Postprandial apoE isoform and conformational changes associated with VLDL lipolysis products modulate monocyte inflammation.

ObjectivePostprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL) and circulating lipopolysaccharide (LPS), has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation.Methods and resultsWe showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4.ConclusionPostprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation

On the cavity method for decimated random constraint satisfaction problems and the analysis of belief propagation guided decimation algorithms

We introduce a version of the cavity method for diluted mean-field spin models that allows the computation of thermodynamic quantities similar to the Franz-Parisi quenched potential in sparse random graph models. This method is developed in the particular case of partially decimated random constraint satisfaction problems. This allows to develop a theoretical understanding of a class of algorithms for solving constraint satisfaction problems, in which elementary degrees of freedom are sequentially assigned according to the results of a message passing procedure (belief-propagation). We confront this theoretical analysis to the results of extensive numerical simulations.Comment: 32 pages, 24 figure

Transport Properties of Random Walks on Scale-Free/Regular-Lattice Hybrid Networks

We study numerically the mean access times for random walks on hybrid disordered structures formed by embedding scale-free networks into regular lattices, considering different transition rates for steps across lattice bonds ($F$) and across network shortcuts ($f$). For fast shortcuts ($f/F\gg 1$) and low shortcut densities, traversal time data collapse onto an universal curve, while a crossover behavior that can be related to the percolation threshold of the scale-free network component is identified at higher shortcut densities, in analogy to similar observations reported recently in Newman-Watts small-world networks. Furthermore, we observe that random walk traversal times are larger for networks with a higher degree of inhomogeneity in their shortcut distribution, and we discuss access time distributions as functions of the initial and final node degrees. These findings are relevant, in particular, when considering the optimization of existing information networks by the addition of a small number of fast shortcut connections.Comment: 8 pages, 6 figures; expanded discussions, added figures and references. To appear in J Stat Phy

Distance, transport mode, and road safety on school journeys in urban India

Background: A third of a billion children travel to school every day in India, yet little is known about this journey. Increasing motorisation in India is likely to have implications for road safety of children. This thesis develops methods to measure distance to school, transport modes, and risk of road traffic injury, on journeys to school in Hyderabad. Methods: Following a systematic review, a self-completion questionnaire was developed to estimate the distance and modes of travel to school in India. Its validity and reliability was assessed using the kappa statistic. A cross-sectional survey using a two-stage stratified cluster sampling design was conducted in government funded, government aided, and private schools in Hyderabad. The relationship between modes of travel and distance to school was analysed using logistic regression, adjusting for confounders. The prevalence of road traffic injury in the previous 12 months during school journeys was estimated, and the impacts of alternative transport scenarios on road injury was modelled. Results: The questionnaire provided reliable information on the usual mode of travel to school, and road injury. Distance to school measured by asking for the nearest landmark to a child’s home was found to be a valid measure of distance compared to a method based on in-depth interviews with children. Forty five schools including 5,842 children aged 11-14 years participated in the survey, with a response rate of 99%. Most children in Hyderabad walked or cycled to school. Others travelled by motorised 2-wheelers, auto-rickshaw, school bus, public transport bus, and car. Greater distance to school was strongly associated with the use of motorised transport. A sixth of all children reported a road injury during school journeys, which was strongly associated with travel mode and distance to school. The overall risk of road injury was 25/100,000 child km per year. Relative to school bus occupants, bicyclists, pedestrians and motorcycle passengers were more likely to be injured, for the same distance travelled. The model showed that road injuries can be prevented under transportation scenarios that restrict distance and motorised vehicles near schools. Conclusions: The questionnaire reliably measured mode of travel to school and estimated distances to school in Hyderabad. Most children walked or cycled to school and if these levels are to be maintained, there is an urgent need to ensure that walking and cycling may be done safely

Distributed flow optimization and cascading effects in weighted complex networks

We investigate the effect of a specific edge weighting scheme $\sim (k_i k_j)^{\beta}$ on distributed flow efficiency and robustness to cascading failures in scale-free networks. In particular, we analyze a simple, yet fundamental distributed flow model: current flow in random resistor networks. By the tuning of control parameter $\beta$ and by considering two general cases of relative node processing capabilities as well as the effect of bandwidth, we show the dependence of transport efficiency upon the correlations between the topology and weights. By studying the severity of cascades for different control parameter $\beta$, we find that network resilience to cascading overloads and network throughput is optimal for the same value of $\beta$ over the range of node capacities and available bandwidth

Scaling of mean first-passage time as efficiency measure of nodes sending information on scale-free Koch networks

A lot of previous work showed that the sectional mean first-passage time (SMFPT), i.e., the average of mean first-passage time (MFPT) for random walks to a given hub node (node with maximum degree) averaged over all starting points in scale-free small-world networks exhibits a sublinear or linear dependence on network order $N$ (number of nodes), which indicates that hub nodes are very efficient in receiving information if one looks upon the random walker as an information messenger. Thus far, the efficiency of a hub node sending information on scale-free small-world networks has not been addressed yet. In this paper, we study random walks on the class of Koch networks with scale-free behavior and small-world effect. We derive some basic properties for random walks on the Koch network family, based on which we calculate analytically the partial mean first-passage time (PMFPT) defined as the average of MFPTs from a hub node to all other nodes, excluding the hub itself. The obtained closed-form expression displays that in large networks the PMFPT grows with network order as $N \ln N$, which is larger than the linear scaling of SMFPT to the hub from other nodes. On the other hand, we also address the case with the information sender distributed uniformly among the Koch networks, and derive analytically the entire mean first-passage time (EMFPT), namely, the average of MFPTs between all couples of nodes, the leading scaling of which is identical to that of PMFPT. From the obtained results, we present that although hub nodes are more efficient for receiving information than other nodes, they display a qualitatively similar speed for sending information as non-hub nodes. Moreover, we show that the location of information sender has little effect on the transmission efficiency. The present findings are helpful for better understanding random walks performed on scale-free small-world networks.Comment: Definitive version published in European Physical Journal

The timing of death in patients with tuberculosis who die during anti-tuberculosis treatment in Andhra Pradesh, South India

Background: India has 2.0 million estimated tuberculosis (TB) cases per annum with an estimated 280,000 TBrelated deaths per year. Understanding when in the course of TB treatment patients die is important for determining the type of intervention to be offered and crucially when this intervention should be given. The objectives of the current study were to determine in a large cohort of TB patients in India:- i) treatment outcomes including the number who died while on treatment, ii) the month of death and iii) characteristics associated with “early” death, occurring in the initial 8 weeks of treatment. Methods: This was a retrospective study in 16 selected Designated Microscopy Centres (DMCs) in Hyderabad, Krishna and Adilabad districts of Andhra Pradesh, South India. A review was performed of treatment cards and medical records of all TB patients (adults and children) registered and placed on standardized anti-tuberculosis treatment from January 2005 to September 2009. Results: There were 8,240 TB patients (5183 males) of whom 492 (6%) were known to have died during treatment. Case-fatality was higher in those previously treated (12%) and lower in those with extra-pulmonary TB (2%). There was an even distribution of deaths during anti-tuberculosis treatment, with 28% of all patients dying in the first 8 weeks of treatment. Increasing age and new as compared to recurrent TB disease were significantly associated with “early death”. Conclusion: In this large cohort of TB patients, deaths occurred with an even frequency throughout anti-TB treatment. Reasons may relate to i) the treatment of the disease itself, raising concerns about drug adherence, quality of anti-tuberculosis drugs or the presence of undetected drug resistance and ii) co-morbidities, such as HIV/ AIDS and diabetes mellitus, which are known to influence mortality. More research in this area from prospective and retrospective studies is needed

Ecology of ficus religiosa accounts for its association with religion

While many plants and trees in specific areas acquire cult significance, very few such as Ficus religiosa L. have acquired a universal status. This hemiepiphyte, Ficus religiosa L., is of dual interest since it venerated by a quarter of the present mankind (Hindus and Buddhists, largely Asian) on one hand and also since these plants are blamed for destruction of buildings due to their ability to grow on buildings. Divergence in views exists whether epiphytic plants exert a destructive influence on buildings. A focused survey of the coastal forts on land and sea has shown uniformly that the naturally growing plants of certain Ficus sp., notably Ficus religiosa L., grow exclusively on the vertical sheer side of rock faces and not either on the ground or on the top surface of these 8-10 centuries old rock structures; also seen on the side of rock piles as recent as 4-5 years as well as in sacred groves of several centuries to millennia old. We could trace the roots through these structures from beginning to the end in many parts of these forts, especially when there are overhanging structures at entrances. The root tips, the point of growth, would be far too insignificant to account for destruction in any of these large rock-and-lime masonry structures while vibration per se was insignificant as the tree was seen in all forts on land or sea. The association with religion of the distinctive Ficus religiosa itself appears to be self-evident from its socio-anthropological association with rock piles, hitherto not visualized for any flora and logically appears to pre-date both Hinduism and Buddhism

Biochemical properties of a bacterially-expressed Bowman-Birk inhibitor from Rhynchosia sublobata (Schumach.) Meikle seeds and its activity against gut proteases of Achaea janata

Crude proteinase inhibitors (CPIs) extracted from the seeds of Rhynchosia sublobata, a wild relative of pigeon pea showed pronounced inhibitory activity on the larval gut trypsin-like proteases of lepidopteran insect pest – Achaea janata. Consequently, a full-length cDNA of Bowman-Birk inhibitor gene (RsBBI1) was cloned from the immature seeds of R. sublobata. It contained an ORF of 360 bp encoding a 119-amino acid polypeptide (13.3 kDa) chain with an N-terminus signal sequence comprising of 22 amino acids. The amino acid sequence and phylogenetic analysis together revealed that RsBBI1 exhibited a close relation with BBIs from soybean and Phaseolus spp. A cDNA sequence corresponding to RsBBI1 mature protein (89 amino acid stretch) was expressed in E. coli. The recombinant rRsBBI1 protein with a molecular mass of 9.97 kDa was purified using trypsin affinity chromatography. The purified rRsBBI1 exhibited non-competitive mode of inhibition of both bovine trypsin (Ki of 358 ± 11 nM) and chymotrypsin (Ki of 446 ± 9 nM). Its inhibitory activity against these proteases was stable at high temperatures (>95 °C) and a wide pH range but sensitive to reduction with dithiothreitol (DTT), indicating the importance of disulphide bridges in exhibiting its activity. Also, rRsBBI1 showed significant inhibitory activity (IC50 = 70 ng) on A. janata larval gut trypsin-like proteases (AjGPs). Conversely, it showed <1% inhibitory activity (IC50 = 8 μg) on H. armigera larval gut trypsin-like proteases (HaGPs) than it has against AjGPs. Besides, in vivo feeding experiments clearly indicated the deleterious effects of rRsBBI1 on larval growth and development in A. janata which suggests it can be further exploited for such properties

Large-scale cultivation of synechocystis sp. PCC6803 for the production of poly(3-hydroxybutyrate) and its potential applications in the manufacturing of bulk and medical prototypes.

Polyhydroxyalkanoates (PHAs) are bioplastics produced by microorganisms under nutrient limiting conditions and in the presence of excess carbon source. PHAs have gained popularity as a sustainable alternative to traditional plastics. However, large scale production of PHAs is economically challenging due to the relatively high costs of organic carbon. Alternative options include using organisms capable of phototrophic or mixotrophic growth. This study aimed at the production of poly(3-hydroxybutyrate) P(3HB), a type of PHA, at pilot scale using the freshwater cyanobacterium Synechocystis sp. PCC6803. First, to identify optimal conditions for P(3HB) production from Synechocystis sp. PCC6803, different supplemental carbon source concentrations and salinity levels were tested at laboratory scale. The addition of 4g/L acetate with no added NaCl led to P(3HB) accumulation of 10.7% dry cell weight on the 28th day of cultivation. Although acetate additions were replicated in an outdoor 400L serpentine photobioreactor, P(3HB) content was lower, implying uncontrolled conditions impact on biopolymer production efficiency. An optimized P(3HB) extraction methodology was developed to remove pigments, and the biopolymer was characterized and subjected to 3D printing (fused deposition modelling) to confirm its processability. This study thus successfully led to the large-scale production of P(3HB) using sustainable and environmentally friendly cyanobacterial fermentation