Energetic Function Research Articles

Introduction to medical orgone therapy

We introduce and present a medical psychotherapeutic technique initiated by Wilhelm Reich in the 1920's and thereafter expanded and refined with essential contributions by Elsworth Baker among others. We outline its theory and technical foundations and also provide an epistemological interpretation of its peculiar body-mind representation based on character- and muscular armoring as a reaction to suffering; armoring of the ocular segment in the aetiology of Bleuler's schizophrenic splitting; and finally the consequences of armoring on the energetic functions as the logical development of Freud's theory of libido, with significant theoretic, therapeutic and nosologic consequences.

Personalised Medicine for Dementia: Collaborative Research of Multimodal Non-pharmacological Treatment with the UK National Health Service (NHS)

The dominant narrative around dementia argues that progression cannot be halted or reversed. However, evidence on multimodal non-pharmacological treatments formulated around a ‘personalised medicine’ approach challenges this view. This paper reviews the current evidence for dementia prevention utilising such treatments and explains the logic of applying personalised medicine. The functional medicine treatment approach to ‘root cause’ analysis is presented as currently practiced with patients experiencing cognitive decline. We report six case studies including in-depth practitioner evaluations, recommendations and follow-ups. We cover the various presentations of memory and concentration problems and the screening process with advanced functional testing. The case studies appear in a table, followed by 10 key points, insights and findings. To our knowledge, this is the first paper reporting practitioner case studies documenting improvements in symptoms of memory decline in patients from the UK, Greece and New Zealand. Four patients had initial presentations and follow-up improvements verified by standardised screening instruments and/or formal diagnosis. Two patients had symptom improvements verified through self-report and proxy-report. Practitioners reported improvements through biomarkers (normalisation of serum levels, folate and homocysteine, thyroid function, blood sugar levels), as well as weight loss, decreased blood pressure and reduction in medications. They also reported improved mental, physical, social, energetic, emotional and spiritual functioning. The next phase is an enhanced intervention alongside the existing UK National Health Service memory assessment pathway. This paper advocates for personalised medicine in the UK for persons living with memory problems and dementia, driven by this increasing evidence base.

Influence of Chemically Disrupted Photosynthesis on Cyanobacterial Thylakoid Dynamics in Synechocystis sp. PCC 6803

The photosynthetic machinery of the cyanobacterium Synechocystis sp. PCC 6803 resides in flattened membrane sheets called thylakoids, situated in the peripheral part of the cellular cytoplasm. Under photosynthetic conditions these thylakoid membranes undergo various dynamical processes that could be coupled to their energetic functions. Using Neutron Spin Echo Spectroscopy (NSE), we have investigated the undulation dynamics of Synechocystis sp. PCC 6803 thylakoids under normal photosynthetic conditions and under chemical treatment with DCMU (3-(3,4-dichlorophenyl)-1,1-dimethylurea), an herbicide that disrupts photosynthetic electron transfer. Our measurements show that DCMU treatment has a similar effect as dark conditions, with differences in the undulation modes of the untreated cells compared to the chemically inhibited cells. We found that the disrupted membranes are 1.5-fold more rigid than the native membranes during the dark cycle, while in light they relax approximately 1.7-fold faster than native and they are 1.87-fold more flexible. The strength of the herbicide disruption effect is characterized further by the damping frequency of the relaxation mode and the decay rate of the local shape fluctuations. In the dark, local thicknesses and shape fluctuations relax twice as fast in native membranes, at 17% smaller mode amplitude, while in light the decay rate of local fluctuations is 1.2-fold faster in inhibited membranes than in native membranes, at 56% higher amplitude. The disrupted electron transfer chain and the decreased proton motive force within the lumenal space partially explain the variations observed in the mechanical properties of the Synechocystis membranes, and further support the hypothesis that the photosynthetic process is tied to thylakoid rigidity in this type of cyanobacterial cell.

Finding the ΔΔG spot: Are predictors of binding affinity changes upon mutations in protein–protein interactions ready for it?

Predicting the structure and thermodynamics of protein–protein interactions (PPIs) are key to a proper understanding and modulation of their function. Since experimental methods might not be able to catch up with the fast growth of genomic data, computational alternatives are therefore required. We present here a review dealing with various aspects of predicting binding affinity changes upon mutations (ΔΔG). We focus on predictors that consider three‐dimensional structure information to estimate the impact of mutations on the binding affinity of a protein–protein complex, excluding the rigorous free energy perturbation methods. Training and evaluation, ΔΔG databases, data selection, and existing ΔΔG predictors are specially emphasized. We also establish the parallel with scoring functions used in docking since those share many similar PPI features with ΔΔG predictors. The field has seen a common evolution of ΔΔG predictors and scoring functions over time, transforming from purely energetic functions to statistical energy‐based and further to machine learning‐based functions. As machine learning has come to age, limitations in terms of quantity, quality and variety of the available data become the bottlenecks for the future development of these computational methods. This can be alleviated by building infrastructures for data generation, collection and sharing. Further developments can be catalyzed by conducting community‐wide blind challenges for method assessment.This article is categorized under: Structure and Mechanism > Molecular Structures Structure and Mechanism > Computational Biochemistry and Biophysics Molecular and Statistical Mechanics > Molecular Interactions

Measuring Health-Related Quality of Life in Sickle Cell Disease Patients Undergoing Automated Red Blood Cell Exchange in the USA, France and the UK

BackgroundSickle cell disease (SCD) is a group of disorders that affects hemoglobin, the molecule in red blood cells that delivers oxygen to cells throughout the body. People with this disorder have atypical hemoglobin molecules called hemoglobin S, which can distort red blood cells into a sickle, or crescent, shape. Additionally, affected red blood cells have a high likelihood of stacking up and causing blockages in the small blood vessels. Both mechanisms of disease may cause damage to organs requiring oxygen, which causes pain and may be deadly. SCD and its complications reduce life expectancy and the nature of its complications and treatments may cause reduced quality of life. Although a rare disease, SCD may cause significant costs to healthcare and society. Depending on the indication, either hydroxyurea or chronic RBC transfusion is employed to treat SCD patients. RBC transfusion, simple or exchange, is first-line treatment for primary and secondary prevention of stroke. When the study was performed, no published research had been completed that compared patient outcomes in terms of Health-Related Quality of Life (HRQoL) for patients treated with automated red blood cell exchange versus simple transfusion.ObjectivesThere are multiple objectives covered within the scope of this study:•To quantify HRQoL as experienced by SCD patients in aRBCx versus simple transfusion.•To determine the drivers of HRQoL amongst SCD patients•To assess whether physicians and patients have a similar view on the impact of aRBCx on HRQoL amongst SCD patients.MethodologyA cross-sectional study was performed amongst 40 SCD patients, 20 from the USA, 10 from France and 10 from the UK as well as amongst 40 SCD treating physicians with experience in both simple transfusion as well as aRBCX. The physicians had the same regional distribution as the patients.ResultsSCD patients undergoing aRBCX reported an HRQoL that was 25% higher compared to the period where they were treated with simple transfusion (0.70 vs. 0.55; p<0.01). The main drivers of HRQoL identified were (correlation efficient): pain reduction (0.57), improved social live (0.49), autonomy in terms of all day living activities and being independent from others (0.56), feeling energetic and physical functioning (0.57) and lastly emotional worry and mental health (0.56), all with p-values < 0.01. Together these variables explain 39% of the HRQoL experienced by SCD patients (R² = 0.39, p < 0.01). 80% of the patients preferred aRBCx over simple transfusion. 87% of the participating physicians believed that switching patients from simple transfusion to automated red blood cell exchange (aRBCX) positively affected the SCD patients' quality of life. Physicians identified the following factors being responsible for the improved HRQoL in patients on aRBCX. Those with an average score of 5.5 or greater on a 7-point scale were: less iron overload, RBCX effectiveness, reduced acute complications, reduced chronic complications, and superior mechanism of action during acute situations.ConclusionSickle cell disease patients that require chronic blood transfusion experience better health-related quality of life when they are treated with automated red blood cell exchange versus simple transfusion. This observation is supported by the opinion of their treating physicians. DisclosuresDierick:Terumo BCT: Employment. Roig:Terumo BCT: Employment.

Intrinsic foot muscles contribute to elastic energy storage and return in the human foot.

The human foot is uniquely stiff to enable forward propulsion, yet also possesses sufficient elasticity to act as an energy store, recycling mechanical energy during locomotion. Historically, this dichotomous function has been attributed to the passive contribution of the plantar aponeurosis. However, recent evidence highlights the potential for muscles to modulate the energetic function of the foot actively. Here, we test the hypothesis that the central nervous system can actively control the foot's energetic function, via activation of the muscles within the foot's longitudinal arch. We used a custom-built loading apparatus to deliver cyclical loads to human feet in vivo, to deform the arch in a manner similar to that observed in locomotion. We recorded foot motion and forces, alongside muscle activation and ultrasound images from flexor digitorum brevis (FDB), an intrinsic foot muscle that spans the arch. When active, the FDB muscle fascicles contracted in an isometric manner, facilitating elastic energy storage in the tendon, in addition to the energy stored within the plantar aponeurosis. We propose that the human foot is akin to an active suspension system for the human body, with mechanical and energetic properties that can be actively controlled by the central nervous system. NEW & NOTEWORTHY The human foot is renowned for its ability to recycle mechanical energy during locomotion, contributing up to 17% of the energy required to power a stride. This mechanism has long been considered passive in nature, facilitated by the elastic ligaments within the arch of the foot. In this paper, we present the first direct evidence that the intrinsic foot muscles also contribute to elastic energy storage and return within the human foot. Isometric contraction of the flexor digitorum brevis muscle tissue facilitates tendon stretch and recoil during controlled loading of the foot. The significance of these muscles has been greatly debated by evolutionary biologists seeking to understand the origins of upright posture and gait, as well as applied and clinical scientists. The data we present here show a potential function for these muscles in contributing to the energetic function of the human foot.

Simulation of toroidicity-induced Alfven eigenmode excited by energetic ions in HL-2A tokamak plasmas

The toroidicity-induced Alfven eigenmode (TAE) excited by energetic (fast) ions was first simulated using the GTC code for HL-2A experiments. The simulation results indicate that the fraction of energetic ions is about 3% in the experiments. The critical density of energetic ions to excite the TAE mode is around 0.023, which is in good agreement with the theoretical expectation of 0.026. The real frequency of TAE with toroidal mode number n = 3 is around 211 kHz and is inversely proportional to the square root of electron density, which is quantitatively in agreement with the experimental observation (Ding et al 2013 Nucl. Fusion 53 043015). The frequency is in resonance with the summations of toroidal precession frequency and transit frequency of passing energetic ions, indicating that resonance with passing energetic ions is dominant for the excitation of the modes in the experiment. It is also checked by the phase space structures of (strength of energetic particle distribution function) that the TAE modes are mainly induced by passing energetic ions in HL-2A. The growth rates of TAE modes increase with fast ion density and its gradient. In addition, lower n TAE modes, such as n = 1 can also be driven by energetic ions when off-axis heating with higher beam energy is employed in the experiment. The width of radial mode structures for lower n modes is usually wider than those for higher n modes. The perpendicular wave vector of the modes and Larmor radius of ions satisfy the relation . Finally, the polarization of the mode shows that the perturbed parallel electric field is much smaller than the electrostatic parallel electric field.

Nutrient supply alters transcriptome regulation in adipose tissue of pre-weaning Holstein calves.

Performance of dairy cows can be influenced by early life nutrient supply. Adipose tissue is diet sensitive and an important component in that process as it is involved in the regulation of energetic, reproductive and immunological functions. However, it is not clear how early life nutrition alters the molecular regulation of adipose tissue in calves and potentially adult individuals. This study aimed at determining how differences in pre-weaning nutrient supply alter gene expression profiles and physiology in omental adipose tissue. A total of 12 female Holstein calves were fed two levels of milk replacer supply: a restricted amount of 11.72 MJ of metabolizable energy (ME) intake per day (n = 6) or an enhanced amount of 1.26 MJ ME intake per kg of metabolic body weight (BW0.75), resulting in supply from 17.58 to 35.17 MJ ME intake per day (n = 6). All calves had ad libitum access to a commercial calf starter and water. Analysis of the transcriptome profiles at 54 ± 2 days of age revealed that a total of 396 out of 19,968 genes were differentially expressed (DE) between groups (p < 0.001, FDR < 0.1). The directional expression of DE genes through Ingenuity Pathway Analysis showed that an enhanced nutrient supply alters adipose tissue physiology of pre-weaned calves. Several biological functions were increased (Z-score > +2), including Lipid Metabolism (Fatty Acid Metabolism), Cell Cycle (Entry into Interphase, Interphase, Mitosis and Cell Cycle Progression), Cellular Assembly and Organization (Cytoskeleton Formation and Cytoplasm Development) and Molecular Transport (Transport of Carboxylic Acid). These changes were potentially orchestrated by the activation/inhibition of 17 upstream regulators genes. Our findings indicate that adipose tissue of calves under an enhanced nutrient supply is physiologically distinct from restricted calves due to an increased development/expansion rate and also a higher metabolic activity through increased fatty acid metabolism.

Abstract B24: Met and VDAC1 as target for breast cancer therapy

Abstract During the past decade, considerable efforts have been devoted to the identification of agents that selectively kill neoplastic breast cancer cells based on their signaling and metabolic alterations. We hypothesis that combination tyrosine kinase and metabolic inhibitors are potential novel therapies for breast cancer. Aberrant signaling through Met-tyrosine kinase receptor and its ligand hepatocyte growth factor/scatter factor (HGF/SF) has been shown to play a critical role in development of tumors and metastasis in a variety of cancers, including breast cancer. We have previously shown that HGF/SF-induced Met-activation leads to diverse metabolic alteration in the tumor. Activation of Met signaling increases glycolytic flux into lactate and increases glycolysis, oxidative phosporylation, oxygen consumption, and tumor blood volume. The voltage-dependent anion channel 1 (VDAC1), located in the mitochondrial outer membrane, functions as gatekeeper for the entry and exit of mitochondrial metabolites, thereby controlling crosstalk between mitochondria and the rest of the cell. VDAC1 is also a key player in mitochondria-mediated apoptosis. Thus, in addition to regulating the metabolic and energetic functions of mitochondria, VDAC1 appears to act as a convergence point for a variety of cell survival and cell death signals, mediated by its association with various ligands and proteins. Shoshan-Barmatz’s lab developed the retro-Tf-D-LP4 peptide, a cell-penetrating VDAC1-based peptide that acts by inducing apoptosis and impairment of cell energy and metabolism. To study the possible therapeutic effect of Met inhibition and alteration of VDAC1 combined therapy on breast tumor cells, we evaluated cell proliferation and motility in BC cells. Using our newly developed single-cell 35 parameters morphokinetic analysis infrastructure, we demonstrate that after 24 hours, the peptide decreased all cell lines velocity (5µM; MDMDA-MB-231_velocity=8.2%, p=0.024. 15µM; MDMDA-MB-231_velocity=62.4%, p&amp;lt;0.001). The peptide in combination with Met inhibitor further decreased cell velocity and acceleration (MDMDA-MB-231_Velocity=85.9%, p&amp;lt;0.001; MDMDA-MB-231_Acceleration=76%, p&amp;lt;0.001). The combined treatment increased cell coordination but abrogated the back-propagating wave. The morphologic effect of the treatment was dependent on the cell line. Cluster analysis of morphokinetic parameters demonstrated that untreated or low doses of treatment MDA-MB-231 and HB2 are clustered together; MCF7 and T47D have slower motility parameters. Upon high-dose combined treatment MDA-MB-231 cells change are clustered with slow-velocity T47D and MCF7. Combined Met inhibition and VDAC1 alteration dramatically reduced cell motility and increased coordinated motility. In vitro experiments show a slight inhibitory effect of VDAC1 on MDA-MB-231 cell proliferation. However, in vivo experiments demonstrate an inhibitory effect on tumor growth. These results indicate that the combined therapy can reduce cell motility and metastasis in triple-negative breast cancer tumors. Citation Format: Guy Namir, Varda Shoshan-Barmatz, Ilan Tsarfaty. Met and VDAC1 as target for breast cancer therapy [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B24.

The energetic behaviour of the human foot across a range of running speeds

The human foot contains passive elastic tissues that have spring-like qualities, storing and returning mechanical energy and other tissues that behave as dampers, dissipating energy. Additionally the intrinsic and extrinsic foot muscles have the capacity to act as dampers and motors, dissipating and generating mechanical energy. It remains unknown as to how the contribution of all passive and active tissues combine to produce the overall energetic function of the foot during running. Therefore, the aim of this study was to determine if the foot behaves globally as an active spring-damper during running. Fourteen participants ran on a force-instrumented treadmill at 2.2 ms−1, 3.3 ms−1 and 4.4 ms−1, while foot segment motion was collected simultaneously with kinetic measurements. A unified deformable segment model was applied to quantify the instantaneous power of the foot segment during ground contact and mechanical work was calculated by integrating the foot power data. At all running speeds, the foot absorbed energy from early stance through to mid-stance and subsequently returned/generated a proportion of this energy in late stance. The magnitude of negative work performed increased with running speed, while the magnitude of positive work remained relatively constant across all running speeds. The proportion of energy dissipated relative to that absorbed (foot dissipation-ratio) was always greater than zero and increased with running speed, suggesting that the foot behaves as a viscous spring-damper.

Alkali endohedrals of C24(BN)12 heterofullerenes: A DFT aqueous phase study

AbstractResults achieved by density functional theory have been reported in terms of the energetic, electronic, vibrational frequencies, and thermochemical functions related to alkali metal endohedral derivatives of C24(BN)12 heterofullerenes in gas and aqueous phases. The endohedral heterofullerene cations are regarded as highly polar structures in both gas and aqueous phases. They indicate thermochemically approved solvation in the aqueous phase. The inclusion reactions are exothermic and spontaneous in the aqueous solution except for K+ cation. The calculated standard reduction potentials of alkali cation endohedral derivatives suggest them as potent oxidizing agents.

Multiscale Computational Analysis of Right Ventricular Mechanoenergetics.

Right ventricular (RV) failure, which occurs in the setting of pressure overload, is characterized by abnormalities in mechanical and energetic function. The effects of these cell- and tissue-level changes on organ-level RV function are unknown. The primary aim of this study was to investigate the effects of myofiber mechanics and mitochondrial energetics on organ-level RV function in the context of pressure overload using a multiscale model of the cardiovascular system. The model integrates the mitochondria-generated metabolite concentrations that drive intracellular actin-myosin cross-bridging and extracellular myocardial tissue mechanics in a biventricular heart model coupled with simple lumped parameter circulations. Three types of pressure overload were simulated and compared to experimental results. The computational model was able to capture a wide range of cardiovascular physiology and pathophysiology from mild RV dysfunction to RV failure. Our results confirm that, in response to pressure overload alone, the RV is able to maintain cardiac output (CO) and predict that alterations in either RV active myofiber mechanics or RV metabolite concentrations are necessary to decrease CO.

Acetylation contributes to hypertrophy-caused maturational delay of cardiac energy metabolism.

A dramatic increase in cardiac fatty acid oxidation occurs following birth. However, cardiac hypertrophy secondary to congenital heart diseases (CHDs) delays this process, thereby decreasing cardiac energetic capacity and function. Cardiac lysine acetylation is involved in modulating fatty acid oxidation. We thus investigated what effect cardiac hypertrophy has on protein acetylation during maturation. Eighty-four right ventricular biopsies were collected from CHD patients and stratified according to age and the absence (n = 44) or presence of hypertrophy (n = 40). A maturational increase in protein acetylation was evident in nonhypertrophied hearts but not in hypertrophied hearts. The fatty acid β-oxidation enzymes, long-chain acyl CoA dehydrogenase (LCAD) and β-hydroxyacyl CoA dehydrogenase (βHAD), were hyperacetylated and their activities positively correlated with their acetylation after birth in nonhypertrophied hearts but not hypertrophied hearts. In line with this, decreased cardiac fatty acid oxidation and reduced acetylation of LCAD and βHAD occurred in newborn rabbits subjected to cardiac hypertrophy due to an aortocaval shunt. Silencing the mRNA of general control of amino acid synthesis 5-like protein 1 reduced acetylation of LCAD and βHAD as well as fatty acid oxidation rates in cardiomyocytes. Thus, hypertrophy in CHDs prevents the postnatal increase in myocardial acetylation, resulting in a delayed maturation of cardiac fatty acid oxidation.

Energetic optimization and evaluation of a drinking water pumping system: application at the Rassauta station

Abstract The energy overconsumption at drinking-water pumping stations creates considerable energy losses. For this reason we have developed an NNGA tool of pumping management which optimizes the consumed energy by the pumping system with respect to the hydraulic functioning conditions in the distribution tank. This tool includes two models: a forecasting model for drinking water demand based on artificial neural networks and an optimization model using genetic algorithms. The results of the NNGA tool were compared with two pumping plans: the plan based on the pumping regulation model, and the plan used by the company of water and sewage of the city of Algiers. The analysis result was done with the help of performed indicators that we have developed and which enable the evaluation and diagnosis of the energetic function's system.

Restoring mitochondrial calcium uniporter expression in diabetic mouse heart improves mitochondrial calcium handling and cardiac function

Diabetes mellitus is a growing health care problem, resulting in significant cardiovascular morbidity and mortality. Diabetes also increases the risk for heart failure (HF) and decreased cardiac myocyte function, which are linked to changes in cardiac mitochondrial energy metabolism. The free mitochondrial calcium level ([Ca2+] m ) is fundamental in activating the mitochondrial respiratory chain complexes and ATP production and is also known to regulate pyruvate dehydrogenase complex (PDC) activity. The mitochondrial calcium uniporter (MCU) complex (MCUC) plays a major role in mediating mitochondrial Ca2+ import, and its expression and function therefore have a marked impact on cardiac myocyte metabolism and function. Here, we investigated MCU's role in mitochondrial Ca2+ handling, mitochondrial function, glucose oxidation, and cardiac function in the heart of diabetic mice. We found that diabetic mouse hearts exhibit altered expression of MCU and MCUC members and a resulting decrease in [Ca2+] m , mitochondrial Ca2+ uptake, mitochondrial energetic function, and cardiac function. Adeno-associated virus-based normalization of MCU levels in these hearts restored mitochondrial Ca2+ handling, reduced PDC phosphorylation levels, and increased PDC activity. These changes were associated with cardiac metabolic reprogramming toward normal physiological glucose oxidation. This reprogramming likely contributed to the restoration of both cardiac myocyte and heart function to nondiabetic levels without any observed detrimental effects. These findings support the hypothesis that abnormal mitochondrial Ca2+ handling and its negative consequences can be ameliorated in diabetes by restoring MCU levels via adeno-associated virus-based MCU transgene expression.

Symbolic Analysis of the Cycle-to-Cycle Variability of a Gasoline–Hydrogen Fueled Spark Engine Model

An study of temporal organization of the cycle-to-cycle variability (CCV) in spark ignition engines fueled with gasoline–hydrogen blends is presented. First, long time series are generated by means of a quasi-dimensional model incorporating the key chemical and physical components, leading to variability in the time evolution of energetic functions. The alterations in the combustion process, for instance the composition of reactants, may lead to quantitative changes in the time evolution of the main engine variables. It has been observed that the presence of hydrogen in the fuel mixture leads to an increased laminar flame speed, with a corresponding decrease in CCV dispersion. Here, the effects of different hydrogen concentrations in the fuel are considered. First, it is observed that return maps of heat release sequences exhibit different patterns for different hydrogen concentrations and fuel–air ratios. Second, a symbolic analysis is used to characterize time series. The symbolic method is based on the probability of occurrence of consecutive states (a word) in a symbolic sequence histogram (SSH). Modified Shannon entropy is computed in order to determine the adequate word length. Results reveal the presence of non-random patterns in the sequences and soft transitions between states. Moreover, the general behavior of CCV simulations results and three types of synthetic noises: white, log-normal, and a noisy logistic map, are compared. This analysis reveals that the non-random features observed in heat release sequences are quite different from synthetic noises.

Inhibition of excessive mitochondrial fission protects the cardiomyocyte against palmitate‐induced lipotoxicity

Mitochondria play the major role in maintaining the optimal cardiac function. Recently, mitochondrial dynamics have been connected with cardiovascular diseases. Cardiac oxidative stress and imbalanced mitochondrial dynamics (decreased fusion and excessive fission) are involved in lipotoxicity‐induced cardiomyopathy. Our aim was to investigate the role of mitochondrial dynamic in H9c2 cells under lipotoxicity. Treatment of H9c2 cells (cardiomyoblast) with 200 μM palmitate resulted in decreased cell viability and decreased ATP production. Palmitate treatment for 3 h elevated protein expression of the dynamin‐related protein‐1 (DRP1, a mitochondrial fission protein) and PTEN‐induced putative kinase 1 (PINK1, marker of mitophagy), but 24 h incubation with palmitate reduced expression of mitochondrial fusion‐ (mitofusin‐2, Mfn2), fission‐ (DRP1 and fission 1 protein, Fis1) and mitophagy‐ related proteins. To correct the mitochondrial imbalance on the initiation of lipotoxicity, we inhibited Drp1 to evaluate whether this action restores mitochondrial function. Knockdown of DRP1 resulted in decreased apoptosis in cells after palmitate treatment for 24 h. To further determine the functional effects of knockdown of DRP1 on palmitate stress in a short‐term or long‐term period (plamitate treatment for 1 h or 24 h), we measured cellular respiration using Seahorse analyzer. Treatment of H9c2 with plamitate for 1 h reduced the oxygen consumption rate and extracellular acidification rate during basal respiration, whereas inhibition of DRP1 maintained the mitochondrial functions. This result indicated that the energetic function was shifted to quiescence in palmitate‐treated cells whereas knockdown of DRP1 cell did not have this effect. Palmitate treatment resulted in a remarkable reduction ATP production while knockdown of DRP1 restored their reductions. Non‐mitochondrial oxygen consumption (e.g. ROS generation) was upregulated with palmitate treatment, but DPR1 suppression decreased ROS generation. However, there was lower basal respiration, ATP production and FCCP‐stimulated maximal respiration in both groups following 24 h‐palmitate treatment which indicated that DRP1 knockdown could not restore mitochondrial oxidative function. In conclusion, palmitate disrupted mitochondrial dynamic and induced cell death, whereas inhibition of mitochondrial fission (DRP1) at the onset of lipotoxicity maintained the mitochondrial function and cell survival; however, it did not restore mitochondrial function after prolonged palmitate stress, demonstrating its limitations.Support or Funding InformationMOST‐104‐2313‐B‐002‐038‐MY3This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

GASTROINTESTINAL MICROBIOTA AND OBESITY. APPROVING PROBIOTICS AS DRUGS FOR TREATMENT OF OBESITY

Once considered as a problem only in high income countries, overweight and obesity now rise in low- and middle-income countries, particularly in urban settings. This situation accelerates the development of different approaches to investigation of obesity, makes the medical community look for new approaches to investigation of the obesity. Human’s microbiome is an imprescriptible part of it. Nevertheless it’s energetic function wasn’t fully appraised. Microbiome takes part in shorty chain fatty acids metabolism. Bacterial cells provide over 70% of daily energy for enterocytes, it’s part in general metabolism takes over 10%. ScFA can change activity of adenosine monophosphate-dependent protein kinase, stimulate leptin synthesis. Microbiome regulates synthesis of glucagon-like peptide, which has contrinsular effect. Right composition of microbiome reduces non-specific inflammation, produces isomers of linoleic acid, which can cause reduction of inflammation too. This article appraises probiotics as drugs for treatment to obesity and eradication of some conditions that can arise during obesity (atherosclerosis, hypertension, depression).

Energy, exergy and techno-economic analysis for biobutanol production: a multi-objective optimization approach based on economic and environmental criteria

Currently, butanol obtained by fermentation is considered as potential biofuel. In this work, it has been simulated and optimized a process to produce acetone, butanol and ethanol by means of lignocellulosic material. To accomplish this task, initially, it was planned the raw material selection, followed by the simulation in MATLAB of simultaneous saccharification, fermentation and separation reactor (SFS) and finally, the stream coming from fermentation was purified. The separation stage was selected from three different options to purify that effluent. The entire process was evaluated under a robust optimization process considering environmental, economic and energetic objective functions by means of a hybrid stochastic method, differential evolution with tabu list. The obtained results showed that the best scheme to produce and purify butanol was the SFS-3C, which considers thermally coupled columns to purify acetone, butanol and ethanol. In general terms, it was obtained as result 0.138 $/kgbutanol, 0.132 points/kgbutanol and 66.8 regarding to the total annual cost, environmental impact and exergy efficiency, respectively.

RM1 Semiempirical Model: Chemistry, Pharmaceutical Research, Molecular Biology and Materials Science

In this review, we show improvements to the semiempirical quantum chemical method RM1 and present a wide range of its applications as reported by researchers of various areas, such as theoretical, organic, physical, analytical, and inorganic chemistry, as well as their interfaces with medicinal chemistry, biology, and materials science. Success of RM1 is seemingly due to its ability to predict structural, energetic, electronic and wave function dependent properties of the investigated systems, coupled with its low computational demand required to perform calculations when compared to ab initio and density functional methods. Moreover, RM1 is widely available in several computational chemistry softwares, such as MOPAC, GAMESS, Amber, Spartan, HyperChem, and AMPAC. This review describes various case studies that perhaps can be of interest to researchers who might need a more solid basis from which to expand the frontier of applicability of RM1 to even more complex problems on larger systems.