Staggerer Mutant Mouse Purkinje Cells Do Not Contain Detectable Calmodulin mRNA

Within the cerebellum calmodulin mRNA is found predominantly in Purkinje cells, with lower levels in granule cells and interneurons. The message shows developmental increases during the first 14 days postnatally. Surviving Purkinje cells of the staggerer (sg/sg) mutant, which are grossly stunted and lack tertiary dendritic spines, contain no detectable calmodulin mRNA, as assayed by Northern blot or an enhanced biotinylated in situ hybridization. This is in contrast to both the Lurcher Purkinje cells and sg/sg granule cells, which express normal levels of this mRNA up until the time they disappear. The sg/sg phenotype can be explained by a defective Purkinje-cell-specific regulatory mechanism for calmodulin.     

Modes of Explanation in Anthropological Population Theory: Biological Determinism vs. Self-Regulation in Studies of Population Growth in Third World Countries

Anthropological theories of population growth in underdeveloped countries are considered and it is argued that most studies have concentrated exclusively on either deterministic or self-regulatory factors in population growth without regard to their probable interaction. A research strategy is proposed in which self-regulatory factors, especially the decision-making activities of individual parents, provide a primary focus of study but with careful attention to deterministic factors which constrain and influence the decision process . [population, underdevelopment, biology and self-regulation in population theory]     

Tetracaine blocks the responses of isolated acinar cells from rat parotid to carbachol but not to substance P

Carbachol and substance P stimulated ⁴⁵Ca²⁺ flux changes, ⁸⁶Rb⁺ efflux, and amylase secretion from acinar cells isolated fromrat parotid. The local anesthetic tetracaine blocked all of these measured responsed to carbachol, but none of the responses to substance P. Tetracaine must act at either the cholinergic receptor or at a subsequent transducing step in the cholinergic stimulus-response sequence. If tetracaine acts at one of the transducing steps between cholinergic receptor occupation and the physiological responses then the action of tetracaine must be at a locus in the cholinergic reaction scheme not shared by substance P, because tetracaine did not block any response of the parotid to substance P.     

Sequence and function of LuxO, a negative regulator of luminescence in Vibrio harveyi

Density-dependent expression of luminescence in Vibrio harveyi is regulated by the concentration of extracellular signal molecules (autoinducers) In the culture medium. A recombinant clone that restored function to one class of spontaneous dim mutants was found to encode a function required for the density-dependent response. Transposon Tn5 Insertions in the recombinant clone were isolated, and the mutations were transferred to the genome of V. harveyi for examination of mutant phenotypes. Expression of luminescence in V. harveyi strains with transposon insertions in one locus, luxO, was independent of the density of the culture and was similar in intensity to the maximal level observed in wild-type bacteria. Sequence analysis of luxO revealed one open reading frame that encoded a protein, LuxO, similar in amino acid sequence to the response regulator domain of the family of two-component, signal transduction proteins. The constitutive phenotype of LuxO∼ mutants indicates that LuxO acts negatively to control expression of luminescence, and relief of repression by LuxO in the wild type could result from interactions with other components in the Lux signalling system.     

Effects of cyclic mechanical stimulation of the cellular components of the heart: In vitro

Summary The response of the cellular components of the heart to cyclic mechanical stimulation is of particular importance because these cells are continually subjected to mechanical forces as a result of changes in blood volume and pressure. To directly investigate how mechanical tension affects these cellular components of the heart, an in vitro system that exposes the particular cell type (cardiac myocytes, endothelial cells, or fibroblasts) to a calibrated increase in cyclical linear stretch was developed. Cells were grown on silastic membranes coated with laminin and subjected to a 10% cyclical distention 10 times a minute for 72 h. Within 24 h of being exposed to the mechanical stretch, the cells became elongated and oriented perpendicular to the direction of the stretch. These results indicate that cyclical mechanical stimulation directly influences the cellular organization of the heart cells in vitro. This work was supported in part by grants HL 33656 and HL 24935 from the National Institutes of Health, Bethesda, MD.     

Multiple signalling systems controlling expression of luminescence in Vibrio harveyi: sequence and function of genes encoding a second sensory pathway

Density-dependent expression of luminescence in Vibrio harveyl is regulated by the concentration of extracellular signal molecules (autoinducers) in the culture medium. One signal-response system is encoded by the luxL,M,N locus. The luxL and luxM genes are required for the production of an autoinducer (probably β-hydroxybutryl homoserine lactone), and the luxN gene is required for the response to that autoinducer. Analysis of the phenotypes of LuxL,M and N mutants indicated that an additional signal-response system also controls density sensing. We report here the identification, cloning and analysis of luxP and luxQ, which encode functions required for a second density-sensing system. Mutants with defects in luxP and luxQ are defective in response to a second autoinducer substance. LuxQ, like LuxN, is similar to members of the family of two-component, signal transduction proteins and contains both a histidine protein kinase and a response regulator domain. Analysis of signalling mutant phenotypes indicates that there are at least two separate signal-response pathways which converge to regulate expression of luminescence in V. harveyl.     

Protein kinase C and NF-κB-dependent CD4 downregulation in macrophages induced by T cell-derived soluble factors: consequences for HIV-1 infection

Upon activation, CD4(+) T cells release cytokines, chemokines, and other soluble factors that influence the kinetics of HIV-1 replication in macrophages (M). In this article, we show that activation of human primary T cells suppresses the early stages of HIV-1 replication in human primary Mφ by downregulating the main cellular receptor for the virus CD4. The secreted factors responsible for this effect have a molecular mass greater than conventional cytokines, are independent of Th1 or Th2 polarization, and are not IFN-γ, IL-16, RANTES, or macrophage inhibitory factor, as revealed by cytokine array analysis and neutralization assays. CD4 downregulation is entirely posttranslational and involves serine phosphorylation of CD4 and its targeting to an intracellular compartment destined for acidification and degradation. CD4 downregulation is dependent on the activities of both protein kinase C and NF-κB as well as the proteasomes. Using high-resolution liquid chromatography-tandem mass spectrometry analysis in conjugation with label-free protein quantitation software, we found that proteins that promote Mφ adherence and spreading, such as attractin, fibronectin, and galectin-3-binding protein, were significantly overrepresented in the activated T cell supernatant fractions. These results reveal the existence of previously unreported anti-HIV-1 proteins, released by activated T cells that downregulate CD4 expression, and are of fundamental importance to understand the kinetics of HIV infection in vivo.     

Rates and intensity of re-infection with human helminths after treatment and the influence of individual, household, and environmental factors in a Brazilian community

This study quantifies the rate and intensity of re-infection with human hookworm and Schistosoma mansoni infection 12 months following successful treatment, and investigates the influence of socio-economic, geographical and environmental factors. A longitudinal study of 642 individuals aged over 5 years was conducted in Minas Gerais State, Brazil from June 2004 to March 2006. Risk factors were assessed using interval censored regression for the rate and negative binomial regression for intensity. The crude rate and intensity of hookworm re-infection was 0·21 per year (95% confidence interval (CI) 0·15-0·29) and 70·9 epg (95% CI 47·2-106·6). For S. mansoni the rate was 0·06 per year (95% CI 0·03-0·10) and intensity 6·51 epg (95% CI 3·82-11·11). Rate and intensity of re-infection with hookworm were highest among males and positively associated with previous infection status, absence of a toilet and house structure. Rate and intensity of S. mansoni re-infection were associated with previous infection status as well as geographical, environmental and socio-economic factors. The implications of findings for the design of anti-helminth vaccine trials are discussed.