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The sovereign debt crisis in the euro area saw credit spreads on sovereign bonds and credit default swaps (CDS) surge for a number of member states. The rise in sovereign yields was accompanied by a significant increase in sovereign CDS market activity. This pattern raised concerns that destabilising speculation via outright short-selling of CDS (so-called ‘naked CDS’) was behind the increase in bond yields. In response, policy-makers introduced a ban on naked CDS trading. We investigate the effect of the ban on the price discovery process of sovereign credit risk, contrasting results for the post-ban period with those obtained prior to the ban. We use intraday data on sovereign CDS and bonds across a number of euro area countries. Our first main finding is that the CDS market dominates the bond market in terms of price discovery. That is, CDS premia in most cases adjust quicker to reflect new information than bond spreads. This result holds also when taking into account transaction costs. Our second main finding is that the ban on short-selling did not alter price discovery dynamics or reduce the efficiency of the market. Finally, we find that prior to the ban, CDS spreads were persistently higher than bond credit spreads, even after controlling for transaction costs. This points to the presence of market frictions that limit the ability of arbitrage forces to fully close pricing gaps between the two markets. However, these pricing discrepancies were in many cases largely eliminated following the introduction of the ban.

With the onset of the euro area sovereign debt crisis, the CDS spreads of the Czech Republic, Hungary, Poland and Slovakia (the Visegrad group) increased even though the Visegrad group maintained solid public finances and ratings on average. Real economic linkages such as trade between the Visegrad group as important trading partner to the GIIPS countries might have led to this increase in sovereign credit risk due to contagion during the sovereign debt crisis period. We aim to analyse whether contagion led to higher sovereign risk in the Visegrad group and furthermore, whether the economic adjustment programmes (EAPs) by the Troika have been able to stabilise and reduce sovereign risk. We analyse 30-min intraday credit default swaps (CDS) data prior to the sovereign debt crisis period (2008–Oct. 2009) and during the sovereign debt crisis period (Oct. 2009–2011). By using a panel VAR methodology we find rather comovement effects in the Visegrad group member countries as they have been only marginally affected by the turmoil in the peripheral countries during the sovereign debt crisis. In contrast, we find strong contagion effects amongst the GIIPS countries in our sample. From an event study, we find that the EAPs have been essential for the GIIPS countries in terms of reducing contagion and sovereign risk across the euro area while the Visegrad group only reacted with a moderate reduction.

We present a methodology for estimating a multivariate 3-regime threshold vector error correction model (TVECM) with an unknown cointegrating vector based on a new dynamic grid evaluation. This model is particularly useful for estimating deviations from parity conditions, such as unknown arbitrage costs in markets with a persistent non-zero basis between two similar financial market instruments traded in the spot and derivative markets. Our proposed 3-regime TVECM can estimate the area where arbitrageurs have no incentives to trade. It is only when the basis exceeds a critical threshold, that is when the potential gain from the basis trade exceeds the overall transaction costs, that we expect arbitrageurs to step in and carry out the respective trade. This leads to non-linear adjustment dynamics and regimes with different characteristics. Our methodology allows overall transaction costs to be quantified in markets where trading costs are opaque or unknown.

We study optimized Taylor rules that incorporate financial stability considerations, which have been little analysed for emerging market economies. Setting the policy interest rate with a greater financial stability consideration reduces monetary policy effectiveness: a greater effort to reduce output volatility in the nontradables sector, where asset bubbles are prone to build, leads to greater inflation volatility.

We study optimized Taylor rules with the appropriate lag structure, which has been little done for emerging market economies. Setting the policy interest rate in response to movements in domestic long-term bond yields, in addition to the output gap, the inflation gap and the exchange rate, can make monetary policy more effective. But a more complex rule can reduce monetary policy effectiveness, notably in the presence of uncertainty about the effects of capital flows on domestic monetary conditions.

Ribosome biogenesis drives cell growth, and the large transcriptional output underlying this process is tightly regulated. The Target of Rapamycin (TOR) kinase is part of a highly conserved signaling pathway linking nutritional and stress signals to regulation of ribosomal protein (RP) and ribosome biogenesis (Ribi) gene transcription. In Saccharomyces cerevisiae, one of the downstream effectors of TOR is Sfp1, a transcriptional activator that regulates both RP and Ribi genes. Here, we report that Sfp1 interacts directly with TOR complex 1 (TORC1) in a rapamycin-regulated manner, and that phosphorylation of Sfp1 by this kinase complex regulates its function. Sfp1, in turn, negatively regulates TORC1 phosphorylation of Sch9, another key TORC1 target that acts in parallel with Sfp1, revealing a feedback mechanism controlling the activity of these proteins. Finally, we show that the Sfp1-interacting protein Mrs6, a Rab escort protein involved in membrane trafficking, regulates both Sfp1 nuclear localization and TORC1 signaling.

Smoking conventional lit-end cigarettes results in exposure of nonsmokers to potentially harmful cigarette smoke constituents present in environmental tobacco smoke (ETS) generated by sidestream smoke emissions and exhaled mainstream smoke. ETS constituent concentrations generated by a conventional lit-end cigarette and a newly developed electrically heated cigarette smoking system (EHCSS) that produces only mainstream smoke and no sidestream smoke emissions were investigated in simulated "office" and "hospitality" environments with different levels of baseline indoor air quality. Smoking the EHCSS (International Organisation for Standardization yields: 5 mg tar, 0.3 mg nicotine, and 0.6 mg carbon monoxide) in simulated indoor environments resulted in significant reductions in ETS constituent concentrations compared to when smoking a representative lit-end cigarette (Marlboro: 6 mg tar, 0.5 mg nicotine, and 7 mg carbon monoxide). In direct comparisons, 24 of 29 measured smoke constituents (83%) showed mean reductions of greater than 90%, and 5 smoke constituents (17%) showed mean reductions between 80% and 90%. Gas-vapor phase ETS markers (nicotine and 3-ethenylpyridine) were reduced by an average of 97% (range 94-99%). Total respirable suspended particles, determined by online particle measurements and as gravimetric respirable suspended particles, were reduced by 90% (range 82-100%). The mean and standard deviation of the reduction of all constituents was 94 +/- 4%, indicating that smoking the new EHCSS in simulated "office" and "hospitality" indoor environments resulted in substantial reductions of ETS constituents in indoor air.

We examine whether sovereign credit risk shocks emanating from the GIIPS countries had an effect on central European countries such as the Czech Republic, Hungary, Poland and Slovakia (the Visegrad group). In addition to the GIIPS and Visegrad group countries we als include Austria, France and Germany as control countries in our dataset. We analyse 30-minute intraday credit default swaps (CDS) data prior to the crisis period (2008-Oct. 2009) and during the crisis period (Oct. 2009-2011) which enables us to analyse changes in the dynamics of sovereign risk contagion between these two datasets. By using a panel VAR methodology we find rather comovement effects in the Visegrad group countries as they have been only marginally affected by the turmoil in the peripheral countries during the sovereign debt crisis. In contrast, we find strong contagion effects between the GIIPS countries in our sample. In addition, we study the effects of the four economic adjustment programmes by the Troika in the period from 2010 until 2011. Even though these bailouts have been essential for the GIIPS countries in terms of reducing contagion risk across the euro area, our analysis shows, that they did not have an effect for the Visegrad group countries.

We find evidence that in the market for euro area sovereign credit risk, arbitrageurs engage in basis trades between credit default swap (CDS) and bond markets only when the CDS-bond basis exceeds a certain threshold. This threshold effect is likely to reflect costs that arbitrageurs face when implementing trading strategies, including transaction costs and costs associated with committing balance sheet space for such trades. Using a threshold vector error correction model, we endogenously estimate these unknown trading costs for basis trades in the market for euro area sovereign debt. During the euro sovereign credit crisis, we find very high transaction costs of around 190 basis points, compared to around 80 basis points before the crisis. Moreover, we find that once the threshold has been exceeded, the basis reverts back towards its long-run equilibrium substantially faster than when the basis is below the threshold. Our findings help explain the persistent non-zero basis or spread between credit risk premia in CDS and sovereign bond markets and suggest that the significant increase in the basis during the crisis was due to sharply higher costs facing arbitrageurs in the market, as well as compensation for increased risk that the trade would go against them in the short run.

We examine the role of the CDS and bond markets during and before the recent euro area sovereign debt crisis as transmission channels for credit risk contagion between sovereign entities. We analyse an intraday dataset for GIIPS countries as well as for France and Germany. Our findings suggest that, prior to the crisis, the CDS and bond markets were similarly important in the transmission of sovereign risk contagion, but that the importance of the bond market waned during the crisis. We find flight-to-safety effects during the crisis period in the German bond market. By using an exogenous macroeconomic news shock, we can show that, during the crisis period, sovereign credit risk was not related to economic fundamentals but rather driven by the announcements of the economic adjustment programmes (EAP) as the magnitude of risk contagion spreading from the country under the EAP did strongly decrease following these announcements. Only after the enlargement of the European Financial Stability Facility in July 2011, we find a strong decrease of interlinkages and a stabilising effect on the joint credit risk contagion across all GIIPS countries.

The Target of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes regulate many different aspects of cell growth in response to intracellular and extracellular cues. Here we report that the AGC kinase Sch9 is a substrate of yeast TORC1. Six amino acids in the C terminus of Sch9 are directly phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin treatment as well as carbon or nitrogen starvation and transiently reduced following application of osmotic, oxidative, or thermal stress. TORC1-dependent phosphorylation is required for Sch9 activity, and replacement of residues phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1 independent. Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation initiation, and entry into G0 phase, but not expression of Gln3-dependent genes. Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt.

We evaluate the important two-loop matrix element of the operator (cbar gamma^mu P_L b) (sbar gamma_mu P_L b) contributing to the inclusive radiative decay B -> X_s gamma. The calculation is performed in the NDR scheme, by means of asymptotic expansions method. The result is given as a series in z = m_c^2/m_b^2 up to O(z^6). We confirm the result of Greub, Hurth and Wyler obtained by a different method up to 0(z^3). Higher-order terms are found to be numerically insignificant., Comment: 18 pages, 6 figures, 1 table

Temporal variation in abundance of larvae and spat of the pearl oyster Pinctada imbricata was studied at several locations on the Colombian coast from May 1997 to June 1998. Larvae were sampled with bongo nets and spat were harvested from collectors at monthly intervals. Abundances of predators ( Cymatium gastropods, and portunid, xanthid and majiid crabs) were also recorded. A relationship between salinity, particulate organic matter and larvae abundance was observed, leading to peaks in abundance of spat on collectors some weeks later. Average catch rates of 10 spat collector −1 month −1 , using collectors made of cheap easily accessible materials, indicate that availability of P. imbricata is sufficient to initiate and support aquaculture of this species. Growth and mortality rates of juveniles in three different culture systems at two densities (20% and 30%, i.e. percentage of available area covered by juveniles) showed that density within the same culture system had no effect on growth, but that growth differed significantly among the three culture systems. Growth in “bag” systems was lower than in boxes whereas growth in “suspended” and “bottom” boxes was similar and comparable to the growth of a natural population. The suspended boxes are the easiest to handle because they do not require SCUBA diving and so these systems are recommended.

Ubiquitin conjugation during endoplasmic-reticulum-associated degradation (ERAD) depends on the activity of Ubc7. Here we show that Ubc1 acts as a further ubiquitin-conjugating enzyme in this pathway. Absence of both enzymes results in marked stabilization of an ERAD substrate and induction of the unfolded-protein response (UPR). Furthermore, basic ERAD activity is sufficient to eliminate unfolded proteins under normal conditions. However, when stress is applied, the UPR is required to increase ERAD activity. We thus demonstrate, for the first time, a regulatory loop between ERAD and the UPR, which is essential for normal growth of yeast cells.

We evaluate matching conditions for the Wilson coefficients of operators mediating the b→sγ and b→s gluon transitions in a large class of extensions of the Standard Model. The calculation is performed at the leading order in flavour-changing couplings and includes two-loop QCD corrections. These corrections can be numerically important when approximate cancellations occur among the new physics contributions and/or the SM one. PACS: 12.60.-i, 14.40.Nd

The fresh-water clam Polymesoda solida (Philippi, 1846) is the principal fishery resource in the Cienaga Poza Verde, Salamanca Island, Colombian Caribbean Sea. Between July 1995 and June 1996, samples were taken to study reproduction, growth, mortality, production and fishery aspects of this population. P. solida is monoecious (hermaphroditic) combined with protogyny. We found an arrhythmic reproductive cycle with several spawning events per year, which could be related to the salinity cycle. The growth parameters of the von Bertalanffy growth equation were: L∞=47.3 mm and K=0.204 yr−1. The following mortality rates were estimated: total mortality, Z=0.748, mean natural mortality, M=0.210 and fishing mortality, F=0.538 yr−1. Somatic production of the population (in g AFDW m−2 yr−1), and the productivity ( P/ B ) were 0.647 and 0.230 respectively. P. solida is exploited in an artisanal (small-scale) fishery by approximately 80 fishermen. During the study period, mean daily catch was calculated as 314.4 kg shell free wet weight, and mean effort as 42 fishermen per day. Maximum exploitation rate, corresponding to the maximum relative yield per recruit and calculated with the relative yield per recruit model of Beverton and Holt, was Emax=0.445. The observed exploitation rate (E=0.719), calculated from fishing mortality, F and total mortality, Z, indicates overexploitation. A reduction of the fishing effort therefore is strongly suggested, to achieve a sustainable exploitation.

We present a calculation of the B0-B0--mixing including Next--to--Leading Order (NLO) QCD corrections within the Two Higgs Doublet Model (2HDM). The QCD corrections at NLO are contained in the factor denoted by eta_2 which modifies the result obtained at the lowest order of perturbation theory. In the Standard Model case, we confirm the results for eta_2 obtained by Buras, Jamin and Weisz. The factor eta_2 is gauge and renormalization prescription invariant and it does not depend on the infrared behaviour of the theory, which constitutes an important test of the calculations. The NLO--calculations within the 2HDM enhance the LO--result up to 18%, which affects the correlation between M_H and V_{td}.

Body size, geographical distribution and biomass make Laternula elliptica one of the most important bivalve species of the Antarctic. A complete study on the population dynamics (reproduction cycle, growth, mortality and productivity) of this species from King George Island gave growth parameters for the von-Bertalanffy-growth-function of: L∞ = 112.2 mm, K = 0.160 yr 1, t0 = 0.000 yr. Total mortality was estimated as Z = 0.392 yr−1. Somatic production and mean biomass of two distinct sub-populations were 8.7 and 67.3 g AFDW m−2 yr−1 at Beach & Glacier and 20.0 and 88.6 g AFDW m−2 yr−1 at Punta Elefante. The following P / B values were calculated; Beach & Glacier = 0.129, Punta Elefante = 0.226. It is suggested that these differences are linked to mortality caused by icebergs which is expected to be higher at the shallower Punta Elefante site.

Despite an important small scale bivalve fishery in Peru, hardly any management plans are applied to exploit the resource. Furthermore, little of the ecological data necessary to develop management strategies have been published so far. The present paper deals with the fishery of the most important infaunal bivalve of Peru, Gari solida , from Bahia Independencia where the largest Peruvian population is located. Growth parameters of the von Bertalanffy growth function were L ∞ =101.6 mm and k =0.495, total mortality was Z =1.64 [yr −1 ], fishing mortality F =1.31 [yr −1 ] and mean natural mortality M =0.38 [yr −1 ]. Total biomass, calculated by direct sampling surveys was 627 t ash-free dry weight (AFDW) in August 1990, 435 t AFDW in February 1991 and 137 t AFDW in October 1991. The observed exploitation rate, calculated from Z and F was E =0.80, whereas exploitation rate corresponding to the maximum yield (calculated by Beverton and Holt yield per recruit model) was E max =0.65. Therefore, it is assumed that the biomass reduction (corresponding to a total decline of 78%) was caused by fishing activities. Other sources reveal a decline of 92% from 1990 to 1994. It is necessary to establish and apply management plans for a sustainable exploitation of this resource.

We have calculated the amplitudes for the and mixing to leading order (LO) with consideration of the external momenta of the heavy quarks. We have assumed them to reside on-shell inside the mesons. The light quarks are taken to be massless. If we compare our results for the relevant diagrams in the K- and B-meson systems with the traditional calculations (all external momenta equal to zero) we realize that the corrections amount to 1.27% and 0.04%, respectively. Hence, the external momenta are irrelevant for the B-system, but they might be relevant for the K-system, since the error branches are much smaller.

The recent sovereign debt crisis in the euro area has seen credit spreads on sovereign bonds and credit default swaps (CDS) surge for a number of member states. While these events have increased interest in understanding the dynamics of sovereign spreads in bond and CDS markets, there is little agreement in the literature as to whether one of the two markets is more important than the other in terms of price discovery of sovereign credit risk.

A modeling approach termed ‘nicotine bridging’ is presented to estimate exposure to mainstream smoke constituents. The method is based on: (1) determination of harmful and potentially harmful constituents (HPHC) and in vitro toxicity parameter-to-nicotine regressions obtained using multiple machine-smoking protocols, (2) nicotine uptake distributions determined from 24-h excretion of nicotine metabolites in a clinical study, and (3) modeled HPHC uptake distributions using steps 1 and 2. An example of ‘nicotine bridging’ is provided, using a subset of the data reported in Part 2 of this supplement (Zenzen et al., 2012) for two conventional lit-end cigarettes (CC) and the Electrically Heated Cigarette Smoking System (EHCSS) series-K6 cigarette. The bridging method provides justified extrapolations of HPHC exposure distributions that cannot be obtained for smoke constituents due to the lack of specific biomarkers of exposure to cigarette smoke constituents in clinical evaluations. Using this modeling approach, exposure reduction is evident when the HPHC exposure distribution curves between the MRTP and the CC users are substantially separated with little or no overlap between the distribution curves.

The conserved Target Of Rapamycin (TOR) growth control signaling pathway is a major regulator of genes required for protein synthesis. The ubiquitous toxic metalloid arsenic, as well as mercury and nickel, are shown here to efficiently inhibit the rapamycin-sensitive TORC1 (TOR complex 1) protein kinase. This rapid inhibition of the TORC1 kinase is demonstrated in vivo by the dephosphorylation and inactivation of its downstream effector, the yeast S6 kinase homolog Sch9. Arsenic, mercury, and nickel cause reduction of transcription of ribosome biogenesis genes, which are under the control of Sfp1, a TORC1-regulated transcriptional activator. We report that arsenic stress deactivates Sfp1 as it becomes dephosphorylated, dissociates from chromatin, and exits the nucleus. Curiously, whereas loss of SFP1 function leads to increased arsenic resistance, absence of TOR1 or SCH9 has the opposite effect suggesting that TORC1 has a role beyond down-regulation of Sfp1. Indeed, we show that arsenic activates the transcription factors Msn2 and Msn4 both of which are targets of TORC1 and protein kinase A (PKA). In contrast to TORC1, PKA activity is not repressed during acute arsenic stress. A normal level of PKA activity might serve to dampen the stress response since hyperactive Msn2 will decrease arsenic tolerance. Thus arsenic toxicity in yeast might be determined by the balance between chronic activation of general stress factors in combination with lowered TORC1 kinase activity.

Dietary nutrient limitation (dietary restriction) is known to increase lifespan in a variety of organisms. Although the molecular events that couple dietary restriction to increased lifespan are not clear, studies of the model eukaryote Saccharomyces cerevisiae have implicated several nutrient-sensitive kinases, including the target of rapamycin complex 1 (TORC1), Sch9, protein kinase A (PKA) and Rim15. We have recently demonstrated that TORC1 activates Sch9 by direct phosphorylation. We now show that Sch9 inhibits Rim15 also by direct phosphorylation. Treatment of yeast cells with the specific TORC1 inhibitor rapamycin or caffeine releases Rim15 from TORC1-Sch9-mediated inhibition and consequently increases lifespan. This kinase cascade appears to have been evolutionarily conserved, suggesting that caffeine may extend lifespan in other eukaryotes, including man.

Vacuole biogenesis depends on specific targeting and retention of peripheral membrane proteins. At least three palmitoylated proteins are found exclusively on yeast vacuoles: the fusion factor Vac8, the kinase Yck3, and a novel adaptor protein implicated in microautophagy, Meh1. Here, we analyze the role that putative acyltransferases of the DHHC family play in their localization and function. We find that Pfa3/Ynl326c is required for efficient localization of Vac8 to vacuoles in vivo , while Yck3 or Meh1 localization is not impaired in any of the seven DHHC deletions. Vacuole-associated Vac8 appears to be palmitoylated in a pfa3 mutant, but this population is refractive to further palmitoylation on isolated vacuoles. Vacuole morphology and inheritance, which both depend on Vac8 palmitoylation, appear normal, although there is a reduction in vacuole fusion. Interestingly, Pfa3 is required for the vacuolar localization of not only an SH4 domain that is targeted by myristate/palmitate (as in Vac8) but also one that is targeted by a myristate/basic stretch (as in Src). Our data indicate that Pfa3 has an important but not exclusive function for Vac8 localization to the vacuole.

Donax dentifer es un bivalvo dominante en comunidades de playa arenosa en la costa del Pacífico colombiano. Se muestreó mensualmente una población de este bivalvo en Bahía Málaga, Pacífico colombiano entre agosto de 1997 y julio de 1998 cuando ocurrió el evento "El Niño" 1997/1998. Se tomaron muestras cuantitativas mensuales usando transectos lineales perpendiculares y paralelos a la línea de costa para determinar la densidad poblacional y realizar una distribución de frecuencias de longitud. Se tomaron también muestras cualitativas mensuales para estudiar la reproducción y establecer relaciones peso-longitud. Se registró la temperatura, oxígeno disuelto, salinidad y pH de la columna de agua en el sitio de muestreo. Adicionalmente se realizó un experimento de marcaje-recaptura para estimar el crecimiento de la población. Los resultados indican que la población tiene un ciclo de reproducción continuo, con dos períodos de desove anuales en diciembre y marzo. Los parámetros de crecimiento de la función de crecimiento de von Bertalanffy fueron K=0.624 año-1 y L∞=29.3 mm. La mortalidad total (Z) fue de Z=2.605 año -1 para los individuos pequeños (entre 2 mm y 5 mm) y menor (Z=1.714 año -1) para los individuos grandes (entre 19 mm y 25 mm). La biomasa promedio anual de la población fue =1.22 g de peso seco libre de cenizas m-2 y la producción somática anual Psom/= 1.215 g de peso seco libre de cenizas m-2, lo que corresponde a una tasa de Psom/= 0.988. Aunque se observó un incremento en la densidad poblacional durante noviembre y abril, no hay evidencia de una clara relación entre la densidad poblacional y la ocurrencia del fenómeno "El Niño". Los cambios en la concentración de oxígeno disuelto mostraron una alta correlación con los parámetros del ciclo reproductivo, posiblemente como consecuencia de la influencia de este parámetro en procesos de asimilación y el ciclo de peso corporal. El crecimiento de D. dentifer fue más lento que en otras especies del género, como cabe esperarse para bivalvos tropicales en comparación con los de altas latitudes. El patrón de mortalidad observado sugiere un efecto selectivo de El Niño 97/98 sobre la población, debido a que los individuos pequeños ocupan las partes bajas de la zona intermareal, donde el grado de exposición al agua marina es alto. La producción poblacional e individual fue mayor para los animales de tallas medias en comparación con los animales pequeños aunque estos últimos fueron los más abundantes en la población.Donax dentifer is a dominant member of the sandy beach communities of the Colombian Pacific coast. A population of this bivalve was monthly sampled in Playa Chucheros at the Bay of Málaga, Colombian Pacific, between August 1997 and July 1998, during the "El Niño 1997/1998" phenomenon. Quantitative samples were taken in perpendicular and parallel to the coastal line transects to determine the population density and a length-frequency distribution. Qualitative samples were taken to study the reproduction and monthly length weight relationship. Sea surface temperature, dissolved oxygen, salinity and pH in the water was monthly registered in the sampling station. Additionally, a tagging-recapture experiment was performed to growth estimations. Results indicate a continuous reproduction cycle with two annual spawning seasons in December and March. The growth parameters of the non-oscillating von Bertalanffy growth funetion were K= 0.62 yr-1 and L∞ = 29.3 mm. Mortality (Z) was higher (2.65 yr-1) for small individuals (between 2 mm and 5 mm) while a lower Z value (1.71 yr-1) were obtained for larger ones (between 19 mm and 25 mm). An annual mean biomass value of B = 1.229 g ash-free dry weight m-2 and an annual somatic production of Psom =1.215 g ash-ftee dry weight m-2 were estimated, which correspond to a Psom / B value of 0.988. Population density increased in November and April, but any population density pattem related with "El Niño" was evident. Low body weight during NovemberDecember seems to show a relation between reproductive cycle in D. dentifer and El Niño 97/98 event. The fluctuation in dissolved oxygen show a high correlation with parameters of the reproductive cycle, which could be relatad to assimilation process and body weight cycle. Growth in D. dentifer in the Colombian Pacific coast was faster than other Donax species, as can be expected for tropical bivalves mollusks in comparison whit high latitude bivalves. The mortality pattern suggest that the population was selectively affected by El Niño 97/98, due to smaller individuals are living in the lowest areas of the beach, where they are exposed to abnormal seawater conditions for a longer time. Individual and population production was higher for medium-size animals than each for small-size ones, which were the most abundant in the population.

Tail-anchored proteins are distinct from other membrane proteins as they are thought to insert into the endoplasmic reticulum (ER) membrane independently of Sec61p translocation pores. These pores not only mediate import but are also assumed to catalyze export of proteins in a process called ER-associated protein degradation (ERAD). In order to examine the Sec61p dependence of the export of tail-anchored proteins, we analyzed the degradation pathway of a tail-anchored ER membrane protein, the ubiquitin-conjugating enzyme 6 (Ubc6p). In contrast to other ubiquitin conjugating enzymes (Ubcs), Ubc6p is naturally short-lived. Its proteolysis is mediated specifically by the unique Ubc6p tail region. Degradation further requires the activity of Cue1p-assembled Ubc7p, and its own catalytic site cysteine. However, it occurs independently of the other ERAD components Ubc1p, Hrd1p/Der3p, Hrd3p and Der1p. In contrast to other natural ERAD substrates, proteasomal mutants accumulate a membrane-bound degradation intermediate of Ubc6p. Most interestingly, mutations in SEC61 do not reduce the turnover of full-length Ubc6p nor cause a detectable accumulation of degradation intermediates. These data are in accordance with a model in which tail-anchored proteins can be extracted from membranes independently of Sec61p.

Rats were given intravenous injections of l-[1-14C]leucine. Twelve minutes after injection, testes, kidneys, livers, and hepatomas were excised rapidly from one group of animals bearing Morris hepatoma 5123tc. From a second group of rats, the blood was removed 90 min after injection. Tissue extracts and serum were divided into three portions each, and albumin was isolated from each of the three portions by one of three different methods. The three different isolation procedures were the following: (A) pretreatment of the tissue extracts and serum with bovine serum albumin and its specific antiserum and subsequent immunoprecipitation of the rat serum albumin, (B) direct immunoprecipitation followed by dissolving the precipitated rat serum albumin in acid/ethanol, precipitation with ether, and ion-exchange chromatography of the redissolved albumin on CM-cellulose, and (C) a modification of a procedure published previously including fractionation with trichloroacetic acid, ethanol, ether, and ammonium sulfate, chromatography on Sephadex G-100 and DEAE-cellulose, and preparative disc electrophoresis in polyacrylamide gel at pH 10.3 and pH 2.7. With method (A), radiochemically pure albumin can be obtained only from serum. Even though testis and kidney do not synthesize albumin, albumin preparations isolated by this procedure from these organs contain significant amounts of radioactivity. Specific radioactivities measured in albumin prepared by method (A) from the four tissues examined are 5–19 times larger than those in preparations isolated by method (C). Thus, method (A) is inappropriate for the isolation of radiochemically pure albumin from the tissues studied. Procedure (B) is sufficient to obtain radiochemically pure albumin from the serum as well as from the other tissues examined except liver. With liver, this method yields an albumin preparation containing 53% more radioactivity than does albumin isolated with method (C). Method (C) is the only procedure yielding radiochemically pure albumin from all sources, including liver. In liver and hepatoma, the properties of the radioactive impurities are very similar to the properties of albumin itself. Therefore, several purification steps and a careful analysis of the distribution of radioactivity among the albumin fractions after chromatographies and electrophoreses are necessary to separate radioactive impurities from the albumin from homogenates of these two sources.

Intraperitoneally injected radioactive amino acids were efficiently incorporated into the protein of Morris hepatomas 5123tc and 9121 implanted into the muscles of the hind legs of totally hepatectomized rats. However, no radioactive protein was released from the hepatomas into the bloodstream. Albumin synthesis was studied in liver and hepatomas by measuring the incorporation of l -[1-14C]leucine. In these experiments, liver and hepatomas were removed within the time required for synthesis and secretion of albumin. Compared with liver a considerably smaller proportion of total protein radioactivity was found in albumin of the hepatomas, suggesting a reduced albumin synthesis in the hepatomas. Despite its reduced synthesis the content of albumin was much larger in the extravascular compartment of the hepatoma tissue than in liver. No albumin synthesis could be demonstrated in a cell-free protein synthesizing system consisting of liver microsomes, pH 5-fraction and an ATP generating system, provided that albumin was purified to constant specific radioactivity. A relatively complicated purification procedure was found to be required for the isolation of radiochemically pure albumin from liver and hepatoma from animals injected with l -[1-14C]leucine. Immunoprecipitation was found to be adequate for isolation of radiochemically pure albumin only from serum, but not from liver or hepatoma. The reason was the presence of a very highly labeled albumin-like protein in liver and hepatoma. This albumin-like protein was isolated from liver microsomes and characterized. It had the same molecular weight and amino acid composition as albumin, within the limits of variation of the methods, and could be precipitated quantitatively by anti-albumin. The amino acid sequence of the N-terminus of the albumin-like protein differed from that of albumin by an oligopeptide extension consisting of Gly-Val-Phe-Ser-Arg. Injected l -[1-14C]leucine was incorporated first into the albumin-like protein and appeared thereafter in albumin. Quantitative conversion of the albumin-like protein into albumin was observed during biosynthesis of albumin in liver cell suspensions. After initial incubation of the liver cells with l -[1-14C]leucine, followed by further incubation with excess non-radioactive leucine, radioactivity remained constant in total protein, but increased in albumin to about the same extent as it decreased in the albumin-like protein. The evidence indicates that the albumin-like protein is a precursor protein involved in the biosynthesis of albumin. The precursor is converted into albumin by removal of the N-terminal oligopeptide extension. This extension could have a function in the mechanism and the regulation of albumin synthesis and secretion. A model describing such a function is discussed.

Radioactive leucine was injected into the portal vein of rats followed after 15 seconds by a 180 fold excess of nonradioactive leucine. An albumin-like protein in the liver became highly labelled within 15 minutes after injection. After 150 minutes, the radioactivity in the albumin-like protein had decreased to one tenth. In the serum, radioactively labelled albumin started to appear after 15 minutes and increased there-after up to 150 minutes after injection. Radioactivity in albumin within the liver remained constant at a low level. These results suggest that the albumin-like protein is a biological precursor protein of serum albumin, i.e. a proalbumin.

Immunologically isolated albumin from rat liver microsomes separates on DEAE-cellulose into almost equal proportions of an albumin-like protein and authentic albumin. Besides this similarity in immunological properties, both albumin species have almost the same molecular weight and amino acid composition. Furthermore, the amino acid sequences appear to be identical apart from an additional pentapeptide at the N-terminus of the albumin-like protein. It is suggested that the albumin-like protein represents a precursor which is converted to albumin by release of a pentapeptide from the N-terminus.

The mechanism of the biosynthesis of albumin was studied in cell suspensions from rat liver. The cells were prepared by continuous perfusion of the liver in situ with 0.05% collagenase and 0.10% hyaluronidase and incubated under conditions optilnized for the incorporation of amino acids into protein. Seven minutes after starting the incubation l-[1-14C]leucine was added, followed after 25 min by a 15 or 30-min chase with an 830-fold excess of non-radioactive l-leucine. Total protein, an albumin-like protein, and albumin were isolated from samples withdrawn immediately after addition of non-radioactive leucine and after the 15 and 30-min chases. The specific radioactivity of total protein was found to remain constant after addition of the non-radioactive l-leucine, whereas that of the albumin-like protein decreased and that of albumin increased with incubation time. The increase in albumin radioactivity accounted for the decrease in radioactivity of the albuminlike protein, suggesting that the latter is a precursor of albumin. The precursor protein differed from albumin by an oligopeptide extension at the N-terminal end.

Invivo, Morris hepatomas 5123tc and 9121 do not secrete serum proteins into the bloodstream. However, they synthesize albumin, at a reduced rate, if compared with liver. The produced albumin accumulates, leading to an enlargement of the Golgi apparatus and the appearance of intracellular vesicles. The proportion and the absolute amount of albumin found within the hepatoma cells is increased compared with liver.

The sequence of radioactively labelled amino acids at the N-terminus of proalbumin was determined by automated Edman-degradation. [3H] Valine, [3H] phenylalanine or [14Carginine was incorporated into protein in vivo for a time period of 10 min after injection. Since albumin remains unlabelled during this time period (Urban et al., 1976), separation of proalbumin and albumin was not required for this work. Hence, compared to previous methods, a shorter purification procedure could be used which increased the yield of anti-albumin-precipitable protein and reduced the risk of proteolysis. Microsomes were prepared from livers removed 10 min after injection of the radioactively labelled amino acids. A buffer extract of the acetone-dried powder from these microsomes was chromatographed on DEAE-cellulose. All protein obtained after chromatography which could be precipitated with antiserum to serum albumin was isolated by immunoprecipitation and subsequent separation of the antigen-antibody complex. The sequence of radioactive amino acids in this antigen preparation suggests that about 20–25% of proalbumin possessed at the N-terminus the pentapeptide sequence X-Val-Phe-Arg-Arg- whereas 75–80% contained the hexapeptide sequence Arg-X-Val-Phe-Arg-Arg-.

The regulation of albumin synthesis and serum protein secretion was studied in regenerating rat liver by measuring incorporation of 14C-leucine. Albumin was isolated to radiochemical purity, utilizing a method which eliminates the influence of precursor pool changes on protein labeling. Changes in the size of the product pool were measured. The following results were obtained. 1. The time period between intracaval injection of 14Cleucine and the appearance of radioactive protein in the blood ("secretion time") decreased from 15 min for normal animals to a minimum of 10 min at 48 hours after removal of 70% of the liver. 2. At 10 min after intracaval injection of 14C-leucine, 3.5% of total protein radioactivity was found in albumin in normal liver, whereas in regenerating liver only 1.4% of the total protein radioactivity was incorporated into albumin. 3. Albumin concentration in the serum decreased from 29.2 mg of albumin per ml of serum for normal rats to a minimum of 17.3 mg of albumin per ml of serum at 4 days after partial hepatectomy. 4. The half-life of albumin was 2.66 days for normal rats and 2.13 days for animals, 48 hours after partial hepatectomy. 5. The intravascular pool of albumin decreased from 100 mg of albumin per 100 g, body wt, in normal rats to 57.8 mg of albumin per 100 g, body wt, in partially hepatectomized animals, 48 hours after operation. The extravascular and the total body pool of albumin also decreased after partial hepatectomy to a minimum at 24 hours after the operation. In contrast to the intravascular pool, the extravascular and the total body pool increased again, reaching a plateau between 2 and 4 days after the operation. 6. During regeneration, the proportion of leucine to other amino acids in total liver protein did not change. Also, this proportion did not differ significantly from that found in serum albumin. 7. The net rate of albumin synthesis changed only slightly from 20.1 mg of albumin per day per g of liver for normal to 23.9 mg albumin per day per g of liver for regenerating liver 48 hours after partial hepatectomy. In contrast, the net rate of synthesis of total liver protein increased from 576 mg protein per day per g of liver in normal rats to 1710 mg of protein per day per g of liver in rats 48 hours after partial hepatectomy.

Adenine nucleotide levels could be precisely and reproducibly adjusted in liver cell suspensions by partially depleting the ATP pool with D-fructose or glycerol. Thus, it was possible to quantitatively correlate rates of protein synthesis and secretion with intracellular levels of ATP and with derived parameters, such as the adenylate energy charge. Half the maximum rate of incorporation of leucine into protein was observed at an energy charge of 0�80, a ratio of ATP to ADP of 2�6, and an ATP level of 1�05 pmol per g of wet cells. Proteins were secreted with half the maximum rate at an energy charge of 0�85, a ratio of ATP to ADP of 3�1 and an ATP concentration of 1 �1 pmol per gof wet cells. Protein secretion dill not depend on continued synthesis. Inhibitors of oxidative phosphorylation inhibited protein secretion in addition to protein synthesis, in contrast to observations by other authors on liver slices.