Tvorba solitona u izotermnoj relativističkoj plazmi s pozitivnim i negativnim ionima

We have studied the phenomenon of solitary wave formation in a relativistic plasma having both positive and negative ions. The state of the plasma is assumed to be isothermal and ions are considered to be warm. The phase velocity, width and amplitude of the soliton are explicitly obtained as functions of σα, σβ, nβ0/nα0, uα0/c, uβ0/c and Q, where σα and σβ are the temperatures of the two kinds of ions, nα0 and nβ0 are the respective equilibrium densities, uα0 and uβ0 are the corresponding streaming velocities and Q is the mass ratio of the negative and positive ions.Proučavana je tvorba solitonskih valova u relativističkoj plazmi koja sadrži pozitivne i negativne ione. Pretpostavljeno je da je plazma izotermna i da su ioni vrući. Odredena je fazna brzina, širina i amplituda solitona u ovisnosti o σα, σβ, nβ0/nα0, uα0/c, uβ0/c i Q, gdje su σα i σβ temperature iona, nα0 i nβ0 pripadne ravnotežne gustoće, uα0 i nβ0 odgovarajuće brzine strujanja, a Q je omjer mase negativnih i pozitivnih iona

Tvorba solitona u izotermnoj relativističkoj plazmi s pozitivnim i negativnim ionima

We have studied the phenomenon of solitary wave formation in a relativistic plasma having both positive and negative ions. The state of the plasma is assumed to be isothermal and ions are considered to be warm. The phase velocity, width and amplitude of the soliton are explicitly obtained as functions of σα, σβ, nβ0/nα0, uα0/c, uβ0/c and Q, where σα and σβ are the temperatures of the two kinds of ions, nα0 and nβ0 are the respective equilibrium densities, uα0 and uβ0 are the corresponding streaming velocities and Q is the mass ratio of the negative and positive ions.Proučavana je tvorba solitonskih valova u relativističkoj plazmi koja sadrži pozitivne i negativne ione. Pretpostavljeno je da je plazma izotermna i da su ioni vrući. Odredena je fazna brzina, širina i amplituda solitona u ovisnosti o σα, σβ, nβ0/nα0, uα0/c, uβ0/c i Q, gdje su σα i σβ temperature iona, nα0 i nβ0 pripadne ravnotežne gustoće, uα0 i nβ0 odgovarajuće brzine strujanja, a Q je omjer mase negativnih i pozitivnih iona

Bayesian Reconstruction of P(r) Directly From Two-Dimensional Detector Images Via a Markov Chain Monte Carlo Method

The interatomic distance distribution, P(r), is a valuable tool for evaluating the structure of a molecule in solution and represents the maximum structural information that can be derived from solution scattering data without further assumptions. Most current instrumentation for scattering experiments (typically CCD detectors) generates a finely pixelated two-dimensional image. In contin­uation of the standard practice with earlier one-dimensional detectors, these images are typically reduced to a one-dimensional profile of scattering inten­sities, I(q), by circular averaging of the two-dimensional image. Indirect Fourier transformation methods are then used to reconstruct P(r) from I(q). Substantial advantages in data analysis, however, could be achieved by directly estimating the P(r) curve from the two-dimensional images. This article describes a Bayesian framework, using a Markov chain Monte Carlo method, for estimating the parameters of the indirect transform, and thus P(r), directly from the two-dimensional images. Using simulated detector images, it is demonstrated that this method yields P(r) curves nearly identical to the reference P(r). Furthermore, an approach for evaluating spatially correlated errors (such as those that arise from a detector point spread function) is evaluated. Accounting for these errors further improves the precision of the P(r) estimation. Experimental scattering data, where no ground truth reference P(r) is available, are used to demonstrate that this method yields a scattering and detector model that more closely reflects the two-dimensional data, as judged by smaller residuals in cross-validation, than P(r) obtained by indirect transformation of a one-dimensional profile. Finally, the method allows concurrent estimation of the beam center and D max, the longest interatomic distance in P(r), as part of the Bayesian Markov chain Monte Carlo method, reducing experimental effort and providing a well defined protocol for these parameters while also allowing estimation of the covariance among all parameters. This method provides parameter estimates of greater precision from the experimental data. The observed improvement in precision for the traditionally problematic D max is particularly noticeable

AQUEOUS BARK EXTRACT OF TERMINALIA ARJUNA PROTECTS AGAINST PHENYLHYDRAZINE INDUCED OXIDATIVE DAMAGE IN GOAT RED BLOOD CELL MEMBRANE BOUND AND METABOLIC ENZYMES

Objective: The objective of the present study is to determine the phenylhydrazine (PHZ) induced oxidative stress mediated alteration in the metabolic status and morphology of the red blood cells (RBC) and amelioration of the same by aqueous bark extract of Terminalia arjuna (TA).Methods: Fresh goat blood collected from local Kolkata Corporation approved slaughter house, was used for the present study. Packed cells were prepared from the freshly collected goat blood and were divided into four groups as follows for further studies i. e Group I: Control (CON), Group II: TA bark extract treated, named T5C (5 mg/ml, incubation mixture; positive control), Group III: PHZ treated (1 mM), Group IV: PHZ treated+TA bark extract at a dose of 5 mg/ml, named as P+T5. ROS, superoxide anion radical, and hydroxyl radical scavenging activity were determined. Intracellular iron and intracellular nitrate concentration were estimated. Activities of various membrane-bound enzymes like Na+/K+-ATPase, Mg2+-ATPase and Ca2+-ATPase and Ach-E were determined. Moreover, the activities of some metabolic enzymes like glucose 6-phosphate dehydrogenase (G6PDH), hexokinase, aldolase, lactase dehydrogenase were also studied. In addition, the morphological structure of RBCs was also determined.Results: PHZ treatment caused significant alterations in RBC morphology as well as altered the activities of membrane-bound as well as metabolic enzymes. All these changes following oxidative stress were found to be ameliorated when the RBCs were co-treated with PHZ and aqueous bark extract of TA. However, aqueous bark extract of TA alone did not exhibit any such changes in RBC.Conclusion: The aqueous bark extract of TA ameliorates PHZ-induced oxidative damages in goat RBC possibly by an antioxidant mechanism(s). The aqueous bark extract of TA may have future therapeutic relevance in oxidative stress-induced damages in RBCs.Keywords: Antioxidant enzymes, Aqueous bark extract, Oxidative stress, Phenylhydrazine, Red blood cells, Terminalia arjun

Site-specific incorporation of citrulline into proteins in mammalian cells

Citrullination is a post-translational modification (PTM) of arginine that is crucial for several physiological processes, including gene regulation and neutrophil extracellular trap formation. Despite recent advances, studies of protein citrullination remain challenging due to the difficulty of accessing proteins homogeneously citrullinated at a specific site. Herein, we report a technology that enables the site-specific incorporation of citrulline (Cit) into proteins in mammalian cells. This approach exploits an engineered E. coli-derived leucyl tRNA synthetase-tRNA pair that incorporates a photocaged-citrulline (SM60) into proteins in response to a nonsense codon. Subsequently, SM60 is readily converted to Cit with light in vitro and in living cells. To demonstrate the utility of the method, we biochemically characterize the effect of incorporating Cit at two known autocitrullination sites in Protein Arginine Deiminase 4 (PAD4, R372 and R374) and show that the R372Cit and R374Cit mutants are 181- and 9-fold less active than the wild-type enzyme. This technology possesses the potential to decipher the biology of citrullination

Development of a Suicide Inhibition-Based Protein Labeling Strategy for Nicotinamide N-Methyltransferase

Nicotinamide N-methyltransferase (NNMT) catalyzes the S-adenosyl-l-methionine-dependent methylation of nicotinamide to form N-methylnicotinamide. This enzyme detoxifies xenobiotics and regulates NAD+ biosynthesis. Additionally, NNMT is overexpressed in various cancers. Herein, we describe the first NNMT-targeted suicide substrates. These compounds, which include 4-chloropyridine and 4-chloronicotinamide, exploit the broad substrate scope of NNMT; methylation of the pyridine nitrogen enhances the electrophilicity of the C4 position, thereby promoting an aromatic nucleophilic substitution by C159, a noncatalytic cysteine. On the basis of this activity, we developed a suicide inhibition-based protein labeling strategy using an alkyne-substituted 4-chloropyridine that selectively labels NNMT in vitro and in cells. In total, this study describes the first NNMT-directed activity-based probes

Halogen Bonding Increases the Potency and Isozyme-selectivity of Protein Arginine Deiminase 1 Inhibitors

Protein Arginine Deiminases (PADs) hydrolyze the side chain of arginine to form citrulline. Aberrant PAD activity is associated with rheumatoid arthritis, multiple sclerosis, lupus, and certain cancers. These pathologies established the PADs as therapeutic targets and multiple PAD inhibitors are known. Herein, we describe the first highly potent PAD1-selective inhibitors (1 and 19). Detailed structure-activity relationships indicate that their potency and selectivity is due to the formation of a halogen bond with PAD1. Importantly, these inhibitors inhibit histone H3 citrullination in HEK293TPAD1 cells and mouse zygotes with excellent potency. Based on this scaffold, we also developed a PAD1-selective activity-based probe that shows remarkable cellular efficacy and proteome selectivity. Based on their potency and selectivity we expect that 1 and 19 will be widely used chemical tools to understand PAD1 biology

Etiologic factors related to unsatisfactory ThinPrep cervical cytology: Evaluation and potential solutions to improve

BACKGROUND: In cervical cytology, the unsatisfactory rates for ThinPrep (TP) are slightly higher compared to SurePath. We examined various causes and explored potential for resolution of this discrepancy. MATERIALS AND METHODS: Totally, 19,422 cases were reviewed and 1000 unsatisfactory specimens were selected and analyzed. 531 specimens were available for wash protocol. Out of 114 unsatisfactory specimens associated with atrophic cellular changes (ACC), 48 were resubmitted by provider and reevaluated. RESULTS: Lubricant and lubricant-like debris/contamination (LUBE) was the most common cause of unsatisfactory specimens (68%; 681/1000) followed by blood (7.5%); ACC only (without other interfering factors) (2.4%); inflammation (3.0%); and combinations thereof (1.9%). 11.5% showed scant cellularity without an identifiable cause. 3.3% were virtually acellular. Wash protocol improved cellularity in 48% (256/531) of cases. However, only 29% (73/256) of those were satisfactory (with more than 5000 cells). Quantitative reduction in LUBE after wash protocol varied with different morphological subtypes. Interpretation patterns on satisfactory specimens after wash protocol were comparable to the results on selected cohort of specimens during the same study period. Out of 114 ACC, wash protocol was performed on 68 ACC specimens leading to satisfactory TP in 24% (16/68). Totally, 48 cases reported as unsatisfactory with ACC, were resubmitted by the providers between 2 weeks and 2 years. 44 (92%) showed increased cellularity, out of which 52% (23/44) did not show ACC. CONCLUSION: LUBE was the most common cause of unsatisfactory TP in addition to interference by blood and association with atrophic changes. Knowing the morphological spectrum of LUBE would help to identify it as the cause of unsatisfactory TP. Communicating the cause of unsatisfactory TP such as LUBE, ACC, and blood would hint the provider to take appropriate precaution during submission of the repeat specimen, leading to improved patient care

Bidirectional Psychoneuroimmune Interactions in the Early Postpartum Period Influence Risk of Postpartum Depression

More than 500,000 U.S. women develop postpartum depression (PPD) annually. Although psychosocial risks are known, the underlying biology remains unclear. Dysregulation of the immune inflammatory response and the hypothalamic–pituitary–adrenal (HPA) axis are associated with depression in other populations. While significant research on the contribution of these systems to the development of PPD has been conducted, results have been inconclusive. This is partly because few studies have focused on whether disruption in the bidirectional and dynamic interaction between the inflammatory response and the HPA axis together influence PPD. In this study, we tested the hypothesis that disruption in the inflammatory-HPA axis bidirectional relationship would increase the risk of PPD. Plasma pro- and anti-inflammatory cytokines were measured in women during the 3rd trimester of pregnancy and on Days 7 and 14, and Months 1, 2, 3, and 6 after childbirth. Saliva was collected 5 times the day preceding blood draws for determination of cortisol area under the curve (AUC) and depressive symptoms were measured using the Edinburgh Postpartum Depression Survey (EPDS). Of the 152 women who completed the EPDS, 18% were depressed according to EDPS criteria within the 6 months postpartum. Cortisol AUC was higher in symptomatic women on Day 14 (p = .017). To consider the combined effects of cytokines and cortisol on predicting symptoms of PPD, a multiple logistic regression model was developed that included predictors identified in bivariate analyses to have an effect on depressive symptoms. Results indicated that family history of depression, day 14 cortisol AUC, and the day 14 IL8/IL10 ratio were significant predictors of PPD symptoms. One unit increase each in the IL8/IL10 ratio and cortisol AUC resulted in 1.50 (p = 0.06) and 2.16 (p = 0.02) fold increases respectively in the development of PPD. Overall, this model correctly classified 84.2% of individuals in their respective groups. Findings suggest that variability in the complex interaction between the inflammatory response and the HPA axis influence the risk of PPD