Structural determinants involved in the activation and regulation of G protein-coupled receptors: lessons from the alpha1-adrenegic receptor subtypes.

The aim of a large number of studies on G protein-coupled receptors was centered on understanding the structural basis of their main functional properties. Here, we will briefly review the results obtained on the alpha1-adrenergic receptor subtypes belonging to the rhodopsin-like family of receptors. These findings contribute, on the one hand, to further understand the molecular basis of adrenergic transmission and, on the other, to provide some generalities on the structure-functional relationship of G protein-coupled receptors.

Impact of increasing mean air temperature on the development of rice and red rice

The objective of this study was to assess the development response of cultivated rice and red rice to different increases in minimum and maximum daily air temperatures, in Santa Maria, Rio Grande do Sul State, Brazil. One hundred years climate scenarios of temperatures 0, +1, +2, +3, +4, and +5ºC, with symmetric and asymmetric increases in minimum and maximum daily air temperatures were created, using the LARS-WG Weather Generator, and a 1969-2003 database. Nine cultivated rice genotypes (IRGA 421, IRGA 416, IRGA 417, IRGA 420, BRS 7 TAIM, BR-IRGA 409, EPAGRI 109, EEA 406 and a hybrid), and two red rice biotypes (awned black hull-ABHRR, and awned yellow hull-AYHRR) were used. The dates of panicle differentiation (R1), anthesis (R4), and all grains with brown hulls (R9) were estimated with a nonlinear simulation model. Overall, the duration of the emergence-R1 phase decreased, whereas the duration of the R1-R4 and R4-R9 phases most often increased, as temperature increased in the climate change scenarios. The simulated rice development response to elevated temperature was not the same, when the increase in minimum and maximum temperature was symmetric or asymmetric.

Employers' attitudes towards long-term unemployed people and the role of activation in Switzerland

Over the last few years, most OECD countries have extended their activation policy to new groups of non-working people, including the long-term unemployed (LTU). However, it is widely known that employers tend to regard LTU people as potentially problematic persons. This is likely to constitute a major obstacle for long-term unemployed jobseekers. On the basis of a survey among employers in a Swiss canton (N = 722), this article aims to shed light on the perception employers have of the long-term unemployed and whether this may matter for their recruitment practices. It also asks what, from the employer point of view, may facilitate access to employment for an LTU person. A key finding is that large companies have a worse image of the long-term unemployed and are less likely to hire them. Furthermore, independent of company size, a test period or the recommendation of a trustworthy person is seen as the factors most likely to facilitate access to jobs for LTU people.

05040-015 Viking Lake Watershed Final Report

Viking Lake State Park is beautiful resource which has been special to residents of Southwest Iowa and visitors from around the region. Unfortunately, Viking Lake itself is being impacted by non-point source pollution. Water quality conditions are becoming the reason that visitors are shying away from the park instead of flocking to it. To combat these non-point source problems the Viking Lake Water Quality Project has been initiated and $327,000 has been allocated through the Section 319/WSPF Program which will address water quality concerns in the watershed. Additionally, IDNR Fisheries is preparing for an entire renovation of Viking Lake in 2006. One funding gap remains, that may prevent this comprehensive water quality project from achieving a successful endpoint. Funds are still needed for the renovation of malfunctioning septic systems at Viking Village housing development which is adjacent to the park, and has been identified as a primary source of contamination entering the lake. The intent of this application is to secure funds so that these septic system problems can be corrected and water quality conditions of this important natural resource restored for public enjoyment.

[Pérouse. Duomo di San Lorenzo]

Référence bibliographique : Weigert, 327

Resistência de genótipos de feijão-de-corda ao pulgão-preto

O objetivo deste trabalho foi avaliar a resistência de genótipos de feijão-de-corda (Vigna unguiculata) ao pulgão-preto (Aphis craccivora). Foram realizados experimentos com e sem chance de escolha em casa de vegetação, na Universidade Federal do Ceará. O delineamento utilizado foi o de blocos ao acaso com vinte tratamentos, representados pelos genótipos 421-07-44, Chumbinho, Zebu, EPACE 10, Frade Preto, Inhumã, João Paulo II, Manteiguinha, Maranhão, Pitiúba, Quarenta Dias, Seridó, Sete Semanas, TVu 1037, TVu 1888, TVu 310, TVu 36, TVu 408P2, TVu 410 e VITA 7. Verificou-se que TVu 408P2, TVu 1037 e TVu 410 foram preteridos por adultos e ninfas do pulgão-preto, em ambos experimentos. Os genótipos TVu 408P2, TVu 410, TVu 36 e TVu 1037 apresentam resistência provavelmente do tipo antibiose ou antixenose. O genótipo 421-07-44 mostrou-se suscetível ao pulgão-preto.

Simulação do rendimento de grãos de arroz irrigado em cenários de mudanças climáticas

O objetivo deste trabalho foi simular o rendimento de grãos de arroz em cenários de mudanças climáticas com aumento da atual concentração de CO2 na atmosfera e da temperatura média do ar em Santa Maria, RS, e verificar as implicações nas recomendações de época de semeadura. Foram utilizados cenários de mudanças climáticas, para os próximos 100 anos, com o dobro da quantidade de CO2 e com aumentos de temperatura do ar de 1, 2, 3, 4 e 5°C. O rendimento de grãos da cultura do arroz foi simulado com o modelo InfoCrop. As simulações foram realizadas para três cultivares de arroz (IRGA 421, IRGA 417 e EPAGRI 109) em sete datas de semeadura, com intervalos mensais, de 20 de julho até 20 de janeiro. Um aumento no rendimento de grãos de arroz irrigado foi observado nos cenários de mudanças climáticas simulado para as três cultivares, com maior incremento na muito precoce (IRGA 421) e menor na de ciclo longo (EPAGRI 109). Se as mudanças climáticas se confirmarem, o período de semeadura recomendado atualmente para cultivares de arroz irrigado deverá ser ampliado.

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Long-term changes in rice development in Southern Brazil, during the last ten decades

The objective of this work was to test long-term trends in the duration of rice development phases in Santa Maria, RS, Brazil. The duration from emergence to V3 (EM-V3), emergence to panicle differentiation (EM-R1), emergence to anthesis (EM-R4), and emergence to all grains with brown hull (EM-R9) was calculated using leaf appearance and developmental models for four rice cultivars (IRGA 421, IRGA 417, EPAGRI 109, and EEA 406), for the period from 1912 to 2011, considering three emergence dates (early, mid, and late). The trend of the time series was tested with the non-parametric Mann-Kendall test, and the magnitude of the trend was estimated with simple linear regression. Rice development has changed over the last ten decades in this location, leading to an anticipation of harvest time of 17 to 31 days, depending on the cultivar maturity group and emergence date, which is related to trends of temperature increase during the growing season. Warmer temperatures over the evaluated time period are responsible for changing rice phenology in this location, since minimum and maximum daily temperature drive the rice developmental models used.

Concilium Meldense-Parisiense, 845-846.

F. 1 Concile de Meaux-Paris, 845-846 (M. G., Capit., II, 395-421). F. 35v Synode de Beauvais, avril 845 (ibid., 387).

Familial frontotemporal dementia with ubiquitin inclusion bodies and without motor neuron disease.

Frontotemporal dementia (FTD) is the second most common degenerative dementia after Alzheimer's disease and its Lewy body variant. Clinical pathology can be subdivided in three main neuropathological subtypes: frontal lobe dementia, Pick's disease and FTD with motor neuron disease (MND), all characterised by distinct histological features. Until recently the presence of ubiquitin-positive intraneuronal inclusions in the dentate gyrus, and the temporal and frontal cortex was usually associated with the MND type. Such inclusions were also observed in a few sporadic cases of FTD without or with parkinsonism (FTDP) in the absence of MND. We present here clinical, neuropathological and immunohistochemical data about a Swiss FTD family with FTDP-like features but without MND. Spongiosis and mild gliosis were observed in the grey matter. No neurofibrillary tangles, Pick bodies, Lewy bodies, senile plaques or prion-positive signals were present. However, ubiquitin-positive intracytoplasmic inclusions were detected in various structures but predominantly in the dentate gyrus. These observations support the existence of a familial form of FTDP with ubiquitin-positive intracytoplasmic inclusions (Swiss FTDP family).

Prévention de la maladie veineuse chronique: quels conseils donner à nos patients [Prevention of chronic venous disease: which advice for our patients?].

Chronic venous disease (CVD) is a major public health problem due to its high prevalence and socioeconomic costs. In absence of adequate care, it can lead to chronic venous insufficiency (CVI). Disturbed venous-flow patterns lead to venous hypertension. Therefore, prevention of CVD involves venous hypertension reduction. In primary prevention, it is essential to inform the patient about necessary lifestyle changes. In case of CVD, it is essential to propose treatment (compression, venoactive drugs, and interventional treatments) to avoid CVI appearance and eventually offer the best therapy solutions for CVI complications.

Inhibition of bicarbonate transport protects embryonic heart against reoxygenation-induced dysfunction.

It has not been well established whether the mechanisms participating in pH regulation in the anoxic-reoxygenated developing myocardium resemble those operating in the adult. We have specially examined the importance of Na+/H+ exchange (NHE) and HCO3-dependent transports in cardiac activity after changes in extracellular pH (pHo). Spontaneously contracting hearts isolated from 4-day-old chick embryos were submitted to single or repeated anoxia (1 min) followed by reoxygenation (10 min). The chronotropic, dromotropic and inotropic responses of the hearts were determined in standard HCO3- buffer at pHo 7.4 and at pHo 6.5 (hypercapnic acidosis). In distinct experiments, acidotic anoxia preceded reoxygenation at pHo 7.4. NHE was blocked with amiloride derivative HMA (1 micro mol/l) and HCO3-dependent transports were inactivated by replacement of HCO3 or blockade with stilbene derivative DIDS (100 micro mol/l). Anoxia caused transient tachycardia, depressed mechanical function and induced contracture. Reoxygenation temporarily provoked cardiac arrest, atrio-ventricular (AV) block, arrhythmias and depression of contractility. Addition of DIDS or substitution of HCO3 at pHo 7.4 had the same effects as acidosis per se, i.e. shortened contractile activity and increased incidence of arrhythmias during anoxia, prolonged cardioplegia and provoked arrhythmias at reoxygenation. Under anoxia at pHo 6.5/reoxygenation at pHo 7.4, cardioplegia, AV block and arrhythmias were all markedly prolonged. Interestingly, in the latter protocol, DIDS suppressed AV block and arrhythmias during reoxygenation, whereas HMA had no effect. Thus, intracellular pH regulation in the anoxic-reoxygenated embryonic heart appears to depend predominantly on HCO3 availability and transport. Furthermore, pharmacological inhibition of anion transport can protect against reoxygenation-induced dysfunction.

Bactericidal synergism between daptomycin and the phage lysin Cpl-1 in a mouse model of pneumococcal bacteraemia.

Combination therapy may improve the outcome of Streptococcus pneumoniae-induced bacteraemia. Here we tested the combination of two antipneumococcal agents, daptomycin and Cpl-1 (the pneumococcal Cp-1 bacteriophage lysin), in a mouse model of pneumococcal bacteraemia. Mice were challenged intraperitoneally (i.p.) with 10(6)CFU of the extremely virulent serotype 2 S. pneumoniae D39 isolate. Subtherapeutic doses of daptomycin (0.4mg/kg) and Cpl-1 (0.4mg/kg and 1mg/kg) were administrated i.p. either alone or in combination by a single bolus injection 1h after bacterial challenge. Survival rates of animals were followed over a period of 7 days. Daptomycin (0.4mg/kg) in combination with Cpl-1 (0.4mg/kg) significantly increased the percentage of surviving mice at Day 7 (80%) compared with the untreated control (0%) and daptomycin or Cpl-1 monotherapy (35% and 0%, respectively). Whilst increasing the concentration of Cpl-1 to 1.0mg/kg did not improve survival when injected alone, its combination with 0.4mg/kg daptomycin further increased the survival rate to 95%. Thus, it was found that the combination of daptomycin with Cpl-1 was synergistic and bactericidal against S. pneumoniae in a mouse model of pneumococcal bacteraemia. To our knowledge, this is the first report of synergism between daptomycin and a phage lysin demonstrated in vivo. Such a combination could represent an interesting alternative therapy for the treatment of pneumococcal bacteraemia/sepsis and possibly other severe pneumococcal infections.