Tissue-fluid interface analysis using biphasic finite element method

Numerical studies on fluid-structure interaction have primarily relied on decoupling the solid and fluid sub-domains with the interactions treated as external boundary conditions on the individual sub-domains. The finite element applications for the fluid-structure interactions can be divided into iterative algorithms and sequential algorithms. In this paper, a new computational methodology for the analysis of tissue-fluid interaction problems is presented. The whole computational domain is treated as a single biphasic continuum, and the same space and time discretisation is carried out for the sub-domains using a penalty-based finite element model. This procedure does not require the explicit modelling of additional boundary conditions or interface elements. The developed biphasic interface finite element model is used in analysing blood flow through normal and stenotic arteries. The increase in fluid flow velocity when passing through a stenosed artery and the drop in pressure at the region are captured using this method.     

How is the individuality of a face recognized?

A familiar face is instantly recognized in a crowd. This cannot be achieved through a feature by feature comparison of the observed face with either an average face (norm-based model of face recognition) or with a set of similarly constructed faces stored in memory (exemplar-based model of face recognition). A modified norm-based model is thus proposed. Instead of memorizing an average face, the normal variations for each facial feature are used to construct a multidimensional volume of face-space devoid of unusual features, here defined as features whose metrics lie below the 5th or above the 95th percentiles for that feature. A face consisting of 100 independently variable features will thus have, on average, 10 unusual features. Face identification then becomes exception-reporting. It requires only 10 such rare features to render a given face a one in 10¹³ faces (P=0.05¹⁰=9.8×10⁻¹⁴). In a world containing 6.7×10⁹ people, such a face would be unique. Faces remembered in this way can have their unusual features exaggerated or attenuated without loss of identity. This is the basis of caricatures and anti-caricatures. It also means that individuals belonging to a foreign race, possessing several features with modes beyond the “usual range” of the own-race population, will all look alike. Features that render a face unique in the own-race population are now shared by everyone in the foreign race.Average faces are more beautiful than the faces used in the averaging process. This makes evolutionary sense. Natural selection increases the frequency of fit features at the expense of maladaptive features. “Usual features” are therefore fitter than “unusual features”, and play an important role in mate selection. Such an existing fundamental sexual attribute could easily have been harnessed for the fast and efficient recognition of individuals in the community.     

Chromium (D-phenylalanine)3 alleviates high fat-induced insulin resistance and lipid abnormalities

High-fat diet has been implicated as a major cause of insulin resistance and dyslipidemia. The objective of this study was to evaluate the impact of dietary-supplementation of chromium (d-phenylalanine)₃ [Cr(d-Phe)₃] on glucose and insulin tolerance in high-fat diet fed mice. C57BL/6-mice were randomly assigned to orally receive vehicle or Cr(d-Phe)₃ (45 μg of elemental chromium/kg/day) for 8-weeks. High-fat-fed mice exhibited impaired whole-body-glucose and -insulin tolerance and elevated serum triglyceride levels compared to normal chow-fed mice. Insulin-stimulated glucose up-take in the gastrocnemius muscles, assessed as 2-[³H-deoxyglucose] incorporation was markedly diminished in high-fat fed mice compared to control mice. Treatment with chromium reconciled the high-fat diet-induced alterations in carbohydrate and lipid metabolism. Treatment of cultured, differentiated myotubes with palmitic acid evoked insulin resistance as evidenced by lower levels of insulin-stimulated Akt-phosphorylation, elevated JNK-phosphorylation, (assessed by Western blotting), attenuation of phosphoinositol-3-kinase activity (determined in the insulin-receptor substrate-1-immunoprecipitates by measuring the extent of phosphorylation of phosphatidylinositol by γ-³²P-ATP), and impairment in cellular glucose up-take, all of which were inhibited by Cr(d-Phe)₃. These results suggest a beneficial effect of chromium-supplementation in insulin resistant conditions. It is likely that these effects of chromium may be mediated by augmenting downstream insulin signaling.     

Prevalence of Dyslipidemia in Urban and Rural India: The ICMR–INDIAB Study

Aim

To study the pattern and prevalence of dyslipidemia in a large representative sample of four selected regions in India.

Methods

Phase I of the Indian Council of Medical Research–India Diabetes (ICMR-INDIAB) study was conducted in a representative population of three states of India [Tamil Nadu, Maharashtra and Jharkhand] and one Union Territory [Chandigarh], and covered a population of 213 million people using stratified multistage sampling design to recruit individuals ≥20 years of age. All the study subjects (n = 16,607) underwent anthropometric measurements and oral glucose tolerance tests were done using capillary blood (except in self-reported diabetes). In addition, in every 5th subject (n = 2042), a fasting venous sample was collected and assayed for lipids. Dyslipidemia was diagnosed using National Cholesterol Education Programme (NCEP) guidelines.

Results

Of the subjects studied, 13.9% had hypercholesterolemia, 29.5% had hypertriglyceridemia, 72.3% had low HDL-C, 11.8% had high LDL-C levels and 79% had abnormalities in one of the lipid parameters. Regional disparity exists with the highest rates of hypercholesterolemia observed in Tamilnadu (18.3%), highest rates of hypertriglyceridemia in Chandigarh (38.6%), highest rates of low HDL-C in Jharkhand (76.8%) and highest rates of high LDL-C in Tamilnadu (15.8%). Except for low HDL-C and in the state of Maharashtra, in all other states, urban residents had the highest prevalence of lipid abnormalities compared to rural residents. Low HDL-C was the most common lipid abnormality (72.3%) in all the four regions studied; in 44.9% of subjects, it was present as an isolated abnormality. Common significant risk factors for dyslipidemia included obesity, diabetes, and dysglycemia.

Conclusion

The prevalence of dyslipidemia is very high in India, which calls for urgent lifestyle intervention strategies to prevent and manage this important cardiovascular risk factor.     

A Structural Biology Approach to Understand Human Lymphatic Filarial Infection

The presence of aspartic protease inhibitor in filarial parasite Brugia malayi (Bm-Aspin) makes it interesting to study because of the fact that the filarial parasite never encounters the host digestive system. Here, the aspartic protease inhibition kinetics of Bm-Aspin and its NMR structural characteristics have been investigated. The overall aim of this study is to explain the inhibition and binding properties of Bm-Aspin from its structural point of view. UV-spectroscopy and multi-dimensional NMR are the experiments that have been performed to understand the kinetic and structural properties of Bm-Aspin respectively. The human aspartic proteases that are considered for this study are pepsin, renin, cathepsin-E and cathepsin-D. The results of this analysis performed with the specific substrate [Phe-Ala-Ala-Phe (4-NO₂)-Phe-Val-Leu (4-pyridylmethyl) ester] against aspartic proteases suggest that Bm-Aspin inhibits the activities of all four human aspartic proteases. The kinetics studies indicate that Bm-Aspin follows a competitive mode of inhibition for pepsin and cathepsin-E, non-competitive for renin and mixed mode for cathepsin-D. The triple resonance NMR experiments on Bm-Aspin suggested the feasibility of carrying out NMR studies to obtain its solution structure. The NMR titration studies on the interactions of Bm-Aspin with the proteases indicate that it undergoes fast-exchange phenomena among themselves. In addition to this, the chemical shift perturbations for some of the residues of Bm-Aspin observed from ¹⁵N-HSQC spectra upon the addition of saturated amounts of aspartic proteases suggest the binding between Bm-Aspin and human aspartic proteases. They also provide information on the variations in the intensities and mode of binding between the proteases duly corroborating with the results from the protease inhibition assay method.     

Estimation of Exponential Parameters in the Presence of Outliers

In the present paper we discuss the estimation of the parameter and survival function of an exponential population. It is assumed that the sample based on which the estimation is done, contains k outliers that are also exponentially distributed with parameter, a constant multiple of that of the original distribution.     

Necroptosis increases with age and is reduced by dietary restriction

Necroptosis is a newly identified programmed cell death pathway that is highly proinflammatory due to the release of cellular components that promote inflammation. To determine whether necroptosis might play a role in inflammaging, we studied the effect of age and dietary restriction (DR) on necroptosis in the epididymal white adipose tissue (eWAT), a major source of proinflammatory cytokines. Phosphorylated MLKL and RIPK3, markers of necroptosis, were increased 2.7‐ and 1.9‐fold, respectively, in eWAT of old mice compared to adult mice, and DR reduced P‐MLKL and P‐RIPK3 to levels similar to adult mice. An increase in the expression of RIPK1 (1.6‐fold) and MLKL (2.7‐fold), not RIPK3, was also observed in eWAT of old mice, which was reduced by DR in old mice. The increase in necroptosis was paralleled by an increase in 14 inflammatory cytokines, including the pro‐inflammatory cytokines IL‐6 (3.9‐fold), TNF‐α (4.7‐fold), and IL‐1β (5.1‐fold)], and 11 chemokines in old mice. DR attenuated the expression of IL‐6, TNF‐α, and IL‐1β as well as 85% of the other cytokines/chemokines induced with age. In contrast, inguinal WAT (iWAT), which is less inflammatory, did not show any significant increase with age in the levels of P‐MLKL and MLKL or inflammatory cytokines/chemokines. Because the changes in biomarkers of necroptosis in eWAT with age and DR paralleled the changes in the expression of pro‐inflammatory cytokines, our data support the possibility that necroptosis might play a role in increased chronic inflammation observed with age.     

Loss of mitochondrial protease ClpP protects mice from diet‐induced obesity and insulin resistance

Caseinolytic peptidase P (ClpP) is a mammalian quality control protease that is proposed to play an important role in the initiation of the mitochondrial unfolded protein response (UPR^mt), a retrograde signaling response that helps to maintain mitochondrial protein homeostasis. Mitochondrial dysfunction is associated with the development of metabolic disorders, and to understand the effect of a defective UPR^mt on metabolism, ClpP knockout (ClpP^?/?) mice were analyzed. ClpP^?/? mice fed ad libitum have reduced adiposity and paradoxically improved insulin sensitivity. Absence of ClpP increased whole‐body energy expenditure and markers of mitochondrial biogenesis are selectively up‐regulated in the white adipose tissue (WAT) of ClpP^?/? mice. When challenged with a metabolic stress such as high‐fat diet, despite similar caloric intake, ClpP^?/? mice are protected from diet‐induced obesity, glucose intolerance, insulin resistance, and hepatic steatosis. Our results show that absence of ClpP triggers compensatory responses in mice and suggest that ClpP might be dispensable for mammalian UPR^mt initiation. Thus, we made an unexpected finding that deficiency of ClpP in mice is metabolically beneficial.     

The binding site of the IclR repressor protein overlaps the promoter of aceBAK.

In Escherichia coli, repression of the aceBAK operon is mediated by the IclR protein. We used an in vitro oligonucleotide selection technique to determine the consensus recognition sequence for MR. Mutational analysis confirmed the contribution of this sequence to repression in vivo and identified the -35 element of the promoter.     

Spectroscopic and photoluminescence characterization of Dy3+ in Sr0.5Ca0.5TiO3 phosphor

The spectroscopic and photoluminescence characteristics of trivalent dysprosium (Dy³⁺)‐doped Sr_0.5Ca_0.5TiO₃ phosphor materials synthesized via solid‐state reaction method were studied. The X‐ray diffraction profile confirmed the orthorhombic perovskite structure of the prepared samples. Judd–Ofelt analysis was carried out to obtain the intensity parameters and predicted radiative properties of Sr_0.5Ca_0.5TiO₃:2wt%Dy³⁺. The photoluminescence spectrum of Dy³⁺‐doped Sr_0.5Ca_0.5TiO₃ showed three emission peaks at 481, 574 and 638 nm corresponding to ⁴F_9/2→⁶H_15/2, ⁴F_9/2→⁶H_13/2 and ⁴F_9/2→⁶H_11/2 transitions respectively. The variation of luminescence intensity with different excitation wavelengths and Dy³⁺ concentrations is discussed. The decay profiles of ⁴F_9/2 excited levels of Dy³⁺ ions show bi‐exponential behaviour and also a decrease in average lifetime with increase in Dy³⁺ concentration. Yellow to blue luminescence intensity ratio, CIE chromaticity co‐ordinates and correlated color temperature were also calculated for different concentrations of Dy³⁺‐doped Sr_0.5Ca_0.5TiO₃ phosphor at different λ_ex. Copyright © 2015 John Wiley & Sons, Ltd.