Reactive oxygen species as a risk factor in verotoxin-1-exposed rats.

It has been suggested the the interaction of Escherichia coli O157-derived verotoxins (VTs) with the vascular endothelium plays a central role in the pathogenesis of the thrombotic microangiopathy and ischemic lesions characteristic of hemolytic uremic syndrome (HUS) and E. coli O157-associated hemorrhagic colitis. Intravenous administration of both E. coli O157-derived VT1 and lipopolysaccharide (LPS) in the rat induced a synergistic increase in thiobarbituric acid (TBA) values in those animal's plasma, as compared with that injected with VT1 or LPS alone. We then hypothesized that an increase in lipid peroxidation in the rat plasma was due to an enhanced production of endothelial cell-derived reactive oxidant. Based on determination of rat sera and cultured human aortic endothelial cells (HAECs), VT1 had little if any effect on LPS-stimulated increase of nitric oxide and the resultant peroxynitrite generations. Both RT-PCR and Western blot studies of reactive oxygen species-related enzymes showed that VT1 markedly decreased the expression of catalase mRNA and protein in HAECs, but caused less alteration in the levels of Cu, Zn-superoxide dismutase, and NADPH oxidase mRNA. Further studies by spin trapping analysis using 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) revealed a time-dependent increase in hydroxyl radicals by VT1 in HAECs. The accumulated data thus suggest that bacterial VT1 reduces mainly catalase levels in endothelial cells, which is synergistically potentiated by LPS, and that the resulting hydroxyl radical participates in endothelium injury through a marked enhancement of lipid peroxidation, leading to HUS.     

Natural hybridization in heliconiine butterflies: the species boundary as a continuum

Background  

To understand speciation and the maintenance of taxa as separate entities, we need information about natural hybridization and gene flow among species.     

How to survive as a pioneer species in the Antarctic benthos: minimum dispersal distance as a function of lifetime and disturbance

Very few details exists concerning the dispersal traits of Antarctic species and dispersal distances in particular are mostly unknown. Especially the general low number of mesoplanktonic larvae has caught attention, leading to the formulation of Thorson’s rule. From this concept, originally concerning only trophic aspects, sometimes a reduced dispersal distance is deduced. Using a generic simulation model we show that in a benthic habitat exposed to iceberg scouring, even short dispersal phases of few hours are sufficient for a pioneer species to persist. This is very surprising for a pioneer species which should be able to disperse widely and colonise distant disturbed areas which are free of superior competitors. Our model revealed that the reason for this is the non-linear dependence of the dispersal distance on the disturbance regime and on species longevity. Thus, it is the combined effect of life history and disturbance traits which is important here: a sufficiently high disturbance frequency due to iceberg scouring and a long individual lifetime due to the low temperature decrease minimum dispersal distances required for persistence and thus coexistence and present an additional explanation for the relative rarity of planktonic larvae.     

Calcium as a limiting factor in the biology of Biomphalaria pfeifferi (Krauss), (Gastropoda: Planorbidae)

The minimum calcium requirements, relative importance of buffering and optimum ratio of calcium to magnesium, calcium to sodium, and calcium to potassium ions were determined for laboratory populations ofBiomphalaria pfeifferi and related to suggested limiting factors for the natural distribution of this species. Snails were reared in a range of concentrations of both calcium bicarbonate and unbuffered calcium sulphate from 0.5 to 20 mg/l as Ca⁺⁺ and also in a series of media with a constant concentration of 2 mg/l as Ca⁺⁺ but with a range of Ca/Mg, Ca/Na and Ca/K ratios of 4.0 to 0.1. Shell growth, survivorship, fecundity, egg fertility, and the net reproductive rate were compared. In calcium bicarbonate cultures a concentration of 2mg/l Ca⁺⁺ appeared to be the lower limit for the survival of laboratory populations but a concentration of 4 mg/l Ca⁺⁺ was needed for a population to thrive. The calcium sulphate salt gave much poorer results, emphasizing the importance of the bicarbonate buffer. In the cationic ratio experiments the low Ca/Mg ratios proved to have the most damaging effects on snail populations but the effects of very low Ca/Na and Ca/K ratios could also be measured. A parallel experiment on the hatching rate of snail eggs, using similar experimental solutions, gave comparable results. The significance of these findings to snail ecology is discussed.     

Depression as a risk factor for ischaemic heart disease in men: population based case-control study

Objective: To determine the relation between depression, anxiety, and use of antidepressants and the onset of ischaemic heart disease. Design: Population based case-control study. Setting: All 5623 patients registered with one general practice. Subjects: 188 male cases with ischaemic heart disease matched by age to 485 male controls without ischaemic heart disease; 139 female cases with ischaemic heart disease matched by age to 412 female controls. Main outcome measure: Adjusted odds ratios calculated by conditional logistic regression. Results: The risk of ischaemic heart disease was three times higher among men with a recorded diagnosis of depression than among controls of the same age (odds ratio 3.09; 95% confidence interval 1.33 to 7.21; P=0.009). This association persisted when smoking status, diabetes, hypertension, and underprivileged area (UPA(8)) score were included in a multivariate model (adjusted 2.75; 1.13 to 6.69; P=0.03). Men with depression within the preceding 10 years were three times more likely to develop ischaemic heart disease than were the controls (3.13; 1.27 to 7.70; P=0.01). Men with ischaemic heart disease had a higher risk of subsequent ischaemic heart disease than men without ischaemic heart disease (adjusted 2.34; 1.34 to 4.10; P=0.003). Depression was not a risk factor for ischaemic heart disease in women on multivariate analysis (adjusted 1.34; 0.70 to 2.56; P=0.38). Anxiety and subsequent ischaemic heart disease were not significantly associated in men or women. Conclusion: Depression may be an independent risk factor for ischaemic heart disease in men, but not in women.

Key messages

• So far, research into whether depression precedes myocardial infarction has been limited
• This case-control study examined the relation between ischaemic heart disease and depression and the differences in this relation between men and women
• Depression may be a risk factor for ischaemic heart disease in men but not women
• This is independent of diabetes, hypertension, deprivation score, and smoking status

     

Habitat type as a determinant of species range sizes: the example of lotic–lentic differences in aquatic Goleoptera

Species differ in the size of their geographical ranges, but it is unclear how this is affected by the intrinsic properties of various habitat types. Using data on range sizes for 490 species of aquatic Coleoptera from the Iberian Peninsula we show that running-water (lotic) species have much smaller distributional ranges than those occurring in standing water (lentic). This robust association of habitat type and range size has independently arisen in at least four monophyletic coleopteran lineages, in Hydradephaga, Hydrophiloidea, Hydraenidae and Byrrhoidea, and several more times within these main groups. We propose that this pattern is due to different evolutionary dynamics of both habitat types: stagnant water bodies are more likely to completely disappear, requiring frequent migration of resident populations. Rivers and streams, on the contrary, have more temporal and spatial continuity, and therefore permit the long-term persistence of local populations. In less permanent habitats species will require a greater geographical mobility, which indirectly results in a larger size range. The less dispersive populations of running water should also have reduced gene flow, increasing the probability of allopatric speciation, and thus reducing the average range of more widespread ancestral species. These differences in population parameters, and the frequency of transitions between the two habitat types, may have strong macroevolutionary consequences, in particular regarding speciation rates and possible morphological specializations.     

Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study

Objective To determine the relation between intake of seafood in pregnancy and risk of preterm delivery and low birth weight.DesignProspective cohort study.Setting Aarhus, Denmark.Participants8729 pregnant women.Results The occurrence of preterm delivery differed significantly across four groups of seafood intake, falling progressively from 7.1% in the group never consuming fish to 1.9% in the group consuming fish as a hot meal and an open sandwich with fish at least once a week. Adjusted odds for preterm delivery were increased by a factor of 3.6 (95% confidence interval 1.2 to 11.2) in the zero consumption group compared with the highest consumption group. Analyses based on quantified intakes indicated that the working range of the dose-response relation is mainly from zero intake up to a daily intake of 15 g fish or 0.15 g n-3 fatty acids. Estimates of risk for low birth weight were similar to those for preterm delivery.Conclusions Low consumption of fish was a strong risk factor for preterm delivery and low birth weight. In women with zero or low intake of fish, small amounts of n-3 fatty acids—provided as fish or fish oil—may confer protection against preterm delivery and low birth weight.

What is already known on this topic

Long chain n-3 fatty acids in amounts above 2 g a day may delay spontaneous delivery and prevent recurrence of preterm deliveryLarge studies have not been carried out to determine to what extent low consumption of n-3 fatty acids is a risk factor for preterm deliveryThe dose-response relation has not been described

What this study adds

Low consumption of fish seems to be a strong risk factor for preterm delivery and low birth weight in Danish womenThis relation is strongest below an estimated daily intake of 0.15 g long chain n-3 fatty acids or 15 g fish     

Family history as a risk factor for recurrent hospitalization for lone atrial fibrillation: a nationwide family study in Sweden

Background

The present study was designed to evaluate which arterial stiffness parameter - AASI or the home arterial stiffness index (HASI) - correlates best with vascular, cardiac and renal damage in hypertensive individuals.

Methods

A cross-sectional study was carried out involving 258 hypertensive patients. AASI and HASI were defined as the 1-regression slope of diastolic over systolic blood pressure readings obtained from 24-hour recordings and home blood pressure over 6 days. Renal damage was evaluated by glomerular filtration rate (GFR) and microalbuminuria; vascular damage by carotid intima-media thickness (IMT), pulse wave velocity (PWV) and ankle/brachial index (ABI); and left ventricular hypertrophy by the Cornell voltage-duration product (VDP) and the Novacode index.

Results

AASI and HASI were not correlated with microalbuminuria, however AASI and HASI- blood pressure variability ratio (BPVR) showed negative correlation with GRF. The Cornell PDV was positively correlated with AASI- BPVR-Sleep (r = 0.15, p < 0.05) and the left ventricular mass index with HASI-BPVR (r = 0.19, p < 0.01). Carotid IMT and PWV were positively correlated with all the parameters except the HASI, while ABI was negatively correlated with AASI and Awake-AASI. After adjusting for age, gender and 24 hours heart rate, statistical significance remains of the IMT with AASI, Awake AASI and AASI-BPVR. PWV with the AASI, Awake-AASI and Sleep-AASI. ABI with AASI and Awake-AASI. Odd Ratio to presence target organ damage was for AASI: 10.47(IC95% 1.29 to 65.34), Awake-AASI: 8.85(IC95% 1.10 to 71.04), Sleep-AASI: 2.19(IC95% 1.10 to 4.38) and AASI-BPVR-night: 4.09 (IC95% 1.12 to 14.92).

Conclusions

After adjusting for age, gender and 24-hour heart, the variables that best associated with the variability of IMT, PWV and ABI were AASI and Awake-AASI, and with GFR was HASI-BPVR.     

Diabetes as a risk factor for Alzheimer's disease: insulin signalling impairment in the brain as an alternative model of Alzheimer's disease

Surprisingly little is known about the mechanisms that trigger the onset of AD (Alzheimer's disease) in sporadic forms. A number of risk factors have been identified that may shed light on the mechanisms that may trigger or facilitate the development of AD. Recently, T2DM (Type 2 diabetes mellitus) has been identified as a risk factor for AD. A common observation for both conditions is the desensitization of insulin receptors in the brain. Insulin acts as a growth factor in the brain and is neuroprotective, activates dendritic sprouting, regeneration and stem cell proliferation. The impairment of this important growth factor signal may facilitate the development of AD. Insulin as well as other growth factors have shown neuroprotective properties in preclinical and clinical trials. Several drugs have been developed to treat T2DM, which re-sensitize insulin receptors and may be of use to prevent neurodegenerative processes in the brain. In particular, the incretins GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insolinotropic polypeptide) are hormones that re-sensitize insulin signalling. Incretins also have similar growth-factor-like properties as insulin and are neuroprotective. In mouse models of AD, GLP-1 receptor agonists reduce amyloid plaque formation, reduce the inflammation response in the brain, protect neurons from oxidative stress, induce neurite outgrowth, and protect synaptic plasticity and memory formation from the detrimental effects caused by β-amyloid production and inflammation. Other growth factors such as BDNF (brain-derived neurotrophic factor), NGF (nerve growth factor) or IGF-1 (insulin-like growth factor 1) also have shown a range of neuroprotective properties in preclinical studies. These results show that these growth factors activate similar cell signalling mechanisms that are protective and regenerative, and suggest that the initial process that may trigger the cascade of neurodegenerative events in AD could be the impairment of growth factor signalling such as early insulin receptor desensitization.     

Socioeconomic status as a risk factor for HIV infection in women in East, Central and Southern Africa: a systematic review

This is a critical, systematic review of the relationship between socioeconomic status (SES) and HIV infection in women in Southern, Central and Eastern Africa. In light of the interest in micro-credit programmes and other HIV prevention interventions structured to empower women through increasing women's access to funds and education, this review examines the epidemiological and public health literature, which ascertains the association between low SES using different measurements of SES and risk of HIV infection in women. Also, given the focus on structural violence and poverty as factors driving the HIV epidemic at a structural/ecological level, as advocated by Paul Farmer and others, this study examines the extent to which differences in SES between individuals in areas with generalized poverty affect risk for SES. Out of 71 studies retrieved, 36 studies met the inclusion criteria including 30 cross-sectional, one case-control and five prospective cohort or nested case-control studies. Thirty-five studies used at least one measurement of female's SES and fourteen also included a measurement of partner's SES. Studies used variables measuring educational level, household income and occupation or employment status at the individual and neighbourhood level to ascertain SES. Of the 36 studies, fifteen found no association between SES and HIV infection, twelve found an association between high SES and HIV infection, eight found an association between low SES and HIV infection and one was mixed. In interpreting these results, this review examines the role of potential confounders and effect modifiers such as history of STDs, number of partners, living in urban or rural areas and time and location of study in sub-Saharan Africa. It is argued that STDs and number of partners are on the causal pathway under investigation between HIV and SES and should not be adjusted as confounders in any analysis. In conclusion, it is argued that in low-income sub-Saharan Africans countries, where poverty is widespread, increasing access to resources for women may initially increase risk of HIV or have no effect on risk-taking behaviours. In some parts of Southern Africa where per capita income is higher and within-country inequalities in wealth are greater, studies suggest that increasing SES may decrease risk. This review concludes that increased SES may have differential effects on married and unmarried women and further studies should use multiple measures of SES. Lastly, it is suggested that the partner's SES (measured by education or income/employment) may be a stronger predictor of female HIV serostatus than measures of female SES.     

Night work as a risk factor for future cause-specific disability pension: A prospective twin cohort study in Sweden

The objectives of the study were to investigate the associations between night work and disability pension (DP) due to all causes, cardiovascular (CVD), mental, and other diagnoses, adjusting for familial confounding. The material of the study included comprehensive survey data on 27 165 Swedish twins born in 1935–1958 that were linked with DP data for the survey period (1998–2003) to 2013. Night work was assessed as years of working nights at least every now and then, and categorized into not at all, 1–10 years and over 10 years. For statistical analyses, Cox proportional hazards regressions were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). The results of the study indicated that over 10 years duration of night work had an age- and sex-adjusted HR of 1.48 (95% CI 1.11–1.98) for DP due to CVD and 1–10 years of night work an HR of 1.28 (95% CI 1.06–1.55) for DP due to mental diagnoses, but attenuated when covariates were adjusted for. Both 1–10 years (HR 1.27, 95% CI 1.17–1.39) and >10 years of night work (HR 1.20, 95% CI 1.08–1.34) were associated with DP due to all causes and other diagnoses. These risks remained after adjusting for covariates. To conclude, even modest exposure in terms of duration of night work is a risk factor for all-cause DP, but also for DP due to mental and other diagnoses. The risk of DP due to CVD seems to be associated with longer (>10 years) periods of night work. All the associations between night work and DP seem to be influenced by various covariates.     

A multifactorial analysis of obesity as CVD risk factor: Use of neural network based methods in a nutrigenetics context

Background  

Obesity is a multifactorial trait, which comprises an independent risk factor for cardiovascular disease (CVD). The aim of the current work is to study the complex etiology beneath obesity and identify genetic variations and/or factors related to nutrition that contribute to its variability. To this end, a set of more than 2300 white subjects who participated in a nutrigenetics study was used. For each subject a total of 63 factors describing genetic variants related to CVD (24 in total), gender, and nutrition (38 in total), e.g. average daily intake in calories and cholesterol, were measured. Each subject was categorized according to body mass index (BMI) as normal (BMI ≤ 25) or overweight (BMI > 25). Two artificial neural network (ANN) based methods were designed and used towards the analysis of the available data. These corresponded to i) a multi-layer feed-forward ANN combined with a parameter decreasing method (PDM-ANN), and ii) a multi-layer feed-forward ANN trained by a hybrid method (GA-ANN) which combines genetic algorithms and the popular back-propagation training algorithm.     

Short-term complexity of cardiac autonomic control during sleep: REM as a potential risk factor for cardiovascular system in aging

Introduction

Sleep is a complex phenomenon characterized by important modifications throughout life and by changes of autonomic cardiovascular control. Aging is associated with a reduction of the overall heart rate variability (HRV) and a decrease of complexity of autonomic cardiac regulation. The aim of our study was to evaluate the HRV complexity using two entropy-derived measures, Shannon Entropy (SE) and Corrected Conditional Entropy (CCE), during sleep in young and older subjects.

Methods

A polysomnographic study was performed in 12 healthy young (21.1±0.8 years) and 12 healthy older subjects (64.9±1.9 years). After the sleep scoring, heart period time series were divided into wake (W), Stage 1–2 (S1-2), Stage 3–4 (S3-4) and REM. Two complexity indexes were assessed: SE(3) measuring the complexity of a distribution of 3-beat patterns (SE(3) is higher when all the patterns are identically distributed and it is lower when some patterns are more likely) and CCE_min measuring the minimum amount of information that cannot be derived from the knowledge of previous values.

Results

Across the different sleep stages, young subjects had similar RR interval, total variance, SE(3) and CCE_min. In the older group, SE(3) and CCE_min were reduced during REM sleep compared to S1-2, S3-4 and W. Compared to young subjects, during W and sleep the older subjects showed a lower RR interval and reduced total variance as well as a significant reduction of SE(3) and CCE_min. This decrease of entropy measures was more evident during REM sleep.

Conclusion

Our study indicates that aging is characterized by a reduction of entropy indices of cardiovascular variability during wake/sleep cycle, more evident during REM sleep. We conclude that during aging REM sleep is associated with a simplification of cardiac control mechanisms that could lead to an impaired ability of the cardiovascular system to react to cardiovascular adverse events.     

Leaf age as a risk factor in contamination of lettuce with Escherichia coli O157:H7 and Salmonella enterica

Outbreaks of Escherichia coli O157:H7 infections have been linked increasingly to leafy greens, particularly to lettuce. We present here the first evidence that this enteric pathogen can multiply on the leaves of romaine lettuce plants. The increases in population size of E. coli O157:H7 in the phyllosphere of young lettuce plants ranged from 16- to 100-fold under conditions of warm temperature and the presence of free water on the leaves and varied significantly with leaf age. The population size was consistently ca. 10-fold higher on the young (inner) leaves than on the middle leaves. The growth rates of Salmonella enterica and of the natural bacterial microflora were similarly leaf age dependent. Both enteric pathogens also achieved higher population sizes on young leaves than on middle leaves harvested from mature lettuce heads, suggesting that leaf age affects preharvest as well as postharvest colonization. Elemental analysis of the exudates collected from the surfaces of leaves of different ages revealed that young-leaf exudates were 2.9 and 1.5 times richer in total nitrogen and carbon, respectively, than middle-leaf exudates. This trend mirrored the nitrogen and carbon content of the leaf tissue. Application of ammonium nitrate, but not glucose, to middle leaves enhanced the growth of E. coli O157:H7 significantly, suggesting that low nitrogen limits its growth on these leaves. Our results indicate that leaf age and nitrogen content contribute to shaping the bacterial communities of preharvest and postharvest lettuce and that young lettuce leaves may be associated with a greater risk of contamination with E. coli O157:H7.     

Cronobacter species (formerly known as Enterobacter sakazakii) in powdered infant formula: a review of our current understanding of the biology of this bacterium

Cronobacter species (formerly known as Enterobacter sakazakii) are opportunistic pathogens that can cause necrotizing enterocolitis, bacteraemia and meningitis, predominantly in neonates. Infection in these vulnerable infants has been linked to the consumption of contaminated powdered infant formula (PIF). Considerable research has been undertaken on this organism in the past number of years which has enhanced our understanding of this neonatal pathogen leading to improvements in its control within the PIF production environment. The taxonomy of the organism resulted in the recognition of a new genus, Cronobacter, which consists of seven species. This paper presents an up-to-date review of our current knowledge of Cronobacter species. Taxonomy, genome sequencing, current detection protocols and epidemiology are all discussed. In addition, consideration is given to the control of this organism in the manufacturing environment, as a first step towards reducing the occurrence of this pathogen in PIF.     

Biliary tract disease as a risk factor for Plesiomonas shigelloides bacteraemia: a nine-year experience in a Hong Kong hospital and review of the literature

We report the epidemiology, clinical disease spectrum, treatment, and outcome of Plesiomonas shigelloides bacteraemia in our hospital over a nine-year period and compare the characteristics of patients with P. shigelloides bacteraemia in our hospital with those reported in the literature. During the nine-year period (1995--2003), a total of seven patients developed P. shigelloides bacteraemia. All cases occurred during the late spring, summer, and early autumn (May-October). All patients were over 75 and had underlying diseases (biliary tract diseases in four and malignancies in three). Six had acute cholangitis and five had polymicrobial bacteraemia. Overall two patients died. Compared with patients with P. shigelloides bacteraemia reported in the literature, patients with P. shigelloides bacteraemia in our hospital were associated with old age (P<0.001), underlying biliary tract diseases (P<0.001), acute cholangitis (P<0.001), and polymicrobial bacteraemia (P<0.001). There are major geographical differences of disease association in P. shigelloides bacteraemia. The sources of P. shigelloides in our patients were probably in the gastrointestinal tract.     

Giardiasis among different tribes of Orang Asli in Malaysia: Highlighting the presence of other family members infected with Giardia intestinalis as a main risk factor

The flagellate protozoan parasite, Giardia intestinalis, is widely distributed throughout the world with a high prevalence in developing countries in the tropics and subtropics, including Malaysia. Approximately 200 million people are infected with the parasite globally, with 500,000 new cases reported annually. This cross-sectional study was conducted among three tribes of Orang Asli communities in Selangor, Perak and Pahang states of Malaysia. The main objective was to determine the prevalence of and risk factors for giardiasis. Stool samples were collected from 500 individuals aged between 2 and 74years (males=219, females=281). The samples were examined with formalin-ether sedimentation and trichrome staining techniques. Socioeconomic data were collected through a pre-tested questionnaire. The overall prevalence of giardiasis was 20.0% with the highest prevalence in the Proto-Malays (33.3%) followed by Negritos (20.1%) and Senois (10.4%). The positive cases showed a decrease with increasing age and most of the positive cases were observed in individuals less than 24years old. Males had significantly higher prevalence than females (χ(2)=5.283, P=0.022). Logistic regression analysis of the overall population studied and the Senoi tribe confirmed that being a child aged less than 15years, being male, the consumption of raw vegetables and the presence of other family members infected with G. intestinalis were the main risk factors for giardiasis. The presence of other family members infected with G. intestinalis was the only risk factor highlighted in the Proto-Malay and Negrito tribes. Diarrhoea was significantly associated with giardiasis. However, the cause and effect relationship has yet to be determined. Thus, screening family members and treating the infected individuals are the main strategies that should be adopted by the public health authority in combating this infection in Orang Asli communities as well as health education regarding good personal and food hygiene practises.     

S-adenosyl-L-homocysteine hydrolase, key enzyme of methylation metabolism, regulates phosphatidylcholine synthesis and triacylglycerol homeostasis in yeast: implications for homocysteine as a risk factor of atherosclerosis

In eukaryotes, S-adenosyl-L-homocysteine hydrolase (Sah1) offers a single way for degradation of S-adenosyl-L-homocysteine, a product and potent competitive inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases. De novo phosphatidylcholine (PC) synthesis requires three AdoMet-dependent methylation steps. Here we show that down-regulation of SAH1 expression in yeast leads to accumulation of S-adenosyl-L-homocysteine and decreased de novo PC synthesis in vivo. This decrease is accompanied by an increase in triacylglycerol (TG) levels, demonstrating that Sah1-regulated methylation has a major impact on cellular lipid homeostasis. TG accumulation is also observed in cho2 and opi3 mutants defective in methylation of phosphatidylethanolamine to PC, confirming that PC de novo synthesis and TG synthesis are metabolically coupled through the efficiency of the phospholipid methylation reaction. Indeed, because both types of lipids share phosphatidic acid as a precursor, we find in cells with down-regulated Sah1 activity major alterations in the expression of the INO1 gene as well as in the localization of Opi1, a negative regulatory factor of phospholipid synthesis, which binds and is retained in the endoplasmic reticulum membrane by phosphatidic acid in conjunction with VAMP/synaptobrevin-associated protein, Scs2. The addition of homocysteine, by the reversal of the Sah1-catalyzed reaction, also leads to TG accumulation in yeast, providing an attractive model for the role of homocysteine as a risk factor of atherosclerosis in humans.