Posibles roles de los receptores a manosa-6-fosfato durante la organogénesis

Los receptores a manosa-6-fosfato (MPRs) son glicoproteínas que presentan como función principal el transporte de las hidrolasas lisosomales al lisosoma. Se conocen hasta el momento dos formas de MPRs: el receptor catión dependiente de 46 kDa (CD-MPR), que necesita iones bivalentes como Ca+2, Mg+2 o Mn+2 en muy bajas concentraciones para interactuar con sus ligandos; y el receptor catión independiente de 300 kDa (CI-MPR) que actúa aún en ausencia de los iones. Estos receptores son los dos únicos miembros de la familia de lectinas de tipo P, puesto que son las únicas lectinas que reconocen los residuos de manosa fosforilada. Como ambos MPRs coexisten en la mayoría de los tipos celulares y presentan similar distribución subcelular, aún se discute el verdadero rol de estos receptores y la razón de su coexistencia en la mayoría de las células. En esta tesis hemos estudiado algunas propiedades de los MPRs durante el desarrollo perinatal de órganos de rata y observamos que ambos receptores poseen diferentes comportamientos en este período. El CI-MPR disminuye su expresión mientras que el número de sitios activos (Bmax) permanece constante y la afinidad se incrementa para ligandos fosfomanosilados durante la maduración, tanto en hígado como en cerebro. Este receptor se presenta en mayor proporción en la membrana plasmática fetal comparado con adultos. Desde nuestros hallazgos postulamos que la función del CI-MPR en los primeros estadíos del desarrollo podría estar orientada al crecimiento y diferenciación celular y que posteriormente su afinidad por las enzimas lisosomales aumenta debido a modificaciones en su estructura. De este modo, en los adultos funciona como transportador de enzimas lisosomales. El CD-MPR en cambio, aumenta su expresión, su número de sitios activos y su afinidad a partir de los 10 días postnatales en hígado, estas propiedades se correlacionan con la mayor expresión de enzimas lisosomales y con una mayor interacción de las enzimas con CD-MPR en este período. Por ello postulamos que este receptor es fundamental en la biogénesis del aparato lisosomal entre los 10 y 20 días de desarrollo. En cerebro, el CD-MPR tiene algunas propiedades diferentes, mientras que la expresión es constante, el número de sitios activos disminuye y la afinidad se incrementa durante el desarrollo. Esto indicaría que en cerebro existe una maduración lisosomal diferente, iniciándose en una etapa temprana del desarrollo y terminando su desarrollo total hacia los 20 días postnatales.

Benthic and planktonic foraminifera of sediment core GIK17957-2

A detailed age model for core 17957-2 of the southern South China Sea was developed based on delta18O, coarse fraction, magnetostratigraphy, and biostratigraphy for the last 1500 kyr. The delta18O record has clear ~100-kyr cycles after the Mid-Pleistocene Revolution (MPR) at the entrance of marine isotopic stage (MIS) 22. Planktonic foraminifera responded to the MPR immediately, showing the increased sea surface temperature (SST) and dissolution after the MPR. Benthic foraminifera did not respond to it until the Brunhes/Matuyama boundary. Since the MPR, the depth of thermocline gradually became shallower until MISs 6-5. This major change within MISs 6-5 was also reflected in the decreased SSTs and increased productivity and Deep Water Mass. Thus two major Pleistocene paleoceanographic changes were found: One was around the MPR; the other occurred within MISs 6-5, which speculatively might be ascribed to the reorganization of surface and deep circulation, possibly induced by tectonic forces.

Benthic foraminiferal faunas of Miocene to Holocene sediments of ODP Site 184-1143 from the southern South China Sea

Deep-sea benthic foraminiferal assemblages from Ocean Drilling Program (ODP) Site 1143 located in the southern South China Sea (SCS) were investigated to evaluate the relationship between faunal composition patterns and paleoceanographic changes during the last 6 million years (late Miocene to Holocene). We used multivariate statistics (correspondence analysis) to analyze carbon-flux-related changes in assemblage composition of benthic foraminifers. Additional proxies for carbon flux and deep-water ventilation include delta13C records of epifaunal Cibicidoides wuellerstorfi and infaunal Uvigerina peregrina var. dirupta and Melonis pompilioides, benthic foraminiferal accumulation rates (BFARs), diversity indices, and relative abundances of indicator species. We observe three significant benthic faunal changes in the southern South China Sea during the last 6 million years. Strong fluctuations in BFAR and relative abundance of productivity indicator species between glacial and interglacial stages after the mid-Pleistocene revolution (MPR) at approximately 0.9 Ma, indicating stronger seasonal carbon flux fluctuations, are accompanied by the extinction of such species as Stilostomella spp. Increases in carbon flux indicator species are coupled with an overall decrease in benthic foraminifer diversity around 3.0 Ma in the late Pliocene. This may indicate increasing carbon flux in a period of productivity maximum caused by enhanced offshore upwelling from intensified winter monsoon wind strength.

Age models of ODP Leg 175 holes

A multiproxy approach including the use of stable isotopes, magnetic characterization analyses, and organic geochemistry has been adopted to consider factors such as productivity and terrigenous input over the past 1.5 m.y. at two areas off the western coast of Africa. These factors can, in turn, be used to consider variability in ocean circulation and upwelling in addition to changes in climate on the African continent. In particular, studies focused on the influence of glacial-interglacial cycles and evidence for the mid-Pleistocene revolution (MPR), a complex change in climate that occurred at ~1 Ma. A comparison of the records from the two areas drilled during Ocean Drilling Program Leg 175, the Congo Basin, at a latitude of 5°S (Holes 1076A and 1077A), and the Walvis Ridge, at 17°S (Hole 1081A), demonstrates that these sites are affected by different localized factors. The sites in the Congo Basin are strongly influenced by freshwater and sediment from the Congo River, whereas the site at the Walvis Ridge is located in the center of oceanic upwelling and contains a more marine signal. Evidence also suggests that the two sites responded differently to both long- and short-term climatic variations. In particular, the response at the Walvis Ridge to the MPR occurred over an extended period, from 1.1 to 0.8 Ma, and was associated with a change in the dominant source of terrigenous input to the site in conjunction with a change in the productivity signal. In the Congo Basin, the response to the MPR was more rapid, occurring between 0.9 and 0.8 Ma. During this period, the influence of the Congo River became significant. However, productivity records only began to respond toward the end of this interval, at 0.8 Ma.

Use of calculus of variations to determine the shape of hovering rotors of minimum power and its application to micro air vehicles

In this paper, calculus of variations and combined blade element and momentum theory (BEMT) are used to demonstrate that, in hover, when neither root nor tip losses are considered; the rotor, which minimizes the total power (MPR), generates an induced velocity that varies linearly along the blade span. The angle of attack of every blade element is constant and equal to its optimum value. The traditional ideal twist (ITR) and optimum (OR) rotors are revisited in the context of this variational framework. Two more optimum rotors are obtained considering root and tip losses, the ORL, and the MPRL. A comparison between these five rotors is presented and discussed. The MPR and MPRL present a remarkable saving of power for low values of both thrust coefficient and maximum aerodynamic efficiency. The result obtained can be exploited to improve the aerodynamic behaviour of rotary wing micro air vehicles (MAV). A comparison with experimental results obtained from the literature is presented.

Proper sorting of the cation-dependent mannose 6-phosphate receptor in endosomes depends on a pair of aromatic amino acids in its cytoplasmic tail

The 67-amino acid cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor (CD-MPR) contains a signal(s) that prevents the receptor from entering lysosomes where it would be degraded. To identify the key residues required for proper endosomal sorting, we analyzed the intracellular distribution of mutant forms of the receptor by Percoll density gradients. A receptor with a Trp19 → Ala substitution in the cytoplasmic tail was highly missorted to lysosomes whereas receptors with either Phe18 → Ala or Phe13 → Ala mutations were partially defective in avoiding transport to lysosomes. Analysis of double and triple mutants confirmed the key role of Trp19 for sorting of the CD-MPR in endosomes, with Phe18, Phe13, and several neighboring residues contributing to this function. The addition of the Phe18-Trp19 motif of the CD-MPR to the cytoplasmic tail of the lysosomal membrane protein Lamp1 was sufficient to partially impair its delivery to lysosomes. Replacing Phe18 and Trp19 with other aromatic amino acids did not impair endosomal sorting of the CD-MPR, indicating that two aromatic residues located at these positions are sufficient to prevent the receptor from trafficking to lysosomes. However, alterations in the spacing of the diaromatic amino acid sequence relative to the transmembrane domain resulted in receptor accumulation in lysosomes. These findings indicate that the endosomal sorting of the CD-MPR depends on the correct presentation of a diaromatic amino acid-containing motif in its cytoplasmic tail. Because a diaromatic amino acid sequence is also present in the cytoplasmic tail of other receptors known to be internalized from the plasma membrane, this feature may prove to be a general determinant for endosomal sorting.

High-Affinity Binding Of The AP-1 Adaptor Complex to Trans-Golgi Network Membranes Devoid Of Mannose 6-Phosphate Receptors

The GTP-binding protein ADP-ribosylation factor (ARF) initiates clathrin-coat assembly at the trans-Goli network (TGN) by generating high-affinity membrane-binding sites for the AP-1 adaptor complex. Both transmembrane proteins, which are sorted into the assembling coated bud, and novel docking proteins have been suggested to be partners with GTP-bound ARF in generating the AP-1-docking sites. The best characterized, and probably the major transmembrane molecules sorted into the clathrin-coated vesicles that form on the TGN, are the mannose 6-phosphate receptors (MPRs). Here, we have examined the role of the MPRs in the AP-1 recruitment process by comparing fibroblasts derived from embryos of either normal or MPR-negative animals. Despite major alterations to the lysosome compartment in the MPR-deficient cells, the steady-state distribution of AP-1 at the TGN is comparable to that of normal cells. Golgi-enriched membranes prepared from the receptor-negative cells also display an apparently normal capacity to recruit AP-1 in vitro in the presence of ARF and either GTP or GTPγS. The AP-1 adaptor is recruited specifically onto the TGN and not onto the numerous abnormal membrane elements that accumulate within the MPR-negative fibroblasts. AP-1 bound to TGN membranes from either normal or MPR-negative fibroblasts is fully resistant to chemical extraction with 1 M Tris-HCl, pH 7, indicating that the adaptor binds to both membrane types with high affinity. The only difference we do note between the Golgi prepared from the MPR-deficient cells and the normal cells is that AP-1 recruited onto the receptor-lacking membranes in the presence of ARF1·GTP is consistently more resistant to extraction with Tris. Because sensitivity to Tris extraction correlates well with nucleotide hydrolysis, this finding might suggest a possible link between MPR sorting and ARF GAP regulation. We conclude that the MPRs are not essential determinants in the initial steps of AP-1 binding to the TGN but, instead, they may play a regulatory role in clathrin-coated vesicle formation by affecting ARF·GTP hydrolysis.

Cloning and expression of the cDNA of chicken cation-independent mannose-6-phosphate receptor.

We cloned and sequenced the 8767-bp full-length cDNA for the chicken cation-independent mannose-6-phosphate receptor (CI-MPR), of interest because, unlike its mammalian homologs, it does not bind insulin-like growth factor II (IGF-II). The cDNA encodes a protein of 2470 aa that includes a putative signal sequence, an extracytoplasmic domain consisting of 15 homologous repeat sequences, a 23-residue transmembrane sequence, and a 161-residue cytoplasmic sequence. Overall, it shows 60% sequence identity with human and bovine CI-MPR homologs, and all but two of 122 cysteine residues are conserved. However, it shows much less homology in the N-terminal signal sequence, in repeat 11, which is proposed to contain the IGF-II-binding site in mammalian CI-MPR homologs, and in the 14-aa residue segment in the cytoplasmic sequence that has been proposed to mediate G-protein-coupled signal transduction in response to IGF-II binding by the human CI-MPR. Transient expression in COS-7 cells produced a functional CI-MPR which exhibited mannose-6-phosphate-inhibitable binding and mediated endocytosis of recombinant human beta-glucuronidase. Expression of the functional chicken CI-MPR in mice lacking the mammalian CI-MPR should clarify the controversy over the physiological role of the IGF-II-binding site in mammalian CI-MPR homologs.

Phineés, tragedia de los tiempos de Cristo.

Mode of access: Internet.

The New Jersey Unemployment Insurance Reemployment Demonstration Project : follow-up report /

"MPR reference no.: 7906."

National Job Corps study: the benefits and costs of Job Corps /

"MPR reference no. 8140-530."

National Job Corps study : the impacts of Job Corps on participants' employment and related outcomes /

"MPR reference no. 8140-530."

High school and beyond : a descriptive summary of 1980 high school seniors, six years later /

"Data series: HSB-80/86-2.0, HSB-80/86-2.1."

Focus for the future : the final report of the national Tech-Prep evaluation /

"MPR reference no.: 8087-220."