Risk Attitude And Wage Growth: Replication And Reconstruction

We replicate Shaw (1996) who found that individual wage growth is higher for individuals with greater preference for risk taking. Expanding her dataset with more American observations and data for Germany, Spain and Italy, we find mixed support for the earlier results. We present and estimate a new model and find that in particular the wage level is sensitive to attitudes towards risk taking. Comments given at the Labour Economics Conference in honour of Niels Westergaard (Nyborg, August 2008) and EALE 2008 (Amsterdam) and at seminars in Maastricht,Reus and Essen (RWI) are gratefully acknowledged. The authors also acknowledge financial support from the Spanish Ministry of Science and Innovation (grant number SEJ2007-66318) and from the Barcelona Economics Program of CREA. JEL code: J24; J30. Key words: wage growth, risk, post-school investment.

Transplanted beta cell response to increased metabolic demand. Changes in beta cell replication and mass

We determined the capacity of transplanted beta cells to modify their replication and mass when stimulated by changes in metabolic demand. Five groups of Lewis rats were studied: group 1 (Tx-Px) had a 95% pancreatectomy 14 d after transplantation of 500 islets; group 2 (Px-Tx) had a 95% pancreatectomy 14 d before transplantation of 500 islets; group 3 (Tx) was transplanted with 500 islets; group 4 (Px) had a 95% pancreatectomy; and group 5 (normal) was neither transplanted nor pancreatectomized. Blood glucose was normal in Tx-Px and Tx groups at all times. Px-Tx and Px groups developed severe hyperglycemia after pancreatectomy that was corrected in Px-Tx group in 83% of rats 28 d after transplantation. Replication of transplanted beta cells increased in Tx-Px (1.15 +/- 0.12%) and Px-Tx (0.85 +/- 0.12%) groups, but not in Tx group (0.64 +/- 0.07%) compared with normal pancreatic beta cells (0.38 +/- 0.05%) (P < 0.001). Mean beta cell size increased in Tx-Px (311 +/- 14 microns2) and Px-Tx (328 +/- 13 microns2) groups compared with Tx (252 +/- 12 microns2) and normal (239 +/- 9 microns2) groups (P < 0.001). Transplanted beta cell mass increased in Tx-Px (1.87 +/- 0.51 mg) and Px-Tx (1.55 +/- 0.21 mg) groups compared with Tx group (0.78 +/- 0.17 mg) (P < 0.05). In summary, changes in transplanted beta cells prevented the development of hyperglycemia in Tx-Px rats. Transplanted beta cells responded to increased metabolic demand increasing their beta cell mass.

Comparative effects of oleoyl-estrone and a specific b3-adrenergic agonist (CL316, 243) on the expression of genes involved in energy metabolism of rat white adipose tissue

Background: The combination of oleoyl-estrone (OE) and a selective b3-adrenergic agonist (B3A; CL316,243) treatment in rats results in a profound and rapid wasting of body reserves (lipid). Methods: In the present study we investigated the effect of OE (oral gavage) and/or B3A (subcutaneous constant infusion) administration for 10 days to overweight male rats, compared with controls, on three distinct white adipose tissue (WAT) sites: subcutaneous inguinal, retroperitoneal and epididymal. Tissue weight, DNA (and, from these values cellularity), cAMP content and the expression of several key energy handling metabolism and control genes were analyzed and computed in relation to the whole site mass. Results: Both OE and B3A significantly decreased WAT mass, with no loss of DNA (cell numbers). OE decreased and B3A increased cAMP. Gene expression patterns were markedly different for OE and B3A. OE tended to decrease expression of most genes studied, with no changes (versus controls) of lipolytic but decrease of lipogenic enzyme genes. The effects of B3A were widely different, with a generalized increase in the expression of most genes, including the adrenergic receptors, and, especially the uncoupling protein UCP1. Discussion: OE and B3A, elicit widely different responses in WAT gene expression, end producing similar effects, such as shrinking of WAT, loss of fat, maintenance of cell numbers. OE acted essentially on the balance of lipolysislipogenesis and the blocking of the uptake of substrates; its decrease of synthesis favouring lipolysis. B3A induced a shotgun increase in the expression of most regulatory systems in the adipocyte, an effect that in the end favoured again the loss of lipid; this barely selective increase probably produces inefficiency, which coupled with the increase in UCP1 expression may help WAT to waste energy through thermogenesis. Conclusions: There were considerable differences in the responses of the three WAT sites. OE in general lowered gene expression and stealthily induced a substrate imbalance. B3A increasing the expression of most genes enhanced energy waste through inefficiency rather than through specific pathway activation. There was not a synergistic effect between OE and B3A in WAT, but their combined action increased WAT energy waste.

Substrate-selective repair and restart of replication forks by DNA translocases

Stalled replication forks are sources of genetic instability. Multiple fork-remodeling enzymes are recruited to stalled forks, but how they work to promote fork restart is poorly understood. By combining ensemble biochemical assays and single-molecule studies with magnetic tweezers, we show that SMARCAL1 branch migration and DNA-annealing activities are directed by the single-stranded DNA-binding protein RPA to selectively regress stalled replication forks caused by blockage to the leading-strand polymerase and to restore normal replication forks with a lagging-strand gap. We unveil the molecular mechanisms by which RPA enforces SMARCAL1 substrate preference. E. coli RecG acts similarly to SMARCAL1 in the presence of E. coli SSB, whereas the highly related human protein ZRANB3 has different substrate preferences. Our findings identify the important substrates of SMARCAL1 in fork repair, suggest that RecG and SMARCAL1 are functional orthologs, and provide a comprehensive model of fork repair by these DNA translocases.

Micro- and nanostructuring of poly(ethylene-2,6-naphthalate) surfaces, for biomedical applications, using polymer replication techniques

Here we investigate the formation of superficial micro- and nanostructures in poly(ethylene-2,6-naphthalate) (PEN), with a view to their use in biomedical device applications, and compare its performance with a polymer commonly used for the fabrication of these devices, poly(methyl methacrylate) (PMMA). The PEN is found to replicate both micro- and nanostructures in its surface, albeit requiring more forceful replication conditions than PMMA, producing a slight increase in surface hydrophilicity. This ability to form micro/nanostructures, allied to biocompatibility and good optical transparency, suggests that PEN could be a useful material for production of, or for incorporation into, transparent devices for biomedical applications. Such devices will be able to be autoclaved, due to the polymer's high temperature stability, and will be useful for applications where forceful experimental conditions are required, due to a superior chemical resistance over PMMA.

A note on the separability principle in economies with single-peaked

We consider the problem of allocating an infinitely divisible commodity among a group of agents with single-peaked preferences. A rule that has played a central role in the analysis of the problem is the so-called uniform rule. Chun (2001) proves that the uniform rule is the only rule satisfying Pareto optimality, no-envy, separability, and continuity (with respect to the social endowment). We obtain an alternative characterization by using a weak replication-invariance condition, called duplication-invariance, instead of continuity. Furthermore, we prove that Pareto optimality, equal division lower bound, and separability imply no-envy. Using this result, we strengthen one of Chun's (2001) characterizations of the uniform rule by showing that the uniform rule is the only rule satisfying Pareto optimality, equal división lower bound, separability, and either continuity or duplication-invariance.

Redirecció de l'especificitat de les cél·lules T contra epítops del VIH restringit per la HLA-A2 mitjaçant transferència genética

Existeixen creixents evidències què la resposta dels limfòcits T CD8+ alpha beta citotòxics (CTLs) és un element fonamental en la infecció produïda pel VIH. Les CTLs VIH especifiques es consideren molt importants en la reducció de la càrrega viral i en la contenció de la infecció. Encara que la combinació dels antiretrovirals (HAART) ha suposat una millora considerable en la lluita contra el VIH induint una important reducció de la càrrega viral i augmentant el nombre de cèl•lules T CD4+, diverses complicacions han fet ressaltar la necessitat de noves alternatives terapèutiques. Les complicacions inclouen: manca de recuperació d’una resposta immune sòlida contra el VIH, toxicitat a llarg termini de la teràpia i el descobriment que les cèl•lules T CD4+ constitueixen un reservori pel virus. Les noves alternatives controlaran la replicació viral i reconstituiran la immunitat. L’eficàcia de la immunoteràpia cel•lular amb transferència adoptiva de CTLs virals específics s’ha provat en diferents infeccions virals humanes, incloent el VIH. Proposem una modificació de la immunoteràpia adoptiva redirigint l’especificitat de les cèl•lules T contra el VIH mitjançant la transfecció dels gens del TCR. En aquest assaig preclínic, ens aprofitarem de la tecnologia dels animals transgènics per les molècules de HLA, amb la finalitat de generar TCRs d’alta afinitat dirigits contra epitops del VIH restringits per la molècula HLA. Aquests TCRs seran induïts in vivo i seleccionats in vitro. Les cadenes alpha i beta dels TCRs VIH específics procedents de les CTLs seran clonades mitjançant tècniques de biologia molecular. Aquests TCRs VIH específics seran transferits a cèl•lules T CD8+ humanes i la seva especificitat i capacitat citolítica contra cèl•lules diana que presentin antígens de VIH-1 s’estudiaran mitjançant la combinació de diverses tècniques noves (FCC, transfecció mitjançant Nucleoefector). Finalment, una construcció retroviral adient per la seva transducció en cèl•lules T humanes s’establirà amb un TCR òptim seleccionat.

Solid-phase synthesis and NMR studies of modified oligonucleotides forming triplex helix and of oligonucleopeptides mimicking the topoisomerase I-DNA covalent complex

Report for the scientific sojourn carried out at the Institut de Biologia Molecular de Barcelona of the CSIC –state agency – from april until september 2007. Topoisomerase I is an essential nuclear enzyme that modulates the topological status of DNA, facilitating DNA helix unwinding during replication and transcription. We have prepared the oligonucleotide-peptide conjugate Ac-NLeu-Asn-Tyr(p-3’TTCAGAAGC5’)-LeuC-CONH-(CH2)6-OH as model compound for NMR studies of the Topoisomerase I- DNA complex. Special attention was made on the synthetic aspects for the preparation of this challenging compound especially solid supports and protecting groups. The desired peptide was obtained although we did not achieve the amount of the conjugate needed for NMR studies. Most probably the low yield is due to the intrinsic sensitive to hydrolysis of the phosphate bond between oligonucleotide and tyrosine. We have started the synthesis and the structural characterization of oligonucleotides carrying intercalating compounds. At the present state we have obtained model duplex and quadruplex sequences modified with acridine and NMR studies are underway. In addition to this project we have successfully resolved the structure of a fusion peptide derived from hepatitis C virus envelope synthesized by the group of Dr. Haro and we have synthesized and started the characterization of a modified G-quadruplex.

Optimal latent period in a bacteriophage population model structured by infection-age

We study the lysis timing of a bacteriophage population by means of a continuously infection-age-structured population dynamics model. The features of the model are the infection process of bacteria, the natural death process, and the lysis process which means the replication of bacteriophage viruses inside bacteria and the destruction of them. We consider that the length of the lysis timing (or latent period) is distributed according to a general probability distribution function. We have carried out an optimization procedure and we have found the latent period corresponding to the maximal fitness (i.e. maximal growth rate) of the bacteriophage population.

Selección de péptidos sintéticos del Virus de la Hepatitis G (GBV-C/HGV) inhibidores del Péptido de Fusión HIV-I

El GB virus C (GBV-C) o virus de l'hepatitis G (HGV) es un virus format per una única cadena de RNA que pertany a la familia Flaviviridae. En els últims anys, s'han publicat nombrosos treballs en els quals s'associa la coinfecció del GBV-C i del virus de la immunodeficiència humana (VIH) amb una menor progressió de l'esmentada malaltia així com amb una major supervivència dels pacients una vegada que la SIDA s'ha desenvolupat. El mecanisme pel qual el virus GBV-C/HGV exerceix un “efecte protector” en els pacients amb VIH encara no està descrit. L’estudi de la interacció entre els virus GBVC/HGV i VIH podria donar lloc al desenvolupament de nous agents terapèutics per al tractament de la SIDA.Treballs recents mostren com la capacitat inhibitòria del virus del GBV-C/HGV és deguda a la seva glicoproteina estructural E2. S’ha vist que aquesta proteina seria capaç d’inhibir la primera fase de replicació de VIH, així com la unió i la fusió amb les membranes cel•lulars. Sobre la base d’aquests estudis, l’objectiu d’aquest treball ha estat seleccionar inhibidors del pèptid de fusió del VIH utilitzant pèptids sintètics de la proteina E2 del GBV-C/HGV. El treball realitzat ha consistit en estudiar, utilitzant assajos biofísics de leakage i de lipid mixing, la capacitat dels pèptids de la proteina estructural del virus del GBV-C/HGV per inhibir la interacció i el procés de desestabilització de membranes induïdes pel pèptid de fusió de la glicoproteina de l’embolcall, GP41, del VIH. Aquests assajos, com es descriu en treballs anteriors, han resultat útils per a la selecció i la identificació de compostos amb activitat específica anti-GP41. Es pot afirmar que efectivament els pèptids seleccionats de la proteina E2 del virus del GBV-C/HGV inhibeixen l’activitat del pèptid de fusió del VIH probablement com a consequència d’un canvi conformacional en aquest darrer.

Beta cell mass and growth after syngeneic islet cell transplantation in normal and streptozocin diabetic C57BL/6 mice

In islet transplantation, nonimmunological factors such as limited growth capacity or increased death rate could reduce the beta cell mass in the graft and lead to failure of the transplant. We studied the evolution of beta cell replication and mass after transplantation of insufficient, minimally sufficient, or excessive islet tissue. Streptozocin diabetic C57BL/6 mice received 150 or 300 syngeneic islets under the kidney capsule and normal mice received 300 islets. In streptozocin diabetic mice 300 islets restored normoglycemia; beta cell replication in transplanted islets was similar to replication in normal pancreas and beta cell mass in the graft remained constant. In contrast, 150 islets were insufficient to achieve normoglycemia; beta cell replication was increased initially but not by 18 or 30 d despite persistent hyperglycemia, and beta cell mass fell progressively. When islets were transplanted into normal recipients, beta cell replication remained normal but beta cells underwent atrophy and mass in the graft was substantially reduced. Therefore, with a successful islet transplant, in diabetic mice beta cell replication and mass remain constant. In contrast, when insufficient islet tissue is transplanted an initial increase in beta cell replication can not compensate for a decline in beta cell mass. When excessive islet tissue is transplanted, beta cell mass is reduced despite normal beta cell replication.

Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation

Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.