BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development

Bone morphogenetic protein-4 (BMP-4) is a multifunctional developmental regulator. BMP-4 is synthesized as an inactive precursor that is proteolytically activated by cleavage following the amino acid motif -Arg-Ser-Lys-Arg-. Very little is known about processing and secretion of BMPs. The proprotein convertases (PCs) are a family of seven structurally related serine endoproteases, at least one of which, furin, cleaves after the amino acid motif -Arg-X-Arg/Lys-Arg-. To examine potential roles of PCs during embryonic development we have misexpressed a potent protein inhibitor of furin, alpha1-antitrypsin Portland (alpha1-PDX) in early Xenopus embryos. Ectopic expression of alpha1-PDX phenocopies the effect of blocking endogenous BMP activity, leading to dorsalization of mesoderm and direct neural induction. alpha1-PDX-mediated neural induction can be reversed by co-expression of downstream components of the BMP-4 signaling pathway. Thus, alpha1-PDX can block BMP activity upstream of receptor binding, suggesting that it inhibits an endogenous BMP-4 convertase(s). Consistent with this hypothesis, alpha1-PDX prevents cleavage of BMP-4 in an oocyte translation assay. Using an in vitro digestion assay, we demonstrate that four members of the PC family have the ability to cleave BMP-4, but of these, only furin and PC6B are sensitive to alpha1-PDX. These studies provide the first in vivo evidence that furin and/or PC6 proteolytically activate BMP-4 during vertebrate embryogenesis.     

Disappearance of antibodies to Cromer blood group system antigens during mid pregnancy

We are reporting the case of a 94-year-old male patient with a 10-year history of Parkinson's disease, who was admitted to our hospital with acute obstruction of esophageal passage. Esophageal obstruction was refractory to endoscopic intervention. However, discontinuation of the pre-existing levodopa medication led to its resolution within hours. While dysphagia is commonly encountered in patients with Parkinson's disease, the observed succession of drug discontinuation and resolution of obstruction in this case suggests an as yet rarely described side effect of levodopa. This potential side effect should be included in the differential diagnosis of dysphagia in Parkinson's disease, especially in the case of older patients, who may exhibit an increased rate of intestinal absorption of levodopa.     

In vitro cleavage of internally quenched fluorogenic human proparathyroid hormone and proparathyroid-related peptide substrates by furin. Generation of a potent inhibitor

The cleavage of parathyroid hormone (PTH) from its precursor proparathyroid hormone (pro-PTH) is accomplished efficiently by the proprotein convertase furin (Hendy, G. N., Bennett, H. P. J., Gibbs, B. F., Lazure, C., Day, R., and Seidah, N. G. (1995) J. Biol. Chem. 270, 9517-9525). We also showed that a synthetic peptide comprising the -6 to +7 sequence of human pro-PTH is appropriately cleaved by purified furin in vitro. The human pro-PTH processing site Lys-Ser-Val-Lys-Lys-Arg differs from the consensus furin site Arg-Xaa-(Lys/Arg)-Arg that is represented by Arg-Arg-Leu-Lys-Arg in the cleavage site of pro-PTH-related peptide (pro-PTHrP). An earlier study demonstrated that an internally quenched fluorogenic substrate bearing an O-aminobenzoyl fluorescent donor at the NH2 terminus and an acceptor 3-nitrotyrosine near the COOH terminus was appropriately cleaved by the convertases furin and PC1 (Jean, F., Basak, A., DiMaio, J., Seidah, N. G., and Lazure, C. (1995) Biochem. J. 307, 689-695). Here, we have synthesized a series of internally quenched fluorogenic substrates based upon the pro-PTH and pro-PTHrP sequences to determine which residues are important for furin cleavage. Purified recombinant furin and PC1 cleaved the human pro-PTH internally quenched substrate at the appropriate site in an identical manner to that observed with the nonfluorescent peptide. Several substitutions in the P6-P3 sequence were well tolerated; however, replacement of the Lys at the P6 position with Gly and replacement of the P3 Lys by an acidic residue led to markedly compromised cleavage by furin. Furin activity was very sensitive to substitution in P' positions. Replacement of Ser at P1' with Gly and Val at P2' with Ala generated substrates that were less well cleaved. Substitution at the P1' position of Val for Ser in conjunction with Ala for Val at P2', as well as a single substitution of Lys for Val at P2', generated specific inhibitors of furin cleavage. The findings of this study open the way to the rational design of inhibitors of furin with therapeutic potential.     

Structure of kaolinite flocs formed in an aqueous medium

The structure evolution of kaolinite flocs during their formation in aqueous medium was studied under a scanning electron microscope by hypercritical drying with liquid CO₂, as a function of Fe electrolyte content. Without any Fe electrolyte, a sediment with uniform porosity formed by accumulation of particles under gravity. Fresh Fe electrolytes made it possible to aggregate the kaolinite particles to flocs with an architecture consistent with diffusion limited aggregation (DLA). With 0.67 mM Fe, a single shrinking DLA flocs layer formed. With 3.33 mM Fe, extensive face to face aggregation of the clay particles occurred and a sediment with preferred horizontal orientation accumulated. With 0.17 mM Fe a shrinking DLA floc layer and a uniformly porous accumulated sediment formed concurrently, while with 1.67 mM Fe a shrinking DLA floes layer and an accumulated sediment with preferred orientation formed concurrently.     

Effect of the composition of some sulphide minerals on cyanidation and use of lead nitrate and oxygen to alleviate their impact

An investigation was carried out on synthetic ores containing high purity pyrite, pyrrhotite and chalcopyrite and on two gold ores currently processed to evaluate the impact of cyanicides on cyanidation and to improve the leaching performance by using a pre-leaching, injecting oxygen and adding lead nitrate. With regard to the synthetic ores, it was found that pyrrhotite did not generate a high cyanide consumption while pyrite and chalcopyrite were detrimental. Pre-leaching was deleterious for the ore containing chalcopyrite while pre-leaching with lead nitrate was very efficient to decrease the reactivity of the ore containing pyrite. The two gold ores studied had very different compositions. The low sulphide ore had a low sulphide content (1.36% S), present as pyrrhotite while the second had a very high sulphide content (20.2% S), in the form of pyrite, pyrrhotite and chalcopyrite. The efficiency of the process conditions was peculiar to the ores. The high sulphide ore required a stronger, longer pre-leaching period (12 h) with greater amounts of lime (7.0 kg/t) and lead nitrate (600 g/t) than the low-sulphide ore. The ore with a low sulphide content required a pre-leaching of only 1 h with a small quantity of Pb(NO₃)₂ (50 g/t) and leaching can be performed at 360 ppm NaCN to allow a recovery of 96.4% Au and a low cyanide consumption at 0.18 kg/t. As for the high sulphide ore, cyanidation had to be conducted at 560 ppm NaCN to recover 88.4% Au with a cyanide consumption of 0.80 kg/t. An increase in the amount of lime enhanced oxidation of soluble sulphides. Lead nitrate stabilized copper and iron dissolution by forming a passivation layer at the surface of sulphide minerals. Lead nitrate also prevented the formation of a passive layer at the surface of gold.     

Collaboration and underlying issues or the surprises of cooperative dialogues

The observation of cooperative dialogues between production and maintenance workers of a dairy has revealed that socio-organisational factors had strong effects on cooperation. In order to better understand the nature of these factors, the sociological literature on autonomy, rule generation, negotiation and conflict is reviewed. A methodology based on inferential pragmatics is developed in order to analyze what takes place socially in operational exchanges and makes it possible to identify rules for cooperative functioning that are specific to this work situation, and that relate to the defence of the territory of each individual. The conclusion stresses that cooperative dialogues are also the place where social stakes are adjusted and discusses potential applications of the proposed framework to the design of cooperative systems.     

Laser-produced plasma light source for extreme ultraviolet lithography

Pulsed Nd:YAG lasers have been developed to achieve high peak power and high pulse repetition rate. These systems are being used as drivers for laser-produced plasmas which efficiently convert the 1064-nm laser output to extreme ultraviolet (EUV) light at 13.5 nm for future microlithography systems. The requirements for laser-produced plasma EUV light sources and their integration in lithography tools for high-volume manufacturing are reviewed to establish the key design issues for high-power lasers and plasma targets. Xenon has been identified as a leading target material to realize the goals of intense EUV emission and clean operation. Recent progress in high-power diode-pumped Nd:YAG lasers and xenon targets for EUV generation is reviewed, showing that laser-produced plasma sources meet the needs for current EUV lithography development tools. Future directions to meet EUV source requirements for high-volume manufacturing tools are discussed.     

3.2 Tbit/s (80 × 40 Gbit/s) phase-shaped binary transmissionover 3 × 100 km with 0.8 bit/s/Hz efficiency

50 GHz-spaced 80 × 40 Gbit/s WDM transmission over 300 km of TeraLight^TM fibre is demonstrated without polarisation demultiplexing, using the PSBT format. A record capacity of 3.2 Tbit/s is thus achieved over the C-band only, with a spectral efficiency of 0.8 bit/s/Hz     

Culturally sanctioned secrets? Latino men's nondisclosure of HIV infection to family, friends, and lovers.

Spanish-speaking Latino men (n?=?107) were more likely than English-speaking Latinos (n?=?85) and Whites (n?=?206) to withhold their HIV-positive serostatus and their gay or bisexual orientation from significant others, especially family members. Similar effects were observed when Latinos were divided by birthplace and when analyses controlled for sociodemographic and medical factors. Reasons for revealing or concealing an HIV diagnosis varied across targets. Although both Latinos and Whites were more likely to withhold their diagnosis from their parents to prevent worrying them than to avoid personal rejection, this tendency was somewhat stronger among Latinos. Our findings suggest that some traditional values may deter Latinos from seeking HIV-related social support in times of need. (PsycINFO Database Record (c) 2010 APA, all rights reserved)