Opponent appetitive-aversive neural processes underlie predictive learning of pain relief

Termination of a painful or unpleasant event can be rewarding. However, whether the brain treats relief in a similar way as it treats natural reward is unclear, and the neural processes that underlie its representation as a motivational goal remain poorly understood. We used fMRI (functional magnetic resonance imaging) to investigate how humans learn to generate expectations of pain relief. Using a pavlovian conditioning procedure, we show that subjects experiencing prolonged experimentally induced pain can be conditioned to predict pain relief. This proceeds in a manner consistent with contemporary reward-learning theory (average reward/loss reinforcement learning), reflected by neural activity in the amygdala and midbrain. Furthermore, these reward-like learning signals are mirrored by opposite aversion-like signals in lateral orbitofrontal cortex and anterior cingulate cortex. This dual coding has parallels to 'opponent process' theories in psychology and promotes a formal account of prediction and expectation during pain.     

Affective and Behavioral Stress Outcomes in Alzheimer's Caregivers

Few investigations have looked at behavioral stress outcomes in Alzheimer's caregivers. This study documented concentration deficits to examine behavioral outcomes of stress in 33 Alzheimer's Disease (AD) caregivers and in 33 age-, sex-, and race-matched controls. As hypothesized, caregivers showed less persistence than controls in solving problems from a standard test of problem-solving ability. In addition, caregivers tended to make more errors than controls on a standard proofreading task ( p < .09). In AD caregivers, cognitive deficits (represented by lower scores on problem-solving and concentration tasks) may be representative of a broader deficit in concentration that impairs the ability of caregivers to provide for their own needs and the needs of the family member for whom they are caring.     

Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation

The only molecular similarity in sex determination found so far among phyla is between the Drosophila doublesex (dsx) and Caenorhabditis elegans mab-3 genes. dsx and mab-3 contain a zinc finger-like DNA-binding motif called the DM domain, perform several related regulatory functions, and are at least partially interchangeable in vivo. A DM domain gene called Dmrt1 has been implicated in male gonad development in a variety of vertebrates, on the basis of embryonic expression and chromosomal location. Such evidence is highly suggestive of a conserved role(s) for Dmrt1 in vertebrate sexual development, but there has been no functional analysis of this gene in any species. Here we show that murine Dmrt1 is essential for postnatal testis differentiation, with mutant phenotypes similar to those caused by human chromosome 9p deletions that remove the gene. As in the case of 9p deletions, Dmrt1 is dispensable for ovary development in the mouse. Thus, as in invertebrates, a DM domain gene regulates vertebrate male development.     

Temporal processing of information: the role of the medial prefrontal cortex and hippocampus: theoretical comment on Gilmartin and McEchron (2005)

M. R. Gilmartin and M. D. McEchron (2005) reported that single cells recorded in the prelimbic cortex of rats during the acquisition of trace fear conditioning display multiple patterns of neuronal firing during the trace. These finding are discussed in the context of the role of the prelimbic cortex in processing temporal information during trace conditioning and delayed matching- or nonmatching-to-sample paradigms based on both electrophysiology and lesion evidence. In addition, evidence is provided for a role of the hippocampus in supporting temporal processing of information and its potential interaction with the prelimbic cortex.     

A comparison of the Fishbein and Ajzen and the Triandis attitudinal models for the prediction of exercise intention and behavior

The main purpose of the study was to compare the efficiency of the Fishbein and Ajzen and the Triandis models to predict (1) the intention to participate regularly in some physical activities during free time within a 3-week period and (2) the exercise behavior within these 3 weeks among a group of 166 subjects, aged 22 to 65 years. Our results show that the Triandis model was as efficient as the Fishbein and Ajzen model in predicting the exercise behavior. However, the results obtained from the Triandis model demonstrate the importance of the habit of exercising in predicting the exercise behavior. Moreover, the Triandis model was superior to the Fishbein and Ajzen model in explaining behavioral intention. Of particular interest was the salience of the affective, social, and personal belief components of the Triandis model. In addition, from a practical perspective, this comparative study showed that (1) to exercise regularly is perceived as hard work, and (2) individuals believe that it is their own responsibility to exercise or not to exercise.     

Nonencapsulated Neisseria meningitidis strain produces amylopectin from sucrose: altering the concept for differentiation between N. meningitidis and N. polysaccharea

Neisseria meningitidis is the causative agent of meningococcal sepsis and meningitis. Neisseria polysaccharea is a nonpathogenic species. N. polysaccharea is able to use sucrose to produce amylopectin, a starch-like polysaccharide, which distinguishes it biochemically from the pathogenic species N. meningitidis. The data presented here indicate that this may be an insufficient criterion to distinguish between these two species. The nonencapsulated Neisseria strain 93246 expressed a phenotype of amylopectin production similar to that of N. polysaccharea. However, strain 93246 reacted with N. meningitidis serotype 4 and serosubtype P1.14 monoclonal antibodies and showed the N. meningitidis L1(8) lipo-oligosaccharide immunotype. Further analyses were performed on four genetic loci in strain 93246, and the results were compared with 7 N. meningitidis strains, 13 N. polysaccharea strains, and 2 N. gonorrhoeae strains. Three genetic loci, opcA, siaD, and lgt-1 in strain 93246, were the same as in N. meningitidis. Particularly, the siaD gene encoding polysialyltransferase responsible for biosynthesis of N. meningitidis group B capsule was detected in strain 93246. This siaD gene was inactivated by a frameshift mutation at the poly(C) tract, which makes strain 93246 identical to other nonencapsulated N. meningitidis strains. As expected, the ams gene encoding amylosucrase, responsible for production of amylopectin from sucrose, was detected in strain 93246 and all 13 N. polysaccharea strains but not in N. meningitidis and N. gonorrhoeae strains. These data suggest that strain 93246 is nonencapsulated N. meningitidis but has the ability to produce extracellular amylopectin from sucrose. The gene for amylopectin production in strain 93246 was likely imported from N. polysaccharea by horizontal genetic exchange. Therefore, we conclude that genetic analysis is required to complement the traditional phenotypic classification for the nonencapsulated Neisseria strains.     

Contribution of epitope specificity to the binding of monoclonal antibodies to the capsule of Cryptococcus neoformans and the soluble form of its major polysaccharide,glucuronoxylomannan

Incubation of encapsulated cryptococci with monoclonal antibodies (MAbs) specific for glucuronoxylomannan (GXM), the major capsular polysaccharide of Cryptococcus neoformans, produces two distinct capsular quellung-type reactions termed rim and puffy. The type of capsular reaction that occurs is determined by the epitope specificity of the MAb and the serotype of the yeast cell. Several biological activities, including opsonic activity, complement activation, and protective efficacy, are associated with the type of capsular reaction produced by a MAb. The goal of this study was to examine the reactivities of two families of anti-GXM MAbs with serotype A and D capsular polysaccharides in several immunochemical assays, including agglutination, immunofluorescence, quantitative precipitation, and enzyme-linked immunosorbent assay, in an effort to identify serological assays that are predictive of the capsular quellung reaction. The results showed that the type of capsular reaction (rim versus puffy) is a qualitative assessment of antibody-capsule interaction that cannot be predicted on the basis of a serological assay. The results further showed that antibody reactivity demonstrated in one serological assay is not necessarily predictive of results in another assay, particularly in cases where one assay examines antibody-capsule interactions, e.g., agglutination, and another assay examines interaction of antibody with soluble GXM. Taken together, the results suggest caution in interpretation of immunochemical assays for anti-GXM antibodies and recommend the use of multiple assays formats when studying anticryptococcal antibodies.     

Introduction of new clones of penicillin-nonsusceptible Streptococcus pneumoniae in Hong Kong

Analysis of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) isolates in Hong Kong by use of a combination of antibiogram typing, serotyping, multilocus sequence typing, and pulsed-field gel electrophoresis indicated that the dissemination of PNSP was the result of the spread of international clones: variants of the Spain(23F)-1 or Spain(6B)-2 clones were the predominant PNSP isolates from 1994 to 1997 and remained so, but Taiwan(19F)-14 and Taiwan serotype 6B clones were disseminated in Hong Kong in 1999 and 2000. Concomitant changes in antibiotic susceptibility profiles, with the rate of susceptibility to chloramphenicol rising from 10% in the period from 1994 to 1997 to 31% (P < 0.001) in 1999 and 2000, were noted to accompany the shift of clones.     

Murine oviduct epithelial cell cytokine responses to Chlamydia muridarum infection include interleukin-12-p70 secretion

Epithelial cells play an important role in host defense as sentinels for invading microbial pathogens. Chlamydia trachomatis is an intracellular bacterial pathogen that replicates in reproductive tract epithelium. Epithelial cells lining the reproductive tract likely play a key role in triggering inflammation and adaptive immunity during Chlamydia infections. For this report a murine oviduct epithelial cell line was derived in order to determine how epithelial cells influence innate and adaptive immune responses during Chlamydia infections. As expected, oviduct epithelial cells infected by Chlamydia muridarum produced a broad spectrum of chemokines, including CXCL16, and regulators of the acute-phase response, including interleukin-1alpha (IL-1alpha), IL-6, and tumor necrosis factor alpha. In addition, infected epithelial cells expressed cytokines that augment gamma interferon (IFN) production, including IFN-alpha/beta and IL-12-p70. To my knowledge this is the first report of a non-myeloid/lymphoid cell type making IL-12-p70 in response to an infection. Equally interesting, infected epithelial cells significantly upregulated transforming growth factor alpha precursor expression, suggesting a mechanism by which they might play a direct role in the pathological scarring seen as a consequence of Chlamydia infections. Data from these in vitro studies predict that infected oviduct epithelium contributes significantly to host innate and adaptive defenses but may also participate in the immunopathology seen with Chlamydia infections.     

Use of multiepitope polyproteins in serodiagnosis of active tuberculosis

Screening of genomic expression libraries from Mycobacterium tuberculosis with sera from tuberculosis (TB) patients or rabbit antiserum to M. tuberculosis led to the identification of novel antigens capable of detecting specific antibodies to M. tuberculosis. Three antigens, Mtb11 (also known as CFP-10), Mtb8, and Mtb48, were tested together with the previously reported 38-kDa protein, in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in TB patients. These four proteins were also produced as a genetically fused polyprotein, which was tested with two additional antigens, DPEP (also known as MPT32) and Mtb81. Sera from individuals with pulmonary and extrapulmonary TB, human immunodeficiency virus (HIV)-TB coinfections, and purified protein derivative (PPD)-positive and PPD-negative status with no evidence of disease were tested. In samples from HIV-negative individuals, the ELISA detected antibodies in >80% of smear-positive individuals and >60% smear-negative individuals, with a specificity of approximately 98%. For this group, smears detected 81.6% but a combination of smear and ELISA had a sensitivity of approximately 93%. The antigen combination detected a significant number of HIV-TB coinfections as well as antibodies in patients with extrapulmonary infections. Improved reactivity in the HIV-TB group was observed by including the antigen Mtb81 that was identified by proteomics. The data indicate that the use of multiple antigens, some of which are in a single polyprotein, can be used to facilitate the development of a highly sensitive test for M. tuberculosis antibody detection.