Molecular profiling of sepsis in mice using Fourier Transform Infrared Microspectroscopy

Sepsis is a life threatening condition resulting from a high burden of infection. It is a major health care problem and associated with inflammation, organ dysfunction and significant mortality. However, proper understanding and delineating the changes that occur during this complex condition remains a challenge. A comparative study involving intra-peritoneal injection of BALB/c mice with Salmonella Typhimurium (infection), lipopolysaccharide (endotoxic shock) or thioglycollate (sterile peritonitis) was performed. The changes in organs and sera were profiled using immunological assays and Fourier Transform Infrared (FTIR) micro-spectroscopy. There is a rapid rise in inflammatory cytokines accompanied with lowering of temperature, respiratory rate and glucose amounts in mice injected with S. Typhimurium or lipopolysaccharide. FTIR identifies distinct changes in liver and sera: decrease in glycogen and protein/lipid ratio and increase in DNA and cholesteryl esters. These changes were distinct from the pattern observed in mice treated with thioglycollate and the differences in the data obtained between the three models are discussed. The combination of FTIR spectroscopy and other biomarkers will be valuable in monitoring molecular changes during sepsis. GRAPHICS] Intra-peritoneal infection with high dose of Salmonella Typhimurium leads to rapid increase in inflammatory cytokines, e.g. Tnf alpha (A). FTIR analysis of liver (B) and sera (C) identifies several metabolic changes: glycogen, protein/lipid, cholesteryl esters and DNA.

Fuzzy State Real-Time Reservoir Operation Model for Irrigation with Gridded Rainfall Forecasts

A short-term real-time operation model with fuzzy state variables is developed for irrigation of multiple crops based on earlier work on long-term steady-state policy. The features of the model that distinguish it from the earlier work are (1) apart from inclusion of fuzziness in reservoir storage and in soil moisture of crops, spatial variations in rainfall and soil moisture of crops are included in the real-time operation model by considering gridded command area with a grid size of 0.5 degrees latitude by 0.5 degrees longitude; (2) the water allocation model and soil moisture balance equations are integrated with the real-time operation model with consideration of ponding water depth for Paddy crop; the model solution specifies reservoir releases for irrigation in a 10-day time period and allocations among the crops on a daily basis at each grid by maintaining soil moisture balance at the end of the day; and (3) the release policy is developed using forecasted daily rainfall data of each grid and is implemented for the current time period using actual 10-day inflow and actual daily rainfall of each grid. The real-time operation model is applied to Bhadra Reservoir in Karnataka, India. The results obtained using the real-time operation model are compared with those of the standard operating policy model. Inclusion of fuzziness in reservoir storage and soil moisture of crops captures hydrologic uncertainties in real time. Considerations of irrigation decisions on a daily basis and the gridded command area result in variations in allocating water to the crops, variations in actual crop evapotranspiration, and variations in soil moisture of the crops on a daily basis for each grid of the command area. (C) 2015 American Society of Civil Engineers.

Differential proteomic and genomic profiling of mouse striatal cell model of Huntington's disease and control; probable implications to the disease biology

Huntington's disease (HD) is an autosomal dominant disorder of central nervous system caused by expansion of CAG repeats in exon1 of the huntingtin gene (Htt). Among various dysfunctions originated from the mutation in Htt gene, transcriptional deregulation has been considered to be one of the most important abnormalities. Large numbers of investigations identified altered expressions of genes in brains of HD patients and many models of HD. In this study we employed 2D SDS-PAGE/MALDI-MS coupled with 2D-DIGE and real-time PCR experiments of an array of genes focused to HD pathway to determine altered protein and gene expressions in STHdh(Q111)/Hdh(Q111) cells, a cell model of HD and compared with STHdh(Q7)/Hdh(Q7) cells, its wild type counterpart. We annotated 76 proteins from these cells and observed differential expressions of 31 proteins (by 2D-DIGE) involved in processes like unfolded protein binding, negative regulation of neuron apoptosis, response to superoxides etc. Our PCR array experiments identified altered expressions of 47 genes. Altogether significant alteration of 77 genes/proteins could be identified in this HD cell line with potential relevance to HD biology. Biological significance: In this study we intended to find out differential proteomic and genomic profiles in HD condition. We used the STHdh cells, a cellular model for HD and control. These are mouse striatal neuronal cell lines harboring 7 and 111 knock -in CAG repeats in their two alleles. The 111Q containing cell line (STHdh(Q111)/Hdh(Q111)) mimics diseased condition, whereas the 7Q containing ones (STHdh(Q7)/Hdh(Q7)), serves as the proper control cell line. Proteomic experiments were performed earlier to obtain differential expressions of proteins in R6/2 mice models, Hdh(Q) knock -in mice and in plasma and CSF from HD patients. However, no earlier report on proteomic alterations in these two HD cell lines and control was available in literature. It was, therefore, an important objective to find out differential expressions of proteins in these two cell lines. In this study, we annotated 76 proteins from STHdh(Q7)/Hdh(Q7) and STHdh(Q111)/Hdh(Q111) cells using 2D-gel/mass spectrometry. Next, by performing 2D-DIGE, we observed differential expressions of 31 proteins (16 upregulated and 15 downregulated) between these two cell lines. We also performed customized qRT-PCR array focused to HD pathway and found differential expressions of 47 genes (8 gene exptessions increased and 39 genes were decreased significantly). A total of 77 genes/proteins (Htt downregulated in both the studies) were found to be significantly altered from both the experimental paradigms. We validated the differential expressions of Vim, Hypk, Ran, Dstn, Hspa5 and Sod2 either by qRT-PCR or Western blot analysis or both. Out of these 77, similar trends in alteration of 19 out of 31 and 38 out of 47 proteins/genes were reported in earlier studies. Thus our study confirmed earlier observations on differential gene/protein expressions in HD and are really useful. Additionally, we observed differential expression of some novel genes/proteins. One of this was Hypk, a Htt-interacting chaperone protein with the ability to solubilize mHtt aggregated structures in cell lines. We propose that downregulation of Hypk in STHdh-Qm (Q111)/Hdh(Q111) has a causal effect towards HD pathogenesis. Thus the novel findings from our study need further research and might be helpful to understand the molecular mechanism behind HD pathogenesis. (C) 2015 Elsevier B.V. All rights reserved.

Mechano-fluorochromic Pt-II Luminogen and Its Cysteine Recognition

A new triphenylamine-based organometallic Pt-II luminogen (1) and its analogous organic compound (2) are reported. The molecules are decorated with aldehyde functionality to improve their photophysical properties by utilising donor-acceptor interactions. The single crystal X-ray structure analysis of PtII analogue 1 revealed that the neighbouring molecules were loosely organised by weak intermolecular C-H center dot center dot center dot pi interactions. Because of the twisted nature of the triphenylamine backbone the compounds showed aggregation-induced emission enhancement in THF/water mixture. Due to their loose crystal packing, upon application of external stimuli these luminogens exhibited mechano-fluorochromic behaviour. The crystalline forms of the compounds displayed a more superior emission efficiency than the grinded samples. Moreover, the compounds showed crystallization-induced emission enhancement (CIEE) and exhibited chemodosimetric response towards cysteine under physiological condition.

Combined Effect of Cryogel Matrix and Temperature-Reversible Soluble-Insoluble Polymer for the Development of in Vitro Human Liver Tissue

Hepatic cell culture on a three-dimensional (3D) matrix or as a hepatosphere appears to be a promising in vitro biomimetic system for liver tissue engineering applications. In this study, we have combined the concept of a 3D scaffold and a spheroid culture to develop an in vitro model to engineer liver tissue for drug screening. We have evaluated the potential of poly(ethylene glycol)-alginate-gelatin (PAG) cryogel matrix for in vitro culture of human liver cell lines. The synthesized cryogel matrix has a flow rate of 7 mL/min and water uptake capacity of 94% that enables easy nutrient transportation in the in vitro cell culture. Youngs modulus of 2.4 kPa and viscoelastic property determine the soft and elastic nature of synthesized cryogel. Biocompatibility of PAG cryogel was evaluated through MTT assay of HepG2 and Huh-7 cells on matrices. The proliferation and functionality of the liver cells were enhanced by culturing hepatic cells as spheroids (hepatospheres) on the PAG cryogel using temperature-reversible soluble-insoluble polymer, poly(N-isopropylacrylamide) (PNIPAAm). Pore size of the cryogel above 100 mu m modulated spheroid size that can prevent hypoxia condition within the spheroid culture. Both the hepatic cells have shown a significant difference (P < 0.05) in terms of cell number and functionality when cultured with PNIPAAm. After 10 days of culture using 0.05% PNIPAAm, the cell number increased by 11- and 7-fold in case of HepG2 and Huh-7 cells, respectively. Similarly, after 10 days of hepatic spheroids culture on PAG cryogel, the albumin production, urea secretion, and CYP450 activity were significantly higher in case of culture with PNIPAAm. The developed tissue mass on the PAG cryogel in the presence of PNIPAAm possess polarity, which was confirmed using F-actin staining and by presence of intercellular bile canalicular lumen. The developed cryogel matrix supports liver cells proliferation and functionality and therefore can be used for in vitro and in vivo drug testing.

EXACT INTERNAL CONTROLLABILITY FOR THE WAVE EQUATION IN A DOMAIN WITH OSCILLATING BOUNDARY WITH NEUMANN BOUNDARY CONDITION

In this paper, we study the exact controllability of a second order linear evolution equation in a domain with highly oscillating boundary with homogeneous Neumann boundary condition on the oscillating part of boundary. Our aim is to obtain the exact controllability for the homogenized equation. The limit problem with Neumann condition on the oscillating boundary is different and hence we need to study the exact controllability of this new type of problem. In the process of homogenization, we also study the asymptotic analysis of evolution equation in two setups, namely solution by standard weak formulation and solution by transposition method.

Mechanism to synthesize a `moving optical mark' at solid-ambient interface for the estimation of thermal diffusivity of solid

supporting unsteady heat flow with its ambient-humidity; invokes phase transformation of water-vapour molecule and synthesize a `moving optical-mark' at sample-ambient-interface. Under tailored condition, optical-mark exhibits a characteristic macro-scale translatory motion governed by thermal diffusivity of solid. For various step-temperature inputs via cooling, position-dependent velocities of moving optical-mark are measured at a fixed distance. A new approach is proposed. `Product of velocity of optical-mark and distance' versus `non-dimensional velocity' is plotted. The slope reveals thermal diffusivity of solid at ambient-temperature; preliminary results obtained for Quartz-glass is closely matching with literature. (C) 2016 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

A glucose-centric perspective of hyperglycemia

Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (>200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and targets. Some are effective in slowing formation of glucose in intestines by inhibiting alpha-glucosidases (e.g., salacia/saptarangi). Knowledge gained from French lilac on active guanidine group helped developing Metformin (1,1-dimethylbiguanide) one of the popular drugs in use. One strategy of keeping sugar content in diets in check is to use artificial sweeteners with no calories, no glucose or fructose and no effect on blood glucose (e.g., steviol, erythrytol). However, the three commonly used non-caloric artificial sweetener's, saccharin, sucralose and aspartame later developed glucose intolerance, the very condition they are expected to evade. Ideal way of keeping blood glucose under 6 mM and HbAlc, the glycation marker of hemoglobin, under 7% in blood is to correct the defects in signals that allow glucose flow into glycogen, still a difficult task with drugs and diets.

Molecular Cage Impregnated Palladium Nanoparticles: Efficient, Additive-Free Heterogeneous Catalysts for Cyanation of Aryl Halides

Two shape-persistent covalent cages (CC1(r) and CC2(r)) have been devised from triphenyl amine-based trialdehydes and cyclohexane diamine building blocks utilizing the dynamic imine chemistry followed by imine bond reduction. The cage compounds have been characterized by several spectroscopic techniques which suggest that CC1(r) and CC2(r) are 2+3] and 8+12] self-assembled architectures, respectively. These state-of-the-art molecules have a porous interior and stable aromatic backbone with multiple palladium binding sites to engineer the controlled synthesis and stabilization of ultrafine palladium nanoparticles (PdNPs). As-synthesized cage-embedded PdNPs have been characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and powder X-ray diffraction (PXRD). Inductively coupled plasma optical emission spectrometry reveals that Pd@CC1(r) and Pd@CC2(r) have 40 and 25 wt% palladium loading, respectively. On the basis of TEM analysis, it has been estimated that as small as similar to 1.8 nm PdNPs could be stabilized inside the CC1(r), while larger CC2(r) could stabilize similar to 3.7 nm NPs. In contrast, reduction of palladium salts in the absence of the cages form structure less agglomerates. The well-dispersed cage-embedded NPs exhibit efficient catalytic performance in the cyanation of aryl halides under heterogeneous, additive-free condition. Moreover, these materials have excellent stability and recyclability without any agglomeration of PdNPs after several cycles.

Groups constrain the use of risky habitat by individuals: a new cost to sociality?

Predation risk can strongly constrain how individuals use time and space. Grouping is known to reduce an individual's time investment in costly antipredator behaviours. Whether grouping might similarly provide a spatial release from antipredator behaviour and allow individuals to use risky habitat more and, thus, improve their access to resources is poorly known. We used mosquito larvae, Aedes aegypti, to test the hypothesis that grouping facilitates the use of high-risk habitat. We provided two habitats, one darker, low-risk and one lighter, high-risk, and measured the relative time spent in the latter by solitary larvae versus larvae in small groups. We tested larvae reared under different resource levels, and thus presumed to vary in body condition, because condition is known to influence risk taking. We also varied the degree of contrast in habitat structure. We predicted that individuals in groups should use high-risk habitat more than solitary individuals allowing for influences of body condition and contrast in habitat structure. Grouping strongly influenced the time spent in the high-risk habitat, but, contrary to our expectation, individuals in groups spent less time in the high-risk habitat than solitary individuals. Furthermore, solitary individuals considerably increased the proportion of time spent in the high-risk habitat over time, whereas individuals in groups did not. Both solitary individuals and those in groups showed a small increase over time in their use of riskier locations within each habitat. The differences between solitary individuals and those in groups held across all resource and contrast conditions. Grouping may, thus, carry a poorly understood cost of constraining habitat use. This cost may arise because movement traits important for maintaining group cohesion (a result of strong selection on grouping) can act to exaggerate an individual preference for low-risk habitat. Further research is needed to examine the interplay between grouping, individual movement and habitat use traits in environments heterogeneous in risk and resources. (C) 2015 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Dynamical generation of flavour

We propose the generation of Standard Model fermion hierarchy by the extension of renormalizable SO(10) GUT with O(N (g) ) family gauge symmetry. In this scenario, Higgs representations of SO(10) also carry family indices and are called Yukawons. Vacuum expectation values of these Yukawon fields break GUT and family symmetry and generate MSSM Yukawa couplings dynamically. We have demonstrated this idea using Higgs irrep, ignoring the contribution of 1 2 0-plet which is, however, required for complete fitting of fermion mass-mixing data. The effective MSSM matter fermion couplings to the light Higgs pair are determined by the null eigenvectors of the MSSM-type Higgs doublet superfield mass matrix . A consistency condition on the doublet (1,2,+/- 1]) mass matrix ( 0) is required to keep one pair of Higgs doublets light in the effective MSSM. We show that the Yukawa structure generated by null eigenvectors of are of generic kind required by the MSSM. A hidden sector with a pair of (S (a b) ; I center dot (a b) ) fields breaks supersymmetry and facilitates 0. SUSY breaking is communicated via supergravity. In this scenario, matter fermion Yukawa couplings are reduced from 15 to just 3 parameters in MSGUT with three generations.

COMPLEX GEODESICS, THEIR BOUNDARY REGULARITY, AND A HARDY-LITTLEWOOD-TYPE LEMMA

We begin by giving an example of a smoothly bounded convex domain that has complex geodesics that do not extend continuously up to partial derivative D. This example suggests that continuity at the boundary of the complex geodesics of a convex domain Omega (sic) C-n, n >= 2, is affected by the extent to which partial derivative Omega curves or bends at each boundary point. We provide a sufficient condition to this effect (on C-1-smoothly bounded convex domains), which admits domains having boundary points at which the boundary is infinitely flat. Along the way, we establish a Hardy-Littlewood-type lemma that might be of independent interest.

Corona Degradation of the Polymer Insulator Samples under Different Fog Conditions

Corona discharges resulting from the metal parts of insulators and the line hardware affect the long term performance of the polymeric insulators used for outdoor application and can lead to its eventual failure. The authors previous work, involved in developing a new methodology to evaluate the performance of polymeric shed materials subjected to corona stresses in the presence of natural fog condition, results revealed more surface hydroxylation thereby resulting in more loss of hydropobhicity. With the increase in industrialization, there is an increase in acidic component of the rain as well as the fog (moisture). The present work, reports the effect of acid fog on the corona performance of the polymeric insulators for both AC and DC excitation, interesting results are obtained. A comparison of the experimental investigations revealed that the acidic fog has more effect than that of the normal fog. This fact has been confirmed by physico-chemical analysis like the scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), x-ray photoelectron spectroscopy (XPS) and contact angle measurement. The effect of DC corona is found to be lesser in comparison with the AC; however the hydroxylation induced by the DC corona under the presence of fog is similar with that of AC excitation.