Search

Organisms necessarily release heat energy in their pursuit of survival. This process is known as cellular thermogenesis and is implicated in many processes from cancer metabolism to spontaneous farm fires. However, the molecular basis for this fundamental phenomenon is yet to be elucidated. Here, we show that the major players involved in the cellular thermogenesis of Escherichia coli are the protein kinases ArcB, GlnL, and YccC. We also reveal the substrate-level control of adenosine triphosphate (ATP)-driven autophosphorylation that governs cellular thermogenesis. Specifically, through live cell microcalorimetry, we find these regulatory proteins, when knocked out in a model E. coli strain, dysregulate cellular thermogenesis. This dysregulation can be seen in an average 25% or greater increase in heat output by these cells. We also discover that both heat output and intracellular ATP levels are maximal during the late log phase of growth. Additionally, we show that microbial thermogenesis can be engineered through overexpressing glnL. Our results demonstrate a correlation between ATP concentrations in the cell and a cell's ability to generate excess heat. We expect this work to be the foundation for engineering thermogenically tuned organisms for a variety of applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Dhatt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

1. Sixty marasmic children were investigated for the absorption of xylose, proteins and fats. Their duodenal juice samples were also analysed for bile salts and microflora. 2. The marasmic children were then studied in three groups of twenty by allocating them to three different dietary schedules: a high-protein diet (30% of the total energy from protein), a high-fat diet (40% of the total energy from fat) and a high-carbohydrate diet (70% of the total energy from carbohydrate) for 2 weeks and the previous measurements repeated. 3. Whereas the high-fat diet resulted in improved fat absorption, along with an increase in total and conjugated bile acids, and the high-carbohydrate diet led to improved xylose absorption, the diet rich in protein resulted in an improvement in the absorption of all three dietary ingredients. It appears that a high-protein diet improves the overall absorption process by improving the intestinal environment as a whole, while high-carbohydrate and high-fat diets bring about adaptive changes related to the respective absorptive processes.

Objective: Severe acute malnutrition (SAM) is a major cause of mortality in children under 5 years and is associated with hepatic steatosis. Bile acids are synthesized in the liver and participate in dietary fat digestion, regulation of energy expenditure, and immune responses. The aim of this work was to investigate whether SAM is associated with clinically relevant changes in bile acid homeostasis. Design: An initial discovery cohort with 5 healthy controls and 22 SAM-patients was used to identify altered bile acid homeostasis. A follow up cohort of 40 SAM-patients were then studied on admission and 3 days after clinical stabilization to assess recovery in bile acid metabolism. Recruited children were 6–60 months old and admitted for SAM in Malawi. Clinical characteristics, feces and blood were collected on admission and prior to discharge. Bile acids, 7α-hydroxy-4-cholesten-3-one (C4) and FGF-19 were quantified. Results: On admission, total serum bile acids were higher in children with SAM than in healthy controls and glycine-conjugates accounted for most of this accumulation with median and interquartile range (IQR) of 24.6 μmol/L [8.6–47.7] compared to 1.9 μmol/L [1.7–3.3] (p = 0.01) in controls. Total serum bile acid concentrations did not decrease prior to discharge. On admission, fecal conjugated bile acids were lower and secondary bile acids higher at admission compared to pre- discharge, suggesting increased bacterial conversion. FGF19 (Fibroblast growth factor 19), a marker of intestinal bile acid signaling, was higher on admission and was associated with decreased C4 concentrations as a marker of bile acid synthesis. Upon recovery, fecal calprotectin, a marker of intestinal inflammation, was lower. Conclusion: SAM is associated with increased serum bile acid levels despite reduced synthesis rates. In SAM, there tends to be increased deconjugation of bile acids and conversion from primary to secondary bile acids, which may contribute to the development of liver disease. [ABSTRACT FROM AUTHOR]

Objective: Neonatal tetanus (NNT) is an important cause of mortality in resource poor countries, particularly sub-Saharan Africa. There are no reports of the long-term outcome of children who survive NNT in African hospitals.Design: In a retrospective study of children discharged from Kilifi District Hospital (KDH), Kenya with NNT, each child was linked with a comparative child (CC) in the community matched for age, sex and locality.Participants: A total of 123 patients were admitted with NNT between 1992 and 1996, of whom 68% died. Twenty-three (59%) of the 39 survivors were traced in the community, 10 had moved away, six had died.Outcome Measures: NNT survivors underwent a neurological and developmental examination and a questionnaire was administered to the parents about the behaviour of the child. A verbal autopsy was used to determine the cause of death in children who had died after discharge.Results: The head circumference of NNT survivors was significantly smaller than that of CC (P=0.037); eight children had microcephaly compared with one CC (P=0.011). NNT survivors had more problems with hand-eye co-ordination tasks (P=0.035), a lower summated developmental score (P=0.023) and more mild neurological abnormalities (P=0.008) than CC. Parents of NNT survivors reported more behavioural problems (P=0.02) than parents of CC.Conclusions: Children who survive NNT have evidence of brain damage that manifests as microcephaly, mild neurological abnormalities, developmental impairment - particularly fine motor difficulties - and behaviour problems. [ABSTRACT FROM AUTHOR]

Provides information on a study which assessed the impact of a daily oral iron supplementation on hematological status, cell-mediated immunity and susceptibility to infections in children. Subjects and methods; Results and discussion.

Zinc absorption was measured in 37 children with malnutrition using the oral zinc tolerance test (22.5 mg elementary zinc) and the results compared with those of a group of healthy control subjects. The increase in plasma zinc was significantly lower in patients with marasmic kwashiorkor than in the control group. The zinc tolerance test was, however, normal in marasmic patients. We conclude that zinc deficiency occurs in some types of protein energy malnutrition, and that malabsorption may aggravate zinc deficiency. It is reasonable to give higher doses of zinc than are usually recommended during oral zinc supplementation in patients with protein energy malnutrition. [ABSTRACT FROM AUTHOR]

Training traditional birth attendants (TBAs) has been promoted as a way to prevent neonatal tetanus in areas of the developing world where TBAs are widespread. The evidence for the effectiveness of this strategy is reviewed. It is concluded that the evidence that training TBAs prevents neonatal tetanus is much weaker than that for vaccination of women with tetanus toxoid either before or during their pregnancy. Vaccination is the method of choice for prevention of neonatal tetanus wherever it is economically practicable. Where TBAs are trained, their tasks should include promotion of tetanus toxoid vaccination coverage. [ABSTRACT FROM PUBLISHER]

Introduction The liver is a central mediator of feeding and fasting transitions, pivoting from carbohydrate-based energy accumulation in the fed state to fatty acid oxidation-dependent (FAO-dependent) energy utilization in the [...], The nuclear receptors PPAR[alpha] (encoded by NR1C1) and farnesoid X receptor (FXR, encoded by NR1H4) are activated in the liver in the fasted and fed state, respectively. PPAR[alpha] activation induces fatty acid oxidation, while FXR controls bile acid homeostasis, but both nuclear receptors also regulate numerous other metabolic pathways relevant to liver energy balance. Here we review evidence that they function coordinately to control key nutrient pathways, including fatty acid oxidation and gluconeogenesis in the fasted state and lipogenesis and glycolysis in the fed state. We have also recently reported that these receptors have mutually antagonistic impacts on autophagy, which is induced by PPAR[alpha] but suppressed by FXR. Secretion of multiple blood proteins is a major drain on liver energy and nutrient resources, and we present preliminary evidence that the liver secretome may be directly suppressed by PPAR[alpha], but induced by FXR. Finally, previous studies demonstrated a striking deficiency in bile acid levels in malnourished mice that is consistent with results in malnourished children. We present evidence that hepatic targets of PPAR[alpha] and FXR are dysregulated in chronic undernutrition. We conclude that PPAR[alpha] and FXR function coordinately to integrate liver energy balance.