A novel templates of piperazinyl-1,2-dihydroquinoline-3-carboxylates: Synthesis,anti-microbial evaluation and molecular docking studies

A series of piperazinyl-1,2-dihydroquinoline carboxylates were synthesized by the reaction of ethyl 4-chloro-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylates with various piperazines and their structures were confirmed by ¹H NMR, ¹³C NMR, IR and mass spectral analysis. All the synthesized compounds were screened for their in vitro antimicrobial activities. Further, the in silico molecular docking studies of the active compounds was performed to explore the binding interactions between piperazinyl-1,2-dihydroquinoline carboxylate derivatives and the active site of the Staphylococcus aureus (CrtM) dehydrosqualene synthase (PDB ID: 2ZCQ). The docking studies revealed that the synthesized derivatives showed high binding energies and strong H-bond interactions with the dehydrosqualene synthase validating the observed antimicrobial activity data. Based on antimicrobial activity and docking studies, the compounds 9b and 10c were identified as promising antimicrobial lead molecules. This study might provide insights to identify new drug candidates that target the S. aureus virulence factor, dehydrosqualene synthase.     

The effects of short-term uniaxial strain on the mechanical properties of mesenchymal stem cells upon TGF-β<Subscript>1</Subscript> stimulation

Cellular mechanical characteristics represent cell ability to produce tissue-specific metabolites. Therefore, to achieve effective cell therapy, a better understanding of the effects of chemo-mechanical stimuli on the mechanical properties of in vitro-treated cells is essential. Herein, we investigated the effects of uniaxial strain on the mechanical properties of mesenchymal stem cells (MSCs) upon transforming growth factor beta 1 (TGF-β₁) stimulation. The MSCs were categorized into control and test groups. In one test group, the MSCs were treated by TGF-β₁ for 6 d, and in the other, they were additionally subjected to 1-d uniaxial strain on day 2. The cell mechanical properties and smooth muscle (SM) gene expression were assessed on days 2, 4, and 6. During the entire experiment, the MSCs treated by TGF-β₁ ± uniaxial strain were induced to differentiate into SM-like cells by significantly upregulation of α-actin, SM22α, and h1-calponin in respect to the control samples. When the MSCs were treated with TGF-β₁ alone, their stiffness and viscosity decreased significantly on day 2 and then increased by increase in culture time. When the cells were subjected to 1-d uniaxial strain upon TGF-β₁ stimulation, their stiffness and viscosity significantly increased on days 2 and 4 and then decreased on day 6 to a level comparable to that of TGF-β₁ group. Different paths were noticeable among the treated samples to reach nearly similar states on day 6. It seems that uniaxial strain activates mechanobiological cascades by which cellular mechanical behavior can be regulated after its removal. However, these effects are transient and would diminish over time. The findings may be helpful in the chemo-mechanical regulation of MSCs.     

A peptide from Testudo horsfieldii tortoise spleen as a potential helper for reducing acute radiation syndrome

The Middle Asian tortoise Testudo horsfieldii is one of the most radioresistant animals, with Lethal Dose (LD) 50/30 around 500 Gy. Extracts were prepared from different organs of the tortoise, and their biological activity was evaluated. Crude extract from the spleen was found to significantly increase survival of mice treated with lethal doses of radiation. In an iterative process, the active extract was purified by chromatography, and the fractions were screened for biological activity. Various vital parameters were monitored: peripheral blood leukocytes, spleen colonies, mitosis in the bone marrow, and survival after 30 days. The process concluded with the isolation, characterization, and synthesis of the tetrapeptide FTGN, which accelerated repopulation of the irradiated bone marrow at very low concentrations both in vivo and ex vivo. A fluorescently labeled derivative of the peptide was found to selectively associate to CD34⁺ stem cells, suggesting that the peptide mediates their proliferation and allows fast repopulation of hematopoietic lineages. Interestingly, the peptide protected animals from alopecia. The studies in experimental animals suggest that treatment with FTGN can potentially benefit patients who suffer bone marrow damage due to radiotherapy or chemotherapy and patients undergoing autologous or allogenic bone marrow transplantation.     

Targeted chromosome elimination from ES-somatic hybrid cells

To engineer a stem cell genome, we developed a technology for targeted elimination of chromosomes from mouse embryonic stem (ES)-somatic hybrid cells. Here we demonstrate the use of a universal chromosome elimination cassette (CEC) for elimination of a single embryonic stem cell (ESC)-derived chromosome 11 or 12, and also both copies of chromosome 6, which harbor pluripotency-associated genes including Nanog. We attribute hybrid-cell pluripotency to the expression of Nanog from the reprogrammed somatic-cell nuclei.     

The Chloroplast Genome Sequence of Date Palm (Phoenix dactylifera L. cv. ‘Aseel’)

Date palm (Phoenix dactylifera L.) is an economically important and widely cultivated palm of the family Arecaceae. We sequenced the complete date palm chloroplast genome (cpDNA) from Pakistani cv. ??Aseel??, using a combination of Sanger-based and next-generation sequencing technologies. Being very similar to a sequence from a Saudi Arabian date palm cultivar ??Khalas?? published recently, the size of the genome was 158,458?bp with a pair of inverted repeat (IR) regions of 27,276?bp that were separated by a large single-copy (LSC) region of 86,195?bp and a small single-copy (SSC) region of 17,711?bp. Genome annotation demonstrated a total of 138 genes, of which 89 were protein coding, 39 were tRNA, and eight were rRNA genes. Comparison of cpDNA sequences of cultivars ??Aseel?? and ??Khalas?? showed following intervarietal variations in the LSC region; (a) two SNPs in intergenic spacers and one SNP in the rpoc1 gene, (b) polymorphism in two mono-nucleotide simple sequence repeats (SSR), and (c) a 4-bp indel in the accD-psaI intergenic spacer. The SSC region has a polymorphic site in the mono-nucleotide SSR located at position 120,710. We also compared cv. ??Aseel?? cpDNA sequence with partial P. dactylifera cpDNA sequence entries deposited in Genbank and identified a number of potentially useful polymorphisms in this species. Analysis of date palm cpDNA sequences revealed a close relationship with Typha latifolia. Occurrence of small numbers of forward and inverted repeats in date palm cpDNA indicated conserved genome arrangement.     

Influenza in Outpatient ILI Case-Patients in National Hospital-Based Surveillance,Bangladesh, 2007–2008

Background

Recent population-based estimates in a Dhaka low-income community suggest that influenza was prevalent among children. To explore the epidemiology and seasonality of influenza throughout the country and among all age groups, we established nationally representative hospital-based surveillance necessary to guide influenza prevention and control efforts.

Methodolgy/Principal Findings

We conducted influenza-like illness and severe acute respiratory illness sentinel surveillance in 12 hospitals across Bangladesh during May 2007–December 2008. We collected specimens from 3,699 patients, 385 (10%) which were influenza positive by real time RT-PCR. Among the sample-positive patients, 192 (51%) were type A and 188 (49%) were type B. Hemagglutinin subtyping of type A viruses detected 137 (71%) A/H1 and 55 (29%) A/H3, but no A/H5 or other novel influenza strains. The frequency of influenza cases was highest among children aged under 5 years (44%), while the proportions of laboratory confirmed cases was highest among participants aged 11–15 (18%). We applied kriging, a geo-statistical technique, to explore the spatial and temporal spread of influenza and found that, during 2008, influenza was first identified in large port cities and then gradually spread to other parts of the country. We identified a distinct influenza peak during the rainy season (May–September).

Conclusions/Significance

Our surveillance data confirms that influenza is prevalent throughout Bangladesh, affecting a wide range of ages and causing considerable morbidity and hospital care. A unimodal influenza seasonality may allow Bangladesh to time annual influenza prevention messages and vaccination campaigns to reduce the national influenza burden. To scale-up such national interventions, we need to quantify the national rates of influenza and the economic burden associated with this disease through further studies.