Abstract: Among all microRNAs (miRNAs) in 12 plant species investigated in this study, only miR398 targeted the copper chaperone for superoxide dismutase (CCS). The nucleotide sequences of miRNA binding sites were located in the mRNA protein-coding sequence (CDS) and were highly homologous. These binding sites in CCS mRNA encoded a conservative GDLGTL hexapeptide. The binding sites for miR398 in the CDS of superoxide dismutase 1 mRNA encoded GDLGN pentapeptide. The conservative miR398 binding site located in the CDS of superoxide dismutase 2 mRNA encoded the GDLGNI hexapeptide. The miR398 binding site in the CDS of superoxide dismutase 3 mRNA encoded the GDLGNI or GDLGNV hexapeptide. Gene expression of the entire superoxide dismutase family in the studied plant species was regulated only by miR398. All members of the miR398 family, i.e. miR398a,b,c were connected to one site for each CuZnSOD and chaperone mRNA.
Abstract: Severe acute respiratory syndrome (SARS) is a respiratory disease in humans which is caused by the SARS coronavirus. The treatment of coronavirus-associated SARS has been evolving and so far there is no consensus on an optimal regimen. The mainstream therapeutic interventions for SARS involve broad-spectrum antibiotics and supportive care, as well as antiviral agents and immunomodulatory therapy. The Protein- Ligand interaction plays a significant role in structural based drug designing. In the present work we have taken the receptor Angiotensin converting enzyme 2 and identified the drugs that are commonly used against SARS. They are Lopinavir, Ritonavir, Ribavirin, and Oseltamivir. The receptor Angiotensin converting enzyme 2 (ACE-2) was docked with above said drugs and the energy value obtained are as follows, Lopinavir (-292.3), Ritonavir (-325.6), Oseltamivir (- 229.1), Ribavirin (-208.8). Depending on the least energy value we have chosen the best two drugs out of the four conventional drugs. We tried to improve the binding efficiency and steric compatibility of the two drugs namely Ritonavir and Lopinavir. Several modifications were made to the probable functional groups (phenylic, ketonic groups in case of Ritonavir and carboxylic groups in case of Lopinavir respectively) which were interacting with the receptor molecule. Analogs were prepared by Marvin Sketch software and were docked using HEX docking software. Lopinavir analog 8 and Ritonavir analog 11 were detected with significant energy values and are probable lead molecule. It infers that some of the modified drugs are better than the original drugs. Further work can be carried out to improve the steric compatibility of the drug based upon the work done above for a more energy efficient binding of the drugs to the receptor.
Abstract: The occurrence and removal of trace organic
contaminants in the aquatic environment has become a focus of
environmental concern. For the selective removal of carbamazepine
from loaded waters molecularly imprinted polymers (MIPs) were
synthesized with carbamazepine as template. Parameters varied were
the type of monomer, crosslinker, and porogen, the ratio of starting
materials, and the synthesis temperature. Best results were obtained
with a template to crosslinker ratio of 1:20, toluene as porogen, and
methacrylic acid (MAA) as monomer. MIPs were then capable to
recover carbamazepine by 93% from a 10-5 M landfill leachate
solution containing also caffeine and salicylic acid. By comparison,
carbamazepine recoveries of 75% were achieved using a nonimprinted
polymer (NIP) synthesized under the same conditions, but
without template. In landfill leachate containing solutions
carbamazepine was adsorbed by 93-96% compared with an uptake of
73% by activated carbon. The best solvent for desorption was
acetonitrile, with which the amount of solvent necessary and dilution
with water was tested. Selected MIPs were tested for their reusability
and showed good results for at least five cycles. Adsorption
isotherms were prepared with carbamazepine solutions in the
concentration range of 0.01 M to 5*10-6 M. The heterogeneity index
showed a more homogenous binding site distribution.
Abstract: Adenylate kinase (AK) catalyse the phosphotransferase
reaction plays an important role in cellular energy homeostasis. The
inhibitors of bacterial AK are useful in the treatment of several
bacterial infections. To the novel inhibitors of AK, docking studies
performed by using the 3D structure of Bacillus stearothermophilus
adenylate kinase from protein data bank (IZIP). 46 Quinoxaline
analogues were docked in 1ZIP and selected the highly interacting
compounds based on their binding energies, for further studies
Abstract: Protein-protein interactions (PPI) play a crucial role in many biological processes such as cell signalling, transcription, translation, replication, signal transduction, and drug targeting, etc. Structural information about protein-protein interaction is essential for understanding the molecular mechanisms of these processes. Structures of protein-protein complexes are still difficult to obtain by biophysical methods such as NMR and X-ray crystallography, and therefore protein-protein docking computation is considered an important approach for understanding protein-protein interactions. However, reliable prediction of the protein-protein complexes is still under way. In the past decades, several grid-based docking algorithms based on the Katchalski-Katzir scoring scheme were developed, e.g., FTDock, ZDOCK, HADDOCK, RosettaDock, HEX, etc. However, the success rate of protein-protein docking prediction is still far from ideal. In this work, we first propose a more practical measure for evaluating the success of protein-protein docking predictions,the rate of first success (RFS), which is similar to the concept of mean first passage time (MFPT). Accordingly, we have assessed the ZDOCK bound and unbound benchmarks 2.0 and 3.0. We also createda new benchmark set for protein-protein docking predictions, in which the complexes have experimentally determined binding affinity data. We performed free energy calculation based on the solution of non-linear Poisson-Boltzmann equation (nlPBE) to improve the binding mode prediction. We used the well-studied thebarnase-barstarsystem to validate the parameters for free energy calculations. Besides,thenlPBE-based free energy calculations were conducted for the badly predicted cases by ZDOCK and ZRANK. We found that direct molecular mechanics energetics cannot be used to discriminate the native binding pose from the decoys.Our results indicate that nlPBE-based calculations appeared to be one of the promising approaches for improving the success rate of binding pose predictions.
Abstract: Viral influenza A subtypes H5N1 and pandemic
H1N1 (pH1N1) have worldwide emerged and transmitted. The most
common anti-influenza drug for treatment of both seasonal and
pandemic influenza viruses is oseltamivir that nowadays becomes
resistance to influenza neuraminidase. The novel long-acting drug,
laninamivir, was discovered for treatment of the patients infected
with influenza B and influenza A viruses. In the present study,
laninamivir complexed with wild-type strain of both H5N1 and
pH1N1 viruses were comparatively determined the structures and
drug-target interactions by means of molecular dynamics (MD)
simulations. The results show that the hydrogen bonding interactions
formed between laninamivir and its binding residues are likely
similar for the two systems. Additionally, the presence of
intermolecular interactions from laninamivir to the residues in the
binding pocket is established through their side chains in accordance
with hydrogen bond interactions.
Abstract: Chikungunya virus (CHICKV) is an arboviruses belonging to family Tagoviridae and is transmitted to human through by mosquito (Aedes aegypti and Aedes albopictus) bite. A large outbreak of chikungunya has been reported in India between 2006 and 2007, along with several other countries from South-East Asia and for the first time in Europe. It was for the first time that the CHICKV outbreak has been reported with mortality from Reunion Island and increased mortality from Asian countries. CHICKV affects all age groups, and currently there are no specific drugs or vaccine to cure the disease. The need of antiviral agents for the treatment of CHICKV infection and the success of virtual screening against many therapeutically valuable targets led us to carry out the structure based drug design against Chikungunya nSP2 protease (PDB: 3TRK). Highthroughput virtual screening of publicly available databases, ZINC12 and BindingDB, has been carried out using the Openeye tools and Schrodinger LLC software packages. Openeye Filter program has been used to filter the database and the filtered outputs were docked using HTVS protocol implemented in GLIDE package of Schrodinger LLC. The top HITS were further used for enriching the similar molecules from the database through vROCS; a shape based screening protocol implemented in Openeye. The approach adopted has provided different scaffolds as HITS against CHICKV protease. Three scaffolds: Indole, Pyrazole and Sulphone derivatives were selected based on the docking score and synthetic feasibility. Derivatives of Pyrazole were synthesized and submitted for antiviral screening against CHICKV.
Abstract: MiRNAs participate in gene regulation of translation.
Some studies have investigated the interactions between genes and
intragenic miRNAs. It is important to study the miRNA binding sites
of genes involved in carcinogenesis. RNAHybrid 2.1 and ERNAhybrid
programmes were used to compute the hybridization free
energy of miRNA binding sites. Of these 54 mRNAs, 22.6%, 37.7%,
and 39.7% of miRNA binding sites were present in the 5'UTRs,
CDSs, and 3'UTRs, respectively. The density of the binding sites for
miRNAs in the 5'UTR ranged from 1.6 to 43.2 times and from 1.8 to
8.0 times greater than in the CDS and 3'UTR, respectively. Three
types of miRNA interactions with mRNAs have been revealed: 5'-
dominant canonical, 3'-compensatory, and complementary binding
sites. MiRNAs regulate gene expression, and information on the
interactions between miRNAs and mRNAs could be useful in
molecular medicine. We recommend that newly described sites
undergo validation by experimental investigation.
Abstract: This paper discusses a new model of Islamic code of
ethics for directors. Several corporate scandals and local (example
Transmile and Megan Media) and overseas corporate (example
Parmalat and Enron) collapses show that the current corporate
governance and regulatory reform are unable to prevent these events
from recurring. Arguably, the code of ethics for directors is under
research and the current code of ethics only concentrates on binding
the work of the employee of the organization as a whole, without
specifically putting direct attention to the directors, the group of
people responsible for the performance of the company. This study
used a semi-structured interview survey of well-known Islamic
scholars such as the Mufti to develop the model. It is expected that
the outcome of the research is a comprehensive model of code of
ethics based on the Islamic principles that can be applied and used by
the company to construct a code of ethics for their directors.
Abstract: Writer identification is one of the areas in pattern
recognition that attract many researchers to work in, particularly in
forensic and biometric application, where the writing style can be
used as biometric features for authenticating an identity. The
challenging task in writer identification is the extraction of unique
features, in which the individualistic of such handwriting styles
can be adopted into bio-inspired generalized global shape for
writer identification. In this paper, the feasibility of generalized
global shape concept of complimentary binding in Artificial
Immune System (AIS) for writer identification is explored. An
experiment based on the proposed framework has been conducted
to proof the validity and feasibility of the proposed approach for
off-line writer identification.
Abstract: This paper has examined the energy consumption characteristics in six different buildings including apartments, offices, commercial buildings, hospitals, hotels and educational facilities. Then 5-hectare (50000m2) development site for respective building-s type has been assumed as case study to evaluate the introduction effect of Combined Heat and Power (CHP). All kinds of CHP systems with different distributed generation technologies including Gas Turbine (GT), Gas Engine (GE), Diesel Engine (DE), Solid Oxide Fuel Cell (SOFC) and Polymer Electrolyte Fuel Cell (PEFC), have been simulated by using HEATMAP, CHP system analysis software. And their primary energy utilization efficiency, energy saving ratio and CO2 reduction ratio have evaluated and compared respectively. The results can be summarized as follows: Various buildings have their special heat to power ratio characteristics. Matching the heat to power ratio demanded from an individual building with that supplied from a CHP system is very important. It is necessary to select a reasonable distributed generation technologies according to the load characteristics of various buildings. Distributed generation technologies with high energy generating efficiency and low heat to power ratio, like SOFC and PEFC is more reasonable selection for Building Combined Heat and Power (BCHP). CHP system is an attractive option for hotels, hospitals and apartments in Japan. The users can achieve high energy saving and environmental benefit by introducing a CHP systems. In others buildings, especially like commercial buildings and offices, the introduction of CHP system is unreasonable.
Abstract: Recent research has shown that milk proteins can
yield bioactive peptides with opioid, mineral binding,
cytomodulatory, antihypertensive, immunostimulating, antimicrobial
and antioxidative activity in the human body. Bioactive peptides are
encrypted in milk proteins and are only released by enzymatic
hydrolysis in vivo during gastrointestinal digestion, food processing
or by microbial enzymes in fermented products. At present
significant research is being undertaken on the health effects of
bioactive peptides. A variety of naturally formed bioactive peptides
have been found in fermented dairy products, such as yoghurt, sour
milk and cheese. In particular, antihypertensive peptides have been
identified in fermented milks, whey and ripened cheese. Some of
these peptides have been commercialized in the form of fermented
milks. Bioactive peptides have the potential to be used in the
formulation of health-enhancing nutraceuticals, and as potent drugs
with well defined pharmacological effects.
Abstract: This study was aimed to study the probability about
the production of fiberboard made of durian rind through latex with
phenolic resin as binding agent. The durian rind underwent the
boiling process with NaOH [7], [8] and then the fiber from durian
rind was formed into fiberboard through heat press. This means that
durian rind could be used as replacement for plywood in plywood
industry by using durian fiber as composite material with adhesive
substance. This research would study the probability about the
production of fiberboard made of durian rind through latex with
phenolic resin as binding agent. At first, durian rind was split,
exposed to light, boiled and steamed in order to gain durian fiber.
Then, fiberboard was tested with the density of 600 Kg/m3 and 800
Kg/m3. in order to find a suitable ratio of durian fiber and latex.
Afterwards, mechanical properties were tested according to the
standards of ASTM and JIS A5905-1994. After the suitable ratio was
known, the test results would be compared with medium density
fiberboard (MDF) and other related research studies. According to
the results, fiberboard made of durian rind through latex with
phenolic resin at the density of 800 Kg/m3 at ratio of 1:1, the
moisture was measured to be 5.05% with specific gravity (ASTM D
2395-07a) of 0.81, density (JIS A 5905-1994) of 0.88 g/m3, tensile
strength, hardness (ASTM D2240), flexibility or elongation at break
yielded similar values as the ones by medium density fiberboard
(MDF).
Abstract: Free Hemoglobin promotes the accumulation of
hydroxyl radicals by the heme iron, which can react with endogenous
hydrogen peroxide to produce free radicals which may cause severe
oxidative cell damage. Haptoglobin binds to Hemoglobin strongly
and Haptoglobin-Hemoglobin binding is irreversible. Peroxidase
activity of Haptoglobin(2-2)-Hemoglobin complex was assayed by
following increase of absorption of produced tetraguaiacol as the
second substrate of Haptoglobin-Hemoglobin complex at 470 nm and
42°C by UV-Vis spectrophotometer. The results have shown that
peroxidase activity of Haptoglobin(2-2)-Hemoglobin complex is
modulated via homotropic effect of hydrogen peroxide as allostric
substrate. On the other hand antioxidant property of Haptoglobin(2-
2)-Hemoglobin was increased via heterotropic effect of the two drugs
(especially ampicillin) on peroxidase activity of the complex. Both
drugs also have mild effect on quality of homotropic property of
peroxidase activity of Haptoglobin(2-2)-Hemoglobin complex.
Therefore, in vitro studies show that the two drugs may help Hp-Hb
complex to remove hydrogen peroxide from serum at pathologic
temperature ature (42 C).
Abstract: Bacterial molecular chaperone DnaK plays an essential role in protein folding, stress response and transmembrane targeting of proteins. DnaKs from many bacterial species, including Escherichia coli, Salmonella typhimurium and Haemophilus infleunzae are the molecular targets for the insect-derived antimicrobial peptide pyrrhocoricin. Pyrrhocoricin-like peptides bind in the substrate recognition tunnel. Despite the high degree of crossspecies sequence conservation in the substrate-binding tunnel, some bacteria are not sensitive to pyrrhocoricin. This work addresses the molecular mechanism of resistance of Helicobacter pylori DnaK to pyrrhocoricin. Homology modelling, structural and sequence analysis identify a single aminoacid substitution at the interface between the lid and the β-sandwich subdomains of the DnaK substrate-binding domain as the major determinant for its resistance.
Abstract: Tuberculosis (TB) is a bacterial infectious disease caused by the obligate human pathogen, Mycobacterium tuberculosis. Multidrug-resistant tuberculosis (MDR-TB) is a global reality that threatens tuberculosis control. Resistance to antibiotic Rifampicin, occurs in 95% of cases through nucleotide substitutions in an 81-bp core region of the rpoB i.e; beta subunit of DNA dependant RNA polymerase. In this paper, we studied the Rifampicin-rpoB receptor interactions In silico. First, homology modeling was performed to obtain the three dimensional structure of Mycobacterium rpoB. Sixty analogs of Rifampicin were prepared using Marvin sketch software. Both original Rifampicin and the analogs were docked with rpoB and energy values were obtained. Out of sixty analogs, 43 analogs had lesser energy values than conventional Rifampicin and hence are predicted to have greater binding affinity to rpoB. Thus, this study offers a route for the development of Rifampicin analogs against multi drug resistant Mycobacterium rpoB.
Abstract: MANEMO is the integration of Network Mobility
(NEMO) and Mobile Ad Hoc Network (MANET). A MANEMO
node has an interface to both a MANET and NEMO network, and
therefore should choose the optimal interface for packet delivery,
however such a handover between interfaces will introduce packet
loss. We define the steps necessary for a MANEMO handover,
using Mobile IP and NEMO to signal the new binding to the
relevant Home Agent(s). The handover steps aim to minimize the
packet loss by avoiding waiting for Duplicate Address Detection
and Neighbour Unreachability Detection. We present expressions for
handover delay and packet loss, and then use numerical examples to
evaluate a MANEMO handover. The analysis shows how the packet
loss depends on level of nesting within NEMO, the delay between
Home Agents and the load on the MANET, and hence can be used
to developing optimal MANEMO handover algorithms.
Abstract: This research studied the hypoglycemic effect of
water soluble polysaccharide (WSP) extracted from yam (Dioscorea
hispida) tuber by three different methods: aqueous extraction, papain
assisted extraction, and tempeh inoculums assisted extraction. The
two later extraction methods were aimed to remove WSP binding
protein to have more pure WSP. The hypoglycemic activities were
evaluated by means in vivo test on alloxan induced hyperglycemic
rats, glucose response test (GRT), in situ glucose absorption test
using everted sac, and short chain fatty acids (SCFAs) analysis. All
yam WSP extracts exhibited ability to decrease blood glucose level in
hyperglycemia condition as well as inhibited glucose absorption and
SCFA formation. The order of hypoglycemic activity was tempeh
inoculums assisted- >papain assisted- >aqueous WSP extracts. GRT
and in situ glucose absorption test showed that order of inhibition
was papain assisted- >tempeh inoculums assisted- >aqueous WSP
extracts. Digesta of caecum of yam WSP extracts oral fed rats had
more SCFA than control. Tempeh inoculums assisted WSP extract
exhibited the most significant hypoglycemic activity.
Abstract: Hypertension is characterized with stress on the heart and blood vessels thus increasing the risk of heart attack and renal diseases. The Renin angiotensin system (RAS) plays a major role in blood pressure control. Renin is the enzyme that controls the RAS at the rate-limiting step. Our aim is to develop new drug-like leads which can inhibit renin and thereby emerge as therapeutics for hypertension. To achieve this, molecular dynamics (MD) simulation and receptor-based pharmacophore modeling were implemented, and three rennin-inhibitor complex structures were selected based on IC50 value and scaffolds of inhibitors. Three pharmacophore models were generated considering conformations induced by inhibitor. The compounds mapped to these models were selected and subjected to drug-like screening. The identified hits were docked into the active site of renin. Finally, hit1 satisfying the binding mode and interaction energy was selected as possible lead candidate to be used in novel renin inhibitors.
Abstract: New graph similarity methods have been proposed in this work with the aim to refining the chemical information extracted from molecules matching. For this purpose, data fusion of the isomorphic and nonisomorphic subgraphs into a new similarity measure, the Approximate Similarity, was carried out by several approaches. The application of the proposed method to the development of quantitative structure-activity relationships (QSAR) has provided reliable tools for predicting several pharmacological parameters: binding of steroids to the globulin-corticosteroid receptor, the activity of benzodiazepine receptor compounds, and the blood brain barrier permeability. Acceptable results were obtained for the models presented here.