Elevated glutamate and NMDA disrupt production of the second messenger cyclic GMP in the early postnatal mouse cortex

The second messenger cyclic guanosine monophosphate (cGMP) plays many roles during nervous system development. Consequently, cGMP production shows complex patterns of regulation throughout early development. Elevated glutamate levels are known to increase cGMP levels in the mature nervous system. A number of clinical conditions including ischemia and perinatal asphyxia can result in elevated glutamate levels in the developing brain. To investigate the effects of elevated glutamate levels on cGMP in the developing cortex we exposed mouse brain slices to glutamate or N‐methyl D ‐aspartate (NMDA). We find that at early postnatal stages when the endogenous production of cGMP is high, glutamate or NMDA exposure results in a significant lowering of the overall production of cGMP in the cortex, unlike the situation in the mature brain. However, this response pattern is complex with regional and cell‐type specific exceptions to the overall lowered cGMP production. These data emphasize that the response of the developing brain to physiological disturbances can be different from that of the mature brain, and must be considered in the context of the developmental events occurring at the time of disturbance. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009     

Inhibition of nicotinamide nucleotide transhydrogenase in rat liver submitochondrial particles by dicyclohexylcarbodi-imide and butanedione

Nicotinamide nucleotide transhydrogenase in rat liver submitochondrial particles is inhibited by treatment with NN'-dicyclohexylcarbodi-imide or butane-2,3-dione. Both inhibitions are pseudo-first-order with respect to enzyme activity. The reaction order with respect to inhibitor is close to unity for butanedione, but is significantly lower than unity for dicyclohexylcarbodi-imide.     

Use of leuprolide to treat endometriosis in a rhesus macaque.

Endometriosis was diagnosed in an aged dysmenorrheic rhesus monkey (Macaca mulatta) after biopsy of a 7 cm abdominal mass which could not be completely resected due to extensive adhesions. A 6-month course of treatment with leuprolide, a gonadotropin-releasing hormone agonist, resulted in cessation of menstrual cycles and marked clinical improvement. Dysmenorrhea and hypovolemic shock occurred 2 months after therapy was completed. Despite supportive treatment and resumption of leuprolide, the primate's clinical deterioration and abdominal mass enlargement necessitated euthanasia. To our knowledge, this is the first report of a case of endometriosis in a rhesus macaque treated with a gonadotropin-releasing hormone agonist. Although prolonged leuprolide therapy was clinically effective, its cost and the difficulty in early diagnosis of endometriosis may limit its use in nonhuman primate medicine.     

Is there Ca2+(Sr2+)-3-hydroxybutyrate symport in rat-liver mitochondria? A reappraisal

The observation in this laboratory that respiration and Sr2+ import were stimulated by the addition of 3-hydroxybutyrate to suspensions of N-ethylmaleimide-treated mitochondria respiring in state 6, after the addition of Sr2+, in a sucrose medium containing choline as substrate, led to the proposal by Moyle and Mitchell [(1977) FEBS Lett. 84, 135-140] that there is a Ca2+(Sr2+)-3-hydroxybutyrate symporter in rat liver mitochondria. However, experiments described in the present paper support a different interpretation. Under the conditions of the experiments by Moyle and Mitchell, the rate of respiration and the poise of Sr2+ accumulation are mainly limited, not by delta mu H+, but by lack of respiratory substrate. Even though N-ethylmaleimide is a potent inhibitor of 3-hydroxybutyrate dehydrogenase, we have found that, somewhat surprisingly, under the special conditions of these experiments, sufficient 3-hydroxybutyrate dehydrogenase activity remains available to account for the 3-hydroxybutyrate-dependent respiratory stimulation and Sr2+ import.     

Functional,Non-Clonal IgMa-Restricted B Cell Receptor Interactions with the HIV-1 Envelope gp41 Membrane Proximal External Region

The membrane proximal external region (MPER) of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is whether the failure to make gp41 MPER-specific broadly neutralizing antibodies like 2F5 and 4E10 is due to structural constraints with the gp41 MPER, or alternatively, if gp41 MPER epitope-specific B cells are lost to immunological tolerance. An equally important question is how B cells interact with, and respond to, the gp41 MPER epitope, including whether they engage this epitope in a non-canonical manner i.e., by non-paratopic recognition via B cell receptors (BCR). To begin understanding how B cells engage the gp41 MPER, we characterized B cell-gp41 MPER interactions in BALB/c and C57BL/6 mice. Surprisingly, we found that a significant (∼7%) fraction of splenic B cells from BALB/c, but not C57BL/6 mice, bound the gp41 MPER via their BCRs. This strain-specific binding was concentrated in IgM^hi subsets, including marginal zone and peritoneal B1 B cells, and correlated with enriched fractions (∼15%) of gp41 MPER-specific IgM secreted by in vitro-activated splenic B cells. Analysis of Igh^a (BALB/c) and Igh^b (C57BL/6) congenic mice demonstrated that gp41 MPER binding was controlled by determinants of the Igh^a locus. Mapping of MPER gp41 interactions with IgM^a identified MPER residues distinct from those to which mAb 2F5 binds and demonstrated the requirement of Fc C_H regions. Importantly, gp41 MPER ligation produced detectable BCR-proximal signaling events, suggesting that interactions between gp41 MPER and IgM^a determinants may elicit partial B cell activation. These data suggest that low avidity, non-paratopic interactions between the gp41 MPER and membrane Ig on naïve B cells may interfere with or divert bnAb responses.     

Acid-Precipitated M Protein Compared with a Column-Eluted M Protein Preparation from Type 12, Group A Streptococci

An M protein preparation of group A streptococci, precipitated with 0.03 m sodium acetate buffer (pH 4.0) was compared with a column-eluted M protein preparation. Absorption spectra and methyl pentose content were similar in both preparations. Acrylamide gel electrophoresis patterns were different. Gel diffusion demonstrated two lines of fusion in the preparations. More antigens could be demonstrated in both preparations by using immunoelectrophoresis. Neither the pH 4 precipitate nor the column-eluted preparation appeared to be a pure M protein preparation.     

驱捕叉角羚的方法

本文介绍美国西部捕捉叉角羚的简易方法--驱捕法。主要论述了围捕设计,聚群技术和捕捉步骤。作者指出,围捕圈要选择在叉角羚集中的方圆8公里内。围捕圈包括翼栏、隐蔽处、围捕栏及围捕栏内的捕捉栏。围捕栏要设置在山脊或隆起地形物之后,以免被驱入的动物发现。另外,围捕圈的入口应确定在盛行风的30度范围内,以便直升飞机在风里工作时能得到最大的机动性。围捕栏内的捕捉栏,便于人们能从较大动物群中分出可以控制一定数量的动物进行捕捉。这个结构能使捕捉动物更容易。适时使用直升飞机及人与人拉起粗帆布形成的人列,是将动物驱入围捕栏的有效手段。此外,捕捉叉角羚时,2个人对付1个动物,能保证捕捉人员和叉角羚均不受伤害。 作者报道了1980-1985年中,每年的11-2月,用此方法成功地活捕到2110只叉角羚,与围捕直接有关的动物死亡仅2.2%。对107头叉角羚进行追踪生物遥测的结果表明,围捕后的死亡率极小以至勿需考虑。用此方法,能在2天内从建起围捕栏,捕捉、标记60-100多只成体叉角羚,然后拆除。 作者认为此项围捕方法,与以前报道过的方法比较,能在较短时间内以最小死亡率捕获到较大数量的叉角羚。