Classical PR Research Articles

A clinico-epidemiological study of pityriasis rosea in patients attending a tertiary care hospital in North Eastern India

Background: Pityriasis Rosea is an acute self limiting disease, probably infective in origin affecting mainly children and young adults and characterised by a distinctive skin eruption and minimal constitutional symptoms. Aim: Our study was done to evaluate the clinical and epidemiological profile of pityriasis rosea in patients attending Dermatology OPD in a tertiary care centre in North Eastern India during the tenure period from June 2019 to May 2020. Materials And Methods: A total of 34 patients of pityriasis rosea diagnosed clinically attending the out patient department of Dermatology were recruited over a period of one year. Clinical and demographic data were noted. Results: Out of 34 patients, 21(61%) were males and 13(38%) were females. Majority of the patients were seen in the age group of 11-30 years. Pruritus was found in the majority of patients. Seasonal variation was evident, with highest incidence in summer followed by winter season. Classical PR was the common type seen and localized and inverse PR were the most common atypical presentation. Conclusion: PR is a common self limiting disorder seen in children and young adults. Knowledge about the disease will help in correct management and prevent unnecessary distress to the patient. Keywords: Pityriasis rosea, Herald patch, Christmas tree pattern, Clinical features, Diagnosis.

Process Operability Algorithms: Past, Present, and Future Developments

In this Article, the recently developed multimodel and NLP-based operability approaches are reviewed and further developed in terms of theory, application, and software infrastructure. Classical pr...

Extending Classical Multirate Signal Processing Theory to Graphs—Part II: M-Channel Filter Banks

This paper builds upon the basic theory of multirate systems for graph signals developed in the companion paper (Part I) and studies $M$ -channel polynomial filter banks on graphs. The behavior of such graph filter banks differs from that of classical filter banks in many ways, the precise details depending on the eigenstructure of the adjacency matrix $\boldsymbol {A}$ . It is shown that graph filter banks represent, (linear and) periodically, shift-variant systems only when $\boldsymbol {A}$ satisfies the noble identity conditions developed in Part I. It is then shown that perfect reconstruction graph filter banks can always be developed when $\boldsymbol {A}$ satisfies the eigenvector structure satisfied by $M$ -block cyclic graphs and has distinct eigenvalues (further restrictions on eigenvalues being unnecessary for this). If $\boldsymbol {A}$ is actually $M$ -block cyclic then these PR filter banks indeed become practical, i.e., arbitrary filter polynomial orders are possible, and there are robustness advantages. In this case, the PR condition is identical to PR in classical filter banks—any classical PR example can be converted to a graph PR filter bank on an $M$ -block cyclic graph. It is shown that for $M$ -block cyclic graphs with all eigenvalues on the unit circle, the frequency responses of filters have meaningful correspondence with classical filter banks. Polyphase representations are then developed for graph filter banks and utilized to develop alternate conditions for alias cancellation and perfect reconstruction, again for graphs with specific eigenstructures. It is then shown that the eigenvector condition on the graph can be relaxed by using similarity transforms.

Escaping Depressions in LRTS Based on Incremental Refinement of Encoded Quad-Trees

In the context of robot navigation, game AI, and so on, real-time search is extensively used to undertake motion planning. Though it satisfies the requirement of quick response to users’ commands and environmental changes, learning real-time search (LRTS) suffers from the heuristic depressions where agents behave irrationally. There have introduced several effective solutions, such as state abstractions. This paper combines LRTS and encoded quad-tree abstraction which represent the search space in multiresolutions. When exploring the environments, agents are enabled to locally repair the quad-tree models and incrementally refine the spatial cognition. By virtue of the idea of state aggregation and heuristic generalization, our EQ LRTS (encoded quad-tree based LRTS) possesses the ability of quickly escaping from heuristic depressions with less state revisitations. Experiments and analysis show that (a) our encoding principle for quad-trees is a much more memory-efficient method than other data structures expressing quad-trees, (b) EQ LRTS differs a lot in several characteristics from classical PR LRTS which represent the space and refine the paths hierarchically, and (c) EQ LRTS substantially reduces the planning amount and curtails heuristic updates compared with LRTS on uniform cells.

Expression of Membrane Progesterone Receptors (mPR/PAQR) in Ovarian Cancer Cells: Implications for Progesterone-Induced Signaling Events

The high mortality rates associated with ovarian cancer are largely due to a lack of highly effective treatment options for advanced stage disease; a time when initial diagnosis most commonly occurs. Recent evidence suggests that the steroid hormone, progesterone, may possess anti-tumorigenic properties. With the discovery of a new class of membrane-bound progesterone receptors (mPRs) belonging to the progestin and adipoQ receptor (PAQR) gene family in the ovary, there are undefined mechanisms by which progesterone may inhibit tumor progression. Therefore, our goal was to define potential mPR-dependent signaling mechanisms operative in ovarian cancer cells. We detected abundant mPRα (PAQR7), mPRβ (PAQR8), and mPRγ (PAQR5), but not classical nuclear PR (A or B isoforms) mRNA expression and mPRα protein expression in a panel of commonly used ovarian cancer cell lines. In contrast to mPR action in breast cancer cells, progesterone alone failed to induce changes in cyclic adenosine monophosphate (cAMP) levels in ovarian cancer cells. However, progesterone enhanced cAMP production by β(1,2)-adrenergic receptors and increased isoproterenol-induced transcription from a cAMP response element (CRE)-driven reporter gene. Independently of β-adrenergic signaling, we additionally observed activation of both JNK1/2 and p38 MAPK in response to progesterone alone. This finding was supported by the results of a screen for potential mPR gene targets. Progesterone induced a significant increase in transcription of the pro-apoptotic marker BAX, whose activity and expression has been linked to JNK1/2 and p38 signaling. Inhibitors of JNK, but not p38, blocked progesterone-induced BAX expression. Taken together, these observations implicate at least two distinct signaling pathways that may be utilized by mPRs in ovarian cancer cells that exhibit regulatory genomic changes. These studies on mPR signaling in ovarian cancer lay the foundation for future work aimed at understanding how progesterone exerts its anti-tumorigenic effects in the ovary and suggest that pharmacologic activation of mPRs, abundantly expressed in ovarian cancers, may provide a new treatment option for patients with advanced stage disease.

Estrogen and progesterone receptors: from molecular structures to clinical targets

Research involving estrogen and progesterone receptors (ER and PR) have greatly contributed to our understanding of cell signaling and transcriptional regulation. In addition to the classical ER and PR nuclear actions, new signaling pathways have recently been identified due to ER and PR association with cell membranes and signal transduction proteins. Bio-informatics has unveiled how ER and PR recognize their ligands, selective modulators and co-factors, which has helped to implement them as key targets in the treatment of benign and malignant tumors. Knowledge regarding ER and PR is vast and complex; therefore, this review will focus on their isoforms, signaling pathways, co-activators and co-repressors, which lead to target gene regulation. Moreover it will highlight ER and PR involvement in benign and malignant diseases as well as pharmacological substances influencing cell signaling and provide established and new structural insights into the mechanism of activation and inhibition of these receptors.

The Prognostic Value of the Proliferation Marker Phosphohistone H3 (PPH3) in Luminal, Basal-Like and Triple Negative Phenotype Invasive Lymph Node-Negative Breast Cancer

Purpose: Prognostic comparison of phosphohistone-H3 (PPH3) with Cytokeratin 5/6 and/or 14 positive (= basal-CK), triple (ER, PR, HER2)-negative (= TNP) and basal-like (= TNP and basal-CK positive) phenotype in invasive breast cancers.Patients and Methods: Classical variables, PPH3, ER, PR, basal-CK and HER2 in 240 T1–2N0M0 patients under 71 years.Results: TNP and basal-like cancers had higher PPH3 expression than the other cancers (mean 48 versus 11, P < 0.001). Fifteen percent of the patients in the whole group, but 32–38% of TNP and basal-like cancers recurred.With multivariate analysis, PPH3 < 13 (n = 156) versus ≥ 13 (n = 84 = 35% of all cases) was the strongest and only prognosticator (10-year survival 96% and 64%, P ≤ 0.001, Hazard ratio = 9.0).Conclusion: PPH3 is the strongest prognosticators in luminal, Triple negative and basal-like T1–2N0M0 invasive breast cancers.

Transcriptional changes in barley–Cochliobolus sativusinteraction

Spot blotch caused by Cochliobolus sativus has been the major yield-reducing factor for barley production during the last decade. In this study, a systematic sequencing of expressed sequence tags (EST) was chosen to obtain a global picture of the assembly of genes involved in pathogenesis. To identify a large number of plant EST, which are induced at different time points, an amplified fragment length polymorphism display of complementary DNA was utilised. Transcriptional changes of 456 EST were observed, of which 22 have no previously described function. On one hand, EST-annotations showed homologies to a number of classical pathogenesis-related or PR genes that play a role in the signal transduction pathway. However, a notable number of EST were derived from hypothetical protein-coding genes with no clear domain sequence identity. Hence, the transcriptomic approach presented here constitutes no prior assumption about the genes activated during the C. sativus-barley interaction.

Early and specific gene expression triggered by rice resistance genePi33in response to infection byACE1avirulent blast fungus

* Our view of genes involved in rice disease resistance is far from complete. Here we used a gene-for-gene relationship corresponding to the interaction between atypical avirulence gene ACE1 from Magnaporthe grisea and rice resistance gene Pi33 to better characterize early rice defence responses induced during such interaction. * Rice genes differentially expressed during early stages of Pi33/ACE1 interaction were identified using DNA chip-based differential hybridization and QRT-PCR survey of the expression of known and putative regulators of disease resistance. * One hundred genes were identified as induced or repressed during rice defence response, 80% of which are novel, including resistance gene analogues. Pi33/ACE1 interaction also triggered the up-regulation of classical PR defence genes and a massive down-regulation of chlorophyll a/b binding genes. Most of these differentially expressed genes were induced or repressed earlier in Pi33/ACE1 interaction than in the gene-for-gene interaction involving Nipponbare resistant cultivar. * Besides demonstrating that an ACE1/Pi33 interaction induced classical and specific expression patterns, this work provides a list of new genes likely to be involved in rice disease resistance.

A New Type of Bacteriophytochrome Acts in Tandem with a Classical Bacteriophytochrome to Control the Antennae Synthesis in Rhodopseudomonas palustris

Phytochromes are chromoproteins found in plants and bacteria that switch between two photointerconvertible forms via the photoisomerization of their chromophore. These two forms, Pr and Pfr, absorb red and far-red light, respectively. We have characterized the biophysical and biochemical properties of two bacteriophytochromes, RpBphP2 and RpBphP3, from the photosynthetic bacterium Rhodopseudomonas palustris. Their genes are contiguous and localized near the pucBAd genes encoding the polypeptides of the light harvesting complexes LH4, whose synthesis depends on the light intensity. At variance with all (bacterio)phytochromes studied so far, the light-induced isomerization of the chromophore of RpBphP3 converts the Pr form to a form absorbing at shorter wavelength around 645 nm, designated as Pnr for near red. The quantum yield for the transformation of Pr into Pnr is about 6-fold smaller than for the reverse reaction. Both RpBphP2 and RpBphP3 autophosphorylate in their dark-adapted Pr forms and transfer their phosphate to a common response regulator Rpa3017. Under semiaerobic conditions, LH4 complexes replace specifically the LH2 complexes in wild-type cells illuminated by wavelengths comprised between 680 and 730 nm. In contrast, mutants deleted in each of these two bacteriophytochromes display no variation in the composition of their light harvesting complexes whatever the light intensity. From both the peculiar properties of these bacteriophytochromes and the phenotypes of their deletion mutants, we propose that they operate in tandem to control the synthesis of LH4 complexes by measuring the relative intensities of 645 and 710 nm lights.

Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens

In the past few years, besides the classical genomic effects of steroid hormones, a plethora of so called rapid non genomic effects have been described in different cell types, which are too rapid to be due to activation of gene expression. Although some of these effects might involve the same nuclear steroid receptors acting on different cellular signalling, others have been ascribed to poorly characterized membrane receptors. Several rapid nongenomic effects of progesterone (P) and estrogens (E) have been recently demonstrated in human spermatozoa. They seem to be mediated by the steroid binding to specific receptors on plasma membrane different from the classical ones. In particular, P has been demonstrated to stimulate calcium influx, tyrosine phosphorylation of sperm proteins, including extracellular signaling regulated kinases, chloride efflux and cAMP increase, finally resulting in activation of spermatozoa through induction of capacitation, hyperactivated motility and acrosome reaction. Conversely, E, by acting rapidly on calcium influx and on protein tyrosine phosphorylation, seem to modulate sperm responsiveness to P. Several attempts have been used to characterize the putative membrane receptors for P (mPR) and E (mER) in spermatozoa, however their isolation still remains elusive. However, in the past few years our laboratory has obtained several evidences supporting the existence and functional activity of mPR and mER in human spermatozoa. To characterize these membrane receptors, we used two antibodies directed against the ligand binding domains of the classical receptors, namely c262 and H222 antibodies for PR and ER respectively, hypothesizing that these regions should be conserved between nongenomic and genomic receptors. In western blot analysis of sperm lysates the antibodies detected a band of about 57 kDa for PR and of 29 kDa for ER, excluding the presence of the classical receptors. On live human spermatozoa, both antibodies were able to block the calcium and AR response to P and E respectively, whereas, antibodies directed against different domains of the classical PR and ER were ineffective.. Moreover, c262 antibody also blocks in vitro human sperm penetration of hamster oocytes. Taken together all these data strongly support the existence of mPR and mER different from the classical ones, mediating rapid effects of these steroid hormones in human spermatozoa.

Communications management for difficult and unpopular projects

Classical PR works on the basis that the public wants to buy the product. But the classic tools – media relations, leaflets, public meetings and exhibitions, and even advertising – all fail instantly when the product offered is unpopular or resisted. The approach for the communications of contentious projects is different and makes use of the “power pyramid”, which is how decisions are made within the democratic system. Stakeholders are the key to the successful communications management of difficult projects. To be successful, contentious projects must utilise a special stakeholder – the third‐party advocate. A mechanism for segmenting these stakeholders and mobilising them – often through a mutually beneficial project – must be in place. This maximises the chances of contentious projects succeeding.

Local and systemic induction of two defense-related subtilisin-like protease promoters in transgenic Arabidopsis plants. Luciferin induction of PR gene expression.

Following a pathogenic attack, plants are able to mount a defense response with the coordinated activation of a battery of defense-related genes. In this study we have characterized the mode of expression of the P69B and P69C genes from tomato (Lycopersicon esculentum Mill.), which encodes two closely related subtilisin-like proteases associated with the defense response. We have compared the mode of gene regulation in heterologous transgenic Arabidopsis plants harboring promoter-beta-glucuronidase (GUS) and promoter-luciferase (LUC) gene fusions for these two genes. These studies revealed that the P69B and P69C promoters are induced by salicylic acid as well as during the course of both a compatible and an incompatible interaction with Pseudomonas syringae. Furthermore, P69B and P69C expression takes place in both the local and the distal (noninoculated) leaves upon inoculation with bacteria but following different and unique tissue-specific patterns of expression that are also different to that described for most other classical PR genes. Also, we report that luciferin, the substrate for the reporter luciferase (LUC) gene, is able to activate expression of PR genes, and this may pose a problem when using this gene reporter system in studies related to plant defense.

Progesterone action in a murine Leydig tumor cell line (mLTC-1), possibly through a nonclassical receptor type.

In a recent report we demonstrated that a high (micromolar) concentration of progesterone (P) specifically down-regulates LH receptor (R) expression and function in murine Leydig tumor cells. The aim of the present study was to characterize further the putative novel R, mediating these P effects in the murine Leydig tumor cell line, mLTC-1. The binding of [3H]P to these cells revealed a high (Kd, approximately 9.3 nmol/liter) and a low affinity (Kd, approximately 284 nmol/liter) component, and the binding displayed with specificity (P > dehydroepiandrosterone > 17-OHP). The binding was apparently different from that of the classical nuclear PR in the following ways. 1) The P/glucocorticoid antagonist RU 486 did not compete with [3H]P binding to the mLTC-1 cells. 2) No expression of the classical PR messenger RNA was detected, despite clear P binding to these cells, by Northern hybridization or RT-PCR. 3) An antibody against the C-terminal end of the classical PR (alpha c-262) revealed in mLTC-1 cells several molecular size protein bands between 45-57 kDa on Western hybridization, whereas these immunoreactive proteins were faintly recognized by another antibody (alpha-PR) directed toward the NH2-terminal region of the classical PR. The sizes of the immunoreactive molecules were relatively similar to those detected using the same antibodies in human sperm lysates, but were at variance with the classical PR (120, 94, and 60 kDa), detected with these antibodies in human uterus. The immunoreactive proteins bound peroxidase-labeled-P, which could be displaced in the presence of a 10-fold excess of free P. 4) An immediate increase in the intracellular free calcium level was observed after P treatment in cultured mLTC-1 cells, whereas it also increased the 45Ca2+ entry within 15 min in these cells. 5) Increasing doses of P (0.1-10 micromol/liter) demonstrated significant inhibition of LH receptor messenger RNA levels in a dose-dependent manner in mLTC-1 cells. In conclusion, a nonclassical PR is expressed and functional in these cells, and it is clearly distinct from the classical nuclear PR. It is apparent that recently reported inhibitory effects of P on LH receptor gene expression and function are mediated through this novel type PR in mouse Leydig cells.

The host-tissue component of influenza viruses.

Serological cross-reactions between influenza viruses of the two major types A and B and between the viruses and extracts of host tissue were investigated to elucidate the nature and source of the antigens concerned. The results render untenable the generally accepted view that virus types A and B are totally unrelated antigenically and that any cross-reactivity which occurs must be due to impurities in the virus preparations used. Strong cross-complement fixation reactions were consistently demonstrable with highly purified viruses provided that the antisera were prepared by immunizing rabbits with heat-degraded viruses in which the specific antigens had been destroyed. Cross-reactions between the viruses and chorio-allantoic membrane extracts showed that the virus-group antigens differed from the dominant membrane antigen which is of the Forssman type. The cross-reacting antigens of the two viruses were also found to be distinguishable from each other by their different responses to heat degradation. With the classical strains PR 8 and Lee propagated in embryonated eggs, the virus-group antigen could not be removed by successive cycles of virus purification. The method of purification was adsorption of virus on human group O red cells followed by spontaneous elution effected by the receptor-destroying enzyme of the virus. The ratio of specific antigen to group antigen remained constant through six successive purification cycles. It is suggested that the host-tissue component of the viruses is an integral part of their structure which may be essential for virus synthesis and may have some determinant function in respect of virus behaviour. The possibility of its fortuitous inclusion within the virus matrix without serving any biological purpose has not been excluded, but in such case its presence would point to a replication mechanism different from simple binary fission.