Key points
Maternal obesity predisposes to metabolic dysfunction in male and female offspring
Maternal high‐fat diet consumption prior to and throughout pregnancy and lactation accelerates offspring ...metabolic ageing in a sex‐dependent manner
This study provides evidence for programming‐ageing interactions
Human epidemiological studies show that maternal obesity (MO) shortens offspring life and health span. Life course cellular mechanisms involved in this developmental programming‐ageing interaction are poorly understood. In a well‐established rat MO model, female Wistar rats ate chow (controls (C)) or high energy, obesogenic diet to induce MO from weaning through pregnancy and lactation. Females were bred at postnatal day (PND) 120. Offspring (F1) of mothers on control diet (CF1) and MO diet (MOF1) delivered spontaneously at terms. Both CF1 and MOF1 ate C diet from weaning throughout the study. Offspring were killed at PND 36, 110, 450 and 650. We determined body and liver weights, liver and serum metabolite concentrations, hormones and oxidative stress biomarkers. Male and female CF1 body weight, total fat, adiposity index, serum leptin, insulin, insulin resistance, and liver weight, fat, triglycerides, malondialdehyde, reactive oxygen species and nitrotyrosine all rose with differing ageing trajectories. Female CF1 triglycerides were unchanged with age. Age‐related increases were greater in MOF1 than CF1 in both sexes for all variables except glucose in males and females and cholesterol in males. Cholesterol fell in CF1 females but not MOF1. Serum corticosterone levels were higher in male and female MOF1 than CF1 and declined with age. DHEA serum levels were lower in male and female MOF1 than CF1. Liver antioxidant enzymes decreased with age (CF1 and MOF1). Conclusions: exposure to the developmental challenge of MO accelerates progeny ageing metabolic and endocrine profiles in a sex specific manner, providing evidence for programming‐ageing interactions.
Key points
Maternal obesity predisposes to metabolic dysfunction in male and female offspring
Maternal high‐fat diet consumption prior to and throughout pregnancy and lactation accelerates offspring metabolic ageing in a sex‐dependent manner
This study provides evidence for programming‐ageing interactions
Haemodynamic, metabolic, and biochemical derangements in critically ill patients affect drug pharmacokinetics and pharmacodynamics making dose optimisation particularly challenging. Appropriate ...therapeutic dosing depends on the knowledge of the physiologic changes caused by the patient's comorbidities, underlying disease, resuscitation strategies, and polypharmacy. Critical illness will result in altered drug protein binding, ionisation, and volume of distribution; it will also decrease oral drug absorption, intestinal and hepatic metabolism, and renal clearance. In contrast, the resuscitation strategies and the use of vasoactive drugs may oppose these effects by leading to a hyperdynamic state that will increase blood flow towards the major organs including the brain, heart, kidneys, and liver, with the subsequent increase of drug hepatic metabolism and renal excretion. Metabolism is the main mechanism for drug clearance and is one of the main pharmacokinetic processes affected; it is influenced by patient-specific factors, such as comorbidities and genetics; therapeutic-specific factors, including drug characteristics and interactions; and disease-specific factors, like organ dysfunction. Moreover, organ support such as mechanical ventilation, renal replacement therapy, and extracorporeal membrane oxygenation may contribute to both inter- and intra-patient variability of drug pharmacokinetics. The combination of these competing factors makes it difficult to predict drug response in critically ill patients. Pharmacotherapy targeted to therapeutic goals and therapeutic drug monitoring is currently the best option for the safe care of the critically ill. The aim of this paper is to review the alterations in drug pharmacokinetics associated with critical illness and to summarise the available evidence.
Helicoverpa armigera is a polyphagous pest sensitive to Cry1Ac protein from Bacillus thuringiensis (Bt). The susceptibility of the different larval instars of H. armigera to Cry1Ac protoxin showed a ...significant 45-fold reduction in late instars compared to early instars. A possible hypothesis is that gut surface proteins that bind to Cry1Ac differ in both instars, although higher Cry toxin degradation in late instars could also explain the observed differences in susceptibility. Here we compared the Cry1Ac-binding proteins from second and fifth instars by pull-down assays and liquid chromatography coupled to mass spectrometry analysis (LC-MS/MS). The data show differential protein interaction patterns of Cry1Ac in the two instars analyzed. Alkaline phosphatase, and other membrane proteins, such as prohibitin and an anion selective channel protein were identified only in the second instar, suggesting that these proteins may be involved in the higher toxicity of Cry1Ac in early instars of H. armigera. Eleven Cry1Ac binindg proteins were identified exclusively in late instar larvae, like different proteases such as trypsin-like protease, azurocidin-like proteinase, and carboxypeptidase. Different aminopeptidase N isofroms were identified in both instar larvae. We compared the Cry1Ac protoxin degradation using midgut juice from late and early instars, showing that the midgut juice from late instars is more efficient to degrade Cry1Ac protoxin than that of early instars, suggesting that increased proteolytic activity on the toxin could also explain the low Cry1Ac toxicity in late instars.
Due to the distinctive characteristics of probiotics, it is essential to pinpoint strains originating from diverse sources that prove efficacious in addressing a range of pathologies linked to ...dysfunction of the intestinal barrier. Nine strains of lactic acid bacteria were isolated from two different sources of tepache kefir grains (KAS2, KAS3, KAS4, KAS7, KAL4, KBS2, KBS3, KBL1 and KBL3), and were categorized to the genus Lacticaseibacillus, Liquorilactobacillus, and Lentilactobacillus by 16S rRNA gene. Kinetic behaviors of these strains were evaluated in MRS medium, and their probiotic potential was performed: resistance to low pH, tolerance to pepsin, pancreatin, bile salts, antibiotic resistance, hemolytic activity, and adhesion ability. KAS7 strain presented a higher growth rate (0.50 h-1) compared with KAS2 strain, who presented a lower growth rate (0.29 h-1). KBS2 strain was the only strain that survived the in vitro stomach simulation conditions (29.3%). Strain KBL1 demonstrated significantly higher viability (90.6%) in the in vitro intestine simulation conditions. Strain KAS2 demonstrated strong hydrophilic character with chloroform (85.6%) and xylol (57.6%) and a higher percentage of mucin adhesion (87.1%). However, strains KBS2 (84.8%) and KBL3 (89.5%) showed the highest autoaggregation values. In terms of adhesion to the intestinal epithelium in rats, strains KAS2, KAS3 and KAS4 showed values above 80%. The growth of the strains KAS2, KAS3, KAS4, KBS2, and KBL3 was inhibited by cefuroxime, cefotaxime, tetracycline, ampicillin, erythromycin, and cephalothin. Strains KBS2 (41.9% and 33.5%) and KBL3 (42.5% and 32.8%) had the highest co-aggregation values with S. aureus and E. coli. The results obtained in this study indicate that lactic acid bacteria isolated from tepache can be considered as candidates for potentially probiotic bacteria, laying the foundations to evaluate their probiotic functionality in vivo and thus to be used in the formulation of functional foods.
Bacillus thuringiensis (Bt) bacteria produce Cry toxins that are able to kill insect pests. Different models explaining the mode of action of these toxins have been proposed. The pore formation model ...proposes that the toxin creates pores in the membrane of the larval midgut cells after interaction with different receptors such as cadherin, aminopeptidase N and alkaline phosphatase and that this pore formation activity is responsible for the toxicity of these proteins. The alternative model proposes that interaction with cadherin receptor triggers an intracellular cascade response involving protein G, adenylate cyclase (AC) and protein kinase A (PKA). In addition, it was shown that Cry toxins induce a defense response in the larvae involving the activation of mitogen-activated kinases such as MAPK p38 in different insect orders. Here we analyzed the mechanism of action of Cry1Ab and Cry1Ac toxins and a collection of mutants from these toxins in the insect cell line CF1 from Choristoneura fumiferana, that is naturally sensitive to these toxins. Our results show that both toxins induced permeability of K+ ions into the cells. The initial response after intoxication with Cry1Ab and Cry1Ac toxins involves the activation of a defense response that involves the phosphorylation of MAPK p38. Analysis of activation of PKA and AC activities indicated that the signal transduction involving PKA, AC and cAMP was not activated during Cry1Ab or Cry1Ac intoxication. In contrast we show that Cry1Ab and Cry1Ac activate apoptosis. These data indicate that Cry toxins can induce an apoptotic death response not related with AC/PKA activation. Since Cry1Ab and Cry1Ac toxins affected K+ ion permeability into the cells, and that mutant toxins affected in pore formation are not toxic to CF1, we propose that pore formation activity of the toxins is responsible of triggering cell death response in CF1cells.
Display omitted
•Cry1Ab and Cry1Ac toxins induced permeability of K+ ions into CF1 cells.•Initial response to Cry1A toxins involves activation of a defense response with phosphorylation of MAPK p38.•The AC/PKA signaling pathway is not involved in the toxicity of Cry1Ab or Cry1Ac to CF1 cells.•Cry1Ab and Cry1Ac toxins activate apoptosis in CF1.
The genus Leuconostoc belongs to a group of lactic acid bacteria usually isolated from fermented vegetables, which includes species involved in the production of exopolysaccharides (EPS) with ...commercial potential. This study was aimed to produce and characterize exopolysaccharides of four strains of Leuconostoc mesenteroides, which were isolated from aguamiel of Agave salmiana. The EPS were obtained with sucrose, pH 6, without agitation and incubation at 30 °C for 24 h. The EPS were precipitated as gummy masses by the addition of ethanol and characterized as the important long chain glucose polymer known as dextran (Strain SF3 with 20 g/L yield). The chemical and rheological properties of the produced EPS were investigated. Dextrans produced by these strains have a backbone chain of α (1 → 6) linkages with α (1 → 3) branching. The rheological behavior of dextran solutions exhibited typical shear thinning and weak gel properties.
Display omitted
•Leuconostoc mesenteroides isolated of Agave salmiana can biosynthesize dextran with varied degrees of α (1 → 3) branching.•Bioengineered α-glucan could form ideal gel.•Dextrans solutions exhibited non-Newtonian behavior.•SEM images demonstrated the compact mesh in the dextrans.
Animal studies indicate that suboptimal conditions during pregnancy adversely impact both maternal health and offspring phenotype, predisposing offspring to development of later-life diseases ...including obesity, diabetes, cardiovascular diseases, and behavioral and reproductive dysfunction. Effective interventions during pregnancy and/or lactation are needed to improve both maternal and offspring health. This review addresses the relationship between adverse perinatal insults and its negative impact on offspring development and presents some maternal intervention studies in animal models, such as maternal nutrition (diet modification, antioxidants, omega-3-6 (n-3-6), probiotics) or physical activity, which can prevent or alleviate negative outcomes in both mother and offspring.
We investigated if supplementing obese mothers (MO) with docosahexaenoic acid (DHA) improves milk long-chain polyunsaturated fatty acid (LCPUFA) composition and offspring anxiety behavior. From ...weaning throughout pregnancy and lactation, female Wistar rats ate chow (C) or a high-fat diet (MO). One month before mating and through lactation, half the mothers received 400 mg DHA kg
d
orally (C+DHA or MO+DHA). Offspring ate C after weaning. Maternal weight, total body fat, milk hormones, and milk nutrient composition were determined. Pups' milk nutrient intake was evaluated, and behavioral anxiety tests were conducted. MO exhibited increased weight and total fat, and higher milk corticosterone, leptin, linoleic, and arachidonic acid (AA) concentrations, and less DHA content. MO male and female offspring had higher ω-6/ ω-3 milk consumption ratios. In the elevated plus maze, female but not male MO offspring exhibited more anxiety. MO+DHA mothers exhibited lower weight, total fat, milk leptin, and AA concentrations, and enhanced milk DHA. MO+DHA offspring had a lower ω-6/ω-3 milk intake ratio and reduced anxiety vs. MO. DHA content was greater in C+DHA milk vs. C. Supplementing MO mothers with DHA improves milk composition, especially LCPUFA content and ω-6/ω-3 ratio reducing offspring anxiety in a sex-dependent manner.
This paper examines whether and when corporate disclosures about a firm's exposure to climate risks matter to financial analysts. More specifically, we investigate the association between climate ...risk disclosure (CRD) and two properties of financial analysts’ earnings forecasts (accuracy and dispersion). We predict that climate risk financial materiality at the industry level moderates this association. Using a sample of 2184 US nonfinancial firm‐year observations over the period 2010–2016, we show that CRD is associated with higher forecast precision and lower dispersion only when climate risks are perceived by investors as being financially material at the industry level. We also find that while corporate disclosures about transition risks are not associated with financial analyst forecast properties, 10‐K disclosures about climate‐related material physical risks reduce analyst forecast error and dispersion.
PDF
