Nucleus accumbens acetylcholine regulates appetitive learning and motivation for food via activation of muscarinic receptors

These experiments tested whether nucleus accumbens muscarinic or nicotinic acetylcholine receptor activation is required for rats to learn to lever press for sucrose. Muscarinic blockade with scopolamine (1.0 microg/side or 10.0 microg/side), but not nicotinic antagonism with mecamylamine (10.0 microg/side), inhibited learning and performance when applied to the core or shell. Further experiments showed that acute accumbens scopolamine treatment increased locomotor activity and reduced sucrose consumption. However, microanalyses of behavioral events in the instrumental chamber revealed that reductions of lever press performance during muscarinic blockade were not due to gross motor dysfunction. Accumbens core scopolamine was subsequently shown to reduce the amount of work rats would expend under a progressive ratio paradigm. These novel results implicate nucleus accumbens muscarinic receptors in the modulation of appetitive learning, performance, and motivation for food.     

The assessment of tubal functional status by tubal perfusion pressure measurements

The measurement of tubal perfusion pressures (TPP) is a recent advance in the field of gynaecoradiology. Measurement of TPP involves a standardized technique using transcervically placed tubal catheters which is reviewed in detail. TPP assesses the functional status of the Fallopian tubes, i.e. their ability to permit pregnancy. Infertile patients with normal TPP demonstrated a higher pregnancy rate (10 out of 23) than patients with elevated TPP (four out of 24, P < 0.05). Analysis of patients who had undergone a laparoscopy as well as measurement of TPP suggest that elevated TPP are highly indicative of tubal endometriosis. Tubal catheterization with wireguides was successful in reducing mildly elevated TPP. The impact of this procedure on pregnancy rates is not known. The use of the gynaecoradiological techniques discussed in this paper has reduced the need for diagnostic laparoscopy at our centre by >60%. This was achieved without compromise in pregnancy rates and has resulted in a considerable reduction in cost.     

Vaccine to confer to nonhuman primates complete protection against multistrain Ebola and Marburg virus infections

Filoviruses (Ebola and Marburg viruses) are among the deadliest viruses known to mankind, with mortality rates nearing 90%. These pathogens are highly infectious through contact with infected body fluids and can be easily aerosolized. Additionally, there are currently no licensed vaccines available to prevent filovirus outbreaks. Their high mortality rates and infectious capabilities when aerosolized and the lack of licensed vaccines available to prevent such infectious make Ebola and Marburg viruses serious bioterrorism threats, placing them both on the category A list of bioterrorism agents. Here we describe a panfilovirus vaccine based on a complex adenovirus (CAdVax) technology that expresses multiple antigens from five different filoviruses de novo. Vaccination of nonhuman primates demonstrated 100% protection against infection by two species of Ebola virus and three Marburg virus subtypes, each administered at 1,000 times the lethal dose. This study indicates the feasibility of vaccination against all current filovirus threats in the event of natural hemorrhagic fever outbreak or biological attack.     

Selective serotonin receptor stimulation of the medial nucleus accumbens differentially affects appetitive motivation for food on a progressive ratio schedule of reinforcement

Previously, we reported that stimulation of selective serotonin (5-HT) receptor subtypes in the nucleus accumbens shell differentially affected consumption of freely available food. Specifically, activation of 5-HT₆ receptors caused a dose-dependent increase in food intake, while the stimulation of 5-HT_1/7 receptor subtypes decreased feeding [34]. The current experiments tested whether similar pharmacological activation of nucleus accumbens serotonin receptors would also affect appetitive motivation, as measured by the amount of effort non-deprived rats exerted to earn sugar reinforcement. Rats were trained to lever press for sugar pellets on a progressive ratio 2 schedule of reinforcement. Across multiple treatment days, three separate groups (N = 8–10) received bilateral infusions of the 5-HT₆ agonist EMD 386088 (at 0.0, 1.0 and 4.0 μg/0.5 μl/side), the 5-HT_1/7 agonist 5-CT (at 0, 0.5, 1.0, or 4.0 μg/0.5 μl/side), or the 5-HT_2C agonist RO 60-0175 fumarate (at 0, 2.0, or 5.0 μg/0.5 μl/side) into the anterior medial nucleus accumbens prior to a 1-h progressive ratio session. Stimulation of 5-HT₆ receptors caused a dose-dependent increase in motivation as assessed by break point, reinforcers earned, and total active lever presses. Stimulation of 5-HT_1/7 receptors increased lever pressing at the 0.5 μg dose of 5-CT, but inhibited lever presses and break point at 4.0 μg/side. Injection of the 5-HT_2C agonist had no effect on motivation within the task. Collectively, these experiments suggest that, in addition to their role in modulating food consumption, nucleus accumbens 5-HT₆ and 5-HT_1/7 receptors also differentially regulate the appetitive components of food-directed motivation.     

Up-regulation of beta-chemokines and down-modulation of CCR5 co-receptors inhibit simian immunodeficiency virus transmission in non-human primates

A non-cognate mechanism of protection against human immunodeficiency virus-1 (HIV-1) infection involves up-regulation of beta-chemokines, which bind and may down-modulate the CCR5 co-receptors, thereby preventing transmission of M-tropic HIV-1. The objective of this investigation was to evaluate this mechanism in vivo in non-human primates. Rhesus macaques were immunized by a modified targeted lymph nodes (TLN) route with recombinant simian immunodeficiency virus (SIV) glycoprotein 120 (gp120) and p27 in alum, and adsorbed recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) with either interleukin (IL)-2 or IL-4. Immunization induced significant increases in the concentrations of CD8 cell-derived suppressor factor (CD8-SF), regulated on activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, and down-modulation of the proportion of cells expressing CCR5 (r = 0.737, P<0.05). The macaques were then challenged with SIVmac 220 by the rectal mucosal route. The plasma SIVmac RNA showed a significant inverse correlation with the CD8-SF or the concentration of the three beta-chemokines (r = 0.831 and 0.824, P<0.01), but a positive correlation between the proportion of CCR5+ cells and SIVmac RNA (r = 0.613, P = 0.05). These results demonstrate for the first time in vivo that immunization up-regulates beta-chemokines, which may down-modulate CCR5 co-receptors, and both functions are significantly correlated with the viral load. Hence, the non-cognate beta-chemokine-CCR5 mechanism should be considered as complementary to specific immunity in vaccination against HIV.     

Who gains or who loses weight? Psychosocial factors among first-year university students

Self-reported weight changes over 7 months and their relation to psychosocial characteristics (self-esteem, depression, social support, perceived stress and transition perception) and eating attitudes and behaviors (restrained eating and Eating Disorder Inventory subscales [EDI]) were assessed in first-year male and female students at six Canadian universities (N=2753). Results showed small but significant weight increases over time in males and females (M=1.5 kg). Males who lost weight versus those who gained reported greater negative well-being and more negative feelings about university transition. Females who either lost or gained weight had higher initial restraint and EDI scores than did weight maintainers. At 3 months, total EDI and body dissatisfaction increased in female weight gainers compared to weight losers, plus greater drive for thinness compared to weight maintainers. Thus, males distressed at the transition from high school to university appear more likely to lose weight while well-adjusted males are more likely to gain weight. For females, however, weight gain is associated with more negative well-being and preoccupations with weight and eating.     

Isolation, cloning, and expression of a 70-kilodalton plasminogen binding protein of Borrelia burgdorferi.

Surface receptors for plasminogen are expressed by many gram-positive and gram-negative bacteria and may play a role in the dissemination of organisms by binding plasminogen, which upon conversion to plasmin can digest extracellular matrix proteins. Two plasminogen binding proteins have been identified for Borrelia burgdorferi, outer surface protein A and a 70-kDa protein (BPBP). We purified BPBP by plasminogen affinity chromatography and obtained its amino acid sequence by Edman degradation of a tryptic digest. The gene coding for BPBP was isolated from a lambda-ZAP II genomic library with probes developed from sequenced portions of the protein. This gene was expressed in Escherichia coli; the recombinant product was seen by antibody raised against native BPBP and also bound 125I-labeled plasminogen. The experimentally derived amino acid sequences corresponded to the predicted sequence encoded by the BPBP gene. The deduced amino acid sequence for BPBP revealed significant similarity to p30, a 30-kDa protein of B. burgdorferi (54% identity and 65% similarity), to a 60-kDa protein in Borrelia coriaceae (66% identity and 80% similarity), to oligopeptide binding protein A of E. coli (34% identity and 57% similarity), and, more generally, to the periplasmic oligopeptide binding family of proteins.     

Oocyte morphology predicts outcome of intracytoplasmic sperm injection

To examine the influence of cytoplasmic morphology on the success rate of intracytoplasmic sperm injection (ICSI), the morphology of 837 metaphase II oocytes was assessed after cumulus stripping. The main abnormalities detected were excessive granularity, cytoplasmic inclusions such as vacuoles, smooth endoplasmic reticulum clustering and refractile bodies. Microinjection was performed in 538 oocytes with normal cytoplasm, 142 out of 161 with excessive granularity and 112 out of 138 with cytoplasmic inclusions. Very poor oocytes were not injected. No difference was found in fertilization rate. The embryos achieved cleaved normally and a similar number of good quality embryos among the three groups was noted. The outcome of transfer of embryos derived solely from normal oocytes (group A: 72 patients, 183 embryos) was compared with those from oocytes with cytoplasmic abnormalities (group B: 34 patients, 85 embryos). In group A, 17 clinical pregnancies (24% per patient, implantation rate 10%) were established. In group B, only one clinical pregnancy (3% per patient, implantation rate 1%) was established, from the transfer of embryos derived from oocytes with homogeneous granularity of the cytoplasm. No pregnancy resulted following the transfer of embryos from eggs with cytoplasmic inclusions. The difference was statistically significant. The outcome of ICSI is dependent on the quality of the oocytes retrieved. Normal fertilization and early embryo development were achieved in oocytes with abnormal cytoplasm morphology, but the resulting embryos failed to demonstrate the same implantation potential as those derived from oocytes with normal cytoplasm.