Bacterial membrane injuries induced by lactacin F and nisin

The combined action of nisin and lactacin F, two bacteriocins produced by lactic acid bacteria, is additive. In this report, the basis of this effect is examined. Channels formed by lactacin F were studied by experiments using planar lipid bilayers, and bactericidal effects were analyzed by flow cytometry. Lactacin F produced pores with a conductance of 1 ns in black lipid bilayers in 1 mM KClat 10 mV at 20°C. Pore formation was strongly dependent on voltage. Although lactacin F formed pores at very low potential (10 mV), the dependence was exponentialabov e 40 mV. The injuries induced by nisin and lactacin F in the membranes of Lactobacillus helveticus produced different flow cytometric profiles. Probably, when both bacteriocins are present, each acts separately; their cooperation may be due to an increase in the number of single membrane injuries

Moral Hazard in Repeated Procurement of Services

This paper analyzes repeated procurement of services as a four-stage game divided into two periods. In each period there is (1) a contest stage à la Tullock in which the principal selects an agent and (2) a service stage in which the selected agent provides a service. Since this service effort is non-verifiable, the principal faces a moral hazard problem at the service stages. This work considers how the principal should design the period-two contest to mitigate the moral hazard problem in the period-one service stage and to maximize total service and contest efforts. It is shown that the principal must take account of the agent's past service effort in the period-two contest success function. The results indicate that the optimal way to introduce this `bias' is to choose a certain degree of complementarity between past service and current contest efforts. This result shows that contests with `additive bias' (`multiplicative bias') are optimal in incentive problems when effort cost is low (high). Furthermore, it is shown that the severity of the moral hazard problem increases with the cost of service effort (compared to the cost of contest effort) and the number of agents. Finally, the results are extended to more general contest success functions. JEL classification: C72; D82 Key words: Biased contests; Moral Hazard; Repeated Game; Incentives.

Effects of prolonged ethanol intake and malnutrition on rat pancreas

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.

Effects of prolonged ethanol intake and malnutrition on rat pancreas

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.

Effects of prolonged ethanol intake and malnutrition on rat pancreas

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.

Effects of prolonged ethanol intake and malnutrition on rat pancreas

Nutritional factors, especially the protein and fat content of the diet, may change pancreatic morphology after ethanol induced injury. This study was performed to delineate the combined effects of a low fat diet and longterm ethanol ingestion on the rat pancreas. Male Sprague-Dawley rats were maintained with five different diets for 12 weeks and the pancreas removed on the day they were killed. Rats fed a very low fat diet without ethanol (5% of total calories as lipid) developed malnutrition, pancreatic steatosis, and reduction in zymogen granules content. Animals fed a 35% lipid diet with ethanol also developed pancreatic steatosis but changes in zymogen granules content were not detected. Both malnutrition and longterm ethanol consumption increased pancreatic cholesterol ester content, and their effects were additive. Pancreatic steatosis was accompanied with hypercholesterolaemia. Amylase, lipase, and cholesterol esterase content were reduced in malnourished rats; but longterm ethanol ingestion, regardless of the nutritional state, increased lipase content and decreased amylase. It is suggested that high serum cholesterol concentrations and increased pancreatic lipase activity could cause accumulation of cholesterol esters in acinar cells. Fat accumulation in the pancreas has been reported as the earliest histopathological feature in alcoholic patients and may be responsible for cytotoxic effects on the acinar cells at the level of the cell membrane. Although it is difficult to extrapolate results in this animal study to the human situation, the results presented in this work might explain the higher incidence of pancreatitis is malnourished populations as well as in alcoholic subjects that is reported in dietary surveys.

AMP-activated protein kinase plays an important evolutionary conserved role in the regulation of glucose metabolism in fish skeletal muscle cells

AMPK, a master metabolic switch, mediates the observed increase of glucose uptake in locomotory muscle of mammals during exercise. AMPK is activated by changes in the intracellular AMP:ATP ratio when ATP consumption is stimulated by contractile activity but also by AICAR and metformin, compounds that increase glucose transport in mammalian muscle cells. However, the possible role of AMPK in the regulation of glucose metabolism in skeletal muscle has not been investigated in other vertebrates, including fish. In this study, we investigated the effects of AMPK activators on glucose uptake, AMPK activity, cell surface levels of trout GLUT4 and expression of GLUT1 and GLUT4 as well as the expression of enzymes regulating glucose disposal and PGC1α in trout myotubes derived from a primary muscle cell culture. We show that AICAR and metformin significantly stimulated glucose uptake (1.6 and 1.3 fold, respectively) and that Compound C completely abrogated the stimulatory effects of the AMPK activators on glucose uptake. The combination of insulin and AMPK activators did not result in additive nor synergistic effects on glucose uptake. Moreover, exposure of trout myotubes to AICAR and metformin resulted in an increase in AMPK activity (3.8 and 3 fold, respectively). We also provide evidence suggesting that stimulation of glucose uptake by AMPK activators in trout myotubes may take place, at least in part, by increasing the cell surface and mRNA levels of trout GLUT4. Finally, AICAR increased the mRNA levels of genes involved in glucose disposal (hexokinase, 6-phosphofructokinase, pyruvate kinase and citrate synthase) and mitochondrial biogenesis (PGC-1α) and did not affect glycogen content or glycogen synthase mRNA levels in trout myotubes. Therefore, we provide evidence, for the first time in non-mammalian vertebrates, suggesting a potentially important role of AMPK in stimulating glucose uptake and utilization in the skeletal muscle of fish.

Influence of process parameters on part quality and mechanical properties for DMLS and SLM with iron-based materials

Rapid manufacturing is an advanced manufacturing technology based on layer-by-layer manufacturing to produce a part. This paper presents experimental work carried out to investigate the effects of scan speed, layer thickness, and building direction on the following part features: dimensional error, surface roughness, and mechanical properties for DMLS with DS H20 powder and SLM with CL 20 powder (1.4404/AISI 316L). Findings were evaluated using ANOVA analysis. According to the experimental results, build direction has a significant effect on part quality, in terms of dimensional error and surface roughness. For the SLM process, the build direction has no influence on mechanical properties. Results of this research support industry estimating part quality and mechanical properties before the production of parts with additive manufacturing, using iron-based powders

Little evidence for association between the TGFBR1*6A variant and colorectal cancer: a family-based association study on non-syndromic family members from Australia and Spain.

Genome-wide linkage studies have identified the 9q22 chromosomal region as linked with colorectal cancer (CRC) predisposition. A candidate gene in this region is transforming growth factor beta receptor 1 (TGFBR1). Investigation of TGFBR1 has focused on the common genetic variant rs11466445, a short exonic deletion of nine base pairs which results in truncation of a stretch of nine alanine residues to six alanine residues in the gene product. While the six alanine (*6A) allele has been reported to be associated with increased risk of CRC in some population based study groups this association remains the subject of robust debate. To date, reports have been limited to population-based case-control association studies, or case-control studies of CRC families selecting one affected individual per family. No study has yet taken advantage of all the genetic information provided by multiplex CRC families. Methods: We have tested for an association between rs11466445 and risk of CRC using several family-based statistical tests in a new study group comprising members of non-syndromic high risk CRC families sourced from three familial cancer centres, two in Australia and one in Spain. Results: We report a finding of a nominally significant result using the pedigree-based association test approach (PBAT; p = 0.028), while other family-based tests were non-significant, but with a p-value < 0.10 in each instance. These other tests included the Generalised Disequilibrium Test (GDT; p = 0.085), parent of origin GDT Generalised Disequilibrium Test (GDT-PO; p = 0.081) and empirical Family-Based Association Test (FBAT; p = 0.096, additive model). Related-person case-control testing using the 'More Powerful' Quasi-Likelihood Score Test did not provide any evidence for association (M-QL5; p = 0.41). Conclusions: After conservatively taking into account considerations for multiple hypothesis testing, we find little evidence for an association between the TGFBR1*6A allele and CRC risk in these families. The weak support for an increase in risk in CRC predisposed families is in agreement with recent meta-analyses of case-control studies, which estimate only a modest increase in sporadic CRC risk among 6*A allele carriers.

A Cartan-Eilenberg approach to Homotopical Algebra

In this paper we propose an approach to homotopical algebra where the basic ingredient is a category with two classes of distinguished morphisms: strong and weak equivalences. These data determine the cofibrant objects by an extension property analogous to the classical lifting property of projective modules. We define a Cartan-Eilenberg category as a category with strong and weak equivalences such that there is an equivalence of categories between its localisation with respect to weak equivalences and the relative localisation of the subcategory of cofibrant objects with respect to strong equivalences. This equivalence of categories allows us to extend the classical theory of derived additive functors to this non additive setting. The main examples include Quillen model categories and categories of functors defined on a category endowed with a cotriple (comonad) and taking values on a category of complexes of an abelian category. In the latter case there are examples in which the class of strong equivalences is not determined by a homotopy relation. Among other applications of our theory, we establish a very general acyclic models theorem.

Visual impairment and multimorbidity in a representative sample of the Spanish population

BACKGROUND: In the context of population aging, visual impairment has emerged as a growing concern in public health. However, there is a need for further research into the relationship between visual impairment and chronic medical conditions in the elderly. The aim of our study was to examine the relationship between visual impairment and three main types of co-morbidity: chronic physical conditions (both at an independent and additive level), mental health and cognitive functioning. METHODS: Data were collected from the COURAGE in Europe project, a cross-sectional study. A total of 4,583 participants from Spain were included. Diagnosis of chronic medical conditions included self-reported medical diagnosis and symptomatic algorithms. Depression and anxiety were assessed using CIDI algorithms. Visual assessment included objective distance/near visual acuity and subjective visual performance. Descriptive analyses included the whole sample (n = 4,583). Statistical analyses included participants aged over 50 years (n = 3,625; mean age = 66.45 years) since they have a significant prevalence of chronic conditions and visual impairment. Crude and adjusted binary logistic regressions were performed to identify independent associations between visual impairment and chronic medical conditions, physical multimorbidity and mental conditions. Covariates included age, gender, marital status, education level, employment status and urbanicity. RESULTS: The number of chronic physical conditions was found to be associated with poorer results in both distance and near visual acuity [OR 1.75 (CI 1.38-2.23); OR 1.69 (CI 1.27-2.24)]. At an independent level, arthritis, stroke and diabetes were associated with poorer distance visual acuity results after adjusting for covariates [OR 1.79 (CI 1.46-2.21); OR 1.59 (CI 1.05-2.42); OR 1.27 (1.01-1.60)]. Only stroke was associated with near visual impairment [OR 3.01 (CI 1.86-4.87)]. With regard to mental health, poor subjective visual acuity was associated with depression [OR 1.61 (CI 1.14-2.27); OR 1.48 (CI 1.03-2.13)]. Both objective and subjective poor distance and near visual acuity were associated with worse cognitive functioning. CONCLUSIONS: Arthritis, stroke and the co-occurrence of various chronic physical diseases are associated with higher prevalence of visual impairment. Visual impairment is associated with higher prevalence of depression and poorer cognitive function results. There is a need to implement patient-centered care involving special visual assessment in these cases.

Empirics of the international inequality in CO2 emissions intensity: explanatory factors according to complementary decomposition methodologies

This paper analyses the international inequalities in CO2 emissions intensity for the period 1971- 2009 and assesses explanatory factors. Multiplicative, group and additive methodologies of inequality decomposition are employed. The first allows us to clarify the separated role of the carbonisation index and the energy intensity in the pattern observed for inequalities in CO2 intensities; the second allows us to understand the role of regional groups; and the third allows us to investigate the role of different fossil energy sources (coal, oil and gas). The results show that, first, the reduction in global emissions intensity has coincided with a significant reduction in international inequality. Second, the bulk of this inequality and its reduction are attributed to differences between the groups of countries considered. Third, coal is the main energy source explaining these inequalities, although the growth in the relative contribution of gas is also remarkable. Fourth, the bulk of inequalities between countries and its decline are explained by differences in energy intensities, although there are significant differences in the patterns demonstrated by different groups of countries.