The biomarkers of fetal growth in intrauterine growth retardation and large for gestational age cases: from adipocytokines to a metabolomic all-in-one tool

Adipose tissue is no longer considered as inert; the literature describes the role it plays in the production of many substances, such as adiponectin, visfatin, ghrelin, S100B, apelin, TNF, IL-6 and leptin. These molecules have specific roles in humans and their potential as biomarkers useful for identifying alterations related to intrauterine growth retardation and large for gestational age neonates is emerging. Infants born in such conditions have undergone metabolic changes, such as fetal hypo- or hyperinsulinemia, which may lead to development of dysmetabolic syndrome and other chronic diseases in adulthood. In this review, these biomarkers are analyzed specifically and it is discussed how metabolomics may be an advantageous tool for detection, discrimination and prediction of metabolic alterations and diseases. Thus, a holistic approach, such as metabolomics, could help the prevention and early diagnosis of metabolic syndrome.     

Tr-Noe and MD studies of Leishmania gp63 SRYD-containing sequences bound to anti-SRYD monoclonal antibody

The I²⁵⁰ASRYDQL²⁵⁷ synthetic octapeptideof the Leishmania major surface glycoproteingp63, which efficiently inhibits parasite attachmentto the macrophage receptors and mimics antigenicallyand functionally the RGDS sequence of fibronectin, wasstudied by 2D TR-NOESY in the presence of an anti-SRYDmonoclonal antibody (mAbSRYD) that recognizes bothSRYD-containing peptides and the cognate protein onintact parasites. Molecular modeling was performedusing distance constraints obtained from TR-NOEs. Thebound structure was compared with that of the freepeptide in DMSO solution and with the crystalstructure of the RYD fragment of the OPG2 Fab, anantireceptor antibody that mimics an RGD cell adhesion site.     

The PPGMRPP repetitive epitope of the Sm autoantigen: Antigenic specificity induced by conformational changes. Application of the Sequential Oligopeptide Carriers (SOCs)

The PPGMRPP sequence, found in several copies in the Sm and U1RNPautoantigens, is the main target of anti-Sm and anti-U1RNP antibodies insystemic lupus erythematosus (SLE) and mixed connective tissue disease(MCTD) patient's sera. It is also recognized, to a lower extent, byanti-Ro/SSA and anti-La/SSB specificities. The PPGMRPP-NH₂peptide amide and the PPGMRPP peptide, which is bound to a pentamericsequential oligopeptide carrier (SOC₅), were examined by¹H-NMR spectroscopy and ELISA assays, using sera from patientswith autoimmune rheumatic diseases. Among the three main conformers foundfor the free PPGMRPP, the extended one was also identified for PPGMRPP-NH₂ and (PPGMRPP)₅-SOC₅.This can be attributed to the absence of ionic interactions between theArg-guanidinium and the carboxylate group in the amide andSOC₅-bound forms of the peptide. Immunoassays using sera fromvarious specificities showed an enhanced anti-Sm and anti-U1RNP recognitionof PPGMRPP-NH₂ and(PPGMRPP)₅-SOC₅, and lowering of the anti-Ro/SSAand anti-La/SSB reactivity. The presence of multiple conformers of freePPGMRPP may explain the unexpected cross-reactivity to the anti-Ro/Lapositive sera, while the prevalence of the extended conformation inPPGMRPP-NH₂ and (PPGMRPP)₅-SOC₅is mainly responsible for the enhanced recognition from the anti-Sm andanti-U1RNP autoantibodies. It is concluded that the antigenic specificity ofPPGMRPP-NH₂ and (PPGMRPP)₅-SOC₅ ismainly induced by conformational changes resulting from the conversion ofthe C-terminal carboxylate group to the amide form.     

Translocator Protein-Mediated Stabilization of Mitochondrial Architecture during Inflammation Stress in Colonic Cells

Chronic inflammation of the gastrointestinal tract increasing the risk of cancer has been described to be linked to the high expression of the mitochondrial translocator protein (18 kDa; TSPO). Accordingly, TSPO drug ligands have been shown to regulate cytokine production and to improve tissue reconstruction. We used HT-29 human colon carcinoma cells to evaluate the role of TSPO and its drug ligands in tumor necrosis factor (TNF)-induced inflammation. TNF-induced interleukin (IL)-8 expression, coupled to reactive oxygen species (ROS) production, was followed by TSPO overexpression. TNF also destabilized mitochondrial ultrastructure, inducing cell death by apoptosis. Treatment with the TSPO drug ligand PK 11195 maintained the mitochondrial ultrastructure, reducing IL-8 and ROS production and cell death. TSPO silencing and overexpression studies demonstrated that the presence of TSPO is essential to control IL-8 and ROS production, so as to maintain mitochondrial ultrastructure and to prevent cell death. Taken together, our data indicate that inflammation results in the disruption of mitochondrial complexes containing TSPO, leading to cell death and epithelia disruption. Significance: This work implicates TSPO in the maintenance of mitochondrial membrane integrity and in the control of mitochondrial ROS production, ultimately favoring tissue regeneration.     

Synthesis and Characterization of High‐Energy,High‐Power Spinel‐Layered Composite Cathode Materials for Lithium‐Ion Batteries

Spinel‐layered composites, where a high‐voltage spinel is incorporated in a layered lithium‐rich (Li‐rich) cathode material with a nominal composition x{0.6Li₂MnO₃ · 0.4[LiCo_0.333Mn_0.333Ni_0.333]O₂} · (1 – x) Li[Ni_0.5Mn_1.5]O₄ (x = 0, 0.3, 0.5, 0.7, 1) are synthesized via a hydroxide assisted coprecipitation route to generate high‐energy, high‐power cathode materials for Li‐ion batteries. X‐ray diffraction patterns and the cyclic voltammetry investigations confirm the presence of both the parent components in the composites. The electrochemical investigations performed within a wide potential window show an increased structural stability of the spinel component when incorporated into the composite environment. All the composite materials exhibit initial discharge capacities >200 mAh g^–1. The compositions with x = 0.5 and 0.7 show excellent cycling stability among the investigated materials. Moreover, the first cycle Coulombic efficiency achieve a dramatic improvement with the incorporation of the spinel component. More notably, the composite materials with increased spinel component exhibit superior rate capability compared with the parent Li‐rich material especially together with the highest capacity retention for x = 0.5 composition, making this as the optimal high‐energy high‐power material. The mechanisms involved in the symbiotic relationship of the spinel and layered Li‐rich components in the above composites are discussed.     

Loss of mitochondrial ATPase ATAD3A contributes to nonalcoholic fatty liver disease through accumulation of lipids and damaged mitochondria

Mitochondrial ATPase ATAD3A is essential for cholesterol transport, mitochondrial structure, and cell survival. However, the relationship between ATAD3A and nonalcoholic fatty liver disease (NAFLD) is largely unknown. In this study, we found that ATAD3A was upregulated in the progression of NAFLD in livers from rats with diet-induced nonalcoholic steatohepatitis and in human livers from patients diagnosed with NAFLD. We used CRISPR-Cas9 to delete ATAD3A in Huh7 human hepatocellular carcinoma cells and used RNAi to silence ATAD3A expression in human hepatocytes isolated from humanized liver-chimeric mice to assess the influence of ATAD3A deletion on liver cells with free cholesterol (FC) overload induced by treatment with cholesterol plus 58035, an inhibitor of acetyl-CoA acetyltransferase. Our results showed that ATAD3A KO exacerbated FC accumulation under FC overload in Huh7 cells and also that triglyceride levels were significantly increased in ATAD3A KO Huh7 cells following inhibition of lipolysis mediated by upregulation of lipid droplet-binding protein perilipin-2. Moreover, loss of ATAD3A upregulated autophagosome-associated light chain 3-II protein and p62 in Huh7 cells and fresh human hepatocytes through blockage of autophagosome degradation. Finally, we show the mitophagy mediator, PTEN-induced kinase 1, was downregulated in ATAD3A KO Huh7 cells, suggesting that ATAD3A KO inhibits mitophagy. These results also showed that loss of ATAD3A impaired mitochondrial basal respiration and ATP production in Huh7 cells under FC overload, accompanied by downregulation of mitochondrial ATP synthase. Taken together, we conclude that loss of ATAD3A promotes the progression of NAFLD through the accumulation of FC, triglyceride, and damaged mitochondria in hepatocytes.     

Effect of operational and design parameters on removal efficiency of pilot-scale FWS constructed wetlands and comparison with HSF systems

In order to investigate the effect of temperature, hydraulic residence time (HRT), vegetation type, substrate material and wetland shape on the performance of free-water surface (FWS) constructed wetlands treating wastewater, 5 pilot-scale units were constructed and operated continuously from December 2004 until March 2007 in parallel experiments. Four of the units (A, B, C, D) were rectangular in plan view with dimensions 3.40 m in length and 0.85 m in width, and contained substrate material at a thickness of 0.45 m. The fifth unit (E) had a trapezoidal plan view shape, with a width at the inlet of 1.15 m and at the outlet of 0.55 m, while the length and the thickness of the substrate were the same as in the other four. All units operated at a water depth of 0.10 m. Units B–E contained clay substrate and unit A contained sand. The four units with clay were planted as follows: two with cattails (B and E), one with common reeds (C), and one with giant reeds (D). Unit A, containing sand, was planted with cattails. Planting and substrate material combinations were appropriate for comparison of the effect of vegetation and material type on the function of the system. Synthetic wastewater was introduced in the units. During the operation period four HRTs (i.e., 6 days, 8 days, 14 days and 20 days) were used, while wastewater temperatures varied from about 0.0 °C to 29.1 °C. The removal performance of the five constructed wetland units was good, since it reached on the average 77.5%, 67.9%, 60.4%, 53.9%, 56.0% and 51.7% for BOD, COD, TKN, ammonia (NH₄-N), ortho-phosphate (PO₄-P) and total phosphorus (TP), respectively. BOD and phosphorus removal efficiencies showed dependence on temperature in most units. The 14-day HRT was found adequate for acceptable removal of organic matter, nitrogen and phosphorus for most temperatures. A 20-day HRT is recommended for acceptable removal of BOD and PO₄-P in the cold season. The unit with the trapezoidal plan view shape showed the best performance, with mean removals of 80.1%, 73.5%, 70.4%, 68.6%, 64.7% and 63.5% for BOD, COD, TKN, NH₄-N, PO₄-P and TP, respectively. The cattail was found statistically more efficient than the other two plants in COD and PO₄-P removal. The unit that contained the clay substrate was found statistically more efficient in phosphorus removal than the unit containing sand. HSF CW units were found more efficient than FWS units in removal of most pollutant.