Nardilysin, a basic residues specific metallopeptidase that mediates cell migration and proliferation

Nardilysin (NRDc), a metallopeptidase of the M16 family, presents, in vitro, cleavage specificity for basic residues. Depending on the cell type, it is cytoplasmic, exported or cell surface associated. As a new receptor for heparin-binding EGF-like growth factor (HB-EGF), NRDc was recently shown to be involved in cellular migration and proliferation. Since for those processes its enzymatic activity is not required, it is now evident that nardilysin fulfills at least two distinct functions, i.e. an HB-EGF modulator and a peptidase.     

PCSK9 reduces the protein levels of the LDL receptor in mouse brain during development and after ischemic stroke

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in cholesterol homeostasis through enhanced degradation of the LDL receptor (LDLR) in liver. As novel inhibitors/silencers of PCSK9 are now being tested in clinical trials to treat hypercholesterolemia, it is crucial to define the physiological consequences of the lack of PCSK9 in various organs. LDLR regulation by PCSK9 has not been extensively described during mouse brain development and injury. Herein, we show that PCSK9 and LDLR are co-expressed in mouse brain during development and at adulthood. Although the protein levels of LDLR and apolipoprotein E (apoE) in the adult brain of Pcsk9(-/-) mice are similar to those of wild-type (WT) mice, LDLR levels increased and were accompanied by a reduction of apoE levels during development. This suggests that the upregulation of LDLR protein levels in Pcsk9(-/-) mice enhances apoE degradation. Upon ischemic stroke, PCSK9 was expressed in the dentate gyrus between 24 h and 72 h following brain reperfusion. Although mouse behavior and lesion volume were similar, LDLR protein levels dropped ～2-fold less in the Pcsk9(-/-)-lesioned hippocampus, without affecting apoE levels and neurogenesis. Thus, PCSK9 downregulates LDLR levels during brain development and following transient ischemic stroke in adult mice.     

Characteristics of the MIS 5 pollen record from Lathuile Gare, 456 m a.s.l., at the SW border of the Lac d’Annecy (northern French Alps)

The layers studied, parts of banquettes, consist of limnic clayey-silty fine sediments with some intercalated horizons of shaly coal and lacustrine mud flow rubble. In the lower part of the record the Bornette interglacial has been established. This is characterised by high values of Corylus and a significant presence of Quercus and Hedera in addition to a wide-spread presence of Buxus, Ulmus and Carpinus. A linkage of this interglacial to the Eemian (MIS 5e) can be considered an applicable hypothesis. Quantitatively, however, Alnus and Picea exceed all these thermophytics. However the lower part of Lathuile Gare is also characterised by palynological duplications untypical of the Eemian, for example two distinct peaks of Corylus linked to a significant decline in Picea in PZ 3 and 5 and higher values of Abies and Picea in PZ 4 and 6. Possibly these duplications can be explained by a rapid sub-aquatic flow causing a doubling of the beds. In the upper part of the Lathuile Gare record two mean climatic recession periods in the lowest and the second uppermost section (PZ 9 and 15) were detected with increased values of NAP and Pinus in PZ 9 and decreased proportions of Picea in PZ 15. They represent the Chaperon b interstadial and the Lathuile stadial correlated hypothetically with the St. Germain Ib (MIS 5c2) and the Melisey II (MIS 5b) stadial. The enclosed middle part, the Chaparon c interstadial, revealing similarities with the St. Germain Ic (MIS 5c1), is dominated by Picea and Pinus. Only a few thermophilous taxa occur in the middle of this interstadial in PZ 11.     

Isolement,action biologique et evolution des substances paragoniales contenues dans le spermatophore d'Acanthoscelides obtectus (Coleoptère)

In Acanthoscelides obtectus, some male secretions deposited in the spermatophore during mating reach the blood of the females and stimulate oögenesis. Water extracts from spermatophores injected into a female abdomen stimulate oögenesis but do not influence egg-laying or sexual receptivity. After column chromatograph of spermatophores, aqueous extracts on Sephadex G 25 Coarse, G 25 Superfine, and G 15, an active fraction has been isolated. This injected into the abdomen of virgin females stimulates oögenesis at low concentrations, but it is toxic at higher concentrations. This fraction was examined by paper electrophoresis at low voltage and then chromatographed on G 10 Sephadex. Two peaks were obtained: the first corresponds to the paragonial substance A which stimulates oögenesis at 0,2 10^?3 μg/μl concentration. The second contains the paragonial substance B. At a 0,3 10^?3 ug/μl concentration this substance is toxic. First this toxicity inhibits oögenesis and then causes the death of most females at higher concentrations. The toxic effect appears 2 or 3 days after injection. These two substances are purified on paper chromatography and the biological activities are contained in a zone of R_f 0.25 to 0.45 (paragonial substance A) and in a zone of 0.16–0.30 R_f (paragonial substance B).The paragonial substances disappear from the spermatophore after mating. Aqueous extracts of spermatophores obtained 6 hr after mating do not stimulate oögenesis and do not have any toxic effect. The chemical nature of these both fractions is not yet determined because the quantity of extracts obtained at the end of the purification is very low.The action of both paragonial substances is similar to the action of hormones. The paragonial substances influence unknown receptors at low concentration after a latent period. The origin of the paragonial B substance was not determined, but this substance which inhibits oögenesis at low concentrations could be an antagonist of paragonial A substance.     

Predator-prey models with delay and prey harvesting

It is known that predator-prey systems with constant rate harvesting exhibit very rich dynamics. On the other hand, incorporating time delays into predator-prey models could induce instability and bifurcation. In this paper we are interested in studying the combined effects of the harvesting rate and the time delay on the dynamics of the generalized Gause-type predator-prey models and the Wangersky-Cunningham model. It is shown that in these models the time delay can cause a stable equilibrium to become unstable and even a switching of stabilities, while the harvesting rate has a stabilizing effect on the equilibrium if it is under the critical harvesting level. In particular, one of these models loses stability when the delay varies and then regains its stability when the harvesting rate is increased. Computer simulations are carried to explain the mathematical conclusions. Received: 1 March 2000 / Revised version: 7 September 2000 /?Published online: 21 August 2001