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Autism Spectrum Disorder is a neurodevelopmental disorder characterized by impaired social and communication skills, repetitive behaviors, and/or restricted interests with a prevalence of as high as 1% of children. Autism spectrum has strongly associated with genetic factors and exhibits wide clinical and heterogeneous genetic architecture. Most genes associated with Autism are involved in neuronal and synaptic development. The neuroligin3, the sex-linked gene on the X chromosome, was the first gene to be associated with a monogenic form of Autism. Neuroligin3 is a postsynaptic cell adhesion protein involved in synapse transmission, brain formation, and neuronal development. In this review, we provide recent findings on different mutations in the Neuroligin3 gene linked to Autism spectrum disorder and their molecular pathway effect. We also give the behavioral, and synaptic alterations reported in the Neuroligin3 animal model of Autism and the potential therapeutic strategies targeting the biological processes and the main symptoms of autism spectrum disorder. In addition, we discuss the use of novel technologies like induced pluripotent stem cells from Autistic patients that have the potential to differentiate in human neurons and therefore have a variety of applications in therapy and biomedical studies to search specific biomarkers, and develop systems for screening chemical molecules in human cells to discover target therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The mechanistic target of rapamycin (mTOR) coordinates the growth and metabolism of eukaryotic cells with a central role in the regulation of many fundamental cellular processes. It is strongly connected to phosphatidylinositol 3-kinase (PI3K) and AKT signaling. Activation of the PI3K/AKT/mTOR pathway leads to a profound disruption in the control of cell growth and survival, which ultimately leads to competitive growth advantage, metastatic competence, angiogenesis and therapeutic resistance., Material and Methods: To explore the common competitive adenosine triphosphate (ATP) inhibitors PI3K/AKT and PI3K/mTOR, we built a 2D mTOR-SAR model that predicted the bioactivity of AKT and PI3K inhibitors towards mTOR. The interaction of the best inhibitors was evaluated by docking analysis and compared to that of the standard AZ8055 and XL388 inhibitors., Results: A mechanistic target of rapamycin-quantitative structure-activity relationship (mTOR-QSAR) model with a correlation coefficient (R 2 ) of 0.80813 and a root mean square error of 0.17756 was obtained, validated and evaluated by a cross-validation leave-one-out method. The best predicted AKT and PI3K inhibitor pIC50 activities were 9.36-9.95 and 9.23-9.87 respectively., Conclusions: After docking and several comparisons, the inhibitors with better predictions showed better affinity and interaction with mTOR compared to AZ8055 and XL388, so we have found that 2 AKT inhibitors and 9 mTOR inhibitors met the Lipinski and Veber criteria and could be future drugs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Termedia.)

Background: Sarcoidosis is a granulomatous disease that mostly affects the lungs. Advanced tissue injury caused by this disease can progress to pulmonary fibrosis with similar characteristics shared with idiopathic pulmonary fibrosis (IPF). The initial presentations of both sarcoidosis and IPF may be shared with other interstitial lung diseases (ILDs). Two populations of macrophages have been described in the alveolar space: small alveolar macrophages (AMs) and large alveolar macrophages. Despite their protective function, these cells may also play a role in the initiation and maintenance of inflammation leading to fibrosis., Objective: The aim of this study was the functional characterization of small and large AM subpopulations in sarcoidosis and IPF as a pathology with respectively mild and advanced tissue injury causing fibrosis, in comparison with non-fibrosis ILDs., Methods: Activation and adhesion surface markers as well as functions of small and large AMs isolated from bronchoalveolar lavage (BAL) were assessed by Flow Cytometry within patients with confirmed sarcoidosis (n= 14), IPF (n= 6), and non-fibrosis ILDs (n= 9)., Results: Our results showed that small AMs are immunologically more active, which may be important for airway inflammation. They are also proportionally more abundant in IPF, and therefore they may be more involved in a fibrosis process associated with the down-regulation of HLA-DR, LeuCAM, and CD62L expression. In Sarcoidosis, the inflammatory process appears to be associated with up-regulation of CD38 expression and oxidative burst activity., Conclusion: A relevant potential of the activation and adhesion markers as well as oxidative burst activity expressed on small and large AMs, in the perspective of differential diagnosis of sarcoidosis and IPF.

Deserts represent extreme environments for microorganisms, and conditions such as high soil salinity, nutrient deficiency, and increased levels of UV radiation make desert soil communities of high biotechnological potential. In this study, we isolated, sequenced, and assembled the genomes of Bacillus safensis strains BcP62 and Bcs93, to which we performed comparative genome analyses. Using the DDH and ANI of both strains with the available B. safensis genomes, we identified three potential subspecies within this group. Intra-species core genome phylogenetic analysis did not result in clustering genomes by niche type, with some exceptions. This study also revealed that the genomes of the analyzed strains possessed plant growth-promoting characteristics, most of which were conserved in all B. safensis strains. Furthermore, we highlight the genetic features of B. safensis BcP62 and Bcs93 related to survival in the Merzouga desert in Morocco. These strains could be potentially used in agriculture as PGPB in extreme environments, given their high tolerability to unfavorable conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Since the COVID-19 pandemic began in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved with many variants of concern emerging across the world., Methodology: In order to monitor the evolution of these variants in Morocco, we analyzed a total of 2130 genomes of the delta variant circulating around the world. We also included 164 Moroccan delta variant sequences in our analysis., Results: Our findings suggest at least four introductions from multiple international sources and a rise of a dominant delta sub-lineage AY.33 in Morocco. Moreover, we report three mutations in the N-terminal domain of the S protein specific to the Moroccan AY.33 isolates, T29A, T250I and T299I. The effect of these mutations on the secondary structure and the dynamic behavior of the S protein N-terminal domain was further determined., Conclusions: We conclude that these mutations might have functional consequences on the S protein of SARS-CoV-2., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Safae El Mazouri, Houda Bendani, Nasma Boumajdi, Tarik Aanniz, Ilham Kandoussi, Saaid Amzazi, Lahcen Belyamani, Azeddine Ibrahimi, Mouna Ouadghiri.)

The leukotoxin (LtxA) of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is a protein exotoxin belonging to the repeat-in-toxin family (RTX). Numerous studies have demonstrated that LtxA may play a critical role in the pathogenicity of A. actinomycetemcomitans since hyper-leukotoxic strains have been associated with severe disease. Accordingly, considerable effort has been made to elucidate the mechanisms by which LtxA interacts with host cells and induce their death. However, these attempts have been hampered by the unavailability of a tertiary structure of the toxin, which limits the understanding of its molecular properties and mechanisms. In this paper, we used homology and template free modeling algorithms to build the complete tertiary model of LtxA at atomic level in its calcium-bound Holo-state. The resulting model was refined by energy minimization, validated by Molprobity and ProSA tools, and subsequently subjected to a cumulative 600ns of all-atom classical molecular dynamics simulation to evaluate its structural aspects. The druggability of the proposed model was assessed using Fpocket and FTMap tools, resulting in the identification of four putative cavities and fifteen binding hotspots that could be targeted by rational drug design tools to find new ligands to inhibit LtxA activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the elevated intake of fat induces lipid buildup, is a multifunctional scavenger receptor signaling those functions in high-affinity tissue uptake of long-chain fatty acids. In this study, we used series of molecular dynamics simulations of the wild type and mutants types K164A CD36 protein interacting with one palmitic acid (PLM) besides simulations of the wild type interacting with the three PLM to find out the mechanism of the functioning of the complex CD36/Fatty acids and the unraveling of the role of the mutation. Additionally we determined whether Lys164, mostly exposed to protein surface, played important roles in fatty acid uptake. These simulations revealed, the conformational changes induced by Lys164 residue and the altered interactions induced by the mutagenesis of surface lysine that was badly influencing the folding, utility, solubility, and stability form of the variant. Furthermore, Lys164 residue provided the structural basis of forming an opening at the region of principal portal for the dissociation of palmitic acid. The results of our simulations revealed hole two fatty acids found in CD36 cavity structure and it was the most preferred to CD36 structure stabilization., (© 2021. The Author(s).)

Background: In order to improve the taste acceptability of certain nutritional oils, it has been decided in this study to introduce them in an emulsion whose surfactant is casein, then to carry out a lacto-fermentation, leading to a dairy-like product with added nutritional value and health benefit. In this context, a plan of mixtures has been proposed for the preparation of emulsions based on argan oil, sodium caseinate and starch, with concentrations ranged between (10-20%) and (0-2%) and (0-1.5%) respectively. All emulsions were homogenized at two high stirring velocities (10,000-20,000 rpm) and two stirring times (5-20 min). The physical stability was assessed by visual analysis and microstructural measurements. The Creaming index was calculated for selected emulsions to predict their creaming behavior., Results: All emulsions showed a creaming behavior except one emulsion that required the highest values of all factors, which showed the highest creaming index with an average particle size of 11.27 μm. The absence or the variation of one or all factors led to various degrees of instabilities verified in all other emulsions. Due to the synergistic action of all parameters, the emulsion stability was attributed to the reduction of droplets size, the increase of continuous phase viscosity and the decrease of coalescence., Conclusion: The parameters that played a major role in the stability of the emulsion consists of: stirring velocity and time, sodium caseinate/oil ratio and starch/sodium caseinate ratio. The underlying structure and the interaction of the fluid droplets within the solid like product is what holds the stability of the product against settling or separation during fermentation., (© 2021. The Author(s).)

The coronavirus disease 19 (COVID-19) is a highly contagious and rapidly spreading infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In some cases, the disease can be fatal which resulted in more than one million deaths worldwide according the WHO. Currently, there is no effective vaccine or treatment for COVID-19, however many small-molecule inhibitors have shown potent antiviral activity against SARS-CoV-2 and some of them are now under clinical trials. Despite their promising activities, the development of these small molecules for the clinical use can be limited by many factors like the off-target effect, the poor stability, and the low bioavailability. The clusters of differentiation CD147, CD209, CD299 have been identified as essential entry co-receptors for SARS-CoV-2 species specificity to humans, although the underlying mechanisms are yet to be fully elucidated. In this paper, protein-protein docking was utilized for identifying the critical epitopes in CD147, CD209 and CD299 which are involved in the binding with SARS-CoV-2 Spike receptor binding domain (RBD). The results of binding free energies showed a high affinity of SARS-CoV-2 RBD to CD299 receptor which was used as a reference to derive hypothetical peptide sequences with specific binding activities to SARS-CoV-2 RBD. Molecular docking and molecular dynamics simulations of the newly designed peptides showed favorable binding features and stability with SARS-CoV-2 RBD and therefore can be further considered as potential candidates in future anti-SARS CoV-2 drug discovery studies., Competing Interests: The authors declare no conflict of interest., (© 2020 Published by Elsevier Ltd.)

SARS-CoV-2, which causes severe pneumonia epidemics, probably originated from Chinese horseshoe bats, but the intermediate and host range is still unknown. ACE2 is the entry receptor for SARS-CoV-2. The binding capacity of SARS-CoV-2 spike protein to ACE2 is the critical determinant of viral host range and cross-species infection. Here, we used an in silico approach to predict the potential animals range with high susceptibility to SARS-CoV-2 by modelling and studying the Spike-ACE2 interaction of 22 domestic and wild animals. Our results showed that all studied animals are potentially susceptible to SARS-CoV-2 infection with a slight difference in the binding affinity and stability of their ACE2-RBD complexes. Furthermore, we identified a specific substitution of tyrosine to histidine at position 41 in ACE2 that likely reduces the affinity to SARS-CoV-2 in horses and greater horseshoe bats. These results may help to provide important insights into SARS-CoV-2 host range which will make it possible to control the spread of the virus and identify animal models that could be used for screening antiviral drugs or vaccine candidates against SARS-CoV-2., Competing Interests: Conflict of interestThe authors declare that they have no competing interests., (© King Abdulaziz City for Science and Technology 2020.)

Background: Large-scale human sequencing projects have described around a hundred-million single nucleotide variants (SNVs). These studies have predominately involved individuals with European ancestry despite the fact that genetic diversity is expected to be highest in Africa where Homo sapiens evolved and has maintained a large population for the longest time. The African Genome Variation Project examined several African populations but these were all located south of the Sahara. Morocco is on the northwest coast of Africa and mostly lies north of the Sahara, which makes it very attractive for studying genetic diversity. The ancestry of present-day Moroccans is unknown and may be substantially different from Africans found South of the Sahara desert, Recent genomic data of Taforalt individuals in Eastern Morocco revealed 15,000-year-old modern humans and suggested that North African individuals may be genetically distinct from previously studied African populations., Results: We present SNVs discovered by whole genome sequencing (WGS) of three Moroccans. From a total of 5.9 million SNVs detected, over 200,000 were not identified by 1000G and were not in the extensive gnomAD database. We summarise the SNVs by genomic position, type of sequence gene context and effect on proteins encoded by the sequence. Analysis of the overall genomic information of the Moroccan individuals to individuals from 1000G supports the Moroccan population being distinct from both sub-Saharan African and European populations., Conclusions: We conclude that Moroccan samples are genetically distinct and lie in the middle of the previously observed cline between populations of European and African ancestry. WGS of Moroccan individuals can identify a large number of novel SNVs and aid in functional characterisation of the genome.

The new SARS-CoV-2 coronavirus is the causative agent of the COVID-19 pandemic outbreak that affected more than 190 countries worldwide with more than 292,000 confirmed cases and over 12,700 deaths. There is at the moment no vaccine or effective treatment for this disease which constitutes a serious global health problem. It is of interest to use a structure based virtual screening approach for the identification of potential inhibitors of the main protease of SARS-CoV-2 (M pro ) from antiviral drugs used to treat other viral disease such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. The crystallographic structure with PDB ID: 6LU7 of M pro in complex with the inhibitor N3 was used as a model in the virtual screening of 33 protease inhibitors collected from the ChEMBL chemical database. Molecular docking analysis was performed using the standard AutoDock vina protocol followed by ranking and selection of compounds based on their binding affinity. We report 10 candidates with optimal binding features to the active site of the protease for further consideration as potential drugs to treat patients infected with the emerging COVID-19 disease., (© 2020 Biomedical Informatics.)

The phosphoinositide 3-kinase (PI3K) pathway is an important regulator of cell proliferation and metabolism. PI3K activation initiates a signal transduction cascade, of which the major effectors are the kinases AKT and mTOR. Aberrant activation of the PI3K/AKT/mTOR pathway is frequently observed in many human malignancies and the combination of compounds simultaneously targeting different related molecules in the PI3K/AKT/mTOR pathway leads to synergistic activity. To explore the competing common ATP inhibitors PI3K/AKT and PI3K/mTOR we developed a model PI3K-SAR 2D which made it possible to predict the bioactivity of inhibitors of AKT and mTOR towards PI3K; the interaction of the best inhibitors was evaluated by docking analysis and compared to that of dactolisib and pictilisib. A PI3K-SAR model with a correlation coefficient (R2) of 0.81706 and an RMSE of 0.16029 was obtained, which was validated and evaluated by a cross-validation method, LOO. The most predicted AKT and mTOR inhibitors present respectively pIC50 activities between 9.26-9.93 and 9.59-9.87. After docking and several comparisons, inhibitors with better predictions showed better affinity and interaction with PI3K compared to pictilisib and dactolisib, so we found that 4 inhibitors of AKT and 14 mTOR inhibitors met the criteria of Lipinski and Veber and could be future drugs., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia Sp. z o. o.)

Background: The textural characteristics of fermented dairy products are important quality parameters that play a major role in their stability and consumer's acceptance. The aim of this study was to investigate the influence of sodium caseinate, starch, lactose and lactic acid bacteria as ferment on the syneresis in a mixed model system, and to evaluate their impact on the acid gel formation throughout pH and zeta potential monitoring. Accordingly, a protocol was designed to perform an experimental design by using a mixture of the selected factors., Results: A significant decrease of syneresis was detected in all mixtures at 8% of sodium caseinate, ranging between a minimum of 1.8% and a maximum of 20.6% compared to the mixtures at 3% of sodium caseinate in which the syneresis decrease had ranged between a minimum of 22.2% and a maximum of 47.8%. The addition of starch had a significant impact on the acidification profile and on the syneresis of the fermented mixed model. Moreover, the monitoring of pH and zeta potential during the lacto-fermentation process has also led to a better understanding of the acid gelation and the syneresis variations., Conclusion: Syneresis varies very closely with sodium caseinate concentration, starch concentration and also with their association, regardless of the concentrations of lactose and ferment. In fact syneresis could be reduced to an optimum level if a sodium caseinate-starch mixed system is employed: Less syneresis gels could be obtained at a sodium caseinate concentration above 5% if starch is used above 1%.

The Concept of reusing existing drugs for new targets is gaining momentum in recent years because of cost-effectiveness as safety and toxicology data are already available. Therefore, it is of interest to re-profile known drugs against the Pim-1 kinase target using molecular docking analysis. Results show that known drugs such as nilotinib, vemurafenib, Idelalisib, and other small kinases inhibitors have high binding ability with Pim-1 kinase for consideration as potential inhibitors.

The Proviral Integration site for Moloney murine leukemia virus (PIM) kinases is serine/threonine kinases that promote growth and survival in multiple cell types, implicated in the pathogenesis of various diseases. Over expression of Pim-1 experimentally leads to tumor formation in mice, whereas there is no observable phenotype concerning the complete knockout of the protein. When it is over expressed it may lead to cancer development by three major ways; by inhibiting apoptosis, by promoting cell proliferation and also through promoting genomic instability. Expression in normal tissues is nearly undetectable. Recent improvements in the development of novel inhibitors of PIMs have been reviewed. Significant progress in the design of PIMs inhibitors, in which it displays selectivity versus other kinases, has been achieved within the last years. However, the development of isoform-selective PIM inhibitors is still an open task. As Pim-1 possesses oncogenic functions and is over expressed in various kinds of cancer diseases, its inhibition provides a new option in cancer therapy. A PubMed literature search was performed to review the currently available data on Pim-1 expression, regulation, and targets; its implication in different types of cancer and its impact on prognosis is described. Consequently, designing new inhibitors of PIMs is now a very active area of research in academic and industrial laboratories.

Globally, congenital toxoplasmosis remains a significant cause of morbidity and mortality, and outbreaks of infection with T. gondii represent a significant, emerging public health burden, especially in the developing world. This parasite is a threat to public health. Disease often is not recognized and is inadequately managed. Herein, we analyze the status of congenital toxoplasmosis in Morocco, Colombia, the United States, and France. We identify the unique challenges faced by each nation in the implementation of optimal approaches to congenital toxoplasmosis as a public health problem. We suggest that developed and developing countries use a multipronged approach, modeling their public health management protocols after those in France. We conclude that education, screening, appropriate treatment, and the development of novel modalities will be required to intervene successfully in caring for individuals with this infection. Gestational screening has been demonstrated to be cost-effective, morbidity-sparing, and life-saving. Recognition of the value and promise of public health interventions to prevent human suffering from this emerging infection will facilitate better patient and societal outcomes.

The YAP oncogene is a known cancer target. Therefore, it is of interest to understand the molecular docking interaction of verteporfin (a derivative of benzo-porphyrin) with the WW domain of YAP (clinically used for photo-dynamic therapy in macular degeneration) as a potential WW domain-ligand modulator by inhibition. A homology protein SWISS MODEL of the human YAP protein was constructed to dock (using AutoDock vina) with the PubChem verteporfin structure for interaction analysis. The docking result shows the possibilities of verteporfin interaction with the oncogenic transcription cofactor YAP having WW1 and WW2 domains. Thus, the ability of verteporfin to bind with the YAP WW domain having modulator activity is implied in this analysis.

CD36 is a multifunctional membrane-type receptor glycoprotein that reacts with oxidized low-density lipoprotein and long-chain fatty acid (LCFA). However, much remains to be understood about the molecular mechanism of the cardio-myopathy observed in CD36-KO mice. In this study, we identify different genes pathways involved in response to CD36 cardio-myopathy phenotype by identifying the differences among biological processes, molecular pathways and networks of interactions that emerge from knocking CD3 and using different bioinformatics tools such as STRING, GeneMANIA and Cytoscape. We were able list all the CD36-regulated genes, their related function and their specific networks. Data analysis showed that CD36-regulated genes differentially expressed are involved in biological processes such as FA metabolism, angiogenesis/apoptosis and cell structure. These results provide the first look at mechanisms involved in CD36 deficiency and development of cardio-myopathy and the opportunity to identify new therapeutic targets.

The membrane protein CD36 is a member of the class B scavenger receptor family. It plays a crucial role in some cardiovascular pathologies and metabolic diseases. Studying the mechanism of action of CD36 receptor is limited due to the absence of its tridimensional crystallized structure. The molecular docking method has allowed us to perform various simulation of the CD36 receptor interaction with their ligands involved in the development of some diseases. In this work, we predicted a tridimensional structure model of CD36 extracellular domain. In addition, we have achieved several tests of rigid and flexible docking by acting on residues proposed in previous experimental researches as essential in fixing of LFCAs. Furthermore, we have acted on regions that appear a key binding site of LFCAs. The physicoc hemical evaluation indicated the reliability of the proposed CD36 structure used for different molecular docking tests. Based on the docking outcome, we were able to propose the different steps of the mechanism allowing the interaction of fatty acids on CD36 receptor and their penetration into the cell cytoplasm. The obtained results and taking in consideration CD36 receptor as a therapeutic target will help us to suggest the mechanism by which an antagonist may inhibit this receptor by acting on its extracellular domain.

The Δ(9-)Tetrahydrocannabinol (THCA) is the primary psychoactive compound of Cannabis Sativa. It is produced by Δ(1-) Tetrahydrocannabinolic acid synthase (THCA) which catalyzes the oxidative cyclization of cannabigerolic acid (CBGA) the precursor of the THCA. In this study, we were interested by the three dimensional structure of THCA synthase protein. Generation of models were done by MODELLER v9.11 and homology modeling with Δ1-tetrahydrocannabinolic acid (THCA) synthase X ray structure (PDB code 3VTE) on the basis of sequences retrieved from GenBank. Procheck, Errat, and Verify 3D tools were used to verify the reliability of the six 3D models obtained, the overall quality factor and the Prosa Z-score were also used to check the quality of the six modeled proteins. The RMSDs for C-alpha atoms, main-chain atoms, side-chain atoms and all atoms between the modeled structures and the corresponding template ranged between 0.290 Å-1.252 Å, reflecting the good quality of the obtained models. Our study of the CBGA-THCA synthase docking demonstrated that the active site pocket was successfully recognized using computational approach. The interaction energy of CBGA computed in 'fiber types' proteins ranged between -4.1 95 kcal/mol and -5.95 kcal/mol whereas in the 'drug type' was about -7.02 kcal/mol to -7.16 kcal/mol, which maybe indicate the important role played by the interaction energy of CBGA in the determination of the THCA level in Cannabis Sativa L. varieties. Finally, we have proposed an experimental design in order to explore the binding energy source of ligand-enzyme in Cannabis Sativa and the production level of the THCA in the absence of any information regarding the correlation between the enzyme affinity and THCA level production. This report opens the doors to more studies predicting the binding site pocket with accuracy from the perspective of the protein affinity and THCA level produced in Cannabis Sativa.

In response to the rapid development of DNA Microarray Technologies, many differentially expressed genes selection algorithms have been developed, and different comparison studies of these algorithms have been done. However, it is not clear how these methods compare with each other, especially when we used different developments tools. Here, we considered three commonly used differentially expressed genes selection approaches, namely: Fold Change, T-test and SAM, using Bioinformatics Matlab Toolbox and R/BioConductor. We used two datasets, issued from the affymetrix technology, to present results of used methods and software's in gene selection process. The results, in terms of sensitivity and specificity, indicate that the behavior of SAM is better compared to Fold Change and T-test using R/BioConductor. While, no practical differences were observed between the three gene selection methods when using Bioinformatics Matlab Toolbox. In face of our result, the ROC curve shows that: on the one hand R/BioConductor using SAM is favored for microarray selection compared to the other methods. And, on the other hand, results of the three studied gene selection methods using Bioinformatics Matlab Toolbox are still comparable for the two datasets used.

We have previously shown that CD36 is a membrane protein that facilitates long chain fatty acid (FA) transport by muscle tissues. We also documented the significant impact of muscle CD36 expression on heart function, skeletal muscle insulin sensitivity as well as on overall metabolism. To identify a comprehensive set of genes that are differentially regulated by CD36 expression in the heart, we used two microarray technologies (Affymetrix and Agilent) to compare gene expression in heart tissues from CD36 KnocK-Out (KO-CD36) versus wild type (WT-CD36) mice. The obtained results using the two technologies were similar with around 35 genes differentially expressed using both technologies. Absence of CD36 led to down-regulation of the expression of three groups of genes involved in pathways of FA metabolism, angiogenesis/apoptosis and structure. These data are consistent with the fact that the CD36 protein binds FA and thrombospondin 1 invoved respectively in lipid metabolism and anti-angiogenic activities. In conclusion, our findings led to validate our data analysis workflow and identify specific pathways, possibly underlying the phenotypic abnormalities in CD36 Knock -Out hearts.

Long-chain fatty acid uptake, which provides a large part of myocardial energy, is impaired in human and murine hearts deficient in the membrane fatty acid translocase, FAT/CD36. We examined myocardial function in CD36-null mice using the working heart. Fatty acid oxidation and stores of glycogen, triglycerides, and ATP were reduced in CD36-deficient hearts and were restored to WT levels by rescue of myocyte CD36. Under normal perfusion conditions, CD36-null hearts had similar cardiac outputs and end-diastolic pressures as WT or transgenic hearts. After 6 min of ischemia, cardiac output decreased by 41% and end diastolic pressure tripled for CD36-null hearts, with no significant changes in WT or transgenic hearts. Null hearts also failed more frequently after ischemia as compared with WT or transgenics. To dissect out contribution of fatty acid uptake, a perfusate-lacking fatty acids was used. This decreased cardiac output after ischemia by 30% in WT hearts as compared with 50% for CD36-deficient hearts. End diastolic pressure, a negative index of myocardial performance, increased after ischemia in all heart types. Addition to the perfusate of a medium-chain fatty acid (caprylic acid) that does not require CD36 for uptake alleviated poor ischemic tolerance of CD36-null hearts. In summary, recovery from ischemia is compromised in CD36-deficient hearts and can be restored by CD36 rescue or by supplying medium-chain fatty acids. It would be important to determine whether the findings apply to the human situation where polymorphisms of the CD36 gene are relatively common.