The influential role of the epigenome in orchestrating genome-wide transcriptional activation instigates the demand for the artificial genetic switches with distinct DNA sequence recognition. Recently, we developed a novel class of epigenetically active small molecules called SAHA-PIPs by conjugating selective DNA binding pyrrole-imidazole polyamides (PIPs) with the histone deacetylase inhibitor SAHA. Screening studies revealed that certain SAHA-PIPs trigger targeted transcriptional activation of pluripotency and germ cell genes in mouse and human fibroblasts, respectively. Through microarray studies and functional analysis, here we demonstrate for the first time the remarkable ability of thirty-two different SAHA-PIPs to trigger the transcriptional activation of exclusive clusters of genes and noncoding RNAs. QRT-PCR validated the microarray data, and some SAHA-PIPs activated therapeutically significant genes like KSR2. Based on the aforementioned results, we propose the potential use of SAHA-PIPs as reagents capable of targeted transcriptional activation.
Utilization of biological materials in synthesis of nanoparticles is one of the hottest topics in modern nanoscience and nanotechnology. In the present investigation, the silver nanoparticles were synthesized by using the leaf and stem extract of Piper nigrum. The synthesized nanoparticle was characterized by UV-vis spectroscopy, X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), energy dispersive X-ray analysis (EDAX), and Fourier Transform Infrared Spectroscopy (FTIR). The observation of the peak at 460 nm in the UV-vis spectra for leaf- and stem-synthesized silver nanoparticles reveals the reduction of silver metal ions into silver nanoparticles. Further, XRD analysis has been carried out to confirm the crystalline nature of the synthesized silver nanoparticles. The TEM images show that the leaf- and stem-synthesized silver nanoparticles were within the size of about 7–50 nm and 9–30 nm, respectively. The FTIR analysis was performed to identify the possible functional groups involved in the synthesis of silver nanoparticles. Further, the antibacterial activity of the green-synthesized silver nanoparticles was examined against agricultural plant pathogens. The antibacterial property of silver nanoparticles is a beneficial application in the field of agricultural nanotechnology.
This paper proposes an artificial bee colony (ABC) algorithm for solving optimal power flow (OPF) problem. The objective of the OPF problem is to minimize total cost of thermal units while satisfying the unit and system constraints such as generator capacity limits, power balance, line flow limits, bus voltages limits, and transformer tap settings limits. The ABC algorithm is an optimization method inspired from the foraging behavior of honey bees. The proposed algorithm has been tested on the IEEE 30-bus, 57-bus, and 118-bus systems. The numerical results have indicated that the proposed algorithm can find high quality solution for the problem in a fast manner via the result comparisons with other methods in the literature. Therefore, the proposed ABC algorithm can be a favorable method for solving the OPF problem.
This paper examines how estimates of the price elasticity of demand for beer vary with the choice of alcohol price series examined. Our most important finding is that the commonly used ACCRA price data are unlikely to reliably indicate alcohol demand elasticities—estimates obtained from this source vary drastically and unpredictably. As an alternative, researchers often use beer taxes to proxy for alcohol prices. While the estimated beer taxes elasticities are more stable, there are several problems with using taxes, including difficulties in accounting for cross-price effects. We believe that the most useful estimates reported in this paper are obtained using annual Uniform Product Code (UPC) “barcode” scanner data on grocery store alcohol prices. These estimates suggest relatively low demand elasticity, probably around −0.3, with evidence that the elasticities are considerably overstated in models that control for beer but not wine or spirits prices.
MyosinVa (MyoVa) mediates F-actin-based vesicular transport toward the plasma membrane and is found at neuronal postsynaptic densities (PSDs), but the role of MyoVa in synaptic development and function is largely unknown. Here, in studies using the dominant negative MyoVa neurological mutant mouse Flailer, we find that MyoVa plays an essential role in activity-dependent delivery of PSD-95 and other critical PSD molecules to synapses and in endocytosis of AMPA-type glutamate receptors (AMPAR) in the dendrites of CNS neurons. MyoVa is known to carry a complex containing the major scaffolding proteins of the mature PSD, PSD-95, SAPAP1/GKAP, Shank and Homer, to dendritic spine synapses. In Flailer, neurons show abnormal dendritic shaft localization of PSD-95, stargazin, dynamin3, AMPA glutamate receptors (AMPARs) and abnormal spine morphology. Flailer neurons also have abnormally high AMPAR miniature current frequencies and spontaneous AMPAR currents that are more frequent and larger than in WT while numbers of NMDAR containing synapses remain normal. The AMPAR abnormalities are consistent with a severely disrupted developmental regulation of long-term depression that we find in cortical Flailer neurons. Thus MyoVa plays a fundamentally important role both in localizing mature glutamate synapses to spines and in organizing the synapse for normal function. For this reason Flailer mice will be valuable in further dissecting the role of MyoVa in normal synaptic and circuit refinement and also in studies of neurological and neuropsychiatric diseases where disruptions of normal glutamate synapses are frequently observed.
Bacterial community composition in the marine environment differs from one geographical location to another. Reports that delineate the bacterial diversity of different marine samples from geographically similar location are limited. The present study aims to understand whether the bacterial community compositions from different marine samples harbour similar bacterial diversity since these are geographically related to each other.
Methods and Principal Findings
In the present study, 16S rRNA deep sequencing analysis targeting V3 region was performed using Illumina bar coded sequencing. A total of 22.44 million paired end reads were obtained from the metagenomic DNA of Marine sediment, Rhizosphere sediment, Seawater and the epibacterial DNA of Seaweed and Seagrass. Diversity index analysis revealed that Marine sediment has the highest bacterial diversity and the least bacterial diversity was observed in Rhizosphere sediment. Proteobacteria, Actinobacteria and Bacteroidetes were the dominant taxa present in all the marine samples. Nearly 62–71% of rare species were identified in all the samples and most of these rare species were unique to a particular sample. Further taxonomic assignment at the phylum and genus level revealed that the bacterial community compositions differ among the samples.
This is the first report that supports the fact that, bacterial community composition is specific for specific samples irrespective of its similar geographical location. Existence of specific bacterial community for each sample may drive overall difference in bacterial structural composition of each sample. Further studies like whole metagenomic sequencing will throw more insights to the key stone players and its interconnecting metabolic pathways. In addition, this is one of the very few reports that depicts the unexplored bacterial diversity of marine samples (Marine sediment, Rhizosphere sediment, Seawater) and the host associated marine samples (Seaweed and Seagrass) at higher depths from uncharacterised coastal region of Palk Bay, India using next generation sequencing technology.
Shortfin mako shark haemoglobin adopts an unliganded deoxy T state conformation, which is shown from the quaternary structural features, interface interactions and heme binding sites of different subunits of haemoglobin with high-resolution X-ray data.
Haemoglobin (Hb) is a tetrameric iron-containing protein that carries oxygen from the lungs to tissues and carbon dioxide from tissues back to the lungs. Pisces are the advanced aquatic vertebrates capable of surviving at wide depth ranges. The shortfin mako shark (SMS) is the pelagic, largest, fastest and most sophisticated species of the shark kingdom with well developed eyes. Mostly the pisces species are cold blooded in nature. Distinctly, the SMSs are warm-blooded animals with an advanced circulatory system. SMSs are capable of maintaining elevated muscle temperatures up to 33 K above the ambient water temperatures at a depth of 150–500 m. SMSs have a diverged air-breathing mechanism compared with other vertebrates. The haemoglobin molecule consists of four polypeptide chains, namely two α chains, each with 140 amino acids and two β chains each having 136 amino acids. The SMS Hb was found to crystallize in monoclinic space group P21 using the hanging-drop vapour-diffusion method at room temperature. The crystal packing parameters for the SMS Hb structure contain one whole biological molecule in the asymmetric unit with a solvent content of 47%. The SMS Hb quaternary structural features interface–interface interactions and heme binding sites are discussed with different state Hbs and the results reveal that SMS Hb adopts an unliganded deoxy T state conformation.
haemoglobin; shark; monoclinic; oxygen transport; crystal structure; heme; tetramer
Objective: Children with a Cleft Palate (CLP) and with or without cleft lips (non-syndromic) universally present with Secretory Otitis Media (SOM). The purpose of this study was to determine the incidence of secretory otitis media that occurs in patients with cleft palates and to confirm the existence of these manifestations by doing a Basic Audiologic Evaluation (BAE).
Material and Methods: A retrospective study was done on forty four male and female children who were within the 2 to 14 years age range, with non-syndromic cleft palates with or without cleft lips, with the symptoms of SOM. Otoscopy examinations were done in all the cases. X-rays of the mastoids (both sides) were done in all the cases to detect the pneumatization of the mastoid air cell system. The Basic Audiologic Evaluation (BAE) includes an evaluation by tympanometry of the middle ear function and an evaluation by pure tone audiometry to establish the type of hearing loss.
Results: A majority of the patients (47.27%) were in the age group of eight-to-fourteen (8-14) years. The Basic Audiologic Evaluation (BAE) revealed that 77.27% of the children had presented with normal hearing; 13.6% had conductive hearing loss and 2.2% had presented with a mixed hearing loss. We noticed that 68.2% of the children had type A curves; 21.2% of the children had type C tympanometry curves; 7.1% had type B curves and 3.5% had Ad curves. The contralateral acoustic reflex was present in 54.5% of the children and 45.5% did not have this reflex. A majority of the patients (46%) showed sclerotic changes in their mastoid air cell systems in the X-rays of the mastoids.
Conclusion: The significantly higher prevalence of SOM in the children with cleft was confirmed by the study. Also, the hearing loss which was associated with SOM was evident and it demonstrated that there was a high prevalence of a mild conductive hearing loss when SOM was present. The cleft palate contributed to the occurrence of the secretory otitis media and it required proper ENT and audiological follow ups.
Cleft palate; Secretory otitis media; Hearing loss
Developing countries like India are facing a double burden of communicable and non-communicable diseases. Stroke is one of the leading causes of death and disability in India. The estimated adjusted prevalence rate of stroke range, 84-262/100,000 in rural and 334-424/100,000 in urban areas. The incidence rate is 119-145/100,000 based on the recent population based studies. There is also a wide variation in case fatality rates with the highest being 42% in Kolkata. Stroke units are predominantly available in urban areas that too in private hospitals. Intravenous (IV) and intra-arterial thrombolysis (IA) are commonly used in India. In the on-going Indo USA National stroke registry the rate of IV thrombolysis is 11%. Stroke rehabilitation is not well developed in India due to lack of personnel. Organised rehabilitation services are available in the country but they are mainly in private hospitals of the cities. Even though India is a leading generic drugs producer still many people can't afford the commonly used secondary prevention drugs. As a first step the Government of India has started the National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases & Stroke (NPCDCS). The government is focusing on early diagnosis, management, infrastructure, public awareness and capacity building at different levels of health care for all the non-communicable diseases including stroke. An organised effort from both the government and the private sector is needed to tackle the stroke epidemic in India.
Stroke; India; Epidemiology; Incidence; Stroke unit; Rehabilitation
The authors sought to determine whether nebivolol treatment results in changes in blood pressure (BP), nitric oxide bioavailability, and vascular function in obese African Americans with recently diagnosed stage 1 hypertension. Forty-three obese, hypertensive African Americans (mean BP: systolic, 148.8±14.3 mm Hg; diastolic, 90.4±8.2 mm Hg) were treated with nebivolol (5–10 mg/d) for 8 weeks. Primary outcomes were change in systolic and diastolic BP and efficacy in reaching normotensive BP. Mean systolic BP decreased by 9.2±14 mm Hg (P<.005) and diastolic BP decreased 6.8±9 mm Hg (P<.005) with 8 weeks of therapy. Significant improvements were seen in arterial compliance with nebivolol treatment as measured by aortic augmentation index (P<.005) and time to wave reflection (P=.013). Nebivolol treatment improved endothelial function as measured by flow-mediated dilation (P<.005). Levels of erythrocyte cellular superoxide dismutase increased with nebivolol, indirectly suggesting increased bioavailability of nitric oxide (P<.005). Monotherapy with nebivolol in obese, hypertensive African Americans results in significant systolic and diastolic BP reduction by mechanisms that include improved vascular function and compliance.
The purpose of the study was to identify the predictors of short-term mortality in patients undergoing percutaneous dilatational tracheostomy (PDT).
Materials and Methods
Retrospective analysis of data pertaining to adult patients who underwent PDT between July 2005 and June 2008 in an urban, academic, tertiary care medical center was done. Clinical and demographic data were analyzed for 483 patients undergoing PDT via multivariate logistic regression.
Mortality data were examined at in-hospital, 14, 30, and 180 days postprocedure. Overall mortality rates were 11% at 14 days, 19% at 30 days, and 40% at 180 days. In-hospital mortality was 30%.
Patients undergoing PDT have significant short-term mortality with 11% dying within 14 days and an in-hospital mortality rate of 30%. We identified an index diagnosis of ventilator-associated pneumonia and trauma to be associated with a higher survival rate, whereas older age, oncological diagnosis, cardiogenic shock, and ventricular-assist devices were associated with higher mortality. There is significant heterogeneity in both underlying diagnosis and patient outcomes, and these factors should be considered when deciding to perform this procedure and discussed with patients/family members to provide a realistic expectation of potential prognosis.
Tracheostomy; Mortality; Critically ill; Intensive care
Our previous analyses using the Stress Recognition subscale of the Safety Attitudes Questionnaire (SAQ) resulted in significant effect estimates with equally opposing explanations. We suspected construct validity issues and investigated such using our own data and correlation matrices of previous published studies.
The correlation matrices for each of the SAQ subscales from two previous studies by Speroff and Taylor were replicated and compared. The SAS Proc Factor procedure and the PRIORS = SMC option were used to perform Common Factor Analysis.
The correlation matrices of both studies were very similar. Teamwork, Safety Climate, Job Satisfaction, Perceptions of Management and Working Conditions were well-correlated. The correlations ranged from 0.53 to 0.76. For Stress Recognition correlations ranged from -0.15 to 0.03. Common Factor Analysis confirmed the isolation of Stress Recognition. CFA returned a strong one-factor model that explained virtually all of the communal variance. Stress Recognition loaded poorly on this factor in both instances, and the CFA indicated that 96.4-100.0% of the variance associated with Stress Recognition was unique to that subscale, and not shared with the other 5 subscales.
We conclude that the Stress Recognition subscale does not fit into the overall safety climate construct the SAQ intended to reflect. We recommend that this domain be omitted from overall safety climate scale score calculations, and clearly identified as an important yet distinct organizational construct. We suggest that this subscale be investigated for its true meaning, characterized as such, and findings conveyed to SAQ end users. We make no argument against Stress Recognition as an important organizational metric, rather we suggest that as a stand-alone construct its current packaging within the SAQ may be misleading for those intent on intervention development and evaluation in healthcare settings if they interpret Stress Recognition results as emblematic of safety climate.
Safety attitudes questionnaire; Stress recognition; Factor analysis
The focal intent of this study was to find out an alternative strategy for the antibiotic usage against bacterial infections. The quorum sensing inhibitory (QSI) activity of marine sponges collected from Palk Bay, India was evaluated against acyl homoserine lactone (AHL) mediated violacein production in Chromobacteriumviolaceum (ATCC 12472), CV026 and virulence gene expressions in clinical isolate Serratiamarcescens PS1. Out of 29 marine sponges tested, the methanol extracts of Aphrocallistesbocagei (TS 8), Haliclona (Gellius) megastoma (TS 25) and Clathriaatrasanguinea (TS 27) inhibited the AHL mediated violacein production in C. violaceum (ATCC 12472) and CV026. Further, these sponge extracts inhibited the AHL dependent prodigiosin pigment, virulence enzymes such as protease, hemolysin production and biofilm formation in S. marcescens PS1. However, these sponge extracts were not inhibitory to bacterial growth, which reveals the fact that the QSI activity of these extracts was not related to static or killing effects on bacteria. Based on the obtained results, it is envisaged that the marine sponges could pave the way to prevent quorum sensing (QS) mediated bacterial infections.
Marine sponges; Quorum sensing inhibition; Acyl homoserine lactone; Serratia marcescens PS1; Biofilm; Bacterial pathogenesis
Oral submucous fibrosis (OSF) is a chronic, progressive, potentially malignant condition affecting the oral cavity and frequently involving the upper part of the aerodigestive tract including the oropharynx and the upper part of the esophagus. It is characterized by juxtaepithelial inflammatory reaction and progressive fibrosis of lamina propria, leading to stiffening of the oral mucosa eventually causing trismus. This condition is associated with significant morbidity and high risk of malignancy. Over the years, several drugs and combinations have been tried for the treatment of submucous fibrosis, but with limited success, because of its unclear molecular pathogenesis. Till date, there are no known effective treatments for OSF. The aim of this article is to emphasize on the molecular changes taking place in OSF and possible therapeutic interventions.
Classification; oral submucous fibrosis; pathogenesis; treatment
Background & objectives:
Subinhibitory concentrations (sub-MICs) of antibiotics, although not able to kill bacteria, but influence bacterial virulence significantly. Fluoroquinolones (FQs) which are used against other bacterial pathogens creates resistance in non-targeted Streptococcus pyogenes. This study was undertaken to characterize the effect of sub-MICs of FQs on S. pyogenes biofilm formation.
Biofilm forming six M serotypes M56, st38, M89, M65, M100 and M74 of S. pyogenes clinical isolates were challenged against four FQs namely, ciprofloxacin, ofloxacin, levofloxacin and norfloxacin. The antibiofilm potential of these FQs was analysed at their subinhibitory concentrations (1/2 to 1/64 MIC) using biofilm assay, XTT reduction assay, scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM).
Among the four FQs tested, ofloxacin and levofloxacin at 1/2 MIC showed the maximum inhibition (92%) of biofilm formation against M56 and M74 serotypes. FQs effectively interfered in the microcolony formation of S. pyogenes isolates at 1/2 to 1/8 sub-MICs. Inhibition of biofilm formation was greatly reduced beyond 1/16 MICs and allowed biofilm formation. XTT reduction assay revealed the increase in metabolic activity of S. pyogenes biofilm against the decrease in FQs concentration. SEM and CLSM validated the potential of sub-MICs of FQs against the six S. pyogenes.
Interpretation & conclusions:
Our results showed that the inhibitory effect all four FQs on S. pyogenes biofilm formation was concentration dependent. FQs at proper dosage can be effective against S. pyogenes and lower concentrations may allow the bacteria to form barriers against the antibiotic in the form of biofilm.
Biofilms; confocal laser scanning microscopy; fluoroquinolones; Streptococcus pyogenes; subinhibitory concentration
Rectourethral fistula is an uncommon but devastating condition. Traumatic rectourethral fistula is still uncommon and repair of traumatic rectourethral fistula involves a complex procedure. Most of the urologists would prefer to repair the fistula through perineal route especially when urethral reconstruction is also required. The repaired ends of the fistula are separated with various interposition flaps and grafts in order to prevent recurrence. Gracilis interposition muscle flap is commonly used. We describe the first case of traumatic rectourethral fistula repair in a 45-year-old man using interposition of a porcine small intestinal submucosal (Biodesign™ (Surgisis®) graft.
Rectourethral fistula; small intestinal submucosa; stricture; trauma
The reactivity of copper complexes of three different 2nd generation bispidine-based ligands (bispidine = 3,7-diazabicyclo[3.3.1]nonane; mono- and bis-tetradentate; exclusively tertiary amine donors) with dioxygen [(reversible) binding of dioxygen by copper(I)] is reported. The UV-vis, electrospray ionization mass spectra (ESI-MS), electron paramagnetic resonance (EPR) and vibrational spectra (resonance Raman,rR) of the dioxygen adducts indicate that, depending on the ligand and reaction conditions, several different species (mono- and dinuclear, superoxo, peroxo and hydroperoxo), partially in equilibrium with each other, are formed. Minor changes in the ligand structure and/or experimental conditions (solvent, temperature, relative concentrations) allow switching between the different forms. With one of the ligands, an end-on-peroxo-dicopper(II) and a mononuclear copper(II)-hydroperoxo complex could be characterized. With another ligand, reversible dioxygen binding was observed, leading to a meta-stable copper(II)-superoxo complex, and the amount of dioxygen involved in the reversible binding to CuI was determined quantitatively. The mechanism of dioxygen binding as well as the preference of each of the three ligands for a particular dioxygen adduct is discussed on the basis of a computational (DFT) analysis.
A β-cyclodextrin (β-Cyd) inclusion complex containing azomethine as a guest was prepared by kneading method with aliquot addition of ethanol. The product was characterized by Fourier Transform Infrared (FTIR) spectrometer, 1H Nuclear Magnetic Resonance (1H NMR) and Thermogravimetric Analyzer (TGA), which proves the formation of the inclusion complex where the benzyl part of azomethine has been encapsulated by the hydrophobic cavity of β-Cyd. The interaction of β-Cyd and azomethine was also analyzed by means of spectrometry by UV-Vis spectrophotometer to determine the formation constant. The formation constant was calculated by using a modified Benesi-Hildebrand equation at 25 °C. The apparent formation constant obtained was 1.29 × 104 L/mol. Besides that, the stoichiometry ratio was also determined to be 1:1 for the inclusion complex of β-Cyd with azomethine.
β-cyclodextrin; azomethine; Schiff bases; inclusion complex
Aromatic-aromatic hydrogen bonds are important in many areas of chemistry, biology and materials science. In this study we have
analyzed the roles played by the π-π interactions in interleukins (ILs) and tumor necrosis factor (TNF) proteins. Majority of π-π
interacting residues are conserved in ILs and TNF proteins. The accessible surface area calculations in these proteins reveal that
these interactions might be important in stabilizing the inner core regions of these proteins. In addition to π-π interactions, the
aromatic residues also form π-networks in ILs and TNF proteins. The results obtained in the present study indicate that π-π
interactions and π-π networks play important roles in the structural stability of ILs and TNF proteins.
π-π interactions; TNF proteins; ILs; structure; stability; π-network
Natural epigenetic processes precisely orchestrate the intricate gene network by expressing and suppressing genes at the right place and time, thereby playing an essential role in maintaining the cellular homeostasis. Environment-mediated alteration of this natural epigenomic pattern causes abnormal cell behavior and shifts the cell from the normal to a diseased state, leading to certain cancers and neurodegenerative disorders. Unlike heritable diseases that are caused by the irreversible mutations in DNA, epigenetic errors can be reversed. Inheritance of epigenetic memory is also a major concern in the clinical translation of the Nobel Prize-winning discovery of induced pluripotent stem cell technology. Consequently, there is an increasing interest in the development of novel epigenetic switch-based therapeutic strategies that could potentially restore the heritable changes in epigenetically inherited disorders. Here we give a comprehensive overview of epigenetic inheritance and suggest the prospects of therapeutic gene modulation using epigenetic-based drugs, in particular histone deacetylase inhibitors. This review suggests that there is a need to develop therapeutic strategies that effectively mimic the natural environment and include the ways to modulate the gene expression at both the genetic and epigenetic levels. The development of tailor-made small molecules that could epigenetically alter DNA in a sequence-specific manner is a promising approach for restoring defects in an altered epigenome and may offer a sustainable solution to some unresolved clinical issues.
epigenetic inheritance; chemical mimics; HDAC inhibitors; regenerative medicine; cancer treatment; programmable genetic switches; histone code; epigenetic switch based therapy; future medicine.
Dengue virus belongs to the virus family Flaviviridae. Dengue hemorrhagic disease caused by dengue virus is a public health
problem worldwide. The viral non structural 2B and 3 (NS2B-NS3) protease complex is crucial for virus replication and hence, it is
considered to be a good anti-viral target. Leaf extracts from Carica papaya is generally prescribed for patients with dengue fever, but
there are no scientific evidences for its anti-dengue activity; hence we intended to investigate the anti-viral activity of compounds
present in the leaves of Carica papaya against dengue 2 virus (DENV-2). We analysed the anti-dengue activities of the extracts from
Carica papaya by using bioinformatics tools. Interestingly, we find the flavonoid quercetin with highest binding energy against
NS2B-NS3 protease which is evident by the formation of six hydrogen bonds with the amino acid residues at the binding site of the
receptor. Our results suggest that the flavonoids from Carica papaya have significant anti-dengue activities.
ADME - Absorption, distribution, metabolism and excretion,
BBB - Blood brain barrier,
CYP - Cytochrome P450,
DENV - – Dengue virus,
DHF - Dengue hemorrhagic fever,
DSS - Dengue shock syndrome,
GCMS - – Gas chromatography- Mass spectrometry,
MOLCAD - Molecular Computer Aided Design,
NS - Non structural,
PDB - Protein data bank,
PMF - Potential Mean Force.
Dengue virus; Carica papaya; Quercetin; ADMET; NS2B-NS3 protease
The effect of various solvent extracts of Gelidiella acerosa on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities was investigated. AChE and BuChE inhibitory activities were analyzed by spectrophotometric method. Phytochemical screening of the compounds present in the solvent extracts was done qualitatively. Characterization of the compounds present in the benzene extract of G. acerosa was done by GC-MS analysis. The results showed that, at 487.80 μg/mL, benzene extract showed significant (P < 0.05) inhibitory activity against both AChE and BuChE with the percentage of inhibition 54.18 ± 5.65 % (IC50 = 434.61 ± 26.53 μg/mL) and 78.43 ± 0% (IC50 = 163.01 ± 85.35 μg/mL), respectively. The mode of inhibition exhibited by benzene extract against the AChE and BuChE was found to be competitive and uncompetitive type of inhibition, respectively. Preliminary phytochemical analysis coupled with GC-MS illustrates that the benzene extract possesses high amount of terpenoids, which could be the reason for potential cholinesterase inhibitory activity.
While tobacco use occurs in many forms all over the world, there is little information on cross-tobacco use. Authors report an unusual case of tobacco use in the form of chewing beedies which are normally smoked (cross-tobacco use). A 22-year-old single female, diagnosed with schizophrenia for the last 6 years, started chewing beedies from the age of 15 years and was using it in a dependent pattern since 7 years. After 3 years of treatment for her schizophrenia, patient's family pressured her to seek tobacco cessation treatment. Initial treatment with nicotine gum replacement and behavioral counseling did not prove useful. Subsequently she was treated with bupropion 300 mg/day and able to successfully abstain. Cross-tobacco use is relatively rare, and merits further study, especially in the mentally ill population.
Beedies; chewing; schizophrenia; tobacco
The current study deals with the evaluation of two coral-associated bacterial (CAB) extracts to inhibit the biofilm synthesis in vitro as well as the virulence production like hemolysin and exopolysaccharide (EPS), and also to assess their ability to modify the adhesion properties, that is cell surface hydrophobicity (CSH) of methicillin-resistant (MRSA) and -susceptible Staphylococcus aureus (MSSA). Out of nine CAB screened, the ethyl acetate extract of CAB-E2 (Bacillus firmus) and CAB-E4 (Vibrio parahemolyticus) have shown excellent antibiofilm activity against S. aureus. CAB-E2 reduced the production of EPS (57–79%) and hemolysin (43–70%), which ultimately resulted in the significant inhibition of biofilms (80–87%) formed by both MRSA and MSSA. Similarly, CAB-E4 was also found to decrease the production of EPS (43–57%), hemolysin (43–57%) and biofilms (80–85%) of test pathogens. CLSM analysis also proved the antibiofilm efficacy of CAB extracts. Furthermore, the CAB extracts strongly decreased the CSH of S. aureus. Additionally, FT-IR analysis of S. aureus treated with CAB extracts evidenced the reduction in cellular components compared to their respective controls. Thus, the present study reports for the first time, B. firmus—a coral-associated bacterium, as a promising source of antibiofilm agent against the recalcitrant biofilms formed by multidrug resistant S. aureus.
Cellular reprogramming involves profound alterations in genome-wide gene expression that is precisely controlled by a hypothetical epigenetic code. Small molecules have been shown to artificially induce epigenetic modifications in a sequence independent manner. Recently, we showed that specific DNA binding hairpin pyrrole-imidazole polyamides (PIPs) could be conjugated with chromatin modifying histone deacetylase inhibitors like SAHA to epigenetically activate certain pluripotent genes in mouse fibroblasts. In our steadfast progress to improve the efficiency of SAHA-PIPs, we identified a novel compound termed, δ that could dramatically induce the endogenous expression of Oct-3/4 and Nanog. Genome-wide gene analysis suggests that in just 24 h and at nM concentration, δ induced multiple pluripotency-associated genes including Rex1 and Cdh1 by more than ten-fold. δ treated MEFs also rapidly overcame the rate-limiting step of epithelial transition in cellular reprogramming by switching “” the complex transcriptional gene network.