Foliar application of Ascophyllum nodosum on improvement of photosynthesis, fruit setting percentage, yield and quality of tomato (Solanum lycopersicum L.)

In recent days, liquid formulations of brown seaweed extract, Ascophyllum nodosum used as a biostimulant in agriculture. Various studies suggest that A. nodosum enhanced the growth and yield of agriculturally important crops, but still, there is a lack of information about the biostimulation effects on photosynthesis, flowering and fruit setting of tomato. Hence, the present study aimed to know the effect of foliar application of A. nodosum on photosynthesis, flowering, fruit setting, yield and quality of tomato. A biostimulant product, MC Set with A. nodosum extract applied to tomato as a foliar spray at rates of three different concentrations such as 1.0 L ha−1 (MS 1), 2.0 L ha−1 (MS 2), 3.0 L ha−1 (MS 3) for six times during flowering of 2nd (30 Days after transplanting – DAT), 3rd (40 DAT) and 4th (50 DAT) cluster and fruit setting of 2nd (60 DAT), 3rd (70 DAT) and 4th (80 DAT) cluster respectively. The MC Set treatments enhanced the plant photosynthesis, flower number and fruit number per cluster, yield and quality traits of tomato. However, the middle concentration MS 2 showed highest photosynthetic rate, stomatal conductance, SPAD value, flower and fruit in 2nd, 3rd and 4th cluster. It also had better average fruit weight and yield per plant and hectare and enhanced the quality parameters such as total soluble solids, ascorbic acid content, lycopene and total sugars compared to control and other two concentrations of MS Set. Hence, using A. nodosum extract on tomato growth could be a better sustainable crop production method.

Susceptibility of human primary neuronal cells to Xenotropic Murine Leukemia Virus-related (XMRV) virus infection

<p>Abstract</p> <p>Background</p> <p>Xenotropic Murine Leukemia Virus-related (XMRV) virus is a recently identified mouse gammaretrovirus that has the ability to infect certain human cells. In this study, we investigated the susceptibility of primary neuronal cell types to infection with XMRV.</p> <p>Findings</p> <p>We observed that the human primary progenitors, progenitor-derived neurons, and progenitor-derived astrocytes supported XMRV multiplication. Interestingly, both progenitors and progenitor-derived neurons were more susceptible compared with progenitor-derived astrocytes. In addition, XMRV-infected Jurkat cells were able to transmit infection to neuronal cells.</p> <p>Conclusions</p> <p>These data suggest that neuronal cells are susceptible for XMRV infection.</p

Exploration of anticancer potential of hydroxamate derivatives as selective HDAC8 inhibitors using integrated structure and ligand based molecular modeling approach

136-147Recently, histone deacetylase inhibitors are evolving as an exhilarating new class of promising antitumor agents for the treatment of multiple malignancies. It may play a pivotal role as a therapeutic target for challenging the globally wide spread disease, cancer. At the same time, the prediction of biological activity of novel compounds, which was once a major challenge in drug design, is also pacing up its speed. This computational study has been performed in Schrodinger suite packages such as sitemap generation, grid formation, Glide for docking, Quikprop for ADME analysis, e-pharmacophore post docking script and Phase for 3D QSAR models designing, that all are available in Maestro version 9.3. Docking not only helps in predicting the preferred orientation of ligand with its target receptor, but also the binding affinity between the ligand and receptor. The application of Phase and e-pharmacophore script predicts some computational models of the provided ligands using 3D QSAR method. This decreases the cost and time of biological experiments. Glide XP reveals that compound 21 with the highest score value as the best compound from the dataset. Also, it shows good R2=0.9834, Q2= 0.7753, stability = 0.5407 and low standard of deviation SD=0.1085 for hypothesis ADDRR.1601, for the PLS factor 5. The outcome of these studies suggests compound 21 as a potential drug molecule for HDAC targets

Exploration of anticancer potential of hydroxamate derivatives as selective HDAC8 inhibitors using integrated structure and ligand based molecular modeling approach

Recently, histone deacetylase inhibitors are evolving as an exhilarating new class of promising antitumor agents for the treatment of multiple malignancies. It may play a pivotal role as a therapeutic target for challenging the globally wide spread disease, cancer. At the same time, the prediction of biological activity of novel compounds, which was once a major challenge in drug design, is also pacing up its speed. This computational study has been performed in Schrodinger suite packages such as sitemap generation, grid formation, Glide for docking, Quikprop for ADME analysis, e-pharmacophore post docking script and Phase for 3D QSAR models designing, that all are available in Maestro version 9.3. Docking not only helps in predicting the preferred orientation of ligand with its target receptor, but also the binding affinity between the ligand and receptor. The application of Phase and e-pharmacophore script predicts some computational models of the provided ligands using 3D QSAR method. This decreases the cost and time of biological experiments. Glide XP reveals that compound 21 with the highest score value as the best compound from the dataset. Also, it shows good R2=0.9834, Q2= 0.7753, stability = 0.5407 and low standard of deviation SD=0.1085 for hypothesis ADDRR.1601, for the PLS factor 5. The outcome of these studies suggests compound 21 as a potential drug molecule for HDAC targets

DNA-binding transcription factor NF-1A negatively regulates JC virus multiplication

JC virus (JCV) DNA replication occurs in the nuclei of infected cells. The level of JCV genome expression depends on nucleotide sequences in the viral regulatory region and their interaction with host-cell nuclear transcription factors. Our previous studies showed a higher level of NF-1X in JCV-permissive cells compared with the other members of the NF-1 family, NF-1A, B and C, which suggests that NF-1X plays a positive role in JCV multiplication. It remained unclear whether a reduction in the level of NF-1A, which is expressed abundantly in JCV-non-permissive cell types, leads to an increase in JCV multiplication. In this study, we show that downregulation of NF-1A expression in JCV-non-susceptible progenitor and HeLa cells results in a reversion to susceptibility for JCV multiplication. These data demonstrate that a higher level of NF-1A protein in JCV-non-permissive cell types, compared with the level of NF-1X, may be acting as a negative regulator at the JCV promoter to control JCV multiplication

Synthesis and antibacterial profile of novel azomethine derivatives of β-phenylacrolein moiety

Purpose: To develop some novel molecules effective against antibiotic-resistant bacterial infections.Methods: A series of azomethines (SB-1 to SB-6) were synthesized from β-phenyl acrolein moiety. The structures of the synthesized compounds were confirmed on the basis of their UV ultra-violet (UV) spectroscopy (λmax: 200 - 400 nm), Fourier transform infra-red (FTIR, vibrational frequency: 500-4000 cm-1), 1H nuclear magnetic resonance (NMR, chemical shift: 0 - 10 ppm), 13C NMR (chemical shift: 0 - 200 ppm), mass spectrometry (m/z values: 0 - 500) and carbon hydrogen nitrogen (CHN) elemental analysis. The new compounds were screened for antibacterial activity by test-tube dilution and disc diffusion methods using gentamicin as reference standard.Results: The structures of azomethine were in full agreement with their spectral data. Among all the synthesized compounds, compounds SB-5 and SB-6 exhibited the highest minimum inhibitory concentration (MIC) of 62.5 μg/mL. At MIC of 250 μg/mL, all compounds SB-1 to SB-6 displayed significant antibacterial activity, compared to gentamycin (p &lt; 0.05). SB-5 and SB-6 were active against S. aureus, P. aeruginosa and K. pneumoniae; SB-3 was active against B. subtilis and S. aureus. SB-4 was active against P. aeruginosa and S. aureus while SB-1 and SB-2 were active against S. aureus.Conclusion: The synthesized compounds possess antibacterial activities compared to those of gentamycin.Keywords: Acrolein, Imines, Azomethine, Antibacterial, Gentamycin, Minimum inhibitory concentratio

XMRV: usage of receptors and potential co-receptors

<p>Abstract</p> <p>Background</p> <p>XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC) patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS). Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors.</p> <p>Methods</p> <p>To study the usage of different receptors and co- receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP- Human osteosarcoma) cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR.</p> <p>Results</p> <p>Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP.</p> <p>Conclusion</p> <p>XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors.</p

One-Step Preservation of Phosphoproteins and Tissue Morphology at Room Temperature for Diagnostic and Research Specimens

BACKGROUND: There is an urgent need to measure phosphorylated cell signaling proteins in cancer tissue for the individualization of molecular targeted kinase inhibitor therapy. However, phosphoproteins fluctuate rapidly following tissue procurement. Snap-freezing preserves phosphoproteins, but is unavailable in most clinics and compromises diagnostic morphology. Formalin fixation preserves tissue histomorphology, but penetrates tissue slowly, and is unsuitable for stabilizing phosphoproteins. We originated and evaluated a novel one-step biomarker and histology preservative (BHP) chemistry that stabilizes signaling protein phosphorylation and retains formalin-like tissue histomorphology with equivalent immunohistochemistry in a single paraffin block. RESULTS: Total protein yield extracted from BHP-fixed, routine paraffin-embedded mouse liver was 100% compared to snap-frozen tissue. The abundance of 14 phosphorylated proteins was found to be stable over extended fixation times in BHP fixed paraffin embedded human colon mucosa. Compared to matched snap-frozen tissue, 8 phosphoproteins were equally preserved in mouse liver, while AMPKβ1 Ser108 was slightly elevated after BHP fixation. More than 25 tissues from mouse, cat and human specimens were evaluated for preservation of histomorphology. Selected tissues were evaluated in a multi-site, independent pathology review. Tissue fixed with BHP showed equivalent preservation of cytoplasmic and membrane cytomorphology, with significantly better nuclear chromatin preservation by BHP compared to formalin. Immunohistochemical staining of 13 non-phosphorylated proteins, including estrogen receptor alpha, progesterone receptor, Ki-67 and Her2, was equal to or stronger in BHP compared to formalin. BHP demonstrated significantly improved immunohistochemical detection of phosphorylated proteins ERK Thr202/Tyr204, GSK3-α/β Ser21/Ser9, p38-MAPK Thr180/Tyr182, eIF4G Ser1108 and Acetyl-CoA Carboxylase Ser79. CONCLUSION: In a single paraffin block BHP preserved the phosphorylation state of several signaling proteins at a level comparable to snap-freezing, while maintaining the full diagnostic immunohistochemical and histomorphologic detail of formalin fixation. This new tissue fixative has the potential to greatly facilitate personalized medicine, biobanking, and phospho-proteomic research

Structure–Activity Relationship Analysis of Benzimidazoles as Emerging Anti-Inflammatory Agents: An Overview

A significant number of the anti-inflammatory drugs currently in use are becoming obsolete. These are exceptionally hazardous for long-term use because of their possible unfavourable impacts. Subsequently, in the ebb-and-flow decade, analysts and researchers are engaged in developing new anti-inflammatory drugs, and many such agents are in the later phases of clinical trials. Molecules with heterocyclic nuclei are similar to various natural antecedents, thus acquiring immense consideration from scientific experts and researchers. The arguably most adaptable heterocyclic cores are benzimidazoles containing nitrogen in a bicyclic scaffold. Numerous benzimidazole drugs are broadly used in the treatment of numerous diseases, showing promising therapeutic potential. Benzimidazole derivatives exert anti-inflammatory effects mainly by interacting with transient receptor potential vanilloid-1, cannabinoid receptors, bradykinin receptors, specific cytokines, 5-lipoxygenase activating protein and cyclooxygenase. Literature on structure–activity relationship (SAR) and investigations of benzimidazoles highlight that the substituent’s tendency and position on the benzimidazole ring significantly contribute to the anti-inflammatory activity. Reported SAR analyses indicate that substitution at the N1, C2, C5 and C6 positions of the benzimidazole scaffold greatly influence the anti-inflammatory activity. For example, benzimidazole substituted with anacardic acid on C2 inhibits COX-2, and 5-carboxamide or sulfamoyl or sulfonyl benzimidazole antagonises the cannabinoid receptor, whereas the C2 diarylamine and C3 carboxamide substitution of the benzimidazole scaffold result in antagonism of the bradykinin receptor. In this review, we examine the insights regarding the SARs of anti-inflammatory benzimidazole compounds, which will be helpful for researchers in designing and developing potential anti-inflammatory drugs to target inflammation-promoting enzymes