Membrane in M5-branes Background

In this paper, we investigate the properties of a membrane in the M5-brane background. Through solving the classical equations of motion of the membrane, we can understand the classical dynamics of the membrane in this background.Comment: 15 pages, typos correcte

Doxycycline Regulated Induction of AKT in Murine Prostate Drives Proliferation Independently of p27 Cyclin Dependent Kinase Inhibitor Downregulation

The PI3 kinase/AKT pathway has been shown to increase degradation of the p27 cyclin dependent kinase inhibitor through phosphorylation of consensus AKT sites on p27 and SKP2, and AKT driven proliferation may be checked by feedback mechanisms that increase p27 expression and induce senescence. However, these AKT sites are not conserved in mouse, and it has not been clear whether AKT negatively regulates murine p27. Transgenic mice with a probasin promoter controlled prostate specific reverse tetracycline transactivator (ARR2Pb-rtTA) were generated and used to achieve doxycycline inducible expression of a tetracycline operon regulated constitutively active myristoylated AKT1 transgene (tetO-myrAKT). Doxycycline induction of myrAKT occurred within 1 day and rapidly induced proliferation (within 4 days) and the development of prostatic intraepithelial neoplasia (PIN) lesions in ventral prostate, which did not progress to prostate cancer. Cells in these lesions expressed high levels of p27, had increased proliferation, and there was apoptosis of centrally located cells. Doxycycline withdrawal resulted in apoptosis of cells throughout the lesions and rapid clearing of hyperplastic glands, confirming in vivo the critical antiapoptotic functions of AKT. Significantly, analyses of prostates immediately after initiating doxycycline treatment further showed that p27 expression was rapidly increased, coincident with the induction of myrAKT and prior to the development of hyperplasia and PIN. These findings establish in vivo that murine p27 is not negatively regulated by AKT and indicate that proliferation in PI3 kinase/AKT pathway driven mouse models is mediated by p27 independent mechanisms that may be distinct from those in human. Further studies using prostate specific doxycycline regulated transgene expression may be useful to assess the acute effects of inducing additional transgenes in adult murine prostate epithelium, and to assess the requirements for continued transgene expression in transgene induced tumors

Utilizing systematic Mendelian randomization to identify potential therapeutic targets for mania

BackgroundMania has caused incalculable economic losses for patients, their families, and even society, but there is currently no effective treatment plan for this disease without side effects.MethodsUsing bioinformatics and Mendelian randomization methods, potential drug target genes and key substances associated with mania were explored at the mRNA level. We used the chip expression profile from the GEO database to screen differential genes and used the eQTL and mania GWAS data from the IEU database for two-sample Mendelian randomization (MR) to determine core genes by colocalization. Next, we utilized bioinformatics analysis to identify key substances involved in the mechanism of action and determined related gene targets as drug targets.ResultsAfter differential expression analysis and MR, a causal relationship between the expression of 46 genes and mania was found. Colocalization analysis yielded six core genes. Five key substances were identified via enrichment analysis, immune-related analysis, and single-gene GSVA analysis of the core genes. MR revealed phenylalanine to be the only key substance that has a unidirectional causal relationship with mania. In the end, SBNO2, PBX2, RAMP3, and QPCT, which are significantly associated with the phenylalanine metabolism pathway, were identified as drug target genes.ConclusionSBNO2, PBX2, RAMP3, and QPCT could serve as potential target genes for mania treatment and deserve further basic and clinical research. Medicinal target genes regulate the phenylalanine metabolism pathway to achieve the treatment of mania. Phenylalanine is an important intermediate substance in the treatment of mania that is regulated by drug target genes

View of Pakistani residents toward coronavirus disease (COVID-19) during a rapid outbreak: A rapid online survey

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Background: Coronavirus disease (COVID-19) is a deadly disease that is affecting most of the countries worldwide. Public understanding, including knowledge about signs and symptoms, mode of transmission, and hygiene of COVID-19, is vital for designing effective control strategies during a public health crisis. The current study is aimed at investigating the public’s perspective about COVID-19, including their knowledge, attitude, and practices. Methods: A rapid online survey comprising 22 items was administered during the rapid outbreak of COVID-19 in Pakistan. Questions were focused on the prevention, transmission, clinical features, and control of COVID-19. In addition, the attitudes and practices of the participants were explored. Descriptive statistics, Mann–Whitney tests, Kruskal–Wallis tests, and regression analysis were carried out during data analysis. Results: A total of 1257 respondents participated in this study. Most of the respondents had good knowledge (good = 64.8%, average = 30.5%, poor = 4.7%) of COVID-19. Gender, marital status, education, and residence were observed to have a significant association with the knowledge score. A vast majority of the survey respondents (77.0%) believed that COVID-19 would be controlled successfully in Pakistan. The practices of wearing a mask (85.8%) and handwashing (88.1%) were common among the participants. Conclusion: The participants demonstrated good knowledge and reasonable attitudes and practices toward most aspects of the COVID-19 outbreak. Improvements in certain areas could be made by mass-level education

Six lanthanide supramolecular frameworks based on mixed m-/p-hydroxybenzoic acid and 1,10-phenanthroline tectons: syntheses, crystal structures, and properties

To further explore the research of the coordination possibilities of lanthanide ions with m-/p-hydroxybenzoic acid isomers in the presence of chelating N-donor ligand 1,10-phenanthroline (phen), six lanthanide supramolecular frameworks based on 3- and 4-hydroxybenzoic acids, namely [Dy(m-L)(m-HL) (phen)]center dot H2O (1) (m-H2L = 3-hydroxybenzoic acid), [Ln(m-HL)(3)(phen)] (Ln = Gd for 2 and Tb for 3), [Ln(p-HL)(3)(phen)(H2O)] (Ln = Dy for 4, Gd for 5, and Tb for 6; p-H2L = 4-hydroxybenzoic acid), were synthesized and characterized. Structural analyses reveal that complex 1 has a two-dimensional (2-D) sheet structure while complexes 2 and 3 take the dinuclear structures in the 3-hydroxybenzoate derivatives. In the 4-hydroxybenzoate derivatives, complexes 4-6 are isostructural and incorporated by monomeric units. Finally, all the complexes exhibit three-dimensional (3-D) supramolecular frameworks (bcu net for I; bct nets for 2, and 4-6; hex net for 3) with the aid of abundant hydrogen bonding, pi center dot center dot center dot pi and C-H center dot center dot center dot pi interactions. The results reveal that the different positions of the-OH substituent and coordination modes of hydroxybenzoic acids adjust the final coordination networks. Moreover, the magnetic and luminescent properties of the complexes have also been investigated and discussed. (C) 2016 Elsevier Ltd. All rights reserved

Selection and evaluation of phosphate-solubilizing bacteria from grapevine rhizospheres for use as biofertilizers

Phosphate-solubilizing bacteria (PSB) have the ability to solubilize insoluble phosphorus (P) and release soluble P. Extensive research has been performed with respect to PSB isolation from the rhizospheres of various plants, but little is known about the prevalence of PSB in the grapevine rhizosphere. In this study, we aimed to isolate and identify PSB from the grapevine rhizosphere in five vineyards of Northwest China, to characterize their plant-growth-promoting (PGP) traits, evaluate the effect of stress on their phosphate-solubilizing activity (PSA), and test their ability to stimulate the growth of Vitis vinifera L. cv. Cabernet Sauvignon. From the vineyard soils, 66 PSB isolates were screened, and 10 strains with high PSA were identified by 16S rRNA sequencing. Sequence analysis revealed that these 10 strains belonged to 4 genera and 5 species: Bacillus aryabhattai, B. megaterium, Klebsiella variicola, Stenotrophomonas rhizophila, and Enterobacter aerogenes. The selected PSB strains JY17 (B. aryabhattai) and JY22 (B. aryabhattai) were positive for multiple PGP traits, including nitrogen fixation and production of indole acetic acid (IAA), siderophores, 1-aminocyclopropane-1-carboxylate (ACC) deaminase, chitinase, and protease. JY17 and JY22 showed strong PSA under stress conditions of high pH, high salt, and high temperature. Therefore, these two isolates can be used as biofertilizers in saline-alkaline soils. The inoculation with PSB significantly facilitated the growth of V. vinifera cv. Cabernet Sauvignon under greenhouse conditions. Use of these PSB as biofertilizers will increase the available P content in soils, minimize P-fertilizer application, reduce environmental pollution, and promote sustainable agriculture

Effect of pharmaceutical promotion and incentives offered by pharmaceutical companies on the prescribing pattern of medical students: a cross-sectional study from a developing nation Pakistan

BackgroundPharmaceutical companies continuously pursue healthcare professionals, starting from the medical college level, which can ultimately lead to irrational prescribing of drugs and antibiotics. Therefore, our main aim was to evaluate the opinions and attitudes of medical students toward pharmaceutical promotion.MethodsThis study utilized a cross-sectional online survey that applied the snowball sampling technique. Data were collected from three public and three private sector medical colleges in Punjab, Pakistan using snowball sampling. A modified version of a pre-structured questionnaire was used to collect data between October 2020 and January 2021. Medical students from the third year onward were captivated. The tool was made available on Google Forms and students could access it by clicking the link shared. The effect of promotion on prescribing pattern and future prescribing of antibiotics were measured. Descriptive statistics, chi-square, and t-test were used to analyze the data.ResultsA total of 1,301 students filled out the survey, but only 1,227 responses were acceptable. The average age was found to be 23.4 ± 1.59 years. Slightly more than half of the respondents were male participants (57.7%), and a significant proportion (84.1%) reported being aware of pharmaceutical promotion. A smaller number (27.7%) felt that physicians who meet medical representatives more frequently tend to prescribe more antibiotics and 46.3% indicated they would be willing to prescribe antibiotics under the promotional influence. Medical students who were male, in senior college years, attended government institutions, and had lower parental income showed significantly higher perception and attitude scores (p < 0.05) which, in turn, may show their inclination to promotional activities. Many students agreed with the view that pharmaceutical promotion (PP) activities may alter prescribing practices and also believed that they contribute to the increased irrational prescribing of drugs and antibiotics.ConclusionThe study revealed that only a small number of students are willing to engage in promotional activities and accept rewards, which influences their choice toward selection of drugs and antibiotics. This study highlighted the necessity of giving proper educational instructions regarding the promotion of drugs to medical students. This study also focused on the educational prerequisites of the students

A novel Brassica–rhizotron system to unravel the dynamic changes in root system architecture of oilseed rape under phosphorus deficiency

Background and Aims: An important adaptation of plants to phosphorus (P) deficiency is to alter root system architecture (RSA) to increase P acquisition from the soil, but soil-based observations of RSA are technically challenging, especially in mature plants. The aim of this study was to investigate the root development and RSA of oilseed rape (Brassica napus L.) under low and high soil P conditions during an entire growth cycle. Methods: A new large Brassica–rhizotron system (approx. 118-litre volume) was developed to study the RSA dynamics of B. napus ‘Zhongshuang11’ in soils, using top-soils supplemented with low P (LP) or high P (HP) for a full plant growth period. Total root length (TRL), root tip number (RTN), root length density (RLD), biomass and seed yield traits were measured. Key Results: TRL and RTN increased more rapidly in HP than LP plants from seedling to flowering stages. Both traits declined from flowering to silique stages, and then increased slightly in HP plants; in contrast, root senescence was observed in LP plants. RSA parameters measured from the polycarbonate plates were empirically consistent with analyses of excavated roots. Seed yield and shoot dry weights were closely associated positively with root dry weights, TRL, RLD and RTN at both HP and LP. Conclusions: The Brassica–rhizotron system is an effective method for soil-based root phenotyping across an entire growth cycle. Given that root senescence is likely to occur earlier under low P conditions, crop P deficiency is likely to affect late water and nitrogen uptake, which is critical for efficient resource use and optimal crop yields