Undernutrition and the development of brain neurotransmitter systems

While there are homeostatic mechanisms to protect the brain against wide fluctuations in the availability of essential nutrients, food deprivation is known to influence brain neurochemistry. Given the growing problem of infant undernutrition and the fact that the developing nervous system appears to be especially vulnerable to this type of insult, numerous studies have been conducted to define the relationship between nutritional factors and cellular growth and maturation in the brain. The data suggest that the development of both neural and nonneural elements are significantly affected by undernutrition. This includes processes and substances important for neurotransmission such as transmitter synthesis, degradation and receptor sites. Because many neuropsychiatric conditions can be traced to dysfunctions in synaptic neurochemistry, it is possible that some of the central nervous system abnormalities which result from childhood undernutrition may be a consequence of a modification in synaptic biochemistry. The present report reviews data relating to this issue with the aim of assessing its relevance to developmental neurobiology.     

Microtubule-kinetosome relationships in the motile cells of the Blastocladiales

Summary Motile cells of four members of the fungal order Blastocladiales have been examined with respect to distribution of intracellular microtubules. In all cases, the cellular microtubules originate from a sleeve of electron opaque material which surrounds the proximal third of the kinetosome. The microtubules run forward in the zoospores, ensheathing the nucleus and the nuclear cap before terminating at the anterior ends of the cells. Each cell contains 27 microtubules which are arranged in 9 groups of 3 tubules each. The significance of these observations with respect to centers of organization for microtubules is discussed.This work was supported by a grant (GB-4529) from the National Science Foundation.     

Inhaled PAF stimulates leukotriene and thromboxane A2 production in humans.

Platelet-activating factor (PAF) is a potent bronchoconstrictor in humans and has been implicated as an inflammatory mediator in asthma. This study was performed to evaluate whether PAF-induced bronchoconstriction in vivo could be mediated through the release of the bronchoconstrictor eicosanoids, thromboxane (Tx) A2 and the cysteinyl leukotrienes. Ten asthmatic subjects were studied on three occasions after bronchial challenges with aerosolized PAF, methacholine, or isotonic saline. PAF caused bronchoconstriction in all 10 subjects (mean maximal percent fall in specific airway conductance 48.2 +/- 4.6) and was matched by methacholine challenge. Saline caused no changes in specific airway conductance. Urinary leukotriene E4 was significantly elevated after inhaled PAF (366.0 +/- 66.9 ng/mmol creatinine, P less than 0.01) compared with methacholine (41.6 +/- 13.3) and saline (33.6 +/- 4.6). The major urinary TxA2 metabolite 2,3-dinor TxB2 was elevated after inhaled PAF (41.3 +/- 7.1 ng/mmol creatinine, P less than 0.01) compared with methacholine (14.0 +/- 2.7) and saline (17.1 +/- 3.9). Urinary 2,3-dinor 6-oxo-prostaglandin F1 alpha after PAF (22.2 +/- 1.4) was raised with respect to the methacholine challenge (13.9 +/- 1.8, P less than 0.02), although no significant increase was observed compared with the saline control (18.6 +/- 3.3). Inhaled PAF leads to the secondary generation of cysteinyl leukotrienes and TxA2, and it is possible that these mediate some of the acute effects of inhaled PAF in vivo.     

HIV Vaccine Trial Exploits a Dual and Central Role for Innate Immunity

Limited understanding of correlates of protection from HIV transmission hinders development of an efficacious vaccine. D. J. M. Lewis and colleagues (J. Virol. 88:11648–11657, 2014, doi:10.1128/JVI.01621-14) now report that vaginal immunization with an HIVgp140 vaccine linked to the 70-kDa heat shock protein downregulated the human immunodeficiency virus (HIV) coreceptor CCR5 (chemokine [C-C motif] receptor 5) and increased expression of the HIV resistance factor APOBEC3G (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3G), in women. These effects correlated with HIV suppression ex vivo. Thus, vaccine-induced innate responses not only facilitate adaptive immunity–they may prove to be critical for preventing HIV transmission.