Juxtaposed half-cystines as disulphide bridged partners in protein tertiary structure

Disulphide bridges involving juxtaposed half-cystines are observed in a number of protein three-dimensional structures analyzed from the Protein Data Bank. These disulphide bridges comprise a 'ring of 8-atoms' corresponding to Calpha1-C'-N-Calpha2-Cbeta2-Sgamma2-Sgamma1-Cbeta1-Calpha1 in the two half-cystines. The presence of such disulphide bridges introduces a 'bend' or 'kink' in the protein polypeptide chain.     

Artificial life and living systems: Insight into artificial life and its implications in life science research

Advanced technology has made it possible to build machines and systems like robots, which are capable of making intelligent decisions. Robots capable of self-replication and perform human functions are also available. The current challenge is to design evolutionary systems with high complexity comparable to that of biological networks. This is proposed to be achieved by ALife (Artificial Life). Here, we describe the promises provided by ALife for life sciences.     

Immune response to the West Nile virus in aged non-human primates

Background

Risk of encephalitis from West Nile virus (WNV) infection increases dramatically with age. Understanding the basis of this susceptibility requires development of suitable animal models. Here, we investigated the immune response to WNV in old non-human primates.

Methodology/Principal Findings

We investigated clinical, immunological and virological correlates of WNV infection in aging non-human primates. Aged (17–30yrs) and adult (6–9yrs) Rhesus macaques (RM) were challenged with WNV in the presence or the absence of the mosquito salivary gland extract (SGE) to approximate natural infection. None of the 26 animals exhibited clinical signs of the disease. Quantitative PCR suggested discrete and short-lived viremia, but infectious virus was never isolated. There was markedly increased, age-independent, proliferation of CD3⁻ non-B cells, followed by B-cell proliferation, which correlated to the loss of detectable WNV genomes. Moreover, animals primed with mosquito salivary gland extract exhibited reduced circulating WNV RNA. While we found the expected age-associated reduction in T cell proliferation, adaptive immunity did not correlate with infection outcome. That was further confirmed in a cohort of thymectomized and/or CD8 T-cell depleted Cynomolgus macaques (CM; N = 15), who also failed to develop WNV disease.

Conclusions/significance

Results are consistent with strong and age-independent innate resistance of macaques against WNV challenge. This animal model is therefore not suitable for vaccine and therapeutic testing against WNV. However, understanding the basis of their innate resistance against WNV in macaques could provide helpful clues to improve anti-WNV protection of older adults.     

Structural plasticity associated with the beta-propeller architecture

The beta-propeller architecture observed in protein tertiary structure and classified into the five different types according to number of 'blades' (or beta-sheets) and a sixth type classified according to the secondary structure composition of the blades (the beta beta alpha beta-molecular unit) is characterized by variations (or plasticity) in the structure. These correspond to the number of beta-strands associated with the blade, the number of amino acid residues associated with equivalent beta-strands in the different blades and the presence of alpha-helices and twisted beta-strands. We have generated a beta-sheet associated beta-strand pattern that may be important for protein structure prediction and modeling. Analysis of the beta-propellers extracted primarily from the SCOP database revealed there are 179 beta-propellers. The examination of the secondary structure corresponding to the beta-propeller using PDBsum that was useful to define the beta-sheet associated beta-strand pattern, combined with visualization on graphics display revealed structural plasticity associated with the beta-propeller architecture. Particularly, the type 6- and 7-bladed beta-propellers known to be associated with sequence and functional diversity are more common and associated with relatively more structural variations compared to the other beta-propeller types.     

Foliar application of fungicide-opera alleviates negative impact of water stress in soybean plants

The modulatory effect of opera was investigated on the physiological and morphological aspects in soybean thriving in water stress environment. The data procured from current investigation indicated that water stress significantly declined the plant growth, leaf area in addition to photosynthetic efficiency, nitrate reductase activity and crop yield at various stages of growth such as vegetative (VS), flowering (FS) and pod filling stage (PFS). However, foliar application of opera (0.15%) was effective to enhance the the leaf area (42%), rate of photosynthesis (194%), and nitrate reductase activity (68%) at FS stage while the maximum enhancement in biomass accumulation (92%) and yield (119%) was observed at PFS stage as compared to their control plants. The opera is applied as foliar spray in field experiments to augment the assimilation of nitrogen and carbon in soybean which contributes to increased crop development and productivity under water stress conditions.     

Ponatinib Is a Pan-BCR-ABL Kinase Inhibitor: MD Simulations and SIE Study

BCR-ABL kinase domain inhibition can be used to treat chronic myeloid leukemia. The inhibitors such as imatinib, dasatinib and nilotinib are effective drugs but are resistant to some BCR-ABL mutations. The pan-BCR-ABL kinase inhibitor ponatinib exhibits potent activity against native, T315I, and all other clinically relevant mutants, and showed better inhibition than the previously known inhibitors. We have studied the molecular dynamics simulations and calculated solvated interaction energies of native and fourteen mutant BCR-ABL kinases (M244V, G250E, Q252H, Y253F, Y253H, E255K, E255V, T315A, T315I, F317L, F317V, M351T, F359V and H396P) complexed with ponatinib. These studies revealed that the interactions between ponatinib and individual residues in BCR-ABL kinase are also affected due to the remote residue mutations. We report that some residues, Met244, Lys245, Gln252, Gly254, Leu370 and Leu298 do not undergo any conformational changes, while the fluctuations in residues from P-loop, β3-, β5- strands and αC- helix are mainly responsible for ponatinib binding to native and all mutant BCR-ABL kinases. Our work provides the molecular mechanisms of native and mutant BCR-ABL kinases inhibition by ponatinib at atomic level that has not been studied before.     

The response of Paracoccus sp. SKG to acetonitrile-induced oxidative stress

Organic solvents enhance intracellular oxidative stress and induce various physiological responses in bacteria. The study shows the morphological changes in Paracoccus sp. SKG when exposed to higher concentrations of acetonitrile, which alter the composition of the membrane fatty acid that accompanies the increase in K⁺ efflux. This enhances the oxidative stress with greater activities of catalase and super oxide dismutase (SOD). The increased oxidative stress results in the generation of free radicals, which was confirmed by electron paramagnetic resonance (EPR) studies. The free radical scavenging activities were measured by ABTS and DPPH to understand the non-enzymatic defensive system during oxidative stress. The studies demonstrate the increase in free radicals in association with enzymatic and non-enzymatic defense systems under solvent stress.     

Enhancement of germination, growth, and photosynthesis in soybean by pre-treatment of seeds with magnetic field

Experiments were conducted to study the effect of static magnetic fields on the seeds of soybean (Glycine max (L.) Merr. var: JS-335) by exposing the seeds to different magnetic field strengths from 0 to 300 mT in steps of 50 mT for 30, 60, and 90 min. Treatment with magnetic fields improved germination-related parameters like water uptake, speed of germination, seedling length, fresh weight, dry weight and vigor indices of soybean seeds under laboratory conditions. Improvement over untreated control was 5-42% for speed of germination, 4-73% for seedling length, 9-53% for fresh weight, 5-16% for dry weight, and 3-88% and 4-27% for vigor indices I and II, respectively. Treatment of 200 mT (60 min) and 150 mT (60 min), which were more effective than others in increasing most of the seedling parameters, were further explored for their effect on plant growth, leaf photosynthetic efficiency, and leaf protein content under field conditions. Among different growth parameters, leaf area, and leaf fresh weight showed maximum enhancement (more than twofold) in 1-month-old plants. Polyphasic chlorophyll a fluorescence (OJIP) transients from magnetically treated plants gave a higher fluorescence yield at the J-I-P phase. The total soluble protein map (SDS-polyacrylamide gel) of leaves showed increased intensities of the bands corresponding to a larger subunit (53 KDa) and smaller subunit (14 KDa) of Rubisco in the treated plants. We report here the beneficial effect of pre-sowing magnetic treatment for improving germination parameters and biomass accumulation in soybean.     

Neural mechanisms of context-dependent processing of CO2 avoidance behavior in fruit flies

The fruit fly, Drosophila melanogaster, innately avoids even low levels of CO₂. CO₂ is part of the so-called Drosophila stress odor produced by stressed flies, but also a byproduct of fermenting fruit, a main food source, making the strong avoidance behavior somewhat surprising. Therefore, we addressed whether feeding states might influence the fly’s behavior and processing of CO₂. In a recent report, we showed that this innate behavior is differentially processed and modified according to the feeding state of the fly. Interestingly, we found that hungry flies require the function of the mushroom body, a higher brain center required for olfactory learning and memory, but thought to be dispensable for innate olfactory behaviors. In addition, we anatomically and functionally characterized a novel bilateral projection neuron connecting the CO₂ sensory input to the mushroom body. This neuron was essential for processing of CO₂ in the starved fly but not in the fed fly. In this Extra View article, we provide evidence for the potential involvement of the neuromodulator dopamine in state-dependent CO₂ avoidance behavior. Taken together, our work demonstrates that CO₂ avoidance behavior is mediated by alternative neural pathways in a context-dependent manner. Furthermore, it shows that the mushroom body is not only involved in processing of learned olfactory behavior, as previously suggested, but also in context-dependent innate olfaction.