Transcriptional Pausing Factor m1bp Regulates Cellular Homeostasis by Suppressing Autophagy and Apoptosis in \u3cem\u3eDrosophila \u3c/em\u3eEye

During organogenesis cellular homeostasis plays a crucial role in patterning and growth. The role of promoter proximal pausing of RNA polymerase II, which regulates transcription of several developmental genes by GAGA factor or Motif 1 Binding Protein (M1BP), has not been fully understood in cellular homeostasis. Earlier, we reported that M1BP, a functional homolog of ZKSCAN3, regulates wingless (wg) and caspase-dependent cell death (apoptosis) in the Drosophila eye. Further, blocking apoptosis does not fully rescue the M1BPRNAi phenotype of reduced eye. Therefore, we looked for other possible mechanism(s). In a forward genetic screen, members of the Jun-amino-terminal-(NH2)-Kinase (JNK) pathway were identified. Downregulation of M1BP ectopically induces JNK, a pro-death pathway, known to activate both apoptosis and caspase-independent (autophagy) cell death. Activation of JNK pathway components can enhance M1BPRNAi phenotype and vice-versa. Downregulation of M1BP ectopically induced JNK signaling, which leads to apoptosis and autophagy. Apoptosis and autophagy are regulated independently by their genetic circuitry. Here, we found that blocking either apoptosis or autophagy alone rescues the reduced eye phenotype of M1BP downregulation; whereas, blocking both apoptosis and autophagy together significantly rescues the M1BP reduced eye phenotype to near wild-type in nearly 85% progeny. This data suggests that the cellular homeostasis response demonstrated by two independent cell death mechanisms, apoptosis and autophagy, can be regulated by a common transcriptional pausing mechanism orchestrated by M1BP. Since these fundamental processes are conserved in higher organisms, this novel functional link between M1BP and regulation of both apoptosis and autophagy can be extrapolated to humans

Serological and molecular approaches for leptospirosis at a tertiary care centre in northern India

Background: Aims and objectives of the study was to determine prevalence rate of leptospirosis and recognition of common epidemiological situation and clinical manifestations of leptospirosis in patients with pyrexia of unknown origin at a tertiary care centre.Methods: This was a hospital based prospective observational study. The duration of study was from August 2015 to July 2016. Patients with clinical symptoms of pyrexia of unknown origin attending Gandhi Memorial and Associated Hospital, King George’s Medical University Lucknow during the study period were enrolled in this study. We performed the IgM ELISA and PCR for the leptospirosis at our centre and for the Micro Agglutination Test (MAT), we sent the serum samples to regional medical research centre Department of Health Research Ministry of Health and Family Welfare, Govt. of India Port Blair.Results: A Total of 104 symptomatic patients were recruited. Of total, IgM ELISA for leptospirosis were positive in 25 patients, PCR in 20 patients and MAT shows significant titres in 3 samples. The ROC curve analysis revealed significant diagnostic accuracy of IgM ELISA with 100.00% sensitivity and 78.22% specificity however showed less positive predictive value (12.0%) but high negative predictive value (100.0%). Most common presentation were fever, jaundice and rashes (40.4%) followed by fever and jaundice (29.8%).Conclusions: Leptospirosis IgM ELISA and PCR showed good detection accuracy. Age, sex, occupation is not significantly associated to the leptospirosis

Lubrication synergy: Mixture of hyaluronan and dipalmitoylphosphatidylcholine (DPPC) vesicles

AbstractPhospholipids and hyaluronan have been implied to fulfil important roles in synovial joint lubrication. Since both components are present in synovial fluid, self-assembly structures formed by them should also be present. We demonstrate by small angle X-ray scattering that hyaluronan associates with the outer shell of dipalmitoylphophatidylcholine (DPPC) vesicles in bulk solution. Further, we follow adsorption to silica from mixed hyaluronan/DPPC vesicle solution by Quartz Crystal Microbalance with Dissipation measurements. Atomic Force Microscope imaging visualises the adsorbed layer structure consisting of non-homogeneous phospholipid bilayer with hyaluronan/DPPC aggregates on top. The presence of these aggregates generates a long-range repulsive surface force as two such surfaces are brought together. However, the aggregates are easily deformed, partly rearranged into multilayer structures and partly removed from between the surfaces under high loads. These layers offer very low friction coefficient (<0.01), high load bearing capacity (≈23MPa), and self-healing ability. Surface bound DPPC/hyaluronan aggregates provide a means for accumulation of lubricating DPPC molecules on sliding surfaces

Synergies in Biolubrication

The objective of this thesis was to advance understanding in the field of biolubrication, finding inspiration from the human synovial joints. This was addressed by investigating the association of key biolubricants and the resulting lubrication performance. Techniques employed during the course of this work were Atomic force microscopy (AFM), Quartz crystal microbalance with dissipation monitoring (QCM-D), X-ray reflectivity (XRR). Key synovial fluid and cartilage components like dipalmitoylphosphatidylcholine (DPPC), hyaluronan (HA), lubricin, and cartilage oligomeric matrix protein (COMP) have been used in the investigations. Focus was towards two lubrication couples; DPPC-hyaluronan and COMP-lubricin. DPPC-hyaluronan mixtures were probed on hydrophilic silica surfaces and COMP-lubricin association structures were explored on weakly hydrophobic poly (methyl methacrylate) (PMMA) surfaces. Investigations of the COMP-lubricin pair revealed that individually these components are unable to reach desired lubrication. However in combination, COMP facilitates firm attachment of lubricin to the PMMA surface in a favourable confirmation that imparts low friction coefficient. DPPC and hyaluronan combined impart lubrication advantage over lone DPPC bilayers. Hyaluronan provides a reservoir of DPPC on the surface and consequently self-healing ability. Other factors like temperature, presence of calcium ions, molecular weight of hyaluronan, and pressure were also explored. DPPC bilayers at higher temperature had higher load bearing capacity. Association between DPPC Langmuir layers and hyaluronan was enhanced in the presence of calcium ions, and lower molecular weight hyaluronan had a stronger tendency to bind to DPPC. At high pressures, DPPC-hyaluronan layers were more stable compared to lone DPPC bilayers.QC 20170210</p

Identification of bioactive agent in Tinospora cordifolia by a slice approach

Candida species cause most fungal infections and contribute significantly to worldwide morbidity and mortality, making them a severe public health threat. Due to their ability to develop resistance to antifungal drugs, these opportunistic fungi defy therapeutic efforts, making them a severe problem in treating and managing Candida infections. Due to co-infection with immune-compromised persons, multidrug-resistant Candida spp. strains have developed as a global concern, which can lead to invasive candidiasis. The life-threatening variant of the illness may be treated quickly and effectively through drug repurposing. Hence, this research was done in tandem with a previous inquiry into the chemicals' ability to fight Candida spp. According to molecular docking and molecular dynamics studies, a total of five compounds, namely Cholesterol, Allopyranose, Melezitose, 1,6-Anhydro-B-D-Glucofuranose, and 1-(3-Cyanophenly)-2-Phenylethane isolated from the sample (in previous study) have the potential to inhibit the growth of further Candida albicans. After ligand binding, the protein-ligand interaction was also studied to know which residues are involved in bond formation. Out of these five ligands, only one ligand violated Lipinski's rule, namely Melezitose. Therefore, the compounds isolated in the previous study have a strong antifungal effect.&nbsp

Identification of bioactive agent in tinospora cordifolia by in- silico approach

Candida species cause most fungal infections and contribute significantly to worldwide morbidity and mortality, making them a severe public health threat. Due to their ability to develop resistance to antifungal drugs, these opportunistic fungi defy therapeutic efforts, making them a severe problem in treating and managing Candida infections. Due to co-infection with immune-compromised persons, multidrug-resistant Candida spp. strains have developed as a global concern, which can lead to invasive candidiasis. The life-threatening variant of the illness may be treated quickly and effectively through drug repurposing. Hence, this research was done in tandem with a previous inquiry into the chemicals' ability to fight Candida spp. According to molecular docking and molecular dynamics studies, a total of five compounds, namely Cholesterol, Allopyranose, Melezitose, 1,6-Anhydro-B-D-Glucofuranose, and 1-(3-Cyanophenly)-2-Phenylethane isolated from the sample (in previous study) have the potential to inhibit the growth of further Candida albicans. After ligand binding, the protein-ligand interaction was also studied to know which residues are involved in bond formation. Out of these five ligands, only one ligand violated Lipinski's rule, namely Melezitose. Therefore, the compounds isolated in the previous study have a strong antifungal effect.&nbsp