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Mixed reality (MR) technology has the potential to enhance building construction inspection and monitoring processes, improving efficiency, accuracy, and safety. This systematic review intends to investigate the present research status on MR in building construction inspection and monitoring. The review covers existing literature and practical case studies that scrutinize current technologies, their applications, challenges, and future trends in this rapidly evolving field. This article follows a methodology known as Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) to enhance the credibility and reliability of research. The study includes articles published between 2018 and 2023, identified through a comprehensive search of Scopus and Google Scholar databases. Findings indicate that MR technology has the potential to enhance visualization, communication, and collaboration between stakeholders, as well as increase efficiency and accuracy in inspection and monitoring tasks by providing real-time interactable data and quick decision-making among the project team members. The adoption of MR technology in the construction industry will not only boost its effectiveness but also improve its productivity. However, limitations such as high costs, technical issues, and user acceptance pose challenges to the widespread adoption of MR in building construction. Future research should address these limitations and investigate MR’s long-term impact on building construction inspection and monitoring.

Heritage Building Information Modeling (HBIM) is an essential technology for heritage documentation, conservation, and management. It enables people to understand, archive, advertise, and virtually reconstruct their built heritage. Creating highly accurate HBIM models requires the use of several reality capture tools, such as terrestrial laser scanning (TLS), photogrammetry, unmanned aerial vehicles (UAV), etc. However, the existing literature did not explicitly review the applications and impacts of TLS in implementing HBIM. This paper uses the PRISMA protocol to present a systematic review of TLS utilization in capturing reality data in order to recognize the status of applications of TLS for HBIM and identify the knowledge gaps on the topic. A thorough examination of the 58 selected articles revealed the state-of-the-art practices when utilizing static TLS technology for surveying and processing captured TLS data for developing HBIM models. Moreover, the absence of guidelines for using static TLS surveys for HBIM data acquisition, the lack of robust automated frameworks for producing/transferring 3D geometries and their attributes from TLS data to BIM entities, and the under-utilized application of TLS for long-term monitoring and change detection were identified as gaps in knowledge. The findings of this research provide stakeholders with a good grasp of static TLS for HBIM and therefore lay the foundation for further research, strategies, and scientific solutions for improving the utilization of TLS when documenting heritage structures and developing HBIM.

The value of Building Information Modelling (BIM) is widely discussed within all construction stages including the data-driven culture across building processes and sustainable impact in the long term. Yet, there is a need to explore the opportunities of BIM in improving construction materials management (CMM) as a core function of supply chain management. Due to the dearth of studies on BIM potential in improving CMM within the sustainability context, the authors examine the effectiveness and efficiency of BIM-enabled materials management, via three data streams: a literature review, an online survey, and interviews with subject matter experts in the field. This study aims to explore the drivers of BIM-enabled sustainable construction materials management. This is the preliminary study designed to test the initial hypotheses based on an online questionnaire application to derive tacit knowledge from industry and academic experts, followed by short interviews with respondents. Grounded in the comprehensive literature review, 24 indicators were defined for survey purposes. Preliminarily, 206 experts from 10 countries responded to the survey. The results show significant differences in the ranking of the indicators among the five factors. In developing countries, among two groups, industry sample awareness scales demonstrated lower understanding than among academic experts. Another finding relates to the significant agreement in scaling the importance of opportunities among industrial and academic sector experts. The research adds knowledge to deepen the understanding of opportunities of BIM-enabled materials management as a part of building project sustainable performance for industry policy and decision-makers. It also brings attention to the lack of sustainability awareness amongst industry experts in developing countries. Although materials constitute a solid part of any construction project cost, there is still a collaboration gap among designers, materials management, and, more broadly, supply chain management experts.

The implementation of Building Information Modeling (BIM) in the Architecture, Engineering and Construction (AEC) industry is growing rapidly. The Oil, Gas and Petrochemical industry (OGPi), however, is still lagging in harnessing the BIM capabilities. Therefore, the main question of this research is: How and what actions should be adopted for deploying BIM in the OGPi? The research is divided into three parts as an action research. This study investigates the second part, namely preparation of an adoption roadmap for deploying BIM in collaboration with Integrated Project Delivery (IPD) in the OGPi. To achieve this goal, an extensive literature review including the most established roadmaps in the AEC industry and also the semi-structured interviews with the OGPi's experts are conducted. Then, an adoption roadmap is derived for OGPi via Innovation Diffusion Theory (IDT), ‘Why, How, What’ questions (Sink model), strategic planning and innovation roadmap as well as the iterative process in the studies and interviews. The prepared roadmap validated by triangulation through focus group meetings and oils the wheels of BIM implementation alongside with IPD in the OGPi firms to grabs BIM merits and harness its challenges. Finally, the major limitations and the required future studies are addressed.

Cholesteryl ester (CE)-rich lipid droplets (LDs) accumulate in steroidogenic tissues under physiological conditions and constitute an important source of cholesterol as the precursor for the synthesis of all steroid hormones. The mechanisms specifically involved in CE-rich LD formation have not been directly studied and are assumed by most to occur in a fashion analogous to triacylglycerol-rich LDs. Seipin is an endoplasmic reticulum protein that forms oligomeric complexes at endoplasmic reticulum-LD contact sites, and seipin deficiency results in severe alterations in LD maturation and morphology as seen in Berardinelli-Seip congenital lipodystrophy type 2. While seipin is critical for triacylglycerol-rich LD formation, no studies have directly addressed whether seipin is important for CE-rich LD biogenesis. To address this issue, mice with deficient expression of seipin specifically in adrenal, testis, and ovary, steroidogenic tissues that accumulate CE-rich LDs under normal physiological conditions, were generated. We found that the steroidogenic-specific seipin-deficient mice displayed a marked reduction in LD and CE accumulation in the adrenals, demonstrating the pivotal role of seipin in CE-rich LD accumulation/formation. Moreover, the reduction in CE-rich LDs was associated with significant defects in adrenal and gonadal steroid hormone production that could not be completely reversed by addition of exogenous lipoprotein cholesterol. We conclude that seipin has a heretofore unappreciated role in intracellular cholesterol trafficking.

Concrete, a material that can be used as a building material and at the same time when mixed with light source, can enhance the beauty of a space as well as open new ways to experiment with it. The vision behind the research is to contribute with the manufacturers who are having “vision of cities that glow from within” through the use of concrete embedded with optic fiber strands. The aim of this research is to determine light transmitting properties of translucent concrete embedded with plastic fiber optics. In this experimental study, the amount of light is calculated that is able to transmit through the concrete. The four concrete blocks of equal size but different in amounts of plastic fiber optic strands are made. The research concluded that the fiber optics has the good light guiding properties which allow light to pass through the concrete in sufficient amount. The concrete with plastic fiber optics is named as translucent concrete, provides endless varieties of applications, not only aesthetically pleasing, but it can also promote safety, privacy and security as well as integrate the idea of saving green energy in the construction industry.

Abstract Coronavirus disease 2019 (COVID-19) is a highly infectious pandemic caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It frequently presents with unremitting fever, hypoxemic respiratory failure, and systemic complications (e.g., gastrointestinal, renal, cardiac, and hepatic involvement), encephalopathy, and thrombotic events. The respiratory symptoms are similar to those accompanying other genetically related beta-coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East Respiratory Syndrome CoV (MERS-CoV). Hypoxemic respiratory symptoms can rapidly progress to Acute Respiratory Distress Syndrome (ARDS) and secondary hemophagocytic lymphohistiocytosis, leading to multi-organ system dysfunction syndrome. Severe cases are typically associated with aberrant and excessive inflammatory responses. These include significant systemic upregulation of cytokines, chemokines, and pro-inflammatory mediators, associated with increased acute-phase proteins (APPs) production such as hyperferritinemia and elevated C-reactive protein (CRP), as well as lymphocytopenia. The neurological complications of SARS-CoV-2 infection are high among those with severe and critical illnesses. This review highlights the central nervous system (CNS) complications associated with COVID-19 attributed to primary CNS involvement due to rare direct neuroinvasion and more commonly secondary CNS sequelae due to exuberant systemic innate-mediated hyper-inflammation. It also provides a theoretical integration of clinical and experimental data to elucidate the pathogenesis of these disorders. Specifically, how systemic hyper-inflammation provoked by maladaptive innate immunity may impair neurovascular endothelial function, disrupt BBB, activate CNS innate immune signaling pathways, and induce para-infectious autoimmunity, potentially contributing to the CNS complications associated with SARS-CoV-2 infection. Direct viral infection of the brain parenchyma causing encephalitis, possibly with concurrent neurovascular endotheliitis and CNS renin angiotensin system (RAS) dysregulation, is also reviewed.

Adipocytes take up long chain FAs through diffusion and protein-mediated transport, whereas FA efflux is considered to occur by diffusion. To identify potential membrane proteins that are involved in regulating FA flux in adipocytes, the expression levels of 55 membrane transporters without known function were screened in subcutaneous adipose samples from obese patients before and after bariatric surgery using branched DNA methodology. Among the 33 solute carrier (SLC) transporter family members screened, the expression of 14 members showed significant changes before and after bariatric surgery. One of them, Slc43a3, increased about 2.5-fold after bariatric surgery. Further investigation demonstrated that Slc43a3 is highly expressed in murine adipose tissue and induced during adipocyte differentiation in primary preadipocytes and in OP9 cells. Knockdown of Slc43a3 with siRNA in differentiated OP9 adipocytes reduced both basal and forskolin-stimulated FA efflux, while also increasing FA uptake and lipid droplet accumulation. In contrast, overexpression of Slc43a3 decreased FA uptake in differentiated OP9 cells and resulted in decreased lipid droplet accumulation. Therefore, Slc43a3 seems to regulate FA flux in adipocytes, functioning as a positive regulator of FA efflux and as a negative regulator of FA uptake.

The latest industrial revolution 4 enabled significant performance improvement through technological advancements. Simultaneously, the industry is setting high-level expectations for changing business practices toward long-term benefits in all three sustainability dimensions. The concept of sustainability embraces all production and operation processes in the Architecture, Engineering, and Construction (AEC) industry. This study systematically explores the literature on sustainability with Enterprise Resource Planning (ERP) and Building Information Modelling (BIM) technologies in the AEC industry and the sustainability vision for their integration. The different types of ERP and BIM implementations have similarities in addressing the broad scope of functionalities. The emergence and proliferation of ERP and BIM have brought crucial changes to the business environment. Further evolution to cloud-based operations is transforming companies from technology-oriented practices to data-centric decision-making smart infrastructures. The narrative literature review investigates the sustainability insights and ideas in ERP and BIM solutions, presenting state of the art on systems integration topics. The relevant literature was retrieved to achieve the research objectives which were qualitatively analyzed to generate the basis for further research.

Abstract Background Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and reduces blood glucose in type 2 diabetes mellitus (T2DM). TCF7L2 rs7903146 polymorphism has been associated with decreased insulin secretion, reduced GLP-1 action, and possible impaired peripheral insulin sensitivity. Objectives To evaluate the postprandial pancreatic hormone response in patients with T2DM carriers of the TCF7L2 variant rs7903146 (CT/TT) compared with noncarriers of this variant (CC) after treatment with the GLP-1 agonist exenatide. Methods Intervention study. Patients with T2DM (n = 162) were genotyped for the TCF7L2 rs7903146 single nucleotide polymorphism (SNP). Individuals with CT/TT and CC genotypes were compared regarding basal serum levels of glucose, glycosylated hemoglobin A1C (HbA1c), HDL, uric acid, insulin, and C-peptide. A subset of 56 individuals was evaluated during a 500-calorie mixed-meal test with measurements of glucose, insulin, proinsulin, C-peptide and glucagon before and after treatment with exenatide for 8 weeks. Results Patients with genotypes CC and CT/TT presented similar glucose area under the curve (AUC) 0–180 min before treatment and a similar decrease after treatment (p

Cholesterol is required for maintenance of plasma membrane fluidity and integrity and for many cellular functions. Cellular cholesterol can be obtained from lipoproteins in a selective pathway of HDL-cholesteryl ester (CE) uptake without parallel apolipoprotein uptake. Scavenger receptor B type 1 (SR-B1) is a cell surface HDL receptor that mediates HDL-CE uptake. It is most abundantly expressed in liver, where it provides cholesterol for bile acid synthesis, and in steroidogenic tissues, where it delivers cholesterol needed for storage or steroidogenesis in rodents. SR-B1 transcription is regulated by trophic hormones in the adrenal gland, ovary, and testis; in the liver and elsewhere, SR-B1 is subject to posttranscriptional and posttranslational regulation. SR-B1 operates in several metabolic processes and contributes to pathogenesis of atherosclerosis, inflammation, hepatitis C virus infection, and other conditions. Here, we summarize characteristics of the selective uptake pathway and involvement of microvillar channels as facilitators of selective HDL-CE uptake. We also present the potential mechanisms of SR-B1-mediated selective cholesterol transport; the transcriptional, posttranscriptional, and posttranslational regulation of SR-B1; and the impact of gene variants on expression and function of human SR-B1. A better understanding of this unique pathway and SR-B1's role may yield improved therapies for a wide variety of conditions.

The use of building information modeling (BIM) for building sustainability assessment (BSA) is a thriving topic within the architecture, engineering, and construction industry. Despite the various research approaches to employing BSA with BIM support, the research is limited to the BIM implications of BSA methods in developing countries. This paper presents how BIM can assist the BSA processes in Kazakhstan, using a previously developed building sustainability assessment framework for Kazakhstan (KBSAF). This framework has 46 assessment indicators grouped into nine assessment categories. The categories and assessment indicators of KBSAF were derived considering the regional variations and country-specific differences in the assessment factors. In this paper, BIM functions for BSA were identified through literature review; their applicability for KBSAF was evaluated by mapping the functions with the assessment indicators of KBSAF and a BIM-based BSA framework (BIM-KBSAF) was proposed. The proposed framework was validated through a three-round Delphi survey. One of the results demonstrates that for KBSAF, BIM can assess 24 out of 46 assessment indicators. The proposed framework could serve as a systematic guide to the application of BIM for BSA. Furthermore, it can facilitate the BSA process and save considerable time and effort.

ACSL4 is a member of the long-chain acyl-CoA synthetase (ACSL) family with a marked preference for arachidonic acid (AA) as its substrate. Although an association between elevated levels of ACSL4 and hepatosteatosis has been reported, the function of ACSL4 in hepatic FA metabolism and the regulation of its functional expression in the liver remain poorly defined. Here we provide evidence that AA selectively downregulates ACSL4 protein expression in hepatic cells. AA treatment decreased the half-life of ACSL4 protein in HepG2 cells by approximately 4-fold (from 17.3 ± 1.8 h to 4.2 ± 0.4 h) without causing apoptosis. The inhibitory action of AA on ACSL4 protein stability could not be prevented by rosiglitazone or inhibitors that interfere with the cellular pathways involved in AA metabolism to biologically active compounds. In contrast, treatment of cells with inhibitors specific for the proteasomal degradation pathway largely prevented the AA-induced ACSL4 degradation. We further show that ACSL4 is intrinsically ubiquitinated and that AA treatment can enhance its ubiquitination. Collectively, our studies have identified a novel substrate-induced posttranslational regulatory mechanism by which AA downregulates ACSL4 protein expression in hepatic cells.

Fat-specific protein 27 (FSP27), a member of the cell death-inducing DNA fragmentation factor α-like effector (Cide) family, is highly expressed in adipose tissues and is a lipid droplet (LD)-associated protein that induces the accumulation of LDs. Using a yeast two-hybrid system to examine potential interactions of FSP27 with other proteins, a direct interaction with the N-terminal region of nuclear factor of activated T cells 5 (NFAT5) was identified. NFAT5 is a transcription factor that induces osmoprotective and inflammatory genes after its translocation to the nucleus. The interaction between FSP27 and NFAT5 was confirmed by bimolecular fluorescence complementation and coimmunoprecipitation. Using immunocytochemistry, NFAT5 is detected in the cytoplasm and in the nucleus under isotonic conditions; however, overexpression of FSP27 inhibited the hypertonic-induced nuclear translocation of NFAT5. Consistent with the suppression of NFAT5 nuclear translocation, in cells transfected with a reporter construct containing the NFAT5 response element from the monocyte chemoattractant protein 1 (MCP1) promoter, FSP27 overexpression repressed hypertonic-induced luciferase activity and the expression of NFAT5 target genes. Knockdown of FSP27 in differentiated 3T3-L1 adipocytes increased the NFAT5-mediated rise in MCP1. These results suggest that FSP27 not only modulates LD homeostasis but also modulates the response to osmotic stress via a physical interaction with NFAT5 at the LD surface.

Building Information Modeling (BIM), also called n-D Modeling or Virtual Prototyping Technology, is a revolutionary development that is quickly reshaping the Architecture-Engineering-Construction (AEC) industry. BIM is both a technology and a process. The technology component of BIM helps project stakeholders to visualize what is to be built in a simulated environment to identify any potential design, construction or operational issues. The process component enables close collaboration and encourages integration of the roles of all stakeholders on a project. The paper presents an overview of BIM with focus on its core concepts, applications in the project life cycle and benefits for project stakeholders with the help of case studies. The paper also elaborates risks and barriers to BIM implementation and future trends.

Here, we report the creation of a single-helix peptide (ATI-5261) that stimulates cellular cholesterol efflux with Km molar efficiency approximating native apolipoproteins. Anti-atherosclerosis activity of ATI-5261 was evaluated in LDLR−/− and apolipoprotein (apo)E−/− mice ∼5–7 months of age, following 13–18 weeks on a high-fat Western diet (HFWD). Treatment of fat-fed LDLR−/− mice with daily intraperitoneal injections of ATI-5261 (30 mg/kg) for 6 weeks reduced atherosclerosis by 30%, as judged by lesion area covering the aorta (7.9 ± 2 vs.11.3 ± 2.5% control, P = 0.011) and lipid-content of aortic sinus plaque (25 ± 5.8 vs. 33 ± 4.9% control, P = 0.014). In apoE−/− mice, the peptide administered 30 mg/kg ip on alternate days for 6 weeks reduced atherosclerosis by ∼45% (lesion area = 15 ± 7 vs. 25 ± 8% control, P = 0.00016; plaque lipid-content = 20 ± 6 vs. 32 ± 8% control, P < 0.0001). Similar reductions in atherosclerosis were achieved using ATI-5261:POPC complexes. Single intraperitoneal injection of ATI-5261 increased reverse cholesterol transport from macrophage foam-cells to feces over 24–48 h. In summary, relatively short-term treatment of mice with the potent cholesterol efflux peptide ATI-5261 reduced substantial atherosclerosis. This was achieved using an L-amino acid peptide, in the presence of severe hypercholesterolemia/HFWD, and did not require daily injections or formulation with phospholipids when administered via intraperitoneal injection.

Building Information Modeling (BIM), also called n-D Modeling or Virtual Prototyping Technology, is a revolutionary development that is quickly reshaping the Architecture-Engineering-Construction (AEC) industry. BIM is both a technology and a process. The technology component of BIM helps project stakeholders to visualize what is to be built in a simulated environment to identify any potential design, construction or operational issues. The process component enables close collaboration and encourages integration of the roles of all stakeholders on a project. The paper presents an overview of BIM with focus on its core concepts, applications in the project life cycle and benefits for project stakeholders with the help of case studies. The paper also elaborates risks and barriers to BIM implementation and future trends.

The Architecture, Engineering and Construction (AEC) industries have long sought techniques to decrease project cost, increase productivity and quality, enhance safety, and reduce project delivery time. Building Information Modeling (BIM) offers the potential to achieve these goals. BIM simulates the construction project in a virtual environment. With BIM technology, an accurate virtual model of a facility is digitally constructed. When completed, the computer-generated model contains precise geometry and relevant data needed to support the programming, fabrication, procurement, construction, and post-construction activities. It can be used by project stakeholders for planning and decision making throughout the project life cycle. BIM represents a new paradigm within AEC, one that encourages integration of the roles of all stakeholders on a project. It has the potential to promote greater efficiency and harmony among players who, in the past, saw themselves as adversaries.

Rat ovarian granulosa rely heavily on lipoprotein-derived cholesterol for steroidogenesis, which is principally supplied by the LDL receptor- and scavenger receptor class B type I (SR-BI)-mediated pathways. In this study, we characterized the hormonal and cholesterol regulation of another member of the LDL receptor superfamily, low density lipoprotein receptor-related protein (LRP), and its role in granulosa cell steroidogenesis. Coincubation of cultured granulosa cells with LDL and N6,O2′-dibutyryl adenosine 3′,5′-cyclic monophosphate (Bt2cAMP) greatly increased the mRNA/protein levels of LRP. Bt2cAMP and Bt2cAMP plus human (h)LDL also enhanced SR-BI mRNA levels. However, there was no change in the expression of receptor-associated protein, a chaperone for LRP, or another lipoprotein receptor, LRP8/apoER2, in response to Bt2cAMP plus hLDL, whereas the mRNA expression of LDL receptor was reduced significantly. The induced LRP was fully functional, mediating increased uptake of its ligand, α2-macroglobulin. The level of binding of another LRP ligand, chylomicron remnants, did not increase, although the extent of remnant degradation that could be attributed to the LRP doubled in cells with increased levels of LRP. The addition of lipoprotein-type LRP ligands such as chylomicron remnants and VLDL to the incubation medium significantly increased the progestin production under both basal and stimulated conditions. In summary, our studies demonstrate a role for LRP in lipoprotein-supported ovarian granulosa cell steroidogenesis.

The LDL receptor and the LDL receptor-related protein (LRP) mediate the removal of chylomicron remnants. The LRP pathway involves sequestration of particles in the space of Disse. It has been proposed that either alone or in combination with other factors, such as apolipoprotein E and proteoglycans, hepatic lipase (HL) may contribute to the sequestration of chylomicron remnants. To test this hypothesis, we generated two lines of transgenic mice producing rat HL as a native or as a membrane-anchored form. These animals express HL at levels similar to normal rat. Chylomicron remnants were perfused in a single nonrecirculating pass into the livers of the rat HL transgenic, HL-deficient, and wild-type (WT) mice for 20 min, and the rate of chylomicron remnant removal was measured. Chylomicron remnants were removed at a rate of ∼50% per pass in WT mice. It was slightly increased in both transgenic mice and reduced in HL-deficient mice compared with the WT mice. Confocal microscopy of liver sections showed that a modest amount of HL colocalized with chylomicron remnant clusters in the transgenic mice, suggesting that HL is a component of the LRP-proteoglycan clusters.These data suggest that HL helps to direct cholesterol to the tissues in which it is localized by a nonenzymatic mechanism.

This study has examined the dimeric/oligomeric forms of scavenger receptor class B type I (SR-BI) and its alternatively spliced form, SR-BII, in a diverse group of cells and tissues: i.e., normal and hormonally altered tissues of mice and rats as well as tissues of transgenic animals and genetically altered steroidogenic and nonsteroidogenic cells overexpressing the SR-B proteins. Using both biochemical and morphological techniques, we have seen that these dimeric and higher order oligomeric forms of SR-BI expression are strongly associated with both functional and morphological expression of the selective HDL cholesteryl ester uptake pathway. Rats and mice show some species differences in expression of SR-BII dimeric forms; this difference does not extend to the use of SR-B cDNA types for transfection purposes. In a separate study, cotransfection of HEK293 cells with cMyc and V5 epitope-tagged SR-BI permitted coprecipitation and quantitative coimmunocytochemical measurements at the electron microscope level, suggesting that much of the newly expressed SR-BI protein in stimulated cells dimerizes and that the SR-BI dimers are localized to the cell surface and specifically to microvillar or double membraned intracellular channels.These combined data suggest that SR-BI self-association represents an integral step in the selective cholesteryl ester uptake process.

Nordihydroguaiaretic acid (NDGA), the main metabolite of Creosote bush, has been shown to have profound effects on the core components of the metabolic syndrome (MetS), lowering blood glucose, free fatty acids (FFA) and triglyceride (TG) levels in several models of dyslipidemia, as well as improving body weight (obesity), insulin resistance, diabetes and hypertension, and ameliorating hepatic steatosis. In the present study, a high-fructose diet (HFrD) fed rat model of hypertriglyceridemia was employed to further delineate the underlying mechanism by which NDGA exerts its anti-hypertriglyceridemic action. In the HFrD treatment group, NDGA administration by oral gavage decreased plasma levels of TG, glucose, FFA, and insulin, increased hepatic mitochondrial fatty acid oxidation and attenuated hepatic TG accumulation. qRT-PCR measurements indicated that NDGA treatment increased the mRNA expression of key fatty acid transport (L-FABP, CD36), and fatty acid oxidation (ACOX1, CPT-2, and PPARα transcription factor) genes and decreased the gene expression of enzymes involved in lipogenesis (FASN, ACC1, SCD1, L-PK and ChREBP and SREBP-1c transcription factors). Western blot analysis indicated that NDGA administration upregulated hepatic insulin signaling (P-Akt), AMPK activity (P-AMPK), MLYCD, and PPARα protein levels, but decreased SCD1, ACC1 and ACC2 protein content and also inactivated ACC1 activity (increased P-ACC1). These findings suggest that NDGA ameliorates hypertriglyceridemia and hepatic steatosis primarily by interfering with lipogenesis and promoting increased channeling of fatty acids towards their oxidation.

This study examined the in vivo relationship between expression of the HDL receptor scavenger receptor class B (SR-BI) and corresponding structural changes in the rat adrenocortical cell microvillar compartment. Using hormonal stimulation and withdrawal protocols, we were able to manipulate adrenal SR-BI levels and carry out qualitative and quantitative measurements correlating SR-BI expression with microvillar mass and microvillar channel formation. Young male rats were used as controls or treated with adrenocorticotropin hormone (ACTH) (24 h), 17α-ethinyl estradiol (17α-E2) (5 days), or dexamethasone (DEX) (24 h). Quantitative Western blot analysis and immunocytochemistry indicated that ACTH and 17α-E2 treatment greatly increased SR-BI expression in the adrenal (especially in the microvillar compartment of adrenocortical cells), whereas DEX treatment led to a decrease of SR-BI by all measurements. At the same time, striking ultrastructural changes occurred in the adrenocortical cell microvillar compartment: e.g., microvillar area and microvillar channel formation and complexity dramatically increased (compared with control values) after ACTH or 17α-E2 treatment, whereas the same values declined after DEX treatment.These measurements illustrate the exceptional flexibility and responsiveness of the microvillar compartment to hormonal stimuli, and suggest that regulation of SR-BI expression and structural configuration of the surface of steroidogenic cells goes hand in hand.

Abstract: This study investigates the relationship between the high density lipoprotein (HDL) receptor (scavenger receptors, SR-BI and SR-BII), selective lipoprotein-cholesteryl ester uptake, and testosterone production in Leydig cells of control, hypocholesterolemic and gonadotrophic hormone (hCG) treated rats. Leydig cells from mature control rats show poor efficiency in incorporation of labeled HDL-cholesteryl esters into testosterone, poor selective uptake of lipoprotein lipids overall, and a dramatic reduction of circulating levels of lipoproteins has no apparent effect on testosterone production or expression of intracellular enzymes synthesizing cholesterol. Leydig cells from control rats show minimal levels of SR-BI and SR-BII. However, similarly aged rats treated with hCG for several days undergo changes consistent with hormone-desensitization. Despite the resulting low levels of testosterone production, SR-BI levels are dramatically increased, Leydig cells now efficiently internalize HDL-supplied cholesteryl esters by the selective cholesterol uptake process, and various other cholesterol-sensitive genes of the cells are up-regulated. Only SR-BII expression remains negligible and unchanged throughout this period. It is of interest that Leydig cell SR-BI of hCG-treated rats is localized in surface microvilli, but is present also in an elaborate and complex channel system within the cytoplasm of the cells. In summary, Leydig cells differ from other rat steroidogenic cells in not depending on exogenous lipoprotein-cholesterol during periods of normal steroid hormone production. However, trophic hormone desensitization is accompanied by increased Leydig cell SR-BI expression and increased selective HDL-cholesteryl ester uptake, presumably in preparation for renewed testosterone production. —Reaven, E., L. Zhan, A. Nomoto, S. Leers-Sucheta, and S. Azhar. Expression and microvillar localization of scavenger receptor class B, type I (SR-BI) and selective cholesteryl ester uptake in Leydig cells from rat testis. J. Lipid Res. 2000. 41: 343–356.

This study addresses the question of whether the level of expression of SR-BI (an HDL receptor) is linked to the expression of selective lipoprotein-cholesteryl ester delivery in a steroidogenic cell model. Rat ovarian granulosa cells are physiologically normal cells which show no selective uptake of HDL-cholesteryl esters and no progestin production until luteinized by trophic hormones or adenylate cyclase stimulators, after which expression of the selective cholesterol pathway and production of steroid hormone is dramatically up-regulated. The current study demonstrates that at every cell stage studied, the protein content and level of expression of SR-BI mRNA are linked to changes that occur in HDL-cholesteryl ester uptake; i.e., SR-BI is not present in basal (non-luteinized) cells, develops slowly (from 6–9 h) after hormone treatment, increases robustly from 9–48 h after stimulation, and remains high after incubation with HDL. In contrast, another structural protein, caveolin, did not follow this pattern; caveolin expression showed an inverse relationship to selective cholesteryl ester uptake, and was most prominent in basal cells and least prominent in luteinized, HDL-incubated cells. Morphologically, SR-BI appears to be associated with cell surface sites showing high levels of cholesteryl ester uptake (after luteinization and/or incubation with HDL labeled with fluorescent cholesteryl esters), and at the electron microscope level, SR-BI is most clearly associated with microvillar regions on the cell surface which also bind HDL-labeled with colloidal gold. Thus, induction of the SR-BI receptor system and induction of the HDL-selective cholesterol uptake pathway in rat granulosa cells appear to be linked morphologically, biochemically, and functionally.—Azhar, S., A. Nomoto, S. Leers-Sucheta, and E. Reaven. Simultaneous induction of an HDL receptor protein (SR-BI) and the selective uptake of HDL-cholesteryl esters in a physiologically relevant steroidogenic cell model.

Within cells, lipids are stored in the form of lipid droplets (LDs), consisting of a neutral lipid core, surrounded by a phospholipid monolayer and an outer layer of protein. LDs typically accumulate either triacylglycerol (TAG) and diacylglycerol or cholesteryl ester (CE), depending on the type of tissue. Recently, there has been an increased interest in the proteins that surround LDs. LD proteins have been found to be quite diverse, from structural proteins to metabolic enzymes, proteins involved in vesicular transport, and proteins that may play a role in LD formation. Previous proteomics analyses have focused on TAG-enriched LDs, whereas CE-enriched LDs have been largely ignored. Our study has compared the LD proteins from CE-enriched LDs to TAG-enriched LDs in steroidogenic cells. In primary rat granulosa cells loaded with either HDL to produce CE-enriched LDs or fatty acids to produce TAG-enriched LDs, 61 proteins were found to be elevated in CE-enriched LDs and 40 proteins elevated in TAG-enriched LDs with 278 proteins in similar amounts. Protein expression was further validated by selected reaction monitoring (SRM) mass spectrometry (MS). SRM verified expression of 25 of 27 peptides that were previously detected by tandem mass tagging MS. Several proteins were confirmed to be elevated in CE-enriched LDs by SRM including the intermediate filament vimentin. This study is the first to compare the proteins found on CE-enriched LDs with TAG-enriched LDs and constitutes the first step in creating a better understanding of the proteins found on CE-enriched LDs in steroidogenic cells.

This study aimed to characterize and compare the effects of obesity on gene expression profiles in two distinct adipose depots, epididymal and bone marrow, at two different ages in mice. Alterations in gene expression were analyzed in adipocytes isolated from diet-induced obese (DIO) C57BL/6J male mice at 6 and 14 months of age and from leptin deficient mice (ob/ob) at 6 months of age using microarrays. DIO affected gene expression in both depots at 6 and 14 months, but more genes were altered in epididymal than bone marrow adipocytes at each age and younger mice displayed more changes than older animals. In epididymal adipocytes a total of 2789 (9.6%) genes were differentially expressed at 6-months with DIO, whereas 952 (3.3%) were affected at 14-months. In bone marrow adipocytes, 347 (1.2%) genes were differentially expressed at 6-months with DIO, whereas only 189 (0.66%) were changed at 14-months. 133 genes were altered by DIO in both fat depots at 6-months, and 37 genes at 14-months. Only four genes were altered in both depots at both ages with DIO. Bone marrow adipocytes are less responsive to DIO than epididymal adipocytes and the response of both depots to DIO declines with age. This loss of responsiveness with age is likely due to age-associated changes in expression of genes related to adipogenesis, inflammation and mitochondrial function that are similar to and obscure the changes commonly associated with DIO. Patterns of gene expression were generally similar in epididymal adipocytes from ob/ob and DIO mice; however, several genes were differentially expressed in bone marrow adipocytes from ob/ob and DIO mice, perhaps reflecting the importance of leptin signaling for bone metabolism. In conclusion, obesity affects age-associated alterations in gene expression in both epididymal and bone marrow adipocytes regardless of diet or genetic background.

Given the emerging roles of miRNAs as potential posttranscriptional/posttranslational regulators of the steroidogenic process in adrenocortical and gonadal cells, we sought to determine miRNA profiles in rat adrenals from animals treated with vehicle, ACTH, 17α-E2 or dexamethasone. Key observations were also confirmed using hormone (Bt2cAMP)-treated mouse Leydig tumor cells, MLTC-1, and primary rat ovarian granulosa cells.RNA was extracted from rat adrenal glands and miRNA profiles were established using microarray and confirmed with qRT-PCR. The expression of some of the hormone-sensitive miRNAs was quantified in MLTC-1 and granulosa cells after stimulation with Bt2cAMP. Targets of hormonally altered miRNAs were explored by qRT-PCR and Western blotting in adrenals and granulosa cells.Adrenals from ACTH, 17α-E2 and dexamethasone treated rats exhibited miRNA profiles distinct from control animals. ACTH up-regulated the expression of miRNA-212, miRNA-182, miRNA-183, miRNA-132, and miRNA-96 and down-regulated the levels of miRNA-466b, miRNA-214, miRNA-503, and miRNA-27a. The levels of miR-212, miRNA-183, miRNA-182, miRNA-132, miRNA-370, miRNA-377, and miRNA-96 were up-regulated, whereas miR-125b, miRNA-200b, miR-122, miRNA-466b, miR-138, miRNA-214, miRNA-503 and miRNA27a were down-regulated in response to 17α-E2 treatment. Dexamethasone treatment decreased miRNA-200b, miR-122, miR-19a, miRNA-466b and miRNA27a levels, but increased miRNA-183 levels. Several adrenal miRNAs are subject to regulation by more than one hormone. Significant cAMP-induced changes in certain miRNAs were also noted in MLTC-1 and granulosa cells. Some of the hormone-induced miRNAs in steroidogenic cells were predicted to target proteins involved in lipid metabolism/steroidogenesis. We also obtained evidence that miR-132 and miRNA-214 inhibit the expression of SREBP-1c and LDLR, respectively.Our results demonstrate that expression of a number of miRNAs in steroidogenic cells of the testis, ovary and adrenal glands is subject to hormonal regulation and that miRNAs and their regulation by specific hormones are likely to play a key role in posttranscriptional/posttranslational regulation of steroidogenesis.

HCV infection is a major cause of chronic liver disease and liver cancer in the United States. To address the pathogenesis caused by HCV infection, recent studies have focused on the direct cytopathic effects of individual HCV proteins, with the objective of identifying their specific roles in the overall pathogenesis. However, this approach precludes examination of the possible interactions between different HCV proteins and organelles. To obtain a better understanding of the various cytopathic effects of and cellular responses to HCV proteins, we used human hepatoma cells constitutively replicating HCV RNA encoding either the full-length polyprotein or the non-structural proteins, or cells constitutively expressing the structural protein core, to model the state of persistent HCV infection and examined the combination of various HCV proteins in cellular pathogenesis. Increased reactive oxygen species (ROS) generation in the mitochondria, mitochondrial injury and degeneration, and increased lipid accumulation were common among all HCV protein-expressing cells regardless of whether they expressed the structural or non-structural proteins. Expression of the non-structural proteins also led to increased oxidative stress in the cytosol, membrane blebbing in the endoplasmic reticulum, and accumulation of autophagocytic vacuoles. Alterations of cellular redox state, on the other hand, significantly changed the level of autophagy, suggesting a direct link between oxidative stress and HCV-mediated activation of autophagy. With the wide-spread cytopathic effects, cells with the full-length HCV polyprotein showed a modest antioxidant response and exhibited a significant increase in population doubling time and a concomitant decrease in cyclin D1. In contrast, cells expressing the non-structural proteins were able to launch a vigorous antioxidant response with up-regulation of antioxidant enzymes. The population doubling time and cyclin D1 level were also comparable to that of control cells. Finally, the cytopathic effects of core protein appeared to focus on the mitochondria without remarkable disturbances in the cytosol.

CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL) but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36(-/-)) mice. Feeding CD36(-/-) mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36(-/-) mice and cholesterol uptake from HDL or LDL by isolated CD36(-/-) hepatocytes was unaltered. However, CD36(-/-) hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36(-/-) macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36(-/-) cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition.

The Architecture, Engineering and Construction (AEC) industries have long sought techniques to decrease project cost, increase productivity and quality, enhance safety, and reduce project delivery time. Building Information Modeling (BIM) offers the potential to achieve these goals. BIM simulates the construction project in a virtual environment. With BIM technology, an accurate virtual model of a facility is digitally constructed. When completed, the computer-generated model contains precise geometry and relevant data needed to support the programming, fabrication, procurement, construction, and post-construction activities. It can be used by project stakeholders for planning and decision making throughout the project life cycle. BIM represents a new paradigm within AEC, one that encourages integration of the roles of all stakeholders on a project. It has the potential to promote greater efficiency and harmony among players who, in the past, saw themselves as adversaries.