Individual differences in extraversion and dopamine genetics predict neural reward responses

Psychologists have linked the personality trait extraversion both to differences in reward sensitivity and to dopamine functioning, but little is known about how these differences are reflected in the functioning of the brain's dopaminergic neural reward system. Here, we show that individual differences in extraversion and the presence of the A1 allele on the dopamine D2 receptor gene predict activation magnitudes in the brain's reward system during a gambling task. In two functional MRI experiments, participants probabilistically received rewards either immediately following a behavioral response (Study 1) or after a 7.5 s anticipation period (Study 2). Although group activation maps revealed anticipation- and reward-related activations in the reward system, individual differences in extraversion and the presence of the D2 Taq1A allele predicted a significant amount of inter-subject variability in the magnitudes of reward-related, but not anticipation-related, activations. These results demonstrate a link between stable differences in personality, genetics, and brain functioning.     

Structure and stability of internodal myelin in mouse models of hereditary neuropathy

Peripheral neuropathies often result in abnormalities in the structure of internodal myelin, including changes in period and membrane packing, as observed by electron microscopy (EM). Mutations in the gene that encodes the major adhesive structural protein of internodal myelin in the peripheral nervous system of humans and mice--P0 glycoprotein--correlate with these defects. The mechanisms by which P0 mutations interfere with myelin packing and stability are not well understood and cannot be provided by EM studies that give static and qualitative information on fixed material. To gain insights into the pathogenesis of mutant P0, we used x-ray diffraction, which can detect more subtle and dynamic changes in native myelin, to investigate myelin structure in sciatic nerves from murine models of hereditary neuropathies. We used mice with disruption of one or both copies of the P0 gene (models of Charcot-Marie-Tooth-like neuropathy [CMT1B] or Dejerine-Sottas-like neuropathy) and mice with a CMT1B resulting from a transgene encoding P0 with an amino terminal myc-tag. To directly test the structural role of P0, we also examined a mouse that expresses P0 instead of proteolipid protein in central nervous system myelin. To link our findings on unfixed nerves with EM results, we analyzed x-ray patterns from unembedded, aldehyde-fixed nerves and from plastic-embedded nerves. From the x-ray patterns recorded from whole nerves, we assessed the amount of myelin and its quality (i.e. relative thickness and regularity). Among sciatic nerves having different levels of P0, we found that unfixed nerves and, to a lesser extent, fixed but unembedded nerves gave diffraction patterns of sufficient quality to distinguish periods, sometimes differing by a few Angstroms. Certain packing abnormalities were preserved qualitatively by aldehyde fixation, and the relative amount and structural integrity of myelin among nerves could be distinguished. Measurements from the same nerve over time showed that the amount of P0 affected myelin's stability against swelling, thus directly supporting the hypothesis that packing defects underlie instability in "live" or intact myelin. Our findings demonstrate that diffraction can provide a quantitative basis for understanding, at a molecular level, the membrane packing defects that occur in internodal myelin in demyelinating peripheral neuropathies.     

Chronological changes of neurofilament 200 kDa immunoreactivity in the lateral olfactory tract after transient forebrain ischemia in gerbils

This study was carried out to investigate the transient ischemia-induced changes of neurofilament 200 kDa (NF-200) immunoreactivity and protein content in the gerbil lateral olfactory tract (LOT) after 5 min of transient forebrain ischemia. Weak NF-200 immunoreactivity was detectable in the LOT in the sham-operated group. In this group, a few somata of mitral cells showed weak NF-200 immunoreactivity. One day after transient ischemia, NF-200 immunoreactivity in the LOT was increased significantly. NF-200 immunoreactivity in the LOT by 15 days after ischemia was similar to that in the 1 day post-ischemic group. In this time period, strong NF-200 immunoreactivity was expressed in the mitral cell processes, but the immunoreactivity in the mitral cell somata was significantly decreased. Thereafter, NF-200 immunoreactivity in the LOT was decreased significantly by 30 days after ischemic insult. At this time after ischemia, NF-200 immunoreactivity in the mitral cell dendrites was significantly decreased. The result of Western blot study showed that the pattern of NF-200 expression was similar to that of immunohistochemistry after ischemia-reperfusion. Our result suggests that changes of NF-200 protein in the gerbil LOT may be related to response to ischemic damage and that the axonal transport followed transient ischemia may be disturbed.     

A case of acute cholestatic hepatitis associated with the seeds of Psoralea corylifolia (Boh-Gol-Zhee)

The potential hepatotoxicity of herbal remedies is usually ignored in daily life. One such compound, Boh-Gol-Zhee (in Chinese, Bu Ku Zi), appeared to be associated with the occurrence of acute cholestatic hepatic injury in the following case. Some alternative medicine therapists claim that Psoralea corylifolia is effective for the treatment of osteoporosis. We observed a case of acute cholestatic hepatitis associated with the use of the seeds of Psoralea corylifolia in amounts over 10 times the usual dose in a postmenopausal woman. Liver biopsy showed zone three necroses, degenerating cells, cholestasis, and infiltrations with inflammatory cells. This case stresses the need to warn of the potential hepatotoxicity of the seed of Psoralea corylifolia, especially in a large dose.     

Multiple congenital brachymetatarsia. A one-stage combined shortening and lengthening procedure without iliac bone graft

We performed nine metatarsal and three proximal phalangeal lengthenings in five patients with congenital brachymetatarsia of the first and one or two other metatarsal bones, by a one-stage combined shortening and lengthening procedure using intercalcary autogenous bone grafts from adjacent shortened metatarsal bones. Instead of the isolated lengthening of the first and the other metatarsal bones, we shortened the adjacent normal metatarsal and used the excised bone to lengthen the short toes, except for the great toe, to restore the normal parabola. One skin incision was used. All the operations were performed bilaterally and the patients were followed up for a mean period of 69.5 months (29 to 107). They all regained a nearly normal parabola and were satisfied with the cosmetic results. Our technique is straightforward and produces good cosmetic results. Satisfactory, bony union is achieved, morbidity is low, and no additional surgery is required for the removal of metal implants.     

Methanol extract of Dioscoreae Rhizoma inhibits pro-inflammatory cytokines and mediators in the synoviocytes of rheumatoid arthritis

Dioscoreae Rhizoma (MDR), the root of Dioscorea tokoro MAKINO, has been used for the treatment of arthritis, muscular pain and urinary diseases in oriental medicine. The present work evaluates a methanol extract of Dioscoreae Rhizoma (MDR). MDR did not show any cytotoxic effect on mouse lung fibroblast cells (mLFCs) or human fibroblast-like synovial cells (hFLSCs). However, it significantly reduced the proliferation of hFLSCs stimulated by interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). MDR significantly inhibited the production of TNF-alpha and IL-1beta as well as down-regulating the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in IL-1beta- and TNF-alpha-stimulated hFLSCs. MDR also effectively reduced the level of reactive oxygen species (ROS) in these cells. Taken together, these findings provide evidence that MDR may be a candidate for the treatment of rheumatoid arthritis (RA).     

Ether-linked biflavonoids from Quintinia acutifolia

The New Zealand tree Quintinia acutifolia has yielded four biflavonoids, the new 2,3,2',3'-tetrahydroochnaflavone (3), and its 7,7'-di-O-methyl derivative (1). The rare 7-O-methyl-2,3,2',3'-tetrahydroochnaflavone (2) and 2',3'-dihydroochnaflavone (4), both previously identified only from members of the Ochnaceae, were also isolated. Structures were determined by spectroscopic methods. This is the first report of biflavonoids from the Grossulariaceae.     

Using machine vision to analyze and classify Caenorhabditis elegans behavioral phenotypes quantitatively

Mutants with abnormal patterns of locomotion, also known as uncoordinated (Unc) mutants, have facilitated the genetic dissection of many important aspects of nervous system function and development in the nematode Caenorhabditis elegans. Although a large number of distinct classes of Unc mutants can be distinguished by an experienced observer, precise quantitative definitions of these classes have not been available. Here we describe a new approach for using automatically-acquired image data to quantify the locomotion patterns of wild-type and mutant worms. We designed an automated tracking and imaging system capable of following an individual animal for long time periods and saving a time-coded series of digital images representing its motion and body posture over the course of the recording. We have also devised methods for measuring specific features from these image data that can be used by the classification and regression tree classification algorithm to reliably identify the behavioral patterns of specific mutant types. Ultimately, these tools should make it possible to evaluate with quantitative precision the behavioral phenotypes of novel mutants, gene knockout lines, or pharmacological treatments.