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The leptin receptor (LepR) acts as a signaling nexus for the regulation of glucose uptake and obesity, among other metabolic responses. The functional role of LepR under leptin-deficient conditions remains unclear. This study reports that epiregulin (EREG) governed glucose uptake in vitro and in vivo in Lepob mice by activating LepR under leptin-deficient conditions. Single and long-term treatment with EREG effectively rescued glucose intolerance in comparative insulin and EREG tolerance tests in Lepob mice. The immunoprecipitation study revealed binding between EREG and LepR in adipose tissue of Lepob mice. EREG/LepR regulated glucose uptake without changes in obesity in Lepob mice via mechanisms, including ERK activation and translocation of GLUT4 to the cell surface. EREG-dependent glucose uptake was abolished in Leprdb mice which supports a key role of LepR in this process. In contrast, inhibition of the canonical epidermal growth factor receptor (EGFR) pathway implicated in other EREG responses, increased glucose uptake. Our data provide a basis for understanding glycemic responses of EREG that are dependent on LepR unlike functions mediated by EGFR, including leptin secretion, thermogenesis, pain, growth, and other responses. The computational analysis identified a conserved amino acid sequence, supporting an evolutionary role of EREG as an alternative LepR ligand. [ABSTRACT FROM AUTHOR]

Chloroplasts offer high-level transgene expression and transgene containment due to maternal inheritance, and are ideal hosts for biopharmaceutical biosynthesis via multigene engineering. To exploit these advantages, we have expressed 12 enzymes in chloroplasts for the biosynthesis of artemisinic acid (precursor of artemisinin, antimalarial drug) in an alternative plant system. Integration of transgenes into the tobacco chloroplast genome via homologous recombination was confirmed by molecular analysis, and biosynthesis of artemisinic acid in plant leaf tissues was detected with the help of C NMR and ESI-mass spectrometry. The excess metabolic flux of isopentenyl pyrophosphate generated by an engineered mevalonate pathway was diverted for the biosynthesis of artemisinic acid. However, expression of megatransgenes impacted the growth of the transplastomic plantlets. By combining two exogenous pathways, artemisinic acid was produced in transplastomic plants, which can be improved further using better metabolic engineering strategies for commercially viable yield of desirable isoprenoid products. [ABSTRACT FROM AUTHOR]

Diabetes poses a high risk for debilitating complications in neural tissues, regulating glucose uptake through insulin-dependent and predominantly insulin-independent pathways. Supramolecular nanostructures provide a flexible strategy for combinatorial regulation of glycemia. Here, we compare the effects of free insulin to insulin bound to positively charged nanofibers comprised of self-assembling amino acid compounds (AACs) with an antioxidant-modified side chain moiety (AAC2) in both in vitro and in vivo models of type 1 diabetes. Free AAC2, free human insulin (hINS) and AAC2-bound-human insulin (AAC2-hINS) were tested in streptozotocin (STZ)-induced mouse model of type 1 diabetes. AAC2-hINS acted as a complex and exhibited different properties compared to free AAC2 or hINS. Mice treated with the AAC2-hINS complex were devoid of hypoglycemic episodes, had improved levels of insulin in circulation and in the brain, and increased expression of neurotransmitter taurine transporter, Slc6a6. Consequently, treatment with AAC2-hINS markedly advanced both physical and cognitive performance in mice with STZ-induced and genetic type 1 diabetes compared to treatments with free AAC2 or hINS. This study demonstrates that the flexible nanofiber AAC2 can serve as a therapeutic platform for the combinatorial treatment of diabetes and its complications. [ABSTRACT FROM AUTHOR]

Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesentery are features of Crohn's disease. Here, we examined the genesis of these TLOs and their impact on disease progression. Whole-mount and intravital imaging of the ileum and ileum-draining collecting lymphatic vessels (CLVs) draining to mesenteric lymph nodes from TNFΔARE mice, a model of ileitis, revealed TLO formation at valves of CLVs. TLOs obstructed cellular and molecular outflow from the gut and were sites of lymph leakage and backflow. Tumor necrosis factor (TNF) neutralization begun at early stages of TLO formation restored lymph transport. However, robustly developed, chronic TLOs resisted regression and restoration of flow after TNF neutralization. TNF stimulation of cultured lymphatic endothelial cells reprogrammed responses to oscillatory shear stress, preventing the induction of valve-associated genes. Disrupted transport of immune cells, driven by loss of valve integrity and TLO formation, may contribute to the pathology of Crohn's disease. [Display omitted] • Ileitis involves the mesentery and drives tertiary lymphoid organ (TLO) formation • TLOs are connected to collecting lymphatic vessels and form at lymphatic valves • TLOs restrict intestinal lymphatic drainage and immune cell migration • TNF cytokine downregulates genes necessary for lymphatic valve maintenance Lymphangitis and the formation of mesenteric tertiary lymphoid organs (TLOs) are features of Crohn's disease. Czepielewski et al. find that the cytokine TNF drives loss of valve integrity and TLO formation, thereby disrupting lymphatic transport in a model of Crohn's-like ileitis. The resulting impairment of immune cell transport may contribute to the pathology of Crohn's disease. [ABSTRACT FROM AUTHOR]

Abstract: Steel pipelines used for oil and gas transportation are joined by girth welding and welds may contain weld imperfections/defects such as lack of fusion, under-cuts, porosity, slag inclusion etc. of certain height and length at certain location along the longitudinal direction of the weld. During the installation and operation, these pipelines are exposed to large plastic deformation. Fracture assessment procedures: BS7910:2005 [1] or R6 [2], are not suitable for such plastic strains (3%). The evolution of crack tip opening displacement (CTOD) of the pipeline with elliptical embedded crack in a girth weld is investigated under biaxial loading conditions using a three dimensional elastic–plastic finite element method. Based on the results, empirical formulas depicting relationship between the CTOD and the global strain are proposed. [Copyright &y& Elsevier]

Abstract: Offshore pipelines installed by reeling method are subjected to large plastic strains. When the steel pipes are joined by girth welding, both surface and embedded cracks are inevitably initiated in welding zone. The pipe lines should have adequate resistance against both crack extension by tearing and unstable fracture during installation as well as during operation. However, common flaw assessment procedures, e.g. BS 7910:2005 , are not explicitly developed for such situations with large plastic strains. The main objective of the current paper is to find a way to assess fracture capability of a practical pipeline subject to large plastic deformation. In our study, the evolution of crack tip opening displacement (CTOD) of the pipeline with semi-eliptical surface crack in weld girth is investigated under biaxial loading conditions (uniaxial tensile and internal pressure) using three dimensional elastic–plastic finite element analysis. The effects of crack depth, ratio of semi-major axis to semi-minor axis and internal pressure are examined. The results show that at moderate levels of global strain, the variation of CTOD with global strain can be well approximated by a simple linear relationship under tensile loading as well as biaxial loading conditions. Comparing the fracture assessment for the welded pipe made by BS 7910:2005 with that made by our current study, it is found that the assessment from BS7910:2005 is over conservative. A CTOD-estimation method for strain -based fracture is suggested for the pipelines when the global strain is 3%. [Copyright &y& Elsevier]

Background: Decubitus ulcers, also known as bedsores or pressure ulcers, affect millions of hospitalized patients each year. The microflora of chronic wounds such as ulcers most commonly exist in the biofilm phenotype and have been known to significantly impair normal healing trajectories. Methods: Bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP), a universal bacterial identification method, was used to identify bacterial populations in 49 decubitus ulcers. Diversity estimators were utilized and wound community compositions analyzed in relation to metadata such as Age, race, gender, and comorbidities. Results: Decubitus ulcers are shown to be polymicrobial in nature with no single bacterium exclusively colonizing the wounds. The microbial community among such ulcers is highly variable. While there are between 3 and 10 primary populations in each wound there can be hundreds of different species present many of which are in trace amounts. There is no clearly significant differences in the microbial ecology of decubitus ulcer in relation to metadata except when considering diabetes. The microbial populations and composition in the decubitus ulcers of diabetics may be significantly different from the communities in non-diabetics. Conclusions: Based upon the continued elucidation of chronic wound bioburdens as polymicrobial infections, it is recommended that, in addition to traditional biofilm-based wound care strategies, an antimicrobial/antibiofilm treatment program can be tailored to each patient's respective wound microflora. [ABSTRACT FROM AUTHOR]

Surface soil moisture has a wide application in climate change, agronomy, water resources, and in many other domain of science and engineering. Measurement of soil moisture at high spatial and temporal resolution at regional and global scale is needed for the prediction of flood, drought, planning and management of agricultural productivity to ensure food security. Recent advancement in microwave remote sensing, especially after the launch of Sentinel operational satellites has enabled the scientific community to estimate soil moisture at higher spatial and temporal resolution with greater accuracy. This study evaluates the potential of Sentinel-1A satellite images to estimate soil moisture in a semi-arid region. Exactly at the time when satellite passes over the study area, we have collected soil samples at 37 different locations and measured the soil moisture from 5 cm below the ground surface using ML3 theta probe. We processed the soil samples in laboratory to obtain volumetric soil moisture using the oven dry method. We found soil moisture measured from calibrated theta probe and oven dry method are in good agreement with Root Mean Square Error (RMSE) 0.025 m 3 /m 3 and coefficient of determination (R 2 ) 0.85. We then processed Sentinel-1A images and applied modified Dubois model to calculate relative permittivity of the soil from the backscatter values ( σ ∘ ). The volumetric soil moisture at each pixel is then calculated by applying the universal Topp's model. Finally, we masked the pixels whose Normalised Difference Vegetation Index (NDVI) value is greater than 0.4 to generate soil moisture map as per the Dubois NDVI criterion. Our modelled soil moisture accord with the measured values with RMSE = 0.035 and R 2 = 0.75. We found a small bias in the modelled soil moisture ( 0.02 m 3 / m 3 ). However, this has reduced significantly ( 0.001 m 3 / m 3 ) after applying a bias correction based on Cumulative Distribution Function (CDF) matching. Our approach provides a first-order estimate of soil moisture from Sentinel-1A images in sparsely vegetated agricultural land. [ABSTRACT FROM AUTHOR]

This study estimates the photovoltaic (PV) energy production from the rooftop solar plant of the National Institute of Technology Karnataka (NITK) and the impact of clouds and aerosols on the PV energy production based on earth observation (EO)-related techniques and solar resource modeling. The post-processed satellite remote sensing observations from the INSAT-3D have been used in combination with Copernicus Atmosphere Monitoring Service (CAMS) 1-day forecasts to perform the Indian Solar Irradiance Operational System (INSIOS) simulations. NITK experiences cloudy conditions for a major part of the year that attenuates the solar irradiance available for PV energy production and the aerosols cause performance issues in the PV installations and maintenance. The proposed methodology employs cloud optical thickness (COT) and aerosol optical depth (AOD) to perform the INSIOS simulations and quantify the impact of clouds and aerosols on solar energy potential, quarter-hourly monitoring, forecasting energy production and financial analysis. The irradiance forecast accuracy was evaluated for 15 min, monthly, and seasonal time horizons, and the correlation was found to be 0.82 with most of the percentage difference within 25% for clear-sky conditions. For cloudy conditions, 27% of cases were found to be within ±50% difference of the percentage difference between the INSIOS and silicon irradiance sensor (SIS) irradiance and it was 60% for clear-sky conditions. The proposed methodology is operationally ready and is able to support the rooftop PV energy production management by providing solar irradiance simulations and realistic energy production estimations. [ABSTRACT FROM AUTHOR]

• Montmorillonite interact differently with crude oils having different compositions. • Concentration and cation type of saline water is important for oil removal from montmorillonite. • Designing of LSW depends upon the ring size of PAH in asphaltenes of crude oil. • Designing of LSW is dependent on the interlayer cations present in montmorillonite. Detailed molecular level insights of the interaction between the reservoir rock-crude oil-brine are very crucial for designing effective injection water during low saline water flooding for optimum oil recovery. Present work is an attempt to study the interaction phenomenon that takes place between different reservoirs components considering clay, two dead crude oils (C1 and C2), and different concentrations of brine (2000–8000 ppm). The clay used in this study is montmorillonite with a stoichiometric composition (Na 0.63 Ca 0.26 K 0.1) (Al 2.66 Ti 0.44 Fe 0.60 Mg 0.61) (Si 6.538 Al 1.46) (OH) 4. Crude oil C1 is lighter having 3 wt% asphaltene dominating with 3–5 fused aromatic ring (FAR) structures while C2 is heavier than C1 containing 7.5 wt% asphaltenes with a significant presence of 5–7 FAR. Experimentation and detailed analysis of the dry (Mt) and oil-treated montmorillonite (MtC1, and MtC2) connote that the polar oil components particularly, asphaltenes are adsorbed onto the interlayer surfaces of montmorillonite. Spectroscopic results of oil treated Mt and saline water reveal that low saline water (2000 ppm) of Na+ and Ca++ ions are equally capable of removing 3–5 ring size FAR of polycyclic aromatic hydrocarbon (PAH) components from the montmorillonite interlayer surfaces. Thus, the present study attests to the fact that the type of cation present in their interlayer surface of montmorillonite, and the ring size of PAH in asphaltenes influence the interaction phenomenon where molecular level insights between oil treated montmorillonite and saline water are valuable for designing effective injection fluids for EOR. [ABSTRACT FROM AUTHOR]

Background: Many studies have been carried out on the growth-modulating efficiency of plants by the colonization of an endophytic fungus Piriformospora indica. However, studies involving the co-culture of alga with endophytic fungal strains for enhanced biodiesel production are rare. In this study, the interaction between P. indica and Parachlorella kessleri-I, a marine algal strain, was assessed at metabolic level. Results: In association with an endophytic fungus, the algal biomass enhanced from 471.6 to 704 mg/L, and the fatty acid methyl ester (FAME) profile of P. kessleri-I increased substantially. In case of FAME profile of co-cultured P. kessleri-I, two essential components of biodiesel, i.e. elaidic acid and oleic acid, increased by 1.4- and 1.8-fold, respectively. To ascertain changes in the metabolic profile of P. kessleri-I by P. indica co-culture, gas chromatography–mass spectrometry (GC–MS)-based untargeted metabolomics study was performed to identify the metabolites involved; and differential nature of the essential metabolites was also confirmed using HPLC and LC–MS. Significant modulation of the bioactive metabolites such as succinate, oxo-propanoate, l-alanine, glutamate, acetate and 1,2 propanediol, hydroxy butane was observed. Conclusion: The metabolites like glutamate and succinate that usually belong to the GABA shunt pathway were observed to be upregulated. The pathway links nitrogen metabolism and carbon metabolism, thus influencing the growth and lipid profile of the algae. These differential metabolites thus indicated the important commensal association between the endophytic fungus and autotrophic marine alga, and established that endophytic fungus can be handy for the sustainability of algal biofuel industries. [ABSTRACT FROM AUTHOR]