Two type I topoisomerases maintain DNA topology in human mitochondria.

Genetic processes require the activity of multiple topoisomerases, essential enzymes that remove topological tension and intermolecular linkages in DNA. We have investigated the subcellular localisation and activity of the six human topoisomerases with a view to understanding the topological maintenance of human mitochondrial DNA. Our results indicate that mitochondria contain two topoisomerases, TOP1MT and TOP3A. Using molecular, genomic and biochemical methods we find that both proteins contribute to mtDNA replication, in addition to the decatenation role of TOP3A, and that TOP1MT is stimulated by mtSSB. Loss of TOP3A or TOP1MT also dysregulates mitochondrial gene expression, and both proteins promote transcription elongation in vitro. We find no evidence for TOP2 localisation to mitochondria, and TOP2B knockout does not affect mtDNA maintenance or expression. Our results suggest a division of labour between TOP3A and TOP1MT in mtDNA topology control that is required for the proper maintenance and expression of human mtDNA.

TOP2B's contributions to transcription.

Transcription is regulated and mediated by multiprotein complexes in a chromatin context. Transcription causes changes in DNA topology which is modulated by DNA topoisomerases, enzymes that catalyse changes in DNA topology via transient breaking and re-joining of one or both strands of the phosphodiester backbone. Mammals have six DNA topoisomerases, this review focuses on one, DNA topoisomerase II beta (TOP2B). In the absence of TOP2B transcription of many developmentally regulated genes is altered. Long genes seem particularly susceptible to the lack of TOP2B. Biochemical studies of the role of TOP2B in transcription regulated by ligands such as nuclear hormones, growth factors and insulin has revealed PARP1 associated with TOP2B and also PRKDC, XRCC5 and XRCC6. Analysis of publicly available databases of protein interactions confirms these interactions and illustrates interactions with other key transcriptional regulators including TRIM28. TOP2B has been shown to interact with proteins involved in chromosome organisation including CTCF and RAD21. Comparison of publicly available Chip-seq datasets reveals the location at which these proteins interact with genes. The availability of resources such as large datasets of protein-protein interactions, e.g. BioGrid and IntAct and protein-DNA interactions such as Chip-seq in GEO enables scientists to extend models and propose new hypotheses.

TOP2B: The First Thirty Years.

Type II DNA topoisomerases (EC 5.99.1.3) are enzymes that catalyse topological changes in DNA in an ATP dependent manner. Strand passage reactions involve passing one double stranded DNA duplex (transported helix) through a transient enzyme-bridged break in another (gated helix). This activity is required for a range of cellular processes including transcription. Vertebrates have two isoforms: topoisomerase IIα and ß. Topoisomerase IIß was first reported in 1987. Here we review the research on DNA topoisomerase IIß over the 30 years since its discovery.

Zoonotic tuberculosis in occupationally exposed groups in Pakistan.

BACKGROUND: Bovine tuberculosis (bTB) remains a public health threat in low-income countries. Data on human tuberculosis (TB) due to Mycobacterium bovis are poorly documented in developing countries. AIMS: To determine the occurrence of active pulmonary TB due to M. bovis in abattoir workers, butchers, livestock farmers and veterinarians and to document their knowledge and practices regarding bTB. METHODS: A cross-sectional study of abattoir workers, butchers, livestock farmers, veterinary doctors and veterinary assistants, which obtained data on socio-demographic conditions, knowledge and practices regarding TB. Sputum samples were collected from respondents with a chronic cough. The chi-squared test was used for statistical analysis. RESULTS: A total of 141 abattoir workers, 317 butchers, 50 livestock farmers, five veterinary doctors and three veterinary assistants took part. Four out of 16 abattoir workers and 1 out of 50 livestock farmers were positive for M. bovis by PCR analysis. Duration of work as an abattoir worker was significantly associated (P < 0.05) with prevalence of zoonotic TB. The knowledge of abattoir workers, butchers, livestock farmers and veterinary assistants regarding transmission of bTB from animals to humans and the symptoms of TB in humans was very poor. Most of these workers did not use protective equipment and appropriate safe working techniques and were considered at high risk of acquiring zoonotic TB. CONCLUSIONS: Zoonotic TB is a significant public health issue among professionally exposed groups in Peshawar, Pakistan and suggests a need for further detailed investigations of the disease in this and similar areas.

Various levels and forms of dietary α-lipoic acid in broiler chickens: Impact on blood biochemistry, stress response, liver enzymes, and antibody titers.

The present experiment was conducted to evaluate the impact of various levels and forms of α-lipoic acid (ALA) on blood biochemistry, immune and stress response, and antibody titers in broiler chickens. The four levels (7.5, 15, 75, and 150 ppm) and 2 sources (powder, P-ALA and encapsulated, E-ALA) of ALA along with negative (C-) and positive control (C+; contains antibiotics) diets consisted of 10 dietary treatments, and these treatments were allocated to 1,200 1-d-old chicks and were replicated 12 times with 10 birds per replicate. Among the blood biochemistry parameters, creatinine levels were almost 3 times lower in E-ALA-supplemented diets compared to the C- diet (0.09 vs. 0.25 mg/dL; P<0.0001). Neither level nor source of ALA affected blood urea nitrogen (BUN), total protein (TP), albumin, globulin, or albumin to globulin ratio (AGR). The supplemented diets decreased serum levels of the liver enzymes aspartate-aminotransferase (AST; P<0.006) and alanine-aminotransferase (ALT; P<0.0003). The Newcastle disease virus (NDV) antibody response in supplemented groups was poor at day zero (P<0.0001) but increased by d 14 (P<0.03). Birds did not respond to infectious bronchitis virus (IBV) vaccination at any observed stage (P>0.05). The concentration of cortisol was reduced in chickens fed ALA-supplemented diets as compared to the C- diet (P<0.001). Results suggest that ALA-supplemented diets ameliorated blood biochemistry profiles and immune responses and reduced stress in broiler chickens. The encapsulated form of ALA was more effective than the powder form.

Growth performance, carcass yield, and quality and chemical traits of meat from commercial korean native ducks with 2-way crossbreeding.

This work was conducted to investigate the performance and meat characteristics of commercial Korean native duck (KND). A total of 180 1-d-old ducklings of 2-way crossbreds from A and B lines (from National Institute of Animal Science) were used in this work and divided into 4 groups (3 replicates/group, 15 birds/replicate). The four groups were 4 crossbreds as AA (A line [♀]×A line [♂]), AB (A line [♀]×B line [♂]), BB (Pure line B strains) and BA (B strains [♀]×A strain [♂]). Ducks were fed diets based on corn-soybean meal for 0 to 3 wk (22.4% crude protein [CP], 2,945 kcal/kg metabolizable energy [ME]) and 3 to 8 wk (18.4% CP, 3,047 kcal/kg ME). As a result of this study, average body weight of 4 crossbreds were 625, 1,617, 2,466, and 2,836 g at 2, 4, 6, and 8 weeks, respectively, and significantly increased over the period of time (p<0.05). Body weight of BB group was greater than other crossbreds at the age of 6 weeks (p<0.05). There was a significant difference in weekly body weight gains (p<0.05), which were 573, 991, 850, and 371 g at 2, 4, 6, and 8 weeks old, respectively. Uniformity of 4 crossbreds was 84.9%, 80.5%, and 72.5% at 6, 7, and 8 weeks, respectively, and there was no difference among crossbreds. Body weight gain of BB crossbred was highest among crossbreds (p<0.05). Weekly feed intake significantly increased with weeks as 669, 1,839, 2,812, and 3,381 g at 2, 4, 6, and 8 weeks respectively (p<0.05). Feed intakes of AA and BB crossbreds were higher at 2 to 4 weeks old than others and that of BB crossbred was highest at 4 to 6 weeks old (p<0.05). Weekly feed conversion ratios were 1.17, 1.86, 3.32, and 9.37 at 0 to 2, 2 to 4, 4 to 6, and 6 to 8 weeks old, respectively, and it increased with age (p<0.05). There was no significant difference in feed conversion ratio among crossbreds. Carcass yields of 4 crossbreds were 73.6%, 71.6%, 73.5%, and 71.7%, respectively, so there was no significant difference among crossbreds. There was no difference in wing, neck, breast and leg ratios among crossbreds. However, back ratios of 4 crossbreds were 17.6%, 18.0%, 15.8%, and 17.6%, respectively, and back ratio of BB was the highest among crossbreds. Finally, these results may provide the basic data on the production, carcass quality, fatty acid and amino acid composition of commercial KND with 2-way crossbreeding.

Evaluation and estimation of diuretic activity of the linalyl acetate in the rats.

This study aimed to explore the diuretic activity of linalyl acetate (LA). LA is an essential oil, it is an integral phyto-constituent of various plants. In this study, acute and chronic diuretic activities were explored by measuring the levels of different electrolytes and pH in the urine of experimental rats. Rats were divided into five groups. The control group was given 10 mg/kg normal saline, the treated group was given 10 mg/kg furosemide, and the remaining 3 groups received different doses of LA including 25, 50, and 75 mg/kg through intraperitoneal route, to determine its diuretic potential. Urine volume for acute diuretic activity was measured for 6 hours however for chronic diuretic activity was measured for 6 days. For a comparative study of LA with a control group and treated group with reference drug, diuretic index was used. Moreover, the underlying mechanism of the diuretic activity was also explored by comparing atropine, L-NAME, and indomethacin. The results of each group with 6 rats in each group were obtained by ± standard error of the mean of every group. Analysis of Variance (ANOVA) was used for statistical analysis. Results revealed that the LA 75 mg/kg dose showed comparable results as of furosemide. Moreover, this study revealed the involvement of muscarinic receptors to produce diuresis in comparison with atropine with very little involvement of prostanoids and no effect on NO pathway induced by indomethacin and L-NAME respectively. It is concluded that LA possess anti-diuretic potential. Muscarinic receptors might be involved in producing diuretic effects.

Exploring the effects of topoisomerase II inhibitor XK469 on anthracycline cardiotoxicity and DNA damage.

Anthracyclines, such as doxorubicin (adriamycin), daunorubicin, or epirubicin, rank among the most effective agents in classical anticancer chemotherapy. However, cardiotoxicity remains the main limitation of their clinical use. Topoisomerase IIß has recently been identified as a plausible target of anthracyclines in cardiomyocytes. We examined the putative topoisomerase IIß selective agent XK469 as a potential cardioprotective and designed several new analogs. In our experiments, XK469 inhibited both topoisomerase isoforms (α and ß) and did not induce topoisomerase II covalent complexes in isolated cardiomyocytes and HL-60, but induced proteasomal degradation of topoisomerase II in these cell types. The cardioprotective potential of XK469 was studied on rat neonatal cardiomyocytes, where dexrazoxane (ICRF-187), the only clinically approved cardioprotective, was effective. Initially, XK469 prevented daunorubicin-induced toxicity and p53 phosphorylation in cardiomyocytes. However, it only partially prevented the phosphorylation of H2AX and did not affect DNA damage measured by Comet Assay. It also did not compromise the daunorubicin antiproliferative effect in HL-60 leukemic cells. When administered to rabbits to evaluate its cardioprotective potential in vivo, XK469 failed to prevent the daunorubicin-induced cardiac toxicity in either acute or chronic settings. In the following in vitro analysis, we found that prolonged and continuous exposure of rat neonatal cardiomyocytes to XK469 led to significant toxicity. In conclusion, this study provides important evidence on the effects of XK469 and its combination with daunorubicin in clinically relevant doses in cardiomyocytes. Despite its promising characteristics, long-term treatments and in vivo experiments have not confirmed its cardioprotective potential.

Influence of monochromatic light on quality traits, nutritional, fatty acid, and amino acid profiles of broiler chicken meat.

The role of monochromatic lights was investigated on meat quality in 1-d-old straight-run broiler chicks (n = 360), divided into 6 light sources with 6 replicates having 10 chicks in each replicate. Six light sources were described as incandescent bulbs (IBL, as a control) and light-emitting diode (LED) light colors as white light (WL), blue light, red light (RL), green light, and yellow light. Among LED groups, the RL increased the concentration of monounsaturated fatty acids (P < 0.001), saturated fatty acids (P < 0.001), and the saturated:polyunsaturated fatty acid ratio (P < 0.001), but reduced the concentration of polyunsaturated fatty acid, n-3 fatty acid, and n-6 fatty acid. The IBL increased the n-3 and sulfur-containing amino acids but reduced the n-6:n-3 nonessential amino acids. The WL improved the concentration of most of the essential amino acids (P < 0.01) and nonessential amino acids (P < 0.01) of breast meat. It can be extracted that the light produced by LED responded similar to the IBL light in influencing nutrient contents of meat. Moreover, LED is not decisive in improving fatty acid composition of meat. However, the role of IBL in reducing n-6:n-3 ratio and enhancing n-3 cannot be neglected. Among LED, WL is helpful in improving essential and nonessential amino acid contents of broiler meat.

Growth performance and hematological traits of broiler chickens reared under assorted monochromatic light sources.

A study was conducted to investigate the effect of different monochromatic lights on growth performance and hematological response of growing broiler chickens. A total of 360 one-day-old broiler chicks were randomly divided into 6 lighting treatments, which were replicated 6 times with 10 chicks in each replicate. Six light treatments include incandescent bulbs (as a control) and light-emitting diode white light, blue light, red light, green light, and yellow light (YL). The birds were provided with similar nutritional specifications and environmental management facilities, except for the lights throughout the experimental period. Growth performance was evaluated in terms of BW, BW gain, feed intake, and feed conversion ratio at weekly intervals. At the end of 5 wk, 2 birds from each replicate were randomly selected for blood collection to determine hematological response. The BW and feed intake was numerically higher in YL at 5 wk of age. But interestingly, this did not result in improved feed conversion ratio in YL; nevertheless, numerical values were lower in YL at 5 wk (P > 0.05). Red blood cells, blood platelet count, and percent hematocrit were numerically higher under YL, whereas white blood cell counts and percent hemoglobin remained unaffected due to light treatments. It was concluded that monochromatic light is a potential light source that might provide a beneficial effect on growth performance but is inconclusive for hematological measures of broilers.

Growth Performance, Carcass Traits and Serum Mineral Chemistry as Affected by Dietary Sodium and Sodium Salts Fed to Broiler Chickens Reared under Phase Feeding System.

A basal diet (0.8 g/kg dNa) was formulated in which each of the two sources (NaHCO3 and Na2SO4) were supplemented in such a way to attain four levels (1.7, 2.6, 3.5, and 4.4 g/kg) of total dNa, respectively, under 4×2 factorial arrangement. Eight dietary treatments were replicated four times, with 40 birds in each replicate (n = 1,280). The diets supplemented with Na2SO4 to attain higher levels of dNa showed highest BW gain and feed intake (FI) during d 1 to 10 (interaction effects) while 2.6 g/kg dNa exhibited improved BW gain and gain:feed (FG) during d 11 to 20. Linear rise in daily water intake (DWI) was associated with diets containing increasing dNa during d 1 to 42 (p≤0.036). During the first 10 d, DWI:FI was found highest in NaHCO3 diets while Na2SO4 diets showed highest DWI:FI during last 10 d of the experiment (p≤0.036). Increasing dNa and changing Na2SO4 with NaHCO3 salt increased pH and resulted in poor growth performance. Dressing weight (p≤0.001) and abdominal fat (p≤0.001; quadratic effect) were reduced, whereas breast (p≤0.001) and thigh (p<0.001) weights were aggravated with increasing dNa (linear effects). Present findings suggested higher levels of dNa from Na2SO4 as the supplemental salt in broiler diets would produce better growth performance, especially in first ten days of life, and improve carcass and body organ characteristics.

Growth Performance, Carcass Characteristics and Plasma Mineral Chemistry as Affected by Dietary Chloride and Chloride Salts Fed to Broiler Chickens Reared under Phase Feeding System.

Requirements of dietary chloride (dCl) and chloride salts were determined by using 4×2 factorial arrangement under four phase feeding program. Four levels (0.31, 0.45, 0.59 and 0.73%) and two sources (NH4Cl and CaCl2) of the dCl were allocated to 1,472 chicks in eight dietary treatments in which each treatment was replicated four times with 46 birds per replicate. The four phase feeding program was comprised of four dietary phases: Prestarter (d 1 to 10), Starter (d 11 to 20), Grower (d 21 to 33) and Finisher (d 34 to 42); and diets were separately prepared for each phase. The cations, anions, pH, dissolved oxygen (DO), temperature, electrical conductivity (EC), total dissolved solids (TDS) and salinity were analyzed in drinking water and were not affected by dietary treatments. BW gain (BWG; p≤0.009) and feed:gain (FG; p≤0.03) were improved in CaCl2 supplemented diets during d 1 to 10. The maximum response of BWG and FG was observed at 0.38% and 0.42% dCl, respectively, for d 34 to 42. However, the level of dCl for BWG during d 21 to 33 (p≤0.04) and d 34 to 42 (p≤0.009) was optimized at 0.60% and 0.42%, respectively. The level of dCl for optimized feed intake (FI; p≤0.006), FG (p≤0.007) and litter moisture (LM; p≤0.001) was observed at 0.60%, 0.38% and 0.73%, respectively, for d 1 to 42. Water intake (DWI) was not affected by increasing dCl supplementation (p>0.05); however, the ratio between DWI and FI (DWI:FI) was found highest at 0.73% dCl during d 1 to 10 (p≤0.05) and d 21 to 33 (p≤0.009). Except for d 34 to 42 (p≤0.006), the increasing level of dCl did not result in a significant difference in mortality during any phase. Blood pH and glucose, and breast and thigh weights (percentage of dressed weight) were improved while dressing percentage (DP) and gastrointestinal health were exacerbated with NH4Cl as compared to CaCl2 supplemented diets (p≤0.001). Higher plasma Na(+) and HCO3 (-) and lower Cl(-) and Ca(++) were observed in NH4Cl supplemented diets (p≤0.001). Increasing supplementation of dCl increased plasma Cl(-) (p≤0.04; quadratically) and linearly reduced plasma K(+) (p≤0.001), Ca(++) (p≤0.003), HCO3 (-) (p≤0.001), and Na(+) (p≤0.001; quadratically). Consequently, higher requirements of dietary chloride are suggested for feed intake; nevertheless, lower levels of dietary chloride are sufficient to support optimal BWG and FG with increasing age. The NH4Cl supplemented diets ameliorate breast and thigh meat yield along with overall energy balance (glucose).

TOP2B Is Required to Maintain the Adrenergic Neural Phenotype and for ATRA-Induced Differentiation of SH-SY5Y Neuroblastoma Cells.

The neuroblastoma cell line SH-SY5Y is widely used to study retinoic acid (RA)-induced gene expression and differentiation and as a tool to study neurodegenerative disorders. SH-SY5Y cells predominantly exhibit adrenergic neuronal properties, but they can also exist in an epigenetically interconvertible alternative state with more mesenchymal characteristics; as a result, these cells can be used to study gene regulation circuitry controlling neuroblastoma phenotype. Using a combination of pharmacological inhibition and targeted gene inactivation, we have probed the requirement for DNA topoisomerase IIB (TOP2B) in RA-induced gene expression and differentiation and in the balance between adrenergic neuronal versus mesenchymal transcription programmes. We found that expression of many, but not all genes that are rapidly induced by ATRA in SH-SY5Y cells was significantly reduced in the TOP2B null cells; these genes include BCL2, CYP26A1, CRABP2, and NTRK2. Comparing gene expression profiles in wild-type versus TOP2B null cells, we found that long genes and genes expressed at a high level in WT SH-SY5Y cells were disproportionately dependent on TOP2B. Notably, TOP2B null SH-SY5Y cells upregulated mesenchymal markers vimentin (VIM) and fibronectin (FN1) and components of the NOTCH signalling pathway. Enrichment analysis and comparison with the transcription profiles of other neuroblastoma-derived cell lines supported the conclusion that TOP2B is required to fully maintain the adrenergic neural-like transcriptional signature of SH-SY5Y cells and to suppress the alternative mesenchymal epithelial-like epigenetic state.

Modelling and numerical computation for flow of micropolar fluid towards an exponential curved surface: a Keller box method.

The numerical analysis of MHD boundary layer non-Newtonian micropolar fluid due to an exponentially curved stretching sheet is developed in this study. In the energy equation effects of viscous dissipation are included. For the mathematical description of the governing equations curvilinear coordinates are used. By utilizing exponential similarity variables, the modelled partial differential equations (PDEs) are reduced into ordinary ones. The resultant non-linear ODEs are numerically solved with two methods shooting and Keller box method. The study reveals that the governing parameters, namely, radius of curvature, material parameter, magnetic parameter, Prandtl number and Eckert number have major effects on the fluid velocity, micro-rotation velocity, surface friction, couple stress and heat transfer rate. The results indicate that the magnetic field diminishes the fluid velocity inside the hydrodynamics boundary layer whereas it enhances the temperature inside the thermal boundary layer. Microrotation profile decreases near the surface, as the magnetic parameter and radius of curvature increases but far away behavior is opposite. The material parameter enhances the velocity and microrotation profile whereas, opposite behaviors is noticed for the temperature distribution. Obtained outcomes are also compared with the existing literature and the comparison shows a good agreement with existing studies.

Hyperhomocysteinemia as an Independent Risk Factor for Coronary Heart Disease. Comparison with Conventional Risk Factors.

The present study was designed to evaluate the strength of association of raised plasma homocysteine concentration as a risk factor for coronary heart disease independent of conventional risk factor. It was a case control study conducted at Punjab Institute of Cardiology Lahore. A total of 210 subjects aged 25 to 60 years comprising of 105 newly admitted patients of CHD as cases and 105 age and sex matched healthy individuals with no history of CHD as control were recruited for the study. Fasting blood samples were obtained from cases and controls. Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) method on automated immunoassay analyzer (Abbott IMX). Total cholesterol, triglyceride and HDL cholesterol were analyzed using calorimetric kit methods. The concentration of LDL cholesterol was calculated using Friedewald formula. The patients were also assessed for traditional risk factors such as age, sex, family history of CVD, hypertension, smoking and physical activity, and were compared with control subjects. The collected data was entered in SPSS version 24 for analysis and interpretation.The mean age in controls and experimental groups were 43.00± 8.42 years and 44.72± 8.59 years with statistically same distribution (p- value= 0.144). The mean plasma homocysteine for cases was 22.33± 9.22 µmol/L where as it was 12.59±3.73 µmol/L in control group. Highly significant difference was seen between the mean plasma level of homocysteine in cases and controls (p˂0.001).Simple logistic regression indicates a strong association of coronary heart disease with hyperhomocysteinemia (OR 7.45), which remained significantly associated with coronary heart disease by multivariate logistic regression (OR 7.10, 95%C1 3.12-12.83, p=0.000). The present study concludes that elevated levels of Plasma homocysteine is an independent risk factor for coronary heart disease independent of conventional risk factors and can be used as an indicator for predicting the future possibility for the onset of CVD.

Risk factors for outbreaks caused by variant strain of Newcastle disease on environmentally controlled broiler chicken farms in Lahore, Pakistan.

Newcastle disease (ND) is a frequently reported disease in poultry among both vaccinated and non-vaccinated flocks in Pakistan. During 2011-2012 poultry industry in Punjab, mainly in Lahore region, faced fatal outbreaks of ND caused by a variant strain. An analytical study was conducted during outbreak period in Lahore region. A total of 114 environmentally controlled farms were selected with the help of convenient sampling method. A questionnaire was designed about the potential risk factors associated with the spread of ND outbreak. The bivariate relationships between ND status and independent variables were investigated by applying the Chi-square and Fisher's exact test. Multivariable logistic model was used to estimate the effect of each studied variable on the outcome by adjusting the other variables in the model. The variables which showed an association with ND outbreaks at commercial poultry farms were improper method for dead birds disposal (OR=4.96; 95% CI 1.63-15.12), use of same feed transporting vehicle at multiple poultry farms (OR=4.92; 95% CI 1.58-15.33), farm to farm distance of less than 1 km (OR=9.32; 95% CI(1.19-73.12), number of sheds at one farm (OR=2.31; 95% CI 0.93-5.69), labor type (OR=2.72; 95% CI 0.83-8.88) and biosecurity (OR= 4.47; 95% CI 0.56-35.66).

Global epidemiology of Equine Influenza viruses; "A possible emerging zoonotic threat in future" an extensive systematic review with evidence.

There are different opinions around the World regarding the zoonotic capability of H3N8 equine influenza viruses. In this report, we have tried to summarize the findings of different research and review articles from Chinese, English, and Mongolian Scientific Literature reporting the evidence for equine influenza virus infections in human beings. Different search engines i.e. CNKI, PubMed, ProQuest, Chongqing Database, Mongol Med, and Web of Knowledge yielded 926 articles, of which 32 articles met the inclusion criteria for this review. Analyzing the epidemiological and Phylogenetic data from these articles, we found a considerable experimental and observational evidence of H3N8 equine influenza viruses infecting human being in different parts of the World in the past. Recently published articles from Pakistan and China have highlighted the emerging threat and capability of equine influenza viruses for an epidemic in human beings in future. In this review article we have summarized the salient scientific reports published on the epidemiology of equine influenza viruses and their zoonotic aspect. Additionally, several recent developments in the start of 21st century, including the transmission and establishment of equine influenza viruses in different animal species i.e. camels and dogs, and presumed encephalopathy associated to influenza viruses in horses, have documented the unpredictable nature of equine influenza viruses. In sum up, several reports has highlighted the unpredictable nature of H3N8 EIVs highlighting the need of continuous surveillance for H3N8 in equines and humans in contact with them for novel and threatening mutations.

Isolation and characterization of bacteria residing in the oral, gut, and fecal samples of different pheasant species.

There is a paucity of research conducted on microbial prevalence in pheasants. The microbiota of captive birds has zoonotic significance and must be characterize. Present study is therefore planned to assess the microbiota from oral, fecal and gut content of captive avian species. It will be helpful in characterization of harmful microbes. Different samples taken from oral, gut and feces of ring-necked pheasants (Phasianus colchicus), green pheasants (Phasianus versicolor), golden pheasant (Chrysolophus pictus) and silver pheasant (Lophura nycthemera). Samples were collected, diluted, and inoculated onto different agar plates (MacConkey, SS agar, MSA and nutrient agar) for cultivation of bacterial species. Colonies of E.coli, Staphylococcus spp. Brachyspira spp. and Campylobacter spp were observed based on colony morphology. Colony forming unit showed E. coli as frequently found bacteria in fecal, oral and gut contents of all the above pheasants. The overall significance difference was found among bacterial species of golden pheasants, green pheasant, ring-necked pheasant, and silver pheasants. It was concluded that E.coli is predominant isolated from heathy pheasants followed by Campylobacter, Staphylococcus and Brachyspira.

Precision therapy with anaplastic lymphoma kinase inhibitor ceritinib in ALK-rearranged anaplastic large cell lymphoma.

BACKGROUND: More than 80% of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) patients harbor the (nucleophosmin) NPM1-ALK fusion gene t(2;5) chromosomal translocation. We evaluated the preclinical and clinical efficacy of ceritinib treatment of this aggressive lymphoma. MATERIALS AND METHODS: We studied the effects of ceritinib treatment in NPM1-ALK+ T-cell lymphoma cell lines in vitro and on tumor size and survival advantage in vivo utilizing tumor xenografts. We treated an NPM1-ALK+ ALCL patient with ceritinib. We reviewed all hematologic malignancies profiled by a large hybrid-capture next-generation sequencing (NGS)-based comprehensive genomic profiling assay for ALK alterations. RESULTS: In our in vitro experiments, ceritinib inhibited constitutive activation of the fusion kinase NPM1-ALK and downstream effector molecules STAT3, AKT, and ERK1/2, and induced apoptosis of these lymphoma cell lines. Cell cycle analysis following ceritinib treatment showed G0/G1 arrest with a concomitant decrease in the percentage of cells in S and G2/M phases. Further, treatment with ceritinib in the NPM1-ALK+ ALCL xenograft model resulted in tumor regression and improved survival. Of 19 272 patients with hematopoietic diseases sequenced, 58 patients (0.30%) harbored ALK fusions that include histiocytic disorders, multiple myeloma, B-cell neoplasms, Castleman's disease, and juvenile xanthogranuloma. A multiple relapsed NPM1-ALK+ ALCL patient treated with ceritinib achieved complete remission with ongoing clinical benefit to date, 5 years after initiation of therapy. CONCLUSIONS: This ceritinib translational study in NPM1-ALK+ ALCL provides a strong rationale for a prospective study of ceritinib in ALK+ T-cell lymphomas and other ALK+ hematologic malignancies.

Modeling and numerical simulation of micropolar fluid over a curved surface: Keller box method.

BACKGROUND: This paper examines the flow behavior of micropolar liquid over a curved surface. MHD fluid is considered. The surface inducing the fluid motion has a prescribed temperature different from the ambient fluid moreover the heat transfer mechanism is investigated. Curvilinear coordinates are used for the mathematical formulation of the flow equation. Similarity variables are derived and are utilized to alter the governing expressions for the flow of momentum and heat transfer characteristic. METHOD: The resulting non-linear ODEs are resolved systematically by two numerically approaches namely; the Keller box method and the shooting method. RESULTS: The numerical results for the temperature and velocity fields has been presented through tables and graphs against the independent parameters and non-dimensional numbers i.e., material parameter, power law index, radius of curvature, magnetic parameter, Prandtl and Eckert numbers, skin friction (drag force) and Nusselt number. Physical explanation of the graph presented is given to understand the performance of fluid flow and heat transport phenomena in different emerging situation. CONCLUSION: The main outcomes in the presence of various flow variables on the skin friction velocity, Nusselt number, temperature are highlighted via graphical sketch and Tables. Velocity field displays a decreasing trend with magnetic parameter, power law index and radius of curvature of the stretching velocity whereas, opposite behavior observed for the material parameter. Near the surface curvature and magnetic parameter shows an enhancement in microrotation profile whereas, it shows reverse behavior when it is far away. Material parameter increases for large values of microrotation profile on the other hand power-law index decreases for large values. For higher values magnetic parameter, radius of curvature and Eckert number temperature profile increases. But temperature reduces subject to material parameter and Prandtl number.