Extracting proteins involved in disease progression using temporally connected networks

Background

Metabolic disorders such as obesity and diabetes are diseases which develop gradually over time in an individual and through the perturbations of genes. Systematic experiments tracking disease progression at gene level are usually conducted giving a temporal microarray data. There is a need for developing methods to analyze such complex data and extract important proteins which could be involved in temporal progression of the data and hence progression of the disease.

Results

In the present study, we have considered a temporal microarray data from an experiment conducted to study development of obesity and diabetes in mice. We have used this data along with an available Protein-Protein Interaction network to find a network of interactions between proteins which reproduces the next time point data from previous time point data. We show that the resulting network can be mined to identify critical nodes involved in the temporal progression of perturbations. We further show that published algorithms can be applied on such connected network to mine important proteins and show an overlap between outputs from published and our algorithms. The importance of set of proteins identified was supported by literature as well as was further validated by comparing them with the positive genes dataset from OMIM database which shows significant overlap.

Conclusions

The critical proteins identified from algorithms can be hypothesized to play important role in temporal progression of the data.

     

Analysis of factors that influence energy expenditure in honeyeaters (Meliphagidae)

The energy expenditure of the tūī (Prosthemadera novaeseelandiae), a meliphagid endemic to New Zealand, was measured and compared with 20 species of honeyeaters (family Meliphagidae) to determine whether its expenditure is influenced either by life in a moist, temperate climate or an island residence. Body mass in the honeyeaters accounted for 91.5% of the variation in basal rate. The combination of body mass, climate and the maximal limit to an altitudinal distribution explained 98.6% of the variation in basal rate with tropical, low-altitude species having the highest mass-independent rate. The basal rates of meliphagids in tropical highlands are similar to those in temperate lowlands, which may reflect similar food supplies. The tūī mass-independent expenditure appears to reflect an active lifestyle in a temperate climate with no evidence that an island residence influenced its rate, whereas sedentary birds on New Zealand have responded to island life with a depressed basal rate. An effective analysis of the variation in energy expenditure requires the inclusion of the ecological and behavioural characteristics that distinguish species.     

Acceleration Workspace of Cooperating Multi-Finger Robot Systems

We present a mathematical method for acceleration workspace analysis of cooperating multi-finger robot systems using a model of point-contact with friction. A new unified formulation from dynamic equations of cooperating multi-finger robots is derived considering the force and acceleration relationships between the fingers and the object to be handled. From the dynamic equation, maximum translational and rotational acceleration bounds of an object are calculated under given constraints of contact conditions, configurations of fingers, and bounds on the torques of joint actuators for each finger. Here, the rotational acceleration bounds can be applied as an important manipulability index when the multi-finger robot grasps an object. To verify the proposed method, we used a set of case studies with a simple multi-finger mechanism system. The achievable acceleration boundary in task space can be obtained successfully with the proposed method and the acceleration boundary depends on the configurations of fingers.     

Overcoming prefertilization barriers in the crossDiplotaxis siettiana × Brassica juncea using irradiated mentor pollen

Hybridization between the nearly extinct speciesDiplotaxis siettiana andBrassica juncea is prevented because of strong prefertilization barriers. Use of mentor pollen ofD. siettiana irradiated with 1000 Gy gamma radiation before the incompatible pollination led to fertilization. 5 d after pollination 17% ovules showed entry of pollen tubes, 10 d after pollination 27% ovules showed small globular embryos which grew no further. No embryos were found in control pollinations. Thus , use of irradiated mentor pollen brings about fertilization in this difficult cross and hybrids can be obtained if embryos are rescued.     

Effect of cold shock and freezing on loss of total lipids and phospholipids of buffalo spermatozoa (Bubalusbubalis)

Buffalo spermatozoa were subjected to cold shock and freezing treatments to assess loss of lipids and phospholipids. Cold shock and freezing resulted in significant loss of 15.8% and 34.6% of total lipids and 6.4% and 19.1% of phospholipids, respectively.     

Modeling of human CCR5 as Target for HIV-I and Virtual Screening with Marine Therapeutic compounds

Marine derivatives are of great pharmaceutical interest as inhibitory compound and search of bioactive compounds from Marine organism which is relatively new to medicinal chemistry. Our main aim in the study is to screen possible inhibitors against CCR5 which acts as co-receptor M-tropic HIV-1, through virtual screening of 122 Marine derived compounds from various organisms known to have biological activity. Homology Model of CCR5 was constructed using MODELLER and the Model was energy minimized and validated using PROCHECK to obtain a stable structure, which was further used for virtual screening of Marine derived compounds through molecular Docking studies using GOLD. The Docked complexes were validated and Enumerated based on the GOLD Scoring function to pick out the best Marine inhibitor based on GOLD score. Thus from the entire 122 Marine compounds which were Docked, we got best 4 of them with optimal GOLD Score. (LAMIVUDINE: 45.0218, BATZELLINE-D: 44.3852.ACYCLOVIR: 43.1362 and THIIOACETAMIDE: 42.7412) Further the Complexes were analyzed through LIGPLOT for their interaction for the 4 best docked Marine compounds. Thus from the Complex scoring and binding ability its deciphered that these Marine compounds could be promising inhibitors for M-tropic HIV-1 using CCR5 as Drug target yet pharmacological studies have to confirm it.     

Variations among cell lines in the synthesis of sphingolipids in de novo and recycling pathways

There are several pathways for the incorporation of sugars into glycosphingolipids (GSL). Sugars can be added to ceramide that contains sphinganine (dihydrosphingosine) synthesized de novo (pathway 1), to ceramide synthesized from sphingoid bases produced by hydrolysis of sphingolipids (pathway 2), and into GSL recycling from the endosomal pathway through the Golgi (pathway 3). We reported previously the surprising observation that SW13 cells, a human adrenal carcinoma cell line, synthesize most of their GSL in pathway 2. We now present data on the synthesis of GSL in four additional cell lines. Approximately 90% of sugar incorporation took place in pathway 2, and 10% or less in pathway 1, in human foreskin fibroblasts and NB41A3 neuroblastoma cells. In contrast, approximately 50-90% of sugar incorporation took place in pathway 1 in C2C12 myoblasts. The C2C12 cells divide more rapidly and synthesize 10-14 times as much GSL as the other three cell lines. In C6 glioma cells, approximately 30% of sugar incorporation occurred in pathway 1 and 60% in pathway 2. There was no relation between the utilization of pathways for GSL and sphingomyelin synthesis in foreskin fibroblasts and C2C12 cells. In both cells pathways 1 and 2 each accounted for 50% of incorporation of choline into sphingomyelin. In five of the six cell lines that we have studied, most GSL synthesis takes place in pathway 2. We suggest that when the need for synthesis is relatively low, as in slowly dividing cells, GSL are synthesized predominantly from sphingoid bases salvaged from the hydrolytic pathway. When cells are dividing more rapidly, the need for increased synthesis is met by upregulating the de novo pathway.      

An approach to delineate primers for a group of poorly conserved sequences incorporating the common motif region

Glutathione synthetase (gshB) has previously been reported to confer tolerance to acidic soil condition in Rhizobium species. Cloning the gene coding for this enzyme necessitates the designing of proper primer sets which in turn depends on the identification of high quality sequence similarity in multiple global alignments. In this experiment, a group of homologous gene sequences related to gshB gene (accession no: gi-86355669:327589-328536) of Rhizobium etli CFN 42, were extracted from NCBI nucleotide sequence databases using BLASTN and were analyzed for designing degenerate primers. However, the T-coffee multiple global alignment results did not show any block of conserved region for the above sequence set to design the primers. Therefore, we attempted to identify the location of common motif region based on multiple local alignments employing the MEME algorithm supported with MAST and Primer3. The results revealed some common motif regions that enabled us to design the primer sets for related gshB gene sequences. The result will be validated in wet lab.