed healthy volunteers for the arcuate fascicle, uncinate fascicle, inferior fronto-occipital fascicle, inferior longitudinal fascicle and the middle longitudinal fascicle. The fiber tracts were characterized for their size, mean fractional anisotropy (FA), for their length, number of streamlines, and lateralization indices were calculated. Results: The MdLF is found constantly and it is clearly delineated from the other fascicles that constitute the language pathways, especially the ventral pathway. It runs within the superior temporal gyrus white matter from the temporal pole, then it extends caudally in the upper part of the sagittal stratum and the posterior part of the corona radiata, to reach the inferior parietal lobule (angular gyrus). We found a leftward asymmetry for all fiber tracts when considering the mean FA. Discussion: Using DTI methods, we confirm that the MdLF connects the angular gyrus and the superior temporal gyrus. On the basis of these findings, the role of the MdLF is discussed. Conclusion: The middle longitudinal fasciculus, connects the angular gyrus and the superior temporal gyrus and its course can be systematically differenciated from those of other fascicles composing both ventral and dorsal routes (IFOF, IFL, AF and UF)

Inferior alveolar nerve block: Alternative technique.

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Thangavelu, K; Kannan, R; Kumar, N Senthil

2012-01-01

Inferior alveolar nerve block (IANB) is a technique of dental anesthesia, used to produce anesthesia of the mandibular teeth, gingivae of the mandible and lower lip. The conventional IANB is the most commonly used the nerve block technique for achieving local anesthesia for mandibular surgical procedures. In certain cases, however, this nerve block fails, even when performed by the most experienced clinician. Therefore, it would be advantageous to find an alternative simple technique. The objective of this study is to find an alternative inferior alveolar nerve block that has a higher success rate than other routine techniques. To this purpose, a simple painless inferior alveolar nerve block was designed to anesthetize the inferior alveolar nerve. This study was conducted in Oral surgery department of Vinayaka Mission's dental college Salem from May 2009 to May 2011. Five hundred patients between the age of 20 years and 65 years who required extraction of teeth in mandible were included in the study. Out of 500 patients 270 were males and 230 were females. The effectiveness of the IANB was evaluated by using a sharp dental explorer in the regions innervated by the inferior alveolar, lingual, and buccal nerves after 3, 5, and 7 min, respectively. This study concludes that inferior alveolar nerve block is an appropriate alternative nerve block to anesthetize inferior alveolar nerve due to its several advantages.

Grooming reciprocity in female tibetan macaques macaca thibetana.

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Xia, Dongpo; Li, Jinhua; Garber, Paul A; Sun, Lixing; Zhu, Yong; Sun, Binghua

2012-06-01

Grooming among nonhuman primates is widespread and may represent an important service commodity that is exchanged within a biological marketplace. In this study, using focal animal sampling methods, we recorded grooming relationships among 12 adult females in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China, to determine the influence of rank and kinship on grooming relationships, and whether females act as reciprocal traders (exchange grooming received for grooming given) or interchange traders (interchange grooming for social tolerance or other commodities). The results showed that: (1) grooming given was positively correlated with grooming received; (2) kinship did not exert a significant influence on grooming reciprocity; and (3) grooming reciprocity occurred principally between individuals of adjacent rank; however, when females of different rank groomed, females tended to groom up the hierarchy (lower ranking individuals groomed higher ranking individuals more than vice versa). Our results support the contention that both grooming reciprocity and the interchange of grooming for tolerance represent important social tactics used by female Tibetan macaques. © 2012 Wiley Periodicals, Inc.

Retroperitoneal arteriovenous malformation extending through the inferior vena cava into the heart and causing inferior vena cava dissection

International Nuclear Information System (INIS)

Sung, Yon Mi; Choe, Yeon Hyeon; Park, Seung Woo; Park, Pyo Won; Sung, Chang Ohk

2005-01-01

We present a case of retroperitoneal arteriovenous malformation extending through the inferior vena cava into the heart, which was associated with dissection of the inferior vena cava in a 32-year-old female. Computed tomography and magnetic resonance imaging showed a double-lumen inferior vena cava and a rod-like solid component attached to a sac-like lesion in the right heart chambers. Digital subtraction angiography showed an arteriovenous malformation draining to the inner lumen of the inferior vena cava. (orig.)

Conceptual control across modalities: graded specialisation for pictures and words in inferior frontal and posterior temporal cortex.

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Krieger-Redwood, Katya; Teige, Catarina; Davey, James; Hymers, Mark; Jefferies, Elizabeth

2015-09-01

Controlled semantic retrieval to words elicits co-activation of inferior frontal (IFG) and left posterior temporal cortex (pMTG), but research has not yet established (i) the distinct contributions of these regions or (ii) whether the same processes are recruited for non-verbal stimuli. Words have relatively flexible meanings - as a consequence, identifying the context that links two specific words is relatively demanding. In contrast, pictures are richer stimuli and their precise meaning is better specified by their visible features - however, not all of these features will be relevant to uncovering a given association, tapping selection/inhibition processes. To explore potential differences across modalities, we took a commonly-used manipulation of controlled retrieval demands, namely the identification of weak vs. strong associations, and compared word and picture versions. There were 4 key findings: (1) Regions of interest (ROIs) in posterior IFG (BA44) showed graded effects of modality (e.g., words>pictures in left BA44; pictures>words in right BA44). (2) An equivalent response was observed in left mid-IFG (BA45) across modalities, consistent with the multimodal semantic control deficits that typically follow LIFG lesions. (3) The anterior IFG (BA47) ROI showed a stronger response to verbal than pictorial associations, potentially reflecting a role for this region in establishing a meaningful context that can be used to direct semantic retrieval. (4) The left pMTG ROI also responded to difficulty across modalities yet showed a stronger response overall to verbal stimuli, helping to reconcile two distinct literatures that have implicated this site in semantic control and lexical-semantic access respectively. We propose that left anterior IFG and pMTG work together to maintain a meaningful context that shapes ongoing semantic processing, and that this process is more strongly taxed by word than picture associations. Copyright © 2015 The Authors. Published by

Hierarchical ordering with partial pairwise hierarchical relationships on the macaque brain data sets.

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Woosang Lim

Full Text Available Hierarchical organizations of information processing in the brain networks have been known to exist and widely studied. To find proper hierarchical structures in the macaque brain, the traditional methods need the entire pairwise hierarchical relationships between cortical areas. In this paper, we present a new method that discovers hierarchical structures of macaque brain networks by using partial information of pairwise hierarchical relationships. Our method uses a graph-based manifold learning to exploit inherent relationship, and computes pseudo distances of hierarchical levels for every pair of cortical areas. Then, we compute hierarchy levels of all cortical areas by minimizing the sum of squared hierarchical distance errors with the hierarchical information of few cortical areas. We evaluate our method on the macaque brain data sets whose true hierarchical levels are known as the FV91 model. The experimental results show that hierarchy levels computed by our method are similar to the FV91 model, and its errors are much smaller than the errors of hierarchical clustering approaches.

Virus-Like Particle Vaccination Protects Nonhuman Primates from Lethal Aerosol Exposure with Marburgvirus (VLP Vaccination Protects Macaques against Aerosol Challenges

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John M. Dye

2016-04-01

Full Text Available Marburg virus (MARV was the first filovirus to be identified following an outbreak of viral hemorrhagic fever disease in Marburg, Germany in 1967. Due to several factors inherent to filoviruses, they are considered a potential bioweapon that could be disseminated via an aerosol route. Previous studies demonstrated that MARV virus-like particles (VLPs containing the glycoprotein (GP, matrix protein VP40 and nucleoprotein (NP generated using a baculovirus/insect cell expression system could protect macaques from subcutaneous (SQ challenge with multiple species of marburgviruses. In the current study, the protective efficacy of the MARV VLPs in conjunction with two different adjuvants: QS-21, a saponin derivative, and poly I:C against homologous aerosol challenge was assessed in cynomolgus macaques. Antibody responses against the GP antigen were equivalent in all groups receiving MARV VLPs irrespective of the adjuvant; adjuvant only-vaccinated macaques did not demonstrate appreciable antibody responses. All macaques were subsequently challenged with lethal doses of MARV via aerosol or SQ as a positive control. All MARV VLP-vaccinated macaques survived either aerosol or SQ challenge while animals administered adjuvant only exhibited clinical signs and lesions consistent with MARV disease and were euthanized after meeting the predetermined criteria. Therefore, MARV VLPs induce IgG antibodies recognizing MARV GP and VP40 and protect cynomolgus macaques from an otherwise lethal aerosol exposure with MARV.

Astrocyte atrophy and immune dysfunction in self-harming macaques.

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Lee, Kim M; Chiu, Kevin B; Sansing, Hope A; Inglis, Fiona M; Baker, Kate C; MacLean, Andrew G

2013-01-01

Self-injurious behavior (SIB) is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP) and Toll-like receptor 2 (TLR2). Morphologic features of astrocytes were determined using computer-assisted camera lucida. There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

Astrocyte atrophy and immune dysfunction in self-harming macaques.

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Kim M Lee

Full Text Available BACKGROUND: Self-injurious behavior (SIB is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. METHODS: We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP and Toll-like receptor 2 (TLR2. Morphologic features of astrocytes were determined using computer-assisted camera lucida. RESULTS: There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. CONCLUSIONS: These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

Function and Innervation of the Locus Ceruleus in a Macaque Model of Functional Hypothalamic Amenorrhea

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Bethea, Cynthia L; Kim, Aaron; Cameron, Judy L

2012-01-01

A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afte...

Distribution of cortical neurons projecting to the superior colliculus in macaque monkeys

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Cerkevich CM

2014-09-01

Full Text Available Christina M Cerkevich,1 David C Lyon,2 Pooja Balaram,3 Jon H Kaas3 1Department of Neurobiology, University of Pittsburgh School of Medicine, Systems Neuroscience Institute, Pittsburgh, PA, USA; 2Department of Anatomy and Neurobiology, University of California, Irvine, CA, USA; 3Department of Psychology, Vanderbilt University, Nashville, TN, USA Abstract: To better reveal the pattern of corticotectal projections to the superficial layers of the superior colliculus (SC, we made a total of ten retrograde tracer injections into the SC of three macaque monkeys (Macaca mulatta. The majority of these injections were in the superficial layers of the SC, which process visual information. To isolate inputs to the purely visual layers in the superficial SC from those inputs to the motor and multisensory layers deeper in the SC, two injections were placed to include the intermediate and deep layers of the SC. In another case, an injection was placed in the medial pulvinar, a nucleus not known to be strongly connected with visual cortex, to identify possible projections from tracer spread past the lateral boundary of the SC. Four conclusions are supported by the results: 1 all early visual areas of cortex, including V1, V2, V3, and the middle temporal area, project to the superficial layers of the SC; 2 with the possible exception of the frontal eye field, few areas of cortex outside of the early visual areas project to the superficial SC, although many do, however, project to the intermediate and deep layers of the SC; 3 roughly matching retinotopy is conserved in the projections of visual areas to the SC; and 4 the projections from different visual areas are similarly dense, although projections from early visual areas appear somewhat denser than those of higher order visual areas in macaque cortex. Keywords: visual cortex, superior colliculus, frontal eye field, posterior parietal cortex, visual system

Comparative study of unilateral versus bilateral inferior oblique recession/anteriorization in unilateral inferior oblique overaction.

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Mostafa, Attiat M; Kassem, Rehab R

2018-05-01

To compare the effect of, and the rate of subsequent development of iatrogenic antielevation syndrome after, unilateral versus bilateral inferior oblique graded recession-anteriorization to treat unilateral inferior oblique overaction. Thirty-four patients with unilateral inferior oblique overaction were included in a randomized prospective study. Patients were equally divided into 2 groups. Group UNI underwent unilateral, group BI bilateral, inferior oblique graded recession-anteriorization. A successful outcome was defined as orthotropia, or within 2 ∆ of a residual hypertropia, in the absence of signs of antielevation syndrome, residual inferior oblique overaction, V-pattern, dissociated vertical deviation, or ocular torticollis. A successful outcome was achieved in 11 (64.7%) and 13 (76.5%) patients in groups UNI and BI, respectively (p = 0.452). Antielevation syndrome was diagnosed as the cause of surgical failure in 6 (35.3%) and 2 (11.8%) patients, in groups UNI and BI, respectively (p = 0.106). The cause of surgical failure in the other 2 patients in group BI was due to persistence of ocular torticollis and hypertropia in a patient with superior oblique palsy and a residual V-pattern and hypertropia in the other patient. The differences between unilateral and bilateral inferior oblique graded recession-anteriorization are insignificant. Unilateral surgery has a higher tendency for the subsequent development of antielevation syndrome. Bilateral surgery may still become complicated by antielevation syndrome, although at a lower rate. In addition, bilateral surgery had a higher rate of undercorrection. Further studies on a larger sample are encouraged.

Attention modulations on the perception of social hierarchy at distinct temporal stages: an electrophysiological investigation.

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Feng, Chunliang; Tian, Tengxiang; Feng, Xue; Luo, Yue-Jia

2015-04-01

Recent behavioral and neuroscientific studies have revealed the preferential processing of superior-hierarchy cues. However, it remains poorly understood whether top-down controlled mechanisms modulate temporal dynamics of neurocognitive substrates underlying the preferential processing of these biologically and socially relevant cues. This was investigated in the current study by recording event-related potentials from participants who were presented with superior or inferior social hierarchy. Participants performed a hierarchy-judgment task that required attention to hierarchy cues or a gender-judgment task that withdrew their attention from these cues. Superior-hierarchy cues evoked stronger neural responses than inferior-hierarchy cues at both early (N170/N200) and late (late positive potential, LPP) temporal stages. Notably, the modulations of top-down attention were identified on the LPP component, such that superior-hierarchy cues evoked larger LPP amplitudes than inferior-hierarchy cues only in the attended condition; whereas the modulations of the N170/N200 component by hierarchy cues were evident in both attended and unattended conditions. These findings suggest that the preferential perception of superior-hierarchy cues involves both relatively automatic attentional bias at the early temporal stage as well as flexible and voluntary cognitive evaluation at the late temporal stage. Finally, these hierarchy-related effects were absent when participants were shown the same stimuli which, however, were not associated with social-hierarchy information in a non-hierarchy task (Experiment 2), suggesting that effects of social hierarchy at early and late temporal stages could not be accounted for by differences in physical attributes between these social cues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Young macaques (Macaca fascicularis) preferentially bias attention towards closer, older, and better tool users.

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Tan, Amanda W Y; Hemelrijk, Charlotte K; Malaivijitnond, Suchinda; Gumert, Michael D

2018-05-12

Examining how animals direct social learning during skill acquisition under natural conditions, generates data for examining hypotheses regarding how transmission biases influence cultural change in animal populations. We studied a population of macaques on Koram Island, Thailand, and examined model-based biases during interactions by unskilled individuals with tool-using group members. We first compared the prevalence of interactions (watching, obtaining food, object exploration) and proximity to tool users during interactions, in developing individuals (infants, juveniles) versus mature non-learners (adolescents, adults), to provide evidence that developing individuals are actively seeking information about tool use from social partners. All infants and juveniles, but only 49% of mature individuals carried out interacted with tool users. Macaques predominantly obtained food by scrounging or stealing, suggesting maximizing scrounging opportunities motivates interactions with tool users. However, while interactions by adults was limited to obtaining food, young macaques and particularly infants also watched tool users and explored objects, indicating additional interest in tool use itself. We then ran matrix correlations to identify interaction biases, and what attributes of tool users influenced these. Biases correlated with social affiliation, but macaques also preferentially targeted tool users that potentially increase scrounging and learning opportunities. Results suggest that social structure may constrain social learning, but the motivation to bias interactions towards tool users to maximize feeding opportunities may also socially modulate learning by facilitating close proximity to better tool users, and further interest in tool-use actions and materials, especially during development.

Social object play among young Japanese macaques (Macaca fuscata) in Arashiyama, Japan.

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Shimada, Masaki

2006-10-01

Social object play (SOP), i.e., social play using portable object(s), among young Japanese macaques (Macaca fuscata; 0-4 years old) in the Arashiyama E troop was studied using a modified sequence sampling method from July to October 2000. SOP was a relatively common activity for most of the young macaques and often continued for long periods. Participants used many kinds of object, including edible natural objects and artificial objects, such as plastic bottles, but they never used provisioned food or wild fruit in SOP bouts. An analysis of long bouts (>/=0.5 min) revealed the following interactive SOP features: (1) at any given time, participants used only one object, and only one participant held the object; (2) during SOP play-chasing, the object holder was likely to be chased by others; (3) during long bouts, the object changed hands frequently; and (4) agonistic competition for an object among young macaques was rare. Combinations of sexes, ages, relative ranks, or matrilines of the object holder and non-holder did not affect the tendency that the holder was chased by non-holder(s) during play-chasing. Even when there was a change in object holders, the repetitiveness of this interactive pattern, i.e., that the holder would be chased during SOP bouts, distinguished the SOP structure from that of other types of social play without object(s). General proximate social play mechanisms, such as self-handicapping or role taking, were associated with SOP. Other mechanisms that affected SOP included the following: (1) young macaques treated an object as a target in play competition, and (2) 'being the holder of a target object' was associated with the 'role of the chasee.'

Subliminal semantic priming changes the dynamic causal influence between the left frontal and temporal cortex.

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Matsumoto, Atsushi; Kakigi, Ryusuke

2014-01-01

Recent neuroimaging experiments have revealed that subliminal priming of a target stimulus leads to the reduction of neural activity in specific regions concerned with processing the target. Such findings lead to questions about the degree to which the subliminal priming effect is based only on decreased activity in specific local brain regions, as opposed to the influence of neural mechanisms that regulate communication between brain regions. To address this question, this study recorded EEG during performance of a subliminal semantic priming task. We adopted an information-based approach that used independent component analysis and multivariate autoregressive modeling. Results indicated that subliminal semantic priming caused significant modulation of alpha band activity in the left inferior frontal cortex and modulation of gamma band activity in the left inferior temporal regions. The multivariate autoregressive approach confirmed significant increases in information flow from the inferior frontal cortex to inferior temporal regions in the early time window that was induced by subliminal priming. In the later time window, significant enhancement of bidirectional causal flow between these two regions underlying subliminal priming was observed. Results suggest that unconscious processing of words influences not only local activity of individual brain regions but also the dynamics of neural communication between those regions.

Isolation of a monoclonal antibody from a phage display library binding the rhesus macaque MHC class I allomorph Mamu-A1*001.

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Nathan Holman

Full Text Available Monoclonal antibodies that bind to human leukocyte antigen (HLA are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001. We induced Mamu-A1*001-binding antibodies by alloimmunizing a female Mamu-A1*001-negative rhesus macaque with peripheral blood mononuclear cells (PBMC from a male Mamu-A1*001-positive donor. A Fab phage display library was constructed with PBMC from the alloimmunized macaque and panned to isolate an antibody that binds to Mamu-A1*001 but not to other common rhesus macaque MHC class I molecules. The isolated antibody distinguishes PBMC from Mamu-A1*001-positive and -negative macaques. Additionally, the Mamu-A1*001-specific antibody binds the cynomolgus macaque MHC class I ortholog Mafa-A1*001:01 but not variants Mafa-A1*001:02/03, indicating a high degree of binding specificity. The Mamu-A1*001-specific antibody will be useful for identifying Mamu-A1*001-positive rhesus macaques, for detecting Mamu-A1*001-positive cells in populations of Mamu-A1*001-negative cells, and for examining disease processes that alter expression of Mamu-A1*001 on cell surfaces. Moreover, the alloimmunization process we describe will be useful for isolating additional MHC allomorph-specific monoclonal antibodies or antibodies against other polymorphic host proteins which are difficult to isolate with traditional technologies.

Dissociated roles of the inferior frontal gyrus and superior temporal sulcus in audiovisual processing: top-down and bottom-up mismatch detection.

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Uno, Takeshi; Kawai, Kensuke; Sakai, Katsuyuki; Wakebe, Toshihiro; Ibaraki, Takuya; Kunii, Naoto; Matsuo, Takeshi; Saito, Nobuhito

2015-01-01

Visual inputs can distort auditory perception, and accurate auditory processing requires the ability to detect and ignore visual input that is simultaneous and incongruent with auditory information. However, the neural basis of this auditory selection from audiovisual information is unknown, whereas integration process of audiovisual inputs is intensively researched. Here, we tested the hypothesis that the inferior frontal gyrus (IFG) and superior temporal sulcus (STS) are involved in top-down and bottom-up processing, respectively, of target auditory information from audiovisual inputs. We recorded high gamma activity (HGA), which is associated with neuronal firing in local brain regions, using electrocorticography while patients with epilepsy judged the syllable spoken by a voice while looking at a voice-congruent or -incongruent lip movement from the speaker. The STS exhibited stronger HGA if the patient was presented with information of large audiovisual incongruence than of small incongruence, especially if the auditory information was correctly identified. On the other hand, the IFG exhibited stronger HGA in trials with small audiovisual incongruence when patients correctly perceived the auditory information than when patients incorrectly perceived the auditory information due to the mismatched visual information. These results indicate that the IFG and STS have dissociated roles in selective auditory processing, and suggest that the neural basis of selective auditory processing changes dynamically in accordance with the degree of incongruity between auditory and visual information.

Grooming reciprocity in male Tibetan macaques.

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Xia, Dong-Po; Li, Jin-Hua; Garber, Paul A; Matheson, Megan D; Sun, Bing-Hua; Zhu, Yong

2013-10-01

In several primate species, adult males are reported to compete for access to reproductive partners as well as forming affiliative and cohesive social bonds based on the exchange of goods or services. We hypothesized that among a broad set of fitness-maximizing strategies, grooming can be used by individual adult males to enhance social relationships through reciprocity and/or through the interchange of grooming for a different but equivalent good or service. We used focal animal sampling and continuously recorded dyadic grooming and agonistic interactions to test a series of predictions regarding male social interactions in a free-ranging group of Tibetan macaques (Macaca thibetana) at Huangshan, China. During the non-mating season or between males of similar rank throughout the year, grooming effort given was matched by grooming effort received. However, lower ranking males groomed higher ranking males at a greater rate and/or for a longer duration during both the mating and non-mating periods. We found that higher ranking males directed less aggression towards males with whom they formed a frequent grooming partnership, indicating that grooming received was interchanged for increased social tolerance. These data suggest that individual male Tibetan macaques employ alternative social strategies associated with grooming reciprocity or interchange depending on dominance rank and rates of aggression, and highlight the importance of both biological markets and grooming reciprocity as behavioral mechanisms used by resident adult males to form and maintain affiliative social bonds. © 2013 Wiley Periodicals, Inc.

Quantitative Proteomic Analysis of Hepatic Tissue of T2DM Rhesus Macaque

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Tingfu Du

2017-01-01

Full Text Available Type 2 diabetes mellitus (T2DM is a metabolic disorder that severely affects human health, but the pathogenesis of the disease remains unknown. The high-fat/high-sucrose diets combined with streptozotocin- (STZ- induced nonhuman primate animal model of diabetes are a valuable research source of T2DM. Here, we present a study of a STZ rhesus macaque model of T2DM that utilizes quantitative iTRAQ-based proteomic method. We compared the protein profiles in the liver of STZ-treated macaques as well as age-matched healthy controls. We identified 171 proteins differentially expressed in the STZ-treated groups, about 70 of which were documented as diabetes-related gene in previous studies. Pathway analyses indicated that the biological functions of differentially expressed proteins were related to glycolysis/gluconeogenesis, fatty acid metabolism, complements, and coagulation cascades. Expression change in tryptophan metabolism pathway was also found in this study which may be associations with diabetes. This study is the first to explore genome-wide protein expression in hepatic tissue of diabetes macaque model using HPLC-Q-TOF/MS technology. In addition to providing potential T2DM biomarkers, this quantitative proteomic study may also shed insights regarding the molecular pathogenesis of T2DM.

Do infant Japanese macaques ( Macaca fuscata) categorize objects without specific training?

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Murai, Chizuko; Tomonaga, Masaki; Kamegai, Kimi; Terazawa, Naoko; Yamaguchi, Masami K

2004-01-01

In the present study, we examined whether infant Japanese macaques categorize objects without any training, using a similar technique also used with human infants (the paired-preference method). During the familiarization phase, subjects were presented twice with two pairs of different objects from one global-level category. During the test phase, they were presented twice with a pair consisting of a novel familiar-category object and a novel global-level category object. The subjects were tested with three global-level categories (animal, furniture, and vehicle). It was found that they showed significant novelty preferences as a whole, indicating that they processed similarities between familiarization objects and novel familiar-category objects. These results suggest that subjects responded distinctively to objects without training, indicating the possibility that infant macaques possess the capacity for categorization.

Testosterone correlates with Venezuelan equine encephalitis virus infection in macaques

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Koterski James

2006-03-01

Full Text Available Abstract Here we briefly report testosterone and cytokine responses to Venezuelan equine encephalitis virus (VEEV in macaques which were used as part of a larger study conducted by the Department of Defense to better characterize pathological responses to aerosolized VEEV in non-human primates. Serial samples were collected and analyzed for testosterone and cytokines prior to and during infection in 8 captive male macaques. Infected animals exhibited a febrile response with few significant changes in cytokine levels. Baseline testosterone levels were positively associated with viremia following exposure and were significantly higher than levels obtained during infection. Such findings suggest that disease-induced androgen suppression is a reasonable area for future study. Decreased androgen levels during physiological perturbations may function, in part, to prevent immunosuppression by high testosterone levels and to prevent the use of energetic resources for metabolically-expensive anabolic functions.

Superior versus inferior Ahmed glaucoma valve implantation.

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Pakravan, Mohammad; Yazdani, Shahin; Shahabi, Camelia; Yaseri, Mehdi

2009-02-01

To compare the efficacy and safety of Ahmed glaucoma valve (AGV) (New World Medical Inc., Rancho Cucamonga, CA) implantation in the superior versus inferior quadrants. Prospective parallel cohort study. A total of 106 eyes of 106 patients with refractory glaucoma. Consecutive patients with refractory glaucoma underwent AGV implantation in the superior or inferior quadrants. Main outcome measures included intraocular pressure (IOP) and rate of complications. Other outcome measures included best corrected visual acuity (BCVA), number of glaucoma medications, and success rate (defined as at least 30% IOP reduction and 5glaucoma surgery, phthisis bulbi, or loss of light perception. Of a total of 106 eyes, 58 and 48 eyes underwent AGV implantation in the superior and inferior quadrants, respectively. Baseline characteristics were comparable in the study groups, except for preoperative IOP, which was higher in the superior group (P = 0.01). Patients were followed for a mean period of 10.6+/-8.49 months and 10.58+/-6.75 months in the superior and inferior groups, respectively (P = 0.477). BCVA was comparable between the groups at all postoperative visits (P>0.122). After 1 year, statistically significant but comparable IOP reduction from baseline (Pglaucoma medications was comparable after 1 year (1.3+/-1.2 vs. 1.9+/-0.8 for superior and inferior implants, respectively, P = 0.256). Success rates were also similar at 1 year: 27 eyes (81.8%) versus 20 eyes (95.2%) for superior and inferior implants, respectively (P = 0.227). However, the overall rate of complications, such as implant exposure necessitating removal, cosmetically unappealing appearance, and endophthalmitis, was higher in the inferior group: 12 eyes (25%) versus 3 eyes (5.2%) for superior and inferior groups, respectively, (P = 0.004). Superior and inferior AGV implants have similar intermediate efficacy in terms of IOP reduction, decrease in number of glaucoma medications, and preservation of vision. However

Use of photogrammetry as a means to assess hybrids of rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques.

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Jadejaroen, Janya; Hamada, Yuzuru; Kawamoto, Yoshi; Malaivijitnond, Suchinda

2015-01-01

Rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques are the most commonly used non-human primate models for biomedical research, but it is difficult to identify these two species in the hybrid zone (15-20°N). In this work, we used morphological values obtained via photogrammetry to assess hybrids of rhesus and long-tailed macaques at Khao Khieow Open Zoo (KKZ; 13°21'N, 101°06'E), eastern Thailand. Long-tailed and rhesus macaques have species-specific tail lengths and contrasts of their yellowish pelages. The accuracy and precision of the relative tail length (%RTL) and the contrast of the yellow hue (Cb*) of the pelage, as obtained from photographs, were compared with the corresponding direct measurements (morphometrics). The photogrammetric and morphometric measurements of %RTL and Cb* were highly significantly correlated (r = 0.989 and 0.980, p photogrammetry can be utilized to identify macaque species or hybrids when species identification relies mainly on tail length and pelage color.

A structural comparison of female-male and female-female mounting in Japanese macaques (Macaca fuscata).

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Ottenheimer Carrier, Lydia; Leca, Jean-Baptiste; Pellis, Sergio; Vasey, Paul L

2015-10-01

In certain populations, female Japanese macaques (Macaca fuscata) mount both males and females. Vasey (2007) proposed that female-female sexual mounting in Japanese macaques may be a neutral evolutionary by-product of a purported adaptation, namely, female-male mounting. In this study, we aim to further examine the proposed link between female-male and female-female mounting in Japanese macaques by comparing the structural characteristics that define both forms of mounting. We do so using Eshkol-Wachman Movement Notation (EWMN), a globographic reference system that can be used to describe the position of body segments. No significant differences were observed in the female mounters' positioning of eight different body segments (i.e., lower torso, mid-torso, upper torso, upper arm, lower arm, upper leg, lower leg, and foot) during female-male and female-female mounting. This finding lends support to the conclusion that female-female and female-male mounting are structurally, and thus, evolutionarily, related. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparison of the vaginal environment in rhesus and cynomolgus macaques pre- and post-lactobacillus colonization.

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Daggett, Gregory J; Zhao, Chunxia; Connor-Stroud, Fawn; Oviedo-Moreno, Patricia; Moon, Hojin; Cho, Michael W; Moench, Thomas; Anderson, Deborah J; Villinger, Francois

2017-10-01

Rhesus and cynomologus macaques are valuable animal models for the study of human immunodeficiency virus (HIV) prevention strategies. However, for such studies focused on the vaginal route of infection, differences in vaginal environment may have deterministic impact on the outcome of such prevention, providing the rationale for this study. We tested the vaginal environment of rhesus and cynomolgus macaques longitudinally to characterize the normal microflora based on Nugent scores and pH. This evaluation was extended after colonization of the vaginal space with Lactobacilli in an effort to recreate NHP models representing the healthy human vaginal environment. Nugent scores and pH differed significantly between species, although data from both species were suggestive of stable bacterial vaginosis. Colonization with Lactobacilli was successful in both species leading to lower Nugent score and pH, although rhesus macaques appeared better able to sustain Lactobacillus spp over time. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantification of 18F-FDG PET images using probabilistic brain atlas: clinical application in temporal lobe epilepsy patients

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Kang, Keon Wook; Lee, Dong Soo; Cho, Jae Hoon; Lee, Jae Sung; Yeo, Jeong Seok; Lee, Sang Gun; Chung, June Key; Lee, Myung Chul

2000-01-01

A probabilistic atlas of the human brain (Statistical Probability Anatomical Maps: SPAM) was developed by the international consortium for brain mapping (ICBM). After calculating the counts in volume of interest (VOI) using the product of probability of SPAM images and counts in FDG images, asymmetric indexes(AI) were calculated and used for finding epileptogenic zones in temporal lobe epilepsy (TLE). FDG PET images from 28 surgically confirmed TLE patients and 12 age-matched controls were spatially normalized to the averaged brain MRI atlas of ICBM. The counts from normalized PET images were multiplied with the probability of 12 VOIs (superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, hippocampus, parahippocampal gyrus, and amygdala in each hemisphere) of SPAM images of Montreal Neurological Institute. Finally AI was calculated on each pair of VOI, and compared with visual assessment. If AI was deviated more than 2 standard deviation of normal controls, we considered epileptogenic zones were found successfully. The counts of VOIs in normal controls were symmetric (AI 0.05) except those of inferior temporal gyrus (p<0.01). AIs in 5 pairs of VOI excluding inferior temporal gyrus were deviated to one side in TLE (p<0.05). Lateralization was correct in 23/28 of patients by AI, but all of 28 were consistent with visual inspection. In 3 patients with normal AI was symmetric on visual inspection. In 2 patients falsely lateralized using AI, metabolism was also decreased visually on contra-lateral side. Asymmetric index obtained by the product of statistical probability anatomical map and FDG PET correlated well with visual assessment in TLE patients. SPAM is useful for quantification of VOIs in functional images

Rapid Expansion of Phenylthiocarbamide Non-Tasters among Japanese Macaques.

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Nami Suzuki-Hashido

Full Text Available Bitter taste receptors (TAS2R proteins allow mammals to detect and avoid ingestion of toxins in food. Thus, TAS2Rs play an important role in food choice and are subject to complex natural selection pressures. In our previous study, we examined nucleotide variation in TAS2R38, a gene expressing bitter taste receptor for phenylthiocarbamide (PTC, in 333 Japanese macaques (Macaca fuscata from 9 local populations in Japan. We identified a PTC "non-taster" TAS2R38 allele in Japanese macaques that was caused by a loss of the start codon. This PTC non-taster allele was only found in a limited local population (the Kii area, at a frequency of 29%. In this study, we confirmed that this allele was present in only the Kii population by analyzing an additional 264 individuals from eight new populations. Using cellular and behavioral experiments, we found that this allele lost its receptor function for perceiving PTC. The nucleotide sequences of the allele including flanking regions (of about 10 kb from 23 chromosomes were identical, suggesting that a non-taster allele arose and expanded in the Kii population during the last 13,000 years. Genetic analyses of non-coding regions in Kii individuals and neighboring populations indicated that the high allele frequency in the Kii population could not be explained by demographic history, suggesting that positive selection resulted in a rapid increase in PTC non-tasters in the Kii population. The loss-of-function that occurred at the TAS2R38 locus presumably provided a fitness advantage to Japanese macaques in the Kii population. Because TAS2R38 ligands are often found in plants, this functional change in fitness is perhaps related to feeding habit specificity. These findings should provide valuable insights for elucidating adaptive evolutionary changes with respect to various environments in wild mammals.

Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques

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Boer, R.J. de; Mohri, H.; Ho, D.D.; Perelson, A.S.

2003-01-01

We determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in SIV-infected and uninfected rhesus macaques. The daily turnover rates of CD4(+) T cells, CD4(-) T cells, CD20(+) B cells, and CD16(+) NK cells in normal uninfected rhesus macaques

Progression of pathogenic events in cynomolgus macaques infected with variola virus.

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Victoria Wahl-Jensen

Full Text Available Smallpox, caused by variola virus (VARV, is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

Focal cortical dysplasia of the temporal lobe with late-onset partial epilepsy: serial quantitative MRI

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Rademacher, J.; Seitz, R.J. [Department of Neurology, Heinrich-Heine University Duesseldorf (Germany); Aulich, A. [Department of Radiology, Heinrich-Heine University, Duesseldorf (Germany); Reifenberger, G. [Department of Neuropathology, Heinrich-Heine University, Duesseldorf (Germany); Kiwit, J.C.W. [Department of Neurosurgery, Heinrich-Heine University, Duesseldorf (Germany); Langen, K.J.; Schmidt, D. [Institute of Medicine, Research Center Juelich, Heinrich-Heine University, Duesseldorf (Germany)

2000-06-01

We describe serial studies of focal cortical dysplasia causing temporal lobe seizures and progressive aphasia in a 54-year-old woman. Initially, MRI volumetry of the temporal lobes showed significant left cortical thickening corresponding to an elevated aminoacid uptake in the left temporoparietal and inferior frontal cortex on SPECT using 3-[{sup 123}I]iodo-{alpha}-methyl-l-tyrosine (IMT). After 1 year there was severe shrinkage of the left temporal lobe, possibly the result of recurrent complex partial seizures. (orig.)

Focal cortical dysplasia of the temporal lobe with late-onset partial epilepsy: serial quantitative MRI

International Nuclear Information System (INIS)

Rademacher, J.; Seitz, R.J.; Aulich, A.; Reifenberger, G.; Kiwit, J.C.W.; Langen, K.J.; Schmidt, D.

2000-01-01

We describe serial studies of focal cortical dysplasia causing temporal lobe seizures and progressive aphasia in a 54-year-old woman. Initially, MRI volumetry of the temporal lobes showed significant left cortical thickening corresponding to an elevated aminoacid uptake in the left temporoparietal and inferior frontal cortex on SPECT using 3-[ 123 I]iodo-α-methyl-l-tyrosine (IMT). After 1 year there was severe shrinkage of the left temporal lobe, possibly the result of recurrent complex partial seizures. (orig.)

Anomalies of the vena cava inferior

International Nuclear Information System (INIS)

Koen, F.R.; Bouwer, A.J.; Bornman, M.S.; Du Plessis, D.J.

1986-01-01

Two cases of anomalous inferior vena cava are presented, with the emphasis on embryology. The firts patient was investigated by venography for a clinically proven varicocele as a probable cause of infertility. A double inferior vena cava was found during venography, and was confirmed by computed tomography (CT). In the second case a left-sided inferior vena cava was an incidental finding when a CT scan was done as a diagnostic procedure in a case of Hodgkin's disease. A short summary of the embryology and the significance of the variants is presented

Total laparoscopic retrieval of inferior vena cava filter.

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Benrashid, Ehsan; Adkar, Shaunak Sanjay; Bennett, Kyla Megan; Zani, Sabino; Cox, Mitchell Wayne

2015-01-01

While there is some local variability in the use of inferior vena cava filters and there has been some evolution in the indications for filter placement over time, inferior vena cava filters remain a standard option for pulmonary embolism prophylaxis. Indications are clear in certain subpopulations of patients, particularly those with deep venous thrombosis and absolute contraindications to anticoagulation. There are, however, a variety of reported inferior vena cava filter complications in the short and long term, making retrieval of the filter desirable in most cases. Here, we present the case of a morbidly obese patient complaining of chronic abdominal pain after inferior vena cava filter placement and malposition of the filter with extensive protrusion outside the inferior vena cava. She underwent successful laparoscopic retrieval of her malpositioned inferior vena cava filters after failure of a conventional endovascular approach.

Total laparoscopic retrieval of inferior vena cava filter

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Ehsan Benrashid

2015-08-01

Full Text Available While there is some local variability in the use of inferior vena cava filters and there has been some evolution in the indications for filter placement over time, inferior vena cava filters remain a standard option for pulmonary embolism prophylaxis. Indications are clear in certain subpopulations of patients, particularly those with deep venous thrombosis and absolute contraindications to anticoagulation. There are, however, a variety of reported inferior vena cava filter complications in the short and long term, making retrieval of the filter desirable in most cases. Here, we present the case of a morbidly obese patient complaining of chronic abdominal pain after inferior vena cava filter placement and malposition of the filter with extensive protrusion outside the inferior vena cava. She underwent successful laparoscopic retrieval of her malpositioned inferior vena cava filters after failure of a conventional endovascular approach.

Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

International Nuclear Information System (INIS)

Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

2009-01-01

Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

Dynamic Interaction of Enterovirus 71 and Dendritic Cells in Infected Neonatal Rhesus Macaques.

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Zhao, Ting; Zhang, Zhixiao; Zhang, Ying; Feng, Min; Fan, Shengtao; Wang, Lichun; Liu, Longding; Wang, Xi; Wang, Qinglin; Zhang, Xiaolong; Wang, Jingjing; Liao, Yun; He, Zhanlong; Lu, Shuaiyao; Yang, Huai; Li, Qihan

2017-01-01

Enterovirus 71 (EV71) is one of the main pathogens responsible for hand, foot, and mouth disease (HFMD). Infection with EV71 can lead to severe clinical disease via extensive infections of either the respiratory or alimentary tracts in children. Based on the previous pathological study of EV71 infections in neonatal rhesus macaques, our work using this animal model and an EV71 chimera that expresses enhanced green fluorescent protein (EGFP-EV71) primarily explored where EV71 localizes and proliferates, and the subsequent initiation of the pathological process. The chimeric EGFP-EV71 we constructed was similar to the wild-type EV71 (WT-EV71) virus in its biological characteristics. Similar clinical manifestations and histo-pathologic features were equally displayed in neonatal rhesus macaques infected with either WT-EV71 or EGFP-EV71 via the respiratory route. Fluorescent signal tracing in tissues from the animals infected with EGFP-EV71 showed that EV71 proliferated primarily in the respiratory tract epithelium and the associated lymphoid tissues. Immunofluorescence and flow cytometry analyses revealed that EV71 was able to enter a pre-conventional dendritic cell (DC) population at the infection sites. The viremia identified in the macaques infected by WT-EV71 or EGFP-EV71 was present even in the artificial presence of a specific antibody against the virus. Our results suggest that EV71 primarily proliferates in the respiratory tract epithelium followed by subsequent entry into a pre-cDC population of DCs. These cells are then hijacked by the virus and they can potentially transmit the virus from local sites to other organs through the blood circulation during the infection process. Our results suggest that the EV71 infection process in this DC population does not interfere with the induction of an independent immune response against the EV71 infection in the neonatal macaques.

Inter-Group Variation in Non-Conceptive Sexual Activity in Female Japanese Macaques: Could it be Cultural?

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Jean-Baptiste Leca

2014-08-01

Full Text Available We compared two non-conceptive sexual behavioral patterns (female-male mounting – FMM – and female-female mounting – FFM across four free-ranging groups of Japanese macaques (Macaca fuscata living at three different field sites in Japan (Arashiyama, Minoo, and Jigokudani. We found marked inter-group differences and covariation in the frequency and form of FMM and FFM. This result supports the view that FMM and FFM in Japanese macaques are developmentally and evolutionarily linked. The customary occurrence, high prevalence, and great diversity of FMM and FFM at Arashiyama may be the result of combined favorable socio-demographic conditions, namely few resident males, most of them being old, sexually under-motivated, and less aggressive and controlling than the average male Japanese macaques. We suggest that FMM and FFM may be cultural sexual practices in the Arashiyama-E group. In most other populations, all the aforementioned favorable socio-demographic conditions are not met, and although female mounting may occasionally be expressed by several group members, it does not reach the group-level tradition status. Our cultural interpretation of female mounting in Japanese macaques is consistent with evidence of the social transmission of courtship behaviors and mating preferences in various animal taxa, including nonhuman primates and humans. Our study may have implications for the evolution of non-conceptive sexuality in humans, including sexual fluidity in women.

Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

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Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

2013-01-01

Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

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Julie Nemecek

Full Text Available Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA to amplify abnormal prion protein (PrP(TSE from highly diluted variant Creutzfeldt-Jakob disease (vCJD-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrP(TSE in tissues and blood. Macaque vCJD PrP(TSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA. Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV, a close relative of the bank vole, seeded with macaque vCJD PrP(TSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N. We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrP(TSE. Meadow vole brain (170N/N PrP genotype was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrP(TSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrP(TSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrP(TSE was more permissive than human PrP(TSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrP(TSE from brains of humans and macaques with vCJD. PrP(TSE signals were reproducibly detected by Western blot in dilutions through 10⁻¹² of vCJD-infected 10% brain homogenates. This is the first report showing PrP(TSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect Pr

PERFORATION OF INFERIOR ALVEOLAR NERVE BY MAXILLARY ARTERY. Perforation of inferior alveolar nerve by maxillary artery

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Prakash B Billakanti

2016-03-01

Full Text Available La fosa infratemporal es un área anatómica clínicamente importante para la administración de agentes anestésicos locales en odontología y cirugía maxilofacial. Fueron estudiadas variaciones en la anatomía del nervio alveolar inferior y la arteria maxilar en la disección infratemporal. Durante la disección rutinaria de la cabeza en el cadáver de un varón adulto, fue observada una variación excepcional en el origen del nervio alveolar inferior y su relación con las estructuras circundantes. El nervio alveolar inferior se originaba en el nervio mandibular por dos raíces y la primera parte de la arteria maxilar estaba incorporada entre ambas. El origen embriológico de esta variación y sus implicaciones clínicas es debatido. Dado que la arteria maxilar transcurría entre las dos raíces del nervio alveolar inferior, y el nervio estaba fijado entre el foramen oval y el foramen mandibular, el atrapamiento vásculo-nervioso pudo causar entume-cimiento o dolor de cabeza e interferir con la inyección de anestésicos locales en la fosa infratemporal.  Variaciones anatómicas en esta región deben ser tenidas en cuenta, especialmente en casos de tratamiento fallido de neuralgia del trigémino. Infratemporal fossa is clinically important anatomical area for the delivery of local anesthetic agents in dentistry and maxillofacial surgery. Variations in the anatomy of the inferior alveolar nerve and maxillary artery were studied in infratemporal dissection. During routine dissection of the head in an adult male cadaver an unusual variation in the origin of the inferior alveolar nerve and its relationship with the surrounding structures was observed. The inferior alveolar nerve originated from the mandibular nerve by two roots and the first part of the maxillary artery was incorporated between them. An embryologic origin of this variation and its clinical implications is discussed. Because the maxillary artery runs between the two roots of

Use of ultrasound imaging for the diagnosis of abnormal uterine bleeding in the bonnet macaque ( Macaca radiata).

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Chaudhari, Uddhav K; Imran, M; Manjramkar, Dhananjay D; Metkari, Siddhanath M; Sable, Nilesh P; Gavhane, Dnyaneshwar S; Katkam, Rajendra R; Sachdeva, Geetanjali; Thakur, Meenakshi H; Kholkute, Sanjeeva D

2017-02-01

Ultrasound is a powerful, low-cost, non-invasive medical tool used by laboratory animal veterinarians for diagnostic imaging. Sonohysterography and transvaginal ultrasound are frequently used to assess uterine anomalies in women presenting with abnormal uterine bleeding (AUB). In the present study, we have evaluated the abdominal ultrasound of bonnet monkeys ( n = 8) showing spontaneous ovulatory ( n = 5) and anovulatory ( n = 3) AUB. The ovulatory ( n = 5) macaques showed cyclic AUB for 7-8 days. The anovulatory ( n = 3) macaques had irregular AUB with menstrual cycles of 40-45 days. The B-mode abdominal, colour Doppler and 3D ultrasound scans were performed during the proliferative phase of the menstrual cycle. Ultrasound examination revealed endometrial polyps in five macaques and endometrial hyperplasia in three animals. The width and length of endometrial polyps was around 0.5-1 cm (average 0.51 ± 0.23 cm × 0.96 ± 0.16 cm) with significant increase in endometrial thickness ( P uterine cavity and colour Doppler ultrasound showed increased vascularity in the endometrial polyps. Endometrial hyperplasia characteristically appeared as a thickened echogenic endometrium ( P < 0.0002). This study demonstrates the use of non-invasive ultrasound techniques in the diagnosis of AUB in macaques.

Sensitivity of neurons in the middle temporal area of marmoset monkeys to random dot motion.

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Chaplin, Tristan A; Allitt, Benjamin J; Hagan, Maureen A; Price, Nicholas S C; Rajan, Ramesh; Rosa, Marcello G P; Lui, Leo L

2017-09-01

Neurons in the middle temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of "neurometric" thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide-anesthetized marmoset monkeys, a species that has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments. NEW & NOTEWORTHY We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural

[Contralateral Recession of the Inferior Oblique Muscle in Grave's Disease Patients with Mild M. rectus inferior fibrosis].

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Eckstein, A; Raczynski, S; Dekowski, D; Esser, J

2015-10-01

The aim of this study was to evaluate the dose effect and the resulting binocular single vision for inferior oblique muscle recession in patients with Grave's orbitopathy. The evaluation covered all patients (n = 13) between 2010-2013 treated with recession of the inferior oblique muscle for vertical deviation caused by inferior fibrosis of the contralateral eye. The inclusion criterion was a small vertical squint angle with excyclotorsion. The corrected vertical squint angle was 3.75° [7 pdpt] (median, min 1.5° [3 pdpt], max 8° [16 pdpt]) in primary position and 5.5° in adduction [11pdpt] (median, min 3°[6 pdpt], max 9°[18pdpt]). Excyclotorsion was 4° [8 pdpt] (median, min 1° [2 pdpt], max 9° [18 pdpt]). Elevation was only slightly impaired and the side difference was 5° (median). The recession distance was preoperatively determined: 0.5° squint angle reduction per mm recession distance (calculation from patients who received surgery before 2010). Inferior oblique recession generated a good field of binocular single vision (BSV) for all patients. All patients reached BSV in the central area (20°) and within 30° of downgaze. Sixty nine percent of the patients were completely diplopia free in downgaze. Diplopia persisted in more than half of the patients in up gaze outside 15°. Squint reduction was 0.5° [1 pdpt] [0.45-0.67]/per mm recession distance in primary position and 0.65° [1.3 pdpt] [0.55-0.76]/per mm for the vertical deviation in adduction. Excyclotorsion was reduced to ≤ 2° in 77 % of the patients. Inferior oblique muscle recession can be very successfully performed on the contralateral eye in patients with mild inferior rectus muscle fibrosis. Surgery at the contralateral yoke muscle prevents the risk of overeffect with resulting diplopia in downgaze, which could occur if small distance recession had been performed at the inferior rectus muscle. An overeffect in relation to inferior oblique recession will only

TMS interferes with lexical-semantic retrieval in left inferior frontal gyrus and posterior middle temporal gyrus: Evidence from cyclical picture naming.

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Krieger-Redwood, Katya; Jefferies, Elizabeth

2014-11-01

We used TMS to investigate the contribution of left inferior frontal gyrus (LIFG) and posterior middle temporal gyrus (pMTG) to lexical/semantic selection and retrieval processes using a cyclical naming paradigm. Participants named pictures that were presented repeatedly across six cycles, either in semantically related or unrelated sets. Previous research has suggested that selection demands are higher for related sets, especially after repetition, since participants experience competition from the activation of semantic neighbours. In contrast, retrieval demands are greater for unrelated sets in the absence of semantic priming, particularly on the first cycle when the target names have not been previously activated. Therefore, this paradigm can reveal independent effects of (i) retrieval demands (i.e., the ease of accessing picture names from visual input) and (ii) selection/competition. We found that rTMS to LIFG and pMTG produced similar behavioural effects: stimulation of both sites disrupted picture naming performance on early cycles (when participants were less practised at producing the picture names) and for semantically-related sets (when there was the potential for increased competition and yet also facilitation from semantic neighbours). There were no effects of TMS when either retrieval or selection requirements were maximal on their own. The data therefore support the view that both LIFG and pMTG contribute to picture name retrieval, with both sites playing a critical role in mediating the semantic facilitation of naming when retrieval demands are high. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fading Perceptual Resemblance: A Path for Rhesus Macaques (Macaca mulatta) to Conceptual Matching?

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Smith, J. David; Flemming, Timothy M.; Boomer, Joseph; Beran, Michael J.; Church, Barbara A.

2013-01-01

Cognitive, comparative, and developmental psychologists have long been intrigued by humans’ and animals’ capacity to respond to abstract relations like sameness and difference, because this capacity may underlie crucial aspects of cognition like analogical reasoning. Recently, this capacity has been explored in higher-order, relational matching-to-sample (RMTS) tasks in which humans and animals try to complete analogies of sameness and difference between disparate groups of items. The authors introduced a new paradigm to this area, by yoking the relational-matching cue to a perceptual-matching cue. Then, using established algorithms for shape distortion, the perceptual cue was weakened and eliminated. Humans’ RMTS performance easily transcended the elimination of perceptual support. In contrast, RMTS performance by six macaques faltered as they were weaned from perceptual support. No macaque showed evidence of mature RMTS performance, even given more than 260,000 training trials during which we tried to coax a relational-matching performance from them. It is an important species difference that macaques show so hesitant a response to conceptual relations when humans respond to them so effortlessly. It raises theoretical questions about the emergence of this crucial capacity during humans’ cognitive evolution and during humans’ cognitive development. PMID:24076537

Anterior ST segment depression in acute inferior myocardial infarction as a marker of greater inferior, apical, and posterolateral damage

International Nuclear Information System (INIS)

Ruddy, T.D.; Yasuda, T.; Gold, H.K.; Leinbach, R.C.; Newell, J.B.; McKusick, K.A.; Boucher, C.A.; Strauss, H.W.

1986-01-01

The clinical significance of anterior precordial ST segment depression during acute inferior myocardial infarction was evaluated in 67 consecutive patients early after onset of symptoms with gated blood pool scans, thallium-201 perfusion images, and 12-lead ECGs. Patients with anterior ST depression (n = 33) had depressed mean values for left ventricular ejection fraction (54 +/- 2% [mean +/- S.E.M.] vs 59 +/- 2%; p = 0.02), cardiac index (3.1 +/- 0.2 vs 3.6 +/- 0.2 L/m2; p = 0.03), and ratio of systolic blood pressure to end-systolic volume (2.0 +/- 0.1 vs 2.5 +/- 0.3 mm Hg/ml; p = 0.04) compared to patients with no anterior ST depression (n = 34). Patients with anterior ST depression had (1) lower mean wall motion values for the inferior, apical, and inferior posterolateral segments (p less than 0.05) and (2) greater reductions in thallium-201 uptake in the inferior and posterolateral regions (p less than 0.05). However, anterior and septal (1) wall motion and (2) thallium-201 uptake were similar in patients with and without ST depression. Thus, anterior precordial ST segment depression in patients with acute inferior wall myocardial infarction represents more than a reciprocal electrical phenomenon. It identifies patients with more severe wall motion impairment and greater hypoperfusion of the inferior and adjacent segments. The poorer global left ventricular function in these patients is a result of more extensive inferior infarction and not of remote septal or anterior injury

Superior temporal gyrus thickness correlates with cognitive performance in multiple sclerosis.

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Achiron, Asaf; Chapman, Joab; Tal, Sigal; Bercovich, Eran; Gil, Hararai; Achiron, Anat

2013-07-01

Decreased cortical thickness that signifies gray matter pathology and its impact on cognitive performance is a research field with growing interest in relapsing-remitting multiple sclerosis (RRMS) and needs to be further elucidated. Using high-field 3.0 T MRI, three-dimensional T1-FSPGR (voxel size 1 × 1 × 1 mm) cortical thickness was measured in 82 regions in the left hemisphere (LH) and right hemisphere (RH) in 20 RRMS patients with low disease activity and in 20 age-matched healthy subjects that in parallel underwent comprehensive cognitive evaluation. The correlation between local cortical atrophy and cognitive performance was examined. We identified seven regions with cortical tissue loss that differed between RRMS and age-matched healthy controls. These regions were mainly located in the frontal and temporal lobes, specifically within the gyrus rectus, inferior frontal sulcus, orbital gyrus, parahippocampal gyrus, and superior temporal gyrus, with preferential left asymmetry. Increased cortical thickness was identified in two visual sensory regions, the LH inferior occipital gyrus, and the RH cuneus, implicating adaptive plasticity. Correlation analysis demonstrated that only the LH superior temporal gyrus thickness was associated with cognitive performance and its thickness correlated with motor skills (r = 0.65, p = 0.003), attention (r = 0.45, p = 0.042), and information processing speed (r = 0.50, p = 0.025). Our findings show that restricted cortical thinning occurs in RRMS patients with mild disease and that LH superior temporal gyrus atrophy is associated with cognitive dysfunction.

Speech-like orofacial oscillations in stump-tailed macaque (Macaca arctoides) facial and vocal signals.

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Toyoda, Aru; Maruhashi, Tamaki; Malaivijitnond, Suchinda; Koda, Hiroki

2017-10-01

Speech is unique to humans and characterized by facial actions of ∼5 Hz oscillations of lip, mouth or jaw movements. Lip-smacking, a facial display of primates characterized by oscillatory actions involving the vertical opening and closing of the jaw and lips, exhibits stable 5-Hz oscillation patterns, matching that of speech, suggesting that lip-smacking is a precursor of speech. We tested if facial or vocal actions exhibiting the same rate of oscillation are found in wide forms of facial or vocal displays in various social contexts, exhibiting diversity among species. We observed facial and vocal actions of wild stump-tailed macaques (Macaca arctoides), and selected video clips including facial displays (teeth chattering; TC), panting calls, and feeding. Ten open-to-open mouth durations during TC and feeding and five amplitude peak-to-peak durations in panting were analyzed. Facial display (TC) and vocalization (panting) oscillated within 5.74 ± 1.19 and 6.71 ± 2.91 Hz, respectively, similar to the reported lip-smacking of long-tailed macaques and the speech of humans. These results indicated a common mechanism for the central pattern generator underlying orofacial movements, which would evolve to speech. Similar oscillations in panting, which evolved from different muscular control than the orofacial action, suggested the sensory foundations for perceptual saliency particular to 5-Hz rhythms in macaques. This supports the pre-adaptation hypothesis of speech evolution, which states a central pattern generator for 5-Hz facial oscillation and perceptual background tuned to 5-Hz actions existed in common ancestors of macaques and humans, before the emergence of speech. © 2017 Wiley Periodicals, Inc.

Macaques can predict social outcomes from facial expressions.

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Waller, Bridget M; Whitehouse, Jamie; Micheletta, Jérôme

2016-09-01

There is widespread acceptance that facial expressions are useful in social interactions, but empirical demonstration of their adaptive function has remained elusive. Here, we investigated whether macaques can use the facial expressions of others to predict the future outcomes of social interaction. Crested macaques (Macaca nigra) were shown an approach between two unknown individuals on a touchscreen and were required to choose between one of two potential social outcomes. The facial expressions of the actors were manipulated in the last frame of the video. One subject reached the experimental stage and accurately predicted different social outcomes depending on which facial expressions the actors displayed. The bared-teeth display (homologue of the human smile) was most strongly associated with predicted friendly outcomes. Contrary to our predictions, screams and threat faces were not associated more with conflict outcomes. Overall, therefore, the presence of any facial expression (compared to neutral) caused the subject to choose friendly outcomes more than negative outcomes. Facial expression in general, therefore, indicated a reduced likelihood of social conflict. The findings dispute traditional theories that view expressions only as indicators of present emotion and instead suggest that expressions form part of complex social interactions where individuals think beyond the present.

Sex-specific heritability of spontaneous lipid levels in an extended pedigree of Indian-origin rhesus macaques (Macaca mulatta.

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Amanda Vinson

Full Text Available The rhesus macaque is an important model for human atherosclerosis but genetic determinants of relevant phenotypes have not yet been investigated in this species. Because lipid levels are well-established and heritable risk factors for human atherosclerosis, our goal was to assess the heritability of lipoprotein cholesterol and triglyceride levels in a single, extended pedigree of 1,289 Indian-origin rhesus macaques. Additionally, because increasing evidence supports sex differences in the genetic architecture of lipid levels and lipid metabolism in humans and macaques, we also explored sex-specific heritability for all lipid measures investigated in this study. Using standard methods, we measured lipoprotein cholesterol and triglyceride levels from fasted plasma in a sample of 193 pedigreed rhesus macaques selected for membership in large, paternal half-sib cohorts, and maintained on a low-fat, low cholesterol chow diet. Employing a variance components approach, we found moderate heritability for total cholesterol (h²=0.257, P=0.032, LDL cholesterol (h²=0.252, P=0.030, and triglyceride levels (h²=0.197, P=0.034 in the full sample. However, stratification by sex (N=68 males, N=125 females revealed substantial sex-specific heritability for total cholesterol (0.644, P=0.004, females only, HDL cholesterol (0.843, P=0.0008, females only, VLDL cholesterol (0.482, P=0.018, males only, and triglyceride levels (0.705, P=0.001, males only that was obscured or absent when sexes were combined in the full sample. We conclude that genes contribute to spontaneous variation in circulating lipid levels in the Indian-origin rhesus macaque in a sex-specific manner, and that the rhesus macaque is likely to be a valuable model for sex-specific genetic effects on lipid risk factors for human atherosclerosis. These findings are a first-ever report of heritability for cholesterol levels in this species, and support the need for expanded analysis of these traits in

Attenuated Disease in SIV-Infected Macaques Treated with a Monoclonal Antibody against FasL

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Maria S. Salvato

2007-01-01

Full Text Available Acute SIVmac infection in macaques is accompanied by high levels of plasma viremia that decline with the appearance of viral immunity and is a model for acute HIV disease in man. Despite specific immune responses, the virus establishes a chronic, persistent infection. The destruction of CD4+ and CD4- lymphocyte subsets in macaques contributes to viral persistence and suggests the importance of mechanisms for depleting both infected and uninfected (bystander cells. Bystander cell killing can occur when FasL binds the Fas receptor on activated lymphocytes, which include T and B cell subpopulations that are responding to the infection. Destruction of specific immune cells could be an important mechanism for blunting viral immunity and establishing persistent infection with chronic disease. We inhibited the Fas pathway in vivo with a monoclonal antibody against FasL (RNOK203. Here we show that treatment with anti-FasL reduced cell death in circulating T and B cells, increased CTL and antibody responses to viral proteins, and lowered the setpoint viremia. By blocking FasL during only the first few weeks after infection, we attenuated SIVmac disease and increased the life span for infected and treated macaques.

Visual cortex and auditory cortex activation in early binocularly blind macaques: A BOLD-fMRI study using auditory stimuli.

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Wang, Rong; Wu, Lingjie; Tang, Zuohua; Sun, Xinghuai; Feng, Xiaoyuan; Tang, Weijun; Qian, Wen; Wang, Jie; Jin, Lixin; Zhong, Yufeng; Xiao, Zebin

2017-04-15

Cross-modal plasticity within the visual and auditory cortices of early binocularly blind macaques is not well studied. In this study, four healthy neonatal macaques were assigned to group A (control group) or group B (binocularly blind group). Sixteen months later, blood oxygenation level-dependent functional imaging (BOLD-fMRI) was conducted to examine the activation in the visual and auditory cortices of each macaque while being tested using pure tones as auditory stimuli. The changes in the BOLD response in the visual and auditory cortices of all macaques were compared with immunofluorescence staining findings. Compared with group A, greater BOLD activity was observed in the bilateral visual cortices of group B, and this effect was particularly obvious in the right visual cortex. In addition, more activated volumes were found in the bilateral auditory cortices of group B than of group A, especially in the right auditory cortex. These findings were consistent with the fact that there were more c-Fos-positive cells in the bilateral visual and auditory cortices of group B compared with group A (p visual cortices of binocularly blind macaques can be reorganized to process auditory stimuli after visual deprivation, and this effect is more obvious in the right than the left visual cortex. These results indicate the establishment of cross-modal plasticity within the visual and auditory cortices. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Spiral CT in aplasia of the pre-renal inferior vena cava as a cause of phlebothrombosis from the femoral veins to the inferior vena cava; Spiral-CT einer Aplasie der praerenalen Vena cava inferior als Ursache einer Phlebothrombose von den Oberschenkelvenen bis in die Vena cava inferior

Energy Technology Data Exchange (ETDEWEB)

Schweiger, U. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Schedel, H. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Thiede, U. [Deutsches Herzzentrum Berlin (Germany). Arbeitsgruppe Digitale Bildbearbeitung; Felix, R. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany)

1994-12-31

The case report focuses on the computed tomography of the thrombotic okklusion of the inferior vena cava, venae iliacae and femorales communes due to congenital interruption of the prerenal inferior vena cava. The embryology of the abnormality was discussed. (orig.) [Deutsch] Anhand einer Fallstudie wurden die Moeglichkeiten der computertomographischen Diagnostik bei einer durch Teilplasie der `praerenalen` Vena cava inferior hervorgerufenen Thrombose der Vv. femorales superficiales et profundae, der grossen Beckenvenen und der Vena cava inferior erlaeutert. In der Diskussion wurde auf die Embryologie der Missbildung eingegangen. (orig.)

Spontaneous extracutaneous systemic mastocytosis in a cynomolgus macaque ()

OpenAIRE

Martina , Z. Zöller; Joachim , Kaspareit

2010-01-01

Abstract A uniform cell population of proliferating mast cells with poor cytoplasmic granularity and few eosinophilic infiltrates was observed in hepatic portal tracts and the cecal submucosa of an adult male cynomolgus macaque (Macaca fascicularis) that was part of a drug safety assessment toxicity study. The proliferating mast cells were positive for Giemsa and toluidine blue staining and had strong immunoreactivity for mast cell tryptase and CD68. Considering size, morphology, i...

Intergroup variation in robbing and bartering by long-tailed macaques at Uluwatu Temple (Bali, Indonesia).

Science.gov (United States)

Brotcorne, Fany; Giraud, Gwennan; Gunst, Noëlle; Fuentes, Agustín; Wandia, I Nengah; Beudels-Jamar, Roseline C; Poncin, Pascal; Huynen, Marie-Claude; Leca, Jean-Baptiste

2017-10-01

Robbing and bartering (RB) is a behavioral practice anecdotally reported in free-ranging commensal macaques. It usually occurs in two steps: after taking inedible objects (e.g., glasses) from humans, the macaques appear to use them as tokens, returning them to humans in exchange for food. While extensively studied in captivity, our research is the first to investigate the object/food exchange between humans and primates in a natural setting. During a 4-month study in 2010, we used both focal and event sampling to record 201 RB events in a population of long-tailed macaques (Macaca fascicularis), including four neighboring groups ranging freely around Uluwatu Temple, Bali (Indonesia). In each group, we documented the RB frequency, prevalence and outcome, and tested the underpinning anthropogenic and demographic determinants. In line with the environmental opportunity hypothesis, we found a positive qualitative relation at the group level between time spent in tourist zones and RB frequency or prevalence. For two of the four groups, RB events were significantly more frequent when humans were more present in the environment. We also found qualitative partial support for the male-biased sex ratio hypothesis [i.e., RB was more frequent and prevalent in groups with higher ratios of (sub)adult males], whereas the group density hypothesis was not supported. This preliminary study showed that RB is a spontaneous, customary (in some groups), and enduring population-specific practice characterized by intergroup variation in Balinese macaques. As such, RB is a candidate for a new behavioral tradition in this species.

A critical period of progesterone withdrawal precedes menstruation in macaques

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Slayden, Ov D; Brenner, Robert M

2006-01-01

Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

Prevalence of Entamoeba nuttalli infection in wild rhesus macaques in Nepal and characterization of the parasite isolates.

Science.gov (United States)

Tachibana, Hiroshi; Yanagi, Tetsuo; Lama, Chamala; Pandey, Kishor; Feng, Meng; Kobayashi, Seiki; Sherchand, Jeevan B

2013-04-01

We have recently resurrected the name Entamoeba nuttalli Castellani, 1908 for a potentially virulent ameba isolate, P19-061405, obtained from a rhesus macaque in Kathmandu, Nepal. The ameba was morphologically indistinguishable from Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii, but located phylogenetically between E. histolytica and E. dispar. To evaluate the prevalence of E. nuttalli infection in wild rhesus macaques, 112 fecal samples were collected in four locations of the Kathmandu Valley. PCR analysis of DNA extracted from the feces showed positive rates of E. nuttalli, E. dispar, E. histolytica and E. moshkovskii of 51%, 12%, 0% and 0%, respectively. A total of 14 E. nuttalli isolates were obtained from four locations, of which 6 were established as axenic cultures. The sequences of the serine-rich protein gene of E. nuttalli isolates differed among four locations although no differences were found in the composition of sequence motifs. Isoenzyme pattern was analyzed in 8 isolates obtained from three locations. In hexokinase, the mobility of the slower migrating band was located between E. histolytica and E. dispar regardless of the culture conditions. These results demonstrate that E. nuttalli is highly prevalent in wild rhesus macaques in Nepal. Rhesus macaques appear to be one of the natural hosts and heterogeneity of the serine-rich protein gene might be useful for geographical typing of isolates. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Quantification of {sup 18}F-FDG PET images using probabilistic brain atlas: clinical application in temporal lobe epilepsy patients

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Kang, Keon Wook; Lee, Dong Soo; Cho, Jae Hoon; Lee, Jae Sung; Yeo, Jeong Seok; Lee, Sang Gun; Chung, June Key; Lee, Myung Chul [Seoul National Univ., Seoul (Korea, Republic of)

2000-07-01

A probabilistic atlas of the human brain (Statistical Probability Anatomical Maps: SPAM) was developed by the international consortium for brain mapping (ICBM). After calculating the counts in volume of interest (VOI) using the product of probability of SPAM images and counts in FDG images, asymmetric indexes(AI) were calculated and used for finding epileptogenic zones in temporal lobe epilepsy (TLE). FDG PET images from 28 surgically confirmed TLE patients and 12 age-matched controls were spatially normalized to the averaged brain MRI atlas of ICBM. The counts from normalized PET images were multiplied with the probability of 12 VOIs (superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, hippocampus, parahippocampal gyrus, and amygdala in each hemisphere) of SPAM images of Montreal Neurological Institute. Finally AI was calculated on each pair of VOI, and compared with visual assessment. If AI was deviated more than 2 standard deviation of normal controls, we considered epileptogenic zones were found successfully. The counts of VOIs in normal controls were symmetric (AI <6%, paired t-test p>0.05) except those of inferior temporal gyrus (p<0.01). AIs in 5 pairs of VOI excluding inferior temporal gyrus were deviated to one side in TLE (p<0.05). Lateralization was correct in 23/28 of patients by AI, but all of 28 were consistent with visual inspection. In 3 patients with normal AI was symmetric on visual inspection. In 2 patients falsely lateralized using AI, metabolism was also decreased visually on contra-lateral side. Asymmetric index obtained by the product of statistical probability anatomical map and FDG PET correlated well with visual assessment in TLE patients. SPAM is useful for quantification of VOIs in functional images.

Postexposure protection of macaques from vaginal SHIV infection by topical integrase inhibitors.

Science.gov (United States)

Dobard, Charles; Sharma, Sunita; Parikh, Urvi M; West, Rolieria; Taylor, Andrew; Martin, Amy; Pau, Chou-Pong; Hanson, Debra L; Lipscomb, Jonathan; Smith, James; Novembre, Francis; Hazuda, Daria; Garcia-Lerma, J Gerardo; Heneine, Walid

2014-03-12

Coitally delivered microbicide gels containing antiretroviral drugs are important for HIV prevention. However, to date, microbicides have contained entry or reverse transcriptase inhibitors that block early steps in virus infection and thus need to be given as a preexposure dose that interferes with sexual practices and may limit compliance. Integrase inhibitors block late steps after virus infection and therefore are more suitable for post-coital dosing. We first determined the kinetics of strand transfer in vitro and confirmed that integration begins about 6 hours after infection. We then used a repeat-challenge macaque model to assess efficacy of vaginal gels containing integrase strand transfer inhibitors when applied before or after simian/human immunodeficiency virus (SHIV) challenge. We showed that gel containing the strand transfer inhibitor L-870812 protected two of three macaques when applied 30 min before SHIV challenge. We next evaluated the efficacy of 1% raltegravir gel and demonstrated its ability to protect macaques when applied 3 hours after SHIV exposure (five of six protected; P infections showed no evidence of drug resistance in plasma or vaginal secretions despite continued gel dosing after infection. We documented rapid vaginal absorption reflecting a short pharmacological lag time and noted that vaginal, but not plasma, virus load was substantially reduced in the breakthrough infection after raltegravir gel treatment. We provide a proof of concept that topically applied integrase inhibitors protect against vaginal SHIV infection when administered shortly before or 3 hours after virus exposure.

No-scalpel vasectomy by electrocauterization in free range rhesus macaques (Macaca mulatta

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A. Raj

2012-02-01

Full Text Available The objective of the study was to standardize a new method of vasectomy in male rhesus macaques (Macaca mulatta. A total of 208 free range male rhesus macaques captured from different locations in Shivalik Hills in a population control programme of the rhesus macaques in India. General anaesthesia was achieved by using a combination of ketamine hydrochloride at 8 mg/kg body weight and xylazine hydrochloride at 2mg/kg body weight intramuscularly in squeeze cage. Surgical procedure of vasectomy was carried out by single-hole no-scalpel technique using a single pre-scrotal skin incision above the median raphae. Spermatic cord was grasped with ringed forceps and was pulled out through the single-hole incision. Vas deferens was separated from the artery-vein complexus and about 3-4 cm portion of vas deferens was resected. Cauterization of both ends of the vas deferens was achieved with electrocautery. The induction time for anaesthesia was 1.40±0.18 min while surgical time for vasectomy was found to be 5.09±0.22 min. Recovery from general anaesthesia was without side-effects after a mean duration of 36.07±1.22 min, whereas the duration of anaesthesia was observed to be 82.27±4.96 min. There were no major complications following the surgery and recovery of animals was smooth. Animals were kept in postoperative care for five days and released at the same capturing site.

Hipometabolismo cerebral em pacientes com esclerose mesial temporal demonstrado pelo FDG-PET Brain hypometabolism in patients with mesial-temporal sclerosis demonstrated by FDG-PET

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PAULO S. DUARTE

2000-09-01

Full Text Available O objetivo deste estudo foi avaliar a extensão do hipometabolismo cerebral em pacientes com esclerose mesial temporal (EMT. MÉTODO: Este estudo retrospectivo incluiu 21 pacientes que apresentavam epilepsia parcial complexa refrataria à terapia e que foram selecionados para cirurgia após análise extensa que incluía: EEG de superfície e estudos de neuroimagem (PET, SPECT e ressonância magnética. Todos os pacientes foram submetidos a intervenção cirúrgica e tiveram confirmação histológica de EMT. Uma análise semi-quantitativa foi realizada, utilizando regiões de interesse (ROIs nas seguintes estruturas: lobos frontais, parietais e occipitais, gânglios da base, tálamos, cerebelo e três diferentes regiões nos lobos temporais, que compreendiam o córtex medial, inferior e lateral. Um índice de assimetria (IA foi calculado, comparando as contagens por pixel nas estruturas homólogas em ambos os hemisférios cerebrais. Os IAs das diferentes estruturas foram então correlacionados. RESULTADOS: Uma correlação significativa foi demonstrada entre os IAs do córtex medial dos lobos temporais e aqueles dos lobos frontais, dos lobos parietais, dos gânglios da base e dos tálamos (r = 0,72, 0,62, 0,47 e 0,47 respectivamente com p The purpose of this study was to evaluate the extent of brain hypometabolism in patients with mesial-temporal sclerosis (MTS. METHOD: This retrospective study included 21 patients who had medically refractory complex partial seizures and were selected for surgical therapy after a comprehensive evaluation which included surface EEG recordings and neuroimaging studies (PET, SPECT and MRI. All patients were subjected to surgical intervention and had an histopathological confirmation of MTS. A semi-quantitative analysis of the PET images was performed using regions of interest in the following structures: frontal, parietal and occipital lobes, basal ganglia, thalami, cerebellum and three different regions in the

Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

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Coffey, Lark L; Pesavento, Patricia A; Keesler, Rebekah I; Singapuri, Anil; Watanabe, Jennifer; Watanabe, Rie; Yee, JoAnn; Bliss-Moreau, Eliza; Cruzen, Christina; Christe, Kari L; Reader, J Rachel; von Morgenland, Wilhelm; Gibbons, Anne M; Allen, A Mark; Linnen, Jeff; Gao, Kui; Delwart, Eric; Simmons, Graham; Stone, Mars; Lanteri, Marion; Bakkour, Sonia; Busch, Michael; Morrison, John; Van Rompay, Koen K A

2017-01-01

Animal models of Zika virus (ZIKV) are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA) could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants.

Evidence that emotion mediates social attention in rhesus macaques.

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Emily J Bethell

Full Text Available BACKGROUND: Recent work on non-human primates indicates that the allocation of social attention is mediated by characteristics of the attending animal, such as social status and genotype, as well as by the value of the target to which attention is directed. Studies of humans indicate that an individual's emotion state also plays a crucial role in mediating their social attention; for example, individuals look for longer towards aggressive faces when they are feeling more anxious, and this bias leads to increased negative arousal and distraction from other ongoing tasks. To our knowledge, no studies have tested for an effect of emotion state on allocation of social attention in any non-human species. METHODOLOGY: We presented captive adult male rhesus macaques with pairs of adult male conspecific face images - one with an aggressive expression, one with a neutral expression - and recorded gaze towards these images. Each animal was tested twice, once during a putatively stressful condition (i.e. following a veterinary health check, and once during a neutral (or potentially positive condition (i.e. a period of environmental enrichment. Initial analyses revealed that behavioural indicators of anxiety and stress were significantly higher after the health check than during enrichment, indicating that the former caused a negative shift in emotional state. PRINCIPLE FINDINGS: The macaques showed initial vigilance for aggressive faces across both conditions, but subsequent responses differed between conditions. Following the health check, initial vigilance was followed by rapid and sustained avoidance of aggressive faces. By contrast, during the period of enrichment, the macaques showed sustained attention towards the same aggressive faces. CONCLUSIONS/SIGNIFICANCE: These data provide, to our knowledge, the first evidence that shifts in emotion state mediate social attention towards and away from facial cues of emotion in a non-human animal. This work

Improved xenobiotic metabolism and reduced susceptibility to cancer in gluten-sensitive macaques upon introduction of a gluten-free diet.

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Karol Sestak

2011-04-01

Full Text Available A non-human primate (NHP model of gluten sensitivity was employed to study the gene perturbations associated with dietary gluten changes in small intestinal tissues from gluten-sensitive rhesus macaques (Macaca mulatta.Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD and gluten-containing (GD diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies,targeting expression of over 20,000 genes.When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories--cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function--this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function and actin-collagen-matrix metalloproteinases (MMP genes.A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research.

Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease

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Mahesh Mohan

2016-10-01

Full Text Available The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD, gluten-free diet (GFD, barley gluten-derived diet (BOMI and reduced gluten barley-derived diet (RGB. It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p < 0.05 following the consumption of dietary gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity of gut microbiome in GS macaques started to change (p = 0.011 towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b were upregulated (p < 0.05 in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911, Prevotella stercorea (NR_041364 and Streptococcus luteciae (AJ297218 that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes

Phenotypic and Functional Characterization of Monoclonal Antibodies with Specificity for Rhesus Macaque CD200, CD200R and Mincle.

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Siddappa N Byrareddy

Full Text Available Lectin-like molecules and their receptors are cell surface molecules that have been shown to play a role in either facilitating infection or serving as transporters of HIV/SIV in vivo. The role of these lectin-like molecules in the pathogenesis of HIV/SIV infection continues to be defined. In efforts to gain further insight on the potential role of these lectin-like molecules, our laboratory generated monoclonal antibodies (mAb against the human analogs of rhesus macaque CD200, CD200R and Mincle, since the rhesus macaques are accepted as the most reliable animal model to study human HIV infection. The characterization of the cell lineages from the blood and various tissues of rhesus macaques that express these lectin-like molecules are described herein. Among the mononuclear cells, the cells of the myeloid lineage of rhesus macaques are the predominant cell lineages that express readily detectable levels of CD200, CD200R and Mincle that is similar to the expression of Siglec-1 and Siglec-3 reported by our laboratory earlier. Subset analysis revealed that a higher frequency of the CD14+/CD16- subset from normal rhesus macaques express CD200, CD200R and Mincle. Differences in the frequencies and density of expression of these molecules by the gated population of CD14+ cells from various tissues are noted with PBMC and bone marrow expressing the highest and the mononuclear cells isolated from the colon and ileum expressing the lowest levels. While a significant frequency of pDCs and mDCs express Siglec-1/Siglec-3, a much lower frequency expresses CD200, CD200R and Mincle in PBMCs from rhesus macaques. The mAb against CD200 and CD200R but not Mincle appear to inhibit the infection of macrophage tropic SIV/SHIV in vitro. We conclude that these mAbs may have potential to be used as adjunctive therapeutic agents to control/inhibit SIV/HIV infection.

Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection

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Stewart, Laurel M.; Koenig, Michelle; Semler, Matthew; Breitbach, Meghan E.; Zeng, Xiankun; Weiler, Andrea M.; Barry, Gabrielle L.; Thoong, Troy H.; Wiepz, Gregory J.; Dudley, Dawn M.; Simmons, Heather A.; Mejia, Andres; Morgan, Terry K.; Salamat, M. Shahriar; Kohn, Sarah; Antony, Kathleen M.; Mohns, Mariel S.; Hayes, Jennifer M.; Schultz-Darken, Nancy; Schotzko, Michele L.; Peterson, Eric; Capuano, Saverio; Osorio, Jorge E.; O’Connor, Shelby L.; O’Connor, David H.; Golos, Thaddeus G.

2018-01-01

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection. PMID:29381706

Agenesia de veia cava inferior associada à trombose venosa profunda Agenesis of inferior vena cava associated with deep venous thrombosis

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Clovis Luis Konopka

2010-09-01

Full Text Available A agenesia da veia cava inferior é uma anomalia congênita rara, que foi recentemente identificada como um importante fator de risco para o desenvolvimento e a recorrência de trombose venosa profunda de membros inferiores em jovens. O objetivo deste trabalho foi relatar o caso de uma paciente que apresentou trombose venosa profunda dois meses após a realização de cirurgia de varizes. A angiotomografia computadorizada demonstrou a presença de anomalia venosa complexa com ausência da veia cava inferior.The agenesis of the inferior vena cava is a rare congenital anomaly, which was recently identified as an important risk factor for the development and recurrence of deep venous thrombosis especially in young people. The goal of this work was to report the case of a patient who presented deep venous thrombosis approximately two months after varicose vein surgery. The computerized angiotomography demonstrated the presence of a complex venous anomaly with absence of the inferior vena cava.

Perturbations de l'homéostasie lymphocytaire T chez le macaque rhésus chinois en phase aiguë d'infection par le SIVmac251

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Ponte, Rosalie

2014-01-01

As a model to study type 1 human immunodeficiency virus (HIV-1) pathogenesis, rhesus macaques infected with the simian immunodeficiency virus (SIV) are under extensive investigation. Two subspecies of rhesus macaques have been defined, based on a different geographic origin. Indian rhesus macaques exhibit a rapid disease progression and acute infection is characterized by a massive CD4 T-cell loss in the intestinal mucosa. This was associated to the translocation of bacterial products through...

The post-birthday world: consequences of temporal landmarks for temporal self-appraisal and motivation.

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Peetz, Johanna; Wilson, Anne E

2013-02-01

Much as physical landmarks help structure our representation of space, temporal landmarks such as birthdays and significant calendar dates structure our perception of time, such that people may organize or categorize their lives into "chunks" separated by these markers. Categories on the temporal landscape may vary depending on what landmarks are salient at a given time. We suggest these landmarks have implications for identity and motivation. The present research examined consequences of salient temporal landmarks for perceptions of the self across time and motivation to pursue successful future selves. Studies 1 and 2 show that temporally extended selves are perceived as less connected to, and more dissimilar from, the current self when an intervening landmark event has been made salient. Study 3 addresses the proposed mechanism, demonstrating that intervening landmarks lead people to categorize pre- and postlandmark selves into separate categories more often than when the same time period contains no salient landmarks. Finally, we examined whether landmark-induced mental contrasting of present state and future desired state could increase goal-pursuit motivation (in an effort to bridge the gap between inferior present and better future states). Studies 4-6 demonstrate that landmark-induced discrepancies between current health and hoped-for future health increased participants' motivation to exercise and increased the likelihood that they acted in line with their future-oriented goals. (c) 2013 APA, all rights reserved.

Endovascular management of inferior vena cava filter thrombotic occlusion.

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Branco, Bernardino C; Montero-Baker, Miguel F; Espinoza, Eduardo; Gamero, Maria; Zea-Vera, Rodrigo; Labropoulos, Nicos; Leon, Luis R

2018-01-01

Objective Inferior vena cava occlusion is a potentially life-threatening complication related to caval filters. We present our experience with filter-induced inferior vena cava occlusion in order to assess the feasibility, safety, and effectiveness of endovascular management. Methods A retrospective review of all patients undergoing inferior vena cava filter placement over a 60-month study period was performed. From this cohort, a total of 10 cases of inferior vena cava occlusion after filter placement were identified. Demographics, clinical data, procedures, and outcomes were extracted. Patients were followed to the last clinic visit or until they died. Results One-hundred eighty filters were placed by our group practice during the study period. Of those, a total of 10 patients were identified. Overall, there were 7 males; the mean age was 57.1 years (25-78 years). The median time between inferior vena cava filter placement and filter occlusion was 105 days (range 5-4745 days). All patients were clinically symptomatic at the time of their presentation. Nine out of 10 patients were successfully managed endovascularly. Trellis™-8 thrombectomy was the most common endovascular strategy performed ( n = 9). Four patients had balloon angioplasty, two of those with stent placement for chronically occluded inferior vena cava/iliac veins. No thromboembolic complications developed during a median follow-up period of 233 days (range 4-1083 days). Conclusions Endovascular management of inferior vena cava occlusion is feasible, safe, and effective in decreasing thrombus burden in the presence of an inferior vena cava filter. Further studies evaluating long-term inferior vena cava patency and optimal surveillance regimen after endovascular management of filter-related inferior vena cava occlusion are warranted.

Functional dissociation between anterior temporal lobe and inferior frontal gyrus in the processing of dynamic body expressions: Insights from behavioral variant frontotemporal dementia.

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Jastorff, Jan; De Winter, Francois-Laurent; Van den Stock, Jan; Vandenberghe, Rik; Giese, Martin A; Vandenbulcke, Mathieu

2016-12-01

Several brain regions are involved in the processing of emotional stimuli, however, the contribution of specific regions to emotion perception is still under debate. To investigate this issue, we combined behavioral testing, structural and resting state imaging in patients diagnosed with behavioral variant frontotemporal dementia (bvFTD) and age matched controls, with task-based functional imaging in young, healthy volunteers. As expected, bvFTD patients were impaired in emotion detection as well as emotion categorization tasks, testing dynamic emotional body expressions as stimuli. Interestingly, their performance in the two tasks correlated with gray matter volume in two distinct brain regions, the left anterior temporal lobe for emotion detection and the left inferior frontal gyrus (IFG) for emotion categorization. Confirming this observation, multivoxel pattern analysis in healthy volunteers demonstrated that both ROIs contained information for emotion detection, but that emotion categorization was only possible from the pattern in the IFG. Furthermore, functional connectivity analysis showed reduced connectivity between the two regions in bvFTD patients. Our results illustrate that the mentalizing network and the action observation network perform distinct tasks during emotion processing. In bvFTD, communication between the networks is reduced, indicating one possible cause underlying the behavioral symptoms. Hum Brain Mapp 37:4472-4486, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Anatomy of fractures of the inferior scapular angle].

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Bartoníček, J; Tuček, M; Malík, J

2018-01-01

The aim of this study is to describe the anatomy of fractures of the inferior angle and the adjacent part of the scapular body, based on 3D CT reconstructions. In a series of 375 scapular fractures, we identified a total of 20 fractures of the inferior angle of the scapular body (13 men, 7 women), with a mean patient age of 50 years (range 3373). In all fractures, 3D CT reconstructions were obtained, allowing an objective evaluation of the fracture pattern with a focus on the size and shape of the inferior angle fragment, propagation of the fracture line to the lateral and medial borders of the infraspinous part of the scapular body, fragment displacement and any additional fracture of the ipsilateral scapula and the shoulder girdle. We identified a total of 5 types of fracture involving the distal half of the infraspinous part of the scapular body. The first type, recorded in 5 cases, affected only the apex of the inferior angle, with a small part of the adjacent medial border. The second type, occurring in 4 cases, involved fractures separating the entire inferior angle. The third type, represented by 4 cases, was characterized by a fracture line starting medially close above the inferior angle and passing proximolaterally. The separated fragment had a shape of a big drop, carrying also the distal half of the lateral pillar in addition to the inferior angle. In the fourth type identified in 5 fractures, the separated fragment was formed both by the inferior angle and a variable part of the medial border. The fifth type, being by its nature a transition to the fracture of the infraspinous part of the body, was recorded in 2 cases, with the same V-shaped fragment. Fractures of the inferior angle and the adjacent part of the scapular body are groups of fractures differing from other infraspinous fractures of the scapular body. Although these fractures are highly variable in terms of shape, they have the same course of fracture line and the manner of displacement

Microscopic mild focal cortical dysplasia in temporal lobe dual pathology: an electrocorticography study.

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Morales Chacón, L; Estupiñán, B; Lorigados Pedre, L; Trápaga Quincoses, O; García Maeso, I; Sanchez, A; Bender del Busto, J; Garcia, M E; Baez Martin, M; Zaldivar, M; Gómez, A; Orozco, S; Rocha Arrieta, L

2009-10-01

Associations between electrophysiological and histological findings might provide an insight into the epileptogenicity of mild focal cortical dysplasia (FCD) in patients with temporal lobe epilepsy (TLE) and a dual pathology. A total of 22 patients with pharmacoresistant TLE were included in the study, 16 of them with histologically confirmed hippocampal sclerosis (HS) associated with neocortical temporal mild Palmini Type-I FCD subtypes and 6 with HS. Intraoperative electrocorticography (ECoG) recordings were analysed for epileptiform discharge frequency and morphology. Associations between histological, and electrocorticography pattern findings in these patients were analysed. Electroclinical outcomes in these patients were also evaluated. Neocortical areas with mild Palmini Type-I FCD showed a significantly higher spike frequency (SF) recorded in the inferior temporal gyrus than those neocortical areas in patients with HS. There was a tendency to higher spike frequency and lower amplitude in neocortical areas with histopathologic subtype IB FCD in relation with IA during intraoperative ECoG. Post-SF excision and amplitude were significantly lower during neocortical post-excision intraoperative ECoG than during neocortical pre-excision recording. There was no difference found in the clinical outcome between patients with and without FCD. Intraoperative electrocorticographic interictal spike frequency recorded in the neocortical inferior temporal gyrus may help to characterize the histopathologic subtypes of mild Palmini Type-I FCD in patients with temporal lobe epilepsy (TLE) and a dual pathology. Our data support the epileptogenicity of neocortical mild FCD in TLE and assessments of ECoG patterns are relevant to determine the extent of the resection in these patients which can influence the electroclinical outcome.

Inferior frontal gyrus activation predicts individual differences in perceptual learning of cochlear-implant simulations.

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Eisner, Frank; McGettigan, Carolyn; Faulkner, Andrew; Rosen, Stuart; Scott, Sophie K

2010-05-26

This study investigated the neural plasticity associated with perceptual learning of a cochlear implant (CI) simulation. Normal-hearing listeners were trained with vocoded and spectrally shifted speech simulating a CI while cortical responses were measured with functional magnetic resonance imaging (fMRI). A condition in which the vocoded speech was spectrally inverted provided a control for learnability and adaptation. Behavioral measures showed considerable individual variability both in the ability to learn to understand the degraded speech, and in phonological working memory capacity. Neurally, left-lateralized regions in superior temporal sulcus and inferior frontal gyrus (IFG) were sensitive to the learnability of the simulations, but only the activity in prefrontal cortex correlated with interindividual variation in intelligibility scores and phonological working memory. A region in left angular gyrus (AG) showed an activation pattern that reflected learning over the course of the experiment, and covariation of activity in AG and IFG was modulated by the learnability of the stimuli. These results suggest that variation in listeners' ability to adjust to vocoded and spectrally shifted speech is partly reflected in differences in the recruitment of higher-level language processes in prefrontal cortex, and that this variability may further depend on functional links between the left inferior frontal gyrus and angular gyrus. Differences in the engagement of left inferior prefrontal cortex, and its covariation with posterior parietal areas, may thus underlie some of the variation in speech perception skills that have been observed in clinical populations of CI users.

The value of extended pedigrees for next-generation analysis of complex disease in the rhesus macaque.

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Vinson, Amanda; Prongay, Kamm; Ferguson, Betsy

2013-01-01

Complex diseases (e.g., cardiovascular disease and type 2 diabetes, among many others) pose the biggest threat to human health worldwide and are among the most challenging to investigate. Susceptibility to complex disease may be caused by multiple genetic variants (GVs) and their interaction, by environmental factors, and by interaction between GVs and environment, and large study cohorts with substantial analytical power are typically required to elucidate these individual contributions. Here, we discuss the advantages of both power and feasibility afforded by the use of extended pedigrees of rhesus macaques (Macaca mulatta) for genetic studies of complex human disease based on next-generation sequence data. We present these advantages in the context of previous research conducted in rhesus macaques for several representative complex diseases. We also describe a single, multigeneration pedigree of Indian-origin rhesus macaques and a sample biobank we have developed for genetic analysis of complex disease, including power of this pedigree to detect causal GVs using either genetic linkage or association methods in a variance decomposition approach. Finally, we summarize findings of significant heritability for a number of quantitative traits that demonstrate that genetic contributions to risk factors for complex disease can be detected and measured in this pedigree. We conclude that the development and application of an extended pedigree to analysis of complex disease traits in the rhesus macaque have shown promising early success and that genome-wide genetic and higher order -omics studies in this pedigree are likely to yield useful insights into the architecture of complex human disease.

Effect of Chronic Social Stress on Prenatal Transfer of Antitetanus Immunity in Captive Breeding Rhesus Macaques (Macaca mulatta).

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Stammen, Rachelle L; Cohen, Joyce K; Meeker, Tracy L; Crane, Maria M; Amara, Rama R; Hicks, Sakeenah L; Meyer, Jerrold S; Ethun, Kelly F

2018-05-15

Because tetanus can cause significant morbidity and mortality in NHP, colonywide vaccination with tetanus toxoid is recommendedfor outdoor breeding colonies of rhesus macaques, with primary immunizations commonly given to infants at 6 mo of age followed by booster vaccines every 10 y. Maternal antibodies are thought to offer protective immunity to infants younger than 6 mo. However, historical colony data from the Yerkes National Primate Research Center show a higher incidence of tetanus among infants (≤ 6 mo old) born to subordinate dams. Whether this higher incidence of infantile tetanus is due to a higher incidence of trauma among subordinate animals or is a stress-induced impairment of maternal antibody protection is unknown. Studies in other NHP species suggest that chronic exposure to social stressors interferes with the receptor-mediated transplacental transfer of IgG. Therefore, the primary aim of this study was to determine whether chronic stress associated with social subordination impairs prenatal transfer of antitetanus immunity in breeding female rhesus macaques. Subjects included 26 high- and 26 low-ranking adult female rhesus macaques that were nearly 5 or 10 y after their initial immunization and their nonimmunized infants. We hypothesized that infants born to subordinate dams that were nearly 10 y after immunization would have the lowest infant-to-dam antibody ratios and thus would be at greatest risk for infection. Results revealed no significant intergroup differences in infant antitetanus IgG levels. However, infant-to-dam IgG ratios against tetanus were significantly lower among subordinate animals compared with dominant macaques, after accounting for the number of years since the dam's initial vaccination. In addition, higher maternal hair cortisol levels predicted lower infant-to-dam tetanus toxoid IgG ratios. Together, these findings suggest that chronic social stress in female rhesus macaques may hamper the prenatal transfer of

A Case of Blunt Trauma of the Eyeball Associated With an Inferior Oblique Muscle and an Inferior Rectus Muscle Rupture.

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Nitta, Keisuke; Kashima, Tomoyuki; Miura, Fumihide; Hiroe, Takashi; Akiyama, Hideo; Kishi, Shoji

2016-01-01

Rupture of the extraocular muscle in the absence of significant injury to the eyeball and adnexa is uncommon. The authors report a case of blunt trauma of the eyeball associated with an inferior oblique muscle and an inferior rectus muscle rupture. A 55-year-old man slipped and fell down hitting his eye on an extended windshield wiper blade. Although he had treatment in the emergency room, he complained of diplopia in the primary position 1 day postoperatively. After noticing ruptures of the inferior oblique muscle and an inferior rectus muscle during exploratory surgery, the authors carefully repaired it. Diplopia in the primary position had disappeared within 1 month after the operation and by 6 months postoperatively. The movement of the eye had almost completely recovered.

Syntactic Structure Building in the Anterior Temporal Lobe during Natural Story Listening

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Brennan, Jonathan; Nir, Yuval; Hasson, Uri; Malach, Rafael; Heeger, David J.; Pylkkanen, Liina

2012-01-01

The neural basis of syntax is a matter of substantial debate. In particular, the inferior frontal gyrus (IFG), or Broca's area, has been prominently linked to syntactic processing, but the anterior temporal lobe has been reported to be activated instead of IFG when manipulating the presence of syntactic structure. These findings are difficult to…

Radiographic measurement of the cardiothoracic ratio in pet macaques from Sulawesi, Indonesia

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Schillaci, Michael A. [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada)], E-mail: schillaci@utsc.utoronto.ca; Parish, Stephanie [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada); Jones-Engel, Lisa [National Primate Research Center, University of Washington, 1705 N.E. Pacific Street, Seattle, WA 98195 (United States)

2009-11-15

The relative size of the heart, as measured by the cardiothoracic ratio, is often used as an index of ventricular hypertrophy-an important measure of myocardial pathophysiology in human primates. Despite its widespread use in human medicine, use of the cardiothoracic ratio in nonhuman primate veterinary medicine has been poorly documented. This report describes the results of our radiographic study of the cardiothoracic ratio in a sample of pet monkeys from Sulawesi, Indonesia. We assessed the effects of age and sex on cardiothoracic ratios, and compared our estimates with those presented in the literature for the Formosan macaque (Macaca cyclopis). Our results indicated a significant difference between the Sulawesi macaque species groupings in cardiothoracic ratios. Sex and age-related differences were not significant. Comparisons of cardiothoracic ratios with published ratios indicated similarity between M. cyclopis and Macaca nigra, but not between M. cyclopis and Macaca tonkeana.

Radiographic measurement of the cardiothoracic ratio in pet macaques from Sulawesi, Indonesia

International Nuclear Information System (INIS)

Schillaci, Michael A.; Parish, Stephanie; Jones-Engel, Lisa

2009-01-01

The relative size of the heart, as measured by the cardiothoracic ratio, is often used as an index of ventricular hypertrophy-an important measure of myocardial pathophysiology in human primates. Despite its widespread use in human medicine, use of the cardiothoracic ratio in nonhuman primate veterinary medicine has been poorly documented. This report describes the results of our radiographic study of the cardiothoracic ratio in a sample of pet monkeys from Sulawesi, Indonesia. We assessed the effects of age and sex on cardiothoracic ratios, and compared our estimates with those presented in the literature for the Formosan macaque (Macaca cyclopis). Our results indicated a significant difference between the Sulawesi macaque species groupings in cardiothoracic ratios. Sex and age-related differences were not significant. Comparisons of cardiothoracic ratios with published ratios indicated similarity between M. cyclopis and Macaca nigra, but not between M. cyclopis and Macaca tonkeana.

Zika Virus Tissue and Blood Compartmentalization in Acute Infection of Rhesus Macaques.

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Lark L Coffey

Full Text Available Animal models of Zika virus (ZIKV are needed to better understand tropism and pathogenesis and to test candidate vaccines and therapies to curtail the pandemic. Humans and rhesus macaques possess similar fetal development and placental biology that is not shared between humans and rodents. We inoculated 2 non-pregnant rhesus macaques with a 2015 Brazilian ZIKV strain. Consistent with most human infections, the animals experienced no clinical disease but developed short-lived plasma viremias that cleared as neutralizing antibody developed. In 1 animal, viral RNA (vRNA could be detected longer in whole blood than in plasma. Despite no major histopathologic changes, many adult tissues contained vRNA 14 days post-infection with highest levels in hemolymphatic tissues. These observations warrant further studies to investigate ZIKV persistence and its potential clinical implications for transmission via blood products or tissue and organ transplants.

Vaccination against H9N2 avian influenza virus reduces bronchus-associated lymphoid tissue formation in cynomolgus macaques after intranasal virus challenge infection.

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Nakayama, Misako; Ozaki, Hiroichi; Itoh, Yasushi; Soda, Kosuke; Ishigaki, Hirohito; Okamatsu, Masatoshi; Sakoda, Yoshihiro; Park, Chun-Ho; Tsuchiya, Hideaki; Kida, Hiroshi; Ogasawara, Kazumasa

2016-12-01

H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Improved Xenobiotic Metabolism and Reduced Susceptibility to Cancer in Gluten-Sensitive Macaques upon Introduction of a Gluten-Free Diet

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Sestak, Karol; Conroy, Lauren; Aye, Pyone P.; Mehra, Smriti; Doxiadis, Gaby G.; Kaushal, Deepak

2011-01-01

Background A non-human primate (NHP) model of gluten sensitivity was employed to study the gene perturbations associated with dietary gluten changes in small intestinal tissues from gluten-sensitive rhesus macaques (Macaca mulatta). Methodology Stages of remission and relapse were accomplished in gluten-sensitive animals by administration of gluten-free (GFD) and gluten-containing (GD) diets, as described previously. Pin-head-sized biopsies, obtained non-invasively by pediatric endoscope from duodenum while on GFD or GD, were used for preparation of total RNA and gene profiling, using the commercial Rhesus Macaque Microarray (Agilent Technologies),targeting expression of over 20,000 genes. Principal Findings When compared with normal healthy control, gluten-sensitive macaques showed differential gene expressions induced by GD. While observed gene perturbations were classified into one of 12 overlapping categories - cancer, metabolism, digestive tract function, immune response, cell growth, signal transduction, autoimmunity, detoxification of xenobiotics, apoptosis, actin-collagen deposition, neuronal and unknown function - this study focused on cancer-related gene networks such as cytochrome P450 family (detoxification function) and actin-collagen-matrix metalloproteinases (MMP) genes. Conclusions/Significance A loss of detoxification function paralleled with necessity to metabolize carcinogens was revealed in gluten-sensitive animals while on GD. An increase in cancer-promoting factors and a simultaneous decrease in cancer-preventing factors associated with altered expression of actin-collagen-MMP gene network were noted. In addition, gluten-sensitive macaques showed reduced number of differentially expressed genes including the cancer-associated ones upon withdrawal of dietary gluten. Taken together, these findings indicate potentially expanded utility of gluten-sensitive rhesus macaques in cancer research. PMID:21533263

Inferiority is compex

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Wade, Jess

2017-07-01

In Inferior: How Science Got Women Wrong and the New Research That's Rewriting the Story, author Angela Saini puts forward the idea that bad science has been used to endorse the cultural prejudice that women are both biologically and psychologically second rate to men.

Genetic Divergence of the Rhesus Macaque Major Histocompatibility Complex

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Daza-Vamenta, Riza; Glusman, Gustavo; Rowen, Lee; Guthrie, Brandon; Geraghty, Daniel E.

2004-01-01

The major histocompatibility complex (MHC) is comprised of the class I, class II, and class III regions, including the MHC class I and class II genes that play a primary role in the immune response and serve as an important model in studies of primate evolution. Although nonhuman primates contribute significantly to comparative human studies, relatively little is known about the genetic diversity and genomics underlying nonhuman primate immunity. To address this issue, we sequenced a complete rhesus macaque MHC spanning over 5.3 Mb, and obtained an additional 2.3 Mb from a second haplotype, including class II and portions of class I and class III. A major expansion of from six class I genes in humans to as many as 22 active MHC class I genes in rhesus and levels of sequence divergence some 10-fold higher than a similar human comparison were found, averaging from 2% to 6% throughout extended portions of class I and class II. These data pose new interpretations of the evolutionary constraints operating between MHC diversity and T-cell selection by contrasting with models predicting an optimal number of antigen presenting genes. For the clinical model, these data and derivative genetic tools can be implemented in ongoing genetic and disease studies that involve the rhesus macaque. PMID:15289473

Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain.

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Noguchi, Kevin K; Johnson, Stephen A; Manzella, Francesca M; Masuoka, Kobe L; Williams, Sasha L; Martin, Lauren D; Dissen, Gregory A; Ikonomidou, Chrysanthy; Schenning, Katie J; Olney, John W; Brambrink, Ansgar M

2018-03-28

Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7-8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

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Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

2016-03-01

Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

Using Hematology Data from Malaria Vaccine Research Trials in Humans and Rhesus Macaques (Macaca mulatta) To Guide Volume Limits for Blood Withdrawal.

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Hegge, Sara R; Hickey, Bradley W; Mcgrath, Shannon M; Stewart, V Ann

2016-12-01

Guidelines on safe volume limits for blood collection from research participants in both humans and laboratory animals vary widely between institutions. The main adverse event that may be encountered in large blood volume withdrawal is iron-deficiency anemia. Monitoring various parameters in a standard blood panel may help to prevent this outcome. To this end, we analyzed the Hgb and MCV values from 43 humans and 46 macaques in malaria vaccine research trials. Although the percentage of blood volume removed was greater for macaques than humans, macaques demonstrated an overall increase of MCV over time, indicating the ability to respond appropriately to frequent volume withdrawals. In contrast, humans showed a consistent declining trend in MCV. These declines in human MCV and Hgb were significant from the beginning to end of the study despite withdrawals that were smaller than recommended volume limits. Limiting the volume withdrawn to no more than 12.5% seemed to be sufficient for macaques, and at 14% or more individual animals tended to fail to respond appropriately to large-volume blood loss, as demonstrated by a decrease in MCV. The overall positive erythropoietic response seen in macaques was likely due to the controlled, iron-fortified diet they received. The lack of erythropoietic response in the human subjects may warrant iron supplementation or reconsideration of current blood volume withdrawal guidelines.

Temporal lobe epilepsy due to meningoencephaloceles into the greater sphenoid wing. A consequence of idiopathic intracranial hypertension?

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Urbach, H.; Jamneala, G.; Mader, I.; Egger, K.; Yang, S. [Medical Center - Freiburg Univ. (Germany). Dept. of Neuroradiology; Altenmueller, D. [Medical Center - Freiburg Univ. (Germany). Dept. of Epileptology

2018-01-15

Antero-inferior temporal lobe meningoencephaloceles are a rare, but increasingly recognized cause of drug-resistant temporal lobe epilepsy (TLE). In order to evaluate whether these lesions are related to idiopathic intracranial hypertension (IIH), we analyzed clinical and MRI findings of a cohort of patients undergoing presurgical work-up. Seizure onset in the anterior temporal lobe was proven by EEG electrodes in 22 patients, and in 21 patients, anterior temporal lobectomy (mostly with sparing of the hippocampus) was performed. MRI signs of IIH (in particular empty sella) and the volumes of the ventricles and external CSF spaces were determined and related to the body mass index (BMI) and clinical outcome. Six of seven obese (BMI > 30 kg/m{sup 2}) compared to four of 15 non-obese patients had partial empty or empty sella (p = 0.007). Bilateral lesions were found in all obese and 11 patients. Seizure freedom (Engel class 1A) was achieved in 12 of 21 patients (5 obese compared to 7 non-obese patients). BMI was related to the volume of the external CSF spaces (r = 0.467), and age at seizure onset was higher in obese patients. Roughly a third of patients with temporal lobe epilepsy due to antero-inferior meningoencephaloceles is obese and has MRI signs of idiopathic intracranial hypertension. (orig.)

Vocalizations during post-conflict affiliations from victims toward aggressors based on uncertainty in Japanese macaques.

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Katsu, Noriko; Yamada, Kazunori; Nakamichi, Masayuki

2017-01-01

We investigated the use of vocalizations called "grunts," "girneys," and "coos" accompanied by post-conflict affiliative interaction between former opponents (reconciliation) in Japanese macaques (Macaca fuscata). Although reconciliation functions to repair bonds, such interactions sometimes entail risks of receiving further aggression. Vocalizations can be used at a distance from the former opponent; thus, we predict that vocalizations are used particularly by victims of a conflict, and are frequently used in situations of uncertainty when it is difficult for them to estimate whether the former opponent will resume aggression. In addition, we predict that vocalizations are effective in preventing further aggression. To test these hypotheses, we conducted observations of post-conflict and matched-control situations in female Japanese macaques living in a free-ranging group. We found that former opponents tended to be attracted to each other within the first minute following a conflict, thus demonstrating reconciliation behavior. Vocalizations were more frequently used by the victims in post-conflict interactions than under control situations; however, this tendency was not found in aggressors. When affiliation with the former opponent occurred, victims were more likely to use vocalizations towards less familiar opponents. These findings suggest that Japanese macaques used vocalizations more often when interacting with less predictable former opponents. Victims were more likely to receive aggression from former aggressors when engaged in affiliations with them than under no such affiliations. No significant differences were found in the probability of the victims receiving aggression, regardless of whether they used vocalizations; thus, whether the victim benefits from using vocalizations in these contexts remains unclear. Japanese macaques form despotic societies and therefore, further aggression was inevitable, to some degree, after a conflict. The use of

Vocalizations during post-conflict affiliations from victims toward aggressors based on uncertainty in Japanese macaques.

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Noriko Katsu

Full Text Available We investigated the use of vocalizations called "grunts," "girneys," and "coos" accompanied by post-conflict affiliative interaction between former opponents (reconciliation in Japanese macaques (Macaca fuscata. Although reconciliation functions to repair bonds, such interactions sometimes entail risks of receiving further aggression. Vocalizations can be used at a distance from the former opponent; thus, we predict that vocalizations are used particularly by victims of a conflict, and are frequently used in situations of uncertainty when it is difficult for them to estimate whether the former opponent will resume aggression. In addition, we predict that vocalizations are effective in preventing further aggression. To test these hypotheses, we conducted observations of post-conflict and matched-control situations in female Japanese macaques living in a free-ranging group. We found that former opponents tended to be attracted to each other within the first minute following a conflict, thus demonstrating reconciliation behavior. Vocalizations were more frequently used by the victims in post-conflict interactions than under control situations; however, this tendency was not found in aggressors. When affiliation with the former opponent occurred, victims were more likely to use vocalizations towards less familiar opponents. These findings suggest that Japanese macaques used vocalizations more often when interacting with less predictable former opponents. Victims were more likely to receive aggression from former aggressors when engaged in affiliations with them than under no such affiliations. No significant differences were found in the probability of the victims receiving aggression, regardless of whether they used vocalizations; thus, whether the victim benefits from using vocalizations in these contexts remains unclear. Japanese macaques form despotic societies and therefore, further aggression was inevitable, to some degree, after a conflict

Macaque cardiac physiology is sensitive to the valence of passively viewed sensory stimuli.

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Eliza Bliss-Moreau

Full Text Available Autonomic nervous system activity is an important component of affective experience. We demonstrate in the rhesus monkey that both the sympathetic and parasympathetic branches of the autonomic nervous system respond differentially to the affective valence of passively viewed video stimuli. We recorded cardiac impedance and an electrocardiogram while adult macaques watched a series of 300 30-second videos that varied in their affective content. We found that sympathetic activity (as measured by cardiac pre-ejection period increased and parasympathetic activity (as measured by respiratory sinus arrhythmia decreased as video content changes from positive to negative. These findings parallel the relationship between autonomic nervous system responsivity and valence of stimuli in humans. Given the relationship between human cardiac physiology and affective processing, these findings suggest that macaque cardiac physiology may be an index of affect in nonverbal animals.

Alpha male replacements and delayed dispersal in crested macaques (Macaca nigra).

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Marty, Pascal R; Hodges, Keith; Agil, Muhammad; Engelhardt, Antje

2017-07-01

In species with a high male reproductive skew, competition between males for the top dominant position is high and escalated fights are common between competitors. As a consequence, challenges incur potentially high costs. Selection should favor males who time an alpha male challenge to maximize chances of a successful outcome minimizing costs. Despite the importance of alpha male replacements for individual males, we know little about the timing of challenges and the condition of the challenger. We investigated the timing and process of alpha male replacements in a species living in multi-male groups with high male reproductive skew, the crested macaque. We studied four wild groups over 6 years in the Tangkoko Reserve, North Sulawesi, Indonesia, during which 16 alpha male replacements occurred. Although unusual for cercopithecines, male crested macaques delayed their natal dispersal until they attained maximum body mass and therefore fighting ability whereupon they emigrated and challenged the alpha male in another group. Accordingly, all observed alpha male replacements were from outside males. Ours is the first report of such a pattern in a primate species living in multi-male groups. Although the majority of alpha male replacements occurred through direct male-male challenges, many also took place opportunistically (i.e., after the alpha male had already been injured or had left the group). Furthermore, alpha male tenures were very short (averaging ca. 12 months). We hypothesize that this unusual pattern of alpha male replacements in crested macaques is related to the species-specific combination of high male reproductive skew with a large number of males per group. Am. J. Primatol. 79:e22448, 2017. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc. © 2015 The Authors. American Journal of Primatology Published by Wiley Periodicals, Inc.

Inferior patellar pole fragmentation in children: just a normal variant?

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Kan, J.H.; Vogelius, Esben S.; Orth, Robert C.; Guillerman, R.P.; Jadhav, Siddharth P. [Texas Children' s Hospital, E.B. Singleton Pediatric Radiology, Houston, TX (United States)

2015-06-15

Fragmentary ossification of the inferior patella is often dismissed as a normal variant in children younger than 10 years of age. The purpose of this study was to determine whether fragmentary inferior patellar pole ossification is a normal variant or is associated with symptoms or signs of pathology using MRI and clinical exam findings as reference. A retrospective review was performed on 150 patients ages 5-10 years who underwent 164 knee radiography and MRI exams (45.1% male, mean age: 7.8 years). The presence or absence of inferior patellar pole fragmentation on radiography was correlated with the presence or absence of edema-like signal on MR images. Clinical notes were reviewed for the presence of symptoms or signs referable to the inferior patellar pole. These data were compared with a 1:1 age- and sex-matched control group without inferior pole fragmentation. Statistical analysis was performed using two-tailed t-tests. Forty of 164 (24.4%) knee radiographs showed fragmentary ossification of the inferior patella. Of these 40 knees, 62.5% (25/40) had edema-like signal of the inferior patellar bone marrow compared with 7.5% (3/40) of controls (P = 0.035). Patients with fragmentary ossification at the inferior patella had a significantly higher incidence of documented focal inferior patellar pain compared with controls (20% vs. 2.5%, P = 0.015). Inferior patellar pole fragmentation in children 5 to 10 years of age may be associated with localized symptoms and bone marrow edema-like signal and should not be routinely dismissed as a normal variant of ossification. (orig.)

Social modulation of cognition: Lessons from rhesus macaques relevant to education.

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Monfardini, Elisabetta; Reynaud, Amélie J; Prado, Jérôme; Meunier, Martine

2017-11-01

Any animal, human or non-human, lives in a world where there are others like itself. Individuals' behaviors are thus inevitably influenced by others, and cognition is no exception. Long acknowledged in psychology, social modulations of cognition have been neglected in cognitive neuroscience. Yet, infusing this classic topic in psychology with brain science methodologies could yield valuable educational insights. In recent studies, we used a non-human primate model, the rhesus macaque, to identify social influences representing ancient biases rooted in evolution, and neuroimaging to shed light on underlying mechanisms. The behavioral and neural data garnered in humans and macaques are summarized, with a focus on two findings relevant to human education. First, peers' mistakes stand out as exceptional professors and seem to have devoted areas and neurons in the primates' brain. Second, peers' mere presence suffices to enhance performance in well-learned tasks, possibly by boosting activity in the brain network involved in the task at hand. These findings could be translated into concrete pedagogical interventions in the classroom. Copyright © 2016 Elsevier Ltd. All rights reserved.

Food resources, distribution and seasonal variations in ranging in lion-tailed macaques, Macaca silenus in the Western Ghats, India.

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Erinjery, Joseph J; Kavana, T S; Singh, Mewa

2015-01-01

The distribution and availability of food was examined to see how it influenced ranging patterns and sleeping site selection in a group of lion-tailed macaques. The home range and core area were 130.48 ha (95% kernel) and 26.68 ha (50% kernel) respectively. The lion-tailed macaques had a longer day range, had a greater number of sleeping sites and used more core areas in the summer as compared to the monsoon and the post-monsoon seasons. The ranging patterns and sleeping site use were influenced by the major food resources used in a particular season. The ranging was mainly influenced by Artocarpus heterophyllus in monsoon, Cullenia exarillata and Toona ciliata in post- monsoon, and Artocarpus heterophyllus and Ficus amplissima in summer. The distribution of these four plant species is, therefore, critical to ranging, and thus to conservation of the lion-tailed macaque.

TRIMe7-CypA, an alternative splicing isoform of TRIMCyp in rhesus macaque, negatively modulates TRIM5α activity

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Na, Lei [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Tang, Yan-Dong [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Biotechnology Institute of Southern Medical University, Guangzhou 510515 (China); Liu, Jian-Dong; Yu, Chang-Qing; Sun, Liu-Ke; Lin, Yue-Zhi; Wang, Xue-Feng [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Wang, Xiaojun, E-mail: xjw@hvri.ac.cn [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Zhou, Jian-Hua, E-mail: jianhua_uc@126.com [Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Harbin Pharmaceutical Group Biovaccine Company, Harbin 150069 (China)

2014-04-04

Highlights: • TRIMe7-CypA expresses in rhesus and pig-tailed, but not long-tailed macaques. • TRIMe7-CypA does not show the restriction to a HIV-GFP report virus in vitro. • It acts as a negative modulator to TRIM5α likely by competitive inhibition. - Abstract: The existence of innate, host-specific restriction factors is a major obstacle to the development of nonhuman primate models for AIDS studies, and TRIM5α is one of the most important of these restriction factors. In recent years, a TRIM5 chimeric gene that was retrotransposed by a cyclophilin A (CypA) cDNA was identified in certain macaque species. The TRIM5α-CypA fusion protein, TRIMCyp, which was expressed in these monkeys, had lost its restriction ability toward HIV-1. We previously found that TRIMe7-CypA, an alternative splicing isoform of the TRIMCyp transcripts, was expressed in pig-tailed and rhesus macaques but absent in long-tailed macaques. In this study, the anti-HIV-1 activity of TRIMe7-CypA in the rhesus macaque (RhTRIMe7-CypA) was investigated. The over-expression of RhTRIMe7-CypA in CrFK, HeLa and HEK293T cells did not restrict the infection or replication of an HIV-1-GFP reporter virus in these cells. As a positive control, rhesus (rh)TRIM5α strongly inhibited the reporter virus. Intriguingly, the anti-HIV-1 activity of RhTRIM5α was significantly reduced in a dose-dependent manner by the co-repression of RhTRIMe7-CypA. Our data indicate that although the RhTRIMe7-CypA isoform does not appear to restrict HIV-1, it may act as a negative modulator of TRIM family proteins, presumably by competitive inhibition.

TRIMe7-CypA, an alternative splicing isoform of TRIMCyp in rhesus macaque, negatively modulates TRIM5α activity

International Nuclear Information System (INIS)

Na, Lei; Tang, Yan-Dong; Liu, Jian-Dong; Yu, Chang-Qing; Sun, Liu-Ke; Lin, Yue-Zhi; Wang, Xue-Feng; Wang, Xiaojun; Zhou, Jian-Hua

2014-01-01

Highlights: • TRIMe7-CypA expresses in rhesus and pig-tailed, but not long-tailed macaques. • TRIMe7-CypA does not show the restriction to a HIV-GFP report virus in vitro. • It acts as a negative modulator to TRIM5α likely by competitive inhibition. - Abstract: The existence of innate, host-specific restriction factors is a major obstacle to the development of nonhuman primate models for AIDS studies, and TRIM5α is one of the most important of these restriction factors. In recent years, a TRIM5 chimeric gene that was retrotransposed by a cyclophilin A (CypA) cDNA was identified in certain macaque species. The TRIM5α-CypA fusion protein, TRIMCyp, which was expressed in these monkeys, had lost its restriction ability toward HIV-1. We previously found that TRIMe7-CypA, an alternative splicing isoform of the TRIMCyp transcripts, was expressed in pig-tailed and rhesus macaques but absent in long-tailed macaques. In this study, the anti-HIV-1 activity of TRIMe7-CypA in the rhesus macaque (RhTRIMe7-CypA) was investigated. The over-expression of RhTRIMe7-CypA in CrFK, HeLa and HEK293T cells did not restrict the infection or replication of an HIV-1-GFP reporter virus in these cells. As a positive control, rhesus (rh)TRIM5α strongly inhibited the reporter virus. Intriguingly, the anti-HIV-1 activity of RhTRIM5α was significantly reduced in a dose-dependent manner by the co-repression of RhTRIMe7-CypA. Our data indicate that although the RhTRIMe7-CypA isoform does not appear to restrict HIV-1, it may act as a negative modulator of TRIM family proteins, presumably by competitive inhibition

Immunogenicity in pig-tailed macaques of poliovirus replicons expressing HIV-1 and SIV antigens and protection against SHIV-89.6P disease

International Nuclear Information System (INIS)

Fultz, Patricia N.; Stallworth, Jackie; Porter, Donna; Novak, Miroslav; Anderson, Marie J.; Morrow, Casey D.

2003-01-01

In the search for an effective vaccine against the human immunodeficiency virus (HIV), novel ways to deliver viral antigens are being evaluated. One such approach is the use of nonreplicating viral vectors encoding HIV and/or SIV genes that are expressed after infection of host cells. Nonreplicating poliovirus vectors, termed replicons, that expressed HIV-1/HXB2 and SIVmac239 gag and various HIV-1 env genes from different clades were tested for immunogenicity and protective efficacy against intravenous challenge of pig-tailed macaques with SHIV-89.6P. To maximize both cellular and humoral immune responses, a prime-boost regimen was used. Initially, macaques were immunized four times over 35 weeks by either the intranasal and intrarectal or the intramuscular (im) route with mixtures of poliovirus replicons expressing HIV-1 gag and multiple env genes. Immunization with replicons alone induced both serum antibodies and lymphocyte proliferative responses. After boosting with purified Env protein, neutralizing antibodies to SHIV-89.6P were induced in four of five immunized animals. In a second experiment, four macaques were immunized im three times over 27 weeks with replicons expressing the SIVmac239 gag and HIV-1/HXB2 env genes. All immunized animals were then boosted twice with purified HIV-1-89.6 rgp140-Env and SIVmac239 p55-Gag proteins. Four control animals received only the two protein inoculations. Immunized and control animals were then challenged intravenously with the pathogenic SHIV-89.6P. After challenge the animals were monitored for virus isolation from peripheral blood mononuclear cells and plasma viremia and for changes in virus-specific antibody titers. Naieve pig-tailed macaques experienced rapid loss of CD4 + T cells and died between 38 and 62 weeks after infection. In contrast, macaques immunized with replicons and proteins rapidly cleared plasma virus and did not experience sustained loss of CD4 + lymphocytes. Furthermore, two of the four macaques

Drenagem anômala de veia pulmonar inferior direita em veia cava inferior associada a apêndice hepático intracardíaco Anomalous drainage of the right inferior pulmonary vein into the inferior vena cava associated to intrathoracic hepatic appendix

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Carlos R Moraes

1988-08-01

Full Text Available Descreve-se o caso de uma paciente de 61 anos de idade, com drenagem anômala de veia pulmonar inferior direita em veia cava inferior, associada a apêndice hepático intratorácico, herniado através de fenda no diafragma. A correção cirúrgica foi realizada por anastomose direta da veia anômala com o átrio esquerdo, pela redução do apêndice hepático para a cavidade abdominal e, finalmente, pelo fechamento do defeito diafragmático. O pós-operatório decorreu sem qualquer complicação. Os autores chamam a atenção para a raridade do caso.The authors present a case of a 61-year-old woman with anomalous drainage of the right inferior pulmonary vein into the inferior vena cava associated to an intrathoracic hepatic appendix herniated through a diaphragmatic defect. Surgical correction was obtained by direct anastomosis of the anomalous vein to the left atrium, reduction of the hepatic appendix to the abdominal cavity and closure of the diphragmatic defect. The postoperative course was unevenftul. The rarity of this condition is stressed.

Plasticity of Ability to Form Cross-Modal Representations in Infant Japanese Macaques

Science.gov (United States)

Adachi, Ikuma; Kuwahata, Hiroko; Fujita, Kazuo; Tomonaga, Masaki; Matsuzawa, Tetsuro

2009-01-01

In a previous study, Adachi, Kuwahata, Fujita, Tomonaga & Matsuzawa demonstrated that infant Japanese macaques (Macaca fuscata) form cross-modal representations of conspecifics but not of humans. However, because the subjects in the experiment were raised in a large social group and had considerably less exposure to humans than to…

The clinical application of inferior vena caval CO2-DSA

International Nuclear Information System (INIS)

Guo Jinhe; Teng Gaojun; Zhu Guangyu; Li Guozhao; Fang Wen; He Shicheng; Deng Tang

2007-01-01

Objective: To explore the feasibility and safety of inferior vena caval CO 2 -DSA and evaluate the results of inferior vena cavography using CO 2 -DSA or iodinated contrast media. Methods: 25 patients diagnosed as deep venous thrombosis of lower limb were prepared to conceive the implantation of inferior vena caval filter. The inferior vena cava and right renal vein CO 2 -DSA and iodinated contrast media DSA were carried out through jugular or femoral vein approach in all patients. Results: The inferior vena caval angiography with CO 2 -DSA or iodinated contrast media were carried out successfully in all patients. The quality of the inferior vena caval angiogram showed: with CO 2 as contrast media, 14 cases obtained excellent images and 11 cases had good images; with iodinated contrast media the images of 18 cases were excellent and 7 cases were good. No thrombus and variation of inferior vena cava were found by the two kinds of angiography. The diameter of inferior vena cava showed: (20.01 ± 0.83) mm with CO 2 contrast media and (20.15 ± 0.92) mm with iodinated contrast media, (P=0.006); having statistical significance between them. The safety of angiography with CO 2 presented only 1 case with transient slight decrease of O 2 saturation. No abnormal changes were found in blood pressure, heart rate and so on. Conclusions: Inferior vena caval CO 2 -DSA is feasible and safe, with statistical significance in the measurement of inferior vena caval diameter comparing with iodinated contrast material but with no influence on the implantation of filter. (authors)

Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

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Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

2013-07-19

HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

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Roger Le Grand

2013-07-01

Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

Naltrexone treatment reverses astrocyte atrophy and immune dysfunction in self-harming macaques.

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Lee, Kim M; Chiu, Kevin B; Didier, Peter J; Baker, Kate C; MacLean, Andrew G

2015-11-01

The role of glia in the development and treatment of behavioral abnormalities is understudied. Recent reports have observed glial activation in several disorders, including depression, autism spectrum disorders and self-injurious behaviors (SIB). In the current study, we examined SIB in the physiologically and anatomically relevant nonhuman primate (NHP) model. At the Tulane National Primate Research Center (TNPRC), approximately 5% of singly housed macaques develop symptoms of SIB. We have previously demonstrated that naltrexone hydrochloride can be effective in reducing SIB. We have also demonstrated that the astrocytes of animals with SIB are distinctly atrophic and display heightened innate immune activation compared with control animals. We have added a third group of animals (five macaques identified with SIB and treated with oral naltrexone at a dose of 3.2mg/kg) to the previous cohort (six macaques with a history of SIB but not treated, and nine animals with no history of SIB) for this study. Gray and white matter astrocytes from frontal cortical tissue were examined following necropsy. Innate immune activation of astrocytes, which was increased in SIB animals, was markedly decreased in animals receiving naltrexone, as was atrophy of both grey and white matter astrocytes. This was concomitant with improved behavioral correlates. Preventing astrocyte activation in select areas of the brain to reduce injurious behavior is an innovative concept with implications for mental health studies. Differences in multiple areas of primate brain would help determine how self-injurious behavior develops. These studies suggest a stronger role for astrocytes in the cellular events associated with self-injurious behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

The presence of the casein kinase II phosphorylation sites of Vpu enhances the CD4+ T cell loss caused by the simian-human immunodeficiency virus SHIVKU-lbMC33 in pig-tailed macaques

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Singh, Dinesh K.; Griffin, Darcy M.; Pacyniak, Erik; Jackson, Mollie; Werle, Michael J.; Wisdom, Bo; Sun, Francis; Hout, David R.; Pinson, David M.; Gunderson, Robert S.; Powers, Michael F.; Wong, Scott W.; Stephens, Edward B.

2003-01-01

The simian-human immunodeficiency virus (SHIV)/ macaque model for human immunodeficiency virus type 1 has become a useful tool to assess the role of Vpu in lentivirus pathogenesis. In this report, we have mutated the two phosphorylated serine residues of the HIV-1 Vpu to glycine residues and have reconstructed a SHIV expressing this nonphosphorylated Vpu (SHIV S52,56G ). Expression studies revealed that this protein was localized to the same intracellular compartment as wild-type Vpu. To determine if this virus was pathogenic, four pig-tailed macaques were inoculated with SHIV S52,56G and virus burdens and circulating CD4 + T cells monitored up to 1 year. Our results indicate that SHIV S52,56G caused rapid loss in the circulating CD4 + T cells within 3 weeks of inoculation in one macaque (CC8X), while the other three macaques developed no or gradual numbers of CD4 + T cells and a wasting syndrome. Histological examination of tissues revealed that macaque CC8X had lesions in lymphoid tissues (spleen, lymph nodes, and thymus) that were typical for macaques inoculated with pathogenic parental SHIV KU-1bMC33 and had no lesions within the CNS. To rule out that macaque CC8X had selected for a virus in which there was reversion of the glycine residues at positions 52 and 56 to serine residues and/or compensating mutations occurred in other genes associated with CD4 down-regulation, sequence analysis was performed on amplified vpu sequences isolated from PBMC and from several lymphoid tissues at necropsy. Sequence analysis revealed a reversion of the glycine residues back to serine residues in this macaque. The other macaques maintained low virus burdens, with one macaque (P003) developing a wasting syndrome between months 9 and 11. Histological examination of tissues from this macaque revealed a thymus with severe atrophy that was similar to that of a previously reported macaque inoculated with a SHIV lacking vpu (Virology 293, 2002, 252). Sequence analysis revealed no

Sexual signalling in female crested macaques and the evolution of primate fertility signals.

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Higham, James P; Heistermann, Michael; Saggau, Carina; Agil, Muhammad; Perwitasari-Farajallah, Dyah; Engelhardt, Antje

2012-06-18

Female signals of fertility have evolved in diverse taxa. Among the most interesting study systems are those of multimale multifemale group-living primates, where females signal fertility to males through multiple signals, and in which there is substantial inter-specific variation in the composition and reliability of such signals. Among the macaques, some species display reliable behavioural and/or anogenital signals while others do not. One cause of this variation may be differences in male competitive regimes: some species show marked sexual dimorphism and reproductive skew, with males fighting for dominance, while others show low dimorphism and skew, with males queuing for dominance. As such, there is variation in the extent to which rank is a reliable proxy for male competitiveness, which may affect the extent to which it is in females' interest to signal ovulation reliably. However, data on ovulatory signals are absent from species at one end of the macaque continuum, where selection has led to high sexual dimorphism and male reproductive skew. Here we present data from 31 cycles of 19 wild female crested macaques, a highly sexually dimorphic species with strong mating skew. We collected measures of ovarian hormone data from faeces, sexual swelling size from digital images, and male and female behaviour. We show that both sexual swelling size and female proceptivity are graded-signals, but relatively reliable indicators of ovulation, with swelling size largest and female proceptive behaviours most frequent around ovulation. Sexual swelling size was also larger in conceptive cycles. Male mating behaviour was well timed to female ovulation, suggesting that males had accurate information about this. Though probabilistic, crested macaque ovulatory signals are relatively reliable. We argue that in species where males fight over dominance, male dominance rank is surrogate for competitiveness. Under these circumstances it is in the interest of females to increase

Sexual signalling in female crested macaques and the evolution of primate fertility signals

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Higham James P

2012-06-01

Full Text Available Abstract Background Female signals of fertility have evolved in diverse taxa. Among the most interesting study systems are those of multimale multifemale group-living primates, where females signal fertility to males through multiple signals, and in which there is substantial inter-specific variation in the composition and reliability of such signals. Among the macaques, some species display reliable behavioural and/or anogenital signals while others do not. One cause of this variation may be differences in male competitive regimes: some species show marked sexual dimorphism and reproductive skew, with males fighting for dominance, while others show low dimorphism and skew, with males queuing for dominance. As such, there is variation in the extent to which rank is a reliable proxy for male competitiveness, which may affect the extent to which it is in females’ interest to signal ovulation reliably. However, data on ovulatory signals are absent from species at one end of the macaque continuum, where selection has led to high sexual dimorphism and male reproductive skew. Here we present data from 31 cycles of 19 wild female crested macaques, a highly sexually dimorphic species with strong mating skew. We collected measures of ovarian hormone data from faeces, sexual swelling size from digital images, and male and female behaviour. Results We show that both sexual swelling size and female proceptivity are graded-signals, but relatively reliable indicators of ovulation, with swelling size largest and female proceptive behaviours most frequent around ovulation. Sexual swelling size was also larger in conceptive cycles. Male mating behaviour was well timed to female ovulation, suggesting that males had accurate information about this. Conclusion Though probabilistic, crested macaque ovulatory signals are relatively reliable. We argue that in species where males fight over dominance, male dominance rank is surrogate for competitiveness. Under these

Anatomy of Inferior Mesenteric Artery in Fetuses

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Ayesha Nuzhat

2016-01-01

Full Text Available Aim. To analyze Inferior Mesenteric Artery in fetuses through its site of origin, length, diameter, and variation of its branches. Method. 100 fetuses were collected from various hospitals in Warangal at Kakatiya Medical College in Andhra Pradesh, India, and were divided into two groups, group I (second-trimester fetuses and group II (third-trimester fetuses, followed by dissection. Result. (1 Site of Origin. In group I fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra in 33 out of 34 fetuses (97.2%. In one fetus it was at first lumbar vertebra, 2.8%. In all group II fetuses, origin of Inferior Mesenteric Artery was at third lumbar vertebra. (2 Length. In group I fetuses it ranged between 18 and 30 mm, average being 24 mm except in one fetus where it was 48 mm. In group II fetuses the length ranged from 30 to 34 mm, average being 32 mm. (3 Diameter. In group I fetuses it ranged from 0.5 to 1 mm, and in group II fetuses it ranged from 1 to 2 mm, average being 1.5 mm. (4 Branches. Out of 34 fetuses of group I, 4 fetuses showed variation. In one fetus left colic artery was arising from abdominal aorta, 2.9%. In 3 fetuses, Inferior Mesenteric Artery was giving a branch to left kidney, 8.8%. Out of 66 fetuses in group II, 64 had normal branching. In one fetus left renal artery was arising from Inferior Mesenteric Artery, 1.5%, and in another fetus one accessory renal artery was arising from Inferior Mesenteric Artery and entering the lower pole of left kidney. Conclusion. Formation, course, and branching pattern of an artery depend on development and origin of organs to attain the actual adult position.

Discovery of novel MHC-class I alleles and haplotypes in Filipino cynomolgus macaques (Macaca fascicularis) by pyrosequencing and Sanger sequencing: Mafa-class I polymorphism.

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Shiina, Takashi; Yamada, Yukiho; Aarnink, Alice; Suzuki, Shingo; Masuya, Anri; Ito, Sayaka; Ido, Daisuke; Yamanaka, Hisashi; Iwatani, Chizuru; Tsuchiya, Hideaki; Ishigaki, Hirohito; Itoh, Yasushi; Ogasawara, Kazumasa; Kulski, Jerzy K; Blancher, Antoine

2015-10-01

Although the low polymorphism of the major histocompatibility complex (MHC) transplantation genes in the Filipino cynomolgus macaque (Macaca fascicularis) is expected to have important implications in the selection and breeding of animals for medical research, detailed polymorphism information is still lacking for many of the duplicated class I genes. To better elucidate the degree and types of MHC polymorphisms and haplotypes in the Filipino macaque population, we genotyped 127 unrelated animals by the Sanger sequencing method and high-resolution pyrosequencing and identified 112 different alleles, 28 at cynomolgus macaque MHC (Mafa)-A, 54 at Mafa-B, 12 at Mafa-I, 11 at Mafa-E, and seven at Mafa-F alleles, of which 56 were newly described. Of them, the newly discovered Mafa-A8*01:01 lineage allele had low nucleotide similarities (Filipino macaque population would identify these and other high-frequency Mafa-class I haplotypes that could be used as MHC control animals for the benefit of biomedical research.

Intermuscular pterygoid-temporal abscess following inferior alveolar nerve block anesthesia-A computer tomography based navigated surgical intervention: Case report and review.

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Wallner, Jürgen; Reinbacher, Knut Ernst; Pau, Mauro; Feichtinger, Matthias

2014-01-01

Inferior alveolar nerve block (IANB) anesthesia is a common local anesthetic procedure. Although IANB anesthesia is known for its safety, complications can still occur. Today immediately or delayed occurring disorders following IANB anesthesia and their treatment are well-recognized. We present a case of a patient who developed a symptomatic abscess in the pterygoid region as a result of several inferior alveolar nerve injections. Clinical symptoms included diffuse pain, reduced mouth opening and jaw's hypomobility and were persistent under a first step conservative treatment. Since image-based navigated interventions have gained in importance and are used for various procedures a navigated surgical intervention was initiated as a second step therapy. Thus precise, atraumatic surgical intervention was performed by an optical tracking system in a difficult anatomical region. A symptomatic abscess was treated by a computed tomography-based navigated surgical intervention at our department. Advantages and disadvantages of this treatment strategy are evaluated.

Intermuscular pterygoid-temporal abscess following inferior alveolar nerve block anesthesia–A computer tomography based navigated surgical intervention: Case report and review

Science.gov (United States)

Wallner, Jürgen; Reinbacher, Knut Ernst; Pau, Mauro; Feichtinger, Matthias

2014-01-01

Inferior alveolar nerve block (IANB) anesthesia is a common local anesthetic procedure. Although IANB anesthesia is known for its safety, complications can still occur. Today immediately or delayed occurring disorders following IANB anesthesia and their treatment are well-recognized. We present a case of a patient who developed a symptomatic abscess in the pterygoid region as a result of several inferior alveolar nerve injections. Clinical symptoms included diffuse pain, reduced mouth opening and jaw's hypomobility and were persistent under a first step conservative treatment. Since image-based navigated interventions have gained in importance and are used for various procedures a navigated surgical intervention was initiated as a second step therapy. Thus precise, atraumatic surgical intervention was performed by an optical tracking system in a difficult anatomical region. A symptomatic abscess was treated by a computed tomography-based navigated surgical intervention at our department. Advantages and disadvantages of this treatment strategy are evaluated. PMID:24987612

Social play among juvenile wild Japanese macaques (Macaca fuscata) strengthens their social bonds.

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Shimada, Masaki; Sueur, Cédric

2018-01-01

Social play and grooming are typical affiliative interactions for many primate species, and are thought to have similar biological functions. However, grooming increases with age, whereas social play decreases. We proposed the hypothesis that both social grooming and social play in juveniles strengthen their social bonds in daily activities. We carried out field research on the social relationships among juvenile wild Japanese macaques in a troop in Kinkazan, Miyagi Prefecture, Japan, from fall 2007 to spring 2008 to investigate this hypothesis. We evaluated three relationships among juveniles, play indices (PI), grooming indices (GI), and 3-m-proximity indices (3mI) of each dyad (i.e., interacting pair), and compared these social networks based on the matrices of the indices. The play and grooming networks were correlated with the association network throughout the two research periods. The multiple network level measurements of the play network, but not the grooming network, resembled those of the association network. Using a causal step approach, we showed that social play and grooming interactions in fall seem to predict associations in the following spring, controlling for the PI and GI matrix in spring, respectively. Social play and grooming for each juvenile were negatively correlated. The results partially support our predictions; therefore, the hypothesis that the biological function of social play among immature Japanese macaques is to strengthen their social bonds in the near future and develop their social life appears to be correct. For juvenile macaques, social play, rather than grooming, functions as an important social mechanism to strengthen affiliative relationships. © 2017 Wiley Periodicals, Inc.

Association of TLR7 variants with AIDS-like disease and AIDS vaccine efficacy in rhesus macaques.

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Roman A Siddiqui

Full Text Available In HIV infection, TLR7-triggered IFN-α production exerts a direct antiviral effect through the inhibition of viral replication, but may also be involved in immune pathogenesis leading to AIDS. TLR7 could also be an important mediator of vaccine efficacy. In this study, we analyzed polymorphisms in the X-linked TLR7 gene in the rhesus macaque model of AIDS. Upon resequencing of the TLR7 gene in 36 rhesus macaques of Indian origin, 12 polymorphic sites were detected. Next, we identified three tightly linked single nucleotide polymorphisms (SNP as being associated with survival time. Genotyping of 119 untreated, simian immunodeficiency virus (SIV-infected male rhesus macaques, including an 'MHC adjusted' subset, revealed that the three TLR7 SNPs are also significantly associated with set-point viral load. Surprisingly, this effect was not observed in 72 immunized SIV-infected male monkeys. We hypothesize (i that SNP c.13G>A in the leader peptide is causative for the observed genotype-phenotype association and that (ii the underlying mechanism is related to RNA secondary structure formation. Therefore, we investigated a fourth SNP (c.-17C>T, located 17 bp upstream of the ATG translation initiation codon, that is also potentially capable of influencing RNA structure. In c.13A carriers, neither set-point viral load nor survival time were related to the c.-17C>T genotype. In c.13G carriers, by contrast, the c.-17C allele was significantly associated with prolonged survival. Again, no such association was detected among immunized SIV-infected macaques. Our results highlight the dual role of TLR7 in immunodeficiency virus infection and vaccination and imply that it may be important to control human AIDS vaccine trials, not only for MHC genotype, but also for TLR7 genotype.

Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine

International Nuclear Information System (INIS)

Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W.L.; Luciw, Paul A.

2008-01-01

Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogenicity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-γ enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by twenty weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus

Radiographic measurement of the cardiothoracic ratio in a feral population of long-tailed macaques (Macaca fascicularis)

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Schillaci, Michael A. [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada)], E-mail: schillaci@utsc.utoronto.ca; Lischka, Andrea R.; Karamitsos, Anisah A. [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada); Engel, Gregory A. [Swedish/Cherry Hill Family Medicine Residency, 550 16th Avenue, Seattle, WA 98122 (United States); Washington National Primate Research Center, University of Washington, Seattle, WA 98195 (United States); Paul, Narinder [Division of Cardiothoracic Imaging, University Health Network, University of Toronto, Toronto, Ontario M5G 2N2 (Canada); Ramoul, Rima [Department of Social Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, Ontario M1C 1A4 (Canada); Rompis, Aida; Putra, Arta; Wandia, I. Nengah [Fakultas Kedokteran Hewan, Udayana University, Denpasar, Bali 80361 (Indonesia); Jones-Engel, Lisa [Washington National Primate Research Center, University of Washington, Seattle, WA 98195 (United States)

2010-05-15

The cardiothoracic ratio is often used as a proxy measure of cardiovascular pathophysiology in humans but less frequently in nonhuman primates, for whom little published data are available to establish normal values. The present study is the first to examine relative cardiac size in a feral population of primates. This report presents estimates of the cardiothoracic ratio in long-tailed macaques (Macaca fascicularis) from Bali, Indonesia. The mean cardiothoracic ratio for the study sample was 0.55, above the commonly used threshold of 0.50 for identifying an enlarged heart in human medicine. Future research on wild populations of macaques is needed and should include multiple assessments of cardiac function including both radiography and echocardiography.

Radiographic measurement of the cardiothoracic ratio in a feral population of long-tailed macaques (Macaca fascicularis)

International Nuclear Information System (INIS)

Schillaci, Michael A.; Lischka, Andrea R.; Karamitsos, Anisah A.; Engel, Gregory A.; Paul, Narinder; Ramoul, Rima; Rompis, Aida; Putra, Arta; Wandia, I. Nengah; Jones-Engel, Lisa

2010-01-01

The cardiothoracic ratio is often used as a proxy measure of cardiovascular pathophysiology in humans but less frequently in nonhuman primates, for whom little published data are available to establish normal values. The present study is the first to examine relative cardiac size in a feral population of primates. This report presents estimates of the cardiothoracic ratio in long-tailed macaques (Macaca fascicularis) from Bali, Indonesia. The mean cardiothoracic ratio for the study sample was 0.55, above the commonly used threshold of 0.50 for identifying an enlarged heart in human medicine. Future research on wild populations of macaques is needed and should include multiple assessments of cardiac function including both radiography and echocardiography.

Maksilektomi Inferior pada Karsinoma Sel Skuamosa Palatum Durum

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Sukri Rahman

2016-01-01

Full Text Available Abstrak          Karsinoma Palatum Durum adalah keganasan daerah kepala dan leher yang jarang terjadi dimana setengah diantaranya merupakan Karsinoma Sel Skuamosa. Pada fase awal keganasan ini dapat bersifat asimptomatis namun dapat juga menimbulkan gejala berupa ulkus yang terasa nyeri pada perkembangan penyakitnya. Operasi maksilektomi inferior merupakan salah satu pilihan tindakan yang dapat dilakukan dalam tatalaksana kasus ini, diikuti oleh pemberian radioterapi. Kasus ini dibuat untuk memahami penatalaksanaan karsinoma palatum durum. Dilaporkan kasus seorang laki-laki 45 tahun dengan diagnosis Karsinoma Sel Skuamosa Palatum Durum (Well to Moderately Differentiated Keratinized stadium IVa (T4aN0M0 dilakukan operasi maksilektomi inferior, namun tidak diikuti dengan radioterapi karena pasien menolak. Maksilektomi inferior merupakan pilihan pembedahan pada tumor yang terbatas pada palatum, lantai sinus maksila dan kavum nasi. Prognosis karsinoma sel skuamosa palatum durum cukup baik dan angka harapan hidup lima tahun akan bertambah bila dilakukan operasi diikuti dengan pemberian radioterapi. Kata kunci: Karsinoma sel skuamosa, maksilektomi inferior, radioterapi AbstractCarcinoma of the hard palate is a rare head and neck cancer in which half of it was Squamous Cell Carcinoma. In the initial phase of this malignancy may be asymptomatic, but can also cause symptoms such as painful ulcers in the development of the disease. Inferior maxillectomy is one of the choice of operation that can be performed, followed by radiotherapy to understand the management of carcinoma of the hard palate. Reported one case of a man 45 years old with diagnosis Squamous Cell Carcinoma of hard palate (Well to Moderately Differentiated Keratinized stage IVa (T4aN0M0 treated by inferior maxillectomy surgery, but not followed by radiotherapy because the patient refused. Inferior Maksilektomi is a surgical option in tumor that limited to the palate, floor of the

Novel full-length major histocompatibility complex class I allele discovery and haplotype definition in pig-tailed macaques.

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Semler, Matthew R; Wiseman, Roger W; Karl, Julie A; Graham, Michael E; Gieger, Samantha M; O'Connor, David H

2017-11-13

Pig-tailed macaques (Macaca nemestrina, Mane) are important models for human immunodeficiency virus (HIV) studies. Their infectability with minimally modified HIV makes them a uniquely valuable animal model to mimic human infection with HIV and progression to acquired immunodeficiency syndrome (AIDS). However, variation in the pig-tailed macaque major histocompatibility complex (MHC) and the impact of individual transcripts on the pathogenesis of HIV and other infectious diseases is understudied compared to that of rhesus and cynomolgus macaques. In this study, we used Pacific Biosciences single-molecule real-time circular consensus sequencing to describe full-length MHC class I (MHC-I) transcripts for 194 pig-tailed macaques from three breeding centers. We then used the full-length sequences to infer Mane-A and Mane-B haplotypes containing groups of MHC-I transcripts that co-segregate due to physical linkage. In total, we characterized full-length open reading frames (ORFs) for 313 Mane-A, Mane-B, and Mane-I sequences that defined 86 Mane-A and 106 Mane-B MHC-I haplotypes. Pacific Biosciences technology allows us to resolve these Mane-A and Mane-B haplotypes to the level of synonymous allelic variants. The newly defined haplotypes and transcript sequences containing full-length ORFs provide an important resource for infectious disease researchers as certain MHC haplotypes have been shown to provide exceptional control of simian immunodeficiency virus (SIV) replication and prevention of AIDS-like disease in nonhuman primates. The increased allelic resolution provided by Pacific Biosciences sequencing also benefits transplant research by allowing researchers to more specifically match haplotypes between donors and recipients to the level of nonsynonymous allelic variation, thus reducing the risk of graft-versus-host disease.

Vocal tract length and formant frequency dispersion correlate with body size in rhesus macaques.

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Fitch, W T

1997-08-01

Body weight, length, and vocal tract length were measured for 23 rhesus macaques (Macaca mulatta) of various sizes using radiographs and computer graphic techniques. linear predictive coding analysis of tape-recorded threat vocalizations were used to determine vocal tract resonance frequencies ("formants") for the same animals. A new acoustic variable is proposed, "formant dispersion," which should theoretically depend upon vocal tract length. Formant dispersion is the averaged difference between successive formant frequencies, and was found to be closely tied to both vocal tract length and body size. Despite the common claim that voice fundamental frequency (F0) provides an acoustic indication of body size, repeated investigations have failed to support such a relationship in many vertebrate species including humans. Formant dispersion, unlike voice pitch, is proposed to be a reliable predictor of body size in macaques, and probably many other species.

Hippocampal Atrophy Is Associated with Altered Hippocampus-Posterior Cingulate Cortex Connectivity in Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis.

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Shih, Y C; Tseng, C E; Lin, F-H; Liou, H H; Tseng, W Y I

2017-03-01

Unilateral mesial temporal lobe epilepsy and hippocampal sclerosis have structural and functional abnormalities in the mesial temporal regions. To gain insight into the pathophysiology of the epileptic network in mesial temporal lobe epilepsy with hippocampal sclerosis, we aimed to clarify the relationships between hippocampal atrophy and the altered connection between the hippocampus and the posterior cingulate cortex in patients with mesial temporal lobe epilepsy with hippocampal sclerosis. Fifteen patients with left mesial temporal lobe epilepsy with hippocampal sclerosis and 15 healthy controls were included in the study. Multicontrast MR imaging, including high-resolution T1WI, diffusion spectrum imaging, and resting-state fMRI, was performed to measure the hippocampal volume, structural connectivity of the inferior cingulum bundle, and intrinsic functional connectivity between the hippocampus and the posterior cingulate cortex, respectively. Compared with controls, patients had decreased left hippocampal volume (volume ratio of the hippocampus and controls, 0.366% ± 0.029%; patients, 0.277% ± 0.063%, corrected P = .002), structural connectivity of the bilateral inferior cingulum bundle (generalized fractional anisotropy, left: controls, 0.234 ± 0.020; patients, 0.193 ± 0.022, corrected P = .0001, right: controls, 0.226 ± 0.022; patients, 0.208 ± 0.017, corrected P = .047), and intrinsic functional connectivity between the left hippocampus and the left posterior cingulate cortex (averaged z-value: controls, 0.314 ± 0.152; patients, 0.166 ± 0.062). The left hippocampal volume correlated with structural connectivity positively (standardized β = 0.864, P = .001), but it had little correlation with intrinsic functional connectivity (standardized β = -0.329, P = .113). On the contralesional side, the hippocampal volume did not show any significant correlation with structural connectivity or intrinsic functional connectivity ( F 2,12 = 0.284, P = .757, R 2

A biosafety evaluation of synchrotron radiation X-ray to skin and bone marrow: single dose irradiation study of rats and macaques.

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Lu, Yifan; Tang, Guanghui; Lin, Hui; Lin, Xiaojie; Jiang, Lu; Yang, Guo-Yuan; Wang, Yongting

2017-06-01

Very limited experimental data is available regarding the safe dosages related to synchrotron radiation (SR) procedures. We used young rats and macaques to address bone marrow and skin tolerance to various doses of synchrotron radiation. Rats were subjected to 0, 0.5, 2.5, 5, 25 or 100 Gy local SR X-ray irradiation at left hind limb. Rat blood samples were analyzed at 2-90 days after irradiation. The SR X-ray irradiated skin and tibia were sectioned for morphological examination. For non-human primate study, three male macaques were subjected to 0.5 or 2.5 Gy SR X-ray on crus. Skin responses of macaques were observed. All rats that received SR X-ray irradiation doses greater than 2.5 Gy experienced hair loss and bone-growth inhibition, which were accompanied by decreased number of follicles, thickened epidermal layer, and decreased density of bone marrow cells (p X-ray but showed significant hair loss when the dose was raised above 2.5 Gy. The safety threshold doses of SR X-ray for rat skin, bone marrow and macaque skin are between 0.5 and 2.5 Gy. Our study provided essential information regarding the biosafety of SR X-ray irradiation.

Individual and social learning processes involved in the acquisition and generalization of tool use in macaques

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Macellini, S.; Maranesi, M.; Bonini, L.; Simone, L.; Rozzi, S.; Ferrari, P. F.; Fogassi, L.

2012-01-01

Macaques can efficiently use several tools, but their capacity to discriminate the relevant physical features of a tool and the social factors contributing to their acquisition are still poorly explored. In a series of studies, we investigated macaques' ability to generalize the use of a stick as a tool to new objects having different physical features (study 1), or to new contexts, requiring them to adapt the previously learned motor strategy (study 2). We then assessed whether the observation of a skilled model might facilitate tool-use learning by naive observer monkeys (study 3). Results of study 1 and study 2 showed that monkeys trained to use a tool generalize this ability to tools of different shape and length, and learn to adapt their motor strategy to a new task. Study 3 demonstrated that observing a skilled model increases the observers' manipulations of a stick, thus facilitating the individual discovery of the relevant properties of this object as a tool. These findings support the view that in macaques, the motor system can be modified through tool use and that it has a limited capacity to adjust the learnt motor skills to a new context. Social factors, although important to facilitate the interaction with tools, are not crucial for tool-use learning. PMID:22106424

Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

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Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

2015-01-01

Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women.

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Laurel A Lagenaur

Full Text Available MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N. The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g, and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21. Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody.

Robust vaginal colonization of macaques with a novel vaginally disintegrating tablet containing a live biotherapeutic product to prevent HIV infection in women.

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Lagenaur, Laurel A; Swedek, Iwona; Lee, Peter P; Parks, Thomas P

2015-01-01

MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and contains a human, vaginal Lactobacillus jensenii that has been genetically enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The objective of this study was to develop a solid vaginal dosage form that supports sustained vaginal colonization of the MucoCept Lactobacillus at levels previously shown, with freshly prepared cultures, to protect macaques from SHIV infection and to test this formulation in a macaque vaginal colonization model. Vaginally disintegrating tablets were prepared by lyophilizing the formulated bacteria in tablet-shaped molds, then packaging in foil pouches with desiccant. Disintegration time, potency and stability of the tablets were assessed. For colonization, non-synchronized macaques were dosed vaginally with either one tablet or five tablets delivered over five days. Vaginal samples were obtained at three, 14, and 21 days post-dosing and cultured to determine Lactobacillus colonization levels. To confirm identity of the MucoCept Lactobacillus strain, genomic DNA was extracted from samples on days 14 and 21 and a strain-specific PCR was performed. Supernatants from bacteria were tested for the presence of the mCV-N protein by Western blot. The tablets were easy to handle, disintegrated within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal administration of the tablets to macaques resulted in colonization of the MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21 days. There was no significant difference in colonization levels for the one or five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR confirmed the presence of the bacteria even in culture-negative macaques. Finally, the presence of mCV-N protein was confirmed by Western blot analysis using a specific anti-mCV-N antibody.

MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.

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Brammer, David W; Gillespie, Patrick J; Tian, Mei; Young, Daniel; Raveendran, Muthuswamy; Williams, Lawrence E; Gagea, Mihai; Benavides, Fernando J; Perez, Carlos J; Broaddus, Russell R; Bernacky, Bruce J; Barnhart, Kirstin F; Alauddin, Mian M; Bhutani, Manoop S; Gibbs, Richard A; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih; Rogers, Jeffrey; Abee, Christian R; Gelovani, Juri G

2018-03-13

Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques ( Macaca mulatta ) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]fluoroacetate ([ 18 F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [ 18 F]fluorothymidine ([ 18 F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1 -rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans. Copyright © 2018 the Author(s). Published by PNAS.

Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1.

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Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Nieder, Andreas; Pourriahi, Paria; Nienborg, Hendrikje

2017-11-22

Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus ("noise-correlation"). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms. SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This

A population MRI brain template and analysis tools for the macaque.

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Seidlitz, Jakob; Sponheim, Caleb; Glen, Daniel; Ye, Frank Q; Saleem, Kadharbatcha S; Leopold, David A; Ungerleider, Leslie; Messinger, Adam

2018-04-15

The use of standard anatomical templates is common in human neuroimaging, as it facilitates data analysis and comparison across subjects and studies. For non-human primates, previous in vivo templates have lacked sufficient contrast to reliably validate known anatomical brain regions and have not provided tools for automated single-subject processing. Here we present the "National Institute of Mental Health Macaque Template", or NMT for short. The NMT is a high-resolution in vivo MRI template of the average macaque brain generated from 31 subjects, as well as a neuroimaging tool for improved data analysis and visualization. From the NMT volume, we generated maps of tissue segmentation and cortical thickness. Surface reconstructions and transformations to previously published digital brain atlases are also provided. We further provide an analysis pipeline using the NMT that automates and standardizes the time-consuming processes of brain extraction, tissue segmentation, and morphometric feature estimation for anatomical scans of individual subjects. The NMT and associated tools thus provide a common platform for precise single-subject data analysis and for characterizations of neuroimaging results across subjects and studies. Copyright © 2017 ElsevierCompany. All rights reserved.

Amblyomma maculatum Feeding Augments Rickettsia parkeri Infection in a Rhesus Macaque Model: A Pilot Study

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Banajee, Kaikhushroo H.; Embers, Monica E.; Langohr, Ingeborg M.; Doyle, Lara A.; Hasenkampf, Nicole R.; Macaluso, Kevin R.

2015-01-01

Rickettsia parkeri is an emerging eschar-causing human pathogen in the spotted fever group of Rickettsia and is transmitted by the Gulf coast tick, Amblyomma maculatum. Tick saliva has been shown to alter both the cellular and humoral components of the innate and adaptive immune systems. However, the effect of this immunomodulation on Rickettsia transmission and pathology in an immunocompetent vertebrate host has not been fully examined. We hypothesize that, by modifying the host immune response, tick feeding enhances infection and pathology of pathogenic spotted fever group Rickettsia sp. In order to assess this interaction in vivo, a pilot study was conducted using five rhesus macaques that were divided into three groups. One group was intradermally inoculated with low passage R. parkeri (Portsmouth strain) alone (n = 2) and another group was inoculated during infestation by adult, R. parkeri-free A. maculatum (n = 2). The final macaque was infested with ticks alone (tick feeding control group). Blood, lymph node and skin biopsies were collected at several time points post-inoculation/infestation to assess pathology and quantify rickettsial DNA. As opposed to the tick-only animal, all Rickettsia-inoculated macaques developed inflammatory leukograms, elevated C-reactive protein concentrations, and elevated TH1 (interferon-γ, interleukin-15) and acute phase inflammatory cytokines (interleukin-6) post-inoculation, with greater neutrophilia and interleukin-6 concentrations in the tick plus R. parkeri group. While eschars formed at all R. parkeri inoculation sites, larger and slower healing eschars were observed in the tick feeding plus R. parkeri group. Furthermore, dissemination of R. parkeri to draining lymph nodes early in infection and increased persistence at the inoculation site were observed in the tick plus R. parkeri group. This study indicates that rhesus macaques can be used to model R. parkeri rickettsiosis, and suggests that immunomodulatory factors

Vicarious Reinforcement In Rhesus Macaques (Macaca mulatta

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Steve W. C. Chang

2011-03-01

Full Text Available What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this reinforcement can motivate them to subsequently deliver or withhold rewards from the other animal. We exploited Pavlovian and instrumental conditioning to associate rewards to self (M1 and/or rewards to another monkey (M2 with visual cues. M1s made more errors in the instrumental trials when cues predicted reward to M2 compared to when cues predicted reward to M1, but made even more errors when cues predicted reward to no one. In subsequent preference tests between pairs of conditioned cues, M1s preferred cues paired with reward to M2 over cues paired with reward to no one. By contrast, M1s preferred cues paired with reward to self over cues paired with reward to both monkeys simultaneously. Rates of attention to M2 strongly predicted the strength and valence of vicarious reinforcement. These patterns of behavior, which were absent in nonsocial control trials, are consistent with vicarious reinforcement based upon sensitivity to observed, or counterfactual, outcomes with respect to another individual. Vicarious reward may play a critical role in shaping cooperation and competition, as well as motivating observational learning and group coordination in rhesus macaques, much as it does in humans. We propose that vicarious reinforcement signals mediate these behaviors via homologous neural circuits involved in reinforcement learning and decision-making.

Vicarious reinforcement in rhesus macaques (macaca mulatta).

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Chang, Steve W C; Winecoff, Amy A; Platt, Michael L

2011-01-01

What happens to others profoundly influences our own behavior. Such other-regarding outcomes can drive observational learning, as well as motivate cooperation, charity, empathy, and even spite. Vicarious reinforcement may serve as one of the critical mechanisms mediating the influence of other-regarding outcomes on behavior and decision-making in groups. Here we show that rhesus macaques spontaneously derive vicarious reinforcement from observing rewards given to another monkey, and that this reinforcement can motivate them to subsequently deliver or withhold rewards from the other animal. We exploited Pavlovian and instrumental conditioning to associate rewards to self (M1) and/or rewards to another monkey (M2) with visual cues. M1s made more errors in the instrumental trials when cues predicted reward to M2 compared to when cues predicted reward to M1, but made even more errors when cues predicted reward to no one. In subsequent preference tests between pairs of conditioned cues, M1s preferred cues paired with reward to M2 over cues paired with reward to no one. By contrast, M1s preferred cues paired with reward to self over cues paired with reward to both monkeys simultaneously. Rates of attention to M2 strongly predicted the strength and valence of vicarious reinforcement. These patterns of behavior, which were absent in non-social control trials, are consistent with vicarious reinforcement based upon sensitivity to observed, or counterfactual, outcomes with respect to another individual. Vicarious reward may play a critical role in shaping cooperation and competition, as well as motivating observational learning and group coordination in rhesus macaques, much as it does in humans. We propose that vicarious reinforcement signals mediate these behaviors via homologous neural circuits involved in reinforcement learning and decision-making.

Activation and Functional Connectivity of the Left Inferior Temporal Gyrus during Visual Speech Priming in Healthy Listeners and Listeners with Schizophrenia.

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Wu, Chao; Zheng, Yingjun; Li, Juanhua; Zhang, Bei; Li, Ruikeng; Wu, Haibo; She, Shenglin; Liu, Sha; Peng, Hongjun; Ning, Yuping; Li, Liang

2017-01-01

Under a "cocktail-party" listening condition with multiple-people talking, compared to healthy people, people with schizophrenia benefit less from the use of visual-speech (lipreading) priming (VSP) cues to improve speech recognition. The neural mechanisms underlying the unmasking effect of VSP remain unknown. This study investigated the brain substrates underlying the unmasking effect of VSP in healthy listeners and the schizophrenia-induced changes in the brain substrates. Using functional magnetic resonance imaging, brain activation and functional connectivity for the contrasts of the VSP listening condition vs. the visual non-speech priming (VNSP) condition were examined in 16 healthy listeners (27.4 ± 8.6 years old, 9 females and 7 males) and 22 listeners with schizophrenia (29.0 ± 8.1 years old, 8 females and 14 males). The results showed that in healthy listeners, but not listeners with schizophrenia, the VSP-induced activation (against the VNSP condition) of the left posterior inferior temporal gyrus (pITG) was significantly correlated with the VSP-induced improvement in target-speech recognition against speech masking. Compared to healthy listeners, listeners with schizophrenia showed significantly lower VSP-induced activation of the left pITG and reduced functional connectivity of the left pITG with the bilateral Rolandic operculum, bilateral STG, and left insular. Thus, the left pITG and its functional connectivity may be the brain substrates related to the unmasking effect of VSP, assumedly through enhancing both the processing of target visual-speech signals and the inhibition of masking-speech signals. In people with schizophrenia, the reduced unmasking effect of VSP on speech recognition may be associated with a schizophrenia-related reduction of VSP-induced activation and functional connectivity of the left pITG.

Spatio-temporal dynamics of the mirror neuron system during social intentions.

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Cacioppo, Stephanie; Bolmont, Mylene; Monteleone, George

2017-10-27

Previous research has shown that specific goals and intentions influence a person's allocation of social attention. From a neural viewpoint, a growing body of evidence suggests that the inferior fronto-parietal network, including the mirror neuron system, plays a role in the planning and the understanding of motor intentions. However, it is unclear whether and when the mirror neuron system plays a role in social intentions. Combining a behavioral task with electrical neuroimaging in 22 healthy male participants, the current study investigates whether the temporal brain dynamic of the mirror neuron system differs during two types of social intentions i.e., lust vs. romantic intentions. Our results showed that 62% of the stimuli evoking lustful intentions also evoked romantic intentions, and both intentions were sustained by similar activations of the inferior frontal gyrus and the inferior parietal lobule/angular gyrus for the first 432 ms after stimulus onset. Intentions to not love or not lust, on the other hand, were characterized by earlier differential activations of the inferior fronto-parietal network i.e., as early as 244 ms after stimulus onset. These results suggest that the mirror neuron system may not only code for the motor correlates of intentions, but also for the social meaning of intentions and its valence at both early/automatic and later/more elaborative stages of information processing.

Lateralization for dynamic facial expressions in human superior temporal sulcus.

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De Winter, François-Laurent; Zhu, Qi; Van den Stock, Jan; Nelissen, Koen; Peeters, Ronald; de Gelder, Beatrice; Vanduffel, Wim; Vandenbulcke, Mathieu

2015-02-01

Most face processing studies in humans show stronger activation in the right compared to the left hemisphere. Evidence is largely based on studies with static stimuli focusing on the fusiform face area (FFA). Hence, the pattern of lateralization for dynamic faces is less clear. Furthermore, it is unclear whether this property is common to human and non-human primates due to predisposing processing strategies in the right hemisphere or that alternatively left sided specialization for language in humans could be the driving force behind this phenomenon. We aimed to address both issues by studying lateralization for dynamic facial expressions in monkeys and humans. Therefore, we conducted an event-related fMRI experiment in three macaques and twenty right handed humans. We presented human and monkey dynamic facial expressions (chewing and fear) as well as scrambled versions to both species. We studied lateralization in independently defined face-responsive and face-selective regions by calculating a weighted lateralization index (LIwm) using a bootstrapping method. In order to examine if lateralization in humans is related to language, we performed a separate fMRI experiment in ten human volunteers including a 'speech' expression (one syllable non-word) and its scrambled version. Both within face-responsive and selective regions, we found consistent lateralization for dynamic faces (chewing and fear) versus scrambled versions in the right human posterior superior temporal sulcus (pSTS), but not in FFA nor in ventral temporal cortex. Conversely, in monkeys no consistent pattern of lateralization for dynamic facial expressions was observed. Finally, LIwms based on the contrast between different types of dynamic facial expressions (relative to scrambled versions) revealed left-sided lateralization in human pSTS for speech-related expressions compared to chewing and emotional expressions. To conclude, we found consistent laterality effects in human posterior STS but not

Complex assembly, crystallization and preliminary X-ray crystallographic studies of rhesus macaque MHC Mamu-A*01 complexed with an immunodominant SIV-Gag nonapeptide

International Nuclear Information System (INIS)

Chu, Fuliang; Lou, Zhiyong; Gao, Bin; Bell, John I.; Rao, Zihe; Gao, George F.

2005-01-01

Crystallization of the first rhesus macaque MHC class I complex. Simian immunodeficiency virus (SIV) infection in rhesus macaques has been used as the best model for the study of human immunodeficiency virus (HIV) infection in humans, especially in the cytotoxic T-lymphocyte (CTL) response. However, the structure of rhesus macaque (or any other monkey model) major histocompatibility complex class I (MHC I) presenting a specific peptide (the ligand for CTL) has not yet been elucidated. Here, using in vitro refolding, the preparation of the complex of the rhesus macaque MHC I allele (Mamu-A*01) with human β 2 m and an immunodominant peptide, CTPYDINQM (Gag-CM9), derived from SIV Gag protein is reported. The complex (45 kDa) was crystallized; the crystal belongs to space group I422, with unit-cell parameters a = b = 183.8, c = 155.2 Å. The crystal contains two molecules in the asymmetric unit and diffracts X-rays to 2.8 Å resolution. The structure is being solved by molecular replacement and this is the first attempt to determined the crystal structure of a peptide–nonhuman primate MHC complex

Risk Factors for Dystocia in Pigtailed Macaques (Macaca nemestrina)

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Stockinger, Diane E; Torrence, Anne E; Hukkanen, Renee R; Vogel, Keith W; Hotchkiss, Charlotte E; Ha, James C

2011-01-01

Dystocia (difficult labor) is an important component of the management of nonhuman primates and results in significant fetal and maternal morbidity and increased use of veterinary resources. Dystocias can arise from abnormalities of the maternal pelvis or fetus or uncoordinated uterine activity. Although risk factors for stillbirths have been established in nonhuman primates, risk factors for dystocias have not. The objective of this study was to determine maternal and fetal risk factors for dystocia in macaques. Retrospective data were collected from 83 pigtailed macaques (Macaca nemestrina) diagnosed with dystocia. The diagnosis of dystocia was made based on clinical or pathologic evidence. Maternal records of age, reproductive history, experimental history, clinical records, and fetal birth weight and any applicable fetal necropsy reports were reviewed. The gestational age of the fetus, the infant's birth weight, total previous births by the dam, and the proportions of both viable delivery (inverse effect) and surgical pregnancy interventions (direct effect) in the dam's history generated a model that maximized the experimental variance for predicting dystocia in the current pregnancy and explained 24% of the dystocia deliveries. The number of total previous births and proportion of previous cesarean sections accounted for the greatest effect. This model can identify individual dams within a colony that are at risk for dystocias and allow for changes in breeding colony management, more intense monitoring of dams at risk, or allocation of additional resources. PMID:21535929

Isquemia aguda de miembros inferiores secundaria a ergortismo

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Franco J. Vallejo, MD

2011-11-01

Full Text Available Paciente de género femenino, de 21 años de edad, quien ingresó por dolor progresivo e intenso en miembros inferiores, y refirió antecedente reciente de ingestión de derivados del ergot. Al examen físico se observó ausencia de pulsos en ambos miembros inferiores. Por angiotomografia se documentó disminución severa, generalizada y bilateral, del calibre de los vasos arteriales de miembros inferiores. Se diagnosticó isquemia arterial aguda secundaria a ergotismo y se inició tratamiento con vasodilatadores y calcio-antagonistas, que resolvió los síntomas en su totalidad.

Passive Removal of Silicone Oil with Temporal Head Position through Two 23-Gauge Cannulas

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Zhong Lin

2016-01-01

Full Text Available Purpose. To report a new approach for removal of silicone oil. Methods. All surgeries were performed using 23-gauge vitrectomy system with two transconjunctival sutureless cannulas. At the beginning, most of the silicone oil was removed by traditional microinvasive vitrectomy system through inferior-temporal cannula. Then, the blood transfusion tube is removed from the inferior-temporal cannula, and the fluid-air exchange is performed. A passive fluid-air exchange was performed to aspirate the residual silicone oil after gradually turning the patient’s head temporally by approximately 90° gradually. Results. After the surgery, all patients had a clear anterior chamber and vitreous cavity on slit lamp and B scan examination, respectively. The mean time taken for silicone oil removal and total surgery was 8.0±1.4 minutes and 12.4±2.5 minutes, respectively. The mean intraocular pressure 1 day, 3 days, 1 week, 1 month, and 3 months after surgery was 9.0±5.8 mmHg, 11.3±7.6 mmHg, 16.1±6.9 mmHg, 17.7±4.8 mmHg, and 17.1±3.5 mmHg, respectively. Conclusion. This new approach may provide a safe and fast method to remove the silicone oil.

An intravaginal ring that releases the NNRTI MIV-150 reduces SHIV transmission in macaques.

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Singer, Rachel; Mawson, Paul; Derby, Nina; Rodriguez, Aixa; Kizima, Larisa; Menon, Radhika; Goldman, Daniel; Kenney, Jessica; Aravantinou, Meropi; Seidor, Samantha; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Robbiani, Melissa; Zydowsky, Thomas M

2012-09-05

Microbicides may prevent HIV and sexually transmitted infections (STIs) in women; however, determining the optimal means of delivery of active pharmaceutical ingredients remains a major challenge. We previously demonstrated that a vaginal gel containing the non-nucleoside reverse transcriptase inhibitor MIV-150 partially protected macaques from SHIV-RT (simian/HIV reverse transcriptase) infection, and the addition of zinc acetate rendered the gel significantly protective. We test the activity of MIV-150 without the addition of zinc acetate when delivered from either ethylene vinyl acetate (EVA) or silicone intravaginal rings (IVRs). MIV-150 was successfully delivered, because it was detected in vaginal fluids and tissues by radioimmunoassay in pharmacokinetic studies. Moreover, EVA IVRs significantly protected macaques from SHIV-RT infection. Our results demonstrate that MIV-150-containing IVRs have the potential to prevent HIV infection and highlight the possible use of IVRs for delivering drugs that block HIV and other STIs.

Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex

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Smiley, John F.; Schroeder, Charles E.

2017-01-01

Prior studies have reported “local” field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be “contaminated” by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such “far-field” activity, in addition to, or in absence of, local synaptic responses. SIGNIFICANCE STATEMENT Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is

Metabolic changes in the visual cortex of binocular blindness macaque monkeys: a proton magnetic resonance spectroscopy study.

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Lingjie Wu

Full Text Available PURPOSE: To evaluate proton magnetic resonance spectroscopy ((1H-MRS in a study of cross-modal plasticity in the visual cortex of binocular blindness macaque monkeys. MATERIALS AND METHODS: Four healthy neonatal macaque monkeys were randomly divided into 2 groups, with 2 in each group. Optic nerve transection was performed in both monkeys in the experimental group (group B to obtain binocular blindness. Two healthy macaque monkeys served as a control group (group A. After sixteen months post-procedure, (1H-MRS was performed in the visual cortex of all monkeys. We compared the peak areas of NAA, Cr, Cho, Glx and Ins and the ratios of NAA/Cr, Cho/Cr, Glx/Cr and Ins/Cr of each monkey in group B with group A. RESULTS: The peak area of NAA and the NAA/Cr ratio in the visual cortex of monkey 4 in group B were found to be dramatically decreased, the peak area of NAA slightly decreased and the NAA/Cr ratio clearly decreased in visual cortex of monkey 3 in group B than those in group A. The peak area of Ins and the Ins/Cr ratio in the visual cortex of monkey 4 in group B slightly increased. The peak area of Cho and the Cho/Cr ratio in the visual cortex of all monkeys in group B dramatically increased compared with group A. The peak area of Glx in the visual cortex of all monkeys in group B slightly increased compared with group A. CONCLUSIONS: (1H-MRS could detect biochemical and metabolic changes in the visual cortex and therefore this technique can be used to provide valuable information for investigating the mechanisms of cross-modal plasticity of binocular blindness in a macaque monkey model.

The Cynomolgus Macaque Natural History Model of Pneumonic Tularemia for Predicting Clinical Efficacy Under the Animal Rule

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Guina, Tina; Lanning, Lynda L.; Omland, Kristian S.; Williams, Mark S.; Wolfraim, Larry A.; Heyse, Stephen P.; Houchens, Christopher R.; Sanz, Patrick; Hewitt, Judith A.

2018-01-01

Francisella tularensis is a highly infectious Gram-negative bacterium that is the etiologic agent of tularemia in animals and humans and a Tier 1 select agent. The natural incidence of pneumonic tularemia worldwide is very low; therefore, it is not feasible to conduct clinical efficacy testing of tularemia medical countermeasures (MCM) in human populations. Development and licensure of tularemia therapeutics and vaccines need to occur under the Food and Drug Administration's (FDA's) Animal Rule under which efficacy studies are conducted in well-characterized animal models that reflect the pathophysiology of human disease. The Tularemia Animal Model Qualification (AMQ) Working Group is seeking qualification of the cynomolgus macaque (Macaca fascicularis) model of pneumonic tularemia under Drug Development Tools Qualification Programs with the FDA based upon the results of studies described in this manuscript. Analysis of data on survival, average time to death, average time to fever onset, average interval between fever and death, and bacteremia; together with summaries of clinical signs, necropsy findings, and histopathology from the animals exposed to aerosolized F. tularensis Schu S4 in five natural history studies and one antibiotic efficacy study form the basis for the proposed cynomolgus macaque model. Results support the conclusion that signs of pneumonic tularemia in cynomolgus macaques exposed to 300–3,000 colony forming units (cfu) aerosolized F. tularensis Schu S4, under the conditions described herein, and human pneumonic tularemia cases are highly similar. Animal age, weight, and sex of animals challenged with 300–3,000 cfu Schu S4 did not impact fever onset in studies described herein. This study summarizes critical parameters and endpoints of a well-characterized cynomolgus macaque model of pneumonic tularemia and demonstrates this model is appropriate for qualification, and for testing efficacy of tularemia therapeutics under Animal Rule. PMID

Predictive Value of Parkinsonian Primates in Pharmacologic Studies: A Comparison between the Macaque, Marmoset, and Squirrel Monkey.

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Veyres, Nicolas; Hamadjida, Adjia; Huot, Philippe

2018-05-01

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate is the gold-standard animal model of Parkinson disease (PD) and has been used to assess the effectiveness of experimental drugs on dyskinesia, parkinsonism, and psychosis. Three species have been used in most studies-the macaque, marmoset, and squirrel monkey-the last much less so than the first two species; however, the predictive value of each species at forecasting clinical efficacy, or lack thereof, is poorly documented. Here, we have reviewed all the published literature detailing pharmacologic studies that assessed the effects of experimental drugs on dyskinesia, parkinsonism, and psychosis in each of these species and have calculated their predictive value of success and failure at the clinical level. We found that, for dyskinesia, the macaque has a positive predictive value of 87.5% and a false-positive rate of 38.1%, whereas the marmoset has a positive predictive value of 76.9% and a false-positive rate of 15.6%. For parkinsonism, the macaque has a positive predictive value of 68.2% and a false-positive rate of 44.4%, whereas the marmoset has a positive predictive value of 86.9% and a false-positive rate of 41.7%. No drug that alleviates psychosis in the clinic has shown efficacy at doing so in the macaque, whereas the marmoset has 100% positive predictive value. The small number of studies conducted in the squirrel monkey precluded us from calculating its predictive efficacy. We hope our results will help in the design of pharmacologic experiments and will facilitate the drug discovery and development process in PD. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Exceptional evolutionary divergence of human muscle and brain metabolomes parallels human cognitive and physical uniqueness.

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Katarzyna Bozek

2014-05-01

Full Text Available Metabolite concentrations reflect the physiological states of tissues and cells. However, the role of metabolic changes in species evolution is currently unknown. Here, we present a study of metabolome evolution conducted in three brain regions and two non-neural tissues from humans, chimpanzees, macaque monkeys, and mice based on over 10,000 hydrophilic compounds. While chimpanzee, macaque, and mouse metabolomes diverge following the genetic distances among species, we detect remarkable acceleration of metabolome evolution in human prefrontal cortex and skeletal muscle affecting neural and energy metabolism pathways. These metabolic changes could not be attributed to environmental conditions and were confirmed against the expression of their corresponding enzymes. We further conducted muscle strength tests in humans, chimpanzees, and macaques. The results suggest that, while humans are characterized by superior cognition, their muscular performance might be markedly inferior to that of chimpanzees and macaque monkeys.

Injury of the Inferior Alveolar Nerve during Implant Placement: a Literature Review

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Gintaras Juodzbalys

2011-01-01

Full Text Available Objectives: The purpose of present article was to review aetiological factors, mechanism, clinical symptoms, and diagnostic methods as well as to create treatment guidelines for the management of inferior alveolar nerve injury during dental implant placement.Material and Methods: Literature was selected through a search of PubMed, Embase and Cochrane electronic databases. The keywords used for search were inferior alveolar nerve injury, inferior alveolar nerve injuries, inferior alveolar nerve injury implant, inferior alveolar nerve damage, inferior alveolar nerve paresthesia and inferior alveolar nerve repair. The search was restricted to English language articles, published from 1972 to November 2010. Additionally, a manual search in the major anatomy, dental implant, periodontal and oral surgery journals and books were performed. The publications there selected by including clinical, human anatomy and physiology studies.Results: In total 136 literature sources were obtained and reviewed. Aetiological factors of inferior alveolar nerve injury, risk factors, mechanism, clinical sensory nerve examination methods, clinical symptoms and treatment were discussed. Guidelines were created to illustrate the methods used to prevent and manage inferior alveolar nerve injury before or after dental implant placement.Conclusions: The damage of inferior alveolar nerve during the dental implant placement can be a serious complication. Clinician should recognise and exclude aetiological factors leading to nerve injury. Proper presurgery planning, timely diagnosis and treatment are the key to avoid nerve sensory disturbances management.

Inferior Oblique Overaction: Anterior Transposition Versus Myectomy.

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Rajavi, Zhale; Feizi, Mohadeseh; Behradfar, Narges; Yaseri, Mehdi; Sayanjali, Shima; Motevaseli, Tahmine; Sabbaghi, Hamideh; Faghihi, Mohammad

2017-07-01

To compare the efficacy of inferior oblique myectomy and anterior transposition for correcting inferior oblique overaction (IOOA). This retrospective study was conducted on 56 patients with IOOA who had either myectomy or anterior transposition of the inferior oblique muscle from 2010 to 2015. The authors compared preoperative and postoperative inferior oblique muscle function grading (-4 to +4) as the main outcome measure and vertical and horizontal deviation, dissociated vertical deviation (DVD), and A- and V-pattern between the two surgical groups as secondary outcomes. A total of 99 eyes of 56 patients with a mean age of 5.9 ± 6.5 years were included (47 eyes in the myectomy group and 52 eyes in the anterior transposition group). There were no differences in preoperative best corrected visual acuity, amblyopia, spherical equivalent, and primary versus secondary IOOA between the two groups. Both surgical procedures were effective in reducing IOOA and satisfactory results were similar between the two groups: 61.7% and 67.3% in the myectomy and anterior transposition groups, respectively (P = .56). After adjustment for the preoperative DVD, there was no statistically significant difference between the two groups postoperatively. The preoperative hypertropia was 6 to 14 and 6 to 18 prism diopters (PD) in the myectomy and anterior transposition groups, respectively. After surgery, no patient had a vertical deviation greater than 5 PD. Both the inferior oblique myectomy and anterior transposition procedures are effective in reducing IOOA with similar satisfactory results. DVD and hypertropia were also corrected similarly by these two surgical procedures. [J Pediatr Ophthalmol Strabismus. 2017;54(4):232-237.]. Copyright 2017, SLACK Incorporated.

Identification of Rotavirus VP6-Specific CD4+ T Cell Epitopes in a G1P[8] Human Rotavirus-Infected Rhesus Macaque

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Wei Zhao

2008-01-01

Full Text Available A non-human primate model was used to evaluate its potential for identification of rotavirus viral protein 6 (VP6 CD4+ T cell epitopes. Four juvenile rhesus macaques were inoculated with a mixed inoculum (G1P[8] and G9P[8] of human rotaviruses. Infection accompanied by G1P[8] shedding was achieved in the two macaques that had no rotavirus immunoglobulin A (IgA in plasma. To measure the interferon gamma (IFN-γ and tumor necrosis factor (TNF anti-viral cytokines produced by peripheral CD4+ cells that recognize VP6 epitopes, whole blood cells from one infected macaque were stimulated in vitro with VP6 peptides. Stimulation with peptide pools derived from the simian rotavirus VP6 161–395 region revealed reactivity of CD4+ T cells with the VP6 281–331 domain. A VP6 301–315 region was identified as the epitope responsible for IFN-γ production while a broader VP6 293–327 domain was linked to TNF production. These results suggest that human rotavirus-infected macaques can be used for identification of additional epitopes and domains to address specific questions related to the development of pediatric vaccines.

Seroconversion to HCoV-NL63 in Rhesus Macaques

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Lia van der Hoek

2009-10-01

Full Text Available HCoV-NL63 is a recently identified respiratory virus. Its pathogenesis has not been fully unraveled because an animal model is currently lacking. Here we examined whether rhesus macaques encounter HCoV-NL63 infections during life, by examining the levels of antibodies to HCoV-NL63 in time. The animals were followed for 7 up till 19 years, and in three animals we observed a steep rise in antibodies during follow up, indicative of a natural infection with HCoV-NL63.

Experimental Oral Herpes Simplex Virus-1 (HSV-1 Co-infection in Simian Immunodeficiency Virus (SIV-Infected Rhesus Macaques

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Meropi Aravantinou

2017-12-01

Full Text Available Herpes simplex virus 1 and 2 (HSV-1/2 similarly initiate infection in mucosal epithelia and establish lifelong neuronal latency. Anogenital HSV-2 infection augments the risk for sexual human immunodeficiency virus (HIV transmission and is associated with higher HIV viral loads. However, whether oral HSV-1 infection contributes to oral HIV susceptibility, viremia, or oral complications of HIV infection is unknown. Appropriate non-human primate (NHP models would facilitate this investigation, yet there are no published studies of HSV-1/SIV co-infection in NHPs. Thus, we performed a pilot study for an oral HSV-1 infection model in SIV-infected rhesus macaques to describe the feasibility of the modeling and resultant immunological changes. Three SIV-infected, clinically healthy macaques became HSV-1-infected by inoculation with 4 × 108 pfu HSV-1 McKrae on buccal, tongue, gingiva, and tonsils after gentle abrasion. HSV-1 DNA was shed in oral swabs for up to 21 days, and shedding recurred in association with intra-oral lesions after periods of no shedding during 56 days of follow up. HSV-1 DNA was detected in explant cultures of trigeminal ganglia collected at euthanasia on day 56. In the macaque with lowest baseline SIV viremia, SIV plasma RNA increased following HSV-1 infection. One macaque exhibited an acute pro-inflammatory response, and all three animals experienced T cell activation and mobilization in blood. However, T cell and antibody responses to HSV-1 were low and atypical. Through rigorous assessesments, this study finds that the virulent HSV-1 strain McKrae resulted in a low level HSV-1 infection that elicited modest immune responses and transiently modulated SIV infection.

Leiomyosarcoma of the inferior turbinate

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Christopher W. Harper, Jr., MD

2017-09-01

Full Text Available We report a case of leiomyosarcoma of the inferior nasal turbinate. The patient, a 68-year-old Caucasian male, presented with 4–6 weeks of epistaxis that was resistant to nasal packing and septal cautery. Upon inspection in the operating room, a small mass was excised from the inferior turbinate. High-power H&E-stained microscopy demonstrated bundles of malignant smooth muscle cells, and immunohistochemical stains were strongly positive for desmin, smooth muscle actin and vimentin, while negative for pankeratin EA1/EA3 and CaM 5.2, suggesting leiomyosarcoma as the diagnosis. Clear margins were obtained at a second surgery. At the time of this writing it is 8 months since his last surgery and he has remained symptom free.

Differential activity in left inferior frontal gyrus for pseudo and real words: an event-related functional MRI study on auditory lexical decision

International Nuclear Information System (INIS)

Xiao Zhuangwei; Xu Weixiong; Zhang Xuexin; Wang Xiaoyi; Weng Xuchu; Wu Renhua; Wu Xiaoping

2006-01-01

Objective: To study lexical processing of pseudo words and real words by using a fast event-related functional MRI (ER-fMRI) design. Methods: Participants did an auditory lexical decision task on a list of pseudo-randomly intermixed real and pseudo Chinese two-character (or two-syllable) words. Pseudo words were constructed by recombining constituent characters of the real words to control for sublexical codes properties. Results: The behavioral performance of fourteen participants indicated that response to pseudowords was significantly slower and less accurate than to real words (mean error rate: 9.9% versus 3.9%, mean reaction time: 1618 ms versus 1143 ms). Processing of pseudo words and real words activated a highly comparable network of brain regions, including bilateral inferior frontal gyrus, superior, middle temporal gyrus, calcarine and lingual gyrus, and left supramarginal gyrus. Mirroring a behavioral lexical effect, left inferior frontal gyrus (IFG) was significantly more activated for pseudo words than for real words. Conclusion: The results indicate that the processing of left inferior frontal gyrus in judging pseudo words and real words is not related to grapheme-to-phoneme conversion, but rather to making positive versus negative responses in decision making. (authors)

Concentrations of dapivirine in the rhesus macaque and rabbit following once daily intravaginal administration of a gel formulation of [14C]dapivirine for 7 days.

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Nuttall, Jeremy P; Thake, Daryl C; Lewis, Mark G; Ferkany, John W; Romano, Joseph W; Mitchnick, Mark A

2008-03-01

Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine ( approximately 0.1 mg/ml [15 microCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of microg/g of tissue) and remained detectable at 24 h (mean, >or=2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application.

Concentrations of Dapivirine in the Rhesus Macaque and Rabbit following Once Daily Intravaginal Administration of a Gel Formulation of [14C]Dapivirine for 7 Days▿

Science.gov (United States)

Nuttall, Jeremy P.; Thake, Daryl C.; Lewis, Mark G.; Ferkany, John W.; Romano, Joseph W.; Mitchnick, Mark A.

2008-01-01

Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [14C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [14C]dapivirine (∼0.1 mg/ml [15 μCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of μg/g of tissue) and remained detectable at 24 h (mean, ≥2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application. PMID:18086845

Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques.

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Chang, W L William; Gonzalez, Denise F; Kieu, Hung T; Castillo, Luis D; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D; Shacklett, Barbara L; Barry, Peter A; Sparger, Ellen E

2017-01-01

Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease.

Deleterious impact of feto-maternal MHC compatibility on the success of pregnancy in a macaque model.

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Aarnink, Alice; Mee, Edward T; Savy, Nicolas; Congy-Jolivet, Nicolas; Rose, Nicola J; Blancher, Antoine

2014-02-01

The impact of feto-maternal histocompatibility on reproduction has inspired long-lasting debates. However, after the review of numerous articles, the impact of HLA allele sharing within couples on fecundity remains questionable. We decided to explore the impact of major histocompatibility complex (MHC) feto-maternal compatibility on reproduction in a cynomolgus macaque facility composed of animals of Mauritian descent. The Mauritian-derived macaque population presents a very restricted MHC polymorphism (only seven founding haplotypes) due to a strong founding bottleneck effect. The MHC polymorphism was investigated in 237 trios (male, female and offspring) using 17 microsatellite markers distributed across the MHC. Haplotypes were confirmed by segregation analysis. We evaluated the relative frequencies of MHC-compatible and MHC-semi-compatible offspring with the mothers. Among the 237 trios, we selected 42 trios for which the identity of the father is certain and for which the theoretical probabilities of fully compatible and semi-compatible offspring were equal. We found 11 offspring fully compatible and 31 offspring semi-compatible with their respective mother. The observed proportions were clearly outside the interval of confidence of 99 % and therefore most probably resulted from a selection of the semi-compatible offspring during pregnancy. We concluded that MHC fully compatible cynomolgus macaque offspring have a selective survival disadvantage in comparison with offspring inheriting a paternal MHC haplotype differing from maternal haplotypes.

Rank-dependent grooming patterns and cortisol alleviation in Barbary macaques.

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Sonnweber, Ruth S; Ravignani, Andrea; Stobbe, Nina; Schiestl, Gisela; Wallner, Bernard; Fitch, W Tecumseh

2015-06-01

Flexibly adapting social behavior to social and environmental challenges helps to alleviate glucocorticoid (GC) levels, which may have positive fitness implications for an individual. For primates, the predominant social behavior is grooming. Giving grooming to others is particularly efficient in terms of GC mitigation. However, grooming is confined by certain limitations such as time constraints or restricted access to other group members. For instance, dominance hierarchies may impact grooming partner availability in primate societies. Consequently specific grooming patterns emerge. In despotic species focusing grooming activity on preferred social partners significantly ameliorates GC levels in females of all ranks. In this study we investigated grooming patterns and GC management in Barbary macaques, a comparably relaxed species. We monitored changes in grooming behavior and cortisol (C) for females of different ranks. Our results show that the C-amelioration associated with different grooming patterns had a gradual connection with dominance hierarchy: while higher-ranking individuals showed lowest urinary C measures when they focused their grooming on selected partners within their social network, lower-ranking individuals expressed lowest C levels when dispersing their grooming activity evenly across their social partners. We argue that the relatively relaxed social style of Barbary macaque societies allows individuals to flexibly adapt grooming patterns, which is associated with rank-specific GC management. © 2015 Wiley Periodicals, Inc.

EFEKTIVITAS TEKNIK MANAJEMEN DIRI UNTUK MENGATASI INFERIORITY FEELING

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Kartika

2016-04-01

Full Text Available Siswa yang memiliki inferiority feeling selalu memandang rendah kemampuan yang dimiliki oleh dirinya. Untuk menutupi harga dirinya yang lemah, mereka akan melakukan kompensasi dengan cara menarik diri, bersikap agresif, ataupun membuat alasan. Sebagai upaya mengatasi inferiority feeling adalah dengan mengimplementasikan konseling kelompok dengan teknik manajemen diri. Teknik ini lebih menekankan pada pengelolaan diri yang timbul dari keinginan diri siswa. Penelitian ini bertujuan untuk menguji efektivitas konseling kelompok dengan menggunakan teknik manajemen diri untuk mengatasi inferiority feeling. Pengambilan subyek penelitian dilakukan secara non random menggunakan teknik purposive sampling. Metode penelitian yang digunakan adalah kuasi eksperimen dengan desain non equivalent pretest posttest design. Hasil penelitian menunjukkan bahwa intervensi menggunakan teknik manajemen diri efektif untuk menurunkan inferiority feeling pada subyek penelitian. Rekomendasi: (a Konselor sekolah, melakukan pemantauan secara berkala kepada siswa yang telah menjalani intervensi untuk melihat pengaruh jangka panjang dari intervensi yang telah diberikan; (b bagi peneliti selanjutnya dapat melakukan penelitian dengan keterlibatan pihak keluarga ataupun sahabat sebagai pendukung dalam memperoleh data mengenai keadaan sesungguhnya yang dialami oleh konsel

The most common Chinese rhesus macaque MHC class I molecule shares peptide binding repertoire with the HLA-B7 supertype

DEFF Research Database (Denmark)

Solomon, C.; Southwood, S.; Hoof, Ilka

2010-01-01

Of the two rhesus macaque subspecies used for AIDS studies, the Simian immunodeficiency virus-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection, providing both insight into pathogenesis and a system for testing novel vaccines. Despite the Chinese rhesus.......3%) of the sequences identified were novel. From all MHC alleles detected, we prioritized Mamu-A1*02201 for functional characterization based on its higher frequency of expression. Upon the development of MHC/peptide binding assays and definition of its associated motif, we revealed that this allele shares peptide...

Neural noise and movement-related codes in the macaque supplementary motor area.

Science.gov (United States)

Averbeck, Bruno B; Lee, Daeyeol

2003-08-20

We analyzed the variability of spike counts and the coding capacity of simultaneously recorded pairs of neurons in the macaque supplementary motor area (SMA). We analyzed the mean-variance functions for single neurons, as well as signal and noise correlations between pairs of neurons. All three statistics showed a strong dependence on the bin width chosen for analysis. Changes in the correlation structure of single neuron spike trains over different bin sizes affected the mean-variance function, and signal and noise correlations between pairs of neurons were much smaller at small bin widths, increasing monotonically with the width of the bin. Analyses in the frequency domain showed that the noise between pairs of neurons, on average, was most strongly correlated at low frequencies, which explained the increase in noise correlation with increasing bin width. The coding performance was analyzed to determine whether the temporal precision of spike arrival times and the interactions within and between neurons could improve the prediction of the upcoming movement. We found that in approximately 62% of neuron pairs, the arrival times of spikes at a resolution between 66 and 40 msec carried more information than spike counts in a 200 msec bin. In addition, in 19% of neuron pairs, inclusion of within (11%)- or between-neuron (8%) correlations in spike trains improved decoding accuracy. These results suggest that in some SMA neurons elements of the spatiotemporal pattern of activity may be relevant for neural coding.

Temporal lobe sulcal pattern and the bony impressions in the middle cranial fossa: the case of the el Sidrón (Spain) neandertal sample.

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Rosas, Antonio; Peña-Melián, Angel; García-Tabernero, Antonio; Bastir, Markus; De La Rasilla, Marco

2014-12-01

Correspondence between temporal lobe sulcal pattern and bony impressions on the middle cranial fossae (MCF) was analyzed. MCF bone remains (SD-359, SD-315, and SD-1219) from the El Sidrón (Spain) neandertal site are analyzed in this context. Direct comparison of the soft and hard tissues from the same individual was studied by means of: 1) dissection of two human heads; 2) optic (white light) surface scans; 3) computed tomography and magnetic resonance of the same head. The inferior temporal sulcus and gyrus are the features most strongly influencing MCF bone surface. The Superior temporal sulcus and middle temporal and fusiform gyri also leave imprints. Temporal lobe form differs between Homo sapiens and neandertals. A wider and larger post-arcuate fossa (posterior limit of Brodmann area 20 and the anterior portion of area 37) is present in modern humans as compared to neandertals. However other traits of the MCF surface are similar in these two large-brained human groups. A conspicuous variation is appreciated in the more vertical location of the inferior temporal gyrus in H. sapiens. In parallel, structures of the lower surface of the temporal lobe are more sagittally orientated. Grooves accommodating the fusiform and the lower temporal sulci become grossly parallel to the temporal squama. These differences can be understood within the context of a supero-lateral deployment of the lobe in H. sapiens, a pattern previously identified (Bastir et al., Nat Commun 2 (2011) 588-595). Regarding dural sinus pattern, a higher incidence of petrosquamous sinus is detected in neandertal samples. © 2014 Wiley Periodicals, Inc.

A neural circuit covarying with social hierarchy in macaques.

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Noonan, MaryAnn P; Sallet, Jerome; Mars, Rogier B; Neubert, Franz X; O'Reilly, Jill X; Andersson, Jesper L; Mitchell, Anna S; Bell, Andrew H; Miller, Karla L; Rushworth, Matthew F S

2014-09-01

Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.

A neural circuit covarying with social hierarchy in macaques.

Directory of Open Access Journals (Sweden)

MaryAnn P Noonan

2014-09-01

Full Text Available Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI, which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI data in 25 group-living macaques. First, a deformation-based morphometric (DBM approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status.

A Neural Circuit Covarying with Social Hierarchy in Macaques

Science.gov (United States)

Neubert, Franz X.; O'Reilly, Jill X.; Andersson, Jesper L.; Mitchell, Anna S.; Bell, Andrew H.; Miller, Karla L.; Rushworth, Matthew F. S.

2014-01-01

Despite widespread interest in social dominance, little is known of its neural correlates in primates. We hypothesized that social status in primates might be related to individual variation in subcortical brain regions implicated in other aspects of social and emotional behavior in other mammals. To examine this possibility we used magnetic resonance imaging (MRI), which affords the taking of quantitative measurements noninvasively, both of brain structure and of brain function, across many regions simultaneously. We carried out a series of tests of structural and functional MRI (fMRI) data in 25 group-living macaques. First, a deformation-based morphometric (DBM) approach was used to show that gray matter in the amygdala, brainstem in the vicinity of the raphe nucleus, and reticular formation, hypothalamus, and septum/striatum of the left hemisphere was correlated with social status. Second, similar correlations were found in the same areas in the other hemisphere. Third, similar correlations were found in a second data set acquired several months later from a subset of the same animals. Fourth, the strength of coupling between fMRI-measured activity in the same areas was correlated with social status. The network of subcortical areas, however, had no relationship with the sizes of individuals' social networks, suggesting the areas had a simple and direct relationship with social status. By contrast a second circuit in cortex, comprising the midsuperior temporal sulcus and anterior and dorsal prefrontal cortex, covaried with both individuals' social statuses and the social network sizes they experienced. This cortical circuit may be linked to the social cognitive processes that are taxed by life in more complex social networks and that must also be used if an animal is to achieve a high social status. PMID:25180883

Acute traumatic spinal cord injury induces glial activation in the cynomolgus macaque (Macaca fascicularis).

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Miller, A D; Westmoreland, S V; Evangelous, N R; Graham, A; Sledge, J; Nesathurai, S

2012-06-01

Traumatic spinal cord injury leads to direct myelin and axonal damage and leads to the recruitment of inflammatory cells to site of injury. Although rodent models have provided the greatest insight into the genesis of traumatic spinal cord injury (TSCI), recent studies have attempted to develop an appropriate non-human primate model. We explored TSCI in a cynomolgus macaque model using a balloon catheter to mimic external trauma to further evaluate the underlying mechanisms of acute TSCI. Following 1hour of spinal cord trauma, there were focal areas of hemorrhage and necrosis at the site of trauma. Additionally, there was a marked increased expression of macrophage-related protein 8, MMP9, IBA-1, and inducible nitric oxide synthase in macrophages and microglia at the site of injury. This data indicate that acute TSCI in the cynomolgus macaque is an appropriate model and that the earliest immunohistochemical changes noted are within macrophage and microglia populations. © 2012 John Wiley & Sons A/S.

Dynamically Allocated Hub in Task-Evoked Network Predicts the Vulnerable Prefrontal Locus for Contextual Memory Retrieval in Macaques.

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Takahiro Osada

2015-06-01

Full Text Available Neuroimaging and neurophysiology have revealed that multiple areas in the prefrontal cortex (PFC are activated in a specific memory task, but severity of impairment after PFC lesions is largely different depending on which activated area is damaged. The critical relationship between lesion sites and impairments has not yet been given a clear mechanistic explanation. Although recent works proposed that a whole-brain network contains hubs that play integrative roles in cortical information processing, this framework relying on an anatomy-based structural network cannot account for the vulnerable locus for a specific task, lesioning of which would bring impairment. Here, we hypothesized that (i activated PFC areas dynamically form an ordered network centered at a task-specific "functional hub" and (ii the lesion-effective site corresponds to the "functional hub," but not to a task-invariant "structural hub." To test these hypotheses, we conducted functional magnetic resonance imaging experiments in macaques performing a temporal contextual memory task. We found that the activated areas formed a hierarchical hub-centric network based on task-evoked directed connectivity, differently from the anatomical network reflecting axonal projection patterns. Using a novel simulated-lesion method based on support vector machine, we estimated severity of impairment after lesioning of each area, which accorded well with a known dissociation in contextual memory impairment in macaques (impairment after lesioning in area 9/46d, but not in area 8Ad. The predicted severity of impairment was proportional to the network "hubness" of the virtually lesioned area in the task-evoked directed connectivity network, rather than in the anatomical network known from tracer studies. Our results suggest that PFC areas dynamically and cooperatively shape a functional hub-centric network to reallocate the lesion-effective site depending on the cognitive processes, apart from

Social relevance drives viewing behavior independent of low-level salience in rhesus macaques

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James Andrew Solyst

2014-11-01

Full Text Available Quantifying attention to social stimuli during the viewing of complex social scenes with eye tracking has proven to be a sensitive method in the diagnosis of autism spectrum disorders years before average clinical diagnosis. Rhesus macaques provide an ideal model for understanding the mechanisms underlying social viewing behavior, but to date no comparable behavioral task has been developed for use in monkeys. Using a novel scene-viewing task, we monitored the gaze of three rhesus macaques while they freely viewed well-controlled composed social scenes and analyzed the time spent viewing objects and monkeys. In each of six behavioral sessions, monkeys viewed a set of 90 images (540 unique scenes with each image presented twice. In two-thirds of the repeated scenes, either a monkey or an object was replaced with a novel item (manipulated scenes. When viewing a repeated scene, monkeys made longer fixations and shorter saccades, shifting from a rapid orienting to global scene contents to a more local analysis of fewer items. In addition to this repetition effect, in manipulated scenes, monkeys demonstrated robust memory by spending more time viewing the replaced items. By analyzing attention to specific scene content, we found that monkeys strongly preferred to view conspecifics and that this was not related to their salience in terms of low-level image features. A model-free analysis of viewing statistics found that monkeys that were viewed earlier and longer had direct gaze and redder sex skin around their face and rump, two important visual social cues. These data provide a quantification of viewing strategy, memory and social preferences in rhesus macaques viewing complex social scenes, and they provide an important baseline with which to compare to the effects of therapeutics aimed at enhancing social cognition.

Contribution of nonneutralizing vaccine-elicited antibody activities to improved protective efficacy in rhesus macaques immunized with Tat/Env compared with multigenic vaccines.

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Florese, Ruth H; Demberg, Thorsten; Xiao, Peng; Kuller, LaRene; Larsen, Kay; Summers, L Ebonita; Venzon, David; Cafaro, Aurelio; Ensoli, Barbara; Robert-Guroff, Marjorie

2009-03-15

Previously, chronic-phase protection against SHIV(89.6P) challenge was significantly greater in macaques primed with replicating adenovirus type 5 host range mutant (Ad5hr) recombinants encoding HIVtat and env and boosted with Tat and Env protein compared with macaques primed with multigenic adenovirus recombinants (HIVtat, HIVenv, SIVgag, SIVnef) and boosted with Tat, Env, and Nef proteins. The greater protection was correlated with Tat- and Env-binding Abs. Because the macaques lacked SHIV(89.6P)-neutralizing activity prechallenge, we investigated whether Ab-dependent cellular cytotoxicity (ADCC) and Ab-dependent cell-mediated viral inhibition (ADCVI) might exert a protective effect. We clearly show that Tat can serve as an ADCC target, although the Tat-specific activity elicited did not correlate with better protection. However, Env-specific ADCC activity was consistently higher in the Tat/Env group, with sustained cell killing postchallenge exhibited at higher levels (p vaccine regimens.

A study using computerized tomography in the clinical practice of temporal lobe epilepsy

International Nuclear Information System (INIS)

Yamamoto, Kunimitsu

1982-01-01

The author has studied about analysis of clinical data and CT findings examined conventional method for 50 cases of temporal lobe epilepsy and how to assess the foci of temporal lobe by CT. According to the examination of conventional neuroradiologic technique and routine work of CT for temporal lobe epilepsy, an extreme space occuping lesions were detected and marked cerebral atrophy, low density area in temporal lobe were found out, but, most of them were not able to detect foci of the temporal lobe and yet, the study of CT number based on the print out data did not give any precise informations about epileptogenic lesions of temporal lobe epilepsy. The method of reversed axial section CT was designed to photograph inferior horn of lateral ventricles with the purpose to delineate the hippocampus and amygdata, and precise pictures from autopsy brain and clinical cases were obtained by that method about scanning angle of reversed axial section CT, various angles are made an experiment on scanning, such as reversed 15 0 , 20 0 , 25 0 , 30 0 , 35 0 . Among them, it is proved that the reversed angle of almost 25 0 is most suitable to delineate mesial temporal structure, so as to say, foci of the temporal lobe. (J.P.N.)

Inactivated polio vaccination using a microneedle patch is immunogenic in the rhesus macaque.

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Edens, Chris; Dybdahl-Sissoko, Naomi C; Weldon, William C; Oberste, M Steven; Prausnitz, Mark R

2015-09-08

The phased replacement of oral polio vaccine (OPV) with inactivated polio vaccine (IPV) is expected to significantly complicate mass vaccination campaigns, which are an important component of the global polio eradication endgame strategy. To simplify mass vaccination with IPV, we developed microneedle patches that are easy to administer, have a small package size, generate no sharps waste and are inexpensive to manufacture. When administered to rhesus macaques, neutralizing antibody titers were equivalent among monkeys vaccinated using microneedle patches and conventional intramuscular injection for IPV types 1 and 2. Serologic response to IPV type 3 vaccination was weaker after microneedle patch vaccination compared to intramuscular injection; however, we suspect the administered type 3 dose was lower due to a flawed pre-production IPV type 3 analytical method. IPV vaccination using microneedle patches was well tolerated by the monkeys. We conclude that IPV vaccination using a microneedle patch is immunogenic in rhesus macaques and may offer a simpler method of IPV vaccination of people to facilitate polio eradication. Copyright © 2015 Elsevier Ltd. All rights reserved.

An experimental investigation of referential looking in free-ranging Barbary macaques (Macaca sylvanus).

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Roberts, Sam G B; McComb, Karen; Ruffman, Ted

2008-02-01

The authors examined looking behavior between 15 Barbary macaque (Macaca sylvanus) infants and their mothers in the presence of a rubber snake (experimental period) and in the absence of the snake (control period). Two of the 15 infants looked referentially at their mother in the experimental period. Including both referential and nonreferential looks, the six older infants (aged 5 to 12 months) displayed a higher frequency of looks to mother than nine younger infants (aged 3 to 4.5 months) in the experimental period, but not in the control period. Older infants looked more to the mother in the experimental condition, whereas the younger infants looked more to the mother in the control condition, or looked equally in the two conditions. These results suggest that age is an important factor in determining looking behavior to mother in situations of uncertainty. Compared to hand-reared chimpanzees or human infants tested in standard social referencing paradigms, the infant macaques displayed a low rate of referential looking. Possible explanations for this are discussed. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

Limited SHIV env diversification in macaques failing oral antiretroviral pre-exposure prophylaxis.

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Zheng, Qi; Ruone, Susan; Switzer, William M; Heneine, Walid; García-Lerma, J Gerardo

2012-05-09

Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in adherent persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP. Four macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12-20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 × 10-3 compared to 1.6 × 10-2 nucleotide substitutions per site per year, respectively, p diversification during early infection might enhance immune control by slowing the selection of escape mutants.

Cerebral blood flow in temporal lobe epilepsy: a partial volume correction study

Energy Technology Data Exchange (ETDEWEB)

Giovacchini, Giampiero [University Milano-Bicocca, Milan (Italy); Bonwetsch, Robert; Theodore, William H. [National Institute of Neurological Diseases and Strokes, Clinical Epilepsy Section, Bethesda, MD (United States); Herscovitch, Peter [National Institutes of Health, PET Department, Clinical Center, Bethesda, MD (United States); Carson, Richard E. [Yale PET Center, New Haven, CT (United States)

2007-12-15

Previous studies in temporal lobe epilepsy (TLE) have shown that, owing to brain atrophy, positron emission tomography (PET) can overestimate deficits in measures of cerebral function such as glucose metabolism (CMR{sub glu}) and neuroreceptor binding. The magnitude of this effect on cerebral blood flow (CBF) is unexplored. The aim of this study was to assess CBF deficits in TLE before and after magnetic resonance imaging-based partial volume correction (PVC). Absolute values of CBF for 21 TLE patients and nine controls were computed before and after PVC. In TLE patients, quantitative CMR{sub glu} measurements also were obtained. Before PVC, regional values of CBF were significantly (p<0.05) lower in TLE patients than in controls in all regions, except the fusiform gyrus contralateral to the epileptic focus. After PVC, statistical significance was maintained in only four regions: ipsilateral inferior temporal cortex, bilateral insula and contralateral amygdala. There was no significant difference between patients and controls in CBF asymmetry indices (AIs) in any region before or after PVC. In TLE patients, AIs for CBF were significantly smaller than for CMR{sub glu} in middle and inferior temporal cortex, fusiform gyrus and hippocampus both before and after PVC. A significant positive relationship between disease duration and AIs for CMR{sub glu}, but not CBF, was detected in hippocampus and amygdala, before but not after PVC. PVC should be used for PET CBF measurements in patients with TLE. Reduced blood flow, in contrast to glucose metabolism, is mainly due to structural changes. (orig.)

Aiding pest control management of long-tailed macaques (Macaca fascicularis fascicularis) in Malaysia by using molecular markers of mitochondrial DNA

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Abdul-Latiff, M. A. B.; Abdul-Patah, P.; Yaakop, S.; Md-Zain, B. M.

2017-10-01

The long-tailed macaques (Macaca fascicularis fascicularis) has been the center of human wildlife conflict in Malaysia since 1970s. This well-adapted and opportunistic primates have been dominating wide range of habitat in Malaysia such as primary and secondary forest, mangrove, as well as human settlements. The conventional practices of translocation by the authorities are threatening the uniqueness of gene pool for this species and ironically contradicting with the ultimate purpose of genetic conservation of this species. The objectives of this study is to determine the level of genetic separation between populations of long-tailed macaques, primarily focusing on populations distributed in northern Peninsular Malaysia. A total of 954 base pairs of control regions mtDNA was sequenced and analyzed from 27 samples of M. fascicularis. The results exhibited a highly homogenous state of populations for long-tailed macaques genetically and this ultimately indicate unsuitable management and planning in terms of pest control management of the species. Authorities are suggested to translocate the species at least within the state boundaries to avoid homogeneity of gene pools for the particular species.

Inferior phrenic artery embolization in the treatment of hepatic neoplasms

International Nuclear Information System (INIS)

Duprat, G.; Charnsangavej, C.; Wallace, S.; Carrasco, C.H.

1988-01-01

Twenty-nine inferior phrenic artery embolizations were performed in 20 patients with primary or metastatic hepatic neoplasms. All patients had interruption of their hepatic arteries by previous infusion of chemotherapy, hepatic arterial embolization or surgical ligation. In one patient, bilateral pleural effusions developed following embolization of the inferior phrenic artery. No other severe complications occurred. Inferior phrenic artery embolization is a safe procedure and permits the continuation of transcatheter treatment of hepatic neoplasms. (orig.)

Inferior phrenic artery embolization in the treatment of hepatic neoplasms

Energy Technology Data Exchange (ETDEWEB)

Duprat, G.; Charnsangavej, C.; Wallace, S.; Carrasco, C.H.

Twenty-nine inferior phrenic artery embolizations were performed in 20 patients with primary or metastatic hepatic neoplasms. All patients had interruption of their hepatic arteries by previous infusion of chemotherapy, hepatic arterial embolization or surgical ligation. In one patient, bilateral pleural effusions developed following embolization of the inferior phrenic artery. No other severe complications occurred. Inferior phrenic artery embolization is a safe procedure and permits the continuation of transcatheter treatment of hepatic neoplasms.

Macaque homologs of EBV and KSHV show uniquely different associations with simian AIDS-related lymphomas.

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A Gregory Bruce

Full Text Available Two gammaherpesviruses, Epstein-Barr virus (EBV (Lymphocryptovirus genus and Kaposi's sarcoma-associated herpesvirus (KSHV (Rhadinovirus genus have been implicated in the etiology of AIDS-associated lymphomas. Homologs of these viruses have been identified in macaques and other non-human primates. In order to assess the association of these viruses with non-human primate disease, archived lymphoma samples were screened for the presence of macaque lymphocryptovirus (LCV homologs of EBV, and macaque rhadinoviruses belonging to the RV1 lineage of KSHV homologs or the more distant RV2 lineage of Old World primate rhadinoviruses. Viral loads were determined by QPCR and infected cells were identified by immunolabeling for different viral proteins. The lymphomas segregated into three groups. The first group (n = 6 was associated with SIV/SHIV infections, contained high levels of LCV (1-25 genomes/cell and expressed the B-cell antigens CD20 or BLA.36. A strong EBNA-2 signal was detected in the nuclei of the neoplastic cells in one of the LCV-high lymphomas, indicative of a type III latency stage. None of the lymphomas in this group stained for the LCV viral capsid antigen (VCA lytic marker. The second group (n = 5 was associated with D-type simian retrovirus-2 (SRV-2 infections, contained high levels of RV2 rhadinovirus (9-790 genomes/cell and expressed the CD3 T-cell marker. The third group (n = 3 was associated with SIV/SHIV infections, contained high levels of RV2 rhadinovirus (2-260 genomes/cell and was negative for both CD20 and CD3. In both the CD3-positive and CD3/CD20-negative lymphomas, the neoplastic cells stained strongly for markers of RV2 lytic replication. None of the lymphomas had detectable levels of retroperitoneal fibromatosis herpesvirus (RFHV, the macaque RV1 homolog of KSHV. Our data suggest etiological roles for both lymphocryptoviruses and RV2 rhadinoviruses in the development of simian AIDS-associated lymphomas and indicate that

Acoustic characteristics used by Japanese macaques for individual discrimination.

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Furuyama, Takafumi; Kobayasi, Kohta I; Riquimaroux, Hiroshi

2017-10-01

The vocalizations of primates contain information about speaker individuality. Many primates, including humans, are able to distinguish conspecifics based solely on vocalizations. The purpose of this study was to investigate the acoustic characteristics used by Japanese macaques in individual vocal discrimination. Furthermore, we tested human subjects using monkey vocalizations to evaluate species specificity with respect to such discriminations. Two monkeys and five humans were trained to discriminate the coo calls of two unfamiliar monkeys. We created a stimulus continuum between the vocalizations of the two monkeys as a set of probe stimuli (whole morph). We also created two sets of continua in which only one acoustic parameter, fundamental frequency ( f 0 ) or vocal tract characteristic (VTC), was changed from the coo call of one monkey to that of another while the other acoustic feature remained the same ( f 0 morph and VTC morph, respectively). According to the results, the reaction times both of monkeys and humans were correlated with the morph proportion under the whole morph and f 0 morph conditions. The reaction time to the VTC morph was correlated with the morph proportion in both monkeys, whereas the reaction time in humans, on average, was not correlated with morph proportion. Japanese monkeys relied more consistently on VTC than did humans for discriminating monkey vocalizations. Our results support the idea that the auditory system of primates is specialized for processing conspecific vocalizations and suggest that VTC is a significant acoustic feature used by Japanese macaques to discriminate conspecific vocalizations. © 2017. Published by The Company of Biologists Ltd.

Depth perception from moving cast shadow in macaque monkey.

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Mizutani, Saneyuki; Usui, Nobuo; Yokota, Takanori; Mizusawa, Hidehiro; Taira, Masato; Katsuyama, Narumi

2015-07-15

In the present study, we investigate whether the macaque monkey can perceive motion in depth using a moving cast shadow. To accomplish this, we conducted two experiments. In the first experiment, an adult Japanese monkey was trained in a motion discrimination task in depth by binocular disparity. A square was presented on the display so that it appeared with a binocular disparity of 0.12 degrees (initial position), and moved toward (approaching) or away from (receding) the monkey for 1s. The monkey was trained to discriminate the approaching and receding motion of the square by GO/delayed GO-type responses. The monkey showed a significantly high accuracy rate in the task, and the performance was maintained when the position, color, and shape of the moving object were changed. In the next experiment, the change in the disparity was gradually decreased in the motion discrimination task. The results showed that the performance of the monkey declined as the distance of the approaching and receding motion of the square decreased from the initial position. However, when a moving cast shadow was added to the stimulus, the monkey responded to the motion in depth induced by the cast shadow in the same way as by binocular disparity; the reward was delivered randomly or given in all trials to prevent the learning of the 2D motion of the shadow in the frontal plane. These results suggest that the macaque monkey can perceive motion in depth using a moving cast shadow as well as using binocular disparity. Copyright © 2015 Elsevier B.V. All rights reserved.

Survey of Treponemal Infections in Free-Ranging and Captive Macaques, 1999–2012

Science.gov (United States)

Klegarth, Amy R.; Ezeonwu, Chigozie A.; Rompis, Aida; Lee, Benjamin P.Y.-H.; Aggimarangsee, Nantiya; Chalise, Mukesh; Cortes, John; Feeroz, M.; Molini, Barbara J.; Godornes, Bess C.; Marks, Michael; Schillaci, Michael; Engel, Gregory; Knauf, Sascha; Lukehart, Sheila A.

2017-01-01

Survey results showed treponemal infection among pet macaques in Southeast Asia, a region with a high prevalence of human yaws. This finding, along with studies showing treponemal infection in nonhuman primates in Africa, should encourage a One Health approach to yaws eradication and surveillance activities, possibly including monitoring of nonhuman primates in yaws-endemic regions. PMID:28418297

Social network community structure and the contact-mediated sharing of commensal E. coli among captive rhesus macaques (Macaca mulatta).

Science.gov (United States)

Balasubramaniam, Krishna; Beisner, Brianne; Guan, Jiahui; Vandeleest, Jessica; Fushing, Hsieh; Atwill, Edward; McCowan, Brenda

2018-01-01

In group-living animals, heterogeneity in individuals' social connections may mediate the sharing of microbial infectious agents. In this regard, the genetic relatedness of individuals' commensal gut bacterium Escherichia coli may be ideal to assess the potential for pathogen transmission through animal social networks. Here we use microbial phylogenetics and population genetics approaches, as well as host social network reconstruction, to assess evidence for the contact-mediated sharing of E. coli among three groups of captively housed rhesus macaques ( Macaca mulatta ), at multiple organizational scales. For each group, behavioral data on grooming, huddling, and aggressive interactions collected for a six-week period were used to reconstruct social network communities via the Data Cloud Geometry (DCG) clustering algorithm. Further, an E. coli isolate was biochemically confirmed and genotypically fingerprinted from fecal swabs collected from each macaque. Population genetics approaches revealed that Group Membership, in comparison to intrinsic attributes like age, sex, and/or matriline membership of individuals, accounted for the highest proportion of variance in E. coli genotypic similarity. Social network approaches revealed that such sharing was evident at the community-level rather than the dyadic level. Specifically, although we found no links between dyadic E. coli similarity and social contact frequencies, similarity was significantly greater among macaques within the same social network communities compared to those across different communities. Moreover, tests for one of our study-groups confirmed that E. coli isolated from macaque rectal swabs were more genotypically similar to each other than they were to isolates from environmentally deposited feces. In summary, our results suggest that among frequently interacting, spatially constrained macaques with complex social relationships, microbial sharing via fecal-oral, social contact-mediated routes may

Gated myocardial SPECT using spatial and temporal filtering

International Nuclear Information System (INIS)

Hatton, R.L.; Hutton, B.F.; Kyme, A.Z.; Larcos, G.

2002-01-01

Full text: Standard protocols for examining myocardial perfusion and motion defects involve the use of gated SPECT images, and a composite of the gated frames. This study examines the usefulness of extracting one or a combination of frames from the gated image to assess perfusion, and whether the addition of a temporal filter to the gated image improves signal to noise. Choice of the most appropriate frame was also considered. Sixteen and eight frame gated SPECT studies were simulated using the dynamic NURBS-based cardiac torso (NCAT) phantom. Variously sized perfusion defects were included in the inferior wall to assess contrast to normal tissue. Scatter and attenuation were not included. Butterworth spatial cutoff frequencies were varied to establish the most appropriate combination of temporal/spatial filters to reduce noise and retain contrast in the images. The 16 frame data produced higher ejection fraction across all spatial filter cutoffs, and generally was unaffected by temporal filtering. Temporal filtering reduced the noise in a uniform liver region in the gated images to within 25% of the composite image noise. The lesion extent and contrast were greater in the end-diastolic frames compared to end-systolic and mid-cycle frames. In conclusion, by using a temporally filtered end-diastolic image from the gated sequence, a favourable balance between noise and contrast can be achieved. Work is progress to confirm these findings in the clinical situation. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

Short-term costs and benefits of grooming in Japanese macaques.

Science.gov (United States)

Schino, Gabriele; Alessandrini, Alessandro

2015-07-01

This study investigated the short-term consequences of giving grooming in Japanese macaques (Macaca fuscata) in order to obtain information on its immediate costs and benefits. Giving grooming was associated with increased aggression received from groomees and decreased aggression received from third parties (but only as long as the groomer maintained proximity to the groomee). Grooming was also associated with decreased scratching rates. These results emphasize the unpredictable outcome of individual grooming interactions and the difficulties of social decision-making for monkeys living in despotic societies.

Prevention of SIV rectal transmission and priming of T cell responses in macaques after local pre-exposure application of tenofovir gel.

Directory of Open Access Journals (Sweden)

Martin Cranage

2008-08-01

Full Text Available The rectum is particularly vulnerable to HIV transmission having only a single protective layer of columnar epithelium overlying tissue rich in activated lymphoid cells; thus, unprotected anal intercourse in both women and men carries a higher risk of infection than other sexual routes. In the absence of effective prophylactic vaccines, increasing attention is being given to the use of microbicides and preventative antiretroviral (ARV drugs. To prevent mucosal transmission of HIV, a microbicide/ARV should ideally act locally at and near the virus portal of entry. As part of an integrated rectal microbicide development programme, we have evaluated rectal application of the nucleotide reverse transcriptase (RT inhibitor tenofovir (PMPA, 9-[(R-2-(phosphonomethoxy propyl] adenine monohydrate, a drug licensed for therapeutic use, for protective efficacy against rectal challenge with simian immunodeficiency virus (SIV in a well-established and standardised macaque model.A total of 20 purpose-bred Indian rhesus macaques were used to evaluate the protective efficacy of topical tenofovir. Nine animals received 1% tenofovir gel per rectum up to 2 h prior to virus challenge, four macaques received placebo gel, and four macaques remained untreated. In addition, three macaques were given tenofovir gel 2 h after virus challenge. Following intrarectal instillation of 20 median rectal infectious doses (MID50 of a noncloned, virulent stock of SIVmac251/32H, all animals were analysed for virus infection, by virus isolation from peripheral blood mononuclear cells (PBMC, quantitative proviral DNA load in PBMC, plasma viral RNA (vRNA load by sensitive quantitative competitive (qc RT-PCR, and presence of SIV-specific serum antibodies by ELISA. We report here a significant protective effect (p = 0.003; Fisher exact probability test wherein eight of nine macaques given tenofovir per rectum up to 2 h prior to virus challenge were protected from infection (n = 6 or had

Some problems with non-inferiority tests in psychotherapy research: psychodynamic therapies as an example.

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Rief, Winfried; Hofmann, Stefan G

2018-02-14

In virtually every field of medicine, non-inferiority trials and meta-analyses with non-inferiority conclusions are increasingly common. This non-inferiority approach has been frequently used by a group of authors favoring psychodynamic therapies (PDTs), concluding that PDTs are just as effective as cognitive-behavioral therapies (CBT). We focus on these examples to exemplify some problems associated with non-inferiority tests of psychological treatments, although the problems also apply to psychopharmacotherapy research, CBT research, and others. We conclude that non-inferiority trials have specific risks of different types of validity problems, usually favoring an (erroneous) non-inferiority conclusion. Non-inferiority trials require the definition of non-inferiority margins, and currently used thresholds have a tendency to be inflationary, not protecting sufficiently against degradation. The use of non-inferiority approaches can lead to the astonishing result that one single analysis can suggest both, superiority of the comparator (here: CBT) and non-inferiority of the other treatment (here PDT) at the same time. We provide recommendations how to improve the quality of non-inferiority trials, and we recommend to consider them among other criteria when evaluating manuscripts examining non-inferiority trials. If psychotherapeutic families (such as PDT and CBT) differ on the number of investigating trials, and in the fields of clinical applications, and in other validity aspects mentioned above, conclusions about their general non-inferiority are no more than a best guess, typically expressing the favored approach of the lead author.

Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved in Immunity and Neurogenesis in Simian Immunodeficiency Virus-Infected Macaques

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John K. Maxi

2016-11-01

Full Text Available Alcohol use disorders (AUD exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+ patients. We have shown that chronic binge alcohol (CBA administration (13–14 g EtOH/kg/wk prior to and during simian immunodeficiency virus (SIV infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; n = 2 macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; n = 2 macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 months post-SIV inoculation were analyzed to determine differentially expressed genes. MetaCore from Thomson Reuters revealed enrichment of genes involved in inflammation, immune responses, and neurodevelopment. Functional relevance of these alterations was examined in vitro by exposing murine neural progenitor cells (NPCs to ethanol (EtOH and HIV trans-activator of transcription (Tat protein. EtOH impaired NPC differentiation as indicated by decreased βIII tubulin expression. These findings suggest a role for neuroinflammation and neurogenesis in CBA/SIV neuropathogenesis and warrant further investigation of their potential contribution to CBA-mediated neurobehavioral deficits.

Is GABA neurotransmission enhanced in auditory thalamus relative to inferior colliculus?

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Cai, Rui; Kalappa, Bopanna I.; Brozoski, Thomas J.; Ling, Lynne L.

2013-01-01

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central auditory system. Sensory thalamic structures show high levels of non-desensitizing extrasynaptic GABAA receptors (GABAARs) and a reduction in the redundancy of coded information. The present study compared the inhibitory potency of GABA acting at GABAARs between the inferior colliculus (IC) and the medial geniculate body (MGB) using quantitative in vivo, in vitro, and ex vivo experimental approaches. In vivo single unit studies compared the ability of half maximal inhibitory concentrations of GABA to inhibit sound-evoked temporal responses, and found that GABA was two to three times (P GABA levels and suggested a trend towards higher GABA concentrations in MGB than in IC. Collectively, these studies suggest that, per unit GABA, high affinity extrasynaptic and synaptic GABAARs confer a significant inhibitory GABAAR advantage to MGB neurons relative to IC neurons. This increased GABA sensitivity likely underpins the vital filtering role of auditory thalamus. PMID:24155003

Inferior ectopic pupil and typical ocular coloboma in RCS rats.

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Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro

2011-08-01

Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F(1) rats nor N(2) (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma.

Cortical Activation during a Cognitive Challenge in Patients with Chronic Temporal Lobe Epilepsy—A Dynamic SPECT Study

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P. J. Kirkpatrick

1993-01-01

Full Text Available In a pilot group of six patients suffering from chronic temporal lobe epilepsy, single photon emission computerized tomography (SPECT has been used to image the changes in relative cerebral blood flow between rest (static scan and conditions of cognitive activation (activated scan. The cognitive challenge used during activation comprised a test of word memory, and the performance was expressed as a word memory score (WMS for each individual. An activation index (AI was calculated from the mean normalized density counts in specific regions of interest (ROIs, and values obtained were analysed for correlation with the WMS. The mean AI was increased significantly in the right lateral temporal cortex, the right and left inferior frontal regions, the left temporal pole, and the right medial temporal cortex. A positive correlation with the WMS was found in the medial temporal cortices, and this relationship was significant for the right medial temporal ROI.

The role of inferior parietal and inferior frontal cortex in working memory.

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Baldo, Juliana V; Dronkers, Nina F

2006-09-01

Verbal working memory involves two major components: a phonological store that holds auditory-verbal information very briefly and an articulatory rehearsal process that allows that information to be refreshed and thus held longer in short-term memory (A. Baddeley, 1996, 2000; A. Baddeley & G. Hitch, 1974). In the current study, the authors tested two groups of patients who were chosen on the basis of their relatively focal lesions in the inferior parietal (IP) cortex or inferior frontal (IF) cortex. Patients were tested on a series of tasks that have been previously shown to tap phonological storage (span, auditory rhyming, and repetition) and articulatory rehearsal (visual rhyming and a 2-back task). As predicted, IP patients were disproportionately impaired on the span, rhyming, and repetition tasks and thus demonstrated a phonological storage deficit. IF patients, however, did not show impairment on these storage tasks but did exhibit impairment on the visual rhyming task, which requires articulatory rehearsal. These findings lend further support to the working memory model and provide evidence of the roles of IP and IF cortex in separable working memory processes. ((c) 2006 APA, all rights reserved).

Reciprocation and interchange of grooming, agonistic support, feeding tolerance, and aggression in semi-free-ranging Barbary macaques.

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Carne, Charlotte; Wiper, Sue; Semple, Stuart

2011-11-01

Evidence from a range of primate species indicates that grooming can be exchanged either for itself or for other rank-related "commodities," such as agonistic support, feeding tolerance, or reduced aggression. Patterns of exchange behavior have been found to vary considerably between species, and understanding the causes of this variation is central to the study of the evolution of primate social systems. It is, therefore, essential that exchange behavior is examined in a wide range of species and settings. This article is the first to explore the reciprocation and interchange of grooming in the Barbary macaque (Macaca sylvanus). We collected focal data on semi-free-ranging adult female Barbary macaques at Trentham Monkey Forest, England, and analyzed dyadic data using Generalized Linear Mixed Models. We found evidence for the reciprocal exchange of grooming and for the interchange of grooming for agonistic support and tolerance while feeding. There was no evidence that grooming was traded for a reduction in aggression; indeed, we found a positive relationship between aggression given and grooming received. This may reflect the "extortion" of grooming from subordinates by dominant animals. These results will facilitate comparative analyses of exchange behavior by adding to the current database a new species, characterized by a different social style from those macaque species previously investigated. © 2011 Wiley Periodicals, Inc.

Functional analysis of frequently expressed Chinese rhesus macaque MHC class I molecules Mamu-A1*02601 and Mamu-B*08301 reveals HLA-A2 and HLA-A3 supertypic specificities

DEFF Research Database (Denmark)

Southwood, Scott; Solomon, Christopher; Hoof, Ilka

2011-01-01

The Simian immunodeficiency virus (SIV)-infected Indian rhesus macaque (Macaca mulatta) is the most established model of HIV infection and AIDS-related research, despite the potential that macaques of Chinese origin is a more relevant model. Ongoing efforts to further characterize the Chinese...... populations. In this study, we have characterized two additional alleles expressed with high frequency in Chinese rhesus macaques, Mamu-A1*02601 and Mamu-B*08301. Upon the development of MHC–peptide-binding assays and definition of their associated motifs, we reveal that these Mamu alleles share peptide...

Shigella flexneri infection in a newly acquired rhesus macaque (Macaca mulatta)

OpenAIRE

Lee, Jae-Il; Kim, Sang-Joon; Park, Chung-Gyu

2011-01-01

A 3.4 year-old rhesus macaque weighing 4.5 kg, was suffering from anorexia, acute mucous and bloody diarrhea. On physical examination, the monkey showed a loss of activity, hunched posture, abdominal pain, dehydration, mild gingivitis and unclean anus with discharge. Whole blood was collected for the examination of electrolytes, hematology and serum chemistry; fresh stool was also collected for bacterial culture. Blood profiles showed leukocytosis (14.5 K/?L) and neutrophilia (11.0 K/?L) on c...

Locating the scala media in the fixed human temporal bone for therapeutic access: a preliminary study.

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Pau, H; Fagan, P; Oleskevich, S

2006-11-01

To investigate the location of the scala media in relation to the round window niche in human temporal bones. Ten human temporal bones were investigated by radical mastoidectomy and promontory drill-out. Temporal bone laboratory. The distance from the scala media to the anterior edge of the round window niche, measured by Fisch's stapedectomy measuring cylinders. The scala media was identified at the transection point of a vertical line 1.6 to 2.2 mm (mean=1.8 mm; standard deviation=0.2) anterior to the anterior edge of the round window niche and a horizontal line 0.2 mm inferior to the lower border of the oval window. This report demonstrates the point of entry into the scala media via the promontory in fixed temporal bone models, which may provide a site of entry for stem cells and gene therapy insertion.

Altered regional homogeneity of brain spontaneous signals in SIV infected rhesus macaque model.

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Zhao, Jing; Jing, Bin; Chen, Feng; Liu, Jiaojiao; Wang, Yuanyuan; Li, Hongjun

2017-04-01

Regional homogeneity (ReHo), a measurement from resting-state functional magnetic imaging (rs-fMRI) to reflect local synchronization of brain activities, has been widely explored in previous studies of neurological diseases. SIV infected model for detecting the neurological changes with progression was studied. In the study, six rhesus macaques infected by simian immunodeficiency virus (SIV) were scanned by resting-state fMRI at the following time points: before SIV inoculation (baseline), 12weeks and 24weeks post inoculation (12wpi, 24wpi). Meanwhile, the immunological parameters including serum percentage of CD4+ T cell, CD4/CD8 ratio and absolute CD4+ T cell number were measured and analyzed. In comparison of baseline, significant decreased ReHo was found in the left superior frontal gyrus, left superior temporal gyrus, left hippocampus, right precuneus, left angular gyrus, and bilateral occipital gyrus; in contrast increased ReHo in putamen at 12wpi. Moreover, at the time of 24wpi, decreased ReHo was observed in the right postcentral gyrus, left precentral gyrus, posterior cingulated gyrus and thalamus, while ReHo was increased in the left putamen, hippocampus, left anterior cingulated cortex and precentral cortex. The correlation analysis revealed that ReHo in the superior frontal gyrus showed negative association with CD4/CD8 ratio and positive with absolute CD4+ T cell number. The correlation analysis showed that percentage of CD4+ was correlated with the ReHo values in right middle frontal gyrus, bilateral thalamus and amygdala positively; negative relationship with left putamen, left superior frontal gyrus, left superior and middle temporal gyrus. The study first indicates that hippocampus, putamen, frontal and occipital lobe were impaired by using rs-fMRI and correlated with immunological parameters. Thus, ReHo value can be utilized as a noninvasive biomarker of spontaneous brain activity changes caused by the progression of neurological impairments

Effect of complement Factor H on anti-FHbp serum bactericidal antibody responses of infant rhesus macaques boosted with a licensed meningococcal serogroup B vaccine.

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Giuntini, Serena; Beernink, Peter T; Granoff, Dan M

2015-12-16

FHbp is a major serogroup B meningococcal vaccine antigen. Binding of complement Factor H (FH) to FHbp is specific for human and some non-human primate FH. In previous studies, FH binding to FHbp vaccines impaired protective anti-FHbp antibody responses. In this study we investigated anti-FHbp antibody responses to a third dose of a licensed serogroup B vaccine (MenB-4C) in infant macaques vaccinated in a previous study with MenB-4C. Six macaques with high binding of FH to FHbp (FH(high)), and six with FH(low) baseline phenotypes, were immunized three months after dose 2. After dose 2, macaques with the FH(low) baseline phenotype had serum anti-FHbp antibodies that enhanced FH binding to FHbp (functionally converting them to a FH(high) phenotype). In this group, activation of the classical complement pathway (C4b deposition) by serum anti-FHbp antibody, and anti-FHbp serum bactericidal titers were lower after dose 3 than after dose 2 (pb deposition and bactericidal titers were similar after doses 2 and 3. Two macaques developed serum anti-FH autoantibodies after dose 2, which were not detected after dose 3. In conclusion, in macaques with the FH(low) baseline phenotype whose post-dose 2 serum anti-FHbp antibodies had converted them to FH(high), the anti-FHbp antibody repertoire to dose 3 was skewed to less protective epitopes than after dose 2. Mutant FHbp vaccines that eliminate FH binding may avoid eliciting anti-FHbp antibodies that enhance FH binding, and confer greater protection with less risk of inducing anti-FH autoantibodies than FHbp vaccines that bind FH. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inferior hilar window on lateral chest radiographs

International Nuclear Information System (INIS)

Park, C.K.; Webb, W.R.; Klein, J.S.

1990-01-01

This paper determines the accuracy of lateral chest radiography in the detection of masses in the inferior hilar window, a normally avascular hilar region anterior to the lower lobe bronchi. Fifty patients with normal thoracic CT scans and 25 with hilar masses/adenopathy were selected retrospectively. The 75 corresponding lateral chest radiographs were blindly evaluated for visibility of the anterior walls of the lower lobe bronchi and the presence and laterality of abnormal soft tissue (>1 cm) in the inferior hilar window. Only a 7 x 7-cm square of the lateral radiograph was viewed

Complete Unique Genome Sequence, Expression Profile, and Salivary Gland Tissue Tropism of the Herpesvirus 7 Homolog in Pigtailed Macaques.

Science.gov (United States)

Staheli, Jeannette P; Dyen, Michael R; Deutsch, Gail H; Basom, Ryan S; Fitzgibbon, Matthew P; Lewis, Patrick; Barcy, Serge

2016-08-01

Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses and are highly prevalent in the human population. Roseolovirus reactivation in an immunocompromised host can cause severe pathologies. While the pathogenic potential of HHV-7 is unclear, it can reactivate HHV-6 from latency and thus contributes to severe pathological conditions associated with HHV-6. Because of the ubiquitous nature of roseoloviruses, their roles in such interactions and the resulting pathological consequences have been difficult to study. Furthermore, the lack of a relevant animal model for HHV-7 infection has hindered a better understanding of its contribution to roseolovirus-associated diseases. Using next-generation sequencing analysis, we characterized the unique genome of an uncultured novel pigtailed macaque roseolovirus. Detailed genomic analysis revealed the presence of gene homologs to all 84 known HHV-7 open reading frames. Phylogenetic analysis confirmed that the virus is a macaque homolog of HHV-7, which we have provisionally named Macaca nemestrina herpesvirus 7 (MneHV7). Using high-throughput RNA sequencing, we observed that the salivary gland tissue samples from nine different macaques had distinct MneHV7 gene expression patterns and that the overall number of viral transcripts correlated with viral loads in parotid gland tissue and saliva. Immunohistochemistry staining confirmed that, like HHV-7, MneHV7 exhibits a natural tropism for salivary gland ductal cells. We also observed staining for MneHV7 in peripheral nerve ganglia present in salivary gland tissues, suggesting that HHV-7 may also have a tropism for the peripheral nervous system. Our data demonstrate that MneHV7-infected macaques represent a relevant animal model that may help clarify the causality between roseolovirus reactivation and diseases. Human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 are classified as roseoloviruses. We have recently discovered that pigtailed macaques are naturally

The effects of inferior olive lesion on strychnine seizure

International Nuclear Information System (INIS)

Anderson, M.C.; Chung, E.Y.; Van Woert, M.H.

1990-01-01

Bilateral inferior olive lesions, produced by systemic administration of the neurotoxin 3-acetylpyridine (3AP) produce a proconvulsant state specific for strychnine-induced seizures and myoclonus. We have proposed that these phenomena are mediated through increased excitation of cerebellar Purkinje cells, through activation of glutamate receptors, in response to climbing fiber deafferentation. An increase in quisqualic acid (QA)-displaceable [ 3 H]AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid] binding in cerebella from inferior olive-lesioned rats was observed, but no difference in [ 3 H]AMPA binding displaced by glutamate, kainic acid (KA) or glutamate diethylester (GDEE) was seen. The excitatory amino acid antagonists GDEE and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10 imine] were tested as anticonvulsants for strychnine-induced seizures in 3AP inferior olive-lesioned and control rats. Neither drug effected seizures in control rats, however, both GDEE and MK-801 produced a leftward shift in the strychnine-seizure dose-response curve in 3AP inferior olive-lesioned rats. GDEE also inhibited strychnine-induced myoclonus in the lesioned group, while MK-801 had no effect on myoclonus. The decreased threshold for strychnine-induced seizures and myoclonus in the 3AP-inferior olive-lesioned rats may be due to an increase in glutamate receptors as suggested by the [ 3 H]AMPA binding data

MRI in patients with temporal lobe epilepsy

International Nuclear Information System (INIS)

Kodama, Kazuhiro

1992-01-01

The present study investigated magnetic resonance imaging (MRI) features in temporal lobe epilepsy and correlated them with clinical variables, such as age, illness duration, past history, and the frequency of seizure. Cerebral MRI was performed in 45 patients with temporal lobe epilepsy of unknown etiology, using a 0.5 T and/or a 1.5 T MRI systems. The temporal lobe was seen as high signal intensity on T2-weighted images and/or proton density-weighted images in 6 patients, although it was missed on CT and T1-weighted images. The high intensity area seemed to reflect sclerosis of the temporal lobe. This finding was significantly associated with partial seizure. Of these patients, 3 had a history of febrile convulsions. Ten patients had slight dilatation of the inferior horn of the lateral ventricle. They were significantly old at the time of onset and examination, as compared with those without dilatation. Furthermore, 6 patients with unilateral dilatation were significantly younger than the other 4 with bilateral dilatation. Nine patients had small multiple high signal areas in white matter, mainly in the parietal lobe, which suggested vascular origin. These patients were significantly old at the time of onset and examination, as compared with those having no such findings. In depicting high signal intensity areas, a 1.5 T MRI system was not always superior to a 0.5 T MRI system. Proton density-weighted images were better than T2-weighted images in some patients. (N.K.)

Evaluation of the kappa-opioid receptor-selective tracer [11C]GR103545 in awake rhesus macaques

International Nuclear Information System (INIS)

Schoultz, Bent W.; Hjornevik, Trine; Willoch, Frode; Marton, Janos; Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro; Aarstad, Erik; Drzezga, Alexander; Matsunari, Ichiro; Henriksen, Gjermund

2010-01-01

The recent development in radiosynthesis of the 11 C-carbamate function increases the potential of [ 11 C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor (κ-OR) with PET. In the present study, [ 11 C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. Regional brain uptake kinetics of [ 11 C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [ 11 C]GR103545 was determined in cells transfected with cloned human opioid receptors. In vitro binding assays demonstrated a high affinity of GR103545 for κ-OR (K i = 0.02 ±0.01 nM) with excellent selectivity over μ-OR (6 x 10 2 -fold) and δ-OR (2 x 10 4 -fold). PET imaging revealed a volume of distribution (V T ) pattern consistent with the known distribution of κ-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. [ 11 C]GR103545 is selective for κ-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET. (orig.)

Connections of the medial posterior parietal cortex (area 7m) in the monkey.

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Leichnetz, G R

2001-06-01

The afferent and efferent cortical and subcortical connections of the medial posterior parietal cortex (area 7m) were studied in cebus (Cebus apella) and macaque (Macaca fascicularis) monkeys using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique. The principal intraparietal corticocortical connections of area 7m in both cebus and macaque cases were with the ipsilateral medial bank of the intraparietal sulcus (MIP) and adjacent superior parietal lobule (area 5), inferior parietal lobule (area 7a), lateral bank of the IPS (area 7ip), caudal parietal operculum (PGop), dorsal bank of the caudal superior temporal sulcus (visual area MST), and medial prestriate cortex (including visual area PO and caudal medial lobule). Its principal frontal corticocortical connections were with the prefrontal cortex in the shoulder above the principal sulcus and the cortex in the shoulder above the superior ramus of the arcuate sulcus (SAS), the area purported to contain the smooth eye movement-related frontal eye field (FEFsem) in the cebus monkey by other investigators. There were moderate connections with the cortex in the rostral bank of the arcuate sulcus (purported to contain the saccade-related frontal eye field; FEFsac), supplementary eye field (SEF), and rostral dorsal premotor area (PMDr). Area 7m also had major connections with the cingulate cortex (area 23), particularly the ventral bank of the cingulate sulcus. The principal subcortical connections of area 7m were with the dorsal portion of the ventrolateral thalamic (VLc) nucleus, lateral posterior thalamic nucleus, lateral pulvinar, caudal mediodorsal thalamic nucleus and medial pulvinar, central lateral, central superior lateral, and central inferior intralaminar thalamic nuclei, dorsolateral caudate nucleus and putamen, middle region of the claustrum, nucleus of the diagonal band, zona incerta, pregeniculate nucleus, anterior and posterior pretectal nuclei, intermediate layer of

Identification of a Novel Enterovirus Species in Rhesus Macaque in China.

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Ao, Yuan-Yun; Yu, Jie-Mei; Zhang, Cui-Yuan; Xin, Yun-Yun; Li, Li-Li; Duan, Zhao-Jun

2016-06-22

Recent studies of Enterovirus (EV) in nonhuman primates (NHPs), which could act as a source of future emerging human viral diseases, have boosted interest in the search for novel EVs. Here, a highly divergent strain of EV, tentatively named SEV-gx, was identified by viral metagenomic analysis from stool samples of rhesus macaques in China. In total, 27 of 280 (9.6%) faecal samples from rhesus macaques were positive for SEV-gx. Its complete genomic sequence is 7,367 nucleotide (nt). Genomic analyses showed that it has a standard genomic organisation for EVs, being more closely related to EV-J strains (approximately 54.0%, 43.0-44.1%, 52.3-55.2%, 61.1-62.7% and 64.0% amino acids identity in polyprotein, P1, P2 and P3 and combined 2C/3CD regions, respectively). It was also shown to have genome characteristics typical of EVs. Phylogenetic analysis of P1, 2C and 3CD aa indicated that SEV-gx can be classified as a distinct cluster in the EVs. All of this evidence demonstrates SEV-gx is a novel species (tentatively named EV-K) in the EV genus, which contributes to our understanding of the genetic diversity and evolution of EVs. Further studies are needed to investigate the potential pathogenicity of SEV-gx in NHPs and humans.

Opioid modulation of GABA release in the rat inferior colliculus

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Forge Andrew

2004-09-01

Full Text Available Abstract Background The inferior colliculus, which receives almost all ascending and descending auditory signals, plays a crucial role in the processing of auditory information. While the majority of the recorded activities in the inferior colliculus are attributed to GABAergic and glutamatergic signalling, other neurotransmitter systems are expressed in this brain area including opiate peptides and their receptors which may play a modulatory role in neuronal communication. Results Using a perfusion protocol we demonstrate that morphine can inhibit KCl-induced release of [3H]GABA from rat inferior colliculus slices. DAMGO ([D-Ala(2, N-Me-Phe(4, Gly(5-ol]-enkephalin but not DADLE ([D-Ala2, D-Leu5]-enkephalin or U69593 has the same effect as morphine indicating that μ rather than δ or κ opioid receptors mediate this action. [3H]GABA release was diminished by 16%, and this was not altered by the protein kinase C inhibitor bisindolylmaleimide I. Immunostaining of inferior colliculus cryosections shows extensive staining for glutamic acid decarboxylase, more limited staining for μ opiate receptors and relatively few neurons co-stained for both proteins. Conclusion The results suggest that μ-opioid receptor ligands can modify neurotransmitter release in a sub population of GABAergic neurons of the inferior colliculus. This could have important physiological implications in the processing of hearing information and/or other functions attributed to the inferior colliculus such as audiogenic seizures and aversive behaviour.

Opioid modulation of GABA release in the rat inferior colliculus

Science.gov (United States)

Tongjaroenbungam, Walaiporn; Jongkamonwiwat, Nopporn; Cunningham, Joanna; Phansuwan-Pujito, Pansiri; Dodson, Hilary C; Forge, Andrew; Govitrapong, Piyarat; Casalotti, Stefano O

2004-01-01

Background The inferior colliculus, which receives almost all ascending and descending auditory signals, plays a crucial role in the processing of auditory information. While the majority of the recorded activities in the inferior colliculus are attributed to GABAergic and glutamatergic signalling, other neurotransmitter systems are expressed in this brain area including opiate peptides and their receptors which may play a modulatory role in neuronal communication. Results Using a perfusion protocol we demonstrate that morphine can inhibit KCl-induced release of [3H]GABA from rat inferior colliculus slices. DAMGO ([D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin) but not DADLE ([D-Ala2, D-Leu5]-enkephalin or U69593 has the same effect as morphine indicating that μ rather than δ or κ opioid receptors mediate this action. [3H]GABA release was diminished by 16%, and this was not altered by the protein kinase C inhibitor bisindolylmaleimide I. Immunostaining of inferior colliculus cryosections shows extensive staining for glutamic acid decarboxylase, more limited staining for μ opiate receptors and relatively few neurons co-stained for both proteins. Conclusion The results suggest that μ-opioid receptor ligands can modify neurotransmitter release in a sub population of GABAergic neurons of the inferior colliculus. This could have important physiological implications in the processing of hearing information and/or other functions attributed to the inferior colliculus such as audiogenic seizures and aversive behaviour. PMID:15353008

A basic review on the inferior alveolar nerve block techniques.

Science.gov (United States)

Khalil, Hesham

2014-01-01

The inferior alveolar nerve block is the most common injection technique used in dentistry and many modifications of the conventional nerve block have been recently described in the literature. Selecting the best technique by the dentist or surgeon depends on many factors including the success rate and complications related to the selected technique. Dentists should be aware of the available current modifications of the inferior alveolar nerve block techniques in order to effectively choose between these modifications. Some operators may encounter difficulty in identifying the anatomical landmarks which are useful in applying the inferior alveolar nerve block and rely instead on assumptions as to where the needle should be positioned. Such assumptions can lead to failure and the failure rate of inferior alveolar nerve block has been reported to be 20-25% which is considered very high. In this basic review, the anatomical details of the inferior alveolar nerve will be given together with a description of its both conventional and modified blocking techniques; in addition, an overview of the complications which may result from the application of this important technique will be mentioned.

Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

Directory of Open Access Journals (Sweden)

Chie Sugimoto

Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

Intermittent pair-housing, pair relationship qualities, and HPA activity in adult female rhesus macaques.

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Hannibal, Darcy L; Cassidy, Lauren C; Vandeleest, Jessica; Semple, Stuart; Barnard, Allison; Chun, Katie; Winkler, Sasha; McCowan, Brenda

2018-05-02

Laboratory rhesus macaques are often housed in pairs and may be temporarily or permanently separated for research, health, or management reasons. While both long-term social separations and introductions can stimulate a stress response that impacts inflammation and immune function, the effects of short-term overnight separations and whether qualities of the pair relationship mediate these effects are unknown. In this study, we investigated the effects of overnight separations on the urinary cortisol concentration of 20 differentially paired adult female rhesus macaques (Macaca mulatta) at the California National Primate Research Center. These females were initially kept in either continuous (no overnight separation) or intermittent (with overnight separation) pair-housing and then switched to the alternate pair-housing condition part way through the study. Each study subject was observed for 5 weeks, during which we collected measures of affiliative, aggressive, anxious, abnormal, and activity-state behaviors in both pair-housing conditions. Additionally, up to three urine samples were collected from each subject per week and assayed for urinary free cortisol and creatinine. Lastly, the behavioral observer scored each pair on four relationship quality attributes ("Anxious," "Tense," "Well-meshed," and "Friendly") using a seven-point scale. Data were analyzed using a generalized linear model with gamma distribution and an information theoretic approach to determine the best model set. An interaction between the intermittent pairing condition and tense pair adjective rating was in the top three models of the best model set. Dominance and rates of affiliation were also important for explaining urinary cortisol variation. Our results suggest that to prevent significant changes in HPA-axis activation in rhesus macaque females, which could have unintended effects on research outcomes, pairs with "Tense" relationships and overnight separations preventing tactile contact

Symplastic Leiomyoma in the Suprarenal Inferior Vena Cava

International Nuclear Information System (INIS)

Kahveci, Volkan; Ogur, Torel; Cipe, Gokhan; Ozdemir, Sevim; Hazinedaroglu, Selcuk

2012-01-01

Leiomyomas are benign tumors of the soft tissue and may develop in any location where smooth muscle is present. Leiomyoma in the inferior vena cava is a rarely seen pathology, and symplastic leiomyoma is also a rare histological variant of leiomyoma. In this case, we present a rare histological variant of symplastic leiomyoma in the inferior vena cava (IVC). This is the first radiologically reported case of a symplastic leiomyoma of the IVC

Computed tomography or necropsy diagnosis of multiple bullae and the treatment of pneumothorax in rhesus macaques (Macaca mulatta).

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Kim, Jong-Min; Han, Sungyoung; Shin, Jun-Seop; Min, Byoung-Hoon; Jeong, Won Young; Lee, Ga Eul; Kim, Min Sun; Kim, Ju Eun; Chung, Hyunwoo; Park, Chung-Gyu

2017-10-01

Pulmonary bullae and pneumothorax have various etiologies in veterinary medicine. We diagnosed multiple pulmonary bullae combined with or without pneumothorax by computed tomography (CT) or necropsy in seven rhesus macaques (Macaca mulatta) imported from China. Two of seven rhesus macaques accompanied by pneumothorax were cured by fixation of ruptured lung through left or right 3rd intercostal thoracotomy. Pneumonyssus simicola, one of the etiologies of pulmonary bullae, was not detected from tracheobronchiolar lavage. To the best of our knowledge, this is the first case report on the CT-aided diagnosis of pulmonary bullae and the successful treatment of combined pneumothorax by thoracotomy in non-human primates (NHPs). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Abstract Linguistic Structure Correlates with Temporal Activity during Naturalistic Comprehension

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Brennan, Jonathan R.; Stabler, Edward P.; Van Wagenen, Sarah E.; Luh, Wen-Ming; Hale, John T.

2016-01-01

Neurolinguistic accounts of sentence comprehension identify a network of relevant brain regions, but do not detail the information flowing through them. We investigate syntactic information. Does brain activity implicate a computation over hierarchical grammars or does it simply reflect linear order, as in a Markov chain? To address this question, we quantify the cognitive states implied by alternative parsing models. We compare processing-complexity predictions from these states against fMRI timecourses from regions that have been implicated in sentence comprehension. We find that hierarchical grammars independently predict timecourses from left anterior and posterior temporal lobe. Markov models are predictive in these regions and across a broader network that includes the inferior frontal gyrus. These results suggest that while linear effects are wide-spread across the language network, certain areas in the left temporal lobe deal with abstract, hierarchical syntactic representations. PMID:27208858

Human amnesia and the medial temporal lobe illuminated by neuropsychological and neurohistological findings for patient E.P.

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Insausti, Ricardo; Annese, Jacopo; Amaral, David G.; Squire, Larry R.

2013-01-01

We present neurohistological information for a case of bilateral, symmetrical damage to the medial temporal lobe and well-documented memory impairment. E.P. developed profound memory impairment at age 70 y and then was studied for 14 y He had no capacity for learning facts and events and had retrograde amnesia covering several decades. He also had a modest impairment of semantic knowledge. Neurohistological analysis revealed bilaterally symmetrical lesions of the medial temporal lobe that eliminated the temporal pole, the amygdala, the entorhinal cortex, the hippocampus, the perirhinal cortex, and rostral parahippocampal cortex. The lesion also extended laterally to involve the fusiform gyrus substantially. Last, the superior, inferior, and middle temporal gyri were atrophic, and subjacent white matter was gliotic. Several considerations indicate that E.P.’s severe memory impairment was caused by his medial temporal lesions, whereas his impaired semantic knowledge was caused by lateral temporal damage. His lateral temporal damage also may have contributed to his extensive retrograde amnesia. The findings illuminate the anatomical relationship between memory, perception, and semantic knowledge. PMID:23620517

Rhesus macaques form preferences for brand logos through sex and social status based advertising.

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Acikalin, M Yavuz; Watson, Karli K; Fitzsimons, Gavan J; Platt, Michael L

2018-01-01

Like humans, monkeys value information about sex and status, inviting the hypothesis that our susceptibility to these factors in advertising arises from shared, ancestral biological mechanisms that prioritize social information. To test this idea, we asked whether rhesus macaques (Macaca mulatta) show choice behavior that is similar to humans in response to sex and social status in advertising. Our results show that monkeys form preferences for brand logos repeatedly paired with images of macaque genitals and high status monkeys. Moreover, monkeys sustain preferences for these brand logos even though choosing them provided no tangible rewards, a finding that cannot be explained by a decision mechanism operating solely on material outcomes. Together, our results endorse the hypothesis that the power of sex and status in advertising emerges from the spontaneous engagement of shared, ancestral neural circuits that prioritize information useful for navigating the social environment. Finally, our results show that simple associative conditioning is sufficient to explain the formation of preferences for brand logos paired with sexual or status-based images.

An experimental examination of female responses to infant face coloration in rhesus macaques.

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Gerald, Melissa S; Waitt, Corri; Maestripieri, Dario

2006-11-01

In many primates, infants possess distinctive coloration that changes as a function of age. This colour is thought to serve the purpose of eliciting caretaking behaviour from the mother as well as other conspecifics. The present study investigated the responses of adult female rhesus macaques (Macaca mulatta) to pictures of infant faces in relation to infant age and facial coloration. Study animals were shown digitized images of neonates and 5-6-month-old infants displaying either unaltered facial colour, pink neonatal colour, or novel (green) facial colour. While infant and neonate faces of all colours elicited the attention of adult females, pink neonatal facial coloration did not appear to be especially attractive to subjects in contrast with the findings from an earlier study [Higley, J.D., Hopkins, W.D., Hirsch, R.M. Marra, L.M. Suomi S.J., 1987. Preferences of female rhesus monkeys (Macaca mulatta) for infantile coloration. Dev. Psychobiol. 20, 7-18]. The results suggest that infant facial colour is not particularly important in mediating infant attractiveness to rhesus macaque females as previously suggested or that other infantile facial characteristics might be more important than colour in eliciting caretaking behaviours amongst females.

Safety study of the Bio-10-SAD Bern strain of the rabies virus on the rhesus macaque monkey species

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Vladimír Vrzal

2013-01-01

Full Text Available Based on a WHO recommendation, residual pathogenicity of the Bio-10-SAD Bern rabies virus strain (component of the Lysvulpen por. ad us. vet. vaccine was tested on rhesus macaque monkeys. Each of the ten monkeys, females, two years old, was administered orally 2 ml × 109 TCID50 of the Bio-10-SAD Bern rabies strain. The animals were monitored for 90 days. Subsequently, the animals were sacrificed and their brains were examined for presence of the vaccination rabies virus by the immunofluorescence and PCR methods. The occurrence of anti-rabies antibodies prior to and following administration of the vaccination rabies virus was also evaluated. No clinical signs of rabies were observed nor did any of the animals die of rabies following application of the virus. No rabies was detected in the study animals by post mortem examination. All of the 10 animals developed anti-rabies antibodies during the 90 days following administration of the rabies virus. It can be concluded, that Bio-10-SAD Bern virus administered at a dose equal to the tenfold maximum dose specified for field uses is safe to monkeys of the rhesus macaque species. This study is the first of its type performed in rhesus macaque monkey species.

Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

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Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

2015-12-01

Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues. © FASEB.

Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography

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Koller, Kristin; Bultitude, Janet H.; Mullins, Paul; Ward, Robert; Mitchell, Anna S.; Bell, Andrew H.

2015-01-01

It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species. PMID:26224780

Asian Elephant (Elephas maximus), Pig-Tailed Macaque (Macaca nemestrina) and Tiger (Panthera tigris) Populations at Tourism Venues in Thailand and Aspects of Their Welfare

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Schmidt-Burbach, Jan; Ronfot, Delphine; Srisangiam, Rossukon

2015-01-01

This study focused on determining the size and welfare aspects of Asian elephant, pig-tailed macaque and tiger populations at facilities open to tourists in Thailand. Data were gathered from 118 venues through direct observations and interviews with staff. A score sheet-based welfare assessment was used to calculate scores between 1 and 10, indicating each venue’s welfare situation. Factors such as freedom of movement for the animals, access to veterinary care, environmental noise quality, hygiene standards and work intensity were included in the score sheet. 1688 elephants, 371 macaques and 621 tigers were found at the venues. 89 venues exclusively kept elephants, 9 designated ‘Monkey schools’ offered macaque shows, 4 venues kept primarily tigers, mostly for petting and photo opportunities, and the remaining venues kept a mix of these animals. A strong imbalance in female to male gender ratios was recorded with about 4:1 for adult elephants and 1:4 for adult macaques. Severely inadequate welfare conditions were common, with 75% of macaques and 99% of tigers being kept at venues with scores less than 5. 86% of elephants were kept in inadequate conditions at venues with scores between 3 and 5, but a significant number of venues with scores above 5 were found. 4.6% of elephants were provided commendable conditions, reaching assessment scores of 8 and above. 71% of venues did not offer any sort of education about animals to visitors. This study is the first to assess welfare aspects of captive wild animals at tourism venues across Thailand. It concludes that significant concerns exist about the welfare of wild animals in the tourism sector of Thailand. Urgent attention needs to be given to address these concerns and prevent further suffering. But also to ensure the demand for wild animals doesn’t have a negative impact on wild populations. PMID:26407173

Asian Elephant (Elephas maximus, Pig-Tailed Macaque (Macaca nemestrina and Tiger (Panthera tigris Populations at Tourism Venues in Thailand and Aspects of Their Welfare.

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Jan Schmidt-Burbach

Full Text Available This study focused on determining the size and welfare aspects of Asian elephant, pig-tailed macaque and tiger populations at facilities open to tourists in Thailand. Data were gathered from 118 venues through direct observations and interviews with staff. A score sheet-based welfare assessment was used to calculate scores between 1 and 10, indicating each venue's welfare situation. Factors such as freedom of movement for the animals, access to veterinary care, environmental noise quality, hygiene standards and work intensity were included in the score sheet. 1688 elephants, 371 macaques and 621 tigers were found at the venues. 89 venues exclusively kept elephants, 9 designated 'Monkey schools' offered macaque shows, 4 venues kept primarily tigers, mostly for petting and photo opportunities, and the remaining venues kept a mix of these animals. A strong imbalance in female to male gender ratios was recorded with about 4:1 for adult elephants and 1:4 for adult macaques. Severely inadequate welfare conditions were common, with 75% of macaques and 99% of tigers being kept at venues with scores less than 5. 86% of elephants were kept in inadequate conditions at venues with scores between 3 and 5, but a significant number of venues with scores above 5 were found. 4.6% of elephants were provided commendable conditions, reaching assessment scores of 8 and above. 71% of venues did not offer any sort of education about animals to visitors. This study is the first to assess welfare aspects of captive wild animals at tourism venues across Thailand. It concludes that significant concerns exist about the welfare of wild animals in the tourism sector of Thailand. Urgent attention needs to be given to address these concerns and prevent further suffering. But also to ensure the demand for wild animals doesn't have a negative impact on wild populations.

Asian Elephant (Elephas maximus), Pig-Tailed Macaque (Macaca nemestrina) and Tiger (Panthera tigris) Populations at Tourism Venues in Thailand and Aspects of Their Welfare.

Science.gov (United States)

Schmidt-Burbach, Jan; Ronfot, Delphine; Srisangiam, Rossukon

2015-01-01

This study focused on determining the size and welfare aspects of Asian elephant, pig-tailed macaque and tiger populations at facilities open to tourists in Thailand. Data were gathered from 118 venues through direct observations and interviews with staff. A score sheet-based welfare assessment was used to calculate scores between 1 and 10, indicating each venue's welfare situation. Factors such as freedom of movement for the animals, access to veterinary care, environmental noise quality, hygiene standards and work intensity were included in the score sheet. 1688 elephants, 371 macaques and 621 tigers were found at the venues. 89 venues exclusively kept elephants, 9 designated 'Monkey schools' offered macaque shows, 4 venues kept primarily tigers, mostly for petting and photo opportunities, and the remaining venues kept a mix of these animals. A strong imbalance in female to male gender ratios was recorded with about 4:1 for adult elephants and 1:4 for adult macaques. Severely inadequate welfare conditions were common, with 75% of macaques and 99% of tigers being kept at venues with scores less than 5. 86% of elephants were kept in inadequate conditions at venues with scores between 3 and 5, but a significant number of venues with scores above 5 were found. 4.6% of elephants were provided commendable conditions, reaching assessment scores of 8 and above. 71% of venues did not offer any sort of education about animals to visitors. This study is the first to assess welfare aspects of captive wild animals at tourism venues across Thailand. It concludes that significant concerns exist about the welfare of wild animals in the tourism sector of Thailand. Urgent attention needs to be given to address these concerns and prevent further suffering. But also to ensure the demand for wild animals doesn't have a negative impact on wild populations.

Exploring the spatio-temporal neural basis of face learning

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Yang, Ying; Xu, Yang; Jew, Carol A.; Pyles, John A.; Kass, Robert E.; Tarr, Michael J.

2017-01-01

Humans are experts at face individuation. Although previous work has identified a network of face-sensitive regions and some of the temporal signatures of face processing, as yet, we do not have a clear understanding of how such face-sensitive regions support learning at different time points. To study the joint spatio-temporal neural basis of face learning, we trained subjects to categorize two groups of novel faces and recorded their neural responses using magnetoencephalography (MEG) throughout learning. A regression analysis of neural responses in face-sensitive regions against behavioral learning curves revealed significant correlations with learning in the majority of the face-sensitive regions in the face network, mostly between 150–250 ms, but also after 300 ms. However, the effect was smaller in nonventral regions (within the superior temporal areas and prefrontal cortex) than that in the ventral regions (within the inferior occipital gyri (IOG), midfusiform gyri (mFUS) and anterior temporal lobes). A multivariate discriminant analysis also revealed that IOG and mFUS, which showed strong correlation effects with learning, exhibited significant discriminability between the two face categories at different time points both between 150–250 ms and after 300 ms. In contrast, the nonventral face-sensitive regions, where correlation effects with learning were smaller, did exhibit some significant discriminability, but mainly after 300 ms. In sum, our findings indicate that early and recurring temporal components arising from ventral face-sensitive regions are critically involved in learning new faces. PMID:28570739

Symptomatic duodenal perforation by inferior vena cava filter.

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Baptista Sincos, Anna Pw; Sincos, Igor R; Labropoulos, Nicos; Donegá, Bruno C; Klepacz, Andrea; Aun, Ricardo

2017-01-01

Objectives Duodenal perforation by an inferior vena cava filter is rare and life threatening. Our objective is to find out number of occurrences and compare diagnosis and treatments. Method The reference list of Malgor's review in 2012 was considered as well as all new articles with eligible features. Search was conducted on specific databases: MEDLINE, Web of Sciences, and Literatura Latino-Americana e do Caribe em Ciências da Saúde. Results Most of the patients presented with upper abdominal pain and the use of radiologic studies was crucial for diagnosis. The most common treatment was laparotomy with filter or strut removal plus duodenum repair. However, clinical conditions of patients must be considered and the endovascular technique with endograft deployment into inferior vena cava may be an alternative. Conclusion Duodenal perforation by an inferior vena cava filter is uncommon and in high-risk surgical patients endovascular repair must be considered.

Male rhesus macaques use vocalizations to distinguish female maternal, but not paternal, kin from non-kin.

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Pfefferle, Dana; Ruiz-Lambides, Angelina V; Widdig, Anja

Recognizing close kin and adjusting one's behavior accordingly (i.e., favor kin in social interactions, but avoid mating with them) would be an important skill that can increase an animals' inclusive fitness. Previous studies showed that philopatric female rhesus macaques ( Macaca mulatta ) bias their social behavior toward maternal and paternal kin. Benefits gained from selecting kin should, however, not only apply to the philopatric sex, for which the enduring spatial proximity facilitates kin discrimination. Given that dispersal is costly, the dispersing sex may benefit from migrating together with their kin or into groups containing kin. In male rhesus macaques, natal migrants bias their spatial proximity toward familiar male kin rather than familiar non-kin. Here, we set up playback experiments to test if males use the acoustic modality to discriminate familiar female kin from non-kin in a non-sexual context. Males responded differently to the presentation of "coo" calls of related and unrelated females, with their reaction depending on the interaction between kin-line (maternal vs paternal kin) and degree of relatedness ( r  = 0.5, 0.25). Specifically, males were more likely to respond to close kin compared to more distant kin or unrelated females, with this effect being significant in the maternal, but not paternal kin-line. The present study adds to our knowledge of kin recognition abilities of the dispersing sex, suggesting that male rhesus macaques are also able to identify kin using the acoustic modality. We discuss that the probability of response might be affected by the potential benefit of the social partner.

Roles of frontal and temporal regions in reinterpreting semantically ambiguous sentences

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Sylvia eVitello

2014-07-01

Full Text Available Semantic ambiguity resolution is an essential and frequent part of speech comprehension because many words map onto multiple meanings (e.g., bark, bank. Neuroimaging research highlights the importance of the left inferior frontal gyrus (LIFG and the left posterior temporal cortex in this process but the roles they serve in ambiguity resolution are uncertain. One possibility is that both regions are engaged in the processes of semantic reinterpretation that follows incorrect interpretation of an ambiguous word. Here we used fMRI to investigate this hypothesis. 20 native British English monolinguals were scanned whilst listening to sentences that contained an ambiguous word. To induce semantic reinterpretation, the disambiguating information was presented after the ambiguous word and delayed until the end of the sentence (e.g., the teacher explained that the BARK was going to be very damp. These sentences were compared to well-matched unambiguous sentences. Supporting the reinterpretation hypothesis, these ambiguous sentences produced more activation in both the LIFG and the left posterior inferior temporal cortex. Importantly, all but one subject showed ambiguity-related peaks within both regions, demonstrating that the group-level results were driven by high inter-subject consistency. Further support came from the finding that activation in both regions was modulated by meaning dominance. Specifically, sentences containing biased ambiguous words, which have one more dominant meaning, produced greater activation than those with balanced ambiguous words, which have two equally frequent meanings. Because the context always supported the less frequent meaning, the biased words require reinterpretation more often than balanced words. This is the first evidence of dominance effects in the spoken modality and provides strong support that frontal and temporal regions support the updating of semantic representations during speech comprehension.

Dynamic adjustments in prefrontal, hippocampal, and inferior temporal interactions with increasing visual working memory load.

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Rissman, Jesse; Gazzaley, Adam; D'Esposito, Mark

2008-07-01

The maintenance of visual stimuli across a delay interval in working memory tasks is thought to involve reverberant neural communication between the prefrontal cortex and posterior visual association areas. Recent studies suggest that the hippocampus might also contribute to this retention process, presumably via reciprocal interactions with visual regions. To characterize the nature of these interactions, we performed functional connectivity analysis on an event-related functional magnetic resonance imaging data set in which participants performed a delayed face recognition task. As the number of faces that participants were required to remember was parametrically increased, the right inferior frontal gyrus (IFG) showed a linearly decreasing degree of functional connectivity with the fusiform face area (FFA) during the delay period. In contrast, the hippocampus linearly increased its delay period connectivity with both the FFA and the IFG as the mnemonic load increased. Moreover, the degree to which participants' FFA showed a load-dependent increase in its connectivity with the hippocampus predicted the degree to which its connectivity with the IFG decreased with load. Thus, these neural circuits may dynamically trade off to accommodate the particular mnemonic demands of the task, with IFG-FFA interactions mediating maintenance at lower loads and hippocampal interactions supporting retention at higher loads.

The development of an instrument to measure global dimensions of maternal care in rhesus macaques (Macaca mulatta).

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McCormack, K; Howell, B R; Guzman, D; Villongco, C; Pears, K; Kim, H; Gunnar, M R; Sanchez, M M

2015-01-01

One of the strongest predictors of healthy child development is the quality of maternal care. Although many measures of observation and self-report exist in humans to assess global aspects of maternal care, such qualitative measures are lacking in nonhuman primates. In this study, we developed an instrument to measure global aspects of maternal care in rhesus monkeys, with the goal of complementing the individual behavioral data collected using a well-established rhesus macaque ethogram during the first months postpartum. The 22 items of the instrument were adapted from human maternal sensitivity assessments and a maternal Q-sort instrument already published for macaques. The 22 items formed four dimensions with high levels of internal reliability that represented major constructs of maternal care: (1) Sensitivity/Responsivity, (2) Protectiveness, (3) Permissiveness, and (4) Irritability. These dimensions yielded high construct validity when correlated with mother-infant frequency and duration behavior that was collected from focal observations across the first 3 postnatal months. In addition, comparisons of two groups of mothers (Maltreating vs. Competent mothers) showed significant differences across the dimensions suggesting that this instrument has strong concurrent validity, even after controlling for focal observation variables that have been previously shown to significantly differentiate these groups. Our findings suggest that this Instrument of Macaque Maternal Care has the potential to capture global aspects of the mother-infant relationship that complement individual behaviors collected through focal observations. © 2014 Wiley Periodicals, Inc.

The Development of an Instrument to Measure Global Dimensions of Maternal Care in Rhesus Macaques (Macaca mulatta)

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McCormack, K.; Howell, B. R.; Guzman, D.; Villongco, C.; Pears, K.; Kim, H.; Gunnar, M.R.; Sanchez, M.M.

2014-01-01

One of the strongest predictors of healthy child development is the quality of maternal care. Although many measures of observation and self-report exist in humans to assess global aspects of maternal care, such qualitative measures are lacking in nonhuman primates. In this study we developed an instrument to measure global aspects of maternal care in rhesus monkeys, with the goal of complementing the individual behavioral data collected using a well-established rhesus macaque ethogram during the first months postpartum. The 22 items of the instrument were adapted from human maternal sensitivity assessments and a maternal Q-sort instrument already published for macaques. The 22 items formed four dimensions with high levels of internal reliability that represented major constructs of maternal care: 1) Sensitivity/Responsivity, 2) Protectiveness, 3) Permissiveness, and 4) Irritability. These dimensions yielded high construct validity when correlated with mother-infant frequency and duration behavior that was collected from focal observations across the first three postnatal months. In addition, comparisons of two groups of mothers (Maltreating versus Competent mothers), showed significant differences across the dimensions suggesting that this instrument has strong concurrent validity, even after controlling for focal observation variables that have been previously shown to significantly differentiate these groups. Our findings suggest that this Instrument of Macaque Maternal Care (IMMC) has the potential to capture global aspects of the mother-infant relationship that complement individual behaviors collected through focal observations. PMID:25066041

Primary research on direct multi-slice spiral CT venography in inferior vena cava

International Nuclear Information System (INIS)

Gong Peiyou; Liu Fengli; Ma Xianying; Zhao Li; Wang Liping; Li Xuehua; Li Jian

2010-01-01

Objective: To investigate the superiority of direct multi-slice spiral CT venography in inferior vena cava. Methods: Twenty-eight patients performed MSCT venography in inferior vena cava, including 2 cases with both indirect and direct venography, 10 cases with indirect venography, 20 cases with direct venography through unilateral or bilateral lower extremity venous injection. The image quality and enhancement degree of the inferior vena cava were compared in double-blind method. Results: Of 10 cases with indirect venography of inferior vena cava, 1 case was failed due to mild enhancement in inferior vena cava. Image quality was good in 2 cases, poor in 7 cases, no excellent case. Of 20 cases with direct venography of inferior vena cava, the enhancement degree was scored 1, 2 degree in 16, 4 cases respectively and no case was scored 3 degree, the image quality was excellent, good in 16, 4 cases and no case was bad. The success rate was 100%. Conclusion: The image quality of direct MSCT venography in inferior vena cava is better than that of indirect method. (authors)

Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques.

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Viraj Kulkarni

Full Text Available HIV sequence diversity and potential decoy epitopes are hurdles in the development of an effective AIDS vaccine. A DNA vaccine candidate comprising of highly conserved p24(gag elements (CE induced robust immunity in all 10 vaccinated macaques, whereas full-length gag DNA vaccination elicited responses to these conserved elements in only 5 of 11 animals, targeting fewer CE per animal. Importantly, boosting CE-primed macaques with DNA expressing full-length p55(gag increased both magnitude of CE responses and breadth of Gag immunity, demonstrating alteration of the hierarchy of epitope recognition in the presence of pre-existing CE-specific responses. Inclusion of a conserved element immunogen provides a novel and effective strategy to broaden responses against highly diverse pathogens by avoiding decoy epitopes, while focusing responses to critical viral elements for which few escape pathways exist.

Emotional states after grooming interactions in Japanese macaques (Macaca fuscata).

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Ueno, Masataka; Yamada, Kazunori; Nakamichi, Masayuki

2015-11-01

In animal societies, the effect of grooming interactions on anxiety reduction is unclear. This study examined the effects of giving and receiving grooming on anxiety reduction in free ranging female Japanese macaques (Macaca fuscata) by measuring rates of self-scratching as an index of anxiety. In this study, the authors used a focal-animal sampling method, targeting 17 females at Katsuyama, Okayama prefecture, Japan. They evaluated affiliative relationships, which were defined by standard proximity rates, and found that females' self-scratching rates were lower after grooming affiliated partners than during matched-control periods (occurring on another day, beginning at approximately the same time of day as the corresponding postgrooming period) and not after grooming unaffiliated partners. Moreover, regardless of affiliative relationships, self-scratching rates were lower after receiving grooming than during matched-control periods. These findings did not change after excluding data in which groomer and groomee were in proximity after the grooming interaction. In addition, multivariable analysis showed that affiliative relationships, but not kinship or rank distances, were related to differences in the rates of self-scratching between giving grooming and matched-control periods. In contrast, neither affiliative relationships nor kinship nor rank distances affected differences in self-scratching rates between receiving grooming and matched-control periods. Therefore, individuals' anxiety levels decreased both after giving grooming to affiliated partners and after receiving grooming, regardless of affiliative relationships. This is the first empirical study to support the notion that giving grooming to affiliated partners is self-rewarding in Japanese macaques. (c) 2015 APA, all rights reserved).

Implante de filtro em veia cava inferior dupla: relato de caso e revisão da literatura Filter placement in duplicated inferior vena cava: case report and review of the literature

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Rafael Demarchi Malgor

2008-06-01

Full Text Available Veia cava inferior dupla é uma variação anatômica rara cuja prevalência é de 0,2-3%. O implante de filtro de veia cava, quando indicado em casos com duplicidade da veia cava inferior, pode ser realizado de diferentes formas: em ambas as veias cavas; em uma delas, embolizando a anastomose entre ambas; em somente uma delas; ou por implante supra-renal. Relatamos um caso de trombose venosa profunda no pós-operatório de implante de prótese de quadril com contra-indicação para tratamento anticoagulante e cuja cavografia evidenciou duplicidade de veia cava inferior. O implante de filtro de veia cava inferior realizado em posição supra-renal mostrou-se opção adequada e segura.Double inferior vena cava is a rare anatomic variation with prevalence ranging between 0.2-3.0%. In cases of duplication, inferior vena cava filter placement options include placing it in both vena cava, coil-embolization of the intervenous segment plus placing a filter in the right inferior vena cava, or suprarenal filter placement. We report a case of deep venous thrombosis after unilateral primary total hip replacement, presenting with contraindications for anticoagulant therapy, in which cavography showed inferior vena cava duplication. Inferior vena cava filter placement was performed in the supra-renal portion and was proved to be an adequate and safe procedure.

In vivo bone strain and finite element modeling of a rhesus macaque mandible during mastication.

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Panagiotopoulou, Olga; Iriarte-Diaz, José; Wilshin, Simon; Dechow, Paul C; Taylor, Andrea B; Mehari Abraha, Hyab; Aljunid, Sharifah F; Ross, Callum F

2017-10-01

Finite element analysis (FEA) is a commonly used tool in musculoskeletal biomechanics and vertebrate paleontology. The accuracy and precision of finite element models (FEMs) are reliant on accurate data on bone geometry, muscle forces, boundary conditions and tissue material properties. Simplified modeling assumptions, due to lack of in vivo experimental data on material properties and muscle activation patterns, may introduce analytical errors in analyses where quantitative accuracy is critical for obtaining rigorous results. A subject-specific FEM of a rhesus macaque mandible was constructed, loaded and validated using in vivo data from the same animal. In developing the model, we assessed the impact on model behavior of variation in (i) material properties of the mandibular trabecular bone tissue and teeth; (ii) constraints at the temporomandibular joint and bite point; and (iii) the timing of the muscle activity used to estimate the external forces acting on the model. The best match between the FEA simulation and the in vivo experimental data resulted from modeling the trabecular tissue with an isotropic and homogeneous Young's modulus and Poisson's value of 10GPa and 0.3, respectively; constraining translations along X,Y, Z axes in the chewing (left) side temporomandibular joint, the premolars and the m 1 ; constraining the balancing (right) side temporomandibular joint in the anterior-posterior and superior-inferior axes, and using the muscle force estimated at time of maximum strain magnitude in the lower lateral gauge. The relative strain magnitudes in this model were similar to those recorded in vivo for all strain locations. More detailed analyses of mandibular strain patterns during the power stroke at different times in the chewing cycle are needed. Copyright © 2017. Published by Elsevier GmbH.

Massive hemothorax due to inferior phrenic artery injury after blunt trauma.

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Aoki, Makoto; Shibuya, Kei; Kaneko, Minoru; Koizumi, Ayana; Murata, Masato; Nakajima, Jun; Hagiwara, Shuichi; Kanbe, Masahiko; Koyama, Yoshinori; Tsushima, Yoshito; Oshima, Kiyohiro

2015-01-01

Injury to the inferior phrenic artery after blunt trauma is an extremely rare event, and it may occur under unanticipated conditions. This case report describes an injury to the left inferior phrenic artery caused by blunt trauma, which was complicated by massive hemothorax, and treated with transcatheter arterial embolization (TAE). An 81 year-old female hit by a car while walking at the traffic intersection was transferred to the emergency department, computed tomography scanning revealed active extravasations of the contrast medium within the retrocrural space and from branches of the internal iliac artery. The patient underwent repeated angiography, and active extravasation of contrast medium was observed between the retrocrural space and the right pleural space originating from the left inferior phrenic artery. The injured left inferior phrenic artery was successfully embolized with N-butyl cyanoacrylate, resulting in stabilization of the patient's clinical condition. Inferior phrenic artery injury should be recognized as a rare phenomenon and causative factor for hemothorax. TAE represents a safe and effective treatment for this complication and obviates the need for a thoracotomy.

Exploring the role of the posterior middle temporal gyrus in semantic cognition: Integration of anterior temporal lobe with executive processes.

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Davey, James; Thompson, Hannah E; Hallam, Glyn; Karapanagiotidis, Theodoros; Murphy, Charlotte; De Caso, Irene; Krieger-Redwood, Katya; Bernhardt, Boris C; Smallwood, Jonathan; Jefferies, Elizabeth

2016-08-15

Making sense of the world around us depends upon selectively retrieving information relevant to our current goal or context. However, it is unclear whether selective semantic retrieval relies exclusively on general control mechanisms recruited in demanding non-semantic tasks, or instead on systems specialised for the control of meaning. One hypothesis is that the left posterior middle temporal gyrus (pMTG) is important in the controlled retrieval of semantic (not non-semantic) information; however this view remains controversial since a parallel literature links this site to event and relational semantics. In a functional neuroimaging study, we demonstrated that an area of pMTG implicated in semantic control by a recent meta-analysis was activated in a conjunction of (i) semantic association over size judgements and (ii) action over colour feature matching. Under these circumstances the same region showed functional coupling with the inferior frontal gyrus - another crucial site for semantic control. Structural and functional connectivity analyses demonstrated that this site is at the nexus of networks recruited in automatic semantic processing (the default mode network) and executively demanding tasks (the multiple-demand network). Moreover, in both task and task-free contexts, pMTG exhibited functional properties that were more similar to ventral parts of inferior frontal cortex, implicated in controlled semantic retrieval, than more dorsal inferior frontal sulcus, implicated in domain-general control. Finally, the pMTG region was functionally correlated at rest with other regions implicated in control-demanding semantic tasks, including inferior frontal gyrus and intraparietal sulcus. We suggest that pMTG may play a crucial role within a large-scale network that allows the integration of automatic retrieval in the default mode network with executively-demanding goal-oriented cognition, and that this could support our ability to understand actions and non

Activations in temporal areas using visual and auditory naming stimuli: A language fMRI study in temporal lobe epilepsy.

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Gonzálvez, Gloria G; Trimmel, Karin; Haag, Anja; van Graan, Louis A; Koepp, Matthias J; Thompson, Pamela J; Duncan, John S

2016-12-01

Verbal fluency functional MRI (fMRI) is used for predicting language deficits after anterior temporal lobe resection (ATLR) for temporal lobe epilepsy (TLE), but primarily engages frontal lobe areas. In this observational study we investigated fMRI paradigms using visual and auditory stimuli, which predominately involve language areas resected during ATLR. Twenty-three controls and 33 patients (20 left (LTLE), 13 right (RTLE)) were assessed using three fMRI paradigms: verbal fluency, auditory naming with a contrast of auditory reversed speech; picture naming with a contrast of scrambled pictures and blurred faces. Group analysis showed bilateral temporal activations for auditory naming and picture naming. Correcting for auditory and visual input (by subtracting activations resulting from auditory reversed speech and blurred pictures/scrambled faces respectively) resulted in left-lateralised activations for patients and controls, which was more pronounced for LTLE compared to RTLE patients. Individual subject activations at a threshold of T>2.5, extent >10 voxels, showed that verbal fluency activated predominantly the left inferior frontal gyrus (IFG) in 90% of LTLE, 92% of RTLE, and 65% of controls, compared to right IFG activations in only 15% of LTLE and RTLE and 26% of controls. Middle temporal (MTG) or superior temporal gyrus (STG) activations were seen on the left in 30% of LTLE, 23% of RTLE, and 52% of controls, and on the right in 15% of LTLE, 15% of RTLE, and 35% of controls. Auditory naming activated temporal areas more frequently than did verbal fluency (LTLE: 93%/73%; RTLE: 92%/58%; controls: 82%/70% (left/right)). Controlling for auditory input resulted in predominantly left-sided temporal activations. Picture naming resulted in temporal lobe activations less frequently than did auditory naming (LTLE 65%/55%; RTLE 53%/46%; controls 52%/35% (left/right)). Controlling for visual input had left-lateralising effects. Auditory and picture naming activated

A Bayesian non-inferiority test for two independent binomial proportions.

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Kawasaki, Yohei; Miyaoka, Etsuo

2013-01-01

In drug development, non-inferiority tests are often employed to determine the difference between two independent binomial proportions. Many test statistics for non-inferiority are based on the frequentist framework. However, research on non-inferiority in the Bayesian framework is limited. In this paper, we suggest a new Bayesian index τ = P(π₁  > π₂-Δ₀|X₁, X₂), where X₁ and X₂ denote binomial random variables for trials n1 and n₂, and parameters π₁ and π₂ , respectively, and the non-inferiority margin is Δ₀> 0. We show two calculation methods for τ, an approximate method that uses normal approximation and an exact method that uses an exact posterior PDF. We compare the approximate probability with the exact probability for τ. Finally, we present the results of actual clinical trials to show the utility of index τ. Copyright © 2013 John Wiley & Sons, Ltd.

Evaluation of the kappa-opioid receptor-selective tracer [{sup 11}C]GR103545 in awake rhesus macaques

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Schoultz, Bent W. [University of Oslo, Department of Chemistry, Oslo (Norway); Hjornevik, Trine; Willoch, Frode [University of Oslo, Centre for Molecular Biology and Neuroscience and Institute of Basic Medical Sciences, Oslo (Norway); Akershus University Hospital, Department of Nuclear Medicine, Loerenskog (Norway); Marton, Janos [ABX Advanced Biochemical Compounds GmbH, Radeberg (Germany); Noda, Akihiro; Murakami, Yoshihiro; Miyoshi, Sosuke; Nishimura, Shintaro [Medical and Pharmacological Research Center Foundation, Basic Research Department, Hakui City, Ishikawa (Japan); Aarstad, Erik [University College of London, Institute of Nuclear Medicine, London (United Kingdom); Drzezga, Alexander [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Matsunari, Ichiro [Medical and Pharmacological Research Center Foundation, Clinical Research Department, Hakui City, Ishikawa (Japan); Henriksen, Gjermund [University of Oslo, Department of Chemistry, Oslo (Norway); Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

2010-06-15

The recent development in radiosynthesis of the {sup 11}C-carbamate function increases the potential of [{sup 11}C]GR103545, which for the last decade has been regarded as promising for imaging the kappa-opioid receptor ({kappa}-OR) with PET. In the present study, [{sup 11}C]GR103545 was evaluated in awake rhesus macaques. Separate investigations were performed to clarify the OR subtype selectivity of this compound. Regional brain uptake kinetics of [{sup 11}C]GR103545 was studied 0-120 min after injection. The binding affinity and opioid subtype selectivity of [{sup 11}C]GR103545 was determined in cells transfected with cloned human opioid receptors. In vitro binding assays demonstrated a high affinity of GR103545 for {kappa}-OR (K{sub i} = 0.02 {+-}0.01 nM) with excellent selectivity over {mu}-OR (6 x 10{sup 2}-fold) and {delta}-OR (2 x 10{sup 4}-fold). PET imaging revealed a volume of distribution (V{sub T}) pattern consistent with the known distribution of {kappa}-OR, with striatum = temporal cortex > cingulate cortex > frontal cortex > parietal cortex > thalamus > cerebellum. [{sup 11}C]GR103545 is selective for {kappa}-OR and holds promise for use to selectively depict and quantify this receptor in humans by means of PET. (orig.)

Membrane transport properties of equine and macaque ovarian tissues frozen in mixtures of dimethylsulfoxide and ethylene glycol.

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Kardak, A; Leibo, S P; Devireddy, R

2007-10-01

The rate at which equine and macaque ovarian tissue sections are first cooled from +25 degrees C to +4 degrees C has a significant effect on the measured water transport when the tissues are subsequently frozen in 0.85 M solutions of glycerol, dimethylsulfoxide (DMSO), or ethylene glycol (EG). To determine whether the response of ovarian tissues is altered if they are suspended in mixtures of cryoprotective agents (CPAs), rather than in solutions of a single CPA, we have now measured the subzero water transport from ovarian tissues that were suspended in mixtures of DMSO and EG. Sections of freshly collected equine and macaque ovaries were suspended either in a mixture of 0.9 M EG plus 0.7 M DMSO (equivalent to a mixture of approximately 5% vv of EG and DMSO) or in a 1.6M solution of only DMSO or only EG. The tissue sections were cooled from +25 degrees C to +4 degrees C and then frozen to subzero temperatures at 5 degrees C/min. As the tissues were being frozen, a shape-independent differential scanning calorimeter technique was used to measure water loss from the tissues and, consequently, the best fit membrane permeability parameters (L(pg) and E(Lp)) of ovarian tissues during freezing. In the mixture of DMSO+EG, the respective values of L(pg) and E(Lp) for equine tissue first cooled at 40 degrees C/min between +25 degrees C and +4 degrees C before being frozen were 0.15 microm/min atm and 7.6 kcal/mole. The corresponding L(pg) and E(Lp) values for equine tissue suspended in 1.6M DMSO were 0.12 microm/min atm and 27.2 kcal/mole; in 1.6M EG, the values were 0.06 microm/min atm and 21.9 kcal/mole, respectively. For macaque ovarian tissues suspended in the mixture of DMSO+EG, the respective values of L(pg) and E(Lp) were 0.26 microm/min atm and 26.2 kcal/mole. Similarly, the corresponding L(Lg) and E(Lp) values for macaque tissue suspended in 1.6M DMSO were 0.22 microm/min atm and 31.4 kcal/mole; in 1.6 M EG, the values were 0.20 microm/min atm and 27.9 kcal

Human presence increases parasitic load in endangered lion-tailed macaques (Macaca silenus in its fragmented rainforest habitats in Southern India.

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Shaik Hussain

Full Text Available BACKGROUND: Understanding changes in the host-parasite relationship due to habitat fragmentation is necessary for better management and conservation of endangered species in fragmented landscapes. Pathogens and parasites can pose severe threat to species in restricted environments such as forest fragments where there is increased contact of wildlife with human and livestock populations. Environmental stress and reduced nutritional level in forest fragments can influence parasite infection and intensity on the native species. In this study, we examine the impact of habitat fragmentation on the prevalence of gastrointestinal parasites in lion-tailed macaques in a fragmented rainforest in Western Ghats. METHODS: The prevalence of different gastrointestinal parasites was estimated from 91 fecal samples collected from 9 lion-tailed macaque groups in nine forest fragments. The parasites were identified up to genus level on the basis of the morphology and coloration of the egg, larva and cyst. The covariates included forest fragment area, group size and the presence/absence of human settlements and livestock in proximity. We used a linear regression model to identify the covariates that significantly influenced the prevalence of different parasite taxa. RESULTS: Nine gastrointestinal parasite taxa were detected in lion-tailed macaque groups. The groups near human settlements had greater prevalence and number of taxa, and these variables also had significant positive correlations with group size. We found that these parameters were also greater in groups near human settlements after controlling for group size. Livestock were present in all five fragments that had human settlements in proximity. CONCLUSION: The present study suggests that high prevalence and species richness of gastrointestinal parasites in lion-tailed macaque groups are directly related to habitat fragmentation, high anthropogenic activities and high host density. The parasite load

The influence of age on wild rhesus macaques' affiliative social interactions.

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Liao, Zhijie; Sosa, Sebastian; Wu, Chengfeng; Zhang, Peng

2018-02-01

The social relationships that individuals experience at different life stages have a non-negligible influence on their lives, and this is particularly true for group living animals. The long lifespan of many primates makes it likely that these animals have various tactics of social interaction to adapt to complex changes in environmental or physical conditions. The different strategies used in social interaction by individuals at different life stages, and whether the position (central or peripheral) or role (initiator or recipient) of an individual in the group social network changes with age, are intriguing questions that remain to be investigated. We used social network analysis to examine age-related differences in social interaction patterns, social roles, and social positions in three affiliative social networks (approach, allogrooming, and social play) in a group of wild rhesus macaques (Macaca mulatta). Our results showed that social interaction patterns of rhesus macaques differ between age classes in the following ways: i) young individuals tend to allocate social time to a high number of groupmates, older individuals prefer to focus on fewer, specific partners; ii) as they grow older, individuals tend to be recipients in approach interactions and initiators in grooming interactions; and iii) regardless of the different social interaction strategies, individuals of all ages occupy a central position in the group. These results reveal a possible key role played by immature individuals in group social communication, a little-explored issue which deserves closer investigation in future research. © 2017 Wiley Periodicals, Inc.

Prominence vs. aboutness in sequencing: a functional distinction within the left inferior frontal gyrus.

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Bornkessel-Schlesewsky, Ina; Grewe, Tanja; Schlesewsky, Matthias

2012-02-01

Prior research on the neural bases of syntactic comprehension suggests that activation in the left inferior frontal gyrus (lIFG) correlates with the processing of word order variations. However, there are inconsistencies with respect to the specific subregion within the IFG that is implicated by these findings: the pars opercularis or the pars triangularis. Here, we examined the hypothesis that the dissociation between pars opercularis and pars triangularis activation may reflect functional differences between clause-medial and clause-initial word order permutations, respectively. To this end, we directly compared clause-medial and clause-initial object-before-subject orders in German in a within-participants, event-related fMRI design. Our results showed increased activation for object-initial sentences in a bilateral network of frontal, temporal and subcortical regions. Within the lIFG, posterior and inferior subregions showed only a main effect of word order, whereas more anterior and superior subregions showed effects of word order and sentence type, with higher activation for sentences with an argument in the clause-initial position. These findings are interpreted as evidence for a functional gradation of sequence processing within the left IFG: posterior subportions correlate with argument prominence-based (local) aspects of sequencing, while anterior subportions correlate with aboutness-based aspects of sequencing, which are crucial in linking the current sentence to the wider discourse. This proposal appears compatible with more general hypotheses about information processing gradients in prefrontal cortex (Koechlin & Summerfield, 2007). Copyright © 2010 Elsevier Inc. All rights reserved.

Significance of localization of mandibular foramen in an inferior alveolar nerve block.

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Thangavelu, K; Kannan, R; Kumar, N Senthil; Rethish, E; Sabitha, S; Sayeeganesh, N

2012-07-01

The mandibular foramen (MF) is an opening on the internal surface of the ramus for divisions of the mandibular vessels and nerve to pass. The aim of this study is to determine the position of the MF from various anatomical landmarks in several dry adult mandibles. A total of 102 human dry mandibles were examined, of which 93 were of dentulous and 9 were of edentulous. The measurements were taken from the anterior border of the ramus (coronoid notch) to the midportion of the MF and then from the midportion of the MF to the other landmarks such as internal oblique ridge, inferior border, sigmoid notch, and condyle were measured and recorded. The data were compared using Student's t-test. The MF is positioned at a mean distance of 19 mm (with SD 2.34) from coronoid notch of the anterior border of the ramus. Superio-inferiorly from the condyle to the inferior border MF is situated 5 mm inferior to the midpoint of condyle to the inferior border distance (ramus height). We conclude that failures in the anesthesia of the inferior alveolar nerve are due to the operator error and not due to the anatomical variation.

Predictors of insubordinate aggression among captive female rhesus macaques.

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Seil, Shannon K; Hannibal, Darcy L; Beisner, Brianne A; McCowan, Brenda

2017-11-01

Cercopithicine primates tend to have nepotistic hierarchies characterized by predictable, kinship-based dominance. Although aggression is typically directed down the hierarchy, insubordinate aggression does occur. Insubordination is important to understand because it can precipitate social upheaval and undermine group stability; however, the factors underlying it are not well understood. We test whether key social and demographic variables predict insubordination among captive female rhesus macaques. To identify factors influencing insubordination, multivariate analyses of 10,821 dyadic conflicts among rhesus macaque females were conducted, using data from six captive groups. A segmented regression analysis was used to identify dyads with insubordination. Negative binomial regression analyses and an information theoretic approach were used to assess predictors of insubordination among dyads. In the best models, weight difference (w = 1.0; IRR = 0.930), age (dominant: w = 1.0, IRR = 0.681; subordinate: w = 1.0, IRR = 1.069), the subordinate's total number of allies (w = 0.727, IRR = 1.060) or non-kin allies (w = 0.273, IRR = 1.165), the interaction of the dominant's kin allies and weight difference (w = 0.938, IRR = 1.046), violation of youngest ascendancy (w = 1.0; IRR = 2.727), and the subordinate's maternal support (w = 1.0; IRR = 2.928), are important predictors of insubordination. These results show that both intrinsic and social factors influence insubordinate behavior. This adds to evidence of the importance of intrinsic factors and flexibility in a social structure thought to be rigid and predetermined by external factors. Further, because insubordination can precipitate social overthrow, determining predictors of insubordination will shed light on mechanisms underlying stability in nepotistic societies. © 2017 Wiley Periodicals, Inc.

Damage to Broca’s area OR the anterior temporal lobe is implicated in stroke-induced agrammatic comprehension: it depends on the task

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Corianne Rogalsky

2015-04-01

Full Text Available The neurobiology of sentence comprehension remains unresolved. Previous large-scale studies of stroke patients have yielded conflicting results regarding sentence comprehension, implicating inferior frontal, anterior temporal and/or posterior temporal regions (Dronkers et al., 2004; Magnusdottir et al., 2013; Thothathiri et al. 2012. Furthermore, only one large-scale lesion study (Magnusdottir et al. 2013 has examined the neural underpinnings of agrammatic comprehension (i.e. substantially worse performance on sentences with noncanonical word orders compared to canonical word order sentences in English, a hallmark of Broca’s aphasia. This one previous study of noncanonical < canonical sentence performance on a sentence picture-matching task implicated damage to the left anterior temporal lobe (ATL and to a lesser degree Broca’s area damage (i.e. < 10% of significant voxels (Magnusdottir et al. 2013. The present study investigated the neurobiology of agrammatic comprehension with two sentence comprehension tasks in the MARC test battery: a sentence-picture matching task (the SOAP Test: a test of syntactic complexity; Love & Oster, 2002 and a sentence plausibility judgment task. Each task contained active, passive, subject-relative and object-relative sentences. Participants included 91 patients with chronic focal cerebral damage. First, we conducted voxel-based lesion symptom mapping (VLSM; Bates et al. 2003 for each sentence type in each task. Consistent with previous studies (Magnusdottir et al. 2013; Thothathiri et al. 2012, the VLSMs identified a significant association between sentence comprehension impairments and damage to a large left temporal-inferior parietal network for all sentences (peak t values were in posterior temporal and inferior parietal voxels; no areas of frontal lobe damage were significant for any sentence type/task. We then conducted VLSMs to identify areas of damage associated specifically with agrammatic

Comparison of feeding behavior between two different-sized groups of Japanese macaques (Macaca fuscata yakui).

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Kurihara, Yosuke; Hanya, Goro

2015-05-13

Group-living animals face intragroup scramble and intergroup contest competitions. Many studies have shown that larger groups bear the costs of intragroup scramble competition, which negatively affects the reproductive success of females. Unlike most primate species, Japanese macaques in the Yakushima coastal forest show increased reproductive success with group size. However, it remains unclear how group size affects the behavior of macaques. The present study examined the effects of group size on the feeding behavior of Japanese macaques in the Yakushima coastal forest. We investigated 9-13 adult females from two different-sized groups via focal animal sampling during October 2012-August 2013. We compared the feeding behavior, including patch use, between the two groups. The larger group had a larger home range and spent more time feeding, especially on mature leaves. This suggests that intragroup feeding competition should be more intense in the larger group than in the smaller group. The feeding of mature leaves might enable the larger group to increase the number of co-feeding individuals. Contrary to the predictions that the larger group travels longer distances and spends more time moving, the smaller group traveled longer distances, and spent more time moving, although the number of visited patches did not differ between the two groups. The immediate consequences of the loss of inter-group encounters could accumulate as daily travel costs, considering that group size is associated with inter-group dominance and that intergroup aggressive encounters occur frequently in the Yakushima coastal forest. This suggests that the smaller group has increased travel costs as a result of intergroup contest competition, which leads to decline in reproductive success. Am. J. Primatol. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Histopathological observation of immunized rhesus macaques with plague vaccines after subcutaneous infection of Yersinia pestis.

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Guang Tian

Full Text Available In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270 and SV2 (200 µg F1 and 100 µg rV270 subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.

Response to social challenge in young bonnet (Macaca radiata) and pigtail (Macaca nemestrina) macaques is related to early maternal experiences.

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Weaver, Ann; Richardson, Rebecca; Worlein, Julie; De Waal, Frans; Laudenslager, Mark

2004-04-01

Previous experience affects how young primates respond to challenging social situations. The present retrospective study looked at one aspect of early experience, the quality of the mother-infant relationship, to determine its relationship to young bonnet and pigtail macaques' responses to two social challenges: temporary maternal separation at 5-6 months and permanent transfer to an unfamiliar peer group at 16-17 months. Relationship quality was measured quantitatively on 30 macaque mother-infant pairs with the Relationship Quality Index (RQI), the ratio of relative affiliation to relative agonism as previously applied to capuchin monkeys. Infants with high RQI values had amicable mother-infant relationships and infants with low RQI values had agonistic mother-infant relationships. Young monkeys with amicable and agonistic relationships showed consistent differences in behavior before, during, and after each social challenge, supporting the hypothesis that juveniles from amicable mother-infant relationships based on the RQI coped more effectively with social challenges than did juveniles from agonistic mother-infant relationships. Results suggest 1) characteristic amicability or agonism in early mother-offspring macaque relationships has the potential to influence offspring behavior in tense social contexts and 2) the RQI is useful as one of a coordinated suite of methods for studying the development of social skills. Copyright 2004 Wiley-Liss, Inc.

Inferior oblique muscle paresis as a sign of myasthenia gravis.

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Almog, Yehoshua; Ben-David, Merav; Nemet, Arie Y

2016-03-01

Myasthenia gravis may affect any of the six extra-ocular muscles, masquerading as any type of ocular motor pathology. The frequency of involvement of each muscle is not well established in the medical literature. This study was designed to determine whether a specific muscle or combination of muscles tends to be predominantly affected. This retrospective review included 30 patients with a clinical diagnosis of myasthenia gravis who had extra-ocular muscle involvement with diplopia at presentation. The diagnosis was confirmed by at least one of the following tests: Tensilon test, acetylcholine receptor antibodies, thymoma on chest CT scan, or suggestive electromyography. Frequency of involvement of each muscle in this cohort was inferior oblique 19 (63.3%), lateral rectus nine (30%), superior rectus four (13.3%), inferior rectus six (20%), medial rectus four (13.3%), and superior oblique three (10%). The inferior oblique was involved more often than any other muscle (pmyasthenia gravis can be difficult, because the disease may mimic every pupil-sparing pattern of ocular misalignment. In addition diplopia caused by paresis of the inferior oblique muscle is rarely encountered (other than as a part of oculomotor nerve palsy). Hence, when a patient presents with vertical diplopia resulting from an isolated inferior oblique palsy, myasthenic etiology should be highly suspected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interspecies sexual behaviour between a male Japanese macaque and female sika deer.

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Pelé, Marie; Bonnefoy, Alexandre; Shimada, Masaki; Sueur, Cédric

2017-04-01

Interspecies sexual behaviour or 'reproductive interference' has been reported across a wide range of animal taxa. However, most of these occurrences were observed in phylogenetically close species and were mainly discussed in terms of their effect on fitness, hybridization and species survival. The few cases of heterospecific mating in distant species occurred between animals that were bred and maintained in captivity. Only one scientific study has reported this phenomenon, describing sexual harassment of king penguins by an Antarctic fur seal. This is the first article to report mating behaviour between a male Japanese macaque (Macaca fuscata yakui) and female sika deer (Cervus nippon yakushimae) on Yakushima Island, Japan. Although Japanese macaques are known to ride deer, this individual showed clearly sexual behaviour towards several female deer, some of which tried to escape whilst others accepted the mount. This male seems to belong to a group of peripheral males. Although this phenomenon may be explained as copulation learning, this is highly unlikely. The most realistic hypothesis would be that of mate deprivation, which states that males with limited access to females are more likely to display this behaviour. Whatever the cause for this event may be, the observation of highly unusual animal behaviour may be a key to understanding the evolution of heterospecific mating behaviour in the animal kingdom.

Propagated but Topologically Distributed Forebrain Neurons Expressing Alpha-Synuclein in Aged Macaques.

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Katsuo Kimura

Full Text Available In neurodegenerative disorders, such as Parkinson's disease (PD, alpha-synuclein (α-syn accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB. This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.

New radioimmunoassay for follicle-stimulating hormone in macaques: ovulatory menstrual cycles. [/sup 125/I tracer technique

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Hodgen, G.D.; Wilks, J.W.; Vaitukaitis, J.L.; Chen, H.C.; Papkoff, H.; Ross, G.

1976-07-01

A sensitive and specific radioimmunoassay system for macaque follicle-stimulating hormone (mFSH) was developed utilizing an antiserum (H-31) prepared in a rabbit against purified ovine FSH as the immunogen. Sera from castrated female, adult male, and juvenile rhesus monkeys, as well as urinary extracts from castrated rhesus and bonnet monkeys, were used to demonstrate parallelism with a standard of partially purified monkey pituitary gonadotropins (LER-M-907-D). An extract of baboon pituitary tissue also showed parallelism with the reference standard. A highly purified pituitary extract (WP-X-105-28), containing approximately 75 percent macaque luteinizing hormone (mLH) and 1 percent mFSH, was used to demonstrate the specificity of this mFSH assay system. Sera and urinary extracts obtained from hypophysectomized monkeys did not show cross-reactivity in the assay. Macaque chorionic gonadotropin (mCG) did not produce an inhibition curve in the assay, as determined from serum samples and urinary extracts collected from pregnant monkeys at the time of peak mCG secretion. Serum concentrations of mFSH were suppressed in ovariectomized monkeys by the administration of ethinyl estradiol for 3 days, but returned to near pretreatment values by 96 h after the last estradiol administration. The determination of serum mFSH concentrations in daily blood samples obtained from 20 rhesus monkeys throughout ovulatory menstrual cycles revealed a pattern similar to that previously reported for the rhesus monkey and the woman. The peak value of serum mFSH during the menstrual cycle coincided with the midcycle surge of mLH in each case. The gonadotropin peaks were preceded by increasing serum concentrations of estradiol and followed by rises in the serum concentrations of progesterone.

Relationship of distraction rate with inferior alveolar nerve degeneration-regeneration shift

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Ying-hua Zhao

2018-01-01

Full Text Available Distraction osteogenesis is an important technique for the treatment of maxillofacial abnormities and defects. However, distraction osteogenesis may cause the injury of the inferior alveolar nerve. The relationship between distraction rate and nerve degeneration-regeneration shift remains poorly understood. In this study, 24 rabbits were randomly divided into four groups. To establish the rabbit mandibular distraction osteogenesis model, the mandibles of rabbits in distraction osteogenesis groups were subjected to continuous osteogenesis distraction at a rate of 1.0, 1.5 and 2.0 mm/d, respectively, by controlling rounds of screwing each day in the distractors. In the sham group, mandible osteotomy was performed without distraction. Pin-prick test with a 10 g blunt pin on the labium, histological and histomorphometric analyses with methylene blue staining, Bodian's silver staining, transmission electron microscopy and myelinated fiber density of inferior alveolar nerve cross-sections were performed to assess inferior alveolar nerve conditions. At 28 days after model establishment, in the pin-prick test, the inferior alveolar nerve showed no response in the labium to a pin pricks in the 2 mm/d group, indicating a severe dysfunction. Histological and histomorphometric analyses indicated that the inferior alveolar nerve suffered more degeneration and injuries at a high distraction rate (2 mm/d. Importantly, the nerve regeneration, indicated by newborn Schwann cells and axons, was more abundant in 1.0 and 1.5 mm/d groups than in 2.0 mm/d group. We concluded that the distraction rate was strongly associated with the inferior alveolar nerve function, and the distraction rates of 1.0 and 1.5 mm/d had regenerative effects on the inferior alveolar nerve. This study provides an experimental basis for the relationship between distraction rate and nerve degeneration-regeneration shift during distraction osteogenesis, and may facilitate reducing nerve

Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques

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Bryan C. Au

2016-02-01

Full Text Available Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag-specific responses through direct injections of recombinant lentivectors (LVs that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months—the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an “off-the-shelf” anti-cancer vaccine that could be made at large scale and injected into patients—even on an out-patient basis.

Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells.

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Wang, Yufei; Bergmeier, Lesley A; Stebbings, Richard; Seidl, Thomas; Whittall, Trevor; Singh, Mahavir; Berry, Neil; Almond, Neil; Lehner, Thomas

2009-02-05

APOBEC3G is an innate intracellular anti-viral factor which deaminates retroviral cytidine to uridine. In vivo studies of APOBEC3G (A3G) were carried out in rhesus macaques, following mucosal immunization with SIV antigens and CCR5 peptides, linked to the 70kDa heat shock protein. A progressive increase in A3G mRNA was elicited in PBMC after each immunization (p<0.0002 to p< or =0.02), which was maintained for at least 17 weeks. Analysis of memory T cells showed a significant increase in A3G mRNA and protein in CD4(+)CCR5(+) memory T cells in circulating (p=0.0001), splenic (p=0.0001), iliac lymph nodes (p=0.002) and rectal (p=0.01) cells of the immunized compared with unimmunized macaques. Mucosal challenge with SIVmac 251 showed a significant increase in A3G mRNA in the CD4(+)CCR5(+) circulating cells (p<0.01) and the draining iliac lymph node cells (p<0.05) in the immunized uninfected macaques, consistent with a protective effect exerted by A3G. The results suggest that mucosal immunization in a non-human primate can induce features of a memory response to an innate anti-viral factor in CCR5(+)CD4(+) memory and CD4(+)CD95(+)CCR7(-) effector memory T cells.

Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques.

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Au, Bryan C; Lee, Chyan-Jang; Lopez-Perez, Orlay; Foltz, Warren; Felizardo, Tania C; Wang, James C M; Huang, Ju; Fan, Xin; Madden, Melissa; Goldstein, Alyssa; Jaffray, David A; Moloo, Badru; McCart, J Andrea; Medin, Jeffrey A

2016-02-19

Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA)-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months-the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an "off-the-shelf" anti-cancer vaccine that could be made at large scale and injected into patients-even on an out-patient basis.

The use of preferred social stimuli as rewards for rhesus macaques in behavioural neuroscience.

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Helen Gray

Full Text Available Macaques are often motivated to perform in neuroscientific experiments by implementing fluid restriction protocols. Daily access to water is controlled and the monkeys are rewarded with droplets of fluid for performing correct trials in the laboratory. Although these protocols are widely used and highly effective, it is important from a 3Rs perspective to investigate refinements that may help to lessen the severity of the fluid restriction applied. We assessed the use of social stimuli (images of conspecifics as rewards for four rhesus macaques performing simple cognitive tasks. We found that individual preferences for images of male faces, female perinea and control stimuli could be identified in each monkey. However, using preferred images did not translate into effective motivators on a trial-by-trial basis: animals preferred fluid rewards, even when fluid restriction was relaxed. There was no difference in the monkeys' performance of a task when using greyscale versus colour images. Based on our findings, we cannot recommend the use of social stimuli, in this form, as a refinement to current fluid restriction protocols. We discuss the potential alternatives and possibilities for future research.

The effect of solicitations on grooming exchanges among female Japanese macaques at Katsuyama.

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Ueno, Masataka; Yamada, Kazunori; Nakamichi, Masayuki

2014-01-01

In group-living primates, individuals often exchange grooming with not only kin but also non-kin. We investigated the effect of soliciting behaviors on grooming exchanges in a free-ranging Japanese macaque (Macaca fuscata) group at Katsuyama. In this study, we used a focal animal sampling method, targeting 14 females. Data were collected for 15.75 ± 2.67 (mean ± SD) hours per focal female. We classified female-female pairs into three pair types: kin pairs, affiliated non-kin pairs, and unaffiliated non-kin pairs. Females received grooming more frequently when they solicited after grooming their partners than when they did not solicit in all pair types. In addition, females received grooming less frequently when they did not groom their unaffiliated non-kin partners before soliciting; prior grooming was not needed to receive grooming from kin or affiliated non-kin partners. The degree of grooming reciprocity did not differ according to the frequency with which females in kin or affiliated non-kin pairs solicited after grooming. On the other hand, grooming reciprocity between unaffiliated non-kin females was more balanced when they solicited frequently after grooming, as compared with when they did not. In conclusion, our study suggests that soliciting behaviors promote grooming exchanges in female Japanese macaques.

Altered organization of face processing networks in temporal lobe epilepsy

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Riley, Jeffrey D.; Fling, Brett W.; Cramer, Steven C.; Lin, Jack J.

2015-01-01

SUMMARY Objective Deficits in social cognition are common and significant in people with temporal lobe epilepsy (TLE), but the functional and structural underpinnings remain unclear. The present study investigated how the side of seizure focus impacts face processing networks in temporal lobe epilepsy. Methods We used functional magnetic resonance imaging (fMRI) of a face processing paradigm to identify face responsive regions in 24 individuals with unilateral temporal lobe epilepsy (Left = 15; Right = 9) and 19 healthy controls. fMRI signals of face responsive regions ispilateral and contralateral to the side of seizure onset were delineated in TLE and compared to the healthy controls with right and left side combined. Diffusion tensor images were acquired to investigate structural connectivity between face regions that differed in fMRI signals between the two groups. Results In temporal lobe epilepsy, activation of the cortical face processing networks varied according to side of seizure onset. In temporal lobe epilepsy, the laterality of amygdala activation was shifted to the side contralateral to the seizure focus while controls showed no significant asymmetry. Furthermore, compared to controls, patients with TLE showed decreased activation of the occipital face responsive region in the ipsilateral side and an increased activity of the anterior temporal lobe in the contralateral side to the seizure focus. Probabilistic tractography revealed that the occipital face area and anterior temporal lobe are connected via the inferior longitudinal fasciculus, which in individuals with temporal lobe epilepsy showed reduced integrity. Significance Taken together, these findings suggest that brain function and white matter integrity of networks subserving face processing are impaired on the side of seizure onset, accompanied by altered responses on the side contralateral to the seizure. PMID:25823855

Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques.

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Rebecca Broeckel

2017-06-01

Full Text Available Chikungunya virus (CHIKV is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs, one (4N12 of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12. Because therapeutic administration of SVIR001 in immunocompetent mice significantly reduced viral load in joint tissues, we evaluated its efficacy in a rhesus macaque model of CHIKV infection. Rhesus macaques that were treated after infection with SVIR001 showed rapid elimination of viremia and less severe joint infiltration and disease compared to animals treated with SVIR002, an isotype control mAb. SVIR001 reduced viral burden at the site of infection and at distant sites and also diminished the numbers of activated innate immune cells and levels of pro-inflammatory cytokines and chemokines. SVIR001 therapy; however, did not substantively reduce the induction of CHIKV-specific B or T cell responses. Collectively, these results show promising therapeutic activity of a human anti-CHIKV mAb in rhesus macaques and provide proof-of-principle for its possible use in humans to treat active CHIKV infections.

MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa.

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Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick; Litterst, Claudia; Levendosky, Keith; Gettie, Agegnehu; Cooney, Michael L; Blanchard, James; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia

2017-03-01

The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad-spectrum microbicide against HIV, herpes simplex virus (HSV), and human papillomavirus. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection, and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and human papillomavirus in murine models. Recently, we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants. Here we established models of ex vivo SHIV-RT/HSV-2 coinfection of vaginal mucosa and SHIV-RT infection of rectal mucosa in macaques (challenge of rectal mucosa with HSV-2 did not result in reproducible tissue infection), evaluated antiviral activity of MZC, and compared quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay readouts for monitoring SHIV-RT infection. MZC (at nontoxic dilutions) significantly inhibited SHIV-RT in vaginal and rectal mucosas and HSV-2 in vaginal mucosa when present during viral challenge. Analysis of SHIV-RT infection and MZC activity by 1-step simian immunodeficiency virus gag quantitative RT-PCR and p27 enzyme-linked immunosorbent assay demonstrated similar virus growth dynamics and MZC activity by both methods and higher sensitivity of quantitative RT-PCR. Our data provide more evidence that MZC is a promising dual compartment multipurpose prevention technology candidate.

Changes in the Response Properties of Inferior Colliculus Neurons Relating to Tinnitus

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Berger, Joel I.; Coomber, Ben; Wells, Tobias T.; Wallace, Mark N.; Palmer, Alan R.

2014-01-01

Tinnitus is often identified in animal models by using the gap prepulse inhibition of acoustic startle. Impaired gap detection following acoustic over-exposure (AOE) is thought to be caused by tinnitus “filling in” the gap, thus, reducing its salience. This presumably involves altered perception, and could conceivably be caused by changes at the level of the neocortex, i.e., cortical reorganization. Alternatively, reduced gap detection ability might reflect poorer temporal processing in the brainstem, caused by AOE; in which case, impaired gap detection would not be a reliable indicator of tinnitus. We tested the latter hypothesis by examining gap detection in inferior colliculus (IC) neurons following AOE. Seven of nine unilaterally noise-exposed guinea pigs exhibited behavioral evidence of tinnitus. In these tinnitus animals, neural gap detection thresholds (GDTs) in the IC significantly increased in response to broadband noise stimuli, but not to pure tones or narrow-band noise. In addition, when IC neurons were sub-divided according to temporal response profile (onset vs. sustained firing patterns), we found a significant increase in the proportion of onset-type responses after AOE. Importantly, however, GDTs were still considerably shorter than gap durations commonly used in objective behavioral tests for tinnitus. These data indicate that the neural changes observed in the IC are insufficient to explain deficits in behavioral gap detection that are commonly attributed to tinnitus. The subtle changes in IC neuron response profiles following AOE warrant further investigation. PMID:25346722

Involuntary switching into the native language induced by electrocortical stimulation of the superior temporal gyrus: a multimodal mapping study.

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Tomasino, Barbara; Marin, Dario; Canderan, Cinzia; Maieron, Marta; Budai, Riccardo; Fabbro, Franco; Skrap, Miran

2014-09-01

We describe involuntary language switching from L2 to L1 evoked by electro-stimulation in the superior temporal gyrus in a 30-year-old right-handed Serbian (L1) speaker who was also a late Italian learner (L2). The patient underwent awake brain surgery. Stimulation of other portions of the exposed cortex did not cause language switching as did not stimulation of the left inferior frontal gyrus, where we evoked a speech arrest. Stimulation effects on language switching were selective, namely, interfered with counting behaviour but not with object naming. The coordinates of the positive site were combined with functional and fibre tracking (DTI) data. Results showed that the language switching site belonged to a significant fMRI cluster in the left superior temporal gyrus/supramarginal gyrus found activated for both L1 and L2, and for both the patient and controls, and did not overlap with the inferior fronto-occipital fasciculus (IFOF), the inferior longitudinal fasciculus (ILF) and the superior longitudinal fasciculus (SLF). This area, also known as Stp, has a role in phonological processing. Language switching phenomenon we observed can be partly explained by transient dysfunction of the feed-forward control mechanism hypothesized by the DIVA (Directions Into Velocities of Articulators) model (Golfinopoulos, E., Tourville, J. A., & Guenther, F. H. (2010). The integration of large-scale neural network modeling and functional brain imaging in speech motor control. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Effect of TSA and VPA treatment on long-tailed macaque (Macaca fascicularis)-pig interspecies somatic cell nuclear transfer].

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Qin, Zu-Xing; Huang, Gao-Bo; Luo, Jun; Ning, Shu-Fang; Lu, Sheng-Sheng; Lu, Ke-Huan

2012-03-01

Long-tailed macaque-pig interspecies somatic cell nuclear transfer (iSCNT) is beneficial to yield embryonic stem cells from iSCNT embryos with similar genetic background as human, which can be used as materials for medical and basic research. The primary objective of this study was to investigate the effects of concentrations and treatment duration of two histone deacetylase inhibitors-Trichostatin A (TSA) and Valproic acid (VPA) and two different embryo culture media (PZM-3 and HECM-10) on the in vitro development of iSCNT embryos. The results suggested that when PZM-3 was used as the embryo culture medium, the blastocyst rate of 10 nmol/L TSA treatment for 48 h was significantly higher than the control group (22.78% vs 9.86%, PTSA treatment could enhance the in vitro developmental potential of long-tailed macaque-pig iSCNT embryos.

Intrinsic Connections of the Core Auditory Cortical Regions and Rostral Supratemporal Plane in the Macaque Monkey.

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Scott, Brian H; Leccese, Paul A; Saleem, Kadharbatcha S; Kikuchi, Yukiko; Mullarkey, Matthew P; Fukushima, Makoto; Mishkin, Mortimer; Saunders, Richard C

2017-01-01

In the ventral stream of the primate auditory cortex, cortico-cortical projections emanate from the primary auditory cortex (AI) along 2 principal axes: one mediolateral, the other caudorostral. Connections in the mediolateral direction from core, to belt, to parabelt, have been well described, but less is known about the flow of information along the supratemporal plane (STP) in the caudorostral dimension. Neuroanatomical tracers were injected throughout the caudorostral extent of the auditory core and rostral STP by direct visualization of the cortical surface. Auditory cortical areas were distinguished by SMI-32 immunostaining for neurofilament, in addition to established cytoarchitectonic criteria. The results describe a pathway comprising step-wise projections from AI through the rostral and rostrotemporal fields of the core (R and RT), continuing to the recently identified rostrotemporal polar field (RTp) and the dorsal temporal pole. Each area was strongly and reciprocally connected with the areas immediately caudal and rostral to it, though deviations from strictly serial connectivity were observed. In RTp, inputs converged from core, belt, parabelt, and the auditory thalamus, as well as higher order cortical regions. The results support a rostrally directed flow of auditory information with complex and recurrent connections, similar to the ventral stream of macaque visual cortex. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

CT diagnosis of tumor thrombus of the renal vein and inferior vena cava

International Nuclear Information System (INIS)

Masuda, Fujio; Chen, Zuicho; Oishi, Yukihiko; Machida, Toyohei

1980-01-01

We used computed tomography (CT) for diagnosis in 4 cases of renal tumor associated with tumor thrombus of the renal vein and inferior vana cava. The results obtained are described below: A total of 4 cases consisting of 3 cases of renal cell carcinoma and one case of squamous cell carcinoma of the renal pelvis, treated at the Jikei University Hospital during the six months period from January to June of 1979, were studied. The affected side was right in 3 cases and left in one case. In all of the former cases the tumor thrombus was extending from the renal vein to the inferior vena cava, while in the latter case it was confined in the renal vein. All these 4 cases received CT together with renal arteriography and inferior venacavography, followed by nephrectomy, and were confirmed of the presence of tumor thrombus in the renal vein and inferior vena cava operatively. CT findings revealed a pronounced enlargement of the renal vein, and tumor thrombus of the renal vein was diagnosed in all of the 4 cases. In 2 of 3 cases in which tumor thrombus extended to the inferior vena cava, the dilated renal vein was found to be connected to the slightly dilated inferior vena cava, while in the remaining one case the outline of the inferior vena cava was obscure, showing no clear dilatation. After contrast enhancement, a filling defect was seen in the inferior vena cava. CT findings of tumor thrombus in the vein indicated a dilatation of the renal vein and inferior vena cava. In addition, a filling defect was found after contrast enhancement, suggesting that CT is helpful as a diagnostic aid. (author)

Neural Correlates of Temporal Complexity and Synchrony during Audiovisual Correspondence Detection.

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Baumann, Oliver; Vromen, Joyce M G; Cheung, Allen; McFadyen, Jessica; Ren, Yudan; Guo, Christine C

2018-01-01

We often perceive real-life objects as multisensory cues through space and time. A key challenge for audiovisual integration is to match neural signals that not only originate from different sensory modalities but also that typically reach the observer at slightly different times. In humans, complex, unpredictable audiovisual streams lead to higher levels of perceptual coherence than predictable, rhythmic streams. In addition, perceptual coherence for complex signals seems less affected by increased asynchrony between visual and auditory modalities than for simple signals. Here, we used functional magnetic resonance imaging to determine the human neural correlates of audiovisual signals with different levels of temporal complexity and synchrony. Our study demonstrated that greater perceptual asynchrony and lower signal complexity impaired performance in an audiovisual coherence-matching task. Differences in asynchrony and complexity were also underpinned by a partially different set of brain regions. In particular, our results suggest that, while regions in the dorsolateral prefrontal cortex (DLPFC) were modulated by differences in memory load due to stimulus asynchrony, areas traditionally thought to be involved in speech production and recognition, such as the inferior frontal and superior temporal cortex, were modulated by the temporal complexity of the audiovisual signals. Our results, therefore, indicate specific processing roles for different subregions of the fronto-temporal cortex during audiovisual coherence detection.

Occurrence of Giardia, Cryptosporidium, and Entamoeba in wild rhesus macaques (Macaca mulatta living in urban and semi-rural North-West India

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John J. Debenham

2017-04-01

Full Text Available Giardia duodenalis, Cryptosporidium spp., and Entamoeba spp. are intestinal protozoa capable of infecting a range of host species, and are important causes of human morbidity and mortality. Understanding their epidemiology is important, both for public health and for the health of the animals they infect. This study investigated the occurrence of these protozoans in rhesus macaques (Macaca mulatta in India, with the aim of providing preliminary information on the potential for transmission of these pathogens between macaques and humans. Faecal samples (n = 170 were collected from rhesus macaques from four districts of North-West India. Samples were analysed for Giardia/Cryptosporidium using a commercially available direct immunofluorescent antibody test after purification via immunomagnetic separation. Positive samples were characterised by sequencing of PCR products. Occurrence of Entamoeba was investigated first by using a genus-specific PCR, and positive samples further investigated via species-specific PCRs for Entamoeba coli, Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii. Giardia cysts were found in 31% of macaque samples, with all isolates belonging to Assemblage B. Cryptosporidium oocysts were found in 1 sample, however this sample did not result in amplification by PCR. Entamoeba spp. were found in 79% of samples, 49% of which were positive for E. coli. Multiplex PCR for E. histolytica, E. dispar and E. moshkovskii, did not result in amplification in any of the samples. Thus in 51% of the samples positive at the genus specific PCR, the Entamoeba species was not identified. This study provides baseline information on the potential for transmission of these zoonotic parasites at the wildlife-human interface.

Durable protection of rhesus macaques immunized with a replicating adenovirus-SIV multigene prime/protein boost vaccine regimen against a second SIVmac251 rectal challenge: role of SIV-specific CD8+ T cell responses.

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Malkevitch, Nina V; Patterson, L Jean; Aldrich, M Kristine; Wu, Yichen; Venzon, David; Florese, Ruth H; Kalyanaraman, V S; Pal, Ranajit; Lee, Eun Mi; Zhao, Jun; Cristillo, Anthony; Robert-Guroff, Marjorie

2006-09-15

Previously, priming with replication-competent adenovirus-SIV multigenic vaccines and boosting with envelope subunits strongly protected 39% of rhesus macaques against rectal SIV(mac251) challenge. To evaluate protection durability, eleven of the protected and two SIV-infected unimmunized macaques that controlled viremia were re-challenged rectally with SIV(mac251). Strong protection was observed in 8/11 vaccinees, including two exhibiting protected macaques. Durable protection was associated with significantly increased SIV-specific ELISPOT responses and lymphoproliferative responses to p27 at re-challenge. After CD8 depletion, 2 of 8 re-challenged, protected vaccinees maintained protection against re-challenge.

Are mirror neurons the basis of speech perception? Evidence from five cases with damage to the purported human mirror system

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Rogalsky, Corianne; Love, Tracy; Driscoll, David; Anderson, Steven W.; Hickok, Gregory

2013-01-01

The discovery of mirror neurons in macaque has led to a resurrection of motor theories of speech perception. Although the majority of lesion and functional imaging studies have associated perception with the temporal lobes, it has also been proposed that the ‘human mirror system’, which prominently includes Broca’s area, is the neurophysiological substrate of speech perception. Although numerous studies have demonstrated a tight link between sensory and motor speech processes, few have directly assessed the critical prediction of mirror neuron theories of speech perception, namely that damage to the human mirror system should cause severe deficits in speech perception. The present study measured speech perception abilities of patients with lesions involving motor regions in the left posterior frontal lobe and/or inferior parietal lobule (i.e., the proposed human ‘mirror system’). Performance was at or near ceiling in patients with fronto-parietal lesions. It is only when the lesion encroaches on auditory regions in the temporal lobe that perceptual deficits are evident. This suggests that ‘mirror system’ damage does not disrupt speech perception, but rather that auditory systems are the primary substrate for speech perception. PMID:21207313

Prior DNA immunization enhances immune response to dominant and subdominant viral epitopes induced by a fowlpox-based SIVmac vaccine in long-term slow-progressor macaques infected with SIVmac251

International Nuclear Information System (INIS)

Radaelli, Antonia; Nacsa, Janos; Tsai, W.-P.; Edghill-Smith, Yvette; Zanotto, Carlo; Elli, Veronica; Venzon, David; Tryniszewska, Elzbieta; Markham, Phil; Mazzara, Gail P.; Panicali, Dennis; Morghen, Carlo De Giuli; Franchini, Genoveffa

2003-01-01

A therapeutic vaccine for individuals infected with HIV-1 and treated with antiretroviral therapy (ART) should be able to replenish virus-specific CD4+ T-cells and broaden the virus-specific CD8+ T-cell response in order to maintain CD8+ T-cell function and minimize viral immune escape after ART cessation. Because a combination of DNA and recombinant poxvirus vaccine modalities induces high levels of virus-specific CD4+ T-cell response and broadens the cytolytic activity in naive macaques, we investigated whether the same results could be obtained in SIVmac251-infected macaques. The macaques studied here were long-term nonprogressors that naturally contained viremia but were nevertheless treated with a combination of antiviral drugs to assess more carefully the effect of vaccination in the context of ART. The combination of a DNA expressing the gag and pol genes (DNA-SIV-gp) of SIVmac239 followed by a recombinant fowlpox expressing the same SIVmac genes (FP-SIV-gp) was significantly more immunogenic than two immunizations of FP-SIV-gp in SIVmac251-infected macaques treated with ART. The DNA/FP combination significantly expanded and broadened Gag-specific T-cell responses measured by tetramer staining, ELISPOT, and intracellular cytokine staining and measurement of ex vivo cytolytic function. Importantly, the combination of these vaccine modalities also induced a sizeable expansion in most macaques of Gag-specific CD8-(CD4+) T-cells able to produce TNF-α. Hopefully, this modality of vaccine combination may be useful in the clinical management of HIV-1-infected individuals

Evaluation of recombinant influenza virus-simian immunodeficiency virus vaccines in macaques.

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Sexton, Amy; De Rose, Robert; Reece, Jeanette C; Alcantara, Sheilajen; Loh, Liyen; Moffat, Jessica M; Laurie, Karen; Hurt, Aeron; Doherty, Peter C; Turner, Stephen J; Kent, Stephen J; Stambas, John

2009-08-01

There is an urgent need for human immunodeficiency virus (HIV) vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express simian immunodeficiency virus (SIV) CD8 T-cell epitopes and evaluated following administration to the respiratory tracts of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions, although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T-cell responses to influenza virus proteins. SIV-specific CD8 T-cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of naïve animals. Further, SIV-specific CD8 T-cell responses could be boosted by recombinant influenza virus-SIV vaccination of animals with already-established SIV infection. Sequential vaccination with influenza virus-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T-cell immunity to conserved internal proteins of influenza A virus. SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T-cell response, but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest that influenza virus-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit cytotoxic T-lymphocyte escape.

Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

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James V Lawler

2006-05-01

Full Text Available The emergence of severe acute respiratory syndrome (SARS in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs infected with SARS-CoV.In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain.SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children.

Chemical composition of axillary odorants reflects social and individual attributes in rhesus macaques.

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Weiß, Brigitte M; Kücklich, Marlen; Thomsen, Ruth; Henkel, Stefanie; Jänig, Susann; Kulik, Lars; Birkemeyer, Claudia; Widdig, Anja

2018-01-01

Scents play an important role in the life of most terrestrial mammals and may transmit valuable information about conspecifics. Olfaction was long considered of low importance in Old World monkeys due to their relative reduction of olfactory structures and low incidence of scent-marking behavior but has been increasingly recognized for mediating social relationships in recent years. Yet, studies investigating the composition of their chemical cues remain scarce. In the present study, we analyzed the potential information content of chemicals present on the skin of rhesus macaques ( Macaca mulatta ). We collected axillary secretions from 60 animals of the semifree-ranging population on Cayo Santiago (Puerto Rico, USA) with precleaned cotton swabs from which the secretions were subsequently extracted and analyzed by gas chromatography-mass spectrometry. Rhesus macaque axillary odorants varied in their overall similarity and composition. This variation was attributable to differences in sex, group membership, and kinship and further appeared to reflect age and rank in parts of our sample. The compounds most strongly associated with this variation primarily comprised larger molecular weight aldehydes and steroids. Such compounds are considered to be perceivable by the primate olfactory system through close-range interactions or through breakdown into smaller molecules by bacterial fermentation. Overall, our results provide additional evidence that odors of Old World monkeys reflect a wealth of potential information about their carrier, which provides the basis for chemical communication via body odors; however, its use by conspecifics needs to be confirmed in bioassays. One prerequisite for olfactory communication is the presence of systematic variation in animal odors that is related to attributes such as age, sex, or kinship. The composition of odors has been examined in numerous mammals but, with the exception of humans, remains poorly understood in Old World

Ambiguity aversion in rhesus macaques

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Benjamin eHayden

2010-09-01

Full Text Available People generally prefer risky options, which have fully specified outcome probabilities, to ambiguous options, which have unspecified probabilities. This preference, formalized in economics, is strong enough that people will reliably prefer a risky option to an ambiguous option with a greater expected value. Explanations for ambiguity aversion often invoke uniquely human faculties like language, self-justification, or a desire to avoid public embarrassment. Challenging these ideas, here we demonstrate that a preference for unambiguous options is shared with rhesus macaques. We trained four monkeys to choose between pairs of options that both offered explicitly cued probabilities of large and small juice outcomes. We then introduced occasional trials where one of the options was obscured and examined their resulting preferences; we ran humans in a parallel experiment on a nearly identical task. We found that monkeys reliably preferred risky options to ambiguous ones, even when this bias was costly, closely matching the behavior of humans in the analogous task. Notably, ambiguity aversion varied parametrically with the extent of ambiguity. As expected, ambiguity aversion gradually declined as monkeys learned the underlying probability distribution of rewards. These data indicate that ambiguity aversion reflects fundamental cognitive biases shared with other animals rather than uniquely human factors guiding decisions.

Evaluation of macular thickness change after inferior oblique muscle recession surgery

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Ece Turan-Vural

2014-01-01

Full Text Available Purpose: This study aimed to evaluate the changes in macular thickness following inferior oblique muscle recession surgery. Materials and Methods: Thirty-eight eyes from 21 patients undergoing ocular muscle surgery were included. Patients were grouped into three groups based on the type of surgical intervention: Group I (n = 12, inferior oblique recession surgery alone; Group II (n = 12, inferior oblique plus horizontal muscle surgery; Group III (n = 14, horizontal muscle surgery alone. Each eye was scanned using the optical coherence tomography (OCT device preoperatively and on the first postoperative day to measure macular thickness. Results: Following surgery, a significant increase in foveal thickness occurred in Group I (P < 0.05 and Group II (P < 0.01. In addition, a statistically significant difference was observed between the groups with regard to the increase in foveal thickness (P = 0.016, with significantly lower changes in Group III. Conclusion: Our findings suggested that inferior oblique muscle recession surgery is associated with an increase in macular thickness.

Prior Exposure to Zika Virus Significantly Enhances Peak Dengue-2 Viremia in Rhesus Macaques

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George, Jeffy; Valiant, William G.; Mattapallil, Mary J.; Walker, Michelle; Huang, Yan-Jang S.; Vanlandingham, Dana L.; Misamore, John; Greenhouse, Jack; Weiss, Deborah E.; Verthelyi, Daniela; Higgs, Stephen; Andersen, Hanne; Lewis, Mark G.; Mattapallil, Joseph J.

2017-01-01

Structural and functional homologies between the Zika and Dengue viruses? envelope proteins raise the possibility that cross-reactive antibodies induced following Zika virus infection might enhance subsequent Dengue infection. Using the rhesus macaque model we show that prior infection with Zika virus leads to a significant enhancement of Dengue-2 viremia that is accompanied by neutropenia, lympocytosis, hyperglycemia, and higher reticulocyte counts, along with the activation of pro-inflammat...

Inferior vena cava filter penetration following Whipple surgical procedure causing ureteral injury.

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Abdel-Aal, Ahmed Kamel; Ezzeldin, Islam B; Moustafa, Amr Soliman; Ertel, Nathan; Oser, Rachel

2015-12-01

We report a case of an indwelling inferior vena cava filter that penetrated the IVC wall after Whipple's pancreatico-duodenectomy procedure performed in a patient with ampullary carcinoma, resulting in right ureteral injury and obstruction with subsequent hydroureter and hydronephrosis. This was incidentally discovered on a computed tomography scan performed as routine follow up to evaluate the results of the surgery. We retrieved the inferior vena cava filter and placed a nephrostomy catheter to relieve the ureteral obstruction. Our case highlights the importance of careful inferior vena cava manipulation during abdominal surgery in the presence of an inferior vena cava filter, and the option of temporary removal of the filter to be placed again after surgery in order to avoid this complication, unless protection is required against clot migration during the surgical procedure.

An electrocorticographic electrode array for simultaneous recording from medial, lateral, and intrasulcal surface of the cortex in macaque monkeys.

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Fukushima, Makoto; Saunders, Richard C; Mullarkey, Matthew; Doyle, Alexandra M; Mishkin, Mortimer; Fujii, Naotaka

2014-08-15

Electrocorticography (ECoG) permits recording electrical field potentials with high spatiotemporal resolution over a large part of the cerebral cortex. Application of chronically implanted ECoG arrays in animal models provides an opportunity to investigate global spatiotemporal neural patterns and functional connectivity systematically under various experimental conditions. Although ECoG is conventionally used to cover the gyral cortical surface, recent studies have shown the feasibility of intrasulcal ECoG recordings in macaque monkeys. Here we developed a new ECoG array to record neural activity simultaneously from much of the medial and lateral cortical surface of a single hemisphere, together with the supratemporal plane (STP) of the lateral sulcus in macaque monkeys. The ECoG array consisted of 256 electrodes for bipolar recording at 128 sites. We successfully implanted the ECoG array in the left hemisphere of three rhesus monkeys. The electrodes in the auditory and visual cortex detected robust event related potentials to auditory and visual stimuli, respectively. Bipolar recording from adjacent electrode pairs effectively eliminated chewing artifacts evident in monopolar recording, demonstrating the advantage of using the ECoG array under conditions that generate significant movement artifacts. Compared with bipolar ECoG arrays previously developed for macaque monkeys, this array significantly expands the number of cortical target areas in gyral and intralsulcal cortex. This new ECoG array provides an opportunity to investigate global network interactions among gyral and intrasulcal cortical areas. Published by Elsevier B.V.