Mu opioid receptors in the medial habenula contribute to naloxone aversion.

The medial habenula (MHb) is considered a brain center regulating aversive states. The mu opioid receptor (MOR) has been traditionally studied at the level of nociceptive and mesolimbic circuits, for key roles in pain relief and reward processing. MOR is also densely expressed in MHb, however, MOR function at this brain site is virtually unknown. Here we tested the hypothesis that MOR in the MHb (MHb-MOR) also regulates aversion processing. We used chnrb4-Cre driver mice to delete the Oprm1 gene in chnrb4-neurons, predominantly expressed in the MHb. Conditional mutant (B4MOR) mice showed habenula-specific reduction of MOR expression, restricted to chnrb4-neurons (50% MHb-MORs). We tested B4MOR mice in behavioral assays to evaluate effects of MOR activation by morphine, and MOR blockade by naloxone. Locomotor, analgesic, rewarding, and motivational effects of morphine were preserved in conditional mutants. In contrast, conditioned place aversion (CPA) elicited by naloxone was reduced in both naïve (high dose) and morphine-dependent (low dose) B4MOR mice. Further, physical signs of withdrawal precipitated by either MOR (naloxone) or nicotinic receptor (mecamylamine) blockade were attenuated. These data suggest that MORs expressed in MHb B4-neurons contribute to aversive effects of naloxone, including negative effect and aversive effects of opioid withdrawal. MORs are inhibitory receptors, therefore we propose that endogenous MOR signaling normally inhibits chnrb4-neurons of the MHb and moderates their known aversive activity, which is unmasked upon receptor blockade. Thus, in addition to facilitating reward at several brain sites, tonic MOR activity may also limit aversion within the MHb circuitry.

A 61-kb ring chromosome shows an ARS-dependent increase in its mitotic stability in the mcm2 mutant of yeast.

We have studied the effects of ARS addition and deletion on the maintenance of a 61-kb ring derivative of chromosome III in a minichromosome maintenance mutant of yeast carrying the mcm2-1 mutation. When this ring chromosome, CIIIR, had either of its two strong origins deleted, the resultant chromosome showed a much greater instability in the mutant as compared to that of the wild-type strain. Integration of more ARSs improved the maintenance of CIIIR in the mutant but not in the wild-type strain. Increase in the size of CIIIR, without any ARS addition, did not improve the stability in either strain. A spontaneous revertant for improved growth at 35 degrees C also co-reverted for minichromosome and CIIIR maintenance. The results suggest that ARS malfunctioning leads to minichromosome and chromosome loss from mutant cells, affecting their growth at higher temperatures.

Justicisaponin-I, a new triterpenoid saponin from Justicia simplex.

A new triterpenoid saponin, named justicisaponin-I, has been isolated from Justicia simplex D. Don. (Acanthaceae). It has been assigned oleanolic acid-3-O-beta-D-glucopyranosyl-4'-O-ferulate structure (1) on the basis of chemical transformation and comprehensive spectral evidence. Justicisaponin-I has produced significant sperm acrosomal membrane stabilizing action and may prove to be a potent antifertility agent.

Humoral immune responses in different clinical forms of tuberculosis.

To assess the antibody responses in different clinical forms of tuberculosis in an attempt to ascertain the specificity of such a response, so that it may be used as a diagnostic tool, 93 tuberculosis cases and 62 normal healthy controls were included in the study. All the cases were diagnosed as tuberculosis by clinical picture including radiological findings, blood picture, fine needle aspiration cytology (FNAC) or histopathological features, sputum examination or urine culture for acid-fast bacilli. IgM and IgG antibodies in the cases and controls were detected by ELISA using A60 antigen from M. bovis and compared with common diagnostic parameters of tuberculosis like presence of acid-fast bacilli in smear and tuberculin response. Antibody responses with A60 antigen has not been found to be specific and often failed to detect a new case.