Scalable inference of heterogeneous reaction kinetics from pooled single-cell recordings.

Mathematical methods combined with measurements of single-cell dynamics provide a means to reconstruct intracellular processes that are only partly or indirectly accessible experimentally. To obtain reliable reconstructions, the pooling of measurements from several cells of a clonal population is mandatory. However, cell-to-cell variability originating from diverse sources poses computational challenges for such process reconstruction. We introduce a scalable Bayesian inference framework that properly accounts for population heterogeneity. The method allows inference of inaccessible molecular states and kinetic parameters; computation of Bayes factors for model selection; and dissection of intrinsic, extrinsic and technical noise. We show how additional single-cell readouts such as morphological features can be included in the analysis. We use the method to reconstruct the expression dynamics of a gene under an inducible promoter in yeast from time-lapse microscopy data.

Toll-like receptor 2 (TLR2) polymorphisms are associated with reversal reaction in leprosy.

BACKGROUND: Leprosy is characterized by a spectrum of clinical manifestations that depend on the type of immune response against the pathogen. Patients may undergo immunological changes known as "reactional states" (reversal reaction and erythema nodosum leprosum) that result in major clinical deterioration. The goal of the present study was to assess the effect of Toll-like receptor 2 (TLR2) polymorphisms on susceptibility to and clinical presentation of leprosy. METHODS: Three polymorphisms in TLR2 (597C-->T, 1350T-->C, and a microsatellite marker) were analyzed in 431 Ethiopian patients with leprosy and 187 control subjects. The polymorphism-associated risk of developing leprosy, lepromatous (vs. tuberculoid) leprosy, and leprosy reactions was assessed by multivariate logistic regression models. RESULTS: The microsatellite and the 597C-->T polymorphisms both influenced susceptibility to reversal reaction. Although the 597T allele had a protective effect (odds ratio [OR], 0.34 [95% confidence interval {CI}, 0.17-0.68]; P= .002 under the dominant model), homozygosity for the 280-bp allelic length of the microsatellite strongly increased the risk of reversal reaction (OR, 5.83 [95% CI, 1.98-17.15]; P= .001 under the recessive model). These associations were consistent among 3 different ethnic groups. CONCLUSIONS: These data suggest a significant role for TLR-2 in the occurrence of leprosy reversal reaction and provide new insights into the immunogenetics of the disease.

Comunicação de Marketing na Formação da Imagem dos Destinos Turísticos: o caso de Cabo Verde

Segundo a Organização Mundial do Turismo (OMT), o turismo é a maior indústria do séc. XXI gerando anualmente milhares de milhões de dólares em divisas para a economia de inúmeros países. Por apresentar um conjunto de características muito específicas, o sucesso desta actividade é fortemente condicionado pela imagem que os turistas e potenciais turistas apresentam relativamente a um determinado destino. Apesar de existirem muitos factores que interferem na formação desta imagem, a comunicação de marketing é apontada, pelos investigadores, como um dos elementos que desempenha um papel crucial neste âmbito. O objecto do presente trabalho de investigação é a comunicação de marketing na formação da imagem dos destinos turísticos particularizando o arquipélago de Cabo Verde. O principal objectivo da pesquisa, é analisar a eficácia da comunicação de marketing de três organizações (Cabo Verde – Investimentos, União Nacional dos Operadores Turísticos e operador Soltropico), na promoção do arquipélago de Cabo Verde, enquanto destino turístico, no mercado português. Para a realização deste estudo empírico, foram definidas três hipóteses. Essas hipóteses foram testadas através do cruzamento da informação proveniente de uma entrevista realizada aos directores de marketing de cada uma das três organizações, com os dados obtidos a partir da análise de conteúdo dos instrumentos de comunicação que têm vindo a ser utilizados pelas respectivas entidades para promover o destino e com as respostas de um conjunto de 115 turistas portugueses, a um questionário cujo assunto se encontra relacionado com os principais atributos de Cabo Verde enquanto destino de férias. A investigação realizada permitiu verificar que, de uma forma geral, existe uma sintonia entre os atributos de Cabo Verde que as organizações têm intenção de divulgar, os atributos deste destino que são transmitidos pelos seus instrumentos comunicação e os principais atributos do arquipélago indicados pelos turistas portugueses. Contudo, os resultados do estudo revelam também a necessidade de se introduzir algumas correcções a nível de conteúdos e imagens que se encontram presentes nos instrumentos de comunicação de algumas das organizações, visando a criação de uma imagem mais atractiva deste destino.

Pääjohtaja Martti Hovi 19/11 1963

Kirje

Polymorphisms in Toll-like receptor 4 (TLR4) are associated with protection against leprosy.

Accumulating evidence suggests that polymorphisms in Toll-like receptors (TLRs) influence the pathogenesis of mycobacterial infections, including leprosy, a disease whose manifestations depend on host immune responses. Polymorphisms in TLR2 are associated with an increased risk of reversal reaction, but not susceptibility to leprosy itself. We examined whether polymorphisms in TLR4 are associated with susceptibility to leprosy in a cohort of 441 Ethiopian leprosy patients and 197 healthy controls. We found that two single nucleotide polymorphisms (SNPs) in TLR4 (896G>A [D299G] and 1196C>T [T399I]) were associated with a protective effect against the disease. The 896GG, GA and AA genotypes were found in 91.7, 7.8 and 0.5% of leprosy cases versus 79.9, 19.1 and 1.0% of controls, respectively (odds ratio [OR] = 0.34, 95% confidence interval [CI] 0.20-0.57, P < 0.001, additive model). Similarly, the 1196CC, CT and TT genotypes were found in 98.1, 1.9 and 0% of leprosy cases versus 91.8, 7.7 and 0.5% of controls, respectively (OR = 0.16, 95% CI 0.06--.40, P < 0.001, dominant model). We found that Mycobacterium leprae stimulation of monocytes partially inhibited their subsequent response to lipopolysaccharide (LPS) stimulation. Our data suggest that TLR4 polymorphisms are associated with susceptibility to leprosy and that this effect may be mediated at the cellular level by the modulation of TLR4 signalling by M. leprae.

The HP-filter in cross-country comparisons

Many empirical studies of business cycles have followed the practise ofapplying the Hodrick-Prescott filter for cross-country comparisons. Thestandard procedure is to set the weight \lambda, which determines the'smoothness' of the trend equal to 1600. We show that if this value isused for against common wisdom about business cycles. As an example, weshow that the long recession occurred inSpain between 1975 and 1985 goesunnotoced by the HP filter. We propose a method for adjusting \lambda byreinterpreting the HP-filter as the solution to a constrained minimizationproblem. We argue that the common practice of fixing \lambda across countriesamounts to chankging the constraints on trend variability across countries.Our proposed method is easy to apply, retains all the virtues of thestandard HP-filter and when applied to Spanish data the results are inthe line with economic historian's view. Applying the method to a numberof OECD countries we find that, with the exception of Spain, Italy andJapan, the standard choice of \lambda=1600 is sensible.

Oxidative and glycogenolytic cCapacities within the developing chick heart.

Cardiac morphogenesis and function are known to depend on both aerobic and anaerobic energy-producing pathways. However, the relative contribution of mitochondrial oxidation and glycogenolysis, as well as the determining factors of oxygen demand in the distinct chambers of the embryonic heart, remains to be investigated. Spontaneously beating hearts isolated from stage 11, 20, and 24HH chick embryos were maintained in vitro under controlled metabolic conditions. O(2) uptake and glycogenolytic rate were determined in atrium, ventricle, and conotruncus in the absence or presence of glucose. Oxidative capacity ranged from 0.2 to 0.5 nmol O(2)/(h.microg protein), did not depend on exogenous glucose, and was the highest in atria at stage 20HH. However, the highest reserves of oxidative capacity, assessed by mitochondrial uncoupling, were found at the youngest stage and in conotruncus, representing 75 to 130% of the control values. At stage 24HH, glycogenolysis in glucose-free medium was 0.22, 0.17, and 0.04 nmol glucose U(h.microg protein) in atrium, ventricle, and conotruncus, respectively. Mechanical loading of the ventricle increased its oxidative capacity by 62% without altering glycogenolysis or lactate production. Blockade of glycolysis by iodoacetate suppressed lactate production but modified neither O(2) nor glycogen consumption in substrate-free medium. These findings indicate that atrium is the cardiac chamber that best utilizes its oxidative and glycogenolytic capacities and that ventricular wall stretch represents an early and major determinant of the O(2) uptake. Moreover, the fact that O(2) and glycogen consumptions were not affected by inhibition of glyceraldehyde-3-phosphate dehydrogenase provides indirect evidence for an active glycerol-phosphate shuttle in the embryonic cardiomyocytes.

Levantamento das espécies de Simulium (Diptera, Simuliidae), Riacho dos Padres, município de Almirante Tamandaré, Paraná, Brasil

De janeiro a agosto de 2002, quinzenalmente, foi levada a efeito a coleta de simulídeos imaturos em substratos naturais e antrópicos no Riacho dos Padres. O trabalho visou proceder ao inventário das espécies e verificar as freqüências relativas. A área de propriedade particular localizada na Região Metropolitana de Curitiba constitui uma microempresa de agronegócio, com criação de peixes, coelhos, ovinos, bovinos, aves domésticas e, ainda, área de lazer com eqüinos para cavalgada de visitantes. A presença constante de animais hospedeiros e a ração fornecida aos peixes garantiram farta alimentação aos simulídeos, o que favoreceu a explosão desta praga. Em todos os substratos foram coletadas 24.021 pupas e um total de 197.812 larvas. A partir de pupas, foram identificadas com as seguintes freqüências: Simulium inaequale (55,24%), Simulium perflavum (16,81%), Simulium pertinax (13,93%), Simulium orbitale (8,03%), Simulium subnigrum (4,92%), Simulium distinctum (1,03%) e Simulium incrustatum (0,04%). Verificou-se também a quantidade de larvas que colonizaram todos os substratos.

Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults.

Although both inflammatory and atherosclerosis markers have been associated with coronary heart disease (CHD) risk, data directly comparing their predictive value are limited. The authors compared the value of 2 atherosclerosis markers (ankle-arm index (AAI) and aortic pulse wave velocity (aPWV)) and 3 inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)) in predicting CHD events. Among 2,191 adults aged 70-79 years at baseline (1997-1998) from the Health, Aging, and Body Composition Study cohort, the authors examined adjudicated incident myocardial infarction or CHD death ("hard" events) and "hard" events plus hospitalization for angina or coronary revascularization (total CHD events). During 8 years of follow-up between 1997-1998 and June 2007, 351 participants developed total CHD events (197 "hard" events). IL-6 (highest quartile vs. lowest: hazard ratio = 1.82, 95% confidence interval: 1.33, 2.49; P-trend < 0.001) and AAI (AAI </= 0.9 vs. AAI 1.01-1.30: hazard ratio = 1.57, 95% confidence interval: 1.14, 2.18) predicted CHD events above traditional risk factors and modestly improved global measures of predictive accuracy. CRP, TNF-alpha, and aPWV had weaker associations. IL-6 and AAI accurately reclassified 6.6% and 3.3% of participants, respectively (P's </= 0.05). Results were similar for "hard" CHD, with higher reclassification rates for AAI. IL-6 and AAI are associated with future CHD events beyond traditional risk factors and modestly improve risk prediction in older adults.