1,3-Propanediol dehydrogenases in Lactobacillus reuteri: impact on central metabolism and 3-hydroxypropionaldehyde production

<p>Abstract</p> <p>Background</p> <p><it>Lactobacillus reuteri </it>metabolizes glycerol to 3-hydroxypropionaldehyde (3-HPA) and further to 1,3-propanediol (1,3-PDO), the latter step catalysed by a propanediol dehydrogenase (PDH). The last step in this pathway regenerates NAD⁺and enables therefore the energetically more favourable production of acetate over ethanol during growth on glucose.</p> <p>Results</p> <p>A search throughout the genome of <it>L. reuteri </it>DSM 20016 revealed two putative PDHs encoded by ORFs lr_0030 and lr_1734. ORF lr_1734 is situated in the <it>pdu </it>operon encoding the glycerol conversion machinery and therefore likely involved in 1,3-PDO formation. ORF lr_0030 has not been associated with PDH-activity so far. To elucidate the role of these two PDHs, gene deletion mutant strains were constructed. Growth behaviour on glucose was comparable between the wild type and both mutant strains. However, on glucose + glycerol, the exponential growth rate of Δlr_0030 was lower compared to the wild type and the lr_1734 mutant. Furthermore, glycerol addition resulted in decreased ethanol production in the wild type and Δlr_1734, but not in Δlr_0030. PDH activity measurements using 3-HPA as a substrate revealed lower activity of Δlr_0030 extracts from exponential growing cells compared to wild type and Δlr_1734 extracts.</p> <p>During biotechnological 3-HPA production using non-growing cells, the ratio 3-HPA to 1,3-PDO was approximately 7 in the wild type and Δlr_0030, whereas this ratio was 12.5 in the mutant Δlr_1734.</p> <p>Conclusion</p> <p>The enzyme encoded by lr_0030 plays a pivotal role in 3-HPA conversion in exponential growing <it>L. reuteri </it>cells. The enzyme encoded by lr_1734 is active during 3-HPA production by non-growing cells and this enzyme is a useful target to enhance 3-HPA production and minimize formation of the by-product 1,3-PDO.</p

Polypill eligibility and equivalent intake in a Swiss population-based study.

The polypill has been advocated for cardiovascular disease (CVD) management. The fraction of the population who could benefit from the polypill in Switzerland is unknown. Assess (1) the prevalence of subjects (a) eligible for the polypill and (b) already taking a polypill equivalent; and (2) the determinants of polypill intake in the first (2009-2012) and second follow-ups (2014-2017) of a population-based prospective study conducted in Lausanne, Switzerland. The first and the second follow-ups included 5038 and 4596 participants aged 40-80 years, respectively. Polypill eligibility was defined as having a high CVD risk as assessed by an absolute CVD risk ≥ 5% with the SCORE equation for Switzerland and/or presenting with CVD. Four polypill equivalents were defined: statin + any antihypertensive with (A) or without (B) aspirin; statin + calcium channel blocker (CCB) (C); and statin + CCB + angiotensin-converting enzyme inhibitor (D). The prevalence of polypill eligibility was 20.6% (95% CI 19.5-21.8) and 27.7% (26.5-29.1) in the first and second follow-up, respectively. However, only around one-third of the eligible 29.5% (95% CI 26.7-32.3) and 30.4% (27.9-33.0) respectively, already took the polypill equivalents. All polypill equivalents were more prevalent among men, elderly and in presence of CVD. After multivariable adjustment, in both periods, male gender was associated with taking polypill equivalent A (OR: 1.93; 95% CI 1.45-2.55 and OR: 1.67; 95% CI 1.27-2.19, respectively) and polypill equivalent B (OR: 1.52; 95% CI 1.17-1.96 and OR: 1.41; 95% CI 1.07-1.85, respectively). Similarly, in both periods, age over 70 years, compared to middle-age, was associated with taking polypill equivalent A (OR: 11.71; CI 6.74-20.33 and OR: 9.56; CI 4.13-22.13, respectively) and equivalent B (OR: 13.22; CI 7.27-24.07 and OR: 20.63; CI 6.51-56.36, respectively). Former or current smoking was also associated with a higher likelihood of taking polypill equivalent A in both periods. A large fraction of the population is eligible for the polypill, but only one-third of them actually benefits from an equivalent, and this proportion did not change over time

Determinants of change in polypharmacy status in Switzerland: the population-based CoLaus study.

This study aimed to assess the prevalence, the change, and the determinants of change in polypharmacy in a population-based sample. Baseline (2003-2006) and follow-up (2009-2012) data are from 4679 participants aged between 35 and 75 years (53.5% women, mean age 52.6 ± 10.6 years) from the population of Lausanne, Switzerland. Polypharmacy was defined by the regular use of ≥5 drugs. Four categories of change were defined: never (no polypharmacy at baseline and follow-up), initiating (no polypharmacy at baseline but at follow-up), maintaining, or quitting. Polypharmacy increased from 7.7% at baseline to 15.3% at follow-up. Cardiovascular drugs were the most prescribed medicines at baseline and follow-up. Gender, age, obesity, smoking, previously diagnosed hypertension, or diabetes or dyslipidemia were significantly and independently associated with initiating and maintaining polypharmacy. In a population-based sample, prevalence of polypharmacy doubled over a 5.6-year period. The main determinants of initiating polypharmacy were age, overweight and obesity, smoking status, and previously diagnosed cardiovascular risk factors

Energetic Cost of Ichthyophonus Infection in Juvenile Pacific Herring (Clupea pallasii)

The energetic costs of fasting and Ichthyophonus infection were measured in juvenile Pacific herring (Clupea pallasii) in a lab setting at three temperatures. Infected herring incurred significant energetic costs, the magnitude of which depended on fish condition at the time of infection (fat versus lean). Herring that were fed continually and were in relatively good condition at the time of infection (fat) never stored lipid despite ad libitum feeding. In feeding herring, the energetic cost of infection was a 30% reduction in total energy content relative to controls 52 days post infection. Following food deprivation (lean condition), infection caused an initial delay in the compensatory response of herring. Thirty-one days after re-feeding, the energetic cost of infection in previously-fasted fish was a 32% reduction in total energy content relative to controls. Body composition of infected herring subsequently recovered to some degree, though infected herring never attained the same energy content as their continuously fed counterparts. Fifty-two days after re-feeding, the energetic cost of infection in previously-fasted fish was a 6% reduction in total energy content relative to controls. The greatest impacts of infection occurred in colder temperatures, suggesting Ichthyophonus-induced reductions in body condition may have greater consequences in the northern extent of herring's range, where juveniles use most of their energy reserves to survive their first winter

Clinical determinants of the PR interval duration in Swiss middle-aged adults: The CoLaus/PsyCoLaus study.

Prolonged PR interval (PRi) is associated with adverse outcomes. However, PRi determinants are poorly known. We aimed to identify the clinical determinants of the PRi duration in the general population. Some clinical data are associated with prolonged PRi. Cross-sectional study conducted between 2014 and 2017. Electrocardiogram-derived PRi duration was categorized into normal or prolonged (&gt;200 ms). Determinants were identified using stepwise logistic regression, and results were expressed as multivariable-adjusted odds ratio (OR) (95% confidence interval). A further analysis was performed adjusting for antiarrhythmic drugs, P-wave contribution to PRi duration, electrolytes (kalemia, calcemia, and magnesemia), and history of cardiovascular disease. Overall, 3655 participants with measurable PRi duration were included (55.6% females; mean age 62 ± 10 years), and 330 (9.0%) had prolonged PRi. Stepwise logistic regression identified male sex (OR 1.41 [1.02-1.97]); aging (65-74 years: OR 2.29 [1.61-3.24], and ≥ 75 years: OR 4.21 [2.81-6.31]); increased height (per 5 cm, OR 1.15 [1.06-1.25]); hypertension (OR 1.37 [1.06-1.77]); and hs troponin T (OR 1.67 [1.15-2.43]) as significantly and positively associated, and high resting heart rate (≥70 beats/min, OR 0.43 [0.29-0.62]) as negatively associated with prolonged PRi. After further adjustment, male sex, aging and increased height remained positively, and high resting heart rate negatively associated with prolonged PRi. Hypertension and hs troponin T were no longer associated. In a sample of the Swiss middle-aged population, male sex, aging and increased height significantly increased the likelihood of a prolonged PRi duration, whereas a high resting heart rate decreased it

Effects of Environmental Temperature on the Dynamics of Ichthyophoniasis in Juvenile Pacific Herring (Clupea pallasii)

The effects of temperature and infection by Ichthyophonus were examined in juvenile Pacific herring (Clupea pallasii) maintained under simulated overwinter fasting conditions. In addition to defining parameters for a herring bioenergetics model (discussed in Vollenweider et al. this issue), these experiments provided new insights into factors influencing the infectivity and virulence of the parasite Ichthyophonus. In groups of fish with established disease, temperature variation had little effect on disease outcome. Ichthyophonus mortality outpaced that resulting from starvation alone. In newly infected fish, temperature variation significantly changed the mortality patterns related to disease. Both elevated and lowered temperatures suppressed disease-related mortality relative to ambient treatments. When parasite exposure dose decreased, an inverse relationship between infection prevalence and temperature was detected. These findings suggest interplay between temperature optima for parasite growth and host immune function and have implications for our understanding of how Ichthyophonus infections are established in wild fish populations

Modeling Ketamine Effects on Synaptic Plasticity During the Mismatch Negativity

This paper presents a model-based investigation of mechanisms underlying the reduction of mismatch negativity (MMN) amplitudes under the NMDA-receptor antagonist ketamine. We applied dynamic causal modeling and Bayesian model selection to data from a recent ketamine study of the roving MMN paradigm, using a cross-over, double-blind, placebo-controlled design. Our modeling was guided by a predictive coding framework that unifies contemporary "adaptation” and "model adjustment” MMN theories. Comparing a series of dynamic causal models that allowed for different expressions of neuronal adaptation and synaptic plasticity, we obtained 3 major results: 1) We replicated previous results that both adaptation and short-term plasticity are necessary to explain MMN generation per se; 2) we found significant ketamine effects on synaptic plasticity, but not adaptation, and a selective ketamine effect on the forward connection from left primary auditory cortex to superior temporal gyrus; 3) this model-based estimate of ketamine effects on synaptic plasticity correlated significantly with ratings of ketamine-induced impairments in cognition and control. Our modeling approach thus suggests a concrete mechanism for ketamine effects on MMN that correlates with drug-induced psychopathology. More generally, this demonstrates the potential of modeling for inferring on synaptic physiology, and its pharmacological modulation, from electroencephalography dat

Depression with atypical features and increase in obesity, body mass index, waist circumference, and fat mass: a prospective, population-based study.

IMPORTANCE: Depression and obesity are 2 prevalent disorders that have been repeatedly shown to be associated. However, the mechanisms and temporal sequence underlying this association are poorly understood. OBJECTIVE: To determine whether the subtypes of major depressive disorder (MDD; melancholic, atypical, combined, or unspecified) are predictive of adiposity in terms of the incidence of obesity and changes in body mass index (calculated as weight in kilograms divided by height in meters squared), waist circumference, and fat mass. DESIGN, SETTING, AND PARTICIPANTS: This prospective population-based cohort study, CoLaus (Cohorte Lausannoise)/PsyCoLaus (Psychiatric arm of the CoLaus Study), with 5.5 years of follow-up included 3054 randomly selected residents (mean age, 49.7 years; 53.1% were women) of the city of Lausanne, Switzerland (according to the civil register), aged 35 to 66 years in 2003, who accepted the physical and psychiatric baseline and physical follow-up evaluations. EXPOSURES: Depression subtypes according to the DSM-IV. Diagnostic criteria at baseline and follow-up, as well as sociodemographic characteristics, lifestyle (alcohol and tobacco use and physical activity), and medication, were elicited using the semistructured Diagnostic Interview for Genetic Studies. MAIN OUTCOMES AND MEASURES: Changes in body mass index, waist circumference, and fat mass during the follow-up period, in percentage of the baseline value, and the incidence of obesity during the follow-up period among nonobese participants at baseline. Weight, height, waist circumference, and body fat (bioimpedance) were measured at baseline and follow-up by trained field interviewers. RESULTS: Only participants with the atypical subtype of MDD at baseline revealed a higher increase in adiposity during follow-up than participants without MDD. The associations between this MDD subtype and body mass index (β = 3.19; 95% CI, 1.50-4.88), incidence of obesity (odds ratio, 3.75; 95% CI, 1.24-11.35), waist circumference in both sexes (β = 2.44; 95% CI, 0.21-4.66), and fat mass in men (β = 16.36; 95% CI, 4.81-27.92) remained significant after adjustments for a wide range of possible cofounding. CONCLUSIONS AND RELEVANCE: The atypical subtype of MDD is a strong predictor of obesity. This emphasizes the need to identify individuals with this subtype of MDD in both clinical and research settings. Therapeutic measures to diminish the consequences of increased appetite during depressive episodes with atypical features are advocated

Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study.

BACKGROUND: Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. METHODS: In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 - 8.5). RESULTS: Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-α (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1β and IL-6 did not significantly differ between the two groups. CONCLUSIONS: Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies