387 research outputs found
Low-carbohydrate diets affect energy balance and fuel homeostasis differentially in lean and obese rats
No full textIn parallel with increased prevalence of overweight people in affluent societies are individuals trying to lose weight, often using low-carbohydrate diets. Nevertheless, long-term metabolic consequences of those diets, usually high in (saturated) fat, remain unclear. Therefore, we investigated long-term effects of high-fat diets with different carbohydrate/protein ratios on energy balance and fuel homeostasis in obese (fa/fa) Zucker and lean Wistar rats. Animals were fed high-carbohydrate (HC), high-fat (HsF), or low-carbohydrate, high-fat, high-protein (LC-HsF-HP) diets for 60 days. Both lines fed the LC-HsF-HP diet displayed reduced energy intake compared with those fed the HsF diet (Zucker, -3.7%) or the HC diet (Wistar rats, -12.4%). This was not associated with lower weight gain relative to HC fed rats, because of increased food efficiencies in each line fed HsF and particularly LC-HsF-HP food. Zucker rats were less glucose tolerant than Wistar rats. Lowest glucose tolerances were found in HsF and particularly in LC-HsF-HP-fed animals irrespective of line, but this paralleled reduced plasma adiponectin levels, elevated plasma resistin levels, higher retroperitoneal fat masses, and reduced insulin sensitivity (indexed by insulin-induced hypoglycemia) only in Wistar rats. In Zucker rats, however, improved insulin responses during glucose tolerance testing and tendency toward increased insulin sensitivities were observed with HsF or LC-HsF-HP feeding relative to HC feeding. Thus, despite adverse consequences of LC-HsF diets on blood glucose homeostasis, principal differences exist in the underlying hormonal regulatory mechanisms, which could have benefits for B-cell functioning and insulin action in the obese state but not in the lean state.
Ethanol-induced c-Fos expression in rat lines selected for low and high alcohol consumption
No full textSelectively bred rat lines, developed to model genetic contributions to alcohol abuse, include the Indiana alcohol-preferring (P) and alcohol-nonpreferring (NP) lines, and the Alko-Alcohol (AA) and Alko-Nonalcohol (ANA) lines. Preferring and nonpreferring lines were compared in their response to intraperitoneal injection of either ethanol or isotonic saline using c-Fos expression as a marker of neuronal activity. Although line differences were noted in several brain regions, the principal finding was that alcohol-nonpreferring lines (NP and ANA) displayed greater c-Fos expression in the locus coeruleus (LC) relative to the alcohol-preferring lines (P and AA) following injection of 3.0 g ethanol/kg. These data point to the LC as an area which may play a role in the differences in voluntary ethanol consumption between rat lines genetically bred for low and high ethanol preference
Effects of high-fat diets with different carbohydrate-to-protein ratios on energy homeostasis in rats with impaired brain melanocortin receptor activity
No full textChanges in dietary macronutrient composition and/or central nervous system neuronal activity can underlie obesity and disturbed fuel homeostasis. We examined whether switching rats from a diet with high carbohydrate content (HC; i.e., regular chow) to diets with either high fat (HF) or high fat/high protein content at the expense of carbohydrates (LC-HF-HP) causes differential effects on body weight and glucose homeostasis that depend on the integrity of brain melanocortin (MC) signaling. In vehicle-treated rats, switching from HC to either HF or LC-HF-HP feeding caused similar reductions in food intake without alterations in body weight. A reduced caloric intake (-16% in HF and LC-HF-HP groups) required to maintain or increase body weight underlay these effects. Chronic third cerebroventricular infusion of the MC receptor antagonist SHU9119 (0.5 nmol/day) produced obesity and hyperphagia with an increased food efficiency again observed during HF (+19%) and LC-HF-HP (+33%) feeding. In this case, however, HF feeding exaggerated SHU9119-induced hyperphagia and weight gain relative to HC and LC-HF-HP feeding. Relative to vehicle-treated controls, SHU9119 treatment increased plasma insulin (2.8–4 fold), leptin (7.7–15 fold), and adiponectin levels (2.4–3.7 fold), but diet effects were only observed on plasma adiponectin (HC and LC-HF-HP<HF). Finally, SHU9119-treated LC-HF-HP-fed rats were less glucose tolerant than others. Relatively low plasma adiponectin levels likely contributed to this effect. Thus HF feeding amplifies obesity induced by impaired MC signaling, provided that the carbohydrate-to-protein (C/P) ratio is high enough. Reduction of the C/P ratio within a HF diet ameliorates hyperphagia and obesity in rats with impaired MC signaling but aggravates associated disturbances in fuel homeostasis.
Ethanol-Induced c-Fos Expression in Catecholamine- and Neuropeptide Y-Producing Neurons in Rat Brainstem
No full textBackground: Previous studies have used c-Fos-like immunoreactivity (cFLI) to examine the neuroanatomical location of cells that are activated in response to ethanol administration. However, the use of cFLI alone fails to reveal the phenotypical identity of cells. In the present study we used double-labeling procedures to identify the neurochemical phenotype of neurons that showed ethanol-induced cFLI in the rat brainstem.
Methods: Individual groups of rats received intraperitoneal injection of ethanol (1.5 g/kg or 3.5 g/kg) or isotonic saline (23 ml/kg). To assess the specificity of cFLI induced by ethanol, we injected other rats with the drug lithium chloride (LiCl; 76 mg/kg). Two hours after injection, rats were killed and their brains were processed for immunohistochemistry.
Results: Both doses of ethanol promoted cFLI in several brainstem regions, including the nucleus of the solitary tract (NTS), the locus coeruleus (LC), and the ventrolateral medulla (VLM). Although LiCl caused significant cFLI in the NTS, this drug promoted only minimal cFLI in the VLM and no significant activation in the LC. We found that a significant proportion of tyrosine hydroxylase (TH)-positive neurons coexpressed ethanol-induced cFLI in the VLM (~75–85%), the NTS (~65–75%), and the LC (~30–65%). Additionally, a significant proportion of neuropeptide Y (NPY)-producing neurons in the VLM coexpressed ethanol-induced cFLI (~60–75%). On the other hand, LiCl promoted activation of TH-positive neurons in the VLM and the NTS but failed to stimulate cFLI in TH-producing neurons in the LC or in NPY-producing neurons of the VLM.
Conclusions: Neurons in the rat brainstem that show ethanol-induced c-Fos expression produce catecholamines and NPY. This research demonstrates the usefulness of double-labeling immunohistochemistry procedures for identifying the neurochemical identity of neurons that are activated after ethanol administration.
Optimal design of experiments with simulation models of nearly saturated queues
No full textexperimental design;simulation models;queueing network;regression analysis
Effects of macronutrient intake in obesity: A meta-analysis of low-carbohydrate and low-fat diets on markers of the metabolic syndrome
No full textThe metabolic syndrome (MetS) comprises cardiometabolic risk factors frequently found in individuals with obesity. Guidelines to prevent or reverse MetS suggest limiting fat intake, however, lowering carbohydrate intake has gained attention too. The aim for this review was to determine to what extent either weight loss, reduction in caloric intake, or changes in macronutrient intake contribute to improvement in markers of MetS in persons with obesity without cardiometabolic disease. A meta-analysis was performed across a spectrum of studies applying low-carbohydrate (LC) and low-fat (LF) diets. PubMed searches yielded 17 articles describing 12 separate intervention studies assessing changes in MetS markers of persons with obesity assigned to LC (<40% energy from carbohydrates) or LF (<30% energy from fat) diets. Both diets could lead to weight loss and improve markers of MetS. Meta-regression revealed that weight loss most efficaciously reduced fasting glucose levels independent of macronutrient intake at the end of the study. Actual carbohydrate intake and actual fat intake at the end of the study, but not the percent changes in intake of these macronutrients, improved diastolic blood pressure and circulating triglyceride levels, without an effect of weight loss. The homeostatic model assessment of insulin resistance improved with both diets, whereas high-density lipoprotein cholesterol only improved in the LC diet, both irrespective of aforementioned factors. Remarkably, changes in caloric intake did not play a primary role in altering MetS markers. Taken together, these data suggest that, beyond the general effects of the LC and LF diet categories to improve MetS markers, there are also specific roles for weight loss, LC and HF intake, but not reduced caloric intake, that improve markers of MetS irrespective of diet categorization. On the basis of the results from this meta-analysis, guidelines to prevent MetS may need to be re-evaluated
Conserved and variable correlated mutations in the plant MADS protein network
No full textAbstract Background Plant MADS domain proteins are involved in a variety of developmental processes for which their ability to form various interactions is a key requisite. However, not much is known about the structure of these proteins or their complexes, whereas such knowledge would be valuable for a better understanding of their function. Here, we analyze those proteins and the complexes they form using a correlated mutation approach in combination with available structural, bioinformatics and experimental data. Results Correlated mutations are affected by several types of noise, which is difficult to disentangle from the real signal. In our analysis of the MADS domain proteins, we apply for the first time a correlated mutation analysis to a family of interacting proteins. This provides a unique way to investigate the amount of signal that is present in correlated mutations because it allows direct comparison of mutations in various family members and assessing their conservation. We show that correlated mutations in general are conserved within the various family members, and if not, the variability at the respective positions is less in the proteins in which the correlated mutation does not occur. Also, intermolecular correlated mutation signals for interacting pairs of proteins display clear overlap with other bioinformatics data, which is not the case for non-interacting protein pairs, an observation which validates the intermolecular correlated mutations. Having validated the correlated mutation results, we apply them to infer the structural organization of the MADS domain proteins. Conclusion Our analysis enables understanding of the structural organization of the MADS domain proteins, including support for predicted helices based on correlated mutation patterns, and evidence for a specific interaction site in those proteins.</p
The association of maternal prenatal psychosocial stress with vascular function in the child at age 10-11 years: findings from the Avon longitudinal study of parents and children
No full textObjective To investigate whether (1) maternal psychosocial stress (depression/anxiety) during pregnancy is associated with offspring vascular function and (2) whether any association differs depending on the gestational timing of exposure to stress. We also investigated whether any association is likely to be due to intrauterine mechanisms by (3) comparing with the association of paternal stress with offspring vascular function and (4) examining whether any prenatal association is explained by maternal postnatal stress.
Methods and results Associations were examined in a UK birth cohort, with offspring outcomes (systolic and diastolic blood pressure, SBP and DBP, endothelial function assessed by brachial artery flow-mediated dilatation (FMD); arterial stiffness assessed by carotid to radial pulse wave velocity (PWV), brachial artery distensibility (DC), and brachial artery diameter (BD) assessed at age 10–11 years (n = 4318). Maternal depressive symptoms and anxiety were assessed at 18 and 32 weeks gestation and 8 months postnatally. Paternal symptoms were assessed at week 19. With the exception of DBP and BD, there were no associations of maternal depressive symptoms with any of the vascular outcomes. Maternal depressive and anxiety symptoms were associated with lower offspring DBP and wider BD, though the latter attenuated to the null with adjustment for confounding factors. Paternal symptoms were not associated with offspring outcomes. Maternal postnatal depressive symptoms were associated with lower offspring SBP.
Conclusions We found no evidence to support the hypothesis that maternal stress during pregnancy adversely affects offspring vascular function at age 10–12 years via intrauterine mechanisms
A New Concept of Ultrafiltration Fouling Control: Backwashing with Low Ionic Strength Water
No full textUltrafiltration (UF) is a proven technology in water treatment nowadays. However, fouling remains a major challenge in the operation of UF, especially in regard to colloidal NOM fouling. In general, a number of colloidal NOM fouling mechanisms may occur, such as adsorption, gel formation. Colloidal NOM fouling is influenced by multivalent cations, ionic strength and pH. In order to control membrane fouling, different pretreatments such as powder activated carbon adsorption, lime softening, ion exchange, conventional media filtration and coagulation with inorganic and polymeric coagulant have been investigated. In-line coagulation is the most commonly used pretreatment for UF of surface water. However, the problem with in-line coagulation is that a large amount of backwash-derived waste sludge containing dosed coagulants is produced. Since the backwash waste sludge with coagulant has to be treated before its discharge (in especially Western Europe), this option creates additional cost for the membrane treatment plant (up to 20% of the total cost of the whole plant). This dissertation investigates the technical possibility of controlling the UF fouling by backwashing with low ionic strength water (demineralized water in the Netherlands), in order to reduce the ionic strength and the amount of multivalent cations and thus reduce NOM fouling. Chapter 1 briefly introduces this dissertation. The effectiveness of deminerlaized water backwashing is generally investigated on a pilot scale (with a 2.4m2 membrane) in Chapter 2. Results show that regarding the removal of NOM foulants via hydraulic backwashes, demineralized water is better than UF and NF permeate. That is probably due to the absence of cations, reducing the charge screening effect and/or Ca-bridging effect between the negatively charged membrane and NOM, leading to a restoration of repulsion force and consequently an easy removal of fouling layer. However, it is not clear which components in backwash water lead to the low foulant removal in this chapter. Therefore, Chapter 3 investigates the influence of backwash water composition on fouling control. Different amount of CaCl2 and NaCl was dosed in demineralized water to test their effect on fouling control. It became clear that the presence of monovalent and divalent cations in backwash water reduces the fouling control efficiency. Moreover, by isolating the organic matter in UF permeate for backwashing, it is found that the organic matter in UF permeate itself does not cause fouling problems when they are in backwash water. In terms of the influence of monovalent and divalent cations, both the elimination of the charge screening effect and the breakdown of the calcium bridging effect are possible mechanisms to explain this improvement. Therefore, these two effects are presumed to be the mechanisms of demineralized water backwashing. The investigation of the hypotheses of demineralized water backwashing is reported in Chapter 4, including the charge screening and the calcium bridging effects. By determining the zeta potential of the membranes and the colloidal NOM compounds at different conditions, the impact of pH and electrolyte valence and concentration on their charge was assessed. Furthermore, the adsorption of calcium on the membranes and the NOM compounds was also illustrated. Results showed that a membrane became less negatively charged when the pH decreased and the concentration of electrolyte increased, proving the presence of the charge screening effect. Furthermore, divalent cation has a much stronger effect on the increase of membrane zeta potential than monovalent cations which is generally in consistent with the DLVO theory. Calcium ions indeed adsorbed on either new or fouled membranes, and bridged NOM and membranes afterwards. However, the interaction of calcium with fouled membranes is more substantial than with new membranes. However, the charge screening effect played a dominant role in the membrane fouling and fouling control by demineralized water backwashing. Most of the fouling caused by calcium bridging is difficult to remove even with a demineralized water backwash. Chapter 5 illustrates the effectiveness of demineralized water backwashing on ultrafiltration fouling of different fractions of NOM. Results of natural waters show the same fouling removal via demineralized water backwashing as the previous chapters. Furthermore, LC-OCD analysis of Schie Canal water showed that biopolymers can be flushed away by hydraulic backwashes of either demineralized water or UF permeate. Compared to almost zero removal of humics and LMW substances by UF permeate backwashes, demineralized water backwashing was able to remove a substantial amount of humics, and a small amount of LMW substances. Fouling of sodium alginate model compound showed a high reversibility no matter what kind of backwash water was used. This is also consistent with the LC-OCD analysis of Schie Canal water. However, not all biopolymers were removed by hydraulic backwashes. A low fouling reversibility was observed for BSA fouling, but BSA may be in the part of unremoved biopolymers with demineralized water. No improvement in fouling control for fouling of Suwannee River humic acid (SRHA) was observed as well when demineralized water was used for the backwash. This is probably because the calcium bridging via carboxyl functional groups is the main mechanism for SRHA fouling, which is difficult to break down. Since the charge screening effect is the main mechanism of demineralized water backwashing, theoretically speaking, its application on seawater treatment is also possible. Chapter 6 demonstrates that demineralized water backwashing can substantially improve seawater UF fouling control, similar to the previous findings in surface canal water. However, the duration of a successful demineralized water backwash should be extended from one to two minutes. This is due to the high salinity of seawater and thus more demineralized water was required to dilute the seawater and limit a higher dispersion effect of seawater than surface water. Monovalent cations in backwash water showed their impact on the fouling control efficiency, indicating the existence of a charge screening effect. Furthermore, the different UF membrane fouling behaviors in winter and spring indicated the impact of a seasonal influence on UF membrane fouling. In spring, the membrane showed more fouling probably due to the algae bloom which is widely considered an important fouling factor. The results of the long-term experiment reconfirmed the effectiveness of backwashing with SWRO permeate (similar quality as demineralized water) on the fouling control of seawater UF. Since it is very easy to access SWRO permeate in a UF-RO desalination plant, this approach can be implemented easily. In order to apply this technique in industry, optimization work was conducted on a pilot scale with a standard membrane element (40 m2) and reported in Chapter 7. Results show that SWRO permeate (having similar qualities as demineralized water) backwashing substantially improved the seawater UF fouling control, consistent with the previous studies with small-scale membrane modules. The effectiveness of SWRO permeate backwashing on UF fouling control was observed at a recovery rate up to 95.8% during a low fouling period. Furthermore, the results of the DEMIFLUSH pilot were similar to the Evides desalination plant having the same operational settings, suggesting that the results obtained from the DEMIFLUSH pilot are applicable to full-scale plants. However, the results of high fouling period are missing. If the optimization results can be repeated in high fouling period as well, the application of SWRO permeate is also economically feasible due to the low consumption of SWRO permeate. Optimization work should be continued to reduce the consumption of SWRO permeate or demineralized water, since the usage of these water is expensive.WatermanagementCivil Engineering and Geoscience
Proteomic signature of the Dravet syndrome in the genetic Scn1a-A1783V mouse model
No full textBackground: Dravet syndrome is a rare, severe pediatric epileptic encephalopathy associated with intellectual and motor disabilities. Proteomic profiling in a mouse model of Dravet syndrome can provide information about the molecular consequences of the genetic deficiency and about pathophysiological mechanisms developing during the disease course. Methods: A knock-in mouse model of Dravet syndrome with Scn1a haploinsufficiency was used for whole proteome, seizure, and behavioral analysis. Hippocampal tissue was dissected from two- (prior to epilepsy manifestation) and four- (following epilepsy manifestation) week-old male mice and analyzed using LC-MS/MS with label-free quantification. Proteomic data sets were subjected to bioinformatic analysis including pathway enrichment analysis. The differential expression of selected proteins was confirmed by immunohistochemical staining. Results: The findings confirmed an increased susceptibility to hyperthermia-associated seizures, the development of spontaneous seizures, and behavioral alterations in the novel Scn1a-A1873V mouse model of Dravet syndrome. As expected, proteomic analysis demonstrated more pronounced alterations following epilepsy manifestation. In particular, proteins involved in neurotransmitter dynamics, receptor and ion channel function, synaptic plasticity, astrogliosis, neoangiogenesis, and nitric oxide signaling showed a pronounced regulation in Dravet mice. Pathway enrichment analysis identified several significantly regulated pathways at the later time point, with pathways linked to synaptic transmission and glutamatergic signaling dominating the list. Conclusion: In conclusion, the whole proteome analysis in a mouse model of Dravet syndrome demonstrated complex molecular alterations in the hippocampus. Some of these alterations may have an impact on excitability or may serve a compensatory function, which, however, needs to be further confirmed by future investigations. The proteomic data indicate that, due to the molecular consequences of the genetic deficiency, the pathophysiological mechanisms may become more complex during the course of the disease. As a result, the management of Dravet syndrome may need to consider further molecular and cellular alterations. Ensuing functional follow-up studies, this data set may provide valuable guidance for the future development of novel therapeutic approaches
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