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Resting Metabolic Rate (RMR) is a pivotal metric reflecting the caloric expenditure necessary for fundamental physiological functions during periods of rest, encompassing vital processes such as blood circulation, brain activity, respiration, fuel metabolism, and thermal regulation. The accurate estimation of RMR holds paramount importance in delineating an individual’s daily energy requirements and assessing their susceptibility to various health conditions, including cardiovascular diseases, hypertension, and diabetes. Additionally, RMR serves as a significant indicator of biological age, aiding in the formulation of personalized dietary plans by nutritionists to assist individuals in achieving their health and wellness objectives. This study aims to develop new models for predicting RMR using General Regression Neural Network (GRNN). Additionally, prediction models based on Multi-Layer Perceptron (MLP) will be created for comparison purposes. For model optimization, we developed an innovative web-based software using the DTREG predictive modeling software library. The implementation of this application was executed using Visual Studio and the C# programming language. To ensure the robustness of the prediction models, two distinct self-created datasets comprising data from female and male patients were employed. A total of 260 female patients and 150 male patients were included in the datasets. Separate GRNN-based and MLP-based models were developed for each dataset, leveraging various variables obtained from Tanita, a smart scale capable of comprehensive body scanning. These variables encompass personal information, body analysis, reference analysis, and segmental body composition analysis, providing detailed insights into impedance, fat percentage, fat mass, non-fat mass, muscle mass, and other metrics. The variables derived from Tanita measurements served as input variables for machine learning model creation, while RMR values obtained using FitMate served as output variables. Evaluation of these prediction models was based on Correlation Coefficient (R), Root Mean Square Error (RMSE), and Mean Absolute Percentage Error (MAPE) metrics to assess their performance, with the outcomes substantiating the efficacy of the proposed models in RMR prediction. The GRNN-based models performed better than the ones built by MLP, demonstrating its feasibility as a tool for predicting RMR accurately. The results have also been compared with up-to-date prediction equations from related literature, and our optimized models perform significantly better than those. The proposed best performing GRNN model achieved an R value of 0.85, RMSE of 134.91 kcal/day, and MAPE of 10.20%, significantly outperforming traditional predictive equations such as the Harris-Benedict and Mifflin-St Jeor equations, which showed RMSE values above 400 kcal/day and MAPE values exceeding 12.5%.

This study was conducted to determine the total oil contents and fatty acid compositions of some commercial almond cultivars. The total oil contents changed significantly (p

The unfolded protein response (UPR) is an elaborate signaling network that evolved to maintain proteostasis in the endoplasmic reticulum (ER) and mitochondria (mt). These organelles are functionally and physically associated, and consequently, their stress responses are often intertwined. It is unclear how these two adaptive stress responses are coordinated during ER stress. The inositol-requiring enzyme-1 (IRE1), a central ER stress sensor and proximal regulator of the UPR ER , harbors dual kinase and endoribonuclease (RNase) activities. IRE1 RNase activity initiates the transcriptional layer of the UPR ER , but IRE1's kinase substrate(s) and their functions are largely unknown. Here, we discovered that sphingosine 1-phosphate (S1P) lyase (SPL), the enzyme that degrades S1P, is a substrate for the mammalian IRE1 kinase. Our data show that IRE1-dependent SPL phosphorylation inhibits SPL's enzymatic activity, resulting in increased intracellular S1P levels. S1P has previously been shown to induce the activation of mitochondrial UPR (UPR mt ) in nematodes. We determined that IRE1 kinase-dependent S1P induction during ER stress potentiates UPR mt signaling in mammalian cells. Phosphorylation of eukaryotic translation initiation factor 2α (eif2α) is recognized as a critical molecular event for UPR mt activation in mammalian cells. Our data further demonstrate that inhibition of the IRE1-SPL axis abrogates the activation of two eif2α kinases, namely double-stranded RNA-activated protein kinase (PKR) and PKR-like ER kinase upon ER stress. These findings show that the IRE1-SPL axis plays a central role in coordinating the adaptive responses of ER and mitochondria to ER stress in mammalian cells., Competing Interests: Conflict of Interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The double-stranded RNA-dependent protein kinase activating protein (PACT), an RNA-binding protein that is part of the RNA-induced silencing complex, plays a key role in miR-mediated translational repression. Previous studies showed that PACT regulates the expression of various miRs, selects the miR strand to be loaded onto RNA-induced silencing complex, and determines proper miR length. Apart from PACT's role in mediating the antiviral response in immune cells, what PACT does in other cell types is unknown. Strikingly, it has also been shown that cold exposure leads to marked downregulation of PACT protein in mouse brown adipose tissue (BAT), where mitochondrial biogenesis and metabolism play a central role. Here, we show that PACT establishes a posttranscriptional brake on mitochondrial biogenesis (mitobiogenesis) by promoting the maturation of miR-181c, a key suppressor of mitobiogenesis that has been shown to target mitochondrial complex IV subunit I (Mtco1) and sirtuin 1 (Sirt1). Consistently, we found that a partial reduction in PACT expression is sufficient to enhance mitobiogenesis in brown adipocytes in culture as well as during BAT activation in mice. In conclusion, we demonstrate an unexpected role for PACT in the regulation of mitochondrial biogenesis and energetics in cells and BAT., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Kawasaki disease (KD) is the leading cause of noncongenital heart disease in children. Studies in mice and humans propound the NLRP3/IL-1β pathway as the principal driver of KD pathophysiology. Endoplasmic reticulum (ER) stress can activate the NLRP3 inflammasome, but the potential implication of ER stress in KD pathophysiology has not been investigated to our knowledge. We used human patient data and the Lactobacillus casei cell wall extract (LCWE) murine model of KD vasculitis to characterize the impact of ER stress on the development of cardiovascular lesions. KD patient transcriptomics and single-cell RNA sequencing of the abdominal aorta from LCWE-injected mice revealed changes in the expression of ER stress genes. Alleviating ER stress genetically, by conditional deletion of inositol-requiring enzyme 1 (IRE1) in myeloid cells, or pharmacologically, by inhibition of IRE1 endoribonuclease (RNase) activity, led to significant reduction of LCWE-induced cardiovascular lesion formation as well as reduced caspase-1 activity and IL-1β secretion. These results demonstrate the causal relationship of ER stress to KD pathogenesis and highlight IRE1 RNase activity as a potential new therapeutic target.

Objective: Saturated and trans fat consumption is associated with increased cardiovascular disease (CVD) risk. Current dietary guidelines recommend low fat and significantly reduced trans fat intake. Full fat dairy can worsen dyslipidemia, but recent epidemiological studies show full-fat dairy consumption may reduce diabetes and CVD risk. This dairy paradox prompted a reassessment of the dietary guidelines. The beneficial metabolic effects in dairy have been claimed for a ruminant-derived, trans fatty acid, trans-C16:1n-7 or trans-palmitoleate (trans-PAO). A close relative, cis-PAO, is produced by de novo lipogenesis and mediates inter-organ crosstalk, improving insulin-sensitivity and alleviating atherosclerosis in mice. These findings suggest trans-PAO may be a useful substitute for full fat dairy, but a metabolic function for trans-PAO has not been shown to date., Methods: Using lipidomics, we directly investigated trans-PAO's impact on plasma and tissue lipid profiles in a hypercholesterolemic atherosclerosis mouse model. Furthermore, we investigated trans-PAO's impact on hyperlipidemia-induced inflammation and atherosclerosis progression in these mice., Results: Oral trans-PAO supplementation led to significant incorporation of trans-PAO into major lipid species in plasma and tissues. Unlike cis-PAO, however, trans-PAO did not prevent organelle stress and inflammation in macrophages or atherosclerosis progression in mice., Conclusions: A significant, inverse correlation between circulating trans-PAO levels and diabetes incidence and cardiovascular mortality has been reported. Our findings show that trans-PAO can incorporate efficiently into the same pools that its cis counterpart is known to incorporate into. However, we found trans-PAO's anti-inflammatory and anti-atherosclerotic effects are muted due to its different structure from cis-PAO., (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Eukaryotic cells can respond to diverse stimuli by converging at serine-51 phosphorylation on eukaryotic initiation factor 2 alpha (eIF2α) and activate the integrated stress response (ISR). This is a key step in translational control and must be tightly regulated; however, persistent eIF2α phosphorylation is observed in mouse and human atheroma., Objectives: Potent ISR inhibitors that modulate neurodegenerative disorders have been identified. Here, the authors evaluated the potential benefits of intercepting ISR in a chronic metabolic and inflammatory disease, atherosclerosis., Methods: The authors investigated ISR's role in lipid-induced inflammasome activation and atherogenesis by taking advantage of 3 different small molecules and the ATP-analog sensitive kinase allele technology to intercept ISR at multiple molecular nodes., Results: The results show lipid-activated eIF2α signaling induces a mitochondrial protease, Lon protease 1 (LONP1), that degrades phosphatase and tensin-induced putative kinase 1 and blocks Parkin-mediated mitophagy, resulting in greater mitochondrial oxidative stress, inflammasome activation, and interleukin-1β secretion in macrophages. Furthermore, ISR inhibitors suppress hyperlipidemia-induced inflammasome activation and inflammation, and reduce atherosclerosis., Conclusions: These results reveal endoplasmic reticulum controls mitochondrial clearance by activating eIF2α-LONP1 signaling, contributing to an amplified oxidative stress response that triggers robust inflammasome activation and interleukin-1β secretion by dietary fats. These findings underscore the intricate exchange of information and coordination of both organelles' responses to lipids is important for metabolic health. Modulation of ISR to alleviate organelle stress can prevent inflammasome activation by dietary fats and may be a strategy to reduce lipid-induced inflammation and atherosclerosis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Chromatin structure in transcribed regions poses a barrier for intragenic transcription. In a comprehensive study of the yeast chromatin remodelers and the Mot1p-NC2 regulators of TATA-binding protein (TBP), we detected synthetic genetic interactions indicative of suppression of intragenic transcription. Conditional depletion of Mot1p or NC2 in absence of the ISW1 remodeler, but not in the absence of other chromatin remodelers, activated the cryptic FLO8 promoter. Likewise, conditional depletion of Mot1p or NC2 in deletion backgrounds of the H3K36 methyltransferase Set2p or the Asf1p-Rtt106p histone H3-H4 chaperones, important factors involved in maintaining a repressive chromatin environment, resulted in increased intragenic FLO8 transcripts. Activity of the cryptic FLO8 promoter is associated with reduced H3 levels, increased TBP binding and tri-methylation of H3K4 and is independent of Spt-Ada-Gcn5-acetyltransferase function. These data reveal cooperation of negative regulation of TBP with specific chromatin regulators to inhibit intragenic transcription.