KINETICS OF THE INNER ENAMEL EPITHELIUM IN THE ADULT RAT INCISOR DURING ACCELERATED ERUPTION

Inner enamel epithelial (IEE) cell production was compared in accelerated and normal eruption (control). Each group consisting of thirty rats received 1 μCi/g tritiated thymidine. The animals were sacrificed at short time intervals up to 14 hr after injection. The excised incisors were cut mid-sagittally and processed autoradiographically.
The fast growing incisor produces twice as many cells as the control. Increased cell production is achieved in two ways: proliferative pool expansion (by 25.5%) and generation time ( t _c) shortening to 16 hr ( t _c= 23 hr in the control). Generation time shortening resulted mainly from a diminution in t _g1= 8.6 hr ( t _g1= 14.1 hr in the control) and t _s which equaled 5.5 hr ( t _s= 7 hr in control). Mitotic times which equaled 0.4 hr and t _g2, 1.5 hr were identical in both groups.
The eruption/IEE cell production ratio equals 1.1 in both groups.     

Identification of a sphingosine-sensitive Ca2+ channel in the plasma membrane of Leishmania mexicana

The disruption of the intracellular Ca²⁺ homeostasis of Leishmania mexicana represents a major target for the action of drugs, such as amiodarone and miltefosine. However, little is known about the mechanism of Ca²⁺ entry to these cells. Here we show the presence of a Ca²⁺ channel in the plasma membrane of these parasites. This channel has many characteristics similar to the human L-type voltage-gated Ca²⁺ channel. Thus, Ca²⁺ entry is blocked by verapamil, nifedipine and diltiazem while Bay K 8644 opened this channel. However, different to its human counterpart, sphingosine was able to open this channel, while other well known sphingolipids had no effect. This fact could have important pharmacological implications.     

Ataxia-telangiectasia fibroblasts have less fibronectin mRNA than control cells but have the same levels of integrin and β-actin mRNA

Summary The cytological behavior of the spindle apparatus was studied in cells prone to nondisjunction (ND), i.e., PHA-stimulated lymphocytes derived from children suffering from different types of neoplasia. These cells, which exhibited a high frequency of nonspecific aneuploidy, revealed an increased resistance of the spindle fibers to colchicine, podophyllotoxin, and cold, wich was several times that of lymphocytes derived from healthy children. The results are in accord with previous findings showing a high resistance of spindle microtubules to the antimicrotubular agents colchicine, podopyllotoxin, vinblastine, and cold in PHA-stimulated lymphocytes derived from individuals prone to meiotic ND. It is therefore assumed that high resistance of the spindle apparatus to antimicrotubule agents characterizes cells at high risk for aneuploidy, and possibly, the overstabilized spindle fibers are responsible for failure of chromosomal disjunction.     

Regulation of output from the plant circadian clock

Plants, like many other organisms, have endogenous biological clocks that enable them to organize their physiological, metabolic and developmental processes so that they occur at optimal times. The best studied of these biological clocks are the circadian systems that regulate daily (approximately 24 h) rhythms. At the core of the circadian system in every organism are oscillators responsible for generating circadian rhythms. These oscillators can be entrained (set) by cues from the environment, such as daily changes in light and temperature. Completing the circadian clock model are the output pathways that provide a link between the oscillator and the various biological processes whose rhythms it controls. Over the past few years there has been a tremendous increase in our understanding of the mechanisms of the oscillator and entrainment pathways in plants and many useful reviews on the subject. In this review we focus on the output pathways by which the oscillator regulates rhythmic plant processes. In the first part of the review we describe the role of the circadian system in regulation at all stages of a plant's development, from germination and growth to reproductive development as well as in multiple cellular processes. Indeed, the importance of a circadian clock for plants can be gauged by the fact that so many facets of plant development are under its control. In the second part of the review we describe what is known about the mechanisms by which the circadian system regulates these output processes.     

Synthesis of Leishmania cap-4 intermediates, cap-2 and cap-3

Synthesis of Leishmania mRNA 5'-cap analogs, m(7)Gpppm(2)(6)AmpAm (cap-2), and m(7)Gpppm(2)(6)AmpAmpCm (cap-3) is reported. Binding affinities of those cap analogs for LeishIF4E proteins were determined using fluorescence spectroscopy. Cap-3 showed similar affinity to LeishIF4Es compared to the mature trypanosomatids cap structure (cap-4).     

Towards clarification of the biological role of microcystins, a family of cyanobacterial toxins

Microcystins constitute a serious threat to the quality of drinking water worldwide. These protein phosphatase inhibitors are formed by various cyanobacterial species, including Microcystis sp. Microcystins are produced by a complex microcystin synthetase, composed of peptide synthetases and polyketide synthases, encoded by the mcyA-J gene cluster. Recent phylogenetic analysis suggested that the microcystin synthetase predated the metazoan lineage, thus dismissing the possibility that microcystins emerged as a means of defence against grazing, and their original biological role is not clear. We show that lysis of Microcystis cells, either mechanically or because of various stress conditions, induced massive accumulation of McyB and enhanced the production of microcystins in the remaining Microcystis cells. A rise in McyB content was also observed following exposure to microcystin or the protease inhibitors micropeptin and microginin, also produced by Microcystis. The extent of the stimulation by cell extract was strongly affected by the age of the treated Microcystis culture. Older cultures, or those recently diluted from stock cultures, hardly responded to the components in the cell extract. We propose that lysis of a fraction of the Microcystis population is sensed by the rest of the cells because of the release of non-ribosomal peptides. The remaining cells respond by raising their ability to produce microcystins thereby enhancing their fitness in their ecological niche, because of their toxicity.     

Foam cell‐derived 4‐hydroxynonenal induces endothelial cell senescence in a TXNIP‐dependent manner

Vascular endothelial cell (VEC) senescence is considered an early event in the development of atherosclerotic lesions. Stressful stimuli, in particular oxidative stress, have been linked to premature senescence in the vasculature. Foam cells are a major source of reactive oxygen species and may play a role in the induction of VEC senescence; hence, we investigated their involvement in the induction of VEC senescence in a co‐culture transwell system. Primary bovine aortic endothelial cells, exposed to the secretome of THP‐1 monocyte‐derived foam cells, were analysed for the induction of senescence. Senescence associated β‐galactosidase activity and the expression of p16 and p21 were increased, whereas phosphorylated retinoblastoma protein was reduced. This senescent phenotype was mediated by 4‐hydroxnonenal (4‐HNE), a lipid peroxidation product secreted from foam cells; scavenging of 4‐HNE in the co‐culture medium blunted this effect. Furthermore, both foam cells and 4‐HNE increased the expression of the pro‐oxidant thioredoxin‐interacting protein (TXNIP). Molecular manipulation of TXNIP expression confirmed its involvement in foam cell‐induced senescence. Previous studies showed that peroxisome proliferator‐activated receptor (PPAR)δ was activated by 4‐hydroalkenals, such as 4‐HNE. Pharmacological interventions supported the involvement of the 4‐HNE‐PPARδ axis in the induction of TXNIP and VEC senescence. The association of TXNIP with VEC senescence was further supported by immunofluorescent staining of human carotid plaques in which the expression of both TXNIP and p21 was augmented in endothelial cells. Collectively, these findings suggest that foam cell‐released 4‐HNE activates PPARδ in VEC, leading to increased TXNIP expression and consequently to senescence.