Alteration of Golgi structure in senescent cells and its regulation by a G protein γ subunit

Cellular senescence is a process wherein proliferating cells undergo permanent cell cycle arrest while remaining viable. Senescence results in enhanced secretion of proteins that promote cancer and inflammation. We report here that the structure of the Golgi complex which regulates secretion is altered in senescent cells. In cells where senescence is achieved by replicative exhaustion or in cells wherein senescence has been induced with BrdU treatment dependent stress, the Golgi complex is dispersed. The expression of a G protein γ subunit, γ11, capable of translocation from the plasma membrane to the Golgi complex on receptor activation increases with senescence. Knockdown of γ11 or overexpression of a dominant negative γ3 subunit inhibits Golgi dispersal induced by senescence. Overall these results suggest that in cellular senescence an upregulated G protein gamma subunit mediates alterations in the structure of the Golgi.     

Cadherin-9 regulates synapse-specific differentiation in the developing hippocampus

Our understanding of mechanisms that regulate the differentiation of specific classes of synapses is limited. Here, we investigate the formation of synapses between hippocampal dentate gyrus (DG) neurons and their target CA3 neurons and find that DG neurons preferentially form synapses with CA3 rather than DG or CA1 neurons in culture, suggesting that specific interactions between DG and CA3 neurons drive synapse formation. Cadherin-9 is expressed selectively in DG and CA3 neurons, and downregulation of cadherin-9 in CA3 neurons leads to a selective decrease in the number and size of DG synapses onto CA3 neurons. In addition, loss of cadherin-9 from DG or CA3 neurons in vivo leads to striking defects in the formation and differentiation of the DG-CA3 mossy fiber synapse. These observations indicate that cadherin-9 bidirectionally regulates DG-CA3 synapse development and highlight the critical role of differentially expressed molecular cues in establishing specific connections in the mammalian brain.     

An improved bioprocess for synthesis of acetohydroxamic acid using DTT (dithiothreitol) treated resting cells of Bacillus sp. APB-6

Acyltransferase activity of amidase from Bacillus sp. APB-6 was enhanced (24 U) by multiple feedings of N-methylacetamide (70 mM) into the production medium. Hyperinduced whole resting cells of Bacillus sp. APB-6 corresponding to 4 g/L (dry cell weight), when treated with 10 mM DTT (dithiothreitol) resulted in 93% molar conversion of acetamide (300 mM) to acetohydroxamic acid in presence of hydroxylamine-HCl (800 mM) after 30 min at 45 °C in a 1 L reaction mixture. After lyophilization, a 62 g powder containing 34% (wt wt⁻¹) acetohydroxamic acid was recovered. This is the first report where DTT has been used to enhance acyltransfer reaction and such high molar conversion (%) of amide to hydroxamates was recorded at 1 L scale.     

Elaboration of nanostructured biointerfaces with tunable degree of coverage by protein nanotubes using electrophoretic deposition

This study shows that electrophoretic deposition (EPD) is a fast and efficient technique for producing protein nanotube-based biointerfaces. Well-shaped collagen-based nanotubes of controlled dimensions are synthesized by a template method combined with the layer-by-layer (LbL) assembly technique. Separation of nanotubes from the template material and collection of nanotubes on ITO glass carried out by EPD leads to a fairly homogeneous distribution of protein nanotubes at the support surface. Biointerfaces with different and tunable densities of protein nanotubes are obtained by changing either the applied voltage, solution concentration of nanotubes, or deposition time. Moreover, it is proved that the collected nanotubes are template-free and keep their biofunctional outermost layer after EPD. A preliminary study of the behavior of preosteoblasts cells with the elaborated biointerfaces indicates a specific interaction of cells with the nanotubes through filopodia. This contribution paves the way to the easy preparation of a large variety of useful nanostructured collagen and other protein-based interfaces for controlling cell-surface interactions in diverse biomaterials applications.     

F2Dock: fast Fourier protein-protein docking

The functions of proteins are often realized through their mutual interactions. Determining a relative transformation for a pair of proteins and their conformations which form a stable complex, reproducible in nature, is known as docking. It is an important step in drug design, structure determination, and understanding function and structure relationships. In this paper, we extend our nonuniform fast Fourier transform-based docking algorithm to include an adaptive search phase (both translational and rotational) and thereby speed up its execution. We have also implemented a multithreaded version of the adaptive docking algorithm for even faster execution on multicore machines. We call this protein-protein docking code F2Dock (F2 = Fast Fourier). We have calibrated F2Dock based on an extensive experimental study on a list of benchmark complexes and conclude that F2Dock works very well in practice. Though all docking results reported in this paper use shape complementarity and Coulombic-potential-based scores only, F2Dock is structured to incorporate Lennard-Jones potential and reranking docking solutions based on desolvation energy .     

Single-particle reconstruction using L(2)-gradient flow

In this paper, we present an iterative algorithm for reconstructing a three-dimensional density function from a set of two dimensional electron microscopy images. By minimizing an energy functional consisting of a fidelity term and a regularization term, an L²-gradient flow is derived. The flow is integrated by a finite element method in the spatial direction and an explicit Euler scheme in the temporal direction. Our method compares favorably with those of the weighted back projection, Fourier method, algebraic reconstruction technique and simultaneous iterative reconstruction technique.     

Secular trends in prevalence of overweight and obesity from 2006 to 2009 in urban asian Indian adolescents aged 14-17 years

The present study examines the secular trends in prevalence of overweight and obesity among urban Asian Indian adolescents in New Delhi (North India). The data were derived from cross-sectional sampling of children, 3493 in year 2006 and 4908 in year 2009, aged 14-17 years studying in privately-funded and government-funded schools. Age, gender and Asian Indian-specific cut offs of body mass index (BMI) were used to define overweight and obesity. The prevalence of obesity increased significantly from 9.8% in 2006 to 11.7% in 2009 (p<0.01), whereas underweight decreased from 11.3% to 3.9% (p<0.001). There was a significantly higher risk of being overweight (OR 1.28; 95% CI, 1.15-1.42) and obese (OR 1.44; 95% CI, 1.24-1.66) in year 2009 than 2006, after adjusting for age, gender and type of school. Males and privately-funded school children had significantly higher increase in prevalence and risk of being overweight and obese over the three years. In conclusion, this study showed an increasing trend in prevalence of overweight and obesity in urban Asian Indian adolescents. More specifically, the study showed the association of this increasing trend of overweight and obesity prevalence with male gender and high socio-economic status, calling for an urgent need for immediate and targeted preventive measures.