Neutron-upscattering enhancement of the triple-alpha process.

The neutron inelastic scattering of carbon-12, populating the Hoyle state, is a reaction of interest for the triple-alpha process. The inverse process (neutron upscattering) can enhance the Hoyle state's decay rate to the bound states of 12C, effectively increasing the overall triple-alpha reaction rate. The cross section of this reaction is impossible to measure experimentally but has been determined here at astrophysically-relevant energies using detailed balance. Using a highly-collimated monoenergetic beam, here we measure neutrons incident on the Texas Active Target Time Projection Chamber (TexAT TPC) filled with CO2 gas, we measure the 3α-particles (arising from the decay of the Hoyle state following inelastic scattering) and a cross section is extracted. Here we show the neutron-upscattering enhancement is observed to be much smaller than previously expected. The importance of the neutron-upscattering enhancement may therefore not be significant aside from in very particular astrophysical sites (e.g. neutron star mergers).

Exploring color tunable emission characteristics of Eu3+-doped La2(MoO4)3 phosphors in the glass-ceramic form.

The glass-ceramic form of phosphor materials can overcome the many serious issues of phosphor/silicone composite in commercial phosphor-converted LEDs and are considered as new-generation color converters. In this report, we have shown a novel approach of developing inorganic red phosphor [Eu3+:La2(MoO4)3] in the glass-ceramic form based on lanthanum molybdate system. The ceramic form of the compound was found to have a glass transition temperature of 1002 °C, as confirmed by TGA and DSC studies. Further, XRD, FTIR and Raman studies also confirmed that the compounds prepared at 1050 °C are in glass-ceramic form, while those prepared at 750 °C are in ceramic form. Photoluminescence studies showed that both the ceramic and glass-ceramic forms of the phosphor are red color-emitting materials. However, the glass-ceramic forms have better color purity and more radiation transition probabilities. Further, the decay kinetics of both ceramic and glass-ceramic forms confirmed that only those Eu3+ ions which exist in the grain boundaries of the ceramics go inside the glass network structure upon heating the compound at or above the glass transition temperature. On the other hand, Eu3+ ions which exist at the La-site in the bulk of the particles are retained in the ceramic form in the glass-ceramic mixture.

Signal conditioning using logarithmic amplifier for biomedical applications of electrical impedance tomography.

OBJECTIVE: The aim of this study was to explore the use of a logarithmic amplifier to improve the spatial resolution (RES) of a low-cost electrical impedance tomography (EIT) system. In an EIT system, the measured signal has a large dynamic range from µV to mV, which requires high-RES (analog to digital conversion) cards. The logarithmic amplifier reduces the dynamic range by expanding lower values and compressing higher values, thereby improving the sensitivity and at the same time preventing the signal from saturation. In addition, a low-RES analog to digital conversion (ADC) cards can be used, making the system cost effective. This work evaluates the performance of a logarithmic amplifier and a linear amplifier used for signal conditioning in a low-cost EIT system. APPROACH: Two EIT systems based on a linear amplifier and logarithmic amplifier were designed. Phantom experiments were carried out with very small amounts of current injection. The signal-to-noise ratio (SNR), image quality, minimum detectable size and minimum detectable conductivity change were obtained. MAIN RESULTS: The logarithmic amplifier-based EIT system increased the average SNR by 4 dB. It also showed improvement in the RES and contrast-to-noise ratio of the images. The minimum size detectable by the logarithmic amplifier-based system was of radius 0.25 cm in a tank of radius 11 cm and the minimum change in conductivity detectable was 11%. SIGNIFICANCE: Logarithmic amplifier-based signal conditioning is a promising technique for improving the spatial RES of a low-cost EIT system that has a low-RES ADC.

Elderly patients with atrial fibrillation in routine clinical practice-peri-procedural management of edoxaban oral anticoagulation therapy is associated with a low risk of bleeding and thromboembolic complications: a subset analysis of the prospective, observational, multinational EMIT-AF study.

BACKGROUND: Annually > 10% of patients with atrial fibrillation on oral anticoagulation undergo invasive procedures. Optimal peri-procedural management of anticoagulation, as judged by major bleeding and thromboembolic events, especially in the elderly, is still debated. METHODS: Procedures from 1442 patients were evaluated. Peri-procedural edoxaban management was guided only by the experience of the attending physician. The primary safety outcome was the rate of major bleeding. Secondary outcomes included the peri-procedural administration of edoxaban, other bleeding events, and the main efficacy outcome, a composite of acute coronary syndrome, non-hemorrhagic stroke, transient ischemic attack, systemic embolic events, deep vein thrombosis, pulmonary embolism, and mortality. RESULTS: Of the 1442 patients, 280 (19%) were < 65, 550 (38%) were 65-74, 514 (36%) 75-84, and 98 (7%) were 85 years old or older. With increasing age, comorbidities and risk scores were higher. Any bleeding complications were uncommon across all ages, ranging from 3.9% in patients < 65 to 4.1% in those 85 years or older; major bleeding rates in any age group were ≤ 0.6%. Interruption rates and duration increased with advancing age. Thromboembolic events were more common in the elderly, with all nine events occurring in those > 65, and seven in patients aged > 75 years. CONCLUSION: Despite increased bleeding risk factors in the elderly, bleeding rates were small and similar across all age groups. However, there was a trend toward more thromboembolic complications with advancing age. Further efforts to identify the optimal management to reduce ischemic complications are needed. TRIAL REGISTRATION: NCT# 02950168, October 31, 2016.

QSAR and molecular docking studies of lethal factor protease inhibitors against Bacillus anthracis.

Bacillus anthracis is considered as a biological warfare agent because it is the causative agent of the serious infectious anthrax disease. Delay in treatment leads to lethal factor-mediated toxaemia which is very critical due to lack of therapeutic options. Consequently, attempts have been made to discover potent lethal factor (LF) protease inhibitors such as small-molecule synthetic 2-thio-1,3-thiazolidine-4-one (rhodanine) compounds. But computed descriptor-based quantitative structure-activity relationship (QSAR) and drug design studies on such aspect are poorly represented. Therefore, an attempt was made for developing QSAR models using structural descriptors for 1,3-thiazolidine-4-one compounds. The models were developed on a series of 49 LF protease inhibitors using the combination of constitutional, functional group, atom-centred fragment and molecular property descriptors. The best QSAR model included four variables, namely, C-040, nR05, GVWAI-80 and ALOGP that correlated well with the anti-LF protease activity with a good correlation coefficient (r = 0.870) of good statistical significance (F4, 29 = 14.09 (α = 0.001) F4, 29 = 6.19). This model was also validated and explained 58.1% of variances of the Bacillus anthracis inhibitory activities of the studied compounds with r2pred = 0.710 which denotes external predictability. Finally, molecular docking was carried out to predict the mode of binding of some highly active congeneric compounds. It was shown that VAL 1403 is an important residue for phenyl ring. TYR 1456 and HIS 1418 are responsible for interaction with the rhodanine nucleus. Therefore, these residues are considered responsible for the inhibition of LF protease anthrax and can predict significant dimension of essential structural features of these inhibitors to evaluate, screen and help priorities of the synthesis of the candidates against anthrax bioterrorism.

Solid state speciation of uranium and its local structure in Sr2CeO4 using photoluminescence spectroscopy.

An effort was taken to carry our speciation study of uranium ion in technologically important cerate host Sr2CeO4 using time resolved photoluminescence spectroscopy. Such studies are not relevant only to nuclear industry but can give rich insight into fundamentals of 5f electron chemistry in solid state systems. In this work both undoped and varied amount of uranium doped Sr2CeO4 compound is synthesized using complex polymerization method and is characterized systematically using X-ray diffraction (XRD), Raman spectroscopy, impedance spectroscopy and scanning electron microscopy (SEM). Both XRD and Raman spectroscopy confirmed the formation of pure Sr2CeO4 which has tendency to decompose peritectically to SrCeO3 and SrO at higher temperature. Uranium doping is confirmed by XRD. Uranium exhibits a rich chemistry owing to its variable oxidation state from +3 to +6. Each of them exhibits distinct luminescence properties either due to f-f transitions or ligand to metal charge transfer (LMCT). We have taken Sr2CeO4 as a model host lattice to understand the photophysical characteristics of uranium ion in it. Emission spectroscopy revealed the stabilization of uranium as U (VI) in the form of UO66- (octahedral uranate) in Sr2CeO4. Emission kinetics study reflects that uranate ions are not homogeneously distributed in Sr2CeO4 and it has two different environments due to its stabilization at both Sr2+ as well as Ce4+ site. The lifetime population analysis interestingly pinpointed that majority of uranate ion resided at Ce4+ site. The critical energy-transfer distance between the uranate ion was determined based on which the concentration quenching mechanism was attributed to electric multipolar interaction. These studies are very important in designing Sr2CeO4 based optoelectronic material as well exploring it for actinides studies.

Macrophage inhibitory cytokine-1/growth differentiation factor-15 as a predictor of colonic neoplasia.

BACKGROUND: Serum macrophage inhibitory cytokine-1 (MIC-1/GDF15) concentration has been associated with colonic adenomas and carcinoma. AIMS: To determine whether circulating MIC-1/GDF15 serum concentrations are higher in the presence of adenomas and whether the level decreases after excision. METHODS: Patients were recruited prospectively from a single centre and stratified into five groups: no polyps (NP); hyperplastic polyps (HP); sessile serrated ademona (SSA); adenomas (AP); and colorectal carcinoma (CRC). Blood samples were collected immediately before and 4 weeks after colonoscopy. MIC-1/GDF15 serum levels were quantified using ELISA. RESULTS: Participants (n=301) were stratified as: NP; n=116 (52%), HP; n=37 (12%), SSA; n=19 (7%), AP; n=68 (23%); and CRC; n=3 (1%). Patients were excluded from the study due to nondiagnostic pathology (n=9, 3%) and exclusion criteria (n=20, 6%). In the 272 remaining subjects (M=149; F=123), age (P=.005), history of colonic polyps (P=.003) and family history of colonic polyps (P=.002) were associated with presence of adenomas. Baseline median MIC-1/GDF15 serum levels increased significantly from NP 609 (460-797) pg/mL, HP 582 (466-852) pg/mL, SSA 561 (446-837) pg/mL to AP 723 (602-1122) pg/mL and CRC 1107 (897-1107) pg/mL; (P<.001). In the pre- and postpolypectomy paired adenoma samples median MIC-1/GDF15 reduced significantly from 722 (603-1164) pg/mL to 685 (561-944) pg/mL (P=.002). A ROC analysis for serum MIC-1/GDF15 to identify adenomatous polyps indicated an area under the curve of 0.71. CONCLUSIONS: Our data suggest that serum MIC-1/GDF15 has the diagnostic characteristics to increase the detection of colonic neoplasia and improve screening.

Spatio-temporal variation in chemical characteristics of PM10 over Indo Gangetic Plain of India.

The paper presents the spatio-temporal variation of chemical compositions (organic carbon (OC), elemental carbon (EC), and water-soluble inorganic ionic components (WSIC)) of particulate matter (PM10) over three locations (Delhi, Varanasi, and Kolkata) of Indo Gangetic Plain (IGP) of India for the year 2011. The observational sites are chosen to represent the characteristics of upper (Delhi), middle (Varanasi), and lower (Kolkata) IGP regions as converse to earlier single-station observation. Average mass concentration of PM10 was observed higher in the middle IGP (Varanasi 206.2 ± 77.4 µg m(-3)) as compared to upper IGP (Delhi 202.3 ± 74.3 µg m(-3)) and lower IGP (Kolkata 171.5 ± 38.5 µg m(-3)). Large variation in OC values from 23.57 µg m(-3) (Delhi) to 12.74 µg m(-3) (Kolkata) indicating role of formation of secondary aerosols, whereas EC have not shown much variation with maximum concentration over Delhi (10.07 µg m(-3)) and minimum over Varanasi (7.72 µg m(-3)). As expected, a strong seasonal variation was observed in the mass concentration of PM10 as well as in its chemical composition over the three locations. Principal component analysis (PCA) identifies the contribution of secondary aerosol, biomass burning, fossil fuel combustion, vehicular emission, and sea salt to PM10 mass concentration at the observational sites of IGP, India. Backward trajectory analysis indicated the influence of continental type aerosols being transported from the Bay of Bengal, Pakistan, Afghanistan, Rajasthan, Gujarat, and surrounding areas to IGP region.

Energy transfer dynamics and luminescence properties of Eu(3+) in CaMoO4 and SrMoO4.

Undoped and europium doped CaMoO4 and SrMoO4 scheelites are synthesized using a complex polymerization method. The phase purity of the sample is confirmed using powder X-ray diffraction (PXRD). X-ray photoelectron spectroscopy (XPS) was carried out to confirm the oxidation states of various constituents and dopant elements and also the presence of oxygen vacancies. Interestingly both CaMoO4 and SrMoO4 on irradiation with UV light give blue and green emission respectively. On europium doping, it was found that molybdate to Eu(3+) ion energy transfer is more efficient in SrMoO4:Eu compared to CaMoO4:Eu. It is also justified using a luminescence lifetime study which shows biexponential decay in the case of CaMoO4:Eu corresponding to both the host and europium ion; whereas a single lifetime is observed in the case of SrMoO4:Eu. Anomalies in host-dopant energy transfer are suitably explained using density functional theory (DFT) calculations and XPS. The actual site symmetry for the europium ion in CaMoO4 and SrMoO4 was also evaluated based on a Stark splitting pattern which turns out to be D2 and C2v respectively although it is S4 for Ca/Ba(2+) in AMoO4. This is also reflected in higher Ω2 values for SrMoO4:Eu than CaMoO4:Eu.

Molecular modelling studies on 2-substituted octahydropyrazinopyridoindoles for histamine H2 receptor antagonism.

The human histamine H2 receptor (hH2HR) is a G-protein coupled receptor protein with seven transmembrane (TM)-spanning helices primarily involved in regulation of gastric acid secretion. Antagonists targeting hH2HR are useful in the treatment of hyperacidic conditions such as peptic ulcers, gastresophageal reflux disease and gastrointestinal bleeding. We have previously reported the antagonism of 2-substituted pyrazinopyridoindoles at the human histamine H1 receptor and mode of binding of these compounds at the hH1HR using in silico methods. Interestingly, some of the compounds in the series also showed promising activity towards hH2HR that prompted us to investigate the mode of binding of these compounds at hH2HR. In the absence of the crystal structure of hH2HR a homology model has been constructed using multiple sequence alignment, using the X-ray crystal structures of Turkey ß1-adrenergic receptor (tß1AR), Human histamine H1 receptor (hH1HR), Human ß2-adrenergic receptor (hß2AR) and Human D3 dopamine receptor (hD3R). The important residues for binding were depicted in TMIII, TMV, TMVI and TMVII by the homology modelled hH2HR for 2-substituted pyrazinopyridoindoles. A comparative study for deducing the selectivity regarding the binding towards hH1HR and hH2HR has been carried out, which may be useful in designing of selective hH1HR/hH2HR antagonists in these classes of compounds.

Resuscitation fluid use in Australian and New Zealand Intensive Care Units between 2007 and 2013.

INTRODUCTION: Recent evidence indicates that the choice of intravenous fluids may affect outcomes in critically ill patients. METHODS: We recorded the administration of resuscitation fluids in patients admitted to Australian and New Zealand adult intensive care units (ICUs) for a 24-h period at 6 time points between 2007 and 2013. Changes in patterns of fluid use over this period were determined using regression analyses. RESULTS: Of the 2825 patients admitted to the 61 ICUs on the 6 study days, 754 (26.7%) patients received fluid resuscitation. Of those receiving fluid resuscitation, the proportion of patients receiving crystalloid significantly increased from 28.9% (41/142) in 2007 to 50.5% (48/95) in 2013 (adjusted odds ratio (OR) 2.93; 95% confidence intervals (CI) 1.35-6.33; p = 0.006); of these, the proportion of patients receiving buffered salt solutions significantly increased from 4.9% (7/142) in 2007 to 31.6% (30/95) in 2013 (OR 7.00; 95% CI 2.14-22.92; p = 0.001). The use of colloids significantly decreased from 59.9% (85/142) in 2007 to 42.1% (40/95) in 2013 (adjusted OR 0.34; 95% CI 0.16-0.74; p = 0.007) due to a significant decrease in the proportion of patients receiving gelatin; 28.9% (41/142) to 2.1% (2/95) (OR 0.10; 95% CI 0.03-0.29; p ≤ 0.001). CONCLUSION: Fluid resuscitation practice in Australia and New Zealand adult ICUs has changed over the 6-year study period. Crystalloid use increased primarily due to an increase in the use of buffered salt solutions while overall the use of colloid has decreased.

The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration.

Rac1-GTPases serve as intermediary cellular switches, which conduct transient and constitutive signals from upstream cues, including those from Ras oncoproteins. Although the sirtuin1 (SIRT1) deacetylase is overexpressed in several human cancers and has recently been linked to cancer cell motility as a context-dependent regulator of multiple pathways, its role in Rac1 activation has not been reported. Similarly, SIRT2 has been demonstrated to be upregulated in some cancers; however, studies have also reported its role in tumor suppression. Here, we demonstrate that SIRT1 and SIRT2 positively regulate the levels of Rac1-GTP and the activity of T-cell lymphoma invasion and metastasis 1 (TIAM1), a Rac guanine nucleotide exchange factor (GEF). Transient inhibition of SIRT1 and SIRT2 resulted in increased acetylation of TIAM1, whereas chronic SIRT2 knockdown resulted in enhanced acetylation of TIAM1. SIRT1 regulates Dishevelled (DVL) protein levels in cancer cells, and DVL along with TIAM1 are known to augment Rac activation; however, SIRT1 or 2 has not been previously linked with TIAM1. We found that diminished sirtuin activity led to the disruption of the DVL1-TIAM1 interaction. We hence propose a model for Rac activation where SIRT1/2 positively modulates the DVL/TIAM1/Rac axis and promotes sustained pathway activation.

A comparative study of glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels in the saliva of diabetic and normal patients.

Diabetes has been reported to affect salivary glands adversely in humans and experimental models. Glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and lactate dehydrogenase (LDH) are salivary enzymes that also are widely distributed in animal tissues. We determined GOT and GPT levels in saliva samples of 100 type 1 and 30 type 2 diabetic patients using reflectance spectrophotometry and compared them to 30 age and sex matched healthy controls. Statistically significant differences were observed in the mean values of GOT and GPT in type 1 diabetics compared to type 2 and control groups. Significantly higher GOT levels were found in the 1-20 year age group of type 1 diabetics. Our findings suggest that salivary gland damage is due to the same immunological attack that affects pancreatic ß cells and results in type 1 diabetes.

In vitro rapid clearance of infectious bursal disease virus in peripheral blood mononuclear cells of chicken lines divergent for antibody response might be related to the enhanced expression of proinflammatory cytokines.

Infectious bursal disease (IBD) is an acute and highly contagious viral disease of young chickens caused by infectious bursal disease virus (IBDV). An effective way to control IBDV would be to breed chickens with a reduced susceptibility to IBDV infection. In the present work, we used chickens selected for high and low specific responses to sheep red blood cells (SRBC) (H and L, respectively) to assess the susceptibility of differential immune competent animals to IBDV infection. The peripheral blood mononuclear cells (PBMCs) of high SRBC line (HL) and low SRBC line (LL) were infected with IBDV and viral RNA loads were determined at different time post-IBDV infection. Chicken orthologues of the T helper 1 (Th1) cytokines, interferon-γ (IFN-γ) and interleukin-2 (IL-2); a Th2 cytokine, IL-10; a pro inflammatory cytokine, IL-6; the CCL chemokines, chCCLi2, chCCLi4 and chCCLi7; colony stimulating factor, GM-CSF; and a anti-inflammatory cytokine, transforming growth factor ß-2 (TGFß-2) were quantified. The expression of chCCLi2, chCCLi4 and chCCLi7 was significantly higher in L line as compared to H line. However, in H line the viral RNA loads were significantly lower than in L line. Therefore, the upregulated chemokines might be associated with the susceptibility to IBDV. The expression of IFN-γ, IL-2 and IL-6 was significantly higher in H line as compared to L line. We assume that the higher proinflammatory cytokines expression in H line might be related to the rapid clearance of virus from PBMCs. Significantly higher levels of IL-10 and TGFß-2 mRNAs in L line might be related to the pathogenesis of IBDV. In conclusion, selection for antibody responses appears to influence the expression profiles of chemokines and cytokines against IBDV. Further, the selection for high SRBC response might improve the immuno-competence of chickens against IBDV.

Cloning, sequencing, and in silico characterization of Omp 28 of Salmonella Typhi (strain MTCC 733) to develop r-DNA vaccine for typhoid fever.

BACKGROUND: Typhoid is one of the most important diseases of human beings caused by Salmonella Typhi. There are many vaccine reported against Salmonella Typhi, but search for new candidate vaccine antigens is still going on because presently available vaccines have several limitations such as short-term immunity, high cost, and allergic reaction. Several approaches such as subunit vaccines, Vi polysaccharide, mutant vaccines, and r-DNA vaccines have been tested. r- DNA vaccines have shown some promising potential (targeted Omp). Omp 28 had shown very promising results and suggests that it should be used in further studies of animal protection against the disease. OBJECTIVE: Cloning, Sequencing and In silico analysis of Omp 28 gene to develop r-DNA vaccine of S. Typhi. MATERIALS AND METHODS: Omp 28 is made up of three identical subunits of 9.6 kDa showing PCR amplicon of 330 bp which has been cloned in the pJET vector. Recombinant clones has been sequenced, and data submitted to NCBI. Secondary structure was deduced by the Chou Fasman and Garnier method. The sequence of Omp 28 was studied for antigenic indexing, epitope mapping, and MHC mapping using various bioinformatics tool. RESULTS AND CONCLUSION: The sequence of Omp 28 has been assigned accession no GQ 907044.1 by NCBI. Secondary structure has shown it has more alpha region. Hydrophobic plot and surface probability plot shows most amino acids are surface exposed which is a requirement to develop a r-DNA vaccine. Antigenic sites are located within surface exposed regions and eight antigenic determinants are present in Omp 28. On Prosite analysis of Protein shown two motifs i.e. anaphylatoxin domain signature motif at position 219-252 and other one was iron sulphur binding region signature motif at position 36-44. On epitope analysis total six major B cell epitopes were observed which can provoke humoral immunity. On T cell epitope mapping several major epitopes has been found in case of MHC class I and MHC class II. It indicates that Omp 28 can provoke cell mediated as well as humoral immunity and can be proven a promising candidates of Salmonella Typhi.

Docking studies of novel pyrazinopyridoindoles class of antihistamines with the homology modelled H(1)-receptor.

Histamine is an important neurotransmitter as it controls a multitude of physiological functions by activating specific receptors on target cells. It exerts its effects by binding to four different histamine receptors (H(1)-H(4)), which all belong to the large family of G protein-coupled receptors (GPCRs). Research and development of H(1) ligand has largely focused on antagonists which are used for their anti-allergy effects in the periphery. Recent understanding of the clinical importance of H(1) receptors in brain, however, suggests the pharmacotherapeutic potential of H(1) agonists in neurodegenerative and neuropsychiatric disorders. Despite the therapeutic importance of the H(1) receptor, for many years the molecular features of the H(1) receptor protein had been unknown. In view of the recently reported crystal structure of human H(1) receptor and in continuation of our work on 3D-pharmacophore on antihistamine H(1) and homology model of histamine H(1) receptor, docking studies have been carried out on some promising pyrazinopyridoindole class of antihistamine H(1), including two outliers, to validate our earlier reported models/hypotheses on H(1)-receptor, where a good explanation between estimated and observed activities has been obtained. In addition, the docking study also provided insights about the optimal activity of the outliers, for which no explanation was reported previously.

Cytokines Expression and Nitric Oxide Production under Induced Infection to Salmonella Typhimurium in Chicken Lines Divergently Selected for Cutaneous Hypersensitivity.

In the present study, the impact of Salmonella Typhimurium on cell-mediated immunity (CMI) was investigated in 5 week-old immuno divergent broiler lines selected for the high and low response to phytohemagglutinin-P. The immune response was assessed in peripheral-blood mononuclear cells (PBMCs) induced with Salmonella Typhimurium at different time intervals (0 h, 0.5 h, 2 h, 4 h, 6 h, 12 h and 24 h). The differential mRNA expression patterns of IFN-γ, IL-2 and iNOS were evaluated by quantitative real time PCR. In-vitro production of nitric oxide (NO) was also estimated in the culture supernatant and correlated with iNOS mRNA expression. Present study showed higher production of NO in the high cell-mediated line (HCMI) as compared to the low cell-mediated line (LCMI) upon stimulation with Salmonella Typhimurium. Correspondingly, higher mRNA expression of iNOS and IFN-γ were observed in high response birds (HCMI); but IL-2 was down regulated in this line compared to the low response birds (LCMI). Significantly (p<0.05) higher expression of iNOS, IFN-γ and higher production of NO in high line indicated that the selection for PHA-P response might be employed for increasing the immune competence against Salmonella Typhimurium in chicken flocks.

Cloning, sequencing and in silico analysis of omp C of salmonella typhimurium.

Salmonella Typhimurium is an important pathogen having a broad host range. In human population it causes mostly gastroenteritis but there are reports in which it was found to be responsible to cause several lethal diseases like endocarditis and meningitis. Poultry products are the major sources of this organism in India as these are consumed at various stages of cooking. The available vaccines have their own limitations such as short-term immunity. Outer membrane proteins have shown some promising potential, so in the present study Omp C of Salmonella Typhimurium was cloned and sequenced to explore the possibility of development of r-DNA vaccine against Salmonella Typhimurium for poultry. The sequence of Omp C was studied for antigenic indexing, epitope mapping, and MHC mapping using various bioinformatic tools. The ORF analysis revealed a complete coding region of approximately 1000 bp. Five major and 13 minor B-cell epitopes were identified having an antigenic index of 1.7. The sequences also showed major histocompatibility complex (MHC) class I and class II binding region indicating a potential of eliciting cell-mediated immune response. The findings indicate that Omp C may be proven as promising candidate for development of r-DNA vaccine against Salmonella Typhimurium.

Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by upregulating ABC transporters.

Development of multidrug resistance (MDR) is a major deterrent in the effective treatment of metastatic cancers by chemotherapy. Even though MDR and cancer invasiveness have been correlated, the molecular basis of this link remains obscure. We show here that treatment with chemotherapeutic drugs increases the expression of several ATP binding cassette transporters (ABC transporters) associated with MDR, as well as epithelial-mesenchymal transition (EMT) markers, selectively in invasive breast cancer cells, but not in immortalized or non-invasive cells. Interestingly, the mere induction of an EMT in immortalized and non-invasive cell lines increased their expression of ABC transporters, migration, invasion, and drug resistance. Conversely, reversal of EMT in invasive cells by downregulating EMT-inducing transcription factors reduced their expression of ABC transporters, invasion, and rendered them more chemosensitive. Mechanistically, we demonstrate that the promoters of ABC transporters carry several binding sites for EMT-inducing transcription factors, and overexpression of Twist, Snail, and FOXC2 increases the promoter activity of ABC transporters. Furthermore, chromatin immunoprecipitation studies revealed that Twist binds directly to the E-box elements of ABC transporters. Thus, our study identifies EMT inducers as novel regulators of ABC transporters, thereby providing molecular insights into the long-standing association between invasiveness and MDR. Targeting EMT transcription factors could hence serve as novel strategies to curb both metastasis and the associated drug resistance.