Meprin A and meprin α generate biologically functional IL-1β from pro-IL-1β

The present study demonstrates that both oligomeric metalloendopeptidase meprin A purified from kidney cortex and recombinant meprin α are capable of generating biologically active IL-1β from its precursor pro-IL-1β. Amino-acid sequencing analysis reveals that meprin A and meprin α cleave pro-IL-1β at the His¹¹⁵-Asp¹¹⁶ bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin β site. The biological activity of the pro-IL-1β cleaved product produced by meprin A, determined by proliferative response of helper T-cells, was 3-fold higher to that of the IL-1β product produced by meprin β or caspase-1. In a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum IL-1β, meprin inhibitor actinonin significantly reduces levels of serum IL-1β. Meprin A and meprin α may therefore play a critical role in the production of active IL-1β during inflammation and tissue injury.     

Genetic Characterization of the Influenza A Pandemic (H1N1) 2009 Virus Isolates from India

Background

The Influenza A pandemic H1N1 2009 (H1N1pdm) virus appeared in India in May 2009 and thereafter outbreaks with considerable morbidity and mortality have been reported from many parts of the country. Continuous monitoring of the genetic makeup of the virus is essential to understand its evolution within the country in relation to global diversification and to track the mutations that may affect the behavior of the virus.

Methods

H1N1pdm viruses were isolated from both recovered and fatal cases representing major cities and sequenced. Phylogenetic analyses of six concatenated whole genomes and the hemagglutinin (HA) gene of seven more isolates from May-September 2009 was performed with reference to 685 whole genomes of global isolates available as of November 24, 2009. Molecular characterization of all the 8 segments was carried out for known pathogenic markers.

Results

The first isolate of May 2009 belonged to clade 5. Although clade 7 was the dominant H1N1pdm lineage in India, both clades 6 and 7 were found to be co-circulating. The neuraminidase of all the Indian isolates possessed H275, the marker for sensitivity to the neuraminidase inhibitor Oseltamivir. Some of the mutations in HA are at or in the vicinity of antigenic sites and may therefore be of possible antigenic significance. Among these a D222G mutation in the HA receptor binding domain was found in two of the eight Indian isolates obtained from fatal cases.

Conclusions

The majority of the 13 Indian isolates grouped in the globally most widely circulating H1N1pdm clade 7. Further, correlations of the mutations specific to clade 7 Indian isolates to viral fitness and adaptability in the country remains to be understood. The D222G mutation in HA from isolates of fatal cases needs to be studied for pathogenicity.     

First evidence of putrescine involvement in mitigating the floral malformation in mangoes: A scanning electron microscope study

Floral malformation is the most destructive disease in mangoes. To date, the etiology of this disease has not been resolved. There are indications that stress-stimulated ethylene production might be responsible for the disease. Putrescine mediates various physiological processes for normal functioning and cellular metabolism. Here, the effect of putrescine in concentration ranging from 10^?1 to 10^?3 M was evaluated on disease incidence during mango flowering seasons of 2012 and 2013. In a scanning electron microscopy (SEM) study, putrescine (10^?2 M)-treated malformed floral buds bloomed into opened flowers with separated sepals and/or petals like healthy, whereas the untreated (control) malformed buds remained deformed. Further, malformed flowers recovered upon putrescine treatment, displaying clearly bilobed anthers, enclosing a large number of normal pollen grains and functional ovary with broad stigmatic surface as compared to control. The present findings provide the first report to demonstrate the role of putrescine in reducing various adverse effects of stress ethylene via decelerating the higher pace of its biosynthesis. It stabilizes the normal morphology, development, and functions of malformed reproductive organs to facilitate successful pollination, fertilization, and, thereby, fruit set in mango flowers. However, putrescine–ethylene-mediated cell signaling network, involving various genes to trigger the response, which regulates a wide range of developmental and physiological processes leading to normal cell physiology, needs to be investigated further.     

Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family

By consensus, the acyl-CoA synthetase (ACS) community, with the advice of the human and mouse genome nomenclature committees, has revised the nomenclature for the mammalian long-chain acyl-CoA synthetases. ACS is the family root name, and the human and mouse genes for the long-chain ACSs are termed ACSL1,3-6 and Acsl1,3-6, respectively. Splice variants of ACSL3, -4, -5, and -6 are cataloged. Suggestions for naming other family members and for the nonmammalian acyl-CoA synthetases are made.     

Biocontrol potential of two novel grapevine associated Bacillus strains for management of anthracnose disease caused by Colletotrichum gloeosporioides

A study was conducted to identify bacterial antagonists for biological control of anthracnose which is one of the economically important diseases of grapes. In India, it is caused by Colletotrichum gloeosporioides. Two hundred and ninety-three bacteria were isolated from the grape ecosystem of 43 spatially distant vineyards in peninsular India. Of these, 25 bacteria substantially inhibited the radial growth of C. gloeosporioides in in vitro studies and 18 bacteria significantly reduced infections in vivo. Of these 18 bacteria, 5 and 3 bacteria also significantly reduced percent disease index (PDI) of downy and powdery mildew diseases, respectively. These bacteria were labelled as strains, DR-38, DR-39, TL-171, DRo-198, TS-204, TS-205, and DR-219, and were identified as Bacillus species based on morphological and molecular characterisation. Aqueous suspensions of all these strains applied as foliar sprays at 1×10⁸ cfu/ml on field grown vines significantly lowered the PDI and the AUDPC (area under disease progress curve) of anthracnose when compared with the untreated control, except DRo-198. Strains TS-204 and TL-171 recorded lower PDIs and AUDPC when compared with the other five strains, and TS-204 could effectively suppress ripe rot of berries, too, in vivo. Strains TS-204 and TL-171 are identified for biocontrol of anthracnose in grapes.     

Self-Assembling Raloxifene Loaded Mixed Micelles: Formulation Optimization, <Emphasis Type="Italic">In Vitro</Emphasis> Cytotoxicity and <Emphasis Type="Italic">In Vivo</Emphasis> Pharmacokinetics

Raloxifene (RLX) has been strongly recommended for postmenopausal women at high risk of invasive breast cancer and for prevention of osteoporosis. However, low aqueous solubility and reduced bioavailability hinder its clinical application. The objective of this study was to explore the potential of RLX loaded mixed micelles (RLX-MM) using Pluronic F68 and Gelucire 44/14 for enhanced bioavailability and improved anticancer activity on human breast cancer cell line (MCF-7). RLX-MM were prepared by solvent evaporation method and optimized using 3² factorial design. The average size, entrapment efficiency and zeta potential of the optimized formulation were found to be 190?±?3.3 nm, 79?±?1.3%, 13?±?0.8 mV, respectively. In vitro study demonstrated 74.68% drug release from RLX-MM in comparison to 42.49% drug release from RLX dispersion. According to the in vitro cytotoxicity assay, GI₅₀ values on MCF-7 breast cancer cell line for RLX-MM and free RLX were found to be 22.5 and 94.71 μg/mL, respectively. Significant improvement (P?<?0.05) in the anticancer activity on MCF-7 cell line was observed in RLX-MM over RLX pure drug. Additionally, oral bioavailability of RLX-MM was improved by 1.5-fold over free RLX when administered in female Wistar rats. Incorporation of RLX in the hydrophobic core and improved solubility of the drug due to hydrophilic shell attributed to the enhanced cytotoxicity and bioavailability of RLX-MM. This research establishes the potential of RLX loaded mixed micelles of Pluronic F68 and Gelucire 44/14 for improved bioavailability and anticancer activity on MCF-7 cell line.