Homodimerization as a molecular switch between low and high efficiency PrPC cell surface delivery and neuroprotective activity

PrP^C is associated with a variety of functions, and its ability to interact with a multitude of partners, including itself, may largely explain PrP multifunctionality and the lack of consensus on the genuine physiological function of the protein in vivo. In contrast, there is a consensus in the literature that alterations in PrP^C trafficking and intracellular retention result in neuronal degeneration. In addition, a proteolytic modification in the late secretory pathway termed the α-cleavage induces the secretion of PrPN1, a PrP^C-derived metabolite with fascinating neuroprotective activity against toxic oligomeric Aβ molecules implicated in Alzheimer disease. Thus, studies focusing on understanding the regulation of PrP^C trafficking to the cell surface and the modulation of α-cleavage are essential. The objective of this commentary is to highlight recent evidences that PrP^C homodimerization stimulates trafficking of the protein to the cell surface and results in high levels of PrPN1 secretion. We also discuss a hypothetical model for these results and comment on future challenges and opportunities.     

Variation in N2 fixation,N and P contents of mycorrhizalVigna unguiculata in relation to the progressive development of extraradical hyphae ofGlomus mosseae

Summary Vigna unguiculata cv. 58–185 grown in a sterile Dek soil was inoculated withRhizobium sp. orRhizobium sp. plusGlomus mosseae. Response of the host plant to the treatments was estimated by periodic measurements of shoot and nodule dry weights, N₂ fixation (C₂H₂ reduction activity) and N and P contents up to the 50th day of the growth cycle. It was only 45 days after planting that shoot dry weight of dually inoculated plants differed significantly from that of plants inoculated withRhizobium sp. alone. Nodule dry weight and N₂ fixation of dually inoculated plants were significantly higher than those of plants inoculated withRhizobium sp. alone from day 20 after planting, but there was no significant difference in N content (%). During the first 20 days, shoot P content (%) of both sets of plants decreased progressively, P content of dually inoculated plants being lower than that of the others. Later, P content of dually inoculated plants increased rapidly whereas P content of the other plants remained constant. Increase in nodule dry weight, N₂ fixation and P content of dually inoculated plants corresponded to the onset of the development of the extra-radical hyphae ofGlomus mosseae. In the rhizosphere.

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Resumen Se cultivóVigna unguiculata cv. 58–185 en un suelo estéril tipo Dek, se inoculó conRhizobium sp. o conRhizobium sp. másGlomus mosseae. La respuesta de la planta huésped a los tratamientos se estudió midiendo periodicamente el peso seco de la parte aerea y de los nódulos, la fijación de N (actividad reductora de C₂H₂) y los contenidos de N y P hasta el 50° día del ciclo de crecimiento. La diferencia entre el peso seco de la parte aerea de las plantas con doble inoculación y aquellas inoculadas conRhizobium sp. unicamente, no fue significativa hasta 45 días despúés de la siembra. A los 20 días de la siembra tanto el peso seco de los nódulos como la fijación de nitrógeno de las plantas con doble inoculación eran significativamente superiores a los valores obtenidos para las plantas con soloRhizobium sp., aunque no se observaron diferencias en el contenido en N (%). Durante los primeros 20 días del ciclo el contenido en P (%) de ambos grupos de plantas disminuyó progresivamente, siendo los valores obtenidos por las plantas con doble inoculación inferiores a los de las demás. Más tarde el contenido en P de las plantas con doble inoculación aumentó rapidamente manteniéndose constante el de las demás. El incremento en el peso seco de los nódulos, en la fijación de N y en el contenido en P de las plantas con doble inoculación se correspondió con el inicio del desarrollo de las hifas extraradiculares deGlomus mosseae.

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Résumé On a inoculéV. unguiculata poussant dans un sol Dek stérile avecRhizobium etRhizobium plusGlomus mosseae. On a recherché la réponse de la plante-hôte à ces deux traitements en estimant périodiquement les poids des nodules et des parties aériennes de la plante, la fixation d'azote (activité réductrice de C₂H₂), les teneurs en N et P jusqu'au 50^e jour du cycle de végétation. C'est seulement au 45^e jour après la plantation que le poids sec des parties aériennes des plantes inoculées avec deux symbiotes (plantes doublement inoculées) diffère significativement de celui des plantes inoculées avec Rhizobium seul. Le poids sec des nodules et la fixation N₂ des plantes doublement inoculées sont significativement plus élevés que ceux des plantes inoculées avecRhizobium seul au 20^e jour après la plantation mais il n'y a pas de différence significative pour la teneur en N (%). Pendant les 20 premiers jours, la teneur en P (%) des parties aériennes des deux catégories de plantes décroit progressivement; la teneur en P des plantes doublement inoculées est plus faible que celle des plantes inoculées seulement avecRhizobium. Plus tard, la teneur en P des plantes doublement inoculées augmente rapidement tandis que celle des autres plantes reste constante. L'accroissement du poids sec des nodules, de la fixation d'azote et de la teneur en P observé chez les plantes doublement inoculées correspond au démarrage du développement des hyphes extra-radicales deGlomus mosseae dans la rhizosphère.

     

IR vibrational CD in model deoxyoligonucleotides: observation of the B----Z phase transition and extended coupled oscillator intensity calculations

The first observation of ir vibrational CD (VCD) in small model DNA molecules is reported. The VCD signals in the 1550-1750-cm-1 spectral region, which originate from coupling of carbonyl stretching modes of the nucleic acid bases, are found to be sensitive to the handedness of the polymer helix. The formalism to calculate VCD intensities of polymers is developed from the exciton model derived earlier by Tinoco [(1963) Radiation Res. 20, 133; (1960) J. Chem. Phys. 33, 1332; (1964) J. Am. Chem. Soc. 86, 297] and Schellman and co-workers [(1975) Biopolymers 14, 173; (1969) J. Phys. Chem. 73, 28]. The resulting equations, which are a direct extension of the dimeric case known as the "coupled oscillator," are used in model calculations of the helical polymers.     

Effects of direct transfer from freshwater to seawater on respiratory and circulatory variables and acid-base status in rainbow trout

Summary The effects of increased ambient salinity (35 mg · ml^-1) were studied at 1, 6, and 24 h after direct transfer of rainbow trout from freshwater to seawater. Two series of experiments were carried out successively. The first series was designed to simultaneously study all the respiratory (except Hb affinity for O₂), circulatory, and acid-base variables in each fish. In this series, fish were fitted with catheters chronically inserted into the cardiac bulbus, the dorsal aorta, and the opercular and buccal cavities. In the second series, designed to study haemoglobin O₂ affinity, fish were fitted with only a dorsal aorta catheter. The ventilatory flow ( ) was markedly increased just after transfer (by 55% at 1 h), then more moderately (by 20% at 6 h and 32% at 24 h). The initial hyperventilation peak was associated with frequent couphing motions. These ventilatory changes resulted essentially from increase in ventilatory amplitude. Initially, standard oxygen consumption (MM}O₂) decreased slightly, the moderately increased (by 12% at 24 h), so that the oxygen convection requirement ( ) increased substantially. In spite of an increased ventilation, the partial pressure of oxygen in arterial blood (P _aO₂) decreased slightly at 1 h, prior to returning to control levels, while partial pressure of carbon dioxide in arterial blood (P _aCO₂) was not significantly decreased. Gill oxygen transfer factor decreased substantially at 1 h (by 35%) then more moderately (by 7% at 1 h and 12% at 24 h). These results suggest a decrease in gas diffusing capacity of the gills. As P _aCO₂ remained approximatively unchanged, the gradual decrease in arterial pH (pH_a) from 7.94 to 7.67 at 24 h must therefore be regarded as a metabolic acidosis. The strong ion difference decreased markedly because the concentration of plasma chloride increased more than that of sodium. Arterial O₂ content (C _aO₂) gradually decreased (by 38% at 24 h) simultaneously with the decrease in pH_a, while the ratio P _aO₂/C _aO₂ increased. In parallel, seawater exposure induced a marked decrease in affinity of haemoglobin for O₂, so that at 24 h, P₅₀ was increased by 26% above the value obtained in freshwater-adapted trout. The increase in could be ascribed initially (at 1 h) to the decrease of P _aO₂ and later to a stimulation of respiratory neurons resulting from the lowered medullary interstitial pH. The decrease in C _aO₂ could be interpreted mainly as a consequence of a decreased affinity of haemoglobin for O₂, likely to be due to the blood acidosis and a predictable increase in chloride concentration within erythrocytes. Cardiac output ( ) slightly decreased at 1 h, then progressively increased by 30% at 24 h. Branchial vascular resistance increased at 1 h by 28%, then decreased by 18% of the control value at 24 h. Systemic vascular resistance decreased markedly by 40% at 24 h. As heart rate (HR) remained significantly unchanged, the cardiac stroke volume initially decreased then increased in relation to the changes in . The increase of , allowing compensation for the effect of decreased C _aO₂ in tissue O₂ supply, was interpreted as a passive consequence of the decrease in total vascular resistance occurring during seawater exposure.Abbreviations a.u. arbitrary units - C _aO₂ arterial oxygen content - pH₅₀ arterial pH at P₅₀ - C _vO₂ venous oxygen content - Hb haemoglobin - HR heart rate - Hct hematocrit - n_Hill Hill coefficient - O₂ standard oxygen consumption - P _aCO₂ arterial partial pressure of carbon dioxide - P _aO₂ arterial partial pressure of oxygen - P _vO₂ oxygen partial pressure in mixed venous blood - P₅₀ oxygen tension at half saturation of haemoglobin - P _VA, P _DA blood pressure in ventral and dorsal aorta - pH_a arterial pH - PIO₂, PEO₂ oxygen partial pressure of inspired and expired water - PO₂ oxygen partial pressure - cardiac output - SEM standard error of mean - S.I.D. strong ion difference - SV cardiac stroke volume - TO₂ gill oxygen transfer factor - U oxygen extraction coefficient - VA ventilatory amplitude - VF ventilatory frequency - VR_G, VR_S branchial and systemic vascular resistances - ventilatory flow - ventilatory oxygen convection requirement     

Differential DNA binding of nuclear proteins to a long terminal repeat region of the MCF13 and Akv murine leukemia viruses.

Long terminal repeat (LTR) sequences of murine leukemia viruses (MLVs) have been demonstrated to be mainly responsible for the pathogenic differences in these retroviruses. A region of the LTR which is downstream of the enhancer elements has been shown to contribute both to enhancer activity as well as to disease specificity of MLVs. We have identified protein-DNA complexes generated by this region of a lymphomagenic MLV (MCF13) and one which is nonpathogenic (Akv). One protein-DNA complex we have observed for this region is unique to MCF13 DNA sequences. Detection of protein involved in this unique MCF13 complex in different cell lines revealed that it was ubiquitous.     

Selection of Bradyrhizobium strains and provenances of Acacia mangium and Faidherbia albida: Relationship with their tolerance to acidity and aluminium

This work was designed to determine the role of the acidity and aluminium stress in the selection of partners in the Acacia symbioses with relevance to the persistence of the microsymbiont Bradyrhizobium in the soil and the growth and nodulation of the host plant respectively. Fifteen strains of Bradyrhizobium from Acacia mangium and Faidherbia albida formed a very homogenous acid tolerant group as indicated by their ability to grow better in a medium at pH 4.5 than in a medium at pH 6.8. By contrast, a growth experiment using an acid liquid media (pH 4.5), containing different concentrations of aluminium successfully identified strains sensitive to aluminium toxicity and those able to grow even in the presence of 100 M AlCl₃.Our results suggest that high amounts of aluminium in the soil rather than acidity (pH 4.5) were a major soil factor for selection of Bradyrhizobium strains capable of establishing a permanently high population under natural conditions.Unlike the behaviour of the microsymbiont, growth and nodulation of Acacia mangium and Faidherbia albida were not affected by aluminium, even at 100 M, but they might be significantly affected by medium acidity (pH 4.5) depending on plant provenances. It is therefore suggested that ability of the host plant to tolerate acidity stress should be taken into account first when screening effective Acacia-Bradyrhizobium combinations for use in afforestation trials.     

Widespread formation of intracellular calcium carbonates by the bloom-forming cyanobacterium Microcystis

The formation of intracellular amorphous calcium carbonates (iACC) has been recently observed in a few cultured strains of Microcystis, a potentially toxic bloom-forming cyanobacterium found worldwide in freshwater ecosystems. If iACC-forming Microcystis are abundant within blooms, they may represent a significant amount of particulate Ca. Here, we investigate the significance of iACC biomineralization by Microcystis. First, the presence of iACC-forming Microcystis cells has been detected in several eutrophic lakes, indicating that this phenomenon occurs under environmental conditions. Second, some genotypic (presence/absence of ccyA, a marker gene of iACC biomineralization) and phenotypic (presence/absence of iACC) diversity have been detected within a collection of strains isolated from one single lake. This illustrates that this trait is frequent but also variable within Microcystis even at a single locality. Finally, one-third of publicly available genomes of Microcystis were shown to contain the ccyA gene, revealing a wide geographic and phylogenetic distribution within the genus. Overall, the present work shows that the formation of iACC by Microcystis is common under environmental conditions. While its biological function remains undetermined, this process should be further considered regarding the biology of Microcystis and implications on the Ca geochemical cycle in freshwater environments.     

Bioguided Fractionation and Isolation of an Antiplasmodial Saponin from the Roots of Nauclea xanthoxylon (A.Chev.) Aubrév. (Rubiaceae)

The root extract of Nauclea xanthoxylon (A.Chev.) Aubrév. displayed significant 50 % inhibition concentration (IC₅₀s) of 0.57 and 1.26 μg/mL against chloroquine resistant and sensitive Plasmodium falciparum (Pf) Dd2 and 3D7 strains, respectively. Bio-guided fractionation led to an ethyl acetate fraction with IC₅₀s of 2.68 and 1.85 μg/mL and subsequently, to the new quinovic acid saponin named xanthoxyloside ( 1 ) with IC₅₀s of 0.33 and 1.30 μM, respectively against the tested strains. Further compounds obtained from ethyl acetate and hexane fractions were the known clethric acid ( 2 ), ursolic acid ( 3 ), quafrinoic acid ( 4 ), quinovic acid ( 5 ), quinovic acid 3-O-β-D-fucopyranoside ( 6 ), oleanolic acid ( 7 ), oleanolic acid 3-acetate ( 8 ), friedelin ( 9 ), β-sitosterol ( 10a ), stigmasterol ( 10b ) and stigmasterol 3-O-β-D-glucopyranoside ( 11 ). Their structures were characterised with the aid of comprehensive spectroscopic methods (1 and 2D NMR, Mass). Bio-assays were performed using nucleic acid gel stain (SYBR green I)-based fluorescence assay with chloroquine as reference. Extracts and compounds exhibited good selectivity indices (SIs) of >10. Significant antiplasmodial activities measured for the crude extract, the ethyl acetate fraction and xanthoxyloside ( 1 ) from that fraction can justify the use of the root of N. xanthoxylon in ethnomedicine to treat malaria.     

Influence of iron depletion on growth and production of catechol siderophores by different Frankia strains

Nine strains of Frankia isolated from six Casuarinaceae (including four Casuarina sp., one Allocasuarina and one Gymnostoma) and one Elaeagnaceae (Hippophae¨ rhamnoides) were screened for growth and production of siderophores in an iron-deficient liquid medium. Siderophore production was detected only in four strains (Cj, G2, CH and G82) using the CAS and Arnow assays. Salicylates formed more than 90% and dihydroxybenzoates formed less than 10% of all catechol-type siderophores produced. Growth of the former strains was less affected by iron deficiency than that of strains Rif, Thr, URU, BR and RT which do not produce siderophores. Optimal siderophore production by strain Cj was noted when iron concentration reached 0.5μm and was completely inhibited at an iron concentration of 10μm. The kinetics of siderophore production by strain Cj showed that siderophore synthesis was detectable during the growth stationary phase. Growth of Cj (a siderophore-producing strain) and of RT (a non-siderophore-producing strain) differed when 2,2-dipyridyl or ethylene di(o-hydroxyphenyl) acetic acid (EDDHA) was added to the iron-deficient growth medium. Frankia strain RT was the most sensitive to the detrimental effect of both iron chelators.     

IR (vibrational) CD of peptide beta-turns: a theoretical and experimental study of cyclo-(-Gly-Pro-Gly-D-Ala-Pro-).

IR vibrational CD (VCD) has been observed for the cyclic pentapeptide cyclo-(-Gly-Pro-Gly-D-Ala-Pro-) in solution in CDBr3. The observed VCD spectra do not resemble the VCD features of any of the previously reported peptide secondary structures, such as alpha-helical, "random coil," or sheet structures, and might be due to the beta-turn contained in this molecule. To shed light onto the origin of the observed spectra, VCD intensity calculations, based on the solution and solid-state structures of cyclo-(-Gly-Pro-Gly-D-Ala-Pro-), have been carried out. In addition, calculated VCD data for pure beta-turns are discussed.