Neutralization properties of simian immunodeficiency viruses infecting chimpanzees and gorillas.

Unlabelled: Broadly cross-reactive neutralizing antibodies (bNabs) represent powerful tools to combat human immunodeficiency virus type 1 (HIV-1) infection. Here, we examined whether HIV-1-specific bNabs are capable of cross-neutralizing distantly related simian immunodeficiency viruses (SIVs) infecting central (Pan troglodytes troglodytes) (SIVcpzPtt) and eastern (Pan troglodytes schweinfurthii) (SIVcpzPts) chimpanzees (n = 11) as well as western gorillas (Gorilla gorilla gorilla) (SIVgor) (n = 1). We found that bNabs directed against the CD4 binding site (n = 10), peptidoglycans at the base of variable loop 3 (V3) (n = 5), and epitopes at the interface of surface (gp120) and membrane-bound (gp41) envelope glycoproteins (n = 5) failed to neutralize SIVcpz and SIVgor strains.

Link between primate lentiviral coreceptor usage and Nef function.

Simian immunodeficiency virus (SIVsmm) infection of sooty mangabeys (Cercocebus atys) is characterized by stable CD4(+) T cell counts despite high plasma levels of CCR5-tropic viruses. However, in rare instances, SIVsmm acquires CXCR4 coreceptor tropism and causes severe CD4(+) T cell depletion, albeit without clinical signs of immunodeficiency. Here, we show that CXCR4-tropic SIVsmm strains lost their ability to downmodulate TCR-CD3 by evolving unusual Nef mutations that initially reduced (I132V) and subsequently disrupted (I123L and L146F) interaction with the CD3 ζ chain.

Synthesis, radiosynthesis, and biological evaluation of carbon-11 and fluorine-18 labeled reboxetine analogues: potential positron emission tomography radioligands for in vivo imaging of the norepinephrine transporter.

Reboxetine analogues with methyl and fluoroalkyl substituents at position 2 of the phenoxy ring 1-4 were synthesized. In vitro competition binding with [(3)H]nisoxetine demonstrated that 1-4 have a high affinity for the norepinephrine transporter (NET) with K(i)'s = 1.02, 3.

Oxytocin, vasopressin, and the neurogenetics of sociality.

There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition. These ancient neuropeptides display a marked conservation in gene structure and expression, yet diversity in the genetic regulation of their receptors seems to underlie natural variation in social behavior, both between and within species. Human studies are beginning to explore the roles of these neuropeptides in social cognition and behavior and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function.

Acoustic startle reflex in rhesus monkeys: a review.

Modulation of the acoustic startle response is a simple and objective indicator of emotionality and attention in rodents and humans. This finding has proven extremely valuable for the analysis of neural systems associated with fear and anxiety. Until recently, there have been few efforts to develop acoustic startle measurement in non-human primates.

Mouse social recognition and preference.

Social recognition in mice is represented by a simple pattern of behavior that can be accurately and reliably quantified by trained observers. The paradigm presented in this unit takes advantage of an ethologically relevant phenomenon marked by a vigorous and species-typical sequence of investigatory behaviors that occurs when conspecifics meet. Recognition is noted by decreased investigation of a previously encountered animal.

Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses.

The intestinal immune system must elicit robust immunity against harmful pathogens but must also restrain immune responses directed against commensal microbes and dietary antigens. The mechanisms that maintain this dichotomy are poorly understood. Here we describe a population of CD11b+F4/80+CD11c- macrophages in the lamina propria that expressed several anti-inflammatory molecules, including interleukin 10 (IL-10), but little or no proinflammatory cytokines, even after stimulation with Toll-like receptor ligands.

Basic residues in the Mason-Pfizer monkey virus gag matrix domain regulate intracellular trafficking and capsid-membrane interactions.

Mason-Pfizer monkey virus (M-PMV) capsids that have assembled in the cytoplasm must be transported to and associate with the plasma membrane prior to being enveloped by a lipid bilayer during viral release. Structural studies have identified a positive-charge density on the membrane-proximal surface of the matrix (MA) protein component of the Gag polyprotein. To investigate if basic amino acids in MA play a role in intracellular transport and capsid-membrane interactions, mutants were constructed in which lysine and arginine residues (R10, K16, K20, R22, K25, K27, K33, and K39) potentially exposed on the capsid surface were replaced singly and in pairs by alanine.

Cerebral volumetric asymmetries in non-human primates: a magnetic resonance imaging study.

Magnetic resonance images (MRI) were collected in a sample of 23 apes, 14 Old World monkeys, and 8 New World monkeys. The total area or volume of the anterior and posterior cerebral regions of each hemisphere of the brain was measured. The results indicated that a rightward frontal and leftward occipital pattern of asymmetry was present at a population level in the great ape sample.

Referential understanding of videos in chimpanzees (Pan troglodytes), orangutans (Pongo pygmaeus), and children (Homo sapiens).

Performance on identical search tasks based on cues directly perceived or indirectly perceived through video were compared among a group of 4 adult chimpanzees (Pan troglodytes), a group of 2 adult orangutans (Pongo pygmaeus), and a group of 36 children (between 2 and 3 years of age). Children comprehended directly perceived cues but had difficulty with video cues. In contrast, chimpanzees and 1 orangutan were successful in using video to guide their search for a hidden object.

Estradiol selectively affects processing of conspecifics' faces in female rhesus monkeys.

Estrogen deficiency following ovariectomy or menopause increases the risk of developing diseases such as osteoporosis and may also lead to memory impairment. Although estrogen replacement therapy (ERT) alleviates many symptoms associated with estrogen loss, it is not clear whether it also benefits cognitive function. The effect of estrogens upon cognition can best be studied in an animal model of human menopause, in which estrogen levels can be experimentally manipulated.

Is the onset of psychoactive drug effects compatible with a protein-synthesis mechanism?

While many have suggested that protein synthesis may mediate the action of antipsychotic drugs, it is difficult to test. In this math modeling study it is found that the time course of action of the drugs are compatible with a protein-synthesis model and, furthermore, that the half-lives required by the model are indeed found in relevant proteins in the brain.

Withdrawal from repeated cocaine alters dopamine transporter protein turnover in the rat striatum.

Several studies have shown that repeated cocaine administration, followed by withdrawal, alters dopamine transporter (DAT) levels in the rat. These changes must arise from changes in either transporter protein production or degradation, or both. Previously, our laboratory developed an approach to measure the synthesis rate, degradation rate constant, and half-life of DAT in the rat striatum and nucleus accumbens after administration of the irreversible dopamine transporter ligand, RTI-76 [3beta-(3-p-chlorophenyl)tropan-2beta-carboxylic acid p-isothiocyanatophenylethyl ester hydrochloride].

Deletion of Epstein-Barr virus regulatory sequences upstream of the EBNA gene promoter Wp1 is unfavorable for B-Cell immortalization.

Transcription of the six Epstein-Barr virus (EBV) EBNA genes is coordinately regulated, being driven by either the Cp promoter, which is encoded within the unique region just upstream of the EBV major internal repeat (IR-1), or by the Wp promoter, which is encoded within the IR-1 repeat and thus present in multiple copies. Previous analyses of Cp- and Wp-initiated transcription have identified a shared cis-regulatory element mapping to the region extending from -169 to -369 bp upstream of the Wp transcription initiation site (M. T.

A new generation of HIV vaccines.

WHO estimates that currently there are 40 million individuals living with HIV and there are 16000 new infections daily, worldwide. The best strategy to control the AIDS epidemic would be the development of an effective vaccine. New strategies for vaccine development have gained momentum over the past decade, some of which show greater promise in macaque models than did earlier protein-subunit or recombinant-canarypox strategies.

Grip morphology and hand use in chimpanzees (Pan troglodytes): evidence of a left hemisphere specialization in motor skill.

Three experiments on grip morphology and hand use were conducted in a sample of chimpanzees. In Experiment 1, grip morphology when grasping food items was recorded, and it was found that subjects who adopted a precision grip were more right-handed than chimpanzees using other grips. In Experiment 2, the effect of food type on grasping was assessed.

Activity of various CART peptides in changing locomotor activity in the rat.

Several CART (cocaine- and amphetamine-regulated transcript) peptides have been identified in the brain. One peptide, rlCART 55-102, has been previously characterized in locomotor and feeding assays in rodents. The present study characterized the locomotor-stimulating effect of several additional CART peptides after intra-VTA administration in rats.

CART promoter CRE site binds phosphorylated CREB.

It has been shown previously that: CART (cocaine- and amphetamine-regulated transcript) mRNA is tightly regulated in brain; protein kinase A (PKA) is involved in CART expression in GH3 cells; and a cyclic AMP-responsive element (CRE) site is present in the proximal promoter region of the CART gene. Thus, the goal of this study was to test if CRE binding protein (CREB) can bind to the consensus CRE site and if phosphorylation of CREB occurs in GH3 cells under conditions of enhanced CART gene expression. Electromobility shift assays showed that a 27-bp oligonucleotide containing the CART CRE site was indeed bound by nuclear factors.

Cocaine- and amphetamine-regulated transcript peptide projections in the ventral midbrain: colocalization with gamma-aminobutyric acid, melanin-concentrating hormone, dynorphin, and synaptic interactions with dopamine neurons.

To date, cocaine- and amphetamine-regulated transcript (CART) peptides have been found to influence feeding, locomotor activity, and conditioned place preference. A common brain structure that could mediate these effects is the ventral tegmental area (VTA). For a better understanding of the anatomical substrates that might underlie CART peptides' role in these behaviors, we performed a series of experiments to elucidate the source, synaptic connectivity, and neurochemical content of CART peptide-immunoreactive (CARTir) terminals in the rat VTA.

Different patterns of immune responses but similar control of a simian-human immunodeficiency virus 89.6P mucosal challenge by modified vaccinia virus Ankara (MVA) and DNA/MVA vaccines.

Recently we demonstrated the control of a mucosal challenge with a pathogenic chimera of simian and human immunodeficiency virus (SHIV-89.6P) by priming with a Gag-Pol-Env-expressing DNA and boosting with a Gag-Pol-Env-expressing recombinant modified vaccinia virus Ankara (DNA/MVA) vaccine. Here we evaluate the ability of the MVA component of this vaccine to serve as both a prime and a boost for an AIDS vaccine.

Gene expression profile for schizophrenia: discrete neuron transcription patterns in the entorhinal cortex.

Background: Several lines of evidence indicate the altered function of the temporal lobe, including the hippocampus and entorhinal cortex (EC), is associated with schizophrenia. We used single-cell gene expression technologies to assess coordinate changes in the expression of multiple genes, including neuronal signaling and synaptic-related markers in EC layer II stellate neurons.

Methods: We used a single-neuron microdissection technique coupled with linear antisense RNA amplification and high density/candidate gene arrays to assess coordinate changes in gene expression.