Binding of dantrolene-Na to the ciliated membrane ofParamecium aurelia

Summary Dantrolene-Na is a muscular relaxant which binds to sarcoplasmic reticulum (SR) with high affinity and decreases the availability of Ca²⁺ channels. The binding of fluorescent compounds, dantrolene-Na, nifedipine and chlortetracycline to the ciliary membrane ofParamecium aurelia has been studied. Dantrolene at the concentrations of 1.9 · 10^–5, 3.8 · 10^–5 and 7.9 · 10^–5 M manifested a punctuated binding pattern to the cell membrane. Isolated cilia also bound dantrolene at their basal portion, whereas deciliated cell bodies lost their dotted binding pattern. Chlortetracycline showed a similar but weaker fluorescent staining. Nifedipine treated cells revealed no sign of fluorescent binding to the membrane and was only taken up in food vacuoles.Based on these observations we propose that dantrolene binding regular arrays ofParamecium cell membrane could be identical to granular plaques observed by electron microscope. The possible functioning of these structures as Ca²⁺ reservoirs is also discussed.     

Detection of plasmid-mediated quinolone resistance in clinical isolates of Enterobacteriaceae strains in Hamadan,West of Iran

Plasmid mediated quinolone resistance (PMQR) determinants have arisen as a significant concern in recent years. The aim of this study was screening of resistant-clinical isolates to fluoroquinolone antibiotics and detection of qnr and aac(6′)-Ib-cr genes.For this purpose we collected 100 fluoroquinolone-resistant Enterobacteriaceae which were from 3 hospitals in Hamadan, west provinces of Iran, between October 2012 and June 2013. The all samples were identified by biochemical tests and confirmed by PCR method. Antimicrobial susceptibility to 14 antimicrobial agents including levofloxacin and ciprofloxacin were determined by disk diffusion methods and ciprofloxacin MIC was obtained by broth microdilution method as Clinical Laboratory Standards Institute (CLSI) recommendations. The isolates were screened for the presence of qnrA, qnrB, qnrS and aac(6′)-Ib-cr genes using PCR assay. Among the screened isolates, 64 strains (64%) of Escherichia coli, 23 strains (23%) of Klebsiella pneumoniae, 13 strains (13%) of Proteus mirabilis were collected as quinolone-resistant isolates. out of 100 isolates, two (2%) were positive for qnrS, seventeen (17%) isolates were positive for qnrB and we did not find qnrA gene in any of the isolates. There were also 32 positive isolates for aac(6′)-Ib-cr determinant. We described the prevalence of qnr and aac(6′)-Ib-cr genes in fluoroquinolone-resistant Enterobacteriaceae in Hamadan city. The carriage rate of multidrug-resistant Enterobacteriaceae in healthy people in Hamadan City is extremely high. Moreover, genes encoding transferable quinolones, in particular aac(6′)-Ib-cr, are highly prevalent in these strains.     

A Dermal Gel Made of Rutilus Kutum Skin Collagen-Chitosan for Deep Burn Healing

International Journal of Peptide Research and Therapeutics - Natural compounds extracted from marine organisms consisting of biological active materials like collagen provide a major source of...     

Design and Synthesis of Fluoroacylshikonin as an Anticancer Agent

A series of shikonin derivatives, selectively acylated by various fluorinated carboxylic acids at the side chain of shikonin, were synthesized and their anticancer activity evaluated, in which eight compounds are reported for the first time. Among all the compounds tested, compound S7 showed the most potent anticancer activity against B16‐F10 (malignant melanoma cells), MG63 (human osteosarcoma cells), and A549 (lung cancer cells) with IC₅₀ 0.39 ± 0.01, 0.72 ± 0.04 and 0.58 ± 0.02 µmol/L. Docking simulation of compound S7 was carried out to position S7 into a tubulin active site to determine the probable binding conformation. All the results suggested that compound S7 may be a potential anticancer agent. Chirality 25:757–762, 2013. © 2013 Wiley Periodicals, Inc.     

Metagenomics analysis of the fecal microbiota in Ring-necked pheasants (Phasianus colchicus) and Green pheasants (Phasianus versicolor) using next generation sequencing

Pheasant reintroduction and conservation efforts have been in place in Pakistan since the 1980 s, yet there is still a scarcity of data on pheasant microbiome and zoonosis. Instead of growing vast numbers of bacteria in the laboratory, to investigate the fecal microbiome, pheasants (green and ring neck pheasant) were analyzed using 16S rRNA metagenomics and using IonS5TMXL sequencing from two flocks more than 10 birds. Operational taxonomic unit (OTU) cluster analysis and phylogenetic tree analysis was performed using Mothur software against the SSUrRNA database of SILVA and the MUSCLE (Version 3.8.31) software. Results of the analysis showed that firmicutes were the most abundant phylum among the top ten phyla, in both pheasant species, followed by other phyla such as actinobacteria and proteobacteria in ring necked pheasant and bacteroidetes in green necked pheasant. Bacillus was the most relatively abundant genus in both pheasants followed by Oceanobacillus and Teribacillus for ring necked pheasant and Lactobacillus for green necked pheasant. Because of their well-known beneficial characteristics, these genus warrants special attention. Bird droppings comprise germs from the urinary system, gut, and reproductive sites, making it difficult to research each anatomical site at the same time. We conclude that metagenomic analysis and classification provides baseline information of the pheasant fecal microbiome that plays a role in disease and health.     

Attributes of the plankton flora at Bushehr,Iran

The plankton flora on the northeastern coast of the Gulf of Persia consists of many diatom species, the coccolithophores Gephyrocapsa oceanica and Coccolithus huxleyi, and the blue-green alga, Trichodesmium thiebautii. These are prevalent throughout the year and always at low concentrations, with an average maximum in January of 14463 cells/liter and minimum in June of 802/liter. Such comparative constancy suggests that the flora has the attribute of stability. The individual species fluctuate in a patternless, uncorrelated manner, so that the flora is characterized by the attribute of unpredictability. The turbidity of the shallow water reduces the light so that light is usually neither limiting nor inhibitory. There is a small amount of nitrate always available and ample phosphate and silicate. Pure culture studies of several species show growth from about 12° to 34°. The water was 34° in August of 1977. The flora's responsiveness to these light, nutrient, and temperature quantities makes possible its recovery to normal after advective disturbance in June 1977.Contribution number 4574 from the Woods Hole Oceanographic Institution.Contribution number 4574 from the Woods Hole Oceanographic Institution.     

Induction of systemic resistance in tomato against broomrape (Phelipanche aegyptiaca)

Rhizosphere dwelling bacteria can increase plant resistance to biotic and abiotic stresses, and they promote plant growth through various mechanisms. In this study, three bioassays were conducted including the following: (a) screening for effective bacterial isolates in the suppression of broomrape, (b) evaluating induced systemic resistance against broomrape and (c) comparing the selected bacterium isolate with plant chemical inducers. Fifteen plant growth‐promoting rhizobacteria (PGPR) were examined to assess their biocontrol potential against Egyptian broomrape (Phelipanche aegyptiaca). Ten isolates significantly reduced the broomrape biomass compared to the control. The Lysinibacillus boronitolerans B124 reduced the dry weight of broomrape plants from 2.15 g in control to 0.45 g. Bacillus megaterium B6 was the best isolate in reducing the number of broomrape tubercles. In addition, the activity of three selected bacterial isolates was investigated in induced systemic resistance to broomrape by split‐root method. The Bacillus pumilus INR7 reduced the number of visible broomrape tubercles by 90%, and B. megaterium B71 and L. boronitolerans B124 were the next two in rank. Compared with the control, L. boronitolerans B124 reduced the dry weight of broomrape from 1.49 g in control to 0.39 g. In a subsequent experiment, L. boronitolerans B124 was evaluated along with some resistance‐inducing volatile compounds. Lysinibacillus boronitolerans B124 decreased the number of broomrapes by 87% on average, while the lowest dry weight of broomrape was observed in methyl jasmonate treatment. In conclusion, PGPR have considerable potential to be used in the integrated management of broomrape. It is also possible to use a mixture of rhizobacteria and defence inducers, such as biogenic volatiles as a promising approach in the management of this noxious parasitic weed.     

Design of a heterosubtypic epitope-based peptide vaccine fused with hemokinin-1 against influenza viruses

Influenza viruses continue to emerge and re-emerge, posing new threats for public health. Control and treatment of influenza depends mainly on vaccination and chemoprophylaxis with approved antiviral drugs. Identification of specific epitopes derived from influenza viruses has significantly advanced the development of epitope-based vaccines. Here, we explore the idea of using HLA binding data to design an epitope-based vaccine that can elicit heterosubtypic T-cell responses against circulating H7N9, H5N1, and H9N2 subtypes. The hemokinin-1(HK-1) peptide sequence was used to induce immune responses against the influenza viruses. Five conserved high score cytotoxic T lymphocyte(CTL) epitopes restricted to HLA-A*0201-binding peptides within the hemagglutinin(HA) protein of the viruses were chosen, and two HA CTL/HK-1 chimera protein models designed. Using in silico analysis, which involves interferon epitope scanning, protein structure prediction, antigenic epitope determination, and model quality evaluation, chimeric proteins were designed. The applicability of one of these proteins as a heterosubtypic epitopebased vaccine candidate was analyzed.     

Assessment of risk management and control measures against coronavirus disease

This article presents the COVID-19 situation and control measures taken by the Government of Pakistan. Two waves of pandemic are faced globally and similar in the study area. We have investigated the risk management decision in two phases. Primarily, strict lockdown was observed from March 2020 to July 2020 and smart lockdown was enforced from August 2020 to December 2020. It has been studied that during strict lockdown, COVID cases reduced gradually but reopening of institutes and smart lockdown strategy resulted gradual increase in confirmed cases and death rates. During first wave of COVID-19 in Pakistan, a total confirmed number of patients of COVID-19 were 263,496 till 18th of July 2020 with total deaths of 5,568 people and 204,276 recoveries, while total number of COVID-19 patients reached 555,511 till 9th of February 2021 with total deaths of 12,026 people. Province of Sindh was affected badly with total number of 251,434 COVID-19 cases followed by Punjab Province with total number of 161,347 COVID-19 till 9th of February 2020.     

Clinical stage drugs targeting inhibitor of apoptosis proteins purge episomal Hepatitis B viral genome in preclinical models

A major unmet clinical need is a therapeutic capable of removing hepatitis B virus (HBV) genome from the liver of infected individuals to reduce their risk of developing liver cancer. A strategy to deliver such a therapy could utilize the ability to target and promote apoptosis of infected hepatocytes. Presently there is no clinically relevant strategy that has been shown to effectively remove persistent episomal covalently closed circular HBV DNA (cccDNA) from the nucleus of hepatocytes. We used linearized single genome length HBV DNA of various genotypes to establish a cccDNA-like reservoir in immunocompetent mice and showed that clinical-stage orally administered drugs that antagonize the function of cellular inhibitor of apoptosis proteins can eliminate HBV replication and episomal HBV genome in the liver. Primary human liver organoid models were used to confirm the clinical relevance of these results. This study underscores a clinically tenable strategy for the potential elimination of chronic HBV reservoirs in patients.Subject terms: Target validation, Hepatitis B, Preclinical research, Translational research